A Systematic Review of the Literature on Chronic Kidney Disease Following Liver Transplantation

Abstract

Chronic kidney disease (CKD) is a serious comorbidity affecting liver transplant recipients (LTRs). Calcineurin inhibitor dosing minimization protocols and everolimus use purportedly increased from 2010, potentially impacting CKD development. This systematic literature review was designed to identify CKD incidence in adult LTRs, focusing on studies published from 2010 onwards. PubMed, Embase, and the Cochrane Database of Systematic Reviews were searched for papers reporting renal function (glomerular filtration rate [GFR]; estimated GFR [eGFR] or Chronic Kidney Disease Epidemiology Collaboration) for adult LTRs ≥6 months after transplantation. Primary outcome: renal function ≥6 months after transplantation, with CKD stage. Bias was assessed using the Cochrane Collaboration bias tool and by reviewing disclosures/industry funding. Of 3960 records identified, 14 publications were included. In at least 1 study arm, mean GFR/eGFR remained stable/improved temporally in 4 and decreased in 8 publications. Where GFR/eGFR decreased, mean eGFR was 71.4–119.6 mL/min/1.73 m 2 (CKD stage 2-stage 1) across studies at baseline, and was 77.2 and 79.1 mL/min/1.73 m 2 (stage 2) at 12 months. The proportion of patients with CKD increased between baseline and follow-up; 23.2–36.8% of patients had CKD stage 3a or higher at 12 months (2 studies). Rates ranged from 85.7–100% (6 months) for patient survival, 81.0% (12 months) to 100.0% (17 months) for graft survival, and 0–40% (12 months) for acute rejection. Most studies carried risk of bias. Evidence of temporal renal function decline highlights the need for continuous renal monitoring of LTRs, particularly regarding potential CKD development/progression.

Evolving challenges with long‐term care of liver transplant recipients

“…120 Elevated creatinine at 1 year, use of cyclosporine as immunosuppression, presence of DM pre-transplant, and posttransplant AKI predict progression to ESRD. 124,125 It is important to review medications that can impact renal function including NSAIDs, antibiotics such as vancomycin, and medications that increase CNI levels (e.g., anti-fungals, anti-epileptics, calcium channel blockers, and protease inhibitors).…”

“…Interestingly, among all non‐renal solid organ transplant recipients, LT recipients have the second highest incidence of post‐operative chronic renal failure despite the lowest level of immunosuppression with CNIs 120 . Elevated creatinine at 1 year, use of cyclosporine as immunosuppression, presence of DM pre‐transplant, and post‐transplant AKI predict progression to ESRD 124,125 . It is important to review medications that can impact renal function including NSAIDs, antibiotics such as vancomycin, and medications that increase CNI levels (e.g., anti‐fungals, anti‐epileptics, calcium channel blockers, and protease inhibitors).…”