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.

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.

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.

Efficacy of low doses of pamidronate in osteopenic patients administered in the early post-renal transplant.

UNLABELLED: This study evaluates the efficacy of low doses of pamidronate after renal transplantation to prevent bone loss in osteopenic patients. Results show that pamidronate is safe and significantly reduced spinal bone loss when administered immediately after renal transplantation. INTRODUCTION: The purpose of this work is to evaluate the efficacy of two intravenous infusions of pamidronate in the immediate post-transplant period in a renal transplant (RT) population. METHODS: In this 12-month, randomized, double-blind, multicenter trial, 39 kidney recipients with diagnosed osteopenia received two doses of 30 mg of disodium pamidronate (n = 24) or placebo (n = 15), at surgery and 3 months post-RT. All patients received calcium and vitamin D. Bone density of the lumbar spine and total femur was measured by dual-energy X-ray absorptiometry (DXA) and X-rays were performed at RT, 6 and 12 months post-RT. Biochemical and hormonal determinations were performed before and after treatment. RESULTS: Pamidronate significantly reduced spinal bone loss, but no significant benefit was found for the incidence of fractures. Elevated baseline intact parathyroid hormone (iPTH) and bone remodeling markers returned to normal levels 3 months post-RT. However, normal procollagen type I N propeptide (PINP) concentrations were only maintained in the pamidronate group. After RT, a comparable graft function was observed in both groups according to creatinine values, 25-hydroxyvitamin-D (25-OH-D) levels were improved, and serum calcium levels normalized after a transient fall during the first 3 months. CONCLUSION: A low dose of pamidronate prevents bone loss in osteopenic patients when administered immediately after RT.

Evolution of secondary hyperparathyroidism after kidney transplantation in patients receiving cinacalcet on dialysis.

BACKGROUND: Secondary hyperparathyroidism (SHPT) is a relevant problem in patients undergoing dialysis, and cinacalcet hydrochloride seems to be the best option for controlling it. After kidney transplantation (KTx), moderate to severe SHPT may persist and cause hypercalcemia and hypophosphatemia, among other deleterious effects. The number of patients receiving cinacalcet before KTx is increasing. OBJECTIVE: To evaluate the evolution of calcemia, phosphatemia, and intact parathyroid hormone (iPTH) after KTx in patients with SHPT receiving cinacalcet on dialysis. PATIENTS AND METHODS: The study included 19 patients (15 men and 4 women; mean [SD] age, 52 [13] years) undergoing dialysis and receiving cinacalcet before KTx. Mean duration of dialysis before KTx was 33 (25) months, and cinacalcet dose was 45 (15) mg/d. Creatinine, calcium, phosphorus, alkaline phosphatase, and iPTH concentrations were evaluated at baseline (day of surgery), at 15 days after surgery, and then monthly for 6 months. In all patients, cinacalcet therapy was discontinued on the day of surgery. RESULTS: After the first month post-KTx, mean (SD) serum creatinine concentration was 1.6 (0.4) mg/dL and remained stable during follow-up. Calcium and phosphorus concentrations were normal in 13 patients after KTx; however, in 6 patients, hypercalcemia (calcium concentration, 11 [1.3] mg/dL) or hypophosphatemia (phosphorus concentration, 1.7 [0.6] mg/dL) developed, with iPTH concentration of 557 (400) pg/mL and alkaline phosphatase concentration of 307 (114) IU/mL. Treatment with cinacalcet resulted in correction of calcium and phosphorus concentrations (10.1 [0.4] mg/dL and 1.7 [0.7] mg/dL, respectively). Patients in whom hypercalcemia or hypophosphatemia developed were receiving cinacalcet, 60 mg/d or more, during dialysis therapy. Patients who received cinacalcet, 30 mg/d, before KTx did not exhibit hypercalcemia or hypophosphatemia after KTx. CONCLUSION: In patients with HPT undergoing dialysis and receiving cinacalcet, 60 mg/d or more, this drug therapy should be continued after KTx to avert development of hypercalcemia or hypophosphatemia.

Objetivos y método de las recomendaciones de la SEN sobre el manejo de las alteraciones del metabolismo óseo-mineral en los pacientes con enfermedad renal crónica / No disponible

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Localising imaging in secondary hyperparathyroidism.

Preoperative imaging has proved its use successful in the localization of solitary parathyroid adenomas in patients with suspected primary hyperparathyroidism. However, due to multiglandular disease at presentation patients with renal hyperparathyroidism need to be analyzed separately, making the usefulness of imaging techniques controversial. Recently, improved methods of functional imaging like parathyroid scan with 99mTc-sestamibi or positron emission tomography, especially when combined with computed tomography, can provide additional quantitative and qualitative information that has yet to be assessed. Nuclear medicine procedures could prove useful not only in preoperative diagnosis, but also in the selection of medical or surgical therapeutic alternatives in secondary hyperparathyroidism patients. There is evidence that 99mTc-sestamibi uptake in parathyroid hyperplasia or adenoma is related to biochemical markers of parathyroid function. We are only beginning to identify the factors involved in radiotracer uptake by parathyroid cells and how it can be modulated to obtain more accurate results. This review analyzes the current use of non-invasive imaging modalities in patients with secondary hyperparathyroidism, taking into account the latest trends in the field combining anatomic and functional modalities and the relevant factors linked to radiotracer uptake in abnormal hyperfunctioning parathyroid glands.

Conversion from tacrolimus to cyclosporine could improve control of posttransplant diabetes mellitus after renal transplantation.

Posttransplant diabetes mellitus (PTDM) occurs in approximately 15% to 20% of renal transplant patients. It has important clinical implications for graft function and survival. Anticalcineurin drugs are associated with an increased risk of developing PTDM. There is a little evidence that conversion from tacrolimus to cyclosporine (CsA)-based immunosuppression improves glucose metabolism and reverses diabetes. This prospective study included nine renal transplant patients (mean age of 34 +/- 20) with PTDM under immunosuppression with tacrolimus. Five were switched directly to CsA and the other four (glycemia > 250 mg/dL) required insulin and were simultaneously switched to CsA. Basal blood levels of tacrolimus were 7.9 +/- 1.9 ng/dL. Conversion was associated with an early, significant improvement of glycemia and HbA1c blood levels (P < .01). At the end of the follow-up, the glycemia (105 +/- 20 mg/dL) and Hb1Ac (5.1 +/- 0.4 mg/dL) were normal. Insulin was discontinued between 3 and 6 months in all patients who required it at the beginning. Cholesterol did not change significantly and triglycerides decreased significantly (basal 210 +/- 85 mg/dL, at 12 months 125 +/- 29, P < .01). Graft function was stable with a mean serum creatinine of 1.7 +/- 0.2 mg/dL. CsA blood levels remained stable during all follow-up periods (P = NS). There were neither episodes of acute rejection nor secondary effects related to the medication. In summary, renal transplant patients receiving tacrolimus who develop PTDM may display better control of hyperglycemia by a switch to CsA.

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.