Multi-target tyrosine kinase inhibitor-associated renal thrombotic microangiopathy: a pooled analysis of 31 cases

Background Multi-target tyrosine kinase inhibitors (TKIs) are cornerstone therapies for solid malignancies, yet their association with renal thrombotic microangiopathy (TMA)—a severe, irreversible adverse event—remains incompletely defined. This study delineates TKI-associated renal TMA’s clinical features, onset patterns, and outcomes. Methods We systematically searched PubMed, Embase, Cochrane Library, and Web of Science for case reports/series of renal TMA linked to 7 multi-target TKIs (sunitinib, sorafenib, etc.) published through January 2026. Key data were extracted and analyzed descriptively. Results Thirty-one cases were included (median age 62 years, 51.6% female). Common tumors: renal cell carcinoma (29.0%), thyroid cancer (16.1%), gastrointestinal stromal tumor (12.9%). Sunitinib was most implicated (48.4%). Median latency: 16 months (0.5–96 months); combination therapy shortened to 3.5 months. Dominant triad: hypertension (58.1%), AKI (77.4%), nephrotic proteinuria (67.9%); classic MAHA was uncommon. Kidney biopsy (87.1%) confirmed TMA. TKI discontinuation: 87.1% (6.5% dose reduction). Among evaluable patients, 90.0% improved, but 53.3% developed residual CKD and 10.0% ESRD. Conclusion TKI-associated renal TMA presents as hypertension-proteinuria-AKI rather than classic hemolysis. Sunitinib confers highest risk, baseline hypertension is a key modifiable factor, and combination therapy accelerates onset. Lifelong monitoring and timely TKI discontinuation are critical, though residual CKD is common.