Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The lipid metabolic disorders in chronic renal insufficiency (CRI) are related to increased hepatic lipid synthesis, reduced triglyceride removal coupled with insulin insensitivity and impaired lipoprotein lipase activity. Growth hormone is lipolytic, and the effects of recombinant human growth hormone (rhGH) on the hypercholesterolemia of CRI are unsettled. To test this question, we gave rhGH for 14 days at a dosage of 3 units/day intraperitoneally to two-stage, 5/6 nephrectomized, male Sprague-Dawley rats (n = 18) compared to sex- and age-matched control (n = 27) and CRI (n = 40) rats. At the end of the study, CRI rats and those treated with rhGH had a similar degree of renal impairment, as assessed by serum concentrations (mean +/- SEM) of urea nitrogen (49 +/- 3 vs. 54 +/- 4 mg/dl), creatinine (0.9 +/- 0.0 vs. 1.0 +/- 0.1 mg/dl) and cumulative food intake (311 +/- 8 vs. 290 +/- 12 g). Serum urea nitrogen (16 +/- 4 mg/dl) and creatinine (0.4 +/- 0.1 mg/dl) concentrations as well as food intake (412 +/- 9 g) of control rats were significantly (p < 0.0001) different. Serum cholesterol concentration of CRI rats treated with rhGH (87 +/- 3 mg/dl) was not higher than those of CRI rats (81 +/- 2 mg/dl, p < 0.1338) but was significantly higher than in control rats (55 +/- 3 mg/dl, p < 0.0001). CRI rats treated with rhGH showed a similar serum albumin concentration and lower serum glucose than CRI rats (0.9 +/- 0.1 vs. 0.9 +/- 0.0 g/dl and 144 +/- 4 vs. 163 +/- 3 mg/dl, p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hypercholesterolemia in rats with chronic renal insufficiency not aggravated by recombinant human growth hormone. 147 89

1. Nifedipine ameliorates cyclosporin A-induced renal impairment in surgically intact (two-kidney) rats. This study investigates the effect of nifedipine on cyclosporin A nephrotoxicity in spontaneously hypertensive rats after either uninephrectomy or uninephrectomy with contralateral renal denervation. 2. Fourteen days after uninephrectomy pair-fed rats were injected for 14 days with cyclosporin A (25 mg/kg body weight) via the subcutaneous route and with nifedipine (0.1 mg/kg body weight) via the intraperitoneal route. Renal and systemic haemodynamics were measured in conscious unrestrained rats. 3. Whole-blood levels of cyclosporin A did not differ between groups (overall 352 +/- 22 ng/ml, means +/- SEM). After uninephrectomy, cyclosporin A decreased the glomerular filtration rate (olive oil versus cyclosporin A: 0.96 +/- 0.04 versus 0.70 +/- 0.06 ml min-1 100 g body weight, P less than 0.02) and effective renal plasma flow (1.94 +/- 0.10 versus 1.38 +/- 0.13, P less than 0.01), and increased renal vascular resistance [(20.2 +/- 1.8) x 10(4) versus (31.6 +/- 3.3) x 10(4) kPa l-1 s [(20.2 +/- 1.8) x 10(3) versus (31.6 +/- 3.3) x 10(3) dyn s cm-5], P less than 0.02] and mean arterial pressure (146.7 +/- 6.7 versus 167.3 +/- 2.9 mmHg, P less than 0.05). Neither renal denervation nor nifedipine prevented the reduction in glomerular filtration rate or effective renal plasma flow induced by cyclosporin A. 4. This study infers that the sympathetic nervous system does not play an active role in cyclosporin A nephrotoxicity and demonstrates that the concomitant administration of nifedipine to rats with reduced renal mass does not ameliorate cyclosporin A-induced renal impairment.
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PMID:Influence of nifedipine on cyclosporin A nephrotoxicity after unilateral nephrectomy in the spontaneously hypertensive rat. 165 73

We have explored the effect of verapamil on renal hemodynamics and the renin-aldosterone system in ten patients with chronic renal disease and hypertension before and after 3 months of therapy. The mean +/- SEM glomerular filtration rates were 55 +/- 7 mL/min pre- and 55 +/- 8 mL/min posttherapy; the renal plasma flow was 231 +/- 29 mL/min pre and 244 +/- 35 mL/min posttherapy. The filtration fraction (0.24 pre; 0.23 post) and the renal vascular resistance (492 +/- 144 pre; 422 +/- 101 post) also remained stable with verapamil therapy. Blood pressure was lower after treatment (P less than .02) in 7 of 10 patients. Urinary albumin excretion was reduced only when blood pressure was lowered. Verapamil had a modest effect on the renin-aldosterone axis. While the mean increase in plasma renin activity from a pretreatment value of 1.8 +/- 0.42 ng/mL/h to 2.1 +/- 0.56 ng/mL/h failed to reach statistical significance, the increases in urinary aldosterone excretion from 8.2 +/- 2.2 mg/24 h to 11.1 +/- 2.3 mg/24 h did (P less than .001). Our results demonstrate that verapamil lowered blood pressure without renal hemodynamic compromise in hypertensive patients with chronic renal disease. The antihypertensive response was associated with a rise in urinary aldosterone excretion, with unchanged serum electrolytes. We conclude that verapamil is effective, safe, and well-tolerated in patients with renal impairment and hypertension, and may be suitable for clinical trials evaluating long-term progression of renal disease.
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PMID:Hemodynamic responses to verapamil monotherapy in patients with renal disease. 181 50

The present study evaluated serum ribonuclease activity (SRA) in patients with inflammatory and neoplastic pancreatic diseases. RNase determination was carried out using t-RNA (T) from E. coli MRE 600 at pH 7.4 and polycytidylic acid (poly-C) (P) at pH 6.6 as RNA substrates with RNase A from bovine pancreas as reference enzyme. Healthy volunteers had a SRA of T: 160 +/- 12 and P: 482 +/- 24 ngeq/mL (mean +/- SEM (n]. In patients with acute interstitial pancreatitis (AIP), SRA was similar to healthy controls (T: 166 +/- 14; P: 474 +/- 30 ngeq/mL). Patients with acute necrotizing pancreatitis (ANP) had increased SRA (T: 278 +/- 49; P: 791 +/- 145 ngeq/mL, p less than 0.01, compared to controls). SRA values were also increased in patients with chronic pancreatitis (CP) with T: 224 +/- 15 ngeq/mL (p less than 0.01) and in patients with pancreatic carcinoma (PCA) with T: 331 +/- 35 (p less than 0.001 vs controls, p less than 0.01 vs CP). Increased SRA was detected in patients with renal insufficiency (T: 2576 +/- 195 ngeq/mL, p less than 0.001). Diagnostic discrimination between AIP and ANP was achieved in 69% using T-SRA (sensitivity 31%, specificity 88%), and in 78% using P-SRA (sensitivity 54%, specificity 92%). Discrimination between CP and pancreatic carcinoma was possible in 68% (sensitivity 67%, specificity 71%). The diagnostic value of serum RNase is limited because of its low sensitivity, but increased T-SRA above a cutoff of 250 ngeq/mL and increased P-SRA above a cutoff of 620 ngeq/mL are specific for detecting pancreatic necrosis in the absence of renal impairment. The kidney is a major site for SRA clearance.
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PMID:Serum ribonuclease activity in the diagnosis of pancreatic disease. 203 16

Repeated large-volume paracentesis (4-6 L/day) is an effective and safe therapy of ascites in patients with cirrhosis provided albumin is infused intravenously. To investigate whether ascites can be safely mobilized in only one paracentesis session ("total paracentesis"), 38 cirrhotic patients with tense ascites were treated with total paracentesis plus intravenous albumin (6-8 g/L ascites removed). Standard liver tests and renal function tests, glomerular filtration rate, free water clearance, plasma volume, plasma renin activity, and plasma aldosterone and norepinephrine concentrations were measured before and after treatment. Total paracentesis was effective in mobilizing ascites in all but 1 patient and did not impair any of the parameters studied. The volume of ascitic fluid removed and the duration of the procedure were 10.7 +/- 0.5 L (mean +/- SEM) and 60 +/- 3 min, respectively. Five of the 38 patients (13%) developed complications during the first hospital stay (hepatic encephalopathy and gastrointestinal hemorrhage in 2 patients each and culture-negative bacterial peritonitis in 1). No patient developed renal impairment. This complication rate, as well as the clinical course of the disease during follow-up, estimated by the probability of readmission to hospital, causes of readmission, and survival probability after treatment, was similar to that reported in patients treated with repeated large-volume paracentesis. These results indicate that total paracentesis associated with intravenous albumin can be safely performed in cirrhotic patients with tense ascites and suggest that these patients could be treated in a single-day hospitalization regime.
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PMID:Total paracentesis associated with intravenous albumin management of patients with cirrhosis and ascites. 229 73

Circulating vitamin D3 metabolites were measured in 31 adult patients with chronic renal failure and 31 adults between 3 and 30 months after renal transplantation. No subject excreted over 1 g urinary protein daily nor received vitamin D or its metabolites. There was a positive correlation between 1,25(OH)2D3 and GFR between 15 and 90 ml/min in both chronic renal failure (r = 0.60, P less than 0.001) and transplant subjects (r = 0.49, P less than 0.01) and between 1,25(OH)2D3 and 25(OH)D3 after transplant (r = 0.69, P less than 0.001), but not in chronic renal failure (r = 0.22, P = ns). There was a weak inverse correlation between 1,25(OH)2D3 and serum phosphate in chronic renal failure (r = 0.36, P less than 0.05) but not post transplant (r = 0.03, P = ns). Compared with 1,25(OH)2D3 concentrations in 16 normal subjects (mean +/- SEM: 39.5 +/- 1.9 pg/ml), chronic renal failure subjects with mild renal impairment (GFR 45-90 ml/min, mean: 61.5 +/- 3.3 ml/min, n = 17) had reduced 1,25(OH)2D3 (28.9 +/- 2.7 pg/ml, P less than 0.01). In transplant subjects with mild impairment (GFR 45-90 ml/min, mean: 61.4 +/- 3.7), 1,25(OH)2D3 was positively (r = 0.79, P less than 0.001) and iPTH inversely correlated (r = 0.51, P less than 0.05) with 25(OH)D3. In each of nine such subjects studied, seasonal variations in 1,25(OH)2D3 (P less than 0.001) and PTH (P less than 0.05, 1-tailed test), as well as in 25(OH)D3 and 24,25(OH)2D3, were observed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Vitamin D3 metabolites in chronic renal failure and after renal transplantation. 313 43

Interstitial fibrosis is a marker of progression of renal impairment in diabetic nephropathy. Transforming growth factor (TGF)-beta 1 is one of a group of pro-fibrotic cytokines and growth factors that have been associated with the development of interstitial fibrosis. We have examined the modulating influence of glucose on the production of TGF-beta 1 by cultured human proximal tubular cells. Incubation of growth-arrested human proximal tubular cells (HPTC) (72 hours in serum free medium) in 25 mmol/L D-glucose resulted in increased expression of TGF-beta 1 mRNA (as assessed by reverse transcription polymerase chain reaction). This was apparent after 6 hours and increased up to 120 hours exposure. TGF-beta 1 secretion, however, as measured by specific enzyme-linked immunoassay, was unaffected by exposure to 25 mmol/L D-glucose. Sequential stimulation of HPTC, first with 25 mmol/L D-glucose for 48 hours and then with platelet-derived growth factor (PDGF) isoforms, resulted in a dose-dependent secretion of TGF-beta 1. Pre-exposure to 5 mmol/L D-glucose or 25 mmol/L L-glucose did not prime for TGF-beta 1 release. At 50 ng/ml PDGF this effect was greatest for the AA isoform (AA 31.4 +/- 7.1, AB 20.98 +/- 8.9, BB 7.8 +/- 2.2, P < 0.05 for all versus control, n = 3, mean +/- SEM ng/10(6) cells/24 hours). These effects were blocked by the addition of antibody to the PDGF alpha-receptor. TGF-beta 1 secretion was inhibited in a dose-dependent manner by pretreatment with cyclohexamide, but was not affected by pretreatment with actinomycin D. Stimulation of HPTC with a single dose of PDGF induced TGF-beta 1 mRNA; however, only after application of a second dose of PDGF (after TGF-beta 1 mRNA induction) did TGF-beta 1 protein secretion occur. We also demonstrated that PDGF stimulation of HPTC induced an inherently more stable TGF-beta 1 mRNA transcript. These findings demonstrate that elevated D-glucose concentration alone is insufficient to lead to increased TGF-beta 1 secretion by HPTC despite increased mRNA expression. However, application of a second stimulus such as PDGF, when TGF-beta 1 mRNA expression is increased, leads to increased protein synthesis and secretion of TGF-beta 1. This implies that elevated glucose concentrations might prime proximal tubular cells for TGF-beta 1 synthesis and thus contribute to the development of interstitial fibrosis.
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PMID:Elevated D-glucose concentrations modulate TGF-beta 1 synthesis by human cultured renal proximal tubular cells. The permissive role of platelet-derived growth factor. 763 30

High calcitonin levels have been reported in chronic renal failure. To study the C cell response in patients with chronic renal failure, an intravenous bolus of pentagastrin was administered to 11 patients and 11 healthy subjects. Samples were obtained at 0, 1, 2, 3, 5 and 10 min for calcitonin assay. In order to detect only the active monomeric calcitonin, an immunoradiometric assay method was used. The influence of calcium, phosphate, alkaline phosphatase and intact parathyroid hormone was also evaluated. Although basal calcitonin levels were higher (p < 0.01) in chronic renal failure (mean +/- SEM: 10.1 +/- 2.9 pmol/l) versus healthy subjects (1.1 +/- 0.3 pmol/l), the area under the curve showed there to be no differences between the two groups. The rising branch of the area under the curve, employed as an expression of the C cell response capacity, showed no differences either (chronic renal failure vs healthy subjects: 5.6 +/- 2 vs 2.6 +/- 0.7 pmol l-1 min-1, p = 0.28). In the chronic renal failure group, a positive correlation was found (r = 0.625, p < 0.05) between the rising branch of the area under the curve and parathyroid hormone. We conclude that monomeric calcitonin is increased in chronic renal failure, but C cells of the thyroid respond to pentagastrin, as they do in normal subjects. This finding is of great clinical importance when a patient with renal impairment is evaluated for medullary thyroid carcinoma. The calcitonin response to pentagastrin seems to be related directly to the degree of secondary hyperparathyroidism in chronic renal failure.
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PMID:Normal calcitonin response to pentagastrin stimulation in patients with chronic renal failure. 835 57

We evaluated the long-term residual renal function in 64 living related kidney donors. Our main objective was to identify baseline factors, including gender and age, that could predict renal impairment after nephrectomy. Forty-four (69%) of the 64 donors were women. The mean +/- SEM age of those studied was 36 +/- 1.3 years and their mean +/- SEM duration of follow-up was 62 +/- 4.9 months (range, 6 to 174). Overall mean serum creatinine concentration after kidney donation was increased compared to baseline values (1.13 mg/dl vs 0.92 mg/dl, respectively, p < 0.001). At the last follow-up visit, post-nephrectomy mean glomerular filtration rate (GFR) values, adjusted for body surface area, age at donation, baseline serum creatinine and duration of follow-up, measured by 99mTc-DTPA were significantly lower in women than in men (72.11 ml/min vs 87.17 ml/min, respectively, p = 0.02). At follow-up, mean effective renal plasma flow, adjusted for the same variables, measured by 131I-hippuran was also significantly lower in women compared to men (318.07 ml/min vs 400.82 ml/min, respectively, p < 0.01). Eleven of twelve patients with post-nephrectomy GFR values less than 60 ml/min were women. Following nephrectomy, serum creatinine concentration increased significantly as a function of greater age at donation in women but not in men. Similarly, in women but not in men, follow-up GFR measurements decreased significantly as a function of age after adjusting for baseline serum creatinine and duration of follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of age and gender on kidney function in renal transplant donors: a prospective study. 835 73

To define the onset of the rise in intact parathyroid hormone (PTH) levels in renal insufficiency, we conducted a cross-sectional study of parameters of mineral metabolism in patients with varying degrees of renal impairment. Using an immunoradiometric assay to measure intact PTH levels, we found elevations in intact PTH levels as creatinine clearance approaches 60 ml/minute (serum creatinine near 1.8) and a significant inverse relationship between indices of renal function and intact PTH levels (r = -0.60, P < 0.001 for intact PTH and creatinine clearance.) Calcium and phosphate levels correlate less strongly with the degree of hyperparathyroidism (r = -0.39, P < 0.001 for total calcium; r = 0.31, P < 0.05 for phosphate). As a group, only patients with severe renal failure (creatinine clearance < 20 ml/minute) had 1,25-dihydroxyvitamin D levels below normal (11 +/- 4 [SEM] pg/dl, normal range 15-60). Intact and n-terminal PTH measurements correlate well in this patient population with varying degrees of renal insufficiency (r = 0.9, P < 0.001). Intact PTH can be elevated in patients with mild to moderate renal insufficiency, thus efforts to prevent the development of secondary hyperparathyroidism in renal failure should be undertaken early in the course of renal insufficiency.
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PMID:Intact parathyroid hormone levels in renal insufficiency. 856 94


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