Long-term outcomes during 37 years of pediatric kidney transplantation: a cohort study comparing ethnic groups.

BACKGROUND: This study aimed to evaluate short- and long-term outcomes of kidney transplantation over 37 years in a national referral center and compare outcomes between Israeli Jewish and Arab children. METHODS: Data on 599 pediatric transplantations performed in 545 children during 1981-2017, including demographic parameters, kidney failure disease profile, and pre-transplant dialysis duration, were retrieved from our computerized database and patient files. Patient and graft survival were estimated using the Kaplan-Meier method. RESULTS: Twenty-year patient survival was 91.4% for live donor (LD) and 80.2% for deceased donor (DD) kidney recipients. Respective 10-year and 20-year graft survival rates for first kidney-only transplants were 75.2% and 47.0% for LD and 60.7% and 38.4% for DD grafts. Long-term graft survival improved significantly (p < 0.001) over the study period for recipients of both LD and DD allografts and reached 7-year graft survival of 92.0% and 71.3%, respectively. The proportion of DD transplantations was higher in the Arab subpopulation: 73.8% vs. 48.4% (p < 0.001). Graft survival was not associated with age at transplantation and did not differ between the Arab (N = 202) and Jewish children (N = 343). Median (IQR) waiting time on dialysis did not differ significantly between the Arab and Jewish children: 18 (10-30) and 15 (9-30) months, respectively (p Mann-Whitney = 0.312). CONCLUSIONS: Good and progressively improving long-term results were obtained in pediatric kidney transplantation at our national referral center, apparently due to expertise gained over time and advances in immunosuppression. Equal access to DD kidney transplant and similar graft survival were found between ethnic groups.

Treatment of BK virus-associated nephropathy with CMX001 after kidney transplantation in a young child.

NC, with renal failure secondary to bilateral dysplastic kidneys, received an LRD renal transplant (tx) at 17 months of age. Her early post-tx course was complicated by persistently elevated blood polyoma BK virus DNA loads. A protocol biopsy at six months post-transplant revealed BKVAN. Blood viral loads did not respond to decreased immunosuppression or treatment with ciprofloxacin and leflunomide. Six months post-tx, her serum creatinine began to rise and we sought experimental therapy to prevent the loss of her graft. At seven months post-tx, with FDA approval under an eIND, the patient was started on a 36-wk course of treatment with the investigational drug. The patient is now more than 24 months after stopping treatment with CMX. BKV viral DNA loads remain at low, but still detectable levels. Urine viral loads have declined, but remain elevated. EBV DNA loads become undetectable. The patient's serum creatinine has declined back to a baseline of 0.5-0.7 mg/dL and has been stable for two yr. Renal function was preserved in association with the use of CMX001 to treat BKV nephropathy in a young pediatric kidney transplant recipient. There were no serious adverse events associated with the use of CMX001. This novel medication may be of value in the treatment of BKVAN in pediatric renal transplant recipients.

Improving renal phenotype and evolving extra-renal features of 17q12 deletion encompassing the HNF1B gene.

BACKGROUND: HNF1B deletion/intragenic mutations are the most commonly identified genetic cause of congenital anomalies of the kidney and urinary tract (CAKUT) suggested by fetal ultrasound findings such as: parenchymal hyperechogenicity, overt cystic changes or gross morphological urinary system (UT) abnormalities. The postnatal evolution of these 17q12 deletions encompassing the HNF1B gene-associated findings has not been assessed in depth. METHODS: In this observational study, we present postnatal follow-up findings in 5 of 6 cases (one pregnancy was terminated on parental request) of fetal-onset cystic/hyperechogenic kidneys eventually diagnosed with 17q12 microdeletion encompassing the HNF1B gene between 2009 and 2017. RESULTS: Complete normalization of kidney parenchymal abnormalities and of depressed neonatal renal function was observed in 4/5 and 5/5 patients within 2-4.9 years and 1.5-8 months, respectively. All 5 patients had preserved normal renal function at 3-11 years of follow-up. The evolving later-onset renal features included: hypomagnesemia, hyperuricemia, urinary tract infection (UTI), and bilateral grade 3-4 vesicoureteral reflux and bladder diverticula in 3, 3, 2, and 1 patient, respectively. HNF1B gene deletion-associated extra-renal manifestations with delayed presentation were global developmental delay/autistic spectrum disorder (ASD), rolandic-type seizures, overweight, and borderline fasting hyperglycemia observed in 1-2 patients each. Family history was positive for small-size or asymptomatic cystic kidneys with normal function, diabetes mellitus, seizures, and mental/psychiatric problems in 3/6 cases. CONCLUSIONS: Fetal-onset HNF1B deletion-associated kidneys' parenchymal abnormalities confirmed postnatally with initially depressed renal function might undergo complete resolution within several years and few months, respectively. However, later-onset urinary tract, metabolic, and neurodevelopmental features of this mutation might appear over years. Therefore, genetic molecular evaluation/diagnosis and continuous follow-up for evolving features are mandatory in affected children.

Neonatal acute kidney injury: recording rate, course, and outcome: one center experience.

Background: Neonates, and particularly preterm newborns, are at increased risk for acute kidney injury (AKI) due to immature kidney function. While specific criteria have been defined for AKI in this particular population, this diagnosis is frequently overlooked, and consequently, is often not recorded in patients' medical files. AKI-associated short- and long-term morbidity and mortality underline the importance of this diagnosis Objective: To assess the recording rate of AKI in the neonatal intensive care unit (NICU), and to identify clinical features that may promote awareness to this condition. Study design: The database of one medical center was searched for serum creatinine values above 1 mg% among all the newborns (more than 48 hours old) who were hospitalized in the neonatal intensive care unit (NICU) during the years 2010-2015, and who underwent at least two blood tests during their hospitalization. The files of patients who met acute kidney injury (AKI) diagnostic criteria were searched for AKI diagnosis, maternal, fetal, and postnatal course and outcome. Results: Of 59 newborns who met AKI criteria, 51 (86%) were preterm and 8 term newborns. The respective mean gestational weeks at birth were: 28 ± 3 and 38.5 ± 1, and mean birth weights: 1002 ± 57 and 3157 ± 375 grams. Mortality rates were 14/51 (27%) versus 1/8 (12.5%). Of the 44 survivors, AKI was recorded in the medical files of 9/37 (24%) preterm versus 5/7 (71%) term-newborns. AKI associated with twin pregnancy in preterm neonates: 22 (43%) versus 1 (12.5%) in term-newborn. Unexpected high frequencies of maternal obstetrical problems and cesarean section delivery: 62.5 and 78%, respectively, along with persistently depressed 5-min Apgar 6.6 ± 3.5 were found in term newborns with AKI. Congenital anomalies of the urinary tract (CAKUT) were suspected prenatally on fetal ultrasound in 3 (6%) and 1 (12.5%) of the respective groups, a 10-fold higher rate than that observed in the general population. AKI recurred in 18 (35%) of the preterm and none of the term neonates. Mild AKI episodes (Stage 1-2) occurred in 30/37 (81%) by contrast to severe events (Stage 3) in 4/7 (57%) preterm and term survivors, respectively. Ventilation duration associated significantly with AKI recurrence, and sepsis with mortality: OR 1.25 (95%CI = 1.09-1.43) (p < .001) and OR = 4.65 (95%CI = 1.26-17.2) (p = .014), respectively. Conclusions: We demonstrated underreporting of AKI, particularly among preterm newborns, a population at high risk of developing recurrent episodes. Our data suggest different clinical profiles of AKI among preterm and term neonates: with later onset, milder but recurrent episodes in the former. Increased alertness for AKI diagnosis is needed for neonates with prolonged respiratory support, treated with diuretics and after sepsis. Newborns suspected of CAKUT (Congenital Anomalies of Kidneys and Urinary Tract) as per fetal ultrasound might need closer observation for AKI occurrence.