Seiichiro Shishido

Outcomes of Pediatric ABO-Incompatible Kidney Transplantations Are Equivalent to ABO-Compatible Controls

BACKGROUNDnDue to the profound shortage of suitable deceased allografts, much effort has been made to investigate whether successful kidney transplantation (KT) is possible across the ABO blood group barrier even for pediatric recipients.nnnMETHODSnWe reviewed 52 consecutive ABO incompatible (ABOic) transplantation performed between September 1989 and March 2011. The mean age at transplantation was 10.6 ± 3.9 years (range, 4.4-19.7), with 35 boys and 17 girls. The donor-to-recipient ABO blood antigen incompatibility was as follows: A1/O (n = 17); B/O (n = 13); A1/B (n = 6); B/A1 (n = 1); A1B/B (n = 9); and A1B/A (n = 6). As a control group, data were collected from 271 pediatric ABO compatible (ABOc) living donor KT in the same period.nnnRESULTSnOverall acute rejection episodes (ARE) among the ABOic group were significantly higher than those of the ABOc group (44% vs 26%; P < .02). However, there was no difference in glomerular filtration rate (GFR) at 1 year after transplantation: 86 ± 31 mL/min for ABOic vs 99 ± 37 mL/min for ABOic, respectively. The 1-y, 5-y, and 10-year patient survival rates were 98%, 92%, and 92% in the ABOic group, respectively, and 99%, 98%, and 97% in the ABOc group, respectively (P = not significant [NS]). The overall 1-, 5-, 10-, and 15-year graft survival rates were 94%, 88%, 86%, and 86% in the ABOic group, respectively, and 95%, 92%, 88%, and 78% in the ABOc group, respectively.nnnCONCLUSIONnABOic KT provided long-term allograft and patient survivals equivalent to ABOc live donor transplantations.

Combination of pulse methylprednisolone infusions with cyclosporine-based immunosuppression is safe and effective to treat recurrent focal segmental glomerulosclerosis after pediatric kidney transplantation

Recurrence of focal segmental glomerulosclerosis (FSGS) in pediatric kidney allografts is associated with poor graft survival. Several therapeutic regimens have been proposed, with conflicting results.

Population pharmacokinetics of mizoribine in pediatric recipients of renal transplantation.

BackgroundAn immunosuppressive agent, mizoribine, is excreted predominantly in the urine. The aim of this study was to investigate the pharmacokinetic variability of mizoribine in pediatric recipients of renal transplantation.MethodsPharmacokinetic data for population analysis were collected from 51 recipients (32 males and 19 females) treated with oral administration of mizoribine (0.83–5.56xa0mg/day/kg). The population pharmacokinetic parameters of mizoribine were estimated using a nonlinear mixed effects model program.ResultsThe pharmacokinetics of mizoribine in pediatric recipients of renal transplantation was well described by a one-compartment model with first-order absorption. The mean value of the absorption lag time (ALAG) and absorption rate constant (KA) was estimated to be 0.363xa0h and 0.554xa0h−1, respectively. Apparent volume of distribution (V/F) was modeled as a function of body weight (WT), and the mean value was estimated to be 1.03xa0·xa0WTxa0L. Oral clearance (CL/F) was modeled as a function of creatinine clearance (CLcr), and the mean value was estimated to be 2.81xa0·xa0CLcrxa0·xa060/1000xa0L/h. In addition, there was a positive correlation between CLcr-corrected CL/F and WT-corrected V/F in the pediatric recipients, indicating large interindividual variability in the bioavailability (F) of mizoribine.ConclusionThe present findings indicated that the rate of renal excretion and also the extent of intestinal absorption of mizoribine are responsible for the large interindividual pharmacokinetic variability of the drug.

Renal complications in 6p duplication syndrome: Microarray‐based investigation of the candidate gene(s) for the development of congenital anomalies of the kidney and urinary tract (CAKUT) and focal segmental glomerular sclerosis (FSGS)

6p duplication syndrome is a rare chromosomal disorder that frequently manifests renal complications, including proteinuria, hypoplastic kidney, and hydronephrosis. We report a girl with the syndrome, manifesting left hydronephrosis, proteinuria/hematuria, and focal segmental glomerular sclerosis (FSGS) resulting in chronic end‐stage renal failure, successfully treated with renal transplantation. Microarray comparative genomic hybridization showed the derivative chromosome 6 to have a 6.4‐Mb duplication at 6p25.3–p25.1 with 32 protein‐coding genes and a 220‐Kb deletion at 6p25.3 with two genes of no possible relation to the renal pathology. Review of the literature shows that variation of renal complications in the syndrome is compatible with congenital anomalies of the kidney and urinary tract (CAKUT). FSGS, observed in another patient with 6p duplication syndrome, could be a non‐coincidental complication. FOXC1, located within the 6.4‐Mb duplicated region at 6p25.3–p25.2, could be a candidate gene for CAKUT, but its single gene duplication effect would not be sufficient. FSGS would be a primary defect associated with duplicated gene(s) albeit no candidate could be proposed, or might occur in association with CAKUT.

Diversity of renal phenotypes in patients with WDR19 mutations: Two case reports

WDR19 has been reported as a causative gene of nephronophthisis‐related ciliopathies. Patients with WDR19 mutations can show various extrarenal manifestations such as skeletal disorders, Caroli disease, and retinal dystrophy, and typically display nephronophthisis as a renal phenotype. However, there is limited information on the renal phenotypes of patients with WDR19 mutations. We report two Japanese infants with Sensenbrenner syndrome caused by WDR19 mutations who demonstrated different features in renal ultrasound and histopathological results, despite several common extrarenal manifestations. Patient 1 had normal sized and hyperechogenic kidneys with several small cysts and histopathological findings compatible with infantile nephronophthisis. Renal ultrasound of Patient 2 showed enlarged kidneys with diffuse microcysts resembling those of autosomal recessive polycystic kidney disease. Her renal histopathology revealed dysplastic kidney with diffuse glomerular cysts. Genetic testing identified compound heterozygous mutations in WDR19 in both patients (Patient 1: c.953delA, c.3533G > A, Patient 2: c.2645 + 1G > T, c.3533G > A). Our patients suggest that WDR19 mutations can cause dysplastic kidney in addition to nephronophthisis pathologically. In addition, differences in pathology of the kidneys from WDR19 mutations may result in heterogeneous features in renal ultrasound findings. Renal phenotypes from WDR19 mutations may thus be more diverse than previously reported. Extrarenal manifestations and genetic testing can therefore help to diagnosis this disease more precisely.

Efficacy of tonsillectomy for the treatment of immunoglobulin A nephropathy recurrence after kidney transplantation

BackgroundPost-transplant recurrent nephritis is the third common complication that leads to graft loss, which affects the long-term graft survival of kidney transplant patients. Immunoglobulin A nephropathy (IgAN) is the most common for recurrent nephritis, with a recurrence rate of 13–53%. In this study, 12 patients diagnosed with recurrent IgAN were divided into two groups, one which underwent tonsillectomy and another which did not, to analyze the effect of treating IgAN recurrent with or without tonsillectomy.MethodsUrinary findings, estimated GFR (eGFR), and histopathological alteration (Banff and Oxford classifications) were examined for >5xa0years after kidney transplantation.ResultsWe found that tonsillectomy protected graft function and prevented pathological alterations. The levels of urinary proteins increased in the no tonsillectomy group, whereas no difference was observed in the severity of hematuria between two groups. eGFR declined and mesangial hypercellularity score increased in the no tonsillectomy group.ConclusionsTonsillectomy not only results in a favorable clinical outcome but also protects against the histological damage caused by recurrent IgAN after kidney transplantation.

Successful third renal transplantation in a child with an occluded inferior vena cava: A novel technique to use the venous interposition between the transplant renal vein and the infrahepatic inferior vena cava

A girl aged 11 years and 3 months with occlusion of the inferior vena cava had experienced two renal transplant graft failures since birth. The third renal transplant from a live donor was carried out. Preoperative evaluation showed that the arteries from the right common to the right external iliac artery were absent, and the ilio‐caval vein was occluded below the level of the renal vein. The donors renal artery was anastomosed to the aorta. The donors ovarian and large saphenous veins were used to extend the transplant renal vein to the recipients patent inferior vena cava. The present report concludes that the extension of a short donor renal vein using other donor veins is a viable therapeutic option for pediatric patients with vascular occlusions.

Multifocal Epstein-Barr Virus–Negative Posttransplantation Lymphoproliferative Disorder Treated With Reduction of Immunosuppression

Posttransplantation lymphoproliferative disorder (PTLD) is associated with significant mortality in kidney transplant recipients. PTLD cases associated with poor prognostic factors that are refractory to reduction of immunosuppression generally require chemotherapy and immunotherapy. We present a patient with PTLD who achieved complete remission after reduction of immunosuppression alone despite having a poor prognosis. A boy with a mutation in the WT1 gene developed bilateral Wilms tumor at 15 months and received a kidney transplant at the age of 4 years. At 13 years of age, the patients condition was managed with methylprednisolone, tacrolimus, and mycophenolate mofetil. He developed Epstein-Barr virus-negative monomorphic PTLD with numerous nodular lesions in the liver, vertebral bodies, and gastric wall. To reduce immunosuppression, we discontinued mycophenolate mofetil treatment, decreased tacrolimus dosage to 1mg/d, and increased methylprednisolone dosage to 2mg/d. The PTLD lesions drastically diminished in size within several days and disappeared 144 days after reduction of immunosuppression, although the patient had several factors indicating a poor prognosis. As of 13 months after reduction of immunosuppression for PTLD, the transplanted kidney was still functional. We conclude that even when patients with PTLD have a poor prognosis, reduction of immunosuppression alone may result in complete remission when the early response is excellent.

Successful Kidney Transplantation in Epstein Syndrome With Antiplatelet Antibodies and Donor-specific Antibodies: A Case Report.

An autosomal dominant hereditary disease, Epstein syndrome (ES) is characterized by sensorineural hearing impairment, macrothrombocytopenia, and hereditary nephritis, and can progress to end-stage kidney disease after puberty. Generally, kidney transplantation is difficult to perform in Epstein syndrome owing to the high risk of perioperative bleeding. Additionally, due to previous platelet transfusions, ES patients sometimes have antihuman leukocyte antigen (HLA) antibodies, including antiplatelet antibodies and donor-specific anti-HLA antibodies (DSA), which may result in refractoriness to platelet transfusion and antibody-mediated rejection (AMR). We report a case of successful kidney transplantation in a patient with ES who had DSA and antiplatelet antibodies. To prevent AMR, we used a desensitization protocol (a combination of plasmapheresis, rituximab, and basiliximab induction). Surveillance biopsy performed at 4 months and 1 year after transplantation showed no pathological findings suggesting AMR. To prevent perioperative bleeding complications, we infused the patient with HLA-matched platelets, thereby maintaining the platelet count at >10.0xa0× 10(4)/μL, and no postoperative episodes of bleeding occurred.

Serum uric acid is an independent predictor of new-onset diabetes after living-donor kidney transplantation

BackgroundWe investigated whether serum uric acid (SUA) levels before kidney transplantation predict new-onset diabetes after kidney transplantation (NODAT) and compared SUA levels with known risk factors for NODAT by prospective cohort study.MethodsA total of 151 adult kidney recipients without diabetes (84 men, 67 women) who underwent living-donor kidney transplantation between 2001 and 2011 were followed in this study. The Cox proportional hazards model was used to analyse the risk of NODAT.ResultsDuring the follow-up period (median 3.3xa0years, range 0–10xa0years), 32 (21.2%) adult kidney recipients without diabetes developed NODAT, and an incidence rate was 5.6 per 100 person-years and a 10-year cumulative incidence of 26.9%. When subjects were stratified by SUA levels into tertiles, the patients in the highest tertile (>u20098.6xa0mg/dl for men, >u20097.7xa0mg/dl for women) had a significantly higher risk of NODAT than the patients in the lower 2 tertiles (log-rank test, Pu2009=u20090.03). In the univariate analysis, increased level of SUA was associated with NODAT (hazard ratio 1.27 [95% CI 1.04–1.55], Pu2009=u20090.01). In the multivariate analysis, increased level of SUA was significantly associated with NODAT after correction by any factors, e.g. (age, sex, family history of diabetes, BMI, HbA1c, serum creatinine, tacrolimus, HCV) factors directly affecting the SUA value (1.26 [1.02–1.56], Pu2009=u20090.03), risk factors for T2DM onset (1.34 [1.10–1.64], Pu2009=u20090.03), and factors previously reported risk factors for NODAT (1.36 [1.11–1.66], Pu2009=u20090.003).ConclusionSUA independently predicts NODAT in living-donor kidney transplantation patients.