scholarly journals 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

Author(s):  
V. E. Syutkin ◽  
A. A. Salienko ◽  
S. V. Zhuravel ◽  
M. S. Novruzbekov

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.

2018 ◽  
Vol 4 (3) ◽  
pp. 37-42
Author(s):  
Elena Kosmacheva ◽  
Anna Babich

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.


Author(s):  
V. E. Syutkin ◽  
A. A. Salienko ◽  
O. D. Olisov ◽  
S. V. Zhuravel ◽  
M. S. Novruzbekov

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.


2013 ◽  
Vol 1 (4) ◽  
pp. 371 ◽  
Author(s):  
Luis H.P. Braga ◽  
Armando J. Lorenzo ◽  
Sumit Dave ◽  
Maria H. Del-Valle ◽  
Antoine E. Khoury ◽  
...  

Introduction: Urinary continence after cloacal repair is difficult to achieveand renal outcome in patients with cloacal malformations has been scarcelyreported. As a result, we reviewed our experience with cloacal malformationsto determine the status of continence and the long-term renal function in thesechildren.Methods: A retrospective chart review from 1990 to 2003 identified 12 patientswith cloacal malformation (1 posterior, 4 complex and 7 classical) who underwentsurgical reconstruction. The confluence was defined as high (commonchannel ≥ 3 cm) and low (< 3 cm) by cystovaginoscopy. Renal ultrasound,voiding cystouretrogram, renal scan and sacral radiograph were performedin all children. Most patients underwent 1-stage abdominoperineal pull-through,applying the principle of total urogenital sinus mobilization. We collected dataregarding hydronephrosis, vesicoureteral reflux and split differential renal function.Renal outcome was evaluated based on glomerular filtration rate and ageadjustedserum creatinine values (μmol/L). Urinary continence was definedas a dry interval > 4 hours.Results: Patients’ mean age at surgery was 20 months (range 7–29 mo). Ofthe 12 children who underwent cloacal repair, 7 (58.3%) had a common channel≥ 3cm. Renal anomalies were identified in 3 of 12 (25%) girls: there were 2 solitary kidneys and 1 pelvic kidney. Lumbar–sacral radiography demonstrated bony abnormalities in 11 of the 12 (91.6%) cases: hemivertebra in 3 cases, sacral agenesis in 4 cases, hypoplastic sacrum in 3 cases and bifid sacrum in 1 case. Total urogenital sinus mobilization through an abdominoperineal approach in a single stage was performed in 8 girls. Follow-up ranged from 4 to 14 years (mean 8.5 yr). Eight (66.6%) children had dry intervals > 4 hours, 5 (62.5%) of them were on clean intermittent catheterization through aMitrofanoff channel and 1 (12.5%) was through the urethra. The remaining 2 (25%) patients were voiding spontaneously. Three (33.3%) patients were totally incontinent, and 1 (8.3%) patient was awaiting reconstruction. The mean measured glomerular filtration rate was 93.5 mL/min/1.73m2 (range 34–152 mL/min/1.73m2). Four (57.1%) of 7 patients who had a common channel ≥ 3 cm ended up needing augmentation cystoplasty, compared with none of the patients with a common channel < 3 cm (57.1% v. 0%, p = 0.038).Conclusion: Urinary continence can be achieved in most patients with cloacalmalformation at the expense of major reconstructive surgery and despite thepresence of associated urological abnormalities. However, these childrenharbour an important risk for renal impairment later in life and should be closelymonitored.


1993 ◽  
Vol 85 (6) ◽  
pp. 733-736 ◽  
Author(s):  
R. Rustom ◽  
J. S. Grime ◽  
P. Maltby ◽  
H. R. Stockdale ◽  
M. J. Jackson ◽  
...  

1. The new method developed to measure renal tubular degradation of small filtered proteins in patients with normal renal function, using radio-labelled aprotinin (Trasylol) (R. Rustom, J. S. Grime, P. Maltby, H. R. Stockdale, M. Critchley, J. M. Bone. Clin Sci 1992; 83, 289–94), was evaluated in patients with chronic renal failure. 2. Aprotinin was labelled with either 99mTc (40 MBq) or 131I (0.1 MBq), and injected intravenously in nine patients, with different renal pathologies. 51Cr-EDTA clearance (corrected for height and weight) was 40 + 5.4 (range 11.2-81) ml min−1 1.73 m−2. Activity in plasma and urine was measured over 24–48 h, and chromatography on Sephadex-G-25-M was used to separate labelled aprotinin from free 99mTcO4− or 131I−. Renal uptake was measured for 99mTc-labelled aprotinin only. 3. The volume of distribution was 20.2 + 2.3 litres. Chromatography showed all plasma activity as undegraded aprotinin, and urine activity only as the free labels (99mTcO4− or 131I−). 4. As in patients with normal renal function, activity in the kidney appeared promptly, with 5.7 + 2.5% of the dose detected even at 5 min. Activity rose rapidly to 9.4 + 1.6% of dose after 1.5 h, then more slowly to 15.0 + 0.5% of dose at 4.5 h, and even more slowly thereafter, reaching 24.1 + 2.8% of dose at 24 h. Extra-renal uptake was again insignificant, and both 99mTcO4− and 131I− appeared promptly in the urine, with similar and uniform rates of excretion over 24 h. 5. Both tubular uptake at 24 h and the rate of tubular metabolism over 24 h were lower than in the patients with normal renal function studied previously, but only the rate of tubular metabolism was directly related to the glomerular filtration rate (r = 0.75, P <0.02). 6. Correction for the reduced glomerular filtration rate yielded values for both tubular uptake (0.67 + 0.14 versus 0.32 + 0.03% of dose/ml of glomerular filtration rate, P <0.005), and tubular metabolism (0.033 + 0.07 versus 0.015 + 0.001% of dose h−1 ml−1 of glomerular filtration rate, P <0.005) that were higher by comparison with those for patients with normal renal function studied previously. 7. Fractional renal degradation of 99mTc-aprotinin (in h−1), derived from the mean rate of urinary excretion of the free isotope over a given interval, divided by the mean cumulative kidney uptake over the same interval, also fell steeply early, and then more slowly to 0.07 + 0.01 h−1 at 14.25 h (between 4.5 and 24 h). 8. It is concluded that the method described previously is also suitable in patients with chronic renal failure, allowing further research into renal disease progression.


2015 ◽  
Vol 41 (1) ◽  
pp. 57-65 ◽  
Author(s):  
Sola Aoun Bahous ◽  
Maya Khairallah ◽  
Jad Al Danaf ◽  
Rim Halaby ◽  
Serge Korjian ◽  
...  

Background/Aims: Renal function decreases over time as a result of reduction in the number of functioning nephrons with age. In recipients and donors of kidney grafts, renal function decline may be linked differently to various parameters, namely arterial stiffness. Methods: We conducted a prospective cohort study including 101 recipients of kidney grafts and their donors aiming at determining the factors correlated to the renal function decline over time. Aortic stiffness was evaluated by the non-invasive measurement of aortic pulse wave velocity. The glomerular filtration rate was estimated using the Modification of Diet in Renal Disease (MDRD) equation and the annualized change was determined. Results: Decline in renal function was estimated at 1-year post-transplantation and annually thereafter (median follow-up 8 years, range 3.6-18.3), as the mean of the annualized decrease in the glomerular filtration rate. In recipients, filtration rate decreased by 4.8 ± 19.7 ml/min/1.73 m2 the first post-transplant year and at a yearly rate of 2.2 ± 3.8 ml/min/1.73 m2 thereafter. The first-year decline was related to smoking and acute rejection. Later decline was significantly associated with donor age and aortic stiffness. In living donors, renal function decline after the first year corresponded to 0.7 ml/min/1.73 m2, was significantly lower than that of recipients (p < 0.001), and was determined by donor age at nephrectomy. Conclusion: Recipients of kidney grafts show a glomerular filtration rate decline over time that is significantly associated with donor age and aortic stiffness after the first post-transplant year, while donors demonstrate a lower decline that is mostly determined by age at nephrectomy.


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