Pediatric nephrologists' perspectives and clinical practices related to genetic testing and education.

BACKGROUND: While genetic testing is now more accessible in pediatric nephrology, little is known about the views of pediatric nephrologists regarding genetic testing in clinical settings. METHODS: An online 41-item survey was developed and distributed via professional listservs to self-identified U.S. licensed pediatric nephrologists from January 22 to May 4, 2021. RESULTS: Pediatric nephrologists had a high referral rate to genetic counseling and agreed on the significant impact of genetic testing on diagnosis, treatment, prognosis, counseling, and kidney transplant planning. Challenges for the utilization of genetic testing among pediatric nephrologists include the need to (1) learn how to counsel patients on the risks and benefits of genetic testing, (2) choose appropriate testing, (3) interpret genetic results, and (4) return those results to patients and families. CONCLUSION: There exists an opportunity to expand genetic testing education for pediatric nephrologists to assist incorporation of genetic testing into clinical practice.

Anti-slit diaphragm antibodies on kidney biopsy identify pediatric patients with steroid-resistant nephrotic syndrome responsive to second-line immunosuppressants.

Podocytopathies represent a group of glomerular disorders associated with minimal changes (MC) or focal segmental glomerulosclerosis (FSGS) lesion patterns at biopsy and heterogeneous responses to steroids. Anti-nephrin antibodies were previously found in such patients, suggesting an autoimmune form of podocytopathy. High resolution confocal microscopy on kidney biopsies of a cohort of 128 pediatric patients revealed localization of IgG along the slit diaphragm in 30% of patients with MC and 25% of those with FSGS, but not in other lesion patterns. Anti-nephrin IgG ELISA assay in the serum and stimulated emission depletion microscopy of kidney biopsies showed IgG-nephrin co-localization only in 77.8% of cases. Similar observations were obtained in a cohort of 48 adult patients with MC or FSGS at kidney biopsy, where IgG-nephrin colocalization was only 44.4%, suggesting the existence of autoantibodies binding to other slit proteins. Patients with anti-slit antibodies showed nephrotic syndrome at onset in 94.4% of cases. Patients with primary steroid-resistance had anti-slit antibodies in 27%, while those with secondary steroid-resistance in 87.5% of cases, irrespective of the histopathological lesion pattern. Steroid-resistant patients with anti-slit antibodies responded to second-line immunosuppressants in 92.3% vs. only 20% of patients that were anti-slit negative. No patient with anti-slit antibodies developed kidney failure vs. 51.7% of those negative for antibodies (66.7% with a genetic cause and 41.2% with a non-genetic cause). Thus, the detection of anti-slit antibodies can identify patients with an autoimmune podocytopathy responsive to treatment with second-line immunosuppressants, irrespective of the histopathological lesion pattern at biopsy.

Basal knowledge in the field of pediatric nephrology and its enhancement following specific training of ChatGPT-4 "omni" and Gemini 1.5 Flash.

BACKGROUND: We aimed to evaluate the baseline performance and improvement of ChatGPT-4 "omni" (ChatGPT-4o) and Gemini 1.5 Flash (Gemini 1.5) in answering multiple-choice questions related to pediatric nephrology after specific training. METHODS: Using questions from the "Educational Review" articles published by Pediatric Nephrology between January 2014 and April 2024, the models were tested both before and after specific training with Portable Data Format (PDF) and text (TXT) file formats of the Educational Review articles removing the last page containing the correct answers using a Python script. The number of correct answers was recorded. RESULTS: Before training, ChatGPT-4o correctly answered 75.2% of the 1395 questions, outperforming Gemini 1.5, which answered 64.9% correctly (p < 0.001). After training with PDF files, ChatGPT-4o's accuracy increased to 77.8%, while Gemini 1.5 improved significantly to 84.7% (p < 0.001). Training with TXT files showed similar results, with ChatGPT-4o maintaining 77.8% accuracy and Gemini 1.5 further improving to 87.6% (p < 0.001). CONCLUSIONS: The study highlights that while ChatGPT-4o has strong baseline performance, specific training does not significantly enhance its accuracy. Conversely, Gemini 1.5, despite its lower initial performance, shows substantial improvement with training, particularly with TXT files. These findings suggest Gemini 1.5's superior ability to store and retrieve information, making it potentially more effective in clinical applications, albeit with a dependency on additional data for optimal performance.

Responding to the workforce crisis: consensus recommendations from the Second Workforce Summit of the American Society of Pediatric Nephrology.

IMPORTANCE: Pediatric patients with complex medical problems benefit from pediatric sub-specialty care; however, a significant proportion of children live greater than 80 mi. away from pediatric sub-specialty care. OBJECTIVE: To identify current knowledge gaps and outline concrete next steps to make progress on issues that have persistently challenged the pediatric nephrology workforce. EVIDENCE REVIEW: Workforce Summit 2.0 employed the round table format and methodology for consensus building using adapted Delphi principles. Content domains were identified via input from the ASPN Workforce Committee, the ASPN's 2023 Strategic Plan survey, the ASPN's Pediatric Nephrology Division Directors survey, and ongoing feedback from ASPN members. Working groups met prior to the Summit to conduct an organized literature review and establish key questions to be addressed. The Summit was held in-person in November 2023. During the Summit, work groups presented their preliminary findings, and the at-large group developed the key action statements and future directions. FINDINGS: A holistic appraisal of the effort required to cover inpatient and outpatient sub-specialty care will help define faculty effort and time distribution. Most pediatric nephrologists practice in academic settings, so work beyond clinical care including education, research, advocacy, and administrative/service tasks may form a substantial amount of a faculty member's time and effort. An academic relative value unit (RVU) may assist in creating a more inclusive assessment of their contributions to their academic practice. Pediatric sub-specialties, such as nephrology, contribute to the clinical mission and care of their institutions beyond their direct billable RVUs. Advocacy throughout the field of pediatrics is necessary in order for reimbursement of pediatric sub-specialist care to accurately reflect the time and effort required to address complex care needs. Flexible, individualized training pathways may improve recruitment into sub-specialty fields such as nephrology. CONCLUSIONS AND RELEVANCE: The workforce crisis facing the pediatric nephrology field is echoed throughout many pediatric sub-specialties. Efforts to improve recruitment, retention, and reimbursement are necessary to improve the care delivered to pediatric patients.

Failure to Thrive With Severe Hypokalemia Yields Cystinosis Diagnosis in a 19-Month-Old Female Child: A Case Report.

Cystinosis is a rare, genetically inherited disease that affects lysosomal storage of cysteine. It is the most common cause of Fanconi syndrome. Mutations have led to early-onset end-stage renal disease as well as other systemic organ failures. In this case, we report a 19-month-old female child who presented acutely to the outpatient clinic with nausea, vomiting, and diarrhea. The patient was previously diagnosed with unspecified renal tubular acidosis and treated with oral electrolytes. Early labs during her acute presentation showed severe hypokalemia and electrolyte imbalance, which necessitated a transfer to a pediatric ICU. Through confirmatory testing, a diagnosis of cystinosis was made. This case is an example of the recognition and treatment of a rare inherited disease.

Social Deprivation and Incidence of Pediatric Kidney Failure in France.

Introduction: Approximately 8 per million children and young adults aged < 20 years initiate kidney replacement therapy (KRT) per year in France. We hypothesize that social deprivation could be a determinant of childhood-onset kidney failure. The objective of this study was to estimate the incidence of pediatric KRT in France according to the level of social deprivation. Methods: All patients < 20 years who initiated KRT from 2010 to 2015 in metropolitan France were included. Data were collected from the comprehensive French registry of KRT French Renal Epidemiology and Information network (REIN). We used a validated ecological index to assess social deprivation, the 2011 French version of the European Deprivation Index (EDI). We estimated the age standardized incidence rates according to the quintiles of EDI using direct standardization and incidence rate ratio using Poisson regression. Results: We included 672 children with kidney failure (58.6% males, 30.7% with glomerular or vascular disease, 43.3% starting KRT between 11 and 17 years). 38.8% were from the most deprived areas (quintile 5 of EDI). The age standardized incidence rate increased with quintile of EDI, from 5.45 (95% confidence interval [CI] = 4.25-6.64) per million children per year in the least deprived quintile to 8.46 (95% CI = 7.41-9.51) in the most deprived quintile of EDI (incidence rates ratio Q5 vs. Q1 1.53-fold; 95% CI = 1.18-2.01). Conclusion: This study showed that even in a country with a universal health care system, there is a strong association between the incidence of pediatric KRT and social deprivation showing that social health inequalities appear from KRT initiation. This study highlights the need to look further into social inequalities in the earliest stage of chronic kidney disease (CKD).

The randomized controlled trial (NAVKIDS2) of a patient navigator program created for children with chronic kidney disease.

Patient navigators enable adult patients to circumnavigate complex health systems, improving access to health care and outcomes. Here, we aimed to evaluate the effects of a patient navigation program in children with chronic kidney disease (CKD). In this multi-center, randomized controlled trial, we randomly assigned children (aged 0-16 years) with CKD stages 1-5 (including children on dialysis or with kidney transplants), from low socioeconomic status backgrounds, and/or residing in remote areas, to receive patient navigation at randomization (immediate) or at six months (waitlist). The primary outcome was self-rated health (SRH) of participating children at six months, using intention to treat analysis. Secondary outcomes included caregivers' SRH and satisfaction with health care, children's quality of life, hospitalizations, and missed school days. Repeated measures of the primary outcome from baseline to six months were analyzed using cumulative logit mixed effects models. Semi-structured interviews were thematically evaluated. Of 398 screened children, 162 were randomized (80 immediate and 82 waitlist); mean age (standard deviation) of 8.8 (4.8) years with 64.8% male. SRH was not significantly different between the immediate and wait-listed groups at six months. There were also no differences across all secondary outcomes between the two groups. Caregivers' perspectives were reflected in seven themes: easing mental strain, facilitating care coordination, strengthening capacity to provide care, reinforcing care collaborations, alleviating family tensions, inability to build rapport and unnecessary support. Thus, in children with CKD, self-rated health may not improve in response to a navigator program, but caregivers gained skills related to providing and accessing care.

Incidence and Pathological Patterns of Nephrotic Syndrome among Infants and Children: A Systematic Review.

Nephrotic syndrome (NS) is known to be a prevalent chronic illness in young patients. Periorbital swelling in children with this condition is a recurring symptom, either with or without generalized edema. The current study aimed to examine the incidence and pattern of nephrotic syndrome in infants and children by thoroughly examining the recently available literature. A thorough search of PubMed, SCOPUS, Web of Science, Science Direct, and Google Scholar was conducted, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) model, to find pertinent material. The Rayyan software (Qatar Computing Research Institute, Ar-Rayyan, Qatar) was utilized during the whole process. Data from a total of 1418 patients from nine trials were considered in this study. Numerous factors influenced the incidence, mean age, sex dominance, and histological patterns in various sample groups. The current findings conclude that variations in socioeconomic, regional, and genetic factors influence the development and pattern of these diseases. The prevalence of pediatric renal disorders differs throughout countries. Season of occurrence, response to corticosteroid treatment, and histopathologic findings appear to differ amongst the diagnosed cases.

A Pilot Comparative Study between Creatinine- and Cystatin-C-Based Equations to Estimate GFR and Kidney Ultrasound Percentiles in Children with Congenital Anomalies of the Kidney and Urinary Tract.

Congenital anomalies affecting the kidneys present significant challenges in pediatric nephrology, needing precise methods for assessing renal function and guiding therapeutic intervention. Bedside Schwartz formula with the cystatin-C-based Full Age Spectrum formula and Chronic Kidney Disease in Children (CKiD) U 25 formula used in estimating glomerular filtration rate (eGFR) and also to assess if the eGFR in association with kidney length percentiles can be a monitoring parameter for the progression of chronic kidney disease in children with congenital anomalies of the kidney and urinary tract (CAKUT). A total of 64 pediatric patients (median age at diagnostic was 12 months with an interquartile range of 2 to 60) were diagnosed with congenital anomalies in the kidney and urinary tract between June 2018 and May 2023 at "Louis Turcanu" Emergency Hospital for Children in Timisoara, Romania. Baseline characteristics, CAKUT types, associated pathologies, CKD staging, and eGFR using creatinine and cystatin C were analyzed. The mean age at the moment of examination was 116.50 months; (65, 180). Chronic kidney disease staging revealed a predominance of patients in CKD stages G1 and A1. Analysis of eGFR methods revealed a small mean difference between eGFR estimated by creatinine and cystatin C, with a moderate-strong positive correlation observed between the eGFR and ultrasound parameters. Using cystatin-C-based formulas for eGFR, in conjunction with ultrasound measurements, may offer reliable insights into renal function in pediatric patients with congenital anomalies affecting the kidney and urinary tract. However, the economic aspect must be taken into consideration because cystatin C determination is approximately eight times more expensive than that of creatinine. An interdisciplinary approach is crucial for managing patients with CAKUT.

Early Rituximab as an Add-On Therapy in Children With the Initial Episode of Nephrotic Syndrome.

Introduction: The approximately 70% 12-month relapse in children experiencing the initial episode of steroid-sensitive nephrotic syndrome (SSNS) is a significant concern, with over 50% developing frequent relapses or steroid-dependent nephrotic syndrome (FRNS/SDNS). There is a lack of strategies to reduce relapse after the onset. Whether early administration of rituximab, which effectively reduces relapses in FRNS/SDNS, may be a solution has not been evaluated. Methods: A prospective, multicenter, open-label, single-arm trial was conducted in China, with a 12-month follow-up. Children aged 1 to 18 years with the first episode of nephrotic syndrome (NS) were screened for eligibility. Proteinuria was evaluated daily using dipsticks. A dose of 375 mg/m2 of rituximab was intravenously infused within 1 week after achieving corticosteroid-induced remission. The main outcome was 12-month relapse-free survival. Results: Out of the initially 66 children screened, 44 were enrolled and received rituximab, with all but 1 participant completing the 12-month follow-up. The median age at diagnosis was 4.3 years (interquartile range [IQR]: 3.4-5.9), and 33 (77%) of the participants were male. In the rituximab group, the 12-month relapse-free survival was significantly higher compared to historical controls (32 of 43 [74.4%] vs. 10 of 33 [30.3%]; P < 0.001; hazard ratio [HR], 3.76; 95% confidence interval [CI], 1.80-7.81). The post hoc analysis revealed a higher 24-month relapse-free survival and a lower incidence of FRNS/SDNS at the 12-month follow-up. Treatment with rituximab was well-tolerated. Conclusion: Our findings support that early administration of rituximab may be associated with a higher 12-month relapse-free survival and a reduced incidence of FRNS/SDNS in children experiencing the initial episode of SSNS.

Clinical conundrums in pediatric kidney transplantation: What we know about the role of angiotensin II type I receptor antibodies in pediatric kidney transplantation and the path forward.

Antibodies to angiotensin II type 1 receptor (AT1R-Abs) are among the most well-studied non-HLA antibodies in renal transplantation. These antibodies have been shown to be common in pediatric kidney transplantation and associated with antibody-mediated rejection (AMR), vascular inflammation, development of human leukocyte donor-specific antibodies (HLA DSA), and allograft loss. As AT1R-Ab testing becomes more readily accessible, evidence to guide clinical practice for testing and treating AT1R-Ab positivity in pediatric kidney transplant recipients remains limited. This review discusses the clinical complexities of evaluating AT1R-Abs given the current available evidence.

Acute kidney injury requiring dialysis in children: a multicentric, emerging country perspective.

BACKGROUND: Acute kidney injury (AKI) is a life-threatening condition, especially in extreme age groups and when kidney replacement therapy (KRT) is necessary. Studies worldwide report mortality rates of 10-63% in pediatric patients undergoing KRT. METHODS: Over 13 years, this multicenter study analyzed data from 693 patients with AKI, all receiving KRT, across 74 hospitals and medical facilities in Rio de Janeiro, Brazil. RESULTS: The majority were male (59.5%), under one year old (55.6%), and treated in private hospitals (76.5%). Sixty-six percent had comorbidities. Pneumonia and congenital heart disease were the most common admission diagnoses (21.5% and 20.2%, respectively). The mortality rate was 65.2%, with lower rates in patients over 12 years (50%). Older age was protective (HR: 2.35, IQR [1.52-3.62] for neonates), and primary kidney disease had a three-fold lower mortality rate. ICU team experience (HR: 0.74, IQR [0.60-0.91]) correlated with lower mortality, particularly in hospitals treating 20 or more patients. Among the deceased, 40% died within 48 h of KRT initiation, suggesting possible late referral or treatment futility. CONCLUSIONS: This study confirms the high mortality in pediatric dialytic AKI in middle-income countries, underlining early mortality and offering critical insights for improving outcomes.

Introducing Exome Sequencing as Part of the Diagnostic Algorithm for Pediatric Nephrology Patients in Bulgaria: A Single-Center Experience.

INTRODUCTION: In pediatric kidney patients, where clinical presentation is often not fully developed, and renal biopsy is too risky or inconclusive, it may be difficult to establish the underlying pathology. In cases such as these, genetic diagnosis may be used to guide treatment, prognosis, and counseling. Given the large number of genes involved in kidney disease, introducing next-generation sequencing with extended gene panels as part of the diagnostic algorithm presents a viable solution. METHODS: A cohort of 87 consecutive independent cases (83 children and 4 terminated pregnancies) with renal disease was recruited. Exome sequencing with MiSeq or NovaSeq 6000 (Illumina) platforms and analysis of extended gene panels were used for genetic testing. RESULTS: Depending on the presenting pathology, the cases were grouped as patients with glomerular disease, ciliopathies, congenital anomalies, renal electrolyte imbalances, and chronic/acute kidney disease. The overall diagnostic yield was approximately 42% (37 out of 87), with most disease-causing mutations found in COL4A3, COL4A4, COL4A5, and PKHD1 genes. A change or clarification of preliminary diagnosis or adjustment of initial treatment plan based on the results of the genetic testing was made for approximately one-third of the children with meaningful genetic findings (11 out of 37). DISCUSSION: Our results prove the value of targeted exome sequencing as a non-invasive, versatile, and reliable diagnostic tool for pediatric renal disease patients. Providing genetic diagnosis will help for a better understanding of disease etiology and will give the basis for optimal clinical management and insightful genetic counseling.

Assessing bias in GFR estimating equations: improper GFR stratification can yield misleading results.

BACKGROUND: Assessing bias (estimated - measured) is key to evaluating glomerular filtration rate (GFR). Stratification by subgroups can indicate where equations perform differently. However, there is a fallacy in the assessment of two instruments (e.g., eGFR and mGFR) when stratifying on the level of only one of those instruments. Here, we present statistical aspects of the problem and a solution for GFR stratification along with an empirical investigation using data from the CKiD study. METHODS: Compared and contrasted biases (eGFR relative to mGFR) with 95% confidence intervals within strata of mGFR only, eGFR only, and the average of mGFR and eGFR using data from the Chronic Kidney Disease in Children (CKiD) study. RESULTS: A total of 304 participants contributed 843 GFR studies with a mean mGFR of 48.46 (SD = 22.72) and mean eGFR of 48.67 (SD = 22.32) and correlation of 0.904. Despite strong agreement, eGFR significantly overestimated mGFR when mGFR < 30 (+ 6.2%; 95%CI + 2.9%, + 9.7%) and significantly underestimated when mGFR > 90 (-12.2%; 95%CI - 17.3%, - 7.0%). Significant biases in opposite direction were present when stratifying by eGFR only. In contrast, when stratifying by the average of eGFR and mGFR, biases were not significant (+ 1.3% and - 1.0%, respectively) congruent with strong agreement. CONCLUSIONS: Stratifying by either mGFR or eGFR only to assess eGFR biases is ubiquitous but can lead to inappropriate inference due to intrinsic statistical issues that we characterize and empirically illustrate using data from the CKiD study. Using the average of eGFR and mGFR is recommended for valid inferences in evaluations of eGFR biases.

Diversity of kidney care referral pathways in national child health systems of 48 European countries.

Background: Primary, secondary and tertiary healthcare services in Europe create complex networks covering pediatric subspecialties, sociology, economics and politics. Two surveys of the European Society for Paediatric Nephrology (ESPN) in 1998 and 2017 revealed substantial disparities of kidney care among European countries. The purpose of the third ESPN survey is to further identify national differences in the conceptualization and organization of European pediatric kidney health care pathways during and outside normal working hours. Methods: In 2020, a questionnaire was sent to one leading pediatric nephrologist from 48 of 53 European countries as defined by the World Health Organization. In order to exemplify care pathways in pediatric primary care nephrology, urinary tract infection (UTI) was chosen. Steroid sensitive nephrotic syndrome (SSNS) was chosen for pediatric rare disease nephrology and acute kidney injury (AKI) was analyzed for pediatric emergency nephrology. Results: The care pathways for European children and young people with urinary tract infections were variable and differed during standard working hours and also during night-time and weekends. During daytime, UTI care pathways included six different types of care givers. There was a shift from primary care services outside standard working hours to general outpatient polyclinic and hospital services. Children with SNSS were followed up by pediatric nephrologists in hospitals in 69% of countries. Patients presenting with community acquired AKI were admitted during regular working hours to secondary or tertiary care hospitals. During nights and weekends, an immediate shift to University Children's Hospitals was observed where treatment was started by intensive care pediatricians and pediatric nephrologists. Conclusion: Gaps and fragmentation of pediatric health services may lead to the risk of delayed or inadequate referral of European children with kidney disease to pediatric nephrologists. The diversity of patient pathways outside of normal working hours was identified as one of the major weaknesses in the service chain.

Hospitalizations after Renal Transplantation in Children: Risk Factors, Causes, and Outcomes.

INTRODUCTION: The aims of this study were to evaluate the frequency and causes of hospitalizations in the posttransplant period of children, investigate the risk factors, and evaluate the relationship between hospitalizations and renal prognosis in the long term. METHODS: We retrospectively reviewed the files of pediatric renal transplant patients, followed at least 6 months after kidney transplantation, in our center. Clinical information including age at transplantation, gender, primary disease, donor type, immuno-suppressive medication, hospitalization dates, and indications (infections and non-infectious) during follow-up period and graft outcomes was recorded. RESULTS: A total of 74 children (46 males) were followed up for a median of 54 months. Among them, 69 patients (93.2%) were hospitalized 446 times. The most common cause of hospitalizations was infections (314 times, 70%). Urinary tract infections were the most important cause followed by upper respiratory tract infections. Forty (54%) patients were hospitalized 132 times (29.5%) for non-infectious reasons. The most common non-infectious reason was nonspecific graft dysfunction (19 patients, 30 times), followed by rejection (17 patients, 27 times). Younger age, use of induction therapy, and having congenital anomalies of kidney and urinary tract (CAKUT) were found to be risk factors for increased hospitalization rates (p < 0.05). The number of hospitalizations was found to be negatively affecting the final glomerular filtration rate of transplant recipients (p: 0.04, r: -0.023). CONCLUSION: Patients with CAKUT, who received induction therapy, and small children were hospitalized more frequently after transplantation. Strategies to prevent hospitalizations will achieve a better graft prognosis.

A pragmatic, open-label, randomized controlled trial of Plasma-Lyte-148 versus standard intravenous fluids in children receiving kidney transplants (PLUTO).

Acute electrolyte and acid-base imbalance is experienced by many children following kidney transplant. This is partly because doctors give very large volumes of artificial fluids to keep the new kidney working. When severe, fluid imbalance can lead to seizures, cerebral edema and death. In this pragmatic, open-label, randomized controlled trial, we randomly assigned (1:1) pediatric kidney transplant recipients to Plasma-Lyte-148 or standard of care perioperative intravenous fluids (predominantly 0.45% sodium chloride and 0.9% sodium chloride solutions). We then compared clinically significant electrolyte and acid-base abnormalities in the first 72 hours post-transplant. The primary outcome, acute hyponatremia, was experienced by 53% of 68 participants in the Plasma-Lyte-148 group and 58% of 69 participants in the standard fluids group (odds ratio 0·77 (0·34 - 1·75)). Five of 16 secondary outcomes differed with Plasma-Lyte-148: hypernatremia was significantly more frequent (odds ratio 3·5 (1·1 - 10·8)), significantly fewer changes to fluid prescriptions were made (rate ratio 0·52 (0·40-0·67)), and significantly fewer participants experienced hyperchloremia (odds ratio 0·17 (0·07 - 0·40)), acidosis (odds ratio 0·09 (0·04 - 0·22)) and hypomagnesemia (odds ratio 0·21 (0·08 - 0·50)). No other secondary outcomes differed between groups. Serious adverse events were reported in 9% of participants randomized to Plasma-Lyte-148 and 7% of participants randomized to standard fluids. Thus, perioperative Plasma-Lyte-148 did not change the proportion of children who experienced acute hyponatremia compared to standard fluids. However fewer fluid prescription changes were made with Plasma-Lyte-148, while hyperchloremia and acidosis were less common.

Advances and potential of regenerative medicine in pediatric nephrology.

The endogenous capacity of the kidney to repair is limited, and generation of new nephrons after injury for adequate function recovery remains a need. Discovery of factors that promote the endogenous regenerative capacity of the injured kidney or generation of transplantable kidney tissue represent promising therapeutic strategies. While several encouraging results are obtained after administration of stem or progenitor cells, stem cell secretome, or extracellular vesicles in experimental kidney injury models, very little data exist in the clinical setting to make conclusions about their efficacy. In this review, we provide an overview of the cutting-edge knowledge on kidney regeneration, including pre-clinical methodologies used to elucidate regenerative pathways and describe the perspectives of regenerative medicine for kidney patients.

Fifteen-year temporal changes in rates of acute kidney injury among children in Denmark.

BACKGROUND: We aimed to examine temporal changes in the annual rate of acute kidney injury (AKI) in Danish children and associated changes in patient characteristics including potential underlying risk factors. METHODS: In this population-based cohort study, we used plasma creatinine measurements from Danish laboratory databases to identify AKI episodes in children aged 0-17 years from 2007 to 2021. For each child, the first AKI episode per calendar year was included. We estimated the annual crude and sex- and age-standardized AKI rate as the number of children with an AKI episode divided by the total number of children as reported by census numbers. Using Danish medical databases, we assessed patient characteristics including potential risk factors for AKI, such as use of nephrotoxic medication, surgery, sepsis, and perinatal factors. RESULTS: In total, 14,200 children contributed with 16,345 AKI episodes over 15 years. The mean annual AKI rate was 148 (95% CI: 141-155) per 100,000 children. From 2007 to 2021, the annual AKI rate demonstrated minor year-to-year variability without any discernible overall trend. The highest AKI rate was recorded in 2007 at 174 (95% CI: 161-187) per 100,000 children, while the lowest rate occurred in 2012 at 129 (95% CI: 118-140) per 100,000 children. In 2021, the AKI rate was 148 (95% CI: 141-155) per 100,000 children. Characteristics of children with AKI were similar throughout the study period. CONCLUSION: The rate of AKI among Danish children was stable from 2007 to 2021 with little variation in patient characteristics over time.

Clinical and Histopathologic Characteristics of Pediatric Patients With Primary Membranous Nephropathy.

Introduction: Primary membranous nephropathy (PMN) is uncommon in children. Therefore, data on the clinical course of affected children are scarce. In recent years, several novel antigens have been implicated in the pathogenesis of PMN. However, the histopathologic characteristics of pediatric patients with PMN remain poorly represented in the literature. Methods: We have retrospectively analyzed the clinical presentation and outcomes data of 21 children with PMN from 3 centers in the United States. In addition, we have identified novel antigens in biopsy specimens from these patients and correlated their presence or absence to clinical outcomes. Finally, we compared the results of the novel antigen staining from our clinical cohort to a validation cohort of 127 biopsy specimens from children with PMN at Arkana Laboratories. Results: The data from the 2 cohorts demonstrated similar overall antigen positivity rates of 62% to 63%, with phospholipase A2 receptor (PLA2R) and exostosin 1 (EXT1) being the most commonly found antigens. Results from the clinical cohort showed that overall, the kidney prognosis for children with PMN was good, with 17 of 21 patients entering a complete or partial remission. Children who were positive for PLA2R or EXT1 were significantly more likely to enter remission than those in the antigen negative group. Conclusion: Approximately 60% of pediatric membranous cases are positive for a novel antigen on kidney biopsy and the clinical prognosis is generally favorable. More studies are needed to understand the clinical implications of each specific novel antigen.