Intensified Multifactorial Intervention in Type 2 Diabetes and Microalbuminuria Reduces End Stage Renal Disease and Mortality: 21 Years Follow-Up of the Steno-2 Study

Jens Oellgaard ([email protected])1 2 3; Peter Gæde1 2, Peter Rossing3 4 7, Hans-Henrik Parving5 6, Oluf Pedersen5 7 1) University of Southern Denmark; 2) Slagelse Hospital; 3) Steno Diabetes Center; 4) University of Aarhus; 5) University of Copenhagen; 6) Rigshospitalet; 7) Novo Nordisk Foundation Center for Basic Metabolic research. Background: Despite declining rates of late diabetic complications in other organ systems, renal complication rates do not decline to the same extent according to epidemiological studies. The objective was to describe renal outcomes over 21.2 years in patients with type 2 diabetes and microalbuminuria and the influence of an intensified, multifactorial treatment regimen. Methods: 160 patients with type 2 diabetes and microalbuminuria assigned to conventional or intensified multifactorial intervention targeting multiple risk factors in a prospective, open-label trial. Duration of the intervention was 8 years, where after all patients were recommended intensified treatment. Total follow-up of up to 21 years of 24 hour urinary albumin excretion rate and GFR (51Cr-EDTA-clearance) assessed at 6 study visits. Information on end stage renal disease (ESRD) and mortality was obtained from national registries. Outcome measures were progression to macroalbuminuria (>300 mg/24h), decline-rates of GFR and progression to end stage renal disease (ESRD) or death. Results: Progression to macroalbuminuria was reduced in the original intensive-therapy group with a hazard-ratio of 0.45 [95 % CI 0.28 – 0.74; p = 0.003]. The decline of GFR was 3.1 ml/min/year in the intensive-therapy group vs. 4.08 in the conventional therapy group [difference 0.51 – 1.51 ml/min/year; p < 0.001]. Progression to ESRD trended towards a decreased hazard with an adjusted (age and sex) hazard-ratio in the intensive group of 0.36 [95 % CI 0.12 – 1.05; p = 0.061], (n 5 vs. 10). ESRD combined with all-cause or cardiovascular mortality was significantly reduced; adjusted HR 0.53 [95 % CI 0.12 – 0.81; p = 0.003] and HR 0.35 [95 % CI 0.19 – 0.65; p = 0.001], respectively. Conclusions: Intensified, multifactorial treatment for 8 years in type 2 diabetes patients with microalbuminuria slows long-term progression in nephropathy and loss of renal function and reduces the risk of end stage renal disease and the mortality rate.