Reply: Chronic kidney disease after liver transplantation: Accurate measurement, early acute kidney injury, and renal-protective strategies.

In this article, we comment on the article by Sessa et al published in the recent issue of the World Journal of Transplantation, who revisit the three-decade single centre cohort of Muñoz-Serrano et al and conclude that chronic kidney disease (CKD) after liver transplantation (LT) is a modifiable determinant of long-term survival rather than an unavoidable consequence of calcineurin inhibitor exposure. We share their central position and welcome the weight they give to perioperative acute kidney injury (AKI), to calcineurin inhibitor minimisation through basiliximab induction and mycophenolate, and to the disciplined control of hypertension and metabolic disease. Our intention is to carry the argument one step further, because three problems lie beneath the literature they assemble and constrain what any inventory of risk factors can deliver. The first is metrological. Almost every reported association, including the signal attached to female sex, and the reported incidence itself, which varies according to the definition of CKD applied, the time point of ascertainment and whether creatinine-based or measured filtration is used, derive from creatinine-based estimates of glomerular filtration, a measure the same authors concede performs poorly in patients who are sarcopenic, oedematous and metabolically deranged. The second concerns timing, since the most powerful and most modifiable determinant of chronic injury is the passage from early AKI to fixed nephropathy, a transition that draws surveillance away from isolated tacrolimus trough concentrations, which did not predict one year disease in the index cohort, towards intrapatient variability and time within the therapeutic range. The third is therapeutic, because the prevailing synthesis omits the sodium glucose cotransporter 2 inhibitors, agents with established renal benefit in non-transplant CKD populations that deserve formal evaluation after LT. Measured accurately, protected early and evaluated pharmacologically, the kidney of the liver transplant recipient is more defensible than current practice assumes.