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Biomedical subjects

K Solez

Publications and source records attributed to K Solez.

At least 73 records · Page 4Linked to original sources
PubMed1989

The protective effect of thromboxane synthetase inhibition on renal function in systemic sepsis.

To study the role of thromboxane in systemic sepsis and renal failure, peritonitis was induced surgically in 22 sheep, leading to local and systemic sepsis. A selective thromboxane synthetase inhibitor, U63,557A (Upjohn Co, Kalamazoo, MI) was given before surgery in five animals and 30 minutes after surgery in five animals. A typical picture of volume-loaded, normotensive, vasodilated septic shock developed in all animals. Twenty four hours after induction of sepsis, the control group showed a marked reduction in glomerular filtration rate (GFR), urine volume, and urinary sodium excretion. Pretreated animals showed no change in GFR and a smaller reduction in urine volume and sodium excretion. The posttreatment group showed no change in any parameters of renal function. Plasma renin activity, urinary TXB2 excretion, and urinary 6-keto PGF1 alpha excretion increased after 24 hours only in the control group. Urinary TXB2 excretion was reduced by 80% in animals given U63,557A before surgery. The results indicate a significant protective effect of U63,557A on renal function during septic shock, probably related to reduced thromboxane synthesis, with no apparent deleterious systemic effects. The results support a role for thromboxane in the pathogenesis of acute renal failure in systemic sepsis.

Animals↗
PubMed1989

Primary acute renal failure ("acute tubular necrosis") in the transplanted kidney: morphology and pathogenesis.

"Acute tubular necrosis" (ATN) in the transplanted kidney, when properly differentiated from other causes of acute renal failure, appears to be a relatively benign condition. It has been widely assumed to be pathologically identical to ATN in the native kidney, but its histopathologic features have not been studied in detail. Because immunosuppressive therapy with cyclosporine adds an additional layer of complexity to the morphologic changes observed, in the present study we have confined our observations to patients immunosuppressed with steroids and azathioprine. Thirteen renal allograft biopsies from patients with ATN and 5 biopsies from patients with normal allograft function were compared with the previously obtained series of 57 native kidney ATN biopsies and 20 control biopsies. Both qualitative and quantitative differences between transplant and native kidney ATN were found. Compared with native kidney ATN, transplant ATN showed significantly less thinning and absence of proximal tubular brush border and less variation in size and shape of cells in individual tubular cross-sections. There were also significantly fewer casts and less dilatation of Bowman's space and a significantly greater number of polarizable crystals presumed to be oxalate in transplant ATN. In native kidney ATN the tubular injury sites were mostly characterized by desquamation of individual epithelial cells leaving areas of bare basement membrane (the "non-replacement" phenomenon). In transplant ATN, sites of tubular injury, although rare and affecting only short tubular segments, were characterized by the actual presence of identifiable necrotic tubular cells, a finding seldom seen in native kidney ATN. There also was a greater interstitial infiltrate of mononuclear inflammatory cells in transplant ATN compared to native kidney ATN. Electron microscopic studies of 9 transplant ATN biopsies showed a mild reduction in proximal tubular brush border compared with controls but this alteration was significantly less than that observed in native kidney ATN. There was no significant alteration in proximal or distal basolateral infoldings and this contrasted sharply with the marked reduction in basolateral infoldings of the plasma membrane observed in native kidney ATN. Disintegrated necrotic cells were found by electron microscopy in transplant ATN whereas these were not observed in native kidney ATN. There were significantly more cells with apoptosis (shrinkage necrosis) in transplant ATN than in native kidney ATN. There were significantly more cells with apoptosis (shrinkage necrosis) in transplant ATN than in native kidney ATN. On the other hand, there were significantly greater numbers of "non-replacement" sites in the distal tubules in native kidney ATN compared to transplant ATN.(ABSTRACT TRUNCATED AT 400 WORDS)

Actins↗
PubMed1989

Central nervous system toxicity of cyclosporine in a rat model.

The central nervous system toxicity of cyclosporine, which is known to be neurotoxic clinically, was investigated in a rat model. Munich-Wistar rats were divided into 3 groups for a 2-week protocol. After baseline EEG and behavioral testing, group 1 (control) received a weight-adjusted volume of parenteral cyclosporine vehicle i.p., group 2 (low-dose) received 5 or 10 mg/kg/day i.p., and group 3 (high-dose) received 20 mg/kg/day i.p. Spontaneous behavior was observed, simple sensorimotor testing performed daily, and awake EEG's recorded 3 times per week. Four of 12 high-dose animals died during study, one after a witnessed tonic-clonic seizure, and two after recording of frankly epileptiform EEG's; there were no deaths in control or low-dose animals. Significant EEG abnormalities developed only at high-dose, with frankly epileptiform EEG's and/or seizures seen in 58 +/- 15% of these rats (P = 0.005, different from controls by life-table analysis). Although some high-dose animals demonstrated hyperirritability and dystonic posturing, behavioral changes were subtle, and animals were often still or rocking slightly during recording of frankly epileptiform EEG's. Walking latency and alley escape behaviors were delayed in high-dose rats, the latter correlating with abnormal EEG's. Serum urea nitrogens were mildly elevated in high-dose animals, but serum creatinine, electrolytes, bilirubin, body magnesium stores, and blood pressure remained normal in all groups. Kidneys showed only mild vacuolation histologically. The brain showed only very focal cortical injury sites related to electrode placement, which did not correlate with EEG changes or mortality. These results suggest that there may be a direct effect of cyclosporine on the central nervous system. This model system should prove useful in defining mechanisms of cyclosporine-related neurotoxicity.

Animals↗
PubMed1988

Ultrastructural investigation of renal biopsies: a discussion of artifacts and special methodology.

The aim of this presentation is to draw attention to the problems inherent in evaluating the ultrastructure of percutaneous renal biopsies and to discuss some of the special techniques which are useful in this area. It is important to realize that the ultrastructure as it appears in this kind of material does not necessarily reflect conditions in vivo. Comparison with suitable reference material may, however, permit reliable conclusions in terms of pathological diagnosis and pathogenesis. It is advocated that purely qualitative methods, which until now have predominated in ultrastructure work with renal biopsies, be replaced by morphometry and semiquantitative methods when it is possible and practical to do so in any research situation.

Biopsy↗
PubMed1988

Vasoactive hormones in the renal response to systemic sepsis.

The pathophysiology of renal dysfunction in generalized sepsis remains unknown. In this study, 24 hours after surgical induction of peritonitis in 20 volume-loaded sheep, three patterns of renal function were seen. In group 1 (n = 8), glomerular filtration rate (GFR) decreased by 70%, urine volume by 85%, absolute sodium excretion by 95%, and fractional sodium excretion by 83%. Group 2 (n = 4) exhibited similar sodium retention but GFR did not fall. Group 3 (n = 8) showed no change in GFR or urine volume and only minimally reduced sodium excretion. Mean arterial pressure fell 17% in group 1 only; central venous pressure, pulmonary capillary wedge pressure, and plasma volume were maintained at or above presepsis values in all groups. Cardiac index was either increased or unchanged, and renal plasma flow was maintained in all groups; there was thus no hemodynamic evidence to suggest volume contraction. Histologic examination showed only minor changes with no consistent pattern. Renal functional changes correlated with other manifestations of severe sepsis--GFR and sodium retention correlated significantly with increased cardiac index, decreased systemic vascular resistance, pulmonary arterial hypertension, leukopenia, hypoproteinemia, and hypoglycemia. All of these changes were most marked in group 1. In groups 1 and 2, plasma renin activity (PRA) increased and urinary kallikrein excretion decreased. PRA correlated inversely with GFR, urine volume, and sodium excretion; urinary kallikrein excretion correlated positively with urine volume and sodium excretion. Urinary excretion of 6-keto-PGF1 alpha was increased in groups 1 and 2 and correlated inversely with mean arterial pressure in group 1 animals. During sepsis, urinary thromboxane B2 excretion continued at presepsis values in all groups. The results suggest that unusual reciprocal changes in activity of the renin-angiotensin and renal kallikrein-kinin systems may play a role in the renal response to sepsis. PGI2 synthesis is increased and may affect systemic hemodynamics and renal function; the role of thromboxane A2 in this context is unknown.

6-Ketoprostaglandin F1 alpha↗
PubMed1988

Renal dysplasia: sonographic findings.

In 38 pediatric patients (predominantly neonates) with a proved pathologic diagnosis of renal dysplasia, a variety of sonographic appearances were seen. When the obstruction was at the level of the ureteropelvic junction (12 patients, 12 kidneys), the typical appearance was of a large kidney containing multiple large or moderate-sized cysts. When the obstruction was at the level of the distal ureter (14 patients, 14 kidneys), a smaller kidney containing a few cysts of variable sizes was usually seen. When the obstruction was at the level of the urethra (eight patients, 13 kidneys), the kidney was typically small with few or no cysts. In four patients (seven kidneys) in whom no cause of the obstruction was evident, the kidneys were small and echogenic. There was one case of segmental dysplasia.

Adolescent↗
PubMed1987

Relation between renal calcium content and renal impairment in 246 human renal biopsies.

Tissue calcium content from 246 diagnostic human renal biopsies was measured to assess whether elevated tissue calcium concentration could be demonstrated to exist early during the course of human renal disease or was only a manifestation of advanced renal impairment. Renal calcium content correlated significantly with serum creatinine (r = +0.23, P less than 0.001, N = 246); serum phosphate P less than 0.001, N = 169) but not with serum calcium (r = -0.10, P greater than 0.1, N = 193). Fivefold greater calcium content was measured in biopsied patients with normal renal function than in normal postmortem renal tissue (35.7 +/- 5.2 vs. 7.6 +/- 0.7 mgCa/100 g wet renal tissue, P less than 0.001). Those biopsied patients with significant functional impairment (SCr greater than 1.5 mg/dl) had a higher mean level of serum phosphorus and serum [Ca] X [P] product than patients with normal renal function (5.19 +/- 0.22 vs. 3.92 +/- 0.11 mg P/dl and 44.8 +/- 1.8 vs. 35.7 +/- 1.2 mg2/dl2, respectively), and slightly higher renal calcium content (85.3 +/- 32.2 vs. 35.7 +/- 5.2 Ca/100 g wet renal tissue, P = 0.06), which correlated with histologic calcium deposition (r = +0.52, P less than 0.02, N = 20). These findings are consistent with the hypothesis that renal calcium deposition begins early in the course of a variety of renal diseases and hence may play a secondary pathogenetic role that accelerates progression to chronic renal failure. Severity of renal calcium deposition is equally closely related to hyperphosphatemia and to the level of renal impairment.

Adult↗
PubMed1987

Early renal pathophysiology in an acute model of cyclosporine nephrotoxicity in rats.

We have recently described a rat model of acute cyclosporine nephrotoxicity characterized by rapid onset of reproducible mild to moderate renal failure. In the present studies, we have examined early pathophysiologic events and morphologic changes in this model. Following acute intraperitoneal administration of 60 mg/kg of parenteral cyclosporine, renal blood flow (RBF) fell 24% from baseline. Intraperitoneal administration of an oral cyclosporine preparation (60 mg/kg) also reduced RBF (25%), as did administration of an equivalent volume of parenteral cremophore (23%). Renal vascular resistance (RVR) increased significantly in all these groups. In contrast, intraperitoneal administration of mineral oil or olive oil oral vehicle produced no significant change in RBF (4% fall from baseline), and RVR actually decreased in these control animals. Following 2 daily doses of these agents, RBF remained significantly lower in rats given parenteral cyclosporine (5.10 mL/min vs 8.54 mL/min in cremophore rats and 7.28 mL/min in oil control rats) and renal vascular resistance remained high. Systemic blood pressure was also significantly lower in cyclosporine-treated rats at 2 days, and GFR was depressed. Morphologic studies revealed a correlation at 2 days between tubular vacuolation and renal blood flow and renal vascular resistance in cyclosporine-treated rats.

Acute Kidney Injury↗
PubMed1987

Viper bite poisoning in India: a review with special reference to renal complications.

Viper bites are a significant cause of mortality in India. Acute renal failure is a common finding in cases of lethal envenomization. Coagulation abnormalities and shock are other key clinical features. Some of the renal lesions appear to reflect a direct toxic effect of venom on kidney parenchyma. Glomerular, tubular, interstitial, and vascular lesions have all been described. Experimentally, viper venom causes mesangiolysis, and this may be a significant factor in the pathogenesis of viper bite-induced glomerular disease. Treatment with antivenom is commonly used but is not supported by controlled trials. Dialysis and supportive treatment appear to be the mainstay of therapy in cases complicated by renal failure.

Acute Kidney Injury↗
PubMed1987

Acute renal failure in man: pathogenesis in light of new morphological data.

The pathogenesis of acute renal failure (ARF) in such common conditions as acute tubular necrosis, acute interstitial nephritis, and primary graft anuria (ischemic transplant ARF) is poorly understood. Animal models may not exactly mimic the situation in man and thus human morphologic studies are of particular importance. Non-replacement of individual sloughed tubular cells and simplification of the brush border and basolateral infoldings of tubular cells are prominent morphologic changes which correlate with the presence of renal failure. It is possible that the initial injury inhibits cell membrane synthesis, thus interfering with proximal tubular sodium reabsorption with resulting activation of the renin angiotensin system and afferent arteriolar vasoconstriction. Tubular backleak, tubular obstruction by casts and debris, and decreased glomerular ultrafiltration coefficient may also play a role. Although poorly studied until now, the renal failure in primary graft anuria may have a completely different pathogenesis from that in acute tubular necrosis and acute interstitial nephritis. Cyclosporine nephrotoxicity is an important component of primary graft anuria, as seen in many transplant centers in the 1980's.

Acute Kidney Injury↗
PubMed1986

Renal blood flow, glomerular filtration rate, and renal morphology in cyclosporine-induced acute renal failure in Munich-Wistar rats.

The mechanism of clinical cyclosporine nephrotoxicity has remained unclear. We have established an animal model of cyclosporine-induced acute renal failure in the male Munich-Wistar rat by giving four daily doses of parenteral cyclosporine 60 mg/kg intraperitoneally (IP). In this model, 20 minutes of bilateral renal ischemia preceding the first cyclosporine dose did not significantly increase the renal failure, but did increase mortality (65% v 17%), which was due in part to the CNS effect of cyclosporine. Pair-fed and pair-watered vehicle and saline controls were used. The renal morphologic changes induced by the castor oil vehicle of the commercial parenteral cyclosporine solution were quantitatively similar to those induced by cyclosporine, although the severity of the changes by light microscopy was considerably less in the vehicle-treated groups. However, by electron microscopy, pale lipid vacuoles were seen only in the cyclosporine-treated groups, whereas dense alterations in lysosomes and dilated endoplasmic reticulum were also seen in other groups. Renal blood flow determined by electromagnetic flow probe showed a significant decline during 2 hours after a single IP injection of cyclosporine (6.6 +/- 0.4 to 5.0 +/- 0.6 mL/min). A similar decline was seen following injection of the castor oil vehicle of the commercial cyclosporine parenteral preparation (6.6 +/- 0.5 to 5.1 +/- 0.5 mL/min), but not after an injection of a similar volume of mineral oil (6.7 +/- 0.3 to 6.3 +/- 0.2 mL/min). These studies suggest that brief renal ischemia does not increase cyclosporine nephrotoxicity significantly in this rat model.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗