Associations of osteoprotegerin with coronary artery calcification among women with systemic lupus erythematosus and healthy controls.

Objective We tested the hypothesis that higher circulating levels of osteoprotegerin (OPG) are related to higher levels of coronary artery calcification (CAC) among women with systemic lupus erythematosus (SLE) compared with healthy controls (HCs). Methods Among 611 women in two age- and race-matched SLE case-control studies, OPG was assayed in stored blood samples (HEARTS: plasma, n cases/controls = 122/124, and SOLVABLE: serum, n cases/controls = 185/180) and CAC was measured by electron beam computed tomography. Results In both studies, SLE patients had higher OPG and CAC levels than HCs. Higher OPG was associated with high CAC (>100 vs.100) among SLE, and with any CAC (>0 vs. 0) among HCs. Multivariable-adjusted OR (95% CI) for OPG tertile 3 vs. 1 was 3.58 (1.19, 10.76), p trend = 0.01 for SLE, and 2.28 (1.06, 4.89), p trend = 0.04 for HCs. Associations were attenuated when age-adjusted, but remained significant for HC women aged ≥ 40 and SLE women aged ≥ 50. ROC analyses identified 4.60 pmol/l as the optimal OPG cutpoint for predicting high CAC (>100) among SLE patients with sensitivity = 0.74 and specificity = 0.61, overall, but 0.92 and 0.52, respectively, for SLE patients aged ≥ 50. Conclusion Our cross-sectional results suggest that higher OPG levels are related to higher CAC levels among women with SLE vs. healthy controls.

A double-blind, randomized, Phase III, multicenter study in 358 pediatric subjects receiving isotretinoin therapy demonstrates no effect on pediatric bone mineral density.

UNLABELLED: This study compared the effects of pediatric acne treatment with two isotretinoin formulations on bone mineral density. We demonstrated no difference in the effect of the two formulations. No effect on pediatric bone mineral density was identified for either formulation. INTRODUCTION: Isotretinoin (13-cis-retinoic acid) is a treatment for recalcitrant nodular acne with a purported effect on bone mineral density (BMD). The side effects of isotretinoin on vertebral bone were evaluated to assess the safety of a new FDA-approved isotretinoin formulation: Lidose-isotretinoin (Cip-Iso). METHODS: This double-blind, randomized, phase III, active control, parallel-group, multicenter study compared the safety, efficacy, and non-inferiority of CIP-Iso to a marketed reference product, Accutane®, in severe recalcitrant nodular acne subjects. Three hundred fifty-eight pediatric male and female subjects aged between 12 and 17 years underwent 20 weeks of treatment with PA lumbar spine dual X-ray absorptiometry (DXA) measurements obtained for bone mineral density (BMD) and Z-scores, 5.5 months apart on visits 1 and 8. One hundred sixty-eight of 358 subjects had height adjusted Z-scores (HAZ) calculated. RESULTS: There was no difference in the least squares (LS) mean Z-score or HAZ of the two drugs at visit 1 or 8. The mean and LS mean Z-score and HAZ were greater than zero at visits 1 and 8 for both drugs. The change in the LS mean spine Z-score, but not HAZ, between visits, was statistically significant for both drugs. There was a mean increase in BMD (g/cm(2)) for both products between visits. CONCLUSIONS: There is no difference in the effect of two formulations of isotretinoin on spine bone density after 6 months of treatment. BMD increased and the small change in spine Z-score over treatment disappeared after height adjustment. Mean positive Z-scores and HAZ in the study were likely due to the exclusion of low and inclusion of high Z-score subjects.

Transplantation outcomes in primary hyperoxaluria.

Optimal transplantation strategies are uncertain in primary hyperoxaluria (PH) due to potential for recurrent oxalosis. Outcomes of different transplantation approaches were compared using life-table methods to determine kidney graft survival among 203 patients in the International Primary Hyperoxaluria Registry. From 1976-2009, 84 kidney alone (K) and combined kidney and liver (K + L) transplants were performed in 58 patients. Among 58 first kidney transplants (32 K, 26 K + L), 1-, 3- and 5-year kidney graft survival was 82%, 68% and 49%. Renal graft loss occurred in 26 first transplants due to oxalosis in ten, chronic allograft nephropathy in six, rejection in five and other causes in five. Delay in PH diagnosis until after transplant favored early graft loss (p = 0.07). K + L had better kidney graft outcomes than K with death-censored graft survival 95% versus 56% at 3 years (p = 0.011). Among 29 year 2000-09 first transplants (24 K + L), 84% were functioning at 3 years compared to 55% of earlier transplants (p = 0.05). At 6.8 years after transplantation, 46 of 58 patients are living (43 with functioning grafts). Outcomes of transplantation in PH have improved over time, with recent K + L transplantation highly successful. Recurrent oxalosis accounted for a minority of kidney graft losses.

Special report on the 2007 adult and pediatric Position Development Conferences of the International Society for Clinical Densitometry.

The International Society for Clinical Densitometry (ISCD) conducts Position Development Conferences (PDCs) for the purpose of establishing standards and guidelines in the field of bone densitometry. Topics for consideration are selected according to clinical relevance, a perceived need for standardization, and the likelihood of achieving agreement. Questions regarding nomenclature, indications, acquisition, analysis, quality control, interpretation, and reporting of bone density tests for each topic area are assigned to task forces for a comprehensive review of the scientific literature. The findings of the review and recommendations are then presented to an international panel of experts at the PDC. The expert panel votes on potential Official Positions for appropriateness, necessity, quality of the evidence, strength of the recommendation, and applicability (worldwide or variable according to local requirements). Recommendations that are approved by the ISCD Board of Directors become Official Positions. The first Pediatric PDC was 20-21 June 2007 in Montreal, QC, Canada. The most recent Adult PDC was held 20-22 July 2007, in Lansdowne, VA, USA. This Special Report summarizes the methodology of the ISCD PDCs and presents selected Official Positions of general interest.

Refractory hypercalcemia in an infant secondary to talc pleurodesis resolving after renal transplantation.

Talc pleurodesis is the definitive therapy of recurrent pneumothorax and has not been associated with metabolic complications. We report an anephric male infant who developed severe hypercalcemia 6 months following talc pleurodesis for recurrent peritoneal dialysis-related hydrothorax. The etiology of hypercalcemia was related to persistently elevated 1,25-dihydroxyvitamin D(3) (1,25[OH]2D) levels. The source appeared to be the extrarenal production of 1,25(OH)2D from macrophages in a large thoracic talc granuloma. Hypercalcemia was controlled with a combination of a low calcium diet, low calcium dialysis, ketoconazole and hydroxychloroquine, but elevated 1,25(OH)2D levels persisted. At 32 months of age the child underwent renal transplantation with alemtuzumab pre-conditioning. The hypercalcemia resolved immediately, with normalization of serum 1,25(OH)2D levels and without hypercalciuria. This case demonstrates that hypercalcemia is a potential complication of talc pleurodesis from the extrarenal production of 1,25(OH)2D and that alemtuzumab, a monoclonal antibody directed against the CD52 antigen (which is expressed on almost all macrophages), may have a role in the treatment of hypercalcemia associated with granulomatous conditions.

Secondary contributors to bone loss in osteoporosis related hip fractures.

UNLABELLED: Osteoporosis treatment of patients with hip fractures is necessary to prevent subsequent fractures. Secondary causes for bone loss are present in more than 80% of patients with hip fractures, and therefore, assessment of Vitamin D status, disorders in calcium absorption and excretion, monoclonal gammopathies, and renal function should be performed. Identifying and managing these disorders will improve detection and enhance treatment aimed at reducing the risk of recurrent fractures in older adults. INTRODUCTION: The purpose of this study was to determine the prevalence of disorders affecting bone and mineral metabolism in individuals with osteoporotic hip fractures. METHODS: Community dwelling individuals with hip fractures (HFx) 50 years of age and older. Assessment for vitamin D, renal and parathyroid status, calcium absorption, and plasma cell disorders. RESULTS: Of 157 HFx, mean age 70 +/- 10 years, HFx had higher creatinine (p = 0.002, 95% C.I. -0.09, 0.05); lower 25 OH vitamin D (p = 0.019, 95% C.I. 6.5, 2.7), albumin (p = 0.007, 95% C.I. 0.36, 0.009), and 24-h urine calcium (p = 0.024, 95% CI 51, 21) as compared to controls. More than 80% of HFx had at least one previously undiagnosed condition, with vitamin D insufficiency (61%), chronic kidney disease (16%) (CKD), monoclonal gammopathy (6%), and low calcium absorption (5%) being the most common. One case each of multiple myeloma and solitary plasmocytoma were identified. CONCLUSIONS: Osteoporosis treatment of HFx is necessary to prevent subsequent fractures. Secondary causes for bone loss are remarkably common in HFx; therefore, assessment of vitamin D status, disorders in calcium absorption and excretion, protein electrophoresis, and renal function should be performed. Identifying and correcting these disorders will improve detection and enhance treatment aimed at reducing the risk of recurrent fractures in older adults.

Hypercalciuria is the main renal abnormality finding in Human Immunodeficiency Virus-infected children in Venezuela.

Kidney involvement in children with Human Immunodeficiency Virus (HIV) infection is increasing in prevalence in parallel with the longer survival of HIV-infected patients and the side-effects of new antiretroviral drugs. However, there are only a few reports describing renal tubular disorders in HIV+ children. This is a cross-sectional, case series study evaluating kidney disease in 26 Venezuelan HIV-infected children. The study cohort consisted of 15 girls and 11 boys, with a median age of 5.9 years (25-75th percentile: 3.6-7.8), who had been treated with antiretrovirals for 2.8 +/- 0.4 years, Overall, the patients were short for their age and gender (Z-height: -3.1; 25-75th percentile: -4.94 to -1.98), and 15 showed signs of mild to moderate malnutrition. All of the children had a normal estimated glomerular filtration rate (136 +/- 22.6 ml/min/1.73 m2), and glomerular involvement was only observed in one patient with isolated proteinuria. None had nephromegaly. In contrast, tubular disorders were commonly found. Hypercalciuria was detected in 16 of the patients (UCa/Cr = 0.28; 25-75th percentile: 0.17-0.54 mg/mg), with five of these showing crystalluria. Eight children showed hyperchloremia, and three had frank metabolic acidosis. Kidney stones were absent in all, but one boy had bilateral medullary nephrocalcinosis. Conclusion, in Venezuelan children, HIV infection per se, or its specific treatment, was commonly associated with renal tubular dysfunction, especially hypercalciuria and acidosis, potentially leading to nephrocalcinosis and growth impairment. We recommend renal tubular evaluation during the follow-up of children with HIV infection.

The optimal approach to the patient with oxalosis.

There are many challenges in oxalosis, including prompt, clinical recognition of this inborn error of metabolism, management of its many medical problems, provision of adequate care at end-stage kidney disease, and optimizing both the timing and results of liver and kidney allografts. This review provides a framework for the interested clinician to understand the many problems, and to begin to assimilate knowledge about an increasingly recognized, metabolic disorder. It ends with potential, innovative therapies that are not yet at the patient's bedside.

Zinc nutritional status modifies renal osteodystrophy in uremic rats.

BACKGROUND: Previous studies from our laboratories suggested that zinc depletion reduces the circulating level of 1,25-dihydroxycholecalciferol (1,25(OH)2D, calcitriol) in calcium- and phosphorus-depleted rats with normal renal function, and rats with uremia. Since calcitriol synthesis is in part dependent on renal function, we studied levels of circulating vitamin D metabolites, PTH response, mineral balance and bone histomorphometry in animals with different zinc nutritional and renal functional status. METHODS: Fifty-eight male Sprague-Dawley rats were pair-fed zinc-replete (+) or -deplete (-) diets for two weeks. Thereafter, half of each paired group underwent nephrectomy (N), while half had sham (S) operations. Animals were observed for eight weeks after surgery. External mineral balances of zinc, calcium, phosphate and magnesium were determined before surgery, and 1, 2 and 7 weeks after surgery. Plasma creatinine, zinc, calcium, phosphorus, magnesium, 25-hydroxycholecalciferol, calcitriol and PTH were determined at sacrifice. Static and dynamic bone histomorphometry was determined by standard techniques. RESULTS: After an 8-week observation period, zinc-depleted animals had lower plasma zinc levels, and nephrectomized animals had lower creatinine clearances than respective controls at sacrifice. Plasma calcium and phosphorus concentrations were similar in all four groups at sacrifice. Plasma magnesium concentrations were similar in groups with renal insufficiency, regardless of zinc nutritional status. Plasma 25-hydroxycholecalciferol and calcitriol levels were similar in all groups. There was no difference between mean PTH concentration in sham-operated animals, regardless of zinc nutritional status. Although nephrectomized groups' PTH levels were increased compared to S controls, PTH levels were increased in +Zn/N animals compared to the -Zn/N group. Zinc-deplete groups had consistent negative net zinc balance, however, there was no consistent effect of nephrectomy on external calcium, phosphorus, or magnesium balance, when nephrectomized groups of different zinc nutritional status were compared. Nephrectomized animals had histomorphometric changes indicative of higher bone turnover and abnormal mineralization. Zinc deficiency was associated with less evidence of increased parathyroid hormone activity on bone in nephrectomized rats. CONCLUSIONS: Zinc depletion limits the increase in plasma PTH concentration and the expression of secondary hyperparathyroid bone disease during the development of renal insufficiency in the renal ablation model of uremia in rats. The mechanism underlying this effect is unknown, but may involve a direct effect of zinc on the synthesis, release, metabolic clearance, and/or action of PTH on the cellular level, on the interrelationship of calcitriol and PTH, or a direct effect of zinc on bone mineral metabolism. These data highlight the potential relevance of zinc nutritional status to mineral metabolism in patients with chronic renal insufficiency and end-stage renal disease.

Persistent hypoparathyroidism following magnesium repletion in burn-injured children.

Children suffering severe burns develop hypocalcemia, magnesium (Mg) depletion, hypoparathyroidism, and renal resistance to parathyroid hormone (PTH) infusion. We hypothesized that Mg depletion accounted for both the hypoparathyroidism and the renal resistance to PTH, and that Mg repletion would improve both. Due to a lack of PTH for infusion, we studied only the effect of Mg repletion on the relationship between ionized Ca (iCa) and PTH in the serum of 14 sequentially recruited children burned > or =40% total body surface area. All received a urinary Mg retention test a median of 20 days post burn (range 8-137 days). Seven (50%) of the children remained Mg depleted, which was not attributable to burn size or to time from burn to study. Combined enteral and parenteral Mg intakes were not different between the depleted and repleted groups, 12.2+/-4.4 (SD) mg/kg per day and 14.2+/-6.2 mg/kg per day, respectively. Both groups had low intact PTH levels in relation to serum iCa concentration, indicating persistent hypoparathyroidism. We conclude that Mg depletion is not the chief cause of hypoparathyroidism following thermal injury and we postulate that the persistent hypoparathyroidism is consistent with a reduced set-point for Ca suppression of PTH secretion.

New developments in calcium and vitamin D metabolism.

During the past review year, researchers have discovered the molecular pathogeneses of disorders of calcium, vitamin D and bone. This review discusses the roles of the extracellular calcium sensor, the renal 25-hydroxyvitamin D-1-alpha-hydroxylase, the vitamin D receptor, and new factors for bone cell embryogenesis and function as a way of introduction to this exciting area of medicine.

Lumbar and radial bone mineral density in children and adolescents with X-linked hypophosphatemia: evaluation with dual X-ray absorptiometry.

OBJECTIVE: To evaluate the bone mineral status of children being treated for X-linked hypophosphatemia, including potential differences between cortical bone in the radial diaphysis and combined cortical and trabecular bone in the lumbar spine. DESIGN AND PATIENTS: Forty-four bone mineral evaluations were performed in 11 children and adolescents with X-linked hypophosphatemia. Bone mineral density (BMD) of the lumbar spine and the radial diaphysis were measured by dual X-ray absorptiometry (DXA), second metacarpal cortical thickness was measured on hand radiographs, and these results were expressed as Z-scores (standard deviations from the mean). RESULTS: For the 11 initial examinations, Z-scores (mean+/-SD) were: radial BMD, -2.73+/-1.15, lumbar BMD, +1.28+/-1.53; and cortical thickness, -2.21+/-0.95. Lumbar BMD Z-scores were significantly greater than those for radial BMD and cortical thickness. On follow-up examinations there was a mild increase in radial BMD and decrease in lumbar BMD. Although these changes were statistically significant, they were quite small and the discordance between radial and lumbar BMD was not corrected. CONCLUSIONS: Children and adolescents who are being treated for X-linked hypophosphatemia manifest a bone mineral disorder characterized by decreased BMD in the appendicular skeleton and increased BMD in the lumbar spine. Although current therapy is successful in its anti-rachitic effects, it does not correct this bone mineral disorder and additional therapeutic trials should be considered.

Isolated hypercalciuria with mutation in CLCN5: relevance to idiopathic hypercalciuria.

UNLABELLED: Isolated hypercalciuria with mutation in CLCN5: Relevance to idiopathic hypercalciuria. BACKGROUND: Idiopathic hypercalciuria (IH) is the most common risk factor for kidney stones and often has a genetic component. Dent's disease (X-linked nephrolithiasis) is associated with mutations in the CLCN5 chloride channel gene, and low molecular weight (LMW) proteinuria was universally observed in affected males. We sought to identify mutations in CLCN5 or abnormalities in LMW protein excretion in a large group of patients with IH and in a rat model of genetic hypercalciuria. METHODS: One hundred and seven patients with IH (82 adults and 25 children) and one asymptomatic hypercalciuric man with a known inactivating mutation in CLCN5 were studied. Secondary causes of hypercalciuria were excluded in all. The excretion of retinol-binding protein and beta2-microglobulin was measured by immunoassay in 101 patients with IH. Mutation analysis of the CLCN5 gene was performed in 32 patients with IH and in the genetic hypercalciuric stone-forming (GHS) rat strain. RESULTS: LMW protein excretion was normal in 92 patients with IH, and only slight abnormalities were found in the other nine, none of whom had a mutation in CLCN5. One 27-year-old man who had a CLCN5 mutation was found to have isolated hypercalciuria without LMW proteinuria, renal failure, or other evidence of renal disease. Mutation analysis was normal in 32 patients with IH. The CLCN5 sequence was normal in the GHS rat. CONCLUSIONS: Inactivation of CLCN5 can be found in the setting of hypercalciuria without other features of X-linked nephrolithiasis. However, mutations in CLCN5 do not represent a common cause of IH.

Fomepizole treatment of ethylene glycol poisoning in an infant.

The enzyme alcohol dehydrogenase metabolizes ingested ethylene glycol (EG) to the toxic compounds glycolic and oxalic acids. Renal failure, acidosis, hypocalcemia, and death may follow. Traditional treatment of EG poisoning may require ethanol, a competitive substrate of alcohol dehydrogenase, and hemodialysis, that removes both EG and its toxic metabolites. A new alcohol dehydrogenase inhibitor, fomepizole (4-methylpyrazole), was approved in 1997 for patients at least 12 years old with suspected or confirmed EG poisoning. Fomepizole has not been studied adequately in the pediatric population. We present a case of an 8-month-old male infant who drank up to 120 mL of EG and developed acidosis and oxalate crystalluria. He was treated with fomepizole and hemodialysis. Even after the completion of hemodialysis, fomepizole appeared to effectively block the production of EG toxic metabolites and to allow the resolution of acidosis; the patient recovered within 48 hours. This is the first report of fomepizole treatment of EG poisoning in an infant.4-methylpyrazole, fomepizole, poisoning, ethylene glycol, hemodialysis, infant, child, pediatrics.

Plasma calcium oxalate supersaturation in children with primary hyperoxaluria and end-stage renal failure.

BACKGROUND: Children with primary hyperoxaluria type 1 (PH 1) are at great risk to develop systemic oxalosis in end-stage renal disease (ESRD), as endogenous oxalate production exceeds oxalate removal by dialytic therapy. As oxalate accumulates, calcium oxalate (CaOx) tissue deposition occurs. Children with other causes of ESRD, however, are not prone to CaOx deposition despite elevated plasma oxalate (POx) levels. METHODS: Our study objective was to examine the potential mechanisms for these observations. We measured POx, sulfate, citrate, and calculated CaOx saturation (betaCaOx) in 7 children with ESRD caused by PH 1 and in 33 children with non-PH-related ESRD. Maintenance hemodialysis (HD) was performed in 6 PH 1 and 22 non-PH patients: Pre- and post-HD levels were analyzed at this point and were repeated twice within 12 months in 5 PH 1 and 14 non-PH patients. Samples were obtained only once in 12 patients (one PH 1) on peritoneal dialysis (PD). After liver-kidney or kidney transplantation, plasma levels were measured repetitively. RESULTS: The mean POx was higher in PH 1 (125.7 +/- 17.9 micromol/liter) than in non-PH patients (44.2 +/- 3.3 micromol/liter, P < 10(-4)). All other determined anions did not differ between the two groups. betaCaOx was higher in PH 1 (4.71 +/- 0.69 relative units) compared with non-PH children (1.56 +/- 0.12 units, P < 10(-4)). POx and betaCaOx were correlated in both the PH 1 (r = 0.98, P < 2 x 10(-4)) and the non-PH group (r = 0.98, P < 10(-4)). POx and betaCaOx remained stable over time in the non-PH children, whereas an insignificant decline was observed in PH 1 patients after six months of more aggressive dialysis. betaCaOx was supersaturated (more than 1) in all PH 1 and in 25 out of 33 non-PH patients. Post-HD betaCaOx remained more than 1 in all PH 1, but in only 2 out of 22 non-PH patients. In non-PH children, POx and betaCaOx decreased to normal within three weeks after successful kidney transplantation, whereas the levels still remained elevated seven months after combined liver-kidney transplantation in two PH 1 patients. CONCLUSION: Systemic oxalosis in PH 1 children with ESRD is due to higher POx and betaCaOx levels. As betaCaOx remained supersaturated in PH 1 even after aggressive HD, oxalate accumulation increases, and CaOx tissue deposition occurs. Therefore, sufficient reduction of POx and betaCaOx is crucial in PH 1 and might only be achieved by early, preemptive, combined liver-kidney transplantation or liver transplantation alone.

Immunoradiometric assay for intact human osteocalcin(1-49) without cross-reactivity to breakdown products.

BACKGROUND: Osteocalcin (Oc), a serum marker of bone turnover, circulates in several forms. We developed an assay for intact human Oc and investigated its clinical features. METHODS: We generated goat antibodies and N- and C-terminal Oc. The former was used on solid phase (polystyrene beads), and the latter was used as the tracer in an IRMA. RESULTS: The assay was linear with no cross-reactivity to Oc(1-43), total imprecision (CV) of <10%, and recovery of 100% +/- 10%. Assay values for intact Oc in EDTA plasma samples were unchanged at 18-25 degrees C for 6 h. Values for intact Oc in serum, EDTA plasma, and heparin plasma samples did not change after storage on ice for 8 h. Serum samples from patients with various conditions were stored at -70 or -135 degrees C for up to 5 years and yielded z-scores comparable to an Oc(1-43) IRMA for all conditions except for renal failure. In renal failure, the Oc(1-43) assay values were increased, whereas the intact assay values were in the reference interval. CONCLUSION: Decreases in Oc assay values are inhibited by calcium chelation, and slowed by reduced temperatures. The described assay for intact Oc allows improved specificity for bone compared with an assay for Oc(1-43).

Think of genetic hypercalciuria when a child has urinary tract findings.

Genetic hypercalciuria, one of the most common mineral disorders in childhood, is frequently associated with a variety of urinary tract problems. Identifying and treating genetic hypercalciuria alleviates urinary tract problems and optimizes peak bone mass growth in affected children. Advanced practice pediatric nurses play a key role in identifying and coordinating care for children with genetic hypercalciuria.

Increased risk of fracture in patients receiving solid organ transplants.

The success of organ transplantation is related to advances in immunosuppressive therapy. These medications are associated with medical complications including bone damage. The objective of this study was to estimate and compare age, gender-specific fracture incidence between transplant recipients, and a large sample representative of the civilian noninstitutionalized United States population using the 1994 National Health Interview Survey (NHIS). This was a cohort study set in tertiary care centers. Five hundred and thirty-nine individuals who received abdominal organ and 61 heart transplants surviving at least 30 days at our institution from 1986 to 1996 were included in the study. Incident fractures were ascertained by mail, in-person interview, telephone survey, or medical record review. All fractures were verified. Organ-, age-, and gender-specific fracture numbers and rates and person-years of observation, were calculated for the transplant patients. Weighted age- and gender-specific fracture rates from the 1994 NHIS were applied to the number of person-years of observation for each organ-specific age and gender category of transplant patients to generate an expected number of fractures. The ratio of observed to expected number of fractures was used to compare fracture experience of transplant patients to that of the national sample from the 1994 NHIS. Fifty-six of 600 (9.3%) patients had at least one fracture following 1221 person-years of observation. The sites of initial symptomatic fracture were as follows: foot (n = 22), arm (n = 8), leg (n = 7), ribs (n = 6), hip (n = 4), spine (n = 3), fingers (n = 3), pelvis (n = 2), and wrist (n = 1). Fracture incidence was 13 times higher than expected in male heart recipients age 45-64 years; nearly 5 times higher in male kidney recipients age 25-44 and age 45-64 years; and 18 times and 34 times higher in female kidney recipients age 25-44 years and 45-64 years compared with NHIS data. We have shown an increased incidence of fractures and estimated the magnitude of this problem in patients undergoing solid organ transplantation. Our work defines the need for a long-term prospective study of fracture risk in these patients.

Oxalate, citrate, and sulfate concentration in human milk compared with formula preparations: influence on urinary anion excretion.

BACKGROUND: Nephrocalcinosis is not uncommon in preterm infants, and elevated urinary oxalate excretion is known to be one of the main risk factors. When oxalate excretion was found to be higher in formula-fed than in human milk-fed infants, the formulas' oxalate content was thought to be responsible. METHODS: The oxalate concentration in human milk (21 samples obtained during lactogenesis; 17 samples obtained during established lactation) and of 16 formula preparations was examined. Citrate and sulfate concentrations were also measured, because both anions influence urinary saturation. RESULTS: The mean (+/- SE) oxalate content of human milk increased approximately 27% from early lactogenesis (70.4 +/- 6.4 micromol/1) to established lactation (96.4 +/- 9.5 micromol/l; p < 0.05). The latter was not different from the mean oxalate concentration of formula (98.2 +/- 11.4 micromol/l), however a fourfold range of measurements was recorded in both groups. The mean citrate content of human milk increased only slightly after early lactogenesis (2.66 +/- 0.22 mmol/l), but remained significantly lower than in formula (3.34 +/- 0.23 mmol/l; p < 0.05). The mean sulfate concentration did not increase and was 13 times lower in human milk (52.1 +/- 9.5 micromol/l) than in formula (688.7 +/- 95.4 micromol/l; p < 0.0001). CONCLUSIONS: The higher oxalate excretion in formula-fed infants is not because of the milk's oxalate concentration. Urinary citrate and sulfate excretion may be influenced by their higher concentrations in formula preparations, which may be of clinical importance in the population that is at risk for development of nephrocalcinosis.

Plasma calcium-oxalate saturation in children with renal insufficiency and in children with primary hyperoxaluria.

BACKGROUND: Calcium-oxalate (CaOx) deposition and systemic oxalosis are uncommon in children with chronic renal failure (CRI), but frequent in children with primary hyperoxaluria type I (PH-1). We hypothesized a difference in plasma CaOx saturation (betaCaOx) and its determining factors would explain this discrepancy. METHODS: Therefore, in addition to common biochemical measurements, plasma-oxalate (POx), citrate (PCit) and sulfate (PSulf) (plasma anions) were measured and betaCaOx was calculated in 17 PH-1 patients with normal renal function receiving pyridoxine and citrate therapy, in 54 children with CRI (SCr 0.9 to 5.9 mg/dl), and in 50 healthy children (NL). Plasma anions were analyzed by ion-chromatography and betaCaOx was calculated using a PC-based program for solution equilibria. RESULTS: Compared to NL, all plasma anion levels and betaCaOx were higher in PH-1 and CRI; POx, PCit and betaCaOx were higher in PH-1 than in CRI (P < 0.05), but PSulf was higher in CRI (P < 0.01). BetaCaOx and POx were correlated in all groups (r = 0.63 to 0.95, P < 10(-4)). POx and betaCaOx were both inversely correlated to a decrease in GFR in CRI patients. PCit and PSulf did not influence betaCaOx. Although supersaturation (betaCaOx > 1) was found in 7 CRI and in 4 PH-1 patients, eye examinations were suspicious for CaOx depositions only in the PH-1 patients, while systemic oxalosis was confirmed in one PH patient because of oxalate osteopathy. CONCLUSIONS: In PH-1, POx and betaCaOx are elevated even with normal renal function, which increases the likelihood of CaOx crystal deposition. Therefore, more effective therapy to decrease betaCaOx is crucial to reduce the risk of systemic oxalosis. In children with CRI unknown, but presumably protective substances, help prevent the risk of systemic oxalosis, despite increased POx and betaCaOx levels, often to supersaturation levels.