Posttransplant Hyperparathyroidism Research Articles

Impact of hyperparathyroidism on allograft histology and function after kidney transplantation: Rethinking its causal role in graft dysfunction.

The causal relationship between hyperparathyroidism and kidney graft dysfunction remains inconclusive. Applying Bradford-Hill's temporality and consistency causation principles, we assessed the effect of parathyroid hormone (iPTH) on graft histology and eGFR trajectory on kidney transplant recipients (KTRs) with normal time-zero graft biopsies. Retrospective cohort study evaluating the effect of hyperparathyroidism on interstitial fibrosis and tubular atrophy (IF/TA) development in 1232 graft biopsies. Pre-transplant hyperparathyroidism was categorized by KDIGO or KDOQI criteria, and post-transplant hyperparathyroidism by iPTH>1× and>2× the URL 1 year after transplantation. We included 325 KTRs (56% female, age 38±13 years, follow-up 4.2 years [IQR: 2.7-5.8]). Based on pre-transplant iPTH levels, 26% and 66% exceeded the KDIGO and KDOQI targets, respectively. There were no significant differences in the development of>25% IF/TA between KTRs with pre-transplant iPTH levels above and within target range according to KDIGO (53%vs. 62%, P=.16, HR.94 [95% CI:.67-1.32]) and KDOQI (60%vs. 60%, P=1.0, HR 1.19 [95% CI:.88-1.60]) criteria. Similarly, there were no differences when using 1 year post-transplant iPTH cut-offs>88 pg/mL (58%vs. 64%, P=.33) and>176 pg/mL (55%vs. 62%, P=.19). After adjusting for confounders, no significant differences were observed in eGFR trajectories among the iPTH strata. In young KTRs who received a healthy graft, no association was found between increased pre- and post-transplant iPTH levels and graft dysfunction, as assessed histologically and through eGFR trajectory. The concept of hyperparathyroidism as a risk factor for graft dysfunction in recipients at low risk requires reevaluation.

Factors Associated With Persistent Post-transplant Hyperparathyroidism After Index Renal Transplantation

IntroductionSecondary hyperparathyroidism (SHP) is common in end-stage renal disease and may progress to persistent post-transplant hyperparathyroidism (PTHP) following renal transplantation (RT). We sought to describe the frequency and determine factors associated with the incidence of PTHP for patients undergoing RT at a single institution that restricts RT for patients with uncontrolled SHP with a parathyroid hormone (PTH) of >800pg/mL at time of initial transplant evaluation. MethodsWe conducted a single-institution retrospective study of adults undergoing index RT from 2012 to 2020 who had a calcium and PTH level within 12 mo prior to RT and at least 6 mo following RT. PTHP was defined as calcium of >10 mg/dL with an elevated PTH > 88pg/mL at six or more months following RT. Univariate analysis and multivariable logistic regression were performed for factors associated with developing PTHP. ResultsWe identified 1110 patients with RT, 65 were excluded for prior RT, 549 did not have a pre-RT and post-RT calcium, and PTH laboratories for inclusion, yielding 496 for analysis. Following RT, 39 patients (7.9%) developed PTHP, compared to those who did not develop PTHP; these patients had significantly higher pre-RT PTH, pre-RT calcium, and frequency of calcimimetic therapy. In multivariable logistic regression factors significantly associated with PTHP were pre-RT calcium of more than 10 mg/dL with an odds ratio (OR) of 3.57 (95% confidence interval [CI] 1.52-8.39, P = 0.003) and pre-RT calcimimetic therapy with an OR 1.30 (95% CI 1.06-2.85, P = 0.041). Compared with patients who had a pre-RT PTH of less than 200 pg/mL, a PTH of 200-399 pg/mL increased risk of PTHP with an OR of 4.52 (95% CI 1.95-21.5, P = 0.048) and a PTH of > 400 pg/mL increased risk of PTHP with an OR of 7.17 (95% CI 1.47-34.9, P = 0.015). In this cohort, 11 patients (28.2%) with PTHP underwent parathyroidectomy (PTx) at a mean of 1.4 y post-RT (standard deviation 0.87). ConclusionsFor patients required to have a PTH < 800pg/mL for initial transplant candidacy, the subsequent incidence of PTHP is relatively low at 7.9%. Risk factors for PTHP include higher pre-RT calcium and PTH levels and pre-RT calcimimetic therapy. PTx remains underused in the treatment of PTHP. Further study is warranted to determine the optimal PTH cutoff for transplant candidacy and recommendation for PTx in patients requiring calcimimetic therapy for SHP.

Systematic Review of the Treatment of Persistent Hyperparathyroidism Following Kidney Transplantation.

Chronic kidney disease-mineral and bone disorder is one of the complications associated with chronic kidney disease. About 10-50% of patients following kidney transplantation have persistent hyperparathyroidism. Hypercalcaemic hyperparathyroidism has a negative impact on the kidney transplant outcome; therefore, it requires treatment. The data regarding the treatment of persistent hyperparathyroidism provided in scientific publications are divergent and contradictory. Therefore, the aim of our systematic review was to evaluate the efficacy of persistent hyperparathyroidism treatment in patients following kidney transplantation. The Cochrane, PubMed, and Scopus databases were browsed independently by two authors. The search strategy included controlled vocabulary and keywords. The effectiveness of calcitriol, paricalcitol, cinacalcet, and parathyroidectomy was compared and analysed. The mean calcium and parathormone (PTH) concentrations per patient in the group of paricalcitol increased by 1.27% and decreased by 35.14% (n = 248); in the group of cinacalcet decreased by 12.09% and 32.16% (n = 368); and in the group of parathyroidectomy decreased by 19.06% and 86.49% (n = 15) at the end of the study compared to the baseline (n = 244, n = 342 and n = 15), respectively. Paricalcitol, cinacalcet, and parathyroidectomy decreased the intact PTH level. Cinacalcet and parathyroidectomy lowered calcium levels in renal transplant patients with hypercalcaemia. Conversely, paricalcitol increased the serum calcium concentration. Cinacalcet seems to be a good candidate in the treatment of post-transplant hyperparathyroidism.

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 Pinteraction > .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.

Parathyroidectomy and Cinacalcet Use in Medicare-Insured Kidney Transplant Recipients

Posttransplant hyperparathyroidism is common, and treatment practices are poorly characterized. The goal of this study was to examine the incidence, associations, and outcomes of posttransplant parathyroidectomy and calcimimetic use in a cohort of Medicare-insured US kidney transplant recipients. Retrospective observational cohort study. We used the US Renal Data System to extract demographic, clinical, and prescription data from Medicare Parts A, B, and D-insured patients who received their first kidney transplant in 2007-2013. We excluded patients with pretransplant parathyroidectomy. Calendar year of transplantation and pretransplant patient characteristics. (1) Incidence of and secular trends in parathyroidectomy and cinacalcet use in the 3 years after transplant; (2) 90-day outcomes after posttransplant parathyroidectomy and cinacalcet initiation. Temporal trends and pretransplant correlates of parathyroidectomy and cinacalcet use were assessed using proportional hazards models and multivariable Poisson regression, respectively. The inclusion criteria were met by 30,127 patients, of whom 10,707 used cinacalcet before transplant, 551 underwent posttransplant parathyroidectomy, and 5,413 filled≥1 prescription for cinacalcet. The rate of posttransplant parathyroidectomy was stable over time. By contrast, cinacalcet use increased during the period studied. Long dialysis vintage and pretransplant cinacalcet use were strongly associated with posttransplant parathyroidectomy and cinacalcet use. Roughly 1 in 4 patients were hospitalized within 90 days of posttransplant parathyroidectomy, with hypocalcemia-related diagnoses being the most common complication. Parathyroidectomy (vs cinacalcet initiation) was not associated with an increase in acute kidney injury. We lacked access to laboratory data to help assess the severity of secondary/tertiary hyperparathyroidism. The cohort was limited to Medicare beneficiaries. Almost one-fifth of our study cohort was treated with parathyroidectomy and/or cinacalcet. Further studies are needed to establish the optimal treatment for posttransplant hyperparathyroidism.

Prevalence and risk factors for postrenal transplant hyperparathyroidism: A cross-sectional study

Introduction: Chronic kidney disease (CKD) commonly results in secondary hyperparathyroidism. Even after a successful renal transplant, residual parathyroid overactivity persists. We studied its prevalence and risk factors in Indian patients. Patients and Methods: Patients who underwent renal transplantation in our unit from 2013 to 2019 and completed 3 months of the posttransplant period were included. We excluded patients with advanced allograft dysfunction and those on medications with the potential impact of divalent cations. A detailed history, physical examination, and laboratory parameters were obtained. Results: There were 110 subjects, of whom 78% were male. The mean age group was 38 ± 12 years. Chronic glomerulonephritis was the most common etiology of CKD (54%). Posttransplant vintage was 48 ± 44 months. The mean serum parathyroid hormone (PTH) level was 135 ± 176 pg/ml. Sixty-seven percent of them had raised serum PTH levels above 70 pg/ml. The patients were asymptomatic. Hypercalcemia and hypophosphatemia were rare. The mean 25 OH Vitamin D levels were low (23 ± 8 ng/ml) with 41% of the subjects showing either deficiency or insufficiency. Higher serum PTH levels were significantly associated with female sex, lower estimated glomerular filtration rate, and lower serum 25 OH Vitamin D levels. Serum parathormone levels were significantly negatively correlated with serum calcium (r 2 = −0.39. P = 0.0003) and Vitamin D levels (r 2 = −0.50. P = 0.002). Conclusions: Posttransplant hyperparathyroidism (PTHP) persists even after many years of normal allograft function. Hypercalcemia and hypophosphatemia are insensitive tests to identify the condition. Vitamin D deficiency has a strong correlation with PTHP.

Causes of hypercalcemia in renal transplant recipients: persistent hyperparathyroidism and others.

Hypercalcemia is common in patients after kidney transplantation (KTx) and is associated with persistent hyperparathyroidism in the majority of cases. This retrospective, single-center study evaluated the prevalence of hypercalcemia after KTx. KTx recipients were evaluated for 7 years after receiving kidneys from living or deceased donors. A total of 301 patients were evaluated; 67 patients had hypercalcemia at some point during the follow-up period. The median follow-up time for all 67 patients was 62 months (44; 80). Overall, 45 cases of hypercalcemia were classified as related to persistent post-transplant hyperparathyroidism (group A), 16 were classified as “transient post-transplant hypercalcemia” (group B), and 3 had causes secondary to other diseases (1 related to tuberculosis, 1 related to histoplasmosis, and 1 related to lymphoma). The other 3 patients had hypercalcemia of unknown etiology, which is still under investigation. In group A, the onset of hypercalcemia after KTx was not significantly different from that of the other groups, but the median duration of hypercalcemia in group A was 25 months (12.5; 53), longer than in group B, where the median duration of hypercalcemia was only 12 months (10; 15) (P<0.002). The median parathyroid hormone blood levels around 12 months after KTx were 210 pg/mL (141; 352) in group A and 72.5 pg/mL (54; 95) in group B (P<0.0001). Hypercalcemia post-KTx is not infrequent and its prevalence in this center was 22.2%. Persistent hyperparathyroidism was the most frequent cause, but other important etiologies must not be forgotten, especially granulomatous diseases and malignancies.

Safety and Efficacy of a 3-Year Therapy With Cinacalcet in Persistent Hyperparathyroidism After Renal Transplant

BackgroundPersistent post-transplant hyperparathyroidism (PPTHP) can occur in 20% to 50% of renal transplant recipients. The aim of this study was to analyze safety and efficacy of long-term cinacalcet therapy in a group of renal transplant recipients with PPTHP. MethodsA single center retrospective cohort study including renal transplant recipients, adults (>18 years old) with PPTHP and hypercalcemia. Inclusion criteria for cinacalcet therapy was increased parathormone levels (PTH > 65 pg/mL) associated with serum calcium >11.5 mg/dL any time after transplant or calcium >10.2 mg/dL within the first year after transplant. The follow-up period was 3 years. Demographic, laboratory data and adverse events were assessed. ResultsForty-six patients were included, mean age of 50 ± 11 years old, majority of white race (60%), male (58%), with a pretransplant length on dialysis of 67 ± 34 months. Cinacalcet therapy was started 37 ± 40 months after transplant, and normal calcium levels were achieved after 6 months of therapy. PTH levels presented a steady reduction over time, reaching levels near normal after 36 months (317 ± 242 vs 145 ± 72 pg/mL, baseline × month 36, P < .05). Renal function remained stable over time (GFR > 60 mL/min/1.73 m2) and no acute rejection episodes were observed. Most common adverse events were mild gastrointestinal symptoms. In 6 patients (12.5%) treatment was interrupted due to adverse events. Only 1 case (2%) was classified as treatment failure. ConclusionCinacalcet therapy proved to be efficient for PPTHP and safe for graft and patient. Long-term treatment reduced PTH levels to near normal range.

The conundrum of parathyroidectomy vs cinacalcet for treatment of post-transplant hyperparathyroidism.

O hiperparatireoidismo persistente em pacientes transplantados renais tem sido associado a aumento da mortalidade, maior risco de perda de aloenxerto e maior risco de o paciente desenvolver fraturas e doencas osseas.1,2 O tratamento do hiperparatireoidismo persistente apos transplante renal permanece controverso para os especialistas em transplante. Existem opinioes divergentes quanto a se o cinacalcet ou a paratireoidectomia levam a melhores resultados para o paciente. Assim, o objetivo de qualquer tratamento seria nao apenas melhorar os resultados laboratoriais, mas tambem aprimorar ou [...]

Management of Post-transplant Hyperparathyroidism and Bone Disease.

Significant advances in immunosuppressive therapies have been made in renal transplantation, leading to increased allograft and patient survival. Despite improvement in overall patient survival, patients continue to require management of persistent post-transplant hyperparathyroidism. Medications that treat persistent hyperparathyroidism include vitamin D, vitamin D analogues, and calcimimetics. Medication side effects such as hypocalcemia or hypercalcemia, and adynamic bone disease, may lead to a decrease in the drugs. When medical management fails to control persistent post-transplant hyperparathyroidism, treatment is a parathyroidectomy. Surgical techniques are not uniform between centers and surgeons. Undergoing the surgery may include a subtotal technique or a technique including total parathyroid gland resection with partial heterotopic gland reimplantation. In addition, there are possible post-surgical complications. The ideal treatment for persistent post-transplant hyperparathyroidism is the treatment and prevention of the condition while patients are being managed for their late-stage chronic kidney disease and end-stage renal disease.

Recent Changes in Chronic Kidney Disease-Mineral and Bone Disorders and Associated Fractures After Kidney Transplantation.

The management of chronic kidney disease-mineral and bone disorders has recently changed. We investigated the modifications of chronic kidney disease-mineral and bone disorder with a special focus on the incidence of fractures in the first year after kidney transplantation (KT). We retrospectively compared 2 groups of patients who consecutively underwent transplantation at our center 5 years from each other. Group 1 consisted of patients (n = 152) transplanted between 2004 and 2006, whereas patients in group 2 (n = 137) underwent KT between 2009 and 2011. During the end-stage renal disease phase at the time of transplant, cinacalcet, and native vitamin D were used significantly more frequently in group 2. Median intact parathyroid hormone levels were lower and severe hyperparathyroidism decreased significantly. Vitamin D deficiency dropped from 64% to 20%. After transplantation, persistent hyperparathyroidism (parathyroid hormone > 130 ng/L) and bone turnover markers were significantly reduced in group 2. Native vitamin D supplementation increased over time, whereas the use of active vitamin D was unchanged. The 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels were significantly higher. The fracture incidence at 1 year decreased significantly (3.1% vs 9.1%; P = 0.047). No steroid sparing was observed in group 2. Bisphosphonates after KT were more frequently used in group 2. Recent changes in clinical practice are associated with reductions in pretransplant and posttransplant hyperparathyroidism, vitamin D deficiency, and fracture risk after KT.

Kidney transplantation and hyperparathyroidism

Successful kidney transplantation eliminates endocrine and metabolic disorders that predispose to the development of hyperparathyroidism, the complication typical for the chronic kidney disease; but the process of recovery from mineral and bone disorders is slowed down. The highest incidence of post-transplant hyperparathyroidism is recorded in the first postoperative year. The risk factors for its development or persistence include the high blood levels of parathyroid hormone, calcium, phosphorus, and/or alkaline phosphatase, a prolonged dialysis therapy, severe hyperparathyroidism in the preoperative period, vitamin D deficiency, a suboptimal transplanted kidney function, and also the recipient's previous history of subtotal or incomplete parathyroidectomy. The characteristic clinical and laboratory signs of posttransplant hyperparathyroidism are bone lesions, kidney graft abnormalities, hypercalcemia, and hypophosphatemia. The diagnostic algorithm includes monitoring the markers of mineral and bone metabolism, determining the bone mineral density, and imaging of thyroid glands. Correction of post-transplant hyperparathyroidism is performed surgically or pharmacologically. The article specifies the indications to, the extent and timing of parathyroidectomy, discusses the use of native vitamin D formulations, its analogues, and calcimimetics.

Natural History of Serum Calcium and Parathyroid Hormone Following Renal Transplantation

BackgroundHyperparathyroidism is common in end-stage renal disease. It often persists following renal transplantation (RTx) and remains elusive to manage due to the lack of evidence base. We therefore present observational data describing the natural history and management of hypercalcemia and hyperparathyroidism following RTx. MethodsSingle-center experience of 216 adult patients undergoing kidney transplantation between January 1, 2011, and December 31, 2012. Data included calcium and parathyroid hormone (PTH) pretransplant and post-transplant at 1, 13, 26, and 52 weeks. Hyperparathyroidism management modalities were also noted. ResultsPersistent hyperparathyroidism (secondary/tertiary) following transplantation was observed in 71 (32.9%) patients. Mean PTH level decreased in the first 3 months post-RTx (3.95 ± 0.14 vs 3.61 ± 0.13 pmol/L; P < .01). Thereafter it remained relatively static until 1 year post-RTx (3.39 ± 0.14 pmol/L). Mean adjusted calcium level rose in the 3 months post-RTx and then remained largely unchanged until 1 year (2.39 ± 0.2 mmol/L, 2.49 ± 0.21 mmol/L, 2.47 ± 0.23 mmol/L at pretransplant, 3 months, and 12 months, respectively). Cinacalcet use pretransplant was significantly associated with reduced post-transplant hyperparathyroidism (15% vs 4.7% respectively, P = .006). There was no association between PTH (3.62 ± 4.16 mmol/L) or adjusted calcium levels (2.51 ± .17 mmol/L) at 6 months and estimated glomerular filtration rate at 1 year (r2 = 0.16 and r2 = 0.23, respectively). ConclusionTertiary hyperparathyroidism following RTx is common. However, no association was observed between either post-transplant PTH or adjusted calcium and graft function.

Bone disease in post-transplant patients

Mineral and bone disorders are common problems in organ transplant recipients. Successful transplantation solves many aspects of abnormal mineral and bone metabolism, but the degree of improvement is frequently incomplete. Posttransplant bone disease can affect long-term outcomes as well as increase the likelihood of fracture. In this article, we reviewed the major posttransplant bone diseases and recent advances in treatment strategies. Pretransplant bone disease and immunosuppressants are important risk factors for posttransplant bone disease. Corticosteroid withdrawal may result in minimal or no protection against fractures, with increased risk for acute rejection. Vitamin D analogue and bisphosphonate are frequently used to prevent and treat posttransplant osteoporosis. Posttransplant hyperparathyroidism increases the risk for all-cause mortality and graft loss, but not major cardiovascular events. Cinacalcet was well tolerated and effectively controlled hypercalcemic hyperparathyroidism; however, it did not improve bone mineral density and discontinuation led to parathyroid hormone rebound. Six-month paricalcitol supplementation reduced parathyroid hormone levels and attenuated bone remodeling and mineral loss in case of posttransplant hyperparathyroidism. Posttransplant bone diseases present in various forms, including osteoporosis, hyperparathyroidism, adynamic bone disease, and osteonecrosis. Prophylactic and therapeutic approaches to both pretransplant and posttransplant periods should be considered.

The consequences of pediatric renal transplantation on bone metabolism and growth

During childhood, growth retardation, decreased final height and renal osteodystrophy are common complications of chronic kidney disease (CKD). These problems remain present in patients undergoing renal transplantation, even though steroid-sparing strategies are more widely used. In this context, achieving normal height and growth in children after transplantation is a crucial issue for both quality of life and self-esteem. The aim of this review is to provide an overview of pathophysiology of CKD-mineral bone disorder (MBD) in children undergoing renal transplantation and to propose keypoints for its daily management. In adults, calcimimetics are effective for posttransplant hyperparathyroidism, but data are missing in the pediatric population. Fibroblast growth factor 23 levels are associated with increased risk of rejection, but the underlying mechanisms remain unclear. A recent meta-analysis also demonstrated the effectiveness of rhGH therapy in short transplanted children. In 2013, the daily clinical management of CKD-MBD in transplanted children should still focus on simple objectives: to optimize renal function, to develop and promote steroid-sparing strategies, to provide optimal nutritional support to maximize final height and avoid bone deformations, to equilibrate calcium/phosphate metabolism so as to provide acceptable bone quality and cardiovascular status, to correct all metabolic and clinical abnormalities that can worsen both bone and growth (mainly metabolic acidosis, anemia and malnutrition), promote good lifestyle habits (adequate calcium intake, regular physical activity, no sodas consumption, no tobacco exposure) and eventually to correct native vitamin D deficiency (target of 25-vitamin D >75 nmol/l).

Oral Paricalcitol Reduces the Prevalence of Posttransplant Hyperparathyroidism: Results of an Open Label Randomized Trial

Postkidney transplant hyperparathyroidism is a significant problem. Vitamin D receptor agonists are known to suppress parathyroid hormone (PTH) secretion. We examined the effect of oral paricalcitol on posttransplant secondary hyperparathyroidism by conducting an open label randomized trial in which 100 incident kidney transplant recipients were randomized 1:1 to receive oral paricalcitol, 2 μg per day, for the first year posttransplant or no additional therapy. Serial measurements of serum PTH, calcium and bone alkaline phosphatase, 24-h urine calcium and bone density were performed. The primary endpoint was the frequency of hyperparathyroidism 1-year posttransplant. Eighty-seven patients completed the trial. One-year posttransplant, 29% of paricalcitol-treated subjects had hyperparathyroidism compared with 63% of untreated patients (p = 0.0005). Calcium supplementation was discontinued in two control and 15 treatment patients due to mild hypercalcemia or hypercalcuria. Paricalcitol was discontinued in four patients due to hypercalcuria/hypercalcemia and in one for preference. Two subjects required decreasing the dose of paricalcitol to 1 μg daily. Hypercalcemia was asymptomatic and reversible. Incidence of acute rejection, BK nephropathy and renal function at 1 year were similar between groups. Moderate renal allograft fibrosis was reduced in treated patients. Oral paricalcitol is effective in decreasing posttransplant hyperparathyroidism and may have beneficial effects on renal allograft histology.

Cinacalcet for the Treatment of Hyperparathyroidism in Kidney Transplant Recipients

Hyperparathyroidism is present in up to 50% of transplant recipients 1 year after transplant, often despite good graft function. Posttransplant patients frequently have hypercalcemia-associated hyperparathyroidism, limiting the role of vitamin D analogues and sometimes requiring parathyroidectomy. Multiple observational studies have investigated treatment of posttransplant hyperparathyroidism with the calcimimetic agent cinacalcet. We performed a systematic review and meta-analysis of prospective and retrospective studies from 2004 through January 26, 2012, using MEDLINE. We identified studies evaluating treatment with cinacalcet in renal transplant recipients with hyperparathyroidism. We performed random effects meta-analysis to determine changes in calcium, phosphorus, parathyroid hormone, and serum creatinine. Twenty-one studies with 411 kidney transplant recipients treated with cinacalcet for hyperparathyroidism met inclusion criteria. Patients were treated for 3 to 24 months. By meta-analysis, calcium decreased by 1.14 mg/dL (95% confidence interval, -1.00 to -1.28), phosphorus increased by 0.46 mg/dL (95% confidence interval, 0.28-0.64), parathyroid hormone decreased by 102 pg/mL (95% confidence interval, -69 to -134), and there was no significant change in creatinine (0.02 mg/dL decrease; 95% confidence interval, -0.09 to 0.06). Cinacalcet resulted in hypocalcemia in seven patients. The most common side effect was gastrointestinal intolerance. From nonrandomized studies, cinacalcet appears to be safe and effective for the treatment of posttransplant hyperparathyroidism. Larger observational studies and randomized controlled trials, performed over longer follow-up times and looking at clinical outcomes, are needed to corroborate these findings.

Impact of parathyroidectomy on allograft outcomes in kidney transplantation

We performed retrospective, multi-center study of the impacts of parathyroidectomy (PTX) after or before kidney transplantation on allograft outcomes. A total of 63 patients who underwent PTX after kidney transplantation were identified. Deterioration in eGFR by more than 25% at 1 month after PTX occurred in 20% of the patients. The baseline eGFR was significantly lower in impairment group than nonimpairment group [adjusted odds ratio (OR) 0.87, 95% confidence interval (CI) 0.77-0.99, P = 0.033]. Low iPTH concentration after PTX was also a significant risk factor for the renal impairment (OR 0.96, CI 0.94-0.99, P = 0.009). A total of 37 patients who underwent PTX before transplantation were identified. Thirty-six percent of the patients had persistent hyperparathyroidism by 1 year after transplantation. A high iPTH level before PTX was a significant risk factor for persistent post-transplant hyperparathyroidism (adjusted OR 1.002, CI 1.000-1.005, P = 0.039). Finally, eGFR values during the first 5 years after transplantation were significantly lower in the patients who underwent PTX at less than 1 year after transplantation, than the pretransplant PTX patients (P = 0.032). As PTX after kidney transplantation has a risk of deterioration of allograft function, pretransplant PTX should be considered for patients with severe hyperparathyroidism, who could undergo post-transplant PTX.

Clinical Impact of Hypercalcemia in Kidney Transplant

Hypercalcemia (HC) has been variably reported in kidney transplanted (KTx) recipients (5–15%). Calcium levels peak around the 3rd month after KTx and thereafter slightly reduce and stabilize. Though many factors have been claimed to induce HC after KTx, the persistence of posttransplant hyperparathyroidism (PT-HPT) of moderate-severe degree is universally considered the first causal factor. Though not proven, there are experimental and clinical suggestions that HC can adversely affect either the graft (nephrocalcinosis) and other organs or systems (vascular calcifications, erythrocytosis, pancreatitis, etc.). However, there is no conclusive evidence that correction of serum calcium levels might avoid the occurrence of these claimed clinical effects of HC. The best way to reduce the occurrence of HC after KTx is to treat as best we can the secondary hyperparathyroidism (SHP) during the uraemic stages. The indication to Parathyroidectomy (PTX), either before or after KTx, in order to prevent or to treat, respectively, HC after KTx, is still a matter of debate which has been revived by the availability of the calcimimetic cinacalcet for the treatment of PT-HPT. However, we still need to better clarify many points as regards the potential adverse effects related to either PTX or cinacalcet use in this clinical set, and we are waiting for the results of future randomized controlled trials to achieve some more definite conclusions on this topic.

Treatment of Hyperparathyroidism With Cinacalcet in Kidney Transplant Recipients

Background After successful kidney transplantation, hyperparathyroidism can persist in 10%–50% of patients and can harmfully affect bone metabolism. Calcimimetic cinacalcet is a new treatment option in the management of persistent hyperparathyroidism in these patients. Methods This prospective, clinical study of 11 patients included those who had a serum intact parathyroid hormone (iPTH) concentration >65 ng/L, a serum creatinine concentration was <200 μmol/L, stable kidney graft function, and were >1 year since transplantation. Patients were not treated with drugs other than calcitriol that could influence bone metabolism. During the 6-month observation period, in which the stability of measured parameters was determined, and in the 12-month treatment period (cinacalcet 30 mg/d), we followed serum concentrations of calcium, phosphate, iPTH, creatinine, vitamin 25OH D 3, bone-specific alkaline phosphatase (ALP), osteocalcin, collagen degradation fragments (CTX), urinary calcium excretion, and bone mineral density (BMD). Results During the treatment period, the serum calcium concentration decreased significantly (from 2.50 ± 0.12 to 2.32 ± 0.12 mmol/L; P < .01). Serum iPTH concentration decreased significantly (from 247 [range, 199–362] at time 0 to 198 [range, 165–233] ng/L after 1 month of treatment; P < .05), but increased slightly thereafter. After 6 months of treatment, the serum concentration of ALP and CTX increased significantly, but decreased thereafter. There were no significant changes in the other parameters assessed. Renal function remained stable during the treatment period. The BMD of the lumbar spine, hip, and forearm did not change during the 12 months of treatment. Conclusion Cinacalcet was effective in treating posttransplant hyperparathyroidism, resulting in decreased calcemia and transient decreased iPTH. ALP and CTX transiently increased during therapy, but other markers of bone metabolism remained unchanged. Twelve months of cinacalcet treatment did not result in a change in BMD. Cinacalcet seems to be a safe drug with no negative effect on renal function.