SNF472, a novel inhibitor of vascular calcification, could be administered during hemodialysis to attain potentially therapeutic phytate levels.

BACKGROUND: Cardiovascular calcification (CVC) is a major concern in hemodialysis (HD) and the loss of endogenous modulators of calcification seems involved in the process. Phytate is an endogenous crystallization inhibitor and its low molecular mass and high water solubility make it potentially dialyzable. SNF472 (the hexasodium salt of phytate) is being developed for the treatment of calciphylaxis and CVC in HD patients. We aimed to verify if phytate is lost during dialysis, and evaluate SNF472's behaviour during dialysis. METHODS: Dialyzability was assessed in vitro using online-hemodiafiltration and high-flux HD systems in blood and saline. SNF472 was infused for 20 min and quantified at different time points. RESULTS: Phytate completely dialyzed in 1 h at low concentrations (10 mg/l) but not when added at 30 or 66.67 mg/l SNF472. In bypass conditions, calcium was slightly chelated during SNF472 infusion but when the system was switched to dialysis mode the calcium in the bath compensated this chelation. CONCLUSION: Phytate dialyses with a low clearance. The administration of SNF472 as an exogenous source of phytate allows to attain supra-physiological levels required for its potential therapeutic properties. As SNF472 is infused during the whole dialysis session, the low clearance would not affect the drug's systemic exposure.

Primary hyperparathyroidism regression associated to cinacalcet therapy proved by 99mTc-MIBI scintigraphy / Seguimiento mediante gammagrafía con 99mTc-MIBI en un caso de hiperparatiroidismo primario tratado con cinacalcet

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Relationship Between Vitamin D Blood Levels and Cancer Development in Renal Transplant Patients: A Case-Control Study.

BACKGROUND: Malignancy is one of the most common long-term complications in renal transplant patients, often related to immunosuppressive treatment although other factors could be considered. Vitamin D plays an important role in reducing cancer risk. After kidney transplantation (KT), 25-hydroxyvitamin D (25OH-D, or calcidiol) insufficiency concerns >85%. The main aim of the present study was to determine the relationship between calcidiol blood levels and cancer development in KT recipients. METHODS: This was a retrospective observational case-control study including patients who received transplants in our hospital from 2003 to 2009 with a follow-up period to 2015. A total of 738 patients were included; 94 of them developed malignancy process, 80 of whose tumor data were analyzed in the cancer group, and the rest composed the control group. At the moment of cancer presentation, age, sex, primary kidney disease, time after surgery, immunosuppressant schedule, and 25OH-D blood levels were collected. RESULTS: The mean patient age was 57 years. The percentages of man and women were 59.5% and 41.5%. The predominant etiology of kidney disease was chronic glomerulonephritis in 31.9%. There were no significant differences between sex, primary kidney disease, immunosuppressant schedule, or incidence of neoplasm in each group of patients. There were no significant differences in 25OH-D blood levels. The incidence of cancer was 7.1%-13.7% per year. The mean time between the graft surgery and the event was 5.6 years. CONCLUSIONS: In patients with functioning KT, we found no correlation between blood levels of calcidiol and the incidence of cancer.

Transición coordinada del paciente con cistinosis desde la medicina pediátrica a la medicina del adulto / A coordinated transition model for patients with cystinosis: from pediatrics to adult care

Introducción: El aumento de la supervivencia de los pacientes con cistinosis y la propia complejidad de la enfermedad explican la necesidad de implementar un proceso de transición guiada desde la medicina pediátrica hasta la del adulto, que permita garantizar el continuumasistencial y posibilite el empoderamiento del paciente desde el cuidado tutelado al autocuidado. Métodos: Revisión bibliográfica, opinión de expertos, encuestas anónimas a pacientes, familiares y asociaciones. Resultados: Elaboración de un documento de transición coordinada, con propuestas concretas por especialidades y de mejora de la adherencia terapéutica y del autocuidado del paciente. El nefrólogo desempeña un papel clave en la transición en la cistinosis debido a la afectación renal que domina la patología y porque la mayoría de los pacientes han recibido un trasplante renal antes de la edad adulta. Conclusión: Se presenta un documento que establece unas recomendaciones y un cronograma para guiar la transición de los adolescentes y adultos jóvenes con cistinosis en nuestro ámbito (AU)

Introduction: Improved outcome and longer life-expectancy in patients with cystinosis, and disease complexity itself, justify planning a guided-transition of affected patients from Pediatrics to adult medicine. The aims of the process are to guarantee the continuum of care and patient empowerment, moving from guardian-care to self-care. Methods: review of articles, expert opinion and anonymous surveys of patients, relatives and patient advocacy groups. Results: elaboration a new document to support and coordinate the transition of patients with cystinosis providing specific proposals in a variety of medical fields, and adherence promotion. Nephrologists play a key role in transition due the fact that most cystinotic patients suffer severe chronic kidney disease, and need kidney transplantation before adulthood. Conclusion: we present a document providing recommendations and suggesting a chronogram to help the process of transition of adolescents and young adults with cystinosis in our area (AU)

A coordinated transition model for patients with cystinosis: from pediatrics to adult care. / Transición coordinada del paciente con cistinosis desde la medicina pediátrica a la medicina del adulto.

INTRODUCTION: Improved outcome and longer life-expectancy in patients with cystinosis, and disease complexity itself, justify planning a guided-transition of affected patients from Pediatrics to adult medicine. The aims of the process are to guarantee the continuum of care and patient empowerment, moving from guardian-care to self-care. METHODS: review of articles, expert opinion and anonymous surveys of patients, relatives and patient advocacy groups. RESULTS: elaboration a new document to support and coordinate the transition of patients with cystinosis providing specific proposals in a variety of medical fields, and adherence promotion. Nephrologists play a key role in transition due the fact that most cystinotic patients suffer severe chronic kidney disease, and need kidney transplantation before adulthood. CONCLUSION: we present a document providing recommendations and suggesting a chronogram to help the process of transition of adolescents and young adults with cystinosis in our area.

Desensitization in ABO-Incompatible Kidney Transplantation With Low ABO Iso-Agglutinin Titers.

BACKGROUND: In ABO-incompatible (ABOi) kidney transplantation (KT) with low iso-agglutinin (IG) titers (IGT), standard pre-conditioning treatment might be excessive. To try to answer this question, we evaluated the pre-conditioning requirements of a group of ABOi KT with low ABO IGT in our center. Our main objective was to assess desensitization requirements for ABOi KT with low IGT (<16) at Hospital Clinic of Barcelona from 2006 to 2014. METHODS: A retrospective study of desensitization (rituximab and plasma exchange [PE]) requirements for ABOi KT with IGT <16 was conducted. RESULTS: One and 5 years after KT, patient survival was 100%. Renal graft survival was 90% at 1 and 5 years after KT. Mean PE performed before KT was 1.7 (standard deviation [SD], 1.703); 50% of the patients did not receive PE after transplantation, 30% received 2 sessions of PE, and 20% received only 1. The average is 0.8 (SD, 0.91).Follow-up IG determinations remained with low titers (≤8/8). No rebounds of titers were observed during the first 4 to 6 months after transplantation. CONCLUSIONS: Recipients with IGT ≤8 required none or only 1 PE session to reach acceptable titers (titers ≤4) to perform ABOi KT safely. This information is useful to assess the possibility of a minimized desensitization protocol in ABOi KT donors with low titers of IG to reduce adverse effects, reduce cost, and simplify pre-transplant logistics.

Pre-Emptive Retransplantation in Patients With Chronic Kidney Graft Failure.

INTRODUCTION: The aim of this study was to compare the group of patients receiving a new kidney transplant before starting dialysis again (pre-reTR) with a group of patients receiving a new kidney transplant after restarting dialysis (reTR). METHODS: This retrospective cohort included all the kidney retransplantations (second transplantations) between 2000 and 2012 performed at our center and their follow-up until July 2014. We analysed graft and patient survival, rejection rates, and immunologic parameters of these patients. RESULTS: We studied 18 patients who had pre-reTR and 83 who had reTR. In the pre-reTR group no patient had panel-reactive assay (PRA) >10% at any time. In the reTR group 26.5% had PRA >10% at the time of transplantation (P = .014) and 54.2% had a historical highest PRA >10% (P < .001). The rejection rate was 11.1% in the pre-reTR group and 27.7% in the reTR group during the first year post-retransplantation (P = .227). Patient survival rate was 100% in the pre-reTR group at 5 years of follow-up, whereas in the reTR group at 1 year it was 95.2% and 85.9% at 5 years after retransplantation. Allograft survival at 1 and 5 years was 88% and 89%, respectively, in the pre-reTR group. On the other hand, in the reTR group it was 89% after the first year and 65% at 5 years post-retransplantation. CONCLUSION: Pre-emptive renal retransplantation is a feasible option that should be assessed in patients with kidney graft failure and may help to minimize the morbidity associated with dialysis reinitiation.

Economic analysis of the treatment of end-stage renal disease treatment: living-donor kidney transplantation versus hemodialysis.

INTRODUCTION: End-stage renal disease (ESRD) is a major public health problem in the Spanish health system. Kidney transplantation is the treatment of choice, offering better survival and cost-effectiveness than other alternatives. This study aimed to compare the cost of living-donor kidney transplantation (LDKT) during the first year after transplantation with that of hemodialysis (HD). METHOD: A prospective, descriptive study of cost and efficacy was performed in the Hospital Clinic in Barcelona from January to December 2011. We included 106 patients (57 undergoing HD and 49 receiving a LDKT). The costs of LDKT (donor and recipient) and HD were calculated based on our economic database program. RESULTS: The mean age of recipients and donors was 46 ± 15 and 52 ± 10 years, respectively, and 67% of the recipients were men. In HD patients, the mean age was 67 ± 11 years and 62% were men. The total cost of LDKT was €29,897.91 (€8,128.44 for donors and €21,769.47 for recipients). The total cost of HD was €43,000.88 (€37,917 for HD and related procedures plus €5,082 for transport). LDKT represented a savings of €13,102.97 per patient/year and the payback period was less than 1 year. Quality-adjusted life years were higher in LDKT than in HD patients. CONCLUSION: LDKT is cost effective during the first year after transplantation and is associated with enhanced quality of life. From both the medical and economic points of view, pre-emptive LDKD should be encouraged in Spain to reduce the health budget for ESRD.

Efficacy of a simple dosage scheme to convert from shorter-acting erythropoiesis-stimulating agent to continuous erythropoietin receptor activator in kidney transplantation patients.

INTRODUCTION: Anemia after kidney transplantation (KT) has a negative impact on graft and patient survival. Anemia management includes iron supplements and erythropoiesis-stimulating agents (ESAs). Most ESAs require short frequency of administration and conversion to ESAs with longer half-life are complex. OBJECTIVE: This study was performed to assess the efficacy of continuous erythropoietin receptor activator (CERA) in hemoglobin (Hb) maintenance after conversion from shorter-acting ESAs with a simple conversion scheme in kidney transplant recipients. METHOD: This is an open-label, prospective, single-arm, single-center, 12-month follow-up study including 77 anemic KT patients with stable renal function. Baseline and monthly measurements of Hb, iron, and creatinine were performed. The conversion scheme from darbepoetin alfa or epoetin was as follows: <30 µg or 5000 IU/week was switched to 75 µg/mo; between 30-50 or 5000-8000 was switched to 100 µg/mo; >50 µg or 8000 IU was changed to 150 µg/month of CERA. Dose adjustments were performed to maintain Hb levels between 10 g/dL and 12 g/dL. RESULTS: The mean age was 57 ± 19 years. The mean time of conversion after KT was 61 ± 49 months. Before conversion, 62.9% of patients were administered epoetin and 37.1% with darbepoetin alfa. Baseline Hb is noted at 10.6 ± 1.3 g/dL. Thirteen percent of patients started receiving CERA at doses of 50 µg/mo, 66% at 75 µg/mo, 13% at 100 µg/mo, and 8% at 150 µg/mo. During the first month, 21% required dose adjustment (6% were increased, 15% were decreased). The final Hb was 11.2 ± 0.8 g/dL. Iron and creatinine levels remained stable during the follow-up examination. CONCLUSION: We propose a simple scheme of conversion from short-acting ESAs to a once-monthly dose of CERA that provides sustained Hb levels within the recommended target with small dose adjustments and low CERA doses.

The JAK2 46/1 haplotype does not predispose to CALR-mutated myeloproliferative neoplasms.

Somatic mutations in the CALR gene were recently discovered in a substantial proportion of Philadelphia-negative chronic myeloproliferative neoplasm (cMPN) patients lacking JAK2 and MPL mutations. Somatically acquired defects are not the only pathogenic mechanism involved in these disorders. Since germline JAK2 46/1 haplotype predisposes to cMPN-associated mutations, including JAK2V617F and MPLW515K7L, we evaluated whether the 46/1 haplotype also confers susceptibility to CALR-mutated cMPN, both in sporadic and familial cases. The single-nucleotide polymorphism rs10974944, which tags 46/1, was investigated in 155 sporadic MPN patients and 270 unrelated controls, as well as in 11 familial cMPN cases and 36 unaffected relative controls. As described elsewhere, the 46/1 haplotype was overrepresented, both in sporadic and familial cMPN. In sporadic cMPN, the JAK2 46/1 haplotype was closely associated with JAK2V617F (p = 0.0003) but not with JAK2-nonmutated cases. Analysis of CALR-mutated sporadic cMPN (n = 22) showed no association between CALR mutations and 46/1 haplotype (p = 0.87). Regarding the familial cMPN, the prevalence of carriers of the G allele was higher in familial (81.8%) than in sporadic (62%) cMPN, but it did not differ significantly (p = 0.3). Although we described a family with carriers of both JAK2V617F and CALR mutations, due to the low number of CALR-mutated familial cases, we could not determinate whether the JAK2 46/1 haplotype predisposes or does not to CALR-mutated familial cMPN. We conclude, for the first time, that the 46/1 haplotype, unlike JAK2V617F and MPLW515K7L, is not associated with CALR-mutated cMPN.

A randomized study evaluating cinacalcet to treat hypercalcemia in renal transplant recipients with persistent hyperparathyroidism.

Persistent hyperparathyroidism (HPT) after kidney transplantation (KTx) is associated with hypercalcemia, hypophosphatemia and abnormally high levels of parathyroid hormone (PTH). In this randomized trial, cinacalcet was compared to placebo for the treatment of hypercalcemia in adult patients with persistent HPT after KTx. Subjects were randomized 1:1 to cinacalcet or placebo with randomization stratified by baseline corrected total serum calcium levels (≤11.2 mg/dL [2.80 mmol/L] or >11.2 mg/dL [2.80 mmol/L]). The primary end point was achievement of a mean corrected total serum calcium value<10.2 mg/dL (2.55 mmol/L) during the efficacy period. The two key secondary end points were percent change in bone mineral density (BMD) at the femoral neck and absolute change in phosphorus; 78.9% cinacalcet- versus 3.5% placebo-treated subjects achieved the primary end point with a difference of 75.4% (95% confidence interval [CI]: 63.8, 87.1), p<0.001. There was no statistical difference in the percent change in BMD at the femoral neck between cinacalcet and placebo groups, p=0.266. The difference in the change in phosphorus between the two arms was 0.45 mg/dL (95% CI: 0.26, 0.64), p<0.001 (nominal). No new safety signals were detected. In conclusion, hypercalcemia and hypophosphatemia were effectively corrected after treatment with cinacalcet in patients with persistent HPT after KTx.

Hermansky-Pudlak syndrome. Overview of clinical and molecular features and case report of a new HPS-1 variant.

Hermansky-Pudlak syndrome (HPS) is a rare, autosomal recessive disorder affecting lysosome-related organelles (LRO), including dense platelet granules. HPS causes oculocutaneous hypopigmentation, bleeding diathesis and granulomatous colitis or pulmonary fibrosis. To date, there is no curative treatment and the clinical management depends on the severity of symptoms. A prompt diagnosis of HPS patients could improve their quality of life and clinical management. However, the absence of a specific platelet function test, the wide molecular heterogeneity, and the lack of phenotype-genotype correlations hamper the rapid diagnosis. Nine subtypes of HPS have been identified as a result of mutations in nine genes that codify for proteins involved in formation and shuttle of the LRO. The molecular characterization of patients and knowledge derived from animal models of HPS contribute to the understanding of biogenesis and function of the LRO. This paper describes a patient with a novel homozygous nonsense mutation causing HPS and provides a review of the literature focusing on recent advances in the molecular characterization and physiopathology of HPS.

Evaluation of two-step haemoglobin screening with HemoCue for blood donor qualification in mobile collection sites.

BACKGROUND AND OBJECTIVES: Inaccuracy of fingerstick haemoglobin compromises donor's health and losses blood donations. We evaluated the benefit of double haemoglobin screening with HemoCue. STUDY DESIGN AND METHODS: Blood donors underwent fingerstick screening by HemoCue and were driven for donation if capillary haemoglobin was within the regulatory range. Those failing were drawn venous blood and donated if their venous haemoglobin determined with HemoCue was acceptable. RESULTS: Of 276 605 donor clinic visits, 10 011 (3·6%) were assessed by two-step haemoglobin screening using HemoCue, because of low (n = 9444) or high (n = 567) capillary haemoglobin. Among these, 2561 (25·6%) were deemed eligible [recovered donations]. The recovery rate was 23·8% and 55·0% among donors presenting with low and high capillary haemoglobin, respectively. In both categories of attempted donations, capillary and venous haemoglobin with HemoCue correlated significantly in recovered donors (R(2)  ≈ 0·5-0·7) but not in deferred visits (R(2)  < 0·15). Venous haemoglobin with HemoCue and by haematological analyzer significantly correlated in all donations attempts (R(2)  ≈ 0·7). Donors presenting with low capillary haemoglobin showed small bias between capillary and venous haemoglobin by HemoCue (-2·4 ± 6·2 g/l), fingerstick haemoglobin and venous haemoglobin with counter (1·3 ± 7·3 g/l), and venous haemoglobin with HemoCue and counter (3·7 ± 3·9 g/l). This bias was slightly greater in donors with high capillary haemoglobin (-7·5 ± 7·8, 13·7 ± 7·5, and 6·2 ± 7·5, respectively). Double haemoglobin screening by HemoCue reached an accuracy of 87·3% for qualifying donors presenting with low fingerstick haemoglobin. CONCLUSIONS: Double haemoglobin measurement with HemoCue [fingerstick and venous blood if required] is feasible and allows a significant recovery of blood donations.

Los nefrólogos españoles y el manejo de las alteraciones del metabolismo óseo-mineral en la enfermedad renal crónica / Spanish nephrologists and the management of mineral and bone metabolism disorders in chronic kidney disease

El presente estudio fue diseñado para evaluar la percepción actual de los nefrólogos españoles en el manejo clínico de las alteraciones del metabolismo óseo y mineral en la enfermedad renal crónica (CKD-MBD). Para ello se empleó un procedimiento semiestructurado de consenso profesional a distancia, por correo electrónico (método Delphi modificado), a un panel representativo del colectivo nefrológico, bajo la dirección de un comité coordinador. Para analizar la opinión grupal y el tipo de consenso alcanzado sobre cada cuestión planteada, se empleó la posición de la mediana de puntuaciones del grupo y el «nivel de concordancia» alcanzado por los encuestados. Sobre un total de 86 cuestiones se logró un consenso en acuerdo y desacuerdo en 70 (81,4 %), de los cuales un 60,5 % (52 ítems) lo fueron en términos de acuerdo con la aseveración y un 20,9 % (18 ítems) en desacuerdo. En 16 ítems (18,6 %) no se consiguió suficiente unanimidad de criterio en el panel, bien por disparidad de opinión profesional, bien por falta de criterio establecido en una mayoría del comité de expertos. Aceptando las limitaciones del estudio, consideramos que los ítems en los que hubo consenso refuerzan algunos conceptos de CKD-MBD con su repercusión en la práctica clínica diaria y permiten valorar el grado de homogeneidad que podríamos esperar en esta área. Los ítems en los que no hubo consenso nos ayudan a conocer las áreas de incertidumbre y resultan de gran utilidad para precisar en qué aspectos existe una mayor necesidad de profundización y de emprender estudios prospectivos que permitan mejorar el manejo de estas alteraciones (AU)

This study was designed to assess the current perception of Spanish nephrologists in the clinical management of mineral and bone metabolism disorders in chronic kidney disease (CKD-MBD). As such, we used a semi-structured distance professional consensus procedure via e-mail (modified Delphi method) on a representative nephrologist panel, under the direction of a coordinating committee. To analyse the group's opinion and the type of consensus reached on each issue raised, we used the median of the group's scores and the "level of agreement" reached by those surveyed. On a total of 86 issues, a consensus agreement and disagreement was achieved in 70 (81.4%), of which 60.5% (52 items) agreed with the statement and 20.9% (18 items) disagreed. In 16 items (18.6%), there was insufficient unanimity in the panel's opinion, either due to professional opinion disparity or due to the lack of opinion established in the majority of the expert committee. Accepting the study's limitations, we considered that the items for which there was a consensus reinforce some CKD-MBD concepts with their impact on daily clinical practice and allow the degree of homogeneity that we could expect in this area to be assessed. The items in which there was no consensus help us to know the areas of uncertainty and are very useful for clarifying which aspects have a greater need for further knowledge and which areas require prospective studies to be conducted to improve the management of these disorders (AU)

Spanish nephrologists and the management of mineral and bone metabolism disorders in chronic kidney disease.

This study was designed to assess the current perception of Spanish nephrologists in the clinical management of mineral and bone metabolism disorders in chronic kidney disease (CKD-MBD). As such, we used a semi-structured distance professional consensus procedure via e-mail (modified Delphi method) on a representative nephrologist panel, under the direction of a coordinating committee. To analyse the group's opinion and the type of consensus reached on each issue raised, we used the median of the group's scores and the "level of agreement" reached by those surveyed. On a total of 86 issues, a consensus agreement and disagreement was achieved in 70 (81.4%), of which 60.5% (52 items) agreed with the statement and 20.9% (18 items) disagreed. In 16 items (18.6%), there was insufficient unanimity in the panel's opinion, either due to professional opinion disparity or due to the lack of opinion established in the majority of the expert committee. Accepting the study's limitations, we considered that the items for which there was a consensus reinforce some CKD-MBD concepts with their impact on daily clinical practice and allow the degree of homogeneity that we could expect in this area to be assessed. The items in which there was no consensus help us to know the areas of uncertainty and are very useful for clarifying which aspects have a greater need for further knowledge and which areas require prospective studies to be conducted to improve the management of these disorders.

Long-term follow-up after conversion from tacrolimus to cyclosporin in renal transplant patients with new-onset diabetes mellitus after transplantation.

INTRODUCTION: The relationship between anticalcineurin (CNI) drugs and the development new-onset diabetes mellitus after kidney transplantation (NODAT) is well established. Among these agents cyclosporine shows lesser diabetogenicity than tacrolimus. It has been described that conversion from tacrolimus to cyclosporine improves glycemic control; however, there are no studies showing whether this reduced risk is maintained upon long-term follow-up. OBJECTIVE: To evaluate whether CNI drugs conversion from tacrolimus to cyclosporine helps to maintain better glycemic control. MATERIALS AND METHODS: We retrospectively evaluated the evolution of glucose metabolism at 5 years after conversion from tacrolimus to cyclosporine in eight patients (six men) with NODAT. Mean age was 42.8 ± 15 years, and time after transplantation to conversion 128 ± 40 months. We analyzed fasting serum glucose, lipid metabolism, renal function, and cyclosporine levels at 0, 6, 12, 24, 36, 48, and 60 months after conversion. RESULTS: At 6 months after conversion, improved glucose metabolism was observed (268 ± 161 versus 121 ± 31 mg/dL; P < .01) although it was minimal in one case with persistent high blood glycemic levels. Only two patients maintained a normal glucose at the end of follow-up. Five subjects showed increased glycemia at 12 to 24 months after conversion requiring antidiabetic therapy: three patients, insulin and two oral antidiabetic agents. Two patients lost their allografts due to chronic rejection at 32 and 50 months respectively. Among the other six patients, renal function remained stable (1.9 ± 0.6 versus 2.11 ± 0.97 mg/dL; P = NS). There was no significant differences among the other variables. Cyclosporine levels remained stable during the follow-up. CONCLUSION: Conversion of renal transplant patients with NODAT from tacrolimus to cyclosporine improves glucose metabolism in the short term but glycemia increases thereafter.

Cinacalcet treatment for stable kidney transplantation patients with hypercalcemia due to persistent secondary hyperparathyroidism: a long-term follow-up.

BACKGROUND: Cinacalcet is an effective treatment for hypercalcemia due to persistent hyperparathyroidism (HPT) in patients who have undergone kidney transplantation (KT). Few data are available about their long-term follow-up. OBJECTIVE: We aimed to evaluate the long-term efficacy of cinacalcet in functioning stable KT subjects with hypercalcemia secondary to persistent HPT. MATERIAL AND METHODS: Twenty-three patients (6 men) with a stable KT showed persistent hypercalcemia (>12 months) secondary to HPT (parathyroid hormone by radioimmunoassay [iPTH] > 150 pg/mL). The mean age was 54 ± 13 years. Time after KT to beginning cinacalcet treatment was 36.5 ± 37.9 (range 12 to 172) months. Initial cinacalcet doses were 30 mg/d. Median follow-up was 53 ± 7.4 months (range 42 to 60 months). We determined serum calcium, phosphorus, alkaline phosphatase, iPTH, creatinine, and immunosuppressant concentrations at baseline as well as 3, 6, and 12 months and after every 6 months thereafter. RESULTS: Initial serum calcium was 11 ± 0.65 mg/dL and mean calcium during treatment, 10.25 ± 0.81 mg/dL (P < .001). Initial serum phosphorus was 2.8 ± 0.58 mg/dL and mean value serum phosphorus during the treatment period, 3.13 ± 0.6 mg/dL (P = 0.015). Initial iPTH was 260 ± 132 pg/mL and during the treatment period; 237 ± 131 pg/mL (P = ns). There was no change in renal function nor in immunosuppressant blood levels. Doses of cinacalcet at the end of the follow-up were 40.4 ± 18.9 mg/d. CONCLUSION: Cinacalcet was effective for long-term control of hypercalcemia related to persistent HPT for patients with stable KT.

Cinacalcet de novo in persistent hypercalcemia after kidney transplantation secondary to hyperparathyroidism: long-term follow-up and effect of withdrawal.

BACKGROUND: Secondary hyperparathyroidism that persists after kidney transplantation (KT), is the main cause of hypercalcemia. Cinacalcet has been used to control hypercalcemia in KT patients. OBJECTIVE: The aim of this study was to evaluate the effect of de novo cinacalcet in KT patients with hypercalcemia and the evolution after its withdrawal. METHODS: This observational study included 41 KT patients (17 men) with persistent hypercalcemia (>6 months), defined as serum calcium (sCa) ≥10.5 mg/dL, and a mean age of 51.1 ± 13.3 years with a functional allograft for >12 months. The time after surgery to begin cinacalcet was 33 months (range, 12.5-81.3). The initial dose of cinacalcet was 30 mg/d. In a subgroup of 14 patients cinacalcet was stopped after 1 year. We studied the evolution of serum levels of calcium, phosphorus, intact pathyroid hormone (iPTH), and serum creatinine. RESULTS: Calcemia normalized in all patients (sCa <10.2 mg/dL). iPTH decreased (basal 267 ± 212 pg/mL vs final: 219 ± 160 pg/mL; P = ns) Serum phosphorus increased (basal 2.85 ± 0.48 mg/dL vs final 3.16 ± 0.50 mg/dL; P = ns). Renal function remained stable (basal creatinine 1.49 ± 0.48 vs final 1.47 ± 0.32 mg/dL; P = ns). After stopping cinacalcet, in group 1 calcemia persisted at normal levels in 50% (n = 7), but the drug had to be reintroduced in the other 50% after 10 ± 7.9 months. No adverse events were documented. CONCLUSIONS: Cinacalcet is an effective alternative for the treatment of hypercalcemia in patients with persistent hyperparathyroidism after KT. Once the treatment is started, there is presently no invice to disclose to who tolerate its withdrawal or the time to do so.

Withdrawal of cinacalcet at the time of renal transplantation is not a risk factor for allograft calcifications in the early posttransplantation period.

BACKGROUND: Secondary hyperparathyroidism is a relevant problem in patients on dialysis. Cinacalcet in regular clinical practice increases the percentage of patients achieving treatment targets for PTH, Ca and P. We evaluated allograft calcification in serial protocol biopsies after transplantation among patients receiving Cinacalcet on dialysis but discontinued after surgery. METHODS: This retrospective single-centre study included kidney allograft recipients who were receiving Cinacalcet for more than 6 months before surgery and had it withdrawn thereafter. The 46 patients including 17 women showed a mean overall age of 54 ± 30 years. Protocol graft biopsy was performed at 3 and at 12 months. Biochemical analyses at the time of biopsy included blood levels of creatinine, phosphorus, calcium, alkaline phosphatases, iPTH, and proteinuria. RESULTS: Any biopsy showed nephrocalcinosis either intratubular calcifications, or in the parenchyma. There were no changes in calcemia (10.22 ± 0.7 to 10.27 ± 0.7 mg/dL), in alkaline phosphatase (259 ± 119.6 to 255 ± 122.3 mg/dL) nor in iPTH (317 ± 220.2 to 320 ± 168.8 pg/mL) between 3 and 12 months respectively. There was a slight but non-significant increase in serum phosphorus (2.79 ± 0.8 to 3.22 ± 0.9 mg/dL), serum creatinine (1.53 ± 0.6 to 1.84 ± 1.2 mg/dL) and proteinuria (528 ± 603 to 879 ± 1398 mg/24h) between 3 and 12 months respectively. CONCLUSIONS: Withdrawal of Cinacalcet at the time of renal transplantation was not a risk factor for allograft calcifications in the early post-transplant period.