Alfred J. Fish

This study was designed to elucidate the cellular basis of risk of or protection from nephropathy in patients with type 1 diabetes. Entry criteria included diabetes duration of > or =8 years (mean duration, 22.5 years) and glomerular filtration rate (GFR) >30 ml x min(-1) x 1.73 m(-2). Patients were classified, on the basis of the estimated rate of mesangial expansion, as "fast-track" (upper quintile) or "slow-track" (lower quintile). A total of 88 patients were normoalbuminuric, 17 were microalbuminuric, and 19 were proteinuric. All three groups had increased glomerular basement membrane (GBM) width and mesangial fractional volume [Vv(Mes/glom)], with increasing severity from normoalbuminuria to microalbuminuria to proteinuria but with considerable overlap among groups. Vv(Mes/glom) (r = 0.75, P < 0.001) and GBM width (r = 0.63, P < 0.001) correlated with albumin excretion rate (AER), whereas surface density of peripheral GBM per glomerulus [Sv(PGBM/glom)] (r = 0.50, P < 0.001) and Vv(Mes/glom) (r = -0.48, P < 0.001) correlated with GFR. Vv(Mes/glom) and GBM width together explained 59% of AER variability. GFR was predicted by Sv(PGBM/glom), AER, and sex. Fast-track patients had worse glycemic control, higher AER, lower GFR, more hypertension and retinopathy, and, as expected, worse glomerular lesions than slow-track patients. Thus, there are strong relationships between glomerular structure and renal function across the spectrum of AER, but there is considerable structural overlap among AER categories. Given that normoalbuminuric patients may have advanced glomerulopathy, the selection of slow-track patients based on glomerular structure may better identify protected patients than AER alone.

This study was designed to define quantitatively the function of the rat glomerular mesangium in the uptake and processing of intravenously administered protein macromolecules (radiolabeled aggregated human IgG, AHIgG-(125)I), to relate this function to that of the general reticuloendothelial system, and to examine the effects of increased glomerular permeability to protein on the mesangial cell system.Mesangial localization of human IgG as demonstrated by immunofluorescent microscopy showed good correlation with concentrations of AHIgG-(125)I in preparations of isolated glomeruli. In normal rats the concentrations of AHIgG-(125)I in glomeruli were similar to those of lung, liver, and spleen and demonstrated a rapid decrease with increasing time intervals after aggregate administration. In rats given aminonucleoside of puromycin a marked increase in mesangial uptake of aggregates was found while studies of nephrotic lungs, liver, spleen, and blood showed no such differences. Glomerular levels of AHIgG-(125)I in aminonucleoside animals could not be correlated with the quantity of proteinuria. Nephrotic and control animals given unaggregated human IgG showed little glomerular localization by immunofluorescent microscopy; no difference in the concentration of this protein in nephrotic as compared to control glomerular isolates was found.Thus, the mesangium in normal animals functions in a manner analogous to that of the general reticuloendothelial system. In nephrotic rats the mesangial uptake of macromolecules is makedly increased, a finding not observed in other tissues.

Abstract The not uncommon association in clinical practice of problems existing simultaneously in the kidney and ear, prompted a closer look at these two distant organs, revealing in fact that they may be comparable in a variety of ways. Anatomical similarities were seen especially at the ultra‐structural level. Physiological mechanisms of fluid and electrolyte balance are present in both organs, and this common function is reflected in similar pharmacological actions of certain drugs. Congenital syndromes which have both renal and hearing defects have been the subject of much investigation attempting to relate a single etiological process in a common pathogenesis. To investigate a possible existence of shared antigenicity the tools of immunochemistry and immunohistochemistry were employed in experimental studies comparing the kidney with the lateral cochlear wall. The experimental animals chosen were the rat and guinea pig. Anti‐rat sera and anti‐guinea pig sera were produced using the goat or rabbit respectively as the antibody producing animal. In order to produce the antisera, specimens of stria vascularis were dissected from the cochlea. The collected specimens were then placed in saline and Complete Freunds Adjuvant, emulsified and then injected into subcutaneous sites of rabbits. After about 10 days the blood was withdrawn and the serum extracted from the blood. This crude serum was then used in subsequent experiments as the anticochlea antibody (AC Ab). In a similar manner glomerular basement membrane antibody was prepared (AGBM Ab). Two methods of immunofluorescent staining were used, namely, the indirect and direct method. In the indirect method, frozen sections of normal cochlea or renal tissue specimens were treated with the previously prepared AC Ab or AGBM Ab and then counterstained with Fluorescein labeled goat anti‐rabbit gamma globulin serum (GARG‐Fl). In the direct method tissue specimens from guinea pigs that had been injected with either AC Ab or AGBM Ab were stained directly with GARG‐Fl. In a third part of the experiments, the left cochlea from each animal injected with either AGBM Ab or AC Ab was taken for light histology. The results of these experiments are summarized in Tables I, II, and III. Of marked significance in our studies is the observation that AC Ab is capable of staining renal tubular epithelium. This presents compelling evidence of antigenically similar epithelial components. In conclusion, there is a fascinating similarity between the cochlea and the kidney. This similarity extends through a variety of modalities. There is even experimental evidence of a possibility of antigenically similar epithelial components.