Diabetic nephropathy develops in less than half of all patients with diabetes. To study heredity as a possible risk factor for diabetic kidney disease, we examined the concordance rates for diabetic nephropathy in two sets of families in which both probands and siblings had diabetes mellitus. In one set, the probands (n = 11) had no evidence of diabetic nephropathy, with normal creatinine clearance and a urinary albumin excretion rate below 45 mg per day. In the other set, the probands (n = 26) had undergone kidney transplantation because of diabetic nephropathy. Evidence of nephropathy was found in 2 of the 12 diabetic siblings of the probands without nephropathy (17 percent). Of the 29 diabetic siblings of probands with diabetic nephropathy, 24 (83 percent) had evidence of nephropathy (P less than 0.001), including 12 with end-stage renal disease. No significant differences were noted between the sibling groups with respect to the duration of diabetes, blood pressure, glycemic control, or glycosylated hemoglobin levels. Logistic regression analysis found nephropathy in the proband to be the only factor significantly predictive of the renal status of the diabetic sibling. We conclude that diabetic nephropathy occurs in familial clusters. This is consistent with the hypothesis that heredity helps to determine susceptibility to diabetic nephropathy. However, this study cannot rule out the possible influences of environmental factors shared by siblings.
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Department of Medicine, University of Minnesota, Minneapolis.
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Locatelli, F., Canaud, B., Eckardt, K.-U., Stenvinkel, P., Wanner, C., Zoccali, C.
(2003). The importance of diabetic nephropathy in current nephrological practice. Nephrol Dial Transplant
18: 1716-1725
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Wang, Y., Ng, M. C.Y., Lee, S.-C., So, W.-Y., Tong, P. C.Y., Cockram, C. S., Critchley, J. A.J.H., Chan, J. C.N.
(2003). Phenotypic Heterogeneity and Associations of Two Aldose Reductase Gene Polymorphisms With Nephropathy and Retinopathy in Type 2 Diabetes. Diabetes Care
26: 2410-2415
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Susztak, K., Sharma, K., Schiffer, M., McCue, P., Ciccone, E., Bottinger, E. P.
(2003). Genomic Strategies for Diabetic Nephropathy. J. Am. Soc. Nephrol.
14: S271-278
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Ohmit, S. E., Flack, J. M., Peters, R. M., Brown, W. W., Grimm, R.
(2003). Longitudinal Study of the National Kidney Foundation's (NKF) Kidney Early Evaluation Program (KEEP). J. Am. Soc. Nephrol.
14: S117-121
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Iyengar, S. K., Fox, K. A., Schachere, M., Manzoor, F., Slaughter, M. E., Covic, A. M., Orloff, S. M., Hayden, P. S., Olson, J. M., Schelling, J. R., Sedor, J. R.
(2003). Linkage Analysis of Candidate Loci for End-Stage Renal Disease due to Diabetic Nephropathy. J. Am. Soc. Nephrol.
14: S195-201
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(2003). Genetic Determinants of Diabetic Nephropathy: The Family Investigation of Nephropathy and Diabetes (FIND). J. Am. Soc. Nephrol.
14: S202-204
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Amin, R., Schultz, C., Ong, K., Frystyk, J., Dalton, R. N., Perry, L., Orskov, H., Dunger, D. B.
(2003). Low IGF-I and Elevated Testosterone During Puberty in Subjects With Type 1 Diabetes Developing Microalbuminuria in Comparison to Normoalbuminuric Control Subjects: The Oxford Regional Prospective Study. Diabetes Care
26: 1456-1461
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Huang, C., Kim, Y., Caramori, M. L. A., Fish, A. J., Rich, S. S., Miller, M. E., Russell, G. B., Mauer, M.
(2002). Cellular Basis of Diabetic Nephropathy: II. The Transforming Growth Factor-{beta} System and Diabetic Nephropathy Lesions in Type 1 Diabetes. Diabetes
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Lane, P. H.
(2002). Diabetic kidney disease: impact of puberty. Am. J. Physiol. Renal Physiol.
283: F589-F600
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Fava, S., Hattersley, A. T.
(2002). The role of genetic susceptibility in diabetic nephropathy: evidence from family studies. Nephrol Dial Transplant
17: 1543-1546
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Rogus, J. J., Warram, J. H., Krolewski, A. S.
(2002). Genetic Studies of Late Diabetic Complications: The Overlooked Importance of Diabetes Duration Before Complication Onset. Diabetes
51: 1655-1662
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Caramori, M. L., Kim, Y., Huang, C., Fish, A. J., Rich, S. S., Miller, M. E., Russell, G., Mauer, M.
(2002). Cellular Basis of Diabetic Nephropathy: 1. Study Design and Renal Structural-Functional Relationships in Patients With Long-Standing Type 1 Diabetes. Diabetes
51: 506-513
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Schena, F. P., Cerullo, G., Rossini, M., Lanzilotta, S. G., D'Altri, C., Manno, C.
(2002). Increased Risk of End-Stage Renal Disease in Familial IgA Nephropathy. J. Am. Soc. Nephrol.
13: 453-460
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Solini, A., Dalla Vestra, M., Saller, A., Nosadini, R., Crepaldi, G., Fioretto, P.
(2002). The Angiotensin-Converting Enzyme DD Genotype Is Associated With Glomerulopathy Lesions in Type 2 Diabetes. Diabetes
51: 251-255
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Fava, S., Azzopardi, J., Ellard, S., Hattersley, A. T.
(2001). ACE Gene Polymorphism as a Prognostic Indicator in Patients With Type 2 Diabetes and Established Renal Disease. Diabetes Care
24: 2115-2120
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Huang, W., Gallois, Y., Bouby, N., Bruneval, P., Heudes, D., Belair, M.-F., Krege, J. H., Meneton, P., Marre, M., Smithies, O., Alhenc-Gelas, F.
(2001). Genetically increased angiotensin I-converting enzyme level and renal complications in the diabetic mouse. Proc. Natl. Acad. Sci. USA
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Tarnow, L., Grarup, N., Hansen, T., Parving, H.-H., Pedersen, O.
(2001). Diabetic microvascular complications are not associated with two polymorphisms in the GLUT-1 and PC-1 genes regulating glucose metabolism in Caucasian type 1 diabetic patients. Nephrol Dial Transplant
16: 1653-1656
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Nannipieri, M., Manganiello, M., Pezzatini, A., De Bellis, A., Seghieri, G., Ferrannini, E.
(2001). Polymorphisms in the hANP (Human Atrial Natriuretic Peptide) Gene, Albuminuria, and Hypertension. Hypertension
37: 1416-1422
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Poirier, O., Nicaud, V., Vionnet, N., Raoux, S., Tarnow, L., Vlassara, H., Parving, H.-H., Cambien, F.
(2001). Polymorphism Screening of Four Genes Encoding Advanced Glycation End-Product Putative Receptors: Association Study With Nephropathy in Type 1 Diabetic Patients. Diabetes
50: 1214-1218
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Mead, P. A., Wilkinson, R., Thomas, T. H.
(2001). Na/Li Countertransport Abnormalities in Type 1 Diabetes With and Without Nephropathy Are Familial. Diabetes Care
24: 527-532
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HADJADJ, S., BELLOUM, R., BOUHANICK, B., GALLOIS, Y., GUILLOTEAU, G., CHATELLIER, G., ALHENC-GELAS, F., MARRE, M.
(2001). Prognostic Value of Angiotensin-I Converting Enzyme I/D Polymorphism for Nephropathy in Type 1 Diabetes Mellitus: A Prospective Study. J. Am. Soc. Nephrol.
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Zychma, M. J., Zukowska-Szczechowska, E., Lacka, B. I., Grzeszczak, W.
(2000). Angiotensinogen M235T and chymase gene CMA/B polymorphisms are not associated with nephropathy in type II diabetes. Nephrol Dial Transplant
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Shpichinetsky, V., Raz, I., Friedlander, Y., Goldschmidt, N., Wexler, I. D., Ben-Yehuda, A., Friedman, G.
(2000). The Association between Two Common Mutations C677T and A1298C in Human Methylenetetrahydrofolate Reductase Gene and the Risk for Diabetic Nephropathy in Type II Diabetic Patients. J. Nutr.
130: 2493-2497
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van Ittersum, F. J., de Man, A. M. E., Thijssen, S., de Knijff, P., Slagboom, E., Smulders, Y., Tarnow, L., Donker, A. J. M., Bilo, H. J. G., Stehouwer, C. D. A.
(2000). Genetic polymorphisms of the renin-angiotensin system and complications of insulin-dependent diabetes mellitus. Nephrol Dial Transplant
15: 1000-1007
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Tarnow, L., Stehouwer, C. D. A., Emeis, J. J., Poirier, O., Cambien, F., Hansen, B. V., Parving, H.-H.
(2000). Plasminogen activator inhibitor-1 and apolipoprotein E gene polymorphisms and diabetic angiopathy. Nephrol Dial Transplant
15: 625-630
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SOMA, J., SAITO, T., TAGUMA, Y., CHIBA, S., SATO, H., SUGIMURA, K., OGAWA, S., ITO, S.
(2000). High Prevalence and Adverse Effect of Hepatitis C Virus Infection in Type II Diabetic-Related Nephropathy. J. Am. Soc. Nephrol.
11: 690-699
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GAMBARO, G., VAN DER WOUDE, F. J.
(2000). Glycosaminoglycans: Use in Treatment of DiabeticNephropathy. J. Am. Soc. Nephrol.
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