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Biomedical subjects

S M Mauer

Publications and source records attributed to S M Mauer.

At least 73 records · Page 4Linked to original sources
PubMed1990

Manifestations of renal allograft rejection in small children receiving adult kidneys.

We were concerned that clinical manifestations of rejection (R) might be subtle in small children transplanted with adult kidneys. We retrospectively analyzed the first rejection episode (biopsy proven) in 22 children (R group) under age 4 years [mean age, 23.7 +/- 2.2 months (+/- SEM); mean weight, 9.4 +/- 0.4 kg] receiving an adult-related donor kidney. We matched these patients for age, date of transplant, donor source and immunosuppression with 36 children without R (control or C group). We compared both groups at similar intervals from transplantation, based on the time of R (5.38 +/- 1.2 months) in the R group and analyzed the immediate 8-week period prior to R and the corresponding interval in the C group. Hypertension occurred in 82% (18/22) of the R versus 8% (3/36) of the C group (P less than 0.01). Fever longer than 7 days occurred in 45% (10/22) of the R versus 0% (0/36) of the C group (P less than 0.01). Increased creatinine occurred in only 45% (10/22) of the R versus 3% (1/30) of the C group (P less than 0.01). Cyclosporine did not influence these manifestations of R. The clinical manifestations did not predict the R grades on biopsy, which were moderate to severe in 13 and mild in 9 of the R patients. Graft survival was higher at 3 years in the C (95%) than in the R patients (65%), (P less than 0.004). Thus, clinical manifestations of acute R can be subtle in small children with adult renal allografts. Renal biopsy should not be delayed until the creatinine is elevated in these patients.

Adult↗
PubMed1990

De novo hemolytic uremic syndrome following renal transplantation.

We report a case of complete recovery of renal function in a patient with de novo hemolytic uremic syndrome (HUS) following renal transplantation. This 3-year-old girl had none of the factors known to contribute to the development of HUS in transplant recipients. This case illustrates the usefulness of renal biopsy in the accurate diagnosis and management of dysfunction in the allograft following renal transplantation.

Biopsy↗
PubMed1990

Should there be an expanded role for kidney biopsy in the management of patients with type I diabetes?

Diabetic nephropathy is the single most important cause of end-stage renal disease (ESRD) in the United States. Further, the increased risk of mortality from type I diabetes is almost entirely confined to patients developing clinical diabetic nephropathy. Nonetheless, kidney biopsy has had little role in the clinical assessment of diabetic patients or in the design of clinical research in diabetic nephropathy. The development of dipstick-positive proteinuria in patients with type I diabetes of more than 10 years' duration is regularly associated with advanced structural changes of diabetic nephropathology; in these patients, clinical parameters, especially the rate of decline of glomerular filtration rate (GFR), are accurate monitors of disease progression. Microalbuminuria indicates a very high risk of overt proteinuria and thus ESRD. This increased risk is associated with levels of urinary albumin excretion (UAE; greater than 30 micrograms/min [45 mg/24 h]), which are frequently accompanied by hypertension and reduced or decreasing GFR. At this stage, lesions of diabetic nephropathy are usually already well established. Thus, microalbuminuria is more a marker of early nephropathy than a predictor of later renal injury. Before these clinical stages of nephropathy, there are no accurate predictors of renal risk. Renal biopsy may serve this role by indicating those patients who are developing significant lesions during the "silent" phase of the disease. In large measure, this value of the biopsy derives from evidence that the lesions tend to develop linearly over time and can be measured by techniques that are relatively easily established in standard surgical pathology environments. Renal biopsies can serve to assure the majority of diabetic patients that they are developing serious lesions slowly, if at all.(ABSTRACT TRUNCATED AT 250 WORDS)

Albuminuria↗
PubMed1990

Studies of renal autoregulation in pancreatectomized and streptozotocin diabetic rats.

We studied renal autoregulation in pancreatectomized Munich-Wistar diabetic rats and in their sham-operated controls. In a second experiment we studied renal autoregulation in untreated and insulin treated streptozotocin diabetic Munich-Wistar rats and their nondiabetic controls. In the first experiment the diabetic rats had higher baseline renal blood flows (RBF). There was a fall in renal vascular resistance (RVR) and sustained RBF in both diabetic and control rats as renal perfusion pressures (RPP) was reduced from 130 and 110 mm Hg. As RPP was reduced from 110 and 80 mm Hg, there was no significant Change in RVR in control rats and RBF began to fall. Below RPP of 80 mm Hg RVR rose and RBF fell sharply in these rats. In contrast, there was a progressive fall in RVR as RPP was lowered to 60 mm Hg in the diabetic rats and, thus, RBF was much better sustained in these animals. In the second experiment the plasma glucose level was 502 +/- 52 mg/dl (X +/- SD) in the untreated diabetic rats and only modestly reduced to 411 +/- 49 mg/dl in the insulin treated animals. Untreated streptozotocin diabetic rats had moderately reduced and insulin-treated diabetic rats had mildly reduced baseline RVR and RBF. However, in these animals as in the pancreatectomized rats the increases in RVR noted in control rats at subautoregulatory RPPs were not seen. Thus, regardless of whether baseline RBFs were increased or decreased, diabetic rats sustained RBF at markedly reduced RPPs far more efficiently than did nondiabetic rats. The pathogenesis of these abnormalities in diabetic rats was not learned in these studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Renal transplantation in infants.

The timing of renal transplantation in infants is controversial. Between 1965 and 1989, 79 transplants in 75 infants less than 2 years old were performed: 23 who were 12 months or younger, 52 who were older than 12 months; 63 donors were living related, 1 was living unrelated, and 15 were cadaver donors; 75 were primary transplants and 4 were retransplants. Infants were considered for transplantation when they were on, or about to begin, dialysis. All had intra-abdominal transplants with arterial anastomosis to the distal aorta. Sixty-four per cent are alive with functioning grafts. The most frequent etiologies of renal failure were hypoplasia (32%) and obstructive uropathy (20%); oxalosis was the etiology in 11%. Since 1983 patient survival has been 95% and 91% at 1 and 5 years; graft survival has been 86% and 73% at 1 and 5 years. For cyclosporine immunosuppressed patients, patient survival is 100% at 1 and 5 years; graft survival is 96% and 82% at 1 and 5 years. There was no difference in outcome between infants who were 12 months or younger versus those who were aged 12 to 24 months; similarly there was no difference between infants and older children. Sixteen (21%) patients died: 5 after operation from coagulopathy (1) and infection (4); and 11 late from postsplenectomy sepsis (4), recurrent oxalosis (3), infection (2), and other causes (2). Routine splenectomy is no longer done. There has not been a death from infection in patients transplanted since 1983. Rejection was the most common cause of graft loss (in 15 patients); other causes included death (with function) (7), recurrent oxalosis (3), and technical complications (3). Overall 52% of patients have not had a rejection episode; mean creatinine level in patients with functioning grafts is 0.8 +/- 0.2 mg/dL. Common postoperative problems include fever, atelectasis, and ileus. At the time of their transplants, the infants were small for age; but with a successful transplant, their growth, head circumference, and development have improved. Transplantation in infants requires an intensive multidisciplinary approach but yields excellent short- and long-term survival rates that are no different from those seen in older children or adults. Living donors should be used whenever possible. Patients with a successful transplantation experience improved growth and development, with excellent rehabilitation.

Adolescent↗
PubMed1990

The use of cadaver kidneys for transplantation in young children.

The role of cadaver kidney transplantation in the management of end-stage renal disease in young children is controversial. To assess the current risk-benefit ratio of cadaver first and second kidney transplants in recipients under 6 years of age, we compared the outcome of 19 transplants performed between 1984 and 1989 using a quadruple-drug regimen (Minnesota antilymphocyte globulin, azathioprine, prednisone, cyclosporine) with the outcome of 25 transplants performed prior to 1984 without the use of cyclosporine at a single institution. Twenty-five transplants were in children under the age of 3 years. In the last decade patient survival has significantly improved. One-year patient survival improved from 53% before 1979 to 90% since 1979 (P less than 0.05). The use of the quadruple-drug regimen since 1984 was associated with a significant improvement in one-year cadaver graft function from 40% before 1979 to 78% in recipients under 6 years of age, and from 22% to 82% in recipients under 3 years of age (P less than 0.05). With the quadruple-drug regimen, one-year and four-year graft function rates for children under 6 years of age were 83% for first cadaver transplants and 72% for second cadaver transplants, which were essentially the same results as in older children and adults. Children who received kidneys from donors over 4 years of age achieved the best result, with 87% one-year graft function compared with 50% for kidneys from donors under 4 years old. In 15 children with successful transplants, 8 (53%) showed accelerated growth, 5 (33%) had normal-velocity growth, and only 2 children (14%) with suboptimal renal function had poor growth following transplantation. Therefore, we believe that with a quadruple-drug immunosuppressive protocol, cadaver renal transplantation using kidneys from adults or pediatric donors over 4 years old is an acceptable form of treatment in young children with end-stage renal disease for whom there are no suitable living-related donors.

Adolescent↗
PubMed1990

Doppler evaluation of renal transplants in children: a prospective analysis with histopathologic correlation.

Duplex Doppler sonography recently has been used to evaluate renal transplants. Some authors have stated that high resistive indexes (RIs) occur in the presence of acute renal transplant rejection. RIs less than 0.7 are considered as probably excluding acute transplant rejection. We performed a prospective study of duplex sonographic examinations of pediatric patients (mean age, 8 years; 13 boys, two girls) with renal allografts and clinically suspected transplant disease. The results of 22 duplex studies were correlated with histopathologic data obtained between July 1987 and June 1988. RIs of the arcuate arteries in patients with acute rejection (n = 14) averaged 0.62 (range, 0.50-0.80). The RI in patients with chronic rejection (n = 1) was 0.59. RIs in patients with acute tubular necrosis (n = 3) averaged 0.66 (range, 0.59-0.72). RIs in patients with cyclosporine A toxicity (n = 4) averaged 0.66 (range, 0.58-0.79). Tubulointerstitial rejection was predominant, with only two patients showing minimal acute vascular rejection. Thirteen of 14 pediatric patients with histologically proved renal transplant rejection had a resistive index of less than 0.70. This study refutes the concept that resistive indexes of less than 0.7 exclude acute rejection.

Adolescent↗
PubMed1990

Effect of cyclosporin on generalized Shwartzman reaction in diabetic rats.

The effect of cyclosporin (CsA) on the endotoxin-induced generalized Shwartzman reaction (GSR) was studied in diabetic and nondiabetic rats. After 4.5 wk of diabetes, CsA (20 mg/kg) or intralipid as a control substance was given intraperitoneally daily for 10 days. Next, diabetic rats were given either high-dose (2 mg/kg or low-dose (0.1 mg/kg) endotoxin (Escherichia coli 026:B6 lipopolysaccharide B) as a single injection. The rats were killed at intervals of 1, 4, 8, and 24 h. No significant glomerular thrombi were seen in the nondiabetic control animals, whereas the severity of glomerular thrombi in the diabetic animals was dependent on the presence or absence of CsA, endotoxin dose, and degree of glycemic control. In the diabetic rats, glomerular thrombi occurred maximally at 4 h but were no longer present at 24 h. The CsA/high-dose-endotoxin rats had fewer glomerular thrombi than rats receiving the intralipid/high-dose endotoxin, but this difference was not statistically significant. The CsA/low-dose-endotoxin rats had increased glomerular thrombi compared with the intralipid/low-dose-endotoxin rats (P less than 0.01). Insulin treatment reduced the glomerular capillary thrombi in the CsA/low-dose-endotoxin diabetic animals. Thus, CsA aggravates the GSR with low-dose endotoxin but has no significant effect when high-dose endotoxin is given. Improved glycemic control reduces the GSR in CsA-treated rats. Thus, the interrelationships of diabetes, endotoxin, and CsA on the GSR are complex, and the pathogenesis of these events is unclear.

Animals↗
PubMed1989

The effects of pancreas transplantation on the glomerular structure of renal allografts in patients with insulin-dependent diabetes.

The microvascular complications of diabetes mellitus may be caused, in part, by poor glycemic control. Diabetic patients who have received renal allografts may have new glomerular lesions that are manifested structurally by increases in mesangial and glomerular volume. Successful pancreas transplantation produces long-term normoglycemia and provides a unique opportunity to evaluate the impact of the normalization of the blood glucose level on the development of the renal lesions typical of diabetes mellitus in transplanted kidneys. We obtained biopsy specimens from the functioning renal allografts of 12 patients with insulin-dependent (Type I) diabetes before successful pancreas transplantation (performed one to seven years after renal transplantation) and repeated the biopsy at least 1.9 years later. In renal biopsy specimens obtained before pancreas transplantation, the mesangial volume was normal or modestly increased and the glomerular basement membrane was moderately thickened. At follow-up, no progression could be detected in any structural measure in the glomerulus. Furthermore, the recipients of pancreas transplants had smaller glomerular volumes than 13 matched diabetic patients who were recipients of renal allografts but who did not undergo pancreas transplantation (mean +/- SD, 1.80 +/- 0.55 vs. 2.47 +/- 0.73 x 10(6) microns 3; P = 0.02) and showed markedly less mesangial expansion (mesangial-volume fraction, 0.19 +/- 0.07 vs. 0.31 +/- 0.10 microns 3 per cubic micrometer; P = 0.004). We conclude that successful pancreas transplantation is associated with significantly less severe diabetic glomerulopathy in kidneys previously transplanted into diabetic patients. These data support the hypothesis that normoglycemia can prevent the progression of diabetic glomerulopathy in humans.

Adult↗
PubMed1989

Glomerular lesions and urinary albumin excretion in type I diabetes without overt proteinuria.

Since several studies have suggested that a slight increase in urinary albumin excretion (microalbuminuria) is predictive of nephropathy in patients with diabetes mellitus, we studied the relation of albumin excretion to renal structure in patients with insulin-dependent (Type I) diabetes. Renal biopsy specimens were evaluated with light- and electron-microscopical morphometric techniques in 48 patients who had had diabetes for 5 to 40 years and who excreted less than 200 mg of urinary albumin per 24 hours. Patients in Group I (n = 26) had normal urinary albumin excretion, creatinine clearance, and blood pressure; those in Group II (n = 10) had increased urinary albumin excretion but normal creatinine clearance and blood pressure; those in Group III (n = 12) had increased urinary albumin excretion and hypertension, decreased creatinine clearance, or both. Glomerular structure varied similarly, ranging from normal to abnormal in Groups I and II, but was consistently abnormal in Group III. The thickness of the glomerular basement membrane, the fractional volume of the mesangium, and the mesangial volume per glomerulus in Group III exceeded the corresponding values in the other groups significantly. Thus, microalbuminuria, when present with hypertension, decreased creatinine clearance, or both, indicates established abnormalities of glomerular structure. Normal albumin excretion, or microalbuminuria without these other functional abnormalities, does not accurately predict the severity of the underlying glomerular lesions in patients with Type I diabetes.

Adolescent↗
PubMed1989

The predictive value of microalbuminuria.

An elevated urinary albumin excretion (termed microalbuminuria) has been proposed as a predictor for later development of clinical diabetic nephropathy (hypertension, falling glomerular filtration rate [GFR], and urinary albumin excretion greater than 300 mg/24 h). However, review of the original reports on the predictability of microalbuminuria revealed a concomitant presence of elevated BP and a propensity to falling GFR. Thus, the predictability of microalbuminuria rests on the added evaluation of BP and GFR. Additional investigation is needed to address the possibility that microalbuminuria and either a rising BP or a falling GFR or both indicates established diabetic nephropathy rather than predicting its development.

Albuminuria↗
PubMed1989

Effects of dietary protein content in streptozotocin-diabetic rats.

We evaluated the influence of increased dietary protein intake on glomerular structure and function in Lewis rats made diabetic with streptozotocin. We found that diabetic animals on a 20% or 50% protein diet ate approximately 50% more protein and excreted about 50% more urinary urea nitrogen than did their respective similarly-fed nondiabetic controls. The 50% protein diet was associated with higher glomerular filtration rates (GFR) and renal blood flows (RBF) at two months in both diabetic and control animals compared to their respective controls on the lower protein diet. However, GFR and RBF were not significantly higher in the diabetic animals on the 50% protein diet in the controls on the 20% diet and were slightly, albeit not significantly lower than controls on the 50% diet. Glomerular capillary pressure (PGC) tended to be lower in the diabetic compared to their respective controls, while the high protein diet was associated with higher PGC in diabetic and nondiabetic animals. The PGC in the 50% diabetic rats was not different from the PGC in the nondiabetic rats. Urinary albumin excretion (UAE) rate was greater in the diabetic than in the nondiabetic animals. UAE was greatest in the high protein diabetic animals at six months. Glomerular basement membrane thickness after six months of diabetes was increased essentially equally in both normal and high-protein fed diabetic groups and was largely uninfluenced by diet in the controls. Fractional mesangial volume was increased and relative filtration surface was decreased only in the 50%-protein diet diabetic rats at six months. Thus, high protein diet was associated with increased fractional mesangial volume in diabetic rats, but this could not be explained by increased glomerular capillary flows or pressures. The mechanism of acceleration of mesangial expansion by high protein diet in diabetic animals was not elucidated by these studies.

Animals↗
PubMed1989

A 10-year experience with 290 pancreas transplants at a single institution.

Since our report at the 1984 American Surgical Association meeting of 100 pancreas transplants from 1966 through 1983, another 190 have been performed. The current series, begun in 1978, now numbers 276 cases, and includes 133 nonuremic recipients of pancreas transplants alone (PTA), 46 simultaneous pancreas/kidney transplants (SPK), and 97 pancreas tranplants after a kidney transplant (PAK). Duct management techniques used were free intraperitoneal drainage in 44 cases, duct occlusion in 44, enteric drainage in 89, and bladder drainage in 128. The 1-year patient and graft survival rates in the entire cohort of 276 were 91% and 42%. One-year patient survival rates were 88% in the first 100, 91% in the second 100, and 92% in the last 76 cases; corresponding 1-year graft survival rates were 28%, 47%, and 56% (p less than 0.05). A prospective comparison of bladder drainage (n = 82) versus enteric drainage (n = 46) in PAK/PTA cases since November 1, 1984 favored bladder drainage (1-year graft survival rates of 52% vs. 41%) because of urinary amylase monitoring. The best results were in recipients of primary SPK bladder-drained transplants (n = 39), with a 1-year pancreas graft survival rate of 75%, kidney graft survival rate of 80%, and patient survival rate of 95%. Logistic regression analysis, with 1-year graft function as the independent variable, showed significant (p less than 0.05) predictors of success (odds ratio) to be technique: bladder drainage (5.8) versus enteric drainage (2.5) versus duct injection (1.0); category: SPK (6.0) versus PAK from same donor (3.2) versus PAK from different donor (1.2) versus PTA (1.0); and donor HLA DR mismatch: 0 (5.0) versus 1 (2.5) versus 2 (1.0) antigens. On April 1, 1989, 90 patients had functioning grafts (60 euglycemic and insulin-free for more than 1 year, 10 for 5 to 10 years); these, along with 24 others whose grafts functioned for 1 to 6 years before failing, are part of an expanding cohort in whom the influence of inducing a euglycemic state on pre-existing secondary complications of diabetes is being studied. Only preliminary data is available. In regard to neuropathy, at more than 1 year after transplant in patients with functioning grafts, conduction velocities in some nerves were increased over baseline. In regard to retinopathy, deterioration in grade occurred in approximately 30% of the recipients by 3 years, whether the graft functioned continuously or failed early, but thereafter retinopathy in the patients with functioning grafts remained stable.(ABSTRACT TRUNCATED AT 400 WORDS)

Diabetes Mellitus↗
PubMed1989

Long-term survival following kidney transplantation in 100 type I diabetic patients.

Between December 1966 and April 1978, 265 uremic patients with type I diabetes received primary renal allografts at the University of Minnesota. One hundred of the diabetic patients were alive with a functioning graft 10 years after transplantation. The actual 10-year patient and primary graft functional survival rates overall were 40% and 32%, respectively. For recipients of HLA-identical sibling (n = 45), mismatched living-related (n = 121), and cadaver donor grafts (n = 99), the actual 10-year patient survival rates were 64%, 33%, and 36%, respectively, and the actual 10-year graft functional survival rates were 62%, 28%, and 22%, respectively. The differences in patient and graft survival rates between HLA-identical graft recipients and recipients of mismatched related and cadaver grafts were significant (P less than 0.001). Of the 100 patients who survived into a second decade, at 15 years posttransplant 51% were alive, and 41% had functioning grafts. For recipients of HLA-identical sibling, mismatched living-related donor grafts, and cadaver donor grafts who survived 10 years, 47%, 57%, and 43%, respectively, were alive at 15 years, and 31%, 45%, and 43%, respectively, had functioning grafts. For recipients who made it to the second decade, patient and primary graft survival rates thereafter were not statistically different by donor source. Twenty-three patients died in the second decade after transplantation, 10 of cardiovascular disease. Twenty-five patients lost graft function in the second decade, 19 from death with a functioning graft. In regard to diabetic complications, recurrence of diabetic nephropathy was common, but only two patients lost graft function solely for this reason. In 21 patients (42 eyes) followed prospectively for 10 years, visual acuity deteriorated in 26%, was stable in 64%, and improved in 10% of eyes. Neurophysiological test results indicated that correction of uremia does not stop the progression of diabetic neuropathy in recipients of kidney transplants alone. Even without cyclosporine, nearly two-thirds of recipients of HLA-identical kidney grafts, more than one-quarter of recipients of mismatched living-related donor grafts, and more than one-fifth receiving cadaver grafts enjoyed an extension of life for more than 10 years.

Age Factors↗
PubMed1989

Long-term study of normal kidneys transplanted into patients with type I diabetes.

We examined the rate of development of the lesions of diabetic nephropathy in transplanted kidneys residing for 6-14 yr in type I (insulin-dependent) diabetic kidney-allograft recipients. Although each recipient had end-stage diabetic nephropathy with his/her own kidneys, there was marked variability in the rate of development of mesangial expansion observed in the transplanted kidneys. The progression of glomerular pathology, including widening of the glomerular basement membrane and expansion of the mesangium, did not correlate significantly with several potential risk factors (e.g., donor source--cadaver or living related, histocompatibility match, age of the recipient or donor, age at onset of diabetes, duration of diabetes before renal failure, immunosuppressive drug dose, blood pressure, and severity of lesions of chronic rejection). However, there was a direct albeit imprecise relationship between the index of mesangial expansion at the final biopsy and the index of glycemic control (r = .61, P less than .01). These observations suggest that currently unknown factor(s) may modulate the progression of diabetic renal disease, even in a population that had uniformly demonstrated nephropathy risk. Our data support the hypothesis that in addition to glycemic control per se, there are risk factors intrinsic to the kidney itself.

Adolescent↗
PubMed1989

Effects of sorbinil on glomerular structure and function in long-term-diabetic rats.

We investigated the role of the aldose reductase pathway in the pathogenesis of the nephropathy of rats with sever (non-insulin-treated) streptozocin-induced diabetes of 6 mo duration. The initial experiment included four groups of rats: diabetic and control animals on a 20% protein diet, which were untreated or treated with sorbinil (an aldose reductase inhibitor). Food intake was increased by diabetes but was uninfluenced by sorbinil, whereas urinary urea nitrogen excretion was increased and body weight was decreased by both variables. Glomerular basement membrane (GBM) width was increased by diabetes and decreased by sorbinil. No other structural changes were noted. We speculated that sorbinil could have slowed the abnormal rate of GBM thickening in diabetic rats and the normal increase in GBM width in control rats by inducing a mild catabolic state. The second experiment also involved four groups of rats: diabetic and control animals on a 50% protein diet, which were untreated or treated with sorbinil. In these studies, diabetes was again associated with reduced body weight, but sorbinil had no influence on urinary urea nitrogen. Urinary albumin excretion, which was increased by diabetes, was not affected by sorbinil. GBM width was increased by diabetes, but in contrast to animals on 20% protein diets, the animals on 50% protein diets and treated with sorbinil did not have reduced GBM widths. Mesangial volume fraction was greater in diabetic animals than in controls, and sorbinil largely prevented mesangial expansion in them. Surprisingly, the control animals on the 50% protein diet and given sorbinil had increased mesangial volume fraction compared with control rats on the same diet not given the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldehyde Reductase↗