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.

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.

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.

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.

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.

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.

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.

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.

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.

Vasa recta hyalinosis reflects severe arteriolopathy in renal allografts.

AIM: We examined the clinicopathologic significance of hyalinosis in the vasa recta in the medulla of allograft kidney biopsies. METHOD: We analyzed biopsy specimens from January 2010 to December 2015, obtained from both the cortex and medulla (including the vasa recta) ≥ 1 year after living-donor kidney transplantation. We excluded biopsy specimens from recipients who had undergone transplantation due to diabetic nephropathy or who had diabetes mellitus after transplantation. We evaluated hyaline arteriolopathy in the cortex using the aah score determined by the Banff 2007 classification. RESULT: Among 381 biopsy specimens obtained from 248 transplant recipients ≥ 1 year after transplantation, 36 specimens obtained from 34 recipients showed vasa recta hyalinosis (VRH) in the medulla. Among these 36 specimens, 17 had a score of aah3, 16 had a score of aah2, and 3 had a score of aah1. The incidence of VRH was 1.9% at ≥ 1 to < 4 years, 7.1% at ≥ 4 to < 8 years, and 50.0% at ≥ 8 years. The aah scores and the proportion of hyalinosis in the arteriolar media among all muscular arterioles in the cortex were significantly higher in the VRH group at ≥ 8 years in the late-phase biopsy (P < 0.01). The graft survival was worse in the VRH group (P = 0.024), although there was no significant difference in the graft survival between the ≥ aah2 and < aah2 groups at ≥ 8 years in the late-phase biopsy (P = 0.159). CONCLUSION: VRH in renal allografts reflects severe arteriolopathy of the cortex. VRH in the late-phase biopsy may be a prognostic factor for graft survival.

Management of patients with severe Epstein syndrome: Review of four patients who received living-donor renal transplantation.

AIM: Epstein syndrome is a hereditary disease characterized by macrothrombocytopaenia and progressive nephritis. The abnormality of the MYH9 gene has a strong relationship to the severity of the disease. Severe Epstein syndrome progresses to end-stage renal disease rapidly after adolescence. There is no established therapy. We sought to clarify appropriate management of Epstein syndrome nephropathy. METHODS: Epstein syndrome patients who underwent renal transplantation at our institution between March 2009 and March 2017 were enrolled. Epstein syndrome was diagnosed based on clinical features and genetic testing. Patient medical records were reviewed retrospectively. RESULTS: Four male patients with Epstein syndrome, all with severe MYH9 gene mutations (p.R702C in three and p.S96L in one), were enrolled. Despite treatment with renin-angiotensin system blockers, nephropathy was refractory and progressed rapidly, and the patients required dialysis or renal transplantation after adolescence. Early preparation for treatment based on early and accurate diagnosis of Epstein syndrome enabled two patients to undergo pre-emptive renal transplantation. For these patients, we kept the platelet count above 100 × 109 /L until day 7 after renal transplantation with platelet transfusions for macrothrombocytopaenia, and no postoperative bleeding episodes occurred. CONCLUSION: Epstein syndrome nephropathy due to a severe MYH9 gene mutation can be refractory and progress rapidly; therefore, early and accurate diagnosis is important for safer therapeutic options including pre-emptive renal transplantation. By keeping the platelet count above 100 × 109 /L during the perioperative period, renal transplantation can be a safe treatment option for severe Epstein syndrome nephropathy.

Change in the quality of life of caregivers of pediatric department patients undergoing kidney transplantation: a single-center prospective study.

BACKGROUND: Caregivers of patients with chronic kidney disease experience great burdens. Changes in these caregivers' quality of life (QOL) before and after their children underwent kidney transplantation (KTx) were evaluated in this prospective study. METHODS: The sequential QOL scores of 31 caregivers (median age 38.5 years) whose children (5.8 years) underwent KTx from 2012 to 2014 were studied. The same questionnaires were administered before and 1, 3, and 12 months after KTx. We evaluated whether the following factors were associated with QOL: pre-transplant dialysis, recipient's mental and/or motor disability, and acute rejection or infections after KTx. RESULTS: The average QOL score before KTx (3.40) was higher than that of the general population (3.23). Despite a temporal decrease at 1 month (3.15), the final QOL scores were maintained at 3 months (3.40) and 1 year (3.42) after KTx. The mean QOL scores were significantly higher for caregivers of patients with than without dialysis before KTx [3.46 vs. 3.28 (p = 0.041) at 3 months and 3.53 vs. 3.18 (p = 0.001) at 1 year, respectively]. Conversely, these scores were significantly lower for caregivers of patients with than without disabilities [2.97 vs. 3.20 (p = 0.021) at 1 month, 3.18 vs. 3.46 (p = 0.006) at 3 months, and 3.10 vs. 3.50 (p = 0.001) at 1 year, respectively]. CONCLUSION: Dialysis of children before KTx was a particularly larger burden for caregivers. The child's comorbidities and social adaptation problems might be focused after KTx, we need to evaluate for more long-term QOL of caregivers.

Long-term outcome of congenital nephrotic syndrome after kidney transplantation in Japan.

BACKGROUND: Congenital nephrotic syndrome is difficult to manage, particularly the Finnish type (CNF), with patients experiencing severe edema, sepsis and thrombosis before kidney transplantation. Further, nephrosis and thrombosis remain problematic after transplantation. METHODS: Of 22 CNF patients managed at our hospital, 14 who underwent kidney transplantation were retrospectively studied. CNF was diagnosed according to standard criteria. RESULTS: The study population consisted of 3 males and 11 females. Mean gestation period was 36 ± 1.4 weeks and mean birth weight was 2442 ± 454 g (mean placenta to body weight ratio: 0.4). All patients started dialysis at 2.4 ± 1.3 years and underwent kidney transplantation at 5.2 ± 2.0 years. The kidneys were donated by the parents (n = 13), and cadaver (n = 2), including overlap. Mean follow-up period after transplantation was 14.3 ± 8.9 years, and mean age at last observation was 19.5 ± 8.5 years. Two patients had recurrent proteinuria after kidney transplantation; one underwent retransplantation following graft failure and eventually required dialysis, while the second had complete remission after intensive immunosuppressive therapy. There were no cases of thrombosis or serious infections. Mean eGFR at the time of last observation was 57.3 ± 16.5 ml/min/1.73 m2, while mean height SD score was - 2.1 ± 0.9 at the time of transplantation and - 1.5 ± 1.5 at last observation. CONCLUSIONS: Long-term outcome in these 14 CNF patients showed satisfactory graft survival, improved height SD score, and favorable development. Although recurrent proteinuria after transplant was not predictive, it was associated with graft survival rate.

Protocol graft biopsy in kidney transplantation.

Accurate interpretation of renal allograft biopsy is necessary to guide therapy, especially when an episode biopsy is taken to rescue the graft. Contrarily, a protocol biopsy is carried out routinely to identify baseline conditions (biopsy at 0 or 1 h), subclinical rejection, histological change under current immunosuppression regimen, drug nephrotoxicity, viral infection, and recurrence of glomerulonephritis. Semiquantitative scoring for active lesions including tubulitis, glomerulitis, capillaritis, arteritis, arteriopathy, and others such as polyomavirus infection are key factors in transplant pathology. Recently, the Banff classification has proposed several novel concepts focused on antibody-mediated rejection (ABMR). This review presents the interpretation of transplant pathology from rejection to infection, recurrence of glomerulonephritis, and drug nephrotoxicity, with a description of ABMR according to the 2013 and 2017 Banff classification.

Interlobular hyaline arteriopathy reflects severe arteriolopathy in renal allografts.

AIM: The present study was performed to examine the clinicopathological significance of hyaline deposits in the smooth muscle of the interlobular artery (interlobular hyaline arteriopathy [IHA]) in renal allografts. METHODS: Tissue specimens that included the interlobular artery from biopsies performed from January 2012 to December 2015, as well as specimens from biopsies performed ≥1 year after living kidney transplantation were analyzed. Biopsies of recipients with new-onset diabetes mellitus after transplantation were excluded, as well as those of recipients who had undergone transplantation because of diabetic nephropathy. Arteriolopathy was evaluated using the aah score determined by the Banff 2007 classification. RESULTS: In total, 51 specimens with IHA lesions were identified among 381 biopsies obtained from 243 recipients performed ≥1 year after kidney transplantation. Among these 51 biopsies, 18 specimens had a score of aah3, 29 had a score of aah2, and four had a score of aah1. The incidence of IHA lesions was 3.6% at ≥1 to <4 years, 18.5% at ≥4 to <8 years, and 54.1% at ≥8 years. Older kidney grafts exhibited more IHA lesions. Among the biopsy specimens obtained ≥8 years after transplantation, no significant differences in the recipient or donor age, duration after transplantation, or prevalence of hypertension were observed between the IHA and non-IHA groups. The aah scores were significantly higher in the IHA group ≥8 years after transplantation as determined by the mean score test (P < 0.01). CONCLUSION: IHA in renal allografts is associated with severe arteriolopathy.

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 donor's renal artery was anastomosed to the aorta. The donor's ovarian and large saphenous veins were used to extend the transplant renal vein to the recipient's 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.

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.