Osmotic Nephrosis Research Articles

Osmotic nephrosis due to the use of anti-adhesive membrane intraperitoneally

A common strategy for the prevention of intra-abdominal adhesions post-operatively has been the application of adhesion barriers into the peritoneal cavity. Side effects of these barriers are infection, abscesses and inadequate wound healing. There is no information about such a side effect of these materials on renal function. The aim of this study was to evaluate the effect of two different, commercially available polysaccharide-based anti-adhesive materials on renal function. In 24 adult Wistar rats, an abdominal midline incision was performed, and an anti-adhesion membrane was placed in the peritoneal cavity so as to cover its whole surface. Four rats were used as the control group. In 12 rats, a membrane of macromolecular polysaccharides, weighing 40 mg/cm2, was placed intra-abdominally and in 8 rats, a hyaluronic acid-hydroacidmethylcellulose membrane weighing 0.4 mg/cm2 was placed. At 24 or 70 h, the rats were sacrificed, and we evaluated changes in serum creatinine, urea, uric acid, K and Na, and histologic examination of the kidney was performed. The use of the thicker macromolecular membrane was associated with a rise in serum creatinine and urea levels, vacuolization of all the tubular epithelial cells and mild interstitial infiltration. Rats in which the hyaluronic acid-hydroacidmethylcellulose membrane was used did not show any creatinine elevation, and they presented milder histologic lesions. Polysaccharide and cellulose anti-adhesive membrane cause renal damage with tubular cell vacuolization. The severity of kidney damage is relative to the quantity of the membrane material used.

Hemoglobinuria and Acute Kidney Injury Requiring Hemodialysis Following Intravenous Immunoglobulin Infusion

Intravenous immunoglobulin (IVIG), a product initially developed for patients with immunodeficiencies, now has multiple other indications and increasing off-label use. IVIG generally is well tolerated, with few adverse effects. Antibody-mediated (Coombs-positive) hemolysis is known to occur after IVIG infusion, but often is subclinical and previously has not been reported to lead to acute kidney injury (AKI). The predominantly known mechanism of AKI after IVIG infusion has been osmotic nephrosis, primarily associated with sucrose-containing formulations. We present a case of a bone marrow transplant recipient who was treated with a sucrose-free IVIG product and subsequently developed Coombs-positive hemolysis leading to AKI requiring hemodialysis, who ultimately died secondary to infectious complications. The severity of this case emphasizes the importance of identifying populations who may be at increased risk of pigment-mediated kidney injury before consideration of IVIG therapy.

Calcineurin inhibitor toxicity in a renal transplant recipient.

A 40-year-old Caucasian male who suffered end-stage renal disease due to unknown cause received a living-related renal allograft on 28 July 2008. Rabbit anti-thymocyte globulin was utilized for immediate post-transplant immunosuppressive induction, followed by maintenance immunosuppression with tacrolimus, mycophenolate mofetil and prednisone. Metoprolol was also administered for hypertension. Nadir serum creatinine occurred on post-transplant day number 7 (serum creatinine 2.2 mg/dL). At that time, the blood tacrolimus level was 14.8 ng/mL (reference range 5.0–20.0 ng/mL). The patient's serum creatinine abruptly rose to 2.6 mg/dL 3 days later, at which time his blood tacrolimus level was 46.8 ng/mL. A renal allograft biopsy (Figures ​(Figures11 and ​and2—see2—see Online Supplementary Material for colour illustrations) was performed a few days later, which revealed isometrically vacuolated proximal tubular epithelial cells and focal nodular arteriolar hyaline. The tubular epithelial cell isometric vacuolization seen was very focal, affecting only a few tubules in the biopsy sample. Isometric vacuolization describes the finding of numerous equally sized tiny clear cytoplasmic vacuoles. A diagnosis of acute calcineurin inhibitor toxicity (toxic tubulopathy) was made. These small, uniformly sized tubular epithelial cell cytoplasmic vacuoles are caused by toxic levels of the calcineurin inhibitors cyclosporine and tacrolimus and are due to dilatations of smooth endoplasmic reticulum by aqueous fluid [1,2,3]. This type of cytoplasmic hydropic change is light microscopically indistinguishable from that seen in osmotic nephrosis caused by hypertonic sucrose solutions, mannitol, high molecular weight dextrans, radiocontrast material or intravenous immunoglobulin. However, in contrast to those seen in calcineurin inhibitor toxicity, isometric vacuoles induced by the latter agents represent distended lysosomes rather than dilated smooth endoplasmic reticulum [4]. Ethylene glycol poisoning and hypokalaemia cause very large, coarse cytoplasmic vacuoles, easily distinguished by light microscopy from the numerous tiny vacuoles seen in calcineurin inhibitor toxicity and osmotic nephrosis [4]. In the case of calcineurin inhibitor toxicity, the typical cytoplasmic hydropic change may be so focal as to affect only a few tubules within a given biopsy [3]. Another, more serious acute toxic effect of calcineurin inhibitors is thrombotic microangiopathy, which was not seen in this biopsy. The patient's tacrolimus dose was lowered, followed by a reduction in his blood tacrolimus level and serum creatinine (2.1 mg/dL, 2 weeks post-biopsy). Fig. 1 Renal biopsy, stained with haematoxylin and eosin, reveals isometric vacuolization of proximal tubular epithelial cells. Tubular epithelial cell vacuolization is only focal (arrow), as seen by surrounding normal appearing tubules (original magnification ... Fig. 2 High-power view of involved renal tubule reveals marked epithelial cell swelling due to numerous tiny clear cytoplasmic vacuoles (original magnification ×600). For colour illustration, please see online supplementary materials.

Colloid-induced kidney injury: experimental evidence may help to understand mechanisms

Fluid resuscitation is widely used, and many patients are therefore exposed to plasma volume expanders. Among these, colloids, particularly hydroxyethyl starches, have been shown in recent experiments and clinical studies to induce acute kidney injury. The mechanisms of colloid-induced acute kidney injury remain incompletely elucidated. The risks associated with colloid osmotic pressure elevation in vivo and the high incidence of osmotic nephrosis lesions in experimental models and clinical studies indicate that hydroxyethyl starches can no longer be considered safe.

Osmotic nephrosis is not the exclusive HES associated phenomenon but occurs also after Ringers lactate infusion in an isolated renal perfusion model

Osmotic nephrosis is not the exclusive HES associated phenomenon but occurs also after Ringers lactate infusion in an isolated renal perfusion model

Osmotic Nephrosis: Acute Kidney Injury With Accumulation of Proximal Tubular Lysosomes Due to Administration of Exogenous Solutes

Osmotic nephrosis describes a morphological pattern with vacuolization and swelling of the renal proximal tubular cells. The term refers to a nonspecific histopathologic finding rather than defining a specific entity. Osmotic nephrosis can be induced by many different compounds, such as sucrose, hydroxyethyl starch, dextrans, and contrast media. It has a broad clinical spectrum that includes acute kidney injury and chronic kidney failure in rare cases. This article discusses the pathological characteristics, pathogenesis, and various clinical entities of osmotic nephrosis.

Blood Volume Expansion With Hyperoncotic Colloids Deteriorates Allograft Function in a Canine Model of Renal Transplantation

Purpose We investigated the effects of acute maximal hydratation with hemoce (H) and dextran-40 (D40) on the postoperative graft function, following renal transplantation (RT) in a canine model. Methods After induction of anesthesia with pentobarbital (5 mg/kg), 18 beagle dogs were randomized to receive either saline solution to increase the central venous pressure (CVP) to 5 mm Hg (GI); H solution to increase the CVP to 10 mm Hg (GII); or D40 to achieve 15 mm Hg (GIII), before reperfusion. A pulmonary artery catheter was used to measure CVP, mean pulmonary artery pressure, and cardiac output (CO). The surgical procedure consisted of autotransplantation of the dog’s left kidney an hour prior to cold ischemia with University of Wisconsin solution, followed by contralateral nephrectomy. Diuresis, creatinine (Cr), and BUN levels were measure at 24 hours before RT, as well as 24, 48, and 72 hours after the procedure. Results Only in the treated groups did cardiac filling presures and CO increase as a result of hydration. Only in the GI group did serum Cr and blood urea nitrogen significantly peak at the second postoperative day while it continued to increase at two (GII) and three (GIII) times greater than GI on the third day. Histological examination showed osmotic nephrosis like-lesions only among treated grafts. Conclusion We concluded that maximal hydration with H and D40 colloid deteriorated postoperative graft function after RT. We believe that in the future the effects of any colloid solution should be tested in an animal model in the fashion as we have described, in order to know which one, and at what dose, is the safest to improve kidney allograft outcome.

Osmotic nephrosis in a renal transplant recipient

CASE PRESENTATION A 59-year-old Hispanic male with a history of type II diabetes mellitus, hypertension, and end-stage renal disease (on hemodialysis for 2 years) was called in for a kidney transplant. He was in his usual health, having received dialysis earlier in the day. The kidney donor was from an expanded criteria pool and was a 59-year-old Caucasian male with diabetes mellitus who expired following a cerebrovascular accident. He had a terminal creatinine of 1.3mg/dl (114.92 μmol/l (nl range 0.6-1.2 mg/dl/53.04-106.08 μmol/l)) and no evidence of proteinuria. A donor renal biopsy revealed 10-15% tubular atrophy and interstitial fibrosis. There was a six-antigen mismatch, and cold ischemia time was 31 h. The final complement-dependent cytotoxic and flow cytometry crossmatch were negative. Renal transplantation was performed. At the time of transplantation, the patient received alemtuzumab (Campath; anti-CD52 monoclonal antibody) and solumedrol as induction therapy. The patient had an intra-operative episode of hypotension that resolved with a 500 ml bolus of normal saline and 250 ml of 6% hetastarch lactate electrolyte solution. At the completion of surgery, the patient was stable and was extubated and moved to recovery. On physical exam, he was normotensive with normal sinus rhythm, clear lungs, good dorsalis pedis pulses, and no peripheral edema. He had been anuric before surgery, but had made 10 ml of urine during the first hour. One hour after surgery, the patient's systolic blood pressure dropped to 80 mmHg. In an effort to sustain his blood pressure, he was given multiple boluses of normal saline, lactate Ringers solution, and an additional 11 of 6% hetastarch. He was eventually started on vasopressin and moved to the Intensive Care Unit. His hematocrit remained stable, but his potassium was elevated at 6.0 mM/I. Continuous renal replacement therapy was initiated. Renal ultrasound initially was unable to demonstrate arterial or venous blood flow. After 4 h, his blood pressure improved and he was weaned off vasopressin. A repeat ultrasound 24 h later showed restoration of arterial and venous blood flow. Maintenance immunosuppression was started on post-operative day 1 and included tacrolimus and mycophenolate mofetil. His tacrolimus trough level ranged between 9 and 13 ng/ml. The patient remained oliguric and hemodialysis-dependent during the first week. Due to delayed graft function and a creatinine of 6.2 mg/dl (548.08 μmol/l), renal allograft biopsy was performed on post-operative day 8.

Drug-induced acute kidney injury

The purpose of this review is to describe the most prevalent mechanisms of drug-induced acute kidney injury, to define the risk factors for nephrotoxicity, and to analyze the available evidence for preventive measures. Drug toxicity remains an important cause of acute kidney injury that, in many circumstances, can be prevented or at least minimized by vigilance and early intervention. Recent studies have resulted in increased insight into the subcellular mechanisms of drug nephrotoxicity. Further improvement is to be expected from the identification of early markers of nephrotoxicity and an increasing involvement of a clinical pharmacist. The main mechanisms of nephrotoxicity are vasoconstriction, altered intraglomerular hemodynamics, tubular cell toxicity, interstitial nephritis, crystal deposition, thrombotic microangiopathy, and osmotic nephrosis. Before prescribing a potentially nephrotoxic drug, the risk-to-benefit ratio and the availability of alternative drugs should be considered. Modifiable risk factors should be corrected. The correct drug dosage should be prescribed. Patients should be pre-hydrated and the glomerular filtration rate should be frequently monitored during the administration of a potentially nephrotoxic drug. Studies are needed to further elucidate the mechanisms of nephrotoxicity to design more-rational prevention and treatment strategies. Computer-based prescriber-order entry and an appropriately trained intensive care unit pharmacist are particularly helpful to minimize medication errors and adverse drug events.

Nephrotoxicity Related to New Therapeutic Compounds

Toxic nephropathy is an important cause of reversible renal injury. This article focuses on the nephrotoxicity of several new therapeutic compounds. Selective cyclooxygenase-2 inhibitor is associated with sodium retention, hypertension, ankle edema, and acute renal failure. The incidence of renal complication is similar to conventional nonsteroidal anti-inflammatory drugs. Bisphosphonates, especially when used in high dose for prolonged duration, can cause toxic acute tubular necrosis and renal failure. Pamidronate is also associated with a specific form of collapsing focal segmental glomerulosclerosis similar to one found in patients with human immunodeficiency virus (HIV) infection. Acyclic nucleoside phosphonate, a new group of antiviral agents, can cause Fanconi-like syndrome and progressive renal impairment. On the other hand, indinavir, a potent protease inhibitor for the treatment of HIV infection, can cause crystalluria, renal stone, acute tubular obstruction and chronic interstitial nephritis. Intravenous immune globulin and hydroxyethyl starch, a new plasma expander, are associated with acute renal failure with characteristic renal histology known as osmotic nephrosis. In short, physicians should be cautious about possible renal toxicity during the use of any new therapeutic agents.

Synergistic effect of intravenous immunoglobulins and iodinated contrast media on renal function.

Acute renal failure is one of the side effects while using intravenous immunoglobulins. This complication is also observed with iodinated contrast media. Herein, we describe a patient with acute renal failure who received intravenous immunoglobulins and iodinated contrast media concomitantly. Both drugs are responsible for osmotic nephrosis. The same effect on renal cells may explain a synergistic effect on renal function.

Intravenous immunoglobulin and the kidney—a two-edged sword

To review the literature on the use and efficacy of intravenous immunoglobulin (IVIG) in glomerulonephritis and to evaluate the nephrotoxic effect of IVIG. A structured literature search of articles published on the efficacy of IVIG in the treatment of nephritis between 1985 and 2003 was conducted. All articles dealing with lupus nephritis, IgA nephropathy, Henoch Schonlein purpura, antineutrophil cytoplasmic antibodies (ANCA) associated vasculitis, primary membranous glomerulonephritis, and primary chronic nephritis were reviewed. The same literature search was conducted for the nephrotoxic effects of IVIG. Two groups of patients were defined: (a) a group of patients with IVIG nephrotoxic effect published as case reports, and (b) a group of patients whose data were collected by the Food and Drug Administration (FDA). All existing data of both groups were pooled and compared. One hundred six patients with lupus nephritis were treated with IVIG. In most reports proteinuria, nephrotic syndrome, and values of creatinine clearance were improved. In 3 cases improvement in World Health Organization (WHO) class was noted, and in 2 cases a reduction of immune deposits was demonstrated. In the other forms of autoimmune nephropathy, although the number of reported cases was small, improvement was noted in most patients. Thirty-two reports entailing 78 patients with IVIG-induced nephrotoxicity were found and their data were compared with those of 88 patients reported to the FDA. No specific differences were noted between the 2 groups of patients, as their age and indications for using IVIG were similar. Most of the patients who developed renal toxicity (72% in the literature and 90% in the FDA group) received sucrose -containing IVIG products. A high percentage of patients (31% in the literature and 40% in the FDA group) required hemodialysis. Mortality occurred in 10 and 15%, respectively. Renal histology done in a minority of the cases demonstrated vacuolization and swelling of the proximal tubules consistent with osmotic injury. On one hand, there are encouraging reports on the efficacy of IVIG in different types of glomerulonephritis (mainly lupus nephritis) resistant to conventional therapy, but the exact success rate and clinical indications remain undetermined. On the other hand, IVIG and the kidney is a two-edged sword, since nephrotoxicity can be a serious rare complication of IVIG therapy. Products containing sucrose as a stabilizer are mainly associated with such injury through the mechanism of osmotic nephrosis. Preexisting renal disease, volume depletion, and old age are risk factors for such toxicity.

Acute renal injury following methanol poisoning: analysis of a case series.

The objective of this paper is to document the prevalence of indicators of acute renal injury in a series of methanol-poisoned patients treated in an intensive care unit and to discuss the possible mechanisms. This is a retrospective analysis of the medical records of 25 consecutive patients admitted to the intensive care unit after severe intentional methanol poisoning. Acute renal impairment was defined as a serum creatinine concentration higher than 177 micro mol/L and/or a urinary output on admission and for the first 24 h below 0.5 ml/kg/h. Clinical pathological signs of acute renal injury were found in 15 patients. In comparison with the 10 other patients taken as control group, the patients who developed renal injury had a lower blood pH value on admission, a higher serum osmolality, and a higher peak formate concentration. Two factors contributing to renal injury could be identified: hemolysis and myoglobinuria. The role of osmotic changes (osmotic nephrosis) or of a direct cytotoxic effect of formic acid remains speculative. Analysis of proteinuria suggests that proximal tubular cells may be preferentially affected. Results of histopathological evaluation of the kidney on a limited sample size (n = 5) were inconclusive but suggestive of possible hydropic changes in the proximal tubule secondary to methanol toxicity. Acute renal injury may be associated with other signs of severity in methanol poisoning, but it is almost always reversible in survivors. Indicators of acute renal injury were identified. The pathophysiology of this acute renal injury is multifactorial and far more complex than shock-related tubular necrosis.

Anuric Acute Renal Failure Caused by Dextran 40 Administration

Dextran 40 is largely used in clinical medicine as a plasma substitute because of its beneficial effects on the microcirculation and antithrombogenic properties. An unusual adverse reaction of dextran administration is oligoanuric acute renal failure. We report two cases of anuric ARF induced by dextran 40. Diuresis and renal function were quickly resumed after plasmapheresis treatment. Renal biopsy revealed normal kidneys except for swelling and vacuolation of renal tubules suggestive of osmotic nephrosis.

Osmotic nephrosis due to high-dose immunoglobulin therapy containing sucrose (but not with glycine) in a patient with immunoglobulin A nephritis

Acute renal failure has been described as a complication of immunoglobulin therapy. It is not clear whether the immunoglobulin per se or the sucrose that is used as a stabilizer is the cause. We describe a patient with immunoglobulin A nephropathy who was treated with sucrose-containing immunoglobulin. He developed acute renal failure with osmotic nephrosis found on kidney biopsy. When using a glycine-containing immunoglobulin no acute renal impairment was observed in this patient.

Acute Renal Failure following Immunoglobulin Therapy

Intravenous IgG infusion has infrequently been reported to cause acute renal failure. In almost all these reports, a sucrose containing IgG product was believed to be the cause of renal injury. Sucrose-induced osmotic nephrosis has been well described in the literature. In this report, we describe a case of acute anuric renal failure following a large infusion of intravenous IgG containing sucrose. Urine cytology demonstrated typical osmotic injury to the renal tubular epithelial cells. Early recovery of renal function was achieved by dialytic removal of sucrose from the circulation.

L'hydroxyéthylamidon peut-il être utilisé lors de la réanimation des sujets en état de mort cérébrale pour don d'organe ?

In France, most of the kidney grafts are obtained from brain dead organ donors. Brain death induces numerous changes, especially in haemodynamic status, requiring the infusion of large volumes of fluid. The aim of this study was to evaluate the effect of hydroxyethyl starch (HES) on the organ donors and the kidney graft function in recipients. We compared two groups of brain dead organ donors and the kidney grafts, differing by the infused solutions : either a combination of HES (Elohes®, Biosedra) and 4 % human albumin solutions (HES group), or albumin alone in the control group (Albumin group). In the two groups, sex-ratio, age, cause of brain death and duration of therapy were similar. Fluid requirements were identical in the two groups : respectively 2,211 ± 1,512 mL in the Albumin group vs 2,452 ± 1,094 mL in the HES group (p = 0.17). However, the volume of albumin was significantly decreased in the HES group : 711 ± 822 mL (p = 0.0001). Therefore the cost was lower in the latter : 638 ± 633 vs 1766 ± 788 FF. The coagulation status was not significantly different between the two groups. Amylasemia was higher in the HES group, but the difference was not significant. In the Albumin group, urinary output increased, but not significantly and creatinemia was decreased : 113.9 ± 62 vs 131.5 ± 44 μmol · L −1 (p < 0.05). The two groups of recipients were also similar for sex-ratio, age, kind of graft, cause of the chronic renal failure and ischaemia times. The lowest creatininemias during the first week were respectively : 167 ± 127 vs 146 ± 67 μmol · L −1 (p = 0.55). No dialysis was required. Four renal biopsies in the HES group showed an osmotic nephrosis without any deleterious consequence on the renal function. It is concluded that HES can be used safely for renal harvesting in brain dead patients and that it decreases the cost of organ donation.

The use of urinary N-acetyl-β- D-glucosaminidase (NAG) for the detection of contrast-media-induced ‘osmotic nephrosis’ in rats

Excretion of urinary N-acetyl-β-glucosaminidase (NAG), lactate dehydrogenase (LDH), alkaline phosphatase (ALP) and γ-glutamyltransferase (γ-GT) was studied following single intravenous administrations of a non-ionic monomeric contrast medium (iohexol) at doses of 5.0, 7.5, 10.0 and 12.5 g iodine/kg body wt in rats. Measurements of urinary enzymes, serum urea nitrogen and serum creatinine were carried out on the 2nd, 3rd, 4th and 8th days after treatment. Histological examinations of kidneys were performed on days 3 and 8. From 5.0 g iodine/k onwards urinary NAG showed a dose-dependent and significant (multiple comparison, α = 0.05) increase in the first 18-h urine samples after application. A significant increase in urinary LDH could be observed only at the highest dose of 12.5 g iodine/kg. All other biochemical parameters showed no differences when compared to the control group. The dose-dependent increase in lysosomal NAG correlated with the histological findings i.e. there was dose-dependent vacuolization of proximal tubular cells, so-called ‘osmotic nephrosis’.

A histopathological study on the renal lesions in the patients who died in the ICU and CCU

For clarifying the pathogenesis of the acute renal failure which is regarded as one of the most important complications in the patients who died in the ICU and CCU, the histopathological study of the renal lesions has been performed in this communication and the results obtained were as follows:1) There was no typical case of classifical lower nephron nephrosis (LNN) type I in this study. However, a few cases of LNN type II revealed interstitial focal edema-fibrosis variant were obserbed. Incidentally in both group striking anemia in intra-renal vasculature constitutes the common features.2) Approximately 8% of the LNN type I group associated with shock kidney (SK) type III which suggested the alteration, of renal change resulted from incorporation of intensive care medical units.3) The author failed to observe the osmotic nephrosis which was anticipated by the massive infusional therapy and majority of them disclosed focal nephrotic type. Moreover, no case of renal hemosiderosis is encountered. This fast also may support a view that the changes of the renal lesions have been alterated remarkably after incorporation of infusional therapy based on theoretical back ground.4) In the entity of specific varities, intra-glomerular stasis, intra-glomerular micro-thrombosis formation, acute renal infarction, renal cortical necrosis, renal vascular paralysis, acute tubular necrosis and renal, or pen-pelvic hemorrhages are frequently observed. Majority of them manifested clinical symptomes of acute renal failure. Moreover, it is of noteworthy that the marked increase of the intra-glomerular micro-thrombosis is observed recently, which also supports the view of alteration of renal lesions after installation of critical care units.5) In the entity of renal cortical necrosis, renal pre-infarction or renal pre-cortical necrosis which may reflect the extremely acute cases of renal impairment.6) The renal or pen-pelvic hemorrhages are frequently observed in various underlying disease conditions. This fact is justified as one of the most noteworthy pathological changes which suggest the causation of severe shock conditions.

Effect of mannitol, dextran (Macrodex®), allopurinol, and methylprednisolone on the morphology of the proximal tubule of the rat kidney made ischemic in vivo

Rats were anesthetized and their lift kidneys were made ischemic for 1 h by clamping of the aorta just above the left renal artery. Mannitol (2.5 g/kg), Dextran 70 (0.6 g/kg), methylprednisolone (50 and 100 mg/kg), and allopurinol (100 mg/kg body weight) were administered before, during, or after the ischemia period in order to test the effect of each of these drugs upon this model of renal injury. At 24 h after the release of the aortic clamp the left kidneys of the drug treated animals wwere perfusion fixed and processed for light and electron microscopy. Dextran administration to animals with ischemic kidneys gave rise to a pronounced vacuolization ("osmotic nephrosis"), in the entire proximal tubule and especially in the pars recta. This was in contrast to dextran administration to rats with nonischemic kidenys, which showed no or very mild "osmotic nephrosis." This demonstrates that ischemia makes rat kidneys more susceptible to the development of "osmotic nephrosis." In controls (no drug treatment) one hour of renal ischemia gave partial necrosis of pars recta of the proximal tubule, while the pars convoluta tubule survived. Mannitol treatment significantly reduced the amount of necrosis of the pars recta, whereas dextran, methylprednisolone, and allopurinol had no or a negative effect on the survival of the cells of the pars recta segment. It is suggested that mannitol protects against the development of necrosis by increasing medullary blood flow in combination with a counteractive influence on the cellular swelling, which is known to occur in ischemia.