PubMed Health⌕ Search

Biomedical subjects

Isidro B Salusky

Publications and source records attributed to Isidro B Salusky.

At least 19 recordsLinked to original sources
PubMed2005

Sevelamer controls parathyroid hormone-induced bone disease as efficiently as calcium carbonate without increasing serum calcium levels during therapy with active vitamin D sterols.

Little is known about the impact of various phosphate binders on the skeletal lesions of secondary hyperparathyroidism (2 degrees HPT). The effects of calcium carbonate (CaCO3) and sevelamer were compared in pediatric peritoneal dialysis patients with bone biopsy-proven 2 degrees HPT. Twenty-nine patients were randomly assigned to CaCO3 (n = 14) or sevelamer (n = 15), concomitant with either intermittent doses of oral calcitriol or doxercalciferol for 8 mo, when bone biopsies were repeated. Serum phosphorus, calcium, parathyroid hormone (PTH), and alkaline phosphatase were measured monthly. The skeletal lesions of 2 degrees HPT improved with both binders, and bone formation rates reached the normal range in approximately 75% of the patients. Overall, serum phosphorus levels were 5.5 +/- 0.1 and 5.6 +/- 0.3 mg/dl (NS) with CaCO3 and sevelamer, respectively. Serum calcium levels and the Ca x P ion product increased with CaCO3; in contrast, values remained unchanged with sevelamer (9.6 +/- 01 versus 8.9 +/- 0.2 mg/dl; P < 0.001, respectively). Hypercalcemic episodes (>10.2 mg/dl) occurred more frequently with CaCO3 (P < 0.01). Baseline PTH levels were 980 +/- 112 and 975 +/- 174 pg/ml (NS); these values decreased to 369 +/- 92 (P < 0.01) and 562 +/- 164 pg/ml (P < 0.01) in the CaCO3 and the sevelamer groups, respectively (NS between groups). Serum alkaline phosphatase levels also diminished in both groups (P < 0.01). Thus, treatment with either CaCO3 or sevelamer resulted in equivalent control of the biochemical and skeletal lesions of 2 degrees HPT. Sevelamer, however, maintained serum calcium concentrations closer to the lower end of the normal physiologic range, thereby increasing the safety of treatment with active vitamin D sterols.

Adolescent↗
PubMed2005

Intravenous calcitriol for treatment of hyperparathyroidism in children on hemodialysis.

This double-blind, placebo-controlled study evaluated the safety and efficacy of intravenous (i.v.) calcitriol (Calcijex) for treatment of secondary hyperparathyroidism (secondary HPT) in pediatric end-stage renal disease (ESRD) patients on hemodialysis (HD). After a 2 to 6-week washout period of all vitamin D compounds, patients with two consecutive PTH values > 400 pg mL(-1), calcium levels < or = 10.5 mg dL(-1) and calcium x phosphorus product values < or = 70 mg2 dL(-2) were eligible for the treatment phase. Patients received a bolus injection of calcitriol or placebo three times a week, immediately after dialysis for up to 12 weeks. Initial doses (0.5-1.5 microg) were based on the severity of secondary HPT. The dose was increased every two weeks by 0.25 microg until there was at least a 30% decrease in PTH from baseline, or Ca > 11.0 mg dL(-1), or Ca x P > 75 mg2 dL(-2). Overall, 11/21 (52%) patients in the calcitriol group had two consecutive > or = 30% decreases from baseline in serum PTH compared with 5/26 (19%) patients in the placebo group (P=0.03). The mean total alkaline phosphatase decreased from 274 to 232 IU L(-1) in the calcitriol group and increased from 547 to 669 IU L(-1) in the placebo group (P=0.002). The mean bone-specific alkaline phosphatase decreased from 72.5 to 68 microg L(-1) in the calcitriol group and increased from 105.3 to 148.5 microg L(-1) in the placebo group (P=0.03). The incidence of two consecutive occurrences of elevated calcium x phosphorus (Ca x P > 75 mg2 dL(-2)) product was higher in the calcitriol group than in the placebo group (P=0.01). Two consecutive occurrences of phosphorus > 6.5 mg dL(-1) occurred in 71% of the calcitriol group and 46% of the placebo group (P=0.14). Calcium levels > 10.5 mg dL(-1) were more common in the calcitriol group than in the placebo group (P=0.01). There was a direct relationship between serum phosphorus concentration and the percentage change in PTH from baseline in both the calcitriol group (r=0.46; P<0.0001) and the placebo group (r=0.21; P=0.0005). This study demonstrates that i.v. calcitriol, at initial doses of 0.5-1.5 microg, effectively reduces PTH levels in pediatric HD patients and that patients should be closely monitored for hyperphosphatemia and elevated Ca x P product.

Acetates↗
PubMed2005

Are new vitamin D analogues in renal bone disease superior to calcitriol?

Progression of chronic kidney disease is associated with an early reduction in serum calcitriol levels; thus, therapy with calcitriol should be initiated early in the course of chronic kidney disease to prevent the development of secondary hyperparathyroidism. Initial studies demonstrated a potential role of calcitriol in the prevention of growth retardation in children with chronic kidney disease prior to dialysis. But the optimal parathyroid hormone (PTH) levels that will maximize growth response during calcitriol treatment remain to be defined. Therapy with calcitriol has been shown to control the biochemical and skeletal manifestations of secondary hyperparathyroidism, but patients developed hypercalcemia, hyperphosphatemia and adynamic osteodystrophy. Thus, new vitamin D analogues with a lower hypercalcemic response have been developed. Although comparative studies are lacking, current evidence indicates that these new active vitamin D sterols (19-nor-paracalcitol and doxercalciferol) adequately control secondary hyperparathyroidism with minimal changes in serum calcium and phosphorus levels during treatment with calcium-containing binders. The long-term effect of such therapies on the skeleton and the process of vascular calcifications remain to be evaluated.

Calcitriol↗
PubMed2005

Calcification of the coronary arteries in the absence of atherosclerotic plaque.

Arterial calcification in the coronary arteries frequently indicates concomitant atherosclerotic plaque but can be present in the medial layers with no evidence of plaque. Calcification of the medial layer of arteries is seen most often in the peripheral arteries but also is widely recognized In the coronary arteries. We describe 2 patients who had marked medial and intimal calcification of the coronary arteries with little or no accompanying atherosclerosis.

Calcinosis↗
PubMed2004

New PTH assays and renal osteodystrophy.

Parathyroid hormone (PTH) levels have been used instead of bone histomorphometric analysis in renal failure, but the assessment of tetracycline-labeled bone biopsy remains the most reliable method to diagnose the different subtypes of renal osteodystrophy. The availability of the first-generation immunometric PTH assay (1(st) PTH-IMA) allowed the distinction between the different types of renal bone diseases. However, 1(st) PTH-IMA not only detects the intact hormone PTH(1-84), but also additional PTH truncated fragments. A second-generation immunometric PTH assay (2(nd) PTH-IMA) recognizes only PTH(1-84) and possible PTH fragments that are truncated at the carboxyl-terminus, but not PTH(7-84). In addition, whether assessment of the ratio PTH(1-84) and amino-terminally truncated PTH(1-84) fragments is a better predictor of bone turnover remains controversial. An initial study using the 2(nd) PTH-IMA suggested that the ratio between PTH(1-84) and amino-terminally truncated PTH(1-84) fragments more accurately predicts bone turnover in adult patients treated with hemodialysis. However, subsequent studies using the Scantibodies assay have failed to better predict the underlying bone disease in adults undergoing maintenance hemodialysis. Furthermore, a different 2(nd) PTH-IMA (Immutopics) with similar, but not identical, in vitro characteristics did not show a superior predictive value of the ratio in pediatric patients treated with peritoneal dialysis. Although the 2(nd) PTH-IMA may provide important new insights into the physiology of parathyroid gland function, at present, measurement of PTH using either 1(st) or 2(nd) PTH-IMAs provides similar accuracy for predicting bone turnover in patients treated with dialysis. Thus, the current data do not yet support the claim that 2(nd) PTH-IMAs provide an advantage over 1(st) PTH-IMAs for the diagnosis of the different subtypes of renal bone diseases.

Bone and Bones↗
PubMed2004

Bone histology in steroid-treated children with non-azotemic nephrotic syndrome.

Patients with nephrotic syndrome (NS) and normal glomerular filtration rate (GFR) frequently exhibit abnormalities of calcium and vitamin D homeostasis, mainly hypocalcemia and reduced circulating vitamin D metabolites. These abnormalities have been linked to alterations of bone histology in adults with non-azotemic NS, particularly osteomalacia and excessive bone resorption. Whether similar abnormalities of bone histology occur in children and adolescents with NS, particularly in those requiring prolonged treatment with corticosteroids, remains largely unknown. Thus, bone histomorphometry and selected bone-modulating hormones were studied in eight children (aged 2-16 years) with normal GFR (range 85-169 ml/min per 1.73 m(2)) and NS. All patients received corticosteroids for at least 12 months prior to bone biopsy. At the time of bone biopsy, the urine protein/creatinine ratio was elevated (2.1+/-3.6), while the average concentrations of parathyroid hormone (36+/-13 pg/ml), 25-hydroxyvitamin D [25(OH) D] (22+/-14 ng/ml), and 1,25(OH)(2)D (59+/-22 pg/ml) were normal. Bone histomorphometry displayed focal osteomalacia (OM) and mild increased bone resorption in most patients. The mineralization lag time, an indicator of the degree of osteomalacia, correlated with the time elapsed since the original diagnosis of NS ( r=0.93, P<0.0005). Overt hyperparathyroidism was not evident, but increased eroded perimeter and elevated bone formation rate (BFR) were evident in two patients, suggesting high-turnover bone disease. The BFR was inversely correlated with the administered dose of prednisone at the time of biopsy ( r=-0.78, P<0.05) and one patient exhibited low bone turnover changes. The growth velocity standard deviation score (SDS) at time of biopsy ranged from -1.6 to 3.2, resulting in a height SDS range of -1.9 to 0.6. The height SDS at time of bone biopsy correlated inversely with the dose of administered glucocorticoid ( r=-0.71, P<0.05) and with the duration of the disease ( r=-0.7, P=0.05). These data, albeit preliminary, demonstrate that children with NS treated with prolonged corticosteroid therapy exhibit bone histopathological changes without a concomitant impairment in GFR. While the OM appears to be related to the disease process, the alterations of bone formation and the adynamic changes are likely the result of the corticosteroid therapy. The potential consequences of these findings on adult bone mass and ultimate height deserve further studies.

Adolescent↗
PubMed2004

Special aspects of renal osteodystrophy in children.

Renal osteodystrophy represents a spectrum of skeletal lesions that range from high-turnover to low-turnover bone disease. Similar factors are involved in the pathogenesis of renal osteodystrophy in adult and pediatric patients with chronic kidney disease (CKD). However, growth retardation and the development of bone deformities are specific complications that occurred in pediatric patients with CKD. Metabolic acidosis, renal osteodystrophy, malnutrition, and disturbances in the insulin growth factor (IGF)/growth hormone (GH) are among the main factors involved and they are discussed briefly in this article. In addition to disturbances in bone remodeling, longitudinal bone growth occurs at the growth plate cartilage by endochondral ossification. Although young rats with experimental CKD have growth retardation, the characteristics of the growth plate are markedly different between animals with severe secondary hyperparathyroidism and those with calcium-induced adynamic osteodystrophy. These disturbances may suggest potential molecular mechanisms by which endochondral bone formation may be altered in renal failure, consequently leading to growth retardation.

Acidosis, Renal Tubular↗
PubMed2003

Sevelamer hydrochloride: an effective phosphate binder in dialyzed children.

This pilot study was designed to evaluate the efficacy and acceptability of sevelamer hydrochloride as a phosphate binder in pediatric patients treated with dialysis. A 6-month open-label trial of sevelamer hydrochloride (Renagel) was initiated in 17 patients, aged 11.8+/-3.7 years, undergoing hemodialysis ( n=3) or peritoneal dialysis ( n=14). Following a 2-week washout period of the phosphate binders, serum phosphorus increased from 5.2+/-1.3 mg/dl to 7.5+/-2.2 mg/dl ( P<0.0002). After initiation of therapy with sevelamer hydrochloride, serum phosphorus levels decreased to 6.2+/-1.2 mg/dl ( P<0.01) during the first 8 weeks and final values were 6.3+/-1.5 mg/dl. Serum calcium concentration decreased during the washout period from 9.4+/-0.9 mg/dl to 8.9+/-1.5 mg/dl ( P<0.01); values remained unchanged thereafter. The serum calcium-phosphorus ion product decreased during the first 8 weeks and values did not change subsequently. Serum bicarbonate, parathyroid hormone, total cholesterol, low-density lipoprotein and high-density lipoprotein cholesterol, and triglyceride levels did not change. The initial prescribed dose of sevelamer hydrochloride was 121+/-50 mg/kg (4.5+/-5 g/day) and the final prescribed dose was 163+/-46 mg/kg (6.7+/-2.4 g/day). Sevelamer hydrochloride was well tolerated and without adverse effects related to the drug.

Adolescent↗
PubMed2003

Bone density measurements in pediatric patients with renal osteodystrophy.

Peripheral quantitative computed tomography (pQCT) can selectively measure the densities of cortical and trabecular bone, but there is limited information about its use in patients with renal osteodystrophy. Thus pQCT (Norland XCT-2000, Stratec, Pforzheim, Germany) was performed at the ultradistal radius in 21 patients aged 16+/-3.6 (SD) years on continuous cycling peritoneal dialysis. Trabecular bone density (TBD) was higher in patients, 206+/-16 mg/cm(3), than in controls, 182.7+/-24.8 mg/cm(3) ( P<0.0001), whereas cortical bone density (CBD) was lower in patients, 946.5+/-147.5 mg/cm(3), than in controls, 1,153+/-25.4 mg/cm(3) ( P<0.001). TBD was inversely correlated with age ( r=-0.59, P=0.05), height ( r=-0.59, P<0.01), and weight ( r=-0.51, P<0.05). In contrast, CBD was positively correlated with age ( r=0.53, P<0.05), height ( r=0.56, P<0.05), and weight ( r=0.53, P<0.05). CBD was inversely related to serum alkaline phosphatase ( r=-0.71, P<0.001) and parathyroid hormone levels ( r=-0.50, P<0.05). In patients with adynamic bone, TBD was less, 192+/-9 mg/cm(3), than in those with high-turnover lesions, 215+/-13 mg/cm(3), P<0.001. CBD, however, was lower in patients with high-turnover lesions, 900+/-151 mg/cm(3), than in those with low turnover, 1,022+/-111 mg/cm(3), P<0.05. Compared with controls, in patients with high-turnover lesions, CBD was lower ( P<0.0001) and TBD higher ( P<0.0001). These findings suggest that pQCT may be an additional tool in the assessment of renal osteodystrophy.

Adolescent↗
PubMed2003

Sudden blindness caused by anterior ischemic optic neuropathy in 5 children on continuous peritoneal dialysis.

The authors report the occurrence of sudden blindness in 5 children (mean age, 32 months; range, 11 to 60) during continuous peritoneal dialysis regimen. All children presented with loss of light perception, visual fixation and ocular pursuit, and bilateral mydriasis unreactive to bright light. Fundoscopic examination found signs of anterior ischemic optic neuropathy with disc swelling, edema, and hemorrhages. Whereas 1 patient was dehydrated, the 4 other patients appeared well and not dehydrated. Nevertheless, blood pressure was below the normal range in all of them. Therefore, hypovolemia is highly suspected to have been the cause of ischemic optic neuropathy in all cases. Treatment consisted of steroids (4 patients), anticoagulation or antiagregation drugs (3 patients), plasma or macromolecules infusions (2 patients), vasodilatators (2 patients), and transient dialysis interruption (1 patient). One child with hepatic cirrhosis died 4 days later of acute liver insufficiency owing to ischemic hepatic necrosis. The other children had only partial improvement of vision during the following months. Because the prognosis of ischemic optic neuropathy is very poor, diagnosis and treatment of chronic hypovolemia in children on continuous peritoneal dialysis is essential to prevent such a devastating complication.

Blindness↗
PubMed2003

Parathyroid hormone (PTH), PTH-derived peptides, and new PTH assays in renal osteodystrophy.

Parathyroid hormone (PTH), PTH-derived peptides, and new PTH assays in renal osteodystrophy. Reliable measurements of parathyroid hormone (PTH) concentrations in serum or plasma are critical for the appropriate diagnosis and management of patients with renal osteodystrophy. With the introduction of second generation immunometric assays for PTH, it is now possible to measure exclusively full-length, biologically active PTH(1-84). In contrast, first generation immunometric assays that have been used widely for many years detect not only PTH(1-84), but also other large amino-terminally-truncated, PTH-derived peptides. This development will require a careful re-evaluation of PTH measurements, as determined by either first or second generation immunometric assays, and their relationship to bone histology and bone remodeling rates in patients with end-stage renal disease (ESRD). Such information is essential for proper clinical management, but only limited bone biopsy data are available to guide the interpretation of PTH results using second generation PTH assays. The different performance characteristics of first and second generation immunometric PTH assays also makes it possible to quantify the plasma levels of amino-terminally-truncated, PTH-derived peptides, which may accumulate disproportionately in patients with ESRD. Recent experimental evidence indicates that one or more of these peptides can modify bone cell activity and skeletal remodeling, possibly by interacting with a PTH receptor distinct from the type I PTH receptor that binds to the amino-terminal portion of PTH and mediates the classical biological actions of the hormone. The putative C-PTH receptor interacts with mid- and/or carboxyterminal regions of PTH and other amino-terminally-truncated PTH-derived peptides; signaling through it may contribute to the skeletal resistance to PTH that characterizes ESRD. The current review discusses certain aspects of the molecular structure of PTH and its interaction with various receptors, briefly comments about selected components of PTH secretion, highlights recent technical advances in PTH assays, and summarizes the effects of various PTH-derived peptides on bone cells and on skeletal metabolism.

Chronic Kidney Disease-Mineral and Bone Disorder↗
PubMed2003

Similar predictive value of bone turnover using first- and second-generation immunometric PTH assays in pediatric patients treated with peritoneal dialysis.

BACKGROUND: Accurate measurements of the concentration of parathyroid hormone (PTH) in serum or plasma are essential for the proper assessment of renal osteodystrophy. The first-generation immunometric PTH assay (1st PTH-IMA) not only detects the intact hormone, but also additional PTH fragments truncated at the amino N-terminally truncated PTH-derived fragments [ntPTH(1-84)]. A second-generation immunometric PTH assay (2nd PTH-IMA) recognizes only PTH(1-84) and possibly PTH fragments that are truncated at the carboxyl-terminus but not PTH(7-84). Whether estimates of the ratio between PTH(1-84) and ntPTH(1-84) fragments are a better predictor of bone turnover remains controversial. METHODS: Thirty-three patients aged 12.8 +/- 4.4 years treated with continuous cycling peritoneal dialysis (CCPD) for 13 +/- 9 months underwent iliac crest bone biopsy. PTH levels were measured by two newly developed first-generation and second-generation PTH-IMA. The ntPTH(1-84) fragments were calculated by subtracting PTH values determined using the 2nd PTH-IMA from values obtained using 1st PTH-IMA that detects both PTH(1-84) and relatively large ntPTH(1-84). RESULTS: Determinations of PTH levels by both assays were highly correlated (r = 0.89, P < 0.001). The relationships between first-generation and second-generation PTH-IMA and bone formation were similar (r = 0.67, P < 0.0001 and r = 0.64, P < 0.0001, respectively). When patients were grouped according to the presence or absence of secondary hyperparathyroidism, the ratio PTH(1-84) to ntPTH(1-84) did not differ between groups. CONCLUSION: PTH concentrations determined by either the first- or the second-generation PTH-IMA were found to be better predictors of bone formation than the PTH(1-84) to ntPTH(1-84) fragments ratio.

Adolescent↗
PubMed2002

Cell biology of renal osteodystrophy.

Renal osteodystrophy, a well-recognized complication of chronic renal failure, encompasses a spectrum of skeletal disorders ranging from high-turnover lesions of secondary hyperparathyroidism, the most common histologic lesion in pediatric patients with end-stage renal disease, to low-turnover lesions of adynamic renal osteodystrophy, which has become a common skeletal lesion in adults with chronic renal failure. Several advances have been made in the understanding of the pathogenesis of secondary hyperparathyroidism, particularly the critical roles of calcium, phosphorus, and vitamin D in promoting excess parathyroid hormone (PTH) synthesis and secretion, and parathyroid gland hyperplasia in renal failure. These insights will guide the development of more effective strategies for the prevention and management of renal bone disease.

Animals↗
PubMed2002

Growth hormone and the skeleton in pediatric renal allograft recipients.

Recombinant human growth hormone has been utilized to augment linear growth in pediatric renal allograft recipients. The skeletal changes that accompany growth hormone therapy have not been described in children. Thus, 23 stable prepubertal pediatric kidney recipients, aged 10 +/- 3 years, with a mean transplant time of 3.4 +/- 2.5 years and histological findings of normal bone formation and adynamic bone on bone biopsies were prospectively randomized into two groups. These comprised a treated group that received 12 months of growth hormone and a control group that did not receive any treatment. Anthropometric measurements and blood for serum calcium, phosphorus, parathyroid hormone (PTH), osteocalcin, and insulin-like growth factor-I (IGF-I) were obtained every 3 months. Measurements of bone mass by dual-energy X-ray absorptiometry were performed at the beginning and end of the study period. All patients underwent an initial and final bone biopsy procedure after double tetracycline labeling. Annual growth velocity increased and standard deviation scores for height improved in the treated group. Serum IGF-I levels increased in the treated group and the increase was evident in patients with normal bone formation who received growth hormone but not in patients with adynamic bone. Serum calcium, phosphorus, osteocalcin, and PTH levels did not differ between the treated and control groups. Bone mass did not change in the treated group, but declined after 12 months in the control group. Bone formation rates did not increase with growth hormone treatment. Thus, growth hormone therapy improves linear growth and maintains bone mass, but does not favorably affect bone formation rates in stable pediatric renal allograft recipients.

Age Determination by Skeleton↗