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Multifactorial Treatment Effective at Improving Prognosis in Those with Diabetic Nephropathy

Cohort study determines how patient outcomes have changed since multifactorial treatment of CV risk factors and RAS inhibition have become standard of care…. 

Diabetic nephropathy is currently the leading cause of ESRD in both Europe and the U.S., and is a growing problem in other countries where the incidence of type 2 diabetes is on the rise. It is characterized by elevated urinary albumin excretion rate (UAER), increased BP, and decline in renal function, leading to ESRD. Patients with diabetic nephropathy are also at an increased risk of CV disease. A previous trial conducted at the Steno Diabetes Center showed that long-term multifactorial treatment consisting of aggressive control of blood pressure, lipids, and glucose, as well as lifestyle advice and acetylsalicylic acid reduced the progression of CVD and microvascular complications and decreased mortality by 50% in type 2 diabetics with microalbuminuria. Following this study, the Steno Diabetes Center implemented new treatment strategies for their patients in 2002 based on these results. For patients with elevated UAER, inhibition of the renin-angiotensin system (RAS) was also recommended based on previous studies showing that RAS inhibition can delay the onset of a doubling in serum creatinine, development of ESRD, or death. A second study was conducted at the Steno Diabetes Center to evaluate how these new treatment strategies affect the loss of renal function and the prognosis of patients with T2DM and DN from 2000-2010 by assessing change in glomerular filtration rate (GFR), doubling of plasma creatinine or progression to ESRD, and mortality rate. As previous studies only evaluated the effects of RAS inhibition up to 5 years, this study aimed to look at long-term effects of RAS inhibition past 5 years.

This study compared the results of the above outcomes to a previous cohort of patients followed with the same criteria, same methods, and at the same hospital at a time before multifactorial treatment was initiated and RAS inhibition was more commonly used. The present cohort consisted of 543 patients with T2DM and DN that were followed from 2000-2010. GFR was measured each year, with annual decline in GFR determined in those patients having at least 3 measurements over a minimum of 3 years. Plasma creatinine, development of ESRD, HbA1C, BP, UAER, and cholesterol were also assessed.

The mean GFR at baseline for this cohort of patients was 74 mL/min/1.73m2, and more than 93% of the patients were receiving RAS inhibition. During the median 7.8 years of this study, the mean annual GFR decline was 4.4 mL/min/1.73m2, compared to 5.2 mL/min/1.73m2 in the previous cohort. Development of ESRD or doubling of plasma creatinine occurred in 19% of patients, and 37% died from 3.3-8.8 years. Mortality from onset of DN was compared for the present cohort and the past cohort from 1983-2003, and crude mortality risk was found to be reduced by 42%. After adjustment for age, reduction in mortality was found to be even greater at 50%. A model accounting for competing risks of ESRD and death found prior CV disease and lower GFR to be predictors of mortality, while HbA1C, albuminuria, and low GFR were predictors of ESRD.

When compared to the previous cohort, the present cohort had significant improvement in modifiable risk factors such as total cholesterol, BMI, UAER, BP, HbA1C, and smoking status. Almost all patients in the present cohort were being treated with RAS inhibitors, compared to only about 50% is the previous cohort. As a result, renal prognosis was better, as seen with a slower deterioration of renal function. A decrease of almost 50% in all cause mortality was also seen after age adjustment. Findings for improvements in risk factors and outcomes also suggest that the benefits of multifactorial intervention may apply after onset of established DN as well. Systolic BP and cholesterol were not seen to have an impact on the outcomes of this study, which may be due to 83% of the participants being on statin therapy and >90% being on antihypertensive treatment.

Overall, the annual decline in GFR was seen to be lower in the present cohort, there was an improvement in the prognosis of type 2 diabetics with DN, and mortality was greatly reduced, which is thought to be due to better control of modifiable risk factors and a rise in the use of RAS inhibition.

Practice Pearls:
  • Annual decline in GFR was found to be significantly lower in the present cohort compared to patients in an earlier, comparable cohort.
  • Mortality was also greatly reduced in the present cohort, along with renal endpoints.
  • These improvements are thought to depend on better control of modifiable CV risk factors and to coincide with an increase in the use of RAS inhibition.

Andrѐsdόttir, G. et al. "Improved Survival and Renal Prognosis of Patients With Type 2 Diabetes and Nephropathy With Improved Control of Risk Factors" Diabetes Care. 2014; 38: 8p.