Incidence and Types of Infection in Children with Nephrotic Syndrome

Abstract

Background: Nephrotic syndrome (NS) is one of the most common chronic glomerular diseases in childhood and represents a significant proportion of pediatric renal disorders worldwide. It is clinically characterized by heavy proteinuria (≥40 mg/m²/hour or ≥3+ on dipstick), hypoalbuminemia (serum albumin <2.5 g/dL), generalized edema, and hyperlipidemia. The condition most commonly affects children between 2 and 8 years of age, with a slight male predominance. Although many children respond well to corticosteroid therapy, the disease often follows a relapsing–remitting course, leading to repeated hospital visits and prolonged treatment exposure. The pathophysiology of nephrotic syndrome involves increased permeability of the glomerular basement membrane, resulting in significant urinary loss of plasma proteins, particularly albumin. In addition to albumin, important immune proteins such as immunoglobulins (especially IgG) and complement factors (e.g., factor B and properdin) are also lost in the urine. This loss compromises the body’s humoral immune defense, predisposing affected children to bacterial infections. Furthermore, defects in T-cell function and impaired cell-mediated immunity have been observed in nephrotic syndrome, which further increases susceptibility to infections. Another important contributing factor is the presence of generalized edema. The accumulation of protein-rich interstitial and peritoneal fluid provides a favorable medium for bacterial growth, increasing the risk of infections such as spontaneous bacterial peritonitis and cellulitis. Malnutrition, which is common in children with chronic illness, may further weaken immune defenses and exacerbate vulnerability. Treatment-related immunosuppression also plays a significant role. Corticosteroids, which are the mainstay of therapy, suppress inflammatory and immune responses. In frequently relapsing or steroid-dependent cases, additional immunosuppressive agents such as cyclophosphamide, calcineurin inhibitors, or mycophenolate mofetil may be used, further increasing the risk of opportunistic and severe infections. Prolonged therapy and repeated relapses amplify this risk over time. Infections remain one of the most serious and potentially life-threatening complications of nephrotic syndrome in children. Common infections include urinary tract infections, respiratory tract infections, peritonitis, septicemia, and skin infections. In developing countries, limited access to healthcare, delayed presentation, poor sanitation, and incomplete vaccination coverage may contribute to higher infection rates and worse outcomes. In fact, infections are a leading cause of hospitalization, relapse, and mortality among children with nephrotic syndrome. Given the substantial burden of infectious complications and their impact on morbidity and survival, early recognition, preventive strategies, vaccination, close monitoring during relapses, and prompt, appropriate antimicrobial therapy are essential. Understanding the mechanisms and risk factors associated with infection in nephrotic syndrome is therefore crucial for improving clinical outcomes in this high-risk pediatric population. Objective: The primary objective of this study was to determine the incidence of infections among children diagnosed with nephrotic syndrome during the study period. The study aimed to quantify how frequently infectious complications occur in both newly diagnosed and relapsing cases, thereby highlighting the burden of infection in this vulnerable pediatric population. A secondary objective was to identify and categorize the spectrum of infections observed in these patients. This included determining the most common sites of infection—such as urinary tract, respiratory tract, peritoneum, skin, and bloodstream—and identifying the predominant causative microorganisms through microbiological evaluation. Understanding the pattern of infections would help in guiding empirical antibiotic therapy and preventive strategies. In addition, the study sought to evaluate clinical and laboratory risk factors associated with increased susceptibility to infections. These factors included age, gender, nutritional status, presence and severity of edema, frequency of relapses, duration and dose of corticosteroid therapy, use of other immunosuppressive agents, serum albumin levels, and other relevant laboratory parameters. By analyzing these variables, the study aimed to determine significant predictors of infection and identify high-risk groups requiring closer monitoring and early intervention. Overall, the objective was to generate comprehensive data that could contribute to improved clinical management, timely diagnosis, and prevention of infectious complications in children with nephrotic syndrome. Methods: This prospective observational study was conducted in the Department of Pediatrics at People University of Medical and Health Sciences hospital over a period of 06 months. A total of 120 children aged 1–14 years diagnosed with nephrotic syndrome, including both newly diagnosed and relapse cases, were enrolled after obtaining informed consent from parents or guardians. Detailed clinical history and thorough physical examination were performed for each patient. Laboratory investigations included complete blood count, serum albumin, renal function tests, urine routine examination, urine culture, blood culture (where indicated), chest radiography, and ascitic fluid analysis in suspected cases of peritonitis. Infections were diagnosed based on clinical features supported by laboratory and microbiological evidence. Patients were monitored throughout hospitalization and follow-up visits for the development of infectious complications. Data were entered and analyzed using SPSS version 26. Descriptive statistics were calculated for frequencies and percentages, and inferential statistics were applied to determine associations between infection risk and variables such as serum albumin levels, steroid therapy, age, and relapse status. A p-value of < 0.05 was considered statistically significant. Results: Out of 120 enrolled children, 56 (46.7%) developed one or more infectious episodes during the study period. The most frequently observed infections were urinary tract infections (28%), respiratory tract infections (24%), peritonitis (18%), and skin and soft tissue infections (15%). Less common infections included sepsis and cellulitis. Gram-negative organisms were the predominant causative agents, particularly Escherichia coli in urinary tract infections and Klebsiella species in peritonitis cases. Statistical analysis revealed that severe hypoalbuminemia (serum albumin <2.0 g/dL), presence of edema, and ongoing corticosteroid therapy were significantly associated with a higher risk of infection (p < 0.05). Additionally, infections were more common during relapse episodes compared to remission phases. Conclusion: Infections are frequent and significant complications in children with nephrotic syndrome, particularly during relapse and while receiving steroid therapy. Urinary tract infections and respiratory tract infections were the most common infectious manifestations, with Gram-negative organisms predominating. Identification of risk factors such as severe hypoalbuminemia and immunosuppressive therapy is essential for early intervention. Preventive strategies, vigilant monitoring, and prompt treatment can substantially reduce morbidity and improve clinical outcomes in this vulnerable pediatric population.