BackgroundMembranoproliferative glomerulonephritis (MPGN) is a rare glomerular disorder characterized by immune complex or complement-mediated injury, often leading to nephrotic syndrome, hypertension, and progressive renal dysfunction. Its management remains challenging, particularly in pediatric patients with coexisting renal pathologies.Case presentationWe report a case of an 11-years-old girl who presented with nephrotic syndrome, severe hypertension, and impaired renal function. Renal biopsy confirmed immune complex-mediated MPGN (IC-MPGN), and genetic testing revealed a homozygous, pathogenic missense PKHD1 variant (NM_138694.3:c.4870C > T; p.(Arg1624Trp), leading to a diagnosis of autosomal recessive polycystic kidney disease (ARPKD). Initial treatment with prednisolone and mycophenolate mofetil failed to halt disease progression, and the patient became dialysis dependent. Pegcetacoplan, a complement C3 inhibitor, was subsequently initiated. After 11 weeks of pegcetacoplan therapy, the patient achieved renal recovery and was successfully weaned from dialysis. Proteinuria decreased from nephrotic to sub-nephrotic levels without significant adverse effects.ConclusionTo our knowledge, this is the first pediatric case of IC-MPGN with genetically confirmed ARPKD successfully treated with pegcetacoplan. The case illustrates that renal recovery occurred following initiation of proximal complement inhibition with pegcetacoplan.

Introduction:Thrombotic microangiopathies (TMAs) are a group of rare, life-threatening disorders characterized by a classic triad of MAHA, severe thrombocytopenia, and ischemic tissue injury. Thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) are the main types of TMAs. Based on the cause, HUS can be classified as typical or atypical. Case Presentation:We present the case of a 4-year-old child referred to King Fahad Medical City in Riyadh, Saudi Arabia, with complaints of bloody diarrhea, vomiting, and fever. The condition progressed to altered consciousness, seizures, and quadriparesis. Result:Upon admission, the patient received plasma infusion and underwent peritoneal dialysis. Eculizumab therapy was initiated 1 week after the presentation. Hematological and renal parameters improved rapidly, but neurological recovery was gradual, with significant progress observed over 6 years of follow-up. Conclusion:This case highlights that severe neurological manifestations can be an initial feature of HUS, not just TTP. Eculizumab was effective and life-saving in pediatric patients with TMA and severe neurological involvement, though CNS recovery may take years.

Post-infectious glomerulonephritis (PIGN) and atypical hemolytic uremic syndrome (aHUS) can overlap due to alternative complement pathway dysregulation. We report a 4-year-old boy with edema, hypertension, hematuria, and reduced urine output. Laboratory findings included hemoglobin of 11.5 g/dL, platelets of 350 × 109/L, protein/creatinine ratio of 0.6 g/mmol, serum creatinine of 125 μmol/L, C3 of 0.3 g/L, and biopsy-confirmed PIGN. Despite supportive care, corticosteroids, and mycophenolate mofetil, kidney function remained impaired. Ten weeks later, the patient developed thrombotic microangiopathy (TMA) with hemoglobin of 6.5 g/dL, platelet count of 90 × 109/L, and creatinine of 180 μmol/L. Eculizumab was initiated promptly, resulting in rapid hematologic normalization and kidney recovery. Genetic testing revealed mutations in CFHR1/CFHR3 and CD46, confirming susceptibility to complement-mediated aHUS. This case shows that PIGN may trigger aHUS in genetically predisposed children and underscores the need for early recognition and prompt complement inhibition to prevent kidney injury and achieve remission.

Lupus nephritis (LN) affects approximately 60–70

INTRODUCTION:Pegcetacoplan is a novel C3/C3b inhibitor with potential as a treatment for C3 glomerulopathy (C3G) and primary immune-complex membranoproliferative glomerulonephritis (IC-MPGN), both caused by complement system dysfunction. METHODS:We conducted a real-world observational cohort study to evaluate the efficacy and safety of pegcetacoplan in pediatric and adult patients, largely resistant to conventional immunosuppression. These patients were treated outside clinical trials and identified through the CompCure registry and an international survey. Changes in urine protein-to-creatinine ratio (uPCR), estimated glomerular filtration rate (eGFR), and serum C3 at one, three, six and twelve months were evaluated. RESULTS:25 patients (18 C3 glomerulonephritis, 3 Dense Deposit Disease, 4 primary IC-MPGN) initiated pegcetacoplan therapy at a median age of 14.9 years at a median 2.7 years after diagnosis. Median uPCR at baseline was 3.5 g/g, mean eGFR was 74 ml/min per 1.73 m2, and 19 of 25 patients had low serum C3. After pegcetacoplan initiation we observed a rapid and sustained reduction of proteinuria: uPCR decreased by 81% in six months, with 68% of patients achieving under 1 g/g and 12% achieving complete and 64% partial remission. Serum C3 increased to the normal or supranormal range in all but one case with suspected non-adherence. The eGFR significantly increased by month three (9.4 ml/min per 1.73 m2) and six (12 ml/min per 1.73m2) and remained stable at twelve months in patients with available follow-up data. Sequential biopsies available in four cases showed variable changes, ranging from complete disappearance to persistence of C3 deposits, of chronic lesions, and occasional tubulo-epithelial damage. No serious adverse events occurred during 222 months of cumulative exposure. CONCLUSIONS:Pegcetacoplan demonstrated rapid and sustained efficacy with good safety despite two potential drug-related concerns in C3G and primary IC-MPGN, highlighting its potential for broader application and the need for further research to optimize patient selection and treatment strategies.

Atypical hemolytic uremic syndrome (aHUS) is a severe condition marked by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury (AKI). It may result from complement gene mutations or be triggered by other underlying conditions. Glucose-6-phosphate dehydrogenase (G6PD) is an enzyme that protects red blood cells, and its deficiency can cause hemolytic anemia when triggered by certain factors. We report two cases of children diagnosed with G6PD deficiency who initially presented with clinical features of aHUS. In both cases, young boys developed severe AKI and hemolysis, requiring dialysis and treatment with complement inhibitors. A genetic study identified pathogenic mutations in the G6PD gene. Misdiagnosis delayed appropriate management of their underlying condition, highlighting the importance of considering G6PD deficiency in the differential diagnosis of hemolytic anemia, particularly in pediatric patients from high-risk ethnic backgrounds or those with severe hemolysis. To our knowledge, this is the first reported case series in Saudi Arabia linking G6PD deficiency to clinical presentations of aHUS.

Atypical hemolytic uremic syndrome (aHUS) is a life‑threatening condition characterized by microangiopathic hemolytic anemia, thrombocytopenia, as well as acute kidney injury (AKI). It can occur primarily due to complement gene mutations or secondary to another underlying condition. Several cases with Wilms' tumor gene 1 (WT1) mutations that presented with aHUS have been reported. Here, we report four cases of children diagnosed with WT1 mutations and presented initially with aHUS. There are two boys and two girls who presented with thrombotic microangiopathy (TMA), high lactate dehydrogenase, fragmented red blood cell (RBCs), and severe hypertension. All of them were anuric from the first presentation. Therapy with C5 inhibitors was initiated immediately and was associated with hematological remission without renal recovery. Renal replacement therapy (RRT) was started for all of the patients. A renal biopsy was conducted on two patients and showed global glomerulosclerosis. A genetic study identified pathogenic mutations in the WT1 gene. Two of the patients became dialysis dependent, and two patients underwent renal transplantation without the recurrence of aHUS. Our case series emphasizes that a diagnosis of WT1 mutation can be considered in children with aHUS with severe renal manifestations without a response to C5 inhibitors and with global glomerulosclerosis on renal biopsy. To our knowledge, this is the first report of a series of cases of WT1 mutations in pediatric patients presenting with clinical manifestation manifestations of aHUS. This unique finding highlights an association between HUS and WT1 mutation.

Background This study aimed to determine the prevalence and etiology of kidney failure (KF) among children below 15 years of age receiving chronic dialysis in Saudi Arabia and describe their dialysis modalities. Methods This cross-sectional descriptive study was conducted on 8 August 2022, encompassing all 23 pediatric dialysis centers in Saudi Arabia. Data gathered comprised patient demographics, causes of KF, and the dialysis methods employed. Collected data underwent analysis to determine prevalence of children undergoing chronic dialysis, discern underlying causes of KF, and evaluate distribution of patients across different dialysis modalities. Results The prevalence of children on chronic dialysis is 77.6 per million children living in Saudi Arabia, equating to 419 children. The predominant underlying cause of KF was congenital anomalies of the kidneys and urinary tract (CAKUT), representing a substantial 41% of cases. Following this, others or unknown etiologies accounted for a noteworthy 25% of cases, with focal segmental glomerulosclerosis (FSGS) comprising 13%, glomerulonephritis at 11%, and congenital nephrotic syndrome contributing 10% to etiological distribution. Regarding dialysis modalities employed, 67% of patients were on peritoneal dialysis (PD), while the remaining 33% were on hemodialysis (HD). Conclusions This first nationwide study of pediatric chronic dialysis in Saudi Arabia sheds light on the prevalence of children undergoing chronic dialysis and underlying causes of their KF, thereby contributing to our understanding of clinical management considerations. This research serves as a stepping stone for the development of national registries. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information .

Background: Atypical hemolytic uremic syndrome (aHUS) is a rare, life-threatening thrombotic microangiopathy (TMA), which has been treated successfully with eculizumab. The optimal duration of eculizumab in treating patients with aHUS remains poorly defined. Methods: We conducted a multicenter retrospective study in the Arabian Gulf region for children of less than 18 years of age who were diagnosed with aHUS and who discontinued eculizumab between June 2013 and June 2021 to assess the rate and risk factors of aHUS recurrence. Results: We analyzed 28 patients with a clinical diagnosis of aHUS who had discontinued eculizumab. The most common reason for the discontinuation of eculizumab was renal and hematological remission (71.4%), followed by negative genetic testing (28.6%). During a median follow-up period of 24 months after discontinuation, 8 patients (28.5%) experienced HUS relapse. The risk factors of recurrence were positive genetic mutations (p = 0.020). On the other hand, there was no significant relationship between the relapse and age of presentation, the need for acute dialysis, the duration of eculizumab therapy before discontinuation, or the timing of eculizumab after the presentation. Regarding the renal outcomes after discontinuation, 23 patients were in remission with normal renal function, while 4 patients had chronic kidney disease (CKD) (three of them had pre-existing chronic kidney disease (CKD) before discontinuation, and one case developed a new CKD after discontinuation) and one patient underwent transplantation. Conclusions: The discontinuation of eculizumab in patients with aHUS is not without risk; it can result in HUS recurrence. Eculizumab discontinuation can be performed with close monitoring of the patients. It is essential to assess risk the factors for relapse before eculizumab discontinuation, in particular in children with a positive complement variant and any degree of residual CKD, as HUS relapse may lead to additional loss of kidney function. Resuming eculizumab promptly after relapse is effective in most patients.

Background and ObjectivePeritoneal dialysis (PD) associated peritonitis is the most common cause of morbidity, mortality, and treatment failure in patients undergoing PD. We aimed to identify the incidence, pathogens, antibiotic susceptibility, and the outcome of peritoneal dialysis (PD)-associated peritonitis in children.MethodsData from medical records of children who underwent PD between 2007 and 2018 in King Fahad Medical City were retrospectively collected. All children aged <14 years undergoing chronic PD were included. The demographic characteristics of patients, peritonitis rates, and clinical outcomes‏ were collected.ResultsIn total, 131 children [boys, 68 (51.9%)] underwent automated PD for 305 years. The most common age group was 6–12 years (61 patients, 46.6%). A total of 74.0% of patients were new to dialysis; 25.2% were transferred from hemodialysis. Peritonitis incidence was 0.6 episodes/patient-year. Gram-positive and -negative organisms were identified in 50.1% and 22% episodes, respectively, whereas cultures remained negative in 20.5% episodes. Coagulase-negative Staphylococcus was the most common isolated organism (22.1%), followed by methicillin-sensitive S. aureus (11.1%). Peritonitis was resolved in 153 (73.6%) episodes, whereas 52 (25.0%) episodes required removal through the catheter. The multivariate logistic regression analysis found the exit site infection to be a risk factor for catheter removal. Three (1.4%) episodes caused death due to peritonitis complicated by septic shock‏.ConclusionsOur data showed that the most common organisms causing peritonitis were similar to those reported in the previous international registry. The rate of peritonitis was high, but markedly improved in the past two years.

Background Encapsulating peritoneal sclerosis is a rare but potentially lethal complication of long-term peritoneal dialysis that is associated with significant morbidity and mortality. The occurrence of encapsulating peritoneal sclerosis varies worldwide, but is increased in patients maintained on peritoneal dialysis for 5–8 years. The etiology of encapsulating peritoneal sclerosis remains unidentified, and a high index of clinical suspicion is required for diagnosis. Case presentation We report a 5-year-old Saudi female with end-stage renal disease secondary to nephronophthisis type 2. She underwent peritoneal dialysis for 30 months, with four episodes of peritonitis. She presented with clinical signs of peritonitis. Three days later, she developed septic shock, which required pediatric intensive care unit admission. The peritoneal dialysis catheter was removed because of refractory peritonitis. Her course was complicated by small bowel perforation, and severe adhesions were revealed on abdominal ultrasound and computed tomography, consistent with a diagnosis of EPS. This finding was later confirmed by diagnostic laparotomy performed twice and complicated by recurrent abdominal wall fistula. She received total parenteral nutrition for 6 months and several courses of antibiotics. The patient received supportive treatment including nutritional optimization and treatment for infection. No other treatments, such as immunosuppression, were administered to avoid risk of infection. Following a complicated hospital course, the patient restarted oral intake after 6 months of total parenteral nutrition dependency. Her abdominal fistula resolved completely, and she was maintained on hemodialysis for few years before she received a kidney transplant. Conclusion When treating patients using peritoneal dialysis, it is important to consider encapsulating peritoneal sclerosis with refractory peritonitis, which is not always easy to identify, particularly if the patient has been maintained on peritoneal dialysis for less than 3 years. Early identification of encapsulating peritoneal sclerosis and appropriate conservative treatment, including nutritional optimization and treatment of infections, are essential to achieve a better prognosis.

Glomerular diseases are considered to be a significant cause of chronic kidney disease. Kidney biopsy continues to be an essential diagnostic tool. We review the renal biopsies which were done on children below the age of 14 years in the past 10 years (from January 2008 to September 2018) in a single tertiary pediatric hospital in Saudi Arabia to determine the patterns of renal disease among Saudi children as well-correlating clinical presentation with histopathological diagnosis. A total of 203 pediatric kidney biopsies were performed. The mean age was 7.3 ± 3.9 years (3 months to 14 years). There were 105 males and 98 females. The most frequent indication for renal biopsy was nephrotic syndrome in 58.9% of patients, followed by acute glomerulo- nephritis in 20.8%. Other indications included significant proteinuria, persistent microscopic hematuria, acute kidney injury of uncertain etiology, in the remaining 20% of biopsies. Clinical diagnosis was consistent with histopathological diagnosis in 92% of the cases. Minimal change disease was the most common cause of primary glomerular diseases in 37.4%, followed by focal segmental glomerulosclerosis in 20.2%. Lupus nephritis represents the most common cause of the secondary renal disease (8.4%). Complications of kidney biopsy were observed in only 16.3% of patients, of whom 9.9% had perirenal hematomas and 6.4% of the patients developed either microscopic hematuria or macroscopic hematuria.

Introduction: Genetic defects that determine uncontrolled activation of the alternative complement pathway have been well documented, which account for approximately 40–60% of atypical hemolytic uremic syndrome (aHUS) cases worldwide. In Saudi Arabia, nearly half of the marriages are consanguineous, resulting in a high prevalence of such genetic diseases. Recent studies have demonstrated the effectiveness of eculizumab against aHUS. Objective: We report our experience of using plasma therapy or/and eculizumab to treat children with aHUS in a tertiary care center in Saudi Arabia and to compare their clinical characteristics, genetic mutations, and treatment outcomes. Methods: A retrospective cohort study was conducted between January 2010 and May 2017. Data, including demographic parameters, clinical presentation, hospital stay duration, need for dialysis, renal recovery, genetic mutations, and outcomes, were obtained from electronic medical records of all eligible patients. Results: Overall, 21 children with aHUS were included, of which 12 (57.1%) received eculizumab therapy and 9 (42.9%) received only plasma therapy. End-stage renal disease occurred in 7 children (33.3%), of which 4 (57.1%) received only plasma therapy and 3 (42.9%) received eculizumab therapy whose genetic mutations were not related to the complement dysregulation system. No child who received eculizumab therapy showed recurrence; however, 3 children (33.3%) who received plasma therapy alone showed recurrence. Genetic mutations were detected in 12/20 (60%) of those who underwent genetic screening. Conclusions: Children who received eculizumab therapy showed good renal recovery and maintained remission compared with children who received plasma therapy alone. Genetic mutations were detected in 60% of the patients, which was associated with a high prevalence of consanguineous marriages.

Background: Dense deposit disease (DDD), a subtype of C3 glomerulopathy, is a rare disease that occurs secondary to hyperactivity of the alternative complement pathway. Renal biopsy typically reveals electron-dense deposits in the glomerular basement membrane. However, treatment options are limited. Till date, to the best of our knowledge, no evidence exists for specific treatment influencing the disease course. Eculizumab, a monoclonal antibody, has been reported to prevent membrane attack complex formation by binding to C5 and leads to improvement in clinical findings. However, the number of reported cases in which eculizumab was administered, particularly in children, is limited. Subjects and Methods: In this report, we present our experience with three pediatric cases of DDD receiving eculizumab treatment. All three patients were diagnosed with DDD on kidney biopsy. All patients showed acute kidney injury, high blood pressure, proteinuria >1 g/day, and decreased C3 levels. Immunosuppressive therapy, which included high-dose methylprednisolone, prednisolone, mycophenolate mofetil, or plasma exchange (in the third patient), as well as antihypertensive drugs, was administered to all the patients. Eculizumab treatment was initiated early in two patients but was initiated later in the third patient, who underwent dialysis initially. Results: The two patients with early initiation of eculizumab treatment showed significant improvement of proteinuria and renal function within weeks of treatment. C3 levels were normalized in one patient but remained decreased in the other. The third patient showed no response. She ultimately progressed to end-stage renal disease and eventually needed maintenance dialysis. Conclusions: Early initiation of eculizumab was associated with decreased proteinuria and improved renal function in two patients. These findings were in agreement with previous reports on the beneficial effects of eculizumab in DDD patients.

Atypical hemolytic uremic syndrome (aHUS) is a rare, life-threatening illness characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury (AKI). Plasma therapy, previously considered the primary treatment for this condition, is associated with death and permanent kidney injury in over 50% of patients. Eculizumab, a monoclonal antibody that blocks C5, is far more effective and is the current treatment of choice, but it is not widely available. An 18-month-old boy presented with AKI, anemia, and normal platelet count. While managed initially as proliferative antineutrophil cytoplasmic antibody-associated glomerulonephritis, a diagnosis of partial HUS was suggested by low levels of complement C3, complement factor I (CFI) and complement Factor B (CFB), and histological changes suggesting microangiopathy without thrombi. Later, next-generation sequencing indicated homozygous pathogenic mutations in CFI and heterozygous variations in C3 and CFB. Corticosteroid pulses and plasmapheresis were ineffective in resolving the need for dialysis, and hypertension was refractory to polytherapy. Therapy with eculizumab, initiated only after 5 months on dialysis, was associated with rapid increase in urine output, control of hypertension, and slow but complete renal recovery. Dialysis was discontinued after 5 months of eculizumab therapy, and renal function has been within normal range after 33 months of initiating therapy with eculizumab. Our case emphasizes that a diagnosis of aHUS should be considered in the appropriate clinical setting even in the absence of thrombocytopenia. Kidney biopsy and genetic testing are useful in confirming the diagnosis. Therapy with eculizumab in patients with severe AKI may be associated with complete renal recovery even if therapy is delayed by several months.