Calciotropic hormones and the risk of hip and nonspine fractures in older adults: the Health ABC Study

The effects of vitamin D and parathyroid hormone (PTH) levels on incident fracture remain uncertain. To test the hypothesis that increasing serum 25‐hydroxyvitamin D [25(OH)D] and decreasing PTH levels are associated with decreased risk of hip and any nonspine fracture, we conducted a prospective cohort study among 2614 community‐dwelling white and black participants, aged ≥70 years, from the Health, Aging and Body Composition (Health ABC) Study. Serum and plasma samples were drawn at year 2, which formed the baseline for this analysis. Serum 25(OH)D and intact PTH (1‐84) were measured using radioimmunoassay with DiaSorin reagents and EDTA plasma with a two‐site immunoradiometric assay kit, respectively. Incident fractures (hip and any nonspine) were assessed after year 2, every 6 months, by self‐report and validated by radiology reports. The median (interquartile range) follow‐up times for hip and any nonspine fractures were 6.4 (6.1–6.5) and 6.4 (5.5–6.5) years, respectively. Cox proportional hazards regression was used to estimate the hazard ratios (HR) with 95% confidence intervals (CI) for fracture. There were 84 hip and 247 nonspine fractures that occurred over the follow‐up period. The multivariable adjusted HRs (95% CIs) of hip fracture for participants in the lowest (≤17.78 ng/mL), second (17.79 to 24.36 ng/mL), and third quartiles (24.37 to 31.94 ng/mL) of 25(OH)D were 1.92 (0.97 to 3.83), 0.75 (0.32 to 1.72) and 1.86 (1.00 to 3.45), respectively, compared with participants in the highest 25(OH)D quartile (>31.94 ng/mL) (p trend = 0.217). Additional adjustment for IL‐6 (p = 0.107), PTH (p = 0.124), and hip areal bone mineral density (p = 0.137) attenuated HRs of hip fracture in the lowest quartile by 16.3%, 17.4%, and 26.1%, respectively. There was no evidence of an association between 25(OH)D and any nonspine fractures, or between PTH and hip or any nonspine fractures. We found limited evidence to support an association between calciotropic hormones and hip and nonspine fractures in older men and women. © 2012 American Society for Bone and Mineral Research.     

Increased Fracture Risk in Normocalcemic Postmenopausal Women with High Parathyroid Hormone Levels: A 16-Year Follow-Up Study

High PTH levels increase bone turnover and decrease bone mineral density (BMD). Low plasma 25-hydroxyvitamin D (25OHD) levels cause secondary hyperparathyroidism, but the relative contribution of low 25OHD and high PTH levels on risk of fracture is largely unknown. Within the cohort of women (n = 2,016) included in the Danish Osteoporosis Prevention Study (DOPS), we studied risk of fracture according to parathyroid status. Analyses were performed on effects of high PTH levels (i.e., in the upper tertile, ≥4.5 pmol/L) on risk of incident fractures at different 25OHD levels during 16 years of follow-up. Incident fractures were assessed using a nationwide hospital discharge register. In addition, effects of high PTH levels on BMD and vertebral fractures were assessed by DXA scans and spinal X-ray examination after 10 years of follow-up. High PTH levels were associated with a decreased body mass index, adjusted BMD, and an increased risk of any fracture (HR = 1.41, 95% CI 1.11–1.79) as well as an increased risk of osteoporotic fractures (HR = 1.59, 95% CI 1.20–2.10). Plasma 25OHD levels per se did not affect fracture risk, but high PTH levels were associated with an increased fracture risk only at 25OHD levels <50 nmol/L and 50–80 nmol/L. High PTH levels did not increase risk of fracture at 25OHD levels >80 nmol/L. In conclusion, PTH levels in the upper part or above the upper level of the reference interval increase risk of fracture in the presence of low vitamin D levels.     

Influence of Pre-renal Transplant Secondary Hyperparathyroidism on Later Evolution After Transplantation

Persistence of secondary hyperparathyroidism (SHPT) is common after renal transplantation. Good diagnosis and treatment are important to avoid complications. The objective of our work was to perform a retrospective analysis of the evolution of SHPT after renal transplantation.We selected patients who had received a kidney transplant at our hospital between 2000 and 2014. The biochemical variables of chronic kidney disease–metabolic bone disorders (CKD-MBD) were collected at pretransplantation and at 3, 6, 12, and 24 months post-transplantation. Treatments related to SHPT were also analyzed.Five hundred forty-three renal transplants were included. The average preoperative parathyroid hormone (PTH) was 241.14 pg/mL, 115.7 pg/mL at 3 months, and at 12 and 24 months postoperatively, PTH levels stabilized to 112 pg/mL. Treatment related to SHPT was present in 27.3% of patients during the preoperative period, 40.4% at 3 months postoperatively, 24.2% at 12 months postoperatively, and 23.2% at 24 months postoperatively. There was a significant association between requiring some type of treatment preoperatively and the rest of the postoperative periods (P < .005).The sample was later divided into 3 groups based on preoperative PTH (1: <150 pg/mL, n = 223 [41.1%]; 2: 150–300 pg/mL, n = 173 [31.9%]; 3: >300 pg/mL, n = 147 [27.1%]) and their evolutions were compared. Higher levels of postoperative PTH in group pre-PTH 3 were observed. Group 3 also presented with greater need for treatment in the postoperative periods, with significant association (P < .05). A regression analysis was performed and found that postoperative PTH were dependent on preoperative PTH adjusted by glomerular filtration.In conclusion, parameters related to CKD-MBD (mainly PTH) after kidney transplant, dependent on preoperative levels and glomerular filtration. Patients with a greater grade of SHPT presented with higher levels of postoperative PTH despite receiving more intensive treatment.     

Long-term follow-up study on bone mineral density and fractures after simultaneous pancreas-kidney transplantation

BACKGROUND: In type 1 diabetic patients with end-stage renal failure, low bone mass is prevalent and the incidence of fractures high after simultaneous pancreas kidney transplantation (SPK). Data are scarce on preexisting skeletal morbidity or the long-term effects of SPK on bone mass and risk of fractures. METHODS: We conducted a prospective study addressing these issues in 19 consecutive SPK recipients before and at 3, 6, and 12 months, and 2.5 to 4 years after establishment of graft function. RESULTS: Prior to transplantation, 13 patients (68%) had hyperparathyroidism, 7 of whom had osteoporosis. Mean bone mineral density (BMD) was significantly lower at the femoral neck than at the lumbar spine (T-scores -2.0 +/- 0.89 vs. -0.66 +/- 0.84). There was a significant decrease in BMD at both lumbar spine and femoral neck at 6 months post-transplantation (-6.0 +/- 5.4% and -6.9 +/- 4.3%, respectively). No further loss was observed in the following 6 months. At 1 year post-transplantation, 9 patients had osteoporosis associated with hyperparathyroidism in 8, and none had sustained a clinical fracture. A significant albeit small increase in BMD was observed 6 months after start of alfacalcidol 0.25 microg/day. At end-evaluation, osteoporosis and hyperparathyroidism persisted in the patients in whom it was documented at 1 year. Five patients who had lower BMD at the femoral neck pretransplantation sustained a clinical fracture. CONCLUSION: Cortical osteoporosis is prevalent in SPK recipients at the time of transplantation, progresses early post-transplantation, and is associated with relatively high incidence of fractures. Reversal of persistent hyperparathyroidism with the use of alfacalcidol may contribute to a decrease in skeletal morbidity.     

Bone Disease After Liver Transplantation: A Long-Term Prospective Study of Bone Mass Changes, Hormonal Status and Histomorphometric Characteristics

After liver transplantation there is a high incidence of fractures, with important rates of bone loss during the first months. However, the long-term evolution of bone mass and metabolism parameters have been scarcely studied. In order to determine the incidence and risk factors involved in the development of skeletal fractures and to analyze the long-term evolution of bone mass, bone turnover and hormonal status after liver transplantation, a 3-year prospective study was performed in 45 patients following liver transplantation. Serum osteocalcin, parathyroid hormone (PTH), 25-hydroxyvitamin D (25-OH D) and testosterone levels (men), and bone mass at the lumbar spine and femur were measured before and sequentially at different time points during 3 years. Spinal X-rays were obtained during the first year. Histomorphometric analysis of bone biopsies obtained in 24 patients within the first 12 hours after surgery and 6 months after transplantation was performed. Fifteen patients (33%) developed fractures after liver transplantation, and pre- transplant risk factors for fractures were age and low bone mass (odd”s ratio for osteoporosis, 95% confidence interval: 5.69, 1.32–24.53). Serum PTH, osteocalcin, 25-OH D, testosterone and creatinine levels increased after transplantation. Moreover, PTH correlated with creatinine and osteocalcin values. Bone mass decreased during the first 6 months and reached baseline values at the lumbar spine the second year, with posterior significant recovery at the femoral neck. Long term evolution of femoral neck BMD correlated with PTH levels. Six months after transplantation bone histomorphometric data showed an increase in bone formation parameters. After liver transplantation there is a high incidence of fractures, specially in elderly patients and those with osteoporosis. Bone mass decreased in the short-term period and improved, initially at the lumbar spine and later at the femur, according to histomorphometric evidences of an increase in bone formation. The increase in creatinine values induces a secondary hyperparathyroidism that influences the changes in femoral bone mass. Treatment of osteoporosis shortly after liver transplantation may be important in the prevention of bone fractures, particularly in patients with low bone mass. Received: June 2000 / Accepted: November 2000     

Hyperparathyroidism in Patients With X-Linked Hypophosphatemia

X-linked hypophosphatemia (XLH) is characterized by increased activity of circulating FGF23 resulting in renal phosphate wasting and abnormal bone mineralization. Hyperparathyroidism may develop in XLH patients; however, its prevalence, pathogenesis, and clinical presentation are not documented. This observational study (CNIL 171036 v 0) recruited XLH adult patients in a single tertiary referral center. Each patient was explored in standardized conditions and compared with two healthy volunteers, matched for sex, age, and 25-OH vitamin D concentrations. The primary endpoint was the proportion of patients with hyperparathyroidism. The secondary endpoints were the factors influencing serum parathyroid hormone (PTH) concentrations and the prevalence of hypercalcemic hyperparathyroidism. Sixty-eight patients (51 women, 17 men) were enrolled and matched with 136 healthy volunteers. Patients had higher PTH concentrations compared with healthy controls (53.5 ng/L, interquartile range [IQR] 36.7–72.7 versus 36.0 ng/L, IQR 27.7–44.0, p < .0001). Hyperparathyroidism was observed in 17 patients of 68 (25%). In patients, a positive relationship between PTH and calcium concentrations and a negative relationship between PTH and phosphate concentrations were observed. Seven (10%) patients (3 premenopausal women, 1 postmenopausal woman, and 3 men) were diagnosed with hypercalcemic hyperparathyroidism. All underwent parathyroid surgery, with consecutive normalization of calcium and PTH concentrations. Hyperparathyroidism is a frequent complication in XLH adult patients. Disruption of the physiological regulation of PTH secretion contributes to parathyroid disease. Early-onset hypercalcemic hyperparathyroidism can be effectively and safely cured by surgical resection. © 2020 American Society for Bone and Mineral Research.     

Fractures in patients with primary hyperparathyroidism: nationwide follow-up study of 1201 patients

Abstract Parathyroid hormone (PTH) increases bone turnover and may thus increase fracture risk. As PTH secretion is increased in primary hyperparathyroidism, surgical cure may prevent fractures. We studied fracture risk before and after diagnosis in patients treated surgically and conservatively for primary hyperparathyroidism. All 1201 patients with newly diagnosed primary hyperparathyroidism (PHPT) between 1982 and 1996 in Denmark were identified through the Danish Hospital Discharge Register. Each patient was compared with three age- and gender-matched controls randomly drawn from the background population. Those who were treated surgically (n = 841; mean age 58.6 ± 14.6 years) were significantly younger than those who were not (n = 360; 65.5 ± 16.8 years; 2p < 0.01); they had higher plasma ionized calcium (1.58 ± 0.16 vs. 1.50 ± 0.10 mmol/L; 2p = 0.03) and tended to have lower lumbar spine bone mineral Z-scores (–0.72 ± 1.35 vs. 0.05 ± 1.05; 2p = 0.06). Before diagnosis, fracture risk was elevated in both those who subsequently underwent surgery [incidence rate ratio (IRR) 1.45, 95% CI 1.05–1.99] and in those who did not (IRR 1.59, 95% CI 1.10–2.29). After diagnosis, no difference in fracture risk was present between surgically and nonsurgically treated patients. The risk of death was significantly lower in the operated patients than in those who did not have surgery (RR 0.58, 95% CI 0.47–0.73). No differences in fracture risk could be demonstrated between those who had and those who did not have surgery, taking age, gender, and previous fractures into account. Electronic Publication     

Vitamin D, parathyroid hormone levels and bone mineral density in community-dwelling older women: The Rancho Bernardo Study

Vitamin D (25(OH)D) increases the efficiency of intestinal calcium absorption. Low levels of serum calcium stimulate the secretion of parathyroid hormone (PTH), which maintains serum calcium levels at the expense of increased bone turnover, bone loss and increased risk of fractures. We studied the association between 25(OH)D and PTH levels, and their associations with bone mineral density (BMD), bone loss, and prevalence of hip fractures in 615 community-dwelling postmenopausal aged 50–97 years. Mean level of 25(OH)D and PTH were 102.0 nmol/l±35.0 nmol/l and 49.4 ng/l±23.2 nmol/l, respectively; 49% of women were current hormone therapy users. The overall prevalence of vitamin D insufficiency (25(OH)D<50 nmol/l) was 2%, and prevalence of high PTH levels (>65 ng/l) was 17.4%. In multiple linear regression analyses hip BMD was negatively and independently associated with PTH levels ( p =0.04), and positively and independently associated with 25(OH)D levels ( p =0.03). There were only 23 women (3.7%) who experienced a hip fracture. In age-adjusted analyses there were no significant differences of 25(OH)D and PTH levels by hip fracture status. Across the entire range of values, the overall correlation between 25(OH)D and PTH was moderate ( r =–0.20). However, after the threshold vitamin D level of 120 nmol/l, all PTH values were below 65 ng/l. Further studies are necessary to identify the optimal vitamin D levels necessary to prevent secondary hyperparathyroidism.     

Impact of Cytomegalovirus Disease in D+/R– Kidney Transplant Patients Receiving 6 Months Low‐Dose Valganciclovir Prophylaxis

Late‐onset cytomegalovirus (CMV) disease remains common in CMV serology naïve kidney transplant patients of CMV serology positive organs (D+/R–) despite the use of antiviral prophylaxis. We studied clinical efficacy of 6‐month low‐dose valganciclovir (VGCV) prophylaxis, risk factors for late‐onset CMV disease and its impact on kidney transplant outcomes. Between October 2005 and December 2009, 166 consecutive D+/R– kidney alone and simultaneous pancreas and kidney transplant patients received VGCV 450 mg daily for 6 months after transplantation. After a median follow‐up of 3.2 years, 30 cases of CMV disease occurred within the first 2 years after transplantation with a cumulative incidence of 11.5 and 18.1% at 1 and 2 years, respectively. The use of an induction agent with rabbit antithymocyte globulin and older donor age were factors associated with the risk of late‐onset CMV disease (AHR 2.91, 95% CI 1.18–7.20, p = 0.021 and AHR 1.03, 95% CI 1.01–1.06, p = 0.016, respectively). Late‐onset CMV disease was associated with increased risk for death‐uncensored graft loss (AHR 2.95, 95% CI 1.15–7.61, p = 0.025). In conclusion, late‐onset CMV disease continues to negatively impact kidney transplant outcome despite 6‐month low‐dose VGCV prophylaxis. Investigations focusing on novel preventive approaches should be emphasized.     

Bone disease after kidney transplantation

Kidney transplantation is the optimal form of renal replacement therapy for many with end-stage kidney disease. However, kidney transplantation comes with a unique set of medical complications, important among them is bone disease. Posttransplant bone disorders are manifestations of pathologic processes occurring posttransplant that are superimposed on preexisting disorders of bone and mineral metabolism secondary to kidney failure and/or diabetes mellitus. As a consequence of early rapid bone loss, which is seen commonly within the first 3 to 6 months of transplant, the fracture risk posttransplant increases and has been reported as high as 5% to 44%. Posttransplant fractures occur more commonly at peripheral than central sites. Patients with a history of diabetes mellitus are at particular risk for fracture. Parathyroid hormone (PTH) and osteocalcin levels generally decrease after transplantation. Alkaline phosphatase and urinary collagen cross-links are unpredictable. Bone histology varies. No single biomarker unequivocally distinguishes between the various bone disorders found on biopsy examination. Immunosuppression is a major cause of posttransplant bone disorders. Glucocorticoids lead to decreased bone formation whereas the calcineurin inhibitors appear to cause increased bone turnover. Evaluating and managing posttransplant bone disease is an integral part of posttransplant medical care.     

Vitamin D insufficiency and hyperparathyroidism in children with chronic kidney disease

Chronic kidney disease (CKD) is associated with altered calcium-phosphate homeostasis and hyperparathyroidism due to decreased activity of 1alpha-hydroxylase and impaired activation of 25-hydroxyvitamin D3 [25(OH)D3]. In some patients these problems start earlier because of vitamin D deficiency. A retrospective review of patients followed in the chronic renal insufficiency clinic at Children's Hospital of Michigan assessed the prevalence of vitamin D deficiency in CKD stages 2-4 and evaluated the effect of treatment with ergocalciferol on serum parathormone (PTH). Blood levels of 1,25 dihydroxyvitamin D3, 25(OH)D3, and parathormone (PTH) were examined in 57 children (40 boys; mean age 10.6 years). Of 57 subjects, 44 (77.2%) had 25(OH)D3 levels 30 ng/ml was 67.84 +/- 29.09 ng/ml and in the remaining patients was elevated, at 120.36 +/- 86.42 ng/ml (p = 0.05). Following ergocalciferol treatment (22), PTH decreased from 122.13 +/- 82.94 ng/ml to 80.14 +/- 59.24 ng/ml (p < 0.001) over a period of 3 months. We conclude that vitamin D deficiency is common in children with CKD stages 2-4 and is associated with hyperparathyroidism in the presence of normal 1,25 dihydroxyvitamin D3. Its occurrence before significant renal impairment is noteworthy. Early diagnosis and appropriate treatment is emphasized.     

Risk factors for fractures in kidney transplantation

BACKGROUND: Risk factors for fracture after kidney transplantation need to be identified to target patients most likely to benefit from preventive measures. METHODS: Medical records were reviewed for 1572 kidney transplants done at a single center between February, l963 and May, 2000 with 6.5+/-5.4 years of follow-up. RESULTS: One or more fractures occurred in 300 (19.1%), with multiple fractures in 101 (6.4%). After excluding fractures of the foot or ankle (n=130 transplants, 8.3%), avascular necrosis (n=86, 5.5%), and vertebral fractures (n=28, 1.8%), there were one or more fractures in 196 (12.5%), with a cumulative incidence of 12.0%, 18.5%, and 23.0% at 5, 10, and 15 years, respectively. In multivariate Cox proportional hazards analysis, age had no effect on fractures in men. Compared with men and younger women, women 46-60 and >60 years old were, respectively, 2.11 (95% confidence interval 1.43-3.12, P=0.0002) and 3.47 (2.16-5.60, P<0.0001) times more likely to have fractures. Kidney failure from type 1 and 2 diabetes increased the risk by 2.08 (1.47-2.95, P<0.0001) and 1.92 (1.15-3.20, P=0.0131), respectively. A history of fracture pretransplant increased the risk by 2.15 (1.49-3.09, P<0.0001). Each year of pretransplant kidney failure increased the risk by 1.09 (1.05-1.14, P<0.0001). Obesity (body mass index >30 kg/m2) was associated with 55% (17-76%, P=0.0110) less risk. Different immunosuppressive medications, acute rejections, and multiple other factors were not independently associated with fractures. CONCLUSIONS: The population of transplant patients at high risk for fracture can be identified using age/gender, pretransplant fracture history, diabetes, obesity, and years of pretransplant kidney failure.     

Hyperparathyroidism at 1 year after kidney transplantation is associated with graft loss

BackgroundHyperparathyroidism persists in many patients after kidney transplantation. The purpose of this study was to evaluate the association between post-transplant hyperparathyroidism and kidney transplantation outcomes.MethodsWe identified 824 participants from a prospective longitudinal cohort of adult patients who underwent kidney transplantation at a single institution between December 2008 and February 2020. Parathyroid hormone levels before and after kidney transplantation were abstracted from medical records. Post-transplant hyperparathyroidism was defined as parathyroid hormone level ≥70 pg/mL 1 year after kidney transplantation. Cox proportional hazards models were used to estimate the adjusted hazard ratios of mortality and death-censored graft loss by post-transplant hyperparathyroidism. Models were adjusted for age, sex, race/ethnicity, college education, parathyroid hormone level before kidney transplantation, cause of kidney failure, and years on dialysis before kidney transplantation. A Wald test for interactions was used to evaluate the risk of death-censored graft loss by age, sex, and race.ResultsOf 824 recipients, 60.9% had post-transplant hyperparathyroidism. Compared with non-hyperparathyroidism patients, those with post-transplant hyperparathyroidism were more likely to be Black (47.2% vs 32.6%), undergo dialysis before kidney transplantation (86.9% vs 76.6%), and have a parathyroid hormone level ≥300 pg/mL before kidney transplantation (26.8% vs 9.5%) (all P < .001). Patients with post-transplant hyperparathyroidism had a 1.6-fold higher risk of death-censored graft loss (adjusted hazard ratio = 1.60, 95% confidence interval: 1.02–2.49) compared with those without post-transplant hyperparathyroidism. This risk more than doubled in those with parathyroid hormone ≥300 pg/mL 1 year after kidney transplantation (adjusted hazard ratio = 4.19, 95% confidence interval: 1.95–9.03). The risk of death-censored graft loss did not differ by age, sex, or race (all P_interaction > .05). There was no association between post-transplant hyperparathyroidism and mortality.ConclusionThe risk of graft loss was significantly higher among patients with post-transplant hyperparathyroidism when compared with patients without post-transplant hyperparathyroidism.     

Incidence and risk factors for hip or other bone fractures among hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study

The available data on bone fractures in hemodialysis (HD) patients are limited to results of a few studies of subgroups of patients in the United States. This study describes the prevalence of hip fractures and the incidence and risk factors associated with hip and other fractures in representative groups of HD facilities (n=320) and patients (n=12 782) from the 12 countries in the second phase of the Dialysis Outcomes and Practice Patterns Study (2002-2004). Among prevalent patients, 2.6% had a prior hip fracture. The incidence of fractures was 8.9 per 1000 patient years for new hip fractures and 25.6 per 1000 for any new fracture. Older age (relative risk (RR)(HIP)=1.91, RR(ANY)=1.33, P<0.0001), female sex (RR(HIP)=1.41, P=0.02; RR(ANY)=1.59, P<0.0001), prior kidney transplant (RR(HIP)=2.35, P=0.04; RR(ANY)=1.76, P=0.007), and low serum albumin (RR(HIP)=1.85, RR(ANY)=1.45, per 1 g/dl lower, P<0.0001) were predictive of new fractures. Elevated risk of new hip fracture was observed for selective serotonin reuptake inhibitors and combination narcotic medications (RR=1.63, RR=1.74, respectively, P<0.05). Several medications were associated with risk of any new fracture: narcotic pain medications (RR=1.67, P=0.02), benzodiazepines (RR=1.31, P=0.03), adrenal cortical steroids (RR=1.40, P<0.05), and combination narcotic medications (RR=1.72, P=0.001). Parathyroid hormone (PTH) levels >900 pg/ml were associated with an elevated risk of any new fracture (RR=1.72, P<0.05) versus PTH 150-300. The results suggest that greater selectivity in prescribing several classes of psychoactive drugs and more efficient treatment of secondary hyperparathyroidism may help reduce the burden of fractures in HD patients.     

Post-transplant hypophosphatemia: Tertiary 'Hyper-Phosphatoninism'?

Hypophosphatemia is a common complication of kidney transplantation. Tertiary hyperparathyroidism has long been thought to be the etiology, but hypophosphatemia can occur despite low parathyroid hormone (PTH) levels and can persist after high PTH levels normalize. Furthermore, even in the setting of normal allograft function, hypophosphatemia, and hyperparathyroidism, calcitriol levels remain inappropriately low following transplantation, suggesting that mechanisms other than PTH contribute. Fibroblast growth factor-23 (FGF-23) induces phosphaturia, inhibits calcitriol synthesis, and accumulates in chronic kidney disease. We performed a prospective, longitudinal study of 27 living donor transplant recipients to test the hypotheses that excessive FGF-23 accounts for hypophosphatemia and decreased calcitriol levels following kidney transplantation. Hypophosphatemia <2.5 mg/dl developed in 85% of subjects, including one who had previously undergone parathyroidectomy; 37% developed phosphate < or =1.5 mg/dl. The mean pre-transplant FGF-23 level was 1,218+/-542 RU/ml. Within the first week following transplantation, mean levels decreased to 557+/-579 RU/ml, which were still above normal. FGF-23 was independently associated with serum phosphate (P < 0.01), urinary excretion of phosphate (P < 0.01), and calcitriol levels (P < 0.01); PTH was not independently associated with any of these parameters. We calculated area under the curve for FGF-23 and PTH between the pre- and first post-transplant levels as a summary measure of early exposure to these phosphaturic hormones. An area under the FGF-23 curve greater than the median was associated with a relative risk of developing hypophosphatemia < or =1.5 mg/dl of 5.3 (P = 0.02) compared with lower levels. Increased area under the PTH curve was not associated with greater risk of hypophosphatemia. Excessive FGF-23 exposure in the early post-transplant period appears to be more strongly associated with post-transplant hypophosphatemia than PTH.     

Less-than-subtotal parathyroidectomy increases the risk of persistent/recurrent hyperparathyroidism after parathyroidectomy in tertiary hyperparathyroidism after renal transplantation

BACKGROUND: The optimal surgical approach for tertiary hyperparathyroidism (HPT) after kidney transplantation is unknown. Existing studies are limited by small sample size, lack of adjustment for kidney function, and no long-term follow-up. METHODS: We retrospectively analyzed 74 patients with tertiary HPT who underwent parathyroidectomy at two centers since 1978. Persistent HPT was defined as parathyroid hormone (PTH) concentrations in excess of the K/DOQI target range for the corresponding estimated creatinine clearance (eCrCl). RESULTS: Seventy-four patients had 83 operations (72 subtotal and 11 less-than-subtotal parathyroidectomies). Mean follow-up time was 5.4 +/- 4.7 years. Calcium concentrations decreased significantly after parathyroidectomy (2.83 vs 2.28 mmol/L, P < 0.001), as did eCrCl (54.5 vs 44.9 mL/min, P < 0.001) and PTH (382 vs 132 pg/mL, P < 0.001). In the multivariable regression analysis, only the type of operation and postoperative eCrCl were significantly correlated with PTH at follow-up. A limited parathyroidectomy was associated with a fivefold increase in risk of persistent or recurrent hyperparathyroidism. CONCLUSIONS: The use of limited parathyroidectomy for tertiary HPT after kidney transplantation has a higher risk of persistent/recurrent HPT. Subtotal parathyroidectomy is recommended for patients with tertiary HPT.     

Parathyroid hormone levels in long-term renal transplant children and adolescents

Secondary hyperparathyroidism is a common complication of chronic renal failure. Kidney transplantation corrects renal insufficiency and most metabolic abnormalities but hyperparathyroidism persists in 50% of children after transplantation. The aim of this study was to investigate parathyroid hormone (PTH) course and potential risk factors for hyperparathyroidism in children after renal transplant. We collected data from 145 transplanted children (mean follow-up 4.7 years). Intact PTH level (iPTH) rapidly decreased in the first 6 months post-transplant and continued to decline in the following years. iPTH was above the normal range in 69.1% of the patients at the time of transplant and in 47% 1 year later, this improvement continuing thereafter. Hypercalcemia was present in 20.3% of the patients before transplant and in 6.3 and 4.1% of patients 6 months and 1 year after transplant, respectively. Hypophosphatemia was present in 5.5% of the patients at 6 months, and 45.5% of the patients needed phosphorus supplements during the first 6 months after transplant. Multivariate analysis indicated pre-transplant hyperparathyroidism, dialysis duration, creatinine clearance and hypophosphatemia as predictors of persistent hyperparathyroidism. In kidney transplanted children, serum iPTH normalized in the long term in the majority of cases. Thus, parathyroidectomy should be reserved for selected patients.     

Vitamin D status among patients with hip fracture and elderly control subjects in Yekaterinburg, Russia

Purpose Vitamin D deficiency leads to secondary hyperparathyroidism and osteomalacia, and both conditions are associated with fractures, the most severe being hip fracture. The serum 25-hydroxyvitamin D level depends on latitude and season. Yekaterinburg is situated at a high latitude and the duration of winter is about 5 months. Methods In this study, the serum 25(OH)D and PTH concentrations, and the prevalence of hypovitaminosis D in elderly people, inhabitants of Yekaterinburg, were investigated. The study was performed on 63 people with hip fracture (mean age, 68.8 years) and 97 independently living elderly people (mean age, 70.2 years). Results Serum 25(OH)D (mean±SD) in the hip fracture group was 22.4±11.4 nmol/L, significantly lower than in control group, which was 28.1±10.1 nmol/L. The percentage of patients with severe hypovitaminosis D (<25 nmol/L) in the hip fracture group was 65%, compared to 47% in the control group (p<0.05). The prevalence of hypovitaminosis D among hip fracture patients, as well as among independently living elderly people in Yekaterinburg, was high. Conclusion Supplementation of vitamin D in elderly people with and without fracture might prevent secondary hyperparathyroidism, osteomalacia and fractures.     

Elevated calcium phosphate product after renal transplantation is a risk factor for graft failure

BACKGROUND: Abnormal mineral metabolism is not uncommon after renal transplant (TXP). In dialysis patients, elevated serum phosphorous (P), calcium (Ca), CaP product, and parathyroid hormone (PTH) are associated with increased morbidity and mortality. The effect of these abnormalities on recipient and graft survival after renal transplantation is unknown. METHODS: We retrospectively analyzed 422 kidney-only transplants performed between June 1996 and June 2003. Cases with graft or recipient survival less than three months, pre-TXP parathyroidectomy (PTX), cinacalcet therapy and incomplete records were excluded, leaving 303 cases for analysis using Cox models that included post-TXP PTX, levels of albumin-adjusted Ca(Ca(adj)), P, Ca(adj)P product and PTH. RESULTS: There was an 11-25% prevalence of abnormal serum Ca(adj), P or Ca(adj)P product within the first year post-TXP. At least 24% of recipients not undergoing PTX with an equation estimated GFR of 40-60 mL/min had PTH levels >130 pg/mL at one yr post-TXP. This is above levels recommended by the U.S National Kidney Foundation kidney disease quality initiative for patients with stages I-IV chronic kidney disease. Adjusted Ca > 10.5 mg/dL at three months post-TXP was an independent risk for recipient death (OR 3.0; 95% CI: 1.2-7.4). A Ca(adj)P product >35 mg(2)/dL(2) at six months (OR 4.0; 95% CI: 1.2-13.1), and Ca >10.5 mg/dL at 12 months post-TXP (OR 4.0; 95% CI: 1.2-14) were independent risks for death-censored graft loss. Twenty-two recipients underwent PTX for severe hyperparathyroidism. CONCLUSION: Abnormalities of mineral metabolism are common early after renal TXP. An elevated serum Ca(adj) at three months post-TXP increases the risk for recipient death, while an elevated Ca(adj)P and Ca(adj) later in the first post-TXP year increases the risk of long-term death-censored graft loss.     

Influence of parathyroidectomy on mortality in hemodialysis patients: a prospective observational study

BACKGROUND: In hemodialysis patients, the relationships between serum PTH and phosphorus levels and mortality are debated because both high and low turnover bone diseases increase the risk of vascular calcifications. Furthermore, the prevalence of hypoparathyroidism is increasing, and there is a fear that this state is associated with an increase in bone fractures. METHODS: We performed a cross-sectional study to determine the prevalence and the causes of hypoparathyroidism (defined as basal and post-hypocalcemic-challenge serum PTH levels < 55 pg/mL) in 97 patients undergoing chronic hemodialysis treatment in our unit. We then prospectively observed patients with low PTH levels (< 55 pg/mL, n = 26) and those with hyperparathyroidism defined as a PTH levels > 200 pg/mL (n = 25) during eight years for all causes of mortality and bone fractures. Kaplan-Meyer survival curves were adjusted for age and sex. RESULTS: Hypoparathyroidism was present in 30% of our patients. The main causes of hypoparathyroidism were parathyroidectomy (77%) and aluminium and iron overload. Survival did not differ between patients with hypoparathyroidism and hyperparathyroidism and between patients with serum phosphorus < or > 2 mmol/L. Parathyroidectomy was associated with better survival (p < 0.01). Similarly, incidence of bone fractures did not differ for the two groups. CONCLUSIONS: Parathyroidectomy is the main cause of hypoparathyroidism in hemodialysis patients and is associated with a lower mortality risk. This result suggests that a more aggressive treatment of secondary hyperparathyroidism could decrease mortality in this high-risk population.