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Kidney News | February 2018 KidneyNewsFebruary 2018 | Vol. 10, Number 2 Microvascular Complications of Diabetic Kidney Disease Addressed in Report By Eric Seaborg kidney disease and says that the cause of disease is misdi- MD, professor of internal medicine and chief of nephrol- agnosed for many patients. ogy at Wake Forest School of Medicine, the lead author “Vascular complications are the major cause of mor- on the renal section of the statement. bidity and mortality in diabetic patients,” according to Agents that block the renin-angiotensin aldosterone “Diabetic Microvascular Disease: An Endocrine Society system (RAAS), such as angiotensin-converting enzyme Scientific Statement.” The kidney, eye, and peripheral (ACE) inhibitors and angiotensin receptor blockers nervous system form the triad of “classical diabetes micro- (ARBs), are effective at slowing the progression of DKD vascular target tissues. Microvascular renal disease is … a in patients with high levels of proteinuria. New glucose- major contributor to the development of end-stage kid- lowering agents, including sodium-glucose cotrans- ney disease (ESKD) in the developed world.” porter-2 (SGLT-2) inhibitors and glucagon-peptide 1 The best practices in therapy are not a surprise. “The (GLP-1) agonists, provide hope for slowing progression latest research shows that maintaining tight control over of established DKD or preventing its development. blood sugar levels and blood pressure can help to reduce The statement reviews the various pathways to micro- the risk of complications such as diabetic nephropathy,” vascular damage (see sidebar) and notes that some of the ef- said Eugene J. Barrett, MD, PhD, of the University of fectiveness of medications may stem from disrupting these Virginia, who chaired the task force that developed the pathways. For example, ACE inhibitors may contribute statement. not only by lowering systemic blood pressure, but could also decrease glomerular capillary pressure by inhibiting nnovative therapies and a better understanding of “Therapies to prevent or slow the development of the kidney’s production of angiotensin II. Angiotensin II the underlying mechanisms of diabetic kidney dis- DKD are multifactorial and include lowering blood sugar may lead to kidney damage through the induction of local ease (DKD) are slowing its progression, according to levels with medications, diet, and exercise, as well as treat- factors, including extracellular matrix protein synthesis via Ia new Endocrine Society scientific statement on diabetic ing hypertension and hyperlipidemia,” the statement says. transforming growth factor-b and inflammatory cytokines. microvascular complications. The statement also describes There are several medications that slow the progression the slow progress in finding genetic markers for diabetic of DKD, but they do not halt it, said Barry I. Freedman, Continued on page 2 > Method Could Help Monitor Transplant Referrals from Dialysis Clinics Inside By Tracy Hampton Findings or patients with end stage renal disease (ESRD), Clinical Journal of the American Society of Nephrology ar- Risk equation predicts outcomes barriers to kidney transplantation can come from ticle, a new method may be effective for assessing dialysis in pediatric CKD a range of sources. Referral to a transplant center is centers’ performance in this area. Transplant Innovations F “In the past several years, the Centers for Medicare an essential first step for patients who may be transplant candidates, and it’s one that relies on actions taken by the & Medicaid Services has focused on increasing referrals and Policy leadership and staff at dialysis centers. among dialysis facilities as part of the Statement of Work Increasing living donation; how well The Centers for Medicare & Medicaid Services, as well for the 18 End Stage Renal Disease Networks. However, has KAS worked; normothermic perfusion to preserve organs, and as the kidney community, have called for the development these data are not routinely collected and are not available where transplant may be headed of quality measures for dialysis facilities to improve per- to the public to determine whether some dialysis facilities are appropriately referring patients for kidney transplanta- formance and equity in access to kidney transplantation, Policy Update but little progress has been made. As described in a recent Continued on page 4 > Telehealth, AKI among ASN’s top policy targets in 2018 Industry Spotlight Products for contrast-induced AKI and stone assessment 2 | ASN Kidney News | February 2018 Microvascular er the risks of hypoglycemia. To this end, the National Kidney Foundation Kidney Disease Outcomes Qual- Complications ity Initiative (KDOQI) guidelines recommend a target Cellular and Biochemical Continued from page 1 HbA1c of ~7%. A target HbA1c >7% is recommended Pathways in Diabetic in those with comorbidities or limited life expectancy and at risk for hypoglycemia. Glycemic control helps Kidney Disease More biopsies needed? maintain the glomerular filtration rate (GFR), a pri- Freedman said an important point in the statement is that mary focus for preventing the advance of “Multiple levels of breakthroughs have “a significant number of people whose kidney disease is DKD. happened in the last 10 years in attributed to diabetes may be misdiagnosed.” In several Kidney function itself can af- our understanding of what studies, renal biopsies demonstrated that 30% or more of fect the metabolism and safety could be causing cells to be proteinuric patients with type 2 diabetes had non-diabetic of blood sugar–lowering dysfunctional when ex- forms of kidney disease. medications, and should posed to high glucose,” “Most patients who have diabetes and progressive kid- be adjusted according to a said George L. King, patient’s estimated GFR ney disease do not get kidney biopsies,” Freedman said. MD, chief scientific of- “Doctors assume that because the patient has diabetes and (eGFR). To reduce the ficer at Harvard’s Joslin kidney failure, it is most likely diabetic kidney disease. But risk of prolonged hypo- many biopsy studies, particularly in those with shorter glycemia, KDOQI guide- Diabetes Center, who diabetes durations and without diabetic retinopathy, have lines suggest using second- served on the task force shown a large percentage had other kidney disease. Mis- generation glipizide rather that developed that En- classification is not infrequent.” than first-generation sulfonyl- docrine Society scientific This misdiagnosis issue is serious not only for patients, ureas when eGFR is <60 mL/ statement. who may not receive the most appropriate treatment, but min/1.73 m2. The guidelines urge The statement lays out many it also interferes with research. If a large percentage of the caution when initiating meglitinides cellular mechanisms linked to patients in a diabetic kidney disease treatment trial do not when eGFR is <30. According to US Food vascular complications: nonenzymatic actually have DKD, researchers may miss the effect of a and Drug Administration guidelines, patients should glycation and the formation of advanced treatment that is actually effective, Freedman said. The in- not start metformin when their eGFR is <45 and avoid glycation end products; enhanced reac- it altogether when it is <30. When a patient’s eGFR clusion of misdiagnosed patients could also contribute to tive oxygen production and actions; and the difficulties in the search for DKD genes. is between these levels, clinicians should follow them endoplasmic reticulum stress. Biochemi- The statement notes that its findings apply to both closely. Patients with advanced nephropathy may need type 1 and type 2 diabetes—along with secondary forms their doses adjusted if they are taking b-glucosidase cal pathways implicated include the ac- of diabetes resulting from genetic mutations, pharma- inhibitors, dipeptidyl peptidase 4 (DPP4) inhibitors, tivation of the polyol pathway, excessive ceuticals, or surgical interventions—because despite the SGLT-2 inhibitors, incretin mimetics, and islet amy- oxidants, chronic inflammation, the dia- disparate pathogenesis of these conditions, they all share loid polypeptide (IAPP) analogs. cylglycerol–protein kinase C pathway, Src microvascular dysfunction as a chronic outcome. And it As kidney function declines to an eGFR of <30, it can homology-2 domain-containing phos- covers much more than the renal aspects of the disease. affect the accuracy of tests used to assess glycemic con- phatase-1, the renin-angiotensin system, trol, especially the HbA1c. In the late stages of DKD and the kallikrein-bradykinin system. Mixed success in genetics for diabetic and ESRD, red blood cell survival drops, and clinicians A better understanding of these path- kidney disease often prescribe medications to treat anemia. This can ways could help in slowing the develop- lead to inaccurately low HbA1c values and provide a A bright spot in research in recent years has been the iden- ment and progression of diabetic kidney false sense of security. Interpretation of HbA1c in pa- tification of genes related to non-diabetic forms of kidney disease. Some efforts have not succeeded, tients with ESRD requires complex statistical adjust- disease. ment. Frequent measurements of serum glucose or such as with protein kinase C. Clinical tri- “We have had great success in identifying the genetic novel assays such as glycated albumin or fructosamine als have shown that angiotensin-convert- basis of non-diabetic kidney disease. Results have changed
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