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Biomedical subjects

S M Mauer

Publications and source records attributed to S M Mauer.

At least 91 records · Page 5Linked to original sources
PubMed1989

Mesangial expansion as a central mechanism for loss of kidney function in diabetic patients.

Diabetic nephropathy leading to kidney failure is a major complication of both type I (insulin-dependent) and type II (non-insulin-dependent) diabetes mellitus, and glomerular structural lesions (especially expansion of the mesangium) may constitute the principal cause of decline in kidney function experienced by a significant fraction of diabetic patients. Although the biochemical bases of these mesangial abnormalities remain unknown, an understanding of the natural history of diabetic nephropathy from a combined structural and functional approach can lead to greater pathophysiological insight. Work in animals has supported the concept that the metabolic disturbances of diabetes mellitus cause diabetic nephropathy, with structural and functional lesions prevented or reversed with improved or normalized glycemic control. Additional research must address this fundamental issue in humans, especially the response of advancing mesangial lesions to improved glycemic control. Factors not directly related to the metabolic perturbations of diabetes may serve to accelerate or diminish the pathophysiological processes of diabetic nephropathy. The elucidation and management of these factors, when coupled with improved glycemic control, may moderate the development or progression of diabetic kidney lesions in humans.

Albuminuria↗
PubMed1989

Mean glomerular volume and rate of development of diabetic nephropathy.

We studied kidney glomerular structure and function in two groups of type I (insulin-dependent) diabetic subjects with 14-16 yr (group 1, n = 16) and 24-26 yr (group 2, n = 13) duration of diabetes and compared them to a group of 18 nondiabetic subjects with similar age ranges. Within each diabetic group, subjects were selected for normal kidney function (urinary albumin excretion less than 40 mg/24 h, normal blood pressure, creatinine clearance greater than 90 ml.min-1.1.73 m-2) or for nephropathy (urinary albumin excretion greater than 200 mg/24 h). Morphometric analysis of glomeruli revealed a significantly larger mean glomerular volume in subjects with nephropathy (group 2). Mesangial volumes were significantly greater in the nephropathic than the normoalbuminuric diabetic subjects in each group, but filtration surface per glomerulus was constant among all subjects. The percentage of sclerosed glomeruli was also significantly increased in the nephropathic subjects compared with the subjects with normal kidney function, in whom sclerosed glomeruli did not exceed 8%. In addition, there was a significant correlation between percentage of globally sclerosed glomeruli and glomerular volume in group 2 (rs = .79, P less than .01) but not group 1 (rs = -.20, NS) subjects. Thus, glomerular size or individual capacity for glomerular expansion may determine the rate of progression of the loss of kidney function in subjects destined to develop diabetic nephropathy.

Adolescent↗
PubMed1989

Results of pediatric kidney transplantation at the University of Minnesota.

In all, 473 renal transplants were performed at the University of Minnesota in 386 children 1-17 years old between August 14, 1963 and December 31, 1988. Standard immunosuppressive protocols, pretransplant blood transfusions, and discontinuation of routine splenectomy have led to improving graft and patient survival rates. Children receiving living-related donor kidneys had better graft and patient survival rates, compared to cadaver kidneys. Graft and patient survival rates were better in children who received primary grafts, compared to retransplants. Children who received DST plus conventional immunosuppression had poorer graft survival, compared to quadruple immunosuppression during the same era. Recently, 1-year graft survival rates with quadruple immunosuppression are equal for children receiving primary, living-related donor or cadaver kidneys. Graft and patient survival rates in children 1-4 years old are identical to those in children 5-17 years old. Age no longer appears to be a risk factor for children undergoing kidney transplantation. Good patient and graft survival rates can be achieved at centers specializing in kidney transplantation for small children. Currently, transplantation is the treatment of choice for all children who are candidates for renal replacement therapy.

Adolescent↗
PubMed1989

Morphology of diabetic glomerulopathy and relationship to hypertension.

The mutual relationship between elevated blood pressure and structural changes in the kidney is still an area with more open questions than clear answers. Indirect evidence is available concerning one aspect: When hypertension is present it has a significant impact on the further progression of the structural changes. This evidence is available only in terms of the effect of antihypertensive treatment on the preservation of renal function. Since it has been shown that the demise in renal function in long-term diabetics is closely related to the development of advanced diabetic glomerulopathy, it seems likely that normalization of the blood pressure leads to a slowing of this development. Structural studies to elucidate these interactions are, however, not available. An intriguing question is whether the relationship is interactive also in the other direction. Focusing on the alterations within the glomeruli, the fact is that the glomerulopathy develops over several years before it come to the stage when clinical signs appear. Thus, diabetics with "incipient nephropathy" clearly demonstrate basement membrane (BM) accumulation, showing as increased BM-thickness and increase in mesangial matrix volume. Since this is the most likely point of time for hypertension to develop the necessary condition obtains, that the development of hypertension might be triggered by structural abnormalities in the kidney. The mechanisms of action at this point of time remain speculative. The relationship between structural parameters characterizing diabetic glomerulopathy and the blood pressure level was studied in a series of 14 IDDM patients, representing a span of renal functional impairment. Mean blood pressure in the group was 117 mmHg, with a range from 87-122 mmHg.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1989

Glomerular capillary morphology in normal humans.

Knowledge of quantitative glomerular structure in normal man is limited. At the time of renal transplantation, 28 living-related normal kidney donors had renal biopsies performed. Tissue was processed for light and electron microscopy using standard techniques. Standard stereologic techniques were used to determine mean glomerular volume, capillary length density, fractional volumes of mesangium and capillary lumen, surface densities of the peripheral capillary, mesangial-epithelium interface, and the lumenal-mesangial interface. Volume of total mesangium/glomerulus, capillary lumenal volume/glomerulus, peripheral capillary filtration surface/glomerulus, capillary mesangial-epithelial surface/glomerulus, capillary lumenal-mesangial surface/glomerulus, capillary length/glomerulus, and average capillary diameter were calculated. There were no significant differences between males and females in any structural parameter. There were no significant correlations between age or body surface area and any structural parameter. In comparison with these normal values, previously reported diabetic patients with clinical nephropathy demonstrate markedly expanded mesangial volume/glomerulus and a diminished filtration surface/glomerulus. The availability of these normal values will allow comparison with functional data in normal humans and greater understanding of human glomerular disease.

Adult↗
PubMed1988

Progression of diabetic retinopathy after pancreas transplantation for insulin-dependent diabetes mellitus.

We studied the effect of successful pancreas transplantation and consequent normoglycemia (mean total hemoglobin A1, 7.0 percent; range, 5.8 to 8.3) on visual function and diabetic retinopathy in 22 patients with Type I diabetes mellitus (study group). Sixteen similar patients in whom pancreas transplantation had been unsuccessful (mean total hemoglobin A1, 12.0 percent; range, 8.0 to 18.0) served as a control group. The majority of patients in both groups had advanced proliferative retinopathy. At a mean follow-up of 24 months we found no significant difference between the groups in the rate of progression of retinopathy, expressed as a score. Success of the transplantation did not prevent progression of retinopathy across the range of retinopathy studied. Progressive retinopathy was observed more commonly in patients with low retinopathy scores (nonproliferative or mild proliferative retinopathy) at base line in both the study group (13 of 17 eyes, or 76 percent) and the control group (7 of 12 eyes, or 58 percent). Further analysis suggested the possibility that after three years of euglycemia, the study group had less deterioration than the control group, particularly in eyes with advanced retinopathy. We observed no difference in the rate of loss of vision between the two groups. This study provides evidence that pancreas transplantation and subsequent normoglycemia neither reverse nor prevent the progression of diabetic retinopathy.

Adolescent↗
PubMed1988

Anaphylactoid purpura: characteristics of 16 patients who progressed to renal failure.

Renal insufficiency occurs in at least 1.5% of children with anaphylactoid purpura (AP). We reviewed the records of 16 children who developed end-stage renal disease (ESRD group) secondary to AP and matched them for age, era of onset, renal histology, and clinical severity at onset with 16 children who had AP but whose creatine clearance returned to and remained normal (recovery group). We reviewed creatinine clearances at 1, 3, 5, and 10 years after onset. A creatinine clearance greater than 70 ml/min per 1.73 m2 was present in 50% of the patients in the ESRD group at 3 years and in 25% at 5 years after onset. In contrast, all patients in the recovery group had a creatinine clearance greater than 70 ml/min per 1.73 m2 by 3 years (7 of 16 had a creatinine clearance greater than 125 ml/min per 1.73 m2) and all were normal 95-125 ml/min per 1.73 m2) by 5 years. Thus, the presence of an increased creatinine clearance (greater than 125 ml/min per 1.73 m2) at 3 years predicted recovery, while failure to reach a creatinine clearance of greater than 70 ml/min per 1.73 m2 at 3 years predicted progression to ESRD. There was no evidence of recurrent systemic AP or nephritis in the 14 patients who underwent renal allograft transplantation. We conclude that long-term evaluation of patients over many years is required to identify those who will progress to ESRD from AP and that recurrence of AP in the renal transplant is uncommon.

Adolescent↗
PubMed1988

The outcome of renal transplantation in children with posterior urethral valves.

The effect of vesical dysfunction on the survival and function of renal transplants was evaluated by a retrospective study in which 18 children with posterior urethral valves and 18 children with vesicoureteral reflux were randomly matched with 36 children used as controls. There was no statistically significant difference in patient survival among the 3 groups. Five years after transplantation 50 per cent of the grafts in children with posterior urethral valves were functioning, while 73 and 75 per cent, respectively, of the grafts were functioning in children with vesicoureteral reflux and in the control group. Renal function during the 5 years was significantly better in children in the control group and in those with vesicoureteral reflux than in children with posterior urethral valves. We believe that the presence of an abnormal bladder may alter graft survival and adversely affect the function of the transplanted kidney.

Adolescent↗
PubMed1988

Single-center 1-15-year results of renal transplantation in patients with systemic lupus erythematosus.

Initially, poor long-term prognosis in patients with SLE and fear of recurrent disease dissuaded renal transplantation in this group of patients. However, in 1975 the Advisory Committee to the Renal Transplant Registry reported satisfactory 1-2-year results in 56 patients with SLE from 36 institutions. Subsequently, renal transplantation for SLE patients with end-stage renal disease has become more accepted, though it has been recommended that transplantation be postponed for at least one year after initiating dialysis. Five cases of recurrent lupus nephritis have been reported in the literature. However, since the long-term outcome after transplantation in this group of patients is not well established, we have examined the long-term outcome in SLE patients who underwent renal transplantation at the University of Minnesota. Thirty-two SLE patients receiving 33 transplants between December 1969 and December 1987 were studied retrospectively and compared with controls matched for age, sex, donor source, HLA match, date of transplant, and diabetic status. A total of 69% (22/32) of patients underwent less than 1 year of dialysis prior to transplantation, and 50% (16/32) experienced biopsy-proved acute rejection, which was reversible in 67% (11/16). Actuarial graft function and patient survival rate in SLE patients were not significantly different from those in the matched control group. Duration of prior dialysis did not affect outcome. Surviving grafts have excellent function as measured by serum creatinine (1.3 +/- 0.4 mg/dl, means +/- SD). Causes of death were sepsis (5) and myocardial infarction (1). One patient lost the graft from rejection after withdrawal of immunosuppression because of a malignancy one month posttransplant. Three patients lost graft function due to chronic rejection. To date no patients have had evidence of recurrent SLE nephritis.

Follow-Up Studies↗
PubMed1988

Measuring the volume density of the glomerular mesangium.

Volume density (Vv) is a morphometric parameter used to detect pathological changes within renal tissue. To establish the most efficient technique, Vv of the mesangium in renal biopsies was studied. First, a digitizing tablet was used to trace mesangial and total glomerular areas, subsequently used to calculate Vv of the mesangium. Secondly, a point counting technique was tested using either a 16-point or an 81-point grid; the number of grid points falling on the mesangium and glomerulus was used to calculate mesangial Vv. The digitizing tablet, the 81-point grid and the 16-point grid all gave equivalent Vv for the 15 biopsies. The 81-point grid and the 16-point grid were, respectively, 1.9 and 3.2-fold faster than the digitizing tablet. Since all techniques gave comparable results, the 16-point grid was the most efficient.

Biopsy↗
PubMed1988

Pancreas transplantation in nonuremic, type I diabetic recipients.

Between July 1978 and January 1988, 111 of 210 pancreas transplants were in nonuremic, nonkidney (NUNK) recipients in whom complications of diabetes were judged more serious than the potential side effects of antirejection therapy. In all NUNK cases, the 1-year patient survival rate (PSR) and graft survival rate (GSR) were 90% and 39%. Since November 1984, 1-year PSR and GSR for 62 NUNK recipients of pancreas transplants alone (PTA) were 93% and 48%, compared to 89% and 37% for 28 pancreas transplants after (PAK) and 89% and 73% for 20 simultaneous (SPK) with a kidney transplant. The 1-year GSR for 1984-88 technically successful (TS) PTA cases (n = 47) was 63%, versus 75% for PAK (n = 13) and 86% for SPK (n = 17) cases. The 1-year GSRs, by technique and source for 1984-88 PTA cases, were 58% for bladder-drained cadaver (n = 30), 51% for enteric-drained related (n = 32), and 29% for enteric-drained cadaver (n = 17) donor transplants, and 75% (n = 24), 77% (n = 16), and 38% (n = 13) for the corresponding TS cases. Of NUNK recipients, 35 have had grafts function for more than 1 year and all but 3 were treated with cyclosporine (CsA). In the CsA-treated recipients, serum creatinine increased and creatinine clearances decreased by a magnitude of 40% during the first 6 months but thereafter remained stable in all but 2 patients. In the patients with functioning grafts studied at 1 year, retinopathy remained stable in 59% and progressed in 41% of the eyes (n = 39). Motor nerve conduction velocities were significantly increased and muscle action potentials remained stable in 24 patients with functioning grafts studied at 1 year, while in 14 patients in whom transplants failed there was a significant decrease in evoked muscle action potentials. A sustained euglycemic, insulin-independent state can be established in nonuremic, nonkidney diabetic recipients of pancreas transplants alone, with a beneficial effect on neuropathy, lack of an immediate benefit on advanced retinopathy, and an effect on nephropathy compounded by the influence of CsA on renal function.

Cyclosporins↗
PubMed1987

Low-dose cyclosporine therapy combined with standard immunosuppression in pediatric renal transplantation.

A new immunosuppressive regimen combining anti-lymphocyte globulin, azathioprine, prednisone, and low doses of cyclosporine was used in 28 children aged 9 months to 17 years (mean 5.8 years) who received primary renal allografts between July 1, 1984, and September 25, 1986. After a mean follow-up of 17.3 months, the patient and graft survival is 100% (18 of 18) for mismatched related kidneys, and 90% (nine of 10) for cadaver kidneys. The single graft failure was the result of a death from technical complications. Serum creatinine concentration after transplantation ranged from 0.3 to 1.7 mg/dL (mean 0.85 mg/dL). The probability of a rejection episode in the first year was 45% and 60% for mismatched-related and cadaver kidneys, respectively. Cyclosporine nephrotoxicity was recognized in only one (3.7%) of 27 children, and was rapidly reversed after cyclosporine was discontinued. An initial group of nine children was weaned from cyclosporine therapy 6 to 12 months after transplantation, but two (22%) had rejection episodes. Our preliminary experience suggests that the use of a quadruple immunosuppressive regimen for both living related and cadaver renal transplants in children is associated with an improved graft function rate and a low incidence of complications.

Adolescent↗
PubMed1987

Growth and development in infants after renal transplantation.

Between January 1, 1978, and August 31, 1985, 13 infants aged 6 to 11 months received primary renal transplants (12, living related donor; one cadaver) at the University of Minnesota. Twelve infants are alive with functioning grafts (10 primary and two second transplants) after 4 months to 7.5 years. To assess the long-term outcome, we analyzed growth and development in the first nine infants 2 to 7.5 years after receiving their first transplant. Before transplantation, head circumference and height standard deviation scores in six of nine infants were less than -2. Five had seizures; four had delayed mental development, and six delayed motor development. The mean increment in height standard deviation scores for six boys after transplantation was +1.4 (P less than 0.05), and one achieved complete catch-up growth. The mean difference in height standard deviation scores for three infant girls with primary hyperoxaluria was -2.1; nevertheless, two infants with oxalosis are currently alive 2.7 to 3.3 years later. All eight surviving children achieved normal head circumference (mean improvement +2.2 SDS, P less than 0.001), and no child had further seizures. Of seven infants reassessed with the Bayley Scales after transplantation, mental development was normal in all and motor development was normal in five. Our findings suggest that early living related renal transplantation is an important option in the management of end-stage renal disease in infants.

Body Height↗
PubMed1987

Observations of glomerular epithelial cell structure in patients with type I diabetes mellitus.

Overt proteinuria is a hallmark of diabetic nephropathy while microalbuminuria is thought to be a predictor of later onset of diabetic nephropathy. Yet the mechanisms for abnormal urinary protein leak in diabetes have not been defined. We studied 28 patients with type I diabetes for 7 to 33 years. Creatinine clearance, urinary albumin excretion rate (UAE), and multiple blood pressures were obtained in each patient. A renal biopsy was performed in each patient and in 28 normal subjects. Quantitative stereology was used to determine foot process (FP) width, filtration slit length density (FSLV) and filtration slit length/glomerulus (FSLG). FP width was slightly wider than normal in diabetic patients with UAE less than 250 mg/24 hr while FP was significantly wider than both of these groups in diabetics with UAE greater than 250 mg/24 hr. FSLV and FSLG were similar in normals and diabetics with UAE less than 250 mg/24 hr but both were reduced in diabetics with UAE greater than 250 mg/24 hr. UAE correlated with FP width (P less than 0.05), FSLG (P less than 0.01) and most precisely and FSLV (P less than 0.001). Diabetics with microalbuminuria had values for all the structural parameters measured here not different from diabetics with UAE in the normal range. Perturbations of epithelial cell structure are present in diabetes mellitus especially in patients with nephropathy. The exact relationships between albuminuria and epithelial cell structure remains to be elucidated.

Adult↗