The early decline in renal function in patients with type 1 diabetes and proteinuria predicts the risk of end-stage renal disease

Jan Skupien^1,2, James H Warram¹, Adam M Smiles¹, Monika A Niewczas^1,2, Tomohito Gohda^1,2,3, Marcus G Pezzolesi^1,2, Diego Cantarovich⁴, Robert Stanton^1,5 and Andrzej S Krolewski^1,2

1. ¹Research and Clinic Divisions, Joslin Diabetes Center, Boston, Massachusetts, USA
2. ²Department of Medicine, Brigham and Women Hospital, Boston, Massachusetts, USA
3. ³Division of Nephrology, Department of Internal Medicine, Juntendo University School of Medicine, Tokyo, Japan
4. ⁴Institut de Transplantation, Urologie et Néphrologie, Nantes University Hospital, Nantes, France
5. ⁵Renal Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA

Kidney International (2012) 82, 589–597; doi:10.1038/ki.2012.189; published online 23 May 2012

Abstract:

The risk of end-stage renal disease (ESRD) remains high in patients with type 1 diabetes and proteinuria; however, little is known about the rate of decline in their renal function. To help determine this, we enrolled patients with type 1 diabetes and proteinuria whose estimated glomerular filtration rate (eGFR) was normal (equal to or above 60 ml/min per 1.73 m²). 

Using a minimum of five serial measurements of serum creatinine for 161 patients, we determined individual trajectories of eGFR change and the occurrence of ESRD during 5–18 years of follow-up. The rates were linear for 110 patients, for 24 the nonlinear rate was mild enough to satisfy a linear model, and the rates were clearly nonlinear for only 27 patients. Overall, in more than one-third of patients, the eGFR decline was less than 3.5 ml/min per 1.73 m² per year and the lifetime risk of ESRD could be considered negligible. In the remainder of patients, eGFR declined with widely different slopes and ESRD developed within 2 to 18 years. 

Based on up to 5 years observation, when renal function was within the normal range, the estimates of early eGFR slope predicted the risk of ESRD during subsequent follow-up better than the baseline clinical characteristics of glycated hemoglobin, blood pressure, or the albumin to creatinine ratio. Thus, the early slope of eGFR decline in patients with type 1 diabetes and proteinuria can be used to predict the risk of ESRD

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