Nephrology

First described in 2000 in a case series of 15 patients, nephrogenic systemic fibrosis (NSF) is a rare scleroderma-like fibrosing skin condition associated with gadolinium exposure in end stage renal disease (ESRD).¹ Patients with advanced chronic kidney disease (CKD) or ESRD are at the highest risk for this condition when exposed to gadolinium-based contrast dyes.

Nephrogenic systemic fibrosis is a devastating and rapidly progressive condition, making its prevention in at-risk populations of utmost importance. In this article, the authors describe a case of a patient who developed NSF in the setting of gadolinium exposure and multiple inflammatory dermatologic conditions. This case illustrates the possible role of a pro-inflammatory state in predisposing to NSF, which may help further elucidate its mechanism of action.

Case Presentation

A 61-year-old Hispanic male with a history of IV heroin use with ESRD secondary to membranous glomerulonephritis on hemodialysis and chronic hepatitis C infection presented to the West Los Angeles VAMC with fevers and night sweats that had persisted for 2 weeks. His physical examination was notable for diffuse tender palpable purpura and petechiae (including his palms and soles), altered mental status, and diffuse myoclonic jerks, which necessitated endotracheal intubation and mechanical ventilation for airway protection. Blood cultures were positive for methicillin-sensitive Staphylococcus aureus (MSSA). Laboratory results were notable for an elevated sedimentation rate of 53 mm/h (0-10 mm/h), C-reactive protein of 19.8 mg/L (< 0.744 mg/dL), and albumin of 1.2 g/dL (3.2-4.8 g/dL). An extensive rheumatologic workup was unrevealing, and a lumbar puncture was unremarkable. A biopsy of his skin lesions was consistent with leukocytoclastic vasculitis.

The patient’s prior hemodialysis access, a tunneled dialysis catheter in the right subclavian vein, was removed given concern for line infection and replaced with an internal jugular temporary hemodialysis line. Given his altered mental status and myoclonic jerks, the decision was made to pursue a magnetic resonance imaging (MRI) scan of the brain and spine with gadolinium contrast to evaluate for cerebral vasculitis and/or septic emboli to the brain.

The patient received 15 mL of gadoversetamide contrast in accordance with hospital imaging protocol. The MRI revealed only chronic ischemic changes. The patient underwent hemodialysis about 18 hours later. The patient was treated with a 6-week course of IV penicillin G. His altered mental status and myoclonic jerks resolved without intervention, and he was then discharged to an acute rehabilitation unit.

Eight weeks after his initial presentation the patient developed a purulent wound on his right forearm (Figure 1) 

The patient was discharged to continue physical and occupational therapy to preserve his functional mobility, as no other treatment options were available. 

Discussion

Nephrogenic systemic fibrosis is a poorly understood inflammatory condition that produces diffuse fibrosis of the skin. Typically, the disease begins with progressive skin induration of the extremities. Systemic involvement may occur, leading to fibrosis of skeletal muscle, fascia, and multiple organs. Flexion contractures may develop that limit physical function. Fibrosis can become apparent within days to months after exposure to gadolinium contrast.

Beyond renal insufficiency, it is unclear what other risk factors predispose patients to developing this condition. Only a minority of patients with CKD stages 1 through 4 will develop NSF on exposure to gadolinium contrast. However, the incidence of NSF among patients with CKD stage 5 who are exposed to gadolinium has been estimated to be about 13.4% in a prospective study involving 18 patients.²

In a 2015 meta-analysis by Zhang and colleagues, the only clear risk factor identified for the development of NSF, aside from gadolinium exposure, was severe renal insufficiency with a glomerular filtration rate of < 30 mL/min/1.75m².³ Due to the limited number of patients identified with this disease, it is difficult to identify other risk factors associated with the development of NSF. Based on in vitro studies, it has been postulated that a pro-inflammatory state predisposes patients to develop NSF.^4,5 The proposed mechanism for NSF involves extravasation of gadolinium in the setting of vascular endothelial permeability.^5,6 Gadolinium then interacts with tissue macrophages, which induce the release of inflammatory cytokines and the secretion of smooth muscle actin by dermal fibroblasts.^6,7

Treatment of NSF has been largely unsuccessful. Multiple modalities of treatment that included topical and oral steroids, immunosuppression, plasmapheresis, and ultraviolent therapy have been attempted, none of which have been proven to consistently limit progression of the disease.⁸ The most effective intervention is early physical therapy to preserve functionality and prevent contracture formation. For patients who are eligible, early renal transplantation may offer the best chance of improved mobility. In a case series review by Cuffy and colleagues, 5 of 6 patients who underwent renal transplantation after the development of NSF experienced softening of the involved skin, and 2 patients had improved mobility of joints.⁹

Conclusion

The case presented here illustrates a possible association between a pro-inflammatory state and the development of NSF. This patient had multiple inflammatory conditions, including MSSA bacteremia, leukocytoclastic vasculitis, and pyoderma gangrenosum (the latter 2 conditions were thought to be associated with his underlying chronic hepatitis C infection), which the authors believe predisposed him to endothelial permeability and risk for developing NSF. The risk of developing NSF in at-risk patients with each episode of gadolinium exposure is estimated around 2.4%, or an incidence of 4.3 cases per 1,000 patient-years, leading the American College of Radiologists to recommend against the administration of gadolinium-based contrast except in cases in which benefits clearly outweigh risks.¹⁰ However, an MRI with gadolinium contrast can offer high diagnostic yield in cases such as the one presented here in which a diagnosis remains elusive. Moreover, the use of linear gadolinium-based contrast agents such as gadoversetamide, as in this case, has been reported to be associated with higher incidence of NSF.⁵ Since this case, the West Los Angeles VAMC has switched to gadobutrol contrast for its MRI protocol, which has been purported to be a lower risk agent compared with that of linear gadolinium-based contrast agents (although several cases of NSF have been reported with gadobutrol in the literature).¹¹

Providers weighing the decision to administer gadolinium contrast to patients with ESRD should discuss the risks and benefits thoroughly, especially in patients with preexisting inflammatory conditions. In addition, although it has not been shown to effectively reduce the risk of NSF after administration of gadolinium, hemodialysis is recommended 2 hours after contrast administration for individuals at risk (the study patient received hemodialysis approximately 18 hours after).¹² Given the lack of effective treatment options for NSF, prevention is key. A deeper understanding of the pathophysiology of NSF and identification of its risk factors is paramount to the prevention of this devastating disease.

First described in 2000 in a case series of 15 patients, nephrogenic systemic fibrosis (NSF) is a rare scleroderma-like fibrosing skin condition associated with gadolinium exposure in end stage renal disease (ESRD).¹ Patients with advanced chronic kidney disease (CKD) or ESRD are at the highest risk for this condition when exposed to gadolinium-based contrast dyes.

Nephrogenic systemic fibrosis is a devastating and rapidly progressive condition, making its prevention in at-risk populations of utmost importance. In this article, the authors describe a case of a patient who developed NSF in the setting of gadolinium exposure and multiple inflammatory dermatologic conditions. This case illustrates the possible role of a pro-inflammatory state in predisposing to NSF, which may help further elucidate its mechanism of action.

Case Presentation

A 61-year-old Hispanic male with a history of IV heroin use with ESRD secondary to membranous glomerulonephritis on hemodialysis and chronic hepatitis C infection presented to the West Los Angeles VAMC with fevers and night sweats that had persisted for 2 weeks. His physical examination was notable for diffuse tender palpable purpura and petechiae (including his palms and soles), altered mental status, and diffuse myoclonic jerks, which necessitated endotracheal intubation and mechanical ventilation for airway protection. Blood cultures were positive for methicillin-sensitive Staphylococcus aureus (MSSA). Laboratory results were notable for an elevated sedimentation rate of 53 mm/h (0-10 mm/h), C-reactive protein of 19.8 mg/L (< 0.744 mg/dL), and albumin of 1.2 g/dL (3.2-4.8 g/dL). An extensive rheumatologic workup was unrevealing, and a lumbar puncture was unremarkable. A biopsy of his skin lesions was consistent with leukocytoclastic vasculitis.

The patient’s prior hemodialysis access, a tunneled dialysis catheter in the right subclavian vein, was removed given concern for line infection and replaced with an internal jugular temporary hemodialysis line. Given his altered mental status and myoclonic jerks, the decision was made to pursue a magnetic resonance imaging (MRI) scan of the brain and spine with gadolinium contrast to evaluate for cerebral vasculitis and/or septic emboli to the brain.

The patient received 15 mL of gadoversetamide contrast in accordance with hospital imaging protocol. The MRI revealed only chronic ischemic changes. The patient underwent hemodialysis about 18 hours later. The patient was treated with a 6-week course of IV penicillin G. His altered mental status and myoclonic jerks resolved without intervention, and he was then discharged to an acute rehabilitation unit.

Eight weeks after his initial presentation the patient developed a purulent wound on his right forearm (Figure 1) 

The patient was discharged to continue physical and occupational therapy to preserve his functional mobility, as no other treatment options were available. 

Discussion

Nephrogenic systemic fibrosis is a poorly understood inflammatory condition that produces diffuse fibrosis of the skin. Typically, the disease begins with progressive skin induration of the extremities. Systemic involvement may occur, leading to fibrosis of skeletal muscle, fascia, and multiple organs. Flexion contractures may develop that limit physical function. Fibrosis can become apparent within days to months after exposure to gadolinium contrast.

Beyond renal insufficiency, it is unclear what other risk factors predispose patients to developing this condition. Only a minority of patients with CKD stages 1 through 4 will develop NSF on exposure to gadolinium contrast. However, the incidence of NSF among patients with CKD stage 5 who are exposed to gadolinium has been estimated to be about 13.4% in a prospective study involving 18 patients.²

In a 2015 meta-analysis by Zhang and colleagues, the only clear risk factor identified for the development of NSF, aside from gadolinium exposure, was severe renal insufficiency with a glomerular filtration rate of < 30 mL/min/1.75m².³ Due to the limited number of patients identified with this disease, it is difficult to identify other risk factors associated with the development of NSF. Based on in vitro studies, it has been postulated that a pro-inflammatory state predisposes patients to develop NSF.^4,5 The proposed mechanism for NSF involves extravasation of gadolinium in the setting of vascular endothelial permeability.^5,6 Gadolinium then interacts with tissue macrophages, which induce the release of inflammatory cytokines and the secretion of smooth muscle actin by dermal fibroblasts.^6,7

Treatment of NSF has been largely unsuccessful. Multiple modalities of treatment that included topical and oral steroids, immunosuppression, plasmapheresis, and ultraviolent therapy have been attempted, none of which have been proven to consistently limit progression of the disease.⁸ The most effective intervention is early physical therapy to preserve functionality and prevent contracture formation. For patients who are eligible, early renal transplantation may offer the best chance of improved mobility. In a case series review by Cuffy and colleagues, 5 of 6 patients who underwent renal transplantation after the development of NSF experienced softening of the involved skin, and 2 patients had improved mobility of joints.⁹

Conclusion

The case presented here illustrates a possible association between a pro-inflammatory state and the development of NSF. This patient had multiple inflammatory conditions, including MSSA bacteremia, leukocytoclastic vasculitis, and pyoderma gangrenosum (the latter 2 conditions were thought to be associated with his underlying chronic hepatitis C infection), which the authors believe predisposed him to endothelial permeability and risk for developing NSF. The risk of developing NSF in at-risk patients with each episode of gadolinium exposure is estimated around 2.4%, or an incidence of 4.3 cases per 1,000 patient-years, leading the American College of Radiologists to recommend against the administration of gadolinium-based contrast except in cases in which benefits clearly outweigh risks.¹⁰ However, an MRI with gadolinium contrast can offer high diagnostic yield in cases such as the one presented here in which a diagnosis remains elusive. Moreover, the use of linear gadolinium-based contrast agents such as gadoversetamide, as in this case, has been reported to be associated with higher incidence of NSF.⁵ Since this case, the West Los Angeles VAMC has switched to gadobutrol contrast for its MRI protocol, which has been purported to be a lower risk agent compared with that of linear gadolinium-based contrast agents (although several cases of NSF have been reported with gadobutrol in the literature).¹¹

Providers weighing the decision to administer gadolinium contrast to patients with ESRD should discuss the risks and benefits thoroughly, especially in patients with preexisting inflammatory conditions. In addition, although it has not been shown to effectively reduce the risk of NSF after administration of gadolinium, hemodialysis is recommended 2 hours after contrast administration for individuals at risk (the study patient received hemodialysis approximately 18 hours after).¹² Given the lack of effective treatment options for NSF, prevention is key. A deeper understanding of the pathophysiology of NSF and identification of its risk factors is paramount to the prevention of this devastating disease.

First described in 2000 in a case series of 15 patients, nephrogenic systemic fibrosis (NSF) is a rare scleroderma-like fibrosing skin condition associated with gadolinium exposure in end stage renal disease (ESRD).¹ Patients with advanced chronic kidney disease (CKD) or ESRD are at the highest risk for this condition when exposed to gadolinium-based contrast dyes.

Nephrogenic systemic fibrosis is a devastating and rapidly progressive condition, making its prevention in at-risk populations of utmost importance. In this article, the authors describe a case of a patient who developed NSF in the setting of gadolinium exposure and multiple inflammatory dermatologic conditions. This case illustrates the possible role of a pro-inflammatory state in predisposing to NSF, which may help further elucidate its mechanism of action.

Case Presentation

A 61-year-old Hispanic male with a history of IV heroin use with ESRD secondary to membranous glomerulonephritis on hemodialysis and chronic hepatitis C infection presented to the West Los Angeles VAMC with fevers and night sweats that had persisted for 2 weeks. His physical examination was notable for diffuse tender palpable purpura and petechiae (including his palms and soles), altered mental status, and diffuse myoclonic jerks, which necessitated endotracheal intubation and mechanical ventilation for airway protection. Blood cultures were positive for methicillin-sensitive Staphylococcus aureus (MSSA). Laboratory results were notable for an elevated sedimentation rate of 53 mm/h (0-10 mm/h), C-reactive protein of 19.8 mg/L (< 0.744 mg/dL), and albumin of 1.2 g/dL (3.2-4.8 g/dL). An extensive rheumatologic workup was unrevealing, and a lumbar puncture was unremarkable. A biopsy of his skin lesions was consistent with leukocytoclastic vasculitis.

The patient’s prior hemodialysis access, a tunneled dialysis catheter in the right subclavian vein, was removed given concern for line infection and replaced with an internal jugular temporary hemodialysis line. Given his altered mental status and myoclonic jerks, the decision was made to pursue a magnetic resonance imaging (MRI) scan of the brain and spine with gadolinium contrast to evaluate for cerebral vasculitis and/or septic emboli to the brain.

The patient received 15 mL of gadoversetamide contrast in accordance with hospital imaging protocol. The MRI revealed only chronic ischemic changes. The patient underwent hemodialysis about 18 hours later. The patient was treated with a 6-week course of IV penicillin G. His altered mental status and myoclonic jerks resolved without intervention, and he was then discharged to an acute rehabilitation unit.

Eight weeks after his initial presentation the patient developed a purulent wound on his right forearm (Figure 1) 

The patient was discharged to continue physical and occupational therapy to preserve his functional mobility, as no other treatment options were available. 

Discussion

Nephrogenic systemic fibrosis is a poorly understood inflammatory condition that produces diffuse fibrosis of the skin. Typically, the disease begins with progressive skin induration of the extremities. Systemic involvement may occur, leading to fibrosis of skeletal muscle, fascia, and multiple organs. Flexion contractures may develop that limit physical function. Fibrosis can become apparent within days to months after exposure to gadolinium contrast.

Beyond renal insufficiency, it is unclear what other risk factors predispose patients to developing this condition. Only a minority of patients with CKD stages 1 through 4 will develop NSF on exposure to gadolinium contrast. However, the incidence of NSF among patients with CKD stage 5 who are exposed to gadolinium has been estimated to be about 13.4% in a prospective study involving 18 patients.²

In a 2015 meta-analysis by Zhang and colleagues, the only clear risk factor identified for the development of NSF, aside from gadolinium exposure, was severe renal insufficiency with a glomerular filtration rate of < 30 mL/min/1.75m².³ Due to the limited number of patients identified with this disease, it is difficult to identify other risk factors associated with the development of NSF. Based on in vitro studies, it has been postulated that a pro-inflammatory state predisposes patients to develop NSF.^4,5 The proposed mechanism for NSF involves extravasation of gadolinium in the setting of vascular endothelial permeability.^5,6 Gadolinium then interacts with tissue macrophages, which induce the release of inflammatory cytokines and the secretion of smooth muscle actin by dermal fibroblasts.^6,7

Treatment of NSF has been largely unsuccessful. Multiple modalities of treatment that included topical and oral steroids, immunosuppression, plasmapheresis, and ultraviolent therapy have been attempted, none of which have been proven to consistently limit progression of the disease.⁸ The most effective intervention is early physical therapy to preserve functionality and prevent contracture formation. For patients who are eligible, early renal transplantation may offer the best chance of improved mobility. In a case series review by Cuffy and colleagues, 5 of 6 patients who underwent renal transplantation after the development of NSF experienced softening of the involved skin, and 2 patients had improved mobility of joints.⁹

Conclusion

The case presented here illustrates a possible association between a pro-inflammatory state and the development of NSF. This patient had multiple inflammatory conditions, including MSSA bacteremia, leukocytoclastic vasculitis, and pyoderma gangrenosum (the latter 2 conditions were thought to be associated with his underlying chronic hepatitis C infection), which the authors believe predisposed him to endothelial permeability and risk for developing NSF. The risk of developing NSF in at-risk patients with each episode of gadolinium exposure is estimated around 2.4%, or an incidence of 4.3 cases per 1,000 patient-years, leading the American College of Radiologists to recommend against the administration of gadolinium-based contrast except in cases in which benefits clearly outweigh risks.¹⁰ However, an MRI with gadolinium contrast can offer high diagnostic yield in cases such as the one presented here in which a diagnosis remains elusive. Moreover, the use of linear gadolinium-based contrast agents such as gadoversetamide, as in this case, has been reported to be associated with higher incidence of NSF.⁵ Since this case, the West Los Angeles VAMC has switched to gadobutrol contrast for its MRI protocol, which has been purported to be a lower risk agent compared with that of linear gadolinium-based contrast agents (although several cases of NSF have been reported with gadobutrol in the literature).¹¹

Providers weighing the decision to administer gadolinium contrast to patients with ESRD should discuss the risks and benefits thoroughly, especially in patients with preexisting inflammatory conditions. In addition, although it has not been shown to effectively reduce the risk of NSF after administration of gadolinium, hemodialysis is recommended 2 hours after contrast administration for individuals at risk (the study patient received hemodialysis approximately 18 hours after).¹² Given the lack of effective treatment options for NSF, prevention is key. A deeper understanding of the pathophysiology of NSF and identification of its risk factors is paramount to the prevention of this devastating disease.

SAN FRANCISCO – Primary hyperparathyroidism was detected in 7% of 742 patients with recurrent kidney stones at a single tertiary care clinic, and the patients’ primary care physicians may have missed the diagnosis because several affected patients’ calcium levels were in the high normal range.

Of the 53 patients diagnosed with primary hyperparathyroidism (hPTH), 72% had high normal serum calcium levels. After examining the charts of those patients, researchers found that 11 of the 53 patients (21%) had been tested for parathyroid hormone and serum calcium levels and could have been identified by their primary care physicians.

SOURCE: Boyd C et al. AUA 2018, Abstract MP13-03.

SAN FRANCISCO – Primary hyperparathyroidism was detected in 7% of 742 patients with recurrent kidney stones at a single tertiary care clinic, and the patients’ primary care physicians may have missed the diagnosis because several affected patients’ calcium levels were in the high normal range.

Of the 53 patients diagnosed with primary hyperparathyroidism (hPTH), 72% had high normal serum calcium levels. After examining the charts of those patients, researchers found that 11 of the 53 patients (21%) had been tested for parathyroid hormone and serum calcium levels and could have been identified by their primary care physicians.

SOURCE: Boyd C et al. AUA 2018, Abstract MP13-03.

SAN FRANCISCO – Primary hyperparathyroidism was detected in 7% of 742 patients with recurrent kidney stones at a single tertiary care clinic, and the patients’ primary care physicians may have missed the diagnosis because several affected patients’ calcium levels were in the high normal range.

Of the 53 patients diagnosed with primary hyperparathyroidism (hPTH), 72% had high normal serum calcium levels. After examining the charts of those patients, researchers found that 11 of the 53 patients (21%) had been tested for parathyroid hormone and serum calcium levels and could have been identified by their primary care physicians.

SOURCE: Boyd C et al. AUA 2018, Abstract MP13-03.

SAN FRANCISCO – Testosterone replacement therapy was associated with heightened risk for kidney stones, according to an analysis of more than 50,000 men with low testosterone.

When researchers compared hypogonadal men to age- and comorbidity-matched controls, they found a statistically significantly higher number of clinical diagnoses of a kidney stone, or of patients undergoing a kidney stone–related procedure.

Jim Kling/MDedge News

Dr. McClintock said the study is convincing in part because it used data from TRICARE, which sets a lower testosterone level even than AUA guidelines for determining if a patient is eligible for testosterone therapy.

“It would suggest that those are the real low testosterone patients, not necessarily men who heard an ad or went to a test center,” noted Patrick Shepherd Lowry, MD, associate professor of urology at Scott & White Medical Center, Temple, Texas, who attended the presentation but was not involved in the study. “It’s preliminary, but it’s very interesting. It hasn’t been shown before.”

The Department of Defense funded the study. Dr. McClintock reported having no relevant financial disclosures.

SOURCE: McClintock T. AUA Annual Meeting. Abstract MP13-19.

SAN FRANCISCO – Testosterone replacement therapy was associated with heightened risk for kidney stones, according to an analysis of more than 50,000 men with low testosterone.

When researchers compared hypogonadal men to age- and comorbidity-matched controls, they found a statistically significantly higher number of clinical diagnoses of a kidney stone, or of patients undergoing a kidney stone–related procedure.

Jim Kling/MDedge News

Dr. McClintock said the study is convincing in part because it used data from TRICARE, which sets a lower testosterone level even than AUA guidelines for determining if a patient is eligible for testosterone therapy.

“It would suggest that those are the real low testosterone patients, not necessarily men who heard an ad or went to a test center,” noted Patrick Shepherd Lowry, MD, associate professor of urology at Scott & White Medical Center, Temple, Texas, who attended the presentation but was not involved in the study. “It’s preliminary, but it’s very interesting. It hasn’t been shown before.”

The Department of Defense funded the study. Dr. McClintock reported having no relevant financial disclosures.

SOURCE: McClintock T. AUA Annual Meeting. Abstract MP13-19.

SAN FRANCISCO – Testosterone replacement therapy was associated with heightened risk for kidney stones, according to an analysis of more than 50,000 men with low testosterone.

When researchers compared hypogonadal men to age- and comorbidity-matched controls, they found a statistically significantly higher number of clinical diagnoses of a kidney stone, or of patients undergoing a kidney stone–related procedure.

Jim Kling/MDedge News

Dr. McClintock said the study is convincing in part because it used data from TRICARE, which sets a lower testosterone level even than AUA guidelines for determining if a patient is eligible for testosterone therapy.

“It would suggest that those are the real low testosterone patients, not necessarily men who heard an ad or went to a test center,” noted Patrick Shepherd Lowry, MD, associate professor of urology at Scott & White Medical Center, Temple, Texas, who attended the presentation but was not involved in the study. “It’s preliminary, but it’s very interesting. It hasn’t been shown before.”

The Department of Defense funded the study. Dr. McClintock reported having no relevant financial disclosures.

SOURCE: McClintock T. AUA Annual Meeting. Abstract MP13-19.

BOSTON – A lot of people do well with HIV thanks to potent antiretrovirals, but there’s still at least one group that needs extra attention: HIV patients with chronic kidney disease (CKD), according to Lene Ryom, MD, PhD, an HIV researcher at the University of Copenhagen.

She was the lead investigator on a review of 2,467 HIV patients with CKD – which is becoming more common in HIV as patients live longer – and 33,427 HIV patients without CKD.

decade3d/Thinkstock

The subjects were all participants in the D:A:D project [Data Collection on Adverse Events of Anti-HIV Drugs], an ongoing international cohort study based at the University of Copenhagen, and funded by pharmaceutical companies, among others.

Dr. Ryom had no disclosures.

[email protected]

SOURCE: Ryom L et al. CROI, Abstract 75.

BOSTON – A lot of people do well with HIV thanks to potent antiretrovirals, but there’s still at least one group that needs extra attention: HIV patients with chronic kidney disease (CKD), according to Lene Ryom, MD, PhD, an HIV researcher at the University of Copenhagen.

She was the lead investigator on a review of 2,467 HIV patients with CKD – which is becoming more common in HIV as patients live longer – and 33,427 HIV patients without CKD.

decade3d/Thinkstock

The subjects were all participants in the D:A:D project [Data Collection on Adverse Events of Anti-HIV Drugs], an ongoing international cohort study based at the University of Copenhagen, and funded by pharmaceutical companies, among others.

Dr. Ryom had no disclosures.

[email protected]

SOURCE: Ryom L et al. CROI, Abstract 75.

BOSTON – A lot of people do well with HIV thanks to potent antiretrovirals, but there’s still at least one group that needs extra attention: HIV patients with chronic kidney disease (CKD), according to Lene Ryom, MD, PhD, an HIV researcher at the University of Copenhagen.

She was the lead investigator on a review of 2,467 HIV patients with CKD – which is becoming more common in HIV as patients live longer – and 33,427 HIV patients without CKD.

decade3d/Thinkstock

The subjects were all participants in the D:A:D project [Data Collection on Adverse Events of Anti-HIV Drugs], an ongoing international cohort study based at the University of Copenhagen, and funded by pharmaceutical companies, among others.

Dr. Ryom had no disclosures.

[email protected]

SOURCE: Ryom L et al. CROI, Abstract 75.

AUSTIN, TEX. – Canagliflozin can improve renal outcomes in patients with type 2 diabetes, even when they have mild or moderate kidney disease, new data from the CANVAS program suggested.

“The effect of canagliflozin on composite renal outcomes was large, particularly in people with preserved kidney function,” Brendon L. Neuen, MBBS, of University of New South Wales, Sydney, and his associates wrote in a poster. Baseline renal function also did not appear to affect the safety of canagliflozin, the investigators reported at a meeting sponsored by the National Kidney Foundation.

In patients with diabetes mellitus, increased proximal reabsorption of glucose and sodium decreases the amount of sodium reaching the macula densa in the distal convoluted tubule. This results in reduced use of adenosine triphosphate for sodium reabsorption, which thereby decreases adenosine release and vasoconstriction of afferent arterioles. Left unchecked, this dampening of the tubuloglomerular feedback mechanism increases glomerular filtration and leads to diabetic nephropathy.

Sodium glucose cotransporter 2 (SGLT2) inhibitors such as canagliflozin (Invokana) and empagliflozin (Jardiance) help mitigate this pathology by vasoconstricting afferent arterioles. Previously, in an exploratory analysis of the multicenter, placebo-controlled EMPA-REG OUTCOME (Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes) trial, empagliflozin led to modest but statistically significant long-term reductions in urinary albumin secretion for diabetic patients, regardless of their baseline urinary albumin to creatinine ratio (Lancet Diabetes Endocrinol. 2017 Aug;5[8]:610-21). Treatment with empagliflozin also significantly reduced the risk of developing microalbuminuria or macroalbuminuria (P less than .0001).

The multicenter, double-blind, placebo-controlled CANVAS (Canagliflozin Cardiovascular Assessment Study) and CANVAS-R (A Study of the Effects of Canagliflozin on Renal Endpoints in Adult Participants with Type 2 Diabetes Mellitus) trials included more than 10,000 adults with type 2 diabetes and high cardiovascular risk. In the primary analysis, canagliflozin significantly reduced the risk of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke compared with placebo (N Engl J Med. 2017 Aug 17;377[7]:644-57).

Dr. Neuen and his associates compared the effects of canagliflozin on renal outcomes and safety among CANVAS patients whose estimated glomerular filtration rate (eGFR) was preserved (greater than 60 mL/min per 1.73 m²) or reduced (less than 60 ml/min per 1.73 m²). Actual mean eGFRs in each of these groups were 83 mL/min per 1.73 m² and 49 mL/min per 1.73 m², respectively. Compared with placebo, canagliflozin acutely reduced eGFR in patients with either preserved (average, –2.2 mL/min per 1.73 m²) or reduced (–2.83 mL/min/1.73 m² ) baseline kidney function (P = 0.21).

SOURCE: Neuen BL et al. SCM 2018.
 

AUSTIN, TEX. – Canagliflozin can improve renal outcomes in patients with type 2 diabetes, even when they have mild or moderate kidney disease, new data from the CANVAS program suggested.

“The effect of canagliflozin on composite renal outcomes was large, particularly in people with preserved kidney function,” Brendon L. Neuen, MBBS, of University of New South Wales, Sydney, and his associates wrote in a poster. Baseline renal function also did not appear to affect the safety of canagliflozin, the investigators reported at a meeting sponsored by the National Kidney Foundation.

In patients with diabetes mellitus, increased proximal reabsorption of glucose and sodium decreases the amount of sodium reaching the macula densa in the distal convoluted tubule. This results in reduced use of adenosine triphosphate for sodium reabsorption, which thereby decreases adenosine release and vasoconstriction of afferent arterioles. Left unchecked, this dampening of the tubuloglomerular feedback mechanism increases glomerular filtration and leads to diabetic nephropathy.

Sodium glucose cotransporter 2 (SGLT2) inhibitors such as canagliflozin (Invokana) and empagliflozin (Jardiance) help mitigate this pathology by vasoconstricting afferent arterioles. Previously, in an exploratory analysis of the multicenter, placebo-controlled EMPA-REG OUTCOME (Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes) trial, empagliflozin led to modest but statistically significant long-term reductions in urinary albumin secretion for diabetic patients, regardless of their baseline urinary albumin to creatinine ratio (Lancet Diabetes Endocrinol. 2017 Aug;5[8]:610-21). Treatment with empagliflozin also significantly reduced the risk of developing microalbuminuria or macroalbuminuria (P less than .0001).

The multicenter, double-blind, placebo-controlled CANVAS (Canagliflozin Cardiovascular Assessment Study) and CANVAS-R (A Study of the Effects of Canagliflozin on Renal Endpoints in Adult Participants with Type 2 Diabetes Mellitus) trials included more than 10,000 adults with type 2 diabetes and high cardiovascular risk. In the primary analysis, canagliflozin significantly reduced the risk of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke compared with placebo (N Engl J Med. 2017 Aug 17;377[7]:644-57).

Dr. Neuen and his associates compared the effects of canagliflozin on renal outcomes and safety among CANVAS patients whose estimated glomerular filtration rate (eGFR) was preserved (greater than 60 mL/min per 1.73 m²) or reduced (less than 60 ml/min per 1.73 m²). Actual mean eGFRs in each of these groups were 83 mL/min per 1.73 m² and 49 mL/min per 1.73 m², respectively. Compared with placebo, canagliflozin acutely reduced eGFR in patients with either preserved (average, –2.2 mL/min per 1.73 m²) or reduced (–2.83 mL/min/1.73 m² ) baseline kidney function (P = 0.21).

SOURCE: Neuen BL et al. SCM 2018.
 

AUSTIN, TEX. – Canagliflozin can improve renal outcomes in patients with type 2 diabetes, even when they have mild or moderate kidney disease, new data from the CANVAS program suggested.

“The effect of canagliflozin on composite renal outcomes was large, particularly in people with preserved kidney function,” Brendon L. Neuen, MBBS, of University of New South Wales, Sydney, and his associates wrote in a poster. Baseline renal function also did not appear to affect the safety of canagliflozin, the investigators reported at a meeting sponsored by the National Kidney Foundation.

In patients with diabetes mellitus, increased proximal reabsorption of glucose and sodium decreases the amount of sodium reaching the macula densa in the distal convoluted tubule. This results in reduced use of adenosine triphosphate for sodium reabsorption, which thereby decreases adenosine release and vasoconstriction of afferent arterioles. Left unchecked, this dampening of the tubuloglomerular feedback mechanism increases glomerular filtration and leads to diabetic nephropathy.

Sodium glucose cotransporter 2 (SGLT2) inhibitors such as canagliflozin (Invokana) and empagliflozin (Jardiance) help mitigate this pathology by vasoconstricting afferent arterioles. Previously, in an exploratory analysis of the multicenter, placebo-controlled EMPA-REG OUTCOME (Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes) trial, empagliflozin led to modest but statistically significant long-term reductions in urinary albumin secretion for diabetic patients, regardless of their baseline urinary albumin to creatinine ratio (Lancet Diabetes Endocrinol. 2017 Aug;5[8]:610-21). Treatment with empagliflozin also significantly reduced the risk of developing microalbuminuria or macroalbuminuria (P less than .0001).

The multicenter, double-blind, placebo-controlled CANVAS (Canagliflozin Cardiovascular Assessment Study) and CANVAS-R (A Study of the Effects of Canagliflozin on Renal Endpoints in Adult Participants with Type 2 Diabetes Mellitus) trials included more than 10,000 adults with type 2 diabetes and high cardiovascular risk. In the primary analysis, canagliflozin significantly reduced the risk of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke compared with placebo (N Engl J Med. 2017 Aug 17;377[7]:644-57).

Dr. Neuen and his associates compared the effects of canagliflozin on renal outcomes and safety among CANVAS patients whose estimated glomerular filtration rate (eGFR) was preserved (greater than 60 mL/min per 1.73 m²) or reduced (less than 60 ml/min per 1.73 m²). Actual mean eGFRs in each of these groups were 83 mL/min per 1.73 m² and 49 mL/min per 1.73 m², respectively. Compared with placebo, canagliflozin acutely reduced eGFR in patients with either preserved (average, –2.2 mL/min per 1.73 m²) or reduced (–2.83 mL/min/1.73 m² ) baseline kidney function (P = 0.21).

SOURCE: Neuen BL et al. SCM 2018.
 

Compared with a liberal fluid regimen, a restrictive perioperative regimen that was aimed at zero balance did not improve disability-free survival among high-risk patients undergoing major abdominal surgery and led to a significantly increased risk of acute kidney injury, researchers reported.

dtimiraos/iStock/Getty Images

In an international, randomized trial with 366 median days of follow-up, estimated 1-year rates of disability-free survival were 81.9% with the restrictive intravenous fluid regimen and 82.3% with the liberal regimen (hazard ratio for death or disability, 1.05; P = .61), according to Paul S. Myles, MPH, DSc, and his associates.

Rates of acute renal injury were 8.6% in the restrictive IV fluid group and 5.0% with the liberal fluid therapy (P less than .001), the researchers reported online May 10 in the New England Journal of Medicine.

Guidelines recommend a restrictive intravenous fluid strategy to promote early recovery after major abdominal surgery, noted Dr. Myles of Alfred Hospital in Melbourne and his colleagues. “However, the supporting evidence is limited, and there is concern about impaired organ perfusion.”

Therefore, they randomly assigned, 3,000 patients to receive either the restrictive fluid regimen or a liberal regimen during major abdominal surgery and up to 24 hours after. Median intravenous volume was 3.7 L (interquartile range, 2.9-4.9 L) in the restrictive group and 6.1 L (IQR, 5.0-7.4 L) in the liberal fluid group. All patients were deemed high risk based on their age (at least 70 years) or because they had heart disease, diabetes, kidney disease, or morbid obesity.

Patients who received the restrictive regimen had higher rates of surgical site infection (16.5% vs. 13.6% with liberal fluids; P = .02) and were more likely to receive renal replacement therapy (0.9% vs. 0.3%; P = .048). However, these trends were no longer significant after the researchers controlled for the effects of testing for multiple variables.

“Our findings should not be used to support excessive administration of intravenous fluid,” the researchers cautioned. “Rather, they show that a regimen that includes a modestly liberal administration of fluid is safer than a restrictive regimen.”

Funders included the Australian National Health and Medical Research Council (NHMRC), the Health Research Council of New Zealand, the Australian and New Zealand College of Anaesthetists, and Monash University, Melbourne. Dr. Myles reported receiving grant support from NHMRC. He had no other disclosures.

SOURCE: Myles PS et al. New Engl J Med. 2018 May 10. doi: 10.1056/NEJMoa1801601.

Compared with a liberal fluid regimen, a restrictive perioperative regimen that was aimed at zero balance did not improve disability-free survival among high-risk patients undergoing major abdominal surgery and led to a significantly increased risk of acute kidney injury, researchers reported.

dtimiraos/iStock/Getty Images

In an international, randomized trial with 366 median days of follow-up, estimated 1-year rates of disability-free survival were 81.9% with the restrictive intravenous fluid regimen and 82.3% with the liberal regimen (hazard ratio for death or disability, 1.05; P = .61), according to Paul S. Myles, MPH, DSc, and his associates.

Rates of acute renal injury were 8.6% in the restrictive IV fluid group and 5.0% with the liberal fluid therapy (P less than .001), the researchers reported online May 10 in the New England Journal of Medicine.

Guidelines recommend a restrictive intravenous fluid strategy to promote early recovery after major abdominal surgery, noted Dr. Myles of Alfred Hospital in Melbourne and his colleagues. “However, the supporting evidence is limited, and there is concern about impaired organ perfusion.”

Therefore, they randomly assigned, 3,000 patients to receive either the restrictive fluid regimen or a liberal regimen during major abdominal surgery and up to 24 hours after. Median intravenous volume was 3.7 L (interquartile range, 2.9-4.9 L) in the restrictive group and 6.1 L (IQR, 5.0-7.4 L) in the liberal fluid group. All patients were deemed high risk based on their age (at least 70 years) or because they had heart disease, diabetes, kidney disease, or morbid obesity.

Patients who received the restrictive regimen had higher rates of surgical site infection (16.5% vs. 13.6% with liberal fluids; P = .02) and were more likely to receive renal replacement therapy (0.9% vs. 0.3%; P = .048). However, these trends were no longer significant after the researchers controlled for the effects of testing for multiple variables.

“Our findings should not be used to support excessive administration of intravenous fluid,” the researchers cautioned. “Rather, they show that a regimen that includes a modestly liberal administration of fluid is safer than a restrictive regimen.”

Funders included the Australian National Health and Medical Research Council (NHMRC), the Health Research Council of New Zealand, the Australian and New Zealand College of Anaesthetists, and Monash University, Melbourne. Dr. Myles reported receiving grant support from NHMRC. He had no other disclosures.

SOURCE: Myles PS et al. New Engl J Med. 2018 May 10. doi: 10.1056/NEJMoa1801601.

Compared with a liberal fluid regimen, a restrictive perioperative regimen that was aimed at zero balance did not improve disability-free survival among high-risk patients undergoing major abdominal surgery and led to a significantly increased risk of acute kidney injury, researchers reported.

dtimiraos/iStock/Getty Images

In an international, randomized trial with 366 median days of follow-up, estimated 1-year rates of disability-free survival were 81.9% with the restrictive intravenous fluid regimen and 82.3% with the liberal regimen (hazard ratio for death or disability, 1.05; P = .61), according to Paul S. Myles, MPH, DSc, and his associates.

Rates of acute renal injury were 8.6% in the restrictive IV fluid group and 5.0% with the liberal fluid therapy (P less than .001), the researchers reported online May 10 in the New England Journal of Medicine.

Guidelines recommend a restrictive intravenous fluid strategy to promote early recovery after major abdominal surgery, noted Dr. Myles of Alfred Hospital in Melbourne and his colleagues. “However, the supporting evidence is limited, and there is concern about impaired organ perfusion.”

Therefore, they randomly assigned, 3,000 patients to receive either the restrictive fluid regimen or a liberal regimen during major abdominal surgery and up to 24 hours after. Median intravenous volume was 3.7 L (interquartile range, 2.9-4.9 L) in the restrictive group and 6.1 L (IQR, 5.0-7.4 L) in the liberal fluid group. All patients were deemed high risk based on their age (at least 70 years) or because they had heart disease, diabetes, kidney disease, or morbid obesity.

Patients who received the restrictive regimen had higher rates of surgical site infection (16.5% vs. 13.6% with liberal fluids; P = .02) and were more likely to receive renal replacement therapy (0.9% vs. 0.3%; P = .048). However, these trends were no longer significant after the researchers controlled for the effects of testing for multiple variables.

“Our findings should not be used to support excessive administration of intravenous fluid,” the researchers cautioned. “Rather, they show that a regimen that includes a modestly liberal administration of fluid is safer than a restrictive regimen.”

Funders included the Australian National Health and Medical Research Council (NHMRC), the Health Research Council of New Zealand, the Australian and New Zealand College of Anaesthetists, and Monash University, Melbourne. Dr. Myles reported receiving grant support from NHMRC. He had no other disclosures.

SOURCE: Myles PS et al. New Engl J Med. 2018 May 10. doi: 10.1056/NEJMoa1801601.

Coaching adults with stage 3 chronic kidney disease (CKD) to increase water intake did not significantly slow decline in kidney function, results of a randomized clinical trial show.

Compared with coaching to maintain water intake, coaching to increase water intake did in fact increase water intake but did not prevent a decrease in estimated glomerular filtration rate (eGFR) over 1 year, according to findings of the study, which was published in JAMA..

However, the study may have been underpowered to detect a clinically important difference in this primary endpoint, and certain secondary endpoints did suggest a favorable effect of the intervention, according to William F. Clark, MD, of the London (Ontario) Health Sciences Centre and his coauthors.

“The increased water intake achieved in this trial was sufficient to lower vasopressin secretion, as assessed by plasma copeptin concentrations,” Dr. Clark and his colleagues said in their report

An increasing number of studies suggest that drinking water may benefit the kidneys. In some human studies, water intake was associated with reduced risk of kidney stones and better kidney function.

However, it remains unknown whether increasing water intake would benefit patients with CKD. To evaluate this question, Dr. Clark and colleagues initiated CKD WIT (Chronic Kidney Disease Water Intake Trial), a randomized clinical trial conducted in 9 centers in Ontario.

The study included 631 patients with stage 3 CKD and a 24-hour urine volume below 3 L. Patients randomized to the hydration group were coached to increase water intake gradually to 1-1.5 L/day for 1 year, while those randomized to the control group were coached to maintain their usual water intake.

SOURCE: Clark WF et al. JAMA. 2018;319(18):1870-9.

Coaching adults with stage 3 chronic kidney disease (CKD) to increase water intake did not significantly slow decline in kidney function, results of a randomized clinical trial show.

Compared with coaching to maintain water intake, coaching to increase water intake did in fact increase water intake but did not prevent a decrease in estimated glomerular filtration rate (eGFR) over 1 year, according to findings of the study, which was published in JAMA..

However, the study may have been underpowered to detect a clinically important difference in this primary endpoint, and certain secondary endpoints did suggest a favorable effect of the intervention, according to William F. Clark, MD, of the London (Ontario) Health Sciences Centre and his coauthors.

“The increased water intake achieved in this trial was sufficient to lower vasopressin secretion, as assessed by plasma copeptin concentrations,” Dr. Clark and his colleagues said in their report

An increasing number of studies suggest that drinking water may benefit the kidneys. In some human studies, water intake was associated with reduced risk of kidney stones and better kidney function.

However, it remains unknown whether increasing water intake would benefit patients with CKD. To evaluate this question, Dr. Clark and colleagues initiated CKD WIT (Chronic Kidney Disease Water Intake Trial), a randomized clinical trial conducted in 9 centers in Ontario.

The study included 631 patients with stage 3 CKD and a 24-hour urine volume below 3 L. Patients randomized to the hydration group were coached to increase water intake gradually to 1-1.5 L/day for 1 year, while those randomized to the control group were coached to maintain their usual water intake.

SOURCE: Clark WF et al. JAMA. 2018;319(18):1870-9.

Coaching adults with stage 3 chronic kidney disease (CKD) to increase water intake did not significantly slow decline in kidney function, results of a randomized clinical trial show.

Compared with coaching to maintain water intake, coaching to increase water intake did in fact increase water intake but did not prevent a decrease in estimated glomerular filtration rate (eGFR) over 1 year, according to findings of the study, which was published in JAMA..

However, the study may have been underpowered to detect a clinically important difference in this primary endpoint, and certain secondary endpoints did suggest a favorable effect of the intervention, according to William F. Clark, MD, of the London (Ontario) Health Sciences Centre and his coauthors.

“The increased water intake achieved in this trial was sufficient to lower vasopressin secretion, as assessed by plasma copeptin concentrations,” Dr. Clark and his colleagues said in their report

An increasing number of studies suggest that drinking water may benefit the kidneys. In some human studies, water intake was associated with reduced risk of kidney stones and better kidney function.

However, it remains unknown whether increasing water intake would benefit patients with CKD. To evaluate this question, Dr. Clark and colleagues initiated CKD WIT (Chronic Kidney Disease Water Intake Trial), a randomized clinical trial conducted in 9 centers in Ontario.

The study included 631 patients with stage 3 CKD and a 24-hour urine volume below 3 L. Patients randomized to the hydration group were coached to increase water intake gradually to 1-1.5 L/day for 1 year, while those randomized to the control group were coached to maintain their usual water intake.

SOURCE: Clark WF et al. JAMA. 2018;319(18):1870-9.

How to handle opioid constipation. Bath emollients are a washout for childhood eczema. Does warfarin cause acute kidney injury? And there may be a new option for postpartum depression.

Listen to the MDedge Daily News podcast for all the details on today’s top news.


 

How to handle opioid constipation. Bath emollients are a washout for childhood eczema. Does warfarin cause acute kidney injury? And there may be a new option for postpartum depression.

Listen to the MDedge Daily News podcast for all the details on today’s top news.


 

How to handle opioid constipation. Bath emollients are a washout for childhood eczema. Does warfarin cause acute kidney injury? And there may be a new option for postpartum depression.

Listen to the MDedge Daily News podcast for all the details on today’s top news.


 

A 45-year-old man with end-stage renal disease secondary to hypertension presented with abdominal pain, nausea, vomiting, and fever. He had been on peritoneal dialysis for 15 years.

Results of initial laboratory testing were as follows:

• Sodium 137 mmol/L (reference range 136–144)
• Potassium 3.7 mmol/L (3.5–5.0)
• Bicarbonate 31 mmol/L (22–30)
• Creatinine 17.5 mg/dL (0.58–0.96)
• Blood urea nitrogen 57 mg/dL (7–21)
• Lactic acid 1.7 mmol/L (0.5–2.2)
• White blood cell count 14.34 × 10⁹/L (3.70–11.0).

Blood cultures were negative. Peritoneal fluid analysis showed a white blood cell count of 1.2 × 10⁹/L (reference range < 0.5 × 10⁹/L) with 89% neutrophils, and an amylase level less than 3 U/L (reference range < 100). Fluid cultures were positive for coagulase-negative staphylococci and Staphylococcus epidermidis.

CAUSES AND CLINICAL FEATURES

Encapsulating peritoneal sclerosis is a devastating complication of peritoneal dialysis, occurring in 3% of patients on peritoneal dialysis. The mortality rate is above 40%.^1,2 It is characterized by an initial inflammatory phase followed by extensive intraperitoneal fibrosis and encasement of bowel. Causes include prolonged exposure to peritoneal dialysis or glucose degradation products, a history of severe peritonitis, use of acetate as a dialysate buffer, and reaction to medications such as beta-blockers.³

Clinical features result from inflammation, ileus, and peritoneal adhesions and include abdominal pain, nausea, and vomiting. A high peritoneal transport rate, which often heralds development of encapsulating peritoneal sclerosis, leads to failure of ultrafiltration and to fluid retention.

CT is recommended for diagnosis and demonstrates peritoneal calcification with bowel thickening and dilation.

TREATMENT

Treatment entails stopping peritoneal dialysis, changing to hemodialysis, bowel rest, and corticosteroids. Successful treatment has been reported with a combination of corticosteroids and azathioprine.^4,5 A retrospective study showed that adding the antifibrotic agent tamoxifen was associated with a decrease in the mortality rate.⁶ Bowel obstruction is a common complication, and surgery may be indicated. Enterolysis is a new surgical technique that has shown improved outcomes.⁷         

A 45-year-old man with end-stage renal disease secondary to hypertension presented with abdominal pain, nausea, vomiting, and fever. He had been on peritoneal dialysis for 15 years.

Results of initial laboratory testing were as follows:

• Sodium 137 mmol/L (reference range 136–144)
• Potassium 3.7 mmol/L (3.5–5.0)
• Bicarbonate 31 mmol/L (22–30)
• Creatinine 17.5 mg/dL (0.58–0.96)
• Blood urea nitrogen 57 mg/dL (7–21)
• Lactic acid 1.7 mmol/L (0.5–2.2)
• White blood cell count 14.34 × 10⁹/L (3.70–11.0).

Blood cultures were negative. Peritoneal fluid analysis showed a white blood cell count of 1.2 × 10⁹/L (reference range < 0.5 × 10⁹/L) with 89% neutrophils, and an amylase level less than 3 U/L (reference range < 100). Fluid cultures were positive for coagulase-negative staphylococci and Staphylococcus epidermidis.

CAUSES AND CLINICAL FEATURES

Encapsulating peritoneal sclerosis is a devastating complication of peritoneal dialysis, occurring in 3% of patients on peritoneal dialysis. The mortality rate is above 40%.^1,2 It is characterized by an initial inflammatory phase followed by extensive intraperitoneal fibrosis and encasement of bowel. Causes include prolonged exposure to peritoneal dialysis or glucose degradation products, a history of severe peritonitis, use of acetate as a dialysate buffer, and reaction to medications such as beta-blockers.³

Clinical features result from inflammation, ileus, and peritoneal adhesions and include abdominal pain, nausea, and vomiting. A high peritoneal transport rate, which often heralds development of encapsulating peritoneal sclerosis, leads to failure of ultrafiltration and to fluid retention.

CT is recommended for diagnosis and demonstrates peritoneal calcification with bowel thickening and dilation.

TREATMENT

Treatment entails stopping peritoneal dialysis, changing to hemodialysis, bowel rest, and corticosteroids. Successful treatment has been reported with a combination of corticosteroids and azathioprine.^4,5 A retrospective study showed that adding the antifibrotic agent tamoxifen was associated with a decrease in the mortality rate.⁶ Bowel obstruction is a common complication, and surgery may be indicated. Enterolysis is a new surgical technique that has shown improved outcomes.⁷         

A 45-year-old man with end-stage renal disease secondary to hypertension presented with abdominal pain, nausea, vomiting, and fever. He had been on peritoneal dialysis for 15 years.

Results of initial laboratory testing were as follows:

• Sodium 137 mmol/L (reference range 136–144)
• Potassium 3.7 mmol/L (3.5–5.0)
• Bicarbonate 31 mmol/L (22–30)
• Creatinine 17.5 mg/dL (0.58–0.96)
• Blood urea nitrogen 57 mg/dL (7–21)
• Lactic acid 1.7 mmol/L (0.5–2.2)
• White blood cell count 14.34 × 10⁹/L (3.70–11.0).

Blood cultures were negative. Peritoneal fluid analysis showed a white blood cell count of 1.2 × 10⁹/L (reference range < 0.5 × 10⁹/L) with 89% neutrophils, and an amylase level less than 3 U/L (reference range < 100). Fluid cultures were positive for coagulase-negative staphylococci and Staphylococcus epidermidis.

CAUSES AND CLINICAL FEATURES

Encapsulating peritoneal sclerosis is a devastating complication of peritoneal dialysis, occurring in 3% of patients on peritoneal dialysis. The mortality rate is above 40%.^1,2 It is characterized by an initial inflammatory phase followed by extensive intraperitoneal fibrosis and encasement of bowel. Causes include prolonged exposure to peritoneal dialysis or glucose degradation products, a history of severe peritonitis, use of acetate as a dialysate buffer, and reaction to medications such as beta-blockers.³

Clinical features result from inflammation, ileus, and peritoneal adhesions and include abdominal pain, nausea, and vomiting. A high peritoneal transport rate, which often heralds development of encapsulating peritoneal sclerosis, leads to failure of ultrafiltration and to fluid retention.

CT is recommended for diagnosis and demonstrates peritoneal calcification with bowel thickening and dilation.

TREATMENT

Treatment entails stopping peritoneal dialysis, changing to hemodialysis, bowel rest, and corticosteroids. Successful treatment has been reported with a combination of corticosteroids and azathioprine.^4,5 A retrospective study showed that adding the antifibrotic agent tamoxifen was associated with a decrease in the mortality rate.⁶ Bowel obstruction is a common complication, and surgery may be indicated. Enterolysis is a new surgical technique that has shown improved outcomes.⁷         

To the Editor: I read with interest the thoughtful review of cardiorenal syndrome by Drs. Thind, Loehrke, and Wilt¹ and the accompanying editorial by Dr. Grodin.² These articles certainly add to our growing knowledge of the syndrome and the importance of treating volume overload in these complex patients.

Indeed, we and others have stressed the primary importance of renal dysfunction in patients with volume overload and acute decompensated heart failure.^3,4 We have learned that even small rises in serum creatinine predict poor outcomes in these patients. And even if the serum creatinine level comes back down during hospitalization, acute kidney injury (AKI) is still associated with risk.⁵

Nevertheless, clinicians remain frustrated with the practical management of patients with volume overload and worsening AKI. When faced with a rising serum creatinine level in a patient being treated for decompensated heart failure with signs or symptoms of volume overload, I suggest the following:

Perform careful bedside and chart review searching for evidence of AKI related to causes other than cardiorenal syndrome. Ask whether the rise in serum creatinine could be caused by new obstruction (eg, urinary retention, upper urinary tract obstruction), a nephrotoxin (eg, nonsteroidal anti-inflammatory drugs), a primary tubulointerstitial or glomerular process (eg, drug-induced acute interstitial nephritis, acute glomerulonephritis), acute tubular necrosis, or a new hemodynamic event threatening renal perfusion (eg, hypotension, a new arrhythmia). It is often best to arrive at a diagnosis of AKI due to cardiorenal dysfunction by exclusion, much like the working definitions of hepatorenal syndrome.⁶ This requires review of the urine sediment (looking for evidence of granular casts of acute tubular necrosis, or evidence of glomerulonephritis or interstitial nephritis), electronic medical record, vital signs, telemetry, and perhaps renal ultrasonography.

In the absence of frank evidence of “overdiuresis” such as worsening hypernatremia, with dropping blood pressure, clinical hypoperfusion, and contraction alkalosis, avoid the temptation to suspend diuretics. Alternatively, an increase in diuretic dose, or addition of a distal diuretic (ie, metolazone) may be needed to address persistent renal venous congestion as the cause of the AKI.³ In this situation, be sure to monitor electrolytes, volume status, and renal function closely while diuretic treatment is augmented. In many such cases, the serum creatinine may actually start to decrease after a more robust diuresis is generated. In these patients, it may also be prudent to temporarily suspend antagonists of the renin-angiotensin-aldosterone system, although this remains controversial.

Management of such patients should be done collaboratively with cardiologists well versed in the treatment of cardiorenal syndrome. It may be possible that the worsening renal function in these patients represents important changes in cardiac rhythm or function (eg, low cardiac output state, new or worsening valvular disease, ongoing myocardial ischemia, cardiac tamponade, uncontrolled bradycardia or tachyarrythmia). Interventions aimed at reversing such perturbations could be the most important steps in improving cardiorenal function and reversing AKI.

To the Editor: I read with interest the thoughtful review of cardiorenal syndrome by Drs. Thind, Loehrke, and Wilt¹ and the accompanying editorial by Dr. Grodin.² These articles certainly add to our growing knowledge of the syndrome and the importance of treating volume overload in these complex patients.

Indeed, we and others have stressed the primary importance of renal dysfunction in patients with volume overload and acute decompensated heart failure.^3,4 We have learned that even small rises in serum creatinine predict poor outcomes in these patients. And even if the serum creatinine level comes back down during hospitalization, acute kidney injury (AKI) is still associated with risk.⁵

Nevertheless, clinicians remain frustrated with the practical management of patients with volume overload and worsening AKI. When faced with a rising serum creatinine level in a patient being treated for decompensated heart failure with signs or symptoms of volume overload, I suggest the following:

Perform careful bedside and chart review searching for evidence of AKI related to causes other than cardiorenal syndrome. Ask whether the rise in serum creatinine could be caused by new obstruction (eg, urinary retention, upper urinary tract obstruction), a nephrotoxin (eg, nonsteroidal anti-inflammatory drugs), a primary tubulointerstitial or glomerular process (eg, drug-induced acute interstitial nephritis, acute glomerulonephritis), acute tubular necrosis, or a new hemodynamic event threatening renal perfusion (eg, hypotension, a new arrhythmia). It is often best to arrive at a diagnosis of AKI due to cardiorenal dysfunction by exclusion, much like the working definitions of hepatorenal syndrome.⁶ This requires review of the urine sediment (looking for evidence of granular casts of acute tubular necrosis, or evidence of glomerulonephritis or interstitial nephritis), electronic medical record, vital signs, telemetry, and perhaps renal ultrasonography.

In the absence of frank evidence of “overdiuresis” such as worsening hypernatremia, with dropping blood pressure, clinical hypoperfusion, and contraction alkalosis, avoid the temptation to suspend diuretics. Alternatively, an increase in diuretic dose, or addition of a distal diuretic (ie, metolazone) may be needed to address persistent renal venous congestion as the cause of the AKI.³ In this situation, be sure to monitor electrolytes, volume status, and renal function closely while diuretic treatment is augmented. In many such cases, the serum creatinine may actually start to decrease after a more robust diuresis is generated. In these patients, it may also be prudent to temporarily suspend antagonists of the renin-angiotensin-aldosterone system, although this remains controversial.

Management of such patients should be done collaboratively with cardiologists well versed in the treatment of cardiorenal syndrome. It may be possible that the worsening renal function in these patients represents important changes in cardiac rhythm or function (eg, low cardiac output state, new or worsening valvular disease, ongoing myocardial ischemia, cardiac tamponade, uncontrolled bradycardia or tachyarrythmia). Interventions aimed at reversing such perturbations could be the most important steps in improving cardiorenal function and reversing AKI.

To the Editor: I read with interest the thoughtful review of cardiorenal syndrome by Drs. Thind, Loehrke, and Wilt¹ and the accompanying editorial by Dr. Grodin.² These articles certainly add to our growing knowledge of the syndrome and the importance of treating volume overload in these complex patients.

Indeed, we and others have stressed the primary importance of renal dysfunction in patients with volume overload and acute decompensated heart failure.^3,4 We have learned that even small rises in serum creatinine predict poor outcomes in these patients. And even if the serum creatinine level comes back down during hospitalization, acute kidney injury (AKI) is still associated with risk.⁵

Nevertheless, clinicians remain frustrated with the practical management of patients with volume overload and worsening AKI. When faced with a rising serum creatinine level in a patient being treated for decompensated heart failure with signs or symptoms of volume overload, I suggest the following:

Perform careful bedside and chart review searching for evidence of AKI related to causes other than cardiorenal syndrome. Ask whether the rise in serum creatinine could be caused by new obstruction (eg, urinary retention, upper urinary tract obstruction), a nephrotoxin (eg, nonsteroidal anti-inflammatory drugs), a primary tubulointerstitial or glomerular process (eg, drug-induced acute interstitial nephritis, acute glomerulonephritis), acute tubular necrosis, or a new hemodynamic event threatening renal perfusion (eg, hypotension, a new arrhythmia). It is often best to arrive at a diagnosis of AKI due to cardiorenal dysfunction by exclusion, much like the working definitions of hepatorenal syndrome.⁶ This requires review of the urine sediment (looking for evidence of granular casts of acute tubular necrosis, or evidence of glomerulonephritis or interstitial nephritis), electronic medical record, vital signs, telemetry, and perhaps renal ultrasonography.

In the absence of frank evidence of “overdiuresis” such as worsening hypernatremia, with dropping blood pressure, clinical hypoperfusion, and contraction alkalosis, avoid the temptation to suspend diuretics. Alternatively, an increase in diuretic dose, or addition of a distal diuretic (ie, metolazone) may be needed to address persistent renal venous congestion as the cause of the AKI.³ In this situation, be sure to monitor electrolytes, volume status, and renal function closely while diuretic treatment is augmented. In many such cases, the serum creatinine may actually start to decrease after a more robust diuresis is generated. In these patients, it may also be prudent to temporarily suspend antagonists of the renin-angiotensin-aldosterone system, although this remains controversial.

Management of such patients should be done collaboratively with cardiologists well versed in the treatment of cardiorenal syndrome. It may be possible that the worsening renal function in these patients represents important changes in cardiac rhythm or function (eg, low cardiac output state, new or worsening valvular disease, ongoing myocardial ischemia, cardiac tamponade, uncontrolled bradycardia or tachyarrythmia). Interventions aimed at reversing such perturbations could be the most important steps in improving cardiorenal function and reversing AKI.