Inflammation of the filtering units (glomeruli) in both kidneys. Damage to the glomeruli hampers the removal of waste products, salt, and water from the bloodstream, which may cause serious complications. This condition occurs worldwide; in the US and Europe, it is one of the most common causes of chronic kidney failure.
Some types of glomerulonephritis are caused by the immune system making antibodies to eliminate microorganisms (usually infectious bacteria, such as those that cause streptococcal infections of the throat). The antibodies combine with bacterial antigens to form particles called immune complexes. These particles circulate in the bloodstream and become trapped in the glomeruli, triggering an inflammatory process that may damage the glomeruli and prevent them from working normally. Glomerulonephritis also occurs in certain autoimmune disorders, such as systemic lupus erythematosus. Infectious diseases such as malaria and schistosomiasis are causes in tropical countries.
Mild glomerulonephritis may cause no symptoms, and it may only be dis-covered during routine urine testing; alternatively, the condition may remain undetected until the kidney damage has reached an advanced stage and accumulated waste products have started to produce symptoms. Some people develop symptoms suddenly. They may experience a dull ache over the kidneys. The urine may become bloodstained because when damaged the glomeruli allow red blood cells to escape into the urine. Protein may also be lost into the urine, causing oedema (the nephrotic syndrome); this is a common condition in affected children. Hypertension (high blood pressure) is a potentially serious complication. Long-term glomerulonephritis is a common cause of chronic kidney failure.
Diagnosis and treatment
Diagnosis involves kidney function tests, urinalysis (the microscopic and chemical analysis of urine), and, in most cases, kidney biopsy (removal of a small tissue sample for microscopic analysis). Treatment for glomerulonephritis is usually given in hospital, and depends on the cause and the severity of the disease.
Children with nephrotic syndrome usually respond to corticosteroid drugs.
Glomerulonephritis caused by a streptococcal infection usually clears up after the infection is successfully treated with antibiotic drugs.
Adults tend to respond less well to treatment, but kidney failure may some-times be prevented or delayed.
Drugs may be prescribed to control hypertension, and a special diet may be given to reduce the workload on the kidneys. Temporary dialysis may be necessary to help remove waste products from the blood, and diuretic drugs may be given to help treat any oedema (fluid retention). A few people with severe glomerulonephritis respond to treatment with immunosuppressant drugs (which reduce the activity of the immune system); others may undergo plasmapheresis (a procedure that removes immune complexes and other harmful substances from the bloodstream).
Glomerulonephritis in more detail - technical
Glomerulonephritis means ‘inflammation of glomeruli’ and, although inflammation is not apparent in all varieties (‘glomerulopathy’ is sometimes used to denote this), the name sticks. Most types of glomerulonephritis seem to be immunologically mediated and several respond to immunosuppressive drugs. Deposition of antibody occurs in many types of glomerulonephritis but frequently the presumed mechanisms involve cellular immunity, which is more difficult to investigate. Although deposition of circulating immune complexes was previously thought to be a common mechanism, it now seems that most granular deposits of immunoglobulin are formed ‘in situ’ by antibodies which complex about glomerular antigens, or about other antigens (‘planted’ antigens, e.g. viral or bacterial ones) that have localised in glomeruli.
Classifications of glomerulonephritis are largely histopathological and may appear daunting, but the details are largely a specialist concern.
Clinically important types are described in the text.
Minimal change nephropathy
Minimal change disease occurs at all ages but accounts for nephrotic syndrome in most children and about one-quarter of adults. Proteinuria usually remits on high-dose corticosteroid therapy (1 mg/kg prednisolone for 6 weeks), although some patients who respond incompletely or relapse frequently need maintenance corticosteroids, cytotoxic therapy or other agents. Minimal change disease does not progress to CKD; the main problems are those of the nephrotic syndrome and complications of treatment.
Primary focal segmental glomerulosclerosis (FSGS)
FSGS is a histological description with many causes. As FSGS is a focal process, abnormal glomeruli may not be seen on renal biopsy if only a few are sampled, leading to an initial diagnosis of minimal change nephropathy. Juxtamedullary glomeruli are more likely to be affected in early disease.
The primary FSGS group that present with idiopathic nephrotic syndrome and no other cause of renal disease typically show little response to corticosteroid treatment and often progress to renal failure. This disease frequently recurs after renal transplantation, and sometimes proteinuria recurs almost immediately. However, a proportion of patients with FSGS do respond to corticosteroids (a good prognostic sign). In other patients with the histological appearances of FSGS but lesser proteinuria, focal scarring reflects healing of previous focal glomerular injury, such as HUS, cholesterol embolism or vasculitis. In others, it seems to represent particular types of nephropathy: for example, those associated with HIV infection, some podocyte toxins and massive obesity. Associations with numerous other forms of injury and renal disorders are reported. There is no specific treatment for most of these.
This is the most common cause of nephrotic syndrome in adults. A proportion of cases are associated with known causes (see box) but most are idiopathic. Of this group, approximately one-third remit spontaneously, one-third remain in a nephrotic state, and one-third show progressive loss of renal function. Short-term treatment with high doses of corticosteroids and alkylating agents (e.g. cyclophosphamide) may improve both the nephrotic syndrome and the long-term prognosis. However, because of the toxicity of these regimens, most nephrologists reserve such treatment for those with severe nephrotic syndrome or deteriorating renal function.
IgA nephropathy and Henoch–Schönlein purpura IgA nephropathy
This is the most commonly recognised type of glomerulonephritis and can present in many ways. Haematuria is the earliest sign and is almost universal, proteinuria a later feature, and hypertension very common. There may be severe proteinuria or in some cases progressive loss of renal function. The disease is a common cause of ESRD (end stage renal disease). A particular hallmark in young adults is acute self-limiting exacerbations, often with gross haematuria, in association with minor respiratory infections. This may be so acute as to resemble acute post-infectious glomerulonephritis, with fluid retention, hypertension and oliguria with dark or red urine. Characteristically, the latency from clinical infection to nephritis is short: a few days or less. Occasionally, IgA nephropathy progresses rapidly and crescent formation may be seen. The response to immunosuppressive therapy is usually poor. The management of less acute disease is largely directed towards the control of blood pressure in an attempt to prevent or retard progressive renal disease. In children, and occasionally in adults, a systemic vasculitis occurring in response to similar infections is called Henoch–Schönlein purpura. A characteristic petechial rash (cutaneous vasculitis, typically affecting buttocks and lower legs) and abdominal pain (gastrointestinal vasculitis) usually dominate the clinical picture, with mild glomerulonephritis being indicated by haematuria. When the disease occurs in older children or adults, the glomerulonephritis is usually more prominent. Renal biopsy shows mesangial IgA deposition and appear-ances indistinguishable from acute IgA nephropathy.
Glomerulonephritis associated with infection
Bacterial infections, usually subacute (typically subacute bacterial endocarditis), may cause a variety of histological patterns of glomerulonephritis, most typically with membranous and mesangiocapillary lesions, and usually with plentiful immunoglobulin deposition and often evidence of complement consumption (low serum C3). In the developed world, hospital-acquired infections are now a common cause of these syndromes.
World-wide, glomerulonephritis occurs more commonly following hepatitis B, hepatitis C, schistosomiasis, leishmaniasis and possibly malaria and other chronic infec-tions. FSGS associated with HIV infection is prevalent in black races. Proving a causative relationship between renal disease and infection in individual cases is difficult. Acute and chronic infections may also cause interstitial renal disease.
Acute post-infectious glomerulonephritis
This is most common following infection with certain strains of streptococcus and therefore is often called post-streptococcal nephritis, but it can occur following other infections. It is much more common in children than adults but is now rare in the developed world. The latency is usually about 10 days after a throat infection or longer after skin infection, suggesting an immune mechanism rather than direct infection. An acute nephritis of varying severity occurs. Sodium retention, hypertension and oedema are particularly pronounced. There is also reduction of GFR, proteinuria, haematuria and reduced urine volume. Characteristically, this gives the urine a red or smoky appearance. There are low serum concentrations of C3 and C4 and evidence of streptococcal infection (perform antistreptolysin O (ASO) titre, culture of throat swab, and other microbiological sampling if skin infection is suspected). Renal function begins to improve spontaneously within 10–14 days, and management by fluid and sodium restriction and use of diuretic and hypotensive agents is usually adequate. Remarkably, the renal lesion in almost all children and many adults seems to resolve completely despite the severity of the glomerular inflammation and proliferation seen histologically.
Rapidly progressive (crescentic) glomerulonephritis
This describes an extreme inflammatory nephritis which causes rapid loss of renal function over days to weeks. Renal biopsy shows crescentic lesions often associated with necrotising lesions within the glomerulus (focal segmental (necrotising) glomerulonephritis). It is typically seen in Goodpasture’s disease, where there are specific anti-GBM antibodies, and in small-vessel vasculitides, but can also be seen in SLE (systemic lupus erythematosis) and occasionally IgA and other nephropathies.