Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0035078 (renal failure)
 31,970 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Retention of inorganic phosphate (Pi) and associated hyperphosphatemia are important development of hyperparathyroidism secondary to renal failure. The beneficial effect of a low-Pi diet in the prevention of hyperparathyroidism can be attributed to the decrease in PTH secretion. This effect of Pi may be mediated by specific molecules in the parathyroid cell membrane. A complementary DNA encoding a Na(+)-Pi co-transporter, termed rat PiT-1, has been isolated from rat parathyroid. The amount of PiT-1 mRNA in the parathyroid is controlled by vitamin D and dietary Pi, which are the most important regulators of PTH secretion. The parathyroid Pi transporter may mediate the effects of extracellular Pi and PTH secretion in secondary hyperparathyroidism. In this study, we focus on the function of Na/Pi co-transporters in the parathyroid glands as inorganic Pi sensor.
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PMID:Secondary hyperparathyroidism and phosphate sensing in parathyroid glands. 1101 90

Control of serum phosphorus (P) levels is a central goal of managing patients with chronic renal failure (CRF). Hyperphosphatemia develops invariably with kidney failure, and inadequate control of serum P leads to an elevated calcium-phosphorus (Ca x P) product. Further contributing to an elevated Ca x P product is the fact that hemodialysis patients are generally in a net positive calcium balance-dietary intake of calcium, ingestion of calcium-based phosphate binders, calcium absorption from dialysate, and abnormalities in bone buffering and turnover all contribute to the calcium burden in hemodialysis patients. In addition, treatment with calcitriol to manage secondary hyperparathyroidism increases intestinal absorption of both calcium and P. These abnormalities in divalent ion metabolism can result in a number of harmful conditions in CRF patients, including vascular calcification, cardiovascular disease, calciphylaxis, and death. We are now beginning to realize that our current therapeutic approaches to CRF management may not only be ineffective in controlling P and Ca x P product, but may actually contribute to serious calcific and cardiovascular hazards in these patients. Elevated P and Ca x P product are both significant predictors of cardiovascular mortality in hemodialysis patients. These effects are observed at P and Ca x P product levels that were considered safe until recently. Based on current national studies, we now recommend that serum P levels and Ca x P product of patients with CRF be maintained between 3.0-5.0 mg/dl and less than 55 mg2/dl2, respectively. Achieving these more rigorous treatment goals will require a shift in our therapeutic management strategies to incorporate aggressive use of calcium-free phosphate binders and, when necessary, use of less calcemic vitamin D analogs.
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PMID:Prevalence and clinical consequences of elevated Ca x P product in hemodialysis patients. 1107 8

Tumor lysis syndrome (TLS) is a rare serious acute complication of cancer therapy, reported mainly following chemotherapy in patients with large tumor load and chemosensitive disease. These are mainly patients with non-Hodgkin's lymphoma, leukemia and rarely in solid tumors. It is less frequently described after radiotherapy for lymphoid and hematological malignancies. TLS following radiotherapy for solid tumors is a very rare complication. In this report/review we describe a seventy-three-year-old male patient with progressive metastatic carcinoma of the breast to the lungs, liver and bone. He was referred for radiotherapy because of generalized bony pains. The patient was planned for sequential hemi-body irradiation starting with the more symptomatic upper half body. After premedication, he was given 8.5 Gy to the mid point at the maximum chest separation with anterior lung attenuator limiting uncorrected lung dose to 6.15 Gy. A further 3.5 Gy electron boost to the fungating breast tumor was given to the 100%. Forty-eight hours after irradiation he developed hyperkalemia, hyperphosphatemia, hyperuricemia, hypocalcemia and renal failure. These clinical and biochemical changes are typical of tumor lysis syndrome (TLS). Despite hydration, and treating the hyperuricemia, the patient developed coma and died eight days after irradiation. The prophylaxis and management of TLS and in high-risk patients are described to avoid this frequently fatal complication.
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PMID:Tumor lysis syndrome following hemi-body irradiation for metastatic breast cancer. 1110 26

Secondary hyperparathyroidism (SH) and hyperplasia of the parathyroid glands (PTG) are universal complications in patients with CRF. In early renal failure, reduction in serum calcitriol and moderate decreases in ionized calcium contribute to greater synthesis and secretion of PTH. As renal disease progresses, a reduction in parathyroid expression of vitamin D receptor and calcium receptor renders the PTG more resistant to both calcitriol and calcium. High dietary phosphorus (P), independent of calcium and calcitriol, further enhances uremia-induced PTG hyperplasia and PTH synthesis and secretion, the latter by posttranscriptional mechanisms. Once SH develops, dietary P restriction can return the high serum PTH levels toward normal, however, parathyroid hyperplasia persists. Studies in our laboratory identified 2 of the mechanisms involved in the opposing effects of high and low dietary P content on PTG growth. Whereas high dietary P increases parathyroid expression of transforming growth factor alpha (TGFalpha), a growth promoter, P restriction induces the cyclin-dependent kinase inhibitor p21, an inducer of growth arrest. Both effects of P are specific for the PTG. No increase in either protein was observed in liver or intestine. TGFalpha induction of hyperplasia involves binding to the epidermal growth factor receptor and activation of mitogen activated protein (MAP) kinases cascades. p21 blocks progression through the cycle and cell division by inactivating cyclin/cyclin-dependent kinase complexes. Preventing hyperphosphatemia and elevated Ca x P product in renal failure not only ameliorates the progression of SH and bone disease but also the morbidity and mortality resulting from vascular calcification.
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PMID:Role of phosphorus in the pathogenesis of secondary hyperparathyroidism. 1115 62

Control of hyperphosphatemia in renal failure is often difficult to achieve. Although calcium-containing phosphate binders have become the preferred phosphate binders, many patients require the addition of an aluminum-containing phosphate binder (APB). Enhanced aluminum absorption has been noted when APBs are administered with citrate-containing products such as citrate/citric acid solution (CCA). Alternative phosphate binders such as calcium acetate may also increase aluminum absorption. This study investigated the effect of CCAs on aluminum absorption when aluminum antacids (APBs) were administered concurrently and 2 hours apart. The effects of the alternative alkalinizing agent sodium bicarbonate and the alternate phosphate binding agent calcium acetate on aluminum absorption were also studied. During five 2-day phases, ten normal volunteers randomly received three times daily with standardized meals aluminum hydroxide alone and concurrently with NaHCO3, calcium acetate, CCA, or with CCA 2 hours postprandially. Twenty-four hour urines were collected on the second day of each phase and aluminum excretion was determined using inductively coupled plasma emission spectroscopy. Urine aluminum excretion was statistically significantly (P <.005) elevated in subjects receiving Al(OH)3 and CCA both with meals, 269.3 +/- 146.3 microg/d, and 2 hours after meals, 303.3 +/- 142.9 microg/d, compared with 79.2 +/- 52.0 microg/d during treatment with Al(OH)3 alone. Administration of CCA 2 hours after APB does not permit the safe use of these agents concurrently. Concomitant administration of sodium bicarbonate and calcium acetate with APBs appears to be safe, as aluminum absorption was not affected.
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PMID:Impact of oral bases on aluminum absorption. 1130 54

Secondary hyperparathyroidism occurs early in the course of chronic renal failure. Early in the course, a deficit of calcitriol and an abnormality in the calcium sensor receptor may be the important factors; later, with advanced renal failure, hyperphosphatemia becomes an additional important pathogenic factor. Important clinical problems in dialysis patients are as follows: (1) hyperphosphatemia, which contributes to high morbidity and mortality of dialysis patients (a clinical approach to maintaining a normal serum phosphorus is essential and is discussed in this review); (2) a high calcium X phosphorus product leading to coronary artery calcifications (factors leading to calcifications are also discussed); and (3) calciphylaxis, which has been observed with increasing frequency in these patients (an increase in the total calcium load may be the most important pathogenic factor leading to this syndrome). Therapeutic considerations regarding the use of new vitamin D analogues devoid of a hypercalcemic and/or a hyperphosphatemic effect are also mentioned.
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PMID:Secondary hyperparathyroidism in chronic renal failure: pathogenic and clinical aspects. 1168 84

Secondary hyperparathyroidism complicating chronic kidney disease requires therapy to minimize the effects of parathyroid hormone (PTH) on bone and other tissues. Low levels of calcitriol in blood play a major role in the initiation and maintenance of hyperparathyroidism. Accordingly, administration of calcitriol has been demonstrated to be an effective form of therapy. While this therapy is effective in controlling hyperparathyroidism, side effects of calcitriol, including increased intestinal absorption of calcium and phosphate, often complicate therapy by giving rise to hypercalcemia and hyperphosphatemia, which may be important risk factors for extraskeletal calcifications. Over the last several years, interest has turned toward vitamin D analogs, which may be able to affect parathyroid function with lesser effects on calcium and phosphorus in serum, and thereby, minimizing the undesirable toxicities of vitamin D therapy. Two vitamin D analogs are available in this country for the control of hyperparathyroidism in the setting of advanced kidney disease, and include 19-nor-1,25-dihydroxyvitamin D(2) (paricalcitol), and more recently, 1-alpha-hydroxyvitamin D(2) (doxercalciferol). 19-nor-1,25-dihydroxyvitamin D(2) is widely used and was evaluated extensively in animals, revealing that this vitamin D sterol had a selective effect on increasing PTH suppression, with lesser effects on calcium and phosphorus metabolism. These studies lead to clinical trials which showed the efficacy of this therapy in that PTH could be lowered satisfactorily in patients with calcium and phosphorus values within the normal range. The selectivity of 19-nor-1,25-dihydroxyvitamin D(2) seen in animals has also been found in humans, such that therapy with this sterol can achieve control of hyperparathyroidism with a wider therapeutic window than the predecessor, calcitriol. 1-alpha-hydroxyvitamin D(2) has recently been introduced, but in contrast to paracalcitol, there is little reason to believe that there is any selectivity in its actions in terms of suppressing PTH, compared with its ability to raise serum calcium or phosphorus in serum. However, this vitamin D sterol can effectively decrease PTH levels in patients with advanced renal failure. Comparative studies of paricalcitol and doxercalciferol have not been undertaken at the present time. Further studies on the mechanism of actions might explain the differences between these sterols and their effects on the intestinal absorption of calcium and phosphate. At the present, the use of vitamin D analogs can achieve control of hyperparathyroidism with a wider therapeutic window than the native sterol, calcitriol.
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PMID:Vitamin D analogues for the management of secondary hyperparathyroidism. 1168 85

Paricalcitol was evaluated for the treatment of secondary hyperparathyroidism (SHPT) in a long-term, prospective, open-label study of 37 patients with end-stage renal failure resistant to intravenous calcitriol. All patients had an intact parathyroid hormone (iPTH) level of 600 pg/mL or greater before being converted from calcitriol to paricalcitol therapy. Paricalcitol therapy was initiated at a 1:4 calcitriol to paricalcitol dose conversion ratio for the initial 14 patients and a 1:3 dose ratio for the next 23 patients. Subsequent dosing was based on iPTH, calcium, and phosphorus determinations. All patients underwent hemodialysis three times weekly and received structured nutritional counseling. Mean iPTH level (baseline, 901 +/- 58 pg/mL) decreased rapidly during the initial 2 months and was 165 +/- 24 pg/mL at 16 months. Alkaline phosphatase levels decreased from 280 +/- 27 IU at baseline to 65 +/- 12 IU at 16 months. Mean calcium and phosphorus levels did not change significantly over the 16 months of paricalcitol therapy. The baseline mean calcium level of 9.4 +/- 0.2 mg/dL increased to 9.7 +/- 0.2 mg/dL (P = 0.86), and phosphorus level decreased from 6.1 +/- 0.2 to 5.8 +/- 0.2 mg/dL (P = 0.77). The greater paricalcitol doses afforded by the initial dose conversion ratio of 1:4 produced unacceptably rapid iPTH suppression and subsequent hypercalcemia. Mean doses of paricalcitol decreased six- to sevenfold throughout the course of therapy while maintaining acceptable iPTH suppression. Eight patients developed hypercalcemia, which successfully managed by dietary counseling, phosphate-binder adjustment, and paricalcitol dose reduction. Six patients developed hyperphosphatemia; 3 patients responded adequately to dietary manipulation and phosphate binders, but 3 patients had repeated episodes. Three patients did not respond adequately to paricalcitol therapy and required parathyroidectomy. In summary, paricalcitol was successful at controlling SHPT in patients resistant to calcitriol therapy with minimal impact on calcium and phosphorus homeostasis. The 1:3 initial dose conversion provided the smoothest iPTH control with only a single episode of hypercalcemia in patients treated with this initial dose. Doses of paricalcitol decreased over time.
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PMID:Paricalcitol in dialysis patients with calcitriol-resistant secondary hyperparathyroidism. 1168 87

Tumoral calcinosis is characterized by periarticular deposition of calcium phosphate, usually in the setting of normocalcemia and hyperphosphatemia. The term tumoral calcinosis can be used to describe lesions with periarticular deposition of calcium phosphate resulting either from a primary disorder or a secondary disorder, such as renal failure with associated secondary hyperparathyroidism. Treatment entails phosphate deprivation, control of any primary disease processes such as secondary hyperparathyroidism, and resection for recalcitrant symptoms. We present a case of tumoral calcinosis involving the foot which required resection and ultimately hyperparathyroidectomy.
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PMID:Tumoral calcinosis of the foot. 1172 46

Cardiovascular complications caused by an accelerated atherosclerotic disease represent the largest single cause of mortality in chronic renal failure patients. The rapidly developing atherosclerosis of the uremic syndrome appears to be caused by a synergism of different mechanisms, such as malnutrition, oxidative stress and genetic factors. Recent studies provide evidence that chronic inflammation plays an important role in the pathogenesis of cardiovascular diseases. Hyperphosphatemia and an increased calcium-phosphate ion product have also been associated with an increased risk of death. Cardiovascular calcifications secondary to increases in phosphate and calcium load in dialysis patients might exert an important contribution to the excess cardiovascular mortality and morbidity in dialysis patients. Elevated serum levels of plasma C-reactive protein (CRP) are associated with the extent and severity of the atherosclerotic processes as well as with an increased risk of experiencing myocardial infarction and sudden cardiac death in apparently healthy subjects. In patients affected by pre-dialytic renal failure increased levels of CRP and IL-6 were recorded in 25% of our population; CRP and IL-6 were inversely related with renal function. These data suggest the activation--even in the predialytic phase of renal failure--of mechanisms known to contribute to the enhanced cardiovascular morbidity and mortality of the uremic syndrome. In recent years we have investigated the hypothesis that the chronic inflammatory state of the uremic patient could be at least in part due to the dialytic technique. We have shown that the increase of CRP in stable dialysis patients may be due to the stimulation of monocyte/macrophage by backfiltration of dialysate contaminants. During conventional dialysis, a positive calcium balance and a concomitant inflammatory state may act as cofactors in the development of cardiovascular calcifications. We suggest that this hypothesis should be verified by clinical studies. A reevaluation of the ideal calcium levels in the dialysate is warranted: a neutral intradialytic calcium balance is probably more appropriate, although not easily attainable.
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PMID:Vascular calcifications as a footprint of increased calcium load and chronic inflammation in uremic patients: a need for a neutral calcium balance during hemodialysis? 1185 66


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