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)

Rats were subjected to a two-stage 5/6 nephrectomy and treated with aluminum for 2 and 4 weeks with a cumulative dose of 4.2 and 8.4 mg of aluminum, respectively. Other animals were parathyroidectomized and loaded with 8.4 mg of aluminum for 4 weeks. Histomorphometry and electron microscopy (tibiae), aluminum tissue (bone, kidney, liver) determination, serum (Ca, Mg, Zn, P, urea, creatinine, alkaline phosphatase, 1,25(OH)2D3, PTH) and urine (creatinine, A1) revealed that: (a) a dose of 8.4 mg aluminum was sufficient to induce rickets within 4 weeks of treatment and was associated with decreased serum calcitriol values and high aluminum accumulation within organs (electron-dense material was found in osteoblasts only); (b) previous parathyroidectomy prevented the occurrence of any aluminum-induced alteration of bone. It was associated with higher calcitriol and phosphorus values than in corresponding non-parathyroidectomized rats and significantly reduced aluminum accumulation within organs. The results was influenced neither by a drop in serum calcium values nor by different degrees of renal failure. We suggest that aluminum-induced rickets in growing uremic rats is prevented or delayed when previous parathyroidectomy has been performed.
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PMID:The influence of early parathyroidectomy on aluminum-induced rickets in growing uremic rats. 276 4

Osteocalcin (OC), also called Bone Gla Protein (BGP), is a bone matrix protein of 5800 MW synthesized by osteoblasts. Since OC is mainly metabolized in the kidney, its blood concentration is altered in renal failure. The relationship between OC and the calcium-phosphorus regulating hormones (parathyroid hormone, calcitonin) and the biochemical parameters of bone metabolism (serum calcium, serum phosphorus and serum alkaline phosphatase) was studied in 30 patients on chronic hemodialysis (mean age: 51 years; mean duration of dialysis treatment: 39 months). OC levels were significantly elevated in all patients on chronic hemodialysis (34.7 +/- 31.5 ng/ml) when compared to healthy subjects (6.25 +/- 1.39 ng/ml, p less than 0.001). In 2 patients the OC levels were excessively high (127.54 ng/ml; 148.02 ng/ml), which was associated with severe renal osteodystrophy due to secondary hyperparathyroidism. When divided into 2 groups in the patients with secondary hyperparathyroidism the mean OC value was markedly elevated (50.5 +/- 12.7 ng/ml) compared to the patients without secondary hyperparathyroidism (24.1 +/- 2.8 ng/ml) (p less than 0.05). 70 per cent of the patients on chronic hemodialysis with OC levels greater than 30 ng/ml showed moderate to severe scintigraphic findings of bone disease. In neither of the 2 groups could a correlation between OC and serum alkaline phosphatase be demonstrated. The results indicate, that OC levels could be useful additional parameter in hemodialyzed patients with secondary hyperparathyroidism and OC levels could reflect bone formation in these patients.
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PMID:[Osteocalcin in chronic hemodialysis patients as an additional parameter in the diagnosis of advanced secondary hyperparathyroidism]. 278 25

Aluminum toxicity is the presumed cause of aluminum-associated osteomalacia. In animal models, osteomalacia has been produced after a prolonged course of aluminum. In the present study, rats with renal failure received 20 mg intraperitoneal aluminum during a 2 day period. This model allows sequential observations in the development of osteomalacia. Rats were sacrificed and studied 5, 12, 25, and 40 days after aluminum administration. No differences were observed in serum calcium, phosphorus, or creatinine as a consequence of aluminum administration. Compared with control rats, parathyroid hormone was decreased at 12 and 25 days. A direct correlation was present between plasma and bone aluminum at 12 days (r = 0.92, p less than 0.01), 25 days (r = 0.85, p less than 0.005), and 40 days (r = 0.88, p less than 0.001) but not 5 days after aluminum administration. Plasma aluminum peaked at 5 days (727 +/- 89 micrograms/liter, mean +/- SEM) and bone aluminum at 40 days (273 +/- 40 micrograms/g). Aluminum had profound effect on bone histology. At 5 days there was a decrease in osteoblast surface and osteoid surface; at 12 days osteoblast surface and osteoid surface returned to normal but osteoclast surface decreased. Subsequently there was a progressive increase in osteoid surface and osteoid volume. Bone formation rate measured at 12, 25, and 40 days was decreased at these intervals. In conclusion, (1) high plasma aluminum may be directly toxic to the osteoblast; (2) progressive osteoid accumulation is secondary to matrix (osteoid) deposition, which exceeds the depressed bone formation rate; (3) the progressive decrease in plasma aluminum and increase in bone aluminum suggest that bone has a high affinity for aluminum but may have a relatively slow rate of uptake at any given time; (4) aluminum may directly decrease parathyroid hormone; (5) the correlation between plasma and bone aluminum suggest an exchange is present; and (6) aluminum toxicity may independently affect the osteoblast and bone mineralization.
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PMID:The evolution of osteomalacia in the rat with acute aluminum toxicity. 281 14

Rates of progression of renal failure were calculated for a group of 277 patients who had five or more clinic visits. The goals of therapy in the absence of ongoing immunological processes were control of blood pressure to diastolic pressures less than 85 mm Hg and serum phosphate less than 1.60 mmol/L (5 mg/dL). The mean rate of progression expressed as the slope of the reciprocal creatinine versus time was -0.0054 +/- 0.0009 dL/mg/mo (mean +/- SEM), and the median was -0.00315 dL/mg/mo. Approximately 25% of these patients had rates of progression less than -0.001 dL/mg/mo. The rate of progression was inversely correlated with the creatinine concentration at entry (P less than 0.004) and with the frequency of clinic visits (P less than 0.01). The "renal survival" time from a creatinine of 880 mumol/L (10 mg/dL) to dialysis was 10.0 +/- 1.2 months (mean +/- SEM). These data provide rates of progression for a group of patients without specific dietary intervention but with vigorous control of blood pressure and phosphorus.
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PMID:Progression of chronic renal failure. 281 31

Antacids used to decrease phosphorus absorption in patients with renal failure may be toxic. To find more efficient or less toxic binders, a three-part study was conducted. First, theoretical calculations showed that phosphorus binding occurs in the following order of avidity: Al3+ greater than H+ greater than Ca2+ greater than Mg2+. In the presence of acid (as in the stomach), aluminum can therefore bind phosphorus better than calcium or magnesium. Second, in vitro studies showed that the time required to reach equilibrium varied from 10 min to 3 wk among different compounds, depending upon solubility in acid and neutral solutions. Third, the relative order of effectiveness of binders in vivo was accurately predicted from theoretical and in vitro results; specifically, calcium acetate and aluminum carbonate gel were superior to calcium carbonate or calcium citrate in inhibiting dietary phosphorus absorption in normal subjects. We concluded that: (a) inhibition of phosphorus absorption by binders involves a complex interplay between chemical reactions and ion transport processes in the stomach and small intestine; (b) theoretical and in vitro studies can identify potentially better in vivo phosphorus binders; and (c) calcium acetate, not previously used for medical purposes, is approximately as efficient as aluminum carbonate gel and more efficient as a phosphorus binder than other currently used calcium salts.
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PMID:Reduction of dietary phosphorus absorption by phosphorus binders. A theoretical, in vitro, and in vivo study. 291 Sep 21

Uremic sera are known to inhibit thymidine incorporation of normal lymphocytes. The nature of the factor(s) responsible for this inhibitory effect has not been completely elucidated. In this study a possible correlation was investigated between a number of uremic blood constituents altered with the progression of the disease and the immunoinhibitory effect of the respective sera. No such correlation was found with the values of hematocrit, urea, creatinine, calcium and phosphorus. On the other hand a significant negative correlation emerged between H+ and Mg2+ ion levels and the inhibition imposed on normal lymphocyte thymidine incorporation. This apparently paradoxical result would indicate that with regard to these two parameters the greater the severity of renal failure the smaller would be the immunoinhibitory effect of the respective serum. The inhibition imposed by uremic serum on immune functions is probably a multifactorial phenomenon, in which H+ and Mg2+ might play a role antagonistic to inhibitory factors.
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PMID:The effect of several uremic parameters on uremic serum inhibition of lymphocyte blastogenesis. 298 12

Phosphorus is the sixth most abundant element in the body after oxygen, hydrogen, carbon, nitrogen, and calcium. It comprises about 1% of the total body weight of humans. Eighty-five percent of it is stored in the bone in the form of hydroxyapatite crystal; 14% is in the soft tissues in the form of energy-storing bonds with nucleotides (ATP, GTP), nucleic acids in chromosomes and ribosomes, 2,3-DPG in the red blood cells, and phospholipids in the cells' membranes. Less than 1% is in the extracellular fluids. Phosphate balance is maintained by multiple systems. The gut is responsible for the absorption of two thirds of the 4-30 mg/kg/day of phosphate intake. Absorption sites are all along the gut; in humans the most active site is the jejunum. The kidney filters 90% of the plasma phosphate and reabsorbs it in the tubuli. In states of hypophosphatemia the kidney can reabsorb the filtered phosphates very efficiently, reducing the amount excreted in the urine virtually to zero. The healthy kidney can excrete high loads of phosphate and rid the body of phosphate overload. Through the vitamin D-PTH axis the endocrine system regulates the phosphate balance by influencing the kidney, gut, and bone. Other hormones, including thyroid, insulin, glucagon, glucocorticosteroid, and thyrocalcitonin, play a lesser role in regulation of phosphate metabolism. Because of the complex control of phosphate homeostasis, various clinical conditions may lead to hypophosphatemia. These include nutritional repletion, gastrointestinal malabsorption, use of phosphate binders, starvation, diabetes mellitus, and increased urinary losses due to tubular dysfunction. The clinical picture of phosphate depletion is manifested in different organs and is due mainly to the fall in intracellular levels of ATP and decreased availability of oxygen to the tissues, secondary to 2,3-DPG depletion. The various manifestations of phosphate depletion are listed in Table 2. The treatment of hypophosphatemia consists of administering enteral or parenteral phosphate salts. An important aspect of dealing with the potentially serious effects of phosphate depletion is to prevent the depletion from happening in the first place. Hyperphosphatemia can occur in renal failure, hemolysis, tumor lysis syndrome, and rhabdomyolysis. The treatment of hyperphosphatemia usually consists of fluid administration (in the absence of kidney failure). In chronic hyperphosphatemia, phosphate binders such as aluminum and magnesium salts can reduce the phosphate load. The use of these phosphate binders is limited by their potential side effects.
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PMID:Consequences of phosphate imbalance. 306 Jan 61

A 14.5-year-old boy with end-stage renal failure due to familial primary hyperoxaluria underwent cadaver donor renal transplantation. The graft function was stable for a period of 22 months, while he was on conventional immunosuppressive therapy (prednisolone and azathioprine) and additional oral pyridoxine, phosphorus, and magnesium supplementation. When ciclosporin A was introduced instead of azathioprine, the blood levels of oxalate rose, and oxalate deposition in the renal tubuli became evident. These observations suggest that ciclosporin A interferes with oxalate metabolism and, therefore, should be given with utmost caution in patients with primary hyperoxaluria.
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PMID:Recurrence of oxalate deposition in a renal transplant during ciclosporin A therapy. 307 54

Previous studies in several animal species have demonstrated that the kidneys are the primary site of mevalonate metabolism by the oxidative or shunt pathway. To determine the role of the human kidney in mevalonate oxidation, we studied mevalonate shunt activity in patients undergoing hemodialysis for varying degrees of renal failure. Surprisingly, at least half of the uremic patients and even anephric patients had normal ability to oxidize mevalonate by the shunt pathway. In addition, we found a strong negative correlation (R = -0.94) between mevalonate shunt activity and serum phosphorus levels in uremic patients. The resulting inhibition of mevalonate oxidation by high serum phosphorus levels was reversed by lowering the serum phosphorus in one patient. Finally, a positive correlation was found between mevalonate oxidation and serum PTH levels. The results of this study suggest that, in humans, extrarenal tissues can be major contributors to mevalonate oxidation. It is therefore probable that in humans, in contrast to other animals, the kidney is not the primary site of mevalonate metabolism by this oxidative pathway. Finally, the strong negative correlation between serum phosphorus levels and the ability of uremic patients to oxidize mevalonate suggests a regulatory role for the phosphate ion in the mevalonate shunt pathway.
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PMID:Role of the kidneys in the metabolism of circulating mevalonate in humans. 308 36

Twelve anaemic patients on haemodialysis were treated with recombinant human erythropoietin, starting with 72 IU/kg/week. The dose was doubled after 2 weeks until an increase of 2 g/dl of haemoglobin was observed. The effects on various parameters were studied during a 3-month period. Haemoglobin increased from 6.70 +/- 0.74 to 10.49 +/- 1.04 g/dl (mean +/- SD, P less than 0.001), potassium from 5.51 +/- 0.50 to 6.06 +/- 0.65 mmol/l (P less than 0.005), phosphate from 1.78 +/- 0.40 to 2.17 +/- 0.40 mmol/l (P less than 0.001) and the calcium phosphorus product from 4.3 to 5.2 (P less than 0.001). Three patients developed marked periarticular inflammation due to calcified deposits with a high calcium-phosphorus product of 6.8. An increase in arterial blood pressure was observed in three previously well-controlled hypertensive patients, one of whom developed hypertensive encephalopathy. We conclude that recombinant human erythropoietin is very effective in treating the anaemia of end-stage renal failure on haemodialysis. Regular estimations of serum potassium and phosphate are mandatory. In hypertensive individuals a further increase in blood pressure is possible.
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PMID:Human recombinant erythropoietin in anaemic patients on maintenance haemodialysis. Secondary effects of the increase of haemoglobin. 314 24


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