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Medline ® Abstracts for References 7,8,10

of 'Acute kidney injury (AKI) in minimal change disease and other forms of nephrotic syndrome'

7
TI
Structural basis for reduced glomerular filtration capacity in nephrotic humans.
AU
Drumond MC, Kristal B, Myers BD, Deen WM
SO
J Clin Invest. 1994;94(3):1187.
 
Previous studies have established that in a variety of human glomerulopathies the reduced glomerular filtration rate (GFR) is due to a marked lowering of the ultrafiltration coefficient (Kf). To identify the factors which lower Kf, we measured the filtering surface area per glomerulus, filtration slit frequency, basement membrane thickness, and GFR and its determinants in patients with minimal change and membraneous nephropathies and in age-matched healthy controls. Overall values of Kf for the two kidneys were calculated from GFR, renal plasma flow rate, systemic colloid osmotic pressure, and three assumed values for the transcapillary pressure difference. "Experimental" values of the glomerular hydraulic permeability (kexp) were then calculated from Kf, glomerular filtering surface area, and estimates of the total number of nephrons of the two kidneys. Independent estimates of the glomerular hydraulic permeability (kmodel) were obtained using a recent mathematical model that is based on analyses of viscous flow through the various structural components of the glomerular capillary wall. Individual values of basement membrane thickness and filtration slit frequency were used as inputs in this model. The results indicate that the reductions of Kf in both nephropathies can be attributed entirely to reduced glomerular hydraulic permeability. The mean values of kexp and kmodel were very similar in both disorders and much smallerin the nephrotic groups than in healthy controls. There was good agreement between kexp and kmodel for any given group of subjects. It was shown that, in both groups of nephrotics, filtration slit frequency was a more important determinant of the water flow resistance than was basement membrane thickness. The decrease in filtration slit frequency observed in both disorders caused the average path length for the filtrate to increase, thereby explaining the decreased hydraulic permeability.
AD
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge 02139.
PMID
8
TI
Foot process fusion and glomerular filtration rate in minimal change nephrotic syndrome.
AU
Bohman SO, Jaremko G, Bohlin AB, Berg U
SO
Kidney Int. 1984;25(4):696.
 
Reduced glomerular filtration rate (GFR), not due to hypovolemia, has been reported in patients in the proteinuric phase of the minimal change nephrotic syndrome (MCNS). A group of children with MCNS was studied to investigate the possible relationship between the fusion of glomerular epithelial foot processes and the reduction in GFR. The degree of foot process fusion was estimated as the harmonic true mean of foot process width and the length density of epithelial slit pores as determined by quantitative electron microscopic stereology. In the patients investigated GFR ranged between 40 and 127 ml/min/1.73 m2 body surface area, the filtration fraction between 6.9 and 22.5%, and the serum albumin concentration between 14 and 46 g/liter. The mean foot process width, which varied between 330 and 870 nm, showed a close correlation with GFR (r = -0.859) and the filtration fraction (r = -0.812), as well as with the serum albumin concentration (r = -0.756). As expected, a reduction of epithelial slit pore length occurred concomitant with the broadening of the foot processes. These results agree with the hypothesis that the reduction in the total length of glomerular epithelial slit pores, due to the fusion of foot processes, results in a reduced glomerular capillary permeability to water and small solutes.
AD
PMID
10
TI
Normal glomerular permeability and its modification by minimal change nephrotic syndrmone.
AU
Robson AM, Giangiacomo J, Kienstra RA, Naqvi ST, Ingelfinger JR
SO
J Clin Invest. 1974 Nov;54(5):1190-9.
 
It has been suggested that the glomerular basement membrane restricts the passage of large molecules only, the barrier to filtration of smaller molecules being at the level of the epithelial slit pore. This hypothesis was investigated by measuring glomerular permeability to (125)I-labeled polydisperse polyvinyl pyrrolidone (PVP) in 16 children with idiopathic nephrotic syndrome (INS) and in 6 children of comparable age who had no evidence of renal disease. Studies were performed in the patients with INS before, during, and after treatment with steroids. PVP in blood and urine samples was separated according to molecular size by solumn chromatography, to permit the calculation of permeability to inert macromolecules of sizes ranging from 8,000 mol wt. In untreated INS, glomerular permeability to molecules>40 A was normal; permeability to smaller molecules was markedly reduced, frequently to 20% or less of normal. There was an average decrease in inulin clearance (C(in)) of 24%. Glomerular permeability and C(in) returned to normal in INS treated with steroids only when proteinuria disappeared. The results support the concept, derived from studies with ultrastructural tracers, that the final barrier to filtration may be at the level of the epithelial slit pore. Thus fusion of the epithelial foot processed with obliteration of the slit pores was associated with impaired passage of smaller molecules of PVP into the urine. Reversal of the pathologic abnormality resulted in return of permeability to normal. The decreased C(in) seen in INS may not reflect true glomerular filtration rate, but may result from restricted passage of inulin molecules (mol wt 5,000) through the epithelial slit pore.
AD
PMID