Impact of acute kidney injury and renal recovery status in deceased donor to kidney transplant outcome: results from the Thai national transplant registry.

The influence of acute kidney injury (AKI) and renal recovery in deceased donor (DD) on long-term kidney transplant (KT) outcome has not previously been elucidated in large registry study. Our retrospective cohort study included all DDKT performed in Thailand between 2001 and 2018. Donor data was reviewed case by case. AKI was diagnosed according to the KDIGO criteria. Renal recovery was defined if DD had an improvement in AKI to the normal or lower stage. All outcomes were determined until the end of 2020. This study enrolled 4234 KT recipients from 2198 DD. The KDIGO staging of AKI was as follows: stage 1 for 710 donors (32.3%), stage 2 for 490 donors (22.3%) and stage 3 for 342 donors (15.6%). AKI was partial and complete recovery in 265 (17.2%) and 287 (18.6%) before procurement, respectively. Persistent AKI was revealed in 1906 KT of 990 (45%) DD. The ongoing AKI in DD significantly increases the risk of DGF development in the adjusted model (HR 1.69; 95% CI 1.44-1.99; p < 0.001). KT from DD with AKI and partial/complete recovery was associated with a lower risk of transplant loss (log-rank P = 0.04) and recipient mortality (log-rank P = 0.042) than ongoing AKI. KT from a donor with ongoing stage 3 AKI was associated with a higher risk of all-cause graft loss (HR 1.8; 95% CI 1.12-2.88; p = 0.02) and mortality (HR 2.19; 95% CI 1.09-4.41; p = 0.03) than stage 3 AKI with renal recovery. Persistent AKI, but not recovered AKI, significantly increases the risk of DGF. Utilizing kidneys from donors with improving AKI is generally safe. KT from donors with persistent AKI stage 3 results in a higher risk of transplant failure and recipient mortality. Therefore, meticulous pretransplant evaluation of such kidneys and intensive surveillance after KT is recommended.

Lipid management to mitigate poorer postkidney transplant outcomes.

PURPOSE OF REVIEW: Lipid disorder is a prevalent complication in kidney transplant recipients (KTRs) resulting in cardiovascular disease (CVD), which influences on patient outcomes. Immunosuppressive therapy demonstrated the major detrimental effects on metabolic disturbances. This review will focus on the effect of immunosuppressive drugs, lipid-lowering agents with current management, and future perspectives for lipid management in KTRs. RECENT FINDINGS: The main pathogenesis of hyperlipidemia indicates an increase in lipoprotein synthesis whilst the clearance of lipid pathways declines. Optimization of immunosuppression is a reasonable therapeutic strategy for lipid management regarding immunologic risk. Additionally, statin is the first-line lipid-lowering drug, followed by a combination with ezetimibe to achieve the low-density lipoprotein cholesterol (LDL-C) goal. However, drug interaction between statins and immunosuppressive medications should be considered because both are mainly metabolized through cytochrome P450 3A4. The prevalence of statin toxicity was significantly higher when concomitantly prescribed with cyclosporin, than with tacrolimus. SUMMARY: To improve cardiovascular outcomes, LDL-C should be controlled at the target level. Initiation statin at a low dose and meticulous titration is crucial in KTRs. Novel therapy with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, which is highly effective in reducing LDL-C and cardiovascular complications, and might prove to be promising therapy for KTRs with statin resistance or intolerance.

Preemptive Living-Related Kidney Transplantation Is a Cost-Saving Strategy Compared With Post-dialysis Kidney Transplantation in Thailand.

Background: Compared with other kidney replacement therapies, preemptive kidney transplantation (KT) provides better clinical outcomes, reduces mortality, and improves the quality of life of patients with end-stage kidney disease (ESKD). However, evidence related to the cost-effectiveness of preemptive living-related KT (LRKT) is limited, especially in low- and middle-income countries, such as Thailand. This study compared the cost-effectiveness of LRKT with those of non-preemptive KT strategies. Methods: Cost and clinical data were obtained from adult patients who underwent KT at Siriraj Hospital, Mahidol University, Thailand. A decision tree and Markov model were used to evaluate and compare the lifetime costs and health-related outcomes of LRKT with those of 2 KT strategies: non-preemptive LRKT and non-preemptive deceased donor KT (DDKT). The model's input parameters were sourced from the hospital's database and a systematic review. The primary outcome was incremental cost-effectiveness ratios (ICERs). Costs are reported in 2020 United States dollars (USD). One-way and probabilistic sensitivity analyses were performed. Results: Of 140 enrolled KT patients, 40 were preemptive LRKT recipients, 50 were non-preemptive LRKT recipients, and the rest were DDKT recipients. There were no significant differences in the baseline demographic data, complications, or rejection rates of the three groups of patients. The average costs per life year gained were $10,647 (preemptive LRKT), $11,708 (non-preemptive LRKT), and $11,486 (DDKT). The QALY gained of the preemptive option was 0.47 compared with the non-preemptive strategies. Preemptive LRKT was the best-buy strategy. The sensitivity analyses indicated that the model was robust. Within all varied ranges of parameters, preemptive LRKT remained cost-saving. The probability of preemptive LRKT being cost-saving was 79.4%. Compared with non-preemptive DDKT, non-preemptive LRKT was not cost-effective at the current Thai willingness-to-pay threshold of $5113/QALY gained. Conclusions: Preemptive LRKT is a cost-saving strategy compared with non-preemptive KT strategies. Our findings should be considered during evidence-based policy development to promote preemptive LRKT among adults with ESKD in Thailand.

QuantiFERON-Cytomegalovirus Assay for Prediction of Cytomegalovirus Viremia in Kidney Transplant Recipients: Study From High Cytomegalovirus Seroprevalence Country.

Background: Early studies showed the utility of pretransplant QuantiFERON-Cytomegalovirus (QF-CMV) assays for CMV-disease prediction post kidney transplant (KT). However, recent data are conflicting. Methods: This prospective cohort study enrolled adult patients undergoing KT between July 2017 and May 2019. Patients with antithymocyte globulin therapy or negative pretransplant CMV IgG were excluded. QF-CMV assays were performed on transplantation day and one month thereafter, and CMV viral loads were obtained 1, 3, and 6 months posttransplantation. The primary outcome was CMV viremia within 6 months. The QF-CMV assay-posttransplant CMV viremia association was analyzed. Results: Fifty-five patients were enrolled (male, 58.2%; mean (SD) age, 46.5 (10.2) years). Fifty-two (94.5%) received CMV-seropositive donor kidneys. Over 6 months, 29 patients developed CMV viremia (52.7%), with 14 (25.5%) having significant viremia requiring antiviral therapy. The CMV-viremia incidence of patients with nonreactive and reactive baseline QF-CMV assays did not differ significantly (55.3% and 47.1%; p = 0.573). Among patients with reactive pretransplant QF-CMV assays, there was a trend toward a lower incidence of CMV viremia for those who were persistently reactive at 1 month after KTs, although there was no statistically significant difference (50% vs 83%; p = 0.132). Conclusions: Our study could not support the use of single-timepoint pretransplant or 1-month posttransplant QF-CMV assays as a predictor for posttransplant CMV viremia in CMV seropositive KT recipients. Investigation of the association between dynamic QF-CMV-status changes and CMV-viremia incidence are needed.

Efficacy of Bortezomib as an Adjunctive Therapy for Refractory Chronic Active Antibody-Mediated Rejection in Kidney Transplant Patients: A Single-Center Experience.

BACKGROUND: Chronic active antibody-mediated rejection (CAMR) has unsatisfactory prognosis in spite of intensive standard antihumoral treatment. Efficacy of additional bortezomib in CAMR remains uncertain. METHODS: A retrospective chart review was conducted among kidney transplant patients with biopsy-proven CAMR. Our standard CAMR protocol included plasma exchange, intravenous immunoglobulin, and rituximab. Repeated treatment was provided for refractory cases. Patients receiving at least 1 course of bortezomib were enrolled as the bortezomib group. Allograft outcome was compared among patients receiving repeated standard protocol alone and the bortezomib group. RESULTS: Thirteen and 15 patients were assigned to the bortezomib and control groups, respectively. Repeated bortezomib protocol was given for 1, 2, 3, and 4 courses in 6, 4, 1, and 2 patients, respectively. With a median follow-up time after treatment of 41.8 (18.3-47.4) months, the bortezomib group had a lower rate of glomerular filtration rate declination (-4.20 ± 4.89 mL/min/y vs -12.33 ± 10.44 mL/min/y; P = .014), a higher rate of disappearance of donor specific antibodies (69.2% vs 25%; P = .03), a lower rate of allograft loss (15.4% vs 66.7%; P = .006), and better allograft survival (P = .006). CONCLUSION: In CAMR, additional bortezomib treatment was more effective in eliminating donor specific antibodies and improving allograft survival than standard protocol treatment.

A Study of the Pharmacokinetic Comparison between the Generic and Original Form of Mycophenolate Mofetil Among Thai Renal Transplant Patients.

BACKGROUND: Mycophenolic acid (MPA) is one of the main immunosuppressive regimens used after kidney transplantation (KT). The less expensive, generic form of mycophenolate mofetil (MMF) (Immucept®) is recently available in Thailand. Comparisons of the pharmacokinetic profiles between the original and generic forms of MMF among post-KT patients are limited. METHODS: This prospective cohort study recruited KT patients receiving stable doses of MMF 1000 mg daily along with tacrolimus and steroids. All participants were prescribed CellCept® 500 mg every 12 hours for at least 2 weeks before measuring the MPA area under the curve from 0 to 12 hours (AUC0-12). CellCept® was switched to Immucept® 500 mg every 12 hours for 2 weeks and MPA AUC0-12 was remeasured. RESULTS: Twenty patients with a median follow-up time of 35.4 (11.13-198.83) months were enrolled. Mean MPA AUC0-12 of Immucept® was higher than CellCept® without statistical significance (48.27 ± 2.31 µg⋅hr/mL vs 42.19±15.20 µg⋅hr/mL; P value = .59). No difference was revealed regarding the minimum measured concentration, maximum measured concentration, and time point with maximum concentration between both drugs. While on CellCept®, 5 patients (25%) had an MPA AUC0-12 < 30.0 µg⋅hr/mL, but 3 patients (15%) had MPA AUC0-12 < 30.0 µg⋅hr/mL when receiving Immucept®. However, 3 (15%) and 6 (30%) patients had MPA AUC0-12 > 60.0 µg⋅hr./mL when treated with CellCept® and Immucept®, respectively. CONCLUSION: Generic MMF exhibited a comparable pharmacodynamic profile as the original formulation. MPA AUC0-12 was more than 30.0 µg⋅hr/mL among most patients receiving MMF 1000 mg/day.

Effect on Dosage Change and Intrapatient Variability After Conversion From Twice-Daily to Once-Daily Tacrolimus Among Thai Kidney Transplant Patients With and Without CYP3A4/5 Inhibitors.

BACKGROUND: Converting to once-daily tacrolimus (Advagraf [Adv]) among renal transplant patients results in better drug adherence. Data regarding dosage and intrapatient variability changes after conversion among patients with CYP3A4/5 inhibitors (CYPinh) is lacking. METHOD: A retrospective chart review among all kidney transplant recipients at Siriraj Hospital was performed. Patients were enrolled who had been on standard release twice-daily tacrolimus and subsequently replaced it with Adv for at least 6 months with no change in CYPinh type or dosage. RESULTS: Fifty-three patients were eligible. Conversion occurred at a mean time after transplant of 51.25 (SD, 40.30) months. Ten patients (18.9%) did not receive CYPinh, while 19 (35.8%), 21 (39.6%), and 3 (5.7%) received diltiazem, ketoconazole or fluconazole, and both diltiazem and ketoconazole, respectively. After conversion, median increment of tacrolimus dosage was 14.29% (-50% to 167%), while no significant change in IPV was demonstrated (17.46% [SD, 11.25%] vs 14.83% [SD, 6.78]; P = .11). Patients receiving azole had less dosage increment than those not receiving CYPinh (P = .02). After conversion, 14 of 22 patients with IPV > 17% (63.6%) had reduced IPV to ≤ 17%, while 25.8% of patients with lower IPV had an increase in IPV > 17%. CONCLUSION: Conversion to Adv required a dosage increment of 30% to achieve the same trough level. Concomitant use of CYPinh significantly reduced tacrolimus dose increment. A trend was noted toward improved IPV after conversion. Conversion to Adv resulted in better IPV among patients with high IPV while receiving twice-daily tacrolimus.

Correlation Between Apparent Diffusion Coefficient Values of the Renal Parenchyma and Estimated Glomerular Filtration Rates on 3-T Diffusion-Weighted Echo-Planar Magnetic Resonance Imaging.

OBJECTIVE: To evaluate the relationship between the apparent diffusion coefficient (ADC) values of renal parenchyma and estimated glomerular filtration rates (eGFR). METHODS: Data on 216 patients examined by 3-T magnetic resonance imaging for various reasons were retrospectively collected. RESULTS: There was a significant linear correlation between the ADC values and eGFRs (r = 0.254, P < 0.001). The ADC values in patients with an eGFR of less than 60 mL/min per 1.73 m were significantly lower than those with an eGFR of 60 mL/min per 1.73 m or greater. The mean ADC value of patients with grouped stage 2 disease was significantly higher than those with grouped stage 3 of chronic kidney disease (P < 0.01). CONCLUSIONS: The ADC value of renal parenchyma may be a promising marker for the determination of patients with normal to mild reduction in renal function (eGFR ≥60 mL/min per 1.73 m) versus those with a moderate to severe reduction in renal function (eGFR <60 mL/min per 1.73 m).

Clinical accuracy of RIFLE and Acute Kidney Injury Network (AKIN) criteria for predicting hospital mortality in critically ill patients with multi-organ dysfunction syndrome.

BACKGROUND: The Acute Dialysis Quality Initiative (ADQI) group developed RIFLE criteria and the Acute Kidney Injury Network published AKIN classification that modified form RIFLE criteria. OBJECTIVE: The authors aimed to compare the ability of RIFLE and AKIN criteria to measure the incidence of acute kidney injury (AKI) and to predict clinical outcomes in critically illpatients. MATERIAL AND METHOD: A retrospective cohort study, in Siriraj Hospital, Bangkok. The critically ill patients admitted to medical intensive care unit (ICU) during January 2006-December 2008 were classified according to the maximum RIFLE and AKIN classification reached during their hospital stay Demographic data, hospital mortality, hospital length of stay, need of renal replacement therapy was collected. RESULTS: Three hundred patients were included in this study, AKI occurred in 200 (66.7%) patients: Risk 12.7%, Injury 20.7%, Failure 33.3% defined by RIFLE criteria. According to AKIN criteria, AKI occurred 230 (76.7%) patients: stage 1 16%, stage 2 13.3% and stage 3 47.3%. AKIN classification was diagnosed AKI, approximately 10% more than RIFLE (p < 0.001). The hospital mortality was 51.7% and the mortality in patients with AKI was significantly higher than patients without AKI (p < 0.001). The predictive ability using the AUC-ROC showed poor discrimination for the prediction of mortality of both RIFLE and AKIN: 0.63 and 0.69, respectively. However, AKIN showed superior prediction of mortality than RIFLE (p = 0.003). The APACHE II had the best discriminative accuracy for mortality (AUC = 0.80), followed by the SAPS3 scores (AUC = 0.77) and SAPS2 (AUC = 0.76). CONCLUSION: AKIN criteria improved sensitivity for detection of AKI and its discrimination for prediction of in-hospital mortality was better than that of RIFLE criteria. However, APACHE II had the best discriminative value for prediction of mortality in the critically ill patients.