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Complement component 3 glomerulonephritis (C3GN) is a rare kidney disease characterized by complement dysregulation that results in prominent complement component 3 (C3) deposition in the kidneys. The clinical course of C3GN varies from mild hematuria to progressive chronic kidney disease. In most patients, C3GN is driven by acquired factors, namely, autoantibodies that target C3 or C5 convertases. Genetic variations in complement-related genes are less frequent. We report the case of a 9-year-old Korean boy who presented with microscopic hematuria and a persistently low C3 level and had biopsy findings of C3GN, with the presence of a C3 gene mutation: a frameshift mutation associated with C3 deficiency. However, the patient did not exhibit any other symptoms of complement deficiency. Direct DNA sequencing of his family members revealed the same genetic mutation in his father and older brother. This case report is significant because there are very few such reports worldwide concerning gene mutations related to C3 deficiency to be discovered in patients with C3GN. Explaining C3GN pathogenesis is challenging; therefore, additional research is required in the future.

Distinguishing lupus nephritis (LN) from other glomerulopathies, such as immunoglobulin A nephropathy (IgAN), poses a diagnostic challenge owing to overlapping clinical and histopathologic findings. Lupus anticoagulant-hypoprothrombinemia syndrome (LAHPS) is a rare and potentially fatal disorder characterized by the presence of lupus anticoagulant and acquired factor II deficiency. We report a pediatric case of LN with LAHPS, which was initially diagnosed as IgAN. An 8-year-old girl presented with gross hematuria with nephrotic syndrome. Based on the kidney biopsy results, treatment for IgAN with membranoproliferative pattern was initiated. Two months later, she developed left upper extremity swelling with multiple vein thromboses requiring anticoagulation; treatment led to remission, allowing discontinuation of immunosuppressants within 8 months. Gross hematuria recurred 10 months later and was accompanied by hypocomplementemia; positive antinuclear, anti-double stranded DNA, and triple antiphospholipid antibodies; and factor II deficiency, prompting revision of the diagnosis to LN and LAHPS. Initial delay in LN diagnosis was attributed to the patient’s young age, nonspecific symptoms, and inconclusive laboratory and histopathological findings. Immunosuppressive therapy for IgAN partially improved LN, further complicating the diagnosis. This case emphasized the importance of clinical suspicion; integrating clinical, serological, and histopathological data; and considering LAHPS in differential diagnosis of glomerulonephritis with coagulopathy.

Hematuria is the presence of blood in the urine and is classified as either gross hematuria or microscopic hematuria. There are many causes of hematuria, and the differential diagnosis depends on the presence or absence of comorbidities and whether it is glomerular or non-glomerular. When hematuria in children is symptomatic or persistent, an evaluation of the cause is essential. The causes of hematuria and basic approaches to its diagnosis are discussed in this review.

Rationale & Objective: Atypical hemolytic uremic syndrome (aHUS) is a rare form of thrombotic microangiopathy (TMA) caused by complement dysregulation. Ravulizumab is a C5i approved for the treatment of aHUS. This analysis assessed long-term outcomes of ravulizumab in adults and pediatric patients with aHUS. Study Design: This analysis reports 2-year data from 2 phase 3, single-arm studies. Setting & Participants: One study included C5i-naïve adults (NCT02949128), and the other included 2 cohorts of pediatric patients (C5i-naïve and those who switched to ravulizumab from eculizumab [pediatric switch patients]; NCT03131219). Exposure: Patients received intravenous ravulizumab every 4-8 weeks, with the dose depending on body weight. Outcomes: The primary endpoint in the studies of C5i-naïve patients was complete TMA response, which consisted of platelet count normalization, lactate dehydrogenase normalization, and ≥25% improvement in serum creatinine concentrations from baseline, at 2 consecutive assessments ≥4 weeks apart. Analytical Approach: All analyses used descriptive statistics. No formal statistical comparisons were performed. Results: In total, 86 and 92 patients were included in efficacy and safety analyses, respectively. Complete TMA response rates over 2 years were 61% and 90% in C5i-naïve adults and pediatric patients, respectively. The median increase in estimated glomerular filtration rate from baseline was maintained over 2 years in C5i-naïve adults (35 mL/min/1.73 m2) and pediatric patients (82.5 mL/min/1.73 m2). Most adverse events and serious adverse events occurred during the first 26 weeks. No meningococcal infections were reported. Improvement in the Functional Assessment of Chronic Illness Therapy – Fatigue score achieved by 26 weeks was maintained over 2 years. Limitations: Limitations were the small sample of pediatric switch patients and limited availability of genetic data. Conclusions: Long-term treatment with ravulizumab is well tolerated and associated with improved hematologic and renal parameters and quality of life in adults and pediatric patients with aHUS. Plain-Language Summary: This research tested a drug called ravulizumab for the treatment of atypical hemolytic uremic syndrome (aHUS). aHUS is a rare disease that causes clots in tiny blood vessels. This can damage the kidneys and other organs. We analyzed data from 2 clinical trials in which children and adults with aHUS received ravulizumab through a tube placed in a vein (intravenous line). They received ravulizumab every 4-8 weeks depending on their weight. We found that treating patients for 2 years with ravulizumab was associated with improved blood health, kidney function, and quality of life and was well tolerated. These results support ravulizumab as a long-term treatment for people with aHUS.

Abstract Introduction Proteinuria is a modifiable risk factor for chronic kidney disease (CKD) progression in children. Finerenone, a selective, non-steroidal, mineralocorticoid receptor antagonist (MRA) has been approved to treat adults with CKD associated with type 2 diabetes mellitus (T2DM) following results from the phase III clinical trials FIDELIO-DKD (NCT02540993) and FIGARO-DKD (NCT02545049). In a pre-specified pooled analysis of both studies (N = 13,026), finerenone was shown to have an acceptable safety profile and was efficacious in decreasing the risk of adverse kidney and cardiovascular outcomes and of proteinuria. Objective FIONA and the associated open-label extension (OLE) study aim to demonstrate that combining finerenone with an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) is safe, well-tolerated, and effective in sustainably reducing urinary protein excretion in children with CKD and proteinuria. Design FIONA (NCT05196035; Eudra-CT: 2021–002071-19) is a randomized (2:1), double-blind, placebo-controlled, multicenter, phase III study of 6 months’ duration in approximately 219 pediatric patients. Patients must have a clinical diagnosis of CKD (an eGFR ≥ 30 mL/min/1.73 m2 if ≥ 1 to

Abstract Background The purpose of this study was to examine the prevalence of hypertension in Korean adolescents, its long-term trends, and factors associated with the development of hypertension. Methods Data of the Korea National Health and Nutrition Examination Survey (KNHANES) from 2007 to 2020 were combined into three time periods (2007–2011, 2012–2016, and 2017–2020). A total of 11,146 Korean adolescents aged 10–18 were included in the analysis. The definition of hypertension was based on the 2017 American Academy of Pediatrics guidelines for hypertension. Results The age-adjusted prevalence of hypertension was 5.47%, 7.85%, and 9.92% in 2007–2011, 2012–2016, and 2017–2020, respectively. Long-term trend analysis using Joinpoint analysis over the observation period showed a significantly increasing trend in hypertension prevalence with a mean annual percentage change of 6.4%. Boys, those aged 13–15, those aged 16–18, overweight/obese, and those living in urban areas were more likely to develop hypertension (OR 1.980, 1.492, 3.180, 2.943, and 1.330, respectively). Conclusion The prevalence of hypertension in Korean adolescents was higher than the global prevalence of hypertension and showed an increase over a 13–year period. Targeted strategies for prevention and early detection of hypertension are needed in this population.

X-linked hypophosphatemia (XLH), the most common cause of hypophosphatemic rickets, affects one in every 20,000 people. Although conventional therapy for XLH was introduced approximately 4 decades ago, the temporary replacement of oral phosphate salts and activated vitamin D cannot completely control chronic hypophosphatemia, leaving patients with incomplete healing and residual skeletal deformity as well as at risk of endocrine abnormalities and adverse drug reactions. However, understanding the pathophysiology has led to the development of a targeted therapy, burosumab, a fibroblast growth factor-23 inhibitor that was recently approved in Korea for the treatment of XLH. This review provides insight into the diagnosis, evaluation, treatment, and recommended follow-up for a typical case of XLH and reviews its pathophysiology.

Purpose Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers (ARBs) are frequently employed to counteract the detrimental effects of proteinuria on glomerular diseases. However, the effects of ARBs remain poorly examined in pediatric patients with immunoglobulin A (IgA) nephropathy. Herein, we evaluated the efficacy and safety of losartan, an ARB, in pediatric IgA nephropathy with proteinuria. Methods This prospective, single-arm, multicenter study included children with IgA nephropathy exhibiting proteinuria. Changes in proteinuria, blood pressure, and kidney function were prospectively evaluated before and 4 and 24 weeks after losartan administration. The primary endpoint was the difference in proteinuria between baseline and 24 weeks. Results In total, 29 patients were enrolled and received losartan treatment. The full analysis set included 28 patients who received losartan at least once and had pre- and post-urinary protein to creatinine ratio measurements (n=28). The per-protocol analysis group included 22 patients who completed all scheduled visits without any serious violations during the study period. In both groups, the mean log (urine protein to creatinine ratio) value decreased significantly at 6 months. After 24 weeks, the urinary protein to creatinine ratio decreased by more than 50% in approximately 40% of the patients. The glomerular filtration rate was not significantly altered during the observation period. Conclusions Losartan decreased proteinuria without decreasing kidney function in patients with IgA nephropathy over 24 weeks. Losartan could be safely employed to reduce proteinuria in this patient population. ClinicalTrials.gov trial registration (NCT0223277)

Purpose To analyze electrocardiograms (ECGs) of patients with a salt-losing tubulopathy (SLT) and to determine the frequency and risk factors for long QT and arrhythmia. Methods A total of 203 patients aged

Here, we present the case of a 2-month-old male infant with hyponatremic hypertensive syndrome resulting from stenosis of the right proximal and mid-renal arteries. The patient exhibited nephrotic-range proteinuria, low serum albumin, increased serum creatinine, and elevated renin and aldosterone levels. Doppler ultrasonography and computed tomography angiography revealed decreased vascular flow in the small right renal artery. Following a successful percutaneous balloon angioplasty, the patient experienced a decrease in blood pressure and normalization of serum electrolyte levels within a few days. However, it took 3 months for the proteinuria to resolve completely. This case is significant as it represents the first reported instance of a neonate presenting with clinical features resembling congenital nephrotic syndrome caused by renal artery stenosis that was successfully treated with percutaneous renal angioplasty.

Purpose This article was to investigate the association between urinary tract infections (UTIs) and high weight status in infancy. Methods We conducted a nationwide matched cohort study from January 2018 to December 2020 using data from the Korean National Health Insurance System and the Korean National Health Screening Program for Infants and Children. We analyzed the association between UTI diagnosis codes and high weight status (which was defined as being in the 90th percentile or higher of weight-for-age). Results We found that 22.8% of infants with UTIs exhibited high weight status, compared to 20.0% of non-UTI infants (P

Background Donor–recipient size mismatching is commonly occurs in pediatric kidney transplantation (KT). However, its effect on graft survival remains unknown. This study aimed to determine the effect of donor–recipient size mismatch on the long-term survival rate of transplant kidneys in pediatric KT. Methods A total of 241 pediatric patients who received KT were enrolled. The medical records of all patients were retrospectively reviewed, and the correlation between donor–recipient size mismatch and graft function and long-term graft outcome was analyzed according to donor–recipient size mismatch. Results Recipients and donors’ mean body weight at the time of KT were 34.31 ± 16.85 and 56.53 ± 16.73 kg, respectively. The mean follow-up duration was 96.49 ± 52.98 months. A significant positive correlation was observed between donor–recipient body weight ratio (DRBWR) or donor–recipient body surface area ratio (DRBSR) and graft function until 1 year after KT. However, this correlation could not be confirmed at the last follow-up. The results of long-term survival analysis using Fine and Gray’s subdistribution hazard model showed no significant difference of the survival rate of the transplant kidney according to DRBWR or DRBSR. Conclusion Donor–recipient size mismatch in pediatric KT is not an important factor in determining the long-term prognosis of transplant kidneys.

Background Identifying genetic mutations in individuals with inherited cystic kidney disease is necessary for precise treatment. We aimed to elucidate the genetic characteristics of cystic kidney disease in the Korean population. Methods We conducted a 3-year prospective, multicenter cohort study at eight hospitals from May 2019 to May 2022. Patients with more than three renal cysts were enrolled and classified into two categories, typical autosomal dominant polycystic kidney disease (ADPKD) and atypical PKD. We identified the clinical characteristics and performed a genetic analysis using a targeted gene panel. Results A total of 725 adult patients were included in the study, of which 560 (77.2%) were diagnosed with typical ADPKD and 165 (22.8%) had atypical PKD. Among the typical ADPKD cases, the Mayo imaging classification was as follows: 1A (55, 9.9%), 1B (149, 26.6%), 1C (198, 35.8%), 1D (90, 16.3%), and 1E (61, 11.0%). The atypical PKD cases were classified as bilateral cystic with bilateral atrophic (31, 37.3%), lopsided (27, 32.5%), unilateral (nine, 10.8%), segmental (eight, 9.6%), bilateral cystic with unilateral atrophic (seven, 8.4%), and asymmetric (one, 1.2%). Pathogenic variants were found in 64.3% of the patients using the ciliopathy-related targeted gene panel. The typical ADPKD group demonstrated a higher discovery rate (62.3%) than the atypical PKD group (41.8%). Conclusion We present a nationwide genetic cohort’s baseline clinical and genetic characteristics for Korean cystic kidney disease.

Purpose This article was to collect data on the safety of coronavirus disease 2019 (COVID-19) vaccines in children with underlying medical conditions. Methods We constructed a prospective cohort of children and adolescents aged 5 to 19 years who had received at least one dose of COVID-19 vaccine. Patients diagnosed with and treated for chronic kidney disease, autoimmune disease, or other chronic conditions at the Seoul National University Children’s Hospital were recruited from June to December 2022. A mobile survey questionnaire was sent to their guardians. The presence of adverse events on the day (day 0), 3 weeks (day 21), and 6 months (day 180) after the 1st dose of COVID-19 vaccine was recorded by the guardians. Results A total of 73 children participated. The median age was 14 years, and 64.4% of the patients were male. On the day of immunization, 65.8% of the patients reported at least one adverse event. Pain at the injection site, fatigue, headache, arthralgia, and myalgia were the most common symptoms. The prevalence of adverse events decreased over time (65.8% on day 0, 27.4% between days 0 and 21, and 24.6% between days 21 and 180). Severe acute respiratory syndrome coronavirus 2 infection after the 1st dose occurred in 17 patients (23.3%) and one of the patients (5.88%) was hospitalized due to infection. Conclusions Adverse events after COVID-19 vaccination were generally mild in children and adolescents with underlying medical conditions. Our findings provide evidence for the safety of COVID-19 vaccination in the vulnerable pediatric population.

Purpose Hematuria and proteinuria have various causes and consequential outcomes in children. Immunosuppressants are needed in some children with biopsy-proven glomerulonephropathy but have many adverse effects. Since the clinical practice patterns of Korean pediatric nephrologists are diverse, we surveyed their opinions. Methods Using a clinical vignette, the survey was emailed to all Korean Society of Pediatric Nephrology members. The questionnaires included diagnosis, examination, medications, and dietary recommendations for patients with hematuria and proteinuria. Results A total of 32 clinicians (5.48%, 22 pediatric certificated nephrologists) responded to the survey. Most responders (87.5%) suspected immunoglobulin A nephropathy, and 68.8% replied that kidney biopsies were a diagnostic tool. Renin-angiotensin system inhibition (62.5%) or steroids (18.8%) were selected as the treatment. Salt and protein intakes were usually encouraged as dietary reference intakes (34.4% and 65.6%, respectively). Conclusions Children with abnormal urinalysis have various causes, treatments, and prognoses. As treatments such as immunosuppressants can have many adverse effects, it is necessary to confirm an accurate diagnosis and indications of treatments before starting the treatment. Recommendations for a diet should not hinder growth.

Abstract The genotype–phenotype correlation of the X-linked Alport syndrome (XLAS) has been well elucidated in males, whereas it remains unclear in females. In this multicenter retrospective study, we analyzed the genotype–phenotype correlation in 216 Korean patients (male:female = 130:86) with XLAS between 2000 and 2021. The patients were divided into three groups according to their genotypes: the non-truncating group, the abnormal splicing group, and the truncating group. In male patients, approximately 60% developed kidney failure at the median age of 25.0 years, and kidney survival showed significant differences between the non-truncating and truncating groups (P

BackgroundWe evaluated the long-term clinical outcomes of nephrocalcinosis (NC) according to etiology and grade in preschool-age children with NC.MethodsWe retrospectively analyzed the clinical outcomes and disease grade of children with NC classified into three groups according to etiology: prematurity, tubular disorders, and others.ResultsOverall, 67 children were diagnosed with NC [median age, 0.76 years; interquartile range (IQR) 0.46–2.14 years]. The etiologies of NC included prematurity (28.4%), tubular disorders (25.4%), and others (46.3%). Moreover, 56 (83.6%) children were asymptomatic and diagnosed accidentally through kidney ultrasonography. Newly diagnosed underlying diseases were greater in the tubular disorders group than in the other two groups (P = 0.001). Significantly more newly diagnosed NCs were grade 3 than grade 1 (P = 0.003). The median estimated glomerular filtration rate (eGFR) changed from 96.1 (IQR 68.8–119.2) ml/min/1.72 m2 at diagnosis to 90.9 (IQR 76.4–106.4) ml/min/1.72 m2 at the last follow-up, without a significant difference (P = 0.096). Changes in the kidney function did not differ according to etiology. However, patients without improvement in NC grade showed a decrease in eGFR from 98.1 (IQR 71.1–132.9) to 87.4 (IQR 74.0–104.1) ml/min/1.73 m2 (P = 0.023), while patients with improved NC grade did not show any change in the kidney function.ConclusionsEarly recognition, especially in NC grade 3, can help uncover further diagnoses, such as tubular disorders. Long-term kidney function depends on whether the NC grade improves.

The Korean Society of Nephrology (KSN) has published a clinical practice guideline (CPG) document for maintenance hemodialysis (HD). The document, 2021 Clinical Practice Guideline on Optimal HD Treatment, is based on an extensive evidence-oriented review of the benefits of preparation, initiation, and maintenance therapy for HD, with the participation of representative experts from the KSN under the methodologists’ support for guideline development. It was intended to help clinicians participating in HD treatment make safer and more effective clinical decisions by providing user-friendly guidelines. We hope that this CPG will be meaningful as a recommendation in practice, but not on a regulatory rule basis, as different approaches and treatments may be used by health care providers depending on the individual patient’s condition. This CPG consists of eight sections and 15 key questions. Each begins with statements that are graded by the strength of recommendations and quality of the evidence. Each statement is followed by a summary of the evidence supporting the recommendations. There are also a link to full-text documents and lists of the most important reports so that the readers can read further (most of this is available online).

Purpose Chronic kidney disease (CKD) has various underlying causes in children. Identification of the underlying causes of CKD is important. Genetic causes comprise a significant proportion of pediatric CKD cases. Methods In this study, we performed whole-exome sequencing (WES) to identify genetic causes of pediatric CKD. From January to June 2021, WES was performed using samples from pediatric patients with CKD of unclear etiology. Results Genetic causes were investigated using WES in 37 patients (17 males) with pediatric CKD stages 1 (n=5), 2 (n=7), 3 (n=2), 4 (n=2), and 5 (n=21). The underlying diseases were focal segmental glomerulosclerosis (n=9), congenital anomalies of the kidney and urinary tract including reflux nephropathy (n=8), other glomerulopathies (n=7), unknown etiology (n=6), and others (n=7). WES identified genetic causes of CKD in 12 of the 37 patients (32.4%). Genetic defects were discovered in the COL4A4 (n=2), WT1 (n=2), ACTN4, CEP290, COL4A3, CUBN, GATA3, LAMA5, NUP107, and PAX2 genes. WT1 defects were found in patients whose pathologic diagnosis was membranoproliferative glomerulonephritis, and identification of CUBN defects led to discontinuation of immunosuppressive agents. Genetic diagnosis confirmed the clinical diagnosis of hypoparathyroidism, sensorineural deafness, and renal disease; Alport syndrome; and Joubert syndrome in three of the patients with CKD of unknown etiology (COL4A4 [n=2], CUBN [n=1]). Extrarenal symptoms were considered phenotypic presentations of WT1, PAX2, and CEP290 defects. Conclusions WES provided a genetic diagnosis that confirmed the clinical diagnosis in a significant proportion (32.4%) of patients with pediatric CKD.

BK polyomavirus (BKPyV) is a ubiquitous virus residing in the kidney tubules and is clinically significant only in immunocompromised patients. In clinical practice, BKPyV is a causative pathogen of BKPyV-associated nephropathy (BKVAN) in kidney allograft recipients or hemorrhagic cystitis of hematopoietic stem cell transplant recipients. Currently, there is no effective treatment for BKVAN; therefore, careful monitoring and prudent modification of immunosuppression are necessary to prevent BKVAN. In this article, the epidemiology, pathophysiology, and current management strategies for BKVAN are reviewed.

Atypical hemolytic uremic syndrome (aHUS) is a rare disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury without any association with preceding diarrhea. Dysregulation of the complement system is the most common cause of aHUS, and monoclonal humanized anti-C5 antibodies are now recommended as the first-line treatment for aHUS. However, if the complement pathway is not the cause of aHUS, C5 inhibitors are ineffective. In this study, we report the second reported case of aHUS caused by DGKE mutations in Republic of Korea. The patient was an 11-month-old infant who presented with prodromal diarrhea similar to typical HUS, self-remitted with conservative management unlike complement-mediated aHUS but recurred with fever. While infantile aHUS often implies genetic dysregulation of the complement system, other rare genetic causes, such as DGKE mutation, need to be considered before deciding long-term treatment with C5 inhibitors.

Nephrocalcinosis often occurs in infants and is caused by excessive calcium or vitamin D supplementation, neonatal primary hyperparathyroidism, and genetic disorders. Idiopathic infantile hypercalcemia (IIH), a rare cause of nephrocalcinosis, results from genetic defects in CYP24A1 or SLC34A1. Mutations in CYP24A1, which encodes 25-hydroxyvitamin D 24-hydroxylase, disrupt active vitamin D degradation. IIH clinically manifests as failure to thrive and hypercalcemia within the first year of life and usually remits spontaneously. Herein, we present a case of IIH wih CYP24A1 mutations. An 11-month-old girl visited our hospital with incidental hypercalcemia. She showed failure to thrive, and her oral intake had decreased over time since the age of 6 months. Her initial serum parathyroid hormone level was low, 25-OH vitamin D and 1,25(OH)2 vitamin D levels were normal, and renal ultrasonography showed bilateral nephrocalcinosis. Whole-exome sequencing revealed compound heterozygous variants in CYP24A1 (NM_000782.4:c.376C>T [p.Pro126Ser] and c.1310C>A [p.Pro437His]). Although her hypercalcemia and poor oral intake spontaneously resolved in approximately 8 months, we suggested that her nephrocalcinosis and renal function be regularly checked in consideration of potential asymptomatic renal damage. Hypercalcemia caused by IIH should be suspected in infants with severe nephrocalcinosis, especially when presenting with failure to thrive.

IntroductionBartter syndrome (BS) is a rare salt-wasting tubulopathy caused by mutations in genes encoding sodium, potassium, or chloride transporters of the thick ascending limb of the loop of Henle and/or the distal convoluted tubule of the kidney. BS is characterized by polyuria, failure to thrive, hypokalemia, metabolic alkalosis, hyperreninemia, and hyperaldosteronism. Potassium and/or sodium supplements, potassium-sparing diuretics, and nonsteroidal anti-inflammatory drugs can be used to treat BS. While its symptoms and initial management are relatively well known, long-term outcomes and treatments are scarce.MethodsWe retrospectively reviewed 54 Korean patients who were clinically or genetically diagnosed with BS from seven centers in Korea.ResultsAll patients included in this study were clinically or genetically diagnosed with BS at a median age of 5 (range, 0–271) months, and their median follow-up was 8 (range, 0.5–27) years. Genetic diagnosis of BS was confirmed in 39 patients: 4 had SLC12A1 gene mutations, 1 had KCNJ1 gene mutations, 33 had CLCNKB gene mutations, and 1 had BSND mutation. Potassium chloride supplements and potassium-sparing diuretics were administered in 94% and 68% of patients, respectively. The mean dosage of potassium chloride supplements was 5.0 and 2.1 mEq/day/kg for patients younger and older than 18 years, respectively. Nephrocalcinosis was a common finding of BS, and it also improved with age in some patients. At the last follow-up of 8 years after the initial diagnosis, 41% had short stature (height less than 3rd percentile) and impaired kidney function was observed in six patients [chronic kidney disease (CKD) G3, n = 4; CKD G5, n = 2].ConclusionBS patients require a large amount of potassium supplementation along with potassium-sparing agents throughout their lives, but tend to improve with age. Despite management, a significant portion of this population exhibited growth impairment, while 11% developed CKD G3–G5.

BackgroundChildren with chronic kidney disease (CKD) are at high risk of mineral bone disorder (MBD), which leads to fractures, growth retardation, and cardiovascular disease. We aimed to comprehensively understand the relationship between renal function and factors related to MBD and evaluate the prevalence and distribution characteristics of MBD, specifically among Korean patients from the KNOW-PedCKD cohort.MethodsFrom the baseline data of the KNOW-PedCKD cohort, we examined the prevalence and distribution of MBD in 431 Korean pediatric CKD patients, including the level of corrected total calcium, serum phosphate, serum alkaline phosphatase, serum intact parathyroid hormone (iPTH), fibroblast growth factor 23 (FGF-23), serum vitamin D, fractional excretion of phosphate (FEP), and bone densitometry Z-scores.ResultsThe median serum calcium level remained relatively normal regardless of the CKD stage. The levels of 1,25-dihydroxy vitamin D, urine calcium-to-creatinine ratio, and bone densitometry Z-score significantly decreased with advancing CKD stage, while those of serum phosphate, FGF-23, and FEP significantly increased with CKD stage. The prevalence of hyperphosphatemia (17.4%, 23.7%, and 41.2% from CKD stages 3b, 4, and 5, respectively) and hyperparathyroidism (37.3%, 57.4%, 55.3%, and 52.9% from CKD stages 3a, 3b, 4, and 5, respectively) significantly increased with the CKD stage. Prescriptions of medications, such as calcium supplements (39.1%, 42.1%, 82.4%), phosphate binders (39.1%, 43.4%, 82.4%), and active vitamin D (21.7%, 44.7%, and 64.7%) significantly increased with CKD stage 3b, 4, and 5, respectively.ConclusionsThe results demonstrated the prevalence and relationship of abnormal mineral metabolism and bone growth according to CKD stage in Korean pediatric CKD patients for the first time.

Single gene pathogenic mutations have been implicated in up to 30% of pediatric steroid-resistant nephrotic syndrome (SRNS) cases, mostly in infantile patients. Among them is LAMA5, which has been recently discovered and encodes the laminin α5 chain. The laminin α5β2γ1 heterotrimer is an essential component of the glomerular basement membrane and is necessary for embryogenesis and immune modulation. Biallelic LAMA5 variants have been identified in one adult and ten pediatric nephrotic syndromes (NS) patients with variable phenotypes. Biallelic truncating mutations in this gene have recently been proven to cause SRNS. Here, we present another case of infantile SRNS related to novel compound heterozygous variations of LAMA5 (c.3434G > A, p.Cys1145Tyr and c.6883C > T, p.Gln2295*), the first reported case with one missense and one nonsense allele. A 10-month-old female patient presented with eyelid edema and massive proteinuria without any extrarenal symptoms or family history. The patient was diagnosed with SRNS. Renal biopsy revealed focal segmental glomerulosclerosis with widely effaced epithelial foot processes and a “moth-eaten” appearance. She progressed to end stage kidney disease (ESKD), requiring dialysis at 31 months of age, and underwent a deceased-donor kidney transplant at 6 years of age. Four months after transplantation, she developed Ebstein-Barr Virus (EBV) infection related to post-transplantation lymphoproliferative disorder (PTLD). After chemotherapy, the patient remained healthy with adequate renal function without disease recurrence for the past 7 years. We also identified previous cases of biallelic LAMA5 variants associated with the nephrotic phenotype and analyzed the available clinical and genetic information. All reported patients had an onset of NS ranging from 3 months to 8 years, with no other syndromic features. Response to therapy and renal outcomes varied greatly; most patients exhibited steroid resistance, five progressed to ESKD, and two received kidney transplantation (KT). There was one report of PTLD. Our patient’s phenotype was markedly more severe than those with biallelic missense variants and somewhat less severe than those with two truncating variants. LAMA5 defects may also play a role in PTLD, though no conclusions can be made with such limited cases. LAMA5 should be considered a candidate gene for SRNS and should be actively tested in cases with no other genetic diagnosis.

C1q nephropathy is a rare glomerulopathy that typically presents with nephrotic syndrome in children. Treatment with immunosuppressive agents renders patients vulnerable to infection and its complications. Gastroenteritis is common in children, and rotavirus is a leading cause. Extraintestinal manifestations of rotavirus have recently been reported; however, there is a paucity of cases exploring the involvement of a rotavirus on the respiratory system. Acute respiratory distress syndrome (ARDS) is a rapid onset respiratory failure characterized by noncardiogenic pulmonary edema and hypoxemia. Causes of ARDS include sepsis, pneumonia, pancreatitis, aspiration, and trauma. In this paper, we report a case of ARDS after rotavirus infection in a child with C1q nephropathy who had been treated with immunosuppressive agents.

Chronic kidney disease (CKD)-mineral and bone disorder (CKD-MBD) is a common complication of CKD, often accompanied by extra-skeletal calcification in adult patients. As increased vascular calcification is predicted to increase cardiovascular mortality and morbidity, the revised Kidney Disease: Improving Global Outcomes guidelines recommend avoiding calcium-containing phosphate chelators. However, extra-skeletal calcification is less commonly noticed in pediatric patients. Here, we report our experience of such a complication in pediatric patients receiving maintenance peritoneal dialysis. Extra-skeletal calcification was noticed at the corneas, pelvic cavity, and soft tissues of the lower leg in 4 out of 32 patients on maintenance peritoneal dialysis. These patients experienced the aggravation of extra-skeletal calcifications during peritoneal dialysis, and 2 of them underwent excisional operations. It is required to monitor extra-skeletal calcifications in children on kidney replacement therapy.

Purpose Nephrotic syndrome (NS) is the most common form of glomerulopathy in children. Most pediatric patients respond to glucocorticosteroid treatment (steroid-sensitive NS, SSNS), while approximately 10–15% will remain unresponsive or later become steroid-resistant. There has been a long-standing effort to find biomarkers that may predict steroid responsiveness. Methods We systematically reviewed current studies which investigated clinically relevant biomarkers for predicting steroid responsiveness in pediatric NS. We performed a PubMed and EMBASE search to identify eligible articles. We collected data on urinary markers, blood/serum markers (including cellular phenotypes and mRNA expression), genotypes and HLA allele frequency. Results A total of 659 articles were identified following electronic and manual searches. After reviewing the titles, abstracts, and full texts, 72 eligible articles were finally included. Vitamin D-binding protein (VDBP) seemed to be significantly elevated in SRNS than in SSNS, in both serum and urine specimen, although further validation is required. Conclusions The present paper narratively illustrates current understandings of potential biomarkers that may help predict steroid responsiveness. Further investigation and collaboration involving a larger number of patients are necessary.

The Korean Society of Nephrology (KSN) has published a clinical practice guideline (CPG) document for maintenance hemodialysis (HD). The document, 2021 Clinical Practice Guideline on Optimal HD Treatment, is based on an extensive evidence-oriented review of the benefits of preparation, initiation, and maintenance therapy for HD, with the participation of representative experts from the KSN under the methodologists’ support for guideline development. It was intended to help clinicians participating in HD treatment make safer and more effective clinical decisions by providing user-friendly guidelines. We hope that this CPG will be meaningful as a recommendation in practice, but not on a regulatory rule basis, as different approaches and treatments may be used by health care providers depending on the individual patient’s condition. This CPG consists of eight sections and 15 key questions. Each begins with statements that are graded by the strength of recommendations and quality of the evidence. Each statement is followed by a summary of the evidence supporting the recommendations. There is also a link to full-text documents and lists of the most important reports so that the readers can read further (most of this is available online).

Background The clinical features of pediatric rhabdomyolysis differ from those of the adults with rhabdomyolysis; however, multicenter studies are lacking. This study aimed to investigate the characteristics of pediatric rhabdomyolysis and reveal the risk factors for acute kidney injury (AKI) in such cases. Methods This retrospective study analyzed the medical records of children and adolescents diagnosed with rhabdomyolysis at 23 hospitals in South Korea between January 2007 and December 2016. Results Among 880 patients, those aged 3 to 5 years old composed the largest subgroup (19.4%), and all age subgroups were predominantly male. The incidence of AKI was 11.3%. Neurological disorders (53.6%) and infection (39.0%) were the most common underlying disorder and cause of rhabdomyolysis, respectively. The median age at diagnosis in the AKI subgroup was older than that in the non-AKI subgroup (12.2 years vs. 8.0 years). There were no significant differences in body mass index, myalgia, dark-colored urine, or the number of causal factors between the two AKI-status subgroups. The multivariate logistic regression model indicated that the following factors were independently associated with AKI: multiorgan failure, presence of an underlying disorder, strong positive urine occult blood, increased aspartate aminotransferase and uric acid levels, and reduced calcium levels. Conclusions Our study revealed characteristic clinical and laboratory features of rhabdomyolysis in a Korean pediatric population and highlighted the risk factors for AKI in these cases. Our findings will contribute to a greater understanding of pediatric rhabdomyolysis and may enable early intervention against rhabdomyolysis-induced AKI.

Atypical hemolytic uremic syndrome (aHUS) is a rare disease caused by complement dysregulation that may involve the extra-renal system. Without appropriate prophylactic treatment, aHUS commonly recur after kidney transplantation (KT). In contrast, cytomegalovirus (CMV) infection is common in KT recipients and may affect various organ systems. Herein, we report a case of recurrent aHUS complicated by CMV enteritis. This 17-year-old KT recipient with aHUS having a CFH mutation was admitted to the hospital for gastric pain and vomiting. With worsening hemogram, recurrence of aHUS involving the gastrointestinal (GI) system was suspected. Upon treatment with anti-C5 antibody, the patient’s blood counts soon improved, but her GI symptoms did not. Esophagogastroduodenoscopy revealed multiple ulcers in the duodenum with pathologic findings consistent with aHUS and CMV enteritis; however, she did not have CMV antigenemia despite these findings. Treatment with ganciclovir resolved GI symptoms within 7 days. This case shows that recurrence of aHUS is often induced by intercurrent infection, and common infections after allograft transplantation, such as CMV, should always be suspected and confirmed for a proper treatment, particularly because CMV enteritis may not accompany CMV antigenemia.

Purpose This study evaluated the diagnostic performance of contrast-enhanced voiding urosonography (ce-VUS) using a second-generation ultrasound contrast agent for the diagnosis of vesicoureteral reflux (VUR) and intrarenal reflux (IRR), and compared it with that of standard fluoroscopic voiding cystourethrography (VCUG). Methods Thirty-two consecutive children from April to October 2019 were included in this study. ce-VUS and VCUG were performed simultaneously by two operators with intravesical infusion of a mixture of ultrasound contrast medium, iodinated contrast medium and water. Two pediatric radiologists independently reviewed the ce-VUS and VCUG images and reported the presence and degree of VUR (grades I-V), and the presence and type of IRR. Results Twenty-seven of 63 urinary systems showed VUR. Interobserver agreement for VUR grading was very good for both examinations (κ=0.87; 95% confidence interval [CI], 0.82 to 0.92 for ce-VUS and κ=0.92; 95% CI, 0.87 to 0.96 for VCUG). The detection rate of VUR showed no significant difference between the two examinations (P=0.370). Four cases of VUR were missed on ce-VUS, while one case of VUR was missed on VCUG. All four false-negative cases on ce-VUS were grade 1 VUR. The two examinations showed very good agreement regarding VUR grading (κ =0.89; 95% CI, 0.81 to 0.96). IRR was more frequently detected with ce-VUS than with VCUG (10 cases with ce-VUS vs. 3 cases with VCUG, P=0.016). Conclusion ce-VUS showed very good agreement with VCUG for detecting grade 2 VUR and above, while grade 1 VUR was sometimes missed with ce-VUS. IRR was more frequently detected with ce-VUS than with VCUG.

Atypical progeroid syndrome (APS) is a rare type of progeroid syndrome mainly caused by heterozygous missense mutations in the LMNA (MIM 150330) gene. APS has heterogeneous clinical manifestations, and its kidney manifestations, particularly in children, are rarely documented. Here, we report the first pediatric case of APS with focal segmental glomerulosclerosis (FSGS). A 10-year-old boy with progeroid features was referred to the nephrology clinic because of hyperuricemia. He had dark skin, protruding eyes, and beaked nose and was very thin, suggesting lipodystrophy. He had been treated for recurrent urinary tract infection during infancy, and liver biopsy for persisting hepatitis showed steatohepatitis. He also had hypertrophic cardiomyopathy (HCMP) with mitral and tricuspid valve regurgitation. Genetic studies were performed considering his multisystem symptoms, and he was diagnosed as having APS according to exome sequencing findings (c.898G > C, p.Asp300His of LMNA). During the first visit to the nephrology clinic, he had minimal proteinuria (urine protein/creatinine ratio of 0.23 mg/mg), which worsened during follow-up. In three years, his urine protein/creatinine ratio and N-acetyl-b-D-glucosaminidase/creatinine ratio increased to 1.52 and 18.7, respectively. The kidney biopsy result was consistent with findings of FSGS, peri-hilar type, showing segmental sclerosis of 1 (5%) glomerulus out of 21 glomeruli. An angiotensin receptor blocker was added to manage his proteinuria. This is the first pediatric report of FSGS in an APS patient with confirmed LMNA defect, who manifested progeroid features, lipodystrophy, HCMP with heart valve dysfunction, and steatohepatitis. Our case suggests that screening for proteinuric nephropathy is essential for managing APS patients since childhood.

Abstract Background This study aimed to use whole-exome sequencing (WES) to diagnose ultra-rare renal diseases and the clinical impact of such an approach on patient care. Methods Clinical, radiological, pathological, and genetic findings were reviewed in the patients and their family members. Results Nine patients from nine unrelated Korean families were included in the study and evaluated. WES identified eight different conditions in these patients, i.e., autosomal dominant tubulointerstitial kidney disease associated with UMOD mutation; recurrent urinary stones associated with APRT deficiency; Ayme-Gripp syndrome associated with MAF mutation; short rib-thoracic dysplasia associated with IFT140 mutation; renal coloboma syndrome associated with PAX2 mutations; idiopathic infantile hypercalcemia associated with CYP24A1 mutation; and hypomagnesemia associated with TRPM mutation. Eleven different mutations, including seven novel mutations, were identified, i.e., four truncating mutations, six missense mutations, and one splice-acceptor variant. After genetic confirmation, strategies for the management of the following: medications, donor selection for renal transplantation, and surveillance for extra-renal manifestations were altered. In addition, genetic counseling was provided for the patients and their family members with respect to family member screening for affected but yet unidentified patients and future reproductive planning. Conclusion As WES can effectively identify ultra-rare genetic renal diseases, facilitate the diagnosis process, and improve patient care, it is a good approach to enable a better understanding of ultra-rare conditions and for the establishment of appropriate counseling, surveillance, and management strategies.

C3 glomerulonephritis (C3GN), a rare condition associated with dysregulation of the alternative pathway of the complement system, is histopathologically characterized by isolated or dominant C3 deposition in the renal glomeruli. We report a case of C3GN associated with anti-complement factor H (CFH) autoantibodies and CHF-related protein deficiency in an adolescent male. A 16-year-old adolescent male was admitted to a hospital with a 1-month history of generalized edema prior to presentation. Persistent microscopic hematuria and low serum C3 levels were incidentally detected at 7 and 10 years of age, respectively. Laboratory test results revealed hypoalbuminemia, nephrotic-range proteinuria, microscopic hematuria, and normal serum creatinine levels. The serum C3 and C4 levels were 17 mg/dL (normal 80–150 mg/dL) and 22 mg/mL (17–40 mg/mL), respectively. Renal biopsy showed typical features of C3GN. Further investigations revealed positive results on plasma anti-CFH autoantibody testing and a homozygous deletion of CFHR1 and CFHR3, which encode CFH-related proteins 1 and 3, respectively. Proteinuria persisted despite treatment with intravenous methylprednisolone, mycophenolate mofetil, and angiotensin-receptor blocker; however, his renal function remained stable. In conclusion, anti-CFH autoantibodies serve as important contributors to C3GN. This is the first case report that describes C3GN in an adolescent Korean male with anti-CFH autoantibodies and homozygous CFHR1 and CFHR3 deletion.

Chronic kidney disease (CKD) in children is associated with various complications, including poor growth and development, mineral bone disorder, cardiovascular disease, kidney failure, and mortality. Slowing down the progression of CKD is important since CKD is often not curable. Prospective cohort studies have been conducted to understand the progression and outcomes of CKD in children, and these studies have identified non-modifiable and modifiable risk factors. Recognition of known risk factors and early intervention are important to delay the progression of kidney function decline in children.

Pediatric kidney transplantation is the best option since it can achieve near normal glomerular filtration rate, adequate fluid balance, and autonomic endocrine function of the kidney in end-stage kidney disease. However, pediatric kidney transplantation is difficult because children are developing and growing, management and complications of pediatric kidney transplantation are different from those of adults. This review covers the current status of pediatric kidney transplantation in Korea, key considerations that must be taken before kidney transplantation in children, and management strategy of immunosuppression and common complications.

Abstract Background Inherited cystic kidney disease is a spectrum of disorders in which clusters of renal cysts develop as the result of genetic mutation. The exact methods and pipelines for defining genetic mutations of inherited cystic kidney disease are not clear at this point. This 3-year, prospective, multicenter, cohort study was designed to set up a cohort of Korean patients with inherited cystic kidney disease, establish a customized genetic analysis pipeline for each disease subtype, and identify modifying genes associated with the severity of the disease phenotype. Methods/design From May 2020 to May 2022, we aim to recruit 800 patients and their family members to identify pathogenic mutations. Patients with more than 3 renal cysts in both kidneys are eligible to be enrolled. Cases of simple renal cysts and acquired cystic kidney disease that involve cyst formation as the result of renal failure will be excluded from this study. Demographic, laboratory, and imaging data as well as family pedigree will be collected at baseline. Renal function and changes in total kidney volume will be monitored during the follow-up period. Genetic identification of each case of inherited cystic kidney disease will be performed using a targeted gene panel of cystogenesis-related genes, whole exome sequencing (WES) and/or family segregation studies. Genotype-phenotype correlation analysis will be performed to elucidate the genetic effect on the severity of the disease phenotype. Discussion This is the first nationwide cohort study on patients with inherited cystic kidney disease in Korea. We will build a multicenter cohort to describe the clinical characteristics of Korean patients with inherited cystic kidney disease, elucidate the genotype of each disease, and demonstrate the genetic effects on the severity of the disease phenotype. Trial registration This cohort study was retrospectively registered at the Clinical Research Information Service ( KCT0005580 ) operated by the Korean Center for Disease Control and Prevention on November 5th, 2020.

Abstract Background Ocular involvement in catastrophic antiphospholipid syndrome (CAPS), a rare, life-threatening form of antiphospholipid syndrome (APS) that results in multiorgan failure and a high mortality rate, has rarely been reported. Case presentation A 15-year-old girl presented with sudden vision blurring in both eyes. She had marked optic disc swelling and macular exudates in the right eye and intra-arterial white plaques, a few retinal blot hemorrhages, and a white ischemic retina in the left eye. Systemic examination revealed she had acute kidney injury with thrombotic microangiopathy (TMA), multiple cerebral infarcts, valvular dysfunction, and a high titer of triple aPL. Thus, she was diagnosed with CAPS involving the brain, eyes, heart, and kidneys. Plasma exchange and the administration of glucocorticoids, immunoglobulin, warfarin, and rituximab brought a sustained recovery of the TMA, visual symptoms, and echocardiographic findings. Conclusions Ocular involvement of both vaso-occlusive retinopathy, an APS-related thrombotic microangiopathy, and neuroretinitis, a non-thrombotic microangiopathy, can occur as an initial presentation of CAPS.

Abstract Background Cardiovascular disease (CVD) is the most common cause of mortality in pediatric chronic kidney disease (CKD) patients. Left ventricular (LV) hypertrophy (LVH) is associated with LV diastolic dysfunction (LVDD) development and is used as an early marker of CVD in pediatric CKD. This study aimed to assess the prevalence and risk factors of LVDD and the association between LVH and LVDD in Korean pediatric CKD patients. Methods Data were collected using the baseline data of the Korean cohort study for outcome in patients with pediatric chronic kidney disease, a nationwide, 10-year, prospective, observational cohort study of pediatric CKD. A total of 244 patients were included in the final analysis. Two-dimensional echocardiography and tissue Doppler images were used to evaluate LVH and LVDD. LVH was defined as an LV mass index (LVMI) ≥38 g/m2.7 and LV-wall thickness z-score > 1.64. LVDD was defined as a mitral peak velocity of early filling to early diastolic mitral annular velocity (E/E’) > 14. Univariate and multivariate logistic regression analyses were performed to evaluate risk factors of LVDD. Results In this study, the male-to-female ratio was 2.2 (168:76) and median age was 11.2 years. The average estimated glomerular filtration rate was 57.4 ml/min/1.73 m2, and no patients received renal replacement therapy. The mean value of LVMI and E/E’ was 37.0 g/m2.7 and 7.4, respectively. The prevalence of LVH was 40.1 and 17.4% by LVMI ≥38 g/m2.7 and LV-wall thickness z-score, respectively. The prevalence of LVDD was 4.5%, and patients with LVH showed greater risk of LVDD (odds ratio 7.3, p = 0.012). In the univariate analysis, young age, low hemoglobin level, higher LVMI, and higher LV-wall thickness z-score were associated with LVDD. In the multivariate analysis, young age, low hemoglobin level, and higher LV-wall thickness z-score were independently associated with LVDD. Conclusion This study shows that LVH patients have a greater risk of LVDD and that anemia is the only modifiable risk factor for LVDD in Korean pediatric CKD patients.

Gorham-Stout syndrome is a rare bone disorder characterized by progressive massive osteolysis and proliferation of vascular and lymphatic vessels. A 15-year-old boy was initially diagnosed with Gorham-Stout at the age of 8 years based on clinical and radiological findings. Following diagnosis, he was treated with pamidronate, interferon alfa, propranolol, oral corticosteroids, and sirolimus. He developed proteinuria at the age of 15 and progressed into the nephrotic range 2 years later. A renal biopsy revealed focal segmental glomerulosclerosis, not otherwise specified variant. The sequential increase in proteinuria associated with medications suggested that the focal segmental glomerulosclerosis may be caused by pamidronate and sirolimus, but cannot completely rule out the possibility of kidney involvement of GSS itself.

Atypical hemolytic uremic syndrome (aHUS) is an extremely rare and life-threatening disorder. Typical HUS is often caused by Shiga toxin-positive Escherichia coli, while aHUS is caused by dysregulation of the alternative pathway of the complement system in association with genetic abnormalities or development of autoantibodies. Eculizumab, a humanized anti-complement 5 monoclonal antibody, is recommended for the treatment of aHUS, but its long-term safety and efficacy in pediatric patients remain under review. In this paper, we report a pediatric case of aHUS with anti-complement factor H autoantibodies, who was treated successfully with eculizumab.

Abstract Backgrounds Glomerular diseases, a set of debilitating and complex disease entities, are related to mortality and morbidity. To gain insight into pathophysiology and novel treatment targets of glomerular disease, various types of biospecimens linked to deep clinical phenotyping including clinical information, digital pathology, and well-defined outcomes are required. We provide the rationale and design of the KOrea Renal biobank NEtwoRk System TOward Next-generation analysis (KORNERSTONE). Methods The KORNERSTONE, which has been initiated by Korea Centres for Disease Control and Prevention, is designed as a multi-centre, prospective cohort study and biobank for glomerular diseases. Clinical data, questionnaires will be collected at the time of kidney biopsy and subsequently every 1 year after kidney biopsy. All of the clinical data will be extracted from the electrical health record and automatically uploaded to the web-based database. High-quality digital pathologies are obtained and connected in the database. Various types of biospecimens are collected at baseline and during follow-up: serum, urine, buffy coat, stool, glomerular complementary DNA (cDNA), tubulointerstitial cDNA. All data and biospecimens are processed and stored in a standardised manner. The primary outcomes are mortality and end-stage renal disease. The secondary outcomes will be deterioration renal function, remission of proteinuria, cardiovascular events and quality of life. Discussion Ethical approval has been obtained from the institutional review board of each participating centre and ethics oversight committee. The KORNERSTONE is designed to deliver pioneer insights into glomerular diseases. The study design allows comprehensive, integrated and high-quality data collection on baseline laboratory findings, clinical outcomes including administrative data and digital pathologic images. This may provide various biospecimens and information to many researchers, establish the rationale for future more individualised treatment strategies for glomerular diseases. Trial registration NCT03929887 .

Thrombotic microangiopathy (TMA) is defined by specific clinical characteristics, including microangiopathic hemolytic anemia, thrombocytopenia, and pathologic evidence of endothelial cell damage, as well as the resulting ischemic end-organ injuries. A variety of clinical scenarios have features of TMA, including infection, pregnancy, malignancy, autoimmune disease, and medications. These overlapping manifestations hamper differential diagnosis of the underlying pathogenesis, despite recent advances in understanding the mechanisms of several types of TMA syndrome. Atypical hemolytic uremic syndrome (aHUS) is caused by a genetic or acquired defect in regulation of the alternative complement pathway. It is important to consider the possibility of aHUS in all patients who exhibit TMA with triggering conditions because of the incomplete genetic penetrance of aHUS. Therapeutic strategies for aHUS are based on functional restoration of the complement system. Eculizumab, a monoclonal antibody against the terminal complement component 5 inhibitor, yields good outcomes that include prevention of organ damage and premature death. However, there remain unresolved challenges in terms of treatment duration, cost, and infectious complications. A consensus regarding diagnosis and management of TMA syndrome would enhance understanding of the disease and enable treatment decision-making.

Background: X-linked hypophosphatemia (XLH) is the most frequent form of hypophosphatemic rickets and is caused by mutations in the PHEX gene. We analyzed genotype-phenotype correlations in XLH patients with proven PHEX mutations.Methods:PHEX mutations were detected in 55 out of 81 patients who clinically presented with hypophosphatemic rickets. The patients were grouped into nontruncating (n = 9) and truncating (n = 46) mutation groups; their initial presentation as well as long-term clinical findings were evaluated according to these groups.Results: Initial findings, including presenting symptoms, onset age, height standard deviation scores (SDS), and laboratory tests, including serum phosphate level and tubular resorption of phosphate, were not significantly different between the two groups (onset age: nontruncating mutation group, 2.0 years, truncating mutation group, 2.2 years; height SDS: nontruncating mutation group, −1.9, truncating mutation group, −1.7; serum phosphate: nontruncating mutation group, 2.5 mg/dL, truncating mutation group, 2.6 mg/dL). However, at their last follow-up, the serum phosphate level was significantly lower in patients with truncating mutations (nontruncating mutation group: 3.2 mg/dl, truncating mutation group: 2.3 mg/dl; P = 0.006). Additionally, 62.5% of patients with truncating mutations developed nephrocalcinosis at their last follow-up, while none of the patients with nontruncating mutations developed nephrocalcinosis (P = 0.015). Orthopedic surgery due to bony deformations was performed significantly more often in patients with truncating mutations (52.3 vs. 10.0%, P = 0.019).Conclusion: Although considerable inconsistency exists regarding the correlation of truncating mutations and their disease phenotype in several other studies, we cautiously suggest that there would be genotype-phenotype correlation in some aspects of disease manifestation after long-term follow-up. This information can be used when consulting patients with confirmed XLH regarding their disease prognosis.

Background Primary hyperoxaluria (PH), a rare inborn error of glyoxylate meta bolism causing overproduction of oxalate, is classified into three genetic subgroups: type 1–3 (PH1–PH3) caused by AGXT, GRHPR, and HOGA1 gene mutations, respectively. We performed a retrospective case series study of Korean pediatric patients with PH. Methods In total, 11 unrelated pediatric patients were recruited and their phenotypes and genotypes were analyzed by a retrospective review of their medical records. Results Mutational analyses revealed biallelic AGXT mutations (PH1) in nine patients and a single heterozygous GRHPR and HOGA1 mutation in one patient each. The c.33dupC was the most common AGXT mutation with an allelic frequency of 44%. The median age of onset was 3 months (range, 2 months–3 years), and eight patients with PH1 presented with end stage renal disease (ESRD). Patients with two truncating mutations showed an earlier age of onset and more frequent retinal involvement than patients with one truncating mutation. Among eight PH1 patients presenting with ESRD, five patients were treated with intensive dialysis followed by liver transplantation (n=5) with/without subsequent kidney transplantation (n=3). Conclusion Most patients presented with severe infantile forms of PH. Patients with two truncating mutations displayed more severe phenotypes than those of patients with one truncating mutation. Sequential liver and kidney transplantation was adopted for PH1 patients presenting with ESRD. A larger nation-wide multicenter study is needed to confirm the genotype-phenotype correlations and outcomes of organ transplantation.

Background: Atypical hemolytic uremic syndrome (aHUS) is a rare, life-threatening disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, and renal impairment caused by uncontrolled activation of the complement system. About 20% of patients show extrarenal manifestations, with central nervous system involvement being the most frequent. We described the clinical course and management of aHUS in an infant, that was caused by a complement 3 (C3) gene mutation with severe extrarenal manifestations. Case Presentation: A 4-month-old girl visited our hospital for jaundice and petechiae. Laboratory tests revealed microangiopathic hemolytic anemia, thrombocytopenia, and hyperazotemia. She was diagnosed with aHUS with a C3 p.E1160K mutation. Daily fresh-frozen plasma (FFP) therapy was administered; however, she experienced the severe extrarenal manifestations of pulmonary hemorrhage and gastrointestinal bleeding. With aggressive treatment, supportive care, and daily FFP transfusion, the patient recovered and was discharged after 72 days of hospital stay, on a regular FFP transfusion. Four months after diagnosis, she was switched to eculizumab treatment. Twenty months have passed since then and she has been relapse-free until now. Conclusion: aHUS is rare but has a devastating course if not properly treated. Severe extrarenal manifestations, such as pulmonary hemorrhage and gastrointestinal bleeding, can develop in aHUS caused by a C3 mutation. In our case, long-term management with eculizumab resulted in relapse-free survival.