Ian Dittmer

By 2005, human organ trafficking, commercialization, and transplant tourism had become a prominent and pervasive influence on transplantation therapy. The most common source of organs was impoverished people in India, Pakistan, Egypt, and the Philippines, deceased organ donors in Colombia, and executed prisoners in China. In response, in May 2008, The Transplantation Society and the International Society of Nephrology developed the Declaration of Istanbul on Organ Trafficking and Transplant Tourism consisting of a preamble, a set of principles, and a series of proposals. Promulgation of the Declaration of Istanbul and the formation of the Declaration of Istanbul Custodian Group to promote and uphold its principles have demonstrated that concerted, strategic, collaborative, and persistent actions by professionals can deliver tangible changes. Over the past 5 years, the Declaration of Istanbul Custodian Group organized and encouraged cooperation among professional bodies and relevant international, regional, and national governmental organizations, which has produced significant progress in combating organ trafficking and transplant tourism around the world. At a fifth anniversary meeting in Qatar in April 2013, the DICG took note of this progress and set forth in a Communiqué a number of specific activities and resolved to further engage groups from many sectors in working toward the Declaration's objectives.

BACKGROUND: Metabolic acidosis adversely affects both protein and bone metabolism in patients with chronic renal failure, and could also affect morbidity and mortality. This trial aimed to investigate the effects of different dialysate bicarbonate concentrations on control of acid base balance, and nutritional status. METHODS: Forty-six stable haemodialysis patients were dialysed using LowBic. (30 mmol/l) or HighBic. (40 mmol/l) bicarbonate dialysate in a single blind double crossover trial, of two consecutive six-month periods. Blood gas analysis, anthropometric indices and dialysis dose were measured, in addition to biochemical indices. RESULTS: Predialysis 'arterial' plasma pH values were significantly higher when using the HighBic. dialysate (LowBic. 7.38 +/- 0.05, HighBic. 7.43 +/- 0.04, P < 0.001), as was predialysis serum total CO2 at all times during the study (P < 0.01). Kt/V, (LowBic. 1.27 +/- 0.19, HighBic. 1.27 +/- 0.25), urea generation rates (UGR) (LowBic. 1.99 +/- 0.77, HighBic. 1.92 +/- 0.77 mmol/min), and normalized protein catabolic rate (NPCR) (LowBic. 1.04 +/- 0.26, HighBic. 0.99 +/- 0.28 g/kg/day) did not differ, and values of parathroid hormone (PTH) were comparable. Triceps skinfold thickness (TSF) showed a significant change (LowBic. 14.8 +/- 6.9-11.8 +/- 5.5, HighBic. 14.9 +/- 6.3-15.8 +/- 6.4 mm, P < 0.05) which was reversed following dialysate change (HighBic. 11.8 +/- 5.5-13.3 +/- 7.2, LowBic. 15.8 +/- 6.4-13.8 +/- 6.7 mm, P < 0.05). No differences in mid upper arm circumference were found. CONCLUSIONS: Bicarbonate dialysate concentrations of 40 mmol/l were safe, well tolerated, and produced better control of acidosis, with an increase in TSF, compared to a bicarbonate concentration of 30 mmol/l.

Background1-year data from this trial showed the noninferiority of a novel once-daily extended-release tacrolimus (LCPT; Envarsus XR) to immediate-release tacrolimus (IR-Tac) twice daily after kidney transplantation.Study DesignFinal 24-month analysis of a 2-armed, parallel-group, randomized, double-blind, double-dummy, multicenter, phase 3 trial.Setting & Participants543 de novo kidney recipients randomly assigned to LCPT (n = 268) or IR-Tac (n = 275); 507 (93.4%) completed the 24-month study.InterventionLCPT tablets once daily at 0.17 mg/kg/d or IR-Tac twice daily at 0.1 mg/kg/d; subsequent doses were adjusted to maintain target trough ranges (first 30 days, 6-11 ng/mL; thereafter, 4-11 ng/mL). The intervention was 24 months; the study was double blinded for the entirety.Outcomes & MeasurementsTreatment failure (death, transplant failure, biopsy-proven acute rejection, or loss to follow up) within 24 months. Safety end points included adverse events, serious adverse events, new-onset diabetes, kidney function, opportunistic infections, and malignancies. Pharmacokinetic measures included total daily dose (TDD) of study drugs and tacrolimus trough levels.Results24-month treatment failure was LCPT, 23.1%; IR-Tac, 27.3% (treatment difference, −4.14% [95% CI, −11.38% to +3.17%], well below the +10% noninferiority criterion defined for the primary 12-month end point). Subgroup analyses showed fewer treatment failures for LCPT versus IR-Tac among black, older, and female recipients. Safety was similar between groups. From month 1, TDD was lower for LCPT; the difference increased over time. At month 24, mean TDD for LCPT was 24% lower than for the IR-Tac group (P < 0.001), but troughs were similar (means at 24 months: LCPT, 5.47 ± 0.17 ng/mL; IR-Tac, 5.8 ± 0.30 ng/mL; P = 0.4).LimitationsTrial participant eligibility criteria may limit the generalizability of results to the global population of de novo kidney transplant recipients.ConclusionsResults suggest that once-daily LCPT in de novo kidney transplantation has comparable efficacy and safety profile to that of IR-Tac. Lower TDD reflects LCPT’s improved bioavailability and absorption. 1-year data from this trial showed the noninferiority of a novel once-daily extended-release tacrolimus (LCPT; Envarsus XR) to immediate-release tacrolimus (IR-Tac) twice daily after kidney transplantation. Final 24-month analysis of a 2-armed, parallel-group, randomized, double-blind, double-dummy, multicenter, phase 3 trial. 543 de novo kidney recipients randomly assigned to LCPT (n = 268) or IR-Tac (n = 275); 507 (93.4%) completed the 24-month study. LCPT tablets once daily at 0.17 mg/kg/d or IR-Tac twice daily at 0.1 mg/kg/d; subsequent doses were adjusted to maintain target trough ranges (first 30 days, 6-11 ng/mL; thereafter, 4-11 ng/mL). The intervention was 24 months; the study was double blinded for the entirety. Treatment failure (death, transplant failure, biopsy-proven acute rejection, or loss to follow up) within 24 months. Safety end points included adverse events, serious adverse events, new-onset diabetes, kidney function, opportunistic infections, and malignancies. Pharmacokinetic measures included total daily dose (TDD) of study drugs and tacrolimus trough levels. 24-month treatment failure was LCPT, 23.1%; IR-Tac, 27.3% (treatment difference, −4.14% [95% CI, −11.38% to +3.17%], well below the +10% noninferiority criterion defined for the primary 12-month end point). Subgroup analyses showed fewer treatment failures for LCPT versus IR-Tac among black, older, and female recipients. Safety was similar between groups. From month 1, TDD was lower for LCPT; the difference increased over time. At month 24, mean TDD for LCPT was 24% lower than for the IR-Tac group (P < 0.001), but troughs were similar (means at 24 months: LCPT, 5.47 ± 0.17 ng/mL; IR-Tac, 5.8 ± 0.30 ng/mL; P = 0.4). Trial participant eligibility criteria may limit the generalizability of results to the global population of de novo kidney transplant recipients. Results suggest that once-daily LCPT in de novo kidney transplantation has comparable efficacy and safety profile to that of IR-Tac. Lower TDD reflects LCPT’s improved bioavailability and absorption.