There are currently several known genetic causes of the hereditary forms of FSGS.

Some researchers found SuPAR as a cause of FSGS.

Another gene that has been associated with this syndrome is the COL4A5 gene.

In children and some adults, FSGS presents as a nephrotic syndrome, which is characterized by edema (associated with weight gain), hypoalbuminemia (low serum albumin, a protein in the blood), hyperlipidemia and hypertension (high blood pressure). In adults, it may also present as kidney failure and proteinuria, without a full-blown nephrotic syndrome.

Minimal change disease has been called by many other names in the medical literature, including minimal change nephropathy, minimal change nephrosis, minimal change nephrotic syndrome, minimal change glomerulopathy, foot process disease (referring to the foot processes of the podocytes), nil disease (referring to the lack of pathologic findings on light microscopy), nil lesions, lipid nephrosis, and lipoid nephrosis.

There is a genetic predisposition, first-degree relatives have a great increase in the chance of VUR. The gene frequency is estimated to be 1:600. The American Academy of Pediatrics recommends that children from 2 to 24 months presenting with a UTI should be investigated for VUR.

Minimal change disease is most common in very young children but can occur in older children and adults. It is by far the most common cause of nephrotic syndrome in children between the ages of 1 and 7, accounting for the majority (about 90%) of these diagnoses. Among teenagers who develop nephrotic syndrome, it is caused by minimal change disease about half the time. It can also occur in adults but accounts for less than 20% of adults diagnosed with nephrotic syndrome. Among children less than 10 years of age, boys seem to be more likely to develop minimal change disease than girls. Minimal change disease is being seen with increasing frequency in adults over the age of 80.

People with one or more autoimmune disorders are at increased risk of developing minimal change disease. Having minimal change disease also increases the chances of developing other autoimmune disorders.

Nephrotic syndrome can affect any age, although it is mainly found in adults with a ratio of adults to children of 26 to 1.

The syndrome presents in different ways in the two groups: the most frequent glomerulopathy in children is minimal change disease (66% of cases), followed by focal segmental glomerulosclerosis (8%) and mesangiocapillary glomerulonephritis (6%). In adults the most common disease is mesangiocapillary glomerulonephritis (30-40%), followed by focal and segmental glomeruloesclerosis (15-25%) and minimal change disease (20%). The latter usually presents as secondary and not primary as occurs in children. Its main cause is diabetic nephropathy. It usually presents in a patient’s 40s or 50s.

Of the glomerulonephritis cases approximately 60% to 80% are primary, while the remainder are secondary.

There are also differences in epidemiology between the sexes, the disease is more common in men than in women by a ratio of 2 to 1.

The epidemiological data also reveals information regarding the most common way that symptoms develop in patients with nephrotic syndrome: spontaneous remission occurs in up to 20% or 30% of cases during the first year of the illness. However, this improvement is not definitive as some 50% to 60% of patients die and / or develop chronic renal failure 6 to 14 years after this remission. On the other hand, between 10% and 20% of patients have continuous episodes of remissions and relapses without dying or jeopardizing their kidney. The main causes of death are cardiovascular, as a result of the chronicity of the syndrome, and thromboembolic accidents.

The treatment of nephrotic syndrome can be symptomatic or can directly address the injuries caused to the kidney.

The epidemiology of rapidly progressive glomerulonephritis according to Hedger, et al., is an incidence rate of 3.9 individuals per million (3.3–4.7) with a 95% confidence intervals.

There are three main mechanisms to cause proteinuria:

- Due to disease in the glomerulus

- Because of increased quantity of proteins in serum (overflow proteinuria)

- Due to low reabsorption at proximal tubule (Fanconi syndrome)

Proteinuria can also be caused by certain biological agents, such as bevacizumab (Avastin) used in cancer treatment. Excessive fluid intake (drinking in excess of 4 litres of water per day) is another cause.

Also leptin administration to normotensive Sprague Dawley rats during pregnancy significantly increases urinary protein excretion.

Proteinuria may be a sign of renal (kidney) damage. Since serum proteins are readily reabsorbed from urine, the presence of excess protein indicates either an insufficiency of absorption or impaired filtration. People with diabetes may have damaged nephrons and develop proteinuria. The most common cause of proteinuria is diabetes, and in any person with proteinuria and diabetes, the cause of the underlying proteinuria should be separated into two categories: diabetic proteinuria versus the field.

With severe proteinuria, general hypoproteinemia can develop which results in

diminished oncotic pressure. Symptoms of diminished oncotic pressure may include ascites, edema and hydrothorax.

Congenital nephrotic syndrome can be successfully controlled with early diagnosis and aggressive treatment including albumin infusions, nephrectomy, medications and ultimately a kidney transplant. Most children live fairly normal life post-transplant but will spend significant time hospitalised pre-transplant and have numerous surgeries to facilitate treatment.

Due to the protein (albumin) losses many patients have reduced muscle tone and may experience delays in certain physical milestones such as sitting, crawling and walking. Similarly many patients experience growth delays due to protein loss. Delays vary from mild to significant but most patients experience growth spurts once they receive their transplanted kidney. Physical therapy may be useful for the child to strengthen muscle tone.

Undiagnosed cases are often fatal in the first year due to blood clots, infections or other complications.

Proteinuria may be a feature of the following conditions:

- Nephrotic syndromes (i.e. intrinsic renal failure)

- Pre-eclampsia

- Eclampsia

- Toxic lesions of kidneys

- Amyloidosis

- Collagen vascular diseases (e.g. systemic lupus erythematosus)

- Dehydration

- Glomerular diseases, such as membranous glomerulonephritis, focal segmental glomerulonephritis, minimal change disease (lipoid nephrosis)

- Strenuous exercise

- Stress

- Benign orthostatic (postural) proteinuria

- Focal segmental glomerulosclerosis (FSGS)

- IgA nephropathy (i.e. Berger's disease)

- IgM nephropathy

- Membranoproliferative glomerulonephritis

- Membranous nephropathy

- Minimal change disease

- Sarcoidosis

- Alport's syndrome

- Diabetes mellitus (diabetic nephropathy)

- Drugs (e.g. NSAIDs, nicotine, penicillamine, lithium carbonate, gold and other heavy metals, ACE inhibitors, antibiotics, or opiates (especially heroin)

- Fabry's disease

- Infections (e.g. HIV, syphilis, hepatitis, poststreptococcal infection, urinary schistosomiasis)

- Aminoaciduria

- Fanconi syndrome in association with Wilson disease

- Hypertensive nephrosclerosis

- Interstitial nephritis

- Sickle cell disease

- Hemoglobinuria

- Multiple myeloma

- Myoglobinuria

- Organ rejection:

- Ebola virus disease

- Nail patella syndrome

- Familial Mediterranean fever

- HELLP Syndrome

- Systemic lupus erythematosus

- Granulomatosis with polyangiitis

- Rheumatoid arthritis

- Glycogen storage disease type 1

- Goodpasture's syndrome

- Henoch–Schönlein purpura

- A urinary tract infection which has spread to the kidney(s)

- Sjögren's syndrome

- Post-infectious glomerulonephritis

The "APOL1" gene has been proposed as a major genetic risk locus for a spectrum of nondiabetic renal failure in individuals of African origin, these include HIV-associated nephropathy (HIVAN), primary nonmonogenic forms of focal segmental glomerulosclerosis, and hypertension affiliated chronic kidney disease not attributed to other etiologies. Two western African variants in APOL1 have been shown to be associated with end stage kidney disease in African Americans and Hispanic Americans.

Management of sickle nephropathy is not separate from that of overall patient management. In addition, however, the use of ACE inhibitors has been associated with improvement of the hyperfiltration glomerulopathy. Three-year graft and patient survival in kidney transplant recipients with sickle nephropathy is lower when compared to those with other causes of end-stage kidney disease.

The frequency is unknown, but the disease is considered to be very rare.

Osmotic nephrosis refers to structural changes that occur at the cellular level in the human kidney. Cells, primarily of the straight proximal tubule, swell due to the formation of large vacuoles in the cytoplasm. These vacuoles occur in the presence of large amounts of certain solutes circulating in the tubules. However, despite the condition's name, the solutes do not cause change through osmotic forces but through pinocytosis. Once inside the cytoplasm, pinocytic vacuoles combine with each other and with lysosomes to form large vacuoles that appear transparent under microscopic examination.

There may be no symptomatic presentation with this condition, or it may confused with other nephrotic conditions such as Tubular calcineurin-inhibitor toxicity. Affected cells of the proximal tubule may be passed in the urine, but a kidney biopsy is the only sure way to make a diagnosis.

Responsible exogenous solutes include sucrose-containing IVIg, mannitol, dextran, contrast dye, and hydroxyethyl starch. Prevention includes standard preventions for iatrogenic kidney damage. Osmotic nephrosis is usually reversible but can lead to chronic renal failure.

Chronic kidney disease (CKD) has numerous causes. The most common causes of CKD are diabetes mellitus and long-term, uncontrolled hypertension. Polycystic kidney disease is another well-known cause of CKD. The majority of people afflicted with polycystic kidney disease have a family history of the disease. Other genetic illnesses affect kidney function, as well.

Overuse of common drugs such as ibuprofen, and acetaminophen (paracetamol) can also cause chronic kidney disease.

Some infectious disease agents, such as hantavirus, can attack the kidneys, causing kidney failure.

Diabetic nephropathy in type 2 diabetes can be more difficult to predict because the onset of diabetes is not usually well established. Without intervention, 20-40 percent of patients with type 2 diabetes/microalbuminuria, will evolve to macroalbuminuria.

Diabetic nephropathy is the most common cause of end-stage kidney disease, which may require hemodialysis or even kidney transplantation. It is associated with an increased risk of death in general, particularly from cardiovascular disease.

Nephrosis is any of various forms of kidney disease (nephropathy). In an old and broad sense of the term, it is any nephropathy, but in current usage the term is usually restricted to a narrower sense of nephropathy without inflammation or neoplasia, in which sense it is distinguished from nephritis, which involves inflammation. It is also defined as any purely degenerative disease of the renal tubules. Nephrosis is characterized by a set of signs called the nephrotic syndrome. Nephrosis can be a primary disorder or can be secondary to another disorder. Nephrotic complications of another disorder can coexist with nephritic complications. In other words, nephrosis and nephritis can be pathophysiologically contradistinguished, but that does not mean that they cannot occur simultaneously.

Types of nephrosis include amyloid nephrosis and osmotic nephrosis.

Congenital nephrotic syndrome is a very rare form of nephrotic syndrome. It occurs predominantly in families of Finnish origin and manifests shortly after birth. It is an inherited disorder. The condition is caused by a defect in the protein nephrin, which is found in the kidney.

Proteins and fats are excreted in the urine, and there is an abnormally high fat level in the blood. Swelling occurs due to kidney failure, combined with the loss of blood protein. This is because proteins in the blood normally keep fluids in the blood stream, and when protein level is low, the fluid can leak into the body tissues.

Some of the proteins lost in the urine are immune system antibodies that fight infections. The disorder commonly results in infection, malnutrition, and kidney failure.

The incidence of diabetic nephropathy is higher in diabetics with one or more of the following conditions:

- Poor control of blood glucose

- Uncontrolled High blood pressure

- Type 1 diabetes mellitus, with onset before age 20

- Past or current cigarette use

- A family history of diabetic nephropathy

The long-term use of lithium, a medication commonly used to treat bipolar disorder and schizoaffective disorders, is known to cause nephropathy.

Despite expensive treatments, lupus nephritis remains a major cause of morbidity and mortality in people with relapsing or refractory lupus nephritis.

Sickle cell nephropathy is a type of nephropathy associated with sickle cell disease which causes kidney complications as a result of sickling of red blood cells in the small blood vessels. The hypertonic and relatively hypoxic environment of the renal medulla, coupled with the slow blood flow in the vasa recta, favors sickling of red blood cells, with resultant local infarction (papillary necrosis). Functional tubule defects in patients with sickle cell disease are likely the result of partial ischemic injury to the renal tubules.

Also the sickle cell disease in young patients is characterized by renal hyperperfusion, glomerular hypertrophy, and glomerular hyperfiltration. Many of these individuals eventually develop a glomerulopathy leading to glomerular proteinuria (present in as many as 30%) and, in some, the nephrotic syndrome. Co-inheritance of microdeletions in the -globin gene (thalassemia) appear to protect against the development of nephropathy and are associated with lower mean arterial pressure and less protein in the urine.

Mild increases in the blood levels of nitrogen and uric acid can also develop. Advanced kidney failure and high blood urea levels occur in 10% of cases. Pathologic examination reveals the typical lesion of "hyperfiltration nephropathy" namely, focal segmental glomerular sclerosis. This finding has led to the suggestion that anemia-induced hyperfiltration in childhood is the principal cause of the adult glomerulopathy. Nephron loss secondary to ischemic injury also contributes to the development of azotemia in these patients.

In addition to the glomerulopathy described above, kidney complications of sickle cell disease include cortical infarcts leading to loss of function, persistent bloody urine, and perinephric hematomas. Papillary infarcts, demonstrable radiographically in 50% of patients with sickle trait, lead to an increased risk of bacterial infection in the scarred kidney tissues and functional tubule abnormalities. The presence of visible blood in the urine without pain occurs with a higher frequency in sickle trait than in sickle cell disease and likely results from infarctive episodes in the renal medulla. Functional tubule abnormalities such as nephrogenic diabetes insipidus result from marked reduction in vasa recta blood flow, combined with ischemic tubule injury. This concentrating defect places these patients at increased risk of dehydration and, hence, sickling crises. The concentrating defect also occurs in individuals with sickle trait. Other tubule defects involve potassium and hydrogen ion excretion, occasionally leading to high blood potassium, metabolic acidosis, and a defect in uric acid excretion which, combined with increased purine synthesis in the bone marrow, results in high blood uric acid levels.

About a third of untreated patients have spontaneous remission, another third progress to require dialysis and the last third continue to have proteinuria, without progression of renal failure.

Reflux nephropathy is kidney damage (nephropathy) due to urine flowing backward (reflux) from the bladder toward the kidneys; the latter is called vesicoureteral reflux (VUR). Longstanding VUR can result in small and scarred kidneys during the first five years of life in affected children. The end results of reflux nephropathy can include high blood pressure, excessive protein loss in the urine, and eventually kidney failure.

When reflux nephropathy is suspected as a cause of kidney disease, other conditions to consider include chronic pyelonephritis, obstructive uropathy, and analgesic overuse.

The term "reflux nephropathy" was introduced in 1973.