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.

More specifically, glomerulosclerosis can refer to:

- Focal segmental glomerulosclerosis

- Nodular glomerulosclerosis (diabetic)

Ask-Upmark kidneys are a cause of secondary hypertension that can be curable.

Chronic allograft nephropathy, abbreviated CAN and also known as sclerosing/chronic allograft nephropathy, is the leading cause of kidney transplant failure and happens month to years after the transplant.

It is thought to be congenital or the consequence of vesicoureteral reflux.

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.

Glomerulosclerosis, also known as glomerular sclerosis, refers to a hardening of the glomerulus in the kidney. It is a general term to describe scarring of the kidneys' tiny blood vessels, the glomeruli, the functional units in the kidney that filter urine from the blood.

Proteinuria (large amounts of protein in urine) is one of the signs of glomerulosclerosis. Scarring disturbs the filtering process of the kidneys and allows protein to leak from the blood into urine. However, glomerulosclerosis is one of many causes of proteinuria. A kidney biopsy (removal of tiny part of kidney with a needle) may be necessary to determine whether a patient has glomerulosclerosis or another kidney problem. About 15 percent of people with proteinuria turn out to have glomerulosclerosis.

Both children and adults can develop glomerulosclerosis and it can result from different types of kidney conditions. One frequently encountered type of glomerulosclerosis is caused by diabetes. Drug use or infections may cause focal segmental glomerulosclerosis (FSGS), a very chronic kidney condition. FSGS may also occur in patients with AIDS but most are of unknown cause.

Early stages of glomerulosclerosis may not produce any symptoms but the most important warning sign is proteinuria, usually discovered in routine medical exams. Losing large amounts of protein may cause swelling in the ankles and accumulation of fluid in the abdomen.

Scarred glomeruli cannot be repaired and many patients with glomerulosclerosis get worse over time until their kidneys fail. This condition is called end-stage renal disease (ESRD) and the patients must begin dialysis treatment or receive a kidney transplant. ESRD may be reached within a year or up to ten or more of diagnosis of glomerulosclerosis but time will vary.

Treatments for glomerulosclerosis depend on what caused the scarring of the glomeruli. This is determined by renal biopsy. Immunosuppressive drugs stop proteinuria in some patients, but once the treatments have ended proteinuria will continue. The drugs may sometimes damage the patient's kidneys even more.

Controlling the patient's blood pressure may control the progression of kidney failure. ACE inhibitors, a type of blood pressure medicine, preserve kidney function in patients with diabetes. ACE inhibitors may also slow down kidney failure for patients without diabetes. Low protein diets may also lighten the work done by kidneys to process waste. Some patients will need to control their cholesterol through diet or both diet and medicine.

Studies of the life expectancy of patients with Alport syndrome are rare, but one 2012 study of 456 male patients from across Europe who received a kidney transplant found that they had somewhat increased life expectancy compared to matched controls (the controls were "randomly selected from the same age, year, and modality categories").

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.

Alport syndrome is a genetic disorder affecting around 1 in 50,000 children, characterized by glomerulonephritis, end-stage kidney disease, and hearing loss. Alport syndrome can also affect the eyes, though the changes do not usually affect sight, except when changes to the lens occur in later life. Blood in urine is universal. Proteinuria is a feature as kidney disease progresses.

The disorder was first identified in a British family by University of Edinburgh Medical School graduate Cecil A. Alport in 1927. Alport Syndrome once also had the label hereditary nephritis, but this is misleading as there are many other causes of hereditary kidney disease and 'nephritis'.

Alport syndrome is caused by an inherited defect in type IV collagen—a structural material that is needed for the normal function of different parts of the body. Since type IV collagen is found in the ears, eyes, and kidneys, this explains why Alport syndrome affects different seemingly unrelated parts of the body (ears, eyes, kidneys, etc.).

CAN is characterized by a gradual decline in kidney function and, typically, accompanied by high blood pressure and hematuria.

85% of MGN cases are classified as "primary membranous glomerulonephritis"—that is to say, the cause of the disease is idiopathic (of unknown origin or cause). This can also be referred to as "idiopathic membranous nephropathy". One study has identified antibodies to an M-type phospholipase A receptor in 70% (26 of 37) cases evaluated. Other studies have implicated neutral endopeptidase and cationic bovine serum albumin as antigens.

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

Transplant glomerulopathy, abbreviated TG, is a disease of the glomeruli in transplanted kidneys. It is a type of renal injury often associated with chronic antibody-mediated rejection. However, transplant glomerulopathy is not specific for chronic antibody-mediated rejection; it may be the result of a number of disease processes affecting the glomerular endothelium.

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 prognosis for nephrotic syndrome under treatment is generally good although this depends on the underlying cause, the age of the patient and their response to treatment. It is usually good in children, because minimal change disease responds very well to steroids and does not cause chronic renal failure. Any relapses that occur become less frequent over time; the opposite occurs with mesangiocapillary glomerulonephritis, in which the kidney fails within three years of the disease developing, making dialysis necessary and subsequent kidney transplant. In addition children under the age of 5 generally have a poorer prognosis than prepubescents, as do adults older than 30 years of age as they have a greater risk of kidney failure.

Other causes such as focal segmental glomerulosclerosis frequently lead to end stage renal disease. Factors associated with a poorer prognosis in these cases include level of proteinuria, blood pressure control and kidney function (GFR).

Without treatment nephrotic syndrome has a very bad prognosis especially "rapidly progressing glomerulonephritis", which leads to acute kidney failure after a few months.

Diffuse proliferative nephritis (DPN) or glomerulonephritis (DPGN) is a type of glomerulonephritis that is the most serious form of renal lesions in SLE and is also the most common, occurring in 35% to 60% of patients. Most of the glomeruli show endothelial and mesangial proliferation affecting the entire glomerulus, leading to diffuse hypercellularity of the glomeruli, producing in some cases epithelial crescents that fill Bowman's space. When extensive, immune complexes create an overall thickening of the capillary wall, resembling rigid "wire loops" on routine light microscopy. Electron microscopy reveals electron-dense subendothelial immune complexes (between endothelium and basement membrane). Immune complexes can be visualized by staining with fluorescent antibodies directed against immunoglobulins or complement, resulting in a granular fluorescent staining pattern. In due course, glomerular injury gives rise to scarring (glomerulosclerosis). Most of these patients have hematuria with moderate to severe proteinuria, hypertension, and renal insufficiency.

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.

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.

It is characterized by glomerular basement membrane thickening (referred to as "tram-tracking of the basement membrane"), increased mesangial matrix and segmental and global glomerulosclerosis.

The differential diagnosis of tram-tracking includes membranoproliferative glomerulonephritis (especially hepatitis C), and thrombotic microangiopathies.

Sequence analysis shows that "Pax2" is the only known gene associated with the disease. Mutations in Pax2 have been identified in half of renal coloboma syndrome victims.

Patients with ESKD are at increased overall risk for cancer. This risk is particularly high in younger patients and gradually diminishes with age. Medical specialty professional organizations recommend that physicians do not perform routine cancer screening in patients with limited life expectancies due to ESKD because evidence does not show that such tests lead to improved patient outcomes.

Focal segmental glomerulosclerosis is characterised by a sclerosis of segments of some glomerules. It is likely to present as a nephrotic syndrome. This form of glomerulonephritis may be associated with conditions such as HIV and heroin abuse, or inherited as Alport syndrome. The cause of about 20–30% of focal-segmental glomerulosclerosis is unknown. On microscopy, affected glomerules may show an increase in hyalin, a pink and homogenous material, fat cells, an increase in the mesangial matrix and collagen. Treatment may involve corticosteroids, but up to half of people with focal segmental glomerulonephritis continue to have progressive deterioration of kidney function, ending in kidney failure.

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.