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)

Endogenous digitalis-like factors have been implicated in the adaptations that accompany renal insufficiency and in the pathogenesis of hypertension. We recently described several fractions of normal human plasma that inhibit NaK-ATPase and exhibit apparent digoxin-like immunoreactivity. To determine if hypertension and/or renal insufficiency affect plasma levels of these factors, we examined four patient groups: normotensive controls; hypertensive subjects with normal renal function; hypertensives with moderate renal insufficiency; and chronic dialysis patients. Plasma levels of digoxin-like immunoreactivity and NaK-ATPase inhibitory activity were significantly increased in hypertensive patients with mild renal failure (7.6 +/- 1.1 ouabain equivalents, mean +/- SEM, N = 21 vs 4.1 +/- 1.1 in normotensive controls, N = 20, P less than 0.05). NaK-ATPase inhibitory activity tended to be higher in patients with primary hypertension and normal renal function (5.5 +/- 0.7 ouabain equivalents, P less than 0.07); in dialysis patients, it was not different from controls. There was no correlation between NaK-ATPase inhibitory activity and blood pressure in any group. There was a significant rise in plasma NaK-ATPase inhibitory activity during dialysis (+ 1.8 +/- 0.7 ouabain equivalents, N = 22, P less than 0.03). As we have found that NaK-ATPase inhibitory activity in the plasma of normal humans can be separated into three distinct fractions, EI1, EI2, and EI3, we analyzed the plasma of 10 dialysis patients further. The increase in NaK-ATPase inhibitory activity could be attributed to fractions EI1 and EI3. These results suggest that plasma NaK-ATPase inhibitors increase with chronic renal insufficiency, but not hypertension alone. Although hemodialysis may acutely raise plasma levels, long-term dialysis returns them to the normal range.
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PMID:Endogenous digitalis-like factors in hypertension and chronic renal insufficiency. 302 36

There is increasing evidence for endogenous, circulating compounds that interact with the digitalis receptor of [Na,K]ATPase and with antidigoxin antisera. Circulating levels of these digitalis-like compounds increase in response to fluid or salt loading and appear to play a role in diseases characterized by fluid and salt retention, e.g. renal failure, liver disease, acromegaly, experimental and human hypertension, and preeclampsia. Because of assay nonspecificity, many diverse substances are being measured. Of the few compounds currently identified as having "digitalis-like" activity, none appears to be the natural ligand of the digitalis receptor and none appears linked with hypertension. Nevertheless, research still suggests that digitalis-like factors may have a central role in essential hypertension and related disorders.
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PMID:Endogenous digitalis-like natriuretic factors. 303 37

The hypothesis that endogenous digitalis-like compounds might participate in body sodium and water homeostasis have led us to investigate the presence in plasma of compounds interacting with digoxin antibodies in man and rats. The apparent levels of digoxin-equivalents in plasma of control subjects (n = 21) and patients with essential hypertension (n = 48) or end-stage renal failure (n = 13) were 24.7 +/- 3.2, 34.4 +/- 4.4 and 98.7 +/- 17.4 pg/ml, p less than 0.05 and p less than 0.01 respectively. Positive correlations were observed between systolic and diastolic blood pressure and the apparent immunoreactivity of plasma. No relationship was found with the renal Na+ excretion or the plasma renin activity. The apparent digoxin-like immunoreactivity of the plasma was correlated with its ability to inhibit ouabain binding to the erythrocyte Na+ pump and to reduce the renal Na+,K+-ATPase activity. In rats with experimental hypertension, the plasma cross-reactivity with antidigoxin antibodies was also enhanced when compared to control rats (71.6 +/- 10.2 pg/ml, n = 12 and 57.3 +/- 5.0 pg/ml, n = 33 in Na+ loaded rats and in rats with reduced renal mass respectively compared to 43.4 +/- 3.7 pg/ml, n = 36, p less than 0.05). In spontaneously hypertensive rats (SHR), the apparent levels of digoxin- equivalents were higher than that of age-matched WKY normotensive rats. This increase was already present in prehypertensive SHR (3 week-old) (105.8 +/- 12.4 vs 40.0 +/- 6.5 pg/ml, n = 9 and 8, p less than 0.001) and persisted after hypertension has developed (134 +/- 12.6 vs 85 +/- 7.9 pg/ml, n = 7 and 8, p less than 0.005 in 30 week-old rats). The apparent affinity of the erythrocyte Na+,K+ cotransport for intracellular Na+ and the maximal rate of the Na+ pump were correlated with the plasma digoxin-like levels. These results confirm the presence in plasma of compounds possessing some of the functional and structural properties of cardioactive steroids, associated with a rise in blood pressure.
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PMID:Endogenous digitalis-like compounds in essential and experimental hypertension. 365 54

Common bile duct ligation (CBDL) in rats was used to induce liver disease and secondary kidney damage. The biochemical changes in the liver, kidney and plasma were studied at 3, 6, 10 and 21 days post CBDL. The observed alterations climaxed at the 6th day following ligation. Renal, activities of aldolase (ALD), lactic dehydrogenase (LDH), isocitric dehydrogenase (ICDH), sorbitol dehydrogenase (SDH), and alkaline phosphatase (ALP), were lowered in CBDL rats. Further, microsomal Na,K-ATPase and Mg-ATPase and mitochondrial oxidative-phosphorylation were inhibited. In the liver from CBDL rats the activities of aspartate aminotransferase (AST), Mg-ATPase and ALP were elevated, while SDH, ALD, malic dehydrogenase (MDH), LDH, malic enzyme (ME) and Na,K-ATPase were lowered. Plasma enzymes, AST, ALP, MDH, LDH, ALD, acid phosphatase (ACP) and ICDH and the metabolites bile acids, bilirubin, creatinine and urea were elevated. Addition of bile acids or bilirubin at concentrations comparable to those found in the plasma of CBDL rats, to the reaction mixture of the various enzymes strongly inhibited most, particularly mitochondrial oxidative phosphorylation. High concentrations of these substances in the blood may explain the development of renal failure during liver disease and its reversibility when liver function returns to normal.
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PMID:Biochemical changes in liver, kidney and blood associated with common bile duct ligation. 378 11

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

The digitalis-like activities of plasma extracts from 108 patients and normal subjects were measured by their ability to compete with ouabain for binding to the digitalis sites of the Na+-pump. High levels were found in 18 of 54 untreated patients with moderate hypertension, 10 of 14 patients with end-stage renal failure and six patients with active acromegaly. These levels returned to control values after dialysis in the patients with renal insufficiency and high levels of the inhibitor, and after successful surgery and cobalt therapy in seven acromegalic patients. An increase in circulating Na+, K+-ATPase inhibitor was also found in rats after chronic sodium loading. These results indicate that levels of the circulating compound with digitalis-like properties do not result from high blood pressure but, rather, are related to blood volume and Na+ balance.
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PMID:Investigation of the endogenous Na+-pump inhibitor in essential hypertension and blood volume expansion. 610 Jul 47

To assess the effects of altered renal function on Na-K-ATPase, the following groups of rats were studied: 1. rats with suprarenal vena cava ligation (SVCL), la. DOCA-treated rats with SVCL, 2. rats with infrarenal vena cava ligation (IVCL), 3. rats with glycerol-induced acute renal failure, 4. rats with bilateral ureteric ligation, and 5. K-exalate-treated rats with SVCL. In group 1, acute renal failure with hyperkalemia developed and medullary Na-K-ATPase increased from 95 +/- 5 in control to 155 +/- 7 mumol Pi/mg prot/h, P less than 0.001, DOCA did not prevent the increase of Na-K-ATPase. In group 2, medullary Na-K-ATPase decreased from 130 +/- 10 in control to 88 +/- 7, P less than 0.01, in rats with IVCL. In group 3, cortical Na-K-ATPase decreased from 55 +/- 5 to 27 +/- 6, P less than 0.02. In group 4, Na-K-ATPase was unchanged. In group 5, maintenance of normokalemia prevented the rise in Na-K-ATPase. These experiments demonstrated a K-dependent activation of medullary Na-K-ATPase after SVCL but not in other forms of renal failure. Because SVCL diminishes drastically GFR per nephron, the present findings imply that increased loads of Na and K per nephron are not a prerequisite for an increase in medullary Na-K-ATPase. Hyperkalemia in presence of increased renal venous pressure seems to be causally related to the rise in medullary Na-K-ATPase activity.
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PMID:Renal function and Na-K-ATPase in rats after suprarenal ligation of inferior vena cava. 612 57

Na+,K+-ATPase activity was assessed indirectly in three groups of subjects of differing age, and in a group of patients with renal failure, by measuring the 86-rubidium uptake in the patients' own erythrocytes. The inhibiting action of digoxin on this activity was also measured in vitro. Erythrocyte 86Rb uptake was found to be lower in the elderly as was the calculated volume of distribution of digoxin. Sensitivity to the inhibiting action of digoxin increased with age. In the renal failure group 86Rb uptake was diminished and the sensitivity to digoxin was variable. This suggested that Na+,K+-ATPase activity could be one determinant of the volume of distribution of digoxin and that quantitative and qualitative changes of this enzyme could explain features of the pharmacokinetics of digoxin in renal failure and in old age.
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PMID:Digoxin in the elderly and in renal failure. Contribution of erythrocyte 86-rubidium uptake tests. 626 20

Na+, K+-ATPase activity in erythrocytes (RBC) has been assessed indirectly by the 86Rb uptake method in 10 patients with acute renal failure (ARF), 11 patients with chronic renal failure (CRF) on haemodialysis and 13 patients treated by kidney transplantation, and compared to age-matched healthy controls. In each patients, the sensitivity of 86Rb uptake to digoxin (IC50) has been measured. Na+, K+-ATPase activity was decreased in patients with ARF and in patients with CRF but not in transplanted patients. IC50 was lowered in transplanted patients. The implications of these findings are discussed in terms of possible mechanisms of the changes in Na+, K+-ATPase activity in RBC of patients with renal failure.
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PMID:Cation transport in erythrocytes of patients with renal failure. 630 Jul 13

The high incidence of cardiac complications in endstage renal failure is not only related to the chronic pressure load of the left ventricle, although the proportion of patients with elevated blood pressure increases from 53 to 81% as reno-parenchymal disease progresses. Other factors as anemia, hyperparathyroidism, autonomic neuropathy and retention of electrolytes, metabolic products of toxins may cause damage to the heart. It is a matter of discussion whether uremia itself causes cardiomyopathy. Findings of a reduced Ca++-uptake during beta-adrenergic stimulation and a reduced reaction of (Na+, K+)-ATPase to digitalis suggest a basic change of myocardial membrane metabolism. Retention of an "endogenous digitalis" could help to explain some contradictory results.
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PMID:[Reno-cardiac interactions in kidney failure (author's transl)]. 700 26


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