# Immunosuppression Protocols in Glomerular Disease

**Avacopan evidence and regulatory update:** The ADVOCATE article was retracted on 29 June 2026; its reported efficacy and comparative-safety results should not be used as established evidence. On 27 April 2026, FDA's CDER proposed withdrawal of TAVNEOS approval because a valid demonstration of efficacy could no longer be established and material facts in the application were untrue. FDA also identified serious liver-injury concerns. This is a proposed withdrawal, not a completed US withdrawal; FDA advises clinicians and patients to discuss available treatment options while the process is pending. [Retraction notice](https://pubmed.ncbi.nlm.nih.gov/42377355/) · [FDA notice, 27 April 2026](https://www.fda.gov/drugs/drug-alerts-and-statements/cder-proposes-withdraw-approval-tavneos).

Evidence-based dosing, monitoring, and supportive care for immunosuppressive therapy in glomerulonephritis

KDIGO GN 2021 RAVE 2010 ALMS 2009 AURORA 2021 ADVOCATE 2021 — RETRACTED 2026

Andrew Bland, MD, FACP, FAAP \| University of Dubuque PA Program

## 1. Pulse Methylprednisolone

### Dosing

- **Standard pulse:** 500–1000 mg IV daily for 3 consecutive days
- Infuse over 30–60 minutes in 100–250 mL normal saline
- Typically followed by oral prednisone taper (see Section 2)

### Indications

| Condition | Typical Pulse Dose | Notes |
|----|----|----|
| Rapidly progressive GN (RPGN) / crescentic GN | 1000 mg IV x 3 days | Start empirically before biopsy if clinical suspicion high; follow with cyclophosphamide or rituximab |
| Severe lupus nephritis (Class III/IV with crescents) | 500–1000 mg IV x 3 days | Per KDIGO 2021 GN and ACR/EULAR lupus nephritis guidelines |
| Anti-GBM disease | 1000 mg IV x 3 days | Combined with plasmapheresis and cyclophosphamide; dialysis-dependent patients with 100% crescents have poor renal prognosis |
| ANCA vasculitis with severe renal/pulmonary involvement | 500–1000 mg IV x 3 days | Followed by an individualized oral taper. ADVOCATE was retracted in 2026; it no longer supports an avacopan steroid-sparing recommendation. |

### Monitoring During Pulse Therapy

- **Blood glucose:** Check every 6 hours; insulin sliding scale often needed; hyperglycemia common even in non-diabetics
- **Blood pressure:** Monitor closely; may cause acute hypertension
- **Infection surveillance:** Ensure no active untreated infection before pulsing; hold if febrile
- **Electrolytes:** Sodium retention and hypokalemia possible
- **Mental status:** Steroid psychosis can occur with high-dose IV steroids; more common in elderly patients
- **Cardiac:** Rare arrhythmias reported with rapid infusion; ensure adequate infusion time

**Clinical Pearl:** Do not delay pulse steroids in suspected RPGN while awaiting biopsy. Crescentic GN is a nephrology emergency — irreversible damage accrues within days to weeks.

## 2. Oral Prednisone Taper Schedules

### Rapid Taper — RPGN / ANCA Vasculitis

Used after pulse methylprednisolone for severe disease. Goal: minimize cumulative steroid exposure while controlling active inflammation.

Weeks 1–2:Prednisone 1 mg/kg/day (max 60–80 mg/day) Weeks 3–4:40 mg/day Weeks 5–6:30 mg/day Weeks 7–8:20 mg/day Weeks 9–10:15 mg/day Weeks 11–12:10 mg/day Weeks 13–16:7.5 mg/day Weeks 17–20:5 mg/day Weeks 21–24:2.5 mg/day, then discontinue (or physiologic replacement if adrenal suppression suspected) **ADVOCATE evidence correction:** The 2021 article was retracted in 2026. Its reported remission, steroid-sparing, and kidney-recovery results are historical claims, not validated support for an induction or tapering protocol. [Read the retraction notice](https://pubmed.ncbi.nlm.nih.gov/42377355/).

### Standard Taper — Nephrotic Syndrome (MCD/FSGS)

Used for primary nephrotic syndromes. Duration depends on response.

Weeks 1–8:Prednisone 1 mg/kg/day (max 80 mg/day); assess for remission at 8 weeks Weeks 9–12:If in remission: 0.5 mg/kg every other day Weeks 13–16:Reduce by 5–10 mg every 2 weeks Weeks 17–20:10 mg every other day Weeks 21–24:5 mg every other day, then discontinue Total duration:~24 weeks (6 months); FSGS may require up to 16 weeks of full-dose before declaring steroid-resistant

### Lupus Nephritis Taper (post-pulse)

Weeks 1–4:0.5–1 mg/kg/day (typically 40–60 mg/day) Month 2:Taper to 30 mg/day Month 3:Taper to 20 mg/day Month 4:Taper to 15 mg/day Month 5:Taper to 10 mg/day Month 6+:Taper to 5–7.5 mg/day; maintain low-dose long-term per rheumatology guidance; target ≤5 mg/day by 12 months

## Steroid Adverse Effect Monitoring

| Adverse Effect | Monitoring | Prevention / Management |
|----|----|----|
| Hyperglycemia / new-onset diabetes | Fingerstick glucose QID during pulse; fasting glucose and HbA1c monthly during taper | Insulin for inpatient; metformin or insulin outpatient; SGLT2i caution if nephrotic |
| Osteoporosis | DEXA at baseline if expected ≥3 months of therapy | Calcium 1000–1200 mg/day + vitamin D 800–1000 IU/day; bisphosphonate if T-score ≤−1.5 or prednisone ≥7.5 mg/day ≥3 months (see Section 8) |
| Avascular necrosis | Clinical: hip/knee pain; MRI if symptomatic | Minimize cumulative dose; early orthopedic referral |
| Infections (opportunistic) | PCP prophylaxis (see Section 9); HBV screening pre-treatment | TMP-SMX DS daily or 3x/week; monitor for CMV, fungal infections |
| Hypertension | BP at each visit | Sodium restriction; antihypertensives as needed |
| Cataracts / glaucoma | Ophthalmology referral if ≥6 months of therapy | Annual eye exam |
| Adrenal suppression | AM cortisol if on ≥3 months and tapering below 7.5 mg/day | Do not abruptly discontinue; taper to physiologic dose (5 mg prednisone = ~20 mg cortisol); stress-dose steroids for surgery/illness |
| Weight gain / Cushing features | Weight at each visit | Dietary counseling; exercise; minimize dose |
| Psychiatric effects | Screen for mood changes, insomnia, psychosis | Dose reduction; short-acting steroids; psychiatry referral if severe |
| GI effects (peptic ulcer) | Symptoms; consider H. pylori testing | PPI if concurrent NSAID use; avoid NSAIDs when possible |
| Myopathy | Proximal muscle weakness | Minimize dose; physical therapy |

## 3. Cyclophosphamide

### IV Pulse Protocols

| Protocol | Dosing | Duration | Primary Indication |
|----|----|----|----|
| **Euro-Lupus (low-dose)** | 500 mg IV every 2 weeks | 6 doses (3 months) | Lupus nephritis Class III/IV; non-inferior to NIH protocol in European cohorts (PMID: 12209517) |
| **NIH Protocol (high-dose)** | 0.5–1 g/m² IV monthly | 6 months induction, then quarterly for 1–2 years (historical) | Severe proliferative lupus nephritis; higher toxicity but remains option for refractory disease |
| **ANCA Vasculitis (CYCLOPS)** | 15 mg/kg IV (max 1.2 g) every 2–3 weeks | 3–6 months induction | ANCA vasculitis with renal involvement; reduced cumulative dose vs. daily oral |
| **Anti-GBM Disease** | 2–3 mg/kg/day oral (preferred) or pulse IV | 2–3 months | Combined with plasmapheresis and steroids |

### Dose Adjustments

- **Renal impairment:** Reduce dose by 25% if eGFR \<25 mL/min; further adjust for dialysis patients
- **Age ≥60 years:** Reduce dose by 25% (increased bone marrow toxicity)
- **Obesity:** Use ideal body weight for BSA-based dosing

### Monitoring

- **WBC nadir:** Check CBC at day 10–14 after each dose; target WBC nadir \>3,000/μL; absolute neutrophil count \>1,500/μL
- **CBC before each dose:** Hold if WBC \<3,500/μL; dose-reduce by 25% if nadir WBC 2,000–3,000/μL
- **Urinalysis:** Monitor for hemorrhagic cystitis (microscopic hematuria)
- **Hepatic function:** LFTs at baseline and periodically

### Hemorrhagic Cystitis Prevention

- **Mesna (2-mercaptoethanesulfonate):** 20% of cyclophosphamide dose given at 0, 4, and 8 hours after IV cyclophosphamide
- Aggressive IV hydration (2–3 L) on day of infusion
- Encourage frequent voiding; void before bedtime
- Morning administration preferred to allow daytime hydration and voiding

### Fertility Preservation

- **GnRH agonists (leuprolide):** Administer 10–14 days before first cyclophosphamide dose; continue monthly during treatment to suppress ovarian function
- **Sperm cryopreservation:** Offer to all male patients of reproductive age before initiation
- **Oocyte/embryo cryopreservation:** Consider if time permits before urgent treatment
- **Cumulative dose threshold:** Risk of premature ovarian failure increases with cumulative dose \>10 g and age \>30 years

**Malignancy Risk:** Cumulative cyclophosphamide exposure increases long-term risk of bladder cancer, myelodysplastic syndromes, and lymphoma. Limit cumulative lifetime exposure when possible. Euro-Lupus protocol preferred over NIH for reduced toxicity.

## 4. Rituximab

### Dosing Protocols

| Protocol | Dosing | Indication | Key Trial Data |
|----|----|----|----|
| **RAVE Protocol** | 375 mg/m² IV weekly x 4 doses | ANCA vasculitis induction | Non-inferior to cyclophosphamide for induction of remission; superior for relapsing disease (PMID: 20647199) |
| **RITUXVAS Protocol** | 375 mg/m² IV weekly x 4 doses + 2 pulses IV cyclophosphamide (15 mg/kg) with doses 1 and 3 | Severe renal vasculitis | Comparable remission and adverse event rates to standard cyclophosphamide (PMID: 20647198) |
| **Rheumatoid arthritis dosing** | 1000 mg IV x 2 doses, 2 weeks apart | Used off-label for membranous nephropathy, lupus nephritis, frequently relapsing MCD/FSGS | MENTOR trial: non-inferior to cyclosporine for membranous nephropathy; superior sustained remission at 24 months (PMID: 31269364) |
| **Maintenance** | 500 mg IV every 6 months | ANCA vasculitis maintenance (MAINRITSAN trial) | Superior to azathioprine for relapse prevention at 28 months (PMID: 25372085) |

### Pre-infusion Protocol

- Acetaminophen 650–1000 mg PO
- Diphenhydramine 50 mg IV or PO
- Methylprednisolone 100 mg IV (or equivalent)
- First infusion: start at 50 mg/hr, escalate by 50 mg/hr every 30 min to max 400 mg/hr
- Subsequent infusions: may start at 100 mg/hr if prior infusion tolerated

### Monitoring

- **B-cell depletion:** CD19/CD20 count before each dose; verify depletion (\<5 cells/μL) at 2 weeks post-infusion
- **Immunoglobulin levels:** Quantitative IgG, IgA, IgM at baseline and every 6 months; hold rituximab if IgG \<400 mg/dL and recurrent infections
- **IgG replacement:** Consider IVIG or SCIG if IgG \<300 mg/dL or recurrent serious infections with IgG \<500 mg/dL
- **Infection screening:** HBV serologies (HBsAg, anti-HBc, anti-HBs) mandatory before first dose; HBV reactivation risk is well-documented
- **JC virus / PML risk:** Rare but devastating; counsel patients to report new neurological symptoms (cognitive changes, visual disturbances, motor weakness); no reliable screening test for JC virus; risk increases with prior immunosuppression and prolonged B-cell depletion
- **Vaccination timing:** Complete vaccinations at least 4 weeks before rituximab; live vaccines contraindicated; response to vaccines is blunted for 6–12 months post-infusion

**Hypogammaglobulinemia:** Prolonged rituximab use causes cumulative IgG decline. The KDIGO 2021 GN guideline recommends checking immunoglobulins before each re-dosing cycle and holding if IgG is critically low with infections.

## 5. Mycophenolate Mofetil (MMF)

### Key Trial Data

| Trial | Comparison | Result |
|----|----|----|
| **ALMS Induction (2009)** | MMF 3 g/day vs. IV cyclophosphamide (NIH) | Similar response rates overall; MMF with fewer severe infections and amenorrhea (PMID: 19369404) |
| **ALMS Maintenance (2011)** | MMF vs. azathioprine for LN maintenance | MMF superior in preventing treatment failure (renal flare, rescue therapy needed) (PMID: 22087680) |
| **IMPROVE (2010)** | MMF vs. azathioprine for ANCA vasculitis maintenance | MMF inferior to azathioprine for relapse prevention in ANCA vasculitis (PMID: 21060104) |

### Dosing

- **Target dose:** 2–3 g/day in divided doses (BID)
- **Titration:** Start at 500 mg BID; increase by 500 mg/week as tolerated to target
- **Mycophenolate sodium (Myfortic):** Enteric-coated formulation; 720 mg Myfortic ~ 1000 mg MMF
- **Renal dosing:** No formal renal adjustment, but GI side effects may be more frequent in CKD

### GI Side Effects and Management

- Diarrhea, nausea, and abdominal pain are the most common dose-limiting effects (up to 30–45% of patients)
- Strategies: split into TID dosing; switch to Myfortic (enteric-coated); take with food; temporary dose reduction
- Rule out CMV colitis or C. difficile if new diarrhea develops on immunosuppression

### Therapeutic Drug Monitoring (TDM)

- **Mycophenolic acid (MPA) AUC:** Target AUC_(0–12) of 30–60 mg·h/L for lupus nephritis
- **Trough level (C0):** Target 1.5–3.0 μg/mL (less reliable than AUC but more practical)
- TDM most useful when: subtherapeutic response despite adequate dose, drug interactions suspected, or significant renal impairment
- **Drug interactions:** Antacids and cholestyramine reduce absorption; proton pump inhibitors may modestly reduce MPA levels

**Teratogenicity:** MMF is FDA pregnancy category X. Effective contraception is mandatory. Discontinue at least 6 weeks before planned conception. Switch to azathioprine if pregnancy is desired.

## 6. Calcineurin Inhibitors in Glomerular Disease

### Voclosporin (AURORA Trial)

| Parameter | Detail |
|----|----|
| Trial | AURORA 1 (Phase 3, 2021) — Rovin BH et al. *Lancet* 2021;397(10289):2070-2080. PMID: 33971155 |
| Design | Voclosporin 23.7 mg BID + MMF + low-dose steroids vs. placebo + MMF + low-dose steroids |
| Primary Endpoint | Complete renal response at 52 weeks: 41% voclosporin vs. 23% placebo (p \< 0.001) |
| Dosing | 23.7 mg BID (fixed dose); no therapeutic drug monitoring required |
| Advantages | Fixed dosing; more predictable PK than cyclosporine/tacrolimus; faster remission |
| Monitoring | eGFR (hold if \>20% decline); BP; potassium; glucose; lipids |
| FDA Approval | January 2021 for active lupus nephritis in combination with background immunosuppression |

### Tacrolimus in Membranous Nephropathy

- **Dosing:** 0.05–0.1 mg/kg/day in divided doses; target trough 4–8 ng/mL
- **Efficacy:** Achieves remission in 60–80% of MN patients; however, high relapse rate (40–50%) after discontinuation
- **Monitoring:** Trough levels weekly until stable, then monthly; renal function (nephrotoxicity risk); potassium; glucose; magnesium
- **Duration:** Typically 6–12 months; slow taper over 4–6 months to reduce relapse risk
- Often used in combination with low-dose steroids

### Cyclosporine in Podocytopathies (MCD/FSGS)

- **Dosing:** 3–5 mg/kg/day in divided doses; target trough 100–175 ng/mL
- **FSGS:** Used as second-line for steroid-resistant or steroid-dependent disease (KDIGO 2021)
- **MCD:** Alternative to prolonged steroid courses in frequently relapsing disease
- **MENTOR Trial comparison:** Rituximab was non-inferior to cyclosporine for induction of remission in MN, and superior for sustained remission at 24 months

### CNI Drug Interactions

**Critical Interactions — CYP3A4 and P-glycoprotein:**

- **Azole antifungals** (fluconazole, voriconazole, itraconazole): Dramatically increase CNI levels (2–5x); reduce CNI dose by 50–75% and monitor trough closely
- **Macrolides** (erythromycin, clarithromycin): Increase CNI levels; use azithromycin instead (minimal interaction)
- **Diltiazem/verapamil:** Increase CNI levels by 30–50%; may be used intentionally as "CNI-sparing" in transplant
- **Grapefruit juice:** Increases cyclosporine absorption; avoid
- **Rifampin, phenytoin, carbamazepine:** Potent CYP3A4 inducers; dramatically decrease CNI levels; avoid if possible

## 7. Complement Inhibitors

### Eculizumab / Ravulizumab in aHUS

| Agent | Dosing | Notes |
|----|----|----|
| **Eculizumab** | 900 mg IV weekly x 4, then 1200 mg IV every 2 weeks | First-line for atypical HUS; start empirically when TTP excluded (ADAMTS13 \>10%); dramatic improvement in renal recovery (PMID: 23738544) |
| **Ravulizumab** | Weight-based loading dose, then maintenance every 8 weeks | Long-acting C5 inhibitor; non-inferior to eculizumab with less frequent dosing; FDA-approved for aHUS (PMID: 32299680) |

- **Mandatory pre-treatment:** Meningococcal vaccination (MenACWY + MenB) at least 2 weeks before first dose; if urgent, vaccinate and provide ciprofloxacin prophylaxis until 2 weeks after vaccination
- **Duration:** Lifelong in most genetic aHUS; trial of withdrawal may be considered in complement factor H antibody-mediated disease after antibody titers normalize
- **Monitoring:** CH50 (should be near-zero on therapy); CBC, LDH, haptoglobin, schistocytes for TMA activity

### Avacopan and ADVOCATE: Historical Trial, Retracted Evidence

| Issue | Teaching interpretation |
|----|----|
| Historical design | Avacopan, a C5a receptor inhibitor, was compared with a prednisone taper on background rituximab or cyclophosphamide. |
| Publication status | The 2021 ADVOCATE report was retracted on 29 June 2026. [Retraction notice](https://pubmed.ncbi.nlm.nih.gov/42377355/). |
| Originally reported benefits | The reported remission, steroid-sparing, kidney-recovery, and comparative-safety results are not presented here as reliable evidence. |
| Current clinical interpretation | The retraction neither proves absence of drug benefit nor validates any alternative regimen. Reassess independent evidence and current regulatory/guideline advice before selecting avacopan or a steroid taper. |

### Emerging Complement Therapeutics in GN

- **Iptacopan** (oral factor B inhibitor): Under investigation for C3 glomerulopathy and IgA nephropathy
- **Narsoplimab** (MASP-2 inhibitor): Targets the lectin pathway; investigated in IgA nephropathy
- **Pegcetacoplan** (C3 inhibitor): Being studied in C3G

## 8. Bone Protection During Steroid Therapy

Glucocorticoid-induced osteoporosis (GIOP) is the most common form of secondary osteoporosis. Bone loss is most rapid in the first 3–6 months of therapy.

| Intervention | Dose / Detail | Indication |
|----|----|----|
| **Calcium supplementation** | 1000–1200 mg/day (diet + supplements) | All patients on prednisone ≥2.5 mg/day for ≥3 months |
| **Vitamin D** | 800–1000 IU/day cholecalciferol (D3); target 25(OH)D ≥30 ng/mL | All patients on prednisone ≥2.5 mg/day for ≥3 months |
| **Bisphosphonates** | Alendronate 70 mg weekly or risedronate 35 mg weekly or zoledronic acid 5 mg IV annually | Prednisone ≥7.5 mg/day for ≥3 months; OR any dose if T-score ≤−1.5; OR prior fragility fracture. **Caution:** Avoid if eGFR \<30–35 mL/min (risk of adynamic bone disease in CKD; bisphosphonates accumulate and may worsen low-turnover bone disease) |
| **Denosumab** | 60 mg SC every 6 months | Alternative to bisphosphonates; does not require renal dose adjustment; preferred in CKD 4–5 if no evidence of adynamic bone. **Caution:** Must not discontinue abruptly (rebound bone loss and vertebral fractures) |
| **DEXA scan** | At baseline if anticipated ≥3 months of glucocorticoid therapy | Repeat at 1 year; use FRAX with glucocorticoid adjustment |

**ACR/KDIGO Caveat:** In advanced CKD (stages 4–5), standard osteoporosis treatments may be inappropriate. Check PTH and bone-specific alkaline phosphatase to differentiate high-turnover (secondary hyperparathyroidism) from low-turnover (adynamic) bone disease before initiating bisphosphonates.

## 9. Infection Prophylaxis

### Pneumocystis jirovecii (PCP) Prophylaxis

| Agent | Dose | Notes |
|----|----|----|
| **TMP-SMX (first-line)** | 1 DS tablet (160/800 mg) daily or 3 times per week | Continue for duration of immunosuppression + 1–3 months after; also provides coverage for Nocardia, Listeria, Toxoplasma |
| **Dapsone (alternative)** | 100 mg daily | Check G6PD before starting; monitor methemoglobin levels |
| **Atovaquone (alternative)** | 1500 mg daily with food | Most expensive; well-tolerated; use if sulfa-allergic and G6PD-deficient |
| **Pentamidine inhaled (alternative)** | 300 mg monthly via nebulizer | Does not prevent extrapulmonary PCP; bronchospasm risk |

### Indications for PCP Prophylaxis

- Prednisone ≥20 mg/day (or equivalent) for ≥4 weeks
- Any patient receiving cyclophosphamide, rituximab, or combination immunosuppression
- Triple immunosuppression (e.g., CNI + MMF + prednisone as in lupus nephritis)
- KDIGO 2021 GN guideline: recommend PCP prophylaxis for all patients receiving intensive immunosuppression for GN

### Hepatitis B Screening and Management

- **Mandatory screening** before rituximab, cyclophosphamide, or high-dose steroids: HBsAg, anti-HBc (total), anti-HBs
- **HBsAg positive:** Start antiviral prophylaxis (entecavir or tenofovir) before immunosuppression; continue for 12–18 months after last dose
- **HBsAg negative / anti-HBc positive (occult HBV):** Monitor HBV DNA and ALT monthly; start antiviral if DNA becomes detectable. Pre-emptive antiviral recommended if receiving rituximab (high reactivation risk)
- **Vaccinate:** If anti-HBs negative and HBsAg negative, vaccinate before immunosuppression if possible

### Vaccination Timing

| Vaccine | Timing | Notes |
|----|----|----|
| Influenza (inactivated) | Annually; can give on immunosuppression | May have reduced efficacy; still recommended |
| Pneumococcal (PCV20 or PCV15 + PPSV23) | Before immunosuppression if possible | Per ACIP 2023 adult schedule |
| COVID-19 (mRNA) | Updated booster per current recommendations | Reduced antibody response on rituximab; time 4–6 months after last dose if possible |
| Hepatitis B | Before immunosuppression | If anti-HBs negative; high-dose series (40 mcg x 3) for CKD/dialysis |
| Meningococcal (MenACWY + MenB) | At least 2 weeks before eculizumab/ravulizumab | Mandatory for complement inhibitor therapy |
| Live vaccines (MMR, varicella, zoster live) | Contraindicated on immunosuppression | Give ≥4 weeks before starting IS; Shingrix (recombinant, non-live) IS safe |

**Practical Tip:** Use the pre-immunosuppression window (often 2–4 weeks while awaiting biopsy results and insurance authorization) to administer vaccinations. Prioritize: pneumococcal, hepatitis B (if non-immune), and Shingrix (age ≥50).

## Quick Reference: Immunosuppressive Agents Summary

| Agent | Key Indications in GN | Major Toxicities | Essential Monitoring |
|----|----|----|----|
| **Pulse Methylprednisolone** | RPGN, severe LN, anti-GBM | Hyperglycemia, hypertension, psychosis, infection | Glucose Q6H, BP, infection signs |
| **Oral Prednisone** | Most GN as part of induction/maintenance | Osteoporosis, diabetes, AVN, cataracts, adrenal suppression | Glucose, DEXA, weight, BP, eye exam |
| **Cyclophosphamide** | ANCA vasculitis, severe LN, anti-GBM | Bone marrow suppression, hemorrhagic cystitis, infertility, malignancy | CBC at nadir (day 10–14), UA, fertility counseling |
| **Rituximab** | ANCA vasculitis, MN, relapsing MCD/FSGS, refractory LN | Infusion reactions, hypogammaglobulinemia, PML (rare), HBV reactivation | CD19/CD20, IgG levels, HBV serologies |
| **MMF** | Lupus nephritis (induction + maintenance), ANCA maintenance (second-line) | GI (diarrhea, nausea), bone marrow suppression, teratogenicity | CBC, LFTs, MPA levels (optional) |
| **Voclosporin** | Active lupus nephritis (FDA-approved) | Nephrotoxicity, hypertension, hyperkalemia, infections | eGFR, BP, K+, glucose |
| **Tacrolimus** | Membranous nephropathy, MCD/FSGS (steroid-dependent) | Nephrotoxicity, tremor, diabetes, hyperkalemia | Trough levels, SCr, K+, glucose, Mg2+ |
| **Eculizumab / Ravulizumab** | Atypical HUS | Meningococcal infection (REMS), infusion reactions | CH50, LDH, haptoglobin, schistocytes, vaccination status |
| **Avacopan** | ANCA vasculitis; ADVOCATE efficacy evidence retracted — reassess independent evidence | Hepatotoxicity, infections | LFTs monthly x 6 months then quarterly |

## References

1.  KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. *Kidney Int.* 2021;100(4S):S1-S276. PMID: 34556256
2.  Stone JH, Merkel PA, Spiera R, et al. Rituximab versus cyclophosphamide for ANCA-associated vasculitis (RAVE). *N Engl J Med.* 2010;363(3):221-232. PMID: 20647199
3.  Jones RB, Tervaert JW, Hauser T, et al. Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis (RITUXVAS). *N Engl J Med.* 2010;363(3):211-220. PMID: 20647198
4.  Guillevin L, Pagnoux C, Karras A, et al. Rituximab versus azathioprine for maintenance in ANCA-associated vasculitis (MAINRITSAN). *N Engl J Med.* 2014;371(19):1771-1780. PMID: 25372085
5.  **\[RETRACTED — historical citation\]** Jayne DRW, Merkel PA, Schall TJ, Bekker P; ADVOCATE Study Group. Avacopan for the Treatment of ANCA-Associated Vasculitis. *N Engl J Med.* 2021;384:599–609. [PMID 33596356](https://pubmed.ncbi.nlm.nih.gov/33596356/). Retracted 29 June 2026: [Rubin EJ, retraction notice; PMID 42377355](https://pubmed.ncbi.nlm.nih.gov/42377355/).
6.  Appel GB, Contreras G, Dooley MA, et al. Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis (ALMS). *J Am Soc Nephrol.* 2009;20(5):1103-1112. PMID: 19369404
7.  Dooley MA, Jayne D, Ginzler EM, et al. Mycophenolate versus azathioprine as maintenance therapy for lupus nephritis (ALMS maintenance). *N Engl J Med.* 2011;365(20):1886-1895. PMID: 22087680
8.  Houssiau FA, Vasconcelos C, D'Cruz D, et al. Immunosuppressive therapy in lupus nephritis: the Euro-Lupus Nephritis Trial. *Arthritis Rheum.* 2002;46(8):2121-2131. PMID: 12209517
9.  Rovin BH, Teng YKO, Ginzler EM, et al. Efficacy and safety of voclosporin versus placebo for lupus nephritis (AURORA 1): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. *Lancet.* 2021;397(10289):2070-2080. PMID: 33971155
10. Fervenza FC, Appel GB, Barbour SJ, et al. Rituximab or cyclosporine in the treatment of membranous nephropathy (MENTOR). *N Engl J Med.* 2019;381(1):36-46. PMID: 31269364
11. Legendre CM, Licht C, Muus P, et al. Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome. *N Engl J Med.* 2013;368(23):2169-2181. PMID: 23738544
12. Rondeau E, Scully M, Ariceta G, et al. The long-acting C5 inhibitor, ravulizumab, is effective and safe in adult patients with atypical hemolytic uremic syndrome naive to complement inhibitor treatment. *Kidney Int.* 2020;97(6):1287-1296. PMID: 32299680
13. Hiemstra TF, Walsh M, Mahr A, et al. Mycophenolate mofetil vs azathioprine for remission maintenance in ANCA-associated vasculitis (IMPROVE). *JAMA.* 2010;304(21):2381-2388. PMID: 21060104
14. Aringer M, Costenbader K, Daikh D, et al. 2019 European League Against Rheumatism/American College of Rheumatology Classification Criteria for Systemic Lupus Erythematosus. Arthritis Rheumatol. 2019;71(9):1400-1412. [PubMed](https://pubmed.ncbi.nlm.nih.gov/31385462/)
15. Buckley L, Humphrey MB. Glucocorticoid-Induced Osteoporosis. N Engl J Med. 2018;379(26):2547-2556. [PubMed](https://pubmed.ncbi.nlm.nih.gov/30586507/)

Andrew Bland, MD, FACP, FAAP \| University of Dubuque PA Program \| urinenephrology.org

© 2025. For educational use only. Not a substitute for clinical judgment.


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