South African GASTROENTEROLOGY Review | Volume 17 Issue 3 2019

THE SOUTH AFRICAN GASTROENTEROLOGY REVIEW 2019 | ISSUE 3 | 5 REVIEW Renal dysfunction after liver transplantation Nina Diana Division of Nephrology, Charlotte Maxeke Johannesburg Academic Hospital, University of Witwatersrand, Johannesburg, South Africa Introduction Chronic kidney disease (CKD) after liver transplantation has become a frequently identified clinical entity. Despite progress in perioperative and postoperative management, many patients are left with CKD. 1 Riordan et al. estimated the prevalence of the various CKD stages at 1- and 5-years post liver transplant. They revealed that 94.32% of patients surviving to 1 year had an abnormal GFR and, in those surviving to 5 years 71.11% had a GFR <60 ml/min/1.73m². The 10 year cumulative incidence of patients with a GFR <30 ml/min/1.73m² was 6.52%. 2 There has also been substantial growth in the number of kidney transplant candidates placed on the waiting list following a prior liver transplant. 3 Compared to patients with preserved renal function, CKD post liver transplant is associated with increased risks of cardiovascular events, hospitalization, recurrent acute kidney injury (AKI), end stage renal disease (ESRD), hepatic allograft dysfunction and loss, and mortality. 4-6 The risk of death increases significantly once GFR <30 ml/min/1.73 m²: HR = 2.67 (95% CI = 1.80–3.96) for GFR = 29–15 ml/min/1.73 m² and HR = 5.47 (95% CI = 3.10–9.65) for GFR <15 ml/min/1.73 m². 7 Gonwa et al. found that at 13 years post liver transplant, survival of patients with ESRD was 28.2% compared with 54.6% in those with preserved renal function. 8 Risk factors for development and progression of CKD post liver transplantation Identifying which patients are at higher risk for developing CKD is a great challenge. Historically, the most accepted factors are kidney function prior to transplantation, demographics and comorbidities of each patient, AKI episodes in the peri-transplantation period, and chronic exposure to calcineurin inhibitors (CNIs). Duration and degree of renal impairment prior to liver transplantation have been strongly associated with progression of kidney disease. The risk is most pronounced in recipients with sustained GFR <30ml/min/1.73m² for the 90 days before transplantation. There is a 31% risk of ESRD over 3 years post-transplant in patients with GFR<30ml/ min/1.73m², as compared with a <10% risk in those who always had an GFR > 30ml/min/1.73 m² or whose GFR fluctuated between these two ranges. 9 Studies have shown both female gender and rising recipient age confer greater risk for the development of CKD, possibly related to overestimation of pre- transplant renal function in the context of lower muscle mass. 4,10 Diabetes and hypertension are both common co-morbidities and increase the risk for renal disease. Hepatitis C virus infection is another important risk factor for the development of CKD in liver transplant recipients. Risks are related to the association of HCV infection and glomerulonephritis as well as the increased possibility of developing hyperglycaemia and new onset diabetes after transplantation. 11 In a meta-analysis the presence and severity of non-alcoholic fatty liver disease has been associated with an increased risk and severity of CKD. 12 Other risk factors include African American ethnicity and body mass index >35kg/m². 13 AKI during the peri-transplant period creates an additional risk for post-transplant CKD. 14,15 Mechanisms during and after surgery that increase the risk of AKI development include hypotension and hypoperfusion, sepsis, administration of nephrotoxic agents, and aggressive diuresis. Renal recovery is not common once dialysis extends beyond 4 weeks duration. 16 CNI associated nephrotoxicity increases with duration of exposure and may have limited potential for reversibility, due to mostly irreparable histologic damage to all compartments of the kidney. These changes may lead to ESRD. Other factors contributing to the risk of CKD associated with CNIs is their association with insulin resistance and hyperlipidaemia. 17 Evaluation of renal function prior to liver transplantation GFR estimation equations that depend on serum creatinine overestimate GFR in patients with chronic liver disease due to poor nutritional status and sarcopenia, increased tubular secretion of creatinine, increased volume of distribution due to accumulation of extracellular fluid, reduced hepatic conversion of creatine to creatinine, and possibly high serum bilirubin interacting with the creatinine assay. Overestimation is greatest at lower GFRs and in more Correspondence Nina Diana email: ninadiana1@gmail.com