Elsevier

Journal of Hepatology

Volume 61, Issue 2, August 2014, Pages 286-292
Journal of Hepatology

Research Article
Chronic kidney disease and associated mortality after liver transplantation – A time-dependent analysis using measured glomerular filtration rate

https://doi.org/10.1016/j.jhep.2014.03.034Get rights and content

Background & Aims

The 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.

Methods

A database that prospectively tracks all LTx recipients at this academic transplant program from 1985 to 2012 was queried to identify all adult primary LTx recipients. Our post-LTx protocol incorporates GFR measurement by iothalamate clearance at regular intervals. A multistate model was used to assess the prevalence of CKD, kidney transplant, and death after LTx. Time-dependent Cox regression analysis was performed to evaluate the impact of mGFR and eGFR changes on survival.

Results

A total of 1211 transplant recipients were included. At the time of LTx, the median age was 54 years, 60% were male and 86% were Caucasian. At 25 years after LTx, 54% of patients died, 9% underwent kidney transplantation, whereas 7%, 21%, and 18% had mGFR >60, 59–30, and <30 ml/min/1.73 m2 respectively. The risk of death increased when mGFR decreased below 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. Compared to mGFR, eGFR underestimated mortality risk in LTx recipients with an eGFR of 30–90 ml/min/1.73 m2.

Conclusions

An overwhelming majority of LTx recipients develop CKD. The risk of death increases exponentially when GFR <30 ml/min/1.73 m2. Creatinine-based eGFR underestimates the mortality risk in a large proportion of patients.

Introduction

Advances in immunosuppression and perioperative management have revolutionized liver transplantation (LTx) outcomes in the past 3 decades [1]. Improved long-term survival has led in turn to increased prevalence of ‘late’ complications after LTx such as chronic kidney disease (CKD). CKD has become one of the leading causes of morbidity and death after LTx [2]. Although calcineurin inhibitor-toxicity is typically considered a major contributor, other risk factors for CKD include perioperative acute kidney injury, diabetes mellitus, hypertension, and chronic hepatitis C infection [3], [4], [5].

The reported prevalence of CKD after LTx ranges between 10% and 45% [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17]. The wide range is largely attributed to the different criteria used to define CKD and different follow-up lengths, which make the existing literature difficult to compare. Moreover, renal function was assessed using creatinine-based equations, which is influenced by factors other than renal function, namely muscle mass [18] and tends to overestimate GFR in patients after liver transplantation [19]. Studies using measured GFR (mGFR) to assess the prevalence and mortality impact of CKD in these patients are limited [20]. Most of the studies describe the prevalence and mortality risk associated with advanced stages of kidney failure, which affect a relatively small proportion of LTx patients. These studies underestimate the true burden of CKD, because they do not assess the long-term outcomes in liver recipients who do not reach these end stages [21].

In this work, we analyze the prevalence of CKD by its severity and assess its impact on patient survival. We take advantage of the data resources available to this program from protocolized measurement of GFR by iothalamate clearance in liver recipients. Using mGFR, we aimed to determine (a) the prevalence of the entire spectrum of renal dysfunction after LTx and (b) the impact of CKD on patient survival after LTx.

Section snippets

Patients

Data on all adults undergoing primary LTx at Mayo Clinic, Rochester, MN between 1985 and 2012 were extracted from a prospective database tracking all LTx recipients. We excluded patients who underwent simultaneous multiple organ transplant and those who underwent a repeated LTx. The study was approved by our institutional review board.

Data

All laboratory data, including mGFR, were extracted from the LTx database and the institutional laboratory file. Outcome of follow-up, including patient survival

Patients

A total of 1266 patients met the eligibility criteria. Of these, 1211 (96%) were alive at 4 months after LTx and were included in the analysis. The median age at LTx was 54 (range 19–73) years; the majority of the recipients were male and white (Table 1). The median follow-up time for the overall study period was 6 (range 0–26.4) years, expectedly longer for the pre-MELD era (11 years) than for the MELD era (3 years). GFR was measured at least once at LTx, at 4 months or later post-LTx in 95% of

Discussion

As of 2014, CKD remains a prevalent complication after liver transplantation and carries a substantial mortality risk. In this study, we describe the full spectrum of renal dysfunction, assessed by measured GFR, after LTx in a large sample of subjects followed up to 25 years. An overwhelming majority of liver recipients develop moderate to severe CKD within the first year post-LTx, while only a small fraction of patients maintain normal renal function long-term. Of all patients undergoing LTx,

Financial support

National Institute of Diabetes and Digestive and Kidney Diseases DK-34238 and DK-92336 (WRK).

Conflict of interest

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.

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