Remission of Nephrotic-Range Albuminuria in Type 1 Diabetic Patients

Abstract

OBJECTIVE -To evaluate the cumulative incidence of nephrotic-range albuminuria (NRA), the frequency of remission, and the impact on progression, we analyzed data from a prospective cohort study of type 1 diabetic patients with diabetic nephropathy.RESEARCH DESIGN AND METHODS -All of the albuminuric type 1 diabetic patients (n ϭ 321, 121 women), who had at least yearly measurements of glomerular filtration rate (GFR) with a 51 Cr-EDTA plasma clearance technique and were followed for at least 3 years, were evaluated. NRA, defined as persistent albuminuria Ͼ2,500 mg/24 h, occurred in 126 patients (35 women) aged (mean Ϯ SD) 34 Ϯ 8 years, with duration of diabetes 22 Ϯ 8 years and follow-up time from onset of NRA (median [range]) 8.7 (3.0 -20.9) years. Remission of NRA was defined as sustained albuminuria Ͻ600 mg/24 h for at least 1 year.RESULTS -The cumulative incidence of NRA was 39%. Remission was induced in 28 of 126 (22%) patients; 21 were predominantly treated with ACE inhibitors, 7 with non-ACE inhibitor medications. Remission lasted 3.6 (1.0 -18.1) years. More women (37%) than men (16%) obtained remission (P ϭ 0.01). In the remission group compared with the no-remission group, mean arterial blood pressure (mean Ϯ SEM) was reduced (102 Ϯ 1 vs. 106 Ϯ 1 mmHg, P Ͻ 0.01), the rate of decline in GFR was diminished (3.8 Ϯ 0.6 vs. 7.5 Ϯ 0.5 ml ⅐ min -1 ⅐ year -1 , P Ͻ 0.001), and serum cholesterol was lower (5.3 Ϯ 0.2 vs. 6.1 Ϯ 0.1 mmol/l, P Ͻ 0.01) during the whole follow-up period. No difference in glycemic control was found between groups (HbA 1c 9.2 vs. 9.4%, NS).CONCLUSIONS -In contrast to observations made before the use of antihypertensive treatment, our prospective observational study suggests that aggressive antihypertensive treatment with and without ACE inhibitors can induce long-lasting remission in a sizeable fraction of type 1 diabetic patients with NRA. The group of patients obtaining remission is characterized by slow progression of diabetic nephropathy and improved cardiovascular risk profile. Diabetes Care 24:1972-1977, 2001D iabetic nephropathy is a chronic progressive kidney disease with high morbidity and mortality (1). The natural history of diabetic nephropathy, i.e., without antihypertensive treatment, is a progressive and irreversible course without recovery or cure (2) and is characterized by an early elevation of arterial blood pressure, increasing albuminuria, and a relentless mean decline in glomerular filtration rate (GFR) of ϳ10 -12 ml ⅐ min -1 ⅐ year -1 (3-5). The degree of albuminuria is closely related to the progression of diabetic nephropathy, as previously reviewed by Rossing (6). Diabetic patients with nephrotic-range albuminuria (NRA) have the fastest decline in GFR (7) and the shortest survival time (2,8). Recently, Hebert et al. (9) have challenged the concept that a relentless progression is inevitable in all type 1 diabetic patients with nephrotic-range proteinuria. Remission, defined as a reduction of proteinuria from Ͼ3,500 mg per 24 h to Ͻ1,000 mg per 24 h, was demonstra...

Clinical impact of albuminuria in diabetic nephropathy

“…Remission was defined as albuminuria <200 microg/min sustained for at least one year and a decrease of at least 30% from preremission levels, and regression as rate of decline in GFR equal to the natural aging process: < or =1 ml/min/year during the investigation period in this report. Moreover, remission of nephrotic-range albuminuria in type 1 diabetic patients was also reported at Steno Diabetes Center (35). In this report, remission was induced in 28 of 126 (22%) patients; 21 were predominantly treated with angiotensin converting enzyme (ACE) inhibitors, 7 with non-ACE inhibitor medications.…”

Halting the Progression of Chronic Nephropathy

“…A clear reduction in the incidence of macrovascular and microvascular end points was also documented in the UKPDS trial that compared tight BP control with either captopril or atenolol (defined as Ͻ150/85) versus usual, although a large part of the reduction of microvascular complications was due to a reduction in retinal photocoagulation (23). However, Parving et al (24) found that tight BP control was associated with remission of type 1 diabetic nephropathy, and Weidman et al (25) found a strong relation between the degree of BP reduction and reduction in proteinuria in diabetic nephropathy.…”

Major Barriers against Renin–Angiotensin–Aldosterone System Blocker Use in Chronic Kidney Disease Stages 3–5 in Clinical Practice: A Safety Concern?

“…2,3 Control of blood pressure and proteinuria are the most important interventions in order to slow the rate of deterioration in renal functions. [4][5][6] The activation of renin-angiotensin-aldosterone system (RAAS) had been shown to play a key role in both systemic and glomerular hypertension and also proteinuria. RAAS blockers are effective in slowing the progression of CKD independent of their antihypertensive effects.…”