Impact of Remote Ischemic Preconditioning Conducted in Living Kidney Donors on Renal Function in Donors and Recipients Following Living Donor Kidney Transplantation: A Randomized Clinical Trial

Abstract

Although remote ischemic preconditioning (RIPC) has been shown to have renoprotective effects, few studies have assessed the effects of RIPC on renal function in living kidney donors. This study investigated whether RIPC performed in living kidney donors could improve residual renal function in donors and outcomes in recipients following kidney transplantation. The donors were randomized into a control group (n = 85) and a RIPC group (n = 85). The recipients were included according to the matched donors. Serum creatinine (sCr) concentrations and estimated glomerular filtration rate (eGFR) were compared between control and RIPC groups in donors and recipients. Delayed graft function, acute rejection, and graft failure within one year after transplantation were evaluated in recipients. sCr was significantly increased in the control group (mean, 1.13; 95% confidence interval (CI), 1.07–1.18) than the RIPC group (1.01; 95% CI, 0.95–1.07) (p = 0.003) at discharge. Donors with serum creatinine >1.4 mg/dL at discharge had higher prevalence of chronic kidney disease (n = 6, 26.1%) than donors with a normal serum creatinine level (n = 8, 5.4%) (p = 0.003) after one year. sCr concentrations and eGFR were similar in the RIPC and control groups of recipients over the one-year follow-up period. Among recipients, no outcome variables differed significantly in the RIPC and control groups. RIPC was effective in improving early renal function in kidney donors but did not improve renal function in recipients.

Effect of remote ischaemic preconditioning on mortality and morbidity after non-cardiac surgery: meta-analysis

“…In one multicentre, international trial 51 , RIPC decreased the incidence of delayed graft function (secondary outcome), and at 5-year follow-up there was a sustained improvement in eGFR after RIPC immediately before surgery compared with that in controls ( P = 0.004) (primary outcome) 57 . Another trial 56 reported that creatinine levels were increased significantly in the donor control group at discharge ( P = 0.003), and donors with high creatinine levels at discharge had a higher prevalence of chronic kidney disease after 1 year ( P = 0.003) (both secondary outcomes).…”

“…Live-donor renal transplantation and the effects of RIPC were investigated in four trials 51–53 , 56 that measured estimated glomerular filtration rate (eGFR), creatinine concentration, urinary volume, levels of serum cystatin C, plasma neutrophil gelatinase-associated lipocalin (NGAL), urinary neutrophil gelatinase-associated lipocalin, urinary retinol-binding protein (RBP), urinary N -acetyl- d -glucosaminidase, and urinary liver-type fatty acid-binding protein, and outcomes in relation to graft function and rejection. One trial 56 also investigated the incidence of chronic kidney disease 1 year after surgery in donors, according to the Kidney Disease Improving Global Outcomes criteria. Another trial 51 assessed changes in tissue pathology.…”

Renal Delivery of Pharmacologic Agents During Machine Perfusion to Prevent Ischaemia-Reperfusion Injury: From Murine Model to Clinical Trials

“…More recently, Bang et al. investigated whether RIPC performed in living kidney donors using a blood pressure cuff placed on upper arm (3 cycles of inflation to 200mmHg for 5 minutes followed by deflation of the cuff for 5 minutes) could improve kidney function and outcomes in both donors and recipients; serum creatinine levels for donors at discharge was significantly lower in donors who received RIPC, while no significant difference in serum creatinine, eGFR, risk for DGF, acute rejection and graft failure between the recipients of the two groups ( 135 ). Several pharmacological donor pre-treatments have been recently investigated in this setting.…”

Randomised sham-controlled double-blind trial evaluating remote ischaemic preconditioning in solid organ transplantation: a study protocol for the RIPTRANS trial

“…24 A larger trial of 170 living kidney donor-recipient pairs with RIPC done on donors reported lower postoperative creatinine values on donors after RIPC but no long-term benefits for donors or recipients. 25 The largest kidney transplant RIPC trial to date, the REPAIR trial, showed that a RIPC performed in both donor and recipient immediately before a living-donor kidney surgery improved the estimated glomerular filtration for the whole follow-up period of 5 years. 26 27 The kidney allografts from living donors are subjected to very short ischaemia (in Finland this is typically less than 2 hours) and even greater benefits could be obtained if RIPC is performed in deceased donors, where ischaemia times are much longer (median 15 hours for kidney allografts in Finland, even longer in other countries).…”