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).

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.

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.

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.

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.

Some symptoms that are present in nephrotic syndrome, such as edema and proteinuria, also appear in other illnesses. Therefore, other pathologies need to be excluded in order to arrive at a definitive diagnosis.

- Edema: in addition to nephrotic syndrome there are two other disorders that often present with edema; these are heart failure and liver failure. Congestive heart failure can cause liquid retention in tissues as a consequence of the decrease in the strength of ventricular contractions. The liquid is initially concentrated in the ankles but it subsequently becomes generalized and is called anasarca. Patients with congestive heart failure also experience an abnormal swelling of the heart cardiomegaly, which aids in making a correct diagnosis. Jugular venous pressure can also be elevated and it might be possible to hear heart murmurs. An echocardiogram is the preferred investigation method for these symptoms. Liver failure caused by cirrhosis, hepatitis and other conditions such as alcoholism, IV drug use or some hereditary diseases can lead to swelling in the lower extremities and the abdominal cavity. Other accompanying symptoms include jaundice, dilated veins over umbilicus (caput medusae), scratch marks (due to widespread itching, known as pruritus), enlarged spleen, spider angiomata, encephalopathy, bruising, nodular liver and anomalies in the liver function tests. Less frequently symptoms associated with the administration of certain pharmaceutical drugs have to be discounted. These drugs promote the retention of liquid in the extremities such as occurs with NSAIs, some antihypertensive drugs, the adrenal corticosteroids and sex hormones.

Acute fluid overload can cause edema in someone with kidney failure. These people are known to have kidney failure, and have either drunk too much or missed their dialysis. In addition, when Metastatic cancer spreads to the lungs or abdomen it causes effusions and fluid accumulation due to obstruction of lymphatic vessels and veins, as well as serous exudation.

- Proteinuria: the loss of proteins from the urine is caused by many pathological agents and infection by these agents has to be ruled out before it can be certain that a patient has nephrotic syndrome. Multiple myeloma can cause a proteinuria that is not accompanied by hypoalbuminemia, which is an important aid in making a differential diagnosis; other potential causes of proteinuria include asthenia, weight loss or bone pain. In diabetes mellitus there is an association between increases in glycated hemoglobin levels and the appearance of proteinuria. Other causes are amyloidosis and certain other allergic and infectious diseases.

More specifically, glomerulosclerosis can refer to:

- Focal segmental glomerulosclerosis

- Nodular glomerulosclerosis (diabetic)

Orthostatic proteinuria (synonyms: orthostatic albuminuria, postural proteinuria) is a benign condition. A change in renal hemodynamics, which in some otherwise normal individuals, causes protein (mostly albumin) to appear in urine when they are in the standing position. Urine formed when these individuals are lying down is protein-free.

There is normal urinary protein excretion during the night but increased excretion during the day, associated with activity and upright posture. Total urinary protein excretion may be increased but levels above 1 g per 24 hours are more likely to be associated with underlying renal disease. The exact cause of orthostatic proteinuria is not known.

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.

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.

Microalbuminuria (moderate increase in the levels of urinary albumin) is a non-specific finding in patients with vascular disease that is associated with increased risk of cardiovascular events. The majority of patients with benign nephrosclerosis have proteinuria in the range from 0.5 to 1 g/ 24hr. In the case of glomerular damage occurring in HN, hematuria can occur as well.

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.

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 many cases of asymptomatic microscopic hematuria without proteinuria, no etiology is found. Common causes of microscopic hematuria in pediatric populations include:

- hypercalciuria–suspected in a child with family history of kidney stones; can be asymptomatic or can cause painful urination

- benign familial hematuria–a genetic disorder causing persistent microscopic hematuria

- IgA nephropathy

- sickle cell trait or disease

- Alport syndrome–a genetic disorder causing recurrent microscopic hematuria with proteinuria, hearing loss, and progressive kidney failure

Signs and symptoms of chronic kidney disease, including loss of appetite, nausea, vomiting, itching, sleepiness or confusion, weight loss, and an unpleasant taste in the mouth, may develop.

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.

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:

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.

The classic presentation (in 40–50% of the cases) is episodic hematuria, which usually starts within a day or two of a non-specific upper respiratory tract infection (hence "synpharyngitic"), as opposed to post-streptococcal glomerulonephritis, which occurs some time (weeks) after initial infection. Less commonly gastrointestinal or urinary infection can be the inciting agent. All of these infections have in common the activation of mucosal defenses and hence IgA antibody production. Groin pain can also occur. The gross hematuria resolves after a few days, though microscopic hematuria may persist. These episodes occur on an irregular basis every few months and in most patients eventually subsides, although it can take many years. Renal function usually remains normal, though rarely, acute kidney failure may occur (see below). This presentation is more common in younger adults.

A smaller proportion (20-30%), usually the older population, have microscopic hematuria and proteinuria (less than 2 gram/day). These patients may not have any symptoms and are only clinically found if a physician decides to take a urine sample. Hence, the disease is more commonly diagnosed in situations where screening of urine is compulsory (e.g., schoolchildren in Japan).

Very rarely (5% each), the presenting history is:

- Nephrotic syndrome (3-3.5 grams of protein loss in the urine, associated with a poorer prognosis)

- Acute kidney failure (either as a complication of the frank hematuria, when it usually recovers, or due to rapidly progressive glomerulonephritis which often leads to chronic kidney failure)

- Chronic kidney failure (no previous symptoms, presents with anemia, hypertension and other symptoms of kidney failure, in people who probably had longstanding undetected microscopic hematuria and/or proteinuria)

A variety of systemic diseases are associated with IgA nephropathy such as liver failure, celiac disease, rheumatoid arthritis, reactive arthritis, ankylosing spondylitis and HIV. Diagnosis of IgA nephropathy and a search for any associated disease occasionally reveals such an underlying serious systemic disease. Occasionally, there are simultaneous symptoms of Henoch–Schönlein purpura; see below for more details on the association. Some HLA alleles have been suspected along with complement phenotypes as being genetic factors.

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.

Microscopic hematuria does not discolor the urine and is thus found incidentally on urinalysis or light microscopy. It is defined as greater than three red blood cells per high powered field. In many of these cases, no source or cause is found. Any part of the kidneys or urinary system can cause microscopic hematuria. Causes can be separated into glomerular, arising from the filtering system of the kidney, and non-glomerular, arising from the kidney (outside the glomerulus), ureters, urinary bladder, prostate, or urethra.

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.

Most patients with thin basement membrane disease are incidentally discovered to have microscopic hematuria on urinalysis. The blood pressure, kidney function, and the urinary protein excretion are usually normal. Mild proteinuria (less than 1.5 g/day) and hypertension are seen in a small minority of patients. Frank hematuria and loin pain should prompt a search for another cause, such as kidney stones or loin pain-hematuria syndrome. Also, there are no systemic manifestations, so presence of hearing impairment or visual impairment should prompt a search for hereditary nephritis such as Alport syndrome.

It is the most common genetic cause of end stage renal disease (renal failure) in childhood and adolescence.

Histologically, IgA nephropathy may show mesangial widening and focal and segmental inflammation. Diffuse mesangial proliferation or crescentic glomerulonephritis may also be present. Immunoflourescence shows mesangial deposition of IgA often with C3 and properdin and smaller amounts of other immunoglobulins (IgG or IgM). Early components of the classical complement pathway (C1q or C4) are usually not seen. Electron microscopy confirms electron-dense deposits in the mesangium that may extend to the subendothelial area of adjacent capillary walls in a small subset of cases, usually those with focal proliferation.