The Injury Atlas
PSEUDO
Pseudo-AKI
The great mimic — a rise in creatinine from blocked tubular secretion (OCT2/MATE), NOT true injury. The GFR is intact; confirm with cystatin C before stopping effective therapy.
22agents
Severity mix
Mild· 22
Reversibility
Variable· 1Reversible· 21
Signature offenders
15Agents for which pseudo-aki is the defining renal lesion.
BosutinibDevelops over months of therapy; time to grade 3b eGFR is shortest with later-line use.Long-term bosutinib is associated with a gradual, generally reversible decline in eGFR. In a long-term analysis, renal adverse events occurred in roughly 6-13% across lines of therapy, and a notable fraction reached grade 3b or worse eGFR (<45 mL/min/1.73 m2), with many recovering on follow-up; the pattern resembles the eGFR decline seen with imatinib.MildAlectinibCreatinine rise within weeks of starting therapy (mean eGFR declines over the first 90 days); reverses after discontinuation.Alectinib is associated with creatinine elevations that are usually benign. In a real-world ALK-inhibitor cohort, alectinib was the most-used agent (91 of 191 treatments) and creatinine-based AKI/CKD events were frequent (10% AKI within 90 days, 14% CKD at 1 year) but mostly mild and reversible, with few treatment changes attributed to AKI and none requiring dialysis.MildBrigatinibCreatinine changes typically emerge within weeks and tend to reverse on discontinuation.As an ALK inhibitor, brigatinib is associated with creatinine elevations that are generally benign. In a real-world ALK-inhibitor cohort, creatinine-based AKI/CKD events occurred but were mostly mild and reversible across agents including brigatinib; class reviews note elevated creatinine, occasional edema, and rare electrolyte disturbances. A distinct, early-onset pulmonary event (within the first week) is a separate non-renal class concern.MildLorlatinibMetabolic effects and edema appear within weeks of starting therapy.Lorlatinib is characterized by prominent metabolic effects - hypercholesterolemia and hypertriglyceridemia occur in the majority of patients (the leading grade 3/4 toxicity in the CROWN trial) - plus peripheral edema. Direct renal toxicity is limited and, like other ALK inhibitors, creatinine elevations are generally mild and reversible. Renal effects are not well quantified specifically for lorlatinib.MildCeritinibPrerenal AKI can occur whenever GI toxicity causes significant fluid loss, often early in therapy.Ceritinib causes frequent gastrointestinal toxicity (nausea, vomiting, diarrhea in the majority of patients), which can lead to volume depletion and prerenal AKI; as an ALK inhibitor it can also produce generally mild, reversible creatinine elevations. The prerenal AKI risk is largely a downstream effect of GI losses and is not precisely quantified.MildCapmatinibEarly — within the first cycles.Increased blood creatinine is a common treatment-related adverse event (~21% in GEOMETRY mono-1; higher in some Asian subsets), and peripheral edema is the single most common adverse event (~47%); most events are grade 1-2 and reversible.MildTepotinibEarly — within the first cycles.Blood creatinine increase and peripheral edema are the main treatment-related adverse events in the VISION program; both are common and generally mild to moderate and manageable, rarely leading to discontinuation.MildAbemaciclibEarly — within the first weeks (median onset ~3 weeks), stable thereafter, reversible on discontinuation.A benign serum-creatinine rise occurs in roughly one-fifth of patients (~20% in a single-center series; a class effect across CDK4/6 inhibitors), almost always grade 1–2 and without true GFR loss. In a dedicated CDK4/6-inhibitor cohort, ~73% of creatinine rises were confirmed pseudo-AKI by cystatin C–based eGFR.MildPalbociclibOften within the first 1-2 cycles (median onset roughly 30-35 days); creatinine plateaus and reverses after dose hold or discontinuation.A reversible rise in serum creatinine is common, but true structural kidney injury is uncommon. CDK4/6 inhibitors block the proximal-tubule transporters that secrete creatinine, producing a 'pseudo-AKI' picture. In a single-centre cohort, 17.5% of palbociclib-treated patients met creatinine-based AKI criteria, and when cystatin C was available, 73% of those events proved to be pseudo-AKI rather than a true GFR decline.MildRibociclibFirst cycles (median onset roughly 6 weeks for the creatinine signal); reversible on hold or discontinuation. QTc effects are dose- and concentration-dependent and seen early.Like other CDK4/6 inhibitors, ribociclib produces a frequent, reversible creatinine rise via inhibition of tubular creatinine secretion (pseudo-AKI ~14% in a class-effect analysis); clinically meaningful structural AKI is uncommon. A retrospective cohort of palbociclib/ribociclib patients found a >=20% creatinine-clearance decline in about 23%.MildRepotrectinibEarly after initiation; stable thereafter (a step change, not a progressive decline).An apparent rise in serum creatinine is described that often reflects inhibition of tubular creatinine secretion rather than a true fall in GFR (pseudo-AKI). Genuine intrinsic nephrotoxicity is not a characteristic feature and is not well quantified. This pattern is increasingly recognized across kinase inhibitors (e.g., ALK TKIs, where most creatinine-based eGFR changes do not require treatment change).MildTucatinibWithin the first weeks of therapy; plateaus and is fully reversible within days of discontinuation.A mild creatinine increase is common and expected, but it reflects inhibition of tubular creatinine secretion (a 'pseudo-AKI' artifact) rather than true GFR loss. Dedicated transporter/PK studies show tucatinib inhibits renal OCT2 and MATE1/MATE2-K without changing iohexol-measured GFR.MildEntrectinibWithin the first weeks of therapy; reversible on discontinuation.A mild blood-creatinine increase is recognized and is attributed to reduced tubular creatinine secretion rather than true GFR decline (a pseudo-AKI pattern). It is typically modest, early and reversible; a meaningful structural-AKI rate is not established.MildZongertinibNot established; any creatinine change would emerge during early therapy by class analogy.Renal data are not established. In Beamion LUNG-1 the toxicity profile was mainly low-grade (diarrhea, rash) with no drug-related interstitial lung disease; renal events were not a defining signal. By analogy to other HER2/TKI agents (tucatinib), any creatinine rise is most likely a benign tubular-secretion (pseudo-AKI) effect rather than true injury.MildLarotrectinibEarly (days to weeks), stable/plateauing, and fully reversible on interruption or discontinuation.The larotrectinib-specific creatinine effect is not separately quantified; the mechanism is extrapolated from the TKI class (the tucatinib OCT2/MATE study and crizotinib's ~21% early, reversible, secretion-driven rise). The clinically important real toxicities are hepatic (transaminase elevation) and neurologic, not renal.Mild
Also associated
7Agents that cause pseudo-aki as a secondary pattern alongside a different signature lesion.
NilotinibVascular events accrue over months to years of therapy.Nilotinib carries a recognized risk of arterial occlusive events and metabolic effects (dysglycemia, hyperlipidemia), but direct renal toxicity is limited; in comparative CML cohorts nilotinib generally did not cause significant eGFR decline relative to imatinib. Any kidney impact is largely mediated through vascular disease and perfusion rather than intrinsic nephrotoxicity.MildCrizotinibCreatinine rise often within weeks and reverses on discontinuation; cysts develop and grow over months.Crizotinib commonly causes a reversible rise in serum creatinine and is distinctively associated with the development and progression of complex renal cysts. Peripheral edema and electrolyte disturbances (including hypophosphatemia and hypokalemia) are reported. In real-world ALK-inhibitor cohorts, creatinine-based AKI/CKD events are frequent but mostly mild and reversible; frank kidney failure is uncommon.MildOlaparibCreatinine rise within weeks of starting therapy; reverses on discontinuation.Olaparib commonly causes a reversible, dose-dependent rise in serum creatinine. In a 66-patient study, median creatinine rose ~14% (and creatinine-based eGFR fell ~13%) on treatment, while cystatin C and cystatin C-based eGFR were unchanged - indicating no true GFR decline. Thrombotic microangiopathy is a rare, case-level event for the PARP-inhibitor class.MildRucaparibWithin the first weeks of treatment.Early reversible serum-creatinine elevation is common and partly drug-specific: rucaparib is a recognized inhibitor of renal cation transporters, and a pooled meta-analysis found markedly higher odds of creatinine rise vs placebo across the class, but grade >=3 renal events were rare (<1%).MildTalazoparibThe pharmacokinetic effect is present from initiation in patients with reduced renal function; cytopenias accrue over the first cycles.Renal clearance is a major elimination route (~two-thirds of dose), so exposure rises with declining renal function: dedicated PK studies show higher AUC and more myelosuppression in moderate-severe impairment, mandating dose reduction. Class-level mild creatinine elevation may occur; severe intrinsic nephrotoxicity is uncommon.MildSotorasibWhen AKI occurs, it is acute during the first weeks–months of therapy, typically tracking GI toxicity.Clinically significant nephrotoxicity is uncommon and case-level in humans (the dominant on-target/off-tumor toxicity is hepatotoxicity). Proximal tubular toxicity is prominent in rats via a reactive mercapturate-pathway metabolite. Human renal incidence is not well quantified.MildAdagrasibEarly — within the first weeks of therapy.Renal effects are usually mild: a creatinine rise (partly from inhibited tubular creatinine secretion) plus prerenal AKI from GI losses. The KRYSTAL-1 registrational program reported renal-related lab changes; a dedicated PubMed-indexed pseudo-AKI/albuminuria study for adagrasib does not yet exist, so the precise incidence is unquantified.Mild