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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2021  |  Volume : 32  |  Issue : 1  |  Page : 204-208
Clinical and Histopathological Profile of Adolescent onset Idiopathic Nephrotic Syndrome in North Indian Children

1 Department of Pediatrics, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India
2 Department of Pediatrics, Division of Pediatric Nephrology, Lady Hardinge Medical College and Kalawati Saran Children’s Hospital, New Delhi, India
3 Department of Pediatrics, Postgraduate Institute of Medical Education and Research and Dr. Ram Manohar Lohia Hospital, New Delhi, India
4 Department of Pathology, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research, New Delhi, India
5 Department of Biostatistics, All India Institute of Medical Science, New Delhi, India

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Date of Web Publication16-Jun-2021


Adolescent onset idiopathic nephrotic syndrome (INS) is marked by increased incidence atypical features and non-minimal change disease in histopathology. The objective of the study was to analyze the clinical features and histopathological spectrum of adolescent-onset INS. It was conducted in a Pediatric nephrology clinic of a tertiary care hospital in North India. We retrospectively evaluated clinical features, biochemical investigations and histopathology of 33 adolescents with idiopathic NS registered in pediatric nephrology clinic. Twenty-three (70.0%) adolescents had steroid resistant nephrotic syndrome. Hematuria was present in 39%, hypertension 36% and acute kidney injury (AKI) in 27%. Three-fourth of adolescents who underwent biopsy had non-minimal change disease in histopathology. Adolescent onset INS have increased incidence of AKI, hypertension, and non-minimal change disease.

How to cite this article:
Kapoor K, Saha A, Dubey NK, Batra VV, Upadhyay AD. Clinical and Histopathological Profile of Adolescent onset Idiopathic Nephrotic Syndrome in North Indian Children. Saudi J Kidney Dis Transpl 2021;32:204-8

How to cite this URL:
Kapoor K, Saha A, Dubey NK, Batra VV, Upadhyay AD. Clinical and Histopathological Profile of Adolescent onset Idiopathic Nephrotic Syndrome in North Indian Children. Saudi J Kidney Dis Transpl [serial online] 2021 [cited 2022 Nov 28];32:204-8. Available from: https://www.sjkdt.org/text.asp?2021/32/1/204/318525

   Introduction Top

The adolescent age signifies the transition period where the occurrence of histopathological lesions in patients with nephrotic syndrome (NS) is different from that seen in young children[1] as well as that seen in adults.[2] Adolescent onset idiopathic NS (INS) may have increased incidence of acute kidney injury (AKI), hypertension, and nonminimal change disease. Historically, there has been no clear consensus on the indications of renal biopsy in adolescents who present with the INS. There is a need to define criteria for pretreatment biopsies in this age group. There are few published studies reporting clinico-pathological profile of adolescent onset INS.[3],[4],[5],[6] We conducted a retrospective analysis of medical records of children with onset of NS during adolescent period. The objective of the study was to evaluate the clinical features, steroid responsiveness and histopathological spectrum of adolescent onset nephrotic syndrome.

   Methods Top

Study design and patient selection

We reviewed the medical records of children with INS with the onset of disease in adolescence who presented to pediatric nephrology clinic in a tertiary care hospital in North India, from October 2010 to January 2013 period. Adolescent age was defined as 10–19 years according to WHO.[7] NS was diagnosed according to the criteria of the ISKDC, presence of proteinuria (>40 mg/m2/h), hypoalbuminemia (<25 g/L), edema, and usually hypercholesterolemia (>200 mg/dL).[8]

Those with secondary NS, i.e., clinical features of systemic lupus erythematosus, Henoch-Schonlein purpura, and/or laboratory (hepatitis B virus surface antigen or HIV positivity) evidence of systemic disease were excluded. Remission, relapse, frequent relapses, steroid dependence, and steroid resistance [steroid-resistant NS (SRNS)] were defined as per the Indian society of pediatric nephrology guidelines (ISPN).[8] AKI was defined as serum creatinine level was 0.3 mg/dL or more above the normal upper limit for age.[9] Clinical assessment of each participant included reviewing medical records with respect to history, blood pressure measurement, height, weight, urine analysis, and quantification of proteinuria, serum electrolytes, blood urea, serum creatinine, complement 3 and 4 levels, histopathology, treatment, and response to therapy.

Laboratory investigations included nephrotic parameters, complement levels, hepatitis B surface antigen, hepatitis C virus and HIV in all patients. Ultrasound-guided percutaneous renal biopsy was performed in children with low complement level, SRNS and in steroid sensitive before starting calcineurin inhibitors. Light microscopy and immunofluorescence microscopy reports were obtained from the original biopsy results. All renal biopsies from the study period were reviewed by the same pathologist who considered following criteria: Minimal change disease (MCD) was defined as normal-appearing glomeruli by light microscopy or minimal focal segmental increase in mesangial cells, with negative immunofluorescence. Diffuse mesangial hyper-cellularity was characterized by the presence of four or more mesangial cell nuclei in the stalk regions of most glomeruli. Focal and segmental glomerulosclerosis (FSGS) was defined by the presence of at least one glomerulus containing a segmental area of sclerosis, with or without a corresponding area of IgM and C3 staining on immunofluorescence. Membranoproliferative glomerulonephritis (MPGN) was diagnosed with intense mesangial proliferation and diffuse thickening of the glomerular basement membrane with the appearance of “double contours” by light microscopy. Idiopathic membranous nephropathy (IMN) was diagnosed based on glome-rular basement membrane thickening by light microscopy, granular deposition of IgG and C3 in immunofluorescent microscopy and sub epithelial electron dense deposits on electron microscopy. Antibodies to the M-type phospholipase A2 receptor (PLA2R), bovine serum albumin (BSA), and cationic BSA were measured by Western blotting in sera of five patients with IMN and then detecting for both total IgG as well as specifically for the IgG4 subclass.

Treatment was as per ISPN guidelines for children with NS.[8],[10] For children with SRNS complete remission (CR) was defined as urine spot protein creatinine (Up/Uc) <0.2 g/g; serum albumin >2.5 g/dL and no edema. Partial remission (PR) as Up/Uc between 0.2 g/g and 2 g/g, serum albumin >2.5 g/dL, and no edema. No remission (NR) was definied a as Up/Uc >0.2 g/g, serum albumin < 2.5g/dL or edema.

   Results Top

Thirty-three children were registered in the pediatric nephrology clinic during the study period who had onset of INS in the adolescent period. The mean age of children at the onset of disease was 11.96 ± 1.75 years. The mean duration of follow up of patients was 18.2 ± 1.92 months. Twenty-three were males and 10 were females. The mean body mass index of participants was 17.39 ± 3.3 kg/m2. At the onset of disease, hematuria was present in 13 children (39%) and hypertension in 12 (36%). Gross hematuria was present in three and 10 patients had microscopic hematuria. AKI was present in nine children (27%). Infections were present in 10 (30%) children, three children had septicemia, three had pneumonia, three had spontaneous bacterial peritonitis and one had urinary tract infection. Low C3 was found only in children with MPGN (5 patients).

Twenty-three children had SRNS (70%). Two-thirds of children with SRNS course had initial steroid resistance and one-third had initially steroid sensitive course and developed resistance in follow-up. The mean duration from onset of NS to develop resistance to steroids in late resistance was 10.5 ± 8.04 months. [Table 1] shows histopathology spectrum of subjects. Hypertension, hematuria, and renal insufficiency at the onset of disease were more common in those with steroid resistance [Table 2]. Among 23 children with steroid resistance, 12 children with MCD and FSGS were treated with CNI. Histopathology revealed MPGN in five children who were treated with MMF or six pulses of Cyclophosphamide and long-term prednisolone. All six children with IMN were treated with long-term prednisolone and cyclosporin was started in one who failed to attain remission. Anti-PLA2R antibodies were found in one patient with IMN. Western blot analysis of serum sample showed minimal amounts of IgG4 subclass, but greater amounts of IgG1 and IgG3, anti-PLA2R. Among those who were steroid sensitive, two children with frequently relapsing/steroid-dependent course required steroid-sparing drugs. The outcome of children is shown in [Table 1].
Table 1: Disease profile in children with adolescent-onset idiopathic nephrotic syndrome.

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Table 2: Histopathological profile of adolescents with idiopathic nephrotic syndrome and comparison with previous studies.

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   Discussion Top

The present study showed a high prevalence of hypertension (36%), hematuria (39%) and AKI (27%) in adolescents at onset of nephrotic syndrome. Renal insufficiency and older age of onset are independent predictors of ESRD.[13] Hypertension in NS appears more frequently in teenagers than in younger children.[14]

Renal biopsy was done in 70% of patients in the present study. Histopathology showed MCD in 26% and non-MCD was found in 74% of 23 adolescents who were diagnosed as SRNS. In the sentinel data published by ISKDC 60% of patients >12 years of age had non-MCD. [Table 2] shows the comparison of histopathological profiles with previous studies. In a study by Baqi et al,[5] FSGS was the most common lesion due to ethnic differences as 83% population was African-American. FSGS is more common in African American.[15] Only 7% of children had MPGN in their study as children with gross hematuria at the onset of disease were excluded. In a study by Hogg et al[4] and Takada et al[3] all adolescents with NS were biopsied. MCD was the predominant lesion. In a recent study from north India, all adolescents with NS were biopsied, 37% had FSGS and 31% had MCD.[12] The reduction in MCD and increase in FSGS as age increases have been noted in other studies as well. Mubarak et al noted MCD in 51% of NS in age <12 years and in only 28.9% in adolescents, a finding which is similar to ours.[11]

In comparison to these studies, idiopathic membranous nephropathy was more frequent while FSGS had decreased incidence in our study. In a cross-sectional study of HPE pattern of pediatric nephrotic patients, FSGS was the most common lesion followed by membranous in children with non-MCD. Majority of patients were >10 years; half were steroid resistant and mean age of onset of disease was 11.5 years.[16] The authors recommended renal biopsy in all patients. The role of antibodies to m-type PLA2R in the pathogenesis of IMN has been described in many studies in adults accounting for increased circulating levels of antibodies and staining in 70% cases of IMN but there few case series described in children.[17] Anti PLA2R along with BSA and neural endo-peptidase correlate with disease activity and have causal role.

Adolescents with SRNS had increased frequency of hypertension, hematuria and renal insufficiency in comparison to those with SSNS. Childhood-onset NS is marked by increase steroid responsiveness, frequent relapses, and minimal change disease as the most common lesion in HPE.[18] On the other hand, adult-onset NS has been associated with a higher prevalence of hypertension, renal impairment slower response to steroids, and non-MCD in HPE, but a lower tendency to relapse.[19],[20]

There is no consensus on criteria to guide renal biopsy in adolescents with NS. The ISKDC recommended a trial of steroids based on their finding of a predominance of steroid-responsive MCNS in pediatric patients.[3] Adult nephrologists, on the other hand, biopsy before initiating treatment because of the greater likelihood of finding steroid-resistant glome-rular lesions. Most of the pediatric nephrologists recommend a trial of steroids in adolescents with INS because the most important predictor for kidney survival in childhood NS is not kidney pathology, but the achievement and maintenance of remission following any therapy.[21] Gulati et al, suggested renal biopsy in adolescents with abnormal clinical and biochemical features and those who were steroid resistant.

There are some limitations to our study, such as the small sample size, short follow-up period, and retrospective study design. Nevertheless, our results showed that adolescents with idiopathic onset NS have a higher prevalence of steroid resistance and complications. Renal biopsy should be done in those with abnormal clinical and biochemical features. Larger prospective cohort studies are needed to define criteria for pretreatment renal biopsy in adolescents.

Conflict of interest: None declared.

   References Top

White RH, Glasgow EF, Mills RJ. Clinicopathological study of nephrotic syndrome in childhood. Lancet 1970;1:1353-9.  Back to cited text no. 1
Rathi M, Bhagat RL, Mukhopadhyay P, et al. Changing histologic spectrum of adult nephrotic syndrome over five decades in north India: A single center experience. Indian J Nephrol 2014;24:86-91.  Back to cited text no. 2
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Takada T, Yangihahra T, Kuwabra H, Igarrhic T, Yoshigumi A, Kihora I. Clinicopathologic study in 50 adolescent patients with primary nephrotic syndrome. Pediatr Nephrol 1989;3:C9.  Back to cited text no. 3
Hogg RJ, Silva FG, Berry PL, Weng JE. Report of Southwest Pediatric Nephrology study group. Glomerular lesions in adolescents with gross hematuria or the nephrotic syndrome. Pediatr Nephrol 1993;7:27-31.  Back to cited text no. 4
Baqi N, Singh A, Balachandra S, et al. The paucity of minimal change disease in adolescents with primary nephrotic syndrome. Pediatr Nephrol 1998;12:105-7.  Back to cited text no. 5
Gulati S, Sural S, Sharma RK, Gupta A, Gupta RK. Spectrum of adolescent-onset nephrotic syndrome in Indian children. Pediatr Nephrol 2001;16:1045-8.  Back to cited text no. 6
WHO. The Global Strategy for Women’s, Children’s, and Adolescents’ Health (2016–30); 2015. Available from: http://www.who. int/life-course/partners/global-strategy/ewec-global strategyreport-200915.pdf?ua=1. [Last accessed on 2017 Dec 22].  Back to cited text no. 7
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Kumar V, Ramachandran R, Kumar A, et al. Antibodies to m-type phospholipase A2 receptor in children with idiopathic membranous nephropathy. Nephrology (Carlton) 2015;20:572-5.  Back to cited text no. 17
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Correspondence Address:
Abhijeet Saha
Department of Pediatrics, Division of Pediatric Nephrology, Lady Hardinge Medical College and Kalawati Saran Children's Hospital, New Delhi
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1319-2442.318525

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