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| ORIGINAL ARTICLE |
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| Year : 2012 | Volume
: 2
| Issue : 1 | Page : 22-24 |
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Nephrotic syndrome in the first year of life
Manisha Sahay1, Swarnalatha Gowrishankar2, Girish Narayen3, Anuradha4
1 Department of Nephrology, Osmania Medical College/ Osmania General Hospital, Hyderabad, Andhra Pradesh, India
2 Department of Histopathology, Apollo Hospital, Hyderabad, Andhra Pradesh, India
3 Department of Nephrology, Osmania Medical College/ Osmania General Hospital; Consultant, Medwin Hospital, Hyderabad, Andhra Pradesh, India
4 Department of Nephrology, Osmania Medical College/ Osmania General Hospital; Consultant, Mediciti Hospital, Hyderabad, Andhra Pradesh, India
| Date of Web Publication | 3-Dec-2012 |
Correspondence Address:
Manisha Sahay
Department of Nephrology, Osmania General Hospital, Afzalgunj, Hyderabad, Andhra Pradesh- 500 012
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/2249-4855.104011
Objective: To study the clinical profile, laboratory data, histopathology, and outcome of infantile nephrotic syndrome (INS).
Materials and Methods: Over a 5 year period, 30 infants with nephrotic syndrome were seen at Osmania General Hospital. They were studied with regard to family history, antenatal details, birth history, clinical features including anthropometry and developmental milestones, laboratory investigations and histopathology of renal tissue (light microscopy and immunofluorescence), and treatment outcome.
Results: There were 17 males and 13 females (1:0.8). The mean age at presentation was 8.6 months (2.5-12 months). History of consanguinity was obtained in 12 infants (40%) and birth asphyxia was present in 8 infants (26%). Eighteen (60%) were growth retarded and 10 (33.3%) had developmental delay. Hypertension was recorded in 8 (26%) and edema in 24 (80%). At presentation, renal failure was evident in 18 (60%) infants. Nephrotic range proteinuria and hypoalbuminemia were found in all and microscopic hematuria in 4 (13%) infants. Histology of renal tissue revealed congenital Finnish type (CNF) in 8 (26%), diffuse mesangial sclerosis (DMS) in 6 (20%), minimal change disease (MCD) in 6 (20%), mesangial proliferation with IgM deposits in 4 (13%), and focal segmental glomerulosclerosis (FSGS) in 4 (13%). Mesangial hypercellularity with cytomegalovirus infection was found in 2 (6.6%) infants. CNF and DMS on histopathology carried a very poor prognosis with none recovering, while the others showed variable response to treatment with steroids and cytotoxic therapy.
Conclusion: INS is a rare disorder. The predominant histopathological lesions are CNF and DMS which carry a very poor prognosis. Keywords: Congenital nephrotic syndrome, genetics of nephrotic syndrome, infantile nephrotic syndrome, nephrotic syndrome
How to cite this article:
Sahay M, Gowrishankar S, Narayen G, Anuradha. Nephrotic syndrome in the first year of life. J Acad Med Sci 2012;2:22-4 |
| Introduction | |  |
Nephrotic syndrome occurring in the first year is called infantile nephrotic syndrome (INS) and comprises of congenital nephrotic syndrome occurring in the first 3 months of life and the late onset INS presenting between 3 and 12 months. [1] It differs from the nephrotic illness in older children, in terms of the histopathological lesion and carries a very poor prognosis. However, it is important to study the histopathology to identify the infants with treatable lesions.
| Materials and Methods | | |
Over a 5 year period, 30 infants who presented with nephrotic syndrome formed the material of this study. A detailed family history including consanguinity, antenatal history including TORCH infections, birth history, period of gestation, size of the placenta was noted (a large placenta being defined as >20% of neonate's weight). A detailed physical examination was done. Laboratory data included a complete renal profile and hemogram, complete urine examination, urine Pr/Cr ratio, 24-h urine protein, plasma glucose, serum creatinine, blood urea, serum electrolytes, serum protein, albumin and globulin, and serum cholesterol. Nephrotic syndrome was defined as 24-h protein more than 50 mg/kg or urine Pr/Cr >2.0 [2] and renal insufficiency defined by low glomerular filtration rate than expected for that age (Schwartz formula). [3] A skeletal survey and ultrasonography of abdomen was done to assess renal size and echotexture. A Renal biopsy was performed after initial stabilization, either under general anesthesia or midazolam anesthesia and subjected to light microscopy (H and E) and immunofluorescence. Infants were treated depending on histopathology findings. Glomerular diseases were managed according to standard recommendations of International Study of Kidney Diseases in Children (ISKDC). [4] The mean follow up was 37 months (6 months to 5 years).
| Results | | |
Of the 30 infants presenting with nephrotic syndrome, 17 were males and 13 were females. During the period of this study, the total number of patients presenting with nephrotic syndrome was 1908, thus INS constituted 1.6% of all patients with nephrotic syndrome. This constituted 1.6% of the 1908 patients with nephrotic syndrome presenting during this period. Six infants (20%) presented before 3 months of age. At presentation, 8 (26%) were hypertensive and 18 infants (60%) were growth retarded. None of them had gross hematuria or congenital anomalies [Table 1] and [Table 2]. Cytomegalovirus (CMV) immunoglobulin M (IgM) was positive in 2 (3.3%). All infants with congenital Finnish nephrotic syndrome had a large placenta and were developmentally retarded. Histopathology finding are given in [Table 3].
All infants with congenital Finnish type (CNF) and diffuse mesangial sclerosis (DMS) progressed to renal failure. They were managed conservatively. Mortality was 100% within 1 year of diagnosis. All six infants with minimal change disease (MCD) responded to steroids, three (50%) with complete remission till follow up, two (33.3%) with infrequent relapses, one (16.6%) succumbing to infection. Two (50%) infants with focal segmental glomerulosclerosis (FSGS) remitted with steroids and were in remission till last follow up while 2 (50%) were steroid resistant and remitted with cyclophosphamide. While 2 (50%) infants with mesangial deposits of IgM showed good response to steroids, 2 others (50%) with frequent relapses remitted completely with cyclophosphamide infants with CMV infection were treated with Ganciclovir with remission of proteinuria.
| Discussion | | |
Nephrotic syndrome is uncommon before the first year of life. In several large series of children with nephrotic syndrome, only a small proportion were younger than 1 year. [5],[6] In our study, INS constituted 1.6% of total number of nephrotics with 20% being of the congenital variety. INS is a heterogeneous group with variable etiology and poor prognosis for normal renal function. [1] Infantile nephrotic syndrome has been associated with defects in the nephrin gene (NPHS1), phospholipase C epsilon 1 gene (PLCE1), and the Wilms tumor suppressor gene (WT1). Mutations in the podocin gene (NPHS2) are associated with a familial, autosomal-recessive form of FSGS. Mutations in the α-actinin-4 gene (ACTN4) and the gene TRPC6 are associated with autosomal-dominant forms of familial FSGS. [7],[8] Pierson syndrome (mutation in LAMB2, which encodes laminin beta 2), Galloway Mowat syndrome, nail-patella syndrome (mutation in LMX1B), and Schimke immuno-osseous dys plasia (SMARCAL1 mutation) are other forms of nephrotic syndrome with genetic basis. However, genetic studies were not done in our study.
Finnish type is the most common and best known of all types of INS. Our study showed CNF in 26%. CNF seen most commonly in Finland is inherited as an autosomal recessive trait. Other associations described with CNF, e.g. atopy, microcephaly, ocular and neurological abnormalities, micropenis, psychomotor retardation, infantile spasms, high alphafetoprotein levels in amniotic fluid, and prematurity. Infants are small for gestational age. Postural deformities and breech presentation are common. A large placenta is an early sign of the disease. In our study, a history of large placenta was obtained in 30% (5/30), 60% of the infants were born prematurely, and 50% were small for gestational age with 40% having birth asphyxia. All patients with CNF have nephrotic syndrome at onset, present or progress to renal failure in the absence of any specific treatment. [9] All the infants with CNF progressed to end-stage renal disease (ESRD) within 1 year of diagnosis and expired.
Another type of nephrotic syndrome that can develop during the first few months is DMS. It can manifest before the age of 3 months but most cases are detected later in infancy. [10],[11] Because of the small number of published cases, the exact mode of inheritance has not been determined but Ozen et al have reported autosomal recessive inheritance in their series. [10] Pregnancy and delivery are uneventful. Placental weight is normal. Infants with DMS typically have no congenital malformation. Steroids and immunosuppressive drugs have no effect on progression of the disease. The renal pathology in advanced cases of DMS is very characteristic with contracted glomeruli.
Certain forms of nephrotic syndrome usually found in older children sometimes occur during the first year of life. [12] In our study MCD was seen in 20%, FSGS and Mesangial GN were seen in 20% and 13%, respectively. The prognosis of infantile MCD is variable and is worse than MCD at an older age. Our children with MCD treated with steroids were in remission at last follow up. INS associated with FSGS and mesangial hypercellularity with IgM has variable response to steroids and a poor prognosis. 50% of our infants with FSGS and 50% of those with IgM deposits responded to steroids while the rest needed cytotoxic therapy (cyclophosphamide) with response in 30% with FSGS and 35% in those with IgM nephropathy. Idiopathic membranous glomerulonephritis as a cause of nephrotic syndrome has been described in a few infants. None of our patients had membranous lesions. CNS associated with congenital infections is uncommonly reported with syphilis and toxoplasma. Prednisolone treatment results in complete recovery. CNS is rarely associated with CMV [13] and Rubella and a causal role remains doubtful. In our study, 2 (6.6%) had CMV infection and remitted with Ganciclovir. Other TORCH infections were not seen. Congenital nephrotic syndrome may be part of a few malformation syndromes, the most common of which is the Drash syndrome, combining glomerulopathy, male pseudohermophroditism, and Wilms tumor which were not seen in our study. [14]
The etiology of INS is heterogeneous. With the prognosis and treatment depending on the etiology it is necessary to analyze all available information including family history, perinatal and obstetric findings, weight of placenta, clinical manifestations, lab values, and renal pathology before arriving at a final diagnosis.
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| 14. | Habib R, Loirat C, Gubler MC, Niaudet P, Bensman A, Levy M, et al. The nephropathy associated with male pseudohermaphroditism and Wilms tumor (Drash syndrome): A distinctive glomerular lesion: Report of 10 cases. Clin Nephrol 1985;24:269-78.
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[Table 1], [Table 2], [Table 3]
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