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Signature βοΈ
Definitions π
- β sCr β₯25% within 1-3 months
- Failure of sCr to β post-transplantation
Timing β±οΈ
- Immediate: < 1 week post-transplantation
- Early: 1 week to 3 months post-transplantation
- Late: > 3 months post-transplantation
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DDx π³οΈβπ
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- β Vascular Inflow
- Immediate: thrombosis
- Early/late: renal artery stenosis
- β Vascular Outflow
- Hypercoagulability: e.g. SLE-related APS
- Stasis: e.g. post-surgical hematoma, lymphocele β compression
- β Urinary Outflow
- Ureter: stenosis (e.g. post-ischemic scarring, post-viral scarring)
- Compression: fluid leak vs. PTLD
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- Hemodynamic (Afferent Arteriolar Vasoconstriction)
- Dose/level-dependent β sCr
- Reversible within 24-72hr of dose reduction
- Endothelial (Thrombotic Microangiopathy)
- Renal-limited = likely no MAHA
- Irreversible & often clinically indistinguishable from rejection
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- Asymptomatic HTN (i.e. JGA inflammation) > systemic inflammation β graft pain/tenderness (i.e. immunosuppression generally masks profound inflammation)
- Non-specific UA findings (proteinuria, pyuria)
- Non-specific US findings (i.e. primarily used to assess for structural pathology)
- β donor-derived cell-free DNA (dd-cfDNA)
- β donor-specific antibody (DSA)
- Recurrent disease π»
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- Viral
- CMV interstitial nephritis vs. glomerulopathy
- BK virus interstitial nephritis vs. glomerulopathy
- Bacterial
- Pyelonephritis
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PrinciplesβοΈ
Diagnostic Armamentarium, 1st Pass π§°
- Structural
- Ultrasound β Doppler β CT/MRI
- Calcineurin inhibitor toxicity
- [CNI level] β β dose if supratherapeutic, re-assess
- Acute rejection
- [dd-cfDNA]
- Fractional dd-cfDNA >1% *or* serially β levels are associated with acute rejection
- β % = β PPV for rejection (β % = β 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 β DSA titers in a patient with a preexisting DSA can occur in patients with acute rejection & has been associated with antibody-mediated rejection
- β [DSA] level does not rule-out antibody-mediated rejection owing to unmeasured antibodies against non-HLA antigens
- Recurrent disease
- Urine microscopy β dysmorphic RBCs suggestive of GN
- Urine protein quantification
- Infections
- Urine culture β rule-out pyelonephritis (mimicking rejection)
- CMV viral load β rule-out CMV nephritis (mimicking rejection)
- BK viral load β rule-out BK nephropathy (mimicking rejection)
Diagnostic Armamentarium, 2nd Pass π§°
- Biopsy
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References π