Determinants of Progression from Microalbuminuria to Proteinuria in Patients Who Have Type 1 Diabetes and Are Treated with Angiotensin-Converting Enzyme Inhibitors

Abstract

The aims of this study were to assess the frequency and determinants of (1) treatment with angiotensin-converting enzyme inhibitors (ACE-I) and (2) progression to proteinuria in the presence of ACE-I treatment in patients with type 1 diabetes and microalbuminuria. A clinic-based cohort study of patients with type 1 diabetes was begun in 1991. The patients who were included in this study (n ‫؍‬ 373) are the cohort members who received a diagnosis of microalbuminuria during a 2-yr baseline observation and were followed for 10 yr with frequent assessments of urinary albumin excretion and biennial examinations. Progression to proteinuria occurred when the median urinary albumin excretion during a 2-yr interval exceeded 299 g/min. During the decade-long study, the proportion of patients who had a history of microalbuminuria and were treated with ACE-I rose from 17 to 67%. Patients who started this treatment had (on average) higher BP, higher urinary albumin excretion, and longer diabetes duration than those who did not. Microalbuminuria often progressed to proteinuria (6.3/100 person-years) in those who were treated. Poor glycemic control and elevated serum cholesterol were the major determinants/predictors of this progression. Although treatment with ACE-I increased during the past decade, it was not completely effective, because microalbuminuria progressed to proteinuria in many treated patients. Poor glycemic control and elevated serum cholesterol were the major determinants/predictors for progression while on ACE-I treatment. The mechanisms that are responsible for the frequent failure of ACE-I to prevent progression of microalbuminuria to proteinuria in a clinical setting are not clear.

Risk for ESRD in Type 1 Diabetes Remains High Despite Renoprotection

“…Also the single determination of ACEI/ARB treatment might not be sufficient to detect a statistically significant effect of these drugs on risk of ESRD. However, incorporating changes over time in usage of these drugs, as we have done previously, 30 most likely would not change our findings.…”

Combination therapy with AT1 blocker and vitamin D analog markedly ameliorates diabetic nephropathy: Blockade of compensatory renin increase

“…Thus, reduction of albuminuria is a major target for renoprotective therapy in both type 1 and type 2 diabetes. Clinical studies have demonstrated that ACEIs and ARBs can reduce albuminuria in diabetic patients; however, not all patients respond to the treatment (44), in many cases because of incomplete blockade of the RAS. Vitamin D also has antiproteinuric activity.…”

Cardiac Autonomic Neuropathy and Early Progressive Renal Decline in Patients with Nonmacroalbuminuric Type 1 Diabetes

“…Although rates of complications appear to have declined substantially over the past 2 decades, such improvements may not apply to the rates of ESRD (3). Furthermore, despite advances aimed at improving glycemic control and inhibiting deleterious neurohormonal pathways, such as the renin-angiotensin-aldosterone system (RAAS), evidence from population databases and clinical trials imply that the incidence of DN has been postponed but not outright prevented (4)(5)(6)(7). Finally, the overall prevalence of DN continues to increase in proportion to the rising prevalence of diabetes (3,8).…”

“…To date, several studies have explored the causal relationship between cardiac autonomic neuropathy and renal impairment (6,12,(17)(18)(19). In the nondiabetic population, the Atherosclerosis Risk in Communities studywhich followed 13,241 adults, 12% of whom had baseline type 2 diabetes-demonstrated that low HRV was associated with the subsequent development of ESRD and CKDrelated hospitalization after 16 years of follow-up (17).…”