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Biomedical subjects

I B Salusky

Publications and source records attributed to I B Salusky.

At least 19 recordsLinked to original sources
PubMed2006

Survival predictability of time-varying indicators of bone disease in maintenance hemodialysis patients.

Although renal osteodystrophy and vitamin D analogs may be related to survival in maintenance hemodialysis (MHD) patients, most studies have examined associations between baseline values and survival without accounting for variations in clinical and laboratory measures over time. We examined associations between survival and quarterly laboratory values and administered paricalcitol in a 2-year (July 2001-June 2003) cohort of 58,058 MHD patients from all DaVita dialysis clinics in USA using both time-dependent Cox models with repeated measures and fixed-covariate Cox models with only baseline values. Whereas hypercalcemia and hyperphosphatemia were robust predictors of higher death risk in all models, the association between serum calcium and mortality was different in time-varying models. Changes in baseline calcium and phosphorus values beyond the Kidney Disease Outcome Quality Initiative recommended targets were associated with increased mortality. Associations between high serum parathyroid hormone and increased death risk were masked by case-mix characteristics of MHD patients. Time-varying serum alkaline phosphatase had an incremental association with mortality. Administration of any dose of paricalcitol was associated with improved survival in time-varying models. Controlling for nutritional markers may introduce overadjustment bias owing to their strong collinearity with osteodystrophy surrogates. Whereas both time-dependent and fixed-covariate Cox models result in similar associations between osteodystrophy indicators and survival, subtle but potentially clinically relevant differences between the two models exist, probably because fixed models do not account for variations of osteodystrophy indices and changes in medication dose over time.

Aged↗
PubMed2006

A new era in phosphate binder therapy: what are the options?

Dietary restriction of phosphorus and current dialysis prescription are unable to maintain phosphorus levels within the recommended range (2.7-5.5 mg/dl) in patients with advanced chronic kidney disease (CKD). Therefore, phosphate binders that limit the absorption of dietary phosphorus are commonly prescribed for this patient group. The first phosphate binders were introduced more than 30 years ago and included aluminum salts; however, although effective binders, the use of these agents was subsequently restricted because of concerns over aluminum accumulation in the central nervous system, bone, and hematopoietic cells. In subsequent years, calcium salts, namely calcium carbonate and calcium acetate, became the most widely used phosphate binders; however, increasing evidence now suggests that prolonged use of these agents increases the total body calcium load, induces adynamic bone, and potentially increases the risk of cardiovascular and soft tissue calcification. Sevelamer is the first phosphate-binding agent that is non-absorbed, calcium-free, and metal-free. To date, this agent has been shown to effectively control serum phosphorus levels in patients with CKD. It may also attenuate coronary and aortic calcification and has a number of other beneficial effects on lipid metabolism and inflammation among others. Lanthanum carbonate is another new agent that is reported to provide similar phosphate control to calcium-based phosphate binders but concerns that the long-term administration of such compound may lead to tissue accumulation may limit its use.

Chelating Agents↗
PubMed2001

Non-invasive assessments of cardiovascular disease in patients with renal failure.

Vascular calcification is common in patients with chronic renal failure, and it may contribute to the very high mortality rate from cardiovascular causes in the end-stage renal disease population. Vascular calcification in chronic renal failure can arise from the calcification of the intimal layer of arteries as a result of atherosclerosis or from medial wall calcification due largely to alterations in mineral metabolism. Although several reports indicate that coronary artery calcification, as measured by electron-beam computed tomography, is quite common in patients with end-stage renal disease who are treated with dialysis, the clinical significance of these findings remain uncertain. In the general population, electron-beam computed tomography evidence of coronary calcification serves as a useful index of atherosclerotic burden and has value as a predictor of adverse coronary events. The relationship between coronary artery calcification and atherosclerotic cardiovascular disease has not been adequately studied, however, in patients with end-stage renal disease, and calcification scores in this population may reflect both intimal and medial wall calcification. Assessments using coronary angiography are needed to determine the diagnostic value of electron-beam computed tomography as a predictor of atherosclerotic cardiovascular disease in patients with chronic renal failure. Nevertheless, electron-beam computed tomography makes it possible to detect the presence and monitor the progression of coronary calcification in those undergoing long-term dialysis. The technique may provide important information about the impact of new therapeutic strategies aimed at reducing the risks of vascular calcification in those with chronic renal failure.

Cardiovascular Diseases↗
PubMed2000

Coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis.

BACKGROUND: Cardiovascular disease is common in older adults with end-stage renal disease who are undergoing regular dialysis, but little is known about the prevalence and extent of cardiovascular disease in children and young adults with end-stage renal disease. METHODS: We used electron-beam computed tomography (CT) to screen for coronary-artery calcification in 39 young patients with end-stage renal disease who were undergoing dialysis (mean [+/-SD] age, 19+/-7 years; range, 7 to 30) and 60 normal subjects 20 to 30 years of age. In those with evidence of calcification on CT scanning, we determined its extent. The results were correlated with the patients' clinical characteristics, serum calcium and phosphorus concentrations, and other biochemical variables. RESULTS: None of the 23 patients who were younger than 20 years of age had evidence of coronary-artery calcification, but it was present in 14 of the 16 patients who were 20 to 30 years old. Among those with calcification, the mean calcification score was 1157+/-1996, and the median score was 297. By contrast, only 3 of the 60 normal subjects had calcification. As compared with the patients without coronary-artery calcification, those with calcification were older (26+/-3 vs. 15+/-5 years, P<0.001) and had been undergoing dialysis for a longer period (14+/-5 vs. 4+/-4 years, P< 0.001). The mean serum phosphorus concentration, the mean calcium-phosphorus ion product in serum, and the daily intake of calcium were higher among the patients with coronary-artery calcification. Among 10 patients with calcification who underwent follow-up CT scanning, the calcification score nearly doubled (from 125+/-104 to 249+/-216, P=0.02) over a mean period of 20+/-3 months. CONCLUSIONS: Coronary-artery calcification is common and progressive in young adults with end-stage renal disease who are undergoing dialysis.

Adolescent↗
PubMed2000

Implications of intermittent calcitriol therapy on growth and secondary hyperparathyroidism.

Secondary hyperparathyroidism is the most common skeletal lesion in pediatric patients undergoing maintenance dialysis. The present review summarizes a prospective randomized study that evaluated the biochemical and skeletal responses to intermittent calcitriol therapy in 33 pediatric patients on peritoneal dialysis with secondary hyperparathyroidism. Also, the effect of intermittent calcitriol therapy on linear growth was evaluated in 16 of 33 patients who had completed the clinical trial. Serum parathyroid hormone levels decreased by 62% from 648+/-125 pg/ml in patients treated with intermittent intraperitoneal (IP) calcitriol, and values remained unchanged from pre-treatment levels of 670+/-97 pg/ml with oral calcitriol therapy. Overall serum total and ionized calcium levels were higher in patients treated with IP calcitriol during the study. In contrast to these biochemical findings, the skeletal lesions of secondary hyperparathyroidism improved after 12 months of treatment in both groups and adynamic bone occurred in 33% of the patients. Z-scores for height decreased from -1.80 /-0.3 to -2.00+/-0.3, P<0.01, after 12 months of intermittent calcitriol therapy. Such findings suggest that an intermittent schedule of calcitriol administration adversely affects chondrocyte activity within epiphyseal cartilage in pre-pubertal children with end-stage renal disease.

Animals↗
PubMed2000

Surgical aspects of dialysis in newborns and infants weighing less than ten kilograms.

PURPOSE: Renal failure occurs in children with moderate frequency. Surgical aspects of establishing and maintaining dialysis access in small infants are exceptionally challenging. The purpose of this review is to evaluate the authors' experience with dialysis access for infants less than 10 kg, particularly with respect to the surgical care required. METHODS: A retrospective review was conducted between 1991 and 1999 of all pediatric dialysis patients weighing 10 kg or less (n = 29). Age at start of dialysis, duration of dialysis, modes of dialysis, and complications specific to peritoneal (PD) and hemodialysis (HD) were examined. RESULTS: The mean age at start of dialysis was 10.4 months and continued for an average duration of 16.3 months. Seventy-two percent of all patients required both modes of dialysis. HD and PD duration averaged 7.8 and 10.5 months, respectively. Catheter durability was 3.1 and 4.5 months per catheter for HD and PD, respectively. There was no significant difference in complications when comparing HD and PD. Patients who weighed 5 to 10 kg had significantly longer PD catheter durability than patients 0 to 5 kg (P = .001). Forty-one percent of patients terminated dialysis after transplantation, whereas 24% died awaiting transplantation. CONCLUSION: Despite a large number of operations required, infants less than 10 kg can be bridged successfully, by surgical intervention and subsequent dialysis, to transplantation.

Body Weight↗
PubMed2000

Altered diurnal regulation of blood ionized calcium and serum parathyroid hormone concentrations during parenteral nutrition.

BACKGROUND: Little is known about parathyroid gland function in patients receiving total parenteral nutrition (TPN). OBJECTIVE: Our objective was to determine whether parathyroid gland function is abnormal in TPN recipients. DESIGN: Six patients with a mean (+/-1 SD) age of 45.5 +/- 8.0 y who had been receiving TPN for 18.7 +/- 2. 8 y underwent bone biopsy, bone mass measurements with dual-energy X-ray absorptiometry, and dynamic tests of parathyroid gland function. Diurnal variations in blood ionized calcium (iCa(2+)) and serum parathyroid hormone (PTH) concentrations were also assessed. Results were compared with those of healthy volunteers. RESULTS: Bone mass and bone formation were subnormal in all patients. Basal serum PTH concentrations were moderately higher in the TPN recipients than in healthy volunteers, and values obtained every 30 min over 24 h were significantly higher (P < 0.001) in TPN recipients (5.0 +/- 0.9 pmol/L) than in healthy volunteers (2.6 +/- 0.6 pmol/L). The percentage increase in serum PTH during citrate-induced hypocalcemia was lower in the TPN recipients, consistent with secondary hyperparathyroidism. Evening infusions of calcium-containing TPN eliminated the nocturnal rise in serum PTH, increased the amplitude of change for iCa(2+) and PTH over 24 h, increased the orderliness of change for iCa(2+) and PTH as measured by approximate entropy (ApEn), and enhanced the synchrony of change between iCa(2+) and PTH. Treatment for 10 d with calcium-free TPN restored the nocturnal rise in serum PTH and increased ApEn for PTH. ApEn for iCa(2+) remained low, suggesting that a component of nutrient solutions, but not calcium per se, enhances the regularity of PTH release in TPN recipients. CONCLUSION: Parathyroid gland function is abnormal in long-term TPN recipients, which may contribute to disturbances in bone metabolism.

Adult↗
PubMed2000

Impaired growth, delayed ossification, and reduced osteoclastic activity in the growth plate of calcium-supplemented rats with renal failure.

Linear growth is reduced in prepubertal children with adynamic renal osteodystrophy, suggesting that the proliferation and/or differentiation of epiphyseal growth plate chondrocytes is abnormal in this disorder. To examine this issue, in situ hybridization and histochemistry were used to measure selected markers of endochondral bone formation and bone resorption in the proximal tibia of subtotally nephrectomized rats fed a high calcium diet to induce biochemical changes consistent with adynamic osteodystrophy. Blood ionized calcium concentrations were higher and serum PTH levels were lower in nephrectomized, calcium-supplemented rats than in either intact or nephrectomized control animals. Linear growth and tibial length were reduced, but messenger RNA levels for type II collagen, type X collagen, and the PTH/PTHrP receptor did not differ from control values in nephrectomized rats given supplemental calcium. In contrast, both the width of epiphyseal cartilage and the height of the zone of hypertrophic chondrocytes were greater in calcium-supplemented nephrectomized rats. These morphological changes were associated with decreases in histochemical staining for tartrate-resistant acid phosphatase and lower levels of messenger RNA expression for the matrix metalloproteinase MMP-9/gelatinase B immediately adjacent to the epiphyseal growth plate. Diminished chondroclastic/osteoclastic activity alters growth plate morphology and adversely affects linear bone growth in calcium-supplemented, nephrectomized rats.

Acid Phosphatase↗
PubMed2000

Vitamin D receptor as a candidate tumor-suppressor gene in severe hyperparathyroidism of uremia.

Most chronic renal failure patients with severe refractory hyperparathyroidism harbor at least one monoclonal parathyroid tumor, but the specific acquired genetic defects that confer this clonal selective advantage remain poorly understood. Somatic inactivation of the vitamin D receptor (VDR) gene could contribute to clonal outgrowth, because a parathyroid cell containing this lesion would have an impaired response to the antiproliferative influence of 1,25-dihydroxyvitamin D3. Furthermore, diminished expression of VDR protein has been described in uremia-associated parathyroid tumors. Therefore, to assess VDR gene inactivation's potential pathogenetic role in this disease, we rigorously analyzed the VDR gene in 59 parathyroid tumors surgically resected from uremic patients. First, Southern blotting and/or PCR analyses of 29 tumor samples from 14 genetically informative patients revealed no allelic losses at the VDR locus. Next, direct DNA sequencing of all VDR splice junctions, associated intronic sequences, and virtually the entire VDR-coding region for all 59 tumors revealed no acquired mutations. Last, 37 tumor DNA samples were subjected to comparative genomic hybridization, and no chromosomal losses in the VDR region (12cen-q12) were observed. These observations suggest that inactivating defects within the VDR gene do not commonly contribute to the primary pathogenesis of severe refractory hyperparathyroidism in uremia.

Adult↗
PubMed1999

[Children with chronic renal failure: evaluation of the nutritional status and management].

Since malnutrition is a well recognized problem in children with chronic renal failure, nutritional management of these children is essential. This review describes methods for nutritional assessment and suggests guidelines for providing maximal dietary support in children with chronic renal insufficiency. Optimal nutritional management includes an adequate caloric and protein intake, a restriction of phosphorus intake and an appropriate intake of electrolytes and vitamins.

Acid-Base Equilibrium↗
PubMed1999

Prevention of renal osteodystrophy in predialysis patients.

Impaired calcitriol synthesis is one of the major factors contributing to the development of secondary hyperparathyroidism in patients with chronic renal failure. Vitamin D therapy, particularly 1alpha-hydroxyvitamin D3, even in low doses, has been shown to be effective in the treatment of secondary hyperparathyroidism in patients with mild-to-moderate chronic renal failure. Complications associated with calcitriol and alfacalcidol therapy, which include hypercalcemia and progressive deterioration of renal function, have been reported in some patients. The majority of the studies reviewed, however, demonstrated that daily calcitriol and alfacalcidol doses below 0.25 microg are rarely associated with hypercalcemia, hyperphosphatemia, or progressive decline in renal function. In addition, these complications usually resolve with the reduction in dose or discontinuation of the medication. Thus, vitamin D therapy may be valuable in the treatment of patients with mild-to-moderate chronic renal failure who may be at high risk of developing secondary hyperparathyroidism.

Calcitriol↗
PubMed1999

A novel immunoradiometric assay detects full-length human PTH but not amino-terminally truncated fragments: implications for PTH measurements in renal failure.

In 8 adolescents with end-stage renal disease (ESRD), basal PTH concentrations measured with a novel immunoradiometric assay (IRMA) (Scantibodies Laboratory, Inc.; S-IRMA) were invariably lower than those estimated with an established assay (Nichols Institute; N-IRMA) (263 +/- 228 versus 645 +/- 442 pg/ml, respectively; p<0.00001). During in vivo dynamic testing, set points for calcium-regulated PTH release were indistinguishable for both IRMAs (1.21 +/- 0.05 versus 1.22 +/- 0.06). However, maximal PTH concentrations were significantly lower when measured by S-IRMA then by N-IRMA (557 +/- 448 and 1114 +/- 606 pg/ml, respectively); minimum PTH concentrations were 41 +/- 65 pg/ml (5.0 +/- 4.2% of maximum) and 189 +/- 137 pg/ml (13.6 +/- 7.2% of maximum), respectively. Correlation between PTH and blood ionized calcium indicated that PTH measured by S-IRMA decreased more readily than the concentrations determined by N-IRMA. The N-IRMA showed indistinguishable cross-reactivity with hPTH(1-84) and hPTH(7-84), while the S-IRMA detected only the full-length peptide. Furthermore, the radiolabeled detection antibody of the N-IRMA interacted equivalently with hPTH(1-34) and hPTH(2-34), while the S-IRMA showed crossreactivity only with hPTH(1-34). These differences in assay specificity could explain the observed differences in ESRD, and suggest that PTH concentrations estimated by the S-IRMA reflect more accurately the amount of biologically active PTH in the circulation. Since low concentrations of PTH are frequently associated with adynamic bone disease, our findings may have significant implications for the treatment of renal osteodystrophy with calcium and/or biologically active vitamin D analogs.

Adolescent↗
PubMed1999

Growth retardation in children with chronic renal failure.

Growth retardation is a major obstacle to full rehabilitation of children with chronic renal failure (CRF). Several factors have been identified as contributors to impaired linear growth and they include protein and calorie malnutrition, metabolic acidosis, growth hormone resistance, anemia, and renal osteodystrophy. Although therapeutic interventions such as the use of recombinant human growth hormone, recombinant human erythropoietin, and calcitriol have made substantial contributions, the optimal therapeutic strategy remains to be defined. Indeed, growth failure persists in a substantial proportion of children with renal failure and those treated with maintenance dialysis. In addition, the increasing prevalence of adynamic lesions of renal osteodystrophy and its effect on growth have raised concern about the continued generalized use of calcitriol in children with CRF. Recent studies have shown the critical roles of parathyroid hormone-related protein (PTHrP) and the PTH/PTHrP receptor in the regulation of endochondral bone formation. The PTH/PTHrP receptor mRNA expression has been shown to be down-regulated in kidney and growth plate cartilage of animals with renal failure. Differences in the severity of secondary hyperparathyroidism influence not only growth plate morphology but also the expression of selected markers of chondrocyte proliferation and differentiation in these animals. Such findings suggest potential molecular mechanisms by which cartilage and bone development may be disrupted in children with CRF, thereby contributing to diminished linear growth.

Bone Development↗
PubMed1998

Intermittent calcitriol therapy in secondary hyperparathyroidism: a comparison between oral and intraperitoneal administration.

BACKGROUND: Intermittent oral or intravenous doses of calcitriol given two or three times per week are commonly used to treat secondary hyperparathyroidism (secondary HPT). This study was undertaken to compare the biochemical and skeletal responses to thrice weekly intraperitoneal (i.p.) versus oral doses of calcitriol in children with secondary HPT undergoing peritoneal dialysis (CCPD). METHODS: Forty-six patients aged 12.5+/-4.8 years on CCPD for 22+/-25 months were randomly assigned to treatment with oral (p.o.) or i.p. calcitriol for 12 months; 17 subjects given p.o. calcitriol and 16 subjects given i.p. calcitriol completed the study. Bone biopsies were performed at the beginning and at the end of the study, while determinations of serum and total ionized calcium, phosphorus, alkaline phosphatase, parathyroid hormone (PTH) and calcitriol levels were done monthly. RESULTS: Serum total and ionized calcium levels were higher in subjects treated with i.p. calcitriol, P < 0.0001, whereas serum phosphorus levels were higher in those given p.o. calcitriol, P < 0.0001. For the i.p. group, serum PTH levels decreased from pre-treatment values of 648+/-125 pg/ml to a nadir of 169+/-57 pg/ml after nine months. In contrast, serum PTH levels did not change from baseline values of 670+/-97 pg/ml in subjects given p.o. calcitriol, P < 0.0001 by multiple regression analysis. Serum alkaline phosphatase levels were also lower in patients treated with i.p. calcitriol, P < 0.0001, but there was no difference between groups in the average dose of calcitriol given thrice weekly. The skeletal lesions of secondary HPT improved in both groups, 33% of patients developed adynamic bone lesion. CONCLUSION: Differences in the bioavailability of calcitriol and/or in phosphorus metabolism may account for the divergent biochemical response to p.o. and i.p. calcitriol.

Administration, Oral↗
PubMed1998

Growth of long bones in renal failure: roles of hyperparathyroidism, growth hormone and calcitriol.

BACKGROUND: The treatment of secondary hyperparathyroidism (2 degrees HPT) associated with chronic renal failure adversely affects skeletal growth. METHODS: We assessed epiphyseal growth plate morphology by quantitative histology and measured mRNA levels for selected markers of chondrocyte proliferation and differentiation by in situ hybridization in the growth plate cartilage of subtotally nephrectomized rats with either mild or advanced 2 degrees HPT. RESULTS: The width of the growth plate cartilage in the proximal tibia and mRNA levels for PTH/PTHrP receptor were unchanged in rats with mild 2 degrees HPT, however, they were markedly less in nephrectomized rats with advanced 2 degrees HPT than in intact controls. Treatment with growth hormone 10 IU/kg/day increased growth plate thickness both in mild and in advanced 2 degrees HPT and raised mRNA levels for type II and type X collagen in rats with advanced 2 degrees HPT. The administration of calcitriol 50 ng/kg/day attenuated these responses in animals with advanced 2 degrees HPT. Overall, PTH/PTHrP receptor mRNA levels did not correspond to the serum levels of PTH indicating that PTH/PTHrP receptor expression is down-regulated in renal failure by a PTH-independent mechanism. CONCLUSION: Calcitriol counteracts the trophic actions of growth hormone on epiphyseal growth plate cartilage and modifies chondrocyte differentiation in vivo, and these mechanisms may contribute to disturbances in longitudinal bone growth in renal failure.

Animals↗