Acute Allograft Dysfunction

Definitions 📚

• ↑ sCr ≥25% within 1-3 months
• Failure of sCr to ↓ post-transplantation

Timing ⏱️

• Immediate: < 1 week post-transplantation
• Early: 1 week to 3 months post-transplantation
• Late: > 3 months post-transplantation

• Recurrent disease 👻

Diagnostic Armamentarium, 1st Pass 🧰

• Structural
• Ultrasound ⊕ Doppler → CT/MRI

• Calcineurin inhibitor toxicity
• [CNI level] → ↓ dose if supratherapeutic, re-assess

• Acute rejection
• [dd-cfDNA]
• Fractional dd-cfDNA >1% *or* serially ↑ levels are associated with acute rejection
• ↑ % = ↑ PPV for rejection (↓ % = ↑ NPV for absence of rejection)
• Levels of dd-cfDNA cannot be used to distinguish between T-cell mediated rejection, antibody-mediated rejection, & non-rejection related donor damage (i.e. it is just a non-specific marker of donor injury resulting in leak of donor DNA)
• [DSA]
• The development of antibodies directed against the donor's HLA antigens or ↑ DSA titers in a patient with a preexisting DSA can occur in patients with acute rejection & has been associated with antibody-mediated rejection
• ⊖ [DSA] level does not rule-out antibody-mediated rejection owing to unmeasured antibodies against non-HLA antigens

• Recurrent disease
• Urine microscopy → dysmorphic RBCs suggestive of GN
• Urine protein quantification

• Infections
• Urine culture → rule-out pyelonephritis (mimicking rejection)
• CMV viral load → rule-out CMV nephritis (mimicking rejection)
• BK viral load → rule-out BK nephropathy (mimicking rejection)

Diagnostic Armamentarium, 2nd Pass 🧰

• Biopsy

• Kidney transplantation in adults: Evaluation and diagnosis of acute kidney allograft dysfunction

• Kidney transplantation in adults: Clinical features and diagnosis of acute kidney allograft rejection

• Chronic Kidney Allograft Disease: New Concepts and Opportunities