Glomerulonephritis

Glomerulonephritis (GN) is glomerular inflammation or injury driven by an immune-mediated mechanism — immune-complex deposition, complement dysregulation, ANCA-associated pauci-immune small-vessel vasculitis, or direct anti-glomerular-basement-membrane (anti-GBM) antibody attack — rather than the more diffuse hemodynamic and structural injury that dominates most of this platform's Chronic Kidney Disease chapter. That distinction matters clinically: a correctly identified GN subtype frequently has a genuinely treatable, and sometimes reversible, immune driver, so RAAS blockade alone is not the ceiling of therapy the way it can be for other causes of proteinuric CKD — etiology-specific immunosuppression, chosen by subtype and risk, is often central.

The single most useful triage tool in this chapter is recognizing which of 2 syndromic patterns a patient's presentation fits. Nephritic syndrome — hematuria (often with dysmorphic red cells or red cell casts), hypertension, and variable, usually sub-nephrotic proteinuria, sometimes with reduced GFR — points toward IgA nephropathy, post-infectious GN, ANCA-associated vasculitis, lupus nephritis, or anti-GBM disease. Nephrotic syndrome — heavy proteinuria (classically 3.5 g/day or more), hypoalbuminemia, edema, and hyperlipidemia — points toward membranous nephropathy, minimal change disease, or focal segmental glomerulosclerosis (FSGS), though several of these etiologies can also present with mixed or overlapping features.^[1] This framework, not a single "glomerulonephritis" label, is what should drive the initial workup in Assessment & Diagnosis.

Nephritic versus nephrotic — why the distinction matters

Both syndromes reflect glomerular injury, but the pattern of injury differs in a way that changes the differential and the urgency. Nephritic syndrome reflects an inflammatory process disrupting the glomerular capillary wall enough to let red cells and a variable amount of protein through, often with an active, proliferative lesion on biopsy — some of its causes (ANCA vasculitis, anti-GBM disease, aggressive lupus nephritis) can progress to irreversible kidney failure within days to weeks if untreated (see Red Flags & Refer). Nephrotic syndrome reflects podocyte injury that lets protein, but not usually red cells, cross a structurally more intact capillary wall, producing the classic tetrad of heavy proteinuria, hypoalbuminemia, edema, and hyperlipidemia, and carries its own distinct complications — most importantly infection risk and venous thromboembolism (VTE) from urinary loss of immunoglobulins and anticoagulant proteins (see Complications in Red Flags & Refer).^[1]

• Recent group A streptococcal pharyngitis or skin infection (impetigo) — post-streptococcal GN, especially in children.^[3]
• A recent upper respiratory infection with concurrent gross hematuria — the synpharyngitic pattern classic for IgA nephropathy.^[2]
• Systemic lupus erythematosus — the leading secondary cause of GN covered in this chapter; renal involvement should be actively screened for in every SLE patient (see the Systemic Lupus Erythematosus chapter).^[4]
• Known or newly diagnosed ANCA-associated vasculitis, or systemic features suggesting one (sinusitis, pulmonary nodules/hemorrhage, mononeuritis multiplex, palpable purpura) alongside renal findings.^[5]
• Malignancy, hepatitis B infection, or certain drugs (e.g., NSAIDs, gold, penicillamine) — recognized secondary causes of membranous nephropathy; screen for these rather than assuming primary (anti-PLA2R-driven) disease by default, particularly in an older patient.^[6]
• Obesity, reduced nephron mass (a solitary kidney, low birth weight), or vesicoureteral reflux — drivers of secondary/adaptive FSGS, which does not respond to immunosuppression.^[4]
• A family history of kidney failure at a young age, or FSGS not responding as expected to immunosuppression — raises suspicion for a genetic FSGS variant; genetic testing is increasingly used to identify these non-immunosuppression-responsive forms.^[4]
• NSAID use, certain infections, and rarely other drugs — associated with minimal change disease, particularly a new or relapsing presentation in an adult.
• Male sex and older age generally track with a higher incidence of most primary GN subtypes, though pattern varies by specific disease.
• Hepatitis B, hepatitis C, and HIV infection — each associated with specific glomerular lesions (membranous nephropathy, membranoproliferative patterns/cryoglobulinemic GN, and HIV-associated nephropathy respectively) and should be screened for as part of a GN workup.^[1]

Complications

Left inadequately treated, the nephritic-pattern diseases in this chapter can progress to permanent nephron loss and CKD, and — for the most aggressive forms (ANCA-associated vasculitis, anti-GBM disease, aggressive lupus nephritis) — to rapidly progressive glomerulonephritis (RPGN) and irreversible kidney failure within days to weeks; see below.^[1][5] Nephrotic syndrome carries its own distinct complication set independent of the underlying diagnosis: a genuinely elevated venous thromboembolism risk from urinary loss of antithrombin and other anticoagulant proteins, historically reported in as many as roughly 1 in 4 adults with nephrotic syndrome and highest with membranous nephropathy and severe hypoalbuminemia;^[7] an elevated infection risk from urinary immunoglobulin loss, compounded further once immunosuppression is started; and, with sustained nephrotic-range proteinuria and dyslipidemia, elevated long-term cardiovascular risk.^[1] The etiology-specific immunosuppression used to treat several of these diseases carries its own real complications — corticosteroid toxicity, cyclophosphamide's dose-dependent gonadal toxicity and long-term malignancy risk, and calcineurin-inhibitor nephrotoxicity among them (see Drug Tables and Monitoring & Follow-Up) — which is exactly why confirming a specific, immunosuppression-responsive diagnosis before treating matters as much as it does.^[4]

Urinalysis with microscopy — the single most informative bedside test

A properly examined, fresh urine sediment is central to recognizing glomerular disease. Dysmorphic red blood cells — especially acanthocytes (ring-shaped cells with irregular protruding blebs) — and red blood cell casts are strong, specific markers of a glomerular bleeding source, with reported specificity and positive predictive value in the 90%-100% range for glomerular disease, distinguishing it from a lower urinary tract or urologic source of hematuria; sensitivity is more variable, so a negative or equivocal sediment does not rule glomerular disease out on its own.^[8] This platform's separate Hematuria chapter should be used for the complete triage framework when the diagnosis is genuinely uncertain (isolated hematuria without other nephritic/nephrotic features); this chapter assumes glomerular disease is already suspected or confirmed.

Quantifying proteinuria

A spot urine protein-to-creatinine ratio (or albumin-to-creatinine ratio) is the standard way to quantify and follow proteinuria — a planned 24-hour urine collection is an acceptable alternative but adds collection burden without materially improving accuracy for most purposes.^[1] Nephrotic-range proteinuria is generally defined as 3.5 g/day (or an equivalent protein-to-creatinine ratio) or greater; the specific numeric trend over time, not a single value, is what should drive treatment decisions in Choose Initial Treatment.

Complement levels and autoimmune serologies — narrowing the differential before biopsy

• Low complement (C3 and/or C4) points toward post-infectious GN, lupus nephritis, or a membranoproliferative/C3-glomerulopathy pattern.
• Normal complement is typical of IgA nephropathy, ANCA-associated vasculitis, anti-GBM disease, membranous nephropathy, minimal change disease, and primary FSGS.
• ANCA (PR3 and MPO) for suspected ANCA-associated vasculitis; a positive result alongside RPGN or pulmonary-renal features should prompt urgent referral, not outpatient follow-up (see Red Flags & Refer).^[5]
• Anti-GBM antibody for suspected anti-GBM disease, particularly with pulmonary-renal features.
• ANA and anti-dsDNA for suspected lupus nephritis in a patient with known or newly suspected SLE.^[4]
• Streptococcal serologies (ASO, anti-DNase B) and a history of recent throat or skin infection support post-infectious GN.^[3]
• Serum anti-PLA2R antibody for suspected primary membranous nephropathy — a strongly positive result in the right clinical context can support the diagnosis without requiring biopsy in some cases, and its titer is useful for tracking immunologic response to treatment (see Monitoring & Follow-Up).^[6][4]
• Hepatitis B and C serologies, and HIV testing where clinically indicated, given their association with specific secondary GN patterns.^[1]

Renal biopsy

Biopsy — light microscopy, immunofluorescence, and electron microscopy together — is often required for a definitive diagnosis and is frequently what determines the specific immunosuppressive regimen chosen, since several etiologies with overlapping clinical presentations require materially different treatment (e.g., primary versus secondary/genetic FSGS, or lupus nephritis class). The Canadian Society of Nephrology's current commentary specifically notes that testing availability for the serologies above (complement assays, anti-PLA2R, genetic testing) varies by province, which can affect how much a given case can be narrowed before biopsy is pursued.^[4] An expedited, urgent biopsy is warranted whenever RPGN is suspected (see Red Flags & Refer); in other presentations, biopsy timing is individualized by the treating nephrologist.

• Reduce proteinuria toward a specific, disease-appropriate target — commonly under 0.5-1 g/day, with the most recent IgA nephropathy-specific guidance targeting under 0.5 g/day and ideally under 0.3 g/day where achievable — rather than treating any reduction as sufficient.^[2]
• Preserve or stabilize kidney function, recognizing that in several GN subtypes this depends on treating the underlying immune process directly, not only on RAAS blockade and blood pressure control.
• Treat the underlying immune-mediated process specifically where a treatable etiology is identified — etiology-specific immunosuppression is often not optional adjunct therapy in this chapter's conditions the way it can be elsewhere in nephrology.
• Distinguish immunosuppression-responsive disease (primary FSGS, most MCD, moderate-to-high-risk membranous nephropathy, ANCA vasculitis, active lupus nephritis) from disease that will not respond to immunosuppression (secondary/adaptive or genetic FSGS) before committing a patient to its risks.^[4]
• Manage the syndrome-specific complications of nephrotic syndrome — edema, dyslipidemia, infection risk, and VTE risk — alongside the disease-specific treatment, not as an afterthought.
• Recognize and act on RPGN and pulmonary-renal syndrome without delay (see Red Flags & Refer) — these are the presentations in this chapter where treatment delay most directly costs irreversible kidney function.

• Sodium restriction (roughly under 2 g/day) to support blood pressure control and reduce edema — one of the most effective non-drug interventions in both nephritic and nephrotic presentations.
• Individualized fluid restriction for significant edema, guided by the degree of volume overload rather than applied reflexively to every patient.
• Protein intake at a normal (not high) level — avoid the older practice of high-protein diets to compensate for urinary protein loss, which does not correct hypoalbuminemia and may accelerate progression.
• Weight management where obesity is a contributing driver, particularly relevant to secondary/adaptive FSGS.
• Smoking cessation and standard cardiovascular risk-factor management, given the elevated cardiovascular risk that accompanies sustained nephrotic-range proteinuria and dyslipidemia.
• Vaccination review and completion before starting significant immunosuppression wherever the clinical timeline allows — live vaccines are generally deferred once immunosuppression is underway; complete standard immunizations (influenza, pneumococcal, hepatitis B) ahead of induction therapy rather than after.
• Nephrotoxin avoidance (regular NSAID use, unnecessary contrast exposure) — see the Chronic Kidney Disease chapter's nephrotoxin stewardship table, which applies identically here.

Patient education

Teach every patient started on significant immunosuppression the specific infection-prevention behaviours that matter most for their regimen — hand hygiene, avoiding known sick contacts where practical, and prompt same-day reporting of fever rather than waiting it out — since the threshold for treating a fever as urgent is genuinely lower during induction therapy (see Complications in Red Flags & Refer).^[1] Reinforce that a RAAS inhibitor and, where used, an SGLT2 inhibitor are working even when the patient feels well and cannot be stopped without discussion, since their benefit is measured in proteinuria trend and long-term kidney survival, not day-to-day symptoms. Teach nephrotic patients to recognize possible VTE symptoms specifically — new leg swelling or pain, sudden chest pain or shortness of breath, flank pain — as a reason to seek care immediately rather than attributing new swelling to their known edema.^[7] Daily weight and simple edema tracking helps patients and the care team recognize a genuine fluid-status change early. Discuss fertility preservation before cyclophosphamide is started in anyone of reproductive age, and confirm effective contraception is in place before starting mycophenolate mofetil in anyone who could become pregnant, given its teratogenicity.

Pregnancy

ACE inhibitors, ARBs, and mycophenolate mofetil are all contraindicated in pregnancy and should be stopped before conception is attempted where feasible, or as soon as pregnancy is confirmed. Cyclophosphamide is also contraindicated in pregnancy given teratogenicity. Hydroxychloroquine is safe and should be continued through pregnancy in lupus nephritis given its benefit to both mother and fetus. Tacrolimus is generally considered the calcineurin inhibitor of choice when one is needed in pregnancy. Active GN in pregnancy, particularly lupus nephritis or any RPGN presentation, needs joint nephrology/obstetric (maternal-fetal medicine) management from the outset rather than being managed from this chapter's general framework alone.

Breastfeeding

Prednisone, hydroxychloroquine, and tacrolimus are generally considered compatible with breastfeeding at usual doses. Mycophenolate mofetil and cyclophosphamide are generally avoided during breastfeeding. Confirm the compatibility of any other agent in this chapter against current lactation references before assuming it is safe, rather than extrapolating from the pregnancy contraindication alone.

Pediatrics

Minimal change disease and post-streptococcal GN are disproportionately pediatric presentations, each generally carrying a more favourable prognosis in children than the equivalent presentation in an adult; dosing and regimen specifics should follow pediatric nephrology direction rather than the adult framework in this chapter.

Fertility preservation

Cyclophosphamide's gonadal toxicity is dose-dependent — discuss fertility preservation options with any patient of reproductive age before starting it wherever the clinical urgency allows, and observe the cumulative-dose limits in Drug Tables.

Older adults

New-onset membranous nephropathy in an older adult should specifically prompt a secondary-cause workup (malignancy screening appropriate to age, hepatitis B/C testing) before assuming primary disease. Older adults also carry a higher baseline infection risk on significant immunosuppression — apply an even lower threshold for infection-prevention counselling and prompt evaluation of fever.

Renal impairment / dialysis

Cyclophosphamide dosing should be reduced for reduced eGFR per current product/regimen guidance; several agents in this chapter require dose or interval adjustment as kidney function changes through disease progression — see the Chronic Kidney Disease chapter's general renal-dosing principles, which apply throughout this chapter as well.

Monitor the urine protein-to-creatinine ratio and serum creatinine/eGFR at a frequency individualized to disease activity and treatment phase — more often during induction immunosuppression or after any RAAS-inhibitor dose change, less often once in stable remission.

RAAS blockade

Serum creatinine and potassium 2-4 weeks after starting or up-titrating an ACE inhibitor or ARB, and periodically thereafter — identical to the Chronic Kidney Disease chapter's approach.

Immunosuppression-specific monitoring

• Corticosteroids: blood glucose, blood pressure, and bone health with prolonged use; taper per the specific regimen rather than stopping abruptly.
• Cyclophosphamide: CBC (cytopenias), track cumulative lifetime dose explicitly against fertility- and malignancy-risk thresholds, and monitor for hemorrhagic cystitis with oral regimens.
• Mycophenolate mofetil and azathioprine: CBC and liver enzymes periodically.
• Calcineurin inhibitors (tacrolimus/cyclosporine): trough drug levels, renal function, blood pressure, and glucose.
• Rituximab: screen for hepatitis B before the first dose; monitor for infusion reactions and infection; CD19/CD20 B-cell counts are sometimes used to help time re-dosing in maintenance regimens.
• Confirm Pneumocystis jirovecii prophylaxis is in place and actually being taken throughout any period of sustained high-dose immunosuppression (see Pharmacologic Treatment Options).

Disease-specific markers

Serum anti-PLA2R antibody titer can be followed in primary membranous nephropathy — a falling or undetectable titer (immunologic remission) often precedes clinical remission and can support a treatment-response decision before proteinuria has fully normalized.^[6] Complement levels can be followed in lupus nephritis and post-infectious GN as a marker of disease activity alongside proteinuria and renal function. ANCA titer trends are not, on their own, a reliable guide to when to adjust maintenance therapy in ANCA-associated vasculitis and should not replace clinical and laboratory reassessment.^[1]

VTE and infection surveillance in nephrotic syndrome

Reassess VTE risk (serum albumin trend, degree and persistence of proteinuria) at each visit while nephrotic-range proteinuria persists, and maintain a low threshold to investigate new leg swelling, chest symptoms, or flank pain as a possible thrombotic event rather than simply worsening edema.^[7]

1. Membranous nephropathy not achieving remission after an adequate rituximab course: reassess anti-PLA2R titer trend and consider cyclophosphamide-based therapy or a repeat rituximab course, in conjunction with nephrology.^[6][4]
2. Steroid-resistant minimal change disease or primary FSGS: escalate to a calcineurin inhibitor; reconfirm the diagnosis (and consider genetic testing for FSGS specifically) if response remains inadequate, since a genetic or secondary form will not respond to further immunosuppression regardless of agent.^[4]
3. ANCA-associated vasculitis relapse on maintenance therapy: reinduction following the same principles as initial induction, with nephrology/rheumatology reassessment of whether avacopan or a change in maintenance agent is appropriate.^[5][4]
4. Lupus nephritis not responding to first-line induction: reassess adherence and hydroxychloroquine use specifically, then escalate per the Systemic Lupus Erythematosus chapter's framework rather than empirically layering on additional agents from this chapter alone.
5. Persistent nephrotic-range proteinuria despite disease-specific treatment: reconfirm the diagnosis is correct (repeat biopsy is occasionally warranted) before assuming simple treatment failure, and reassess VTE/infection risk as ongoing, not resolved.
6. Rapidly progressive glomerulonephritis not responding to initial immunosuppression: urgent reassessment by nephrology for plasma exchange consideration (particularly with anti-GBM disease or severe pulmonary hemorrhage) and confirmation the diagnosis and regimen are correct.^[1]

• Starting empiric immunosuppression before a specific diagnosis is confirmed, ideally by biopsy — the regimens in this chapter are not interchangeable, and using the wrong one exposes a patient to real toxicity for no benefit.
• Treating secondary/adaptive or genetic FSGS with immunosuppression — it will not respond, and the harm from immunosuppression is real and avoidable.^[4]
• Stopping or reducing a RAAS inhibitor for an expected, modest initial eGFR decline rather than confirming it is outside the acceptable range first — see the Chronic Kidney Disease chapter's identical principle.
• Starting an SGLT2 inhibitor concurrently with induction immunosuppression rather than waiting for stable maintenance therapy.^[4]
• Missing VTE risk assessment in severe nephrotic syndrome, particularly membranous nephropathy, until after a clot has already occurred.^[7]
• Forgetting Pneumocystis jirovecii prophylaxis during sustained high-dose immunosuppression.
• Attributing hematuria in a patient with known GN risk factors to a lower urinary tract or urologic cause without examining the urine sediment for dysmorphic red cells/red cell casts first.^[8]
• Treating a rising creatinine with an active urine sediment as routine GN follow-up rather than recognizing possible RPGN and escalating urgently.^[1]
• Assuming ANCA titer trends alone are sufficient to guide maintenance-therapy adjustments in ANCA-associated vasculitis.^[1]
• Managing lupus nephritis purely from this chapter's general GN framework rather than integrating with the patient's complete SLE care in the Systemic Lupus Erythematosus chapter.
• Not screening for hepatitis B before starting rituximab, given reactivation risk.

How to use this table: Doses require patient-specific confirmation, including renal/hepatic adjustment where relevant, and follow the specific disease/regimen chosen in Choose Initial Treatment above rather than a single fixed protocol. Select any drug name to open its complete Pharmasist Drug Database page. Cumulative-dose and fertility-related cautions for cyclophosphamide are especially important to track over a patient's whole treatment course, not just at a single visit.

Renin-Angiotensin System Blockade — Foundational Across Every GN Subtype

Start regardless of which etiology-specific immunosuppression is also used. Titrate to the highest approved/tolerated dose for the proteinuria-lowering effect, not just to a blood pressure target.

Corticosteroids

Regimen, dose, and taper length are specific to the indication — do not extrapolate one indication's regimen to another within this table.

Etiology-Specific Immunosuppression

Selected by the specific diagnosed GN subtype and its severity, per Choose Initial Treatment — not interchangeable between conditions in this chapter.

Supportive and Adjunctive Therapy

Manage the syndrome-specific complications of nephrotic syndrome alongside disease-specific treatment, not after it.