Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Review of experimental work indicates that renal papillary necrosis (RPN) is more readily induced by mixtures of analgesics which include phenacetin or paracetamol, than by either of the latter drugs alone. In an experiment in which moderate doses of analgesics were given to rats over a long period, it was shown that aspirin had a greater nephrotoxic effect than either phenacetin or paracetamol although less than in combination with either. In a study of the evolution of aspirin-induced damage, the earliest changes were shown to occur in the interstitial cells. There was also loss of medullary mucopolysaccharides. Occlusive lesions were demonstrated in the vasa recta. Using partial papillectomy, it was shown that the development of analgesic-induced cortical lesions did not depend on the presence of papillary necrosis. It was suggested that the early papillary changes might be due to ischemia, medullary blood flow being reduced as a result of aspirin's action as an inhibitor of prostagladin synthesis. The lesions in the vasa recta might cause ischemia at a late stage, leading to total RPN.
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PMID:Experimental renal papillary necrosis. 71 67

Many renal structural and functional abnormalities have been associated with sickle cell disease. The patients have an impaired urinary concentrating ability but an intact diluting capacity. There are defects in both urinary acidification and potassium excretion, although overt metabolic acidosis and hyperkalemia occur infrequently. Proximal tubular function is supranormal, as manifested by increased reabsorption of phosphate and increased secretion of creatinine. The former results in mild hyperphosphatemia, while the latter causes substantial overestimation of the glomerular filtration rate (GFR) by creatinine clearance. Both GFR and renal plasma flow are increased in young patients with sickle cell disease, but prostaglandin inhibitors decrease the GFR. The GFR progressively decreases with increasing age. Proteinuria, and even nephrotic syndrome, are relatively frequent; the most common renal lesion in children is focal glomerular sclerosis, which may be associated with progressive deterioration in renal function. Glomerular hyperfiltration has been implicated in the pathogenesis of the glomerular lesions, as well as in the development of renal failure. In patients with end-stage renal disease, both hemodialysis and kidney transplantation have been successful. Recurrent hematuria is a relatively common problem in patients with sickle cell disease. The bleeding usually remits spontaneously, but occasionally requires therapy with aminocaproic acid. Papillary necrosis may occur, and is thought to result from medullary ischemia.
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PMID:Renal abnormalities in sickle cell disease. 217 77

Renal papillary necrosis is a frequent complication of unsuccessful renal transplantation in rats, occurring in both isografts and allografts. Papillary necrosis does not occur alone, but only and inevitably in association with severe cortical damage. The pattern of the lesion is different from other forms of papillary necrosis in that the least severe lesions occur in the outer medulla and the more severe lesions involve both medulla and papilla. The incidence of papillary necrosis is increased in isografts, but not in allografts, by longer preservation times. It is suggested that the principal underlying cause may be damage to medullary capillaries, occurring either during preservation or as a consequence of rejection and leading to medullary ischemia.
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PMID:Papillary necrosis in experimental renal transplantation in the rat. 306 Aug 23

An enhanced frequency and morbidity of urinary tract infections (UTI) have been observed in association with alcoholism and liver disease. The causes of these phenomena may relate, in part, to the defects in humoral and cellular immune mechanisms that occur in alcoholism. Urinary catheterization is the most common cause of UTI in hospitalized alcoholics. The severity of the sequelae of UTI in alcoholism is demonstrated by the unusually frequent occurrence of renal papillary necrosis (RPN) in conjunction with pyelonephritis in these patients. Indeed, in over 90% of the reported cases of RPN occurring with alcoholism or liver disease, pyelonephritis has been a contributing factor. The proclivity to medullary ischemia and RPN in this patient group may be, at least in part, a result of interstitial renal edema secondary both to infection and the effect of ethanol per se and to renal arterial vasoconstriction that occurs in cirrhosis. The frequency with which death due to sepsis or renal failure occurs in association with UTI in alcoholics obliges the physician to exercise caution in the prevention and treatment of UTI in these patients.
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PMID:Urinary tract infections and renal papillary necrosis in alcoholism. 370 22

Thirty-five cases of renal medullary crest necrosis morphologically similar to the renal papillary necrosis of analgesic nephropathy as described in man and rats are reported in horses receiving maintenance dosages of phenylbutazone. The primary lesion is a well-demarcated focal medullary necrosis resulting in sequestration of fragments of the renal crest. Renal cortical lesions are considered secondary to the medullary necrosis and consist of segmental pallor as a result of tubular dilatation, filtrate retention, and interstitial edema. Ischemia in concert with phenylbutazone is suggested as the etiology. Renal medullary crest necrosis is presented as more appropriate morphological terminology for this lesion in the equine species than renal papillary necrosis as is used in man and rats.
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PMID:Renal medullary crest necrosis associated with phenylbutazone therapy in horses. 664 37

Inhibition of renal vasodilatory prostaglandins (PGs) and secondary ischemia due to inhibition of cyclooxygenase (COX) activity has been suggested as a possible mechanism for development of analgesic-related renal papillary necrosis (RPN) in rats. Recently, it has been shown that COX exists in two related but unique isoforms, COX-1 and COX-2. It is unclear what potential roles these isoforms play in the maintenance of blood flow in the renal papilla or genesis of RPN. We evaluated the effect of 2 papillotoxic agents, including a nonsteroidal anti-inflammatory drug, indomethacin, and a chemical agent, 2-bromoethanamine hydrobromide (2-BEA), on COX-1 and COX-2 in the renal papilla as a means of assessing what changes occur in the expression of these isoforms during the development of RPN. Female Wistar rats approximately 10-17 wk old were treated with either indomethacin (75 mg/kg, single dose, or 10 mg/kg/day for 5 days) or 2-BEA (100 mg/kg/day for 4 days) to create lesions of RPN. In this study, a single 75-mg/kg dose of indomethacin did not cause light microscopic changes of RPN. However, RPN was observed in animals administered indomethacin at 10 mg/kg/day for 1 wk or 2-BEA for 5 days. The immunohistochemical analyses of kidneys showed that both COX-1 and COX-2 were present in the renal papilla of control rats. In animals treated with indomethacin (75 mg/kg), a slight to moderate decrease in both isoforms was observed in essentially normal renal papillary cells within 2 hr, that was followed by an increase in COX-2 immunoreactivity in the renal papilla, macula densa, and thick ascending limbs (both 10- and 75-mg/kg animals). This COX-2 immunoreactivity was greatest in animals with concomitant indomethacin-induced gastrointestinal injury, suggesting a possible role of inflammatory cytokines in COX-2 induction. No changes in the expression of COX isoforms in the intact papilla occurred as a result of 2-BEA; however, cells undergoing degeneration and necrosis lost immunoreactivity to both COX isoforms. The possible mechanism that leads to an initial decrease in COX immunoreactivity in indomethacin-treated animals is not known; however, a reversible ultrastructural change in the papillary cells cannot be ruled out. This decrease in COX isoforms in the renal papilla may contribute to the development of RPN through the loss of vasodilatory PGs.
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PMID:Effect of papillotoxic agents on expression of cyclooxygenase isoforms in the rat kidney. 950 96

Sickle cell anemia and the related hemoglobinopathies are associated with a large spectrum of renal abnormalities. The patients have impaired urinary concentrating ability, defects in urinary acidification and potassium excretion, and supranormal proximal tubular function. The latter is manifest by increased secretion of creatinine and by reabsorption of phosphorus and beta(2)-microglobulin. Young patients with sickle cell disease (SCD) have supranormal renal hemodynamics with elevations in both effective renal plasma flow (ERPF) and glomerular filtration rate (GFR). These parameters decrease with age as well as following the administration of prostaglandin inhibitors. Proteinuria, a common finding in adults with sickle cell disease, may progress to the nephrotic syndrome. Proteinuria, hypertension, and increasing anemia predict end-stage renal disease (ESRD). While ESRD can be managed by dialysis and/or renal transplantation, there may be an increased rate of complications in renal transplant recipients with SCD. Hematuria is seen in individuals with all of the SCDs as well as with sickle cell trait. In most cases the etiology of the hematuria turns out to be benign. However, there does appear to be an increased association between SCD and renal medullary carcinoma. Therefore, those SCD patients who present with hematuria should initially undergo a thorough evaluation in order to exclude this aggressive neoplasm. Papillary necrosis may occur due to medullary ischemia and infarction. Erythropoietin levels are usually lower than expected for their degree of anemia and decrease further as renal function deteriorates. An abnormal balance of renal prostaglandins may be responsible for some of the changes in sickle cell nephropathy. Acute renal failure is a component of the acute multiorgan failure syndrome (MOFS). Finally, progression of sickle cell nephropathy to ESRD may be slowed by adequate control of hypertension and proteinuria. However, the prevention of the renal complications of SCD will require a cure for this genetic disorder.
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PMID:Renal abnormalities in sickle cell disease. 1142 1

The complications of partial nephrectomy include hemorrhage, urinary leak, infection, formation of urinary fistula, and the development of renal insufficiency. We report a unique case of a patient who was found to have necrotic-appearing, bleeding, renal papillae after undergoing laparoscopic partial nephrectomy. A 66-year-old man was diagnosed with a left-sided, solid, enhancing, 2.5-cm, exophytic renal mass. Laparoscopic partial nephrectomy was performed, and the warm ischemia time was 31 minutes. He recovered uneventfully from surgery, but he started having episodes of gross hematuria approximately 5 months later. Computed tomography scan showed changes consistent with previous partial nephrectomy but no other abnormality. Ureterorenoscopy allowed us to identify several necrotic-appearing papillae in the same kidney that had undergone laparoscopic partial nephrectomy. A papilla in the lower pole was actively bleeding, and it was successfully obliterated using neodymium:yttrium-aluminum-garnet laser technology. Papillary necrosis can be a rare complication of laparoscopic or open partial nephrectomy. Additional study and close follow-up of patients who undergo partial nephrectomy is warranted.
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PMID:Delayed hematuria secondary to bleeding papilla--potential complication of laparoscopic partial nephrectomy. 1851 94

Sickle cell disease (SCD) is a major health problem in many countries. Sickle cell nephropathy (SCN) is now a well-characterized entity with specific manifestations, risk factors and prognosis. The presence of sickled erythrocytes in the renal medullary vessels is the hallmark of the disease with a variety of renal complications. Renal manifestations of SCD include renal ischemia, microinfarcts, renal papillary necrosis and renal tubular abnormalities with variable clinical presentations. Proximal tubule dysfunction generally impairs urinary concentration, while more distal tubule dysfunction may impair potassium excretion, leading to hyperkalemia. Glomerular disease with proteinuria may develop due to ischemia and results in a compensatory increase in the renal blood flow and glomerular filtration rate; such hyperfiltration, combined with glomerular hypertrophy, probably contributes to glomerulosclerosis. Acute and chronic kidney disease are the expected outcomes of the disease. Both dialysis and kidney transplantation are effective renal replacement therapies for end-stage renal disease due to SCN, with a higher advantage for transplantation. Whether bone marrow transplantation in the early stage of the disease can halt the progression of SCN is unknown and awaits clinical studies.
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PMID:An update on sickle cell nephropathy. 2462 90