Altered Distribution Pattern of Na+-K+-ATPase and Succinate Dehydrogenase Activities along the Nephron in Human Acute Post-Transplant Renal Failure

Abstract

Summary:The catalytic activities of Na+-K + -ATPase and succinate dehydrogenase, marker enzymes for active salt reabsorptive capacity of renal basolateral plasma membranes and for respiratory capacity of mitochondrial cristae membranes, were studied in the maintenance phase of human acute post-transplant renal failure. Biopsies of 4 kidney-allografts taken at transplantation Operation and additionally at different posttransplantation periods, either with good function or in various stages of dysfunction, were compared with the unaffected part of a human kidney nephrectomized due to hypernephroma. In single nephron segments, Na + -K + -ATPase activity was determined after microdissection by microfluorometry, and succinate dehydrogenase activity was determined by a microphotometric procedure in stained cryosections.In intraoperative and postoperative biopsies of a well-functioning allograft, both Na + -K + -ATPase and succinate dehydrogenase activities did not differ from those of normal renal tissue. In contrast, the catalytic activities were found to be decfeased in the distal tubules of 2 anüric allografts when compared with their intraoperative controls. In addition, succinate dehydrogenase activity was reduced in distal tubules of a recovering allograft. Catalytic activities appeared to be unaffected in glomeruli, proximal tubules, and collecting ducts.It is suggested that the predominant distal tubular alterations with regard to these parameters are a consequence of increased distal tubular vulnerability due to circulatory and metabolic conditions. Verändertes Verteilungsmuster der Na + -K+-ATPase-und Succinat-Dehydrogenase-Aktivitäten entlang des Nephrons bei akutem Nierenversagen nach Nierentransplantation beim MenschenZusammenfassung: Die katalytischen Aktivitäten von Na der Erholungsphase war die Succinat-Dehydrogenase-Aktivität ebenfalls vermindert. In den Glomeruli, proximalen Tubuli und Sammelrohren wurden unveränderte katalytische Aktivitäten gemessen.Die bezüglich dieser Kenngrößen vorwiegend distal lokalisierten tubulären Veränderungen sind als Folge einer größeren Vulnerabilität dieser Nephronabschnitte auf Grund der Durchblutungs-und Stoffwechselverhältnisse anzusehen.

Catalytic Activities of Alkaline Phosphatase and N-Acetyl-ß-D-Glucosaminidase in Human Cortical Nephron Segments: Heterogeneous Changes in Acute Renal Failure and Acute Rejection Following Kidney Allotransplantation

“…The unspecific overshoot of activity of the latter enzyme in the maintenance and recovery phases of acute post-transplant renal failure, detected in the whole nephron, is considered to be reactive to various cellular alterations following transplantation. These alterations include markedly decreased areas of basolateral and inner mitochondrial membranes in distal tubules (14) äs well äs distorted brush-border membranes in proximal tubules. This complexity of cellular reactivity to injury implies that it is difficult to Interpret enzymuria with respect to the nature and degree of renal damage.…”

“…It is localized within the enz y mes of basolateral interdigitations and mitothe lysosomes of tubular cells (8) and contributes to chondrial inner membranes, Na+-K+-ATPase and the intracellular degradation of carbohydrate-consuccinate dehydrogenase were selectively reduced in taining macromolecules (9). distal tubules of biopsies taken from human kidney allografts in the maintenance phase o£äcute renal Brush-border membranes and lysosomes are cellular failure (14). These enzyme activities were found to be compartments which undergo alterations in exper-unchanged in proximal tubules, but in this part of imentally mduced acute renal failure (10).…”

Nephrotoxicity of Cyclosporine A in the Rat

“…H ei delberg, FRG) were used for staining with the periodic acid-Schiff reaction. for lyophilizat ion, and for staining for succinate dehydrogenase activity [16],…”

“…The degree and tubular location of mito chondrial alterations in biopsies of human kidney allografts have been previously deter mined by microphotometrical, histochemical investigation for the activity of succinate de hydrogenase [succinate: (acceptor) oxidoreductase (EC 1.3.99.1 )] [16], Therefore, this method was used here to analyze the integrity of the mitochondrial inner membranes along the rat nephron after administration of cyclo sporine A. This study should provide evi dence of the location and degree of altered function in the mitochondrial cristae mem branes, of the effects of the duration and dos age of cyclosporine A treatment, chosen ac cording to previous reports [3.4,10.11,13], as well as of the reversibility of these effects.…”