Findings almost always include some degree of haematuria and proteinuria Proteinuria.
Clinical signs often include hypertension and oedema. In patients with glomerulonephritis, it is important to treat even mild hypertension effectively.
In rapidly progressive glomerulonephritis (RPGN), renal function deteriorates progressively over a few days or months. Workup and treatment of RPGN should be started urgently, often as an emergency case.
The clinical pictures of different types of glomerulonephritis vary and cannot be used to define the type of disease with certainty. The course of disease also varies in patients with the same type of disease.
The classification of glomerulonephritis into different groups has changed in recent years from a classification based on histology to one based more on pathophysiology.
Accurate diagnosis of glomerulonephritis nearly always requires renal biopsy.
Pathogenesis
A group of inflammatory diseases of the renal glomeruli leading to structural and functional changes, such as changes in glomerular permeability
The disease is initiated by immunological mechanisms, probably based on an underlying genetically defined reaction pattern (induced by the patient's own or foreign antigens, microbes, medicines).
The condition occurs either as a primary disease restricted to the kidneys or part of a systemic disease (SLE, systemic vasculitis).
May be associated with e.g. infections, complement system disorders, haematological diseases and different malignancies.
Clinical pictures of different types of glomerulonephritis
Glomerulonephritis can have various clinical presentations.
Clinical picture of nephritis
Rapidly progressive glomerulonephritis
Nephrotic syndrome
Asymptomatic haematuria and/or proteinuria
Renal failure
Different types of glomerulonephritis may have a similar clinical picture and, on the other hand, the clinical picture of the same type of glomerulonephritis may vary in individual patients.
The clinical picture often includes hypertension and, in patients with nephrosis, oedema.
A nephritic clinical picture is an acute condition and may lead to acute renal failure but the symptoms may also be milder and self-limited.
Plasma creatinine levels may be normal or elevated and the estimated glomerular filtration rate (eGFR) may be normal or decreased.
Untreated, all forms may lead to chronic renal failure.
Chronic forms of disease are often asymptomatic.
Glomerulonephritis may be associated with many systemic diseases, of which SLE Systemic Lupus Erythematosus (Sle) and different types of vasculitis are the most significant Vasculitides. In the follow-up of systemic diseases, urinary findings should be monitored, even if infrequently, and especially in association with any disease activation.
Acute nephritis or rapidly progressive glomerulonephritis (RPGN)
Aetiology
Primary renal disease caused by an infection or a systemic disease
Often associated with vasculitis (granulomatous polyangitis [GPA], microscopic polyangitis [MPA]), SLE or basement membrane nephritis (Goodpasture's syndrome).
Acute glomerulonephritis occurring after a streptococcal disease (1-3 weeks after the primary infection) is an example of a classic postinfectious glomerulonephritis.
Acute glomerulonephritis may also occur in connection with or after other infections (endocarditis, shunt nephritis, sepsis, viral hepatitis).
Henoch-Schönlein purpura nephritis, IgA nephropathy and membranoproliferative glomerulonephritis can sometimes be rapidly progressive.
Symptoms and findings
Haematuria, often red cell casts in urine (urinalysis, urine cells) ("nephritic sediment"), proteinuria (urine albumin/creatinine ratio, 24-hour urinary protein excretion)
Often elevated plasma creatinine levels
Oedema, hypertension
Depending on the aetiology, often additionally general symptoms (in patients with systemic disease often mild fever, fatigue, rash, respiratory, joint or gastrointestinal tract symptoms)
In rapidly progressive glomerulonephritis, renal function deteriorates progressively within a few days or weeks.
Laboratory tests may help to confirm the diagnosis.
Positive ANCA antibodies in patients with vasculitis
Hypocomplementaemia (serum complement C3, serum complement C4) and positive DNA antibodies in patients with SLE
Positive basement membrane antibodies in patients with basement membrane nephritis
Serum and urine protein fractions can reveal paraproteinemia.
Cryoglobulins
Serum antistreptolysin, serum antistaphylolysin can reveal a preceding infection.
Treatment and prognosis
Treatment according to aetiology, and supportive treatment: treatment of hypertension and renal failure Treatment of Chronic Renal Failure
For postinfectious glomerulonephritis treatment of the infection and supportive treatment
For basement membrane nephritis and vasculitis plasma exchange
For rapidly progressive glomerulonephritis sufficiently aggressive immunosuppressive treatment started early enough will improve the prognosis decisively.
Treatment and follow-up take place in specialized care during the active phase of the disease. After the end of possible immunosuppressive therapy in a stable remission situation, follow-up may also be transferred to primary care.
Among the most common form of glomerulonephritis causing nephrotic syndrome in adults
May be primary or secondary to, for example, obesity or loss of nephrons.
Minimal change glomerulonephritis (MCN)
The most common form of glomerulonephritis causing nephrosis in children but may also occur in adults
Triggered by various medicines, infections
Adults sometimes have this as a paraneoplastic phenomenon.
Membranous glomerulonephritis (MGN)
A common cause of nephrosis in adults
May be either idiopathic or associated with other diseases (SLE) or malignancies, for instance.
Antibodies to phospholipase-A2-receptor (PLA2R) can often be detected in the idiopathic disease, in a small share of patients antibodies to thrombospondin type-1 domain containing 7A (THSD7A).
Membranoproliferative glomerulonephritis (MPGN)
There may be various underlying disorders such as infections (viral hepatitis, endocarditis, shunt nephritis), SLE, acquired or congenital disorders of the complement system or malignancies (solid tumours or haematological malignancies).
IgA nephropathy Iga Nephropathy may sometimes present with a clinical picture of nephrosis.
Symptoms and findings
Oedema, weight gain
Proteinuria > 3 g/day, plasma albumin < 30 g/l, often additionally haematuria
Sometimes elevated plasma creatinine levels and hypertension
Severe nephrosis may be associated with acute renal failure.
Hyperlipidaemia, increased risk of venous thrombosis
In IgA mesangial glomerulonephritis, glucocorticoid therapy should be considered if proteinuria of > 1 g/day continues despite antiproteinuric treatment or the GFR starts to decline.
Treatment of membranoproliferative glomerulonephritis depends on the aetiology
The long-term prognosis of minimal change glomerulonephritis is good. In other forms of glomerulonephritis, the prognosis depends on how well proteinuria can be controlled.
Initial treatment with immunosuppression and follow-up are carried out in specialized care. In a stable situation, it may sometimes be possible to transfer the follow-up to primary care.
Clinical picture of haematuria-proteinuria
Aetiology
May be primary or associated with systemic diseases.
IgA mesangial glomerulonephritis Iga Nephropathy is the most common type of primary glomerulonephritis causing haematuria and proteinuria.
Membranous glomerulonephritis, membranoproliferative glomerulonephritis and secondary focal segmental glomerulosclerosis, ANCA vasculitis confined to the kidneys and SLE may also sometimes present with haematuria and proteinuria.
For vasculitis or SLE usually immunomodulatory treatment. For IgA mesangial glomerulonephritis, glucocorticoid therapy should be considered if the daily urinary protein levels do not fall to below 1 g/day or if the GFR has decreased or is starting to decrease.
If in membranous glomerulonephritis or focal segmental glomerulosclerosis proteinuria stays below 2 to 3 g/day, the long-term prognosis is quite good and no immunomodulatory treatment is needed.
In chronic proteinuric kidney disease, an SGLT2 inhibitor improves prognosis and is recommended to be started if GFR > 25 ml/min.
Initial treatment with possible immunosuppression in specialized care; at a later stage, treatment and follow-up is often transferred to primary care.
Referral indications
In primary care, the following can usually be monitored:
Isolated microhematuria (normal creatinine and no proteinuria) without a suspicion of an underlying disease. Does not require renal biopsy, follow-up every 1-2 years and referral if the situation changes.
Isolated minor (< 1 g/day) proteinuria without a suspicion of a systemic disease. Follow-up annually and referral if the situation changes. In young patients (< 30 yrs), however, readily consultation.
Non-urgent referral
Haematuria, proteinuria and normal or stable creatinine
Urgent referral
Gradually increasing creatinine
Nephrotic-level proteinuria (> 3 g/day) and profuse oedema
Suspected SLE or vasculitis
Emergency referral
Severe renal failure or suspected RPGN
Very profuse oedema and oliguria in nephrosis
References
Ghaddar M, Barratt J, Barbour SJ. An update on corticosteroid treatment for IgA nephropathy. Curr Opin Nephrol Hypertens 2023;32(3):263-270. [PubMed]
Sethi S, De Vriese AS, Fervenza FC. Acute glomerulonephritis. Lancet 2022;399(10335):1646-1663. [PubMed]
The EMPA-KIDNEY Collaborative Group, Herrington WG, Staplin N, et al. Empagliflozin in Patients with Chronic Kidney Disease. N Engl J Med 2023;388(2):117-127. [PubMed]