Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q92565 (GFR)
 4,179 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the mammalian kidney, the use of the ratio, delta net T-Na+/delta Q-O2, provides an overestimate of the energy requirements for unidirectional active Na+ transport. In the proximal tubule, the overestimate of the energy cost for T-Na+ is due to these phenomena: (1) The "leaky" characteristics of the proximal tubule does not permit an accurate estimate to be made of the active fraction of the unidirectional flux of Na+. Thus, the net Na+ or net HCO3- reabsorption rate alone cannot be used to determine the stoichiometry for unidirectional extrusion of Na+ (with HCO3-) by the Na,K-ATPase, since backflux of HCO3- into the lumen occurs. (2) There is a moiety of active Na+ with Cl- along the pars recta. Whether this reabsorptive rate is altered and O2 uptake also changed when GFR or NaHCO3 reabsorption is varied is not yet known. (3) The occurrence of energy-requiring synthetic functions (substrate-interconversions) in the proximal tubule, coupled, in part, to the rate of Na+ entry into the proximal tubule cells, results in changes in renal O2 uptake proportional to some (undetermined) fraction of the change in Na+ reabsorption. The utilization of a portion of these reabsorbed substrates in endergonic syntheses must account for a portion of the Na+-stimulated suprabasal O2 uptake rate. Hence, the presence of synthetic functions in the proximal tubule also contributes to the overestimation of the energy value of net Na+ reabsorption when the ratio, delta net TNa-+/delta Q-O2, is used.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Relationship between energy requirements for Na+ reabsorption and other renal functions. 351 12

Blood and urine samples were collected at timed intervals for up to 120 min after the start of a 30-min infusion of 30 IU bovine parathyroid hormone (PTH) into 6 normal male subjects. Infusions were performed before and after 7 days' treatment with lithium carbonate. A highly significant increase in the maximum renal tubular reabsorption capacity for calcium (TmCa/GFR) from 2.02 +/- 0.04 to 2.17 +/- 0.07 mmol/l (p less than 0.02) produced a significant rise in plasma calcium. Lithium had no effect on basal fasting PTH or nephrogenous cyclic AMP (cAMP). Changes in nephrogenous cAMP and TmP/GFR in response to PTH were not altered by lithium. The absorption of 47Ca following an oral calcium load was increased in 5 out of 6 subjects also treated for 1 week with lithium. These results suggest that lithium has a direct effect on calcium transport, both at the level of the renal tubule and the gut, which is not mediated by stimulation of parathyroid activity or via modification of PTH-stimulated adenylate cyclase.
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PMID:Effect of lithium on the metabolic response to parathyroid hormone. 358 84

Adequate nutrition plays a key role in the conservative management of chronic renal failure. Recent experience favours initiation of dietary measures at an earlier stage of renal failure (RF) than hitherto advocated. The requirements of protein and energy are preferably calculated according to height rather than age. Protein intake is often far in excess of the recommended (minimum) intake of 0.25 g per cm body height (taken as 100%). With the aim to keep serum urea concentration close to normal, intake in mild RF (GFR 33-50 ml/min per 1.73 m2) is restricted to 150%, in moderate RF (15-33 ml/min) to 120%, and in severe RF (less than 15 ml/min) to the minimum. High quality protein (greater than 70% of animal origin) is advocated in case of severe restriction. Further limitations are possible with administration of essential amino acids and keto analogues. Energy requirements vary with height (56-75 kJ per cm body height). Many patients require a supplementation, e.g. oligosaccharides. Intestinal phosphate absorption (and renal excretion) is adjusted according to the degree of RF by reduction of intake and administration of phosphate binders (aluminium hydroxide or calcium carbonate). Vitamin D is now often given as one of its polar metabolites. Severe dietary restrictions require a high motivation of the patient, family and staff and are only successful when a good state of health can be maintained.
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PMID:[Nutrition of pediatric patients with chronic renal failure]. 373 19

The role of acidosis in the renal phosphate leak in Fanconi syndrome (FS) was studied in maleate-induced FS in rats. Clearance studies were performed in the following groups: 1) intact rats served as control, 2) rats with maleate-induced FS, 3) rats with FS receiving intravenous bicarbonate (HCO3-), 4) intact rats receiving intravenous 0.03 N HCl (inducing acidosis similar to that of Group 2), 5) rats with FS receiving intravenous phosphate buffer and NaCl, and 6) rats with FS receiving intravenous phosphate buffer and bicarbonate similar to Group 3. In Group 2 serum pH and fractional excretion of phosphate (CP/GFR) averaged 7.31 +/- 0.08 (mean +/- SE) and 1.00 +/- 0.06, respectively, and differed significantly from Group 1, in which the corresponding values were 7.41 +/- 0.01 and 0.12 +/- 0.02, respectively. In Group 3, intravenous HCO3- corrected pH to 7.43 +/- 0.01 and reduced CP/GFR to 0.33 +/- 0.05, both results were different from the corresponding rates in Group 2 (P less than 0.0005). In Group 4, intravenous HCl reduced serum pH to 7.31 +/- 0.02 (P not significant as compared with Group 2) and increased CP/GFR to 0.186 +/- 0.030, the latter was higher than CP/GFR in control rats (P less than 0.01) but was lower than that in HCO3- -treated FS rats. In Group 5 serum pH was 7.31 +/- 0.021, similar to Group 2. CP/GFR was 0.84 +/- 0.031, significantly lower than in Group 2 (P less than 0.05). In Group 6 serum pH was 7.43 +/- 0.013 and CP/GFR was 0.86 +/- 0.044.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of bicarbonate and phosphate on renal phosphate leak in experimental Fanconi syndrome. 381 43

cis-Diamminedichloroplatinum (CDDP), a widely used cancer chemotherapeutic agent, has been shown to cause dose-dependent acute renal failure (ARF) probably secondary to a direct nephrotoxic effect on proximal tubule cells. The aim of this study was to determine whether administration of ATP-MgCl2 could ameliorate the deleterious effects of CDDP. Isolated rat kidneys were perfused for 2 hr with a 3.5 g % dextran T-110-Krebs HCO3 solution containing 100 micrograms/ml of CDDP. [3H]Inulin was added to measure GFR. Trace amounts of 14C-methylated cytochrome c (cyt) were added to the perfusate to determine the protein reabsorptive capacity (a sensitive indicator of tubular damage) of isolated perfused rat kidneys. Cyt, inulin radioactivity, and [Na+] were measured in the perfusate and urine in control and CDDP-treated kidneys. In additional experiments, ATP-MgCl2 was added simultaneously (0.3 mM) or 1 hr (2 mM) after CDDP treatment. The results indicate that after 2 hr of perfusion, CDDP treatment led to a marked inhibition of protein reabsorption with only a minimal decrease in Na+ and H2O absorption. Furthermore, GFR was not significantly altered despite a marked diuresis. Post-treatment with ATP-MgCl2 led to partial alleviation of the nephrotoxic effect of CDDP after 1 hr of perfusion. ATP-MgCl2 treatment simultaneously with CDDP, however, fully protected the protein reabsorptive capacity of CDDP-treated kidneys. The potential for administering ATP-MgCl2 simultaneously with CDDP suggests a new therapeutic modality in preventing ARF due to CDDP therapy.
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PMID:Reduction of the drug-induced nephrotoxicity by ATP-MgCl2. 1. Effects on the cis-diamminedichloroplatinum-treated isolated perfused kidneys. 387 63

The increased plasma bicarbonate concentration seen in hypercapnia implies that tubular bicarbonate reabsorption must be increased in the presence of an elevated Paco2. In contrast to early reports, more recent experimental data in acute hypercapnia have been interpreted to show that the observed increment in tubular reabsorption of bicarbonate factored for glomerular filtration rate (THCO3/GFR) is largely related to the concurrent changes in renal sodium reabsorption and to the increment in the filtered load of bicarbonate, and that acute hypercapnia per se causes little or no change in the tubular handling of bicarbonate. We reexamined this question by observing the changes in renal function occurring in the presence of a moderate elevation of plasma bicarbonate concentration in two groups of dogs. In group I, the elevation occurred as a result of acute hypercapnia during the administration of an "isometric" solution; in group II, it was caused by the infusion of identical amounts of an isotonic solution with the same concentration of sodium as in group I, but a higher bicarbonate concentration, in the presence of eucapnia. A subset of group II provided controls for the decrease in renal perfusion pressure that occurred spontaneously in group I. With increasing filtered loads of bicarbonate, fractional excretion (FE) of HCO3 increased in group II, whereas it dropped markedly in group I. Furthermore, the relative reabsorption rate of HCO3 compared with that of Cl (assessed by changes in fractional reabsorption (FR) of HCO3/Cl) decreased in group II, whereas it increased in group I. Although FENa also decreased in group II, the opposite changes in FR(HCO3/Cl) could not be attributed solely to concurrent changes in sodium handling, indicating that in the presence of acute hypercapnia there is a preferential reabsorption of bicarbonate that tends to perpetuate the increase in plasma bicarbonate concentration. By contrast, THCO3/GFR rose in both groups. The data are interpreted to reveal that acute hypercapnia, although causing a drop in renal perfusion pressure and in natriuresis, also has an additional specific effect on raising preferential bicarbonate reabsorption. This effect can be detected best by monitoring changes in the anionic composition of tubular reabsorbate, whereas it may not be unveiled by following changes in THCO3/GFR. Changes in THCO3/GFR may not yield useful information regarding the integrated response of the kidney to acid-base perturbations, and the conclusions of previous studies based on changes in this parameter must be carefully reexamined.
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PMID:Effect of acute hypercapnia on renal bicarbonate reabsorption in the dog. 393 72

The metabolic pathogenesis of the complex renal tubular dysfunction of type II renal tubular acidosis and Fanconi's syndrome (RTA II/FS) acutely induced by maleic acid could depend on the occurrence of a positive feedback loop in cells of the proximal renal tubule: impaired mitochondrial oxidation----increased glucose uptake----increased formation and concentration of phosphorylated glycolytic intermediates----limitation on availability of cellular inorganic phosphate----more severely impaired mitochondrial oxidative metabolism. To test this hypothesis we intravenously administered maleic acid both alone and after initiating intravenously administered neutral sodium phosphate, sodium sulfate, or sodium chloride to 10 unanesthetized trained female dogs undergoing water diuresis. We made the following observations: 1) Administration of maleic acid alone predictably induced dose-dependent increments in urine flow (V) and in renal clearance of HCO3-, Na+, K+, and alpha-aminonitrogen and a pronounced increase in the renal clearance and excretion of citrate. 2) Prior phosphate loading, which increased the plasma concentration of phosphate from 2.5 +/- 0.20 to 11.3 +/- 2 mg/dl: a) attenuated the increment in renal clearance of HCO3- by one-half even though the filtered load of bicarbonate was higher by 37%, owing to the higher values of both GFR and plasma bicarbonate concentration that obtained with phosphate loading; b) prevented the increment in renal clearance and excretion of alpha-aminonitrogen; c) significantly attenuated the increments in V and renal clearance of K+; but d) did not affect the increment in renal clearance and excretion of citrate.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phosphate loading attenuates renal tubular dysfunction induced by maleic acid in the dog. 398 58

The mechanisms of metabolic acidosis and hyperkalemia were investigated in a patient with chronic mineralocorticoid-resistant renal hyperkalemia (5.3 to 6.8 mM), metabolic acidosis (arterial blood pH 7.27, total CO2 17 mM), arterial hypertension, undetectable plasma renin activity (less than 0.10 ng/ml/hr), high plasma aldosterone (32 to 100 ng/dl), normal GFR (131 +/- 2.5 ml/min/1.73 m2). During hyperkalemic period, urine was highly acidic (pH 4.6 to 5.0), urinary NH4 excretion (13 mumoles/min) and urinary net acid excretion (24 mumoles/min) were not supernormal as expected from a chronic acid load. During NaHCO3 infusion, maximal tubular HCO3 reabsorption (Tm HCO3) was markedly diminished (19 mmoles/liter GF), fractional excretion of HCO3 (FE HCO3) when plasma HCO3 was normalized, was 20%. Urine-minus-blood PCO2 increased normally (31 mmHg) during NaHCO3 infusion, and urinary pH remained maximally low (less than 5.3) when buffer urinary excretion sharply increased after NH4Cl load. When serum K was returned toward normal limits, metabolic acidosis disappeared, urinary NH4 excretion rose normally after short NH4Cl loading while urinary pH remained maximally low (4.9 to 5.2), Tm HCO3 returned to normal value (24.8 mmoles/liter GF), and FE HCO3 became nil. The renal handling of K was improved with acute NaHCO3 loading and normalized after DDAVP nasal insufflation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Type II pseudohypoaldosteronism: proximal tubular acidosis and distal tubular hyperkalemia corrected by DDAVP]. 408 72

Chronic renal failure represents the most common disorder responsible for chronic stable metabolic acidosis. This type of metabolic acidosis has been characterized as "hyperchloremic" in pre-end-stage disease and the "anion-gap" form as the GFR falls below 20 ml/min. The early hyperchloremic, hyperkalemic variety may result from disease of the juxtaglomerular apparatus, a distal acidification defect, or volume depletion. The anion-gap acidosis of advanced renal disease occurs as a result of the inability of the diminished nephron mass to keep pace with the metabolic acid load which depletes extracellular fluid bicarbonate. Total ammonium excretion diminishes despite an adaptive increase in ammonia production per nephron. The observation that the serum bicarbonate rarely falls below 15 mEq/L and the anion gap stays below 20 mEq/L despite positive hydrogen ion balance attests to the important role of extrarenal buffers. Bone buffers, primarily calcium carbonate, titrate a portion of the excess hydrogen ions at the expense of progressive loss of bone salts. Parathyroid hormone (PTH) appears to be involved in the control of bone buffering capacity. Both PTH-dependent and PTH-independent mechanisms must therefore be considered. PTH mediates bone buffering capacity by activating intracellular shifts of calcium, phosphorus, and carbonate or by stimulation of bone carbonic anhydrase. A direct effect of pH on bone mineral mobilization has been demonstrated. Adequate alkali therapy to maintain serum bicarbonate levels of 20-22 mEq/L may prevent bone dissolution and minimize risk of volume overload.
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PMID:Acid-base physiology in uremia. 716 51

Although nephrotoxicity is common following exposure to lead, the dose-response relationship in adults with occupational exposure is not well understood because information is lacking on early nephrotoxic effects. By the time serum urea nitrogen and creatinine levels are elevated, renal damage may be advanced and not fully reversible. Detailed investigations of renal glomerular and tubular function were performed in six adults with occupational exposure to lead. In all patients, the serum creatinine and urea nitrogen concentrations were within the normal range. GFR was decreased in all but two. Glucose reabsorptive capacity (TmG) was decreased in all, and this decrease was disproportionately greater than expected from the reduced GFR in all but one. Normal values for renal plasma flow (RFP) were observed in four of the six, and for rho-aminohippurate (PAH) secretory capacity (TmPAh) in all but one. Bicarbonate reabsorptive capacity (TmHCO3) and urinary excretion of beta2-microglobulin were normal in all. Routine clinical laboratory tests are insensitive for the detection of early renal effects of heavy metal exposure. Measurements of renal tubular reabsorptive capacity for glucose appears to be a sensitive method for the early detection of renal effect of lead.
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PMID:Occupational exposure to lead: effects on renal function. 723 Jun 12


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