Friday, July 29, 2016

Calcineurin Inhibitor Nephrotoxicity Through the Lens of Longitudinal Histology: Comparison of Cyclosporine and Tacrolimus Eras

Transplantation - Most Popular Articles Calcineurin Inhibitor Nephrotoxicity Through the Lens of Longitudinal Histology: Comparison of Cyclosporine and Tacrolimus Eras

imageBackground: The contribution of calcineurin inhibitors (CNI) nephrotoxicity to progressive kidney transplant injury remains debated, with little long-term data from the modern tacrolimus (TAC) era using lower doses. Methods: This longitudinal cohort study evaluated histological evidence of CNI nephrotoxicity from normal donor kidneys of successful kidney-pancreas transplant recipients during cyclosporine (CSA) and TAC eras, analyzed by intention-to-treat. Results: From 200 patients, 1622 adequate prospective protocol (84.3%) and indication (15.7%) kidney biopsies yielded 8.1 ± 4.1 samples per patient, over 7.4 ± 4.4 years posttransplant. The TAC era demonstrated less rejection and reduced early immune-mediated tubular damage, compared with CSA (P < 0.001). The incidences of acute mild arteriolopathy, striped interstitial fibrosis, glomerular congestion, and tubular microcalcification were all greater with CSA (hazard ratios of 1.70, 9.35, and 3.78, respectively) and maximal within the first posttransplant year, compared with TAC-treated patients (P < 0.001). However, the 1-, 5-, and 10-year prevalence moderate arteriolar hyalinosis was similar: CSA was 5.4%, 38.4%, and 79.1%; and TAC was 4.3%, 33.6% and 77.2%, respectively (P = NS). Morphometric measurement demonstrated lumenal narrowing from inwards collapse of hyalinized arteriolar walls unable to maintain its structural integrity. Severe hyalinosis was calculated to reduce arteriolar blood flow to 20 ± 34% of normal. Severity of arteriolar hyalinosis correlated with contemporaneous glomerulosclerosis (r = 0.44, P < 0.001), and subsequent progression in 1356 sequential biopsy pairs, consistent with glomerular ischemia. Conclusions: Tacrolimus-based therapy appeared superior to the CSA era, with less early CNI nephrotoxicity and fewer rejection episodes, but comparable chronic arteriolar toxicity. Calcineurin inhibitors are imperfect long-term maintenance immunosuppressive agents because of frequent and irreversible chronic toxicity.


http://journals.lww.com/transplantjournal/Fulltext/2016/08000/Calcineurin_Inhibitor_Nephrotoxicity_Through_the.26.aspx

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Alberto Reino Buelvas

Phosphate-Binding Agents in Adults With CKD: A Network Meta-analysis of Randomized Trials

American Journal of Kidney Diseases Phosphate-Binding Agents in Adults With CKD: A Network Meta-analysis of Randomized Trials

Guidelines preferentially recommend noncalcium phosphate binders in adults with chronic kidney disease (CKD). We compare and rank phosphate-binder strategies for CKD.


http://www.ajkd.org/article/S0272-6386(16)30253-0/abstract?rss=yes

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Alberto Reino Buelvas

A Randomized Study Comparing Parathyroidectomy with Cinacalcet for Treating Hypercalcemia in Kidney Allograft Recipients with Hyperparathyroidism

Journal of the American Society of Nephrology current issue A Randomized Study Comparing Parathyroidectomy with Cinacalcet for Treating Hypercalcemia in Kidney Allograft Recipients with Hyperparathyroidism

Tertiary hyperparathyroidism is a common cause of hypercalcemia after kidney transplant. We designed this 12-month, prospective, multicenter, open–label, randomized study to evaluate whether subtotal parathyroidectomy is more effective than cinacalcet for controlling hypercalcemia caused by persistent hyperparathyroidism after kidney transplant. Kidney allograft recipients with hypercalcemia and elevated intact parathyroid hormone (iPTH) concentration were eligible if they had received a transplant ≥6 months before the study and had an eGFR>30 ml/min per 1.73 m2. The primary end point was the proportion of patients with normocalcemia at 12 months. Secondary end points were serum iPTH concentration, serum phosphate concentration, bone mineral density, vascular calcification, renal function, patient and graft survival, and economic cost. In total, 30 patients were randomized to receive cinacalcet (n=15) or subtotal parathyroidectomy (n=15). At 12 months, ten of 15 patients in the cinacalcet group and 15 of 15 patients in the parathyroidectomy group (P=0.04) achieved normocalcemia. Normalization of serum phosphate concentration occurred in almost all patients. Subtotal parathyroidectomy induced greater reduction of iPTH and associated with a significant increase in femoral neck bone mineral density; vascular calcification remained unchanged in both groups. The most frequent adverse events were digestive intolerance in the cinacalcet group and hypocalcemia in the parathyroidectomy group. Surgery would be more cost effective than cinacalcet if cinacalcet duration reached 14 months. All patients were alive with a functioning graft at the end of follow-up. In conclusion, subtotal parathyroidectomy was superior to cinacalcet in controlling hypercalcemia in these patients with kidney transplants and persistent hyperparathyroidism.




http://jasn.asnjournals.org/cgi/content/short/27/8/2487?rss=1

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Alberto Reino Buelvas