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)

The isolated kidney has not been reported to acidify urine maximally. To study this defect, kidneys from dogs fed NH4Cl were perfused with autologous blood. Perfusate pH was 7.20 +/- 0.03 [HCO3] was 14 +/- 1 mEq/L, and urine pH was abnormally high, 6.60 +/- 0.08. When corrected for difference in GFR, UNH4+V was similar to that seen in vivo, but UTAV and UNet H+V were low. FEHCO3- was 2.3% +/- 0.8% and HCO3- excretion persisted to a small degree at perfusate [HCO3-] of 8 to 9 mEq/L. In response to HCO3- infusions, large increases in excretion were not seen until perfusate values were over 24 to 26 mEq/L. HCO3- Tmax was 2.94 +/- 0.07 mEq/dl of glomerular filtrate. The isolated kidney failed to raise U-B PCO2 with HCO3- infusion secondary to low urine [HCO3-] and [Pi]. During perfusion in another group of kidneys from dogs fed NH4Cl and given DOC, perfusate pH and [HCO3-] were similar to those in the first group. Urine pH was also inappropriately high, 7.12 +/- 0.09, and there was no UNet H+V. In response to Na2SO4 infusion, urinary pH fell to 5.00 +/- 0.27. Log10UUAV was correlated to urine pH during the control perfusions in both groups and after Na2SO4 in the NH4Cl + DOC group. Thus production of a low urine pH in the isolated kidney may be mediated by changes in transtubular potential difference resulting from increased distal nephron delivery of Na+ and nonabsorbable anion. The defect in acidification is similar to that observed in incomplete forms of clinical type 1 (distal) renal tubular acidosis.
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PMID:Production of maximally acid urine by the isolated dog kidney. 3 5

In rats with renal failure produced by excision of one kidney and infarction of large portions of the other kidney, given a low calcium, high phosphorus diet for 2-3 weeks, GFR was reduced by 80 percent, the fractional excretion of sodium increased from 7 to 23 percent, that of bicarbonate from 16 to 23 percent and that of water from 4 to 13 percent. Single nephron GFR in the remaining nephrons was nearly doubled and end-proximal TF/P(In) was depressed from 2.3 to 1.8, and proximal TF/P(HCO3) from 0.52 to 0.35, the latter figure corresponding to an increase of absolute proximal HCO(3) reabsorption from 1.7 to 3.5 nEq/min or from 2.8 to 3.2 Eq/L of single nephron glomerular filtrate. Acute parathyroidectomy had no influence on the fall of GFR or the rise of SNGFR in the remaining nephrons and failed to cause any significant changes in proximal tubular bicarbonate reabsorption. Parathyroidectomy, on the other hand, practically prevented the rise of the fractional excretion of sodium and of water and inverted the rise of the fractional excretion of bicarbonate to a fall. The data are interpreted to indicate that secondary hyperparathyroidism in renal failure impairs distal nephron bicarbonate and sodium reabsorption and, thus, contributes to the maintenance of sodium balance, but could possibly aggravate acidosis.
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PMID:A micropuncture study of HCO3 reabsorption by the hypertrophied proximal tubule. 73 50

The role of nephron loss, extracellular fluid volume (ECFV) expansion and body potassium stores on bicarbonate reabsorption in chronic renal failure (CRF) was evaluated. In 17 CRF and 3 control subjects, tubular HCO3 reabsorption was studied by HCO3 1M titration technique; ECFV (22Na space at 4th hour) and cell K content (muscle biopsy) were also determined. Nephron loss per se does not cause any change of HCO3 reabsorption rate per unit GFR. With ECFV expansion induced by HCO3 infusion, a Tm HCO3 is rapidly reached only in controls and in CRF patients showing a significant basal ECFV expansion. In these subjects reabsorbed HCO3/Na ratio is constant, suggesting that under these conditions, HCO3 reabsorption depends on the same mechanisms that control Na reabsorption. In cell K depleted CRF patients, HCO3 reabsorption rises more than in controls and no Tm HCO3 is detected, at least within the limits of isotonic ECFV expansion induced by titration; in these subjects HCO3 reabsorption does not appear to be limited by natriuretic factors. In CRF subjects with normal ECFV and cell K, there is a greater HCO3 tolerance to ECFV expansion induced by titration technique than in controls.
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PMID:Studies on bicarbonate reabsorption in chronic renal failure. 74 Jun 80

The effects of two potent inhibitors of renal bicarbonate reabsorption--maleate and acetazolamide--were investigated in the rat using clearance techniques. Acetazolamide given in high dose (50 mg/kg body wt) inhibited fractional bicarbonate reabsorption by ca. 30%, maleate (2.58 nmol/kg body wt) by 25%, and maleate plus acetazolamide by 54-72%. GFR was depressed, and urine volume was increased by both drugs in an additive manner. Maleate was equally effective as inhibitor of HCO3- reabsorption in the presence and absence of carbonic anhydrase activity. It is suggested that the site of action of both drugs is predominantly proximal, but they act on different steps in the transcellular HCO3- transport. A hypothetical mechanism of maleate action is presented, which takes into account the changes in passive HCO3- flux through the basolateral membrane.
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PMID:Additive inhibition of renal bicarbonate reabsorption by maleate plus acetazolamide. 82 58

Respones to bumetanide were studied in five ewes. During ADH infusion urine flow increased from less than 1-0 to approximately 11-5 cm3 min-1 within 30 min of intravenous injection of 0-02 mg kg-1 bumetanide and returned to approximately 2-0 cm3 min-1 within 3 h of dosing. The diuresis was accompanied by large increases in sodium and chloride excretion and smaller increases in potassium and free hydrogen ion excretion. Bicarbonate excretion and TCH20 were reduced. Plasma potassium and chloride concentrations decreased slightly while arterial bicarbonate pH and pCO2 slightly increased. A transient increase in GFR and RPF was followed by a small reduction in GFR. No change in CH20 was observed after bumetanide injection during water diuresis. Increasing the dose of bumetanide over the range 0-002 to 0-20 mg kg-1 resulted in more pronounced and prolonged responses. The results show that bumetanide is a potent diuretic in sheep with its main site of action on the ascending limb of Henle's loop.
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PMID:The effects of bumetanide on renal function and blood composition in sheep. 103 Aug 18

Bicarbonate reabsorption in the thick ascending limb of Henle's loop was examined by studies of free-water clearance (CH2O) and free-water reabsorption (TcH2O). During maximal water diuresis in the dog, CH2O/GFR was taken as an indes of sodium reabsorption in, and urine flow (V/GFR) as an index of delivery of filtrate to, this scarbonate, infusion of a nonreabsorbable solute (hypotonic mannitol) and administration of an inhibitor of bicarbonate reabsorption (acetaent, but less than that achieved with hypotonic saline infusion. This suggests that sodium that sodium bicarbonate is not reabsorbed in the ascending limb. Rather, it is the sodium chloride, swept out of the proximal tubule by osmotic diuresis due to nonreabsorbed mannitol or sodium bicarbonate, that is reabsorbed in the ascending limb thereby increasing CH2O, whereas the nonreabsorption of mannitol and sodium bicarbonate results in a depressed CH20 per unit V when compared with hypotonic saline. V/GFR is not a satisfactory index of delivery to the ascending limb during osmotic diuresis, since it includes water obligated by nonreabsorbable solutes. When a better index of delivery, the sum of the clearances of chloride (CC1) and free-water (CH2O) is used, hypotonic bicarbonate infusion, hypotonic mannitol infusion and acetazolamide administration increase CH2O/GFR per unit delivery to the same extent as odes hypotonic saline infusion. Studies in dogs and rats on TcH2O also indicate that sodium bicarbonate is an impermeant solute in the ascending limb. Osmotic diuresis due to sodium bicarbonate diuresis, produced either by inhibition of sodium bicarbonate reabsorption (acetazolamide, L-lysine mono-hydrochloride) or infusion of sodium bicarbonate, or mannitol diuresis both produced marked chloruresis and increased TcH2O to the same extent as did hypertonic saline infusion. If chloride excretion was almost eliminated by hemodialysis against a chloride-free dialysate (dogs) or prolonged feeding of a salt-free diet (rats), TcH2O formation was unimpaired if hypertonic saline was infused but virtually obliterated during mannitol or sodium bicarbonate diuresis. Sodium reabsorption in the ascending limb, therefore, appears to be dependent upon chloride as the accompanying anion. At any given rate of bicarbonate excretion, more cloride is delivered out of the proximal tubule (as estimated from CC1 + CH2O) with hypotonic sodium bicarbonate infusion than with acetazolamide administration. This suggests that magnitude of the chlorutesis accompanying bicarbonate diuresis depends, not only on osmotic diuresis due to nonreabsorbed sodium bicarbonate, but also on the extent to which concomitant changes in effective extracellular volume influence overall sodium chloride reabsorption.
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PMID:Evidence against bicarbonate reabsorption in the ascending limb, particularly as disclosed by free-water clearance studies. 120 62

Studies were undertaken in Munich-Wistar rats to assess the influence of changes in filtered bicarbonate (FLHCO3), induced by changes in GFR, on Na+/H+ exchange activity in renal brush border membrane vesicles (BBMV). Whole-kidney and micropuncture measurements of GFR, FLHCO3, and whole-kidney and proximal tubule HCO3 reabsorption (APRHCO3) were coupled with BBMV measurements of H+ gradient-driven 22Na+ uptake in each animal studied. 22Na+ uptake was measured at three Na+ concentration gradients to allow calculation of Vmax and Km for Na+/H+ exchange. GFR was varied by studying animals under conditions of hydropenia, plasma repletion, and acute plasma expansion. The increase in GFR, FLHCO3, and APRHCO3 induced by plasma administration correlated directly with an increase in the Vmax for Na+/H+ exchange in BBMV. The Km for sodium was unaffected. In the plasma-expanded rats, the Vmax for Na+/H+ exchange was 22% greater than in the hydropenic rats (P less than 0.025) whereas APRHCO3 was 86% greater (P less than 0.001). These results indicate that increases in FLHCO3, induced by acute increases in GFR, stimulate Na+/H+ exchange activity in proximal tubular epithelium. This stimulation is a mechanism which can, in part, account for the delivery dependence of proximal bicarbonate reabsorption.
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PMID:Effect of acute changes in glomerular filtration rate on Na+/H+ exchange in rat renal cortex. 131 51

The effects of a very low-protein diet (VLPD) supplemented with amino acids and ketoanalogues (KA) and with 1 g of calcium carbonate and 1000 IU of vitamin D2, were studied in 17 patients with advanced renal failure (GFR < or = 20 ml/min) over a period of one year. The protein intake was 0.3 g protein/kg body wt/day. Daily phosphorus and calcium intake were respectively 1,500 mg and 300 mg. Sequential bone densitometry was performed and bone histomorphometry after double tetracycline labeling was evaluated, before and after one year of diet. Calcium and phosphate metabolism parameters were monitored every two months. In spite of a significant decrease of GFR, phosphorus, parathyroid hormone (1-84) and osteocalcin plasma levels decreased significantly, while low plasma bicarbonate normalized, and calcitriol and calcium levels remained respectively low and normal. Before the diet, histological study disclosed four cases of mixed osteopathy: osteomalacia associated with osteitis fibrosa (OM/OF), nine pure osteitis fibrosa (OF) and four with normal bone remodeling (NB). After one year of diet, the OM component of OM/OF disappeared, as evidenced by a normalization of the mineral apposition rate and osteoid thickness. In the patients presenting pure OF, a significant decrease in osteoblastic and osteoclastic surfaces, in the number of osteoclasts, and in the bone formation rate (BFR) were found. Vertebral mineral density measured by quantitative computerized tomodensitometry did not change significantly. In conclusion, this study not only confirms the beneficial effects of VLPD + KA + calcium on uremic hyperparathyroid bone disease in advanced renal failure assessed using static bone histomorphometry, but also shows a correction of histodynamic bone parameters.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ketodiet, physiological calcium intake and native vitamin D improve renal osteodystrophy. 145 6

This study was undertaken to evaluate the effects of dietary K intake, independent of whether the accompanying anion is Cl- or HCO3-, on urinary Ca excretion in healthy adults. The effects of KCl, KHCO3, NaCl and NaHCO3 supplements, 90 mmol/day for four days, were compared in ten subjects fed normal constant diets. Using synthetic diets, the effects of dietary KCl-deprivation for five days followed by recovery were assessed in four subjects and of KHCO3-deprivation for five days followed by recovery were assessed in four subjects. On the fourth day of salt administration, daily urinary Ca excretion and fasting UCa V/GFR were lower during the administration of KCl than during NaCl supplements (delta = -1.11 +/- 0.28 SEM mmol/day; P less than 0.005 and -0.0077 +/- 0.0022 mmol/liter GFR; P less than 0.01), and lower during KHCO3 than during control (-1.26 +/- 0.29 mmol/day; P less than 0.005 and -0.0069 +/- 0.0019 mmol/liter GFR; P = 0.005). Both dietary KCl and KHCO3 deprivation (mean reduction in dietary K intake -67 +/- 8 mmol/day) were accompanied by an increase in daily urinary Ca excretion and fasting UCaV/GFR that averaged on the fifth day +1.31 +/- 0.25 mmol/day (P less than 0.005) and +0.0069 +/- 0.0012 mmol/liter GFR (P less than 0.005) above control. Both daily urinary Ca excretion and fasting UCaV/GFR returned toward or to control at the end of recovery. These observations indicate that: 1) KHCO3 decreases fasting and 24-hour urinary Ca excretion; 2) KCl nor NaHCO3, unlike NaCl, do not increase fasting or 24-hour Ca excretion and 3) K deprivation increases both fasting and 24-hour urinary Ca excretion whether the accompanying anion is Cl- or HCO3-. The mechanisms for this effect of K may be mediated by: 1) alterations in ECF volume, since transient increases in urinary Na and Cl excretion and weight loss accompanied KCl or KHCO3 administration, while persistent reductions in urinary Na and Cl excretion and a trend for weight gain accompanied K deprivation; 2) K mediated alterations in renal tubular phosphate transport and renal synthesis of 1.25-(OH)2-vitamin D, since KCl or KHCO3 administration tended to be accompanied by a rise in fasting serum PO4 and TmPO4 and a fall in fasting UPO4 V/GFR, a fall in serum 1,25-(OH)2-D and a decrease in fasting UCa V/GFR, while dietary KCl or KHCO3 deprivation were accompanied by a reverse sequence.
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PMID:Potassium administration reduces and potassium deprivation increases urinary calcium excretion in healthy adults [corrected]. 164 46

Although numerous studies have documented the effects of the renal nerves on kidney function, the mechanisms involved in the diuresis have yet to be elucidated. The present study was undertaken to examine the effect of acute unilateral renal denervation (DNX) on proximal tubular absorption of fluid and bicarbonate and to determine if acute DNX was associated with changes in Na-K-ATPase activity. Acute DNX caused significant increases in urine flow and absolute and fractional excretions of Na, HCO3 and K compared to the contralateral control kidney (INN) or sham denervated kidneys in normal rats as well as in rats made alkalotic by the I.V. infusion of 150 mM NaHCO3. These effects were seen without significant changes in GFR. When proximal convoluted tubules (PCT) were perfused with bicarbonate-Ringer's solution DNX resulted in a 67% decrease in fluid reabsorption (INN: 3.0 +/- 0.2 vs DNX: 1.0 +/- 0.1 nl/min/mm; p less than 0.001) and a 40% decline in bicarbonate (total CO2) reabsorption (INN: 151.3 +/- 8.8 vs DNX: 94.5 +/- 10.1 pmol/min/mm; p less than 0.01). Acute DNX caused a significant reduction in Na-K-ATPase activity measured in microsomes derived from the outer cortex of the kidney (INN: 13.2 +/- 1.3 vs DNX: 10.9 +/- 0.7 mumol PO4/mg prot/hr; p less than 0.01) while Mg-ATPase was unaffected. Sham denervation had no effect on any of the above parameters. These results indicate that the renal nerves play an important role in the regulation of bicarbonate and fluid reabsorption in the PCT. The diuresis, natriuresis, and bicarbonaturia associated with acute unilateral renal denervation may be the direct result of inhibition of Na-K-ATPase activity.
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PMID:Sodium and bicarbonate reabsorption in microperfused proximal tubules from the denervated rat kidney: relationship to cortical Na-K-ATPase activity. 217 83


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