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S M Mauer

Publications and source records attributed to S M Mauer.

242 records · Page 14Linked to original sources
PubMedDate not supplied

Structural-functional relationships in type I insulin-dependent diabetes mellitus in humans.

The major renal pathologic changes of diabetes include thickening of all renal extracellular basement membranes and mesangial matrix and, to a lesser extent, mesangial cell expansion. Two renal lesions appear critical in diabetic nephropathy. Mesangial expansion out of proportion to the size of the glomerulus is closely and inversely related to measures of peripheral capillary wall filtration surface and to clinical features of proteinuria, hypertension, and decreasing glomerular filtration rate (GFR). Arteriolar hyalinosis is related to global glomerulosclerosis, and both are correlated with the clinical features of nephropathy. These lesions are markedly advanced by the time renal dysfunction is clinically detectable. Relationships of structure and function early in the course of the diabetes have not been examined satisfactorily.

Arterioles↗
PubMedDate not supplied

The effects of normalization of dietary protein intake and carotid artery ligation on the renal autoregulatory abnormalities of streptozotocin diabetic rats.

We studied renal autoregulation in nondiabetic and streptozotocin diabetic Münich-Wistar rats 6 weeks after diabetes induction. We had previously shown that diabetic rats had greater preservation of renal blood flow (RBF) at reduced renal perfusion pressures (RPP) than control rats and speculated that this could be due to higher protein intake in the diabetic rats. Because of hyperphagia, the diabetic rats in the present study on a 24% protein diet (D-24) had 70% or greater increase in dietary protein intake compared to controls on the same diet (C-24). Diabetic rats on a 14% protein diet (D-14) had a dietary protein intake similar to C-24 and less than that of D-24 animals. Baseline glomerular filtration rate (GFR) and renal blood flow were lower and renal vascular resistance (RVR) was higher in the D-14 compared to the C-24 or D-24 rats. Nonetheless, at markedly reduced RPP both diabetic groups had better sustained RBFs and lower RVRs than the controls. Thus, increased dietary protein intake cannot explain the autoregulatory abnormalities in diabetes. Bilateral carotid artery ligation increased systemic blood pressure similarly in the C-24, D-24, and D-14 rats. All three groups responded with increased RVR to carotid artery ligation. Following carotid artery ligation, differences were no longer seen between diabetic and control rats for RBF at reduced RPPs. These studies indicate that diabetic rats are capable of generating increased RVR, ruling out impaired vascular constrictive capacity as an explanation of these hemodynamic abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

The effect of cyclosporine on native renal function in non-uremic diabetic recipients of pancreas transplants.

In order to assess the nephrotoxic effect of cyclosporine on native kidneys in pancreas transplant recipients, serum creatinine and creatinine clearance levels were determined before and serially after pancreas transplantation alone in 33 non-uremic Type I diabetic patients. The mean serum creatinine level before transplant was 1.0 +/- 0.3 mg/dl, and the values at 2 weeks, 6 months, 1 to 2 years, and greater than 2 years after transplant were, respectively, 1.5 +/- 0.6, 1.4 +/- 0.4, 1.4 +/- 0.5, and 1.5 +/- 0.2 mg/dl. Mean creatinine clearance level before transplant was 90 +/- 34 ml/min, and the values at the corresponding time points were 55 +/- 23, 62 +/- 22, 58 +/- 13, and 63 +/- 16. Thus, the mean changes in both parameters were approximately 50% in the immediate period after transplant, and there was no additional deterioration by these measures of renal function. The changes were somewhat greater than those reported in newly diagnosed diabetic patients receiving cyclosporine for immunotherapy, but all of the subjects had histologic evidence of diabetic nephropathy at the time of transplant. Although the stabilization of renal function is encouraging, damage to the kidneys may be silent and serial renal biopsies are needed to allow full assessment of the impact of cyclosporine on renal pathologic conditions.

Adult↗
PubMedDate not supplied

Some lessons from the studies of renal biopsies in patients with insulin-dependent diabetes mellitus.

The authors have studied relationships of renal structure and function in more than 100 patients with insulin-dependent diabetes mellitus (IDDM), aged 13-55 years (mean, 30 years) with diabetes for 1-30 years (mean, 19 years). The authors confirmed the unique nature of the diabetic lesions that, in constellation, occur in no other disease. It was found that increased fractional mesangial volume (Vv Mes) is strongly associated with decreased glomerular filtration rate (GFR), proteinuria, and hypertension and that all patients with overt diabetic nephropathy have Vv Mes in excess of 0.35 micron 3/micron 3. This relationship results from constriction of the capillary lumen and filtration surface as a consequence of increased Vv Mes. Global glomerulosclerosis (scarring) is common in IDDM patients and appears related to arteriolar hyalinosis. Focal segmental glomerulosclerosis is a rare lesion in these patients. Having a single kidney (transplanted IDDM patients) is not associated with accelerated lesion development. The presence or absence of microalbuminuria (MA), per se, does not predict underlying glomerular structure, which may vary from the normal range to a level of pathology bordering on that regularly associated with overt nephropathy. However, when MA is associated with hypertension, or reduced GFR or both, urine albumin excretion (UAE) generally exceeds 40 mg/24 hr, and glomerular pathology is always present. The authors concluded that diabetic nephropathy is a unique renal disorder that cannot be caused by hemodynamic factors alone. The authors further conclude that MA becomes a predictor only when other features of overt nephropathy are already present and that serious diabetic glomerular lesions can be present in patients with normal UAE.

Adolescent↗
PubMedDate not supplied

Effect of glycemic control on early diabetic renal lesions. A 5-year randomized controlled clinical trial of insulin-dependent diabetic kidney transplant recipients.

OBJECTIVE: To determine whether optimized glycemic control in type I diabetic recipients of renal allografts will prevent or delay diabetic renal lesions in the allograft. DESIGN: Prospective, controlled, and randomized trial of glycemic control in an inception cohort of type I diabetic renal allograft recipients. The experimental group underwent maximized glycemic control, and the standard group was treated in the same way as other patients in the transplant clinic. Patients underwent baseline (before transplant) and 5-year posttransplant allograft biopsies. SETTING: University of Minnesota Hospital and Clinic and the Clinical Research Center and Hennepin County Medical Center, Minneapolis. PATIENTS: Type I diabetics with terminal diabetic renal failure undergoing renal transplantation. Forty-eight patients randomized to maximized or standard control completed the trial. INTERVENTION: Subcutaneous insulin given several times a day or continuously (maximized group) and once or twice each day (standard group) was used throughout the trial. A significant difference for hemoglobin A1 level was maintained (mean +/- SD: standard, 0.117 +/- 0.013; maximized, 0.096 +/- 0.016; P < 0.001). MAIN OUTCOME: The primary end point of this trial was the difference between the groups in renal glomerular mesangial expansion as determined by electron microscopy. RESULTS: There was a more than twofold increase in the volume fraction of mesangial matrix per glomerulus in the standard group (mean +/- SD, 0.043 +/- 0.034) compared with the maximized group (0.019 +/- 0.038; P = .024). The threefold increase in arteriolar hyalinosis, the greater widening of the glomerular basement membrane, and increase of volume fraction of the total mesangium in the patients who received standard treatment all approached significance (P = .10 or less). The incidence of severe hypoglycemic episodes was greater in the maximized group (1.7 per patient per year) than in the standard treatment group (< 0.1 per patient per year; P < .001). CONCLUSIONS: This trial indicates a causal relationship between hyperglycemia and an important lesion of diabetic nephropathy, mesangial matrix expansion, in renal allografts transplanted into diabetic recipients. In addition, the results with other lesions central to the development of diabetic nephropathy support the major conclusion.

Adult↗