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 pharmacokinetics of (Z)-[[[(2-aminothiazol-4-yl)[[(2S,3S)-2-(hydroxymethyl)-4-oxo-1- sulfoazetidin-3-yl]carbamoyl]methylene]amino]oxo]acetic acid, disodium salt (carumonam, Ro 17-2301) after a 2 g intravenous infusion (20 min) were evaluated in 10 healthy volunteers and 20 patients with various degrees of renal failure. The main results of the kinetic parameters in healthy volunteers (mean + SD) corrected for zero infusion time and 70 kg body weight were: t1/2 alpha, 29 +/- 12 min; t1/2 beta, 108 +/- 27 min; AUCtot, 327 +/- 40 mg h/l; Vdss, 12.2 +/- 1.5 l/70 kg; urinary recovery, 78.7 +/- 8.2%; total clearance 103 +/- 13 ml/min; renal clearance, 85 +/- 13 ml/min. Because of the large variation in the degree of renal insufficiency, calculations of the mean values for the pharmacokinetic parameters in the patient group were not generally justified with the exception of the volume of distribution (Vdss = 14.4 +/- 3.0 l/70 kg). To derive dose recommendations, a regression analysis was performed using values from both the volunteer and patient group for the total area under curve (AUCtot) and glomerular filtration rate (GFR), divided by the mean AUCtot value for the volunteers. This curve can be interpreted as giving the dose reduction factor (DRF) as a function of GFR, where by definition, DRF = 1 for healthy (and young) subjects. Using this method of equivalent areas, no (or only a slight) dose reduction is necessary for patients with GFR values above 40 ml/min.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pharmacokinetics and dose recommendations of carumonam in renal failure. 356 60

An epidemic of renal disease is occurring among the Zuni Indians in western New Mexico. In 1985, 1.6% of Zunis had clinically recognized renal disease and 1% had renal insufficiency. The incidence of end-stage renal disease (ESRD) in 1984 and 1985 was 14 times the rate for US whites, and three times the rates of other Indians in ESRD network 6. One third of the cases of renal disease and ESRD is due to type 2 diabetes, but the etiology of disease in most of the remainder is unknown. Affected subjects range from early childhood to old age. Early signs are hematuria, mild to moderate proteinuria, normal BP, and low total hemolytic complement, normal or low C3 and C4 levels, in about 40% of the cases. The clinical course varies from benign to rapidly progressive renal failure. Biopsies usually reflect an immune-complex mediated mesangiopathic glomerulonephritis, with IgA, IgG, IgM, and C3 variably present in the mesangium. In some cases, there is a very strong familial pattern suggesting autosomal dominant inheritance or a marked communal exposure effect. This may be a genetic disease educed by the consanguinity in the ethnically homogeneous Zuni population. Mesangiopathic renal disease is common in some Oriental populations, and this phenomenon may reflect the American Indians' Oriental ancestry. This disease may also be due to toxic exposures related to jewelry-making, potting, Zuni water, Zuni salt, or herbal or other products used for medicinal or religious purposes. This epidemic is much morbidity and generating huge costs for ESRD treatment. Further study is needed to better understand its etiology.
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PMID:Epidemic renal disease of unknown etiology in the Zuni Indians. 359 94

A family is described in which autosomal recessive inheritance of retinitis pigmentosa and chronic renal failure occurred. Several features, including late onset of renal failure, lack of salt wasting, the presence of hypertension and blindness in the sixth decade, are unusual and suggest that this may be a previously undescribed syndrome.
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PMID:A family with retinitis pigmentosa and ESRD with late presentation, hypertension and absence of polyuria or salt wasting. 369 52

The present paper describes the use of a quantitative renal vascular casting method to study the changes associated with kidney disease. Several animal models of hypertension (spontaneously hypertensive rat, SHR, with its normotensive rat the Wistar Kyoto, WKY; Dahl salt sensitive DS - hypertensive, and salt resistant DR - normotensive) were examined at time points when the systemic blood pressure was rising (6 and 12 weeks of age) and following renal denervation (in SHR-WKY rats). The SHR appears to have a smaller caliber afferent arteriole at both 6 and 12 weeks of age. This difference is probably not entirely due to sympathetic vasoconstriction since the strain related afferent arteriolar diameter difference was still present after renal denervation. In the Dahl rats, there is not much of an intrarenal vascular difference between the DS and DR rats with the only real finding of a smaller distal afferent arteriolar diameter found in outer cortical nephrons of the DR. The two models of acute renal failure (ARF) that were studied include, the glycerol model (known to initially cause an intense vasoconstriction) and gentamicin, a nephrotoxic antibiotic. Two time points were examined for each of these models. As expected in the glycerol model there was an intense vasoconstriction at three hours which essentially was gone at 3 days - a time when the renal failure was fulminant. The glomerulus appeared to be contracted at three hours as well. In the gentamicin model no renal vascular alteration was seen at 6 days, when renal failure was mild while at 10 days, when renal failure was pronounced, outer cortical afferent arterioles appeared to be moderately constricted. In the 5/6 nephrectomy model of chronic renal failure, the glomeruli were smaller in rats in renal failure than in the controls.
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PMID:Quantitative renal vascular casting in nephrology research. 373 22

Fifty-five patients with chronic urinary retention and incipient or actual renal failure were studied. In the majority of patients renal function improved after bladder decompression, irrespective of whether or not a diuresis occurred. Excessive loss of salt and water was rarely a matter of concern and most patients did not require intravenous fluid replacement. Several lost weight and experienced a fall in blood pressure during the period of diuresis without adverse effect upon renal functional recovery. A profound fall in blood pressure occurred in only three patients, all of whom required long-term sodium supplementation. It is concluded that the problem of salt and water loss after bladder decompression in patients with renal failure is exaggerated and difficult to predict. Over-enthusiastic replacement of fluid in strict accordance with output could readily lead to fluid overload and prolongation of the diuretic period. Therefore fluid replacement should be determined by the clinical condition of the patient and measurement of improving renal function with less emphasis on urine output and its electrolyte content.
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PMID:Diuresis and renal functional recovery in chronic retention. 397 Oct 92

We evaluated the utility of chloride titrator sticks for facilitating the assessment of dietary salt intake, in a systematic series of clinical trials. These inexpensive devices were applied daily to 24-h or nocturnal urine specimens, thereby avoiding the inter- and intra-subject variability in salt excretion which confounds the use of occasional 24-h urine collections. Chloride and sodium concentrations in urine were highly correlated (r greater than 0.92) in either nocturnal, diurnal, or 24-h collections. The quantitative chloride titrator estimates and measured chloride concentrations were highly correlated as well (r greater than 0.99). The qualitative chloride titrator was graded on a simple scale, and was successfully employed by outpatients attempting to limit their salt intake. Commonly used antihypertensive medications did not interfere with the determinations. Additional chloride intake, such as supplemental potassium chloride, interfered with estimates of salt ingestion, but if the daily amount of potassium chloride supplement was constant, adjustments in interpretation could be made. Renal insufficiency introduced a systematic over-estimation of salt intake by the qualitative chloride tirator, but only at high salt intakes. Relative estimates of salt intake in subjects with renal failure were still possible. We conclude that chloride titrators can facilitate the management of patients who require a prescribed salt intake.
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PMID:The efficacy of quantitative and qualitative chloride titrators in the estimation of human salt intake. 398 52

In patients with chronic uremia we have previously demonstrated a significant inhibition of the Na-K-ATPase enzyme which represents the specific receptor protein for cardiac glycosides. Since an endogenous inhibitor of this enzyme was previously shown to react with a digoxin antibody, in the present study we determined digoxin-like immunoreacting activity(ies) (DLIA) by a radioimmunoassay in 15 nondialyzed patients with chronic renal failure. In native serum, DLIA ranged from 0 to 1.70 ng/ml and was unrelated to the degree of renal failure. After gel filtration of serum, DLIA exclusively eluted in the small molecular weight salt (FIII) and post-salt (FIV) fractions and averaged 0.22 +/- 0.04 and 0.20 +/- 0.05 ng/ml in fractions III and IV, respectively. Total activities ranged from 0.11 to 0.88 ng/ml with a mean of 0.42 +/- 0.06 ng/ml and closely correlated with the degree of renal impairment (p less than 0.001). The results confirm the presence of small molecular weight digoxin-like immunoreacting substance(s) in uremic serum. The variable activities in native serum and the lack of correlation between the degree of renal failure and DLIA in serum fraction IV previously shown to possess the Na-K-ATPase-inhibiting activity, however, indicate that DLIA may not reflect specifically the endogenous sodium pump inhibitor and that unspecific binding to this digoxin antibody of uremic toxins or other endogenous compounds, such as steroids other than aldosterone, may have occurred.
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PMID:Digoxin-like immunoreacting substance(s) in the serum of patients with chronic uremia. 401 Aug 43

In 6 hypertensive patients with terminal renal failure maintained on hemodialysis, the effects of 'salt subtraction' and of sequential ultrafiltrating were evaluated. Following each of 3 weekly hemodialysis sessions, salt subtraction was carried out by ultrafiltrating 1 liter and simultaneously infusing an equal volume of 5% dextrose. This resulted in a net sodium loss without hypovolemia. After a 2-week period of this procedure, the blood pressure prior to dialysis was lower (156/76 +/- 12/5 mm Hg) than after a comparable number of sequential ultrafiltration sessions (181/88 +/- 10/6 mm Hg; mean +/- SEM). This difference was not statistically significant. At the same time, body weight was comparable at 64.4 +/- 3 and 64.7 +/- 4 kg, respectively. Neither plasma renin activity nor plasma catecholamines responded with a clear increase to either procedure. The limited effect on blood pressure and the renin system of a marked sodium removal during salt subtraction suggests that sodium must still be present in excess in these patients. The procedure of salt subtraction appears safe and subjectively well tolerated, but it can probably not be used as the sole means of decreasing total body sodium without associating dietary measures to reduce sodium intake.
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PMID:Salt subtraction in patients on maintenance hemodialysis. Efficacy and limitations. 405 Aug 88

We have examined the effect of normal and uremic human sera on the transtubular flow of fluid in isolated perfused segments of rabbit proximal convoluted and straight renal tubules. Proximal convoluted and straight tubules absorbed fluid from the lumen when the external bath was normal rabbit serum. Normal human sera in the bath depressed net fluid absorption in both tubular segments, but more importantly, uremic human serum caused proximal straight tubules to secrete fluid into the lumen. Fluid secretion was also demonstrated indirectly by observing in nonperfused proximal straight, but not proximal convoluted tubules, that the normally collapsed lumens opened widely in uremic serum. Nonperfused proximal straight tubules developed expanded lumens even after a 25-fold dilution of human uremic serum with normal rabbit serum, whereas lumen expansion occurred only in undiluted normal human serum, on the average. Serum from acutely uremic rabbits possessed secretory activity but normal rabbit serum did not. The secretory effect of uremic sera in proximal straight tubules was inhibited by cooling and ouabain and probenecid. The secretory activity of uremic sera was removed by dialysis, but not by freezing or boiling. Para-aminohippurate and benzoate caused fluid secretion in proximal straight tubules but urea, creatinine, guanidinosuccinate, and urate did not. On the basis of these results, we suggest that the secretory factor in serum may be a substance or group of substances possibly related to the hippurate class of organic molecules that are accumulated to relatively high concentrations in renal failure. The secretory material in the serum of uremic patients may significantly influence the transport of salt and water in relatively intact residual nephrons.
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PMID:Fluid secretion in isolated proximal straight renal tubules. Effect of human uremic serum. 473 63

Blood pressure control was examined in 75 patients with end-stage renal failure treated by regular twice-weekly haemodialysis. Dietary sodium was restricted and extracellular fluid was removed by ultrafiltration until blood pressure was normal or signs of salt depletion were observed. Failure of these measures constituted an indication for nephrectomy. Of the 75 patients, 18 were never hypertensive, 46 had hypertension which could be corrected by salt and water depletion, and 11 had persistent hypertension which could not be controlled in this way. Nine of these 11 patients underwent bilateral nephrectomy; in each of the seven in whom the post operative result could be evaluated the blood pressure returned rapidly to normal.Plasma renin activity, measured in 34 subjects, was raised above normal in six out of nine patients whose blood pressure could not be controlled by salt and water depletion and in one of the 11 patients whose blood pressure could be so controlled, but was within the normal range in all nine normotensive patients. The mean level of plasma renin activity in the first group was significantly higher than that of each of the other two groups.There was a significant correlation between hypertension during dialysis and after transplantation, suggesting that, in addition to renin, there is a non-renal factor which predisposes certain patients to hypertension in the presence of salt and water excess.
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PMID:Relevance of salt, water, and renin to hypertension in chronic renal failure. 491 35


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