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 pathogenesis of secondary hyperparathyroidism in early renal failure is poorly understood. In the study presented here, parathyroid hormone and GFR in rats with mild renal failure of various durations are evaluated. Parathyroid hormone increased significantly 3 days after nephrectomy and peaked at 2 wk, despite reduction in GFR of < 50%. Parathyroid hormone remained elevated, but there was no difference in serum levels of calcium, phosphorus, and calcitriol between the nephrectomized and sham-operated rats. There were also no differences in both intestinal and kidney vitamin D receptor concentrations between the two groups. Histomorphometric analysis of bone at 6 wk revealed significant increase in osteoid thickness, osteoblast number, erosion surface with osteoclasts, and erosion depth. Employing electrophoretic mobility shift assay, we consistently observed a significant reduction in kidney calcitriol-receptor complex binding to mouse osteopontin vitamin D response element (-70.2 +/- 4.9%, P < 0.001). Western blot analysis also revealed a significant reduction in at least one retinoid X receptor isoform. In conclusion, biochemical and histological evidence of secondary hyperparathyroidism develops in rats with mild renal failure, despite normal calcium, phosphorus, calcitriol, and vitamin D receptor concentrations. These rats also have evidence of reduced renal vitamin D receptor binding to nuclear response elements. This finding, possibly an important early factor in the pathogenesis of secondary hyperparathyroidism, could also play a role in the development of compensatory renal growth of the remnant kidney.
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PMID:Secondary hyperparathyroidism and vitamin D receptor binding to vitamin D response elements in rats with incipient renal failure. 904 46

The purpose of this study was to investigate the effect of unconjugated hyperbilirubinemia on endogenous creatinine clearance and urinary excretion of sodium, phosphorus, lysozyme, and amino acids in full-term infants. Thirty-seven healthy, breast-fed newborns who were not exposed to phototherapy were studied on their third to fifth day of life. Twenty had neonatal hyperbilirubinemia with a mean indirect bilirubin value of 16.4 mg/dl, whereas 17 who were used as controls had a mean indirect bilirubin value of 7.8 mg/dl. Urine was collected, and samples were taken for examination of creatinine, lysozyme, sodium, and phosphorus concentration. Urinary sediment, glucose, and amino acid levels were also measured. Serum total and direct bilirubin, creatinine, sodium, and phosphorus measurements were taken at the beginning of urine collection. Calculations were made for creatinine clearance, fractional excretion of sodium (FENa), and tubular reabsorption of renal phosphate per deciliter glomerular filtrate (TP/GFR). The means (+/-1 SD) of creatinine clearance, FENa, and TP/GFR were 27.0 +/- 14.2 ml/min/1.73 m2, 0.53% +/- 0.49%, and 5.72 +/- 1.16 mg/dl GF, respectively, in the hyperbilirubinemic group compared with 21.1 +/- 9.4 ml/min/1.73 m2, 0.4% +/- 0.47%, and 6.01 +/- 0.51 mg/dl GF, respectively, in the controls. No statistically significant differences were found between the groups for any of the examined parameters of either glomerular or tubular function. Neonatal hyperbilirubinemia < 20.8 mg/dl has no detrimental effect on renal function of healthy, breast-fed, full-term newborns, and no modification in the approach regarding renal function is necessary in these babies.
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PMID:Renal function in full-term neonates with hyperbilirubinemia. 921 80

To assess the effects of growth hormone (GH) on serum 1,25-dihydroxyvitamin D [1,25(OH)2D], we performed the following prospective crossover study in six healthy, young, adult, white men. During each of two admissions for 2 1/2 days to a general clinical research center, subjects were placed on a daily dietary calcium intake of 400 mg. Serum calcium, phosphorus, 1,25(OH)2D, immunoreactive intact parathyroid hormone (PTH), insulin-like growth factor I (IGF-I), IGF binding protein 3 (IGFBP3), tubular reabsorption of phosphate (TMP/GFR) were measured. Recombinant human GH (rhGH, Humatrope) (25 microg/kg/day subcutaneously for 1 week) was administered prior to and during one of the admissions. Results are expressed as mean +/- SEM. Whereas serum 1,25(OH)2D (58.9 +/- 7.7 versus 51.6 +/- 7.4 pg/ml, P< 0.01), serum phosphorus (4.5 +/- 0.1 versus 3.7 +/- 0.1 mg/dl, P < 0.01), TRP (92.0 +/- 0.5 versus 87.8 +/- 0.7 mg/dl, P < 0.005), TMP/GFR (4.6 +/- 0.1 versus 3.5 +/- 0.2, P < 0.005), and urinary calcium (602 +/- 49 versus 346 +/- 25 mg/day, P < 0.001) increased significantly, serum PTH decreased significantly (19.9 +/- 1.9 versus 26.8 +/- 4.0 pg/ml, P < 0.05) and serum calcium did not change when subjects received rhGH. These findings indicate that in humans, GH affects serum 1,25(oh)2D independently of circulating PTH and that this effect is mediated by IGF-I. We propose, therefore, that one potential mechanism by which GH stimulates increases in bone mass is via modest increases in serum 1,25(OH)2D.
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PMID:Increased serum 1,25-dihydroxyvitamin D after growth hormone administration is not parathyroid hormone-mediated. 931 96

The aim of our study was to determine the possible pathophysiological mechanisms of hypophosphataemia in a group of 127 patients admitted to hospital for alcohol-related causes. Blood and fresh urine specimens were taken to determine acid-base and electrolyte parameters. Thirty-seven patients (29.1%) had hypophosphataemia (serum phosphorus < 0.77 mmol/l) with a range of serum phosphorus of 0.32-0.74 mmol/l. In 17 hypophosphataemic patients inappropriate phosphaturia (FEPO4 > 20%, TmPO4/GFR < 0.80 mmol/l) was evident, possibly due to hypomagnesaemia, metabolic acidosis, metabolic alkalosis, or a proximal tubular defect in phosphate transport. The causes of hypophosphataemia in the remaining 20 patients were alcohol withdrawal syndrome, respiratory alkalosis and diarrhoea. Patients with hypophosphataemia were more often found to have hypomagnesaemia and respiratory alkalosis than normophosphataemia patients. In conclusion, hypophosphataemia is frequently observed in alcoholic patients due to various pathophysiological mechanisms, such as inappropriate phosphaturia, increased phosphorus entry into cells and increased gastrointestinal loss of phosphate.
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PMID:Mechanisms of hypophosphataemia in alcoholic patients. 953 3

It has been shown that an acute infusion of dipyridamole increased renal phosphate reabsorption in rats and humans. A prospective study was performed to determine whether chronic treatment by dipyridamole given orally could decrease renal phosphate leak and increase serum phosphorus in patients with idiopathic low renal phosphate threshold (TmPO4/GFR < 0.77 mM). Sixty-four patients with low TmPO4/GFR were included and treated with dipyridamole (75 mg, 4 times daily) for more than 12 mo. Serum phosphorus, TmPO4/GFR, parathyroid hormone, serum calcium, and 1,25-dihydroxyvitamin D were measured sequentially before treatment, and after 3, 6 to 9, and 12 mo of treatment. Under chronic treatment with dipyridamole, TmPO4/GFR and serum phosphorus significantly increased in 80% of patients within 3 mo, with maximal values reached within 9 mo. This improvement persisted after 12 mo of treatment. In 28 patients, 1,25-dihydroxyvitamin D concentrations were above the normal range (> 42 pg/ml) and normalized in parallel with the increase of serum phosphorus. The 24-h calcium excretion (which was initially increased in patients with high vitamin D concentrations) and urolithiasis decreased under treatment. Ionized serum calcium and parathyroid hormone remained unchanged. After 2 yr, treatment was discontinued in three patients; serum phosphorus and TmPO4/GFR decreased within 1 mo after discontinuation. Dipyridamole at a dose of 75 mg 4 times daily increases low TmPO4/GFR and improves hypophosphatemia in patients with renal phosphate losses and can be used to treat these patients.
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PMID:Dipyridamole decreases renal phosphate leak and augments serum phosphorus in patients with low renal phosphate threshold. 964 37

Protein-restricted diets are prescribed in patients with chronic renal failure (CRF) to alleviate uremic symptoms and to slow the progression of CRF. The potential deleterious effects of protein restriction on nutritional status and clinical outcome of patients with CRF have raised concern. In this study, data were collected from 1985 to 1998 on 239 consecutive patients (age 50.2 +/- 15.6 yr) with advanced CRF (GFR 13.1 +/- 4.8 ml/min) to whom a supplemented very low protein diet (SVLPD) providing 0.3 g protein, 35 kcal, and 5 to 7 mg of inorganic phosphorus per kg per day was administered for a mean duration of 29.6 +/- 25.1 mo. The diet was supplemented with essential amino acids and ketoanalogs, calcium carbonate, iron, and multivitamins. During SVLPD, protein intake decreased from 0.85 +/- 0.23 to 0.43 +/- 0.11 g/kg per d, and body mass index and serum albumin concentration remained unchanged overall. Fourteen patients died during SVLPD; death was unrelated to nutritional parameters. Hemodialysis was initiated after SVLPD in 165 patients at a mean GFR of 5.8 +/-1.5 ml/min. During an average of 54 mo on hemodialysis, mortality was low (2.4% after 1 yr) and correlated to age only, not to nutritional parameters observed at the end of SVLPD. Similar results were obtained in 66 transplanted patients (12 were not dialyzed before transplantation). SVLPD can be safely used in patients with CRF without adverse effects on the clinical and nutritional status of the patients. Due to the preservation of nutritional status and the correction of uremic symptoms, the initiation of dialysis was deferred in these patients. The outcome of patients on renal replacement therapy is not affected by prior treatment with SVLPD during the predialysis phase of CRF.
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PMID:Nutrition and outcome on renal replacement therapy of patients with chronic renal failure treated by a supplemented very low protein diet. 1075 30

Comorbid conditions that develop during chronic renal insufficiency (CRI) contribute to the high morbidity and mortality among patients with end-stage renal disease (ESRD). Thus, appropriate management during CRI may lead to improved ESRD outcomes. A retrospective cohort study was performed to describe the management of patients with CRI. A total of 602 patients with CRI (creatinine > or =1.5 mg/dl for women and > or =2.0 mg/dl for men) were seen between October 1994 and September 1998 at five nephrology outpatient clinics in the Boston area. The mean (SD) age of the patients was 63 (15.5) yr, and 53% were male. At the first nephrology visit, mean (SD) serum creatinine was 3.2 (1.6) mg/dl, and mean (SD) predicted GFR was 22.3 (8.9) ml/min per 1.73 m(2). Laboratory tests for iron levels were performed in only 18% of patients, serum parathyroid hormone levels were obtained in only 15%, lipid studies were obtained in fewer than half, and among patients with diabetes, only 28% had a glycosylated hemoglobin level measured. A hematocrit <30% was present in 38%, and abnormal calcium-phosphorus metabolism was noted in 55%. Only 59% of patients who had hematocrit <30% received recombinant human erythropoietin. Among patients who received recombinant human erythropoietin, only 47% received iron. Angiotensin-converting enzyme inhibitor use was recorded for only 65% of patients with diabetes (49% of patients overall). Among patients who were known to have progressed to ESRD, only 41% had permanent access placed before initiation of dialysis. There seems to be room for improvement in the management of patients with CRI, which could result in a slower rate of progression of CRI and reduced severity of comorbid conditions.
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PMID:Management of patients with chronic renal insufficiency in the Northeastern United States. 1142 79

The methods for preventing hyperparathyroid bone disease, the major variety of renal osteodystrophy, from developing in patients with renal impairment are reviewed. With far-advanced chronic renal failure (creatinine clearance [CCr] < 15 to 20 ml/min), when many of these patients are seen by nephrologists, the use of diets very low in protein, and hence also very low in phosphorus content, combined with calcium-containing phosphate binders, have been shown to lower serum intact PTH levels and improve the osseous pathology. However, the degree of dietary restriction required to achieve success may be quite difficult to follow by most patients encountered in clinical practice. In less-advanced renal insufficiency (CCr, 25 to 60 ml/min), the active vitamin D sterols calcitriol or alfacalcidol [1 alpha-hydroxyvitamin D3] have been shown to ameliorate the skeletal lesions of renal osteodystrophy. The results of six double-blind, placebo-controlled studies and five major open-labeled studies with calcitriol or alfacalcidol are reviewed. Skeletal biopsies were improved and sometimes normalized by using calcitriol or alfacalcidol in daily doses of 0.25 to 0.5 microgram/d, and the incidence of hypercalcemia was quite low with these doses. When the dosage was increased in one study, there was a higher incidence of hypercalcemia. Improved bone mineral density of the spine and hip was reported after 1 yr in calcitriol-treated patients compared with results in the placebo group. Another report documented more favorable intact PTH suppression with intermittent dosing of 2.0 micrograms given either once or three times weekly compared with daily dosing (0.5 microgram/d); there was no rise of serum Ca over the 3-mo trial with any protcol. Other data support the greater likelihood of having normal bone if treatment is initiated when CCr exceeds 25 ml/min. There was no risk of more rapid progression of renal insufficiency in any of the studies reviewed, which include 242 patients who were given an active vitamin D sterol. One trial that used a calcitriol dose of 0.5 microgram/d noted a fall in CCr and a rise in serum creatinine, but true GFR (inulin clearance) did not change. A calcitriol-induced reduction of tubular creatinine secretion is suggested. The risk of inducing low bone turnover (adynamic bone) seems to be quite low with 10.4% of alfacalcidol-treated patients versus 6.5% of placebo developing this "lesion" after 2 yr. Despite the lack of Food and Drug Administration approval for use of these sterols in the predialysis state, evidence is compelling that: there are benefits in retarding the development or progression of metabolic bone disease; there is minimal risk, providing that low doses are used; and there is close monitoring of serum Ca, P, and creatinine. The optimal benefits may be obtained if this treatment is started early in the course of renal insufficiency (CCr in the range of 25 to 60 ml/min).
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PMID:Prevention of metabolic bone disease in the pre-end-stage renal disease setting. 1144 72

An athletic 8-year-old boy developed severe muscle weakness over 2 years. At the age of 10 years, investigation for possible neuromuscular disease disclosed hypophosphatemia (1.8 mg/dl) and rickets. There was selective renal tubular wasting of inorganic phosphate (Pi) but no history of toxin exposure, familial bone or kidney disease, or biochemical evidence of vitamin D deficiency. Urine amino acid quantitation was unremarkable. Serum 1,25-dihydroxyvitamin D [1,25(OH)2D] concentration was in the lower half of the reference range. Our presumptive diagnosis was tumor-induced rickets; however, physical examination and bone scanning in search of a neoplasm were unrevealing. Soon after 1,25(OH)2D3 and Pi treatment began, muscle strength improved considerably. After 6 months of therapy, radiographic abnormalities were substantially better. During the next 6 years, physical examinations, a second bone scan, whole-body and nasal sinus magnetic resonance imaging, and octreotide scintigraphy were unremarkable. When his physes fused at the age of 16 years, assessment of his course showed excellent control of his rickets requiring decreasing doses of medication. Furthermore, fasting serum Pi levels and tubular maximum phosphorus/glomerular filtration (TmP/ GFR) values had increased steadily and normalized after 3 years of treatment. Accordingly, therapy was stopped. Seven months after stopping medication, he continues to feel completely well. Fasting serum Pi levels, TmP/GFR, other biochemical parameters of bone and mineral homeostasis, creatinine clearance, and renal sonography are normal. Neither spontaneous or pharmacologic cure of tumor-induced rickets or osteomalacia nor a patient matching ours has been reported. His disorder, which we call pseudo-(tumor-induced) rickets, should be considered when investigation for oncogenic rickets or osteomalacia discloses no causal lesion. Consequently, prolonged medical therapy and futile searches for a neoplasm may be avoided.
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PMID:Pseudo-(tumor-induced) rickets. 1149 80

Although urine phosphate loss has been associated with hypercalciuria, it is debated how frequently renal phosphate leak is present in hypercalciuric patients. We reviewed the records of 100 consecutive adult patients who were diagnosed with idiopathic hypercalciuria and calcium urolithiasis, searching for the presence of renal phosphate leak. The renal phosphate threshold, normalized for the glomerular filtration rate (TmPO4/GFR), of the hypercalciuric patients followed a normal distribution and had a good correlation with serum phosphate ( r=0.77; p<0.0001). There were no correlations between TmPO4/GFR and urinary calcium or between serum phosphorus and urinary calcium. We found only nine patients (9%) with renal phosphate leak. These patients had a mean TmPO4/GFR of 2.19 mg% (0.70 mmol/l) and serum phosphorus of 2.65 mg% (0.85 mmol/l). Nevertheless, urinary calcium was not significantly different between patients with or without low TmPO4/GFR. We conclude that renal phosphate leak is an infrequent finding in patients with idiopathic hypercalciuria and is not associated with a higher urinary calcium loss.
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PMID:Renal phosphate leak in patients with idiopathic hypercalciuria and calcium nephrolithiasis. 1368 23


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