Conditions Related to Nephrotic Syndrome

While diagnosing NS, the clinician has to closely examine other similar conditions, as shown below. It may be noted that this makes a suggested reading only for those who want to go into the detail of understanding Nephrotic Syndrome. Nephrotic Syndrome is the outcome of an ample number of diseases that damage the filtering units of the kidneys in a certain way that allows them to leak protein into the urine. Hence there is an array of diseases, which eventually end up in Nephrotic Syndrome. Some of the diseases that cause Nephrotic Syndrome, such as glomerulonephritis, affect only the kidney. Other diseases that cause Nephrotic Syndromes, such as diabetes and lupus, affect other parts of the body as well. It should be also noted that in the vast majority of cases exact cause couldn’t be pinpointed.

A Local causes (primarily affecting kidneys)

This group categorizes all those conditions, which directly and primarily affect kidneys and damage glomeruli. They are largely termed as nephropathies or glomerulopathies. Glomerulonephritis (GN) occupies a peak position among glomerulopathies causing Nephrotic Syndrome. GN is a group of kidney diseases caused by inflammation of the internal kidney structures (glomeruli). The disease may be caused by specific problems with the body's immune system, but the precise cause of most cases is unknown.

Specific disorders that are associated with glomerulonephritis and hence Nephrotic Syndrome include:

01 Minimal change disease (Nil’s disease)

02 Membranoproliferative GN/ mesangiocapillary glomerulonephritis

03 Focal segmental glomerulosclerosis (FSG) (creates scar tissue in the glomerulus, damaging its protein-repellant membrane)

04 Membranous glomerulonephritis (damages the protein-repellant membrane)

05 IgM Mesangial proliferative GN (affecting the mesangium)

06 Rapidly progressive crescentic glomerulonephritis

07 IgA nephropathy (Berger’s disease) (deposit of specific immunoglobulin A causing an inflammatory reaction and leading to glomerulonephritis)

08 Goodpasture’s syndrome

09 Post-infectious glomerulonephritis

10 Congenital Nephrotic Syndrome

01 Minimal Change Glomerulopathy/ Nil disease/ Lipoid nephrosis/ Idiopathic Nephrotic Syndrome of childhood:
A glomerular disorder characterized clinically by Nephrotic Syndrome and pathologically by the fusion of visceral epithelial foot processes (an alteration of the glomerular capillary walls that can be seen by electron microscopy in renal biopsy specimens). The condition is called minimal change disease because children with this form of Nephrotic Syndrome have normal or nearly normal renal biopsies under a light microscope. This is the most common form of Nephrotic Syndrome in children.

02 Membranoproliferative glomerulonephritis (MPGN)/ mesangiocapillary glomerulonephritis:
A kidney disorder with inflammation of the glomeruli resulting from an abnormal immune response and the deposition of antibodies within the glomerular ultrastructure. MPGN is most common in young adults. Immune deposits are found on the capillaries of the kidney, causing them to thicken and impairing the kidney's filter system. Patients present with high blood pressure and symptoms of Nephrotic Syndrome.

03 Focal segmental glomerulosclerosis: 
Focal segmental glomerulosclerosis is an illness where scar tissue forms in some of the glomeruli of the kidney. The term "focal" means that some of the glomeruli become scarred, while others remain normal. The term "segmental" means that only part of an individual glomerulus is damaged. Focal segmental glomerulosclerosis causes about 10 to 15% of all cases of Nephrotic Syndrome.

04 Membranous glomerulonephritis:
A kidney disease that occurs due to inflammation of the glomerulus and its basement membrane. It is characterized by generalized thickening of the basement membrane of the glomerular vessels. The exact cause is unknown but it appears to be related to the deposition of immune complexes in the basement membrane. This disorder is a common cause of Nephrotic Syndrome. Risk factors include primary renal disease, infectious diseases like malaria and hepatitis B, systemic conditions like lupus and cancers, ill effects of some medications such as gold compounds and penicillamine. This is an unusual lesion in children, accounting for approximately 1% of NS.

05 IgM mesangial proliferative glomerulonephritis: 
It is a form of glomerulonephritis in which the mesangial cells (part of the glomerular capillaries) increase in size, giving the glomeruli a lumpy appearance. The condition appears to be related to some type of immune response because inflammation of the glomeruli is associated with deposits of IgM (a type of antibody). The disorder usually causes Nephrotic Syndrome. It is a rare disorder.

06 Rapidly progressive crescentic glomerulonephritis:
A relatively uncommon form of glomerulonephritis that results in damage within the glomerulus of the kidney. There is a rapid loss of kidney function with the formation of "crescents" on microscopic analysis (kidney biopsy). This disorder may result in Nephrotic Syndrome but ultimately results in renal failure.

07 IgA nephropathy: 
It is a kidney disorder caused by deposits of the protein immunoglobulin A (IgA) inside the glomeruli within the kidney. The IgA protein prevents this filtering process, leading to blood and protein in the urine and swelling in the hands and feet. This chronic kidney disease may progress over a period of 10 to 20 years.

08 Goodpasture's Syndrome: 
It is an uncommon disease that affects both the kidneys and the lungs. The clinical picture includes: bleeding from the lungs, coughing up of blood, and glomerulonephritis. The condition starts, due to an imbalance of the immune system called an autoimmune response. This problem is most common in adults.

09 Postinfectious GN: 
Acute glomerulonephritis often occurs after a streptococcal infection, such as strep throat. When this is the cause, the condition is called postinfectious GN or post-streptococcal GN.

10 Congenital Nephrotic Syndrome: 
The condition probably represents a basic defect in the chemical structure of the basement membrane. Immature glomeruli are found in most samples. Proteinuria is present at birth, and 25% of newborns already have edema. Another 25% of newborns develop clinical edema in the first week of life, and all are edematous by 3 months. Hematuria and hypertension occur in 30-50% of these patients.

B Systemic disease: 

This group categorizes all those diseases which affect a wide spectrum of organs and systems in the body, one amongst them being kidneys. When they affect kidneys, they damage glomeruli and make them leak proteins. To enumerate some of them:

01 Diabetes mellitus

02 SLE

03 Henoch-Schonlein purpura

04 Multiple Myeloma

01 Diabetes mellitus:
Diabetes is a life-long disease marked by elevated levels of sugar in the blood. It can be caused by too little insulin (a chemical produced by the pancreas to regulate blood sugar), resistance to insulin, or both.

Diabetes affects a huge population globally. There are many risk factors for diabetes, including the Family history of diabetes (parent or sibling), Obesity, Age greater than 45 years, and Certain ethnic groups (particularly African-Americans and Hispanic Americans). There is a wide spectrum of complications associated with this condition like coma, retinopathy, Diabetic nephropathy, neuropathy, Peripheral vascular disease, hyperlipidemia, hypertension, atherosclerosis, coronary artery disease, etc. Diabetic nephropathy refers to kidney damage due to diabetes and the condition may present itself in the form of Nephrotic Syndrome.

02 Syastemic lupus erythematosus/ SLE/ Lupus
A chronic, inflammatory autoimmune disorder that may affect many organ systems including the skin, joints, and internal organs like kidneys, heart, lungs, etc. 
In SLE and other autoimmune diseases, the body's defenses are turned against the body when antibodies are produced against its own cells. These antibodies fight against the body's cells and organs, causing chronic diseases. The mechanism or cause of autoimmune diseases is not fully known. The disease affects women more than men. It may occur at any age but appears mostly in people between the ages of 10 and 50 years. Symptoms also vary widely with the individual and are characterized by remissions and exacerbation. Systems affected in SLE can be musculoskeletal system, joints, skin, kidney, nervous system, heart, and lungs. 
Most people with SLE have some deposits of protein within the cells (glomeruli) of the kidney. They may eventually develop Nephrotic Syndrome and renal failure.

03 Henoch- Schonlein purpura:
This relatively rare disorder is characterized by skin purpura (bluish discoloration of the skin), joint pains, abdominal pain, and renal disease (GN). Although Henoch- Schonlein purpura or anaphylactoid purpura is thought to be an immune complex-mediated disease, its exact cause is unknown. It can further result in Nephrotic Syndrome and renal failure.

04 Multiple myeloma/ Plasma cell dyscrasia/ Plasma cell myeloma/ Malignant plasmacytoma/ Plasmacytoma of bone:
Multiple myeloma is a cancer of the plasma cells in the bone marrow. The growth of these extra plasma cells interferes with the production of normal blood cells. This causes anemia, susceptibility to infection, and increased tendencies toward bleeding. Kidney failure is a frequent complication. Multiple myeloma mainly affects older adults. This disease is rare.

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