Diabetic nephropathy is the leading cause of kidney disease in patients starting renal replacement therapy and affects ϳ40% 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 Ͼ20 g/min and Յ199 g/min) and macroalbuminuria (UAE Ն200 g/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 Ͻ7%), treating hypertension (Ͻ130/80 mmHg or Ͻ125/75 mmHg if proteinuria Ͼ1.0 g/24 h and increased serum creatinine), using drugs with blockade effect on the reninangiotensin-aldosterone system, and treating dyslipidemia (LDL cholesterol Ͻ100 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. Diabetes Care 28:176 -188, 2005DEFINITION AND EPIDEMIOLOGY -Diabetic nephropathy is the leading cause of chronic kidney disease in patients starting renal replacement therapy (1) and is associated with increased cardiovascular mortality (2). Diabetic nephropathy has been classically defined by the presence of proteinuria Ͼ0.5 g/24 h. This stage has been referred to as overt nephropathy, clinical nephropathy, proteinuria, or macroalbuminuria. In the early 1980s, seminal studies from Europe revealed that small amounts of albumin in the urine, not usually detected by conventional methods, were predictive of the later development of proteinuria in type 1 (3-5) and type 2 (6) diabetic patients. This stage of renal involvement was termed microalbuminuria or incipient nephropathy.The cumulative incidence of microalbuminuria in patients with type 1 diabetes was 12.6% over 7.3 years according to the European Diabetes (EURODIAB) Prospective Complications Study Group (7) and ϳ33% in an 18-year follow-up study in Denmark (8). In patients with type 2 diabetes, the incidence of microalbuminuria was 2.0% per year and the prevalence 10 years after diagnosis 25% in the U.K. Prospective Diabetes Study (UKPDS) (9). Proteinuria occurs in 15-40% of patients with type 1 diabetes, with a peak incidence around 15-20 years of diabetes (8,10,11). In patients with t...

S20 Introduction S22 Summary of recommendation statements and practice points S30 Chapter 1: Comprehensive care in patients with diabetes and CKD S39 Chapter 2: Glycemic monitoring and targets in patients with diabetes and CKD S47 Chapter 3: Lifestyle interventions in patients with diabetes and CKD S58 Chapter 4: Antihyperglycemic therapies in patients with type 2 diabetes (T2D) and CKD S79 Chapter 5: Approaches to management of patients with diabetes and CKD S87 Methods for guideline development S96 Biographic and disclosure information S106 Acknowledgments S107 References The development and publication of this guideline were supported by KDIGO. The opinions or views expressed in this professional education supplement are those of the authors and do not necessarily reflect the opinions or recommendations of the International Society of Nephrology or Elsevier. Dosages, indications, and methods of use for products that are referred to in the supplement by the authors may reflect their clinical experience or may be derived from the professional literature or other clinical sources. Because of the differences between in vitro and in vivo systems and between laboratory animal models and clinical data in humans, in vitro and animal data may not necessarily correlate with clinical results.

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Increased urinary albumin excretion rate is widely accepted as the first clinical sign of diabetic nephropathy. However, it is possible that some diabetic patients could first manifest reduced glomerular filtration rate (GFR) or hypertension. Relatively advanced diabetic renal lesions can be present in some diabetic patients with long-standing normoalbuminuria, and this might indicate increased risk of progression to microalbuminuria and then to overt diabetic nephropathy. The aim of this study was to identify a group of normoalbuminuric type 1 diabetic patients with low GFR and compare them with normoalbuminuric patients with normal GFR. Altogether, 105 normoalbuminuric type 1 diabetic patients with at least 10 years of diabetes duration that had a renal biopsy performed for research purposes were studied. Patients were divided according to GFR into groups with normal (>90 ml ⅐ min -1 ⅐ 1.73 m -2 ) or reduced (<90 ml ⅐ min -1 ⅐ 1.73 m -2 ) GFR. Clinical and renal structural parameters were compared between these two groups. Glomerular structural parameters were estimated by electron microscopic morphometry. The 23 patients with reduced GFR had more advanced diabetic glomerular lesions. The finding of reduced GFR was much more common among female patients, particularly if retinopathy and/or hypertension were also present. This report confirms that reduced GFR occurs among long-standing normoalbuminuric type 1 diabetic patients and is associated with more advanced diabetic glomerular lesions and, probably, with increased risk of progression. For these reasons, we suggest that regular measurements of GFR be performed in long-standing normoalbuminuric type 1 diabetic female diabetic patients, especially in those with retinopathy or hypertension. Diabetes 52