Sorafenib

Hypertension — representative incidence ~23%.

Hypertension is the dominant renal-vascular signal: a systematic review/meta-analysis of 9 trials (4,599 patients) reported an all-grade incidence of 23.4% (95% CI 16.0-32.9%) and high-grade (grade 3-4) incidence of 5.7% (Wu 2008), and a larger meta-analysis of 93 trials (20,494 patients) gave concordant figures of 21.3% all-grade and 5.9% high-grade, with higher rates in renal-cell and thyroid cancer and rising incidence with longer treatment duration (Yang 2017). Proteinuria is a VEGF-pathway class effect: across VEGF-signalling inhibitors mild/asymptomatic proteinuria is reported in roughly 21-63% and heavy (nephrotic-range) proteinuria in up to about 6.5% of renal-cell carcinoma patients (Izzedine 2009); drug-specific quantitative proteinuria data for sorafenib alone are more limited. Nephrotic-range proteinuria and renal-limited thrombotic microangiopathy are documented but uncommon.

Source: 18221915

Reported injury signatures: Hypertension, Glomerular Injury / Proteinuria, Thrombotic Microangiopathy, Electrolyte Disturbance.

1. HypertensionPrimary
2. Glomerular Injury / ProteinuriaSecondary
3. Thrombotic MicroangiopathySecondary
4. Electrolyte DisturbanceSecondary

Subacute (~1–6 weeks) — Hypertension emerges within the first few weeks; proteinuria over weeks to months; nephrotic syndrome and TMA are variable, generally after weeks to months but occasionally sooner.

• Pre-existing or poorly controlled hypertension
• Pre-existing chronic kidney disease or proteinuria
• Renal cell carcinoma with prior nephrectomy / solitary kidney (reduced renal reserve)
• Concurrent or sequential use of other VEGF-pathway agents or nephrotoxins
• Higher cumulative exposure / longer treatment duration
• High dietary salt intake (from preclinical models)

• Measure and optimize blood pressure before starting, then monitor closely (weekly through the first ~6 weeks)
• Obtain baseline urinalysis/urine protein-to-creatinine ratio and serum creatinine, and repeat during therapy
• Treat emergent hypertension early with standard agents, favoring an ACE inhibitor or ARB when proteinuria is present
• Avoid unnecessary co-administration of additional nephrotoxins or overlapping anti-VEGF agents
• Refer patients with worsening renal function or nephrotic-range proteinuria to nephrology promptly

• Blood pressure — weekly during the first ~6 weeks, then regularly
• Urinalysis / urine protein-to-creatinine ratio for emergent or worsening proteinuria
• Serum creatinine and eGFR
• CBC with peripheral smear, LDH and haptoglobin if thrombotic microangiopathy is suspected
• Serum phosphate and electrolytes (hypophosphatemia signal)

• SHARP (NEJM 2008) — phase III, placebo-controlled in advanced hepatocellular carcinoma; median OS 10.7 vs 7.9 months (HR 0.69); hypophosphatemia and hand-foot skin reaction more frequent with sorafenib
• TARGET — phase III in advanced clear-cell renal cell carcinoma supporting the RCC indication (hypertension and proteinuria as class antiangiogenic effects)
• DECISION — phase III in radioactive iodine-refractory differentiated thyroid cancer, where hypertension is among the common adverse events

• The renal signature is antiangiogenic hypertension plus proteinuria; nephrotic-range proteinuria and renal-limited thrombotic microangiopathy are the severe, less common end of the spectrum.
• As a TKI, sorafenib tends to biopsy as a glomerulopathy (minimal change disease / FSGS) rather than the pure TMA seen with anti-VEGF antibodies like bevacizumab.
• Prefer an ACE inhibitor or ARB for the hypertension — it treats blood pressure and reduces proteinuria simultaneously.
• Hypertension usually does not require stopping the drug; drug withdrawal (not plasma exchange) is the key intervention for VEGF-inhibitor TMA.
• Sorafenib is comparatively less nephrotoxic than lenvatinib — switching from lenvatinib to sorafenib has resolved anti-VEGF nephrotic syndrome while preserving tumor control.
• Watch serum phosphate: hypophosphatemia was more frequent than placebo in the SHARP trial.
• Renal clearance is a minor route and the drug is not appreciably dialyzed, so there is no eGFR-based dose adjustment — dose by toxicity.

• KDIGO (2021) — Management of Blood Pressure in Patients With Chronic Kidney Disease Not Receiving Dialysis: Synopsis of the 2021 KDIGO Clinical Practice GuidelineRecommends standardized office BP measurement and a target systolic BP <120 mm Hg for most CKD patients, with RAAS inhibitors first-line when albuminuria is present — the BP-management basis for anti-VEGF/TKI-induced hypertension and proteinuria.Ann Intern Med · PMID 34152826
• ESC (2022) — 2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS)For VEGF/VEGFR inhibitors, perform baseline cardiovascular risk assessment, monitor blood pressure (weekly during the first cycle, then regularly) and treat to a target <140/90 mmHg with ACE inhibitors/ARBs and dihydropyridine calcium-channel blockers; manage VEGFi-associated hypertension and proteinuria with interruption/dose modification when severe.Eur Heart J · PMID 36017568
• ESC (2022) — European Society of Cardiology quality indicators for the prevention and management of cancer therapy-related cardiovascular toxicity in cancer treatmentAdherence quality indicators require documented baseline cardiovascular risk assessment and structured monitoring of cardiovascular complications (including hypertension) during cancer therapy such as VEGF-pathway inhibitors.Eur Heart J Qual Care Clin Outcomes · PMID 36316010
• UK Consensus Panel (2010) — Using bevacizumab to treat metastatic cancer: UK consensus guidelinesAssess and monitor blood pressure and proteinuria during bevacizumab therapy; treat emergent hypertension to standard targets and interrupt/discontinue the drug for uncontrolled hypertension, nephrotic-range proteinuria or other severe vascular toxicity.Br J Hosp Med (Lond) · PMID 21135762
• ADQI (2026) — The nephrotoxic effects of anti-cancer therapies: consensus report of the 34th Acute Disease Quality Initiative workgroupProvides expert-based statements (modified Delphi) on preventing and managing cisplatin/platinum-associated AKI, including isotonic IV hydration, attention to volume status and concomitant nephrotoxins, and incorporates evidence that IV magnesium supplementation may reduce cisplatin-associated AKI; emphasizes risk stratification and standardized AKI definitions.Nat Rev Nephrol · PMID 41361704
• SIRM (2022) — SIRM-SIN-AIOM: appropriateness criteria for evaluation and prevention of renal damage in the patient undergoing contrast medium examinations-consensus statements from Italian College of Radiology (SIRM), Italian College of Nephrology (SIN) and Italian Association of Medical Oncology (AIOM)Recommends eGFR-based renal risk assessment and pre/post-contrast isotonic saline or sodium bicarbonate hydration; advises maintaining a 5-7 day interval between iodinated contrast administration and cisplatin in cancer patients to reduce additive nephrotoxicity.Radiol Med · PMID 35303246
• KDIGO (2020) — KDIGO Controversies Conference on onco-nephrology: understanding kidney impairment and solid-organ malignancies, and managing kidney cancerIdentifies platinum compounds (especially cisplatin) as leading cytotoxic causes of acute tubular injury, AKI, and electrolyte/magnesium wasting; calls for interdisciplinary onco-nephrology care, accurate GFR estimation, and individualized drug dosing in patients with reduced kidney function.Kidney Int · PMID 33126977
• KDIGO (2020) — KDIGO Controversies Conference on onco-nephrology: kidney disease in hematological malignancies and the burden of cancer after kidney transplantationAddresses chemotherapy-associated AKI/CKD in hematologic cancer, GFR estimation and chemotherapy dosing in patients with reduced kidney function, and management priorities and research gaps for onco-nephrology care.Kidney Int · PMID 33276867
• ADDIKD (2025) — Integrating International Consensus Guidelines for Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD) into everyday practiceProvides GRADE-based, drug-specific dose-adjustment recommendations for anticancer agents in kidney dysfunction (illustrated for methotrexate, cisplatin, carboplatin and nivolumab); the recommendations build on Part 1's standardised CKD-EPI eGFR assessment rather than Cockcroft-Gault creatinine clearance.EClinicalMedicine · PMID 40290844
• ADDIKD (2025) — Aligning kidney function assessment in patients with cancer to global practices in internal medicineThree consensus recommendations: assess kidney function by GFR (measured GFR or CKD-EPI eGFR), classify it using KDIGO categories, and use this uniform approach to dose anticancer drugs — moving cancer medicine away from Cockcroft-Gault estimated creatinine clearance.EClinicalMedicine · PMID 40290845
• ADDIKD (2025) — A methodology for determining dosing recommendations for anticancer drugs in patients with reduced kidney functionEstablishes that, where RCT evidence is lacking, anticancer drug dosing recommendations in kidney dysfunction should be derived by critically appraising observational literature via GRADE combined with structured international multidisciplinary consensus voting.EClinicalMedicine · PMID 40290846
• KDIGO (2013) — Diagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (Part 1)Defines/stages AKI by serum creatinine and urine output; emphasizes avoiding nephrotoxins, maintaining euvolemia/perfusion, dose-adjusting drugs to kidney function, and monitoring high-risk patients — the framework applied to nephrotoxic anti-cancer agents.Crit Care · PMID 23394211
• KDIGO (2021) — Executive summary of the KDIGO 2021 Guideline for the Management of Glomerular DiseasesProvides the staging/treatment framework for drug-associated glomerular lesions (e.g., bisphosphonate- and interferon-related collapsing FSGS, VEGF-inhibitor podocytopathy/proteinuria), including immunosuppression and supportive RAAS-blockade strategies.Kidney Int · PMID 34556300
• KDIGO (2024) — Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of ANCA-Associated VasculitisUpdates immunosuppressive induction (rituximab/cyclophosphamide), incorporates avacopan and lower-dose or glucocorticoid-sparing regimens — the management framework for drug- and checkpoint-inhibitor-associated ANCA/pauci-immune glomerulonephritis.Kidney Int · PMID 38388147
• KDIGO (2024) — Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of Lupus NephritisUpdates first-line lupus nephritis therapy to combination immunosuppression with the addition of belimumab or a calcineurin inhibitor (voclosporin) — informs management of immune-complex/lupus-like glomerulonephritis encountered with immunotherapy.Kidney Int · PMID 38182299
• KDIGO (2025) — Executive summary of the KDIGO 2025 Clinical Practice Guideline for the Management of Immunoglobulin A Nephropathy (IgAN) and Immunoglobulin A Vasculitis (IgAV)Encourages liberal kidney biopsy and stricter proteinuria control (<0.5 g/d, ideally <0.3 g/d) with RAAS blockers, SGLT2 inhibitors, and targeted-release budesonide — the framework for IgA-dominant glomerular lesions, including those triggered by immune-modulating cancer therapy.Kidney Int · PMID 40975525