Nephritic Syndrome

Nephritic syndrome is a clinical syndrome resulting from glomerular inflammation, presenting with hematuria, some degree of proteinuria (generally less severe than in nephrotic syndrome, though the two can overlap), hypertension, and, often, some reduction in renal function, reflecting an inflammatory rather than purely permeability driven process.

Causes are broadly divided into those confined to the kidney and those reflecting a systemic disease process. Post infectious glomerulonephritis, classically following streptococcal infection, is a recognized cause, particularly in children.

IgA nephropathy is the most common cause of primary glomerulonephritis worldwide, often presenting with episodic visible hematuria coinciding with an upper respiratory tract infection.

Systemic causes include ANCA associated vasculitis (granulomatosis with polyangiitis and microscopic polyangiitis), anti-glomerular basement membrane disease (Goodpasture syndrome, particularly when combined with pulmonary hemorrhage), systemic lupus erythematosus (lupus nephritis, see that entry), and IgA vasculitis (Henoch-Schönlein purpura, particularly in children, with the characteristic purpuric rash, arthralgia, and abdominal pain alongside renal involvement).

Hematuria is the hallmark feature, and may be visible (classically described as tea colored or cola colored, reflecting altered blood from its glomerular origin, distinct from the bright red blood typically seen with a lower urinary tract source) or detectable only on urinalysis.

Hypertension and peripheral edema, generally milder than the edema seen in nephrotic syndrome, result from sodium and water retention as renal function declines. Oliguria may be present with more significant renal impairment.

Features of an underlying systemic cause should be actively sought, since their presence substantially narrows the differential and guides urgent further investigation: hemoptysis or dyspnea suggesting pulmonary hemorrhage in ANCA associated vasculitis or anti-GBM disease, sinonasal symptoms and saddle nose deformity in granulomatosis with polyangiitis, purpuric rash and arthralgia in IgA vasculitis, and the broader multisystem features of systemic lupus erythematosus detailed in that entry.

Rapidly progressive glomerulonephritis represents an aggressive form of nephritic syndrome, with renal function deteriorating over days to weeks rather than the more gradual course of other causes, and represents a medical emergency requiring urgent diagnosis and treatment to prevent irreversible renal failure.

Urinalysis confirms hematuria and proteinuria, and urine microscopy looking for dysmorphic red cells and red cell casts is a valuable and specific finding supporting a glomerular source of bleeding, distinguishing it from a lower urinary tract cause. Renal function (urea, creatinine, eGFR) establishes the degree of impairment and its trajectory on serial testing.

Complement levels (C3 and C4) are a useful early test, since a low complement level narrows the differential toward specific causes, including post infectious glomerulonephritis, lupus nephritis, and, less commonly, membranoproliferative glomerulonephritis, while normal complement levels point toward IgA nephropathy, ANCA associated vasculitis, or anti-GBM disease.

Further serological testing is directed by the clinical picture: ANCA (with distinction between PR3-ANCA, typically associated with granulomatosis with polyangiitis, and MPO-ANCA, typically associated with microscopic polyangiitis), anti-GBM antibody, ANA and anti-dsDNA if lupus is suspected, and streptococcal serology (anti-streptolysin O or anti-DNase B titres) if post infectious glomerulonephritis is suspected.

Renal biopsy is generally required to establish the specific histological diagnosis, assess the degree of activity versus chronic scarring, and guide treatment, and should be pursued urgently where rapidly progressive glomerulonephritis is suspected, given the time critical nature of starting immunosuppression before irreversible scarring develops.

Differentials for visible or microscopic hematuria more broadly include lower urinary tract causes such as infection, stones, and malignancy, which should be considered and, where the clinical picture suggests a non-glomerular source, appropriately investigated with imaging and cystoscopy rather than assumed to represent glomerulonephritis.

Management is directed by the underlying cause once established. Post infectious glomerulonephritis is generally managed supportively, with blood pressure and fluid management, since the condition is typically self limiting, particularly in children, with the large majority making a full recovery.

IgA nephropathy management depends on the degree of proteinuria and renal impairment. Lower risk disease, with minimal proteinuria and preserved renal function, is managed with blood pressure control and an ACE inhibitor or ARB to reduce proteinuria. Higher risk disease, with significant proteinuria or declining renal function despite supportive measures, is treated with corticosteroids, and, increasingly, other immunosuppressive or complement targeted therapies in specialist practice as the evidence base in this area continues to evolve.

Rapidly progressive glomerulonephritis, from any of the systemic causes above, requires urgent, aggressive immunosuppression to prevent irreversible renal failure. This typically involves high dose corticosteroids combined with cyclophosphamide or rituximab, with plasma exchange added in specific circumstances, particularly anti-GBM disease with pulmonary hemorrhage or severe ANCA associated vasculitis, given evidence of benefit in these specific high risk presentations.

General supportive measures across all causes include blood pressure control, often requiring an ACE inhibitor or ARB both for its antihypertensive and renoprotective, antiproteinuric effect, and fluid and sodium restriction where volume overload is present. Renal replacement therapy is required in a subset of patients with severe or rapidly progressive disease (see Indications for Dialysis entry).

Referral: nephrology urgently for any suspected rapidly progressive glomerulonephritis, given the time critical need for biopsy and immunosuppression; nephrology on a less urgent basis for other confirmed or suspected glomerulonephritis requiring biopsy and specific management.