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

Eleven patients with different degrees of renal failure with creatinine clearances between 7 and 32 ml/min have been studied. After a standard water overload and control periods of clearances, furosemide 1 g was given/i.v. There followed significant increase of renal plasma flow and glomerular filtration rate. In one case the increase was maintained during a follow up period of 3 hours. A significant increase was evident in phosphate, uric acid, sodium, potassium, and calcium clearances, as well as an increase in the sodium delivery to the distal nephron and a decrease in tubular reabsorption of phosphate. All this may be interpreted as the result of renal vasodilation induced by furosemide and its effect upon the proximal tubule and on Henle's loop.
 ...
PMID:Alterations induced by large doses of furosemide in chronic renal insufficiency. 46 7

Ligandin (GSH-S-transferase B), an abundant intracellular soluble protein in rat proximal tubules, hepatocytes, and small intestinal mucosal cells, is believed to be a component of an organic anion transport system. Its presence in urine was determined immunologically and catalytically in adult, female, Sprague-Dawley rats that were given mercuric chloride or potassium dichromate. These nephrotoxic agents produce severe renal failure, with epithelial necrosis in the proximal tubule. Mercuric chloride perferentially injures the terminal part of the proximal tubule, while potassium dichromate damages more proximal segments. Ligandinuria was consistently detected immunologically and catalytically from 6 to 24 hr following injection of mercuric chloride. Potassium dichromate administration did not result in immunologically detectable liganduria; however, GSH-S-transferase activity, which provides a more sensitive assay, was frequently detected. The findings are consistent with immunofluorescent localization of ligandin in the proximal tubule. Immunologic or enzymatic measurement of ligandin in urine may provide a sensitive index of acute injury to the proximal tubule.
 ...
PMID:Ligandinuria in nephrotoxic acute tubular necrosis. 60 88

Chronic nephron loss is compensated by functional adaptations which preserve electrolyte homeostasis. The response to volume expansion and diuretics was tested in dogs. Three phase recollection micropuncture studies were performed to assess the response of the remnant kidney in various stages of renal failure to furosemide administration (10 mg/Kg) and graded volume expansion (3 percent and 10 percent body weight). After the diuretic maneuvers, mean fractional excretion of sodium, potassium and water rose progressively in normal dogs (Stage I), with a greater increase in the remnant kidneys in the presence (Stage II) and absence (Stage III) of the contralateral kidney. Proximal and distal TF/P (Inulin) ratios were depressed after 3 percent volume expansion. However, proximal TF/P (Inulin) was not further lowered after 10 percent volume expansion and furosemide administration, while distal TF/P (Inulin) ratios were progressively depressed. The distal TF/P (Inulin) ratios in Stage III were significantly lower than in Stage II under analogous conditions. Our results suggest that the adaptive increase in the response of sodium transport by the remnant kidney to the diuretic maneuvers occurs in the loop of Henle, both in the azotemic and the non-azotemic stage. Adaptation of potassium excretion, as revealed by distal micropuncture, took place in the azotemic Stage III. Chronic functional adaptation for electrolyte transport occurs even before azotemia in the distal nephron and includes the proximal tubule with azotemia.
 ...
PMID:Chronic reduction in renal mass: micropuncture studies of response to volume expansion and furosemide. 73 51

Acute renal failure was induced in male rats by the subcutaneous injection of 4 mg HgC12 per kg body weight. Changes in the proximal tubule were studied by light and electron microscopy at six time intervals from 15 min to 24 h. Renal function was monitored at 6 and 24 h. Between 15 min and 3 h changes were similar in all regions of the proximal tubule (pars convoluta and pars recta). Dispersion of cytoplasmic polysome groups was widespread and mitochondrial matrices were condensed in some cells. No changes were noted in the brush border but increased endocytotic activity occurred in some convoluted tubules at 1 and 3 h. At 6 h severe changes had occurred in the pars recta in the medullary rays. Microvilli of the brush border were focally absent, the mitochondria were swollen and the endoplasmic reticulum was dilated. At this time only subtle changes occurred in the pars recta in the outer stripe of the outer medulla. However by 24 h necrosis was widespread throughout the pars recta, yet changes in the proximal convoluted portion were minimal. A significant azotemia, decreased GFR and increased FENa+ and FEK+ occurred at 6 and 24 h after HgC12 injection. Thus HgC12 at 4 mg per kg body weight produced reproducible renal failure and necrosis involving the pars recta of every nephron but necrosis did not begin in the pars recta until after 6 h while acute renal failure was probably initiated much earlier. The following hypothesis is presented. HgC12 initially interacts with the entire proximal tubule. Although injury is sublethal in the pars convoluta it is responsible for greatly diminished sodium reabsorption and is related to the pathogenesis of the renal failure through feedback mechanisms involving the macula densa and release of renin. This results in renal hemodynamic alterations, decreased GFR and other functional disturbances associated with renal failure. The development of necrosis in the pars recta appears to be a relatively late event, possibly due to further accumulation of Hg++ in this region. In any case, the necrosis appears pathogenetically dissociable from the mechanism of acute renal failure.
 ...
PMID:Studies on the pathophysiology of acute renal failure. I. Correlation of ultrastructure and function in the proximal tubule of the rat following administration of mercuric chloride. 82 2

Serum phosphorus concentrations are maintained within narrow limits in humans. In the extracellular fluid most of the phosphorus is present in the inorganic form and at the level of the glomerulus greater than 90% of PO4 is ultrafilterable. The kidney plays a key role in PO4 homeostasis. Micropuncture experiments have demonstrated that 60 to 70% of the filtered PO4 is reabsorbed in the proximal tubule; however, there is evidence that a significant amount of PO4 is reabsorbed in the distal tubule. Phosphate secretion probably plays a minor role in the overall renal regulation of phosphate. In normal individuals the amount of PO4 ingested plays a key role in the amount that ultimately will be excreted in the urine. The reabsorption of PO4 along the nephron is regulated by a series of factors of which parathyroid hormone is the most important one. Hyperphosphatemia is seen frequently in clinical medicine and by far, the most common cause is a decrease in urinary PO4 excretion secondary to renal failure. From the practical point of view, the most effective way to treat hyperphosphatemia is to decrease PO4 absorption in the GI tract by the use of PO4 binders.
 ...
PMID:Hyperphosphatemia. 87 Feb 69

Renal micropuncture studies have greatly changed our views on the pathophysiology of acute renal failure caused by nephrotoxins. Formerly, this type of renal insufficiency was attributed to a direct effect of the nephrotoxins on tubule epithelial permeability. According to that theory, glomerular filtration was not greatly diminished, the filtrate formed being absorbed almost quantitatively and nonselectively across damaged tubule epithelium. Studies in a wide variety of rat models have now shown glomerular filtration to be reduced to a level which will inevitably cause renal failure in and of itself. Passive backflow of filtrate across tubular epithelium is either of minor degree or nonexistent even in models where frank tubular necrosis has occurred. This failure of filtration cannot be attributed to tubular obstruction since proximal tubule pressure is distinctly subnormal in most models studied. Instead, filtration failure appears best attributed to intrarenal hemodynamic alterations. While certain facts tend to incriminate the renin-angiotensin system as the cause of the hemodynamic aberrations, others argue to the contrary. The issue is underactive investigation.
 ...
PMID:Acute renal failure caused by nephrotoxins. 100 Dec 87

Among eight subjects suspected of excessive occupational exposure to lead, detailed examination of renal function identified abnormalities in four. Glomerular filtration rate was less than 87 ml/mim/1.73 m2 in one subject with asymptomatic renal failure, and in three subjects with preclinical renal dysfunction. In the subject with asymptomatic renal failure, chelation therapy increased the glomerular filtration rate, p-aminohippurate (PAH) extraction, the maximal PAH secretion rate (TmPAH) and improved proximal tubule ultrastructure, despite decreased renal plasma flow. This improvement in PAH transport was associated with correction of a proximal tubule defect in tritiated PAH uptake detected by section freeze-dry autoradiography of renal biopsy specimens. In three subjects, the etiologic diagnosis of lead-induced nephropathy was established by exclusion, but tubular dysfunction did not obviously exceed the reduction in blomerular filtration. Proximal tubule abnormalities were seen in each of the three patients who underwent biopsy. These studies suggest that lead nephropathy may be an important occupational hazard in the United States lead industry.
 ...
PMID:Occupational lead nephropathy. 120 35

Acute elevations in intracellular adenosine 3',5'-cyclic monophosphate (cAMP) concentrations are known to increase ionic chloride permeability in diverse tissues. To determine if chronic endogenous increases in cAMP are associated with sustained alterations in membrane ionic permeabilities, renal cortical brush border membrane vesicles (BBMV) were prepared and red blood cells were harvested in a model of chronic renal failure, the 75% nephrectomized rat. Relative ionic permeabilities were determined using the potential-sensitive fluorescent probe 3,3'-dipropylthiadicarbocyanine iodide [diS-C3-(5)]. These studies demonstrate that renal cortical homogenate and RBC cAMP concentrations are increased in chronic renal failure animals. In the same animals relative ionic chloride permeability (PCl/PK) was significantly increased in renal cortical BBMV and RBC ghosts: PNa/PK was not affected. This selective change in permeability results in a significant increase in PCl/PNa and hyperpolarization of BBMV of sufficient magnitude to stimulate Na(+)-dependent glutamine transport. The change in glutamine uptake was not consequent to an alteration in the kinetics of glutamine transport or delayed dissipation of the inward Na+ gradient. Renal hypertrophy per se did not effect renal homogenate cAMP concentration or relative ionic permeability of renal cortical BBMV prepared from kidneys of uninephrectomized animals fed a 40% protein diet. These studies demonstrate that relative ionic chloride permeability and tissue [cAMP] are chronically increased in diverse cells (renal proximal tubule and RBCs) in a rat model of renal failure. These findings suggest that membrane ionic permeability may be altered and electrogenic transport secondarily perturbed in renal failure in association with hormonally-induced chronic elevations of intracellular cAMP concentrations.
 ...
PMID:Altered membrane ionic permeability in a rat model of chronic renal failure. 132 50

Germanium compounds are marketed as nonprescription drugs in Europe and are recommended by the suppliers for AIDS and metastatic cancer disease. We observed a patient with nonmetastatic breast cancer who died because of severe lactic acidosis (plasma lactate concentration = 27 mmol/l) after ingestion of 25 g of elemental germanium over a 2-months period. Renal failure and hepatotoxicity had newly developed during germanium intake. Postmortem examination revealed severe hydropic vacuolation of tubule cells and the presence of inclusion bodies predominantly in straight proximal tubule cells with normal appearance of renal interstitium and glomeruli. The liver showed panlobular steatosis. Urine, blood and tissue (kidney, liver, muscle, pancreas) levels of germanium were high. Lactic acidosis may have been caused by the combined, germanium-induced renal and hepatic failure (underutilization), but it remains to be seen whether germanium can affect lactate production and/or metabolism directly.
 ...
PMID:Abuse of germanium associated with fatal lactic acidosis. 143 51

The C57BL/6J-cpk mouse has a form of autosomal-recessive polycystic kidney disease characterized by the rapid growth of large collecting duct cysts and the development of severe renal failure usually by three to four weeks of age. Previous studies had shown higher steady-state levels of proto-oncogene mRNA in these cystic kidneys. It is now shown using nuclear run-on transcription that the c-fos and c-myc proto-oncogenes are transcribed at higher rates in cystic kidneys, and thus that increased transcription, in part, may account for the increased mRNA levels. c-myc mRNA was detected by in situ hybridization in nephron anlagen and elongating tubules of normal and cystic kidneys during late fetal and early neonatal kidney development. Localization of c-myc expression in the normal kidney decreased with age over the three-week postnatal period. By contrast, c-myc mRNA was found in cysts as early as three days of age, with increased levels at two and three weeks. c-myc expression was also elevated in apparently normal, non-dividing proximal tubules in three-week-old cystic animals. On the basis of these findings, we suggest that c-myc expression is linked to the proliferation of cells engaged in the primary cystogenic process, and that expression of this gene in proximal tubule cells of severely azotemic animals reflects the compensatory response of residual tubular epithelial cells to progressive renal dysfunction.
 ...
PMID:Localization of overexpressed c-myc mRNA in polycystic kidneys of the cpk mouse. 155 5


1 2 3 4 5 6 7 8 9 10 Next >>