Switching the use of calcineurin inhibitors (CNIs), as basal immunosuppression in liver transplantation (LT) patients, for that of mycophenolate mofetil monotherapy (MMF-MT) is currently considered a good measure in recipients with chronic kidney disease (CKD) and other CNI-related adverse effects. We analyzed a retrospective cohort series of 324 LT patients who underwent long-term follow-up and were switched from CNI immunosuppression to MMF-MT due to CKD and other CNI-related adverse effects (diabetes, hypertension, infection). The median time on MMF-MT was 78 months. The indication for MMF-MT was CKD alone or associated with CNI-related adverse effects in 215 patients, diabetes in 61, hypertension in 42, and recurrent cholangitis in 6. Twenty-four (7.4%) patients developed non-resistant acute rejection post-MMF-MT, and 48 (14.8%) patients experienced MMF-related adverse effects, with MMF-MT withdrawn in only 8 (2.5%) patients. In the comparison between the pre-MMF-MT period and the last outpatient review, using a repeated measures model and taking each patient as its own comparator, we demonstrated a significant increase in GFR and significant decrease in creatinine and ALT values, remaining the other variables (diabetes, hypertension, and hematological and AST) within similar levels. Five-year survival post-MMF-MT conversion was 75.3%. MMF-MT significantly improved renal function, was well tolerated, and had a low rejection rate.

Tacrolimus and mycophenolate are important immunosuppressive agents used to prevent organ rejection in post-transplant patients. While highly effective, their use is associated with significant toxicity, requiring careful management. Tacrolimus, a calcineurin inhibitor, is linked to nephrotoxicity, neurotoxicity, metabolic disturbances such as diabetes mellitus and dyslipidemia, and cardiovascular complications such as hypertension and arrhythmias. Mycophenolate, a reversible inhibitor of inosine monophosphate dehydrogenase, frequently causes gastrointestinal disturbances, including diarrhea and colitis, as well as hematologic side effects like anemia and leukopenia, which increase infection risk. Therapeutic drug monitoring (TDM) and pharmacogenomics have emerged as essential strategies for mitigating these toxicities. TDM ensures tacrolimus trough levels are maintained within a therapeutic range, minimizing the risks of nephrotoxicity and rejection. Pharmacogenomic insights, such as CYP3A5 polymorphisms, allow for personalized tacrolimus dosing based on individual metabolic profiles. For mycophenolate, monitoring inosine monophosphate dehydrogenase activity provides a pharmacodynamic approach to dose optimization, reducing gastrointestinal and hematologic toxicities. Emerging tools, including dried blood spot sampling and pharmacokinetic modeling, offer innovative methods to simplify monitoring and enhance precision in outpatient settings. Despite their utility, the toxicity profiles of these drugs, including those of early immunosuppressants such as cyclosporine and azathioprine, necessitate further consideration of alternative immunosuppressants like sirolimus, everolimus, and belatacept. Although promising, these newer agents require careful patient selection and further research. Future directions in immunosuppressive therapy include integrating individual pharmacogenetic data to refine dosing, minimize side effects, and improve long-term graft outcomes. This narrative review underscores the importance of personalized medicine and advanced monitoring in optimizing post-transplant care.

Chronic kidney disease (CKD) is a progressive and irreversible complication in lung transplant patients who have received long-term treatment with tacrolimus. This study aimed to verify long-term tacrolimus exposure values in CKD progression.

We retrospectively analyzed the clinical data of adult lung transplant recipients performed at our center between 2012 and October 2015. Patients who completed the 5-year follow-up period were enrolled in this study. CKD was defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m².

Eighty patients were analyzed. Compared with baseline (109 ± 38.1 mL/min/1.73 m2), the average eGFR values of our patients gradually decreased during the fifth-year post transplantation (46.5%, 58.3 ± 28.3 mL/min/1.73 m2), and the decline in eGFR values was particularly pronounced in the first year (31.2%, 74.6 ± 28.91 mL/min/1.73 m2). Moreover, 10 (12.7%), 21 (26.9%), 24 (31.2%), 28 (41.2%), and 48 (60%) patients had eGFR <60 mL/min/1.73 m² at 3, 6, 1, 3, and 5 years after lung transplantation (LT), respectively. A significant negative correlation was found between tacrolimus dose and eGFR 6 months after LT (P = 0.0414). We found no correlation between the serum tacrolimus concentration and CKD progression.

eGFR constantly decreased and the incidence of CKD increased during the 5-year follow-up period after LT. The tacrolimus dose had a significant negative correlation with eGFR at 6 months after LT. Meanwhile, whole-blood tacrolimus trough concentrations were not correlated with eGFR decline. When possible, lower dosing within 1 year after LT can reduce potential nephrotoxic side effects.

Kidney disease after non-kidney solid organ transplantation (NKSOT) is a common post-transplant complication associated with deleterious outcomes. Kidney disease, both acute kidney injury and chronic kidney disease (CKD) alike, emanates from multifactorial, summative pre-, peri- and post-transplant events. Several factors leading to kidney disease are shared amongst solid organ transplantation in addition to distinct mechanisms unique to individual transplant types. The aim of this review is to summarize the current literature describing kidney disease in NKSOT. We conducted a narrative review of pertinent studies on the subject, limiting our search to full text studies in the English language. Kidney disease after NKSOT is prevalent, particularly in intestinal and lung transplantation. Management strategies in the peri-operative and post-transplant periods including proteinuria management, calcineurin-inhibitor minimization/ sparing approaches, and nephrology referral can counteract CKD progression and/or aid in subsequent kidney after solid organ transplantation. Kidney disease after NKSOT is an important consideration in organ allocation practices, ethics of transplantation. Kidney disease after SOT is an incipient condition demanding further inquiry. While some truths have been revealed about this chronic disease, as we have aimed to describe in this review, continued multidisciplinary efforts are needed more than ever to combat this threat to patient and allograft survival.

One third of cirrhotic patients present impaired kidney function. It has multifactorial causes and has a harmful effect on patients' morbi-mortality before and after liver transplant. Kidney function does not improve in all patients after liver transplantation and liver-transplant recipients are at high risk of developing chronic kidney disease. Causes for renal dysfunction can be divided in three groups: preoperative, peroperative and postoperative factors. To date, there is no consensus for the modality of evaluation the risk for chronic kidney disease after liver transplantation, and for its prevention. In the present review, we describe the outcome of kidney function after liver transplantation, and the prognostic factors of chronic kidney disease to determine a risk stratification for each patient. Furthermore, we discuss therapeutic options to prevent kidney dysfunction in this setting, and highlight the indications of combined liver-kidney transplantation.

We aimed to develop and validate a nomogram model for predicting CKD after orthotopic liver transplantation (OLT).

The retrospective data of 399 patients who underwent transplantation and were followed in our centre were collected. They were randomly assigned to the training set (n = 293) and validation set (n = 106). Multivariable Cox regression analysis was performed in the training set to identify predictors of CKD. According to the Cox regression analysis results, a nomogram model was developed and validated. The renal function of recipients was monitored, and the long-term survival prognosis was assessed.

The incidence of CKD at 5 years after OLT was 25.6%. Cox regression analysis identified several predictors of post-OLT CKD, including recipient age at surgery (HR 1.036, 95% CI 1.006-1.068; p = 0.018), female sex (HR 2.867, 95% CI 1.709-4.810; p < 0.001), preoperative hypertension (HR 1.670, 95% CI 0.962-2.898; p = 0.068), preoperative eGFR (HR 0.996, 95% CI 0.991-1.001; p = 0.143), uric acid at 3 months (HR 1.002, 95% CI 1.001-1.004; p = 0.028), haemoglobin at 3 months (HR 0.970, 95% CI 0.956-0.983; p < 0.001), and average concentration of cyclosporine A at 3 months (HR 1.002, 95% CI 1.001-1.003; p < 0.001). According to these parameters, a nomogram model for predicting CKD after OLT was constructed and validated. The C-indices were 0.75 and 0.80 in the training and validation sets. The calibration curve of the nomogram showed that the CKD probabilities predicted by the nomogram agreed with the observed probabilities at 1, 3, and 5 years after OLT (p > 0.05). Renal function declined slowly year by year, and there were significant differences between patients divided by these predictors. Kaplan-Meier survival analysis showed that the survival prognosis of recipients decreased significantly with the progression of renal function.

With excellent predictive abilities, the nomogram may be a simple and reliable tool to identify patients at high risk for CKD and poor long-term prognosis after OLT.

Most management guidelines and much of the available clinical trial evidence for immunosuppressants in liver transplantation (LT) pertain to Western practice. While evidence from Western studies may not translate to Asian settings, there is a paucity of Asian randomized controlled trials of immunosuppression in liver recipients. Nonetheless, there are notable differences in the indications and procedures for LT between Western and Asian settings. The Asian Liver Transplant Network held its inaugural meeting in Singapore in November 2016 and aimed to provide an Asian perspective on aspects of immunosuppression following LT. Because of their importance to outcome following LT, the meeting focused on (1) reducing the impact of renal toxicity, (2) hepatocellular carcinoma recurrence, and (3) nonadherence with immunosuppressant therapy.

In recent years, the use of mammalian target of rapamycin inhibitors has gained traction in their use as alternative or adjunct immunosuppressants in the post-liver transplantation (LT) setting. The efficacy of everolimus (EVR) in de novo LT is established and a reasonable time to initiate EVR is 30 d from LT surgery. Initiating EVR early post-LT allows for calcineurin inhibitor (CNI) reduction, thus reducing nephrotoxicity in LT recipients. However, data is inadequate on the appropriate timing for conversion from CNI to EVR maintenance in order to achieve optimal renoprotective effect without compromising drug efficacy. Adverse effects of proteinuria, hypercholesterolemia and hyperlipidemia are significantly higher as compared to standard CNI and long-term implications on graft and patient survival in LT is still unclear. Future research to explore strategies to minimise EVR adverse effects will be crucial for the success of EVR as an important alternative or adjunct immunosuppressive therapy in LT.