Epidemiology and Outcomes of Children with Kidney Failure Receiving Kidney Replacement Therapy in Australia and New Zealand.

Introduction: The incidence and outcomes of kidney replacement therapy (KRT) have been well-studied in adults, but much less so in children. This study aimed to investigate the epidemiology and outcomes of KRT in children in Australia and New Zealand from 2000 to 2020. Methods: Children aged <18 years initiating KRT in Australia and New Zealand between January 1, 2000 and December 31, 2020 and reported to the Australia and New Zealand Dialysis and Transplant Registry were included. Patient survival, technique-survival, and graft survival were analyzed by Cox regression analyses. Results: Overall, 1058 children (median [interquartile range (IQR)] age 11 [5-15] years, 41% female, 66% White) were followed-up with for a median period of 12.3 years. First KRT modalities were peritoneal dialysis (PD; 48%), hemodialysis (HD; 34%), and kidney transplantation (KT; 18%). Pre-emptive KT incidence was highest in Caucasian children (80.4%) and lowest in the Indigenous population (3.2%). There was no difference in 5-year patient survival rates between 2011 and 2020 (96.9%, 95% confidence interval [CI] 93.8-98.4) and the preceding decade, 2000-2010 (94.5%, 95% CI 90.4-96.8) (P = 0.79). There was no difference in 5-year death-censored technique survival between 2011 and 2020 (51.2%, 95% CI 39.1-62) and 2000-2010 (48.8%, 95% CI 40.5-56.6) (P = 0.27). However, 5-year derath-censored graft survival was significantly higher in 2011-2020 (88.4%, 95% CI 84.6-91.4) than in 2000-2010 (84.3%, 95% CI 80.4-87.5) (P < 0.001). Conclusions: PD is the most commonly prescribed KRT modality for children in Australia and New Zealand. Patient-survival, technique-survival, and graft survival rates are excellent and graft survival has improved over the last 2 decades.

Comparison of three spot proteinuria measurements for pediatric nephrotic syndrome: based on the International pediatric Nephrology Association 2022 Guidelines.

BACKGROUND: Pediatric nephrotic syndrome (NS) requires routine proteinuria monitoring, which is costly and affects patients' quality of life. The gold-standard 24-h urine protein (UP) measurement is challenging in children, and first-morning urine collection requires specific conditions, making it difficult in outpatient settings. Studies have reported comparability of second or random morning urine sample to the first-morning specimen. This study aimed to compare outcomes of random morning proteinuria measurements to 24-h UP and the roles of the urinary protein creatinine ratio (UPCR) and dipstick tests in pediatric NS, based on International Pediatric Nephrology Association (IPNA) 2022 Guidelines. METHOD: Twenty-four-hour and morning urine samples were collected from 92 pediatric NS patients. These were subjected to automated analyses for 24-h UP, UPCR, and semi-automated dipstick analysis. A blinded doctor performed manual dipstick analysis. RESULTS: UPCR had a stronger correlation with 24-h UP than with automated and manual urine dipstick tests. UPCR had the highest sensitivity and specificity for predicting no remission/relapse and high sensitivity but low specificity for complete remission. The optimal UPCR cutoff for remission was 0.44 mg/mg and for no remission/relapse was 2.08 mg/mg. Automated and manual dipstick tests demonstrated limited sensitivity but high specificity and similar AUC values for remission/relapse. CONCLUSION: UPCR was sensitive and specific for diagnosing no remission/relapse and sensitive but not specific for detecting remission. Manual and automated urine dipstick tests were comparable for remission and no remission/relapse detection. This study supports the IPNA 2022 Guidelines, as 2 mg/mg was the optimal UPCR cutoff for no remission/relapse, while for remission the optimal cutoff was 0.4 mg/mg.

Nephropathy in a Child with Severe Recessive Dystrophic Epidermolysis Bullosa Treated with Cyclophosphamide: A Case Report.

Long-term inflammation and recurrent skin infection in recessive dystrophic epidermolysis bullosa (RDEB) are associated with the presence of immunoglobulin A (IgA)-containing immune complexes in the glomerulus. Only eight pediatric RDEB cases with IgA nephropathy (IgAN) have been documented in English-language literature. Most RDEB patients with IgAN progress to kidney failure within 5 years of diagnosis, indicating that these patients may require more intensive early treatment compared to those with primary IgAN. However, diagnosing IgAN in RDEB cases with severe cutaneous manifestations can be challenging. Herein, we report a rare case of nephropathy in an 11-year-old boy with severe RDEB and a frameshift mutation on the COL7A1 gene, which may manifest as kidney disorders. He presented with persistent hematuria and progressing proteinuria. A presumptive IgAN diagnosis was based on clinical features and increased IgA serum levels, as kidney biopsy was refused by his parents. Nephrotic-range proteinuria persisted despite initial steroid and lisinopril treatment. Monthly intravenous cyclophosphamide (IV CPA; 500 mg/m2) led to proteinuria remission and preservation of kidney function for 2 years posttreatment. We conclude that COL7A1 mutations may result in extracutaneous manifestations, including kidney disorders. The association between IgA-containing immune complex deposits in the glomerulus and recurrent skin infection in RDEB may indicate IgAN, particularly when kidney biopsy is infeasible due to severe skin manifestations. In our case, positive results with IV CPA suggest further investigation is needed to explore its potential role in non-rapidly progressing IgAN in children with RDEB.

Rituximab, Mycophenolic Acid, and Calcineurin Inhibitors Achieve Long-Term Remission in Pediatric Focal Segmental Glomerulosclerosis with Steroid-Resistant and Frequently Relapsing Nephrotic Syndrome: A Report of Two Cases.

Studies investigating the effect of rituximab in children with nephrotic syndrome (NS) due to focal segmental glomerulosclerosis (FSGS) have reported conflicting results, with some concluding that patients may require additional immunosuppressive therapy to achieve and/or maintain long-term remission. We report successful treatment of pediatric FSGS with rituximab infusions, followed by maintenance immunosuppression with mycophenolic acid (MPA) and a calcineurin inhibitor (CNI) in 1 patient with refractory steroid-resistant NS (SRNS), and one with frequently relapsing NS (FRNS). Case 1 is a patient with refractory SRNS due to FSGS. MPA and tacrolimus induced complete remission within 6 months following rituximab treatment. Remission was maintained for over 2 years, and the patient's kidney function and body height also returned to normal ranges within this time. Case 2 is a patient with FRNS due to FSGS, who was treated with rituximab followed by MPA and cyclosporine, which successfully prevented relapses for 18 months, that is, at the end point of the observation. Our case report demonstrates that rituximab and a combination of CNIs and MPA can be effective in achieving complete remission in pediatric refractory SRNS and sustaining remission in pediatric FSGS with FRNS and SRNS for several years. This treatment regimen has the advantage of eliminating the need for long-term high-dose steroid treatments, allowing 1 patient to achieve normal growth and recover from other adverse steroid effects.

Distal renal tubular acidosis presenting with an acute hypokalemic paralysis in an older child with severe vesicoureteral reflux and syringomyelia: a case report.

BACKGROUND: Distal renal tubular acidosis (dRTA) is the most common type of renal tubular acidosis (RTA) in children. Pediatric dRTA is usually genetic and rarely occurs due to acquired issues such as obstructive uropathies, recurrent urinary tract infections (UTIs), and chronic kidney disease (CKD). Although persistent hypokalemia frequently occurs with dRTA, acute hypokalemic paralysis is not frequently reported, especially in older children. CASE PRESENTATION: An eight-year-old girl presented with an acute first episode of paralysis. A physical examination revealed normal vital signs, short stature consistent with her genetic potential, and decreased muscle strength of her upper and lower extremities. Preexisting conditions included stage 4 CKD due to recurrent UTIs, severe vesicoureteral reflux and bilateral hydronephrosis, neurogenic bladder, and multisegment thoracic syringomyelia. Her laboratory work-up revealed hypokalemic, hyperchloremic metabolic acidosis with a normal anion gap. She also had a urine osmolal gap of 1.9 mOsmol/kg with a high urine pH. Intravenous potassium replacement resulted in a complete resolution of her paralysis. She was diagnosed with dRTA and discharged with oral bicarbonate and slow-release potassium supplementation. CONCLUSIONS: This case report highlights the importance of considering dRTA in the differential diagnosis of hypokalemic acute paralysis in children. Additionally, in children with neurogenic lower urinary tract dysfunction and recurrent UTIs, early diagnosis of spinal cord etiology is crucial to treat promptly, slow the progression of CKD, and prevent long-term complications such as RTA.

High Fibroblast Growth Factor 23 as a Biomarker for Severe Cardiac Impairment in Children with Chronic Kidney Disease: A Single Tertiary Center Study.

INTRODUCTION: Left ventricular hypertrophy (LVH) is the most common cardiac abnormality in chronic kidney disease (CKD). Changes in cardiac geometry and functions may occur in an early stage and worsen as CKD progresses. Recently, the role of fibroblast growth factor 23 (FGF23) is being highlighted and investigated in CKD-related cardiomyopathy. However, only a few studies have reviewed the utilization of FGF23 as a diagnostic biomarker in the pediatric CKD population. PURPOSE: This study aimed to identify the role of FGF23 as a biomarker in assessing cardiac changes in children with CKD. PATIENTS AND METHODS: We conducted a cross-sectional study that involved children aged 2 to 18 years old with CKD stages 2 to 5D in Dr. Sardjito General Hospital, Yogyakarta, Indonesia. The level of FGF23 was measured using an immunometric enzyme-linked immunosorbent assay. LVMI, RWT, and left ventricular ejection fraction (LVEF) were assessed with echocardiography. Receiver-operating characteristic (ROC) analyses were conducted to assess the diagnostic performance of FGF23 in detecting LVH with impaired contractility. RESULTS: A total of 43 children with CKD stages 2 to 5D were included, among whom the prevalence of LVH diagnosis was 95.35%. The area under the curve (AUC) of FGF23 to assess LVH and systolic dysfunction was 0.82 (95% CI 0.62-1.0), and the optimal cutoff point was 1413 RU/mL (sensitivity 80%, specificity 78.95%). The median concentration of FGF23 increased with the decreasing eGFR and the increasing LVMI although the systolic and diastolic functions were preserved. CONCLUSION: FGF23 might be used as an early biomarker to detect cardiac changes in pediatric CKD patients, particularly for LVH and impaired systolic function among children with CKD stage 2 and higher.

Silent Hypertensive Crisis in an Adolescent: First Case Report of Pediatric Pheochromocytoma from Indonesia.

Secondary hypertension in children, to the rare extent, can be caused by endocrine factors such as pheochromocytoma, an adrenal tumor that secretes catecholamine. Only a few cases have been reported in the past 3 decades. To the best of our knowledge, this is the first case report of pediatric pheochromocytoma from Indonesia. We reviewed a case of a 16-year-old Indonesian boy with history of silent hypertensive crisis who was referred from a remote area in an island to the pediatric nephrology clinic at Cipto Mangunkusumo Hospital, Jakarta, Indonesia. Despite medications, his symptoms persisted for 14 months. At the pediatric nephrology clinic, pheochromocytoma was suspected due to symptoms of catecholamine secretion presented, which was palpitation, diaphoresis, and weight loss. However, as the urine catecholamine test was unavailable in Indonesia, the urine sample was sent to a laboratory outside the country. The elevated level of urine metanephrine, focal pathological uptake in the right adrenal mass seen on 131I-MIBG, and histopathology examination confirmed the suspicion of pheochromocytoma. Following the tumor resection, he has been living with normal blood pressure without antihypertensive medications. This case highlights that pheochromocytoma should always be included in the differential diagnoses of any atypical presentation of hypertension. In limited resources setting, high clinical awareness of pheochromocytoma is required to facilitate prompt referral. Suspicion of pheochromocytoma should be followed by measurement of urine metanephrine levels. Early diagnosis of pheochromocytoma would fasten the optimal cure, alleviate the symptoms of catecholamine release, and reverse hypertension.

Aetiology, course and treatment of acute tubulointerstitial nephritis in paediatric patients: a cross-sectional web-based survey.

BACKGROUND: Acute tubulointerstitial nephritis (TIN) is a significant cause of acute renal failure in paediatric and adult patients. There are no large paediatric series focusing on the aetiology, treatment and courses of acute TIN. PATIENTS, DESIGN AND SETTING: We collected retrospective clinical data from paediatric patients with acute biopsy-proven TIN by means of an online survey. Members of four professional societies were invited to participate. RESULTS: Thirty-nine physicians from 18 countries responded. 171 patients with acute TIN were included (54% female, median age 12 years). The most frequent causes were tubulointerstitial nephritis and uveitis syndrome in 31% and drug-induced TIN in 30% (the majority of these caused by non-steroidal anti-inflammatory drugs). In 28% of patients, no initiating noxae were identified (idiopathic TIN). Median estimated glomerular filtration rate (eGFR) rose significantly from 31 at time of renal biopsy to 86 mL/min/1.73 m2 3-6 months later (p<0.001). After 3-6 months, eGFR normalised in 41% of patients (eGFR ≥90 mL/min/1.73 m2), with only 3% having severe or end-stage impairment of renal function (<30 mL/min/1.73 m2). 80% of patients received corticosteroid therapy. Median eGFR after 3-6 months did not differ between steroid-treated and steroid-untreated patients. Other immunosuppressants were used in 18% (n=31) of patients, 21 of whom received mycophenolate mofetil. CONCLUSIONS: Despite different aetiologies, acute paediatric TIN had a favourable outcome overall with 88% of patients showing no or mild impairment of eGFR after 3-6 months. Prospective randomised controlled trials are needed to evaluate the efficacy of glucocorticoid treatment in paediatric patients with acute TIN.

Role of dipstick albuminuria in progression of paediatric chronic kidney disease.

OBJECTIVE: Renal function of patients with chronic kidney disease (CKD) is typically evaluated by detecting proteinuria because it is a major predictor of CKD progression. In paediatric patients with CKD, urine albumin-to-creatinine ratio (ACR) is used to detect CKD progression, which is similar to urine protein-to-creatinine ratio (PCR). However, facilities for evaluation of urine ACR and urine PCR may not be widely available. To date, this is the first study that investigated the predictive value of baseline dipstick albuminuria for 1-year and 3-year CKD progression in Indonesian children. We assessed the association between baseline level of dipstick albuminuria and CKD progression in paediatric patients. METHODS: This retrospective cohort study was conducted at the Cipto Mangunkusumo Hospital (CMH) involving 43 children with CKD between 2016 and 2019. The patients were followed up for 1 year and 3 years after enrolment. Risk ratios (RR) for 1-year and 3-year CKD progression were calculated using Fisher's exact test. RESULTS: The RR for 1-year CKD progression in children with baseline dipstick albuminuria <2+ was 2.16 (95% CI: 1.13-4.14, p = 0.02), and the corresponding RR for 3-year CKD progression in these children was 1.70 (95% CI: 0.73-3.97, p=0.21). CONCLUSIONS: Dipstick albuminuria was not associated with 1-year and 3-year CKD progression in children.

Experience of the first 6 years of pediatric kidney transplantation in Indonesia: A multicenter retrospective study.

BACKGROUND: Pediatric kidney transplantation was only introduced in Indonesia in 2013. We therefore aimed to assess the characteristics and outcomes of transplants performed from its inception to January 2019. METHOD: The study had a dual-center retrospective design. We examined the records of kidney transplant recipients and then calculated patient and graft survival rates by Kaplan-Meier survival analysis with 95% confidence intervals (95% CI). RESULTS: In total, 12 kidney transplantations were performed in eleven children during the study period; among these, ten were boys, and nine had renal failure caused by congenital anomaly of the kidney or urinary tract. All donors were living, and all recipients were on dialysis at the time of transplantation, when their median age was 14.5 years (range, 8-19 years). Three patients died of infection in the first year of follow-up and two lost their allograft by the time of their last follow-up (median, 13 months; range, 4-69 months). The 1-year patient survival rate was therefore 68.18% (95% CI, 29.72%-88.61%), which remained unchanged at 3 and 5 years. However, the non-death-censored graft survival rates at 1, 3, and 5 years were 68.18% (95% CI, 29.72%-88.61%), 51.14% (95% CI, 14.5%-79.46%), and 25.57% (95% CI, 1.38%-64.78%), respectively. CONCLUSION: Patient and graft survival rates after pediatric kidney transplantation in Indonesia are lower than those reported in other countries. Closer patient follow-up and stricter adherence to guidelines could improve transplant outcomes, but we must seek to improve the balance between infection and rejection.

Successful Treatment of Hepatitis C Virus Infection Using Direct-Acting Antiviral Agents (DAAs) in Adolescents with Kidney Transplantation: A Case Series.

INTRODUCTION: Hepatitis C virus (HCV) infection is common among end-stage renal disease patients undergoing hemodialysis. The standard treatment for HCV infection has been interferon-ribavirin combination prior to renal transplantation. However, compared to direct-acting antiviral agents (DAAs), the risk of graft rejection is higher with interferon therapy. Many recent studies have investigated the efficacy and safety of DAAs for treating HCV infection in kidney disease in adults; however, it has not been established in pediatric patients. To the best of our knowledge, this is the first report describing successful treatment using the DAAs sofosbuvir/daclatasvir in two pediatric kidney transplant recipients who had HCV genotype 1a infection without liver fibrosis. CASE PRESENTATION: Case 1 describes a 13-year-old Indonesian boy who had undergone hemodialysis since 2014 after being diagnosed with end-stage renal disease (ESRD) secondary to bilateral renal hypoplasia. Later, he had HCV infection and was treated with interferon-based therapy with ribavirin prior to living-related renal transplantation (LRRT). The HCV was undetected and his liver function normalized six months after treatment initiation. However, 10 months after treatment initiation, he had HCV virological breakthrough, leading to cessation of interferon therapy. Plans for LRRT were continued and HCV treatment using DAAs was set up to be given post LRRT. Case 2 describes a 14-year-old Indonesian girl who also had hemodialysis prior to LRRT after she was diagnosed with ESRD secondary to nephrotic syndrome. Later, she had HCV infection and was treated with interferon and ribavirin prior to the live-unrelated renal transplantation. HCV infection did not resolve, in addition, she experienced thrombocytopenia-which is a side effect of interferon-resulting in termination of interferon treatment. Both cases were treated with DAAs one year following renal transplantation after reaching stable graft function, leading to achievement of sustained virological response at 24 weeks. CONCLUSION: Post-transplantation treatment of chronic HCV is preferred in KTRs. The sofosbuvir/daclatasvir regimen as an interferon-free therapy is a safe, effective option for HCV infection in pediatric KTRs, who can tolerate sofosbuvir/daclatasvir well and respond favorably without significant adverse events.

Low-Dose Maintenance Intravenous Iron Therapy Can Prevent Anemia in Children with End-Stage Renal Disease Undergoing Chronic Hemodialysis.

Iron deficiency anemia is common in children with end-stage renal disease (ESRD) on long-term hemodialysis receiving erythropoiesis-stimulating agents. One approach to maintain the iron profile and hemoglobin levels is maintenance therapy with regular low doses of intravenous (IV) iron after initial iron repletion therapy; however, evidence for the benefits of this approach is lacking. This study evaluated the effect of IV iron maintenance therapy on anemia in children on regular hemodialysis. This retrospective cohort study included 41 pediatric ESRD patients with normal hemoglobin and iron status who underwent regular hemodialysis at the Pediatric Dialysis Unit of Cipto Mangunkusumo Hospital, Indonesia, between January 2015 and April 2019. Among these, 21 received IV iron maintenance therapy with two doses of 2 mg/kg of IV iron sucrose every 2 weeks (the treatment group) and 20 did not (the comparison group). Changes in hemoglobin and transferrin saturation were assessed after 6 weeks of observation and compared between the two groups. There was a significant reduction in the mean hemoglobin level compared with the baseline level in the comparison group (21 g/L; 95% CI, 9.3-33 g/L; p=0.001) but not in the treatment group (0.7 g/L; 95% CI, -6.6-8 g/L; p=0.84). The risk of anemia was lower in the treatment group (relative risk = 0.42; 95% CI, 0.22-0.79; p=0.003). Although majority of the patients had high baseline ferritin level, this study indicates that in our setting, ferritin may not be a reliable parameter to review the iron status, as it can be affected by chronic inflammation. Hence, the decision to start IV iron maintenance therapy in patients with hyperferritinemia should consider the patient's clinical condition and morbidity. To conclude, the coadministration of IV iron maintenance therapy is beneficial for maintaining hemoglobin levels and preventing anemia in children with ESRD who are undergoing regular hemodialysis, have achieved the target hemoglobin levels, and have normal iron status.

Effective Management of Peritoneal Dialysis-Associated Hydrothorax in a Child: A Case Report.

Peritoneal dialysis (PD) confers many advantages, including a better quality of life for children with end-stage renal disease; however, the procedure is associated with several complications, including pleuroperitoneal leaks. Here, we report an unusual case of hydrothorax caused by long-term PD in a child, which was further complicated by pneumonia. A 9-year-old boy who had received CAPD for 22 months presented with dyspnea, swelling, and increased body weight. Chest tube drainage yielded 500 mL of transudative fluid. Computed tomography peritoneography revealed increased outflow from the peritoneum to the pleural cavity. PD was suspended, and hemodialysis (HD) was initiated. Video-assisted thoracoscopic surgery was performed; however, because the patient had pneumonia during hospitalization, pleural adhesions with a septated appearance occurred. This resulted in difficulties identifying pleuroperitoneal fistula (PPF). Right pleural effusion resolved following pleurodesis using bleomycin. Regular HD was performed for 10 weeks, and PD was subsequently reinitiated. There was no recurrence of hydrothorax during long-term follow-up. We suspect that the underlying mechanism of hydrothorax in our patient was associated with a PPF that formed either due to a congenital diaphragmatic defect or an acquired defect, resulting in dialysate leakage. Our case demonstrates that a temporary switch from PD to HD, accompanied by pleurodesis, may help resolve hydrothorax that occurs as a complication of long-term PD.

Late diagnosis of Lesch-Nyhan disease complicated with end-stage renal disease and tophi burst: a case report.

Background: Lesch-Nyhan disease (LND) is a rare X-linked recessive inborn error of purine metabolism. Late diagnosis of LND may cause significant morbidity. LND cases have never been reported in Indonesia.Case report: A 15-year-old male who had been diagnosed with cerebral palsy was referred to our hospital due to renal failure requiring emergency dialysis. The patient presented with three classic manifestations of LND: increased uric acid levels, neurological disorders, and self-injurious behaviors. LND was suspected because of an abscess-like lump on the left ankle that was confirmed to be a tophus, which had burst and discharged thick masses containing blood, debris, and white crystal materials. The diagnosis of LND was confirmed by the presence of a deletion to exon 1 of the HPRT1 gene. The patient received oral allopurinol daily and treatment for end-stage renal disease (ESRD), which included regular dialysis and subcutaneous administration of erythropoietin. At a 2-month follow-up, he improved clinically with a 71% decrease in uric acid levels after regular dialysis and allopurinol treatment.Conclusion: In developed countries, LND can be diagnosed as early as 3 days after birth. However, diagnosis in the present case was delayed due to the rarity of the disease and the limited number of facilities in Indonesia that offer genetic counseling. Late diagnosis of LND leads to ESRD and irreversible abnormalities. This is the first case of LND presenting with a unique clinical presentation of tophus burst reported in Indonesia.

Delayed Admission and Management of Pediatric Acute Kidney Injury and Multiple Organ Dysfunction Syndrome in Children with Multiple Wasp Stings: A Case Series.

Multiple wasp stings may cause fatal complications, such as anaphylactic reactions, intravascular hemolysis, rhabdomyolysis, acute kidney injury (AKI), increased levels of liver enzymes, clotting abnormalities, or even death. AKI-related mortality due to multiple wasp stings may reach 25%, occurring within the early onset of disease; therefore, renal function should be continuously monitored within the first few days following the stings. Herein, we report 2 cases of AKI due to multiple stings of wasp (Vespa affinis). In both cases, delayed hospital admissions and gradual loss of kidney function along with hemolysis and anemia without rhabdomyolysis were observed. Diuresis was reduced on the 10th day following the stings in the first case, whereas it occurred on the 5th day in the second case. Both cases had biopsy results of acute tubular injury and acute interstitial nephritis. The first case improved with intermittent hemodialysis, whereas the second required continuous renal replacement therapy and plasma exchange because hemolysis was more severe, which was presumably caused by a greater number of stings and larger amount of toxins involved. Multiple organ dysfunction syndrome was also observed in the second case; hence, high-dose steroid therapy was administered to alleviate interstitial fibrosis. Both cases showed that although AKI occurring after multiple wasp stings usually have fatal consequences. Administering fluid treatment and steroid therapy and selecting accurate renal replacement therapy modalities during the few first days after the stings may result in favorable long-term outcomes.