Diabetes Mellitus (DM)



The metabolic and physiological consequences of diabetes mellitus regularly involve the kidney and lead to renal dysfunction. Although diabetes almost inevitably affects all elements of the kid­ney simultaneously, any given patient may pre­sent with features typically associated with one of the clinical patterns discussed above. Therefore, renal disease in some patients will present as an interstitial process, typically with hypertension and Type IV RTA. Others will have glomerular proteinuria as the initial clinical manifestation of the diabetic renal lesion. In either group, urinary tract infections and pyelonephritis frequently complicate the course of the diabetes.

Diabetic glomerulosclerosis is one of the more significant of the diabetic renal lesions and is the most frequent cause of end-stage renal failure in these patients. Glomerular disease occurs in about half of persons with juvenile-onset, insulin-de­pendent (Type I] diabetes mellitus. The onset of clinically apparent glomerular involvement oc- s curs, in most patients, between 15 and 20 years after the initial diagnosis of DM. Renal disease in DM is first seen as asymptomatic, episodic pro­teinuria, but progression to fixed, moderate to heavy proteinuria occurs rapidly, within one to two years. Glomerulopathy develops uncom­monly in Type I diabetics who are free of pro­teinuria 20 years after diagnosis of DM.

Once proteinuria becomes established, a rapid fall in GFR follows, with the course to end-stage renal failure being complete within five years. Al­though the incidence of the nephrotic syndrome is low in DM, the prevalence of Type I DM in the population makes diabetic glomerulopathy a sig­nificant cause of adult nephrotic syndrome. The appearance of hypertension usually parallels that of proteinuria. Diabetic retinopathy is an invar­iant finding in patients with diabetic glomerulo­pathy and has led to the designation of the reti-norenal syndrome for persons so affected. The onset of the nephrotic syndrome in an individual having Type I DM for less than 10 years, or in the absence of diabetic retinopathy, should alert one to consider a nondiabetic etiology of the renal dis­ease.
The classic glomerular lesion in DM is Kim-melstiel-Wilson nodular glomerulosclerosis. This appears as hyalin nodules lying in the center of peripheral capillary loops, causing the capillaries to lie in a ring surrounding the nodule. This pat­tern is actually seen in less than 25 per cent of cases of diabetic glomerulopathy. The more typ­ical finding, seen most often when heavy protein­uria is present, is that of diffuse glomeruloscle­rosis associated with arteriosclerosis of both afferent and efferent arterioles. Basement mem­brane thickening and interstitial atrophy may be prominent. Immunofluorescent staining may show linear IgG and/or C3 deposition along cap­illaries, but this is thought to represent nonspe­cific trapping. Electron microscopy reveals dif­fuse increases in mesangial matrix material and generalized thickening of basement membranes by BM-like material.

Renal insufficiency is the major limit to sur­vival in diabetics under 40 years of age. Treatment of end-stage renal disease in diabetics is more dif­ficult than in nondiabetic patients, and the sur­vival of diabetics on hemodialysis is less than that for nondiabetics. Continuous ambulatory perito­neal dialysis (CAPD) offers a better prognosis for many diabetics with renal failure. Death from car­diovascular complications is highly likely for the diabetic on dialysis. The most promising treat­ment for diabetic renal failure appears to be renal transplantation from a living, related donor. The diabetic lesion does recur in transplanted kidneys but has not been a significant cause of transplant kidney failure.

A significant number of diabetics display a prominent and characteristic interstitial lesion that appears related to ischemic injury. The syn­drome of hyporeninemic hypoaldosteronism is a feature of this lesion and is a major cause of Type IV renal tubular acidosis. These patients will typ­ically present with hyperkalemia and hyperchlo-remic metabolic acidosis with only a modest re­duction in GFR. Hypertension is prominent in this syndrome. The clinical features of the interstitial lesion almost inevitably merge into the glomer­ular syndrome of diabetic glomerulosclerosis as the patient approaches end-stage renal failure.

Two other renal conditions frequently compli­cate the course of diabetic nephropathy. Papillary necrosis, especially in conjunction with renal in­fection, is common in diabetics. The sloughing of papillary tissue may cause acute ureteral obstruc­tion with colic, may be associated with hematuria and passage of tissue in the urine, and may be identified by the calyceal irregularity seen on IVP. Although bacteriuria is no more prevalent in di­abetics than nondiabetics, the syndrome of acute pyelonephritis, especially in the presence of uri­nary obstruction with papillary tissue, is a more frequent outcome of untreated bacteriuria in the diabetic.





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