Pediatric Nephrology最新文献

The post-transplant course of pediatric kidney transplant recipients is marked by a myriad of challenges, encompassing medical complications, recurrent hospitalizations, physical and dietary restrictions, and mental health concerns such as depression, anxiety, and post-traumatic stress disorder. Moreover, pediatric recipients are at risk of neurodevelopmental impairment, which may result in neurocognitive deficits and pose significant psychosocial obstacles. Addressing these multifaceted demands necessitates a multidisciplinary approach to pediatric kidney transplant care. However, the existing literature on the effective implementation of such a model remains scarce. This review examines the psychosocial and neurodevelopmental challenges faced by pediatric kidney transplant recipients and their families, discussing their impact on long-term transplant outcomes. Furthermore, it provides insights into risk assessment strategies and potential interventions within a multidisciplinary framework, aiming to enhance patient care and optimize post-transplant outcomes.

We describe the unexpected challenges pediatricians may experience when children conceived with assisted reproduction are diagnosed with a rare genetic condition. A local case series triggered a dialogue between many stakeholders with varied expertise. Indeed, diagnosing a genetic disease in a child conceived by embryo, egg, or sperm donation is becoming more common now that genetic testing and in vitro fertilization (IVF) are readily accessible. However, how and whether to share that information with other stakeholders in the gamete donation process has not been fully explored, and the clinical responsibilities of the treating clinician remain ill-defined. This work centers on a patient with a confirmed diagnosis of X-linked nephrogenic diabetes insipidus. Ultimately, we found the same AVPR2 mutation in two children from two families conceived by egg donation. It led to multigenerational cascade diagnoses in the family of the shared, anonymous egg donor. First, we review current genetic testing practices in gamete donation and third-party reproduction. Then, we provide an overview of relevant genomic, ethical, legal, and psychosocial considerations for sharing relevant genomic information. Finally, and to maximize the best interests of genetic relatives, we discuss how a pediatrician can play a role in the early disclosure of relevant clinical information to all stakeholders in the gamete donation process, starting with the fertility clinic. While these clinical cases are cast in a Canadian context, we submit that its important lessons generally apply to medical systems of nearly all developed countries, broadly defined.

Background: Hypertension poses a significant risk as a complication of chronic kidney disease (CKD), contributing to its hastened advancement. Implementing ambulatory blood pressure monitoring (ABPM), a straightforward and non-invasive method proves beneficial in identifying masked hypertension.

Methods: A cross-sectional study was carried out involving children aged 5-15 years diagnosed with CKD to estimate the difference in masked HTN prevalence between the 2014 and 2022 AHA ABPM guidelines. The study encompassed a comprehensive assessment, including 24-h blood pressure monitoring and was performed using ABPM. Left ventricular mass (LVM) was computed based on measurements obtained from M-mode echocardiography. PWV was determined by calculating the ratio of distance (D) to time (t).

Results: We examined a cohort of 138 children diagnosed with CKD. Our findings reveal that, in accordance with the 2022 American Heart Association (AHA) ABPM guidelines, prevalence of masked hypertension stands at 29.7% marking a notable increase of 17.4% compared to the 2014 ABPM guidelines signifying a substantial proportion of undetected hypertensive cases. Furthermore, the prevalence of hypertension is 48.5% as detected by ABPM, marking a notable increase of 22.5%.

Conclusions: A substantial occurrence of masked hypertension was identified in pediatric CKD patients through the application of ABPM. ABPM proves to be an effective tool for uncovering masked hypertension in children with CKD.

Background: Cystic kidney disease is a heterogeneous group of hereditary and non-hereditary pathologic conditions, associated with the development of renal cysts. These conditions may be present both in children and adults. Cysts can even be observed already during the prenatal age, and pediatric patients with cysts need to be clinically monitored. An early clinical and genetic diagnosis is therefore mandatory for optimal patient management. The aim of this study was to perform genetic analyses in patients with echographic evidence of kidney cysts to provide an early molecular diagnosis.

Methods: A cohort of 70 pediatric patients was enrolled and clinically studied at the time of first recruitment and at follow-up. Genetic testing by clinical exome sequencing was performed and a panel of genes responsible for "cystic kidneys" was analyzed to identify causative variants. Sanger validation and segregation studies were exploited for the final classification of the variants and accurate genetic counseling.

Results: Data showed that 53/70 of pediatric patients referred with a clinical suspicion of cystic kidney disease presented a causative genetic variant. In a significant proportion of the cohort (24/70), evidence of hyper-echogenic/cystic kidneys was already present in the prenatal period, even in the absence of a positive family history.

Conclusions: This study suggests that cystic kidney disease may develop since the very early stages of life and that screening programs based on ultrasound scans and genetic testing play a critical role in diagnosis, allowing for better clinical management and tailored genetic counseling to the family.

Background: Post-transplant lymphoproliferative disorder (PTLD) is a devastating complication of immunosuppressive treatment in both solid organ transplantations (SOT) and hematopoietic stem cell transplantations (HSCT). Epstein-Barr virus (EBV) infection precedes PTLD in 90% of patients. Rituximab, a monoclonal anti-CD20 antibody, depletes B-lymphocytes, which are the ultimate reservoir for EBV. Although rituximab therapy is commonly used as a preventive measure for PTLD in high-risk HSCT, it is not established in SOT.

Methods: Pediatric kidney transplant recipients (PKTR) underwent routine EBV-PCR surveillance. Patients with increasing viral loads, despite immunosuppressive dose reduction, were managed with preventive rituximab therapy.

Results: Between 2012 and 2023, we identified eight episodes of asymptomatic EBV-PCR-positive blood tests in seven out of 65 PKTR (11%) under our care. EBV DNAemia emerged 120-720 days post-transplantation. Five of seven patients with EBV DNAemia (71%) were EBV-seronegative prior to transplantation. All five patients did not respond to MMF dose reduction and were therefore treated with preventive rituximab therapy. Following this treatment, EBV PCR clearance was observed in all patients with only minimal complications.

Conclusions: PKTR who are EBV-naïve prior to transplantation are expected to have a higher prevalence of EBV DNAemia. We found that PKTR who were EBV seronegative prior to transplantation were less likely to achieve EBV clearance in response to immunosuppression dose reduction. We suggest that rituximab therapy in PKTR may be safe and effective in EBV clearance and PTLD prevention.

A subgroup of children with frequently-relapsing, steroid-dependent nephrotic syndrome relapse during B-cell depletion after rituximab. A 15-year-old boy with focal segmental glomerulosclerosis became rituximab-refractory after 5 courses of treatments, with a relapse-free period shortened to 1 month. Circulating total and memory B-cells were undetectable at the time of relapse. A single infusion of obinutuzumab sustained relapse-free remission up to the last follow-up at 18 months. There was persistent hypogammaglobulinemia but no infection was observed. Obinutuzumab may be a viable option for attaining long-term remission with reasonable side effect profiles in patients who relapse during B-cell depletion after rituximab.

Cardiorenal syndrome (CRS) refers to concomitant dysfunction of both the heart and kidneys. The pathology in CRS is bidirectional. Many individuals with kidney disease will develop cardiovascular complications. Conversely, rates of acute kidney injury and chronic kidney disease are high in cardiac patients. While our understanding of CRS has greatly increased over the past 15 years, most research has occurred in adult populations. Improving cardiorenal outcomes in children and adolescents requires increased collaboration and research that spans organ systems. The purpose of this review is to discuss key features of CRS and help bring to light future opportunities for pediatric-specific research.

Background: In kidney transplant recipients (KTR), BK polyomavirus-associated nephropathy (BKPyVAN) is a major cause of graft loss. To facilitate the clearance of BKPyV-DNAemia, reduction of immunosuppression is currently the treatment of choice but may increase the risk of graft rejection.

Methods: This international CERTAIN study was designed to determine the risk of alloimmune response and graft dysfunction associated with immunosuppression reduction for BKPyV treatment in 195 pediatric KTR.

Results: BKPyV-DNAemia was associated with a more than twofold increased risk of late T cell-mediated rejection (TCMR) (HR 2.22, p = 0.024), of de novo donor-specific HLA antibodies (dnDSA) and/or antibody-mediated rejection (ABMR) (HR 2.64, p = 0.002), and of graft function deterioration (HR 2.73, p = 0.001). Additional independent risk factors for dnDSA/ABMR development were a higher HLA mismatch (HR 2.72, p = 0.006) and re-transplantation (HR 6.40, p = 0.000). Other independent predictors of graft function deterioration were TCMR (HR 3.98, p = 0.003), higher donor age (HR 1.03, p = 0.020), and re-transplantation (HR 3.56, p = 0.013).

Conclusions: These data indicate that reduction of immunosuppression for BKPyV-DNAemia management is associated with increased alloimmune response in pediatric KTR. Therefore, regular dnDSA screening and close monitoring of graft function in case of BKPyV-DNAemia followed by subsequent reduction of immunosuppressive therapy are recommended.

Background: Many studies have demonstrated the association between low birth weight (LBW) and chronic kidney disease, estimated glomerular filtration rate (eGFR) and kidney volume (KV). However, studies on twins and those investigating numerous perinatal factors beyond LBW, and their associations with various kidney parameters are scarce.

Methods: A two-center cross-sectional study on five-year-old LBW children was conducted between 2021 and 2023. 110 children were enrolled (8 LBW, 58 very LBW (VLBW), 44 extremely LBW (ELBW)); 56 were twins. We examined associations between birth weight (BW), various prenatal, perinatal and postnatal factors, and eGFR, KV, tubular abnormalities and kidney ultrasound abnormalities, both in singletons and twins.

Results: In children with ELBW, eGFR correlated with BW (r = 0.55, P = 0.0018), while in those with BW ≥ 1000 g, eGFR remained constant. Other factors associated with decreased eGFR were hypertensive disorder of pregnancy (93.86 vs. 87.26 ml/min/1.73m², P = 0.0285) in singletons, decreased growth velocity (β = 0.83, P = 0.0277) in twins, and lower total KV (tKV) and relative KV (rKV) in both singletons (r = 0.60, P < 0.0001 for tKV and r = 0.45, P = 0.0010 for rKV) and twins (β = 0.34, P < 0.0001 for tKV and β = 0.23, P = 0.0002 for rKV). Based on the multivariable models excluding KV, BW and gestational age were associated with eGFR in singletons, while male gender, BW, growth velocity, and coffee drinking during pregnancy were associated with eGFR in twins. However, in models that included KV, BW, gestational age and growth velocity were no longer significant. Total KV was associated with BW (r = 0.39, P = 0.0050 for singletons; β = 2.85, P < 0.0001 for twins), body mass index (r = 0.34, P = 0.0145 for singletons; β = 8.44, P < 0.0001 for twins), and growth velocity (β = 1.43, P = 0.0078). Twins born small for gestational age had lower tKV (70.88 vs 89.20 ml, P < 0.0001). Relative KV showed similar associations. Relative kidney volumes were significantly lower for both kidneys compared to the reference population (55.02 vs 65.42 ml/m², P < 0.0001 for right kidney and 61.12 vs 66.25 ml/m², P = 0.0015 for left kidney); however, only 8.6% of children had rKV below 10^th percentile.

Conclusion: Many factors affect eGFR and KV, some of them differ between twins and singletons. Based on multivariable models, eGFR seems to be better predicted by KV than by BW and gestational age in LBW children. Relative kidney volumes were significantly lower in our cohort compared to the reference population, but only 8.6% of rKV were below 10^th percentile.

Congenital sucrase isomaltase deficiency (CSID) is a rare autosomal recessive monogenic disorder of small intestinal malabsorption and manifests typically in early childhood with chronic osmotic diarrhoea. Though there have been case reports in adults presenting with hypercalcemia and renal calculi in CSID, this is quite rare in children. We hereby report a 6-year-old boy who presented with recurrent episodes of calcium oxalate calculi without any gastrointestinal symptoms and was confirmed as having sucrase isomaltase deficiency by genetic analysis.