Giuseppe Cannella

Incidence of cancer after kidney transplant: Results from the north italy transplant program

Background. Patients undergoing kidney transplantation demonstrate a higher risk of developing cancer as the result of immunosuppressive treatment and concurrent infections. Methods. The incidence of cancer in a cohort of patients who underwent kidney transplantation between 1990 and 2000, and who survived the acute phase (10 days), was analyzed as part of the North Italy Transplant program. Results. A total of 3,521 patients underwent transplantation during a 10-year period in 10 of 13 participating centers; the length of follow-up after kidney transplant was 67.7±36.0 months. During the follow-up, 172 patients developed cancer (39 with Kaposi sarcoma, 38 with lymphoproliferative diseases, and 95 with carcinomas [17 kidney, 11 non-basal cell carcinoma of the skin, 10 colorectal, 8 breast, 7 gastric, 7 lung, 6 bladder, and 3 mesothelioma]). The average time to cancer development after transplant was 40.1±33.4 months (range 0–134 months). Twenty-four patients developed cancer within 6 months from the transplant (10 with carcinomas, 7 with Kaposi sarcoma, and 7 with lymphoproliferative diseases). Three patients demonstrated a second primary cancer. The average cancer incidence was 4.9%. The incidence of cancer was 0.01 per year. Independent determinants of cancer development were age, gender, and immunosuppressive protocol including induction. Ten-year mortality was significantly higher in patients with cancer (33.1%) than among patients without cancer (5.3%). The relative risk of death in subjects with cancer was 5.5 (confidence interval 4.1–7.4). Conclusions. These preliminary data underline the importance of long-term surveillance of transplant recipients, choice of immunosuppressive treatment, and careful donor selection.

Secondary hyperparathyroidism in chronic dialysis patients : results of the Italian FARO survey on treatment and mortality

Introduction: Vitamin D receptor activator (VDRA) therapy has been shown to be associated with reduced mortality rates in chronic kidney disease (CKD) patients with secondary hyperparathyroidism (SHPT). However, differences between VDRAs in their ability to reduce both all-cause and cardiovascular-related mortality rates are not yet fully elucidated. Methods: The objective of the current analysis was to determine the effect of VDRA therapy on mortality in an Italian dialysis population, observed prospectively every 6 months for 18 months. Patients were investigated for all-cause and cardiovascular-related mortality risk adjusted for various demographic, clinical, and/or SHPT treatment variables. Results: The cumulative probabilities of all-cause and cardiovascular-related mortality were lower for patients who received any VDRA treatment compared with those who did not (p < 0.001) regardless of all measured variables. Additionally, patients who received paricalcitol and/or cinacalcet (with or without VDRAs) compared with calcitriol showed a significant improvement in both all-cause and cardiovascular-related mortality (p < 0.001). Cinacalcet with or without VDRAs was not associated with a further decrease of mortality hazard ratios compared with paricalcitol monotherapy. Conclusions: VDRA therapy (associated or not with cinacalcet) was associated with improved survival in dialysis patients, independent of demographic and clinical variables.

Management of secondary hyperparathyroidism in Italy: results of the Italian FARO survey.

AIMSnIn recent years, treatment options for secondary hyperparathyroidism (SHPT) have increased (e.g., paricalcitol, calcimimetics). To determine the impact these new treatments have on achieving K/DOQI targets, an observational, prospective survey was undertaken.nnnMETHODSnFour 6-month time-spaced surveys of 2,637 patients in 28 Italian dialysis units were performed. Patient demographic information; use of vitamin D or calcimimetics; and changes in parathyroid hormone (PTH), calcium (Ca) and phosphate (P) levels were evaluated.nnnRESULTSnOver the course of the survey, use of calcitriol decreased (from 62.1% at baseline to 44.5% at month 18; p<0.001), while use of paricalcitol (from 19.9% to 36.9%; p<0.001) and calcimimetics (from 6.4% to 10.8%; p<0.001) increased. This was associated with a decrease in mean PTH values (from 310.3 ± 292.4 pg/mL at baseline to 279.5 ± 250.1 pg/mL at month 18; p=0.0002), while mean Ca and P remained steady. The percentage of patients achieving K/DOQI ranges for PTH (from 26.8% at baseline to 32.0% at month 18, p<0.001), Ca (from 50.4% at baseline to 55.9% at month 18, p<0.001) and the 3 targets combined (PTH, Ca and P; from 8.8% at baseline to 11.5% at month 18, p=0.003) significantly increased (p<0.05). Despite the introduction of newer agents, two thirds of patients did not achieve target levels.nnnCONCLUSIONSnIncreased awareness and newer treatment options for chronic kidney disease patients with SHPT have changed treatment policy and number of patients achieving K/DOQI target levels in Italy. However, the majority of patients did not meet the target ranges, suggesting that new drugs and strategies are still warranted for optimal management of SHPT in chronic kidney disease.

Bone Disease in Long-term Renal Transplant Recipients with Severe Osteopenia: A Cross-sectional Study

Background. Fracture is a disabling clinical outcome after transplantation, but there is little histopathological information on long-term renal recipients with severe osteopenia. Methods. Twenty kidney recipients (8.3±1.9 years after transplantation), 13 males and 7 females (five postmenopausal) with nearly normal renal function, affected by severe osteopenia (T-score: males=−4.9±0.28; females= −5.08±0.47) underwent bone biopsy and morphometric X-ray absorptiometry to evaluate vertebral fractures. Results. Histopathological diagnosis was osteoporosis-osteopenia in seven patients, osteitis fibrosa in six, prevalent osteomalacic lesion in six, and “normal” bone in one patient. Significant increases in osteoid volume (OV/BV), osteoid surface, osteoblastic surface (ObS/BS) and osteoid thickness were observed. OV/BV and Obs/BS ratios were inversely correlated to cumulative doses of MPRED (r2=0.85 P<.0001 for both ratios), whereas age, sex, time after transplantation, iPTH levels, and cumulative cyclosporine A dose were not related to osteoblastic indices. Osteoclast surface was slightly increased. Widened mineralization lag times were observed, with normalcy of the bone formation rate. Half of the patients showed fractured vertebrae. No differences in T scores were found when patients were subdivided into groups “with” or “without” vertebral fractures. A higher prevalence of fractures was observed in patients with osteoporosis-osteopenia compared to other osteopathies (P<0.02). No relationships between bone volume versus T-scores were observed. Conclusions. In long-term renal transplant recipients, severe osteopenia does not predict osteoporosis alone. The main abnormality we found was an increase in osteoblastic activity with a slight mineralization defect. The heterogeneous bone illness we observed would suggest performing bone biopsy in these patients.

Achievement of NKF/K-DOQI Recommended Target Values for Bone and Mineral Metabolism in Incident Hemodialysis Patients: Results of the FARO-2 Cohort

Background: Mineral Bone Disorders (MBD) is prevalent in hemodialysis (HD) patients and associated with increased cardiovascular mortality. The FARO-2 study evaluated the achievement of the NKF/K-DOQI guidelines on recommended target values for serum calcium (Ca), phosphorous (P) and intact parathyroid hormone (PTH) levels on survival in incident HD patients. Methods: Data were collected by questionnaire from 568 incident HD patients followed prospectively over a 3-year period from 26 Italian dialysis units. The cumulative probability of time-to-death for CKD-MBD treatment characteristics was determined by the Kaplan-Meier curves. Results: Serum PTH levels (median values at 6 months vs. 36 months; 225 vs. 254 pg/ml), Ca (8.8 vs. 8.9 g/dl) and P (5.1 vs. 4.8 mg/dl) were not significantly different at 6 months versus follow-up. The majority of incident HD patients (60-70%) who were followed up for 36 months did not achieve the NKF/K-DOQI recommended target values. Survival rates were higher in patients on target for three parameters versus patients off target (survival at 24 months: at target 95.7% (95% CI: 84.0-98.9) versus not on target 71.1% (95% CI: 66.3-75.4, p < 0.01)). The 30.1% of patients on target for three MBD parameters at least once during the follow-up period had better survival rates compared to those not reaching these targets (survival at 24 months: at least once 88.0% (95% CI: 81.9-92.1); 67.7% (95% CI: 61.9-72.8, p < 0.01)). Conclusion: Our findings indicate that incident HD patients who achieved target levels (for three MBD parameters) for at least one visit have a lower risk of mortality.

Pharmacological control of secondary hyperparathyroidism in hemodialysis subjects: a cost consequences analysis of data from the FARO study

Abstract Background and objectives: Secondary hyperparathyroidism (SHPT) is a frequent complication of CKD with incidence, prevalence, and costs increasing worldwide. The objective of this analysis was to estimate therapy cost of SHPT in a sub-population of the FARO study. Materials and Methods: In the FARO study, an observational survey aimed to evaluate patterns of treatment in patients with SHPT who had undergone hemodialysis, pharmacological treatments and biochemical parameters evolution data were collected in four surveys. Patients maintaining the same treatment in all sessions were grouped by type of treatment and evaluated for costs from the Italian National Health Service perspective. Results: Four cohorts were identified: patients treated with oral (PO) calcitriol (nu2009=u2009182), intravenous (IV) calcitriol (nu2009=u200934), IV paricalcitol (nu2009=u200962), and IV paricalcitolu2009+u2009cinacalcet therapy (nu2009=u200920); the cinacalcet monotherapy group was not analysed due to low number of patients (nu2009=u20099). Parathyroid hormone (PTH) level at baseline and effectiveness of treatments in suppressing PTH level were assessed to test comparability among cohorts: calcitriol PO patients were significantly less severe than others (PTH level at baseline lower than 300u2009pg/ml; pu2009<u20090.0001); calcitriol IV patients did not reach significant reduction in PTH level. Paricalcitol and paricalcitolu2009+u2009cinacalcet treatment groups results were comparable, while only the IV paricalcitol cohort’s PTH level, weekly dosage, and cost decreased significantly from the first to the fourth survey (pu2009=u20090.020, pu2009=u20090.012, and pu2009=u20090.0124, respectively). Total costs per week of treatment (including calcium-based phosphate binder and sevelamer) were significantly lower in the paricalcitol vs paricalcitolu2009+u2009cinacalcet cohort (pu2009<u20090.001). Major limitations of this study are related to the survey design: not controlled and lack of comparability between cohorts; however, reflective of true practice patterns. Conclusions: The IV Paricalcitol cohort had significantly lower treatment costs compared with patients treated with paricalcitolu2009+u2009calcimemtics (pu2009<u20090.001), without a significant difference in terms of baseline severity and PTH control.