Glomerulonephritis
Clinical Snapshot
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.
Recognize the Condition
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]
Major etiology categories
Organized by the pattern each most typically produces, though overlap occurs.
IgA nephropathy
The most common primary glomerulonephritis worldwide. Classically presents with synpharyngitic gross hematuria (visible hematuria coinciding with an upper respiratory infection, within a day or two rather than the 1-3 week delay typical of post-streptococcal GN) or with persistent microscopic hematuria and proteinuria found incidentally. Diagnosis requires biopsy showing dominant IgA deposition on immunofluorescence.[2]
Post-infectious / post-streptococcal GN
Classically follows a group A streptococcal throat or skin infection by 1-3 weeks and is more classically a pediatric presentation, though it occurs in adults, often with a worse prognosis. Presents as acute nephritic syndrome — edema, hematuria, hypertension, and proteinuria — and is usually self-limited.[3]
Lupus nephritis
A major secondary cause of GN, occurring in a substantial proportion of patients with systemic lupus erythematosus (SLE) and capable of any biopsy pattern from mild mesangial disease to aggressive diffuse proliferative or membranous-pattern injury. Requires coordination with the patient's overall SLE management — see the Systemic Lupus Erythematosus chapter for the complete disease framework; this chapter covers only the renal-specific treatment principles.[4]
ANCA-associated vasculitis
A pauci-immune (little to no immune-complex deposition on immunofluorescence) small-vessel vasculitis associated with anti-neutrophil cytoplasmic antibodies (PR3-ANCA or MPO-ANCA), often part of a systemic vasculitis (granulomatosis with polyangiitis, microscopic polyangiitis, or eosinophilic granulomatosis with polyangiitis) affecting the lungs, sinuses, or skin alongside the kidney. A leading cause of rapidly progressive glomerulonephritis (RPGN) — see Red Flags & Refer.[5]
Membranous nephropathy
Typically presents with nephrotic-range proteinuria. Primary (idiopathic) membranous nephropathy is usually driven by autoantibodies against the podocyte antigen PLA2R (detectable on serum testing in most primary cases) or, less commonly, THSD7A; secondary membranous nephropathy is associated with malignancy, hepatitis B, or certain drugs, and should be actively screened for, particularly in older adults.[6][4]
Minimal change disease (MCD)
The most common cause of nephrotic syndrome in children and a genuine, if less common, cause in adults. Light microscopy is normal by definition (electron microscopy shows podocyte foot-process effacement), and it is typically highly steroid-responsive.[1]
Focal segmental glomerulosclerosis (FSGS)
A histologic pattern, not a single disease — current classification separates primary FSGS (immune-mediated, immunosuppression-responsive, presents with nephrotic syndrome) from FSGS that is secondary, adaptive (e.g., obesity, reduced nephron mass, reflux), or genetic, none of which respond to immunosuppression and are managed instead with RAAS blockade and treatment of the underlying driver. Distinguishing the two before treating is a genuinely important, easily-missed step.[4][1]
Risk Factors
- 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]
Red Flags & Refer
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]
Any of the following changes the plan from routine outpatient nephrology follow-up to urgent same-day or emergency evaluation.
- Rapidly progressive glomerulonephritis (RPGN) — a rise in serum creatinine over days to a few weeks, with an active urine sediment (dysmorphic red cells and/or red cell casts) — is a nephrology emergency. It reflects severe, often crescentic, glomerular injury (most commonly ANCA-associated vasculitis, anti-GBM disease, or aggressive lupus nephritis) that can progress to irreversible kidney failure within days to weeks without an urgent biopsy and urgent immunosuppression.[1][5]
- Pulmonary-renal syndrome — hemoptysis, dyspnea, or pulmonary infiltrates/hemorrhage occurring alongside RPGN — is a specific, life-threatening presentation of ANCA-associated vasculitis or anti-GBM disease and needs immediate, coordinated respiratory and nephrology involvement, not sequential work-up of each organ separately.[5]
- Severe nephrotic syndrome with a VTE event (a new deep vein thrombosis, pulmonary embolism, or renal vein thrombosis) — treat as an acute VTE emergency in its own right (see the Venous Thromboembolism chapter for acute management) while also urgently reassessing anticoagulation strategy and the underlying GN diagnosis; membranous nephropathy carries a particularly high VTE risk among the nephrotic-range diseases.[7]
- Severe nephrotic syndrome with signs of serious infection (cellulitis, spontaneous bacterial peritonitis, sepsis) — nephrotic patients have a genuinely elevated infection risk from urinary immunoglobulin loss, compounded further once immunosuppression is started; treat infection promptly and do not assume a fever in this population is simply a flare.[1]
- New, significant proteinuria (nephrotic-range or a rapidly rising urine protein-to-creatinine ratio) or a new reduction in eGFR in a patient not already under nephrology care.
- Any positive ANCA, anti-GBM antibody, or new low complement with an active urine sediment — refer urgently for biopsy-directed diagnosis rather than treating empirically.[1]
- Uncontrolled hypertension or volume overload not responding to standard measures in a patient with known or suspected GN.
Assessment & Diagnosis
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.
Treatment Targets
- 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.
Choose Initial Treatment
Start an ACE inhibitor or ARB in essentially every patient with GN and albuminuria/proteinuria, regardless of the specific etiology or whether immunosuppression is also being used — this is a disease-agnostic renoprotective foundation, not a substitute for etiology-specific therapy where one exists.[1] Titrate to the highest approved and tolerated dose, since the proteinuria-lowering effect is dose-dependent, not just to a blood pressure target. Never combine an ACE inhibitor and an ARB. Check serum creatinine and potassium 2-4 weeks after starting or up-titrating — see the Chronic Kidney Disease chapter for the full hyperkalemia-management stepwise approach, which applies identically here.
Choose the regimen by the specific diagnosed subtype and its severity — this is not a one-size-fits-all decision, and starting immunosuppression before a specific diagnosis is confirmed (ideally by biopsy) risks real, avoidable harm for no proven benefit.
Supportive care first, for essentially everyone. Maximized RAAS blockade, blood pressure control, and an SGLT2 inhibitor form the initial foundation; the current KDIGO 2025 guideline specifically encourages a more liberal biopsy policy and a stricter proteinuria target (under 0.5 g/day, ideally under 0.3 g/day) than prior guidance.[2] Individualized risk prediction (e.g., the International IgA Nephropathy Prediction Tool) should guide whether a patient needs more than supportive care.[4] A time-limited systemic glucocorticoid trial can be considered for patients at high risk of progression whose proteinuria remains above target despite 90 days of optimized supportive care; the lower-dose regimen from the TESTING trial is now preferred over older high-dose protocols given a materially better safety profile, though the Canadian Society of Nephrology notes real provincial availability challenges with the specific formulation used in that trial.[2][4]
Risk-stratify every patient — low, moderate, high, or very-high risk of progression — using the trend in proteinuria, eGFR, and serum albumin over time (the Toronto risk-prediction approach), supported where available by the serum anti-PLA2R antibody titer.[6] Low risk: RAAS blockade and observation; many patients undergo spontaneous remission. Moderate-to-high risk: rituximab is a preferred immunosuppressive option, supported by the MENTOR trial's finding that rituximab was noninferior to cyclosporine at 12 months and superior in maintaining remission through 24 months.[6][4] High-risk or resistant disease: cyclophosphamide with glucocorticoids remains an option, respecting cumulative-dose limits (see Drug Tables). Calcineurin inhibitors (tacrolimus/cyclosporine) are an alternative but are not recommended as long-term monotherapy given a high relapse rate on withdrawal.[1] Provincial variability in rituximab funding is a genuine, current access barrier in Canada.[4]
High-dose oral corticosteroids remain first-line for an initial presentation, with current practice favouring a shorter taper than older regimens (see Drug Tables for dosing). Frequently relapsing or steroid-dependent disease is treated first with a repeat, shorter/lower-dose course similar to the initial presentation; genuinely steroid-dependent or -resistant disease is escalated to a steroid-sparing agent — a calcineurin inhibitor, or rituximab, which the current Canadian commentary notes shows real promise for frequently relapsing disease but faces access restriction in Canada.[4][1]
Confirm primary (immune-mediated) FSGS before treating with immunosuppression — secondary/adaptive FSGS (obesity, reduced nephron mass, reflux) and genetic FSGS do not respond to immunosuppression and are managed with RAAS blockade and treatment of the underlying driver instead; genetic testing is increasingly used specifically to make this distinction.[4] Primary FSGS with nephrotic syndrome: high-dose corticosteroids first-line, similar in principle to minimal change disease though generally with a lower remission rate; calcineurin inhibitors for steroid-resistant disease.[1]
Induction: rituximab or cyclophosphamide, combined with a reduced-dose glucocorticoid regimen following the PEXIVAS trial schedule, which achieved similar efficacy to a standard-dose regimen with materially fewer serious infections.[5][1] CanVasc's 2020 update continues to favour cyclophosphamide as the primary agent in many patients given rituximab's cost, while specifically preferring rituximab where fertility preservation matters.[5] Maintenance: rituximab is now preferred over azathioprine per current Canadian commentary, continued for at least 18 months.[4][5] Avacopan, a C5a receptor antagonist that can further reduce glucocorticoid exposure, remains unfunded in Canada in most jurisdictions despite guideline support — a genuine, current access point to flag rather than assume is simply available.[4]
Hydroxychloroquine is mandatory for essentially every patient with lupus nephritis unless specifically contraindicated, independent of the specific induction regimen chosen, given benefits extending beyond the kidney.[4] Induction is typically mycophenolate mofetil or cyclophosphamide (the lower-dose Euro-Lupus regimen is now generally preferred over the older, higher-dose NIH regimen) combined with a reduced cumulative-dose glucocorticoid protocol.[4] Voclosporin, a newer calcineurin inhibitor with trial data in lupus nephritis, is not currently available in Canada; where a calcineurin inhibitor is used, tacrolimus is generally preferred over cyclosporine given a cleaner interaction profile with mycophenolic acid.[4] See the Systemic Lupus Erythematosus chapter for the complete regimen, maintenance therapy, and non-renal management.
Management is primarily supportive — treat any ongoing infection, and manage volume overload and hypertension with diuretics and antihypertensives; the disease is generally self-limited, especially in children.[3] Reserve immunosuppression (glucocorticoids, sometimes with cyclophosphamide) for rapidly declining kidney function or biopsy-proven crescentic disease, not routine cases.[3]
A pre-specified analysis of the DAPA-CKD trial found that dapagliflozin reduced albuminuria and substantially lowered the risk of major adverse kidney events specifically in patients with IgA nephropathy on top of RAAS blockade, supporting a genuine, expanding adjunctive renoprotective role for SGLT2 inhibitors across the proteinuric glomerular diseases in this chapter, not only in IgA nephropathy specifically.[9] Caution: avoid starting an SGLT2 inhibitor concurrently with induction immunosuppression — current Canadian nephrology guidance specifically flags added infection and diabetic ketoacidosis risk during that period, and instead reserves SGLT2 inhibitor initiation for patients already on stable maintenance therapy or with persistent residual proteinuria.[4]
Blood pressure: control to the same disease-appropriate target used in the Chronic Kidney Disease chapter, with a RAAS inhibitor as part of the regimen whenever proteinuria is present. Dyslipidemia of nephrotic syndrome: a statin is reasonable in nephrotic-range proteinuria with a significantly elevated LDL, recognizing that the dyslipidemia often improves as proteinuria responds to disease-specific treatment. Edema: loop diuretics, titrated to the degree of edema and renal function (see Drug Tables). VTE risk: nephrotic syndrome — especially membranous nephropathy — meaningfully raises VTE risk through urinary loss of antithrombin and other anticoagulant proteins, historically reported in as many as roughly 1 in 4 adults with nephrotic syndrome; prophylactic anticoagulation should be specifically considered in patients with severe hypoalbuminemia and heavy, persistent proteinuria, particularly with membranous nephropathy, rather than reserved only for a patient who has already had a clot.[7]
Non-Pharmacologic Treatment
- 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.
Special Populations
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.
Monitoring & Follow-Up
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]
Common Errors to Avoid
- 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.
Clinical Decision Algorithm
Drug Tables
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.
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Ramipril (ACE inhibitor) | Typical adult dose: Start low, titrate to the highest approved/tolerated dose | Hyperkalemia; an expected initial eGFR dip; cough; angioedema | Additive hyperkalemia risk with potassium-sparing diuretics, potassium supplements, and trimethoprim | Never combine with an ARB. Check creatinine/potassium 2-4 weeks after starting or up-titrating. |
| Losartan (ARB) | Typical adult dose: Start low, titrate to the highest approved/tolerated dose | Hyperkalemia; an expected initial eGFR dip | Additive hyperkalemia risk with potassium-sparing diuretics, potassium supplements, and trimethoprim | Reasonable alternative where an ACE inhibitor is not tolerated (e.g., cough). |
Corticosteroids
Regimen, dose, and taper length are specific to the indication — do not extrapolate one indication's regimen to another within this table.
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Prednisone — minimal change disease / primary FSGS induction | Adult induction: High-dose daily or alternate-day regimen per current nephrology protocol, tapered over weeks once remission is achieved | Hyperglycemia, mood/sleep disturbance, weight gain, hypertension, infection risk, osteoporosis with prolonged use | Numerous — review the full medication list before initiation, particularly other agents affecting glucose or bone health | Current practice favours a shorter taper than older regimens once remission is achieved; relapses are generally treated with a shorter/lower-dose course than the initial presentation. |
| Prednisone — ANCA vasculitis / crescentic post-infectious GN induction | Adult induction: Reduced-dose (PEXIVAS-pattern) regimen, tapered per protocol alongside rituximab or cyclophosphamide | Same as above, compounded by concurrent cyclophosphamide/rituximab-related infection risk | Same as above | Current practice follows the PEXIVAS reduced-dose glucocorticoid schedule, which achieved similar efficacy with materially fewer serious infections than older, higher-dose regimens. |
| Methylprednisolone (IV pulse) | Typical use: Short IV pulse course per protocol, then transition to oral maintenance dosing | Same class effects as oral corticosteroids; additional transient hyperglycemia/hypertension with pulse dosing | Same as oral corticosteroids | Used for a brief IV pulse at the start of induction in some severe presentations (e.g., RPGN) before transitioning to oral maintenance dosing. |
Etiology-Specific Immunosuppression
Selected by the specific diagnosed GN subtype and its severity, per Choose Initial Treatment — not interchangeable between conditions in this chapter.
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Rituximab | Membranous nephropathy / ANCA vasculitis: IV infusion, regimen-specific per current protocol (e.g., 2 fixed doses or 4 weekly weight-based doses) | Infusion reactions; increased infection risk; hepatitis B reactivation (screen before use) | Live vaccines should be deferred around dosing per current immunization timing guidance | Moderate-to-high-risk membranous nephropathy, ANCA vasculitis induction/maintenance, and relapsing/steroid-dependent MCD or FSGS. Provincial funding coverage varies in Canada. |
| Cyclophosphamide | IV or oral induction: Regimen-specific (IV pulse or daily oral) per the specific GN subtype and current protocol | Cytopenias, infection risk, hemorrhagic cystitis, gonadal toxicity/infertility (dose-dependent), long-term malignancy risk | Additive myelosuppression with other cytotoxic/immunosuppressive agents | Track cumulative lifetime dose explicitly against fertility- and malignancy-risk thresholds. Reduce the dose for reduced eGFR per current protocol. Discuss fertility preservation before starting where feasible. |
| Mycophenolate mofetil | Adult dosing: Twice daily, per current lupus nephritis or steroid-sparing protocol | GI upset, cytopenias, teratogenicity (absolute pregnancy contraindication) | Reduced absorption with concurrent antacids/iron; cyclosporine (but not tacrolimus) can reduce mycophenolic acid exposure | Central to lupus nephritis induction and maintenance; confirm effective contraception before starting in anyone who could become pregnant. |
| Azathioprine | Adult maintenance: Once or twice daily, weight-based, per current protocol | Cytopenias, hepatotoxicity, GI upset | Markedly increased toxicity with allopurinol/febuxostat (reduce azathioprine dose substantially or avoid combination); check TPMT/NUDT15 status where available before starting | An alternative maintenance agent to rituximab in ANCA vasculitis, and to mycophenolate mofetil in lupus nephritis maintenance. |
| Tacrolimus | Adult dosing: Twice daily, titrated to a target trough level | Nephrotoxicity, hyperglycemia, hypertension, tremor, hyperkalemia | Numerous CYP3A4-mediated interactions — review the full interaction list before starting or adjusting | Preferred over cyclosporine when combined with mycophenolate mofetil, given a cleaner interaction profile. Dose to a target trough level. |
| Cyclosporine | Adult dosing: Twice daily, titrated to a target trough level | Nephrotoxicity, hypertension, hirsutism, gingival hyperplasia, tremor | Numerous CYP3A4-mediated interactions, including a clinically significant increase in statin exposure | An alternative calcineurin inhibitor to tacrolimus; the MENTOR trial's comparator for rituximab in membranous nephropathy, with rituximab superior in maintaining longer-term remission. |
Supportive and Adjunctive Therapy
Manage the syndrome-specific complications of nephrotic syndrome alongside disease-specific treatment, not after it.
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Dapagliflozin (SGLT2 inhibitor) | Adult dosing: Once daily, on top of a maximized RAAS inhibitor | Genital mycotic infection; euglycemic diabetic ketoacidosis risk during acute illness | None significant | Adjunctive renoprotection once a patient is on stable maintenance therapy, or with persistent residual proteinuria. Avoid starting during induction immunosuppression. |
| Rosuvastatin | Adult dosing: Standard statin dosing, adjusted if combined with cyclosporine | Myalgia; transaminitis | Cyclosporine specifically increases rosuvastatin exposure — use the lowest effective dose if combined | For the dyslipidemia of nephrotic syndrome; reassess ongoing need as proteinuria responds to disease-specific treatment. |
| Furosemide | Adult dosing: Titrated to the degree of edema and renal function | Electrolyte disturbance, volume depletion if over-diuresed | None significant | Nephrotic-range hypoalbuminemia can reduce diuretic delivery to its site of action — higher doses are sometimes genuinely needed for equivalent effect. |
| Apixaban | Prophylactic dosing: Individualized per current VTE-prevention protocol for nephrotic syndrome | Bleeding risk | None significant | Consider for prophylaxis in severe nephrotic syndrome (severe hypoalbuminemia with heavy, persistent proteinuria), particularly membranous nephropathy, rather than waiting for a thrombotic event. |
| Warfarin | Dosing: Individualized, titrated to INR | Bleeding risk; unpredictable dose-response | Numerous — review the full interaction list; INR monitoring required | An alternative to a direct oral anticoagulant for VTE prophylaxis/treatment in severe nephrotic syndrome; urinary antithrombin loss itself can complicate anticoagulant effect and monitoring. |
| Sulfamethoxazole/trimethoprim (low-dose prophylaxis) | Prophylactic dosing: Low-dose regimen per local protocol | Hyperkalemia (compounds RAAS-inhibitor-related risk), cytopenias, rash | Trimethoprim blocks renal potassium secretion — monitor potassium closely alongside a RAAS inhibitor | For Pneumocystis jirovecii prophylaxis during sustained high-dose immunosuppression (e.g., cyclophosphamide, or prednisone ≥20 mg/day for ≥4 weeks). |
References
- KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases — Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group. Kidney Int 2021;100(4S):S1-S276
- KDIGO 2025 Clinical Practice Guideline for the Management of Immunoglobulin A Nephropathy (IgAN) and Immunoglobulin A Vasculitis (IgAV) — Kidney International (Rovin BH, Barratt J, Cook HT, Noronha IL, Reich HN, Suzuki Y, Tang SCW, Trimarchi H, Floege J). Kidney Int 2025;108(4):S1-S71
- Management and Outcomes of Acute Post-Streptococcal Glomerulonephritis in Children — World Journal of Nephrology (Ong LT). World J Nephrol 2022;11(5):139-145
- Canadian Society of Nephrology Commentary on the Evolving Kidney Disease Improving Global Outcomes Adult Glomerulonephritis Guidelines — Canadian Journal of Kidney Health and Disease (Jauhal A, Mustafa R, Mathew A, Girard L, Barbour S, Prasad B, Bathini L, Poyah P, Troyanov S, Samanta R, Garland J, Fairhead T, Walsh M, Reich H, Huang SH, Ng J, Marin J, Hladunewich M; Canadian Society of Nephrology). Can J Kidney Health Dis 2026;13
- CanVasc Consensus Recommendations for the Management of Antineutrophil Cytoplasm Antibody-associated Vasculitis: 2020 Update — The Journal of Rheumatology (Mendel A, Ennis D, Go E, Bakowsky V, Baldwin C, Benseler SM, Cabral DA, Carette S, et al.; Canadian Vasculitis Research Network). J Rheumatol 2021;48(4):555-566
- Rituximab or Cyclosporine in the Treatment of Membranous Nephropathy — New England Journal of Medicine (Fervenza FC, Appel GB, Barbour SJ, Rovin BH, Lafayette RA, et al.; MENTOR Investigators). N Engl J Med 2019;381(1):36-46
- A Systematic Review of Prophylactic Anticoagulation in Nephrotic Syndrome — Kidney International Reports (Lin R, McDonald G, Jolly T, Batten A, Chacko B). Kidney Int Rep 2020;5(4):435-447
- Glomerular Hematuria and the Utility of Urine Microscopy: A Review — American Journal of Kidney Diseases (Saha MK, Massicotte-Azarniouch D, Reynolds ML, Mottl AK, Falk RJ, Jennette JC, Derebail VK). Am J Kidney Dis 2022;80(3):383-392
- A Pre-specified Analysis of the DAPA-CKD Trial Demonstrates the Effects of Dapagliflozin on Major Adverse Kidney Events in Patients With IgA Nephropathy — Kidney International (Wheeler DC, Toto RD, Stefánsson BV, et al.; DAPA-CKD Trial Committees and Investigators). Kidney Int 2021;100(1):215-224
Professional reference only. Apply clinical judgment and verify patient-specific decisions against current authoritative guidance and product information.