In a kidney transplant recipient presenting with hematuria, what is the recommended initial evaluation and management?

Post-Kidney Transplant Hematuria: Initial Evaluation and Management

Begin with urgent assessment of graft function and rule out life-threatening causes, followed by systematic diagnostic workup prioritizing infection, rejection, and malignancy. 1

Immediate Clinical Assessment

Timing is critical: Differentiate early (<1 month) versus late (>1 month) post-transplant hematuria, as this fundamentally changes your differential diagnosis. 1

Key Clinical Features to Evaluate

• Quantify the hematuria: Gross versus microscopic, and assess for concurrent proteinuria 1
• Check for graft intolerance syndrome: Fever, graft tenderness, allograft enlargement, or pain suggest acute rejection or infection 2
• Assess graft function: Measure serum creatinine and eGFR immediately 1
• Review medications: Specifically anticoagulants and current immunosuppressive regimen 1
• Associated symptoms: Decreased urine output, fever, or systemic symptoms 1

Diagnostic Workup Algorithm

Laboratory Evaluation (First-Line)

• Urine culture with extended pathogen testing: Standard bacterial culture plus specific testing for atypical organisms (mycobacterial, fungal, viral including BK virus and adenovirus) given immunosuppression 1, 3, 4
• Serum creatinine and eGFR: Essential to assess for acute graft dysfunction 1
• Urinalysis with microscopy: Quantify hematuria and check for proteinuria, casts, and cellular elements 1

Imaging Studies

CT abdomen/pelvis without IV contrast is the preferred initial imaging modality for transplant recipients with hematuria, as it evaluates for hemorrhage, urinary obstruction, nephrolithiasis, peritransplant fluid collections, and masses without risking contrast nephrotoxicity in a potentially dysfunctional graft. 2

Alternative imaging considerations:

• Ultrasound with Doppler: Can assess for hydronephrosis, masses, and vascular complications 2
• CT with contrast: Reserve for cases where masses or vascular abnormalities need better characterization, only if graft function permits 2

Kidney Allograft Biopsy (Definitive Diagnosis)

Perform biopsy when hematuria is accompanied by:

• Unexplained graft dysfunction 1, 5
• Significant proteinuria (>3.0 g/day) 5
• Persistent unexplained hematuria despite negative initial workup 1, 5

The biopsy is critical because it can identify rejection, recurrent glomerular disease, or thrombotic microangiopathy that may not have obvious clinical or hematologic clues initially. 6

Management Based on Etiology

Infection-Related Hematuria

• Treat with culture-directed antibiotics for confirmed urinary tract infections 1
• Temporarily reduce immunosuppression only for severe, life-threatening infections with fever 1
• Do not screen or treat asymptomatic bacteriuria in patients >1 month post-transplant per IDSA guidelines 1

Critical pitfall: Excessive immunosuppression reduction risks triggering acute rejection. 1

Recurrent Glomerular Disease

For patients with history of glomerulonephritis presenting with hematuria and proteinuria:

• IgA nephropathy or FSGS: Initiate ACE inhibitor or ARB therapy for proteinuria >0.5 g/day, regardless of blood pressure 1, 5
• Rapidly progressive crescentic disease: Treat with high-dose corticosteroids and cyclophosphamide, analogous to ANCA vasculitis treatment 1, 5
• Plasma exchange: Consider for primary FSGS with significant proteinuria 1

Graft Intolerance Syndrome (Failed Allograft)

When hematuria occurs in the context of a failing allograft with fever and graft tenderness:

• First-line: High-dose pulse corticosteroids 2
• Rule out infection first: 38% of fevers in failed allografts are infectious (commonly dialysis catheter-related), not rejection 2
• Surgical intervention: Consider transplant nephrectomy for ongoing hemorrhage, unrelenting pain, or when medical management fails 2

Malignancy Screening

Persistent microscopic hematuria (>3 separate occasions) warrants imaging of native kidneys and allograft, followed by cystoscopy if imaging is negative. 7 The incidence of urologic malignancies in transplant recipients is 3.3%, with RCC prevalence of 4.4% and bladder malignancy 2.6%. 7, 4

Screening Protocol for High-Risk Patients

For patients with history of recurrent glomerular diseases:

• First month: Screen for microhematuria at least once to establish baseline 1, 5
• First year: Screen every 3 months 1, 5
• Thereafter: Annual screening 1, 5

Critical Pitfalls to Avoid

• Do not delay biopsy when there is unexplained hematuria with graft dysfunction or proteinuria >3.0 g/day—recurrent disease can occur as early as 19 days post-transplant 1, 5
• Do not assume all hematuria with fever is rejection—infection must be ruled out first, as 38% of fevers in this population are infectious 2
• Do not overlook viral etiologies (BK virus, adenovirus, CMV) when bacterial cultures are negative in immunosuppressed patients 3, 4
• Do not aggressively reduce immunosuppression during infection management without careful consideration, as this may trigger acute rejection 1