Reply to: “Chronic kidney disease after liver transplantation”
Authors: Alina M. Allen, W. Ray Kim, Terry M. Therneau, Joseph J. Larson, Julie K. Heimbach, Andrew D. Rule
Journal: Journal of Hepatology (2014)

We 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. Our assumption that in the majority of cases the renal dysfunction is attributed to calcineurin-inhibitor nephrotoxicity was derived from the detailed chart review of a small subset of patients with normal renal function at the time of LT who developed CKD at 4 months. In this random sample, only 27% of patients had postoperative AKI, defined as increase in creatinine by 0.3 mg/dl from baseline [[1]Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO clinical practice guideline for acute kidney injury.Kidney Int Suppl. 2012; 2: 1-138Abstract Full Text Full Text PDF Scopus (1827) Google Scholar]. Thus, while we acknowledge that postoperative AKI contributes to post-LT CKD, we cannot quantify the degree to which it contributes to CKD based on our data. We wholeheartedly agree that, given the significant impact of perioperative AKI on post-LT outcomes [[2]Charlton M.R. Wall W.J. Ojo A.O. Ginès P. Textor S. Shihab F.S. et al.Report of the first international liver transplantation society expert panel consensus conference on renal insufficiency in liver transplantation.Liver Transpl. 2009; 15: 1-34Crossref PubMed Scopus (7) Google Scholar], every attempt to prevent and reverse it in a timely manner should be made. Leithead and Ferguson also suggest to cautiously interpret our finding concerning the lack of increase in post-LT CKD in the MELD era, which is discordant with other studies of the national database [[3]Israni A.K. Xiong H. Liu J. Salkowski N. Trotter J.F. Snyder J.J. et al.Predicting end-stage renal disease after liver transplant.Am J Transplant. 2013; 13: 1782-1792Crossref PubMed Scopus (53) Google Scholar]. While registry databases provide a large sample size, they are limited by available data (e.g., measured GFR), lack of standardization (e.g., assay for serum creatinine), and completeness (e.g., loss to follow-up). As a single centre study, we can only report what we observed in our patients – post-transplant CKD is clearly an important comorbidity; whether our practice of vigilant monitoring and early intervention was responsible for the lack of the trend observed in other studies, remains uncertain. It may be worth noting that the organ allocation system should not affect the biological incidence of renal morbidity in transplant candidates. The primary reason that more patients are transplanted with reduced renal function is the worsening organ shortage, which results in more patients developing complications of advanced cirrhosis, such as hepatorenal syndrome and AKI. The MELD score identifies these patients as their renal function deteriorates and facilitates access to LT. Should renal function not be a part of the allocation scheme, further progression of renal dysfunction would result in increased requirements for simultaneous kidney transplantation or higher rates of withdrawal from the waiting list. The net effect of the MELD-based allocation may be a reduction in these poor waitlist outcomes at the expense of an increase in incidence of end-stage renal disease (ESRD), although our data did not show this trend. Lastly, we agree that directly measured GFR is not a convenient way to monitor our patients long-term. However, we do believe that clinicians tend to underutilize other measures of GFR, such as creatinine clearance or serum cystatin-C. Likewise, an important message in this paper is that serum creatinine or estimated GFR (often automatically reported by the laboratory) should not be interpreted in isolation. Changes over time in creatinine or eGFR may help the astute clinician to identify or at least suspect CKD. Unfortunately, the current CKD classification [[4]Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO clinical practice guideline for the evaluation and management of chronic kidney disease.Kidney Int Suppl. 2013; 3: 1-150Abstract Full Text Full Text PDF Scopus (1441) Google Scholar] does not encompass changes in serum creatinine and the diagnosis of CKD may be missed, due to absent vigilance of the transplant physician. 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. Chronic kidney disease after liver transplantationJournal of HepatologyVol. 62Issue 1PreviewWe read with interest the report by Allen et al. in a recent issue of the Journal of Hepatology [1]. 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). Full-Text PDF Open AccessChronic 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