What is the differential diagnosis and treatment for a patient with a history of IgA (Immunoglobulin A) vasculitis, presenting with acute kidney injury (AKI), red blood cell casts, new ascites, cirrhosis, and chronic portal vein thrombosis (PVT), and prior kidney biopsy showing IgA vasculitis?

Differential Diagnosis and Treatment for AKI in IgA Vasculitis with Cirrhosis

Primary Differential Diagnosis

This patient most likely has active IgA vasculitis nephritis (IgAVN) causing AKI, but hepatorenal syndrome (HRS) must be systematically excluded given the cirrhosis with new ascites and portal vein thrombosis. The presence of RBC casts strongly suggests active glomerulonephritis rather than HRS, as HRS criteria specifically require absence of microhematuria (>50 RBCs per high power field) 1.

Key Diagnostic Considerations:

Active IgA Vasculitis Nephritis (Most Likely)

• RBC casts are pathognomonic for glomerulonephritis and essentially rule out HRS as the sole cause 1
• Prior kidney biopsy confirmed IgAV, and current purpura/petechiae with leukocytoclastic vasculitis on skin biopsy indicate active systemic disease 2, 3
• IgAV in adults frequently causes severe nephritis with up to one-third progressing to end-stage renal disease 2
• The cirrhosis may actually be contributing to IgAV development, as elevated serum IgA levels in cirrhosis are associated with IgAV 4

Hepatorenal Syndrome (Must Exclude)

• HRS-AKI diagnostic criteria require: cirrhosis with ascites, AKI by ICA-AKI criteria, no response to diuretic withdrawal and albumin (1 g/kg for 2 days), absence of shock, no nephrotoxic drugs, AND absence of proteinuria >500 mg/day and microhematuria >50 RBCs/HPF 1, 5
• This patient fails HRS criteria due to RBC casts and likely significant hematuria 1
• However, HRS can coexist with parenchymal kidney disease 1

Acute Tubular Necrosis (ATN)

• Consider if patient has hypotension, sepsis, or nephrotoxic exposures
• Urinary biomarkers (NGAL, KIM-1, IL-18, L-FABP) can help differentiate ATN from HRS, though not widely available 1

Cirrhosis-Related IgA Nephropathy

• Cirrhosis is well-known to be associated with IgA nephropathy and IgAV 4
• Patients with cirrhosis and IgAV display more elevated serum IgA levels (5.6 g/L vs 3.6 g/L) 4

Immediate Diagnostic Workup

Critical Initial Steps:

• Withdraw all diuretics immediately 1, 5, 6
• Review and discontinue all nephrotoxic drugs (NSAIDs, aminoglycosides, contrast) 1
• Administer albumin 1 g/kg/day IV for 2 consecutive days to assess for HRS and optimize volume status 1, 5
• Obtain urinalysis with microscopy to quantify RBCs, assess for dysmorphic RBCs, and measure proteinuria 1
• Check serum IgA levels (often elevated in both cirrhosis and IgAV) 4
• Assess for infection (spontaneous bacterial peritonitis, other infections) as bacterial infections commonly precipitate AKI in cirrhosis 5

Treatment Algorithm

Stage 1: Initial Management (First 48 Hours)

For ALL patients with this presentation:

• Discontinue diuretics and nephrotoxic agents immediately 1, 5, 6
• Administer IV albumin 1 g/kg/day for 2 days 1, 5
• Treat any identified infections aggressively 5
• Monitor creatinine daily and stage AKI (Stage 1: sCr increase ≥0.3 mg/dL or 1.5-2× baseline; Stage 2: >2-3× baseline; Stage 3: >3× baseline or ≥4.0 mg/dL or RRT) 5

Stage 2: Assess Response and Determine Primary Etiology (Days 2-3)

If NO response to albumin and diuretic withdrawal:

A. If RBC casts persist and/or proteinuria >500 mg/day:

• Diagnosis: Active IgA vasculitis nephritis is the primary driver
• Initiate immunosuppression for IgAV immediately - do not delay for repeat kidney biopsy if clinical picture is clear 1
• Corticosteroids: Prednisone 1 mg/kg/day (maximum 60-80 mg/day) for severe IgAV with nephritis 2, 3
• Consider adding cyclophosphamide or rituximab for severe crescentic glomerulonephritis, though evidence is limited in IgAV 2, 3
• Initiate RAAS blockade (ACE inhibitor or ARB) once hemodynamically stable for long-term renoprotection 7

B. If meets ALL other HRS criteria (no proteinuria, no hematuria, normal renal ultrasound):

• This scenario is unlikely given RBC casts, but if present:
• Initiate vasoconstrictors (terlipressin preferred, or norepinephrine/midodrine + octreotide) PLUS albumin 1
• Do not wait for creatinine to reach 2.5 mg/dL - earlier treatment improves outcomes 1
• For ICA-AKI Stage 2 or 3, start vasoconstrictors immediately if HRS criteria met 1

C. Most likely scenario - Mixed picture:

• Treat BOTH conditions simultaneously:
  • Albumin + vasoconstrictors for HRS component 1
  • Corticosteroids for active IgAV nephritis 2, 3
  • This dual approach addresses both functional (HRS) and inflammatory (IgAV) components

Stage 3: Ongoing Management

Monitor response at 48-72 hours:

• Full response: sCr returns to within 0.3 mg/dL of baseline 1
• Partial response: Regression of at least one AKI stage 1
• No response: Consider renal replacement therapy 5, 6

For IgAV-specific management:

• Continue corticosteroids for 4-6 weeks with gradual taper based on clinical response 2, 3
• Monitor for IgAV relapse (occurs in minority of cases) 4
• Long-term prognosis depends on severity of nephritis - up to one-third of adults with IgAV reach ESRD 2, 3

For cirrhosis management:

• Address underlying liver disease - if alcohol-related (75% of cirrhosis with IgAV), counsel on abstinence 4
• Manage portal hypertension and ascites per standard cirrhosis guidelines
• Monitor for hepatic decompensation as 6/20 patients in one series died during follow-up (though not from IgAV) 4

Critical Pitfalls to Avoid

• Do not assume HRS is the sole diagnosis when RBC casts are present - this indicates glomerulonephritis requiring immunosuppression 1
• Do not delay immunosuppression waiting for repeat kidney biopsy if clinical picture strongly suggests active IgAV 1
• Do not wait for creatinine >2.5 mg/dL to treat HRS - earlier treatment improves outcomes 1
• Do not use NSAIDs or other nephrotoxic agents in this population 1
• Do not overlook infection as AKI precipitant - bacterial infections commonly trigger AKI in cirrhosis 5

Special Consideration: Cirrhosis and IgAV Association

The coexistence of cirrhosis and IgAV is increasingly recognized 4. In a French nationwide series, 60% of patients had cirrhosis and IgAV diagnosed simultaneously, with alcohol-related cirrhosis being most common (75%) 4. These patients were older (mean age 62.7 years) and had higher serum IgA levels compared to IgAV patients without cirrhosis 4. The liver disease did not appear to worsen IgAV outcomes, with 77% achieving remission at 3 months 4.