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)

Normal adults with normal protein intakes have a urinary NH4 excretion of 40 to 50 mmol/24 hours and a variable urinary pH. In cases of metabolic acidosis a urinary pH less than 5.5 suggests an extra-renal origin whilst a urinary pH greater than 5.5 is in favour of renal acidosis, but there are many exceptions to this rule. On the other hand, urinary NH4 excretion is always greater than 70 mmol/24 hours in the first case and less than 40-50 mmol/24 hours in the second; and the use of the urinary anionic gap (Na + K - Cl), negative in the first case and positive in the second, enables the two situations to be distinguished. The acidosis of nephron reduction is easily recognised in cases of severe renal failure with an increase in unmeasured plasma anions whilst tubular acidoses are accompanied by a hyperchloremia. Measurement of fractional HCO3 excretion after an oral loading dose of NaHCO3, preferably by TmCHO3 with respect to GFR, distinguishes proximal tubular acidosis (low TmHCO3) from distal tubular acidosis (normal or high TmHCO3). In the latter case, the presence of hypokalemia suggests a distal tubular acidosis either due to deficiency of the H(+)-ATPase pumps (absence of increased urinary pCO2 after oral loading dose of NaHCO3) or to the inability of the kidney to maintain a normal H+ gradient (normal increase of urinary pCO2. The presence of hyperkalemia suggests diseases associated with hypoaldosteronism (low or inappropriate serum aldosterone concentrations), abnormal transepithelial voltages or with a pseudo-hypoaldosteronism syndrome (high plasma aldosterone concentration). The prevalence of distal tubular acidosis with hyperkalemia is on the increase whilst tubular acidosis with hypokalemia remains rare.
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PMID:[Renal acidosis]. 223 3

Renal vascular resistance (RVR) was related to intrarenal release of renin (RR) and angiotensin II (ANG II) during increases in plasma osmolality (Posmol) or chloride (PCl). Intrarenal infusions of 1.232 M solutions given to in situ kidneys increased Posmol by 7-18%. Hypertonic dextrose (n = 8) reduced RVR (P less than 0.005) but increased RR into plasma (P less than 0.01) and increased lymph renin (LR) (P less than 0.05). The response to hypertonic Na acetate (n = 5) was similar, but hypertonic NaCl (n = 9) increased RVR (P less than 0.02) without changing RR. During infusion of arachidonic acid (AA), hypertonic NaCl increased RVR (P less than 0.02) but decreased RR into plasma and decreased LR (P less than 0.05). Overall group mean changes in RVR were inversely related to LR (r = -0.96; P less than 0.01). An increase in PCl of 12 +/- 1 mmol/l was induced in denervated kidneys by changing an intrarenal 0.616 M infusion of Na acetate to NaCl. Hyperchloremia increased RVR from 14 +/- 2 to 19 +/- 2 mmHg . ml-1 . min-1 . kg-1 (P less than 0.01), reduced GFR from 1.4 +/- 0.1 to 1.1 +/- 0.1 ml . min-1 . kg-1 (P less than 0.01), and reduced ANG II (pg/ml) in renal venous plasma (55 +/- 6 to 35 +/- 6; P less than 0.05) and lymph (366 +/- 111 to 209 +/- 53; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Release of renin and angiotensin II into plasma and lymph during hyperchloremia. 331 Jun 63

A rare syndrome has been described in which mineralocorticoid-resistant hyperkalemia of renal origin occurs in the absence of glomerular insufficiency and renal sodium wasting and in which hyperchloremic acidosis, hypertension, and hyporeninemia coexist. The primary abnormality has been postulated to be a defect of the potassium secretory mechanism of the distal nephron. The present studies were carried out to investigate the mechanism of impaired renal potassium secretion in a patient with this syndrome. When dietary intake of sodium chloride was normal, renal clearance of potassium was subnormal (CK/GFR = 3.6 +/- 0.2%; normal subjects, 9.0 +/- 0.9%, N = 4) despite high normal or supernormal levels of plasma and urinary aldosterone. The fractional clearance of potassium remained subnormal (CK/GFR = 5.1 +/- 0.2%) during superimposed chronic administration of superphysiologic doses of mineralocorticoid hormone. Little increase in renal potassium clearance occurred when the delivery of sodium to distal nephron segments was increased further by the i.v. infusion of sodium chloride, despite experimentally sustained hypermineralocorticoidism. But potassium clearance increased greatly when delivery of sodium to the distal nephron was increased by infusion of nonchloride anions: sulfate (sodium sulfate infusion, low sodium chloride diet; CK/GFR = 63.7 +/- 0.4%) or bicarbonate (sodium bicarbonate plus acetazolamide infusion; CK/GFR = 81.7 +/- 1.7%). These findings indicate that mineralocorticoid-resistant renal hyperkalemia in this patient cannot be attributed to the absence of a renal potassium secretory capability or to diminished delivery of sodium to distal nephron segments; instead it may be dependent on chloride delivery to the distal nephron. We suggest that the primary abnormality in this syndrome increases the reabsorptive avidity of the distal nephron for chloride, which (1) limits the sodium and mineralocorticoid-dependent voltage driving force for potassium and hydrogen ion secretion, resulting in hyperkalemia and acidosis and (2) augments distal sodium chloride reabsorption resulting in hyperchloremia, volume expansion, hyporeninemia, and hypertension.
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PMID:Mineralocorticoid-resistant renal hyperkalemia without salt wasting (type II pseudohypoaldosteronism): role of increased renal chloride reabsorption. 702 72

Depression of GFR and antinatriuresis in response to high chloride has been linked to a cyclooxygenase (COX)-dependent mechanism involving thromboxane A2 (TxA2) and prostaglandin endoperoxide (PGH2), because inhibition of COX prevented the fall in GFR and antinatriuresis produced by hyperchloremia. However, hyperchloremia did not increase, but unexpectedly decreased, renal prostaglandin and TxA2 efflux (Yin et al., 1995). To resolve questions regarding the role of eicosanoids in mediating the renal functional effects of high chloride (117 mM), by stimulating either TxA2 synthesis or TxA2/PGH2 receptors, we compared the ability of indomethacin to block high-chloride effects in the rat isolated kidney with that of BMS 180291 and SQ 29548, antagonists of the TxA2/PGH2 receptor. These antagonists differ in terms of their selectivity and their capacity to inhibit isoforms of the TxA2/PGH2 receptor. Indomethacin and SQ 29548 had identical actions, preventing the decrease of GFR and antinatriuresis evoked by hyperchloremia, e.g., sodium excretion rate in the SQ 29548 and indomethacin groups increased to 7.2 +/- 1.3 and 7.1 +/- 1.2 microEq/min, respectively, compared with 2.6 +/- 0.7 microEq/min in the control group. In contrast, neither BMS 180291 nor the TxA2 synthase inhibitors, OKY 046 and CGS 13080, modified the negative effects of high chloride on GFR or sodium excretion. These results argue against either TxA2 or PGH2 acting as mediator of the effects of high chloride on renal function and suggest a product of COX activity such as a 20-HETE analog of prostaglandin endoperoxide. Evidence to support this proposal was obtained: 1) Hyperchloremia increased 20-HETE release from the rat kidney by 2-fold when compared with low-chloride conditions of renal perfusion. 2) The renal vasoconstrictor action of 20-HETE was shown to be dependent on COX activity and to be antagonized by blockade of the TxA2/PGH2 receptor.
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PMID:Analysis of eicosanoid mediation of the renal functional effects of hyperchloremia. 922 45

Pseudohypoaldosteronism Type II (PHAII) is a very rare disorder characterized by hyperkalemia, hypertension, and slight hyper-chloremic metabolic acidosis. The index patient showed typical features of PHAII, including elevated blood pressure (140-150/90-100 mmHg), hyperkalemia in the range of 5.30-5.60 mmol/l (normal range is 3.50-5.10 mmol/l), accompanied by hyperchloremia of 109.5-112.0 mmol/l (normal 95.0-108.0 mmol/l) and acidosis with bicarbonate levels of 19.5-20.1 mmol/l (normal 22.0-27.0), GFR was 98.95 ml/min (normal > 90). However, these features were absent in his parents. Sequencing analysis found the patient with a WNK4 gene mutation, 1682 C > T in Exon 7, which resulted a missense mutation at codon 561 (P561L). The variation in codon 561 was not found in his parents and 100 unrelated control subjects. The identified WNK4 mutation which has not been described previously is the probable cause of PHAII.
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PMID:A patient with pseudohypoaldosteronism type II caused by a novel mutation in WNK4 gene. 1901 6