**3. Mechanism of nephrotic syndrome**

The development of massive proteinuria is the central abnormality in all cases of nephrotic syndrome. Some of the literature shows the evidence in that nephrotic syndrome may be a significance of glomerular defect, circulating factors, and defect in immunological system.

### **3.1 Glomerular defect**

The most important possible functions of the kidney is the filtration of blood and blood products at glomeruli, which permits the fluid and dirty products while retaining the greater part of blood proteins and all blood cells within the vasculature. These types of process of filtration is made potential by the (GFB), which is made up of specific glomerular epithelial cells (podocytes), endothelial cells, and GBM these distal bottom actions are attached to the GBM (**Figure 1**) [14]. Adjacent podocyte bottom actions are associated to each one other by networks of specific cell-cell junctions called as opening diaphragms. Additionally, the GBM (glomerular basement membrane) has a plentiful supplies of negatively charged molecules of heparin sulfate

**57**

**Figure 1.**

*micrographic view.*

**3.2 Circulatory factors**

*Causes and Pathophysiology of Nephrotic Syndrome in Childhood*

proteoglycan, resultant in these negatively charged heparin sulfate proteoglycan controlled from passage than positively charged molecules with same particles [15]. General healthy system, particle more than 42 Å in diameter is not capable to enter into the GFB [16]. This kind of restrictions based on mostly structural reliability of the podocyte bottom actions and opening diaphragms, by means of the charge of GBM. Loss of negative charge of the GBM occurs in nephrotic syndrome [17–19]. The confirmation, swelling and diffusion podocyte binds to bottom actions, dislocation of opening diaphragms, occurrence of filling junctions, vacuole formation, and deficiency of inclusion of podocytes from the GBM, these type of morphologic changes in podocytes that occur during progress of nephrotic syndrome [20–23]. Mutations in genes encoding some of the opening diaphragms proteins or their transcription factors can cause SRNS and/or FSGS. This mechanism of nephrotic syndrome is additional reinforced by recent observations in humans and experimental animals [4, 10, 11, 14, 24–26]. The subject of many recent reviews in the literature this type of result have been discussed [27–29]. In infants mutations in the gene encoding the opening diaphragms protein nephrin (NPHS1) mostly causes CNF. In addition, in children mutations in NPHS2 are estimated to be responsible for up to 25% of cases of sporadic familial and Steroid resistant nephrotic syndrome (SRNS) [10, 25]. Frasier syndrome and Denys rash syndrome in children occurs due to Mutations in the transcription factor suppressor gene WT1 [30–32]. Mutations in (1) CD2-associated protein (CD2AP); (2) the LIM-homeodomain protein (encoded by LMX1B), which leads to in nail-patella syndrome; (3) the actin-bundling protein α-actinin 4, which leads to adult-onset FSGS; which results in adult-onset FSGS; (4) laminin β2, which results in Pierson syndrome and (5) the chromatin regulator encoded by SMARCAL1. [25, 33–35].

*Components of the glomerular filtration barrier (GFB) during normal glomerular filtration, electron* 

Some of soluble mediators that may alter capillary wall permeability in nephrotic syndrome proved by investigational data to carry the existence [37–39] show to be true for this includes (1) scared decrease of proteinuria subsequent treatment with protein A immunoadsorption in of primary nephrotic syndromes [24], (2) progress of nephrotic syndrome in child babies born to mothers with nephrotic syndrome

*DOI: http://dx.doi.org/10.5772/intechopen.86825*

#### **Figure 1.**

*Renal Diseases*

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.

The development of massive proteinuria is the central abnormality in all cases of nephrotic syndrome. Some of the literature shows the evidence in that nephrotic syndrome may be a significance of glomerular defect, circulating factors, and defect

The most important possible functions of the kidney is the filtration of blood and blood products at glomeruli, which permits the fluid and dirty products while retaining the greater part of blood proteins and all blood cells within the vasculature. These types of process of filtration is made potential by the (GFB), which is made up of specific glomerular epithelial cells (podocytes), endothelial cells, and GBM these distal bottom actions are attached to the GBM (**Figure 1**) [14]. Adjacent podocyte bottom actions are associated to each one other by networks of specific cell-cell junctions called as opening diaphragms. Additionally, the GBM (glomerular basement membrane) has a plentiful supplies of negatively charged molecules of heparin sulfate

**56**

**3. Mechanism of nephrotic syndrome**

in immunological system.

**3.1 Glomerular defect**

*Components of the glomerular filtration barrier (GFB) during normal glomerular filtration, electron micrographic view.*

proteoglycan, resultant in these negatively charged heparin sulfate proteoglycan controlled from passage than positively charged molecules with same particles [15]. General healthy system, particle more than 42 Å in diameter is not capable to enter into the GFB [16]. This kind of restrictions based on mostly structural reliability of the podocyte bottom actions and opening diaphragms, by means of the charge of GBM. Loss of negative charge of the GBM occurs in nephrotic syndrome [17–19]. The confirmation, swelling and diffusion podocyte binds to bottom actions, dislocation of opening diaphragms, occurrence of filling junctions, vacuole formation, and deficiency of inclusion of podocytes from the GBM, these type of morphologic changes in podocytes that occur during progress of nephrotic syndrome [20–23]. Mutations in genes encoding some of the opening diaphragms proteins or their transcription factors can cause SRNS and/or FSGS. This mechanism of nephrotic syndrome is additional reinforced by recent observations in humans and experimental animals [4, 10, 11, 14, 24–26]. The subject of many recent reviews in the literature this type of result have been discussed [27–29]. In infants mutations in the gene encoding the opening diaphragms protein nephrin (NPHS1) mostly causes CNF. In addition, in children mutations in NPHS2 are estimated to be responsible for up to 25% of cases of sporadic familial and Steroid resistant nephrotic syndrome (SRNS) [10, 25]. Frasier syndrome and Denys rash syndrome in children occurs due to Mutations in the transcription factor suppressor gene WT1 [30–32]. Mutations in (1) CD2-associated protein (CD2AP); (2) the LIM-homeodomain protein (encoded by LMX1B), which leads to in nail-patella syndrome; (3) the actin-bundling protein α-actinin 4, which leads to adult-onset FSGS; which results in adult-onset FSGS; (4) laminin β2, which results in Pierson syndrome and (5) the chromatin regulator encoded by SMARCAL1. [25, 33–35].

### **3.2 Circulatory factors**

Some of soluble mediators that may alter capillary wall permeability in nephrotic syndrome proved by investigational data to carry the existence [37–39] show to be true for this includes (1) scared decrease of proteinuria subsequent treatment with protein A immunoadsorption in of primary nephrotic syndromes [24], (2) progress of nephrotic syndrome in child babies born to mothers with nephrotic syndrome

who actually transferred a soluble factor to their fetuses in utero [39], (3) decrease of repeated disease induced by treatment with protein A immunoadsorption due to presumed removal of circulating factors in the reappearance of FSGS in transplanted kidneys in patients with primary FSGS [40], and (4) FSGS recurrence in transplanted kidney patients serum injected in to the experimental animals leads to causing of enhanced glomerular permeability [32] serum of children with FSGS and recognized as components of apolipoproteins, from the suggestive of that an imbalance involving serum permeability factors and permeability inhibitors may have a pathogenic role in FSGS. Moreover, inhibitors of glomerular permeability have also been isolated [33].
