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Biomedical subjects

S M Mauer

Publications and source records attributed to S M Mauer.

At least 145 records · Page 8Linked to original sources
PubMed1983

Transplantation of the adult kidney into the very small child. Technical considerations.

Transplantation of adult kidneys into very small children is not performed in most centers because of concerns regarding the technical difficulty of the procedure. Advantages of the procedure include the possibility of living related donor transplantation and the increased availability of adult donor kidneys as compared with pediatric cadaver donor kidneys. We have transplanted adult kidneys into 12 children aged 11 months to 3.5 years who weighed 5,400 to 8,800 g. Ten children received living related donor and two cadaver donor grafts. Herein we describe in detail the pretransplant management, surgical strategies, intraoperative management, surgical techniques, and postoperative management which we use for transplantation of adult kidneys into very small children. Intraoperative and postoperative complications have been described to illustrate the evolving clinical principles in this area. Since 10 of the children are presently alive, 8 with their original grafts, 16 months to 9 years after transplantation, we advocate this approach for suitable small children with terminal renal failure.

Adolescent↗
PubMed1983

Glomerular manifestations of diabetes in the BB rat.

Morphologic characteristics of the renal glomeruli and tubules of BB rats with spontaneous diabetes mellitus were studied at 30 weeks' duration of diabetes. Whereas the glomerular basement membrane (GBM) was significantly thickened, no changes in the diabetic glomeruli were seen in the peripheral capillary wall area and in the fractional volumes of the mesangial cells or of the mesangial matrix. Light microscopy of the diabetic kidneys were normal, and immunofluorescent examination of diabetic glomeruli showed no increased accumulation of albumin, C3, or IgG. Diabetic rats had increased renal blood flow and glomerular filtration rates. Diabetic rats at 7, 17, and 30 weeks excreted normal amounts of urinary albumin. Thus kidneys of the BB diabetic rat differ from other experimental models of diabetes in that GBM thickening occurs in the absence of mesangial changes and of increased albuminuria. These studies suggest that the mesangium may influence glomerular permeability in diabetes, while thickening of the GBM in diabetes does not necessarily coincide with increased urinary albumin excretion. Furthermore, these results are consonant with the hypothesis that genetic factors may influence the pathological expression of diabetic nephropathy in rats.

Animals↗
PubMed1983

Arachidonic acid deficiency in streptozotocin-induced diabetes.

Fatty acid compositions of phospholipids of heart, liver, kidney, aorta, and serum from rats having streptozotocin-induced diabetes were determined and compared with those of nondiabetic controls. Linoleic and dihomo-gamma-linolenic acids were increased whereas arachidonic acid was decreased in most tissues, suggesting an impairment of delta 5-desaturase activity. Acids derived from linolenic acid were increased in some diabetic tissues from diabetic animals although the linolenic content was normal, indicating less impairment in the desaturation of the omega 3 series of fatty acids. Diabetes suppressed all polyunsaturated acids in the whole animal, but the competition between omega 3 and omega 6 acids favored the excessive suppression of long-chain omega 6 acids and an increase in the proportion of omega 3 acids in lipids of vital tissues. These changes in fatty acid composition of the phospholipids may have significant effects on cellular functions and vasoregulatory control mechanisms in diabetes.

Animals↗
PubMed1983

The development of lesions in the glomerular basement membrane and mesangium after transplantation of normal kidneys to diabetic patients.

Renal allograft biopsies at the time of transplantation (baseline) and 2 yr later were obtained in 6 type I diabetic and 12 nondiabetic patients and studied for glomerular basement membrane (GBM) and mesangial changes. Diabetic patients had significantly greater GBM thickness compared with nondiabetics at 2 yr (P = 0.05, rank sum test), and the increase in GBM thickness comparing baseline and 2-yr biopsies was greater in the diabetic compared with nondiabetic patients (P = 0.005, rank sum test). Similarly, diabetic patients developed significant mesangial thickening by light microscopy while no changes were observed in nondiabetic patients (P = 0.001). Electron microscopic morphometric analysis of the percentage of total mesangium was not different on comparing diabetic and nondiabetic patients at 2 yr. There was an increase in the matrix component of the mesangium in the diabetics at this time, although this did not reach statistical significance (P = 0.06). In addition, the surface density of the peripheral glomerular capillary wall, presumably reflecting mesangial expansion, was decreased in the diabetic and unchanged in the nondiabetic patients (P = 0.005). These studies document, for the first time, the development of GBM and mesangial lesions of diabetic nephropathy in normal living related donor and cadaver kidneys transplanted into diabetic patients and support the hypothesis that these lesions are secondary to the diabetic state.

Adult↗
PubMed1983

Polyantigenic expansion of basement membrane constituents in diabetic nephropathy.

The immunohistopathology of the intrinsic basement membrane-associated antigens were examined in diabetic nephropathy. In early and moderate stages of disease there was polyantigenic expansion of all the intrinsic components of mesangium, glomerular basement membrane (GBM), and tubular basement membrane (TBM) assessed by polyclonal antisera to collagen types IV and V, laminin, and by monoclonal antibodies to type IV collagen and fibronectin and to four other intrinsic components of normal renal extracellular matrices (MBM10, 11, 12, and 15). In the mesangium the first intrinsic antigens to increase were fibronectin and type V collagen. In late stages of disease, there was a diminution in the mesangium of all of these antigens with the exception of type V collagen, which persisted. Additionally, antigens appeared in the mesangium, recognized by MBM11 and MBM15, which are normally present in fetal but not adult mesangial regions. Similarly, in the GBM in late stages of disease, there was a decrease in all of the antigens, except for a persistence of the antigen recognized by MBM15. However, in TBM all of the antigens assessed increased in early, moderate, and severe disease. These studies document the complexity of polyantigenic alterations in the development of diabetic nephropathy.

Animals↗
PubMed1983

Diabetic nephropathy. A perspective.

The earliest manifestations of clinical diabetic nephropathy, including proteinuria, hypertension, and declining GFR, represent very advanced diabetic glomerulopathy with especially prominent mesangial expansion. Mesangial expansion, by restricting glomerular capillary filtration surface and lumenal volume, stimulates compensatory mechanisms analogous to those resulting from a marked reduction in nephron number. These compensatory mechanisms involve alterations in glomerular hemodynamics designed to maintain glomerular filtration but which ultimately injure the kidney. These hemodynamic perturbations are not specific to diabetes but represent a final common pathway toward endstage renal failure that also characterizes the remnant kidney. This thesis concludes that the onset of clinical diabetic nephropathy augurs inevitable decline in kidney function, and that only studies and interventions exercised before clinical nephropathy develops can influence understanding and outcome of diabetic nephropathy.

Basement Membrane↗
PubMed1983

Glucosylated and normal human of rat albumin do not bind to renal basement membranes of diabetic and control rats.

Hyperglucosylated and normal human and rat albumin were injected intravenously into control and streptozotocin-induced diabetic rats. Binding of injected human albumin to renal basement membranes was not observed by immunofluorescence microscopy in the diabetic or control rats irrespective of the form of injected albumin. However, human albumin was found as tubular droplets in both the control and diabetic rats injected with either form of albumin. Spontaneous binding of endogenous rat albumin was observed in a linear pattern on diabetic rat glomerular basement membranes (GBM), but not in the GBM of control rats. No appreciable differences in the intensity of staining for rat albumin was observed in diabetic rats injected with either glucosylated or normal rat albumin. Similarly, no binding of rat albumin to the GBM was observed in control rats irrespective of the type of albumin injected. These studies demonstrate that binding of albumin to renal basement membranes is not dependent on glucosylation.

Animals↗
PubMed1983

Quantitative glomerular morphology of the normal human kidney.

We determined glomerular basement membrane (GBM) width (as the harmonic mean) and relative volumes of the glomerular mesangium and of its cellular and matrix components in 59 male (73% living-related) and 59 female (93% living-related) donors of kidneys for transplantation. The GBM, consistently wider in male (mean, 373 nm.) versus female (mean, 326 nm.) donors, increased in width in all donors until the fourth decade of life when it appeared to decrease in width. The relative volume of the mesangium did not differ as to sex or age (mean, 14.2% of the glomerular volume), nor did either of its components (mean cellular mesangium, 7.1%; mean matrix mesangium, 7.1%). We found no correlations among renal index, GBM width, or the mesangium. No parameter differed in diabetic-related compared with nondiabetic-related donors. Results in cadavers for GBM width and the mesangium were no different from those of living-related donors. These observations yield insights into the development of the human kidney and its glomerular components, and in addition the GBM and mesangial measures will serve as normative values to which surgical or biopsy specimens can be related.

Adolescent↗
PubMed1982

Diabetic glomerulopathy in the uninephrectomized rat resists amelioration following islet transplantation.

Uninephrectomy is known to accelerate the development of both functional and morphological changes seen with experimental diabetic nephropathy in the rat. The present experiments utilized electron and light microscopic morphometric techniques to assess glomerular basement membrane width and the volumes of the total mesangium and its cellular and matrix components of inbred Lewis rats made diabetic at 6 weeks of age and uninephrectomized 9 days later. Immunofluorescent microscopy was used to evaluate IgG and C3 in the mesangium. The reversibility of established diabetic glomerular lesions in uninephrectomized diabetic rats after 7 months of diabetes was studied by performing intraportal transplant of neonatal pancreatic tissue. Renal biopsies were taken 2 months later in transplanted and non-transplanted animals. Islet transplantation lowered plasma glucose to normal levels (29.6 to 7.3 mmol/l) and raised plasma insulin values (6.3 to 53 muU/I). Glomerular basement membrane width in transplanted rats (268 nm) still exceeded the same measure (226 nm) in nondiabetic uninephrectomized rats. In transplanted animals volumes of the mesangium (0.51 x 10(6) micrometers 3) and of its cellular (0.27 x 10(6) micrometers 3) and matrix (0.24 x 10(6) micrometers 3) components remained higher than similar measures in control rats (0.32 x 10(6), 0.17 x 10(6) and 0.15 x 10(6) micrometers 3, respectively). Mesangial IgG in treated animals approached normal, but mesangial C3 remained similar to levels in non-transplanted diabetic control animals. These observations in uninephrectomized-diabetic rats contrast with previous observations in intact diabetic rats in which mesangial volumes and localization of immunoglobulins and complement returned to normal levels following islet transplantation.

Animals↗
PubMed1982

Transplantation of adult kidney into the very small child: long-term outcome.

Adult kidneys were transplanted into 12 children weighing between 5,400 and 8,800 gm. Ten received parental and two received cadaver grafts. Ten of the 12 children are alive 18 months to 9 years post transplant; eight have their original grafts and two required retransplantation-their original grafts were lost at 4 and 9 years because of chronic rejection. All but these two surviving children had normal or accelerated growth rates despite growth retardation prior to transplant. All children evidenced moderate to severe delay in psychomotor development prior to transplant. Seven of the ten survivors now have normal psychomotor function. Two are behind in school, and one with a degenerative central nervous system disease prior to transplant remains profoundly retarded. We conclude that because of donor availability, capacity for good donor-recipient matching, and minimization of time on dialysis, transplantation of adult kidneys into pediatric patients is preferable to awaiting the relatively uncommon pediatric cadaver donor. We further conclude that the procedure is warranted.

Age Factors↗
PubMed1982

Progressive encephalopathy in children with chronic renal insufficiency in infancy.

A retrospective analysis of children with renal failure during the first year of life revealed that 20 of 23 patients developed profound neurologic abnormalities. The encephalopathy was characterized by developmental delay, microcephaly, hypotonia, seizures, dyskinesia, and EEG abnormalities. No patient had been dialyzed, and four had not received aluminum salts prior to the development of neurologic symptoms. Inadequate statural growth and poor nutrition were present in all patients. It is probable that infants with chronic renal insufficiency are more susceptible to the development of this syndrome than are older children or adults because of the significant growth and maturation of the brain that occurs during the first years of life.

Body Height↗
PubMed1982

Diabetic nephropathy in the uninephrectomized dog: microscopic lesions after one year.

Carefully age-matched, purebred male beagle dogs that underwent uninephrectomy one month after they were made diabetic with alloxan were used to establish a model of rapidly developing diabetic nephropathy in a large animal. The diabetic animals, all requiring insulin, were divided into two groups: one group with control by insulin injections permitting elevated fasting and postprandial serum glucose values and substantial glycosuria; the other with better control and with near-normal serum glucose levels and less glycosuria. By 1 year of diabetes both diabetic groups had renal lesions different from the uninephrectomized control animals but differing only slightly from one another. With light microscopy, diabetic dogs had increased mesangial thickening. With electron microscopic morphometry, glomeruli of diabetic subjects demonstrated increased fractional volumes of the total mesangium and of its cellular and matrix components and increased width of the GBM. These quantitative measures of diabetic nephropathy in the dog within 1 year of onset of the disease describe a model potentially useful in evaluating the efficacy of improved diabetic control in preventing or ameliorating diabetic nephropathy.

Animals↗