Nephrology

VIENNA – Urinary tract infections are relatively common and can be quite expensive among patients with newly diagnosed diabetes.

In a large patient database, the infection rate was about 128/1,000 patients, Shengsheng Yu, Ph.D., said at the annual meeting of the European Association for the Study of Diabetes. While only about 4% of these patients were hospitalized, their treatment costs hovered around $3,407 in Germany, where the study was conducted.

These data were extracted from a large German patient claims database, said Dr. Yu of Merck Sharp & Dohme, Whitehouse Station, N.J. The cohort comprised 530,918 patients who had type 2 diabetes during the study years of 2010-2012. Of these, 64,332 had incident disease.

Patients with newly diagnosed diabetes were significantly younger than was the diabetes-prevalent population (70 vs. 73 years), and had a significantly lower than the Charlson comorbidity index (5.4 vs. 7.3 years). Their diabetes was also less severe when measured by the adapted Diabetes Complication Severity Index (1.5 vs. 2.4).

During the study period, roughly 20% of patients had at least 1 urinary tract infection (UTI); 6% had two or more.

UTIs were twice as common in women. Prevalence also grew with advancing age in both sexes. Among those with newly diagnosed diabetes, women developed their UTI significantly more quickly than did men. By the end of the study, 20% of those women had developed one, compared with 10% of the men.

A multivariate analysis determined the risk factors associated with UTIs. These included having had a previous UTI (odds ratio, 3.5), female gender (OR, 1.7), higher Charlson comorbidity status (OR, 1.5), and age (OR, 1.4 for those older than 79 years).

Hemoglobin A1c levels were also a significant independent predictor of UTI, with an odds ratio of 1.5 for levels of 9.5%-10%, compared with 7%-7.5%.

In an analysis of the development of a first UTI after diagnosis, all of those predictive factors remained significant.

The investigators also examined costs associated with inpatient and outpatient treatment. Total costs included antibiotics and the cost of either ambulatory, outpatient, or in-hospital care.

The majority were treated by a physicians as an outpatient, with a median cost of 86 euros (US$111). About 46,500 received a prescription only, at a median cost of 22 euros (US$25). The smallest number (3,445) required hospitalization – a very expensive experience – with a mean cost of 2,627 euros (US$3,407).

During the discussion period, the issue of infection validation was a concern. Many physicians treat on symptoms only, or on a single urinalysis that might show a small amount of blood or protein. The number of culture-proven UTIs is much less, it was suggested.

Dr. Yu admitted that this is a common occurrence and could be affecting the validity of her conclusions somewhat.

She is an employee of Merck.

[email protected]

On Twitter @alz_gal

VIENNA – Urinary tract infections are relatively common and can be quite expensive among patients with newly diagnosed diabetes.

In a large patient database, the infection rate was about 128/1,000 patients, Shengsheng Yu, Ph.D., said at the annual meeting of the European Association for the Study of Diabetes. While only about 4% of these patients were hospitalized, their treatment costs hovered around $3,407 in Germany, where the study was conducted.

These data were extracted from a large German patient claims database, said Dr. Yu of Merck Sharp & Dohme, Whitehouse Station, N.J. The cohort comprised 530,918 patients who had type 2 diabetes during the study years of 2010-2012. Of these, 64,332 had incident disease.

Patients with newly diagnosed diabetes were significantly younger than was the diabetes-prevalent population (70 vs. 73 years), and had a significantly lower than the Charlson comorbidity index (5.4 vs. 7.3 years). Their diabetes was also less severe when measured by the adapted Diabetes Complication Severity Index (1.5 vs. 2.4).

During the study period, roughly 20% of patients had at least 1 urinary tract infection (UTI); 6% had two or more.

UTIs were twice as common in women. Prevalence also grew with advancing age in both sexes. Among those with newly diagnosed diabetes, women developed their UTI significantly more quickly than did men. By the end of the study, 20% of those women had developed one, compared with 10% of the men.

A multivariate analysis determined the risk factors associated with UTIs. These included having had a previous UTI (odds ratio, 3.5), female gender (OR, 1.7), higher Charlson comorbidity status (OR, 1.5), and age (OR, 1.4 for those older than 79 years).

Hemoglobin A1c levels were also a significant independent predictor of UTI, with an odds ratio of 1.5 for levels of 9.5%-10%, compared with 7%-7.5%.

In an analysis of the development of a first UTI after diagnosis, all of those predictive factors remained significant.

The investigators also examined costs associated with inpatient and outpatient treatment. Total costs included antibiotics and the cost of either ambulatory, outpatient, or in-hospital care.

The majority were treated by a physicians as an outpatient, with a median cost of 86 euros (US$111). About 46,500 received a prescription only, at a median cost of 22 euros (US$25). The smallest number (3,445) required hospitalization – a very expensive experience – with a mean cost of 2,627 euros (US$3,407).

During the discussion period, the issue of infection validation was a concern. Many physicians treat on symptoms only, or on a single urinalysis that might show a small amount of blood or protein. The number of culture-proven UTIs is much less, it was suggested.

Dr. Yu admitted that this is a common occurrence and could be affecting the validity of her conclusions somewhat.

She is an employee of Merck.

[email protected]

On Twitter @alz_gal

VIENNA – Urinary tract infections are relatively common and can be quite expensive among patients with newly diagnosed diabetes.

In a large patient database, the infection rate was about 128/1,000 patients, Shengsheng Yu, Ph.D., said at the annual meeting of the European Association for the Study of Diabetes. While only about 4% of these patients were hospitalized, their treatment costs hovered around $3,407 in Germany, where the study was conducted.

These data were extracted from a large German patient claims database, said Dr. Yu of Merck Sharp & Dohme, Whitehouse Station, N.J. The cohort comprised 530,918 patients who had type 2 diabetes during the study years of 2010-2012. Of these, 64,332 had incident disease.

Patients with newly diagnosed diabetes were significantly younger than was the diabetes-prevalent population (70 vs. 73 years), and had a significantly lower than the Charlson comorbidity index (5.4 vs. 7.3 years). Their diabetes was also less severe when measured by the adapted Diabetes Complication Severity Index (1.5 vs. 2.4).

During the study period, roughly 20% of patients had at least 1 urinary tract infection (UTI); 6% had two or more.

UTIs were twice as common in women. Prevalence also grew with advancing age in both sexes. Among those with newly diagnosed diabetes, women developed their UTI significantly more quickly than did men. By the end of the study, 20% of those women had developed one, compared with 10% of the men.

A multivariate analysis determined the risk factors associated with UTIs. These included having had a previous UTI (odds ratio, 3.5), female gender (OR, 1.7), higher Charlson comorbidity status (OR, 1.5), and age (OR, 1.4 for those older than 79 years).

Hemoglobin A1c levels were also a significant independent predictor of UTI, with an odds ratio of 1.5 for levels of 9.5%-10%, compared with 7%-7.5%.

In an analysis of the development of a first UTI after diagnosis, all of those predictive factors remained significant.

The investigators also examined costs associated with inpatient and outpatient treatment. Total costs included antibiotics and the cost of either ambulatory, outpatient, or in-hospital care.

The majority were treated by a physicians as an outpatient, with a median cost of 86 euros (US$111). About 46,500 received a prescription only, at a median cost of 22 euros (US$25). The smallest number (3,445) required hospitalization – a very expensive experience – with a mean cost of 2,627 euros (US$3,407).

During the discussion period, the issue of infection validation was a concern. Many physicians treat on symptoms only, or on a single urinalysis that might show a small amount of blood or protein. The number of culture-proven UTIs is much less, it was suggested.

Dr. Yu admitted that this is a common occurrence and could be affecting the validity of her conclusions somewhat.

She is an employee of Merck.

[email protected]

On Twitter @alz_gal

The incidence of kidney stones in the United States is as high as 11% among men and 6% among women.¹ This translates into a 1-in-11 risk nationwide, with white men being at greater risk than any other cohort. However, for those patients with high-risk medical issues, such as metabolic syndrome, chronic indwelling urinary catheters, frequent catheterization, and/or recurrent urinary tract infections (UTIs), kidney stones are even more common.² Often, the cause of the stones in at-risk patients is an infection. The most frequent source of UTIs is Escherichia coli, but more complicated infections are often caused by Proteus mirabilis.³ Seventy percent of the stones resulting from UTIs are attributed to P mirabilis.⁴

In 2008, a group of microbiology researchers led by Melanie Pearson, PhD, were able to isolate the genome sequence of P mirabilis.⁵Proteus is a gram-negative enteric bacterium that is often found in complicated UTIs. Proteus is more common among patients with the aforementioned high-risk medical issues and is a particularly common cause of UTIs in the nursing home population (particularly in residents with indwelling catheters).³ It is also a potential cause of kidney stones.

While calcium stones are the most common type of stones,¹ infections, though uncommon, are a secondary source. Stones resulting from infection are imminently treatable; the difficulty is in isolating the source of the infection. Proteus is a particularly toxic, difficult-to treat bacterium that can become resistant to antibiotics.³Proteus produces the enzyme urease, which can reduce the acidity of the urine, allowing stones to form. Once stone formation begins, bacteria can sequester within the stone, making them less susceptible to antibiotic treatment.

Proteus often seems to occur randomly. It has been found as a cause of kidney stones, for example, in a patient who four months earlier underwent transurethral resection of the prostate.⁷Proteus has been reported in a nursing home patient with dementia but no known risk factors.⁸Proteus can cause a pyelonephritis to coalesce into a stone; this complicates what is already an insult to the urinary tract and makes treatment all the more complicated.⁹

Pearson’s group from the University of Michigan has spent the past 10 years sequencing the Proteus bacterium in order to try to gain a foothold in the fight against the infection and the kidney stones it can produce. In 2014 they published their findings on the fimbriae of the Proteus organism.¹⁰ Fimbriae are small pili, or adherence factors, found on the surface of a bacterium (more often on gram-negative bacteria than on gram-positive bacteria), which allow the bacteria to attach to urinary tract tissue and prevent them from being easily dislodged.¹¹ Pearson’s group also found that the fimbriae of the Proteus bacterium are more numerous than those of other bacteria, allowing Proteus to more easily attach to tissue than, say, Salmonella enterica.⁵ Thus, Proteus is more likely than other uropathogenic agents to cause a kidney stone, in part because of the “stickiness” of its many fimbriae.

While stones with an infectious cause are less common than others, they are a danger to our most fragile patients. Thus, when an infectious kidney stone forms, it will require aggressive treatment and a hard-hitting plan to minimize recurrence. Proteus is an especially virulent organism that will require all our resources to overcome it.

REFERENCES
1. Scales CD Jr, Smith AC, Hanley JM, Saigal CS; Urologic Diseases in America Project. Prevalence of kidney stones in the United States. Eur Urol. 2012;62(1):160-165.

2. National Kidney Foundation. Diet and kidney stones. kidney.org/atoz/content/diet.cfm. Accessed October 1, 2104.

3. University of Michigan Health System. Bacterium that causes kidney stones and complicated urinary tract infections gives up its genetic secrets (2006). ScienceDaily. sciencedaily.com/releases/2006/05/060524125023.htm. Accessed October 1, 2014.

4. Torzewska A, Budzyńska A, Białczak-Kokot M, Różalski A. In vitro studies of epithelium-associated crystallization caused by uropathogens during urinary calculi development. Microb Pathog. 2014;71-72:25-31.

5. Pearson MM, Sebaihia M, Churcher C, et al. Complete genome sequence of uropathogenic Proteus mirabilis, a master of both adherence and motility. J Bacteriol. 2008;190(11):4027-4037.

6. Wells CG, Chandrashekar KB, Jyothirmayi GN, et al. Kidney stones: current diagnosis and management. Clinician Reviews. 2012;22(2):31-37.

7. Rowe CM, Ghei M, Adamska E. Moans, groans and renal stones: an interesting case of abdominal pain. BMJ Case Rep. 2013 Nov 4.

8. Chew R, Thomas S, Mantha ML, et al. Large urate cystolith associated with Proteus urinary tract infection. Kidney Int. 2012;81(8):802.

9. Shields J, Maxwell AP. Acute pyelonephritis can have serious complications. Practitioner. 2010;254(1728):19, 21, 23-24.

10. Kuan L, Schaffer JN, Zouzias CD, Pearson MM. Characterization of 17 chaperone-usher fimbriae encoded by Proteus mirabilis reveals strong conservation. J Med Microbiol. 2014;63(pt 7):911-922.

11. Proft T, Baker EN. Pili in Gram-negative and Gram-positive bacteria: structure, assembly and their role in disease. Cell Mol Life Sci. 2009;66(4):613-635.

The incidence of kidney stones in the United States is as high as 11% among men and 6% among women.¹ This translates into a 1-in-11 risk nationwide, with white men being at greater risk than any other cohort. However, for those patients with high-risk medical issues, such as metabolic syndrome, chronic indwelling urinary catheters, frequent catheterization, and/or recurrent urinary tract infections (UTIs), kidney stones are even more common.² Often, the cause of the stones in at-risk patients is an infection. The most frequent source of UTIs is Escherichia coli, but more complicated infections are often caused by Proteus mirabilis.³ Seventy percent of the stones resulting from UTIs are attributed to P mirabilis.⁴

In 2008, a group of microbiology researchers led by Melanie Pearson, PhD, were able to isolate the genome sequence of P mirabilis.⁵Proteus is a gram-negative enteric bacterium that is often found in complicated UTIs. Proteus is more common among patients with the aforementioned high-risk medical issues and is a particularly common cause of UTIs in the nursing home population (particularly in residents with indwelling catheters).³ It is also a potential cause of kidney stones.

While calcium stones are the most common type of stones,¹ infections, though uncommon, are a secondary source. Stones resulting from infection are imminently treatable; the difficulty is in isolating the source of the infection. Proteus is a particularly toxic, difficult-to treat bacterium that can become resistant to antibiotics.³Proteus produces the enzyme urease, which can reduce the acidity of the urine, allowing stones to form. Once stone formation begins, bacteria can sequester within the stone, making them less susceptible to antibiotic treatment.

Proteus often seems to occur randomly. It has been found as a cause of kidney stones, for example, in a patient who four months earlier underwent transurethral resection of the prostate.⁷Proteus has been reported in a nursing home patient with dementia but no known risk factors.⁸Proteus can cause a pyelonephritis to coalesce into a stone; this complicates what is already an insult to the urinary tract and makes treatment all the more complicated.⁹

Pearson’s group from the University of Michigan has spent the past 10 years sequencing the Proteus bacterium in order to try to gain a foothold in the fight against the infection and the kidney stones it can produce. In 2014 they published their findings on the fimbriae of the Proteus organism.¹⁰ Fimbriae are small pili, or adherence factors, found on the surface of a bacterium (more often on gram-negative bacteria than on gram-positive bacteria), which allow the bacteria to attach to urinary tract tissue and prevent them from being easily dislodged.¹¹ Pearson’s group also found that the fimbriae of the Proteus bacterium are more numerous than those of other bacteria, allowing Proteus to more easily attach to tissue than, say, Salmonella enterica.⁵ Thus, Proteus is more likely than other uropathogenic agents to cause a kidney stone, in part because of the “stickiness” of its many fimbriae.

While stones with an infectious cause are less common than others, they are a danger to our most fragile patients. Thus, when an infectious kidney stone forms, it will require aggressive treatment and a hard-hitting plan to minimize recurrence. Proteus is an especially virulent organism that will require all our resources to overcome it.

REFERENCES
1. Scales CD Jr, Smith AC, Hanley JM, Saigal CS; Urologic Diseases in America Project. Prevalence of kidney stones in the United States. Eur Urol. 2012;62(1):160-165.

2. National Kidney Foundation. Diet and kidney stones. kidney.org/atoz/content/diet.cfm. Accessed October 1, 2104.

3. University of Michigan Health System. Bacterium that causes kidney stones and complicated urinary tract infections gives up its genetic secrets (2006). ScienceDaily. sciencedaily.com/releases/2006/05/060524125023.htm. Accessed October 1, 2014.

4. Torzewska A, Budzyńska A, Białczak-Kokot M, Różalski A. In vitro studies of epithelium-associated crystallization caused by uropathogens during urinary calculi development. Microb Pathog. 2014;71-72:25-31.

5. Pearson MM, Sebaihia M, Churcher C, et al. Complete genome sequence of uropathogenic Proteus mirabilis, a master of both adherence and motility. J Bacteriol. 2008;190(11):4027-4037.

6. Wells CG, Chandrashekar KB, Jyothirmayi GN, et al. Kidney stones: current diagnosis and management. Clinician Reviews. 2012;22(2):31-37.

7. Rowe CM, Ghei M, Adamska E. Moans, groans and renal stones: an interesting case of abdominal pain. BMJ Case Rep. 2013 Nov 4.

8. Chew R, Thomas S, Mantha ML, et al. Large urate cystolith associated with Proteus urinary tract infection. Kidney Int. 2012;81(8):802.

9. Shields J, Maxwell AP. Acute pyelonephritis can have serious complications. Practitioner. 2010;254(1728):19, 21, 23-24.

10. Kuan L, Schaffer JN, Zouzias CD, Pearson MM. Characterization of 17 chaperone-usher fimbriae encoded by Proteus mirabilis reveals strong conservation. J Med Microbiol. 2014;63(pt 7):911-922.

11. Proft T, Baker EN. Pili in Gram-negative and Gram-positive bacteria: structure, assembly and their role in disease. Cell Mol Life Sci. 2009;66(4):613-635.

The incidence of kidney stones in the United States is as high as 11% among men and 6% among women.¹ This translates into a 1-in-11 risk nationwide, with white men being at greater risk than any other cohort. However, for those patients with high-risk medical issues, such as metabolic syndrome, chronic indwelling urinary catheters, frequent catheterization, and/or recurrent urinary tract infections (UTIs), kidney stones are even more common.² Often, the cause of the stones in at-risk patients is an infection. The most frequent source of UTIs is Escherichia coli, but more complicated infections are often caused by Proteus mirabilis.³ Seventy percent of the stones resulting from UTIs are attributed to P mirabilis.⁴

In 2008, a group of microbiology researchers led by Melanie Pearson, PhD, were able to isolate the genome sequence of P mirabilis.⁵Proteus is a gram-negative enteric bacterium that is often found in complicated UTIs. Proteus is more common among patients with the aforementioned high-risk medical issues and is a particularly common cause of UTIs in the nursing home population (particularly in residents with indwelling catheters).³ It is also a potential cause of kidney stones.

While calcium stones are the most common type of stones,¹ infections, though uncommon, are a secondary source. Stones resulting from infection are imminently treatable; the difficulty is in isolating the source of the infection. Proteus is a particularly toxic, difficult-to treat bacterium that can become resistant to antibiotics.³Proteus produces the enzyme urease, which can reduce the acidity of the urine, allowing stones to form. Once stone formation begins, bacteria can sequester within the stone, making them less susceptible to antibiotic treatment.

Proteus often seems to occur randomly. It has been found as a cause of kidney stones, for example, in a patient who four months earlier underwent transurethral resection of the prostate.⁷Proteus has been reported in a nursing home patient with dementia but no known risk factors.⁸Proteus can cause a pyelonephritis to coalesce into a stone; this complicates what is already an insult to the urinary tract and makes treatment all the more complicated.⁹

Pearson’s group from the University of Michigan has spent the past 10 years sequencing the Proteus bacterium in order to try to gain a foothold in the fight against the infection and the kidney stones it can produce. In 2014 they published their findings on the fimbriae of the Proteus organism.¹⁰ Fimbriae are small pili, or adherence factors, found on the surface of a bacterium (more often on gram-negative bacteria than on gram-positive bacteria), which allow the bacteria to attach to urinary tract tissue and prevent them from being easily dislodged.¹¹ Pearson’s group also found that the fimbriae of the Proteus bacterium are more numerous than those of other bacteria, allowing Proteus to more easily attach to tissue than, say, Salmonella enterica.⁵ Thus, Proteus is more likely than other uropathogenic agents to cause a kidney stone, in part because of the “stickiness” of its many fimbriae.

While stones with an infectious cause are less common than others, they are a danger to our most fragile patients. Thus, when an infectious kidney stone forms, it will require aggressive treatment and a hard-hitting plan to minimize recurrence. Proteus is an especially virulent organism that will require all our resources to overcome it.

REFERENCES
1. Scales CD Jr, Smith AC, Hanley JM, Saigal CS; Urologic Diseases in America Project. Prevalence of kidney stones in the United States. Eur Urol. 2012;62(1):160-165.

2. National Kidney Foundation. Diet and kidney stones. kidney.org/atoz/content/diet.cfm. Accessed October 1, 2104.

3. University of Michigan Health System. Bacterium that causes kidney stones and complicated urinary tract infections gives up its genetic secrets (2006). ScienceDaily. sciencedaily.com/releases/2006/05/060524125023.htm. Accessed October 1, 2014.

4. Torzewska A, Budzyńska A, Białczak-Kokot M, Różalski A. In vitro studies of epithelium-associated crystallization caused by uropathogens during urinary calculi development. Microb Pathog. 2014;71-72:25-31.

5. Pearson MM, Sebaihia M, Churcher C, et al. Complete genome sequence of uropathogenic Proteus mirabilis, a master of both adherence and motility. J Bacteriol. 2008;190(11):4027-4037.

6. Wells CG, Chandrashekar KB, Jyothirmayi GN, et al. Kidney stones: current diagnosis and management. Clinician Reviews. 2012;22(2):31-37.

7. Rowe CM, Ghei M, Adamska E. Moans, groans and renal stones: an interesting case of abdominal pain. BMJ Case Rep. 2013 Nov 4.

8. Chew R, Thomas S, Mantha ML, et al. Large urate cystolith associated with Proteus urinary tract infection. Kidney Int. 2012;81(8):802.

9. Shields J, Maxwell AP. Acute pyelonephritis can have serious complications. Practitioner. 2010;254(1728):19, 21, 23-24.

10. Kuan L, Schaffer JN, Zouzias CD, Pearson MM. Characterization of 17 chaperone-usher fimbriae encoded by Proteus mirabilis reveals strong conservation. J Med Microbiol. 2014;63(pt 7):911-922.

11. Proft T, Baker EN. Pili in Gram-negative and Gram-positive bacteria: structure, assembly and their role in disease. Cell Mol Life Sci. 2009;66(4):613-635.

Kidney stones are found in 11% of the population and are more than twice as common in men as in women.¹ Patients with underlying metabolic conditions (ie, obesity, diabetes, hypertension, hyperuricemia, hypercholesterolemia, hypertension, chronic kidney disease) are much more likely than others to have kidney stones. This is also a population at increased risk for cardiac disease. So if a patient has both kidney stones and heart disease, is kidney stone disease a cause or effect of heart disease? Or are the causes of heart disease also the causes of kidney stones?

For many years, professionals thought the population affected by kidney stones was also the group with risk factors for heart disease—that the metabolic conditions were found in both groups, but that the stones were not meaningful: The finding of kidney stones in the cardiac patient was an incidental, and slightly interesting, finding. Yet a study published recently in the American Journal of Kidney Disease has turned this concept on its head.² Liu and associates have done a meta-analysis of studies involving more than 3.5 million patients to explain exactly how kidney stones are related to cardiac disease.

In 1973, Westlund reported that patients who had kidney stones were just as likely to have had a myocardial infarction (MI).³ He was unable to identify an increased risk for MI in stone formers in his all-male cohort. In 1976, Elmfeldt and colleagues reported twice as many MIs in study subjects with kidney stones as in patients without stones.⁴ However, that same year, Ljunghall and Hedstrand were unable to find a correlation between kidney stones and heart disease in middle-aged men.⁵ Recently, Rule et al, using a 10,800-member study cohort of Minnesota residents, did show a 31% increased incidence of MI in patients with kidney stones.⁶

Liu and his group decided to try to answer this question once and for all. Using a graded system that examined studies of kidney stone patients who also showed signs of cardiac disease, they performed a meta-analysis comparing 50,000 patients with kidney stones and more than 3.5 million controls (patients without kidney stones). Controlling for the standard risk factors within this group (eg, age, gender, BMI, medication use, diabetes, smoking, alcohol use), the investigators identified kidney stones as a separate identifiable risk factor for cardiac disease.

In fact, Liu’s study team was able to quantify exactly how much greater a risk for cardiac disease exists in a kidney stone patient.² Using a multivariate outcomes data plot and defining cardiac disease using hard endpoints (fatal or nonfatal MI or coronary revascularization), the researchers found a 19% increase in cardiac disease among the kidney stone patients.⁷ When the endpoint used was cerebrovascular accident (CVA), patients with kidney stones had a 40% higher rate of stroke.

However, the real shock came when Liu and colleagues looked at the risk factors by gender. Quite simply, women with kidney stones had a higher rate of cardiac disease and stroke than men. In totality, the increased risk for cardiac disease and stroke for a male stone patient was not statistically significant. But in female stone patients, a 40% higher rate of stroke and a 31% higher rate of cardiac disease was discovered. This explains the huge disparity in previous studies. The increased risk for cardiac disease in the kidney stone patient is borne solely by the females of the population!²

Thus, we need to aggressively evaluate and treat our female patients for heart disease when they present with kidney stones. Just as the woman’s symptoms of MI are not “classic,” and one needs to consider gender when evaluating for MI, so do we need to consider gender in the kidney stone patient.⁸

Next time your patient is a woman with a kidney stone, remember to raise cardiac issues with her. The MI you prevent may be in my mother or my sister.

REFERENCES
1. Wells CG, Chandrashekar KB, Jyothirmayi GN, et al. Kidney stones: current diagnosis and management. Clinician Reviews. 2012;22(2):31-37.

2. Liu Y, Li S, Zeng Z, et al. Kidney stones and cardiovascular risk: a meta-analysis of cohort studies. Am J Kidney Dis. 2014;64(3):402-410.

3. Westlund K. Urolithiasis and coronary heart disease: a note on association. Am J Epidemiol. 1973;97(3):167-172.

4. Elmfeldt D, Vedin A, Wilhelmsson C, et al. Morbidity in representative male survivors of myocardial infarction compared to representative population samples. J Chronic Dis. 1976;29(4):221-231.

5. Ljunghall S, Hedstrand H. Renal stones and coronary heart disease. Acta Med Scand. 1976;199(6):481-485.

6. Rule AD, Roger VL, Melton LJ 3rd, et al. Kidney stones associate with increased risk for myocardial infarction. J Am Soc Nephrol. 2010;21(10):1641-1644.

7. Kidney stones linked to coronary heart disease, stroke [press release]. New York, NY: National Kidney Foundation; September 1, 2014. www.kidney.org/news/kidney-stones-linked-coronary-heart-disease-stroke. Accessed September 30, 2014.

8. McSweeney JC, Cody M, O’Sullivan P, et al. Women’s early warning symptoms of acute myocardial infarction. Circulation. 2003;108(21):2619-2623.

Kidney stones are found in 11% of the population and are more than twice as common in men as in women.¹ Patients with underlying metabolic conditions (ie, obesity, diabetes, hypertension, hyperuricemia, hypercholesterolemia, hypertension, chronic kidney disease) are much more likely than others to have kidney stones. This is also a population at increased risk for cardiac disease. So if a patient has both kidney stones and heart disease, is kidney stone disease a cause or effect of heart disease? Or are the causes of heart disease also the causes of kidney stones?

For many years, professionals thought the population affected by kidney stones was also the group with risk factors for heart disease—that the metabolic conditions were found in both groups, but that the stones were not meaningful: The finding of kidney stones in the cardiac patient was an incidental, and slightly interesting, finding. Yet a study published recently in the American Journal of Kidney Disease has turned this concept on its head.² Liu and associates have done a meta-analysis of studies involving more than 3.5 million patients to explain exactly how kidney stones are related to cardiac disease.

In 1973, Westlund reported that patients who had kidney stones were just as likely to have had a myocardial infarction (MI).³ He was unable to identify an increased risk for MI in stone formers in his all-male cohort. In 1976, Elmfeldt and colleagues reported twice as many MIs in study subjects with kidney stones as in patients without stones.⁴ However, that same year, Ljunghall and Hedstrand were unable to find a correlation between kidney stones and heart disease in middle-aged men.⁵ Recently, Rule et al, using a 10,800-member study cohort of Minnesota residents, did show a 31% increased incidence of MI in patients with kidney stones.⁶

Liu and his group decided to try to answer this question once and for all. Using a graded system that examined studies of kidney stone patients who also showed signs of cardiac disease, they performed a meta-analysis comparing 50,000 patients with kidney stones and more than 3.5 million controls (patients without kidney stones). Controlling for the standard risk factors within this group (eg, age, gender, BMI, medication use, diabetes, smoking, alcohol use), the investigators identified kidney stones as a separate identifiable risk factor for cardiac disease.

In fact, Liu’s study team was able to quantify exactly how much greater a risk for cardiac disease exists in a kidney stone patient.² Using a multivariate outcomes data plot and defining cardiac disease using hard endpoints (fatal or nonfatal MI or coronary revascularization), the researchers found a 19% increase in cardiac disease among the kidney stone patients.⁷ When the endpoint used was cerebrovascular accident (CVA), patients with kidney stones had a 40% higher rate of stroke.

However, the real shock came when Liu and colleagues looked at the risk factors by gender. Quite simply, women with kidney stones had a higher rate of cardiac disease and stroke than men. In totality, the increased risk for cardiac disease and stroke for a male stone patient was not statistically significant. But in female stone patients, a 40% higher rate of stroke and a 31% higher rate of cardiac disease was discovered. This explains the huge disparity in previous studies. The increased risk for cardiac disease in the kidney stone patient is borne solely by the females of the population!²

Thus, we need to aggressively evaluate and treat our female patients for heart disease when they present with kidney stones. Just as the woman’s symptoms of MI are not “classic,” and one needs to consider gender when evaluating for MI, so do we need to consider gender in the kidney stone patient.⁸

Next time your patient is a woman with a kidney stone, remember to raise cardiac issues with her. The MI you prevent may be in my mother or my sister.

REFERENCES
1. Wells CG, Chandrashekar KB, Jyothirmayi GN, et al. Kidney stones: current diagnosis and management. Clinician Reviews. 2012;22(2):31-37.

2. Liu Y, Li S, Zeng Z, et al. Kidney stones and cardiovascular risk: a meta-analysis of cohort studies. Am J Kidney Dis. 2014;64(3):402-410.

3. Westlund K. Urolithiasis and coronary heart disease: a note on association. Am J Epidemiol. 1973;97(3):167-172.

4. Elmfeldt D, Vedin A, Wilhelmsson C, et al. Morbidity in representative male survivors of myocardial infarction compared to representative population samples. J Chronic Dis. 1976;29(4):221-231.

5. Ljunghall S, Hedstrand H. Renal stones and coronary heart disease. Acta Med Scand. 1976;199(6):481-485.

6. Rule AD, Roger VL, Melton LJ 3rd, et al. Kidney stones associate with increased risk for myocardial infarction. J Am Soc Nephrol. 2010;21(10):1641-1644.

7. Kidney stones linked to coronary heart disease, stroke [press release]. New York, NY: National Kidney Foundation; September 1, 2014. www.kidney.org/news/kidney-stones-linked-coronary-heart-disease-stroke. Accessed September 30, 2014.

8. McSweeney JC, Cody M, O’Sullivan P, et al. Women’s early warning symptoms of acute myocardial infarction. Circulation. 2003;108(21):2619-2623.

Kidney stones are found in 11% of the population and are more than twice as common in men as in women.¹ Patients with underlying metabolic conditions (ie, obesity, diabetes, hypertension, hyperuricemia, hypercholesterolemia, hypertension, chronic kidney disease) are much more likely than others to have kidney stones. This is also a population at increased risk for cardiac disease. So if a patient has both kidney stones and heart disease, is kidney stone disease a cause or effect of heart disease? Or are the causes of heart disease also the causes of kidney stones?

For many years, professionals thought the population affected by kidney stones was also the group with risk factors for heart disease—that the metabolic conditions were found in both groups, but that the stones were not meaningful: The finding of kidney stones in the cardiac patient was an incidental, and slightly interesting, finding. Yet a study published recently in the American Journal of Kidney Disease has turned this concept on its head.² Liu and associates have done a meta-analysis of studies involving more than 3.5 million patients to explain exactly how kidney stones are related to cardiac disease.

In 1973, Westlund reported that patients who had kidney stones were just as likely to have had a myocardial infarction (MI).³ He was unable to identify an increased risk for MI in stone formers in his all-male cohort. In 1976, Elmfeldt and colleagues reported twice as many MIs in study subjects with kidney stones as in patients without stones.⁴ However, that same year, Ljunghall and Hedstrand were unable to find a correlation between kidney stones and heart disease in middle-aged men.⁵ Recently, Rule et al, using a 10,800-member study cohort of Minnesota residents, did show a 31% increased incidence of MI in patients with kidney stones.⁶

Liu and his group decided to try to answer this question once and for all. Using a graded system that examined studies of kidney stone patients who also showed signs of cardiac disease, they performed a meta-analysis comparing 50,000 patients with kidney stones and more than 3.5 million controls (patients without kidney stones). Controlling for the standard risk factors within this group (eg, age, gender, BMI, medication use, diabetes, smoking, alcohol use), the investigators identified kidney stones as a separate identifiable risk factor for cardiac disease.

In fact, Liu’s study team was able to quantify exactly how much greater a risk for cardiac disease exists in a kidney stone patient.² Using a multivariate outcomes data plot and defining cardiac disease using hard endpoints (fatal or nonfatal MI or coronary revascularization), the researchers found a 19% increase in cardiac disease among the kidney stone patients.⁷ When the endpoint used was cerebrovascular accident (CVA), patients with kidney stones had a 40% higher rate of stroke.

However, the real shock came when Liu and colleagues looked at the risk factors by gender. Quite simply, women with kidney stones had a higher rate of cardiac disease and stroke than men. In totality, the increased risk for cardiac disease and stroke for a male stone patient was not statistically significant. But in female stone patients, a 40% higher rate of stroke and a 31% higher rate of cardiac disease was discovered. This explains the huge disparity in previous studies. The increased risk for cardiac disease in the kidney stone patient is borne solely by the females of the population!²

Thus, we need to aggressively evaluate and treat our female patients for heart disease when they present with kidney stones. Just as the woman’s symptoms of MI are not “classic,” and one needs to consider gender when evaluating for MI, so do we need to consider gender in the kidney stone patient.⁸

Next time your patient is a woman with a kidney stone, remember to raise cardiac issues with her. The MI you prevent may be in my mother or my sister.

REFERENCES
1. Wells CG, Chandrashekar KB, Jyothirmayi GN, et al. Kidney stones: current diagnosis and management. Clinician Reviews. 2012;22(2):31-37.

2. Liu Y, Li S, Zeng Z, et al. Kidney stones and cardiovascular risk: a meta-analysis of cohort studies. Am J Kidney Dis. 2014;64(3):402-410.

3. Westlund K. Urolithiasis and coronary heart disease: a note on association. Am J Epidemiol. 1973;97(3):167-172.

4. Elmfeldt D, Vedin A, Wilhelmsson C, et al. Morbidity in representative male survivors of myocardial infarction compared to representative population samples. J Chronic Dis. 1976;29(4):221-231.

5. Ljunghall S, Hedstrand H. Renal stones and coronary heart disease. Acta Med Scand. 1976;199(6):481-485.

6. Rule AD, Roger VL, Melton LJ 3rd, et al. Kidney stones associate with increased risk for myocardial infarction. J Am Soc Nephrol. 2010;21(10):1641-1644.

7. Kidney stones linked to coronary heart disease, stroke [press release]. New York, NY: National Kidney Foundation; September 1, 2014. www.kidney.org/news/kidney-stones-linked-coronary-heart-disease-stroke. Accessed September 30, 2014.

8. McSweeney JC, Cody M, O’Sullivan P, et al. Women’s early warning symptoms of acute myocardial infarction. Circulation. 2003;108(21):2619-2623.

Each year in the United States alone, more than half a million patients are seen in emergency departments with kidney stones. This translates to a stone incidence of 9% of all males and 6% of all females over the lifespan, or 1 in 11 people.¹ Of these, 53% will have another stone during their lifetime.² Since kidney stones are extremely painful and can cause permanent kidney damage, the ability to predict which patients are likely to have a stone recurrence is extremely valuable. Recently, an online calculator has been developed that can help clinicians predict which first-time kidney stone patients are in the “worrisome” group and which are less likely to have a recurrence.³

Kidney stones (nephrolithiasis) are increasingly common in males, those between ages 30 and 50, and those with certain underlying medical conditions, such as hypertension, diabetes, and gout, as well as those with a history of bariatric surgery.⁴ A family history of stone formation is also predictive.

Since more than half of patients will have a second episode of kidney stones, the ability to identify and aggressively treat at-risk patients is vital. Using a data set of clinical characteristics from more than 2,000 first-time kidney stone patients from Olmsted County, Minnesota, and following these patients longitudinally for more than 20 years, Rule et al identified patients who had a second episode of kidney stones—as well as the characteristics associated with stone recurrence.⁵ They then developed a multivariate calculator, the ROKS nomogram, which can be used after a patient’s first episode of kidney stones to predict the likelihood of stone recurrence at 2, 5, and 10 years.³ The authors of the ROKS stone calculator were inspired by the World Health Organization’s FRAX calculator, which predicts 10-year fracture probability.^5,6

Rule et al identified 11 risk factors that they incorporated into the ROKS calculator. These include, but are not limited to, age, sex, race, family history, hematuria, presence of uric acid stones, and characteristics of the position of the initial stone in the pelvis. Not surprisingly, Rule et al found the kidney stone recurrence rate greatest in younger males who were white and had a family history of stones.

Minnesota, it should be noted, is an area of the country where summers are cooler; since people in warmer climates are at increased risk for kidney stones (particularly during the summer months), it is possible that the ROKS calculator would be even more useful in the South or Southwest than in the original study setting.⁵

A free, downloadable app of the ROKS calculator is available at the QxMD app “Calculate” (iOS: http://qx.md/qx, Android: http://qx.md/android, or web-based http://qxmd.com/ROKS).

Any episode of kidney stones increases the risk for chronic kidney disease and/or kidney failure.⁷ The absolute risk increase, though small, is present; any preventive measures one can offer at-risk patients is valuable. These range from increasing fluids and acidifying the urine to adding medications, including thiazide diuretics and allopurinol, to reduce stone formation. Unfortunately, only 3% of all first-time kidney stone patients are currently treated with medication to prevent a second episode.³ This creates an unnecessary risk for complications in a significant number of patients. By identifying members of the stone population who are likely to have a second event, clinicians can reduce the risk for recurrence.

Close monitoring of a patient with a significant stone history is vital. The ROKS calculator will allow practitioners to identify patients at increased risk for recurrent kidney stones and treat them aggressively—reducing the associated kidney damage and pain.

References
1. Scales CD Jr, Smith AC, Hanley JM, Saigal CS. Urologic Diseases in America Project: prevalence of kidney stones in the United States. Eur Urol. 2012;62:160-165.

2. Ljunghall S. Incidence of upper urinary tract stones. Miner Electrolyte Metab. 1987;13(4):220-227.

3. Rule AD, Lieske JC, Li X, et al. The ROKS Nomogram for Predicting a Second Symptomatic Stone Episode. J Am Soc Nephrol. 2014 Aug 7. [Epub ahead of print]

4. National Kidney Foundation. Kidney stones: how common are kidney stones? www.kidney.org/atoz/content/kidneystones.cfm. Accessed September 24, 2014.

5. Eisner BH, Goldfarb DS. A Nomogram for the Prediction of Kidney Stone Recurrence. J Am Soc Nephrol. 2014 Aug 7. [Epub ahead of print]

6. Kanis JA on behalf of the World Health Organization Scientific Group (2007). Assessment of osteoporosis at the primary healthcare level: report of a WHO Scientific Group. www.iofbonehealth.org/sites/default/files/WHO_Technical_Report-2007.pdf. Accessed September 26, 2014.

7. Alexander RT, Hemmelgarn BR, Wiebe N, et al. Kidney stones and kidney function loss: a cohort study. BMJ. 2012;345:e5287.

Each year in the United States alone, more than half a million patients are seen in emergency departments with kidney stones. This translates to a stone incidence of 9% of all males and 6% of all females over the lifespan, or 1 in 11 people.¹ Of these, 53% will have another stone during their lifetime.² Since kidney stones are extremely painful and can cause permanent kidney damage, the ability to predict which patients are likely to have a stone recurrence is extremely valuable. Recently, an online calculator has been developed that can help clinicians predict which first-time kidney stone patients are in the “worrisome” group and which are less likely to have a recurrence.³

Kidney stones (nephrolithiasis) are increasingly common in males, those between ages 30 and 50, and those with certain underlying medical conditions, such as hypertension, diabetes, and gout, as well as those with a history of bariatric surgery.⁴ A family history of stone formation is also predictive.

Since more than half of patients will have a second episode of kidney stones, the ability to identify and aggressively treat at-risk patients is vital. Using a data set of clinical characteristics from more than 2,000 first-time kidney stone patients from Olmsted County, Minnesota, and following these patients longitudinally for more than 20 years, Rule et al identified patients who had a second episode of kidney stones—as well as the characteristics associated with stone recurrence.⁵ They then developed a multivariate calculator, the ROKS nomogram, which can be used after a patient’s first episode of kidney stones to predict the likelihood of stone recurrence at 2, 5, and 10 years.³ The authors of the ROKS stone calculator were inspired by the World Health Organization’s FRAX calculator, which predicts 10-year fracture probability.^5,6

Rule et al identified 11 risk factors that they incorporated into the ROKS calculator. These include, but are not limited to, age, sex, race, family history, hematuria, presence of uric acid stones, and characteristics of the position of the initial stone in the pelvis. Not surprisingly, Rule et al found the kidney stone recurrence rate greatest in younger males who were white and had a family history of stones.

Minnesota, it should be noted, is an area of the country where summers are cooler; since people in warmer climates are at increased risk for kidney stones (particularly during the summer months), it is possible that the ROKS calculator would be even more useful in the South or Southwest than in the original study setting.⁵

A free, downloadable app of the ROKS calculator is available at the QxMD app “Calculate” (iOS: http://qx.md/qx, Android: http://qx.md/android, or web-based http://qxmd.com/ROKS).

Any episode of kidney stones increases the risk for chronic kidney disease and/or kidney failure.⁷ The absolute risk increase, though small, is present; any preventive measures one can offer at-risk patients is valuable. These range from increasing fluids and acidifying the urine to adding medications, including thiazide diuretics and allopurinol, to reduce stone formation. Unfortunately, only 3% of all first-time kidney stone patients are currently treated with medication to prevent a second episode.³ This creates an unnecessary risk for complications in a significant number of patients. By identifying members of the stone population who are likely to have a second event, clinicians can reduce the risk for recurrence.

Close monitoring of a patient with a significant stone history is vital. The ROKS calculator will allow practitioners to identify patients at increased risk for recurrent kidney stones and treat them aggressively—reducing the associated kidney damage and pain.

References
1. Scales CD Jr, Smith AC, Hanley JM, Saigal CS. Urologic Diseases in America Project: prevalence of kidney stones in the United States. Eur Urol. 2012;62:160-165.

2. Ljunghall S. Incidence of upper urinary tract stones. Miner Electrolyte Metab. 1987;13(4):220-227.

3. Rule AD, Lieske JC, Li X, et al. The ROKS Nomogram for Predicting a Second Symptomatic Stone Episode. J Am Soc Nephrol. 2014 Aug 7. [Epub ahead of print]

4. National Kidney Foundation. Kidney stones: how common are kidney stones? www.kidney.org/atoz/content/kidneystones.cfm. Accessed September 24, 2014.

5. Eisner BH, Goldfarb DS. A Nomogram for the Prediction of Kidney Stone Recurrence. J Am Soc Nephrol. 2014 Aug 7. [Epub ahead of print]

6. Kanis JA on behalf of the World Health Organization Scientific Group (2007). Assessment of osteoporosis at the primary healthcare level: report of a WHO Scientific Group. www.iofbonehealth.org/sites/default/files/WHO_Technical_Report-2007.pdf. Accessed September 26, 2014.

7. Alexander RT, Hemmelgarn BR, Wiebe N, et al. Kidney stones and kidney function loss: a cohort study. BMJ. 2012;345:e5287.

Each year in the United States alone, more than half a million patients are seen in emergency departments with kidney stones. This translates to a stone incidence of 9% of all males and 6% of all females over the lifespan, or 1 in 11 people.¹ Of these, 53% will have another stone during their lifetime.² Since kidney stones are extremely painful and can cause permanent kidney damage, the ability to predict which patients are likely to have a stone recurrence is extremely valuable. Recently, an online calculator has been developed that can help clinicians predict which first-time kidney stone patients are in the “worrisome” group and which are less likely to have a recurrence.³

Kidney stones (nephrolithiasis) are increasingly common in males, those between ages 30 and 50, and those with certain underlying medical conditions, such as hypertension, diabetes, and gout, as well as those with a history of bariatric surgery.⁴ A family history of stone formation is also predictive.

Since more than half of patients will have a second episode of kidney stones, the ability to identify and aggressively treat at-risk patients is vital. Using a data set of clinical characteristics from more than 2,000 first-time kidney stone patients from Olmsted County, Minnesota, and following these patients longitudinally for more than 20 years, Rule et al identified patients who had a second episode of kidney stones—as well as the characteristics associated with stone recurrence.⁵ They then developed a multivariate calculator, the ROKS nomogram, which can be used after a patient’s first episode of kidney stones to predict the likelihood of stone recurrence at 2, 5, and 10 years.³ The authors of the ROKS stone calculator were inspired by the World Health Organization’s FRAX calculator, which predicts 10-year fracture probability.^5,6

Rule et al identified 11 risk factors that they incorporated into the ROKS calculator. These include, but are not limited to, age, sex, race, family history, hematuria, presence of uric acid stones, and characteristics of the position of the initial stone in the pelvis. Not surprisingly, Rule et al found the kidney stone recurrence rate greatest in younger males who were white and had a family history of stones.

Minnesota, it should be noted, is an area of the country where summers are cooler; since people in warmer climates are at increased risk for kidney stones (particularly during the summer months), it is possible that the ROKS calculator would be even more useful in the South or Southwest than in the original study setting.⁵

A free, downloadable app of the ROKS calculator is available at the QxMD app “Calculate” (iOS: http://qx.md/qx, Android: http://qx.md/android, or web-based http://qxmd.com/ROKS).

Any episode of kidney stones increases the risk for chronic kidney disease and/or kidney failure.⁷ The absolute risk increase, though small, is present; any preventive measures one can offer at-risk patients is valuable. These range from increasing fluids and acidifying the urine to adding medications, including thiazide diuretics and allopurinol, to reduce stone formation. Unfortunately, only 3% of all first-time kidney stone patients are currently treated with medication to prevent a second episode.³ This creates an unnecessary risk for complications in a significant number of patients. By identifying members of the stone population who are likely to have a second event, clinicians can reduce the risk for recurrence.

Close monitoring of a patient with a significant stone history is vital. The ROKS calculator will allow practitioners to identify patients at increased risk for recurrent kidney stones and treat them aggressively—reducing the associated kidney damage and pain.

References
1. Scales CD Jr, Smith AC, Hanley JM, Saigal CS. Urologic Diseases in America Project: prevalence of kidney stones in the United States. Eur Urol. 2012;62:160-165.

2. Ljunghall S. Incidence of upper urinary tract stones. Miner Electrolyte Metab. 1987;13(4):220-227.

3. Rule AD, Lieske JC, Li X, et al. The ROKS Nomogram for Predicting a Second Symptomatic Stone Episode. J Am Soc Nephrol. 2014 Aug 7. [Epub ahead of print]

4. National Kidney Foundation. Kidney stones: how common are kidney stones? www.kidney.org/atoz/content/kidneystones.cfm. Accessed September 24, 2014.

5. Eisner BH, Goldfarb DS. A Nomogram for the Prediction of Kidney Stone Recurrence. J Am Soc Nephrol. 2014 Aug 7. [Epub ahead of print]

6. Kanis JA on behalf of the World Health Organization Scientific Group (2007). Assessment of osteoporosis at the primary healthcare level: report of a WHO Scientific Group. www.iofbonehealth.org/sites/default/files/WHO_Technical_Report-2007.pdf. Accessed September 26, 2014.

7. Alexander RT, Hemmelgarn BR, Wiebe N, et al. Kidney stones and kidney function loss: a cohort study. BMJ. 2012;345:e5287.

By age 70, 11% of men and 6% of women in the United States will have had at least one occurrence of kidney stones (nephrolithiasis).^1,2 This translates to a nationwide incidence rate of one in 11. More than 50% of those affected by kidney stones will experience a recurrence.³

Treatments for kidney stones, though available, are underutilized; only 3% of patients are treated after their first occurrence.³ Since treatment depends on the composition of the initial stone, identification is essential. Once the stone type is identified, treatment can be directed at the metabolic abnormality that caused the stone’s formation.

There are five types of stones: calcium-based, struvite, uric-acid, cystine, and the problematic “mixed.” The most common is the calcium-based stone, which accounts for nearly 80% of identified stones.^3,4 It is not the amount of calcium in the diet that usually causes a stone but rather the calcium excreted by the kidney collecting system.

One of the first recommendations for treatment of a calcium-based stone is a low-salt diet.⁴ Extra urinary sodium excretion (as a result of excess consumption) will increase calcium excretion in the urine. Decreasing salt in the diet will reduce sodium in the urine and, by extension, calcium as well. If conservative dietary changes are insufficient, a thiazide diuretic may be prescribed. (At present, a randomized clinical trial assessing treatment with oral potassium vs thiazides vs allopurinol for calcium-based stones is underway. Data from this trial will direct prevention strategies for calcium-based stones in the future.)

Uric acid stones can occur if the urine contains a high level of purine as a result of acidic foods in the diet. This usually means a diet rich in meats, shellfish, and high-purine foods (the same ones that can trigger gout).⁵ Control of the diet, alkalization of the urine, and/or treatment of the underlying high serum uric acid levels with allopurinol are the current recommended treatments.⁶

Struvite stones are caused by kidney infections. Many require long-term low-dose antibiotics in order to reduce reoccurrence.⁶ It is vital to know if a stone is struvite, since the treatment is significantly different from that for other types of stones. 

Cystine stones result from a genetic disorder (cystinuria) that affects an amino acid. Often, these types of stones are seen in younger patients, and any teen who presents with kidney stones should undergo a work-up for the genetic abnormality. (See Zuber K. Woman, 26, with kidney stones. Clinician Reviews. 2011;21(3):8-10.)

When a patient complains of severe, colicky abdominal pain, hematuria, or a sharp pain in the back or flank, the thought of kidney stones must be front and center. Evaluation incudes both serum testing and CT.^5,7 Abdominal plain films and/or an intravenous pyelogram were considered state of the art in the 1980s and 1990s, but helical CT has become the scan of choice since it allows for measurement of the size, position, and level of obstruction. Helical CTs are increasingly available nationwide—and a sensitivity of 95% to 100% makes them the preferred method of evalution.^5,8

REFERENCES
1. Scales CD Jr, Smith AC, Hanley JM, Saigal CS. Urologic Diseases in America Project: Prevalence of kidney stones in the United States. Eur Urol. 2012;62:160-165.

2. Worcester EM, Coe FL. Calcium kidney stones. N Engl J Med. 2010;363:954-963.

3. Rule A, Lieske JC, Li X, et al. The ROKS Nomogram for Predicting a Second Symptomatic Stone Episode. J Am Soc Nephrol. 2014 Aug 7; [Epub ahead of print].

4. National Kidney Foundation. Diet and kidney stones. www.kidney.org/atoz/content/diet.cfm. Accessed September 9, 2104.

5. Jackman SV, Potter SR, Regan F, Jarrett TW. Plain abdominal x-ray versus computerized tomography screening: sensitivity for stone localization after nonenhanced spiral computerized tomography. J Urol. 2000;164(2):308-310.

6. Lipkin ME, Preminger GM. Demystifying the medical management of nephrolithiasis. Rev Urol. 2011;13(1):34-38.

7. National Institute of Diabetes and Digestive and Kidney Diseases. Kidney stones in adults: what are the types of kidney stones?  http://kidney.niddk.nih.gov/KUDiseases/pubs/stonesadults/index.aspx#types. Accessed September 9, 2014.

8. Harrington K, Torreggiani W. CT analysis of renal stone composition: a novel and noninvasive method to analyse stones. Ir Med J. 2014;107(3):69.

By age 70, 11% of men and 6% of women in the United States will have had at least one occurrence of kidney stones (nephrolithiasis).^1,2 This translates to a nationwide incidence rate of one in 11. More than 50% of those affected by kidney stones will experience a recurrence.³

Treatments for kidney stones, though available, are underutilized; only 3% of patients are treated after their first occurrence.³ Since treatment depends on the composition of the initial stone, identification is essential. Once the stone type is identified, treatment can be directed at the metabolic abnormality that caused the stone’s formation.

There are five types of stones: calcium-based, struvite, uric-acid, cystine, and the problematic “mixed.” The most common is the calcium-based stone, which accounts for nearly 80% of identified stones.^3,4 It is not the amount of calcium in the diet that usually causes a stone but rather the calcium excreted by the kidney collecting system.

One of the first recommendations for treatment of a calcium-based stone is a low-salt diet.⁴ Extra urinary sodium excretion (as a result of excess consumption) will increase calcium excretion in the urine. Decreasing salt in the diet will reduce sodium in the urine and, by extension, calcium as well. If conservative dietary changes are insufficient, a thiazide diuretic may be prescribed. (At present, a randomized clinical trial assessing treatment with oral potassium vs thiazides vs allopurinol for calcium-based stones is underway. Data from this trial will direct prevention strategies for calcium-based stones in the future.)

Uric acid stones can occur if the urine contains a high level of purine as a result of acidic foods in the diet. This usually means a diet rich in meats, shellfish, and high-purine foods (the same ones that can trigger gout).⁵ Control of the diet, alkalization of the urine, and/or treatment of the underlying high serum uric acid levels with allopurinol are the current recommended treatments.⁶

Struvite stones are caused by kidney infections. Many require long-term low-dose antibiotics in order to reduce reoccurrence.⁶ It is vital to know if a stone is struvite, since the treatment is significantly different from that for other types of stones. 

Cystine stones result from a genetic disorder (cystinuria) that affects an amino acid. Often, these types of stones are seen in younger patients, and any teen who presents with kidney stones should undergo a work-up for the genetic abnormality. (See Zuber K. Woman, 26, with kidney stones. Clinician Reviews. 2011;21(3):8-10.)

When a patient complains of severe, colicky abdominal pain, hematuria, or a sharp pain in the back or flank, the thought of kidney stones must be front and center. Evaluation incudes both serum testing and CT.^5,7 Abdominal plain films and/or an intravenous pyelogram were considered state of the art in the 1980s and 1990s, but helical CT has become the scan of choice since it allows for measurement of the size, position, and level of obstruction. Helical CTs are increasingly available nationwide—and a sensitivity of 95% to 100% makes them the preferred method of evalution.^5,8

REFERENCES
1. Scales CD Jr, Smith AC, Hanley JM, Saigal CS. Urologic Diseases in America Project: Prevalence of kidney stones in the United States. Eur Urol. 2012;62:160-165.

2. Worcester EM, Coe FL. Calcium kidney stones. N Engl J Med. 2010;363:954-963.

3. Rule A, Lieske JC, Li X, et al. The ROKS Nomogram for Predicting a Second Symptomatic Stone Episode. J Am Soc Nephrol. 2014 Aug 7; [Epub ahead of print].

4. National Kidney Foundation. Diet and kidney stones. www.kidney.org/atoz/content/diet.cfm. Accessed September 9, 2104.

5. Jackman SV, Potter SR, Regan F, Jarrett TW. Plain abdominal x-ray versus computerized tomography screening: sensitivity for stone localization after nonenhanced spiral computerized tomography. J Urol. 2000;164(2):308-310.

6. Lipkin ME, Preminger GM. Demystifying the medical management of nephrolithiasis. Rev Urol. 2011;13(1):34-38.

7. National Institute of Diabetes and Digestive and Kidney Diseases. Kidney stones in adults: what are the types of kidney stones?  http://kidney.niddk.nih.gov/KUDiseases/pubs/stonesadults/index.aspx#types. Accessed September 9, 2014.

8. Harrington K, Torreggiani W. CT analysis of renal stone composition: a novel and noninvasive method to analyse stones. Ir Med J. 2014;107(3):69.

By age 70, 11% of men and 6% of women in the United States will have had at least one occurrence of kidney stones (nephrolithiasis).^1,2 This translates to a nationwide incidence rate of one in 11. More than 50% of those affected by kidney stones will experience a recurrence.³

Treatments for kidney stones, though available, are underutilized; only 3% of patients are treated after their first occurrence.³ Since treatment depends on the composition of the initial stone, identification is essential. Once the stone type is identified, treatment can be directed at the metabolic abnormality that caused the stone’s formation.

There are five types of stones: calcium-based, struvite, uric-acid, cystine, and the problematic “mixed.” The most common is the calcium-based stone, which accounts for nearly 80% of identified stones.^3,4 It is not the amount of calcium in the diet that usually causes a stone but rather the calcium excreted by the kidney collecting system.

One of the first recommendations for treatment of a calcium-based stone is a low-salt diet.⁴ Extra urinary sodium excretion (as a result of excess consumption) will increase calcium excretion in the urine. Decreasing salt in the diet will reduce sodium in the urine and, by extension, calcium as well. If conservative dietary changes are insufficient, a thiazide diuretic may be prescribed. (At present, a randomized clinical trial assessing treatment with oral potassium vs thiazides vs allopurinol for calcium-based stones is underway. Data from this trial will direct prevention strategies for calcium-based stones in the future.)

Uric acid stones can occur if the urine contains a high level of purine as a result of acidic foods in the diet. This usually means a diet rich in meats, shellfish, and high-purine foods (the same ones that can trigger gout).⁵ Control of the diet, alkalization of the urine, and/or treatment of the underlying high serum uric acid levels with allopurinol are the current recommended treatments.⁶

Struvite stones are caused by kidney infections. Many require long-term low-dose antibiotics in order to reduce reoccurrence.⁶ It is vital to know if a stone is struvite, since the treatment is significantly different from that for other types of stones. 

Cystine stones result from a genetic disorder (cystinuria) that affects an amino acid. Often, these types of stones are seen in younger patients, and any teen who presents with kidney stones should undergo a work-up for the genetic abnormality. (See Zuber K. Woman, 26, with kidney stones. Clinician Reviews. 2011;21(3):8-10.)

When a patient complains of severe, colicky abdominal pain, hematuria, or a sharp pain in the back or flank, the thought of kidney stones must be front and center. Evaluation incudes both serum testing and CT.^5,7 Abdominal plain films and/or an intravenous pyelogram were considered state of the art in the 1980s and 1990s, but helical CT has become the scan of choice since it allows for measurement of the size, position, and level of obstruction. Helical CTs are increasingly available nationwide—and a sensitivity of 95% to 100% makes them the preferred method of evalution.^5,8

REFERENCES
1. Scales CD Jr, Smith AC, Hanley JM, Saigal CS. Urologic Diseases in America Project: Prevalence of kidney stones in the United States. Eur Urol. 2012;62:160-165.

2. Worcester EM, Coe FL. Calcium kidney stones. N Engl J Med. 2010;363:954-963.

3. Rule A, Lieske JC, Li X, et al. The ROKS Nomogram for Predicting a Second Symptomatic Stone Episode. J Am Soc Nephrol. 2014 Aug 7; [Epub ahead of print].

4. National Kidney Foundation. Diet and kidney stones. www.kidney.org/atoz/content/diet.cfm. Accessed September 9, 2104.

5. Jackman SV, Potter SR, Regan F, Jarrett TW. Plain abdominal x-ray versus computerized tomography screening: sensitivity for stone localization after nonenhanced spiral computerized tomography. J Urol. 2000;164(2):308-310.

6. Lipkin ME, Preminger GM. Demystifying the medical management of nephrolithiasis. Rev Urol. 2011;13(1):34-38.

7. National Institute of Diabetes and Digestive and Kidney Diseases. Kidney stones in adults: what are the types of kidney stones?  http://kidney.niddk.nih.gov/KUDiseases/pubs/stonesadults/index.aspx#types. Accessed September 9, 2014.

8. Harrington K, Torreggiani W. CT analysis of renal stone composition: a novel and noninvasive method to analyse stones. Ir Med J. 2014;107(3):69.

Kidney stones (nephrolithiasis), seen in 11% of all Americans, may increase patients’ risk for chronic kidney disease (CKD), although current research findings are insufficient to support a well-established relationship.^1,2 Actually, CKD may have a protective effect against the formation of calcium-based stones (which account for about 80% of all stones), since the CKD-affected kidney may fail to concentrate and excrete calcium. However, this effect is often offset by metabolic syndrome, diabetes, and hypertension—all of which increase the risk for calcium-based stones.^4,5 Heredity is also a factor.

After calcium-based stones, the most common types are struvite, uric acid, cysteine, and “mixed” stones. Not so common are the hereditary stones associated with four relatively rare conditions: primary hyperoxaluria (PH), adenine phosphoribosyltransferase (APRT) deficiency, cystinuria, and Dent’s disease. According to the NIH Rare Diseases Clinical Research Network, only 524 patients with these conditions are enrolled in the Mayo Clinic–based Rare Kidney Stone Consortium, indicating the orphan status of these illnesses.⁶

Patients with PH are born with an autosomal recessive error of glyoxylate metabolism that results in an overproduction of calcium oxalate.⁷ The oxalate is deposited in various organs—most often the kidneys, in the form of kidney stones. PH can occur in infants; parents are often alerted by rust spots in diapers, caused by passage of small stones.

There are three types of PH: PH1, PH2, and PH3. PH1 and PH2 account for approximately 90% of cases.⁸ In PH1, the genetic error is linked to an insufficient or absent liver enzyme. About 50% of children with PH1 will develop end-stage renal disease by young adulthood.⁹ One of the suggested treatments is liver transplantation, because replacing the diseased kidney alone would not spare the newly transplanted kidney from the same fate: a shower of stones from the liver. For patients with PH2 (which is generally less severe than PH1), kidney transplantation alone is often effective.¹⁰ In patients with any type of PH, high fluid intake is recommended.

Like PH, APRT/2,8-DHA crystalluria is an autosomal recessive disorder, one that researchers consider underrecognized and underdiagnosed. The majority of cases have been reported from Japan, France, and Iceland.¹¹ Often the stones are misidentified as uric acid or xanthine stones. Patients with APRT deficiency present with a range of symptoms—from stone disease to full kidney failure.¹² Treatment components include administration of allopurinol (a purine analog), increased fluid intake, a mildly purine-restricted diet, and extracorporeal shock-wave lithotripsy, when indicated.¹³

Cystinuria is found in 1% to 2% of patients with kidney stones but about 5% of children with stones¹⁴; it most often presents in early childhood. Patients have impaired renal cysteine transport, which leads to stone formation.¹⁵ Before it became possible to identify the genes responsible for cystinuria, patients were classified according to cystine excretion levels. Treatment includes high fluid intake, mild restriction of protein and sodium, alkalinization of urine, and use of medications including penicillamine and captopril.^16,17

The rare stone-producing illness Dent’s disease is an X-linked recessive condition that can lead to hypercalciuria, stones, CKD, and rickets.¹⁸ It usually presents in childhood, often in children who fail to thrive, and is associated with mutations of at least two genes (accounting for different disease types). Low-molecular-weight proteinuria is almost always present, but renal failure is relatively uncommon. Thiazide therapy has been found effective in treating the hypercalciuria associated with Dent’s disease, and addition of an ACE inhibitor may be helpful in patients with cystinosis.¹⁹

Kidney stones should be suspected in children with a family history of stones and symptoms such as hematuria, flank or abdominal pain, and/or urinary symptoms (dysuria, urinary tract infection). Genetic testing and counseling is frequently advised for these children and their families, as the correct diagnosis guides appropriate treatment.

References
1. Scales CD Jr, Smith AC, Hanley JM, Saigal CS. Urologic Diseases in America Project: Prevalence of kidney stones in the United States. Eur Urol. 2012;62:160-165.

2. Worcester EM, Coe FL. Calcium kidney stones. N Engl J Med. 2010;363:954-963.

3. Rule AD, Krambeck AE, Lieske JC. Chronic kidney disease in kidney stone formers. Clin J Am Soc Nephrol. 2011;6(8):2069-2075.

4. Teichman JM. Clinical practice. Acute renal colic from ureteral calculus. N Engl J Med. 2004;350(7):684-693.

5. National Institute of Diabetes and Digestive and Kidney Diseases. Kidney stones in adults: what are the types of kidney stones? http://kidney.niddk.nih.gov/KUDiseases/pubs/stonesadults/index.aspx. Accessed September 29, 2014.

6. Nazzal L. Spotlight on RDCRN consortia: the Rare Kidney Stone Consortium. http://rarediseasesnetwork.org/spotlight/April2013/RKSC. Accessed September 26, 2014.

7. Hoppe B. An update on primary hyperoxaluria. Nat Rev Nephrol. 2012;8(8):467-475.

8. Hoppe B, Langman CB. A United States survey on diagnosis, treatment, and outcome of primary hyperoxaluria. Pediatr Nephrol. 2003;18(10):986-991.

9. Harambat J, Farque S, Acquaviva C. Genotype-phenotype correlation in primary hyperoxaluria type 1: the p.Gly170Arg AGXT mutation is associated with a better outcome. Kidney Int. 2010;77(5):443-449.

10. Bergstralh EJ, Monico CG, Lieske JC. Transplantation outcomes in primary hyperoxaluria. Am J Transplant. 2010;10(11):2493-2501. 

11. Rare Clinical Diseases Research Network. Diseases in depth: adenine phosphoribosyltransferase (APRT) deficiency. www.rarediseasesnetwork.org/RKSC/professional/APRT/index.htm. Accessed September 29, 2014.

12. Edvardsson V, Palsson R. Adenine phosphoribosyltransferase deficiency and 2,8-dihydroxyadeninuria. In: Moriwaki Y, ed. Genetic Errors Associated with Purine and Pyrimidine Metabolism in Humans: Diagnosis and Treatment. Kerala, India: Research Signpost; 2006:79-93.

13. Edvardsson V, Palsson R, Olafsson I, et al. Clinical features and genotype of adenine phosphoribosyltransferase deficiency in Iceland. Am J Kidney Dis. 2001;38(3):473-480.

14. Stapleton FB. Childhood stones. Endocrinol Metab Clin North Am. 2002;31(4):1001-1015.

15. Mattoo A, Goldfarb DS. Cystinuria. Semin Nephrol. 2008;28(2):181-191.

16. Goldfarb DS, Coe FL, Asplin JR. Urinary cystine excretion and capacity in patients with cystinuria. Kidney Int. 2006;69(6):1041-1047.

17. Perazella MA, Buller GK. Successful treatment of cystinuria with captopril. Am J Kidney Dis. 1993;21(5):504-507.

18. Devuyst O, Thakker RV. Dent’s disease. Orphanet J Rare Dis. 2010;5:28.

19. Ludwig M, Utsch B, Monnens LA. Recent advances in understanding the clinical and genetic heterogeneity of Dent’s disease. Nephrol Dial Transplant. 2006;21(10):2708-2717.

Kidney stones (nephrolithiasis), seen in 11% of all Americans, may increase patients’ risk for chronic kidney disease (CKD), although current research findings are insufficient to support a well-established relationship.^1,2 Actually, CKD may have a protective effect against the formation of calcium-based stones (which account for about 80% of all stones), since the CKD-affected kidney may fail to concentrate and excrete calcium. However, this effect is often offset by metabolic syndrome, diabetes, and hypertension—all of which increase the risk for calcium-based stones.^4,5 Heredity is also a factor.

After calcium-based stones, the most common types are struvite, uric acid, cysteine, and “mixed” stones. Not so common are the hereditary stones associated with four relatively rare conditions: primary hyperoxaluria (PH), adenine phosphoribosyltransferase (APRT) deficiency, cystinuria, and Dent’s disease. According to the NIH Rare Diseases Clinical Research Network, only 524 patients with these conditions are enrolled in the Mayo Clinic–based Rare Kidney Stone Consortium, indicating the orphan status of these illnesses.⁶

Patients with PH are born with an autosomal recessive error of glyoxylate metabolism that results in an overproduction of calcium oxalate.⁷ The oxalate is deposited in various organs—most often the kidneys, in the form of kidney stones. PH can occur in infants; parents are often alerted by rust spots in diapers, caused by passage of small stones.

There are three types of PH: PH1, PH2, and PH3. PH1 and PH2 account for approximately 90% of cases.⁸ In PH1, the genetic error is linked to an insufficient or absent liver enzyme. About 50% of children with PH1 will develop end-stage renal disease by young adulthood.⁹ One of the suggested treatments is liver transplantation, because replacing the diseased kidney alone would not spare the newly transplanted kidney from the same fate: a shower of stones from the liver. For patients with PH2 (which is generally less severe than PH1), kidney transplantation alone is often effective.¹⁰ In patients with any type of PH, high fluid intake is recommended.

Like PH, APRT/2,8-DHA crystalluria is an autosomal recessive disorder, one that researchers consider underrecognized and underdiagnosed. The majority of cases have been reported from Japan, France, and Iceland.¹¹ Often the stones are misidentified as uric acid or xanthine stones. Patients with APRT deficiency present with a range of symptoms—from stone disease to full kidney failure.¹² Treatment components include administration of allopurinol (a purine analog), increased fluid intake, a mildly purine-restricted diet, and extracorporeal shock-wave lithotripsy, when indicated.¹³

Cystinuria is found in 1% to 2% of patients with kidney stones but about 5% of children with stones¹⁴; it most often presents in early childhood. Patients have impaired renal cysteine transport, which leads to stone formation.¹⁵ Before it became possible to identify the genes responsible for cystinuria, patients were classified according to cystine excretion levels. Treatment includes high fluid intake, mild restriction of protein and sodium, alkalinization of urine, and use of medications including penicillamine and captopril.^16,17

The rare stone-producing illness Dent’s disease is an X-linked recessive condition that can lead to hypercalciuria, stones, CKD, and rickets.¹⁸ It usually presents in childhood, often in children who fail to thrive, and is associated with mutations of at least two genes (accounting for different disease types). Low-molecular-weight proteinuria is almost always present, but renal failure is relatively uncommon. Thiazide therapy has been found effective in treating the hypercalciuria associated with Dent’s disease, and addition of an ACE inhibitor may be helpful in patients with cystinosis.¹⁹

Kidney stones should be suspected in children with a family history of stones and symptoms such as hematuria, flank or abdominal pain, and/or urinary symptoms (dysuria, urinary tract infection). Genetic testing and counseling is frequently advised for these children and their families, as the correct diagnosis guides appropriate treatment.

References
1. Scales CD Jr, Smith AC, Hanley JM, Saigal CS. Urologic Diseases in America Project: Prevalence of kidney stones in the United States. Eur Urol. 2012;62:160-165.

2. Worcester EM, Coe FL. Calcium kidney stones. N Engl J Med. 2010;363:954-963.

3. Rule AD, Krambeck AE, Lieske JC. Chronic kidney disease in kidney stone formers. Clin J Am Soc Nephrol. 2011;6(8):2069-2075.

4. Teichman JM. Clinical practice. Acute renal colic from ureteral calculus. N Engl J Med. 2004;350(7):684-693.

5. National Institute of Diabetes and Digestive and Kidney Diseases. Kidney stones in adults: what are the types of kidney stones? http://kidney.niddk.nih.gov/KUDiseases/pubs/stonesadults/index.aspx. Accessed September 29, 2014.

6. Nazzal L. Spotlight on RDCRN consortia: the Rare Kidney Stone Consortium. http://rarediseasesnetwork.org/spotlight/April2013/RKSC. Accessed September 26, 2014.

7. Hoppe B. An update on primary hyperoxaluria. Nat Rev Nephrol. 2012;8(8):467-475.

8. Hoppe B, Langman CB. A United States survey on diagnosis, treatment, and outcome of primary hyperoxaluria. Pediatr Nephrol. 2003;18(10):986-991.

9. Harambat J, Farque S, Acquaviva C. Genotype-phenotype correlation in primary hyperoxaluria type 1: the p.Gly170Arg AGXT mutation is associated with a better outcome. Kidney Int. 2010;77(5):443-449.

10. Bergstralh EJ, Monico CG, Lieske JC. Transplantation outcomes in primary hyperoxaluria. Am J Transplant. 2010;10(11):2493-2501. 

11. Rare Clinical Diseases Research Network. Diseases in depth: adenine phosphoribosyltransferase (APRT) deficiency. www.rarediseasesnetwork.org/RKSC/professional/APRT/index.htm. Accessed September 29, 2014.

12. Edvardsson V, Palsson R. Adenine phosphoribosyltransferase deficiency and 2,8-dihydroxyadeninuria. In: Moriwaki Y, ed. Genetic Errors Associated with Purine and Pyrimidine Metabolism in Humans: Diagnosis and Treatment. Kerala, India: Research Signpost; 2006:79-93.

13. Edvardsson V, Palsson R, Olafsson I, et al. Clinical features and genotype of adenine phosphoribosyltransferase deficiency in Iceland. Am J Kidney Dis. 2001;38(3):473-480.

14. Stapleton FB. Childhood stones. Endocrinol Metab Clin North Am. 2002;31(4):1001-1015.

15. Mattoo A, Goldfarb DS. Cystinuria. Semin Nephrol. 2008;28(2):181-191.

16. Goldfarb DS, Coe FL, Asplin JR. Urinary cystine excretion and capacity in patients with cystinuria. Kidney Int. 2006;69(6):1041-1047.

17. Perazella MA, Buller GK. Successful treatment of cystinuria with captopril. Am J Kidney Dis. 1993;21(5):504-507.

18. Devuyst O, Thakker RV. Dent’s disease. Orphanet J Rare Dis. 2010;5:28.

19. Ludwig M, Utsch B, Monnens LA. Recent advances in understanding the clinical and genetic heterogeneity of Dent’s disease. Nephrol Dial Transplant. 2006;21(10):2708-2717.

Kidney stones (nephrolithiasis), seen in 11% of all Americans, may increase patients’ risk for chronic kidney disease (CKD), although current research findings are insufficient to support a well-established relationship.^1,2 Actually, CKD may have a protective effect against the formation of calcium-based stones (which account for about 80% of all stones), since the CKD-affected kidney may fail to concentrate and excrete calcium. However, this effect is often offset by metabolic syndrome, diabetes, and hypertension—all of which increase the risk for calcium-based stones.^4,5 Heredity is also a factor.

After calcium-based stones, the most common types are struvite, uric acid, cysteine, and “mixed” stones. Not so common are the hereditary stones associated with four relatively rare conditions: primary hyperoxaluria (PH), adenine phosphoribosyltransferase (APRT) deficiency, cystinuria, and Dent’s disease. According to the NIH Rare Diseases Clinical Research Network, only 524 patients with these conditions are enrolled in the Mayo Clinic–based Rare Kidney Stone Consortium, indicating the orphan status of these illnesses.⁶

Patients with PH are born with an autosomal recessive error of glyoxylate metabolism that results in an overproduction of calcium oxalate.⁷ The oxalate is deposited in various organs—most often the kidneys, in the form of kidney stones. PH can occur in infants; parents are often alerted by rust spots in diapers, caused by passage of small stones.

There are three types of PH: PH1, PH2, and PH3. PH1 and PH2 account for approximately 90% of cases.⁸ In PH1, the genetic error is linked to an insufficient or absent liver enzyme. About 50% of children with PH1 will develop end-stage renal disease by young adulthood.⁹ One of the suggested treatments is liver transplantation, because replacing the diseased kidney alone would not spare the newly transplanted kidney from the same fate: a shower of stones from the liver. For patients with PH2 (which is generally less severe than PH1), kidney transplantation alone is often effective.¹⁰ In patients with any type of PH, high fluid intake is recommended.

Like PH, APRT/2,8-DHA crystalluria is an autosomal recessive disorder, one that researchers consider underrecognized and underdiagnosed. The majority of cases have been reported from Japan, France, and Iceland.¹¹ Often the stones are misidentified as uric acid or xanthine stones. Patients with APRT deficiency present with a range of symptoms—from stone disease to full kidney failure.¹² Treatment components include administration of allopurinol (a purine analog), increased fluid intake, a mildly purine-restricted diet, and extracorporeal shock-wave lithotripsy, when indicated.¹³

Cystinuria is found in 1% to 2% of patients with kidney stones but about 5% of children with stones¹⁴; it most often presents in early childhood. Patients have impaired renal cysteine transport, which leads to stone formation.¹⁵ Before it became possible to identify the genes responsible for cystinuria, patients were classified according to cystine excretion levels. Treatment includes high fluid intake, mild restriction of protein and sodium, alkalinization of urine, and use of medications including penicillamine and captopril.^16,17

The rare stone-producing illness Dent’s disease is an X-linked recessive condition that can lead to hypercalciuria, stones, CKD, and rickets.¹⁸ It usually presents in childhood, often in children who fail to thrive, and is associated with mutations of at least two genes (accounting for different disease types). Low-molecular-weight proteinuria is almost always present, but renal failure is relatively uncommon. Thiazide therapy has been found effective in treating the hypercalciuria associated with Dent’s disease, and addition of an ACE inhibitor may be helpful in patients with cystinosis.¹⁹

Kidney stones should be suspected in children with a family history of stones and symptoms such as hematuria, flank or abdominal pain, and/or urinary symptoms (dysuria, urinary tract infection). Genetic testing and counseling is frequently advised for these children and their families, as the correct diagnosis guides appropriate treatment.

References
1. Scales CD Jr, Smith AC, Hanley JM, Saigal CS. Urologic Diseases in America Project: Prevalence of kidney stones in the United States. Eur Urol. 2012;62:160-165.

2. Worcester EM, Coe FL. Calcium kidney stones. N Engl J Med. 2010;363:954-963.

3. Rule AD, Krambeck AE, Lieske JC. Chronic kidney disease in kidney stone formers. Clin J Am Soc Nephrol. 2011;6(8):2069-2075.

4. Teichman JM. Clinical practice. Acute renal colic from ureteral calculus. N Engl J Med. 2004;350(7):684-693.

5. National Institute of Diabetes and Digestive and Kidney Diseases. Kidney stones in adults: what are the types of kidney stones? http://kidney.niddk.nih.gov/KUDiseases/pubs/stonesadults/index.aspx. Accessed September 29, 2014.

6. Nazzal L. Spotlight on RDCRN consortia: the Rare Kidney Stone Consortium. http://rarediseasesnetwork.org/spotlight/April2013/RKSC. Accessed September 26, 2014.

7. Hoppe B. An update on primary hyperoxaluria. Nat Rev Nephrol. 2012;8(8):467-475.

8. Hoppe B, Langman CB. A United States survey on diagnosis, treatment, and outcome of primary hyperoxaluria. Pediatr Nephrol. 2003;18(10):986-991.

9. Harambat J, Farque S, Acquaviva C. Genotype-phenotype correlation in primary hyperoxaluria type 1: the p.Gly170Arg AGXT mutation is associated with a better outcome. Kidney Int. 2010;77(5):443-449.

10. Bergstralh EJ, Monico CG, Lieske JC. Transplantation outcomes in primary hyperoxaluria. Am J Transplant. 2010;10(11):2493-2501. 

11. Rare Clinical Diseases Research Network. Diseases in depth: adenine phosphoribosyltransferase (APRT) deficiency. www.rarediseasesnetwork.org/RKSC/professional/APRT/index.htm. Accessed September 29, 2014.

12. Edvardsson V, Palsson R. Adenine phosphoribosyltransferase deficiency and 2,8-dihydroxyadeninuria. In: Moriwaki Y, ed. Genetic Errors Associated with Purine and Pyrimidine Metabolism in Humans: Diagnosis and Treatment. Kerala, India: Research Signpost; 2006:79-93.

13. Edvardsson V, Palsson R, Olafsson I, et al. Clinical features and genotype of adenine phosphoribosyltransferase deficiency in Iceland. Am J Kidney Dis. 2001;38(3):473-480.

14. Stapleton FB. Childhood stones. Endocrinol Metab Clin North Am. 2002;31(4):1001-1015.

15. Mattoo A, Goldfarb DS. Cystinuria. Semin Nephrol. 2008;28(2):181-191.

16. Goldfarb DS, Coe FL, Asplin JR. Urinary cystine excretion and capacity in patients with cystinuria. Kidney Int. 2006;69(6):1041-1047.

17. Perazella MA, Buller GK. Successful treatment of cystinuria with captopril. Am J Kidney Dis. 1993;21(5):504-507.

18. Devuyst O, Thakker RV. Dent’s disease. Orphanet J Rare Dis. 2010;5:28.

19. Ludwig M, Utsch B, Monnens LA. Recent advances in understanding the clinical and genetic heterogeneity of Dent’s disease. Nephrol Dial Transplant. 2006;21(10):2708-2717.

The long lazy days of summer are ending: The warm evenings, the iced tea, the sounds of kids playing at the pool being overshadowed by the loud moans of the patient with kidney stones ….

Kidney stones (nephrolithiasis) are collections of crystals that coalesce into a hard ball and can lodge in any location of the urinary collecting systems. More than half a million patients seen in US emergency departments each year will receive a diagnosis of nephrolithiasis.¹

But the problem is much more common in the summer, thanks to the double whammy of heat and humidity.^2-4 Research indicates that it is not geographic area but instead the effects of climate that impact stone incidence.⁵ As climate change occurs, it is expected that the incidence of kidney stones will rise.

There is a “stone belt” that covers the southern portion of the United States (see Figure). As reported in Kidney International, this area is growing due to climate change and is expected to reach as far north as Nebraska, Illinois, Pennsylvania, and Oregon by 2095. Thus, the incidence of stone formation will increase throughout the 21st century in many parts of the US.⁶

Kidney stones are more common in men than in women and in white than in nonwhite persons (by three to four times). Peak incidence occurs between ages 20 and 50.¹ Heat plays a greater role in the increased incidence of stone formation in men for unknown reasons.⁶

Stones that lodge in the ureter or the calyces of the kidney will often cause obstruction. When the flow of urine is obstructed, infection, loss of kidney function, and chronic permanent damage can result. Thus, decreasing the incidence of stones is vital at any time of the year—but most significant during the summer. 

All patients with a history of stones require fluid hydration, up to 2.5 L/d, with extra intake during the heat of summer.⁷ Patients who travel to hot, humid regions must be encouraged to increase fluid consumption. Often, foreign travel can be problematic due to a decrease in access to clean drinking water and/or lavatory facilities. It is incumbent upon the practitioner to review risk for kidney stones with patients who plan to travel to warm areas.

As the summer season closes and school starts, this is a perfect time to review the causes, treatment, and most importantly, the methods to decrease recurrent kidney stone formation with patients. Each incident of stone formation for our patients can translate to an increased incidence of chronic kidney disease and a 50% risk for another stone during their lifetime.¹

REFERENCES
1. National Kidney Foundation. Kidney stones. www.kidney.org/atoz/content/kidneystones.cfm. Accessed September 10, 2014.

2.Schade GR, Faerber GJ. Urinary tract stones. Prim Care. 2010;37(3):565-581, ix.

3. Pearle MS, Calhoun E, Curhan GC. Urolithiasis. In: Litwin MS, Saigal CS, eds. Urologic Diseases in America. National Institute of Diabetes and Digestive and Kidney Diseases. 2007:281-320. http://kidney.niddk.nih.gov/statistics/uda/Urologic_Diseases_in_America.pdf. Accessed September 10, 2014.

4. Romero V, Akpinar H, Assimos DG. Kidney stones: a global picture of prevalence, incidence and associated risk factors. Rev Urol. 2010;12(2-3):e86-e96.

5. Eisner BH, Sheth S, Herrick B, et al. The effects of ambient temperature, humidity and season of year on urine composition in patients with nephrolithiasis. BJU Int. 2012;110(11c):E1014–E1017.

6. Fakheri RJ, Goldfarb DS. Ambient temperature as a contributor to kidney stone formation: Implications of global warming. Kidney Int. 2011;79:1178–1185.

7. Lipkin ME, Preminger GM. Demystifying the medical management of nephrolithiasis. Rev Urol. 2011;13(1):34-38.

The long lazy days of summer are ending: The warm evenings, the iced tea, the sounds of kids playing at the pool being overshadowed by the loud moans of the patient with kidney stones ….

Kidney stones (nephrolithiasis) are collections of crystals that coalesce into a hard ball and can lodge in any location of the urinary collecting systems. More than half a million patients seen in US emergency departments each year will receive a diagnosis of nephrolithiasis.¹

But the problem is much more common in the summer, thanks to the double whammy of heat and humidity.^2-4 Research indicates that it is not geographic area but instead the effects of climate that impact stone incidence.⁵ As climate change occurs, it is expected that the incidence of kidney stones will rise.

There is a “stone belt” that covers the southern portion of the United States (see Figure). As reported in Kidney International, this area is growing due to climate change and is expected to reach as far north as Nebraska, Illinois, Pennsylvania, and Oregon by 2095. Thus, the incidence of stone formation will increase throughout the 21st century in many parts of the US.⁶

Kidney stones are more common in men than in women and in white than in nonwhite persons (by three to four times). Peak incidence occurs between ages 20 and 50.¹ Heat plays a greater role in the increased incidence of stone formation in men for unknown reasons.⁶

Stones that lodge in the ureter or the calyces of the kidney will often cause obstruction. When the flow of urine is obstructed, infection, loss of kidney function, and chronic permanent damage can result. Thus, decreasing the incidence of stones is vital at any time of the year—but most significant during the summer. 

All patients with a history of stones require fluid hydration, up to 2.5 L/d, with extra intake during the heat of summer.⁷ Patients who travel to hot, humid regions must be encouraged to increase fluid consumption. Often, foreign travel can be problematic due to a decrease in access to clean drinking water and/or lavatory facilities. It is incumbent upon the practitioner to review risk for kidney stones with patients who plan to travel to warm areas.

As the summer season closes and school starts, this is a perfect time to review the causes, treatment, and most importantly, the methods to decrease recurrent kidney stone formation with patients. Each incident of stone formation for our patients can translate to an increased incidence of chronic kidney disease and a 50% risk for another stone during their lifetime.¹

REFERENCES
1. National Kidney Foundation. Kidney stones. www.kidney.org/atoz/content/kidneystones.cfm. Accessed September 10, 2014.

2.Schade GR, Faerber GJ. Urinary tract stones. Prim Care. 2010;37(3):565-581, ix.

3. Pearle MS, Calhoun E, Curhan GC. Urolithiasis. In: Litwin MS, Saigal CS, eds. Urologic Diseases in America. National Institute of Diabetes and Digestive and Kidney Diseases. 2007:281-320. http://kidney.niddk.nih.gov/statistics/uda/Urologic_Diseases_in_America.pdf. Accessed September 10, 2014.

4. Romero V, Akpinar H, Assimos DG. Kidney stones: a global picture of prevalence, incidence and associated risk factors. Rev Urol. 2010;12(2-3):e86-e96.

5. Eisner BH, Sheth S, Herrick B, et al. The effects of ambient temperature, humidity and season of year on urine composition in patients with nephrolithiasis. BJU Int. 2012;110(11c):E1014–E1017.

6. Fakheri RJ, Goldfarb DS. Ambient temperature as a contributor to kidney stone formation: Implications of global warming. Kidney Int. 2011;79:1178–1185.

7. Lipkin ME, Preminger GM. Demystifying the medical management of nephrolithiasis. Rev Urol. 2011;13(1):34-38.

The long lazy days of summer are ending: The warm evenings, the iced tea, the sounds of kids playing at the pool being overshadowed by the loud moans of the patient with kidney stones ….

Kidney stones (nephrolithiasis) are collections of crystals that coalesce into a hard ball and can lodge in any location of the urinary collecting systems. More than half a million patients seen in US emergency departments each year will receive a diagnosis of nephrolithiasis.¹

But the problem is much more common in the summer, thanks to the double whammy of heat and humidity.^2-4 Research indicates that it is not geographic area but instead the effects of climate that impact stone incidence.⁵ As climate change occurs, it is expected that the incidence of kidney stones will rise.

There is a “stone belt” that covers the southern portion of the United States (see Figure). As reported in Kidney International, this area is growing due to climate change and is expected to reach as far north as Nebraska, Illinois, Pennsylvania, and Oregon by 2095. Thus, the incidence of stone formation will increase throughout the 21st century in many parts of the US.⁶

Kidney stones are more common in men than in women and in white than in nonwhite persons (by three to four times). Peak incidence occurs between ages 20 and 50.¹ Heat plays a greater role in the increased incidence of stone formation in men for unknown reasons.⁶

Stones that lodge in the ureter or the calyces of the kidney will often cause obstruction. When the flow of urine is obstructed, infection, loss of kidney function, and chronic permanent damage can result. Thus, decreasing the incidence of stones is vital at any time of the year—but most significant during the summer. 

All patients with a history of stones require fluid hydration, up to 2.5 L/d, with extra intake during the heat of summer.⁷ Patients who travel to hot, humid regions must be encouraged to increase fluid consumption. Often, foreign travel can be problematic due to a decrease in access to clean drinking water and/or lavatory facilities. It is incumbent upon the practitioner to review risk for kidney stones with patients who plan to travel to warm areas.

As the summer season closes and school starts, this is a perfect time to review the causes, treatment, and most importantly, the methods to decrease recurrent kidney stone formation with patients. Each incident of stone formation for our patients can translate to an increased incidence of chronic kidney disease and a 50% risk for another stone during their lifetime.¹

REFERENCES
1. National Kidney Foundation. Kidney stones. www.kidney.org/atoz/content/kidneystones.cfm. Accessed September 10, 2014.

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