Long-Term Evaluation of Mineral Metabolism After Kidney Transplantation

ObjectivePersistence of abnormalities in mineral metabolism is common after kidney transplantation and appears to have a negative effect on survival. We aimed to evaluate the mineral metabolism and identify risk factors for persistent hyperparathyroidism (HPT) over 10 years.MethodsWe retrospectively analyzed the medical records of 176 consecutive renal transplant patients. Serum creatinine, calcium, phosphorus, and intact parathyroid hormone (iPTH) levels before and after transplantation up to the 10th year post transplantation were recorded for 11 different dates. Calcium > 10.2 mg/dL was considered hypercalcemia, phosphorus < 2.5 mg/dL was considered hypophosphatemia, and iPTH > 2.5 times the upper limit was considered HPT.ResultsAfter a major fall in the first 3 months, iPTH steadily decreased over 5 years. Thereafter, it stabilized at a level of 1.5 times the upper limit. Rates of persistent HPT were 9.2% and 10.7% in the fifth and 10th years, respectively. The rate of hypercalcemia increased up to 21.7% at the ninth month, and after 10 years, it was 5.9%. The rate of hypophosphatemia peaked at 33.3% in the first month, and it was 8.9% in 10th year. Multivariate analysis revealed that calcium (P = .047) and phosphorus (P = .041) at the time of transplantation and female sex (P = .037) were independent predictors of persistent HPT in the first year. iPTH correlated significantly with kidney function and pre-transplant iPTH.ConclusionsHigh serum levels of iPTH, calcium, and phosphorus at the time of transplantation were risk factors for persistent HPT in kidney transplant recipients, especially when renal function was suboptimal.     

Intact parathyroid hormone levels in renal transplant patients with normal transplant function

Bleskestad IH, Bergrem H, Leivestad T, Gøransson LG. Intact parathyroid hormone levels in renal transplant patients with normal transplant function.
Clin Transplant 2011: 25: E566–E570. © 2011 John Wiley & Sons A/S. Abstract: Introduction: Chronic kidney disease mineral and bone disorder (CKD‐MBD) is common in patients who have undergone kidney transplantation. There is limited information on the extent to which patients with normal renal function after transplantation have persistent disturbances in their mineral metabolism. Aim: The aim of the study is to investigate the prevalence of elevated intact parathyroid hormone (iPTH) levels at least one yr after transplantation in patients living with a first renal transplant with normal transplant function. Methods: A retrospective, observational study of 607 patients was collected from the Norwegian Renal Registry. Of these, iPTH was recorded for 360 patients. Results: One hundred and eighty‐eight patients (52%) had elevated iPTH levels. Twenty‐six patients (7%) had iPTH levels >2.5 times the upper limit of normal (ULN). Patients with a pre‐emptive transplant were significantly younger than the patients who had received treatment with dialysis (p < 0.0001). The prevalence of iPTH > ULN was significantly higher in patients with a pre‐emptive transplant (p = 0.037). Conclusions: In post‐transplant patients with normal transplant function, our data indicate that more than 50% have elevated levels of iPTH more than one yr after transplantation. If elevated iPTH level is associated with mortality in this patient population, it may have major impact on clinical treatment guidelines.     

Pharmacokinetics and Pharmacodynamics of Cinacalcet in Patients with Hyperparathyroidism After Renal Transplantation

Cinacalcet is a calcimimetic drug for the treatment of secondary hyperparathyroidism (HPT). In a sequential open-label study, ten patients with persistent HPT after renal transplantation received first 30 and then 60 mg oral cinacalcet once daily over 2 weeks each. Cinacalcet steady state oral clearance was 131.1 ± 20.9 l/h and 92.8 ± 9.5 l/h (mean ± SE) after 30 and 60 mg, respectively. Cinacalcet and parathyroid hormone (PTH) concentrations showed an inverse correlation and were fitted to a simple E_max model (E_max= 80% reduction vs. baseline, EC₅₀= 13 ng/mL). A once daily administration of cinacalcet lowered serum calcium over 24 h without fluctuations. The 8-h fractional urinary excretion of calcium was increased after 60 mg cinacalcet (baseline 0.85 ± 0.17%, 30 mg 1.53 ± 0.35%, 60 mg 1.92 ± 0.37%). Renal function remained stable. Cinacalcet pharmacokinetics and pharmacodynamics showed a pronounced interindividual variability. We conclude that the once daily administration of cinacalcet in patients with secondary HPT after renal transplantation effectively reduced iPTH and serum calcium. The transient calciuria could potentially favor nephrocalcinosis and reduce bone mineral density, suggesting that higher doses of cinacalcet need to be used with caution in renal transplant recipients with severe persistent hyperparathyroidism.     

肾移植术后继发性甲状旁腺功能亢进的临床分析

目的研究肾移植术后合并甲状旁腺功能亢进的受者血清钙、磷代谢及免疫反应性甲状旁腺激素(iPTH)水平的变化趋势,探讨治疗方式的选择。 方法回顾性分析2012年1月至2014年6月在解放军第三〇九医院全军器官移植研究所泌尿外科因尿毒症行肾移植、且术前并发继发性甲状旁腺功能亢进(SHPT)、术后移植肾功能恢复至估算肾小球滤过率(eGFR)>60 mL·min^－1·(1.73 m²)^－1的受者资料。共179例受者纳入研究,平均年龄(34±6)岁(18～61岁),术前慢性肾脏病分级均为5级。肾移植术后常规应用骨化三醇治疗(0.25 μg,1次/d),维持正常血清钙、磷水平。记录肾移植前后受者血清钙、磷及iPTH水平。采用单因素重复测量资料方差分析比较肾移植前和移植后1周、1个月、6个月、12个月和24个月受者血清钙、磷、iPTH水平,采用χ²检验比较低磷血症和高钙血症发生率以及iPTH分布情况。 结果肾移植术后1个月受者血清钙上升至稳定期,同时血清磷下降至稳定期;术后6个月高钙血症和低磷血症发生率最高,分别为8.4%(15/179)和9.5%(17/179)。术后1～6个月受者iPTH下降明显,随后无明显变化,术后24个月仅有27%(48/179)的受者iPTH水平降至完全正常。 结论尿毒症患者行肾移植术后,SHPT均有所缓解,但大部分无法恢复至正常水平,术后需要进行积极的针对性治疗。     

Mineral metabolism in renal transplant recipients discontinuing cinacalcet at the time of transplantation: a prospective observational study

Evenepoel P, Sprangers B, Lerut E, Bammens B, Claes K, Kuypers D, Meijers B, Vanrenterghem Y. Mineral metabolism in renal transplant recipients discontinuing cinacalcet at the time of transplantation: a prospective observational study.
Clin Transplant 2011 DOI: 10.1111/j.1399‐0012.2011.01524.x.
© 2011 John Wiley & Sons A/S. Abstract: Background: The calcimimetic cinacalcet is approved for treating secondary hyperparathyroidism in patients with chronic kidney disease on dialysis. Biochemical profiles and clinical outcomes in patients discontinuing cinacalcet at the time of transplantation are scarce. Methods: We performed a prospective observational cohort study, including 303 incident renal transplant recipients, of whom 21 were on cinacalcet treatment at the time of transplantation. Parameters of mineral metabolism and incidence of parathyroidectomy and nephrocalcinosis in patients discontinuing cinacalcet at the time of transplantation patients (“cinacalcet +”) were compared to cinacalcet‐naïve patients (“cinacalcet –”). Mean follow‐up was 35.6 ± 15.8 months. Results: At the time of transplantation, parameters of mineral metabolism were similar in both groups. Conversely, at month 3, serum ionized calcium (p = 0.0007), calcitriol (p = 0.02), biointact parathyroid hormone (p = 0.06) levels and urinary fractional excretion of phosphorus (p = 0.06) were higher, while serum phosphorus levels (p = 0.06) were lower in “cinacalcet +.” Analysis based on matching at the time of initiation showed that the course of post‐transplant mineral metabolism in cinacalcet‐treated patients (median treatment period 12.5 months) vs. cinacalcet‐naïve patients was identical. “Cinacalcet +” patients are characterized by a high‐incidence proportion of both post‐transplant nephrocalcinosis (45% at month 3) and parathyroidectomy (28.6%). No difference in renal function was observed between “cinacalcet +” and “cinacalcet?” patients. Conclusion: Cinacalcet does not affect the course of secondary hyperparathyroidism in patients awaiting kidney transplantation. Biochemical profiles and a high parathyroidectomy rate suggest rebound hyperparathyroidism in renal transplant recipients discontinuing cinacalcet at the time of transplantation, which may be related to the short exposure time specific to this population. Risk/benefit studies are urgently required to define the role of continued calcimimetic treatment in renal transplant recipients and to determine the optimal treatment of secondary hyperparathyroidism in patients listed for transplantation.     

Therapeutic management of post‐kidney transplant hyperparathyroidism

Copley JB, Wüthrich RP. Therapeutic management of post‐kidney transplant hyperparathyroidism.
Clin Transplant 2011: 25: 24–39. © 2010 John Wiley & Sons A/S. Abstract: Left uncontrolled, persistent post‐kidney transplant hyperparathyroidism (HPT) may lead to or exacerbate pre‐existing bone and cardiovascular disease. Parathyroidectomy has long been the primary treatment option for long‐term uncontrolled HPT in post‐kidney transplant patients. However, patients with contraindications for surgery and parathyroidectomy‐associated complications, including graft loss, highlight the need for other approaches. Conventional medical therapies have limited impact on serum calcium (Ca) and parathyroid hormone (PTH) levels. Bisphosphonates and calcitonin, used to spare bone loss, and phosphorus supplementation, to correct hypophosphatemia, do not directly regulate PTH or Ca. Although vitamin D supplementation can reduce PTH, it is often contraindicated because of hypercalcemia. Studies of the calcimimetic cinacalcet in patients with post‐kidney transplant HPT suggest that it can rapidly reduce serum PTH and Ca concentrations while increasing serum phosphorus concentrations toward the normal range. Although the clearest application for cinacalcet is the non‐surgical treatment of hypercalcemic patients with persistent HPT, current indications for other transplant patients are as yet uncertain. Further studies are needed to determine the utility of cinacalcet in patients with spontaneous resolution of HPT or low bone turnover. This review discusses the pathophysiology of post‐kidney transplant HPT, associated complications, and current options for clinical management.     

Treatment of severe hypercalcemia due to refractory hyperparathyroidism in renal transplant patients with the calcimimetic agent cinacalcet

Calcimimetic agents increase the sensitivity of calcium sensing receptors of parathyroid glands and suppress both serum calcium levels and parathyroid hormone. There are still limited data on the treatment of renal transplant patients with severe hypercalcemia and hyperparathyroidism with calcimimetics (cinacalcet). We describe two such renal transplant patients with chronic kidney disease Stage 3 who presented with persistent hypercalcemia (serum calcium 11.5-12 mg/dl) and refractory hyperparathyroidism (iPTH 194-547 pg/ml). Control of hypercalcemia with cinacalcet (serum calcium <10 mg/dl) resulted also in an improvement of hyperparathyroidism, but with a slower rate than that of the lowering of serum calcium. Addition of a vitamin D analog together with the calcimimetic agent resulted in faster control of the resistant hyperparathyroidism in both patients (iPTH <145 pg/ml) with clinical improvement and without any side effect. It seems that this new agent will improve our clinical approach of renal bone disease permitting a more integrated and successful treatment of hyperparathyroidism and its consequences on patients with chronic kidney disease.     

Subtotal parathyroidectomy with thymectomy for autonomous hyperparathyroidism after renal transplantation

BACKGROUND: There is currently no consensus on the operation that should be performed in patients with tertiary hyperparathyroidism (HPT) after renal transplantation. METHODS:: A retrospective analysis of 70 patients with tertiary HPT who underwent subtotal parathyroidectomy with transcervical thymectomy was performed. RESULTS: Mean (s.d.) follow-up was 5.6(5.0) years. Mean (s.d.) glomerular filtration rate (GFR) at follow-up was 42(29) ml/min and was less than 30 ml/min in 26 patients (37 per cent), 30-60 ml/min in 25 (36 per cent) and more than 60 ml/min in 19 (27 per cent). One patient had persistent disease and was cured after reoperation. No patient was hypercalcaemic. Four patients (6 per cent) with a GFR below 30 ml/min had a parathyroid hormone (PTH) level more than four times the normal value without any signs or symptoms of secondary HPT. One patient (1 per cent) was hypocalcaemic and two (3 per cent) were normocalcaemic, with undetectable or below-normal PTH levels while receiving oral vitamin D and calcium medication. CONCLUSION: Systematic subtotal parathyroidectomy associated with thymectomy is effective in treating most renal transplant recipients with tertiary HPT and also minimizes the recurrence of HPT in patients with declining renal function.     

Early and Severe Hyperparathyroidism Associated with Hypercalcemia After Renal Transplant Treated with Cinacalcet

Bone disease is a common clinical problem following renal transplantation. In renal transplant recipients, multiple underlying factors determine the extent of bone loss and the subsequent risk of fractures. In addition to the well-recognized risk to bone disease posed by steroids, calcineurin inhibitors and pre-existing bone disease, persistent hyperparathyroidism (HPT) contributes to post-transplant bone loss. HPT is usually treated with vitamin D supplements combined with calcium. Patients whose HPT is associated with hypercalcemia pose a difficult therapeutic dilemma which often requires parathyroidectomy. Cinacalcet, a calcium mimetic agent, offers a unique pharmacologic approach to the treatment of patients with post-transplant hypercalcemia and HPT. In this paper, we describe the clinical course and biochemical changes in 10 renal transplant recipients with hypercalcemia and severe HPT early after renal transplantation treated with cinacalcet. Cinacalcet therapy corrected hypercalcemia and decreased parathyroid hormone (PTH) levels in all cases. A transient rise in the level of alkaline phosphatase was noted following initiation of cinacalcet therapy. In this patient population, correction of HPT was not permanent as discontinuing cinacalcet therapy led to a rapid rise in PTH level.     

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.     

Effect of cinacalcet on hypercalcemia and bone mineral density in renal transplanted patients with secondary hyperparathyroidism

BACKGROUND: Persistent secondary hyperparathyroidism (SHP) is the most frequent cause of hypercalcemia observed in approximately 10% of renal transplanted (RT) patients 1 year after surgery. Persistent SHP with hypercalcemia is an important factor of bone loss after renal transplantation. This study prospectively evaluates the effects of Cinacalcet therapy on serum calcium (SCa) and parathyroid hormone (PTH) blood levels, and basically on bone mineral density (BMD) in RT patients with persistent hyperparathyroidism. METHODS: Nine RT patients (eight women, one man) with allograft function more than 6 months were included based on total SCa more than 10.5 mg/dL and intact parathyroid hormone (iPTH) concentration more than 65 pg/mL. After inclusion, patients started on a single daily oral dose of 30 mg of Cinacalcet. At inclusion and every study visit blood levels of creatinine, Ca, P, alkaline phosphatase, iPTH 1,25- dihydroxyvitamin D3, and 25-hydroxyvitamin D3 were assessed. Baseline and at the end of study radial BMD were measured. Study follow-up was 12 months. RESULTS: During the study period, SCa decreased from 11.72+/-0.39 to 10.03+/-0.54 mg/dL (P<0.001). iPTH decreased from 308.85+/-120.12 to 214.66+/-53.75 mg/dL (P<0.05). The mean serum creatinine decreased from 1.58+/-0.34 to 1.25+/-0.27 mg/dL (P=0.03) and the mean radial BMD increased from 0.881+/-0.155 to 0.965+/-0.123 gr/cm2 (P<0.05). There were no significant changes in the other parameters assessed. One patient was excluded for gastrointestinal intolerance. CONCLUSIONS: In RT patients with hypercalcemia secondary to persistent SHP, Cinacalcet corrects hypercalcemia and PTH, simultaneously improving BMD.     

超声引导下微波消融治疗肾移植术后继发性甲状旁腺功能亢进

目的评估超声引导下微波消融(MWA)治疗肾移植术后继发性甲状旁腺功能亢进(SHPT)的安全性和有效性。方法回顾性分析20例肾移植术后接受MWA治疗的SHPT患者,比较消融前后全段甲状旁腺激素(iPTH)、血钙、血磷、血肌酐和血尿素氮水平变化。结果20例患者共34枚甲状旁腺增生结节均一次性完全消融,平均最大径为(1.41±0.61)cm,中位消融时间219 s。消融后iPTH、血钙、血磷水平均明显低于消融前(P<0.05)。血肌酐、血尿素氮水平在消融前后无明显变化(P>0.05)。未见手术相关严重并发症发生。结论超声引导下MWA是治疗肾移植后SHPT安全、有效的方法。     

Cinacalcet for the treatment of hypercalcemia in renal transplanted patients with secondary hyperparathyroidism

Persistent hyperparathyroidism is the most frequent cause of hypercalcemia after renal transplantation, namely, hypercalcemia is observed in about 10% of patients at 1 year. This prospective study evaluated the effect of cinacalcet, a second-generation calcimimetic, on serum calcium and parathyroid hormone (PTH) blood levels among recipients with hypercalcemia due to persistent hyperparathyroidism. Thirteen renal transplanted patients (10 women and 3 men) were included based upon: a total serum calcium >10.5 mg/dL; intact PTH (iPTH) blood levels >65 pg/mL; graft function >6 months, and stable maintenance immunosuppressive therapy. After inclusion, patients initially received 30 mg of cinacalcet once daily. The mean time of initiation was 64 +/- 7 months after transplantation. The follow-up was 6 months. The median dose of cinacalcet was 30 mg/d (5 patients received 60 mg/d). During the study period, renal function remained stable. Serum calcium levels decreased significantly from 11.7 +/- 0.39 to 10.35 +/- 0.8 mg/dL (P < .001). Serum phosphate levels increased from 2.82 +/- 0.34 mg/dL to 3.2 +/- 0.41 mg/dL (P < .05). The mean iPTH levels significantly decreased from 308 +/- 120 to 210 +/- 80 pg/mL (P < .05). There were no significant change in 25-hydroxyvitamin D3 blood levels (from 17.7 +/- 9 to 17.4 +/- 6 ng/mL), but the 1,25-dihydroxyvitamin D3 blood levels decreased from 53.8 +/- 18.2 to 32.6 +/- 9.2 pg/mL (P < .01). There were no significant changes in blood levels of alkaline phosphatase, magnesium, bicarbonate, calciuria, phosphaturia, and immunosuppressive drugs. Cinacalcet was well tolerated in all patients except one who had gastrointestinal discomfort. In summary, cinacalcet corrected hypercalcemia and improved phosphatemia in patients with persistent hyperparathyroidism after transplantation with no negative effects on renal function.     

Vitamin D deficiency in a renal transplant population: safe repletion with moderate doses of calcidiol

Background

Deficits of vitamin D are a common finding in the general population, especially among patients with chronic kidney disease. However, there are not much data about its prevalence after renal transplantation. Our aim was to analyze the calcidiol status among a cohort of kidney transplant recipients, in a region of Spain with a high number of annual sunshine hours, as well as the effects of supplementation with oral calcidiol.

Patients and methods

We included 110 kidney transplant recipients in a retrospective observational study. Measurements of 25-hydroxyvitamin D (25OHD), calcium, phosphate, intact parathyroid hormone (iPTH), serum creatinine and albumin, 24-hour microalbuminuria, and proteinuria were performed at the same time. Patients were classified based on their serum 25OHD levels: normal (>30 ng/mL); insufficiency (16-30 ng/mL); and deficiency (<16 ng/mL). In a second analysis, we included 63 patients with 25OHD <30 ng/mL with adjusted calcium levels below 10.2 mg/dL for treatment with oral calcidiol to approach target levels of 30 to 40 ng/mL. Mineral metabolism parameters were monitored at baseline as well as 6 and 12 months after beginning treatment.

Results

Insufficient or deficient 25OHD levels were present in 106/110 patients (96.3%); they were normal in just four patients (3.6%). Patients with calcidiol deficiency were older. We observed no differences in sex, posttransplant follow up, serum calcium, phosphate, iPTH, glomerular filtration rate, or 24- hour albuminuria or proteinuria. The 63 patients treated with oral calcidiol received a mean dose of 8044 ± 4087 IU/wk at baseline. The 61.3% of them with deficient 25OHD levels at baseline decreased to 2.1% at 6 months and 7.5% at 12 months after treatment. No significant changes in calcium, phosphate or iPTH were observed during the treatment.

Conclusions

Deficits of 25 OHD was frequent after renal transplantation but improved safely with moderate doses of oral calcidiol without negative secondary effects.     

甲状旁腺切除术对肾性继发性甲状旁腺功能亢进患者NLR、PLR的影响

目的 探讨甲状旁腺切除术对肾性继发性甲状旁腺功能亢进(secondary hyperpar-athyroidism,SHPT)患者中性粒细胞/淋巴细胞比值(neutrophil-to-lymphocyte ratio,NLR)、血小板/淋巴细胞比值(platelet-to-lymphocyte ratio,PLR)的影...     

Percutaneous ethanol injection therapy in post-transplant patients with secondary hyperparathyroidism

Persistent hyperparathyroidism is frequent in postrenal transplant patients. Percutaneous ethanol injection therapy (PEIT) is an alternative for treatment of patients with secondary hyperparathyroidism but it was not described in postrenal transplant patients. We report our experience with PEIT to control hyperparathyroidism in the post-transplant period. We performed PEIT under ultrasonographic guidance and local anesthesia in eight patients because of persistent secondary hyperparathyroidism after renal transplantation. Indications for PEIT were: high intact parathyroid hormone (iPTH) levels with hypercalcemia, hypophosphatemia, osteopenia and/or bone pain. All patients had at least one visible parathyroid nodule by ultrasonography. Biochemical assays were performed immediately before PEIT, between 1 and 7 days after last PEIT, and a mean of 8.0 +/- 2.8 months after PEIT. Serum iPTH and calcium levels decreased significantly after treatment and remained unchanged until final control. Serum iPTH decreased from 286.9 +/- 107.2 to 154.6 +/- 42.2 pg/ml (P < 0.01) after PEIT (percentual reduction 36.5 +/- 9.5%). This response was significantly correlated to total ethanol volume used (r: 0.94, P < 0.0001). Hypercalcemia disappeared in six of eight patients treated. Only minor complications were registered. There were no changes in renal function related to the treatment. Our findings show that PEIT is a useful and safe alternative for patients with persistent post-transplant secondary hyperparathyroidism.     

Changes in bone mineral density and selected metabolic parameters over 24 months following renal transplantation

Our aim was to evaluate changes in serum levels of selected bone metabolism indicators and bone density over 24 months following renal transplant. A partial objective was assessment of the effectiveness of prophylactic administration of vitamin D and calcium preparations to prevent progression of osteopathy after kidney transplantation. Forty patients after kidney transplantation were prophylactically given vitamins A and D (800 IU) and calcium (1000 mg) a day. During monitoring, the serum creatinine in all recipients was <200 micromol/L (subgroup A with creatinine concentration < 120 micromol/L versus subgroup B with creatinine 120 to 200 micromol/L). The concentration of serum parathormone, serum level of bone fraction of alkaline phosphatase, serum concentrations of phosphorus and calcium urinary 24-hour excretion of phosphorus and calcium were examined at 2 weeks and 2 years after transplantation. In the same time period, radiographs of thoracic, lumbar spine, and hip joints were obtained. Bone density (BMD) of the lumbar (L) spine and the hip was determined by dual-energy X ray (Lunar Prodigy). Two years after transplantation in subgroup A, the BMD showed decrease in 80% of recipients in the L spine area but hip showed a 15% BMD increase. In subgroup B, the BMD decreased in 95% recipients in L and hip and only 25% showed a BMD increase. No clinical or radiographic sign of fracture was detected in this group. We conclude that prophylactic administration of vitamin D and calcium is not sufficient to prevent the progression of osteopathy after renal transplantation. Changes in bone density evaluated after the kidney transplantation are affected by graft function.     

Absence of effect of 24,25-dihydroxycholecalciferol on serum immunoreactive PTH in patients with persistent hyperparathyroidism after renal transplantation

Three hypercalcemic renal transplant recipients with stable, excellent renal function (creatinine clearance 74 +/- 11.8 ml/min) were treated with 60 micrograms 24,25(OH)2D3 by mouth daily for three months. Immunoreactive c-terminal PTH, intact PTH, 1,25(OH)2D3, 25(OH)D3, 24,25(OH)2D3, and serum and 24 h urine calcium, phosphate, magnesium and creatinine were obtained before, at one week, one month and three months of treatment, and at six weeks post-treatment. Significant elevations in serum levels of 24,25(OH)2D3 were induced by therapy (1.32 +/- .16 ng/ml to 30.06 +/- 5.18 ng/ml at one month). Moderate elevations of c-terminal PTH and normal levels of intact PTH remained unchanged throughout the study. Serum calcium remained elevated, serum phosphate and magnesium remained depressed and creatinine clearance and urinary excretion of calcium, phosphate, and magnesium remained unchanged. Furthermore, 1,25(OH)2D3 and 25(OH)D3 remained in the normal range throughout the study. We conclude that 24,25(OH)2D3 did not have a suppressant effect on levels of iPTH in the clinical setting of persistent hyperparathyroidism after successful renal transplantation.     

Tertiary ''Hyperphosphatoninism'' Accentuates Hypophosphatemia and Suppresses Calcitriol Levels in Renal Transplant Recipients

Hypophosphatemia and inappropriately low calcitriol levels are frequently observed following successful renal transplantation. Fibroblast growth factor-23 (FGF-23) is a recently characterized phosphaturic hormone that inhibits renal 1 alpha-hydroxylase activity and may be involved in the pathogenesis of both phenomena. The following hypotheses were tested: pretransplant FGF-23 predicts posttransplant FGF-23, FGF-23 predicts posttransplant hypophosphatemia and FGF-23 is associated with decreased calcitriol levels independent of renal and parathyroid function. Serum biointact parathyroid hormone (PTH), calcidiol, calcitriol, full-length FGF-23, calcium and phosphate were monitored in 41 renal transplant recipients at the time of transplantation (pre) and 3 months thereafter (post). In addition, serum phosphate nadir in each individual patient was identified and urinary fractional excretion of phosphate (FE(PO4)) at month 3 was calculated. High FGF-23(post) levels were independently associated with high FGF-23(pre), low calcitriol(post) and high calcium(post) levels. FGF-23, but none of the other mineral metabolism indices, was an independent predictor of the phosphate nadir in the early posttransplant period. A high FGF-23(post) level was independently associated with a high FE(PO4). High FGF-23(post) and creatinine levels and low PTH(post) levels were independently associated with low calcitriol(post) levels. In conclusion, our data indicate that persistence of FGF-23 contributes to hypophosphatemia and suboptimal calcitriol levels in renal transplant recipients.     

Eculizumab for Prevention of Antibody-Mediated Rejection in Blood Group-Incompatible Renal Transplantation

Antibody-mediated rejection (AMR) is one of the leading causes of allograft failure especially in patients undergoing ABO-incompatible (ABOi) renal transplantation. We hypothesized that complement inhibition with eculizumab, a C5 inhibitor, would protect against AMR and maintain graft function in ABOi renal transplant recipients. Four patients undergoing living donor kidney transplant from ABOi donors were treated with a 9-week eculizumab course without therapeutic plasma exchange, intravenous immunoglobulin, or splenectomy. All patients had successful transplants and have normal graft function at the time of last follow-up. There were no cases of AMR or acute cellular rejection. Of note, 2 patients were transplanted despite persistent ABO antibody titers of 1:32, conventionally considered a contraindication to proceed in standard protocols. Eculizumab is a promising option to prevent AMR with ABOi renal transplantation without the need for splenectomy, post-transplant therapeutic plasma exchange, and intravenous immunoglobulin. Future multicenter studies are needed to determine long-term efficacy and safety.