Macroalbuminuria and Renal Pathology in First Nation Youth With Type 2 Diabetes

OBJECTIVE To determine the prevalence of macroalbuminuria and to describe the clinical and renal pathological changes associated with macroalbuminuria in a population of Canadian First Nation children and adolescents with type 2 diabetes. RESEARCH DESIGN AND METHODS We conducted a retrospective chart review at a single tertiary care pediatric diabetes center, and a case series was constructed. We collected data on microalbuminuria (≥3 mg/mmol creatinine [26.5 mg/g]) and macroalbuminuria (≥28 mg/mmol creatinine [247.5 mg/g]), estimated glomerular filtration rate, renal pathology, and aggravating risk factors (poor glycemic control, obesity, hypertension, glomerular hyperfiltration, hypercholesterolemia, smoking, and exposure to diabetes in utero). RESULTS We reviewed 90 charts of children and adolescents with type 2 diabetes. A total of 53% had at least one random urine albumin-to-creatinine ratio ≥3 mg/mmol (26.5 mg/g). There were 14 of 90 (16%) who had persistent macroalbuminuria at or within 8 years of diagnosis of diabetes. Of these 14 subjects, 1 had orthostatic albuminuria and 3 had spontaneous resolution of albuminuria. A total of 10 had renal biopsies performed. There were 9 of 10 who exhibited immune complex disease or glomerulosclerosis, and none had classic diabetic nephropathy. CONCLUSIONS This study suggests that the diagnosis of renal disease in children with type 2 diabetes cannot be reliably determined by clinical and laboratory findings alone. Renal biopsy is necessary for accurate diagnosis of renal disease in children and adolescents with type 2 diabetes and macroalbuminuria. The additional burden of nondiabetic kidney disease may explain the high rate of progression to end-stage kidney failure in this population.

[1]  P. Sarafidis Obesity, insulin resistance and kidney disease risk: insights into the relationship , 2008, Current opinion in nephrology and hypertension.

[2]  P. Bennett,et al.  Effect of youth-onset type 2 diabetes mellitus on incidence of end-stage renal disease and mortality in young and middle-aged Pima Indians. , 2006, JAMA.

[3]  J. Dimartino-Nardi,et al.  Prevalence of Retinopathy and Microalbuminuria in Pediatric Type 2 Diabetes Mellitus , 2006, Journal of pediatric endocrinology & metabolism : JPEM.

[4]  J. Flynn,et al.  Microalbuminuria and abnormal ambulatory blood pressure in adolescents with type 2 diabetes mellitus. , 2005, The Journal of pediatrics.

[5]  A. Hattersley,et al.  β-Cell Dysfunction, Insulin Sensitivity, and Glycosuria Precede Diabetes in Hepatocyte Nuclear Factor-1α Mutation Carriers , 2005 .

[6]  Isabel Rey Madeira,et al.  The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. , 2004, Pediatrics.

[7]  B. Rosner,et al.  The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents , 2004 .

[8]  R. Nelson Intrauterine determinants of diabetic kidney disease in disadvantaged populations. , 2003, Kidney international. Supplement.

[9]  H. Dean,et al.  The Prevalence of the HNF-1α G319S Mutation in Canadian Aboriginal Youth With Type 2 Diabetes , 2002 .

[10]  M. Praga Obesity--a neglected culprit in renal disease. , 2002, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[11]  J. Davies,et al.  Genes and Proteins in Renal Development , 2002, Nephron Experimental Nephrology.

[12]  G. Mazzucco,et al.  Different patterns of renal damage in type 2 diabetes mellitus: a multicentric study on 393 biopsies. , 2002, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[13]  U. Alon,et al.  Proteinuria and focal segmental glomerulosclerosis in severely obese adolescents. , 2001, The Journal of pediatrics.

[14]  A F Roche,et al.  CDC growth charts: United States. , 2000, Advance data.

[15]  G. Eisenbarth,et al.  Diabetes-associated autoantibodies in aboriginal children , 2000, The Lancet.

[16]  J. Vilar,et al.  Adverse effects of hyperglycemia on kidney development in rats: in vivo and in vitro studies. , 1999, Diabetes.

[17]  B. Zinman,et al.  Hepatocyte nuclear factor-1 alpha G319S. A private mutation in Oji-Cree associated with type 2 diabetes. , 1999, Diabetes care.

[18]  T. K. Young,et al.  Screening for type-2 diabetes in aboriginal children in northern Canada , 1998, The Lancet.

[19]  H. Morgenstern,et al.  Intrauterine diabetes exposure and the risk of renal disease in diabetic Pima Indians. , 1998, Diabetes.

[20]  R. Dyck,et al.  Non-diabetic end-stage renal disease among Saskatchewan aboriginal people. , 1998, Clinical and investigative medicine. Medecine clinique et experimentale.

[21]  H. Dean NIDDM-Y in First Nation Children in Canada , 1998, Clinical pediatrics.

[22]  B. Bulloch,et al.  Excess prevalence of non diabetic renal disease in native American children in Manitoba , 1996, Pediatric Nephrology.

[23]  R. Dyck,et al.  Rates and outcomes of diabetic end-stage renal disease among registered native people in Saskatchewan. , 1994, CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne.

[24]  E. Ritz,et al.  Renal hemodynamics in recent-onset type II diabetes. , 1992, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[25]  S. Daniels Natural history of type 2 diabetes , 2011 .

[26]  M. Fowler Clinical Practice Recommendations , 2009, Clinical Diabetes.

[27]  A. Hattersley,et al.  Beta-cell dysfunction, insulin sensitivity, and glycosuria precede diabetes in hepatocyte nuclear factor-1alpha mutation carriers. , 2005, Diabetes care.

[28]  H. Dean,et al.  The prevalence of the HNF-1alpha G319S mutation in Canadian aboriginal youth with type 2 diabetes. , 2002, Diabetes care.

[29]  American Diabetes Association: clinical practice recommendations 2002. , 2002, Diabetes care.