Rethinking chronic kidney disease risk after liver transplantation

Table 1 Summary of key non-immunosuppressive chronic kidney disease risk factors post-liver transplantation

Ref.	Risk factor category	Specific predictor	Clinical significance
Muñoz-Serrano et al[1], 2025	Demographics	Female sex	Independent risk factor for CKD at 1 year (OR = 1.88)
Li et al[5], 2018	Pre-transplant status	High pre-LT serum creatinine/Low GFR	Strongest independent predictor of long-term CKD (OR = 7.74 for Cr)
Li et al[5], 2018	Perioperative event	AKI within 7 days post-LT	Major independent determinant of CKD progression (OR = 2.72)
Li et al[5], 2018	Metabolic comorbidity	Hypertension (post-LT)	Powerful independent risk factor for new-onset CKD (OR = 4.833)
Canbay et al[7], 2016	Etiology/comorbidity	NAFLD/NASH cirrhosis	Pre-existing inflammatory/metabolic burden elevates inherent CKD risk
Mallamaci et al[6], 2024	Demographics	Older age	Non-modifiable primary risk factor for CKD

AKI: Acute kidney injury; CKD: Chronic kidney disease; Cr: Creatinine; GFR: Glomerular filtration rate; LT: Liver transplantation; NAFLD: Nonalcoholic fatty liver disease; NASH: Nonalcoholic steatohepatitis; OR: Odds ratio.

Table 2 Comparative profile of tacrolimus vs cyclosporine A post-liver transplantation

Ref.	Clinical outcome	TAC profile (relative to CsA)	CsA profile (relative to TAC)	Supporting evidence type
Muduma et al[12], 2016	Patient mortality	Superior/Lower risk	Higher risk	RCTs/meta-analysis
Muduma et al[12], 2016	New-onset diabetes (NODAT)	Higher risk	Superior/Lower risk	RCTs/meta-analysis
Randhawa et al[11], 1997; Muduma et al[12], 2016	Hypertension	Superior/Lower risk	Higher risk	RCTs/meta-analysis
Muduma et al[12], 2016	Graft loss (overall)	Equivalent	Equivalent	RCTs/meta-analysis
Muduma et al[12], 2016	Graft loss (HCV subgroup)	Higher risk	Superior/Lower risk	Meta-analysis

CsA: Cyclosporine A; HCV: Hepatitis C virus; LT: Liver transplantation; NODAT: New-onset diabetes after transplantation; RCTs: Randomized controlled trials; TAC: Tacrolimus.

Table 3 Efficacy of calcineurin inhibitor minimization strategies on renal outcomes post-liver transplantation

Ref.	Strategy	Primary mechanism of renal protection	Renal outcome	Trade-off/safety signal	Evidence source
Muñoz-Serrano et al[1], 2025; Kong et al[17], 2011	MMF addition/conversion	Reduces the required CNI trough level	Significant long-term eGFR improvement	Low rejection rate; generally well tolerated	Retrospective study Meta-analysis/conversion studies
Lange et al[15], 2018; Hashim et al[16], 2020	Basiliximab induction	Enables delayed CNI initiation	Reduces medium-term renal dysfunction post-LT (7.1% incidence)	Does not adversely affect BPAR or survival	Clinical trial/review
Saliba et al[19], 2022	EVR avoidance	Non-nephrotoxic primary mechanism	Renal function potentially better preserved in actual treatment subgroups	Higher BPAR; higher rate of de novo cancer observed	Observational/follow-up study

BPAR: Biopsy-proven acute rejection; LT: Liver transplantation; CNI: Calcineurin inhibitor; eGFR: Estimated glomerular filtration rate; EVR: Everolimus; MMF: Mycophenolate mofetil.

Table 4 Practical algorithm for maintenance immunosuppression after liver transplantation

Step	Patient factors/clinical scenario	Preferred regimen	Alternative regimen/key considerations
1	Standard risk (normal renal function, no specific comorbidities)	TAC + MMF ± steroids	CsA + MMF ± steroids: Monitor closely for CNI toxicity and NODAT
2	Renal dysfunction (eGFR < 60 mL/minute) or CNI toxicity	EVR + low-dose TAC	Everolimus + MMF (CNI-free): Reserved for patients with severe CNI intolerance due to higher rejection risk; monitor for proteinuria and wound healing
3	History of malignancy (e.g., HCC history, skin cancer)	Everolimus-based regimen	Sirolimus-based regimen: Leverage the antineoplastic effects of mTOR inhibitors to reduce recurrence risk
4	High immunological risk (e.g., autoimmune etiology, young age)	Induction with thymoglobulin followed by TAC + MMF	Standard triple therapy: Consider delayed CNI introduction to protect renal function during the perioperative phase
5	SLKT recipients (Simultaneous liver-kidney transplant)	Standard CNI-based regimen	Individualized approach: Therapy must be tailored to protect the kidney graft while preventing liver rejection

Recommendations adapted from Nedredal et al[20] and Pollok et al[21]. TAC: Tacrolimus; MMF: Mycophenolate mofetil; CsA: Cyclosporine A; CNI: Calcineurin inhibitor; NODAT: New-onset diabetes after transplantation; EVR: Everolimus; HCC: Hepatocellular carcinoma; SLKT: Simultaneous liver-kidney transplantation.