Urinary excretion of thyroid hormone in CKD patients: a proof-of-concept of nephrogenic hypothyroidism.

PURPOSE: Patients with chronic kidney disease (CKD) complicated by hypothyroidism exhibit a higher prevalence of urine protein than that in the general population. This study was aimed at investigating thyroid hormones and thyroid hormone-binding proteins excreted in urine to elucidate the urine protein-associated underlying mechanisms of hypothyroidism. METHODS: Between November 2016 and August 2018, thyroid function (serum free T3 [sFT3], free T4 [sFT4], and thyroid-stimulating hormone [sTSH]), kidney function (estimated glomerular filtration rate [eGFR]), thyroid antibodies and albumin (Alb) were evaluated in 99 Japanese CKD patients with proteinuria at our outpatient clinic. A urine examination was also performed to assess the following parameters: total T3, total T4, TSH, Alb, preAlb, thyroid-binding globulin, and protein. RESULTS: The median patient age at study recruitment was 60 years; 50 patients (50.5%) were male. The median eGFR and Alb level were 20.3 ml/min/1.73 m2 and 3.8 g/dL, respectively. 21 patients (21.2%) were diagnosed with nephrotic syndrome (NS). The median sFT3, sFT4, and sTSH levels were within normal limits. Approximately 70% of the patients had thyroid dysfunction and 51.5% had overt or subclinical hypothyroidism without predominantly antibody positive. Regarding NS and non-NS patients, age and Alb were significantly different between these groups, while sex and eGFR were not significant, but the urinary T4 and TSH levels were higher in the NS group; thus, more severe hypothyroid. CONCLUSION: We found a significant association between hypothyroidism and NS regardless of sex and antibodies. Urinary loss of thyroid hormones must be a factor influencing hypothyroidism independent of autoimmunity.

Mesangiolysis in Pathological Chronic Active Antibody-Mediated Rejection in Kidney Transplant Biopsies.

INTRODUCTION: This study aimed to determine if immune or nonimmune and acute or chronic lesions associated with mesangiolysis (MGLS) occurred in biopsy-proven pathological chronic active antibody-mediated rejection (P-CAABMR) in kidney transplant biopsies. METHODS: We evaluated MGLS in 41 patients with biopsy findings of P-CAABMR from January 2016 to December 2019. Histological scoring was evaluated by Banff classification. Multivariate logistic regression analysis was performed using a forward selection method. RESULTS: Fifteen of the 41 P-CAABMR biopsies (36.6%) cases showed MGLS. The estimated glomerular filtration rate (eGFR) was significantly lower in the MGLS-positive compared with the MGLS-negative group, and proteinuria was significantly higher in the MGLS-positive compared with the MGLS-negative group. In the clinical model, multivariate analysis was performed using covariates of eGFR and duration after transplantation significantly correlated with MGLS by simple analysis, in addition to type of calcineurin inhibitor use (tacrolimus or cyclosporine), donor-specific antibodies, diabetes, and hypertension grade defined by use of antihypertensive therapy or/and blood pressure level. Only hypertension grade was significantly correlated with MGLS. In the pathological model, multivariate analysis was performed using the presence of FSGS and the aah and cg scores significantly correlated with MGLS by simple analysis, in addition to g and ptc scores. The cg score was significantly correlated with hypertension grade, duration after transplantation, g, ah, and aah. CONCLUSION: Lower graft function and higher proteinuria was observed in MGLS of P-CAABMR. The Banff cg score was independently related to MGLS in multivariate analysis. Sustained glomerulitis, calcineurin inhibitor nephrotoxicity, and hypertension may cause Banff cg lesions, leading to MGLS in P-CAABMR.

Vesicoureteral Reflux Causes Interstitial Inflammation in Pediatric Kidney Allograft: A Clinicopathological Analysis of 1-Year Protocol Biopsies.

INTRODUCTION: At present, there is limited evidence of the histological impact of vesicoureteral reflux (VUR) on pediatric kidney allografts. In this study, we aimed to investigate the relationship between VUR diagnosed by voiding cystourethrography (VCUG) and 1-year protocol biopsy results. METHODS: One hundred thirty-eight pediatric kidney transplantations were performed in Toho University Omori Medical Center between 2009 and 2019. We included 87 pediatric transplant recipients who were evaluated for VUR by VCUG prior to or at the time of the 1-year protocol biopsy and underwent a 1-year protocol biopsy after transplantation. We evaluated the clinicopathological findings of the VUR and non-VUR groups, and histological scores were evaluated using the Banff score. Tamm-Horsfall protein (THP) within the interstitium was identified by light microscopy. RESULTS: Of the 87 transplant recipients, 18 cases (20.7%) were diagnosed with VUR by VCUG. The clinical background and findings were not significantly different between the VUR and non-VUR groups. The pathological findings revealed a significantly higher Banff total interstitial inflammation (ti) score in the VUR group than in the non-VUR group. Multivariate analysis indicated a significant relationship between the Banff ti score and THP within the interstitium, and VUR. The 3-year protocol biopsy results (n = 68) revealed a significantly higher Banff interstitial fibrosis (ci) score in the VUR group than in the non-VUR group. CONCLUSION: VUR caused interstitial fibrosis in the 1-year pediatric protocol biopsies, and interstitial inflammation at the 1-year protocol biopsy may affect interstitial fibrosis at the 3-year protocol biopsy.

Prognostic value of the 7-year protocol biopsy of adult kidney allografts: impact of mesangiosclerosis and proteinuria.

AIM: The aim of the present study was to clarify the relationship between the Banff score of the 7-year protocol biopsy and the allograft outcome. METHODS: One-hundred-and-eighty-four patients received kidney transplantation from 2002 to 2008. We excluded patients aged <20 years at transplantation (n = 24), those who did not undergo a 7-year protocol biopsy (n = 66), and those who underwent for-cause biopsy (n = 5). Consequently, 89 patients who underwent a 7-year protocol biopsy were enrolled. We analyzed the relationship between the clinicopathological findings 7 years after transplantation and the estimated glomerular filtration rate (eGFR) change per year and allograft survival. Histological evaluation was performed using the Banff 2015 classification. RESULTS: Among the clinicopathological findings, each Banff mesangial matrix increase (mm) score ≥1 and proteinuria ≥1+ was independently associated with the eGFR decline per year during a median follow-up of 73 months. Furthermore, in the model of the clinicopathological findings including the presence of mm with proteinuria, mm ≥1 alone and mm ≥1 with proteinuria were each independently associated with the eGFR decline. The graft survival was significantly worse for those with mm ≥1 with proteinuria than those with mm ≥1 without proteinuria. CONCLUSION: Among the 7-year protocol biopsy findings, the presence of mm alone and mm with proteinuria were each significant predictors of eGFR decline. The presence of both proteinuria and mm had a negative impact on graft survival. These results underscore the significance of the Banff mm score and proteinuria at the time of the 7-year protocol biopsy to predict the allograft outcome.

Significance of Multinucleated Polyploidization of Tubular Epithelial Cells in Kidney Allografts.

INTRODUCTION: Multinucleated polyploidization (MNP) of tubular epithelial cells is occasionally observed in kidney allografts. The present study aimed to clarify the clinical and pathological significance of MNP of tubular epithelial cells in kidney allografts. METHODS: Fifty-eight 1-year biopsies from 58 patients who underwent kidney transplantation at our hospital from January 2016 to December 2017 were included. MNP was counted in each specimen, and the specimens were divided into two groups by the median value. The differences in clinical and pathological characteristics were compared. Ki67-positive cells were counted among tubular epithelial cells to explore the association between cell cycle and MNP. In an additional cohort, MNP was compared between biopsies after precedent T-cell-mediated rejection and precedent medullary ray injury. RESULTS: The 58 cases were divided into two groups by the median total amount of MNP: group A (MNP > 3) and group B (MNP ≤ 3). Maximum t-score before the 1-year biopsy was significantly higher in group A compared with group B. Other clinical or histological characteristics did not differ significantly. Total amount of Ki67-positive tubular epithelial cells was significantly correlated with total amount of MNP. Significantly higher amount of MNP was observed in cases with precedent T-cell-mediated rejection compared with precedent medullary ray injury. On receiver operating characteristic curve analysis, the cut-off value of MNP to predict precedent T-cell-mediated rejection was 8.5. CONCLUSIONS: MNP in tubular epithelial cells reflects prior tubular inflammation in kidney allografts. High amount of MNP indicates precedent T-cell-mediated rejection rather than precedent medullary ray injury caused by nonimmune etiologies.

Fibroblast growth factor 23-Klotho and mineral metabolism in the first year after pediatric kidney transplantation: A single-center prospective study.

BACKGROUND: The role of fibroblast growth factor 23 (FGF23) levels in mineral metabolism before and after kidney transplantation in pediatric patients is poorly understood. METHODS: We prospectively evaluated 24 patients under 18 years of age (4.5 [3.3-9.8] years) who underwent living kidney transplantation between July 2016 and March 2018, and measured intact FGF23 and serum αKlotho levels, and other parameters of mineral metabolism before and after transplantation (Day 7, 1 and 4 months, and 1 year). Relationships between parameters were examined by linear analysis. RESULTS: FGF23 level was 440.8 [63.4-5916.3] pg/ml pre-transplant and decreased significantly to 37.1 [16.0-71.5] pg/ml at Day 7 post-transplant (-91.6%, p < .001). Thereafter, it remained at normal levels until 1 year. αKlotho level was 785 [568-1292] pg/ml pre-transplant and remained low at Day 7 and 1 month post-transplant, with an increasing trend at 4 months. Post-transplant phosphorus levels were significantly decreased compared with pre-transplant, with a lowest level of 1.7 [1.3-2.9] mg/dl, -5.7 [-6.8, -3.8] SD at Day 4, followed by gradual recovery. Phosphorus levels and the ratio of tubular maximum phosphate reabsorption were significantly and negatively associated with pre-transplant FGF23 until 4 months of post-transplant. Pre-transplant αKlotho was negatively associated with pre-transplant FGF23 but not FGF23 or other parameters after transplantation. CONCLUSION: FGF23 in pediatric kidney transplant patients decreased rapidly after transplantation and associated with post-transplant hypophosphatemia and increased phosphorus excretion. Post-transplant αKlotho was low early post-transplant but tended to increase subsequently. Post-transplant αKlotho was unaffected by pre-transplant FGF23 or other factors, suggesting pre-transplant chronic kidney disease status has no effect.

Changes in graft function after living donor kidney transplantation in children.

BACKGROUND: This study aimed to evaluate the change in graft function in two groups stratified by the estimated glomerular filtration rate (eGFR) at 1 month after transplantation (eGFR-1 M) in pediatric living donor kidney transplant recipients. METHODS: Forty-three pediatric recipients were classified as those with an eGFR-1 M ≥ 90 mL/min/1.73 m2 (n = 19; high eGFR group) or those with an eGFR-1 M of 60-89 mL/min/1.73 m2 (n = 24; middle eGFR group). In the two groups, changes in the eGFR were retrospectively evaluated for 5 years after kidney transplantation. RESULTS: The mean recipient age at transplantation in the high/middle eGFR group was 6.1 ± 3.4/7.8 ± 4.0 years (P = 0.14). The mean eGFR-1, -12, and -60 M (mL/min/1.73 m2) in the high/middle eGFR group were 106.8 ± 2.99/78.5 ± 1.52 (P < 0.001), 79.3 ± 3.22/62.7 ± 2.38 (P < 0.001), and 73.1 ± 4.16/59.2 ± 2.79 (P = 0.006), respectively. The change in the mean eGFR remained mostly parallel in the two groups. In both groups, the eGFR significantly decreased only between 1 and 12 months after transplantation (P < 0.0001). Approximately 70% of the patients had an eGFR-60 M ≥ 60 mL/min/1.73 m2. CONCLUSIONS: The high and middle eGFR groups showed a rapid decline in the eGFR by 1 year after transplantation, but the change thereafter was gradual. In pediatric living donor kidney transplant recipients, the eGFR was relatively well maintained up to 5 years after transplantation. A higher resolution version of the Graphical abstract is available as Supplementary information.

Outcome of ABO-incompatible kidney transplantation using a modified desensitization protocol without plasmapheresis.

OBJECTIVES: Several controversies regarding desensitization strategies for successful ABO-incompatible (ABOi) kidney transplantation still exist. This study aimed to investigate whether pretransplant anti-A/B antibody removal is mandatory in an ABOi kidney transplant recipient with low baseline isoagglutinin titers. METHODS: We adopted a modified desensitization protocol with two doses of rituximab (RTX, 100 mg/body) without pretransplant antibody removal for ABOi kidney transplant recipients with a titer of ≤1:64 (group A; n = 35) and investigated the feasibility of this protocol by comparing it with the clinical outcomes of patients undergoing standard pretransplant plasmapheresis (group B; n = 21). RESULTS: There was no significant difference in the rate of antibody-mediated rejection within the first month after transplantation between the two groups (11.4% in group A vs. 2% in group B, p = 0.6019). Moreover, no differences were observed in the short- and long-term graft outcomes between the groups. However, two major critical acute antibody-mediated events occurred in group A; one patient lost the graft due to hyperacute rejection, and the other patient developed thrombotic microangiopathy after surgery. Risk factors predicting these perioperative complications were not identified. CONCLUSIONS: We conclude that not only B-cell depletion using RTX but also pretransplant antibody removal is still recommended even for patients with low isoagglutinin titers. In addition, a new diagnostic tool is needed for accurate risk stratification.

Long-term social outcome after pediatric kidney transplantation: a single-center experience.

BACKGROUND: Patient and graft survival rates after pediatric kidney transplantation have improved recently. Therefore, the quality of life or social outcome after kidney transplantation has become important for patients and their families. METHODS: Patients who underwent kidney transplantation at < 18 years old and were observed for > 10 years were included in this study. The median age at first kidney transplantation was 9.2 (interquartile range [IQR] = 5.6-13.0) years; there were 56 males and 50 females. The median age at last follow-up was 29.9 (IQR = 22.2-36.0) years. We evaluated the patients' renal function, growth, professional status, and marital status at the last follow-up. RESULTS: The percentage of functioning grafts at the last follow-up was 81.1%; 73 patients (68.9%) had a first graft. The mean estimated GFR was 51.0 ± 20.5 mL/min/1.73 m2. Twenty patients received dialysis for graft failure. The mean final heights of the males and females were 158.1 ± 9.2 cm (- 2.2 standard deviations) and 149.1 ± 6.4 cm (- 1.7 standard deviations), respectively. Excluding 23 students, 63 patients (75.9%) were employed. Office worker was the most common profession. Twelve patients (14.5%) were unemployed. Of patients > 20 years old, 14 (16.7%), three males and 11 females, were married. Five females had one child each. CONCLUSIONS: The graft survival rate was favorable. The final height was short, particularly in male. The rate of employment was relatively high. The rate of marriage and having children were still low. Improving the social outcome is an important problem after pediatric kidney transplantation.

Incidence of malignancy after pediatric kidney transplantation: a single-center experience over the past three decades in Japan.

BACKGROUND: Malignancy after kidney transplantation (KT) is one of the most serious post-transplant complications. This study aimed to investigate the incidence, type, and outcomes of malignancy after pediatric KT. METHODS: We performed a retrospective cohort study on pediatric kidney transplant recipients aged 18 years or younger who received their first transplant between 1975 and 2009. RESULTS: Among the 375 children who underwent KT, 212 were male (56.5%) and 163 were female (43.5%) (median age at KT, 9.6 years [interquartile range {IQR}] 5.8-12.9 years). The incidence of malignancy was 5.6% (n = 21). The cumulative incidences of cancer were 0.8%, 2.5%, 2.8%, 4.2%, 5.5%, and 15.6% at 1, 5, 10, 15, 20, and 30 years post-transplantation, respectively. Of 375 patients, 12 (3.2%) had solid cancer and nine (2.4%) had lymphoproliferative malignancy. The median age at the first malignancy was 21.3 years (IQR 11.5-33.3 years). The median times from transplant to diagnosis were 22.3 years (IQR 12.3-26.6 years) for solid cancer and 2.2 years (IQR 0.6-2.8) for lymphoproliferative malignancies. During follow-up, five recipients died due to malignancy. The causes of death were hepatocellular carcinoma in one patient, squamous cell carcinoma in the transplanted kidney in one patient, malignant schwannoma in one patient, and Epstein-Barr virus-related lymphoma in two patients. The mortality rate was 0.79 per 1000 person-years (95% confidence interval 0.38, 1.85). CONCLUSIONS: Early diagnosis and treatment of malignancies in transplant recipients is an important challenge. Therefore, enhanced surveillance and continued vigilance for malignancy following KT are necessary.

Long-term outcomes of living-donor kidney transplant children weighing less than 15 kg: Comparison of the surgical approach.

INTRODUCTION: Kidney transplantation (KTx) is the most effective treatment for end-stage renal disease in children. OBJECTIVES: We aimed to compare the long-term outcomes and surgical complications of the intraperitoneal approach (IPA) and extraperitoneal approach (EPA) for KTx in children weighing <15 kg. STUDY DESIGN: We performed a retrospective cohort study on pediatric kidney transplant recipients, weighing <15 kg, who received their first living-related kidney transplant between January 1987 and December 2015. Patients were divided into two groups based on the surgical approach (IPA or EPA) during transplant, and clinical data were extracted from the medical records. RESULTS: The median follow-up duration was 14.1 years (interquartile range, 9.0-19.2). Comparing the two groups (IPA group, n = 62; EPA group, n = 38), the median age and body weight were significantly lower in the IPA group (4.2 vs. 4.8 years, P = 0.03; 11.7 vs. 13.0 kg, P < 0.01). There were 26 surgical complications (26%) in 19 patients during the follow-up period. The surgical complication rate was higher in the IPA group (39% vs. 6%). DISCUSSION: We assessed the long-term outcomes of the surgical approaches used for pediatric patients weighing <15 kg who underwent KTx and received a size-mismatched adult donor kidney. There was no significant difference in renal transplantation prognosis using the surgical approach, but IPA-related complications were more frequent in the long term. Therefore, our data suggest that in cases of donor-recipient size mismatch in pediatric KTx, the EPA, associated with fewer surgical complications, is preferable to the IPA if the patient's body size has sufficient space for allograft placement. CONCLUSION: The transplant approach did not influence the long-term outcomes in children weighing <15 kg, but EPA had fewer surgical complications and was technically safe.

Clinicopathological Analysis of Medullary Ray Injury in 1-Year Protocol Paediatric Renal Allograft Biopsies.

AIM: Medullary ray injury was recently reported in renal transplant biopsies. This study was performed to clarify the clinicopathological features of medullary ray injury in paediatric living renal transplant recipients. METHODS: Paediatric recipients who completed a 5-year follow-up after living renal transplantation were enroled. We evaluated the clinical and pathological parameters of the presence or absence of medullary ray injury in their 1-year protocol biopsies. RESULTS: Of 48 1-year protocol biopsies, 18 (37.5%) showed histological evidence of medullary ray injury. The 48 paediatric recipients were classified as those with medullary ray injury (n = 18; MRI-1Y [+] group) and those without medullary ray injury (n = 30; MRI-1Y [-] group) in the 1-year protocol biopsies. The prevalence of histological evidence of calcineurin inhibitor (CNI) nephrotoxicity, chronic obstruction or reflux nephropathy, and imaging findings of vesicoureteral reflux was 66.7, 22.2, and 7.7% in the MRI-1Y (+) group and 33.3, 13.3, and 15.4% in the MRI-1Y (-) group, respectively. Only the prevalence of CNI nephrotoxicity was significantly different between the 2 groups. There was no significant difference in the mean estimated glomerular filtration rate at 1, 3, or 5 years after transplantation between the 2 groups. CONCLUSION: In total, 37.5% of 1-year protocol biopsies showed histological evidence of medullary ray injury. This finding suggests that CNI nephrotoxicity might be the main contributor to medullary ray injury in 1-year protocol biopsies. The presence of medullary ray injury had little influence on renal function, at least during the first 5 years after transplantation.

A cross-sectional nationwide survey of congenital and infantile nephrotic syndrome in Japan.

BACKGROUND: Congenital nephrotic syndrome (CNS) and infantile nephrotic syndrome (INS) cause substantial morbidity and mortality. In Japan, there is a lack of knowledge regarding the characteristics of CNS and INS. This study aimed to clarify the characteristics of CNS and INS in Japan. METHODS: This cross-sectional nationwide survey obtained data from 44 institutions in Japan managing 92 patients with CNS or INS, by means of two survey questionnaires sent by postal mail. Patients aged < 16 years by 1 April 2015, with a diagnosis of CNS or INS, were included in this study. The primary outcome was end-stage kidney disease. RESULTS: A total of 83 patients with CNS or INS were analyzed. The most frequent disease type was non-Finnish (60.2%); 33 patients (39.8%) had Finnish type. Among those with non-Finnish-type disease, 26 had no syndrome and 24 had a syndrome, of which the most frequent was Denys-Drash syndrome (70.8%). Patients with non-Finnish-type disease with syndrome showed the earliest progression to end-stage kidney disease compared with the other two groups, whereas patients with non-Finnish-type disease without syndrome progressed more slowly compared with the other two groups. In the Finnish-type group, the disease was diagnosed the earliest; a large placenta was reported more frequently; genetic testing was more frequently performed (93.8%); mental retardation was the most frequent extra-renal symptom (21.2%); and thrombosis and infection were more frequent compared with the other groups. Patients with non-Finnish-type disease with syndrome had a higher frequency of positive extra-renal symptoms (79.2%), the most common being urogenital symptoms (54.2%). Treatment with steroids and immunosuppressants was more frequent among patients with non-Finnish-type disease without syndrome. Two patients with non-Finnish-type disease without syndrome achieved complete remission. In all groups, unilateral nephrectomy was performed more often than bilateral nephrectomy and peritoneal dialysis was the most common renal replacement therapy. CONCLUSIONS: The present epidemiological survey sheds light on the characteristics of children with CNS and INS in Japan. A high proportion of patients underwent genetic examination, and patient management was in accord with current treatment recommendations and practices. TRIAL REGISTRATION: Not applicable.

Comparison of live donor predonation and post-transplant kidney volumes and glomerular size in pediatric patients weighing less than 15 kg - a retrospective study.

Renal transplantation of adult-size kidneys presents a size mismatch in small children. This study presents a comparison of live donor predonation and recipient post-transplant kidney volumes (k-vol) and glomerular size at 1 year after transplantation. We analyzed 47 pediatric renal transplant recipients weighing <15 kg between 2009 and 2017. The k-vol before and 1 year after transplantation and glomerular size at implant and 1 year post-transplant were evaluated. We estimated the relationships between these changes and graft function, and the factors associated with k-vol. Pretransplant k-vol was 158.1 ± 25.1 ml, and the k-vol at 1 year post-transplant was significantly reduced by -17.2% to 132.3 ± 27.3 ml (P < 0.001). Implant glomerular size showed the diameter was 165.3 ± 15.1 µm and the area 20 737.1 ± 3230.6 µm2 . One-year post-transplant, the glomerular diameter was 150.6 ± 11.4 µm and the area 17 428.3 ± 2577.9 µm2 , significantly reduced compared with implantation values (both P < 0.001). The change in k-vol was affected by pretransplant abdominal cavity (ml/200 ml cavity volume, partial regression coefficient = 0.029, SE = 0.009, P = 0.004) and recipient's weight gain (ml/5% of weight gain, partial regression coefficient = 0.020, SE = 0.006, P = 0.002). In small pediatric transplants, an adult-size kidney is acceptable with reduction in k-vol. Moreover, the post-transplant k-vol might be regulated by pretransplant physique and post-transplant somatic growth.

Long-term outcomes of pediatric kidney transplantation: A single-center experience over the past 34 years in Japan.

OBJECTIVES: To evaluate long-term outcomes and risk factors for graft loss in pediatric kidney transplantation over a 30-year period. METHODS: We retrospectively assessed 400 consecutive kidney transplants carried out in 377 children during 1975-2009. Patients were stratified according to the immunosuppressive regimen (era 1: methylprednisolone and azathioprine; era 2: calcineurin inhibitor-based therapy, including methylprednisolone and azathioprine or mizoribine; era 3: basiliximab induction therapy, including calcineurin inhibitors, methylprednisolone and mycophenolate mofetil). RESULTS: The median age and bodyweight at transplantation were 9.7 years and 20.6 kg, respectively. In total, 364 (91.0%) children received a living related donor transplantation. The acute rejection rate within 1 year post-transplant decreased significantly from 61.0% in era 1 to 14.5% in era 3 (P < 0.001). For transplant eras 1-3, 1-year graft survival was 81%, 93% and 95%; 5-year graft survival was 66%, 86% and 93%; and 10-year graft survival was 47%, 79% and 89%, respectively. The overall 5-, 10- and 20-year patient survival rates were 96%, 93% and 88%, respectively. A Cox multivariate analysis identified cold ischemia time (hazard ratio 1.385, 95% confidence interval 1.251-1.603), acute rejection (hazard ratio 1.682, 95% confidence interval 1.547-3.842), re-transplant (hazard ratio 2.680, 95% confidence interval 1.759-3.982) and donor type (hazard ratio 2.957, 95% confidence interval 1.754-4.691) as independent risk factors for graft loss at 10 years post-transplant. CONCLUSIONS: The progress of immunosuppressive therapy has led to a low incidence of acute rejection and a high graft survival rate across 30 years of pediatric transplantation.

Changes in cardiac function after renal transplantation in children: Significance of pre-transplantation left ventricular hypertrophy.

LVH is a significant risk factor for the development of cardiovascular morbidity. However, few studies have evaluated the changes in cardiac function that occur in pediatric patients with ESRD undergoing RTx. Therefore, we assessed the changes in parameters associated with LVH in children within the first year after RTx. We retrospectively evaluated patients aged < 18 years who underwent initial RTx from April 2014 to December 2016. The patients were divided into 2 groups according to the presence of LVH before RTx. Clinical, biochemical, and echocardiographic parameters including the LVMI before and 1 year after RTx were evaluated in both groups. Twenty-six patients were included in this study. Seven of the 26 patients had LVH before RTx. Among the echocardiographic parameters, the LVMI was significantly improved 1 year after RTx in the initial LVH group (57.79 ± 11.86 vs 42.20 ± 6.03 g/cm2.7 , P = .018), while no change was observed in the initial non-LVH group (32.66 ± 7.52 vs 35.17 ± 12.86 g/cm2.7 , P = .376). Improvement of the ejection fraction was also observed only in the initial LVH group (66.5% ± 5.3% vs 72.2% ± 5.2%, P = .042). Children who had LVH before RTx showed significant improvements in the LVMI and ejection fraction even within 1 year after RTx. To minimize aggravation of cardiac function, early RTx should be considered for patients with LVH.

Donor-Recipient Body Weight Mismatch May Affect Glomerular Basement Membrane Thinning in Electron Microscopic Examination of 1-Hour Renal Allograft Biopsy Specimens.

BACKGROUND: Although an association between body weight mismatch and impaired graft function has been reported, few histologic studies have evaluated this issue, especially using electric microscopic analysis. During routine observations, we have noted a thin glomerular basement membrane (GBM) in the 1-hour biopsy specimen in cases with an overweight recipient and a lightweight donor. Therefore, we hypothesized that donor-recipient body weight mismatch affects the GBM thickness in the 1-hour biopsy specimen. The aim of the present study was to clarify the effect of donor-recipient body weight mismatch on the GBM thickness of the 1-hour biopsy specimen measured using electron microscopy. METHODS: We used an electron microscope to measure the GBM thickness of specimens at 1-hour post-transplantation (n = 24) and at 1 year post-transplantation (n = 17). The GBM thickness of cases with donor-recipient body weight mismatch was compared with those without mismatch. In accordance with a previous study, we defined a donor/recipient body weight ratio of less than 0.9 as donor-recipient body weight mismatch and a ratio of more than 0.9 as no mismatch. RESULTS: At 1-hour post-transplantation, the mean GBM was significantly thinner in the mismatch group than in the nonmismatch group. However, at 1-year post-transplantation, the mean GBM thickness did not significantly differ between the 2 groups. CONCLUSIONS: The GBM thickness at 1-hour post-transplantation is thinner in cases with donor-recipient body weight mismatch than in cases without mismatch. This implies that donor-recipient body weight mismatch may have to be considered when assessing donor-derived thin GBM disease using the 1-hour biopsy specimen.

Can Lipofuscin Deposition on Renal Allograft Tubular Epithelium Be a Surrogate Marker for Kidney Allograft Aging?

BACKGROUND: Lipofuscin is an indicator of aging. We examined the clinicopathologic significance of lipofuscin deposition in the renal tubules of renal allografts. METHOD: We analyzed allograft biopsy specimens from living kidney transplantations from January to December 2015. For controls, we analyzed native kidney biopsy specimens obtained from January 2015 to December 2016. We identified granules with a yellow-to-tan shade in renal tubules as lipofuscin. RESULTS: The donor age at transplantation was significantly older in lipofuscin deposition biopsy specimens than in those without, whereas the time after transplantation age was not different between the 2 groups with renal allografts. In native kidney biopsies, age at biopsy was significantly older in lipofuscin deposition biopsy specimens than in those without. We compared "massive lipofuscin deposition," defined as lipofuscin deposition on both sides of 3 or more renal tubules, and donor-age matched control allograft biopsies without lipofuscin deposition. Comparing these 2 groups, recipient age at transplantation was significantly older in the massive lipofuscin deposition group. CONCLUSION: Lipofuscin deposition on tubular epithelium is not a surrogate marker of aging of kidneys allografts, although lipofuscin deposition was significantly greater in older tissues from native kidneys. The older age of recipients may be associated with massive lipofuscin deposition in renal allografts.

Preserved Kidney Volume, Body Mass Index, and Age Are Significant Preoperative Factors for Predicting Estimated Glomerular Filtration Rate in Living Kidney Donors at 1 Year After Donation.

BACKGROUND: Securing postdonation renal function in the lifetime of donors is a consequential subject for physicians, and precise prediction of postdonation renal function would be considerably beneficial when judging the feasibility of kidney donation. The aim of this study was to investigate the optimum model for predicting eGFR at 1 year after kidney donation. METHODS: We enrolled 101 living-related kidney donors for the development cohort and 44 for the external validation cohort. All patients in each cohort underwent thin-sliced (1 mm) enhanced computed tomography (CT) scans. We excluded individuals with diabetes, glucose intolerance, or albuminuria from this study. We evaluated preoperative factors including age, sex, hypertension, body mass index (BMI), serum uric acid, baseline eGFR, and body surface area (BSA)-adjusted preserved kidney volume (PKV) by using 3-dimensional reconstruction of thin-sliced enhanced CT images. To detect independent predictors, we performed multivariable regression analysis. RESULTS: The multivariable regression analysis revealed that age, BMI, predonation eGFR, and BSA-adjusted PKV were independent predictors of eGFR at 1 year after kidney donation (correlation coefficient: -0.15, -0.476, 0.521, 0.127, respectively). A strong correlation between predicted eGFR and observed eGFR was obtained in the development cohort (r = 0.839, P < .0001). The significance of this predictive model was also confirmed with the external validation cohort (r = 0.797, P < .0001). CONCLUSIONS: Age, BMI, predonation eGFR, and BSA-adjusted PKV may be useful for precisely predicting eGFR at 1 year after living kidney donation and be helpful to determine the feasibility of kidney donation from marginal donors.

Transplantation of adult-size kidneys in small pediatric recipients: A single-center experience.

RTx of adult-size kidneys presents a size mismatch in small pediatric recipients, and there are potential surgical complications. This study reveals the outcomes of intra- and extraperitoneal RTx in low-weight (less than 15 kg) pediatric recipients. We studied 51 pediatric patients weighing less than 15 kg who received a living-related donor renal transplant between 2009 and 2017. The intraperitoneal (group A, n = 24) and extraperitoneal (group B, n = 27) approaches were compared. In group A, the mean age, Ht, and weight were 3.8 ± 1.6 years, 83.7 ± 6.5 cm, 10.5 ± 1.8 kg; in group B, 5.0 ± 1.9 years, 95.3 ± 7.3 cm, and 13.0 ± 1.4 kg. Single renal artery grafts (21 in group A and 16 in group B) and double renal artery grafts (three in group A and 11 in group B) were performed. Of the patients with double renal artery transplants, one in group A and six in group B underwent ex vivo arterial reconstruction. The eGFR (mL/min/1.73 m2 ) at 1-week post-transplant in group A was significantly higher than that in group B; the eGFRs at 4 weeks post-transplant did not differ. One graft was lost in group B because of vascular thrombosis. Post-transplant complications included ileus and transplant ureteral stenosis. There was no significant difference in 5-year graft survival rate (group A 100%, group B 91.7%). Both transplant approaches are feasible to adapt to a size mismatch between the adult-size donor kidney and low-weight pediatric recipients.