Osmotic nephrosis

Abstract: The osmotic diuretic mannitol may be used in diverse clinical settings, such as providing "renal protection" in patients at risk for acute renal failure, decreasing intracranial pressure in patients with intracranial trauma, and preventing the dialysis-disequilibrium syndrome. Mannitol is commonly used after cardiac catheterization, cardiovascular surgery, and exposure to intravenous contrast dyes. This study presents a case in which a long-term renal transplant recipient receiving cyclosporine therapy concomitantly developed acute renal failure after the administration of high-dose mannitol in an attempt to induce an osmotic diuresis. The diagnosis of "osmotic nephrosis" was confirmed by renal biopsy, and the condition was reversed by cessation of the agent. Studies in experimental animals indicate that cyclosporin A can potentiate the tubular toxicity of mannitol, but such an association has not been verified in humans. Numerous studies confirm the nephrotoxic potential of high-dose mannitol, especially in patients with renal insufficiency. The clinical utility of the osmolar gap in preventing mannitol nephrotoxicity is emphasized.

Abstract: The pathophysiology of contrast-induced AKI (CIAKI) is incompletely understood due to the lack of an appropriate in vivo model that demonstrates reduced kidney function before administration of radiocontrast media (RCM). Here, we examine the effects of CIAKI in vitro and introduce a murine ischemia/reperfusion injury (IRI)–based approach that allows induction of CIAKI by a single intravenous application of standard RCM after injury for in vivo studies. Whereas murine renal tubular cells and freshly isolated renal tubules rapidly absorbed RCM, plasma membrane integrity and cell viability remained preserved in vitro and ex vivo, indicating that RCM do not induce apoptosis or regulated necrosis of renal tubular cells. In vivo, the IRI-based CIAKI model exhibited typical features of clinical CIAKI, including RCM-induced osmotic nephrosis and increased serum levels of urea and creatinine that were not altered by inhibition of apoptosis. Direct evaluation of renal morphology by intravital microscopy revealed dilation of renal tubules and peritubular capillaries within 20 minutes of RCM application in uninjured mice and similar, but less dramatic, responses after IRI pretreatment. Necrostatin-1 (Nec-1), a specific inhibitor of the receptor-interacting protein 1 (RIP1) kinase domain, prevented osmotic nephrosis and CIAKI, whereas aninactiveNec-1derivate(Nec-1i)orthepan-caspaseinhibitorzVADdidnot.Inaddition,Nec-1prevented RCM-induceddilationofperitubularcapillaries,suggestinganovelroleunrelatedtocelldeathfortheRIP1 kinase domain in the regulation of microvascular hemodynamics and pathophysiology of CIAKI.

Abstract: Renal biopsies were performed in 211 patients within 10 days of excretory urography or renal arteriography in which diatrizoate, iothalamate or ioxithalamate had been used. In 47 renal specimens, osmotic nephrosis of the proximal tubular cells was found. Previous renal function had been normal in 10 patients, moderately impaired in 19, and severely impaired in 18. Tubular atrophy and/or necrosis was associated with histological features in 29 of 47 patients. Diffuse osmotic nephrosis was more often found in patients biopsied soon after roentgenography and also with severe renal insufficiency, but was not necessarily associated with declining renal function. The mechanism(s) by which contrast media may induce osmotic nephrosis remains unclear.

Abstract: Intravenous immunoglobulin preparations are being used for an increasing number of indications in clinical medicine To minimize adverse reactions, sugar additives such as sucrose are added to some preparations to serve as stabilizing agents We describe a patient treated with an immunoglobulin preparation containing sucrose who developed a fully reversible form of acute renal failure with histologic changes characterized by vacuolization and swelling of renal proximal tubular cells We believe the high concentration of sucrose in the immunoglobulin preparation resulted in osmotic injury to the renal tubules Such changes, which are identical to those described in humans and experimental animals given intravenous infusions of hypertonic sucrose, have come to be known as osmotic nephrosis Risk factors for the development of this lesion are renal insufficiency and volume depletion The risk for such injury can be minimized by further diluting the immunoglobulin preparation and slowing the infusion rate