Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0035078 (renal failure)
 31,970 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The author studied with light microscopy, scanning electron microscopy, and transmission electron microscopy 19 kidney biopsies from patients with oliguric and nonoliguric acute renal failure, two biopsies from patients with renal failure due to bilateral ureteral obstruction, and 15 biopsies with near normal tubules. In acute renal failure, there were no intrinsic lesions of glomeruli, but lesions of varying severity were found in the proximal and distal tubules. Proximal tubular changes included diminished, bizarre or absent brush border, often with no or multiple cilia (often more severe in the straight segment of the proximal tubule); luminal surface blebs or bizarre projections; decreased, flattened, or absent basal-lateral interdigitations simplified cuboidal appearance; bizarre lateral interdigitations; enlarged "contracted" attachment bodies; increased cytosomes, "osmotic" or autophagic; and decreased apical vacuoles. Distal tubule changes included decreased basal-lateral interdigitations of the convoluted segment, some decrease in microvilli, increased cytosomes and luminal casts, and enlarged "contracted" attachment bodies. These changes imply severe diminution of luminal and antiluminal surface area which may decrease sodium and chloride flux and, thus, might induce renal cortical vasoconstriction by tubuloglomerular feedback mechanisms. Tubular changes resulting from partial ureteral obstruction closely resembled those of acute renal failure.
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PMID:Ultrastructure of human acute renal failure. 719 4

The principle water-soluble metabolite of DDT in mammals has been shown to be DDA (bis(p-chlorophenyl)acetic acid). Previous studies suggested that DDA was secreted by the renal proximal tubule and was reabsorbed at an unspecified site in the nephron. Since DDA has been known to produce alterations in cellular functions, the present study examined the possibility that the renal transport of DDA was capable of causing acute nephrotoxicity. When 100 mg/kg of DDA was infused iv into the rat during a 90 min period, there was a significant decrease (congruent to 20%) in the glomerular filtration rate (GFR) after 110 min from the start of administration. During these experiments, there was no change in the mean arterial blood pressure (MABP), urine flow rate (V), renal clearance of tetraethylammonium (CTEA) or fractional reabsorption of Na (FRNa). After 200 mg/kg of DDA was infused iv into the rat during a 90 min period, there was a 60% decrease in the GFR, CTEA and V. However, the decrease in renal function was accompanied by a dramatic reduction in MABP (125 to 60 mmHg). To determine whether DDA could have produced acute renal failure when the perfusion pressure was kept constant, isolated kidney experiments were performed. In these experiments, DDA (1.0 mM) was present in a dextran perfusate and the perfusion pressure was kept constant at 90 mmHg. During these experiments, the GFR, V and FRNa were decreased significantly. The results indicated that a high perfusate concentration of DDA caused acute renal failure in the isolated kidney which was produced even when the perfusion pressure was kept constant. In conclusion, DDA produced renal failure in vivo which was associated with a reduction in renal perfusion pressure; however, perfused kidney experiments indicated that DDA could have caused a direct effect on nephron function.
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PMID:The effect of bis(p-chlorophenyl) acetic acid on the renal function of the rat. 721 46

1. Clearance and micropuncture studies were performed in 27 dogs made uraemic by segmental infarction to examine the factors responsible for phosphate adaptation in chronic renal failure. 2. The animals were studied before and after extracellular volume expansion to 10% of body weight in the presence and absence of parathyroid glands. The results were compared with 19 normal dogs studied under similar experimental conditions. 3. In the dogs with a remnant kidney and intact parathyroids adaptation of phosphate transport was evident, with a high fractional excretion of phosphate. Thyroparathyroidectomy 3 days before study in the dogs with a remnant kidney and moderate renal failure reduced fractional excretion of phosphate to near normal values, indicating a major role of parathyroid hormone in phosphate adaptation. Extracellular volume expansion in these thyroparathyroidectomized uraemic dogs led to an exaggerated phosphaturic response with fractional excretion of phosphate returning towards the value in the uraemic dogs with intact parathyroid glands. Thus acute extracellular volume expansion could also contribute to the increase in fractional phosphate excretion, but extracellular volume probably plays a relative minor role in the adaptation of phosphate excretion. 4. With more advanced renal failure fractional excretion of phosphate remained high, even after thyroparathyroidectomized, indicating that parathyroid hormone-independent factors become important for phosphate adaptation in the advanced stage of renal failure. The nature of parathyroid hormone-independent changes in fractional phosphate reabsorption in chronic renal failure remains unknown. 5. Proximal tubular fluid/plasma ultrafiltrate phosphate ratios were high in all groups of dogs with a remnant kidney regardless of thyroparathyroidectomy or the degree of renal failure. The non-specific nature of the proximal tubule pattern of phosphate transport indicates that phosphate adaptation is primarily determined by alterations in phosphate transport at a site distal to the proximal convoluted tubule. Alternatively, deep nephrons may play a greater role in determination of the overall phosphate adaptation in the chronically diseased kidney.
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PMID:Renal phosphate adaptation in uraemic dogs with a remnant kidney. 723 41

Renal osteodystrophy improves after renal transplantation but, after the procedure, other forms of bone disease emerge. We report a male patient that received a renal allograft four years before, who consulted for low back pain secondary to multiple vertebral compression fractures. The patient had good renal function, a parathormone independent hyperphosphaturia, normal 25-OH cholecalciferol, increased urinary hydroxyproline, decreased osteocalcin, reduced bone density and a bone biopsy revealing osteomalacia. The diagnosis of hypophosphatemic osteomalacia was reached and treatment with phosphates and ergocalciferol was started but, despite this, the patient suffered a new fracture two years later. Two mechanisms can produce hypophosphatemia after a renal transplantation: a parathormone excess due to the previous renal failure, that disappears during the first year after the transplantation or a derangement in renal phosphate transport that can be due to a generalized proximal tubule solute transport derangement (Fanconi syndrome), parathormone hypersensitivity or to an "idiopathic" hyperphosphaturia. Despite a good treatment, bone mass is not recovered and there is a high fracture risk. Mineral metabolism must be closely monitored after a renal allograft and its alterations must be quickly treated.
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PMID:[Hypophosphatemic osteomalacia acquired after renal transplantation: a a cause of severe osteoporosis]. 756 51

In this study, we compared results obtained in protein calorie malnourished (PCM) monkeys and controls given Cd2+ (5 mg Cd2+/kg body wt./day) orally for 24 weeks. After 16 weeks of Cd2+ exposure, an indolent renal failure develops in PCM monkeys which resulted in significant increase in urinary excretion of total protein, Cd2+, Zn2+ and Ca2+ as compared to corresponding to Cd(2+)-treated control group. In isolated proximal tubule brush border membrane vesicles (BBMV), Cd2+, Zn2+ and Ca2+ transport were significantly impaired in Cd(2+)-exposed PCM monkeys as compared to Cd(2+)-treated controls. The mechanism of higher urinary excretion of Cd2+, Zn2+ and Ca2+ was examined by analyzing the kinetic parameters of transport systems. The kinetic studies of Cd2+, Zn2+ and Ca2+ transport systems in the BBMV preparations of Cd(2+)-exposed PCM monkeys exhibited a significant decrease in Vmax and an appreciable increase in Km as compared to Cd(2+)-treated controls. These findings suggested that Cd2+ treatment of PCM monkeys caused either a decrease in the number of transporters in the brush border membrane or an increase in the number of less active transporters for Cd2+, Zn2+ and Ca2+. Furthermore, brush border membrane-bound enzymes, viz. alkaline phosphatase and leucine aminopeptidase, activities were significantly impaired in Cd(2+)-exposed PCM monkeys. Cadmium content in kidney cortex of Cd(2+)-exposed PCM monkeys was 3.34-fold higher than Cd(2+)-exposed controls. These findings also established that Cd2+ not bound to metallothionein (MT) was significantly higher in Cd-exposed PCM monkeys, which may be an important determinant in renal toxicity by interacting with sensitive sites in the renal cells and causing renal damage in Cd-exposed PCM monkeys.
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PMID:Cadmium-induced nephrotoxicity in rhesus monkeys (Macaca mulatta) in relation to protein calorie malnutrition. 762 86

Correlations have been shown between renal excretory function and the extent of immunohistological staining in the kidney of proximal tubular brush border and Tamm-Horsfall protein. These findings confirm the importance of the integrity of the proximal tubule in control of the glomerular filtration rate and also show that the thick limb of the loop of Henle is damaged, as well as the proximal tubule, in renal failure.
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PMID:Morphometric studies of acute renal failure using anti-brush-border and other antisera. 780 Feb 66

To examine the role of peptide leukotrienes in tourniquet-induced renal failure, hindlimbs of rabbits were fastened for 5 h and then released for 6 h. Blood urea nitrogen (BUN) increased significantly at the 3-h release. In the fastened muscle, peptide leukotrienes LTC4, LTD4 and LTE4 increased immediately after or at the 3-h release. LTD4 and LTE4 in the blood increased at the 6-h release. The edematous destruction of renal microvessels and proximal tubule cells was observed at the 3-h release. Glomerular changes were not observed. Immunoreactions of LTC4/D4 were localized in the lysosomes of the macrophages, leukocytes and fibroblasts of the fastened muscles immediately after the release, as well as in the lysosomes of renal proximal tubular cells and on the endothelial cell surface of the renal capillary at the 3-h release. These changes continued up to the end of the release. The lipoxygenase inhibitor attenuated the BUN increase and edema manifestation in the fastened muscle. These results suggest that peptide leukotrienes derived from the fastened skeletal muscle are related to tourniquet-induced renal failure.
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PMID:The role of peptide leukotrienes in renal failure induced by a tourniquet. 792 95

Proteinuria and tubulointerstitial inflammation (TII) correlate with progression to renal failure in human glomerulonephritis. Various forms of experimental nephrotic syndrome are associated with TII. To study the genesis of TII, we utilized the model of albumin overload. Rats received intraperitoneal bovine serum albumin (BSA) for 1 to 14 days, developing heavy proteinuria. A predominantly macrophage interstitial infiltrate was present at days 3, 7 and 14. The urine of the rats contained a factor chemotactic for macrophages which partitioned into the organic phase with ethyl acetate extraction. TLC and HPLC characteristics were those of a novel, non-polar lipid. Supernatant from the culture of proximal tubule (PT) segments after in vivo or in vitro exposure to high concentrations of lipid-replete BSA showed chemotactic activity with similar chromatographic characteristics. PT cultured with delipidated BSA produced little activity. Thus, the generation of this inflammatory factor occurs as a consequence of tubular metabolism of albumin-borne fatty acids and may contribute to the development of proteinuria-associated TII.
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PMID:Tubular catabolism of albumin is associated with the release of an inflammatory lipid. 793 18

The functions of the different nephron segments follow changes in the effective arterial blood volume and the extracellular fluid volume. In syndromes with reduced effective arterial blood volume, for example congestive heart failure, decompensated hepatic cirrhosis and nephrotic syndrome, hyperreabsorption of sodium in the proximal tubule reduces the sodium load in the more distal segments of the nephron. As this is a major site of sodium excretion, reduction in the response to a diuretic may be predicted by a reduced fractional excretion of sodium (< 0.2%). Such diuretic resistance may be overcome with acetazolamide, which increases delivery of sodium to the distal tubule. In syndromes with increased extracellular fluid volume, such as chronic renal failure, distal tubular rejection of sodium leads to a progressive increase in its fractional excretion as the glomerular filtration rate is reduced. The remaining intact nephrons exhibit a relatively increased response to diuretics. The efficacy of loop diuretics in renal failure can be optimized by combination with thiazides. The latter prevent early distal tubular hyperreabsorption following diuretic-induced blockade of sodium transport in the loop of Henle. For these reasons, low-dose combinations of different diuretics induce 'segmental nephron blockade' and are, therefore, potentially more clinically effective and safer than high doses of single compounds.
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PMID:Functional state of the nephron and diuretic dose-response--rationale for low-dose combination therapy. 795 41

In the late 60s, A. Heidland and his collaborators were amongst the first to characterize the renal action of frusemide in preterminal renal failure by giving quantitative information on dose requirements, fractional Na and K excretion, effects on renal haemodynamics, and by recognizing reversible inner ear dysfunction as the major dose-limiting side-effects. These early studies have been largely reconfirmed. They have been extended by more clearly characterizing (a) altered pharmacokinetics of frusemide, e.g. the importance of altered transepithelial transport in the proximal tubule and intratubular protein binding, and (b) the mechanisms underlying altered pharmacodynamics, particularly high baseline fractional Na rejection and increased absolute distal Na reabsorption. Apart from increasing the dose of frusemide, continuous administration by infusion and combination of frusemide with thiazide diuretics have emerged as rational therapeutic strategies in chronic renal failure.
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PMID:Treatment with high doses of loop diuretics in chronic renal failure. 807 24


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