Have you been a practicing hospitalist for five years, a member of SHM for three years, and an attendee at an SHM annual meeting? If so, you may be eligible to set yourself apart as a leader in the hospital medicine movement who is committed to quality, improved outcomes, and exceptional patient care.

Physicians, nurse practitioners, physician assistants, and practice administrators are invited to apply to the Fellow (FHM) or Senior Fellow (SFHM) in Hospital Medicine designation from SHM.

Learn more at www.hospitalmedicine.org/fellow. Applications will be open for the SHM Fellows Class of 2017 from May 23, 2016, to November 18, 2016.

Have you been a practicing hospitalist for five years, a member of SHM for three years, and an attendee at an SHM annual meeting? If so, you may be eligible to set yourself apart as a leader in the hospital medicine movement who is committed to quality, improved outcomes, and exceptional patient care.

Physicians, nurse practitioners, physician assistants, and practice administrators are invited to apply to the Fellow (FHM) or Senior Fellow (SFHM) in Hospital Medicine designation from SHM.

Learn more at www.hospitalmedicine.org/fellow. Applications will be open for the SHM Fellows Class of 2017 from May 23, 2016, to November 18, 2016.

Have you been a practicing hospitalist for five years, a member of SHM for three years, and an attendee at an SHM annual meeting? If so, you may be eligible to set yourself apart as a leader in the hospital medicine movement who is committed to quality, improved outcomes, and exceptional patient care.

Physicians, nurse practitioners, physician assistants, and practice administrators are invited to apply to the Fellow (FHM) or Senior Fellow (SFHM) in Hospital Medicine designation from SHM.

Learn more at www.hospitalmedicine.org/fellow. Applications will be open for the SHM Fellows Class of 2017 from May 23, 2016, to November 18, 2016.

To ensure hospitalists have the latest information about diagnosis, treatment, and transition of hospitalized patients with venous thromboembolism (VTE), SHM has developed:

• An online tool kit, including a literature review; implementation guide; and other references, materials, and tools such as discharge instructions and checklists
• A webinar series with free CME

These resources are now available. Get the scoop at www.hospitalmedicine.org/VTEtreatment.

To ensure hospitalists have the latest information about diagnosis, treatment, and transition of hospitalized patients with venous thromboembolism (VTE), SHM has developed:

• An online tool kit, including a literature review; implementation guide; and other references, materials, and tools such as discharge instructions and checklists
• A webinar series with free CME

These resources are now available. Get the scoop at www.hospitalmedicine.org/VTEtreatment.

To ensure hospitalists have the latest information about diagnosis, treatment, and transition of hospitalized patients with venous thromboembolism (VTE), SHM has developed:

• An online tool kit, including a literature review; implementation guide; and other references, materials, and tools such as discharge instructions and checklists
• A webinar series with free CME

These resources are now available. Get the scoop at www.hospitalmedicine.org/VTEtreatment.

(Reuters Health) - Patients assigned a "nonurgent" status on arrival in the emergency room might still be sick enough to be hospitalized, a new study shows.

Patients deemed by triage nurses to be "nonurgent" often receive diagnostic services and procedures, and some are even admitted to critical care units, researchers found.

Triage was never intended to completely rule out severe illness, only to give patients an estimate of how long they may have to wait to see a doctor, the researchers note.

Dr. Renee Y. Hsia of the University of California, San Francisco and colleagues used a national survey of patient visits to the emergency department (E.D.) between 2009 and 2011, with triage scores assigned by a nurse when the patient arrived. The scores range from one to five, with one through three including immediate, emergency and urgent patients, and four and five being semi-urgent and nonurgent.

They used data on almost 60,000 observations of patients age 18 to 64 collected between 2009 and 2011, which represented 240 million E.D. visits. More than 90 percent had a score of one to

four and were deemed "urgent" visits, while about eight percent had a score of five and were "nonurgent."

Almost half of nonurgent visits involved diagnostic scans, imaging or blood tests, and a third involved procedures like splinting or giving intravenous fluids. For urgent visits, about three-quarters involved diagnostics and half involved procedures.

About four of every 100 non-urgent visits resulted in hospital admission, as reported in JAMA Internal Medicine.

Backache, acute upper respiratory infections, soft-tissue inflammation, and acute sore throat were among the 10 most common diagnoses for both urgent and non-urgent patients.

"Triage is normally done at the very beginning of the visit, usually by a triage nurse," Hsia told Reuters Health by email. "Triaging patients is an extremely difficult task, since patients are what we (as providers) call 'undifferentiated,' since there has not been time to do a full history and physical, and nurses have limited information upon which to base their determination."

"We should not expect triage categorization to be perfect, and one of the goals of this paper is to show that, indeed, triage is not," Hsia said.

Many states have policies that patients with Medicaid insurance who present to the E.D. for "non-urgent" visits will be charged a co-payment, which may keep people from seeking

needed care, even though the triage system is not perfect, she said.

"It is important that we do not blame the patient for going to the E.D. if there were no alternatives that were available in a timely manner," Hsia said.

"Our study cannot distinguish the reasons behind why we found such a high proportion of visits that received diagnostic services or procedures," she said.

Some of the procedures may not have needed to happen in an E.D. setting, but since the patients presented there, they were treated, Hsia added.

(Reuters Health) - Patients assigned a "nonurgent" status on arrival in the emergency room might still be sick enough to be hospitalized, a new study shows.

Patients deemed by triage nurses to be "nonurgent" often receive diagnostic services and procedures, and some are even admitted to critical care units, researchers found.

Triage was never intended to completely rule out severe illness, only to give patients an estimate of how long they may have to wait to see a doctor, the researchers note.

Dr. Renee Y. Hsia of the University of California, San Francisco and colleagues used a national survey of patient visits to the emergency department (E.D.) between 2009 and 2011, with triage scores assigned by a nurse when the patient arrived. The scores range from one to five, with one through three including immediate, emergency and urgent patients, and four and five being semi-urgent and nonurgent.

They used data on almost 60,000 observations of patients age 18 to 64 collected between 2009 and 2011, which represented 240 million E.D. visits. More than 90 percent had a score of one to

four and were deemed "urgent" visits, while about eight percent had a score of five and were "nonurgent."

Almost half of nonurgent visits involved diagnostic scans, imaging or blood tests, and a third involved procedures like splinting or giving intravenous fluids. For urgent visits, about three-quarters involved diagnostics and half involved procedures.

About four of every 100 non-urgent visits resulted in hospital admission, as reported in JAMA Internal Medicine.

Backache, acute upper respiratory infections, soft-tissue inflammation, and acute sore throat were among the 10 most common diagnoses for both urgent and non-urgent patients.

"Triage is normally done at the very beginning of the visit, usually by a triage nurse," Hsia told Reuters Health by email. "Triaging patients is an extremely difficult task, since patients are what we (as providers) call 'undifferentiated,' since there has not been time to do a full history and physical, and nurses have limited information upon which to base their determination."

"We should not expect triage categorization to be perfect, and one of the goals of this paper is to show that, indeed, triage is not," Hsia said.

Many states have policies that patients with Medicaid insurance who present to the E.D. for "non-urgent" visits will be charged a co-payment, which may keep people from seeking

needed care, even though the triage system is not perfect, she said.

"It is important that we do not blame the patient for going to the E.D. if there were no alternatives that were available in a timely manner," Hsia said.

"Our study cannot distinguish the reasons behind why we found such a high proportion of visits that received diagnostic services or procedures," she said.

Some of the procedures may not have needed to happen in an E.D. setting, but since the patients presented there, they were treated, Hsia added.

(Reuters Health) - Patients assigned a "nonurgent" status on arrival in the emergency room might still be sick enough to be hospitalized, a new study shows.

Patients deemed by triage nurses to be "nonurgent" often receive diagnostic services and procedures, and some are even admitted to critical care units, researchers found.

Triage was never intended to completely rule out severe illness, only to give patients an estimate of how long they may have to wait to see a doctor, the researchers note.

Dr. Renee Y. Hsia of the University of California, San Francisco and colleagues used a national survey of patient visits to the emergency department (E.D.) between 2009 and 2011, with triage scores assigned by a nurse when the patient arrived. The scores range from one to five, with one through three including immediate, emergency and urgent patients, and four and five being semi-urgent and nonurgent.

They used data on almost 60,000 observations of patients age 18 to 64 collected between 2009 and 2011, which represented 240 million E.D. visits. More than 90 percent had a score of one to

four and were deemed "urgent" visits, while about eight percent had a score of five and were "nonurgent."

Almost half of nonurgent visits involved diagnostic scans, imaging or blood tests, and a third involved procedures like splinting or giving intravenous fluids. For urgent visits, about three-quarters involved diagnostics and half involved procedures.

About four of every 100 non-urgent visits resulted in hospital admission, as reported in JAMA Internal Medicine.

Backache, acute upper respiratory infections, soft-tissue inflammation, and acute sore throat were among the 10 most common diagnoses for both urgent and non-urgent patients.

"Triage is normally done at the very beginning of the visit, usually by a triage nurse," Hsia told Reuters Health by email. "Triaging patients is an extremely difficult task, since patients are what we (as providers) call 'undifferentiated,' since there has not been time to do a full history and physical, and nurses have limited information upon which to base their determination."

"We should not expect triage categorization to be perfect, and one of the goals of this paper is to show that, indeed, triage is not," Hsia said.

Many states have policies that patients with Medicaid insurance who present to the E.D. for "non-urgent" visits will be charged a co-payment, which may keep people from seeking

needed care, even though the triage system is not perfect, she said.

"It is important that we do not blame the patient for going to the E.D. if there were no alternatives that were available in a timely manner," Hsia said.

"Our study cannot distinguish the reasons behind why we found such a high proportion of visits that received diagnostic services or procedures," she said.

Some of the procedures may not have needed to happen in an E.D. setting, but since the patients presented there, they were treated, Hsia added.

Cord blood donation

Photo courtesy of NHS

New research suggests an RNA-binding protein can be used to expand hematopoietic stem cells (HSCs) derived from umbilical cord blood.

Investigators found the protein, Musashi-2 (MSI2), regulates the function and development of cord-blood derived HSCs, and overexpressing MSI2 can significantly expand both short-term and long-term repopulating HSCs.

“By expanding the stem cells as we have done, many more donated [cord blood] samples could now be used for transplants,” said Kristin Hope, PhD, of McMaster University in Hamilton, Ontario, Canada.

“Providing enhanced numbers of stem cells for transplantation could alleviate some of the current post-transplantation complications and allow for faster recoveries, in turn, reducing overall healthcare costs and wait times for newly diagnosed patients seeking treatment.”

Dr Hope and her colleagues described this exploration of HSC expansion in Nature.

The team first found that expression of MSI2 messenger RNA was elevated in primitive cord blood hematopoietic stem and progenitor cells (HSPCs), but it decreased during differentiation.

They then found that overexpressing MSI2 enhances the activity of cord blood progenitors in vitro and increases the number of short-term repopulating HSCs in vitro and in vivo.

During in vitro culture, MSI2-overexpressing cells were 2.3-fold more abundant than control cells at 7 days and 6-fold more abundant at 21 days. After 7 days, MSI2-overexpressing cells showed a cumulative 9.3-fold increase in colony-forming cells but no changes in cell cycling or death.

MSI2-overexpressing short-term repopulating cells (STRCs) yielded 1.8-fold more primitive CD34+ cells than control STRCs. And the MSI2-overexpressing STRCs prompted a 17-fold increase in functional STRCs.

Furthermore, 100% of mice transplanted with MSI2-overexpressing STRCs were engrafted at 6.5 weeks, compared to 50% of mice transplanted with control STRCs.

Additional transplant experiments showed that MSI2 overexpression also impacted long-term HSCs (LT-HSCs). Compared to control cells, MSI2-overexpressing cells increased the percentage of GFP+ HSCs in the bone marrow 4.6-fold and the frequency of LT-HSCs 3.5-fold.

The researchers said the increase in LT-HSC frequency corresponded to MSI2-overexpressing GFP+ HSCs having expanded in mice 2.4-fold over input. With control HSCs, on the other hand, there was a 1.5-fold decrease.

In ex vivo culture, MSI2 overexpression induced a cumulative 23-fold expansion of secondary LT-HSCs when compared to control LT-HSCs.

Finally, the researchers performed a global analysis of MSI2–RNA interactions and found that MSI2 mediates HSPC self-renewal and ex vivo expansion by coordinating the post-transcriptional regulation of proteins belonging to a shared self-renewal regulatory pathway.

“We’ve really shone a light on the way these stem cells work,” Dr Hope said. “We now understand how they operate at a completely new level, and that provides us with a serious advantage in determining how to maximize these stem cells in therapeutics. With this newfound ability to control the regeneration of these cells, more people will be able to get the treatment they need.”

Cord blood donation

Photo courtesy of NHS

New research suggests an RNA-binding protein can be used to expand hematopoietic stem cells (HSCs) derived from umbilical cord blood.

Investigators found the protein, Musashi-2 (MSI2), regulates the function and development of cord-blood derived HSCs, and overexpressing MSI2 can significantly expand both short-term and long-term repopulating HSCs.

“By expanding the stem cells as we have done, many more donated [cord blood] samples could now be used for transplants,” said Kristin Hope, PhD, of McMaster University in Hamilton, Ontario, Canada.

“Providing enhanced numbers of stem cells for transplantation could alleviate some of the current post-transplantation complications and allow for faster recoveries, in turn, reducing overall healthcare costs and wait times for newly diagnosed patients seeking treatment.”

Dr Hope and her colleagues described this exploration of HSC expansion in Nature.

The team first found that expression of MSI2 messenger RNA was elevated in primitive cord blood hematopoietic stem and progenitor cells (HSPCs), but it decreased during differentiation.

They then found that overexpressing MSI2 enhances the activity of cord blood progenitors in vitro and increases the number of short-term repopulating HSCs in vitro and in vivo.

During in vitro culture, MSI2-overexpressing cells were 2.3-fold more abundant than control cells at 7 days and 6-fold more abundant at 21 days. After 7 days, MSI2-overexpressing cells showed a cumulative 9.3-fold increase in colony-forming cells but no changes in cell cycling or death.

MSI2-overexpressing short-term repopulating cells (STRCs) yielded 1.8-fold more primitive CD34+ cells than control STRCs. And the MSI2-overexpressing STRCs prompted a 17-fold increase in functional STRCs.

Furthermore, 100% of mice transplanted with MSI2-overexpressing STRCs were engrafted at 6.5 weeks, compared to 50% of mice transplanted with control STRCs.

Additional transplant experiments showed that MSI2 overexpression also impacted long-term HSCs (LT-HSCs). Compared to control cells, MSI2-overexpressing cells increased the percentage of GFP+ HSCs in the bone marrow 4.6-fold and the frequency of LT-HSCs 3.5-fold.

The researchers said the increase in LT-HSC frequency corresponded to MSI2-overexpressing GFP+ HSCs having expanded in mice 2.4-fold over input. With control HSCs, on the other hand, there was a 1.5-fold decrease.

In ex vivo culture, MSI2 overexpression induced a cumulative 23-fold expansion of secondary LT-HSCs when compared to control LT-HSCs.

Finally, the researchers performed a global analysis of MSI2–RNA interactions and found that MSI2 mediates HSPC self-renewal and ex vivo expansion by coordinating the post-transcriptional regulation of proteins belonging to a shared self-renewal regulatory pathway.

“We’ve really shone a light on the way these stem cells work,” Dr Hope said. “We now understand how they operate at a completely new level, and that provides us with a serious advantage in determining how to maximize these stem cells in therapeutics. With this newfound ability to control the regeneration of these cells, more people will be able to get the treatment they need.”

Cord blood donation

Photo courtesy of NHS

New research suggests an RNA-binding protein can be used to expand hematopoietic stem cells (HSCs) derived from umbilical cord blood.

Investigators found the protein, Musashi-2 (MSI2), regulates the function and development of cord-blood derived HSCs, and overexpressing MSI2 can significantly expand both short-term and long-term repopulating HSCs.

“By expanding the stem cells as we have done, many more donated [cord blood] samples could now be used for transplants,” said Kristin Hope, PhD, of McMaster University in Hamilton, Ontario, Canada.

“Providing enhanced numbers of stem cells for transplantation could alleviate some of the current post-transplantation complications and allow for faster recoveries, in turn, reducing overall healthcare costs and wait times for newly diagnosed patients seeking treatment.”

Dr Hope and her colleagues described this exploration of HSC expansion in Nature.

The team first found that expression of MSI2 messenger RNA was elevated in primitive cord blood hematopoietic stem and progenitor cells (HSPCs), but it decreased during differentiation.

They then found that overexpressing MSI2 enhances the activity of cord blood progenitors in vitro and increases the number of short-term repopulating HSCs in vitro and in vivo.

During in vitro culture, MSI2-overexpressing cells were 2.3-fold more abundant than control cells at 7 days and 6-fold more abundant at 21 days. After 7 days, MSI2-overexpressing cells showed a cumulative 9.3-fold increase in colony-forming cells but no changes in cell cycling or death.

MSI2-overexpressing short-term repopulating cells (STRCs) yielded 1.8-fold more primitive CD34+ cells than control STRCs. And the MSI2-overexpressing STRCs prompted a 17-fold increase in functional STRCs.

Furthermore, 100% of mice transplanted with MSI2-overexpressing STRCs were engrafted at 6.5 weeks, compared to 50% of mice transplanted with control STRCs.

Additional transplant experiments showed that MSI2 overexpression also impacted long-term HSCs (LT-HSCs). Compared to control cells, MSI2-overexpressing cells increased the percentage of GFP+ HSCs in the bone marrow 4.6-fold and the frequency of LT-HSCs 3.5-fold.

The researchers said the increase in LT-HSC frequency corresponded to MSI2-overexpressing GFP+ HSCs having expanded in mice 2.4-fold over input. With control HSCs, on the other hand, there was a 1.5-fold decrease.

In ex vivo culture, MSI2 overexpression induced a cumulative 23-fold expansion of secondary LT-HSCs when compared to control LT-HSCs.

Finally, the researchers performed a global analysis of MSI2–RNA interactions and found that MSI2 mediates HSPC self-renewal and ex vivo expansion by coordinating the post-transcriptional regulation of proteins belonging to a shared self-renewal regulatory pathway.

“We’ve really shone a light on the way these stem cells work,” Dr Hope said. “We now understand how they operate at a completely new level, and that provides us with a serious advantage in determining how to maximize these stem cells in therapeutics. With this newfound ability to control the regeneration of these cells, more people will be able to get the treatment they need.”

Red blood cells

Image courtesy of NHLBI

The US Food and Drug Administration (FDA) has approved the use of a powder formulation of ferric pyrophosphate citrate (Triferic powder packet) to maintain hemoglobin in adult patients with hemodialysis-dependent chronic kidney disease.

The FDA previously approved ferric pyrophosphate citrate solution (Triferic) in ampule form. It is an iron-replacement drug intended to treat anemia in chronic kidney disease patients receiving hemodialysis.

Triferic is delivered to hemodialysis patients via dialysate, replacing the ongoing iron loss that occurs during their dialysis treatment. The drug is added to the bicarbonate concentrate on-site at the dialysis clinic.

Once in dialysate, Triferic crosses the dialyzer membrane and enters the blood, where it immediately binds to transferrin and is transported to the erythroid precursor cells to be incorporated into hemoglobin.

Triferic is designed to deliver sufficient iron to the bone marrow and maintain hemoglobin without increasing iron stores.

“We are pleased to obtain this FDA approval for the Triferic powder packet,” said Robert L. Chioini, founder, chairman, and chief executive officer of Rockwell Medical, Inc., makers of Triferic.

“The Triferic powder packet is similar to the size of a packet of sugar. It is much smaller and lighter than the current Triferic liquid ampule, and it enables us to place 3-times greater the number of units in an even smaller carton.”

“This presentation is much more convenient for customers, as it reduces storage space and requires fewer reorders to maintain inventory. We expect it to be commercially available shortly.”

Red blood cells

Image courtesy of NHLBI

The US Food and Drug Administration (FDA) has approved the use of a powder formulation of ferric pyrophosphate citrate (Triferic powder packet) to maintain hemoglobin in adult patients with hemodialysis-dependent chronic kidney disease.

The FDA previously approved ferric pyrophosphate citrate solution (Triferic) in ampule form. It is an iron-replacement drug intended to treat anemia in chronic kidney disease patients receiving hemodialysis.

Triferic is delivered to hemodialysis patients via dialysate, replacing the ongoing iron loss that occurs during their dialysis treatment. The drug is added to the bicarbonate concentrate on-site at the dialysis clinic.

Once in dialysate, Triferic crosses the dialyzer membrane and enters the blood, where it immediately binds to transferrin and is transported to the erythroid precursor cells to be incorporated into hemoglobin.

Triferic is designed to deliver sufficient iron to the bone marrow and maintain hemoglobin without increasing iron stores.

“We are pleased to obtain this FDA approval for the Triferic powder packet,” said Robert L. Chioini, founder, chairman, and chief executive officer of Rockwell Medical, Inc., makers of Triferic.

“The Triferic powder packet is similar to the size of a packet of sugar. It is much smaller and lighter than the current Triferic liquid ampule, and it enables us to place 3-times greater the number of units in an even smaller carton.”

“This presentation is much more convenient for customers, as it reduces storage space and requires fewer reorders to maintain inventory. We expect it to be commercially available shortly.”

Red blood cells

Image courtesy of NHLBI

The US Food and Drug Administration (FDA) has approved the use of a powder formulation of ferric pyrophosphate citrate (Triferic powder packet) to maintain hemoglobin in adult patients with hemodialysis-dependent chronic kidney disease.

The FDA previously approved ferric pyrophosphate citrate solution (Triferic) in ampule form. It is an iron-replacement drug intended to treat anemia in chronic kidney disease patients receiving hemodialysis.

Triferic is delivered to hemodialysis patients via dialysate, replacing the ongoing iron loss that occurs during their dialysis treatment. The drug is added to the bicarbonate concentrate on-site at the dialysis clinic.

Once in dialysate, Triferic crosses the dialyzer membrane and enters the blood, where it immediately binds to transferrin and is transported to the erythroid precursor cells to be incorporated into hemoglobin.

Triferic is designed to deliver sufficient iron to the bone marrow and maintain hemoglobin without increasing iron stores.

“We are pleased to obtain this FDA approval for the Triferic powder packet,” said Robert L. Chioini, founder, chairman, and chief executive officer of Rockwell Medical, Inc., makers of Triferic.

“The Triferic powder packet is similar to the size of a packet of sugar. It is much smaller and lighter than the current Triferic liquid ampule, and it enables us to place 3-times greater the number of units in an even smaller carton.”

“This presentation is much more convenient for customers, as it reduces storage space and requires fewer reorders to maintain inventory. We expect it to be commercially available shortly.”

miR-22

Image by Su Jung Song

The microRNA miR-22 is “an essential antitumor gatekeeper” in acute myeloid leukemia (AML), researchers have reported in Nature Communications.

The team found that miR-22 was significantly downregulated in  AML, and forced expression of miR-22 produced antileukemic effects in AML cells

and mouse models of the disease.

Futhermore, nanoparticles carrying miR-22 oligonucleotides appeared to cure AML in some mice.

“Previous research has shown that microRNA miR-22 is linked to breast cancer and other blood disorders [myelodysplastic syndromes], which sometimes turn into AML,” said study author Jianjun Chen, PhD, of the University of Cincinnati in Ohio.

“But we found in this study that it could be an essential antitumor gatekeeper in AML when it is downregulated. When we forced miR-22 expression, we saw difficulty in leukemia cells developing, growing, and thriving.”

Dr Chen and his colleagues first found that miR-22 was significantly downregulated (P<0.05) in samples from AML patients, when compared with normal CD34+ hematopoietic stem/progenitor cells, CD33+ myeloid progenitor cells, and mononuclear cells. The set of AML samples included MLL, t(15;17), t(8;21), and inv(16) AML.

When the researchers forced expression of miR-22 in human AML cells, they found the microRNA significantly inhibited cell viability, growth, and proliferation, while promoting apoptosis.

The team also investigated the role of miR-22 in colony formation induced by MLL-AF10/t(10;11), PML-RARA/t(15;17), and AML1-ETO9a/t(8;21). They found that forced expression of miR-22 significantly inhibited colony formation induced by all of these oncogenic fusion genes.

In mice, forced expression of miR-22 blocked MLL-AF9-mediated leukemogenesis and MLL-AF10-mediated leukemogenesis.

Forced expression of miR-22 also inhibited progression of AML induced by MLL-AF9, AE9a, or FLT3-ITD/NPM1c+ in secondary recipient mice. The researchers said this resulted in “largely normal” morphologies in the peripheral blood, bone marrow, spleen, and liver tissues of these mice.

In addition, the team found that nanoparticles carrying miR-22 oligonucleotides significantly delayed AML progression in secondary recipient mice with MLL-AF9 and AE9a-induced AML. At least 40% of the mice appeared to be completely cured.

In a xenotransplantation model, miR-22 nanoparticles significantly delayed AML progression induced by human MV4;11/t(4;11) cells.

Further investigation into the role miR-22 plays in AML revealed that 3 oncogenes—CRTC1, FLT3, and MYCBP—are “functionally important” targets of miR-22 in AML. And miR-22 represses the CREB and MYC signaling pathways.

The researchers also found DNA copy-number loss in the miR-22 gene locus in AML cases, and they discovered the expression of miR-22 is epigenetically repressed in AML.

“The downregulation, or decreased output, of miR-22 in AML is caused by the loss of the number of DNA being copied and/or stopping their expression through a pathway called TET1/GFI1/EZH2/SIN3A,” Dr Chen explained.

“Our study uncovers a previously unappreciated signaling pathway—TET1/GFI1/EZH2/SIN3A/miR-22/CREB-MYC—and provides new insights into genetic mechanisms causing and progressing AML and also highlights the clinical potential of miR-22-based AML therapy. More research on this pathway and ways to target it are necessary.”

miR-22

Image by Su Jung Song

The microRNA miR-22 is “an essential antitumor gatekeeper” in acute myeloid leukemia (AML), researchers have reported in Nature Communications.

The team found that miR-22 was significantly downregulated in  AML, and forced expression of miR-22 produced antileukemic effects in AML cells

and mouse models of the disease.

Futhermore, nanoparticles carrying miR-22 oligonucleotides appeared to cure AML in some mice.

“Previous research has shown that microRNA miR-22 is linked to breast cancer and other blood disorders [myelodysplastic syndromes], which sometimes turn into AML,” said study author Jianjun Chen, PhD, of the University of Cincinnati in Ohio.

“But we found in this study that it could be an essential antitumor gatekeeper in AML when it is downregulated. When we forced miR-22 expression, we saw difficulty in leukemia cells developing, growing, and thriving.”

Dr Chen and his colleagues first found that miR-22 was significantly downregulated (P<0.05) in samples from AML patients, when compared with normal CD34+ hematopoietic stem/progenitor cells, CD33+ myeloid progenitor cells, and mononuclear cells. The set of AML samples included MLL, t(15;17), t(8;21), and inv(16) AML.

When the researchers forced expression of miR-22 in human AML cells, they found the microRNA significantly inhibited cell viability, growth, and proliferation, while promoting apoptosis.

The team also investigated the role of miR-22 in colony formation induced by MLL-AF10/t(10;11), PML-RARA/t(15;17), and AML1-ETO9a/t(8;21). They found that forced expression of miR-22 significantly inhibited colony formation induced by all of these oncogenic fusion genes.

In mice, forced expression of miR-22 blocked MLL-AF9-mediated leukemogenesis and MLL-AF10-mediated leukemogenesis.

Forced expression of miR-22 also inhibited progression of AML induced by MLL-AF9, AE9a, or FLT3-ITD/NPM1c+ in secondary recipient mice. The researchers said this resulted in “largely normal” morphologies in the peripheral blood, bone marrow, spleen, and liver tissues of these mice.

In addition, the team found that nanoparticles carrying miR-22 oligonucleotides significantly delayed AML progression in secondary recipient mice with MLL-AF9 and AE9a-induced AML. At least 40% of the mice appeared to be completely cured.

In a xenotransplantation model, miR-22 nanoparticles significantly delayed AML progression induced by human MV4;11/t(4;11) cells.

Further investigation into the role miR-22 plays in AML revealed that 3 oncogenes—CRTC1, FLT3, and MYCBP—are “functionally important” targets of miR-22 in AML. And miR-22 represses the CREB and MYC signaling pathways.

The researchers also found DNA copy-number loss in the miR-22 gene locus in AML cases, and they discovered the expression of miR-22 is epigenetically repressed in AML.

“The downregulation, or decreased output, of miR-22 in AML is caused by the loss of the number of DNA being copied and/or stopping their expression through a pathway called TET1/GFI1/EZH2/SIN3A,” Dr Chen explained.

“Our study uncovers a previously unappreciated signaling pathway—TET1/GFI1/EZH2/SIN3A/miR-22/CREB-MYC—and provides new insights into genetic mechanisms causing and progressing AML and also highlights the clinical potential of miR-22-based AML therapy. More research on this pathway and ways to target it are necessary.”

miR-22

Image by Su Jung Song

The microRNA miR-22 is “an essential antitumor gatekeeper” in acute myeloid leukemia (AML), researchers have reported in Nature Communications.

The team found that miR-22 was significantly downregulated in  AML, and forced expression of miR-22 produced antileukemic effects in AML cells

and mouse models of the disease.

Futhermore, nanoparticles carrying miR-22 oligonucleotides appeared to cure AML in some mice.

“Previous research has shown that microRNA miR-22 is linked to breast cancer and other blood disorders [myelodysplastic syndromes], which sometimes turn into AML,” said study author Jianjun Chen, PhD, of the University of Cincinnati in Ohio.

“But we found in this study that it could be an essential antitumor gatekeeper in AML when it is downregulated. When we forced miR-22 expression, we saw difficulty in leukemia cells developing, growing, and thriving.”

Dr Chen and his colleagues first found that miR-22 was significantly downregulated (P<0.05) in samples from AML patients, when compared with normal CD34+ hematopoietic stem/progenitor cells, CD33+ myeloid progenitor cells, and mononuclear cells. The set of AML samples included MLL, t(15;17), t(8;21), and inv(16) AML.

When the researchers forced expression of miR-22 in human AML cells, they found the microRNA significantly inhibited cell viability, growth, and proliferation, while promoting apoptosis.

The team also investigated the role of miR-22 in colony formation induced by MLL-AF10/t(10;11), PML-RARA/t(15;17), and AML1-ETO9a/t(8;21). They found that forced expression of miR-22 significantly inhibited colony formation induced by all of these oncogenic fusion genes.

In mice, forced expression of miR-22 blocked MLL-AF9-mediated leukemogenesis and MLL-AF10-mediated leukemogenesis.

Forced expression of miR-22 also inhibited progression of AML induced by MLL-AF9, AE9a, or FLT3-ITD/NPM1c+ in secondary recipient mice. The researchers said this resulted in “largely normal” morphologies in the peripheral blood, bone marrow, spleen, and liver tissues of these mice.

In addition, the team found that nanoparticles carrying miR-22 oligonucleotides significantly delayed AML progression in secondary recipient mice with MLL-AF9 and AE9a-induced AML. At least 40% of the mice appeared to be completely cured.

In a xenotransplantation model, miR-22 nanoparticles significantly delayed AML progression induced by human MV4;11/t(4;11) cells.

Further investigation into the role miR-22 plays in AML revealed that 3 oncogenes—CRTC1, FLT3, and MYCBP—are “functionally important” targets of miR-22 in AML. And miR-22 represses the CREB and MYC signaling pathways.

The researchers also found DNA copy-number loss in the miR-22 gene locus in AML cases, and they discovered the expression of miR-22 is epigenetically repressed in AML.

“The downregulation, or decreased output, of miR-22 in AML is caused by the loss of the number of DNA being copied and/or stopping their expression through a pathway called TET1/GFI1/EZH2/SIN3A,” Dr Chen explained.

“Our study uncovers a previously unappreciated signaling pathway—TET1/GFI1/EZH2/SIN3A/miR-22/CREB-MYC—and provides new insights into genetic mechanisms causing and progressing AML and also highlights the clinical potential of miR-22-based AML therapy. More research on this pathway and ways to target it are necessary.”

Q) suPAR, a new screening tool for chronic kidney disease, has gotten a lot of press recently. My practice is interested in implementing it, but we can’t find information on how to obtain it. Is it commercially available yet? How can we order it? And importantly for our patients, do insurance plans cover it?

Research has been ongoing regarding biomarkers that could identify those at risk for chronic kidney disease (CKD) long before loss of renal function is apparent. A recently published study suggests that the circulating protein, soluble urokinase-type plasminogen activator receptor (suPAR), may be such a biomarker.

In a study of 3,683 subjects (ages 20 to 90) undergoing cardiac catheterization, and a further evaluation of 347 subjects in the Women’s Interagency HIV Study, Hayek et al found that elevated levels of suPAR were independently associated with CKD and with accelerated loss of renal function. At five-year follow-up, 24% of the 1,335 subjects with an initial estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m² had developed CKD. Risk for progression to CKD was about 41% in those with a baseline suPAR level ≥ 3,040 ng/mL, compared to 12% in those with lower baseline suPAR levels.¹ Thus, the cutoff for high versus low risk appears to be 3,040 ng/mL.

Hayek and associates are not the first or the only investigators studying the connection between suPAR and kidney disease. Evolving research has suggested suPAR may be an initiating factor in the development of focal segmental glomerulosclerosis (FSGS).² However, a recent study did not support this association.³

Currently, in the United States, laboratory testing for suPAR is available only for research purposes and has not been approved by the FDA for direct patient care.⁴ While more research is needed with different cohorts, there is much excitement in the field of nephrology regarding the potential role of suPAR as a biomarker for predicting CKD. —CS

Cindy Smith, DNP, APRN, CNN-NP, FNP-BC
Renal Consultants, PLLC, South Charleston, West Virgina

References
1. Hayek SS, Sever S, Ko Y-A, et al. Soluble urokinase receptor and chronic kidney disease. N Engl J Med. 2015;373:1916-1925.
2. Spinale JM, Mariani LH, Kapoor S, et al. A reassessment of soluble urokinase-type plasminogen activator receptor in glomerular disease. Kidney Int. 2015;87(3):564-574.
3. Wei C, El Hindi S, Li J, et al. Circulating urokinase receptor as a cause of focal segmental glomerulosclerosis.Nature Med. 2011;17: 952-960.
4. Rush University Medical Center. Early warning found for chronic kidney disease: common protein in blood rises months or years before disease develops [news release]. November 5, 2015. www.rush.edu/news/press-releases/early-warning-found-chronic-kidney-disease. Accessed April 11, 2016.

Q) suPAR, a new screening tool for chronic kidney disease, has gotten a lot of press recently. My practice is interested in implementing it, but we can’t find information on how to obtain it. Is it commercially available yet? How can we order it? And importantly for our patients, do insurance plans cover it?

Research has been ongoing regarding biomarkers that could identify those at risk for chronic kidney disease (CKD) long before loss of renal function is apparent. A recently published study suggests that the circulating protein, soluble urokinase-type plasminogen activator receptor (suPAR), may be such a biomarker.

In a study of 3,683 subjects (ages 20 to 90) undergoing cardiac catheterization, and a further evaluation of 347 subjects in the Women’s Interagency HIV Study, Hayek et al found that elevated levels of suPAR were independently associated with CKD and with accelerated loss of renal function. At five-year follow-up, 24% of the 1,335 subjects with an initial estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m² had developed CKD. Risk for progression to CKD was about 41% in those with a baseline suPAR level ≥ 3,040 ng/mL, compared to 12% in those with lower baseline suPAR levels.¹ Thus, the cutoff for high versus low risk appears to be 3,040 ng/mL.

Hayek and associates are not the first or the only investigators studying the connection between suPAR and kidney disease. Evolving research has suggested suPAR may be an initiating factor in the development of focal segmental glomerulosclerosis (FSGS).² However, a recent study did not support this association.³

Currently, in the United States, laboratory testing for suPAR is available only for research purposes and has not been approved by the FDA for direct patient care.⁴ While more research is needed with different cohorts, there is much excitement in the field of nephrology regarding the potential role of suPAR as a biomarker for predicting CKD. —CS

Cindy Smith, DNP, APRN, CNN-NP, FNP-BC
Renal Consultants, PLLC, South Charleston, West Virgina

References
1. Hayek SS, Sever S, Ko Y-A, et al. Soluble urokinase receptor and chronic kidney disease. N Engl J Med. 2015;373:1916-1925.
2. Spinale JM, Mariani LH, Kapoor S, et al. A reassessment of soluble urokinase-type plasminogen activator receptor in glomerular disease. Kidney Int. 2015;87(3):564-574.
3. Wei C, El Hindi S, Li J, et al. Circulating urokinase receptor as a cause of focal segmental glomerulosclerosis.Nature Med. 2011;17: 952-960.
4. Rush University Medical Center. Early warning found for chronic kidney disease: common protein in blood rises months or years before disease develops [news release]. November 5, 2015. www.rush.edu/news/press-releases/early-warning-found-chronic-kidney-disease. Accessed April 11, 2016.

Q) suPAR, a new screening tool for chronic kidney disease, has gotten a lot of press recently. My practice is interested in implementing it, but we can’t find information on how to obtain it. Is it commercially available yet? How can we order it? And importantly for our patients, do insurance plans cover it?

Research has been ongoing regarding biomarkers that could identify those at risk for chronic kidney disease (CKD) long before loss of renal function is apparent. A recently published study suggests that the circulating protein, soluble urokinase-type plasminogen activator receptor (suPAR), may be such a biomarker.

In a study of 3,683 subjects (ages 20 to 90) undergoing cardiac catheterization, and a further evaluation of 347 subjects in the Women’s Interagency HIV Study, Hayek et al found that elevated levels of suPAR were independently associated with CKD and with accelerated loss of renal function. At five-year follow-up, 24% of the 1,335 subjects with an initial estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m² had developed CKD. Risk for progression to CKD was about 41% in those with a baseline suPAR level ≥ 3,040 ng/mL, compared to 12% in those with lower baseline suPAR levels.¹ Thus, the cutoff for high versus low risk appears to be 3,040 ng/mL.

Hayek and associates are not the first or the only investigators studying the connection between suPAR and kidney disease. Evolving research has suggested suPAR may be an initiating factor in the development of focal segmental glomerulosclerosis (FSGS).² However, a recent study did not support this association.³

Currently, in the United States, laboratory testing for suPAR is available only for research purposes and has not been approved by the FDA for direct patient care.⁴ While more research is needed with different cohorts, there is much excitement in the field of nephrology regarding the potential role of suPAR as a biomarker for predicting CKD. —CS

Cindy Smith, DNP, APRN, CNN-NP, FNP-BC
Renal Consultants, PLLC, South Charleston, West Virgina

References
1. Hayek SS, Sever S, Ko Y-A, et al. Soluble urokinase receptor and chronic kidney disease. N Engl J Med. 2015;373:1916-1925.
2. Spinale JM, Mariani LH, Kapoor S, et al. A reassessment of soluble urokinase-type plasminogen activator receptor in glomerular disease. Kidney Int. 2015;87(3):564-574.
3. Wei C, El Hindi S, Li J, et al. Circulating urokinase receptor as a cause of focal segmental glomerulosclerosis.Nature Med. 2011;17: 952-960.
4. Rush University Medical Center. Early warning found for chronic kidney disease: common protein in blood rises months or years before disease develops [news release]. November 5, 2015. www.rush.edu/news/press-releases/early-warning-found-chronic-kidney-disease. Accessed April 11, 2016.

Q) I have a patient with stage 3a chronic kidney disease (glomerular filtration rate, 45-60 mL/min/1.73 m²). I have her on a statin and an ACE inhibitor. Is there anything else I can do to slow the progression of kidney disease?

For patients with stage 3a chronic kidney disease (CKD), ongoing evaluation of risk factors and management can impact the rate of disease progression. The cornerstones of CKD care include identification and treatment of the cause; management of hypertension, albuminuria, and diabetes (if applicable); reduction of cardiovascular (CV) risk; and ­correction of metabolic abnormalities.⁵

When considering factors that can contribute to kidney injury, clinicians should consider possible pre-, intra-, and post-renal processes that could potentially cause injury.

Prerenal: Approximately 20% of cardiac output is directed to the kidneys. Reduced left ventricular function, diastolic dysfunction, and pulmonary hypertension can all contribute to a reduction in renal blood flow and subsequent kidney injury.⁶

Intrarenal: Exploration of possible intra-renal processes begins with a thorough history of any familial disease, hematuria, stones, proteinuria, and exposure to nephrotoxins. The nephrotoxicity profile of all medications should be examined, and patients should be educated about products, particularly OTC medications (eg, NSAIDs, common cold preparations, and herbal or weight-loss products), that can be harmful to the kidneys. Patients should also be made aware of the risk for contrast-induced renal injury, especially when considering imaging or cardiac testing. Since diabetes is a leading cause of kidney disease, good diabetic control can reduce nephropathy and slow disease progression.

Postrenal: Benign prostatic hypertrophy, kidney stones, and neurogenic bladder can all cause injury. These warrant further evaluation and treatment.

CKD often worsens existing hypertension, which is an independent risk factor for kidney failure.⁷ Goal blood pressure (BP) for all patients without significant albuminuria should be < 140/90 mm Hg; for those with urinary albumin ≥ 30 mg/24 h, the goal is < 130/80 mm Hg.⁸ Choice of antihypertensive agents can be tailored to other comorbidities, but an ACE inhibitor or angiotensin receptor blocker should be considered firstline treatment. Nocturnal hypertension is common in patients with CKD and an independent marker of CV risk. By dosing antihypertensive medications at bedtime, the clinician supports CV risk reduction.⁹

CKD is an independent risk factor for CV disease, thus risk factor modification should be aggressively pursued. Regardless of the cause of CKD, cigarette smoking has been associated with a more rapid decline in renal function. Patients should be counseled on the risks and offered interventions to assist in smoking cessation.¹⁰ There is also emerging evidence that exercise likely benefits the vascular health of the kidneys and appears to slow the rate of kidney decline.^11,12 Overall, lifestyle interventions that help mitigate CV risk may directly benefit preservation of kidney function as well.

Metabolic abnormalities increase with CKD progression. Maintaining proper bone health through control of phosphate/acidosis and calcium equilibrium reduces morbidity as it relates to vascular and soft-tissue calcification. This can often be effectively managed through dietary modifications in early to moderate CKD. As the number of functioning nephrons decrease in CKD, so does the ability of the kidney to maintain proper acid/base balance. Persistent metabolic acidosis is related to CKD progression. Acid buffering with oral bicarbonate may be needed to achieve a goal CO₂ of 22 to 32 mEq/L.⁸

Through adoption of a comprehensive approach—one that is inclusive of the patient—optimal outcomes can be achieved for this rapidly growing and often underrecognized population. —CJ, ­AH-B, IS, BB

Crystal Johnson, PA-C
Angela Harker-Bacchus, FNP-BC
Irina Sadovskaya, PA-C
Beverly Benmoussa, FNP-BC
Transplant Nephrology Extra-Renal CKD Clinic, University of Michigan

References
5. Murphree DD, Thelen SM. Chronic kidney disease in primary care. J Am Board Fam Med. 2010;23(4):542-550.
6. Coppolino G, Presta P, Saturno L, Fuiano G. Acute kidney injury in patients undergoing cardiac surgery. J Nephrol. 2013;26(1):32-40.
7. Ravera M, Re M, Defarri L, et al. Importance of blood pressure control in chronic kidney disease. J Am Soc Nephrol. 2006;17(4 suppl 2):S98-S103.
8. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int. 2013;3(suppl):1-150.
9. Hermida RC, Ayala DE, Mojón A, Fernández JR. Bedtime dosing of antihypertensive medications reduces cardiovascular risk in CKD. J Am Soc Nephrol. 2011;22(12):2313-2321.
10. Ricardo AC, Anderson CA, Yang W, et al. Healthy lifestyle and risk of kidney disease progression, atherosclerotic events, and death in CKD: findings from the Chronic Renal Insufficiency Cohort (CRIC) study. Am J Kidney Dis. 2015;65(3):412-424.
11. Gould DW, Graham-Brown MPM, Watson EL, et al. Physiological benefits of exercise in pre-dialysis chronic kidney disease. Nephrology (Carlton). 2014;19(9):519-527.
12. Robinson-Cohen C, Littman AJ, Duncan GE, et al. Physical activity and change in estimated GFR among persons with CKD. J Am Soc Nephrol. 2014;25(2):399-406.

Q) I have a patient with stage 3a chronic kidney disease (glomerular filtration rate, 45-60 mL/min/1.73 m²). I have her on a statin and an ACE inhibitor. Is there anything else I can do to slow the progression of kidney disease?

For patients with stage 3a chronic kidney disease (CKD), ongoing evaluation of risk factors and management can impact the rate of disease progression. The cornerstones of CKD care include identification and treatment of the cause; management of hypertension, albuminuria, and diabetes (if applicable); reduction of cardiovascular (CV) risk; and ­correction of metabolic abnormalities.⁵

When considering factors that can contribute to kidney injury, clinicians should consider possible pre-, intra-, and post-renal processes that could potentially cause injury.

Prerenal: Approximately 20% of cardiac output is directed to the kidneys. Reduced left ventricular function, diastolic dysfunction, and pulmonary hypertension can all contribute to a reduction in renal blood flow and subsequent kidney injury.⁶

Intrarenal: Exploration of possible intra-renal processes begins with a thorough history of any familial disease, hematuria, stones, proteinuria, and exposure to nephrotoxins. The nephrotoxicity profile of all medications should be examined, and patients should be educated about products, particularly OTC medications (eg, NSAIDs, common cold preparations, and herbal or weight-loss products), that can be harmful to the kidneys. Patients should also be made aware of the risk for contrast-induced renal injury, especially when considering imaging or cardiac testing. Since diabetes is a leading cause of kidney disease, good diabetic control can reduce nephropathy and slow disease progression.

Postrenal: Benign prostatic hypertrophy, kidney stones, and neurogenic bladder can all cause injury. These warrant further evaluation and treatment.

CKD often worsens existing hypertension, which is an independent risk factor for kidney failure.⁷ Goal blood pressure (BP) for all patients without significant albuminuria should be < 140/90 mm Hg; for those with urinary albumin ≥ 30 mg/24 h, the goal is < 130/80 mm Hg.⁸ Choice of antihypertensive agents can be tailored to other comorbidities, but an ACE inhibitor or angiotensin receptor blocker should be considered firstline treatment. Nocturnal hypertension is common in patients with CKD and an independent marker of CV risk. By dosing antihypertensive medications at bedtime, the clinician supports CV risk reduction.⁹

CKD is an independent risk factor for CV disease, thus risk factor modification should be aggressively pursued. Regardless of the cause of CKD, cigarette smoking has been associated with a more rapid decline in renal function. Patients should be counseled on the risks and offered interventions to assist in smoking cessation.¹⁰ There is also emerging evidence that exercise likely benefits the vascular health of the kidneys and appears to slow the rate of kidney decline.^11,12 Overall, lifestyle interventions that help mitigate CV risk may directly benefit preservation of kidney function as well.

Metabolic abnormalities increase with CKD progression. Maintaining proper bone health through control of phosphate/acidosis and calcium equilibrium reduces morbidity as it relates to vascular and soft-tissue calcification. This can often be effectively managed through dietary modifications in early to moderate CKD. As the number of functioning nephrons decrease in CKD, so does the ability of the kidney to maintain proper acid/base balance. Persistent metabolic acidosis is related to CKD progression. Acid buffering with oral bicarbonate may be needed to achieve a goal CO₂ of 22 to 32 mEq/L.⁸

Through adoption of a comprehensive approach—one that is inclusive of the patient—optimal outcomes can be achieved for this rapidly growing and often underrecognized population. —CJ, ­AH-B, IS, BB

Crystal Johnson, PA-C
Angela Harker-Bacchus, FNP-BC
Irina Sadovskaya, PA-C
Beverly Benmoussa, FNP-BC
Transplant Nephrology Extra-Renal CKD Clinic, University of Michigan

References
5. Murphree DD, Thelen SM. Chronic kidney disease in primary care. J Am Board Fam Med. 2010;23(4):542-550.
6. Coppolino G, Presta P, Saturno L, Fuiano G. Acute kidney injury in patients undergoing cardiac surgery. J Nephrol. 2013;26(1):32-40.
7. Ravera M, Re M, Defarri L, et al. Importance of blood pressure control in chronic kidney disease. J Am Soc Nephrol. 2006;17(4 suppl 2):S98-S103.
8. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int. 2013;3(suppl):1-150.
9. Hermida RC, Ayala DE, Mojón A, Fernández JR. Bedtime dosing of antihypertensive medications reduces cardiovascular risk in CKD. J Am Soc Nephrol. 2011;22(12):2313-2321.
10. Ricardo AC, Anderson CA, Yang W, et al. Healthy lifestyle and risk of kidney disease progression, atherosclerotic events, and death in CKD: findings from the Chronic Renal Insufficiency Cohort (CRIC) study. Am J Kidney Dis. 2015;65(3):412-424.
11. Gould DW, Graham-Brown MPM, Watson EL, et al. Physiological benefits of exercise in pre-dialysis chronic kidney disease. Nephrology (Carlton). 2014;19(9):519-527.
12. Robinson-Cohen C, Littman AJ, Duncan GE, et al. Physical activity and change in estimated GFR among persons with CKD. J Am Soc Nephrol. 2014;25(2):399-406.

Q) I have a patient with stage 3a chronic kidney disease (glomerular filtration rate, 45-60 mL/min/1.73 m²). I have her on a statin and an ACE inhibitor. Is there anything else I can do to slow the progression of kidney disease?

For patients with stage 3a chronic kidney disease (CKD), ongoing evaluation of risk factors and management can impact the rate of disease progression. The cornerstones of CKD care include identification and treatment of the cause; management of hypertension, albuminuria, and diabetes (if applicable); reduction of cardiovascular (CV) risk; and ­correction of metabolic abnormalities.⁵

When considering factors that can contribute to kidney injury, clinicians should consider possible pre-, intra-, and post-renal processes that could potentially cause injury.

Prerenal: Approximately 20% of cardiac output is directed to the kidneys. Reduced left ventricular function, diastolic dysfunction, and pulmonary hypertension can all contribute to a reduction in renal blood flow and subsequent kidney injury.⁶

Intrarenal: Exploration of possible intra-renal processes begins with a thorough history of any familial disease, hematuria, stones, proteinuria, and exposure to nephrotoxins. The nephrotoxicity profile of all medications should be examined, and patients should be educated about products, particularly OTC medications (eg, NSAIDs, common cold preparations, and herbal or weight-loss products), that can be harmful to the kidneys. Patients should also be made aware of the risk for contrast-induced renal injury, especially when considering imaging or cardiac testing. Since diabetes is a leading cause of kidney disease, good diabetic control can reduce nephropathy and slow disease progression.

Postrenal: Benign prostatic hypertrophy, kidney stones, and neurogenic bladder can all cause injury. These warrant further evaluation and treatment.

CKD often worsens existing hypertension, which is an independent risk factor for kidney failure.⁷ Goal blood pressure (BP) for all patients without significant albuminuria should be < 140/90 mm Hg; for those with urinary albumin ≥ 30 mg/24 h, the goal is < 130/80 mm Hg.⁸ Choice of antihypertensive agents can be tailored to other comorbidities, but an ACE inhibitor or angiotensin receptor blocker should be considered firstline treatment. Nocturnal hypertension is common in patients with CKD and an independent marker of CV risk. By dosing antihypertensive medications at bedtime, the clinician supports CV risk reduction.⁹

CKD is an independent risk factor for CV disease, thus risk factor modification should be aggressively pursued. Regardless of the cause of CKD, cigarette smoking has been associated with a more rapid decline in renal function. Patients should be counseled on the risks and offered interventions to assist in smoking cessation.¹⁰ There is also emerging evidence that exercise likely benefits the vascular health of the kidneys and appears to slow the rate of kidney decline.^11,12 Overall, lifestyle interventions that help mitigate CV risk may directly benefit preservation of kidney function as well.

Metabolic abnormalities increase with CKD progression. Maintaining proper bone health through control of phosphate/acidosis and calcium equilibrium reduces morbidity as it relates to vascular and soft-tissue calcification. This can often be effectively managed through dietary modifications in early to moderate CKD. As the number of functioning nephrons decrease in CKD, so does the ability of the kidney to maintain proper acid/base balance. Persistent metabolic acidosis is related to CKD progression. Acid buffering with oral bicarbonate may be needed to achieve a goal CO₂ of 22 to 32 mEq/L.⁸

Through adoption of a comprehensive approach—one that is inclusive of the patient—optimal outcomes can be achieved for this rapidly growing and often underrecognized population. —CJ, ­AH-B, IS, BB

Crystal Johnson, PA-C
Angela Harker-Bacchus, FNP-BC
Irina Sadovskaya, PA-C
Beverly Benmoussa, FNP-BC
Transplant Nephrology Extra-Renal CKD Clinic, University of Michigan

References
5. Murphree DD, Thelen SM. Chronic kidney disease in primary care. J Am Board Fam Med. 2010;23(4):542-550.
6. Coppolino G, Presta P, Saturno L, Fuiano G. Acute kidney injury in patients undergoing cardiac surgery. J Nephrol. 2013;26(1):32-40.
7. Ravera M, Re M, Defarri L, et al. Importance of blood pressure control in chronic kidney disease. J Am Soc Nephrol. 2006;17(4 suppl 2):S98-S103.
8. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int. 2013;3(suppl):1-150.
9. Hermida RC, Ayala DE, Mojón A, Fernández JR. Bedtime dosing of antihypertensive medications reduces cardiovascular risk in CKD. J Am Soc Nephrol. 2011;22(12):2313-2321.
10. Ricardo AC, Anderson CA, Yang W, et al. Healthy lifestyle and risk of kidney disease progression, atherosclerotic events, and death in CKD: findings from the Chronic Renal Insufficiency Cohort (CRIC) study. Am J Kidney Dis. 2015;65(3):412-424.
11. Gould DW, Graham-Brown MPM, Watson EL, et al. Physiological benefits of exercise in pre-dialysis chronic kidney disease. Nephrology (Carlton). 2014;19(9):519-527.
12. Robinson-Cohen C, Littman AJ, Duncan GE, et al. Physical activity and change in estimated GFR among persons with CKD. J Am Soc Nephrol. 2014;25(2):399-406.

Answer
The radiograph shows a large cavitary lesion within the left mid-lung with evidence of an air fluid level. This finding is strongly suggestive of a postoperative abscess or empyema. Secondarily, there is some pleural thickening within the left lateral apex region. This can be suggestive of scarring or possibly a neoplasm.

The patient was admitted to the ICU for a sepsis workup, and Interventional Radiology was consulted to evaluate for CT-guided drain placement.

Answer
The radiograph shows a large cavitary lesion within the left mid-lung with evidence of an air fluid level. This finding is strongly suggestive of a postoperative abscess or empyema. Secondarily, there is some pleural thickening within the left lateral apex region. This can be suggestive of scarring or possibly a neoplasm.

The patient was admitted to the ICU for a sepsis workup, and Interventional Radiology was consulted to evaluate for CT-guided drain placement.

Answer
The radiograph shows a large cavitary lesion within the left mid-lung with evidence of an air fluid level. This finding is strongly suggestive of a postoperative abscess or empyema. Secondarily, there is some pleural thickening within the left lateral apex region. This can be suggestive of scarring or possibly a neoplasm.

The patient was admitted to the ICU for a sepsis workup, and Interventional Radiology was consulted to evaluate for CT-guided drain placement.

ANSWER
Findings on this ECG include sinus rhythm with frequent, consecutive premature ventricular complexes (PVCs) consistent with nonsustained ventricular tachycardia (NSVT). There is also evidence of a probable left atrial enlargement.

The key to interpreting this ECG is to first locate normal-appearing complexes. These are illustrated by the third, fourth, 10th, and 11th complexes on the rhythm strip (lead I) at the bottom of the ECG. Notice that there is a normal-appearing PQRST complex for each of these beats.

The rate of 82 beats/min is calculated from a sum average of all beats on the 12-lead ECG; however, the R-R interval between the third and fourth and the 10th and 11th beats is roughly 60 beats/min, signifying a normal sinus rhythm. All other beats are PVCs arising from the left ventricle (as evidenced by a right bundle branch pattern in lead V₁).

Careful inspection will reveal retrograde P waves located in the terminal upstroke of the S wave. NSVT is defined as three or more consecutive PVCs at a rate greater than 100 beats/min with a duration of less than 30 seconds. The pauses seen between a PVC and a normally conducting P wave are caused by retrograde conduction from the ventricle to the atrium, with subsequent block within the atrium.

Finally, left atrial enlargement is evidenced by a biphasic P wave in the normally conducting beat seen in lead V₁.

ANSWER
Findings on this ECG include sinus rhythm with frequent, consecutive premature ventricular complexes (PVCs) consistent with nonsustained ventricular tachycardia (NSVT). There is also evidence of a probable left atrial enlargement.

The key to interpreting this ECG is to first locate normal-appearing complexes. These are illustrated by the third, fourth, 10th, and 11th complexes on the rhythm strip (lead I) at the bottom of the ECG. Notice that there is a normal-appearing PQRST complex for each of these beats.

The rate of 82 beats/min is calculated from a sum average of all beats on the 12-lead ECG; however, the R-R interval between the third and fourth and the 10th and 11th beats is roughly 60 beats/min, signifying a normal sinus rhythm. All other beats are PVCs arising from the left ventricle (as evidenced by a right bundle branch pattern in lead V₁).

Careful inspection will reveal retrograde P waves located in the terminal upstroke of the S wave. NSVT is defined as three or more consecutive PVCs at a rate greater than 100 beats/min with a duration of less than 30 seconds. The pauses seen between a PVC and a normally conducting P wave are caused by retrograde conduction from the ventricle to the atrium, with subsequent block within the atrium.

Finally, left atrial enlargement is evidenced by a biphasic P wave in the normally conducting beat seen in lead V₁.

ANSWER
Findings on this ECG include sinus rhythm with frequent, consecutive premature ventricular complexes (PVCs) consistent with nonsustained ventricular tachycardia (NSVT). There is also evidence of a probable left atrial enlargement.

The key to interpreting this ECG is to first locate normal-appearing complexes. These are illustrated by the third, fourth, 10th, and 11th complexes on the rhythm strip (lead I) at the bottom of the ECG. Notice that there is a normal-appearing PQRST complex for each of these beats.

The rate of 82 beats/min is calculated from a sum average of all beats on the 12-lead ECG; however, the R-R interval between the third and fourth and the 10th and 11th beats is roughly 60 beats/min, signifying a normal sinus rhythm. All other beats are PVCs arising from the left ventricle (as evidenced by a right bundle branch pattern in lead V₁).

Careful inspection will reveal retrograde P waves located in the terminal upstroke of the S wave. NSVT is defined as three or more consecutive PVCs at a rate greater than 100 beats/min with a duration of less than 30 seconds. The pauses seen between a PVC and a normally conducting P wave are caused by retrograde conduction from the ventricle to the atrium, with subsequent block within the atrium.

Finally, left atrial enlargement is evidenced by a biphasic P wave in the normally conducting beat seen in lead V₁.