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Biomedical subjects

I B Salusky

Publications and source records attributed to I B Salusky.

At least 37 records · Page 2Linked to original sources
PubMed1998

Diminished linear growth during intermittent calcitriol therapy in children undergoing CCPD.

Daily calcitriol therapy has been reported to improve linear growth in children with renal bone disease, and 1,25-dihydroxyvitamin D is a key regultor of chondrocyte proliferation and differentiation. Whereas large intermittent doses of calcitriol can lower serum parathyroid hormone (PTH) levels and reverse the skeletal changes of secondary hyperparathyroidism, the impact of intermittent calcitriol therapy on linear growth in children is not known. Thus, we studied 16 pre-pubertal patients with bone biopsy-proven secondary hyperparathyroidism who completed a 12-month prospective clinical trial of intermittent calcitriol therapy. Biochemical results and growth data obtained during intermittent calcitriol therapy were compared to values determined during the preceding 12 months of daily calcitriol therapy in each study subject; changes in bone histology were assessed after one year of intermittent calcitriol therapy. Z-scores for height did not change during 12 months of daily calcitriol therapy. Although the skeletal lesions of secondary hyperparathyroidism improved in most patients, Z-scores for height decreased from -1.8 +/- 0.32 to -2.0 +/- 0.33, P < 0.01, during intermittent calcitriol therapy. The largest reductions were seen in patients who developed adynamic bone lesions after 12 months of treatment. Delta Z-scores for height correlated with serum PTH, r = 0.71, P < 0.01, and alkaline phosphatase levels, r = 0.67, P < 0.01, during intermittent calcitriol therapy but not during daily calcitriol therapy. The data suggest that high dose intermittent calcitriol therapy adversely affects linear growth, particularly in patients with the adynamic lesion. The higher doses of calcitriol or the intermittent schedule of calcitriol administration may directly inhibit chondrocyte activity within growth plate cartilage of children with end-stage renal disease.

Adolescent↗
PubMed1998

Bone disease in children and adolescents undergoing successful renal transplantation.

Little is known about the extent and severity of bone disease in children undergoing successful renal transplantation. To address this issue, 47 patients with stable renal function 3.2 +/- 1.7 years after transplantation (Tx) underwent iliac crest bone biopsy. The mean age of patients was 12 +/- 2.0 years; 36 had received cadaveric renal grafts, whereas 11 had undergone living-related Tx. Immunosuppressive drugs included cyclosporine 0.17 +/- 0.4 mg/kg/day, prednisone 7.5 +/- 2.1 mg/kg/day, and either azathioprine 1.6 +/- 0.9 mg/kg/day or mycophenolate mofetil 30 +/- 3 mg/kg/day. In addition to quantitative bone histomorphometry, the bone mineral content (BMC) of the lumbar spine was measured by dual energy X-ray absorptiometry (DXA) in 24/47 patients. Thirty-one transplant recipients had normal bone formation (N-Bfr), 11 had mild hyperparathyroidism (HPT) and 5 had adynamic skeletal lesions (AD). The interval since Tx, duration of dialysis before Tx and cumulative prednisone dose did not differ among groups. Trabecular bone area was highest in subjects with HPT. Unexpectedly, eroded bone perimeter exceeded normal reference values both in patients with AD and in those with N-Bfr; the osteoid area and osteoid perimeter were also elevated in these two groups. Hyperparathyroidism improved or resolved after Tx in all 14 subjects with this skeletal lesion prior to Tx, but one patient developed AD after Tx. Bone histology did not change after Tx in those with N-Bfr during regular dialysis, but bone formation increased after Tx in two of three patients with AD during regular dialysis. Z-scores for height in pre-pubertal patients after Tx were below age-appropriate values in each histologic subgroup, but values did not differ among groups. Z-scores for bone mineral content at the lumbar spine were also less than age-predicted values, -0.67 +/- 1.2. After adjusting for the degree of growth retardation, height-adjusted z-scores for lumbar spine BMC after Tx were above normal in all three histologic groups (0.68 +/- 1.0). The results suggest that reductions in bone mass and post-transplant osteoporosis are not prominent findings in pediatric renal transplant recipients when the influence of growth retardation on bone mass measurements by DXA is carefully considered.

Adolescent↗
PubMed1998

Intermittent calcitriol therapy and growth in children with chronic renal failure.

Intermittent calcitriol (1,25D) therapy has been used for the management of secondary hyperparathyroidism in children with chronic renal failure; however, the development of adynamic bone has been demonstrated in up to 40% of pediatric patients after 12 months of intermittent 1,25D therapy. To assess its effect on linear growth, we compared growth and biochemical data from 16 prepubertal patients with biopsy-proven secondary hyperparathyroidism during 12 months of intermittent 1,25D therapy and the preceding year of daily 1,25D therapy. While Z-scores for height remained stable during daily therapy, values decreased from -1.8 +/- 0.32 to -2.0 +/- 0.33, p < 0.01, during intermittent 1,25D therapy; the largest reductions were seen in those who developed adynamic bone. Reductions in growth may be due to the direct inhibitory effects of large intermittent doses of calcitriol on chondrocyte activity.

Calcitriol↗
PubMed1998

Calcium-sensing by parathyroid glands in secondary hyperparathyroidism.

Calcium-sensing by the parathyroids is abnormal in familial benign hypocalciuric hypercalcemia and in primary hyperparathyroidism (primary HPT), but the role of a calcium-sensing defect in uremic secondary hyperparathyroidism (secondary HPT) remains controversial. To study the regulation of PTH release by calcium, set point estimates were obtained using the four parameter model during in vivo dynamic tests of parathyroid gland function in 31 patients with secondary HPT, 8 patients with advanced secondary HPT studied shortly before undergoing parathyroidectomy (Pre-PTX), 3 patients with primary HPT, and 20 subjects with normal renal function (NL); the response to 2-h i.v. calcium infusions was also evaluated. Neither blood ionized calcium (iCa+2) levels nor the set point for calcium-regulated PTH release differed between secondary HPT and NL; iCa+2 levels and set point values were moderately elevated in Pre-PTX and markedly elevated in primary HPT. Compared with values obtained in NL, the lowest serum PTH levels achieved during calcium infusions, expressed as a percentage of pre-infusion values, were incrementally greater in secondary HPT, Pre-PTX, and primary HPT, whereas the slope of the relationship between iCa+2 and PTH, expressed as the natural logarithm (ln) of percent preinfusion values, decreased incrementally in secondary HPT, Pre-PTX, and primary HPT. The inhibitory effect of calcium on PTH release is blunted both in secondary HPT and primary HPT because of increases in parathyroid gland mass, but a calcium-sensing defect is a late, rather than early, consequence of renal secondary HPT.

Adolescent↗
PubMed1997

Psychological distress and treatment adherence among children on dialysis.

Among 23 pediatric renal dialysis patients, we obtained self-reported assessments of psychological adjustment and biochemical and subjective ratings of adherence. Findings indicate elevated levels of depressive symptoms and substantial nonadherence. Depressive symptoms were associated with higher levels of hopelessness, more negative self-perceptions, and more depressogenic attributional style. The psychological adjustment measures did not significantly correlate with adherence. Nonsignificant associations among different measures of adherence underscore its multifaceted nature. Implications for monitoring the adjustment of children on dialysis, assessing adherence, and future research are discussed.

Adolescent↗
PubMed1997

Suppressive effect of calcium on parathyroid hormone release in adynamic renal osteodystrophy and secondary hyperparathyroidism.

Serum parathyroid hormone (PTH) levels are markedly lower in patients with the adynamic lesion (AD) of renal osteodystrophy than in those with secondary hyperparathyroidism (2 degrees HPT), but serum PTH values are often moderately elevated in AD when compared to subjects with normal renal and parathyroid gland function (NL). To study the inhibitory effect of calcium on PTH release in AD and in 2 degrees HPT, the response to two-hour intravenous calcium infusions was examined in 6 patients with AD, in 31 patients with 2 degrees HPT and in 20 NL. Basal serum PTH levels were 88 +/- 51, 536 +/- 395, and 26 +/- 6 pg/ml, respectively, in AD, 2 degrees HPT and NL, whereas basal ionized calcium levels did not differ. When expressed as a percentage of pre-infusion values, PTH levels at the end of two-hour calcium infusions were higher both in AD (23.2 +/- 5.6%) and in 2 degrees HPT (27.8 +/- 12.3%) than in NL, (11.9 +/- 5.8%, P < 0.001). Both the amplitude of suppression (%) and the rate of decline (min-1) in serum PTH were less in AD and 2 degrees HPT than in NL, P < 0.05 for each parameter; corresponding values for each group, with 95% confidence intervals, were 77% (73 to 82) and 0.039 min-1 (0.030 to 0.048) in AD, 72% (68 to 76) and 0.031 min-1 (0.025 to 0.036) in 2 degrees HPT and 87% (84 to 89) and 0.070 min-1 (0.058 to 0.089) in NL. Neither variable differed between AD and 2 degrees HPT. Basal and nadir serum PTH levels were highly correlated: r = 0.95 and P < 0.05 in AD; r = 0.90 and P < 0.01 in 2 degrees HPT; r = 0.75 and P < 0.01 in NL. The slope of this relationship was less, however, both in AD and in 2 degrees HPT than in NL, P < 0.05 by analysis of co-variance. Thus, serum PTH levels fell below 20% of pre-infusion values in fewer subjects with AD (1 of 6) or 2 degrees HPT (9 of 31) than in NL (17 of 20) (chi 2 = 17.81, P < 0.005). The results indicate that the inhibitory effect of calcium on PTH release in vivo does not differ in AD and 2 degrees HPT despite marked differences in basal serum PTH levels. Variations in functional parathyroid gland mass rather than disturbances in calcium-sensing by the parathyroids probably account not only for the lower basal serum PTH levels in patients with AD compared to those with 2 degrees HPT, but also for the moderately elevated serum PTH values commonly seen in patients with AD.

Adolescent↗
PubMed1997

Tube feeding in children with end-stage renal disease.

Aggressive nutritional support and treatment with peritoneal dialysis (PD) have been advocated in the management of children with end-stage renal disease. In recent years, supplemental enteral feeding has been recommended by the majority of pediatric centers in the US and Europe since it has been shown to improve growth and neurologic development. Tube feeding, most commonly using a nasogastric (NG) or gastrostomy tube (G-tube) must be instituted when voluntary intake does not consistently meet the caloric and protein requirements or when there is poor growth. Recurrent emesis is the most common complication with NG feeds, while PD leak and exit site infection have been described with G-tube feeds. The early initiation of aggressive nutritional therapy to maximize growth potential must be emphasized.

Adolescent↗
PubMed1996

Parathyroid gland function in secondary hyperparathyroidism.

The parathyroid glands play a critical role in the maintenance of calcium homeostasis. It has been suggested that the set-point for calcium-regulated parathyroid hormone (PTH) release is higher in uremic patients than normal subjects. However, these assessments of parathyroid gland function have been performed using methods that differed from the original four-parameter model. Dynamic testing of the parathyroid glands has been performed with standardized infusions of calcium gluconate and sodium citrate in dialysis patients with secondary hyperparathyroidism and in normal volunteers. In addition, similar studies have been carried out before and after 4 months of intermittent calcitriol therapy. The derived values for the set-point were 1.21 + 0.04 mmol/l and 1.24 + 0.06 mmol/l, respectively in control and dialyzed patients (NS). Furthermore, the values for set-point were 1.21 + 0.01 and 1.22 + 0.01 mmol/l (NS), before and after calcitriol therapy. In addition, when subjects were grouped according to the severity of secondary hyperparathyroidism, the set-point calcium-regulated PTH release did not differ between the groups. Calcitriol therapy alters the secretory capacity of the parathyroid glands during hypocalcemia. The degree of parathyroid enlargement and the type of cell proliferation may be more important determinants of the severity of secondary hyperparathyroidism.

Child↗
PubMed1996

The renal bone diseases in children treated with dialysis.

Renal osteodystrophy represents a spectrum from high- to low-turnover bone lesions. The specific pattern, however, may change during selected therapeutic interventions. As in the past, osteitis fibrosa remains the most frequent histologic lesion in pediatric patients on dialysis, although recently the prevalence of low-turnover bone lesions without aluminum toxicity has been increasing in the pediatric population. This may be a consequence of aggressive calcitriol and calcium therapy. The different factors involved in the development of secondary hyperparathyroidism include hyperphosphatemia, hypocalcemia, altered vitamin D synthesis, impairments in parathyroid hormone (PTH) secretion and metabolism, and, recently, possible downregulation of renal PTH/PTH-rP messenger RNA receptor. New developments in molecular biology have demonstrated the relationship between vitamin D and PTH. The use of high-dose pulse intravenous, intraperitoneal, and oral calcitriol therapy has significantly decreased serum PTH levels and retarded the progression of osteitis fibrosa. These therapeutic interventions, however, may have led to the development of adynamic bone lesions. The impact of adynamic bone lesions in the young and growing skeleton remains to be determined.

Bone Diseases↗
PubMed1996

In vivo assessments of calcium-regulated parathyroid hormone release in secondary hyperparathyroidism.

In vivo dynamic tests of parathyroid gland function have provided useful information about the secretory behavior of parathyroids in various clinical disorders, but the limitations of this approach must be recognized when applied to studies of parathyroid gland physiology. Set point abnormalities have been documented in vivo both in primary hyperparathyroidism and in familial hypocalciuric hypercalcemia. Such findings are consistent with in vitro results obtained in studies of dispersed parathyroid cells from patients with primary hyperparathyroidism and with recently described alteration in calcium receptor expression in patients with FHH. The assessment of parathyroid gland function in patients with end-stage renal disease presents distinct methodological problems, however, because of marked variation in the degree of parathyroid gland enlargement. Neither the four parameter model originally used to describe set point abnormalities both in vitro and in vivo or alternative approaches to the assessment of PTH secretion in vivo adequately address this important issue. Results from recent in vivo studies of patients with chronic renal failure do not support the view that the set point for calcium-regulated PTH release is abnormal in secondary hyperparathyroidism or that treatment with calcitriol lowers the set point for calcium-regulated PTH release in patients with uremic secondary hyperparathyroidism. The concept of set point disturbances has strongly influenced discussions about the pathogenesis of secondary hyperparathyroidism, and it has served as a focal point for examining the therapeutic response to calcitriol in patients with this disorder. This matter requires careful reconsideration, however, in light of recent clinical findings and the development of techniques to directly assess the molecular mechanisms responsible for regulating calcium-mediated PTH release in renal failure and other disorders of mineral metabolism. Although knowledge in this area remains limited, the extent of parathyroid hyperplasia and the role of factors that influence the development of parathyroid gland enlargement may ultimately prove to be particularly important modifiers of parathyroid gland function in chronic renal failure.

Animals↗
PubMed1996

Peritoneal membrane transport function in children receiving long-term dialysis.

Accurate characterization of peritoneal solute transport capacity in children has been hampered by a lack of standardized test mechanics and small patient numbers. A standardized peritoneal equilibration test was used to study 95 pediatric patients (mean age, 9.9 +/- 5.6 yr) receiving chronic peritoneal dialysis at 14 centers. Patients were divided into four age groups (< 1, 1 to 3, 4 to 11, 12 to 19 yr) for analysis. Each patient received a 4-h peritoneal equilibration test with an exchange volume of 1100 mL/m2 per body surface area. Dialysate to plasma (D/P) ratios for creatinine (C) and urea (U) and the ratio of dialysate glucose (G) to initial dialysate glucose concentration (D/D0) were determined. Mass transfer area coefficients (MTAC) were calculated for the three solutes and potassium (P). The mean (+/- SD) 4-h D/P ratios for C and U were 0.64 +/- 0.13 and 0.82 +/- 0.09, respectively. The mean 4-h D/D0 for G was 0.33 +/- 0.10. D/P and D/D0 ratio results were similar across age groups. Normalized (for body surface area) mean MTAC (+/- SD) values were as follows: C, 10.66 +/- 3.74; G, 12.93 +/- 5.02; U, 18.43 +/- 4.02; and P, 14.02 +/- 3.94. Whereas a comparison of the normalized MTAC values across age groups with an analysis of variance showed significant age group differences only for glucose (P = 0.001) and potassium (P = 0.036), analysis by quadratic regression demonstrated a nonlinear decrease with age for C (P = 0.016), G (P < 0.001), and P (P = 0.034). In summary, evaluation of D/P and D/D0 ratios obtained from a large group of children in a standardized manner reveals values that are similar across the pediatric age range and not unlike the results obtained in adults. In contrast, normalized MTAC values of young children are greater than the values of older children, possibly as a result of maturational changes in the peritoneal membrane or differences in the effective peritoneal membrane surface area.

Adolescent↗
PubMed1996

In vivo studies of parathyroid gland function in secondary hyperparathyroidism.

In contrast to studies in vitro, in vivo tests of parathyroid gland function in human subjects with secondary hyperparathyroidism present a number of technical and theoretical difficulties. The four-parameter model was originally developed to characterize the secretion of PTH in vitro by a defined number of parathyroid cells in tissue culture, whereas comparisons among in vivo studies in patients with varying degrees of parathyroid gland hyperplasia may not be feasible with this model. Maximum serum PTH levels during hypocalcemic stimuli in vivo reflect not only the amount of PTH released by each parathyroid cell but also the total number of cells available for hormone secretion. Parathyroid gland size varies markedly in patients with secondary hyperparathyroidism, and there is currently no reliable technique for accurately measuring the amount of parathyroid tissue present. Accordingly, in vivo comparisons of calcium-regulated PTH release among subjects with parathyroid glands of substantially different sizes may not be valid with the four-parameter model. Kwan et al. have suggested that parathyroid gland function be assessed over a wide range of different calcium concentrations. In this model, the set point for calcium-regulated PTH secretion is not calculated, but the relationship between serum ionized calcium and PTH levels is examined by linear regression after semilog transformation of the data. Linearizing the calcium-PTH curve eliminates the need for more complex curve-fitting analyses. Differences in parathyroid gland function have been reported before and after calcitriol therapy when this approach is used, but the severity of secondary hyperparathyroidism varied widely in the patients evaluated. Alternatively, the Cica-clamp technique to quantify PTH secretion has been developed by Schwarz et al. By employing sequential standardized hypocalcemia and hypercalcemia, set point values obtained with this method closely agree with in vitro data obtained by Brown in normal parathyroid tissues. Advantages of the Cica-clamp technique include a shorter duration of study, reproducibility of the method, and absence of adverse effects; its utility in evaluating patients with either primary or secondary hyperparathyroidism remains to be determined. Based on data currently available, separate assessments of the pattern of change in serum PTH levels during hypocalcemia and hypercalcemia, expressed as the percent change from baseline values (see Fig 4), may provide more useful information about disturbances in the regulation of PTH release by calcium in patients with secondary hyperparathyroidism. Nevertheless, alterations in the set point for calcium-mediated PTH secretion do not adequately explain the excess PTH secretion of patients with secondary hyperparathyroidism, nor do they account for the reduction in serum PTH levels after treatment with calcitriol.

Animals↗