Nephrotic syndrome (NS) is a chronic renal disorder frequently diagnosed in children and characterized by proteinuria, hypoalbuminemia, hyperlipidemia, and edema. It is commonly classified into idiopathic nephrotic syndrome (INS) and secondary nephrotic syndrome, with the majority of pediatric cases being idiopathic. INS can be further categorized into steroid-sensitive nephrotic syndrome (SSNS) and steroid-resistant nephrotic syndrome (SRNS) based on therapeutic response [1]. The histopathological lesion most often associated with INS is minimal change disease (MCD), accounting for 80-90% of cases [2]. Globally, the estimated incidence of nephrotic syndrome in children is approximately 4.7 per 100,000,

with reported ranges from 1.15 to 16.9 per 100,000 [3]. Infection is a significant complication of nephrotic syndrome, contributing to high morbidity and mortality, especially in developing countries. Before corticosteroids and antibiotics, infections caused 50% of fatalities, with mortality rates reaching 40% in affected children [4]. In Bangladesh and India, the infection rate among children with nephrotic syndrome ranges from 38% to 83% [5]. Internationally, infection prevalence varies widely, from 15% to 38%, with severe bacterial infections (SBI) affecting approximately 15% of patients [6]. The susceptibility of children with nephrotic syndrome to infections is attributed to several factors, including urinary loss of immunoglobulins and complement factors, reduced serum albumin, impaired T-lymphocyte function, and the use of immunosuppressive therapies such as corticosteroids and cytotoxic agents [7,8]. Additional risk factors include tissue edema, which serves as a culture medium for pathogens, and hypovolemia, which reduces spleen perfusion and compromises immune function [8]. These immunological and physiological changes collectively increase the likelihood of bacterial infections [9]. Common infections in children with nephrotic syndrome include pneumonia, urinary tract infections (UTIs), spontaneous bacterial peritonitis (SBP), cellulitis, and sepsis. Among these, pneumonia and UTIs are the most frequently reported, followed by bacteremia, cellulitis, and other infections such as tuberculosis and meningitis [10]. The infection patterns vary geographically, emphasizing the need for localized studies to identify predominant pathogens and their antimicrobial sensitivity [11]. Infections in nephrotic syndrome not only contribute to acute morbidity but also impact long-term disease management. They are known to trigger relapses in SSNS, lead to steroid resistance, and necessitate repeated hospitalizations, which strain healthcare systems and adversely affect patient outcomes [9]. Moreover, Severe infections, including peritonitis and pneumonia, remain a major cause of mortality in nephrotic syndrome, with infection-related deaths accounting for about 1.5% of cases, particularly in developing countries. While corticosteroids and antibiotics have significantly reduced mortality rates, their benefits are often counter balanced by infection-related complications and treatment side effects [10]. Frequent relapses and the emergence of steroid dependency further complicate disease management and increase the burden on families and healthcare providers [1]. Given the high prevalence of infections and their significant impact on disease progression and management, it is crucial to investigate the infection patterns and risk factors in children with nephrotic syndrome. [12]. This study aims to evaluate the hematological and biochemical parameters associated with infections in children with nephrotic syndrome and to identify the causative organisms.

This rigorously designed prospective observational study was conducted at the Department of Paediatrics, Medical College for Woman and Hospital, Dhaka, Bangladesh, between March 2011 to September 2011, the study meticulously examined the incidence, characteristics, and patterns of infections in pediatric patients diagnosed with nephrotic syndrome. Using a purposive sampling method, 65 patients admitted through emergency services or the outpatient department were thoughtfully selected to form a well-characterized study cohort. Participant inclusion followed stringent criteria, ensuring the validity and clinical applicability of the findings.

Inclusion Criteria:

Children aged 2 to 12 years who met the ISKDC diagnostic criteria for nephrotic syndrome [13], including relapse cases admitted during the study period, were eligible irrespective of concurrent infections.

Exclusion Criteria:

Children with acute or chronic renal failure or those with urogenital anomalies were excluded from participation.

Data Collection

Data were comprehensively gathered using a structured and validated questionnaire, encompassing demographic and baseline clinical characteristics (age, gender, residence status, socio-economic classification), clinical and admission details (initial presentation, relapse episodes), laboratory parameters (elevated neutrophil counts, increased white blood cell [WBC] counts, reduced lymphocyte counts, elevated erythrocyte sedimentation rate [ESR], mean serum cholesterol, serum total protein, serum albumin, and serum creatinine levels), microbial analysis (Escherichia coli, Proteus species, Streptococcus species, Klebsiella species, and Haemophilus influenzae), and types of infections (urinary tract infections [UTI], peritonitis, septicemia, pneumonia, pharyngo-tonsillitis, cellulitis). Ethical clearance for the study was obtained from the institutional ethics committee, and informed consent was secured from the guardians of all participants.

Statistical Analysis

Data were analyzed using SPSS software (version 26). Continuous variables were expressed as mean ± standard deviation (SD), while categorical variables were presented as frequencies and percentages. Comparative analysis of quantitative variables was performed using an unpaired t-test, and the chi-square test was applied for categorical variables. A p-value of ≤0.05 was considered statistically significant, ensuring robust and reliable interpretations of the data.

A total of 65 participants were included in the study. The majority (64.62%) were aged 2-5 years, followed by 21.54% in the 6-8 years age group and 13.85% in the 9-12 years age group. The mean age was 4.86±2.74 years. Females constituted 60.00% of the cohort, and 61.54% of participants resided in rural areas. Most belonged to the middle socio-economic class (64.62%), while 35.38% were from the low socio-economic group (Table 1). Figure 1 illustrated that 67.69% of admissions were due to initial attacks, and 32.31% were due to relapses. Among the patients, 55.38% had no infections. Urinary tract infection was the most common, affecting 18.46%, followed by peritonitis (13.85%). Less frequent infections included septicemia (4.62%), pneumonia (3.08%), pharyngo-tonsillitis (3.08%), and cellulitis (1.54%) (Table 2). Table 3 showed that among the 29 children with infections, 82.76% had high neutrophil levels compared to 30.56% without infections (p<0.001). High WBC levels were seen in 55.17% and 50.00% of the infection and non-infection groups, respectively (p=0.876). Low lymphocyte levels were noted in 48.28% of children with infections and 47.22% without (p=0.412). High ESR levels were more frequent in the non-infection group (52.78%) than the infection group (44.83%) (p=0.422). Pus cells were present in 41.38% of children with infections and 61.11% without (p = 0.093). Haematuria was observed in 24.14% and 27.78% of the respective groups (p = 0.539). Laboratory values showed no significant differences between the groups. Mean serum cholesterol levels were 371.45±79.33 mg/dL and 412.28±72.43 mg/dL (p=0.072). Mean serum total protein, albumin, and creatinine levels were also comparable, 4.86±0.27 and 4.36±0.21 gm/dl (Table 3). Among the 29 infected children, Escherichia coli (34.48%) was the most common pathogen, followed by Proteus species (24.14%), Streptococcus species (20.69%), Klebsiella species (17.24%), and Haemophilus influenzae (3.45%) (Table 4). Escherichia coli was the most common pathogen in urinary tract infections (38.46%) and peritonitis (50.00%). Streptococcus pneumoniae predominated in septicemia (50.00%) and pharyngo-tonsillitis (100.00%), while Streptococcus species was solely isolated in cellulitis (100.00%). Pathogens in pneumonia cases were evenly distributed among Escherichia coli, Proteus species, and Haemophilus influenzae (33.33% each) (Table 5).

   Table 1: Socio-demographic profile of the study cohort (N=65).

   Figure 1: Admission profile of the study population (N=65).

   Table 2: Incidence of infections in nephrotic syndrome patients (N=65).

 Table 3: Laboratory investigation results and infection status among the study population of children (N=65).

Table 4: Distribution of pathogenic organisms responsible for infections in studied children (N=29).

Table 5: Distribution of isolated pathogens in studied children based on infection type, body fluid, and skin (N=29).

Children diagnosed with nephrotic syndrome exhibit a compromised immune system, which increases their vulnerability to infections from a wide range of sources [5,14]. The age distribution in the study indicated that younger children were more susceptible to infections than their older counterparts. Specifically, 64.62% of infections in children with nephrotic syndrome occurred between the ages of 2 and 5 years [15]. Similarly, Senguttuvan et al. reported that 62% of children with nephrotic syndrome experienced infections before the age of six, supporting the results of our study [16]. In our cohort, 40% of the children were male and 60% were female. This gender distribution contrasts with previous studies, which found a higher prevalence of nephrotic syndrome in boys compared to girls [12,17]. In our study, 67.69% of the children presented with an initial episode of nephrotic syndrome, while 32.31% experienced a relapse. This is consistent with the findings of Hossain et al. (1982), where initial cases accounted for 72% of the total [18]. Comparable research by Moorani (2011) and revealed that 44.62% of nephrotic syndrome patients had infections in our study [15,18]. However, Eddy and Symons (2003) reported a significantly lower rate of severe infections, with only 19% of affected children in Taiwan experiencing such complications [11]. Urinary tract infections (UTIs) were the most commonly observed infection in our study, accounting for 18.46%. This finding contrasts with the lower incidence of UTIs [12]. Peritonitis, a severe complication of nephrotic syndrome, was suspected in 13.85% of our patients based on clinical signs such as fever, abdominal tenderness, vomiting, and ascites.

Pneumonia was diagnosed in 3.02% of our cohort, a significantly lower rate than the 12.9% [12]. Additionally, Eddy and Symons (2003) found that pneumonia was more common in children under 10 years of age, while UTIs were more prevalent in children older than 10 [11]. In our study, pharyngo-tonsillitis was observed in 3.08% of cases. Moorani (2011) noted a significant decline in the incidence of skin infections among children with nephrotic syndrome, from 28% to just 2% over the years [5]. In our study, only one child was diagnosed with cellulitis, a finding consistent with research conducted in India [16]. Our analysis of hematological parameters revealed that children with infections had significantly elevated neutrophil counts. While serum albumin, cholesterol, and creatinine levels showed marginal significance in our study, previous research has indicated that children with low serum albumin and elevated serum cholesterol are at a substantially higher risk of infection [12,9]. Among the isolated pathogens, Escherichia coli was the most prevalent, accounting for 34.48% of the cases, followed by Proteus species at 24.14%. At least one isolate of Escherichia coli was detected in urine, peritoneal fluid, and blood samples. Klebsiella species were identified in 17.24% of urine samples from patients with UTIs and in blood samples from children with septicemia, consistent with the findings of Adeleke and Asani (2009) [20]. Additionally, Streptococcus species accounted for 20.69% of isolates from patients with septicemia, pharyngo-tonsillitis, and cellulitis in our study. We also identified a single isolate of Haemophilus influenzae in a child with pneumonia. Seasonal variations in infection rates and their impact on nephrotic syndrome were not assessed, potentially limiting the broader applicability of the findings across different time periods.

Infections remain a significant complication in children with nephrotic syndrome, contributing to considerable morbidity. Our study found that the majority of children affected were in the 2-5 years age group, with urinary tract infections being the most common, followed by peritonitis and septicemia. Elevated neutrophil levels were strongly associated with infection, while other hematological parameters showed minimal differences. Escherichia coli was the predominant pathogen, highlighting the importance of targeted microbiological surveillance. These findings underscore the need for proactive infection prevention and management strategies in pediatric nephrotic syndrome to improve clinical outcomes and reduce hospitalization rates.

1. Woroniecki RP, Orlova TN, Mendelev N, Shatat IF, Hailpern SM, Kaskel FJ, Goligorsky MS, O’Riordan E. Urinary proteome of steroid-sensitive and steroid-resistant idiopathic nephrotic syndrome of childhood. American journal of nephrology. 2006 Jul 19;26(3):258-67.
2. Waldman M, Crew RJ, Valeri A, Busch J, Stokes B, Markowitz G, D'Agati V, Appel G. Adult minimal-change disease: clinical characteristics, treatment, and outcomes. Clinical Journal of the American Society of Nephrology. 2007 May 1;2(3):445-53.
3. Martin JA, Kochanek KD, Strobino DM, Guyer B, MacDorman MF. Annual summary of vital statistics—2003. Pediatrics. 2005 Mar 1;115(3):619-34.
4. McGee S, Hirschmann J. Use of corticosteroids in treating infectious diseases. Archives of internal medicine. 2008 May 26;168(10):1034-46.
5. Bagga A, Mantan M. Nephrotic syndrome in children. Indian Journal of medical research. 2005 Jul 1;122(1):13.
6. Myers C, Gervaix A. Streptococcus pneumoniae bacteraemia in children. International journal of antimicrobial agents. 2007 Nov 1;30:24-8.
7. Hogg RJ, Portman RJ, Milliner D, Lemley KV, Eddy A, Ingelfinger J. Evaluation and management of proteinuria and nephrotic syndrome in children: recommendations from a pediatric nephrology panel established at the National Kidney Foundation conference on proteinuria, albuminuria, risk, assessment, detection, and elimination (PARADE). Pediatrics. 2000 Jun 1;105(6):1242-9.
8. Laopornpichayanuwat S. Nephrotic Syndrome in Thai Children: Nakornping Hospital Experience. Siriraj Medical Journal. 2006 Feb 1;58(2):648-53.
9. Tosi MF. Innate immune responses to infection. Journal of Allergy and Clinical Immunology. 2005 Aug 1;116(2):241-9.
10. Davis AT, Freeman A, Guzman-Cottrill J, Jaggi P, Shulman ST, Tan TQ, Yogev R. 112 BACTERIAL INFECTIONS. PEDIATRICS Just the Facts. 2005:387.
11. Eddy AA, Symons JM. Nephrotic syndrome in childhood. The lancet. 2003 Aug 23;362(9384):629-39.
12. Constantinescu AR, Shah HB, Foote EF, Weiss LS. Predicting first-year relapses in children with nephrotic syndrome. Pediatrics. 2000 Mar 1;105(3):492-5.
13. Barnett, H. L. (1982). Early identification of frequent relapsers among children with minimal change nephrotic syndrome The journal of pediatrics. 1982 Oct;101(4):514-18.
14. Niaudet P, Boyer O. Idiopathic nephrotic syndrome in children: clinical aspects. Pediatric nephrology. 2009;6:667-92.
15. Lalita Jyotsna P, Sharma S, Trivedi SS. 50th Golden Jubilee Conference of Indian Society of Hematology & Transfusion Medicine. Indian J. Hematol. Blood Transfus.;25(4):130-99.
16. Senguttuvan P, Ravanan K, Prabhu N, Tamilarasi V. Infections encountered in childhood nephrotics in a pediatric renal unit. Indian Journal of Nephrology. 2004 Jul 1;14(3):85-8.
17. Kim JS, Bellew CA, Silverstein DM, Aviles DH, Boineau FG, Vehaskari VM. High incidence of initial and late steroid resistance in childhood nephrotic syndrome. Kidney international. 2005 Sep 1;68(3):1275-81.
18. Hossain MM, Ara H, Khan MR. A study of nephrotic syndrome in children at IPGMR. Bangladesh Paediatric. 1982;6(1):25-8.
19. Hingorani SR, Weiss NS, Watkins SL. Predictors of peritonitis in children with nephrotic syndrome. Pediatric nephrology. 2002 Aug;17:678-82.
20. Adeleke SI, Asani MO. Urinary tract infection in children with nephrotic syndrome in Kano, Nigeria. Annals of African medicine. 2009 Jan 1;8(1):38-41.