Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q92565 (GFR)
 4,179 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The oophorectomized (OOX) rat has been proposed as a good model of postmenopausal osteoporosis in women. The aim of this study was to compare the effect of OOX in 6-month-old rats to the effects of menopause in women with respect to bone mass, the renal handling of calcium and phosphorus, and calcitropic hormones. To more closely replicate the human situation the rats were pair fed a 0.1% calcium diet. Thirty four, 6-month-old rats were randomized to sham operation or OOX. Whole body and regional bone density was performed at baseline and 6 weeks postoperation. Blood and 24-hour urine samples were obtained at baseline, 1, 3, and 6 weeks and assayed for various biochemical variables, parathyroid hormone (PTH), and calcitriol. The OOX rats lost significantly more bone than the sham-operated rats (change in global bone mineral density, sham -1.7 +/- 2.0%, OOX -3.9 +/- 2.6%, P < 0.001). In the OOX animals, an increase in the 24-hour urine calcium was observed at 1 and 3 weeks, which had returned to sham-operated levels by 6 weeks. In the whole group, the increase in urine calcium at 1 week was negatively correlated with the change in bone mass at 6 weeks (r = -0.39, P = 0. 029). OOX resulted in an increased filtered load of calcium and phosphorus. There was an increase in the maximal renal tubular reabsorption of phosphorus (TmP-GFR) but no clear change in renal calcium handling. Neither calcitriol nor parathyroid hormone showed a significant change as a result of OOX. As in postmenopausal women, following oophorectomy in the rat, there was significant generalized bone loss and a negative calcium balance. This was associated with an initial rise in urine calcium due to a rise in the filtered calcium load; plasma phosphorus and TmP-GFR also rose. The rat model may differ from postmenopausal bone loss in that the initial rise in urine calcium was not present at later time points as occurs in natural menopause in women. Calcitropic hormone levels did not change. This study has shown that the 6-month-old OOX rat fed a 0.1% calcium diet has many similarities of calcium and phosphorus homeostasis to that seen at menopause in women.
 ...
PMID:The effect of estrogen deficiency on bone mineral density, renal calcium and phosphorus handling and calcitropic hormones in the rat. 869 94

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.
 ...
PMID:Secondary hyperparathyroidism and vitamin D receptor binding to vitamin D response elements in rats with incipient renal failure. 904 46

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.
 ...
PMID:Increased serum 1,25-dihydroxyvitamin D after growth hormone administration is not parathyroid hormone-mediated. 931 96

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.
 ...
PMID:Dipyridamole decreases renal phosphate leak and augments serum phosphorus in patients with low renal phosphate threshold. 964 37

The purpose of the present study was to determine the change in bone mineral density (BMD) measured with dual energy X-ray absorptiometry (DXA) in patients with Kock reservoirs for urinary diversion who were examined with the same technique 3 years earlier, and relate the changes to kidney function and variables reflecting bone metabolism. A total of 28 patients with Kock ileal reservoirs to the skin (23) or urethra (5) were reinvestigated 3 years after the first measurement. BMD was measured in the lumbar spine, femur and whole body with DXA. Bone specific alkaline phosphatase, osteocalcin, parathyroid hormone (PTH), calcitonin and chloride were also determined in serum. GFR was determined from the plasma clearance of 51Cr-EDTA. The mean values for BMD expressed in percentage of corresponding mean values for age-matched controls (BMD%) were almost identical after 3 years. Only osteocalcin levels correlated with the BMD% values. However, significant positive correlations were found between GFR and the observed individual changes in BMD% over the 3 years in spite of the fact that most GFR values were fairly normal. Enhanced bone loss was associated with high concentrations of osteocalcin and bone specific alkaline phosphatase. Comparisons with blood gas analyses and determination of 1,25 dihydroxyvitamin D performed in the previous study indicate to us that the relation between reduced GFR and low mineral content might, in part, be related to a low-grade metabolic acidosis and reduced availability of the biologically active vitamin D hormone. The conclusion to be drawn is that urinary diversion with a Kock reservoir does not regularly cause bone demineralization. However, patients with even moderately reduced GFR appear to be at risk for developing osteoporosis in the long-time run.
 ...
PMID:Determinants of bone loss in patients with Kock ileal urinary reservoir. 1057 94

It has previously been reported that in adult patients with sickle-cell anemia the serum phosphate value and the maximum tubular reabsorption of phosphate per liter of glomerular filtrate (TmP/GFR) were significantly higher than in normal controls. This does not appear to have been studied in children with sickle cell anemia (young sicklers) and this prompted us to assess renal phosphate reabsorption in this group of patients. We looked at serum phosphate level and calculated renal phosphate reabsorption (TP/GFR) in children taking random urine and blood samples at the same time and using the formula TP/GFR = Sp - Up x SCr: UCr, in 30 young sicklers all of whom had normal renal function (mean age 7.3 years) and 40 normal matching controls (mean age 6.5 years). The mean serum phosphate value in young sicklers was significantly lower than in controls (4.3 against 5.3 mg/dl) while the mean value of TP/GFR was 4.09 +/- 0.74 mg/dl in young sicklers compared to 4.65 +/- 0.75 mg/dl in the control group (p = 0.0026). Therefore, the TP/GFR in young sicklers was also significantly lower (p = 0.0026) than in the control group. This may be explained by the high serum level of parathyroid hormone reported previously in patients with sickle cell anemia which is expected to lower phosphate reabsorption (TmP/GFR and TP/GFR are identical in children). The lower serum phosphate value and TP/GFR in younger sicklers seems to be in contrast with the relatively high serum phosphate value and TP/GFR previously reported in adults with sickle cell anemia.
 ...
PMID:Renal reabsorption of phosphate in children with sickle cell anemia. 1057 82

Assessment of the tubular reabsorption of calcium (Ca) by infusion is complicated by suppression of parathyroid hormone (PTH) secretion, and by activation of the serpentine Ca sensing receptor in the renal tubule, which inhibits Ca and sodium reabsorption, but little is known about the magnitude of the natriuretic effect of Ca in human subjects. Accordingly, we reanalyzed the relationship between serum Ca and urine Ca and sodium excretion expressed per unit of creatinine clearance (CaE and NaE), and per unit of time (UCa and UNa), during a standard Ca infusion, in 14 healthy volunteers and in 8 primary hyperparathyroid patients. In healthy subjects we observed a large effect of Ca infusion on NaE, which rose as high as 8 mmol/liter GFR. In patients with primary hyperparathyroidism both CaE and NaE during Ca infusion were significantly lower overall than in healthy subjects for comparable values of serum Ca (P < 0.05 by covariance analysis), due mainly to a decline or reversal of the slopes at the highest serum Ca levels. In both controls and primary hyperparathyroid subjects the variance of CaE as dependent variable was explained by both serum Ca and by NaE as independent variables (P < 0.001). We conclude that (1) The natriuretic effect of hypercalcemia was unexpected large and if maintained would lead to substantial depletion of extracellular fluid. (2) Patients with chronic hypercalcemia, including primary hyperparathyroidism, probably have mild sodium depletion, and are more susceptible to volume depletion. (3) Calcium reabsorption during Ca infusion is reduced by suppression of PTH secretion and increased by volume contraction due to sodium depletion. Discrimination between different basal levels of parathyroid function is successful because these effects usually cancel out. (4) The increase in tubular reabsorption of Ca due to volume contraction can initiate a vicious circle, of importance to the pathogenesis and treatment of severe hypercalcemia.
 ...
PMID:Calcium-induced natriuresis: physiologic and clinical implications. 1082 78

Osteoblast differentiation and function can be studied in situ in the metaphysis of growing long bones. Proliferation and apoptosis dominate in the primary spongiosa subjacent to the growth plate, and differentiation and function dominate in the proximal metaphysis. Apoptosis of osteocytes dominates at the termination of the trabeculae in diaphyseal marrow. As parathyroid hormone regulates all phases of osteoblast development, we studied the in vivo regulation by human parathyroid hormone (1-34) (PTH) of apoptosis in bone cells of the distal metaphysis of young male rats. Rats were given PTH at 80 microg/kg per day, once daily, for 1-28 days. Bone cells were defined for flow cytometry as PTH1-receptor-positive (PTH1R(+)) and growth factor-receptor-positive (GFR(+)) cells. Apoptotic cells stained positive for either TdT-mediated dUTP-X nick end labeling (TUNEL) or annexin V (annV(+)) were detected by either flow cytometry or immunohistochemistry. Apoptosis was also assessed at the tissue level by RNAse protection and caspase enzyme activity assays. PTH increased apoptotic osteoblasts in the proliferating zone and apoptotic osteocytes in the terminal trabecular zone, by 40%-60% within 2-6 days of PTH treatment, but values became equivalent to controls after 21-28 days of treatment. This transient increase was confirmed in PTH1R(+), GFR(+) bone cells isolated by flow cytometry. There was no detectable change in the steady-state mRNA levels of selected apoptotic genes. Starting at 3 days, at the tissue level, PTH inhibited activity of caspases, which recognize the DEVD peptide substrate (caspases 2, 3, and/or 7), but not those caspases recognizing LEHD or YVAD peptide sequences. We speculate that the localized and tissue level effects of PTH on apoptosis can be explained on the basis of its anabolic effect on bone. The transient increase in apoptosis in the proliferating zone and terminal trabecular zone may be the result of the increased activation frequency and bone turnover seen with daily PTH treatment. As once-daily PTH increases the number of differentiated osteoblasts, and as these and hematopoietic marrow cells dominate metaphyseal tissue, inhibition of caspase activity may contribute to their prolonged survival, enabling extension of trabecular bone into the diaphyseal marrow to increase bone mass.
 ...
PMID:In vivo regulation of apoptosis in metaphyseal trabecular bone of young rats by synthetic human parathyroid hormone (1-34) fragment. 1091 13

X-linked hypophosphatemia (XLH) is characterized clinically by rickets, hypophosphatemia and hyperphosphaturia. Conventional treatment of XLH with oral phosphate and vitamin D is associated with hypercalcuria and nephrocalcinosis. Recently, intravenous and oral dipyridamole has been reported to decrease fractional excretion of phosphate in adults with idiopathic hyperphosphaturia. Our objective was to determine whether oral dipyridamole therapy reduces urinary phosphate excretion and increases serum phosphate concentration in children with XLH. A prospective study was performed in six children with XLH. The average age of the patients at the start of the study was 12.5+/-1.0 years. The effects of 12 weeks of oral dipyridamole therapy, at 4.4+/-0.4 mg/kg body weight per day, on serum phosphorous, parathyroid hormone (PTH), 1,25 (OH)2 vitamin D, osteocalcin, tubular maximum for phosphate reabsorption (TmP/GFR), urinary calcium excretion, and cyclic adenosine 3',5'-monophosphate (cAMP) excretion, were compared to baseline levels. Our results show that there was no change in serum phosphorous concentration or TmP/GFR after 12 weeks of dipyridamole therapy. Dipyridamole therapy also had no effect on serum PTH, serum 1,25 (OH)2 vitamin D, alkaline phosphatase, osteocalcin levels, urinary calcium or cAMP excretion. We therefore concluded that in children with XLH, a 12-week course of dipyridamole had no effect on serum phosphorous or its urinary excretion. Dipyridamole therapy is unlikely to improve the bone disease in children with XLH.
 ...
PMID:Effect of dipyridamole on serum and urinary phosphate in X-linked hypophosphatemia. 1109 12

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.
 ...
PMID:Management of patients with chronic renal insufficiency in the Northeastern United States. 1142 79


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>