**2.2 Nephrotic syndrome after infancy**

*Renal Diseases*

**2. Causes**

cases increases.

**2.1 Inborn nephrotic syndrome**

cytomegalovirus and syphilis (**Table 1**).

Finnish type (CNF)

Jeune's syndrome Galloway Mowat syndrome

Pierson syndrome

Cockayne syndrome

Congenital syphilis

*Causative factors of congenital nephrotic syndrome (CNS) in 0–3 months of age.*

Minimal change nephrotic syndrome

Congenital cytomegalovirus (CMV) infection

Idiopathic Nonsyndromic DMS

FSGS Infections Congenital toxoplasmosis

The childhood nephrotic syndrome is principally idiopathic or primary, though a limited number of cases are secondary to glomerular and inclusive diseases and other infectious agents. Age reliant is also the etiology factor of nephrotic syndrome. Maximum cases presenting in the first 3 months of lifespan are mentioned as CNS (congenital nephrotic syndrome) and are caused by genetic diseases. While in the remaining of the first year of lifecycle (3–12 months) there has been no effective study of the etiology of nephrotic syndrome reported cases, there are a number of stats shows that up to 40% of reported cases meanwhile this time may also be due to genetic factors [1]. At the time of first year and in the first decade of life, maximum presenting cases are due to primary or idiopathic nephrotic syndrome, at the time of first 10 years of lifecycle the number of secondary nephrotic syndrome

Congenital nephrotic syndrome is the type of nephrotic syndrome which occurs in first 3 months of life and is due to genetic causes mostly by alterations in the gene encrypting nephrin, a podocyte opening diaphragm protein. For the first time, these mutations were expressed in the Finnish, from then the name congenital nephrotic syndrome of the Finnish type (CNF) [1]. Though the incidence of CNF is high in Finland it also occurs in other populations also. Congenital nephrotic syndrome is not either equivalent with CNF, reason is that alterations in other genes encrypting podocyte opening diaphragm proteins, early-onset nephrotic syndrome can also be caused by proteins such as podocin. Upto 40% of all cases of nephrotic syndrome occurring in the first 3 months of life are due to alterations in a sequence of podocin gene [2] in the earliest 3 months of life. Nephrotic syndrome may also be part of multisystemic syndromes such as nail-patella syndrome, Pierson syndrome, Denys-Drash syndrome, and others or a sequence of congenital infections such as

Genetic Mutation in nephrin *(NPHS1)* gene leads to congenital nephrotic syndrome of the

Syndromes Nail-patella syndrome due to mutation in LIM homeodomain protein (LMX1B)

Denys-Drash syndrome due to WT1 mutation with DMS

Mutation in podocin *(NPHS2)* gene results Autosomal recessive FSGS

Mutation in laminin β2 gene leads Congenital nephrotic syndrome

Mutation in *WT1* gene results Autosomal dominant diffuse mesangial Sclerosis (DMS)

Schimke immunoosseous dysplasia with FSGS due to mutation in SMARCAL1

**54**

**Table 1.**

Above the infancy and above the first year of life, maximum of the nephrotic syndrome cases are idiopathic. MCNS (Minimal-Change Nephrotic Syndrome) is the most usual deviation, and is responsible for more than 80% of all cases [3]. Focal segmental glomerulosclerosis (FSGS), Membranoproliferative glomerulonephritis (MPGN), and mesangial multiply glomerulonephritis are the other less common histopathologic types in this age group (**Table 2**). For a few cases in this age group genetic disease is also responsible. 10–25% of all cases of familial and sporadic SRNS were caused by


### **Table 2.**

*Causative factors of nephrotic syndrome above 3 months of life.*

mutations in NPHS2, inherited in an autosomal genetic mode, because it was exposed in one series. Beginning of nephrotic syndrome in untimely childhood, not response to steroid treatment, strong findings of focal segmental glomerulosclerosis (FSGS) on histopathology renal biopsy, progress to ESRD in 5 years of finding, and comprehensively decreases the risk of disease recurrence following renal transplantation are by the phenotype typically associated with NPHS2 mutations [4, 5]. Additional genetic factors consists autosomal dominant transmitted causes such as α-actinin 4, mutations in the Wilms' tumor suppressor gene (WT1), TRPC6 and CD2AP [6–10]. Individually from those in WT1, maximum of these mutations go to result in adult-onset disease. To a number of systemic diseases in children, nephrotic syndrome may also be secondary. Pediatric diseases such as Henoch-Schönlein purpura; diabetes mellitus; systemic lupus erythematosus, especially membranous (WHO Class V) SLE; and sarcoidosis may all exist with nephrotic syndrome. Infective factors can also cause nephrotic syndrome and can be bacterial, viral, or parasitic. Despite it is not so far fully known how these factors cause nephrotic syndrome, it is maybe due to an bizarre immune response to them in the majority of the reported cases, occurring in the progression and aggregation of immune complexes in the glomerulus. The interpretation of these factors as a cause of nephrotic syndrome turn to parallel their prevalence in demanding regions of the world. For example, in Hong Kong and countries in Africa, hepatitis B and C are important causes of nephrotic syndrome [11, 12]. In areas where malaria is endemic, Malaria, particularly quartan malaria, is also an important cause. Eighteen nephrotic syndrome in both adults and children can be caused by Human immunodeficiency virus (HIV).despite the renal abrasion linked with HIV can be changeable, FSGS is the most common histologic finding affiliated with HIV is, particularly the breakdown is different. Despite the result of treatment of the underlying infection on the nephropathy is not well known, but there are details that hepatitis B-associated nephrotic syndrome may be cooperative to treatment of the hepatitis [13]. A list of infective factors associated with nephrotic syndrome is shown in **Table 2**. Drugs such as angiotensin converting enzyme inhibitors (ACEIs), penicillamine, gold, nonsteroidal antiinflammatory drugs (NSAIDs), sickle cell disease, bee stings, lymphoma, leukemia, and various types of food allergies are the other less common causes of nephrotic syndrome. Moreover, in children with obesity the nephrotic syndrome is being seen further recurrently. The histologic scrape most frequently occurs in this setting is FSGS.
