Diabetic kidney disease and diabetic nephropathy are the leading cause of end-stage kidney disease in the United States and most developed countries. Diabetes accounts for 30% to 50% of the incident ...cases of end-stage kidney disease in the United States. Although this represents a significant public health concern, it is important to note that only 30% to 40% of patients with diabetes develop diabetic nephropathy. Specific treatment of patients with diabetic nephropathy can be divided into 4 major arenas: cardiovascular risk reduction, glycemic control, blood pressure control, and inhibition of the renin-angiotensin system (RAS). Recommendations for therapy include targeting a hemoglobin A1c concentration < 7% and blood pressure < 140/90mmHg with therapy anchored around the use of a RAS-blocking agent. The single best evidence-based therapy for diabetic nephropathy is therapy with a RAS-blocking medication. This Core Curriculum outlines and discusses in detail the epidemiology, pathophysiology, diagnosis, and management of diabetic nephropathy.
Patients with diabetes and recent worsening heart failure that had led to hospitalization were randomly assigned to receive sotagliflozin or placebo. At a median of 9 months, the total number of ...deaths from cardiovascular causes and hospitalizations and urgent visits for heart failure was significantly lower with sotagliflozin than with placebo.
BP control is critical in the treatment of patients with chronic kidney disease. Recent guidelines now recommend a BP goal of <130/80 mmHg. Clinical trials using a randomized, intention-to-treat ...design have not established the benefits of this goal; rather, observational data and secondary or subgroup analyses drove the development of the new guidelines. A variety of observations suggest potential adverse events associate with achieving too low a BP in patients with chronic kidney disease, and ongoing randomized trials will have to establish the benefits or risks of meeting this goal.
TGF-
β
has been implicated as a major pathogenic factor in diabetic nephropathy. This randomized, double-blind, phase 2 study assessed whether modulating TGF-
β
1 activity with a TGF-
β
1–specific, ...humanized, neutralizing monoclonal antibody (TGF-
β
1 mAb) is safe and more effective than placebo in slowing renal function loss in patients with diabetic nephropathy on chronic stable renin-angiotensin system inhibitor treatment. We randomized 416 patients aged ≥25 years with type 1 or type 2 diabetes, a serum creatinine (SCr) level of 1.3–3.3 mg/dl for women and 1.5–3.5 mg/dl for men (or eGFR of 20–60 ml/min per 1.73 m
2
), and a 24-hour urine protein-to-creatinine ratio ≥800 mg/g to TGF-
β
1 mAb (2-, 10-, or 50-mg monthly subcutaneous dosing for 12 months) or placebo. We assessed a change in SCr from baseline to 12 months as the primary efficacy variable. Although the Data Monitoring Committee did not identify safety issues, we terminated the trial 4 months early for futility on the basis of their recommendation. The placebo group had a mean±SD change in SCr from baseline to end of treatment of 0.33±0.67 mg/dl. Least squares mean percentage change in SCr from baseline to end of treatment did not differ between placebo (14%; 95% confidence interval 95% CI, 9.7% to 18.2%) and TGF-
β
1 mAb treatments (20% 95% CI, 15.3% to 24.3%, 19% 95% CI, 14.2% to 23.0%, and 19% 95% CI, 14.0% to 23.3% for 2-, 10-, and 50-mg doses, respectively). Thus, TGF-
β
1 mAb added to renin-angiotensin system inhibitors did not slow progression of diabetic nephropathy.
In a trial involving 10,584 patients with diabetes and chronic kidney disease, sotagliflozin resulted in fewer total deaths from cardiovascular causes, hospitalizations for heart failure, and urgent ...visits for heart failure than placebo. Diarrhea, mycotic infections, and diabetic ketoacidosis occurred with sotagliflozin.
Background Previous studies have shown that patients with chronic kidney disease, including those with diabetic nephropathy, are more likely to die of cardiovascular disease than reach end-stage ...renal disease (ESRD). This analysis was conducted to determine whether ESRD is a more common outcome than cardiovascular death in patients with type 2 diabetic nephropathy, significant proteinuria, and decreased kidney function who were selected for participation in a clinical trial. Study Design Retrospective analysis of the DIAMETRIC (Diabetes Mellitus Treatment for Renal Insufficiency Consortium) database derived from 2 prospective randomized controlled clinical trials (IDNT Irbesartan Diabetic Nephropathy Trial and RENAAL Reduction of Endpoints in Non–Insulin-dependent Diabetes With the Angiotensin II Antagonist Losartan). Setting & Participants 3,228 adult patients with type 2 diabetic nephropathy from IDNT and RENAAL were combined to establish the DIAMETRIC database. This is the largest global source of clinical information for patients with type 2 diabetic nephropathy who have decreased kidney function and significant proteinuria. Intervention Angiotensin receptor blocker versus non–angiotensin receptor blocker therapy to slow the progression of type 2 diabetic nephropathy (in the prospective trials). Outcomes & Measurements Incidence rates of ESRD, cardiovascular death, and all-cause mortality. Results Mean follow-up was 2.8 years; 19.5% of patients developed ESRD, approximately 2.5 times the incidence of cardiovascular death and 1.5 times the incidence of all-cause mortality. ESRD was more common than cardiovascular death in all subgroups analyzed with the exception of participants with low levels of albuminuria (albumin excretion <1.0 g/g) and well-preserved levels of kidney function (estimated glomerular filtration rate >45 mL/min/1.73 m2 ) at baseline. Limitations All participants were included in a prospective clinical trial. Conclusions Patients with type 2 diabetic nephropathy, characterized by decreased kidney function and significant proteinuria, are more likely to reach ESRD than die during 3 years' mean follow-up. Given the rapidly increasing number of cases of type 2 diabetes worldwide, this has implications for predicting future renal replacement therapy requirements.
In this study, patients with type 2 diabetes and nephropathy received either aliskiren, an oral direct renin inhibitor, or placebo, in addition to the maximal recommended dose of losartan and optimal ...antihypertensive therapy. Aliskiren was associated with a reduction in the mean urinary albumin-to-creatinine ratio. This direct renin inhibitor may be renoprotective independently of its blood-pressure–lowering effects in this patient population.
In patients with type 2 diabetes and nephropathy, aliskiren was associated with a reduction in the mean urinary albumin-to-creatinine ratio. This direct renin inhibitor may be renoprotective independently of its blood-pressure–lowering effects in this patient population.
The pathogenesis of diabetic nephropathy is multifactorial, and the renin−angiotensin−aldosterone system plays an important role.
1
,
2
Persistent proteinuria is the hallmark of diabetic nephropathy, a condition that is characterized by a progressive rise in blood pressure, a declining glomerular filtration rate, and a high risk of fatal or nonfatal cardiovascular events. The degree of proteinuria is closely associated with the rates of renal and cardiovascular events.
3
,
4
Furthermore, a reduction in proteinuria is associated with a slowing of both the decline in the glomerular filtration rate
5
and the progression to end-stage renal disease.
6
In addition, decreasing proteinuria is associated with . . .
Dietary sodium restriction has been shown to enhance the short-term response of blood pressure and albuminuria to angiotensin receptor blockers (ARBs). Whether this also enhances the long-term renal ...and cardiovascular protective effects of ARBs is unknown. Here we conducted a post-hoc analysis of the RENAAL and IDNT trials to test this in patients with type 2 diabetic nephropathy randomized to ARB or non-renin–angiotensin–aldosterone system (non-RAASi)–based antihypertensive therapy. Treatment effects on renal and cardiovascular outcomes were compared in subgroups based on dietary sodium intake during treatment, measured as the 24-h urinary sodium/creatinine ratio of 1177 patients with available 24-h urinary sodium measurements. ARB compared to non-RAASi–based therapy produced the greatest long-term effects on renal and cardiovascular events in the lowest tertile of sodium intake. Compared to non-RAASi, the trend in risk for renal events was significantly reduced by 43%, not changed, or increased by 37% for each tertile of increased sodium intake, respectively. The trend for cardiovascular events was significantly reduced by 37%, increased by 2% and 25%, respectively. Thus, treatment effects of ARB compared with non-RAASi–based therapy on renal and cardiovascular outcomes were greater in patients with type 2 diabetic nephropathy with lower than higher dietary sodium intake. This underscores the avoidance of excessive sodium intake, particularly in type 2 diabetic patients receiving ARB therapy.
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