Chronic Glomerulonephritis: Definition, Work-Up, and Management
Definition
Chronic glomerulonephritis (CGN) is a slowly progressive immune-mediated kidney disorder characterized by persistent glomerular inflammation leading to gradual loss of kidney function, hypertension, proteinuria, and hematuria 1. Unlike acute presentations, CGN develops insidiously over months to years, ultimately progressing toward end-stage renal disease if untreated 1, 2.
CGN encompasses various histopathologic patterns including IgA nephropathy, focal segmental glomerulosclerosis (FSGS), and proliferative forms of glomerulonephritis 2, 3. The pathophysiology involves immune complex deposition, complement activation, and progressive glomerular scarring with secondary tubulointerstitial fibrosis 4.
Work-Up
Clinical Presentation to Identify
Look specifically for:
- Persistent proteinuria (typically >1 g/24 hours but less than nephrotic range)
- Microscopic or gross hematuria with dysmorphic red blood cells and red cell casts
- Progressive decline in GFR over months to years
- Hypertension (present in majority due to volume expansion and RAAS activation) 2
- Absence of acute nephritic features (no rapid deterioration, oliguria, or severe edema)
Laboratory Evaluation
Initial testing:
- Urinalysis with microscopy (dysmorphic RBCs, RBC casts, proteinuria)
- 24-hour urine protein or spot urine protein-to-creatinine ratio
- Serum creatinine and eGFR
- Complete blood count, comprehensive metabolic panel
- Serum albumin
Immunologic work-up to classify by pathogenesis 5:
- For autoimmunity-related GN: ANA, anti-dsDNA, complement levels (C3, C4), ANCA panel, anti-GBM antibodies
- For infection-related GN: ASO titers, hepatitis B/C serology, HIV testing
- For monoclonal gammopathy-related GN: Serum and urine protein electrophoresis, serum free light chains
- For alloimmunity: Donor-specific antibodies (in transplant recipients)
Kidney biopsy is essential for definitive diagnosis, histopathologic classification, and assessment of disease activity versus chronicity 5. Biopsy determines specific immunosuppressive therapy needs.
Management
Blood Pressure Control (First Priority)
Target systolic BP ≤130 mmHg and diastolic BP ≤80 mmHg in patients with proteinuria ≥30 mg/24 hours 6, 2. For those without significant proteinuria, target ≤140/90 mmHg 2.
ACE inhibitors or ARBs are mandatory first-line agents regardless of baseline blood pressure if proteinuria is present 6:
- Uptitrate to maximally tolerated dose 6
- Monitor serum creatinine and potassium within 1-2 weeks of initiation or dose changes 6
- Accept up to 30% rise in creatinine if stable thereafter
- Counsel patients to hold ACEi/ARB during volume depletion (vomiting, diarrhea, excessive sweating) 6
Common pitfall: Stopping ACEi/ARB prematurely due to mild creatinine elevation—this is expected and acceptable unless >30% rise or progressive increase.
Proteinuria Reduction
Target proteinuria <1 g/day in most chronic GN cases 6. This is disease-dependent but represents a reasonable general goal.
Stepwise approach:
- Maximize ACEi or ARB dose 6
- Add potassium-wasting diuretics (thiazide or loop) for dual benefit of BP control and enabling higher RASi doses 6
- Intensify sodium restriction to <2 g/day (<90 mmol/day) 6
- Consider mineralocorticoid receptor antagonists (spironolactone, eplerenone) for refractory proteinuria, monitoring closely for hyperkalemia 6
Managing Hyperkalemia to Enable RASi Use
Use potassium-binding agents (patiromer, sodium zirconium cyclosilicate) or potassium-wasting diuretics to normalize serum potassium, allowing continuation of RAS blockade 6. This is critical—do not sacrifice RASi therapy due to manageable hyperkalemia.
Treat metabolic acidosis (bicarbonate <22 mmol/L) with oral alkali therapy, as acidosis worsens hyperkalemia 6.
Lifestyle Modifications (Non-Negotiable)
All patients require 6:
- Sodium restriction <2 g/day
- Weight normalization (BMI <25 kg/m²)
- Smoking cessation
- Regular aerobic exercise (150 minutes/week)
These interventions synergistically improve BP control and reduce proteinuria 6.
Lipid Management
Consider statin therapy in patients with nephrotic-range proteinuria or additional cardiovascular risk factors 6. Assess ASCVD risk using LDL-C, apolipoprotein B, triglycerides, and Lp(a) levels 6.
- Align statin intensity to ASCVD risk
- For statin-intolerant patients or those not meeting LDL goals: add ezetimibe, PCSK9 inhibitors, or fibrates 6
Disease-Specific Immunosuppression
The specific immunosuppressive regimen depends entirely on the underlying pathogenesis determined by biopsy 5:
- Autoimmunity-related GN (lupus nephritis, ANCA-associated GN, anti-GBM disease): Requires suppression of adaptive immunity with corticosteroids plus cyclophosphamide, mycophenolate, or rituximab
- Infection-related GN: Treat underlying infection; immunosuppression generally contraindicated
- Autoinflammation-related GN: Target specific cytokine or complement pathways
- Monoclonal gammopathy-related GN: Clone-directed therapy (chemotherapy, proteasome inhibitors)
Critical point: Immunosuppression should only be initiated after biopsy confirmation and pathogenesis classification 5. Non-specific immunosuppression without knowing the underlying cause can be harmful.
Monitoring Disease Activity vs. Chronicity
Biomarkers allow assessment without repeat biopsy in many cases 5:
- Serial proteinuria measurements
- Serum creatinine/eGFR trends
- Disease-specific markers (anti-dsDNA for lupus, ANCA titers, complement levels)
Chronicity indicators (irreversible damage) include:
- Glomerulosclerosis >50% on biopsy
- Severe tubulointerstitial fibrosis
- Progressive eGFR decline despite treatment
Once chronicity dominates, shift focus from immunosuppression to cardio-renoprotective strategies (SGLT2 inhibitors, GLP-1 receptor agonists, continued RASi) and preparation for renal replacement therapy 5.
When to Refer to Nephrology
Immediate referral for:
- Any patient requiring kidney biopsy
- Rapidly declining kidney function (>25% eGFR drop in 3 months)
- Proteinuria >1 g/day despite ACEi/ARB
- Difficult-to-control hypertension
- Need for immunosuppressive therapy
Key Algorithmic Approach
- Confirm CGN diagnosis: Persistent proteinuria + hematuria + gradual GFR decline + hypertension
- Obtain kidney biopsy for histopathologic diagnosis and pathogenesis classification
- Initiate supportive care immediately (ACEi/ARB, BP control, sodium restriction) while awaiting biopsy results
- Classify by immunopathogenesis (autoimmunity, infection, autoinflammation, monoclonal gammopathy, alloimmunity) 5
- Add disease-specific immunosuppression based on biopsy findings and pathogenesis
- Monitor for treatment response with serial proteinuria and kidney function
- Transition to chronic kidney disease management when chronicity predominates over active inflammation