Nephropathy of Diabetes Mellitus



Nephropathy of Diabetes Mellitus


L. Leighton Hill



Diabetes mellitus is the leading cause of end-stage renal disease (ESRD) worldwide. In the United States, diabetic nephropathy accounts for approximately 40% of patients entering dialysis and transplantation programs. Thirty to 40% of patients with insulin-dependent diabetes mellitus (IDDM) eventually develop diabetic nephropathy, and most of these cases progress to ESRD unless preventive and therapeutic measures prove effective over the long term. ESRD from diabetes rarely is seen in the second decade of life, but it is a common development in the third, fourth, and fifth decades. Of great interest and at least partly unexplained at this time is the finding that more than one-half of patients with IDDM do not develop significant nephropathy, regardless of the duration and sometimes the degree of metabolic control. With the tremendous increase in obesity among children, adolescents, and young adults in this country, type 2 or non–insulin-dependent diabetes mellitus (NIDDM) is an emerging epidemic in the pediatric age group. Nephropathy appears to be at least as common in type 2 diabetes as in type 1, so a further significant increase in diabetic nephropathy and ESRD can be expected to occur during the next several decades.


NATURAL HISTORY

The development of significant dipstick-positive proteinuria (30 mg/dL or higher) usually is the first clinical sign of the nephropathy of diabetes mellitus (type 1 or type 2). However, before proteinuria develops, several hemodynamic and morphologic changes occur in the kidney. At the time of diagnosis of type 1 diabetes, increases in glomerular filtration rate, renal blood flow, and filtration fraction are present. Renal size often is increased, and microalbuminuria may be present. These early functional changes appear to be related to glycemic control because improvement in metabolic control is associated with a return of these parameters toward normal. The disappearance of microalbuminuria usually is followed by several years of normal albuminuria. By 5 to 15 years’ duration, 30% to 40% of the patients with diabetes mellitus develop persistent microalbuminuria. The prevalence of hypertension, a condition that accelerates the progression of kidney disease, is greater in diabetic patients with microalbuminuria. The definition of microalbuminuria varies, but the most widely accepted is that of Mogensen, who uses a rate between 20 and 200 μg/minute, with less than 20 μg/minute classified as normal albuminuria and more than 200 μg/minute classified as clinical or overt proteinuria. A value of 20 μg/minute equals approximately 30 mg/day, and 200 μg/minute equals just under 300 mg/24 hours. Random spot urines measuring albumin-to-creatinine ratios have been found to be reliable in the detection of microalbuminuria and overt proteinuria. An albumin-over-creatinine ratio of 0.5 or higher is indicative of clinical or overt proteinuria. Many investigators consider microalbuminuria a reliable predictor of later overt clinical proteinuria, chronic renal insufficiency, and other microvascular complications. However, because microalbuminuria can regress, a demonstration of persistence of microalbuminuria is important. Clinically detectable overt proteinuria in diabetic patients with nephropathy generally is found between 10 and 30 years after the diagnosis of IDDM has been established, with the peak incidence occurring 15 to 20 years after diagnosis. Azotemia usually occurs within 5 to 10 years of the onset of clinically significant proteinuria, and ESRD usually ensues within 1 to 2 years of the development of azotemia. Hypertension is present in approximately three-fourths of patients with significant nephropathy, and the nephrotic syndrome occurs in 5% to 10%. However, this sequence and the timing are not invariable, and extensive nephropathy can occur without proteinuria. The timing and sequence of changes in the kidney in type 2 diabetes in children and adolescents have not been studied as thoroughly, and because the onset of type 2 disease is not as abrupt and distinct, the duration of diabetes often is not as clear. Numerous therapeutic interventions apparently have been successful in altering the natural course of diabetic nephropathy.


PATHOLOGY

The most common pathologic lesion seen in diabetic nephropathy (in type 1 or type 2 diabetes) is diffuse glomerular sclerosis, a generalized widening of the glomerular mesangium with matrix material. The matrix material ultimately invades the
subendothelial space, occludes the capillary lumina, and reduces filtration surface. Other pathologic changes include nodular glomerular sclerosis (Kimmelstiel-Wilson lesion), thickening of the glomerular basement membrane, afferent and efferent glomerular arteriolar hyalinosis, tubulointerstitial changes, and “capsular drops” in the parietal Bowman capsule. The structural progression of nephropathy appears to be similar in type 1 and type 2 diabetes.

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Jul 24, 2016 | Posted by in ORTHOPEDIC | Comments Off on Nephropathy of Diabetes Mellitus
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