Some general secondary causes are listed below:

- Glomerular hypertrophy/hyperfiltration

- Unilateral renal agenesis

- Morbid obesity

- Scarring due to previous injury

- Focal proliferative glomerulonephritis

- Vasculitis

- Lupus

- Toxins (pamidronate)

- Human immunodeficiency virus-associated nephropathy

- Heroin nephropathy

Focal segmental glomerulosclerosis may develop following acquired loss of nephrons from reflux nephropathy. Proteinuria is nonselective in most cases and may be in subnephrotic range (nephritic range <3.0gm/24hr) or nephritic range.

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.

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.

Minimal change disease is characterised as a cause of nephrotic syndrome without visible changes in the glomerulus on microscopy. Minimal change disease typically presents with edema, an increase in proteins passed from urine and decrease in blood protein levels, and an increase in circulating lipids (i.e., nephrotic syndrome) and is the most common cause of the nephrotic syndrome in children. Although no changes may be visible by light microscopy, changes on electron microscopy within the glomerules may show a fusion of the foot processes of the podocytes (cells lining the basement membrane of the capillaries of glomerulus). It is typically managed with corticosteroids and does not progress to chronic kidney disease.

Primary causes of nephrotic syndrome are usually described by their histology:

- Minimal change disease (MCD): is the most common cause of nephrotic syndrome in children. It owes its name to the fact that the nephrons appear normal when viewed with an optical microscope as the lesions are only visible using an electron microscope. Another symptom is a pronounced proteinuria.

- Focal segmental glomerulosclerosis (FSGS): is the most common cause of nephrotic syndrome in adults. It is characterized by the appearance of tissue scarring in the glomeruli. The term "focal" is used as some of the glomeruli have scars, while others appear intact; the term "segmental" refers to the fact that only part of the glomerulus suffers the damage.

- Membranous glomerulonephritis (MGN): The inflammation of the glomerular membrane causes increased leaking in the kidney. It is not clear why this condition develops in most people, although an auto-immune mechanism is suspected.

- Membranoproliferative glomerulonephritis (MPGN): is the inflammation of the glomeruli along with the deposit of antibodies in their membranes, which makes filtration difficult.

- Rapidly progressive glomerulonephritis (RPGN): (Usually presents as a nephritic syndrome) A patient’s glomeruli are present in a "crescent moon" shape. It is characterized clinically by a rapid decrease in the glomerular filtration rate (GFR) by at least 50% over a short period, usually from a few days to 3 months.

They are considered to be "diagnoses of exclusion", i.e. they are diagnosed only after secondary causes have been excluded.

Most types of RPGN are characterized by severe and rapid loss of kidney function featuring severe hematuria (blood in the urine), red blood cell casts in the urine, and proteinuria (protein in the urine), sometimes exceeding 3 g protein/24 h, a range associated with nephrotic syndrome. Some patients also experience hypertension (high blood pressure) and edema. Severe disease is characterized by pronounced oliguria or anuria, which portends a poor prognosis.

Proteinuria is the presence of excess proteins in the urine. In healthy persons, urine contains very little protein; an excess is suggestive of illness. Excess protein in the urine often causes the urine to become foamy, although foamy urine may also be caused by bilirubin in the urine (bilirubinuria), retrograde ejaculation, pneumaturia (air bubbles in the urine) due to a fistula, or drugs such as pyridium.

This is characterised by forms of glomerulonephritis in which the number of cells is not changed. These forms usually result in the nephrotic syndrome. Causes include:

Some people may present as nephrotic syndrome with proteinuria, edema with or without renal failure. Others may be asymptomatic and may be picked up on screening or urinalysis as having proteinuria. A definitive diagnosis of membranous nephropathy requires a kidney biopsy.

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.

Nephrotic syndrome is a collection of symptoms due to kidney damage. This includes protein in the urine, low blood albumin levels, high blood lipids, and significant swelling. Other symptoms may include weight gain, feeling tired, and foamy urine. Complications may include blood clots, infections, and high blood pressure.

Causes include a number of kidney diseases such as focal segmental glomerulosclerosis, membranous nephropathy, and minimal change disease. It may also occur as a complication of diabetes or lupus. The underlying mechanism typically involves damage to the glomeruli of the kidney. Diagnosis is typically based on urine testing and sometimes a kidney biopsy. It differs from nephritic syndrome in that there are no red blood cells in the urine.

Treatment is directed at the underlying cause. Other efforts include managing high blood pressure, high blood cholesterol, and infection risk. A low salt diet and limiting fluids is often recommended. About 5 per 100,000 people are affected per year. The usual underlying cause varies between children and adults.

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.

The clinical signs of minimal change disease are proteinuria (abnormal excretion of proteins, mainly albumin, into the urine), oedema (swelling of soft tissues as a consequence of water retention), and hypoalbuminaemia (low serum albumin). These signs are referred to collectively as nephrotic syndrome. Minimal change disease is unique among the causes of nephrotic syndrome as it lacks evidence of pathology in light microscopy, hence the name.

When albumin is excreted in the urine, its serum (blood) concentration decreases. Consequently, the intravascular oncotic pressure reduces relative to the interstitial tissue. The subsequent movement of fluid from the vascular compartment to the interstitial compartment manifests as the soft tissue swelling referred to as oedema. This fluid collects most commonly in the feet and legs, in response to gravity, particularly in those with poorly functioning valves. In severe cases, fluid can shift into the peritoneal cavity (abdomen) and cause ascites. As a result of the excess fluid, individuals with minimal change disease often gain weight, as they are excreting less water in the urine, and experience fatigue. Additionally, the protein in the urine causes it to become frothy.

The underlying calyces lose their normal concave shape and show clubbing.

The closely related terms membranous nephropathy and membranous glomerulopathy both refer to a similar constellation but without the assumption of inflammation.

Membranous nephritis (in which inflammation is implied, but the glomerulus not explicitly mentioned) is less common, but the phrase is occasionally encountered. These conditions are usually considered together.

By contrast, membranoproliferative glomerulonephritis has a similar name, but is considered a separate condition with a distinctly different causality. Membranoproliferative glomerulonephritis involves the basement membrane and mesangium, while membranous glomerulonephritis involves the basement membrane but not the mesangium. (Membranoproliferative glomerulonephritis has the alternate name "mesangiocapillary hohki", to emphasize its mesangial character.)

The symptoms of reflux nephropathy are comparable to nephrotic syndrome and infection of the urinary tract, though some individuals may not exhibit any evidence (symptom) of reflux nephropathy.

The onset of symptoms is 5 to 10 years after the disease begins. A usual first symptom is frequent urination at night: nocturia. Other symptoms include tiredness, headaches, a general feeling of illness, nausea, vomiting, frequent daytime urination, lack of appetite, itchy skin, and leg swelling.

Rapidly progressive glomerulonephritis (RPGN) is a syndrome of the kidney that is characterized by a rapid loss of renal function, (usually a 50% decline in the glomerular filtration rate (GFR) within 3 months) with glomerular crescent formation seen in at least 50% or 75% of glomeruli seen on kidney biopsies. If left untreated, it rapidly progresses into acute renal failure and death within months. In 50% of cases, RPGN is associated with an underlying disease such as Goodpasture syndrome, systemic lupus erythematosus or granulomatosis with polyangiitis; the remaining cases are idiopathic. Regardless of the underlying cause, RPGN involves severe injury to the kidneys' glomeruli, with many of the glomeruli containing characteristic glomerular crescents (crescent-shaped scars).

It is usually asymptomatic but whitish foam may appear in urine. Swelling of the ankles, hands, belly or the face may occur if losses of albumin are significant and produce low serum protein levels (nephrotic syndrome).

Albuminuria is a pathological condition wherein the protein albumin is abnormally present in the urine. It is a type of proteinuria. Albumin is a major plasma protein (normally circulating in the blood); in healthy people, only trace amounts of it are present in urine, whereas larger amounts occur in the urine of patients with kidney disease. For a number of reasons, clinical terminology is changing to focus on albuminuria more than proteinuria.

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.

Membranoproliferative glomerulonephritis ("MPGN"), also known as mesangiocapillary glomerulonephritis, is a type of glomerulonephritis caused by deposits in the kidney glomerular mesangium and basement membrane (GBM) thickening, activating complement and damaging the glomeruli.

MPGN accounts for approximately 4% of primary renal causes of nephrotic syndrome in children and 7% in adults.

It should not be confused with membranous glomerulonephritis, a condition in which the basement membrane is thickened, but the mesangium is not.

There are three types of MPGN, but this classification is becoming obsolete as the causes of this pattern are becoming understood.

Diabetic nephropathy (diabetic kidney disease) (DN) is the chronic loss of kidney function occurring in those with diabetes mellitus. It is a serious complication, affecting around one-quarter of adult diabetics in the United States. It usually is slowly progressive over years. Pathophysiologic abnormalities in DN begin with long-standing poorly controlled blood glucose levels. This is followed by multiple changes in the filtration units of the kidneys, the nephrons. (There are normally about 3/4-1 1/2 million nephrons in each adult kidney). Initially, there is constriction of the efferent arterioles and dilation of afferent arterioles, with resulting glomerular capillary hypertension and hyperfiltration; this gradually changes to hypofiltration over time. Concurrently, there are changes within the glomerulus itself: these include a thickening of the basement membrane, a widening of the slit membranes of the podocytes, an increase in the number of mesangial cells, and an increase in mesangial matrix. This matrix invades the glomerular capillaries and produces deposits called Kimmelstiel-Wilson nodules. The mesangial cells and matrix can progressively expand and consume the entire glomerulus, shutting off filtration.

The status of DN may be monitored by measuring two values: the amount of protein in the urine - proteinuria; and a blood test called the serum creatinine. The amount of the proteinuria is a reflection of the degree of damage to any still-functioning glomeruli. The value of the serum creatinine can be used to calculate the estimated glomerular filtration rate (eGFR), which reflects the percentage of glomeruli which are no longer filtering the blood.

Treatment with an angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB), which dilates the arteriole exiting the glomerulus, thus reducing the blood pressure within the glomerular capillaries, may delay - but not stop - progression of the disease. Also, three classes of diabetes medications - GLP-1 agonists, DPP-4 inhibitors, and SGLT2 inhibitors - may delay progression.

The proteinuria may become massive, and cause a low serum albumin with resulting generalized body swelling (edema): the nephrotic syndrome. Likewise, the eGFR may progressively fall from a normal of over 90 ml/min/1.73m to less than 15, at which point the patient is said to have end-stage kidney disease (ESKD). Diabetic nephropathy is the most common cause of ESKD, which may require hemodialysis and eventually kidney transplantation to replace the failed kidney function. Diabetic nephropathy is associated with an increased risk of death in general, particularly from cardiovascular disease.

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.