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Query: UMLS:C0035078 (renal failure)
 31,970 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Longitudinal growth; bone and growth zone histology; growth cartilage and bone mineralization (tetracycline technique); bone Ca content (neutron activation analysis); bone radiology; serum and urine chemistry; urinary cAMP and serum 25-OH-vitamin D3 were studied in a long-term model of experimental uremia in the rat. Uremia was induced by two-stage subtotal nephrectomy with irradiation of the remaining parenchyma. Ccr in the experimental group was 113 +/- 5.8 micron1/min X 100 g (19.8% of controls) and serum creatinine 1.67 +/- 0.04 mg% (5.1 X control value). Uremic animals were pair-fed with sham-operated controls. In the proximal tibia delayed transformation of cartilage into primary spongiosa with appearance of chondro-osteoid and delayed transformation of primary spongiosa into secondary spongiosa was observed (rickets). Increased amounts of osteoid were present although 25-OH-vitamin D3-levels were high. There were only modest signs of secondary hyperparathyroidism (osteoclast counts; urinary cAMP). In spite of the presence of bone disease, longitudinal growth was not reduced in uremic animals as compared with pair-fed sham-operated animals, but was significantly reduced as compared with ad lib fed control animals. In contrast, weight gain was significantly diminished in uremic animals as compared with pair-fed sham-operated control animals. It is concluded that diminished intake of food is the major determinant of growth retardation in preterminal experimental renal failure.
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PMID:Skeletal changes and growth in experimental uremia. 19 69

The diuresis of cAMP in primary hyperparathyroidism was significantly higher at 7.3 +/- 2.5 mumol/g creatinine X 24 h (P less than 0.005) than that in healthy subjects (3.5 +/- 0.7 mumol/g creatinine X 24 h). After successful operation on the parathyroid gland, cAMP diuresis usually decreased within 24 hours to normal or subnormal values. In primary or secondary hypoparathyroidism subnormal amounts of cAMP (P less than 0.005) were excreted. The method gives false-negative results in functional disorders of the parathyroid glands accompanied or caused by renal failure.
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PMID:[The diuresis of cyclic adenosine-3'5'-monophosphate (cAMP) in primary and secondary disorders of the parathyroid glands]. 20 Apr 7

Acute elevations in intracellular adenosine 3',5'-cyclic monophosphate (cAMP) concentrations are known to increase ionic chloride permeability in diverse tissues. To determine if chronic endogenous increases in cAMP are associated with sustained alterations in membrane ionic permeabilities, renal cortical brush border membrane vesicles (BBMV) were prepared and red blood cells were harvested in a model of chronic renal failure, the 75% nephrectomized rat. Relative ionic permeabilities were determined using the potential-sensitive fluorescent probe 3,3'-dipropylthiadicarbocyanine iodide [diS-C3-(5)]. These studies demonstrate that renal cortical homogenate and RBC cAMP concentrations are increased in chronic renal failure animals. In the same animals relative ionic chloride permeability (PCl/PK) was significantly increased in renal cortical BBMV and RBC ghosts: PNa/PK was not affected. This selective change in permeability results in a significant increase in PCl/PNa and hyperpolarization of BBMV of sufficient magnitude to stimulate Na(+)-dependent glutamine transport. The change in glutamine uptake was not consequent to an alteration in the kinetics of glutamine transport or delayed dissipation of the inward Na+ gradient. Renal hypertrophy per se did not effect renal homogenate cAMP concentration or relative ionic permeability of renal cortical BBMV prepared from kidneys of uninephrectomized animals fed a 40% protein diet. These studies demonstrate that relative ionic chloride permeability and tissue [cAMP] are chronically increased in diverse cells (renal proximal tubule and RBCs) in a rat model of renal failure. These findings suggest that membrane ionic permeability may be altered and electrogenic transport secondarily perturbed in renal failure in association with hormonally-induced chronic elevations of intracellular cAMP concentrations.
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PMID:Altered membrane ionic permeability in a rat model of chronic renal failure. 132 50

Cystic kidneys of the C57BL/6J-cpk murine model of polycystic kidney disease show a marked overexpression of the proto-oncogenes c-fos, c-myc, and c-Ki-ras, consistent with an increased rate of cell proliferation and an altered state of differentiation. To determine if cystic cells have increased responsiveness to stimulation with mitogenic agents, quiescent primary cultures from normal and cystic cpk kidneys were treated with fetal bovine serum (FBS), 8-bromo-cAMP (cAMP), or epidermal growth factor (EGF). The level of c-fos induction following stimulation by FBS was found to be dramatically higher in cystic cells than in normal cells; whereas induction by cAMP or EGF was essentially the same in both cell types and much less than that seen in FBS-stimulated cells. To determine if this serum hypersensitivity reflects an increased proliferative state in vivo, c-fos induction was examined in cultures derived from normal kidneys stimulated to regenerate by folic acid-induced acute renal injury. As with cystic kidneys, the folic acid-injured kidneys showed increased c-fos responsiveness to FBS in cell culture. These experiments suggest that cystic and regenerating kidneys have an altered phenotypic state in vivo that is manifested in cell culture by serum hypersensitivity. However, whereas the folic acid-injured kidneys ultimately reestablish normal kidney function, cystic kidneys further progress to renal failure, suggesting that cystic epithelial cells are locked in this altered state of differentiation.
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PMID:C-fos expression is hypersensitive to serum-stimulation in cultured cystic kidney cells from the C57BL/6J-cpk mouse. 150 16

This article describes investigations of several aspects of the molecular biology of the human renin gene and the three-dimensional structure of renin and its precursor, prorenin. Because of the importance of the RAS in hypertension, heart failure, renal failure, and possibly other disorders such as atherosclerosis, it is critical to understand the detailed control of this system. This control involves regulation at the transcriptional level, folding of prorenin, sorting of prorenin to a regulated pathway where it is proteolytically cleaved to renin and released in response to secretogogues, constitutive release of uncleaved prorenin, and nonproteolytic activation of prorenin. Currently there is great interest not only in the control of renin in the kidney, the sole source of circulating renin, but also at extrarenal sites where RAS activity may regulate cardiovascular functions. The renin gene was found to be expressed significantly in the renal juxtaglomerular cells and several other cell types. Most tissue culture cells did not express the gene; exceptions were cultured SK-LMS-1 cells and cAMP-stimulated human lung fibroblasts. Cultured human uterine-placental cells expressed the human renin gene at levels higher than in other cell types assessed. Renin mRNA had the same start site in the placental cells as the kidney and was regulated by calcium ionophores and cAMP. Thus, these cells provide primary nontransformed human cells to study the homologous human promoter. Transfected renin promoters showed cell type-specific expression and cAMP responsiveness in these cells in constructs containing as few as 102 bp of 5'-flanking DNA. DNA upstream from this appears to contain an inhibitory element(s) that may have some tissue specificity in its distribution. The cAMP response is not due to cAMP induction of a transcription factor that secondarily affects the renin promoter. A novel element may be involved, since the promoter does not contain a CRE element that mediates many cAMP responses, and the cells do not appear to respond to another known cAMP-responsive transcription factor, AP-2. Studies with transfected vectors expressing a mutant cAMP-responsive protein kinase A regulatory subunit suggest that cAMP is not responsible for basal renin promoter activity in the placental cells. By contrast, cAMP induces in essence gene activation in WI26VA4 transformed human lung fibroblasts in which renin mRNA levels increase by up to 150-fold in response to forskolin. Thus, cAMP may activate renin gene expression under certain circumstances and tissue-specific renin gene expression may be directed by more than one mechanism.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Molecular biology of human renin and its gene. 174 21

Despite elevated parathyroid hormone (PTH) levels, low normal or diminished serum 1,25(OH)2D3 concentrations are found in patients with incipient renal failure. To further assess (indirectly) the reserve capacity of renal production of 1,25(OH)2D3 we studied 9 patients with incipient or moderate renal failure (inulin clearance 31-68ml/min/1.73 m2) and 9 controls, using a novel stimulation test. We measured 1,25 (OH)2D3 levels, free 1,25(OH)2D3 index, cAMP excretion, calciuria and phosphaturia before and after infusion of 2 x 400 U of human (h) PTH (1-38). Baseline 1,25(OH)2D3 levels were not significantly different in patients (42.5 pg/ml, 21.6-51.1) compared with controls (45.0 pg/ml, 37.4-67.3). After infusion of hPTH(1-38), however, median increase in 1,25(OH)2D3 was only +25% versus +86% in controls, despite a greater proportional increase in cAMP/GF ratio. The data suggest subnormal stimulation of renal 1,25(OH)2D3 production in response to exogenous PTH in most patients with incipient renal failure. This may reflect partial exhaustion of biosynthetic reserve capacity.
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PMID:Attenuated rise of 1,25 (OH)2 vitamin D3 in response to parathyroid hormone in patients with incipient renal failure. 201 72

Derangements in leukocyte function occur in patients with primary hyperparathyroidism and in those with uremia, which is a state of secondary hyperparathyroidism, suggesting that parathyroid hormone (PTH) may affect leukocyte function. We examined the interaction between PTH and random migration of human polymorphonuclear leukocytes (PMNL) utilizing a modified Boyden chamber. Intact 1-84 PTH but not its amino-terminal (1-34 PTH) or its carboxy-terminal (53-84 PTH) fragments produced marked and significant (p less than 0.01) stimulation of random migration in a dose-dependent manner. Inactivation of 1-84 PTH abolished its effect and other peptide hormones (calcitonin, glucagon, insulin and vasopressin) did not stimulate migration of PMNL. The effect of PTH on migration was not due to action of the hormone on chemotaxis. PTH did not enhance cAMP or cGMP production by PMNL. The stimulation of PMNL motility by PTH was independent of calcium concentration in media, was not mimicked by calcium ionophore and was not blocked by verapamil. Quinidine also produced significant (p less than 0.01) increase in random migration of PMNL and this effect was not additive to that of PTH. Prolonged exposure to PTH (16-20 h) was associated with significant inhibition of random migration of PMNL. The migration of PMNL from patients with advanced renal failure was significantly (p less than 0.01) reduced and there was a significant (p less than 0.01) inverse relationship between random migration of PMNL and serum levels of PTH. Also PTH produced only modest stimulation of random migration of PMNL in most patients with renal failure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of parathyroid hormone on random migration of human polymorphonuclear leukocytes. 285 73

Insulin secretion may be impaired in chronic renal failure (CRF) and available data suggest that this abnormality may be related to the state of secondary hyperparathyroidism of renal failure. We directly measured insulin release from isolated islets of Langerhans obtained from normal rats, CRF-control and CRF-PTX (parathyroidectomized) rats, and parathyroid hormone (PTH)-treated animals. Both early and total glucose-induced insulin release from islets of CRF-control were markedly and significantly (P less than 0.01) lower than from islets of normal rats. Insulin release from islets of CRF-PTX rats was significantly (P less than 0.01) higher than that from islets of CRF-control rats, and not different from insulin release from islets of normal rats. Forskolin and IBMX, which cause a rise in cAMP, significantly stimulated glucose-induced insulin release from islets of normal, CRF-control and CRF-PTX rats, but the increments from baseline were not significantly different between the three groups. Both early and total insulin release from islets obtained from PTH-treated rats with normal renal function were markedly and significantly (P less than 0.01) lower than values obtained from normal rats. Calcium contents of the pancreas of CRF-control and PTH-treated rats were significantly (P less than 0.01) higher than that in pancreas of normal rats and CRF-PTX animals, and values in the latter two groups of animals were not significantly different. The results show that: 1) CRF impairs insulin release from pancreatic islets; 2) this abnormality is reversed by prior parathyroidectomy; and 3) hyperparathyroidism induced by PTH-treatment in normal rats impairs insulin release from pancreatic islets.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Insulin release from pancreatic islets: effects of CRF and excess PTH. 304 75

Two male infants aged 6 months presented with Escherichia coli septicaemia and urinary tract infection. Despite seemingly appropriate antibiotic therapy, a swinging fever, painful enlargement of both kidneys, sterile leukocyturia and renal failure persisted. Excretory urography, ultrasound scan, computerized tomography and magnetic resonance imaging showed diffuse infiltrative disease. 99mTc dimercaptosuccinic acid uptake was minimal, but a 67Ga-citrate scan showed striking diffuse uptake by both kidneys suggestive of inflammatory cell infiltration. Bilateral renal parenchymal malakoplakia was diagnosed on tissue examination. Bilateral parenchymal involvement of the kidneys by this chronic granulomatous disease has not previously been reported in infancy and is fatal if untreated. The lesion is believed infection-induced, due to defective bacterial activity of the macrophages, possibly related to an abnormally low cGMP/cAMP ratio. Treatment with intracellularly active trimethoprim-sulphamethoxazole, rifampicin and ascorbic acid resulted in complete recovery of the one infant so treated over a period of months.
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PMID:Bilateral renal malakoplakia in infancy. 307 48

We have studied a hypercalcemic patient with sarcoidosis and advanced renal failure. Bone biopsy and urinary cAMP excretion indicated suppression of parathyroid function. 1,25(OH)2D levels were moderately elevated and dropped to low normal levels during prednisolone treatment. Discontinuation of prednisolone treatment caused deterioration of renal function and hypercalcemia, 1,25(OH)2D serum levels being within the normal range. Our data demonstrate the rapid speed at which prednisolone causes a drop in serum 1,25(OH)2D level. Since hypercalcemia was observed both during periods of hypercalciuria and normal serum 1,25(OH)2D levels, increased sensitivity to active vitamin D seems likely. There was no significant correlation between 25(OH)D, 24,25(OH)2D or 25,26(OH)2D. Furthermore there was no correlation between any of these three metabolites and either 1,25(OH)2D or serum calcium.
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PMID:Rapid effect of prednisolone on serum 1,25-dihydroxycholecalciferol levels in hypercalcemic sarcoidosis. 384 60


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