Next Step in Treatment for IgA Nephropathy with Proteinuria 2g and Elevated Creatinine
The next step is to optimize blood pressure control to <120/70 mmHg, add dietary sodium restriction to <2g/day, and reassess proteinuria after 90 days of maximized supportive care before considering immunosuppression. 1, 2
Immediate Optimization of Current Regimen
Blood Pressure Management
- Target blood pressure <120/70 mmHg given the proteinuria of 2g/day, which exceeds the 1g/day threshold for stricter control 2, 3
- Uptitrate telmisartan to the maximum tolerated dose (typically 80mg daily) to achieve both blood pressure and proteinuria targets 1
- Accept up to 30% rise in creatinine during RAS blocker uptitration as a benign hemodynamic effect; only discontinue if the rise exceeds 30% persistently or refractory hyperkalemia develops 2
Dietary and Lifestyle Modifications
- Restrict dietary sodium to <2g/day (<90 mmol/day) to augment the antiproteinuric effect of RAS blockade 1, 2, 3
- Counsel on weight normalization, smoking cessation, and regular physical activity 1
SGLT2 Inhibitor Continuation
- Continue dapagliflozin (Farxiga) as it is now recognized as a disease-modifying agent in IgA nephropathy 3, 4
- The DAPA-CKD trial demonstrated that dapagliflozin reduced the risk of kidney failure in IgA nephropathy patients (hazard ratio 0.29; 95% CI 0.12-0.73) with a favorable safety profile 5
- Network meta-analysis showed dapagliflozin superior to placebo for preventing ESRD (RR 0.30; 95% CI 0.11-0.80) with the lowest serious adverse event risk 6
Risk Stratification and Monitoring Period
90-Day Observation Window
- High-risk progression is defined as proteinuria >0.75-1g/day despite ≥90 days of optimized supportive care 1, 2
- Monitor serum creatinine, potassium, and spot urine protein-to-creatinine ratio monthly during this optimization phase 2
- Check blood pressure at each visit and adjust medications to meet target values 2
Prognostic Context
- Proteinuria >1g/day predicts an average eGFR decline of approximately 3 mL/year 2, 3
- Achieving proteinuria <1g/day is associated with favorable long-term prognosis regardless of baseline level 2, 3
Decision Point After 90 Days of Optimized Care
If Proteinuria Remains ≥0.75-1g/day
Consider adding glucocorticoid therapy using the Pozzi protocol: 1, 2
- Intravenous methylprednisolone: 1g daily for 3 consecutive days at months 1,3, and 5
- Oral prednisone: 0.5 mg/kg every other day for 6 months, then taper by 0.2 mg/kg/day each month over the final 4 months
Critical Eligibility Assessment for Glucocorticoids
This patient requires careful evaluation before glucocorticoid initiation: 1, 2
The current creatinine of 2.08 mg/dL corresponds to an estimated eGFR that may approach or fall below 50 mL/min/1.73m², which is a relative contraindication. Glucocorticoids should be given with extreme caution or avoided entirely in patients with: 1
- eGFR <30 mL/min/1.73m²
- Diabetes
- Obesity (BMI >30 kg/m²)
- Latent infections
- Active peptic ulceration
- Uncontrolled psychiatric disease
- Severe osteoporosis
The risk-benefit ratio must be carefully weighed: Glucocorticoid therapy carries a significantly higher risk of serious adverse events (risk ratio 2.91; 95% CI 1.39-6.07) compared with placebo, and the TESTING trial demonstrated steroid-related mortality even with pneumocystis prophylaxis 3
If Proteinuria Falls Below 0.75g/day
- Continue ACE inhibitor/ARB at maximally tolerated dose indefinitely 2
- Continue dapagliflozin 3, 4
- Monitor proteinuria and renal function every 3-6 months while maintaining strict blood pressure control 2
Therapies to Avoid in This Patient
- Cyclophosphamide or azathioprine: Reserved only for crescentic IgA nephropathy with rapidly deteriorating renal function 2, 3
- Mycophenolate mofetil: Not recommended in non-Chinese patients due to lack of proven benefit 1, 2
- Calcineurin inhibitors: Not first-line for IgA nephropathy 2
- Rituximab: Not recommended for IgA nephropathy 2
Common Pitfalls to Avoid
Premature Immunosuppression
Do not initiate glucocorticoids before completing at least 90 days of optimized supportive care, as many patients will respond to maximal RAS blockade, SGLT2 inhibition, and lifestyle modifications alone 1, 2
Inadequate RAS Blockade Optimization
Ensure telmisartan is uptitrated to maximum tolerated dose before declaring treatment failure; suboptimal dosing is a common reason for persistent proteinuria 2, 3
Overlooking Medication Interactions
If creatinine rises significantly during optimization, exclude volume depletion, drug interactions (particularly non-dihydropyridine calcium channel blockers), and other nephrotoxins before attributing the rise to disease progression 1
Ignoring Infection Screening
If glucocorticoids become necessary, screen for latent infections (tuberculosis, hepatitis) before initiation 2