South African GASTROENTEROLOGY Review | Volume 17 Issue 3 2019

THE SOUTH AFRICAN GASTROENTEROLOGY REVIEW 2019 | ISSUE 3 | 6 REVIEW severe liver disease. 18,19 Inaccurate estimation of pre-transplant GFR may result in incorrect expectations of post-transplant kidney function. More accurate methods, such as I¹² 5 iothalomate, iohexal and inulin clearance, are limited by availability, cost, radiation exposure and complexity. Studies have shown the 4-variable MDRD and CKD-EPI equations fared the best compared with direct measurement of GFR in patients with liver disease. 20 The greatest challenge in evaluating renal function with concomitant liver disease is determining whether the AKI is reversible post liver transplant or whether CKD may be underlying or develop with time. The use of pre-transplant renal biopsy for determining the cause and severity of kidney disease is not well established. A renal biopsy is considered in the following circumstances: urine abnormalities such as microscopic haematuria, proteinuria, red blood cell casts; or if the aetiology of renal dysfunction is not apparent from routine clinical data. Consideration of the biopsy must we weighed up against the increased procedural risk. Risk is reduced by utilizing the transjugular route or performing the renal biopsy at the time of liver transplantation. The amount of renal scarring, indicative of irreversible renal loss is more important than glomerular diagnosis in determining risk of CKD progression. Pitchler et al. suggested the following renal biopsy criteria to determine which patients would be less likely to recover renal function after liver transplantation: > 40% global glomerulosclerosis or > 30% of the interstitium composed of interstitial fibrosis. 21 Simultaneous liver kidney transplant vs liver transplant alone The goal of evaluation of a liver transplant candidate with renal dysfunction is to determine whether they would benefit from a simultaneous kidney allograft at the time of liver transplantation. Model for end-stage liver disease (MELD) score was developed to estimate mortality in patients waiting for a liver transplant and assign organs to sicker patients. Serum creatinine is a component of the scoring system. This has led to an increased number of patients with renal dysfunction at the top of the liver transplant waiting list. 22 An inadvertent consequence of the introduction of MELD scoring for liver allocation in 2002 was a substantial increase in the absolute number of simultaneous liver kidney (SLK) transplants from 135 in 2000 to 731 in 2016 in the USA. This represents an over 300% increase for SLK as a proportion of all liver transplants completed in the USA. 23 This escalation in number of SLK transplants has led to some concerns. Firstly, multi-organ allocation occurs before kidney alone allocation, this results in loss of potential kidney allograft offers to highly sensitized ESRD patients (who have priority on the kidney alone allocation). Majority of kidney allografts allocated for SLK transplants would be prioritized for young candidates, with the longest expected post-transplant survival, on the kidney alone transplant list. 24 Secondly, patient mortality rates and kidney allograft outcomes are significantly better in kidney alone recipients compared to simultaneous liver kidney recipients. The 1-year survival rate of the renal allograft was 83.3% for SLK recipients, significantly lower than the 91.3% for kidney- alone patients. Allograft loss was mainly due to recipient death. 25 Thirdly, Formica et al. showed that recipients without renal impairment had significantly worse (unadjusted) 1- and 5-year survival if they received SLK transplant as opposed to liver transplant alone. These results suggest receiving a SLK transplant without renal dysfunction may potentially even be detrimental. 25 SLK organ allocation criteria In 2016, the US Organ Procurement and Transplant Network (OPTN) and the United Network for Organ Sharing (UNOS) formally approved a new policy for SLK allocation. 25 This policy included medical eligibility criteria with the aim of improving uniformity in SLK allocation. Medical eligibility criteria for SLK transplantation includes patients with CKD, sustained AKI and metabolic disease. CKD, was defined as an estimated GFR of ≤60 ml/ min/1.73 m² for more than 90 days and an estimated GFR of ≤30 ml/min/1.73 m² at the time of listing or ESRD on maintenance dialysis. Sustained AKI was defined as the requirement for acute dialysis for 6 consecutive weeks and/or an estimated GFR ≤25 ml/min/1.73 m² for ≥6 weeks. Metabolic criteria include hyperoxaluria, atypical haemolytic uraemic syndrome (due to mutations in either factor H or factor I), familial non-neuropathic systemic amyloidosis and methylmalonic aciduria. A nephrologist must confirm these criteria. New criteria also include a ‘safety net’ component to ensure a liver transplant recipient who is not initially offered a kidney allograft would be prioritized for a subsequent kidney transplant if they are registered on the kidney waiting list between 60 – 365 days after liver transplantation and are dialysis dependent or have a persistent GFR ≤20ml/min/1.73 m². The safety net considers that prior liver transplant recipients have a much a worse wait list survival compared to kidney alone candidates. 26 Conclusion CKD after liver transplantation has become increasingly common. Reduced kidney function is a predictor of adverse outcomes in these patients. Identifying patients who are a higher risk for CKD post-transplant is a true challenge. Kidney allografts are a precious and limited resource, SLK eligibility criteria aim to standardize kidney allograft allocation and direct the allograft to where it will be most beneficial. ‘Safety net’ criteria remove the concern that if a liver transplant recipient remains with significant CKD, the patient will continue on dialysis and experience a poorer outcome. References 1. Miller B. Chronic kidney disease in solid-organ transplantation. Adv Chronic Kidney Dis. 2006 Jan;13(1):29-34. 2. O’Riordan A, Wong V, McCormick PA, Hegarty JE, Watson AJ. Chronic kidney disease post-liver transplantation. Nephrol Dial Transplant. 2006 Sep;21(9):2630-6. 3. Srinivas TR, Stephany BR, Budev M, Mason DP, Starling RC, Miller C, et al. An Emerging Population: Kidney Transplant Candidates Who Are Placed on the Waiting List after Liver, Heart, and Lung Transplantation. Clin J Am Soc Nephrol. 2010;5:1881-6. 4. Ojo AO, Held PJ, Port FK, Wolfe RA, Leichtman AB, Young EW, et al. Chronic renal failure after transplantation of a nonrenal organ. N Engl J Med. 2003 Sep 4;349(10):931-40. 5. Pawarode A, Fine DM, Thuluvath PJ. Independent risk factors and natural history of renal dysfunction in liver transplant recipients. Liver Transp.l 2003;9:741-7. 6. Fisher NC, Nightingale PG, Gunson BK, Lipkin GW,