Chronic kidney disease after liver transplantation
Authors: Joanna A. Leithead, James W. Ferguson
Journal: Journal of Hepatology (2014)

Chronic kidney disease and associated mortality after liver transplantation – A time-dependent analysis using measured glomerular filtration rateJournal of HepatologyVol. 61Issue 2PreviewThe accuracy of creatinine-based estimated GFR (eGFR) in assessing the prevalence of chronic kidney disease (CKD) and associated mortality after liver transplantation (LTx) is unknown. Using measured GFR (mGFR) by iothalamate clearance, we determined the prevalence of the entire spectrum of renal dysfunction and the impact of CKD on mortality after LTx. Full-Text PDF Reply to: "Chronic kidney disease after liver transplantation"Journal of HepatologyVol. 62Issue 1PreviewWe appreciate the insightful comments of Leithead and Ferguson regarding our recent analysis of prevalence of chronic kidney disease (CKD) after liver transplantation (LT). We agree that peri-operative acute kidney injury (AKI) contributes to the development of chronic kidney disease after LT in a proportion of patients. We did not ascertain the trajectory of renal function in the early postoperative period in all our subjects. Since the first iothalamate clearance measurement was performed at 4 months post-transplantation, we chose this interval as the first point in our time-dependent analysis. Full-Text PDF Open Access We read with interest the report by Allen et al. in a recent issue of the Journal of Hepatology [[1]Allen A. Kim W.R. Therneau T.M. Larson J.J. Heimbach J.K. Rule A.D. Chronic kidney disease and associated mortality after liver transplantation – A time-dependent analysis using measured glomerular filtration rate.J Hepatol. 2014; 61: 286-292Abstract Full Text Full Text PDF PubMed Scopus (104) Google Scholar]. The authors are to be congratulated on highlighting the important problem of chronic kidney disease (CKD) in liver transplant recipients. Instead of concentrating on severe CKD (KDIGO stages 4–5) as in most previous literature, their study additionally describes the incidence of lesser degrees of renal injury (KDIGO stage 3) and has the benefit of an iothalamate-measured glomerular filtration rate (GFR). They found that few patients maintained 'normal' renal function long-term after transplantation, with two thirds developing CKD by 10 years. The majority of patients had stage 3 disease. However, echoing observations in the non-transplant setting, this moderate CKD (GFR <60 ml/min/1.73 m2) was clinically relevant having implications for survival [2Weiner D.E. Tighiouart H. Amin M.G. Stark M.G. MacLeod B. Griffith J.L. et al.Chronic kidney disease as a risk factor for cardiovascular disease and all-cause mortality: a pooled analysis of community-based studies.J Am Soc Nephrol. 2004; 15: 1307-1315Crossref PubMed Scopus (1061) Google Scholar, 3Fried L.F. Katz R. Sarnak M.J. et al.Kidney function as a predictor of non cardiovascular mortality.J Am Soc Nephrol. 2005; 16: 3728-3735Crossref PubMed Scopus (241) Google Scholar]. There are several points worthy of comment. First, although there was clearly a progressive deterioration in renal function with time after transplant, the greatest loss occurred within the first year. The authors speculate that this reflects nephrotoxic immunosuppressive drugs. Little mention was made of the role of peri-operative acute kidney injury (AKI). In our unit, despite optimized pre-transplant renal function and less calcineurin inhibitor exposure in recent years, patients are experiencing more GFR loss from baseline to 1-year [[4]Leithead J.A. Rajoriya N. Gunson B.K. Muiesan P. Ferguson J.W. The evolving use of higher risk grafts is associated with an increased incidence of acute kidney injury after liver transplantation.J Hepatol. 2014; 60: 1180-1186Abstract Full Text Full Text PDF PubMed Scopus (76) Google Scholar]. This is in the context of a rise in the incidence of AKI that has occurred in parallel with a marked rise in the use of higher risk grafts [[4]Leithead J.A. Rajoriya N. Gunson B.K. Muiesan P. Ferguson J.W. The evolving use of higher risk grafts is associated with an increased incidence of acute kidney injury after liver transplantation.J Hepatol. 2014; 60: 1180-1186Abstract Full Text Full Text PDF PubMed Scopus (76) Google Scholar]. We have hypothesized that graft injury may play a critical role in the pathogenesis of AKI in this setting. It is well recognized that AKI can cause permanent structural damage, with progressive tubulo-interstitial fibrosis and long-term repercussions for renal function [[5]Basile S.P. Donohoe D. Roethe K. Osborn J.L. Renal ischemic injury results in permanent damage to peritubular capillaries and influences long-term function.Am J Physiol Renal Physiol. 2001; 281: F887-F899Crossref PubMed Scopus (589) Google Scholar]. Therefore, we suggest that in addition to renal sparing immunosuppression, future strategies to prevent CKD may include therapies that minimize the renal hit at time of transplantation. Second, the apparent lack of era effect on the frequency of CKD is interesting. United States registry data has shown that the introduction of MELD has been accompanied by an increased likelihood of end-stage kidney disease, which has been attributed to greater pre-operative renal dysfunction [[6]Sharma P. Schaubel D.E. Guidinger M.K. Goodrich N.P. Ojo A.O. Merion R.M. Impact of MELD-based allocation on end-stage renal disease after liver transplantation.Am J Transplant. 2011; 11: 2372-2378Crossref PubMed Scopus (95) Google Scholar]. Nevertheless, given that the adjusted hazard ratio for renal failure only rose by 15% after MELD implementation, one might not anticipate a demonstrable difference in this comparatively small study. Without detailed information, regarding additional recipient and donor factors, it is difficult to draw any real conclusions regarding the evolving incidence of CKD. Readers should not be falsely reassured by this data, especially in the face of an escalating use of higher risk grafts. Finally, a major conclusion of the study by Allen et al. was the limited reliability of creatinine-based GFR estimation in predicting mortality in these patients, and that preventative and expectant management, based on the early recognition of renal dysfunction, may require actual measurement of GFR. We argue that measured GFR is time-consuming, costly and not an applicable test for most transplant centres when repeated tests are necessary. Although a useful research tool, a single absolute measure of renal function in an individual patient is less relevant than delta estimated GFR for modifying clinical care. The authors who have taken part in this study declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.