Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0221002 (primary hyperparathyroidism)
 4,921 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nine patients with primary hyperparathyroidism were studied to investigate the renal tubular reabsorption of calcium and sodium. Fasting serum and urine samples were analysed, and the glomerular filtration rate and the renal plasma clearance of lithium were determined simultaneously. Comparison was made with 9 age- and sex-matched normocalcemic controls. In the proximal tubule, there was a significantly higher absolute reabsorption of calcium in patients than in controls, whereas the fractional reabsorption rate of calcium did not differ between the two groups. In the distal tubule, the absolute calcium reabsorption rate was significantly higher in the patients, whereas the fractional reabsorption rate of calcium was significantly lower than in controls. In the patient group there was a significantly positive linear correlation between the increased tubular capacity for calcium reabsorption and the absolute proximal calcium reabsorption rate, but not between the increased capacity and the absolute distal calcium reabsorption rate. No significant differences were found in the renal tubular handling of sodium between patients and controls. Our results suggest that the increased capacity for tubular calcium reabsorption in primary hyperparathyroidism mainly is localized in the proximal tubule, and that the renal tubular handling of calcium and sodium in this disease differs from that in familial hypocalciuric hypercalcemia.
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PMID:Renal tubular reabsorption of calcium and sodium in primary hyperparathyroidism. 222 Feb 60

To address whether a renal tubular dysfunction is encountered in a particular patient subgroup with urolithiasis, the following parameters of tubular function were measured in urine taken in the morning from 214 stone formers after fasting: pH, excretion of lysozyme and gamma-glutamyl transferase (gamma-GT); fractional excretion (FE) of glucose, insulin, Mg, K, and HCO3 after an alkali loading; and the renal threshold for phosphate (TmP/GFR). The following diagnoses were made in the patient group: primary hyperparathyroidism (N = 8), medullary sponge kidneys (N = 21), hyperuricemia (N = 10), cystinuria (N = 2), struvite stone disease (N = 6), idiopathic hypercalciuria of the absorptive (N = 25), dietary (N = 69) or renal (N = 7) type, and normocalciuric idiopathic urolithiasis (N = 66). In 31% of the patients TmP/GFR was below 0.80 mmole/liter and in 13% of the patients, FE HCO3 after alkali loading was above normal. Urinary excretion of lysozyme and that of gamma-GT both were elevated in 17% of the patients. FE glucose, FE insulin, FE Mg, and FE K were elevated in 8, 9, 3, and 7% of the patients, respectively. This study demonstrates that a significant number of stone formers present with signs of renal tubular dysfunction, primarily involving the proximal tubule since apparent leaks of phosphate and of bicarbonate were most frequently encountered. The defects were not specific for a given etiologic group of patients; on the other hand, occurrence was related to the presence of large stones in the pyelocaliceal system at the time data were gathered. Taken together these data suggest that the tubulopathy in nephrolithiasis is the consequence rather than the cause of the stone.
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PMID:Tubulopathy in nephrolithiasis: consequence rather than cause. 287 Dec 16

Human beta-2 microglobulin (beta-2 M) is released into body fluids as a result of cell turnover, excreted by the kidney, and catabolized in the proximal tubule. Urinary excretion rates constitute a sensitive index of renal tubular function. The beta-2 M urine-to-serum ratio was measured in 25 patients with primary hyperparathyroidism (15 preoperative and 10 treated conservatively) in addition to 20 age- and sex-matched control subjects. The ratio was found to be significantly higher in both the operative and the conservatively managed groups compared to controls (p less than 0.05, Mann-Whitney U test). After surgical excision of a single parathyroid adenoma in the 15 operative cases, the beta-2 M urine-to-serum ratio fell to normal limits. These preliminary findings indicate that the urine-to-serum beta-2 M ratio may be of value in detecting change in renal function in asymptomatic patients with hyperparathyroidism. Further studies are indicated to establish whether these subtle changes are associated with long-term morbidity.
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PMID:The beta-2 microglobulin urine-to-serum ratio: an early marker of renal dysfunction in primary hyperparathyroidism. 331 60

The acute inhibitory effects of parathyroid hormone (PTH) on proximal tubule Na(+)-K(+)-ATPase (Na-K) and sodium-dependent phosphate (NaPi) transport have been extensively studied, while little is known about the chronic effects of PTH. Patients with primary hyperparathyroidism, a condition characterized by chronic elevations in PTH, exhibit persistent hypophosphatemia but not significant evidence of salt wasting. We postulate that chronic PTH stimulation results in differential desensitization of PTH responses. To address this hypothesis, we compared the effects of chronic PTH stimulation on Na-P(i) cotransporter (Npt2a) expression and Na-K activity and expression in Sprague Dawley rats, transgenic mice featuring parathyroid-specific cyclin D1 overexpression (PTH-D1), and proximal tubule cell culture models. We demonstrated a progressive decrease in brush-border membrane (BBM) expression of Npt2a from rats treated with PTH for 6 h or 4 days, while Na-K expression and activity in the basolateral membranes (BLM) exhibited an initial decrease followed by recovery to control levels by 4 days. Npt2a protein expression in PTH-D1 mice was decreased relative to control animals, whereas levels of Na-K, NHERF-1, and PTH receptor remained unchanged. In PTH-D1 mice, NpT2a mRNA expression was reduced by 50% relative to control mice. In opossum kidney proximal tubule cells, PTH decreased Npt2a mRNA levels. Both actinomycin D and cycloheximide treatment prevented the PTH-mediated decrease in Npt2a mRNA, suggesting that the PTH response requires transcription and translation. These findings suggest that responses to chronic PTH exposure are selectively regulated at a posttranscriptional level. The persistence of the phosphaturic response to PTH occurs through posttranscriptional mechanisms.
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PMID:Parathyroid hormone (PTH) decreases sodium-phosphate cotransporter type IIa (NpT2a) mRNA stability. 2334 72

This article describes an updated computer model which attempts to simulate known renal reabsorption and secretion activity through the nephron (NEPHROSIM) and its possible relevance to the initiation of calcium-containing renal stones. The model shows that, under certain conditions of plasma composition, de novo nucleation of both calcium oxalate (CaOx) and calcium phosphate (CaP) can take place at the end of the descending limb of the Loop of Henle (DLH), particularly in untreated, recurrent idiopathic CaOx stone-formers (RSF). The model incorporates a number of hydrodynamic factors that may influence the subsequent growth of crystals nucleated at the end of the DLH as they progress down the renal tubules. These include the fact that (a) crystals of either CaOx or CaP nucleated at the end of the DLH and travelling close to the walls of the tubule travel at slower velocities than the fluid flowing at the central axis of the tubule, (b) the transit of CaOx crystals travelling close to the tubule walls may be delayed for up to at least 25 min, during which time the crystals may continue to grow if the relative supersaturation with respect to CaOx (RSS CaOx) is high enough and (c) such CaOx crystals may stop moving or even fall back in upward-draining collecting ducts (CD) owing to the Stokes gravitational effect. The model predicts, firstly, that for small, transient increases in plasma oxalate concentration, crystallisation only takes place in the CD and leads to the formation of small crystals which are comfortably passed in the urine and, secondly, that for slightly greater increases in the filtered load of oxalate, spontaneous and/or heterogeneous nucleation of CaOx may occur both at the end of the DLH and in the CD. This latter situation leads to the passage in the final urine of a mixture of large crystals of CaOx (arising from nucleation at the end of the DLH) and small crystals of CaOx (as a result of nucleation originating in the CD). As a result of the higher calcium and oxalate concentrations in the urine of RSF, these patients have an increased probability of initiating CaOx crystallisation in the DLH and so of going on to form the large crystals and aggregates found in their fresh urines, but not in the fresh urines from normal subjects (N). These predictions are supported by evidence from clinical studies on six RSF and six normal controls (NC) who were maintained for 4 days on a fixed basal diet. Their patterns of CaOx crystalluria were measured on the second day of the basal diet and after a small dose of sodium oxalate was given before breakfast on the fourth day of the study. The model also shows that the tubular fluid of RSF is more likely than that of N to reach the conditions necessary for de novo nucleation of CaP at the end of the DLH. This may occur following either a small increase in ultrafiltrable phosphate, as a result of ingestion of a high phosphate-containing meal, or a small decrease in the proximal tubular reabsorption of phosphate resulting, for example, from increased parathyroid activity. CaP crystals initiated at this point may heterogeneously nucleate the crystallisation of CaOx under the high metastable conditions of RSS CaOx which frequently exist in the urines of RSF. Under certain conditions, it is predicted that CaP crystals, initiated at the end of the DLH and travelling close to the tubular walls where their transit time is increased, might also be able to grow and agglomerate sufficiently to become trapped at some point in the CD and lead to the formation of Randall's Plugs in the Ducts of Bellini. Currently, work is under way to incorporate data on the growth and aggregation of crystals of CaP into NEPHROSIM to confirm the likelihood of this phenomenon occurring. The model shows that an increase in plasma calcium is unlikely to lead to spontaneous nucleation of either CaOx or CaP at the end of the DLH unless the concentration of plasma calcium reaches values usually associated with the cases of primary hyperparathyroidism. The most likely cause of spontaneous CaOx crystal formation at the end of the DLH is a small increase in plasma oxalate; the most likely cause of spontaneous CaP crystal formation at the end of the DLH is either an increase in plasma phosphate or a decrease in the fractional reabsorption of phosphate in the proximal tubule. The model predicts that the maximum volume of CaOx crystalluria that is likely to occur in a given urine is a function of both the RSS CaOx and the oxalate/calcium ratio in the final urine. These data explain why the volume of CaOx crystalluria is in the order UK normals < UK recurrent stone-formers < Saudi Arabian recurrent stone-formers which, in turn, probably accounts for the very high incidence of CaOx-containing stones found in Saudi Arabia compared with that in the UK.
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PMID:Potential role of fluctuations in the composition of renal tubular fluid through the nephron in the initiation of Randall's plugs and calcium oxalate crystalluria in a computer model of renal function. 2540 99