The effect of early everolimus administration on the renal function while reducing the dosage of calcineurin inhibitors in liver transplant recipients in a long-term follow-up

Introduction. The lifelong use of calcineurin inhibitors in liver transplant recipients leads to an increased incidence of chronic kidney disease.Objective. To compare the changes in glomerular filtration rate over five years in liver transplant recipients between those on everolimus with a reduced exposure to calcineurin inhibitors and those on standard doses of calcineurin inhibitors.Material and methods. Fourteen liver transplant recipient switched to everolimus with a minimization of calcineurin inhibitors exposure in the first months after liver transplantation from February 2009 to February 2015 who had received that therapy continuously for at least 60 months were included in the case-control study. Twenty eight liver transplant recipients (matched by sex, etiology of the underlying disease, calcineurin inhibitors) who were followed-up for at least 60 months after liver transplantation, who had received no dose of everolimus, in whom the glomerular filtration rate could be calculated at all points of analysis were selected as a comparison group (1:2). Glomerular filtration rate was calculated immediately before liver transplantation; 12, 24, 36, 48, and 60 months after liver transplantation. The glomerular filtration rate after liver transplantation was also calculated for liver transplant recipients from the main group immediately before the conversion to everolimus.Results. Before liver transplantation, the median of glomerular filtration rate in the main group of liver transplant recipients was lower (81.2 ml/min) than in the comparison group (97.5 ml/min, p=0.01). After liver transplantation, the renal function worsened in both groups of patients. In a pairwise comparison, the medians of glomerular filtration rate were statistically significantly lower after 12 months, 24 months, 36 months, 48 months after liver transplantation, than before liver transplantation. The median of glomerular filtration rate at the time of immunosuppression conversion was 44.3 ml/min. After the conversion of immunosuppression, the median of glomerular filtration rate gradually increased, and after 36 months the differences in glomerular filtration rate reached statistical significance compared with the level before conversion (69.4 ml/min;p=0.048). These differences still increased after 60 months after conversion (72.3 ml/min; p=0.041).Conclusion. Long-term administration of everolimus with minimization of calcineurin inhibitors exposure with the early conversion to this immunosuppression regime provides a steady improvement in renal function in liver transplant recipients with a low glomerular filtration rate in the preoperative and early post-transplant period.

Download Full-text

Effect of cyclosporin and tacrolimus on kidney function in liver recipients

Research Results in Pharmacology ◽

10.3897/rrpharmacology.4.29502 ◽

2018 ◽

Vol 4 (3) ◽

pp. 37-42

Author(s):

Elena Kosmacheva ◽

Anna Babich

Keyword(s):

Chronic Kidney Disease ◽

Liver Transplantation ◽

Renal Function ◽

Glomerular Filtration Rate ◽

Kidney Disease ◽

Glomerular Filtration ◽

Kidney Function ◽

Filtration Rate ◽

Calcineurin Inhibitors

Introduction. Chronic renal failure is a significant issue regarding treatment of patients after liver transplantation. One of the factors determining the impaired renal function after liver transplantation is a long-term immunosuppressive therapy based on calcineurin inhibitors. The objective of the study was to evaluate the dynamics of renal function, depending on the use of various calcineurin inhibitors in the long-term postoperative period in liver recipients in real clinical practice. Materials and methods. A retrospective analysis of the renal function in patients operated in the State Public Health Budget Institution “Scientific Research Institute – S.V. Ochapovsky Regional Clinic Hospital № 1”, Krasnodar Region, was carried out. This article describes dynamics of creatinine level and glomerular filtration rate (GFR) in patients before liver transplant, as well as 6 months, 1, 2 and 3 years after surgery. GFR was calculated using the CKD-EPI formula (Chronic Kidney Disease Epidemiology Collaboration). Statistical processing of the results was carried out using the Statistica 10 software package. Results and discussion. Before transplantation, the level of creatinine in the blood plasma was 82.9±19.8 mmol/l, 6 months later a20.4% increase in creatinine was registered (p=0.004), 12, 24 and 36 months later – it increased by 24.8% (p=0.00001), 24.4% (p=0.0004), and 26.0% (p=0.0005), respectively. Both cyclosporine and tacrolimus caused an increase in the level of creatinine. Baseline GFR was 83.4±25.9, the reduction in GFR occurred in comparison with the baseline by 14.2% (p=0.0005), 18.8% (p=0.00001), 20.2% (p=0.00003), 22.6% % (p=0.00006) 6, 12, 24 and 36 months later, respectively. The degree of the decrease in GFR against the background of tacrolimus therapy did not differ significantly from that in case of cyclosporine. Verification of chronic kidney disease and the administration of statins were recorded in isolated cases. Conclusions. In liver recipients, the level of creatinine rises and GFR decreases. Reduction of kidney function occurs against the background of both inhibitors of calcineurin, in connection with which it is necessary to increase the doctors’ alertness for early detection of a decrease in glomerular filtration rate with further verification of chronic kidney disease.

Download Full-text

Mo1922 Cystatin-C Improves Accuracy of Estimation of Glomerular Filtration Rate in Liver Transplant Recipients

Gastroenterology ◽

10.1016/s0016-5085(12)63875-x ◽

2012 ◽

Vol 142 (5) ◽

pp. S-1000

Author(s):

Alina M. Allen ◽

Andrew D. Rule ◽

Nelson Leung ◽

Chun Fan ◽

Terry M. Therneau ◽

...

Keyword(s):

Glomerular Filtration Rate ◽

Liver Transplant ◽

Glomerular Filtration ◽

Cystatin C ◽

Filtration Rate ◽

Transplant Recipients ◽

Liver Transplant Recipients

Download Full-text

Changes in glomerular filtration rate in liver recipients after reduced exposure to calcineurin inhibitors with concomitant everolimus administration within the first year after immunosuppression conversion

Russian Journal of Transplantology and Artificial Organs ◽

10.15825/25/1995-1191-2021-4-32-41 ◽

2021 ◽

Vol 23 (4) ◽

pp. 32-41

Author(s):

V. E. Syutkin ◽

A. A. Salienko ◽

S. V. Zhuravel ◽

M. S. Novruzbekov

Keyword(s):

Renal Function ◽

Glomerular Filtration Rate ◽

Glomerular Filtration ◽

Filtration Rate ◽

Calcineurin Inhibitors ◽

Deceased Donor ◽

First Year ◽

The Mean ◽

Older Recipients

Objective: to compare changes in estimated glomerular filtration rate (eGFR) in liver recipients with initially normal and impaired eGFR within the first year after immunosuppression conversion.Materials and methods. Enrolled in the study were 215 recipients of deceased-donor livers from February 2009 to February 2020, who received everolimus with dose reduction or complete withdrawal of calcineurin inhibitors (immunosuppression conversion, ISxC) for varying periods of time. GFR was measured using the MDRD-4 formula immediately before ISxC, then 3, 6, and 12 months after orthotopic liver transplantation (LTx). One month was considered an acceptable temporary deviation from the corresponding point.Results. At the time of ISxC, 32 (15%) of 215 recipients had normal renal function. Chronic kidney disease (CKD) increased in 60% of the recipients with normal eGFR by the end of the first year following ISxC; the fall in eGFR was particularly pronounced in older recipients. In the group with a baseline eGFR of 60–89 mL/min/1.73 m2, eGFR normalized in 62% of cases within 12 months; 28% of cases had no changes in renal function. In the subgroup with a pronounced decrease in eGFR at the time of ISxC, increased eGFR was observed as early as 1 month after ISxC, and the maximum was recorded after 3–6 months. The mean eGFR relative to baseline by month 3 after eGFR were higher for ISxC that was done in the first 2 months after LTx (19.7 ± 15.7 ml/minute/1.73 m2) than for ISxC done in the long-term period after LTx (10.1 ± 8.7 ml/minute/1.73 m2, p < 0.05).Conclusion. Changes in eGFR in liver recipients receiving EVR plus low-dose calcineurin inhibitor (CNI) depend on baseline eGFR and are multidirectional. The use of ISxC in the early post-LTx period led to a more pronounced improvement in eGFR. Maximal changes in eGFR were observed by 3–6 months after ISxC.

Download Full-text