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Diabetic nephropathy is the leading cause of kidney disease in patients starting renal replacement therapy and affects approximately 40% of type 1 and type 2 diabetic patients. It increases the risk of death, mainly from cardiovascular causes, and is defined by increased urinary albumin excretion (UAE) in the absence of other renal diseases. Diabetic nephropathy is categorized into stages: microalbuminuria (UAE >20 microg/min and < or =199 microg/min) and macroalbuminuria (UAE > or =200 microg/min). Hyperglycemia, increased blood pressure levels, and genetic predisposition are the main risk factors for the development of diabetic nephropathy. Elevated serum lipids, smoking habits, and the amount and origin of dietary protein also seem to play a role as risk factors. Screening for microalbuminuria should be performed yearly, starting 5 years after diagnosis in type 1 diabetes or earlier in the presence of puberty or poor metabolic control. In patients with type 2 diabetes, screening should be performed at diagnosis and yearly thereafter. Patients with micro- and macroalbuminuria should undergo an evaluation regarding the presence of comorbid associations, especially retinopathy and macrovascular disease. Achieving the best metabolic control (A1c <7%), treating hypertension (<130/80 mmHg or <125/75 mmHg if proteinuria >1.0 g/24 h and increased serum creatinine), using drugs with blockade effect on the renin-angiotensin-aldosterone system, and treating dyslipidemia (LDL cholesterol <100 mg/dl) are effective strategies for preventing the development of microalbuminuria, in delaying the progression to more advanced stages of nephropathy and in reducing cardiovascular mortality in patients with type 1 and type 2 diabetes.

Objective: To analyze the changes in glomerular filtration rate (GFR), urinary albumin excretion rate (UAER), and blood pressure (BP) levels in a cohort of normoalbuminuric and normotensive type 1 diabetic patients., Research Design and Methods: This is an 8.4+/-2.1-year prospective study of 33 normotensive normoalbuminuric (24-h UAER <20 microg/min) type 1 diabetic patients. UAER (radioimmunoassay), GFR (51Cr-EDTA single-injection technique), and GHb (ion-exchange chromatography) were measured at baseline and at 1- to 2-year intervals., Results: The GFR decreased (137.6+/-16.5 to 116.4+/-21.3 ml x min(-1) x 1.73 m(-2) P < 0.05) during the follow-up period. GFR reduction (-0.20+/-0.29 ml x min(-1) x month(-1); P < 0.05) was associated with baseline GFR and mean GHb (R2 = 0.30; beta = 0.072; F = 6.54; P = 0.004). UAER was higher at the end of the study (3.7-7.1 microg/min; P = 0.017). Microalbuminuria was observed in two patients, while macroalbuminuria was observed in one. No changes in UAER were observed when these three patients were excluded from the analysis. Mean blood pressure (MBP) increased during the study (85.8+/-9.7 to 99.6+/-11.6 mmHg; P < 0.001). MBP at the end of the study was associated with age and GFR at baseline (R2 = 0.39; beta = 0.074; F = 9.64; P = 0.001)., Conclusions: In this cohort of normoalbuminuric normotensive type 1 diabetic patients, GFR decreased and BP levels increased during the follow-up period. The predictors for the GFR change were baseline GFR level and metabolic control. For end-of-study MBP, the predictor was baseline GFR level.

Objective: To assess the performance of urinary total protein measurements in timed 24-h urine collection (24-h UP) and in a diurnal random urine specimen (RUS) for the screening and diagnosis of overt diabetic nephropathy., Research Design and Methods: A total of 167 diabetic patients (20 type 1 and 147 type 2 diabetic patients; 78 women and 89 men), aged 20-84 years, collected 217 timed 24-h urine specimens. Albumin was measured by immunoturbidimetry, total protein by sulfosalicylic acid technique, and creatinine by Jaffe's method. According to the timed 24-h urinary albumin excretion rate (UAER), samples were divided into three groups: normoalbuminuric (NORMO) (UAER < 20 micrograms/min; n = 84), microalbuminuric (MICRO) (UAER 20-200 micrograms/min; n = 78), and macroalbuminuric (MACRO) (UAER > or = 200 micrograms/min; n = 55). Eighty-six patients also collected 105 RUSs (NORMO, n = 47; MICRO, n = 37; MACRO, n = 21), and urinary protein concentration (UPC) and urinary protein-to-creatinine ratio (UPCR) were measured. The receiver operating characteristics (ROC) curve approach was used to analyze the performance of the diagnostic tests., Results: Spearman's coefficient of correlation of 24-h UAER versus 24-h UP was 0.95 (P < 0.001), and of 24-h UAER versus UPC and UPCR were 0.77 and 0.72, respectively (P < 0.001). The calculated areas (+/- SEM) under the ROC curve for the diagnosis of over diabetic nephropathy were 0.9987 +/- 0.001 for 24-h UP, 0.9926 +/- 0.006 for UPC, and 0.9751 +/- 0.014 for UPCR. In the ROC curves, the first points with 100% sensitivity were 541 mg (95.7% specificity) for 24-h UP, 431 mg/l (92.9% specificity) for UPC, and 0.2 (76.2% specificity) for UPCR., Conclusions: Measurements of proteinuria presented almost perfect accuracy for the screening and diagnosis of overt diabetic nephropathy. Protein measurement in spot urine is a reliable and simple method for the screening and diagnosis of overt diabetic nephropathy.

Objective: To evaluate the evolution of glomerular filtration rate (GFR) and albumin excretion rate (AER) of normofiltering (NF) and hyperfiltering (HF) normoalbuminuric NIDDM patients., Research Design and Methods: A longitudinal study of 32 normoalbuminuric (AER < 20 micrograms/min) NIDDM patients and 20 age-, sex-, and BMI-matched normal individuals was done. Subjects had their GFR (51Cr-labeled EDTA single-injection method) measured at entry and after 40 and 60 months. At entry, 13 NIDDM patients had GFR values above the upper limit of the normal range in our laboratory (> 137 ml.min-1 x 1.73 m-2) and were considered as HF. In NIDDM patients, the 24-h AER (radioimmunoassay), HbA1c, urinary urea, and mean arterial blood pressure (MBP) were analyzed at entry and after 40 and 60 months., Results: There was a significant decline of GFR in NIDDM patients and normal subjects at 60 months. The decline was significantly greater in HF patients (-0.61 ml.min-1.month-1; P = 0.001) than in NF (-0, 18) and control subjects (-0, 14); the rate of change in NF and control subjects was the same (P > 0.05). In stepwise multiple regression analysis, with GFR decline as the dependent variable and GFR and AER at baseline, age and change in MBP, change in urinary urea, change in HbA1c, and change in therapy as independent variables, only baseline GFR (R2 = 0.19, P = 0.002) and age (R2 = 0.31, P = 0.048) were significantly related to the outcome. At 60 months, AER raised > 20 micrograms/min in three HF and in four NF patients. In logistic regression analysis, only higher initial AER (although still in the normal range; P = 0.037) and an increase in urinary urea (P = 0.021) were significantly related to the later development of microalbuminuria., Conclusions: The GFR of normoalbuminuric NIDDM patients declines significantly over 60 months. This decline is associated to baseline GFR and age. HF NIDDM patients show a faster decline in GFR than NF patients, whose GFR falls at a rate that is compatible with the age-related change observed in normal control subjects. The development of microalbuminuria is related to higher baseline AER and to increases in urinary urea and is similar in NF (4 of 19) and HF (3 of 13) NIDDM patients (P > 0.05).

Objective: To compare the effect of a normal protein diet (test diet) in which chicken and fish were substituted for red meat with a low-protein diet (LPD) on glomerular filtration rate (GFR) in normoalbuminuric insulin-dependent-diabetes mellitus (IDDM) patients., Research Design and Methods: A crossover randomized clinical trial was performed in 15 normoalbuminuric IDDM patients, 9 normofiltering, and 6 hyperfiltering patients. They followed three diets for a 3-week period each: a usual diet (UD), an LPD (0.5 g.kg-1.day-1 of proteins, 7% calories as protein, 33% as fat, and 60% as carbohydrates), and a normoproteic isocaloric test diet in which white meat (chicken and fish) was substituted for red meat of the UD. At the end of each diet, a clinical evaluation and measurements of GFR (51Cr-ethylenediaminetetraacetate (EDTA) single injection technique), urinary albumin excretion (UAE), and plasma amino acids were performed. Dietary compliance was assessed by a 24-h urinary urea and weekly interviews with the dietitian., Results: In all diabetic patients, GFR after the LPD (114.9 +/- 16.5 ml.min-1 x 1.73 m-2) and after the test diet (122.7 +/- 16.7 ml.min-1 x 1.73 m-2) was significantly lower than after the UD (132.0 +/- 27.7 ml.min-1 x 1.73 m-2) (P = 0.001). Similar results were found in the hyperfiltering group: after UD = 161.1 +/- 15.4 ml.min-1 x 1.73 m-2, after LPD = 129.8 +/- 9.0 ml.min-1 x 1.73 m-2, and after the test diet = 136.5 +/- 3.1 ml.min-1 x 1.73 m-2, (P < 0.001). In the normofiltering group, no significant changes in GFR were observed after the three diets. Metabolic control, nutritional indexes, blood pressure (BP), and UAE did not change after the three diets in all patients., Conclusions: A normoproteic diet with chicken and fish as the only meat protein source decreases the GFR in the hyperfiltering normoalbuminuric IDDM patients. The GFR reduction after this diet is similar to that observed after an LPD.