Discovery of New Markers for Diabetic Kidney Disease Progression

Diabetic kidney disease (diabetic nephropathy) is a serious and potentially life threatening complication of type 1 diabetes (T1D). However, not all people with T1D go on to develop diabetic kidney disease. In order to prevent the onset and slow the progression of kidney disease, tools are needed to help determine the population most at risk for this complication. In this study, 628 patients with T1D and normal kidney function were studied for markers that might predict those likely to develop diabetic kidney disease. About 11% of these subjects went on to develop kidney disease over the 12 years of follow up. High levels of two proteins in the blood, TNF receptors 1 and 2 (TNFR1 and TNFR2), were strongly associated with the risk of developing diabetic kidney disease. Blood levels of the protein that activates these receptors did not predict progression to kidney disease. While more studies need to be conducted to understand what role TNFR1 and TNFR2 might play in the development of kidney disease, these findings suggest that measuring blood levels of TNFR1 and TNFR2 could be indicators for risk of this complication. Another, but separate recent finding demonstrated that elevated blood concentrations of TNFR1 and TNFR2 also predicted development of end-stage kidney disease in patients with type 2 diabetes. This increases the potential value of TNFR1 and TNFR2 as possible indicators of kidney disease in both T1D and T2D.

References:

Gohda, T., Niewczas, MA., Ficociello, LH., Walker, WH., Skupien, J., Rosetti, F., Cullere, X., Johnson, AC., Crabtree, G., Smiles, AM., Mayadas, TN., Warram, JH., and Krolewski, AS., (2012). Circulating TNF Receptors 1 and 2 Predict Stage 3 CKD in Type 1 Diabetes. J. Am Soc Nephrol. 23: January.

Ramifications for Individuals with Type 1 Diabetes:

It is difficult to predict progression of diabetic kidney disease. Additional diagnostic tests, such as ones based on these proteins, should help identify patients most at risk of progression to later stage disease in order to target existing treatment and help select the most appropriate patients for clinical trials to test new therapies.

JDRF Involvement:

JDRF funded this work via a grant to Dr. Andrzej Krolewski and a postdoctoral fellowship to Dr. Jan Skupien.