More specifically, glomerulosclerosis can refer to:

- Focal segmental glomerulosclerosis

- Nodular glomerulosclerosis (diabetic)

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.

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.

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.

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.

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:

Hypertensive kidney disease is a medical condition referring to damage to the kidney due to chronic high blood pressure. HN can be divided into two types: benign and malignant. Benign nephrosclerosis is common in individuals over the age of 60 where malignant nephrosclerosis is uncommon and affects 1-5% of individuals with high blood pressure, that have diastolic blood pressure passing 130 mm Hg. It should be distinguished from renovascular hypertension, which is a form of secondary hypertension. In addition, HN can be referred to as hypertensive nephrosclerosis, benign nephrosclerosis, and nephroangiosclerosis.

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 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.

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.

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.

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.

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.

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.)

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.

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.

Thin basement membrane disease must be differentiated from the other two common causes of glomerular hematuria, IgA nephropathy and Alport syndrome. The history and presentation are helpful in this regard:

- In Alport syndrome, there is often a family history of kidney failure, which may be associated with hearing impairment. Also, males tend to be more affected as Alport syndrome is X-linked in most cases.

- In IgA nephropathy, episodes of frank hematuria are more common, and a family history is less common.

A kidney biopsy is the only way to diagnose thin basement membrane disease. It reveals thinning of the glomerular basement membrane from the normal 300 to 400 nanometers (nm) to 150 to 250 nm. However, a biopsy is rarely done in cases where the patient has isolated microscopic hematuria, normal kidney function, and no proteinuria. The prognosis is excellent in this setting unless the clinical manifestations progress, as occurs in most males and some females with Alport syndrome and many patients with IgA nephropathy.

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.

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.

Symptoms can vary from person to person. Someone in early stage kidney disease may not feel sick or notice symptoms as they occur. When kidneys fail to filter properly, waste accumulates in the blood and the body, a condition called azotemia. Very low levels of azotaemia may produce few, if any, symptoms. If the disease progresses, symptoms become noticeable (if the failure is of sufficient degree to cause symptoms). Kidney failure accompanied by noticeable symptoms is termed uraemia.

Symptoms of kidney failure include the following:

- High levels of urea in the blood, which can result in:

- Vomiting or diarrhea (or both) which may lead to dehydration

- Nausea

- Weight loss

- Nocturnal urination

- More frequent urination, or in greater amounts than usual, with pale urine

- Less frequent urination, or in smaller amounts than usual, with dark coloured urine

- Blood in the urine

- Pressure, or difficulty urinating

- Unusual amounts of urination, usually in large quantities

- A buildup of phosphates in the blood that diseased kidneys cannot filter out may cause:

- Itching

- Bone damage

- Nonunion in broken bones

- Muscle cramps (caused by low levels of calcium which can be associated with hyperphosphatemia)

- A buildup of potassium in the blood that diseased kidneys cannot filter out (called hyperkalemia) may cause:

- Abnormal heart rhythms

- Muscle paralysis

- Failure of kidneys to remove excess fluid may cause:

- Swelling of the legs, ankles, feet, face, or hands

- Shortness of breath due to extra fluid on the lungs (may also be caused by anemia)

- Polycystic kidney disease, which causes large, fluid-filled cysts on the kidneys and sometimes the liver, can cause:

- Pain in the back or side

- Healthy kidneys produce the hormone erythropoietin that stimulates the bone marrow to make oxygen-carrying red blood cells. As the kidneys fail, they produce less erythropoietin, resulting in decreased production of red blood cells to replace the natural breakdown of old red blood cells. As a result, the blood carries less hemoglobin, a condition known as anemia. This can result in:

- Feeling tired or weak

- Memory problems

- Difficulty concentrating

- Dizziness

- Low blood pressure

- Normally, proteins are too large to pass through the kidneys, however, they are able to pass through when the glomeruli are damaged. This does not cause symptoms until extensive kidney damage has occurred, after which symptoms include:

- Foamy or bubbly urine

- Swelling in the hands, feet, abdomen, or face

- Other symptoms include:

- Appetite loss, a bad taste in the mouth

- Difficulty sleeping

- Darkening of the skin

- Excess protein in the blood

- With high doses of penicillin, people with kidney failure may experience seizures

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).

Benign nephrosclerosis alone hardly ever causes severe damage to the kidney, except in susceptible populations, such as African Americans, where it may lead to uremia and death. However, all persons with this disease usually show some functional impairment, such as loss of concentration or a variably diminished GFR. A mild degree of proteinuria is a frequent finding.

Acute kidney injuries can be present on top of chronic kidney disease, a condition called acute-on-chronic kidney failure (AoCRF). The acute part of AoCRF may be reversible, and the goal of treatment, as with AKI, is to return the patient to baseline kidney function, typically measured by serum creatinine. Like AKI, AoCRF can be difficult to distinguish from chronic kidney disease if the patient has not been monitored by a physician and no baseline (i.e., past) blood work is available for comparison.