Effectiveness of Antithymocyte Globulin Induction Dosing Regimens in Kidney Transplantation Patients: A Network Meta-analysis

BackgroundAntithymocyte globulin (ATG) is an induction therapy in kidney transplantation, but our knowledge about the relation between outcomes and ATG regimens is limited. We compared ATG effectiveness in kidney transplantation according to dosage and administration schedule.MethodsReports from 1970 until May 2018 in CENTRAL, MEDLINE, EMBASE, and Science Citation Index Expanded were searched. We performed direct and indirect network meta-analysis using Bayesian models and generated rankings for ATG dosage and injection number variations by generation mixed treatment comparison.We compared ATG dose and schedule in kidney transplantation in relation to all-cause death, graft failure, antibody-mediated rejection, T-cell mediated rejection, biopsy-proven acute rejection, and bacterial and viral infection.ResultsTen studies (N = 1065) were analyzed by forming 6 groups: ATG alternate doses, 9 mg/kg, 6 mg/kg, and 4.5 mg/kg; single dose, 6 mg/kg, and 4.5 mg/kg; and control. Compared to placebo, ATG regimen variations were not associated with significant differences in survival, viral infection, renal function, or graft survival. ATG regimens 9 and 4.5 mg alternate dosing tended to reduce biopsy-proven acute rejection but without statistical significance. According to the highest rank probability, the 9 mg alternate dosing group had the highest tendency for cytomegalovirus and bacterial infections but without statistical significance.ConclusionsThe rejection frequency tended to be lower for the 9 and 4.5 mg alternate dosing groups. Infections occurred at a higher rate in the 9 mg alternate dosing group, but the differences in the risk of infection among the groups with different ATG regimens were not statistically significant.     

Effect of Fluvastatin on Cardiovascular Complications in Kidney Transplant Patients: A Systemic Review and Meta-analysis

BackgroundHyperlipidemia and cardiovascular disease are risk factors for long-term renal transplant dysfunction. However, no meta-analyses of randomized controlled trials have investigated the effects of statin treatment on graft function in renal transplant recipients. The aim of the present study was to evaluate the effects of statin use on renal transplant patients using a meta-analysis approach.MethodsWe conducted a systematic review and meta-analysis using random effects modeling. We searched the following databases for all studies published through to June 15, 2018: Cochrane Central Register, OVID MEDLINE, Embase, and PubMed. We reviewed all relevant reviews, registered trials, and relevant conference proceedings to compare clinical outcomes and survival between fluvastatin recipients and controls.ResultsFive trials with a total of 3725 patients were included. Glomerular filtration rates, graft loss, tacrolimus level, antibody-mediated rejection, T cell–mediated rejection, proteinuria, fungal infection (candida), and patient survival rates did not differ between the fluvastatin and control groups. However, major adverse cardiovascular events were 1.547 times more common in the control group than in the fluvastatin group (P = .001).ConclusionsFluvastatin use was associated with a reduction in major adverse cardiac events among kidney transplant patients.     

Efficacy of Ultralow-Dose Valganciclovir Chemoprophylaxis for Cytomegalovirus Infection in ABO-Incompatible Kidney Transplantation Recipients

Background

Cytomegalovirus (CMV) infection can increase morbidity and mortality in kidney transplant (KT) patients. Chemoprophylaxis with valganciclovir (VGCV) is recommended for ABO-incompatible (ABOi) KT patients as it significantly reduces CMV disease and infection. The recommended dose of VGCV for prevention of CMV in a KT recipient is 900 mg once daily, and the treatment duration is 6 months. However, because it is expensive, sufficient amounts might not be administered.

Efficacy and Safety of Induction Therapy in Kidney Transplantation: A Network Meta-Analysis

Background

Rejection and infection can occur after kidney transplantation and are important factors in preserving graft kidney function. The use of immunosuppressant agents in transplantation is therefore important, and the question of which induction therapy should be used as an immunosuppressant is controversial.

Effect of Low-Dose Vs Standard-Dose Valganciclovir in the Prevention of Cytomegalovirus Disease in Kidney Transplantation Recipients: A Systemic Review and Meta-Analysis

Background

Valganciclovir is widely used to prevent post-transplant cytomegalovirus (CMV) infection in kidney transplant patients. However, the currently used dose remains controversial because the continuous use of this drug decreases kidney function and can induce leukopenia.

Early Focal Segmental Glomerulosclerosis as a Cause of Delayed Graft Function With Combined Acute Antibody Rejection: A Case Report

Focal segmental glomerulosclerosis (FSGS) is the most common form of post-transplant glomerulonephritis. We describe a case where a biopsy proved that early recurrence of FSGS on postoperative day 1 was the cause of delayed graft function. A 39-year-old man, on hemodialysis for 15 years due to polycystic kidney disease, received a cadaveric renal transplantation. On postoperative day 1, his hourly urine output decreased from 700–800 mL to 50 mL. The graft biopsy showed a mild acute kidney injury confusing nephrotic syndrome. On postoperative day 45, his creatinine level increased to 3.02 mg/dL with severe proteinuria. A kidney biopsy showed focal segmental glomerulosclerosis. On postoperative day 120, his creatinine level elevated again, concomitant with proteinuria. A kidney biopsy showed FSGS with antibody-mediated rejection. After plasmapheresis, his creatinine level decreased to 1.3 mg/dL with mild proteinuria. Once active in the allograft, de novo FSGS is a potentially aggressive process. In this case, it could be managed because of an accurate diagnosis and appropriate treatment.     

Long-Term Outcomes of Renal Function After Adult Intestinal Transplantation at a Single Small-Volume Center: 2 Cases of Renal Transplantation

PurposeRenal dysfunction more frequently occurs after intestinal transplantation (ITx) than after heart, lung, or liver transplantation. We provide a clinical analysis of renal function after adult ITx.MethodsWe retrospectively analyzed 8 adult ITx patients who survived for at least 6 months between 2004 and 2018. Glomerular filtration rate (GFR) measurements were performed at baseline, at 3 and 6 months post-transplantation, and yearly. The median follow-up duration was 53.5 months.ResultsAll cases were isolated ITx; 3 received living-donor ITx, and 5 received deceased-donor ITx. The mean baseline GFR was 97 mL/min/1.73 m². The GFR had decreased by more than 50% of baseline at 1 year post-transplant. Renal dysfunction was observed in 4 patients. Two patients developed acute kidney injury due to acute rejection and sepsis. One of these patients fully recovered renal function, but the second patient died. Another 2 patients developed chronic kidney disease and required hemodialysis (HD) within 6 and 3 years, respectively. The first living-donor ITx patient lost renal function progressively over 6 years after ITx. She received a renal graft from the same living donor as for the ITx after 3 years of HD. The other patient (deceased-donor ITx) received a kidney from his daughter at 5 months after HD.ConclusionsTo obtain an accurate assessment of renal function, frequent direct measurements of GFR should be performed to facilitate early diagnosis of renal impairment and to determine subsequent strategies to improve renal function after ITx.     

Factors of Acute Kidney Injury Donors Affecting Outcomes of Kidney Transplantation From Deceased Donors

BackgroundThis study aimed to investigate the outcomes of kidney transplantation (KT) from deceased acute kidney injury (AKI) donors and analyzed the factors affecting these outcomes.MethodsAll patients who underwent KT from deceased donors at our institution from 1998 to 2016 were retrospectively reviewed. Recipients were divided into the AKI and non-AKI donor groups. We analyzed delayed graft function (DGF), serum creatinine levels at 1 month and 1 year after KT, cold ischemia time, donors’ initial and terminal serum creatinine levels, Kidney Donor Profile Index, and patient and graft survival in each group.ResultsOf 181 recipients, 30 received kidneys from 21 AKI donors, whereas the remaining 151 received kidneys from donors without AKI. DGF more frequently developed in the AKI donor group than in the non-AKI donor group (40% vs 7.28%; P = .001). Allograft functions at 1 month and 1 year after KT did not differ between the AKI and non-AKI donor groups (1 month: P = .469; 1 year: P = .691). Factors affecting DGF were recipient weight and donor AKI. Recipient factors affecting graft function at 1 year were recipient height, length of hospital stay, serum creatinine levels at 1 month and 6 months, and biopsy-proven acute rejection. Older donor age was the only donor factor that affected graft function at 1 year.ConclusionKT from deceased AKI donors showed a higher DGF rate but favorable patient and graft survival and graft functions. Donor AKI and recipient weight affected DGF, and only older donor age affected graft function at 1 year.     

Changes in Bone Mineral Density After Kidney Transplantation

Background

Numerous studies have shown that osteoporosis is common in kidney transplant recipients. However, the change in bone mineral density after kidney transplantation (KT) is not fully understood.

Impact of Early Hospital Readmissions After Kidney Transplantation on Graft Function

Early hospital readmissions are common after kidney transplantation. This single-center retrospective study investigated the relationship between early hospital readmissions and clinical outcomes. All adult patients receiving a kidney transplant at this center between March 2009 and June 2015 were included. The early hospital readmissions within the first 30 days were numbered, and the diagnosis was ascertained. The patients were divided into None and Readmission groups. Clinical outcomes and patient- and death-censored graft survival were compared. Among the 103 patients included in the study, 32 (31.1%) had 1 or more readmissions within 30 days. Surgical complications, electrolyte imbalance, and acute rejection were common causes of readmission. No differences were observed in baseline characteristics between the two groups. Patients with early readmissions exhibited low renal function at 3, 6, and 12 months postoperatively (P = .002, .020, and .013, respectively). No difference in graft function was found 12 months after transplantation between the None and Readmission groups. Five-year graft and patient survival also showed no difference between the two groups (P?=?.424 and .442, respectively). In conclusion, early readmission after kidney transplantation affected lower graft function until 1 year after kidney transplantation. However, the long-term effect on graft function is limited in this study.     

Clinical Outcomes of Kidney Transplantation in Patients With Biopsy-Proven Glomerulonephritis

Background

The clinical outcomes after kidney transplantation (KT) according to the types of glomerulonephritis (GN) as the cause of end-stage renal disease (ESRD) are various, but there are not many studies on this.

Implementing eHealth in Kidney Transplantation in Finland

Digitalization of health care processes is currently under rapid development. In Finland, a nationwide project called Health Village is coordinating digital health care processes. It is a digital health platform that enables health care organizations to create digital extensions of their clinics.In the Helsinki area, a new electrical medical record (EMR) system named Apotti is being developed. Apotti is based on Epic Systems, and its transplantation module Phoenix was chosen for the basement for the new EMR in transplantation. Both digital services in the Kidney Hub of the Health Village and in Apotti are combined to form the basis of upcoming digital patient care process in kidney transplantation.The Health Village project started in February 2017 to develop eHealth processes in nephrology and kidney transplantation. The decision for Phoenix was made in January 2018. Multidisciplinary teams have developed digital pathways in nephrologic patient care and kidney transplantation since then.The basic structure for eHealth pathways in kidney transplantation will be launched in October 2018. The development of the EMR system is under construction and should be finished by November 2019. Digitalization of health systems in kidney transplantation will harmonize patient care in all parts of Finland. In addition, new models of patient care are providing savings in health care costs. However, the implementation of new systems should be started ahead of time, and the whole process must be well planned to achieve the desired final purpose.     

Impact of Donor Age on the Outcomes of Kidney Transplantation From Deceased Donors With Histologic Acute Kidney Injury

PurposeKidney transplantation from elderly donors with acute kidney injury (AKI) has increased recently due to donor shortage, but the safety and prognosis are not well known. We examined the effect of donor age on the outcomes of kidney transplantation (KT) from donors with histologic AKI.Materials and methodsWe retrospectively analyzed the medical records of 59 deceased-donor KTs with acute tubular necrosis (ATN) on preimplantation donor kidney biopsy between March 2012 and October 2017. Histologic evaluations of ATN, inflammation, glomerulosclerosis (GS), interstitial fibrosis, tubular atrophy, and arterial sclerosis were performed.ResultsTwenty and 39 recipients received kidneys from elderly (> 60, 68.9 ± 5.0 years) and young (≤ 60, 45.9 ± 9.6 years) donors with ATN, respectively. Among the elderly donors, significantly increased donor creatinine was observed in only 44% donors, and there were more diabetic patients and women and a higher proportion of GS than among the young donors. Six months after KT, estimated glomerular filtration rate was significantly lower in recipients who received kidneys from elderly donors compared to young donors. Donor creatinine level and AKI severity did not significantly affect the recipient outcomes in either group. However, the presence of ATN and GS were significant factors that exacerbated renal outcomes after KT from elderly donors only. On multivariate analysis, severe ATN was the strongest independent predictor of elderly recipient renal function.ConclusionsHistologic injury may predict renal outcomes in KT from elderly donors. A donor allocation protocol including preimplantation renal histology should be established for KT from elderly donors.     

Comparison of Posttransplant Outcomes in Living Donor Liver Transplantation for Obese and Nonobese Recipients

Background

Although living donor liver transplantation for obese recipients has increased, it has not been determined that posttransplant outcomes in obese recipients are inferior compared with nonobese recipients.

Analysis of Clinical Outcomes According to the Definition of Slow Graft Function in Deceased Donor Kidney Transplantation

BackgroundSlow graft function (SGF) is considered to be an intermediate state between immediate graft function (IGF) and delayed graft function (DGF). However, the criteria of SGF is still arbitrary, and the clinical outcomes of SGF are not fully understood.MethodsA total of 212 deceased donor kidney transplantation recipients were enrolled. Three schemas were adopted, which classified SGF according to the serum creatinine (Cr) level by a given postoperative day (POD). SGF was defined as Cr ≥ 3.0 mg/dL on POD5, Cr ≥ 2.5 mg/dL on POD7, and Cr ≥ 1.5 mg/dL on POD14 without dialysis in schema I, II, and III, respectively. Estimated glomerular filtration rate (eGFR) after transplantation, acute rejection, and graft survival were compared in each schema. Decreased renal function, defined as eGFR less than 30.0 mL/min/1.73m², was also compared.ResultsIn schema I and III, SGF had significantly lower eGFR at 3 months after transplantation compared with IGF (P < .017), and only schema III maintained the difference until 36 months after transplantation. The incidence of decreased renal function showed significant difference among groups in schema I and III (P < .05). Graft survival did not show significant difference among groups in all schemas. However, SGF and DGF groups showed a higher probability of decreased renal function than the IGF group (P < .017) in schema I and III.ConclusionsIn deceased donor kidney transplantation, certain definitions of SGF identified significantly worse clinical outcomes compared with IGF, suggesting similar impact with DGF. It is necessary to reach a consensus on a clearer definition of SGF with further studies.     

Characteristics of Recipients With 10 or More Years of Allograft Survival in Deceased Donor Kidney Transplantation

Background

The development of immunosuppressants improved the short-term outcomes of deceased donor kidney transplantation (DDKT), but the long-term survival rate was not improved.

Factors Associated With Waiting Time to Deceased Donor Kidney Transplantation in Transplant Candidates

Although a nationwide activation system has been developed to increase deceased donor kidney transplantation (DDKT), there is still enormous discrepancy between transplant need and deceased donor supply in Korea, and therefore waiting time to DDKT is still long. We need to determine the current status of waiting time and the risk factors for long waiting time. We retrospectively analyzed the medical records of the patients on the wait list for DDKT at the Seoul National University Hospital from 2000 to 2017. Among 2,211 wait-listed patients, 606 (27.5%) received DDKT and mean waiting time to DDKT was 45 months. Among them, blood type A was most prevalent (35.6%) and type AB was the least (14.0%). Panel-reactive assay (PRA) was positive in 59 (11.0%) in the first transplant group and 25 (35.0%) in retransplant group. Waiting time in PRA-positive recipients was 63 and 66 months in the first transplant group and retransplant group, respectively. However, waiting time for patients with negative PRA was 42.8 months. Waiting time was shorter in blood type AB (39 months) than other types (46 months). Waiting time was the shortest in children and adolescents. Among patients who were still on the wait list, retransplantation candidates, especially with PRA higher than 50%, had longer waiting time than first transplant candidates. In conclusion, non-AB blood type, positive PRA, and adult age were significantly associated with long waiting time. Therefore, it is necessary to establish a management strategy such as tailored desensitization for highly sensitized patients on the wait list to reduce their waiting time.     

Importance of Timed and Detailed Evaluation of Kidney Transplantation Candidates

Kidney transplant recipients are at increased risk of cardiovascular morbidity and malignant neoplasm, and meticulous evaluation of potential recipients is needed to minimize risks of complications after transplantation. The purpose of this study was to analyze the results of preoperative assessments and document the importance of timed and detailed examinations.

Differences in Pathologic Features and Graft Outcomes of Rejection on Kidney Transplant

BackgroundRejection is still a barrier to long-term allograft survival, but there are not many reports of clinical outcomes according to rejection types. The purpose of this study was to investigate differences in pathologic features and graft outcomes of rejection on kidney transplant (KT).Materials and MethodsWe retrospectively analyzed 139 kidney transplant recipients diagnosed to rejection by allograft biopsy results between 2006 and 2018. We divided kidney transplant recipients into 3 groups as follows: T cell–mediated rejection (TCMR), antibody-mediated rejection, and mixed rejection. We investigated clinical characteristics, pathologic findings, death-censored graft survival rates, and patient survival rates among the 3 groups.ResultsMean follow-up duration was 113.5 (SD, 80.6) months. The mixed rejection group was the youngest significantly. There were no significant differences of the proportion of sex, KT type, KT number, number of HLA mismatches, induction immunosuppressant, and maintenance immunosuppressant among the 3 groups. In pathologic findings, microvascular inflammation and C4d were significantly different among the 3 groups. Death-censored graft survival of mixed rejection was the least. In multivariate analysis, recipient age, TCMR, and positive C4d were the risk factors associated with graft failure. However, patient survival rates showed no significant differences among the 3 groups.ConclusionsOur study showed that mixed rejection had poor prognosis in comparison with TCMR and antibody-mediated rejection groups, and TCMR and positive C4d were the most important risk factors for graft survival. Therefore, constant monitoring through allograft biopsy and early treatment for rejection are very important in post-transplant clinical outcomes.     

Immunologic Characteristics of Mongolian Patients Receiving Kidney Transplantation in a Single Center in Korea

BackgroundAmong foreigners undergoing kidney transplantation (KT) in Korea, Mongolians are the most common, and most of these cases are conducted at our center. We report the immunologic characteristics and clinical outcomes of these patients.MethodsConsecutive Mongolian patients who underwent KT from September 2009 to August 2017 in our center were retrospectively analyzed. Pre- and post-transplant HLA antibody status and clinical data of the Mongolian patients were collected and compared with the Korean patients who underwent living donor KT during the same period.ResultsSixty-two Mongolian and 85 Korean patients received KT and were followed up for 20.9 and 50.8 months (P = .01), respectively. Before transplantation, 17.7% of the Mongolian patients and 7.1% of the Korean patients were highly sensitized (P = .05). The patients were monitored consistently throughout the entire post-transplant period. Follow-up loss occurred in some cases. Of the patients, 32 Mongolian patients and 79 Korean patients were monitored for post-transplant HLA antibodies at any time point. Estimated glomerular filtration rates were comparable between Mongolian and Korean patients at 1 month (77.1 vs 71.5 mL/min/1.73m², P = .21) and 1 year (64.6 vs 68.7 mL/min/1.73m², P = .25) after transplantation but tended to be different at 3 years (57.2 vs 67.3 mL/min/1.73m², P = .06) and 5 years (56.9 vs 73.1 mL/min/1.73m², P = .04) post transplant.ConclusionsMongolian patients undergoing KT in Korea were often highly sensitized. Mean follow-up time was short and follow-up loss was common in Mongolian patients compared with Korean patients. Cautious follow-up is needed for foreigner transplant recipients, especially for those at high-risk immunologically, to achieve better outcomes.