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.

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.

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.

Double-phase parathyroid 99mTc-Sestamibi scintigraphy in chronic haemodialysis patients: correlation with biochemical markers of parathyroid function.

99mTc-Sestamibi identifies the presence of hyperfunctioning autonomous parathyroid glands in patients with secondary hyperparathyroidism (SHP). The objectives of this study were: (i) to evaluate the interdependence between biochemical markers of SHP and 99mTc-Sestamibi uptake; and (ii) to determine whether 99mTc-Sestamibi uptake could be efficiently predicted by any combination of the former variables. Double-phase parathyroid 99mTc-Sestamibi uptake and total serum calcium, phosphorus, intact parathormone, 25-OH vitamin D and 1,25(OH) vitamin D determinations were performed simultaneously in 74 patients (36 female, 38 male) with SHP. Planar images of the neck and upper thorax were obtained in anterior view, 15 min (early phase) and 120 min (delayed phase) after the injection of 740 MBq of 99mTc-Sestamibi. In each patient, a final parathyroid/thyroid (P/T) activity index was obtained by adding the results of the P/T index of all parathyroid lesions. There was a significant correlation between intact parathormone levels and delayed 99mTc-Sestamibi uptake ( r=0.656; P<0.01). Of all the variables, intact parathormone was the only significant predictor of delayed 99Tc-Sestamibi uptake ( r=0.487; P<0.001). Calcium, phosphorus, vitamin D metabolites, age, gender, time spent on haemodialysis and cause of chronic renal failure displayed no significant correlation with 99mTc-Sestamibi uptake. It can be concluded that 99mTc-Sestamibi uptake is a potential predictor of parathyroid function in SHP patients. Hence, 99mTc-Sestamibi scintigraphy could be useful to assess parathyroid function and in the clinical follow-up of these patients.

[Effects of octreotide on serum and urine electrolytes in a patient with parathyroid carcinoma: clinical case]. / Efectos del octreotide sobre los electrolitos en suero y orina de un paciente con carcinoma de paratiroides: caso clínico.

Parathyroid carcinoma (PC) is a rare endocrine tumor whose management is difficult whenever surgery does not achieve complete en bloc resection or recurrence is detected. Medical options (mainly bisphosphonates) are scanty and often associated with toxic side-effects. We present a case report of a patient with recurrent PC after two surgical interventions who was treated with octreotide (SMS-201) taken into account the positive somatostatin staining of the specimen obtained during the last surgery. Short term effects (-2 weeks-) included a decrease in urinary calcium excretion paired with a simultaneous increase in urinary phosphorus excretion. Later on, continuous subcutaneous octreotide administration kept urinary calcium excretion at low levels and this effect was completely reversible/reinducible upon discontinuation/reintroduction of the drug. Neither iPTH nor total serum calcium were modified at short or long term basis. The lack of clear-cut therapeutic effects make this findings a pure clinical observation. Thus, octreotide cannot be recommended for the treatment of parathyroid carcinoma.

Cellular bioenergetics after erythropoietin therapy in chronic renal failure.

After erythropoietin (rHuEPO) therapy, patients with chronic renal failure (CRF) do not improve peak O2 uptake (VO2 peak) as much as expected from the rise in hemoglobin concentration ([Hb]). In a companion study, we explain this phenomenon by the concurrent effects of fall in muscle blood flow after rHuEPO and abnormal capillary O2 conductance observed in CRF patients. The latter is likely associated with a poor muscle microcirculatory network and capillary-myofiber dissociation due to uremic myopathy. Herein, cellular bioenergetics and its relationships with muscle O2 transport, before and after rHuEPO therapy, were examined in eight CRF patients (27 +/- 7.3 [SD] yr) studied pre- and post-rHuEPO ([Hb] = 7.8 +/- 0.7 vs. 11.7 +/- 0.7 g x dl-1) during an incremental cycling exercise protocol. Eight healthy sedentary subjects (26 +/- 3.1 yr) served as controls. We hypothesize that uremic myopathy provokes a cytosolic dysfunction but mitochondrial oxidative capacity is not abnormal. 31P-nuclear magnetic resonance spectra (31P-MRS) from the vastus medialis were obtained throughout the exercise protocol consisting of periods of 2 min exercise (at 1.67 Hz) at increasing work-loads interspersed by resting periods of 2.5 min. On a different day, after an identical exercise protocol, arterial and femoral venous blood gas data were obtained together with simultaneous measurements of femoral venous blood flow (Qleg) to calculate O2 delivery (QO2leg) and O2 uptake (VO2leg). Baseline resting [phosphocreatine] to [inorganic phosphate] ratio ([PCr]/[Pi]) did not change after rHuEPO (8.9 +/- 1.2 vs. 8.8 +/- 1.2, respectively), but it was significantly lower than in controls (10.9 +/- 1.5) (P = 0.01 each). At a given submaximal or peak VO2leg, no effects of rHuEPO were seen on cellular bioenergetics ([PCr]/[Pi] ratio, %[PCr] consumption halftime of [PCr] recovery after exercise), nor in intracellular pH (pHi). The post-rHuEPO bioenergetic status and pHi, at a given VO2leg, were below those observed in the control group. However, at a given pHi, no differences in 31P-MRS data were detected between post-rHuEPO and controls. After rHuEPO, at peak VO2, Qleg fell 20% (P < 0.04), limiting the change in QO2leg to 17%, a value that did not reach statistical significance. The corresponding O2 extraction ratio decreased from 73 +/- 4% to 68 +/- 8.2% (P < 0.03). These changes indicate that maximal O2 flow from microcirculation to mitochondria did not increase despite the 50% increase in [Hb] and explain how peak VO2leg and cellular bioenergetics (31P-MRS) did not change after rHuEPO. Differences in pHi, possibly due to lactate differences, between post-rHeEPO and controls appear to be a key factor in the abnormal muscle cell bioenergetics during exercise observed in CRF patients.