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K Solez

Publications and source records attributed to K Solez.

At least 91 records · Page 5Linked to original sources
PubMed1986

The renal response produced by nonhypotensive sepsis in a large animal model.

We describe an animal model of generalized sepsis, induced in the sheep by cecal perforation, which reproduces the high systemic flow and peripheral vasodilation seen in early human sepsis. Despite volume loading, animals demonstrate a fall in glomerular filtration rate, oliguria, low fractional sodium excretion, maintained urine osmolarity, and increased plasma renin activity. Histologically, kidneys show no consistent abnormality; overall the findings suggest volume contraction or hypoperfusion. This is contradicted, however, by maintained blood pressure and pulmonary capillary wedge pressure, increased cardiac output, and reduced peripheral resistance. Increased Fc lysozyme and low molecular weight proteinuria suggest tubular damage. These paradoxical observations are currently unexplained.

Animals↗
PubMed1986

Selective inhibition of thromboxane synthesis in glycerol-induced acute renal failure.

It has recently been postulated that thromboxane A2 may participate in the pathogenesis of acute myohemoglobinuric experimental acute renal failure. To investigate this further, the effect of selective inhibition of thromboxane synthesis on the course of glycerol-induced acute renal failure was determined. Despite significant inhibition of thromboxane synthesis by 4-imidazole-yl-acetophenone, the functional and morphologic disturbance induced by glycerol was unaltered. Moreover, pretreatment with 4-imidazole-yl-acetophenone failed to prevent the fall in renal blood flow seen following glycerol administration. These results argue against a major role for thromboxane A2 in the pathogenesis of this form of experimental acute renal failure.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Nephrotoxic tubular and interstitial lesions: morphology and classification.

Nephrotoxic renal injury, and especially drug nephrotoxicity is now a common cause of acute renal failure. The most common patterns of renal injury produced by nephrotoxins, tubular damage, and interstitial nephritis, are discussed here. Toxic agents which are primarily tubular toxins include certain antibiotics, cisplatinum, anesthetics, and radiocontrast agents. In tubules injured by toxins, alterations range from subtle ultrastructural abnormalities to extensive tubular necrosis. Mechanisms of tubular injury include direct tubular cell toxicity, and alterations in intrarenal blood flow producing secondary tubular damage. Other commonly used therapeutic agents, including the penicillins, other antibiotics, and non-steroidal anti-inflammatory agents, produce renal dysfunction by inducing interstitial nephritis. Long-term analgesic abuse is associated with a particularly striking interstitial damage with frank papillary necrosis. Criteria for differentiating primary tubular injury with inflammation and primary interstitial nephritis with tubular injury are discussed. Individual commonly-used therapeutic agents are considered in some detail, with discussion of both clinical and morphological aspects of drug nephrotoxicity.

Acute Kidney Injury↗
PubMed1986

Acute renal failure produced by combining cyclosporine and brief renal ischemia in the Munich Wistar rat.

To evaluate the combined effects of a brief ischemic insult and cyclosporine, four groups of male Munich Wistar rats were given: a) parenteral cyclosporine (60 mg/kg i.p.) for 4 days following 20 minutes of bilateral renal ischemia, b) the castor oil cyclosporine vehicle in a comparable volume and the same ischemic insult, c) saline in the same volume and ischemia, or d) saline and sham surgery. The cyclosporine animals ate and drank poorly, and therefore the other groups were pair-fed and watered with them. The cyclosporine-ischemia group developed significant renal failure. The other groups exhibited only a mild rise in blood urea nitrogen. Tubular vacuolization was a prominent feature in the cyclosporine and vehicle groups, but not in the saline groups. Vacuolization was correlated with severity of renal impairment. Lipid stains showed that many of the vacuoles contained lipid. Eosinophilic cytoplasmic inclusions were seen only in the cyclosporine or vehicle- (castor oil) treated animals. These findings emphasize the probable functional importance of tubular lesions in cyclosporine-induced acute renal failure, and suggest that the castor oil vehicle of parenteral cyclosporine may have renal effects of its own.

Acute Kidney Injury↗
PubMed1986

Idiopathic linear glomerular IgA deposition.

Linear deposition of IgA immunoglobulin was found along the glomerular basement membrane in two patients with normal renal function and no pulmonary abnormalities. One patient had recurrent gross hematuria and a mild focal proliferative glomerulonephritis without deposits on electron microscopy; the second patient had a renal cell carcinoma. This observation of linear IgA antibody deposition in the absence of Goodpasture's syndrome or diabetes mellitus extends the spectrum of diseases associated with glomerular basement membrane-IgA deposition.

Adolescent↗
PubMed1985

Mechanisms of lysine-induced acute renal failure in rats.

We have previously found that lysine produces acute renal failure in rats. To define the acute effects of lysine, rats given lysine at 8.9 mg/kg/min, i.v. for 4.5 hr were compared with control rats receiving equiosmolar dextrose. Systemic blood pressure was stable in both groups. Mean intratubular pressure, inulin clearance (CIn), and renal blood flow were determined at 45-min intervals. Intratubular pressures measured with a servonulling micropressure device were elevated by 90 min in lysine-treated animals, with tubular heterogeneity, while pressures in dextrose-treated rats were normal and homogeneous. By 135 min CIn in lysine-treated rats was 45% of CIn in dextrose rats. Urine output fell in lysine-treated rats. Renal blood flow determined by flow probe remained normal in lysine-treated rats through 135 min and did not decline significantly until 180 min. Significant dilatation of surface tubules was documented by intravital microscopy beginning at 90 min in lysine-treated rats. The sequence of elevated intratubular pressure and tubular dilatation, followed by decreased CIn, and then by decreased renal blood flow suggests that lysine produces acute renal failure primarily through tubular obstruction. The tubular obstruction is followed later by an increase in renal vascular resistance.

Acute Kidney Injury↗
PubMed1985

Effects of lysine and other amino acids on kidney structure and function in the rat.

Lysine is a major constituent of amino acid parenteral nutrition solutions which have recently been shown to increase the severity of various types of acute renal failure in the rat. In previous studies the authors have shown that high-dose lysine alone is capable of causing acute renal failure. However, it has remained unclear what the morphologic expression of this type of acute renal failure is in the maintenance phase of the syndrome, whether other amino acids produce a similar lesion, and whether lysine in lower doses also produces acute renal failure. In the present study the authors show that lysine, when given in a dose of 600 mg/rat over 4 hours, produced persisting acute renal failure which at 48 hours was characterized morphologically by a picture similar to that in human "acute tubular necrosis"--little overt tubular necrosis, but a focal loss of individual tubular cells with regenerative changes and mitotic figures. Extensive hyaline cast formation was seen, particularly in the thin limbs of the loops of Henle, and these thin limb casts were shown to contain Tamm-Horsfall protein. Equivalent doses of glycine, arginine, and glutamic acid and lower doses of lysine produced no significant renal morphologic or functional changes.

Amino Acids↗
PubMed1984

Interstitial nephritis, proteinuria, and renal failure caused by nonsteroidal anti-inflammatory drugs. Immunologic characterization of the inflammatory infiltrate.

Nine patients with the unusual combination of renal failure, nephrotic-range proteinuria, and biopsy-proved interstitial nephritis are described. Six of these patients had received nonsteroidal anti-inflammatory agents (three fenoprofen, one ibuprofen, one zomepirac, and one tolmetin). The remaining three patients had no history of exposure to drugs known to cause interstitial nephritis. Immunologic characterization of the infiltrating cells with monoclonal antibodies showed that the majority of cells in most cases were cytotoxic T cells, although some B cells were present in all cases. Giant collecting duct cells were seen in half the patients with drug exposure but in none of the others. Otherwise, there were no conspicuous morphologic differences between patients with and without drug exposure. Many of the patients had associated glomerular abnormalities. Only the zomepirac and tolmetin recipients showed pure interstitial disease. The three fenoprofen recipients and the zomepirac and tolmetin recipients regained normal renal function after the drug was discontinued. The combination of renal failure, nephrotic range proteinuria, and interstitial nephritis is one form of nephrotoxicity observed in patients treated with nonsteroidal anti-inflammatory agents. However, this lesion, which may be mediated by cytotoxic T cells, may also be seen rarely in patients with no apparent drug exposure.

Adult↗
PubMed1984

Characteristics of early routine renal allograft biopsies.

The assumption that renal allograft histology should be perfectly normal during quiescence in the absence of rejection or nephrotoxic insults has not been adequately investigated. To study this, routine renal allograft biopsies were performed at approximately 1 and 4 weeks, when patients often had normal function or stable acute tubular necrosis (ATN). These were compared with biopsies from other patients during autologous ATN or clinically evident allograft rejection. There were two new findings: (1) Almost all biopsies contained an interstitial infiltrate, so that only the presence of vasculitis provided a clear distinction between rejection and quiescence. Most of the biopsies with infiltrates were from patients who had never received cyclosporine, so that an infiltrate does not necessarily signify toxicity due to this drug. (2) A major proportion of the cells in some biopsies appeared to express both the helper/inducer and the cytotoxic/suppressor phenotype, and a similar finding after in vitro stimulation suggests that this represents a cell population that is activated in some way.

Antibodies, Monoclonal↗
PubMed1984

Nephrotoxicity of lysine and of a single dose of aminoglycoside in rats given lysine.

Hyperalimentation solutions have been shown to increase aminoglycoside nephrotoxicity in rats and rabbits. Lysine is a major constituent of hyperalimentation solutions and is known to inhibit tubular reabsorption of protein. To test the effects of lysine on renal function and structure and on aminoglycoside nephrotoxicity, three groups of rats were prepared. Groups 1 and 2 were infused with lysine (55 mumol/kg/min, 1.9 gm/kg total) for 4 hours. In group 2, gentamicin (60 mg/kg) was also infused during the third hour. In group 3, dextrose was given instead of lysine, and gentamicin was given as in group 2. In group 1 (lysine-saline solution), there was a decrease in glomerular filtration rate (GFR) and an increase in 125I-albumin clearance factored by GFR. In group 2 (lysine-gentamicin), the same effects were seen, but the reduction in GFR was significantly greater. Group 3 (dextrose-gentamicin) showed no change in GFR over the 4-hour period, but did show an increase in 125I-albumin clearance factored by GFR. Fractional excretion of sodium rose in group 2 but not in groups 1 and 3. A gradual mild (20%) and nonsignificant fall in renal blood flow followed the combined administration of lysine and gentamicin. In separate 20-hour studies, lysine (1.9 gm/kg intraperitoneally) or gentamicin or tobramycin (60 mg/kg subcutaneously) produced mild renal failure, but the combination of lysine and an aminoglycoside produced substantially greater renal failure. Serum creatinine in experimental groups was significantly correlated with medullary cast formation and tubular necrosis (p less than 0.001). Giant lysosomes with crystalloid inclusions in proximal tubular cells, individual cell necrosis in the pars recta, and casts in the thin limb of the loop of Henle were seen in rats given lysine. We conclude that lysine alone and single large doses of aminoglycosides alone are nephrotoxic, and when the two are combined, toxicity is additive. The nephrotoxicity of lysine may be related to direct tubular toxicity and to tubular obstruction.

Acute Kidney Injury↗
PubMed1984

Glomerular epithelial cell changes after ischemia or dehydration. Possible role of angiotensin II.

Glomerular visceral epithelial cells (podocytes) undergo flattening and spreading of major processes detectable by scanning electron microscopy in early postischemic acute renal failure in both animals and man. The authors examined the kinetics of development of these epithelial cell changes in the renal pedicle-clamping model of ischemic renal failure in the rabbit. They found that these changes develop progressively, increasing with increasing length of ischemia, and occur while the pedicle clamp is still in place. To assess the possible role of angiotensin II and vasopressin in producing the epithelial changes, the authors compared glomerular morphology before and during pedicle clamping in hydrated rabbits and in dehydrated rabbits. Dehydration alone produced changes in glomerular epithelial cells comparable to those seen in the postischemic kidney. The angiotensin-converting enzyme inhibitor captopril did not prevent the podocyte changes in either group. In vitro incubation studies confirmed that both angiotensin II and vasopressin produce glomerular epithelial cell changes with a threshold between 10(-7) M and 10(-8) M, a concentration that may be physiologically significant for angiotensin II, which is synthesized at the glomerulus and may have local paracrine effects. Such local synthesis may not be inhibited by systemic administration of captopril. Angiotensin II may play a role in producing podocyte alterations during renal ischemia, as well as in the dehydrated state.

Angiotensin II↗