Temsirolimus

Glomerular Injury / Proteinuria.

Not firmly quantified for temsirolimus specifically. Proteinuria is the recognized mTOR-inhibitor glomerular signal, but for temsirolimus it is documented mostly at the class/case level rather than in drug-specific renal endpoints (everolimus proteinuria runs high yet is usually grade 1-2 — e.g., 96% all-grade in one first-line mRCC cohort). In the pivotal temsirolimus ARCC trial, metabolic lab abnormalities (hyperglycemia, hyperlipidemia, hypophosphatemia) dominated and frank nephrotoxicity was uncommon; drug-specific AKI and nephrotic syndrome appear only in case reports.

Source: Not firmly quantified for temsirolimus; class/context from Land et al., J Oncol Pharm Pract 2014 (everolimus) and case-level Heras et al., Nefrologia 2009.

Reported injury signatures: Glomerular Injury / Proteinuria, Electrolyte Disturbance, Acute Tubular Necrosis.

1. Glomerular Injury / ProteinuriaPrimary
2. Electrolyte DisturbanceSecondary
3. Acute Tubular NecrosisSecondary

Subacute (~1–6 weeks) — Typically weeks to months into weekly dosing; not firmly characterized for temsirolimus.

• Pre-existing CKD or baseline proteinuria
• Reduced renal mass (post-nephrectomy / solitary kidney in RCC)
• Diabetes or hypertension
• Prior or concurrent VEGF-pathway-targeted therapy
• Hypoalbuminemia

• Baseline and periodic urinalysis / urine protein-to-creatinine ratio
• Baseline renal function (creatinine, eGFR) before and during therapy
• Monitor serum phosphate, glucose and lipids
• Optimize blood pressure and avoid concurrent nephrotoxins

• Baseline and periodic urinalysis / UPCR or UACR for proteinuria
• Serum creatinine and eGFR
• Serum phosphate and potassium
• Fasting glucose and lipid panel (metabolic class effects)
• Blood pressure

• GLOBAL ARCC (Hudes et al., NEJM 2007) — pivotal phase 3 in poor-prognosis metastatic RCC establishing 25 mg IV weekly; hyperglycemia, hyperlipidemia and hypophosphatemia were prominent while frank nephrotoxicity was uncommon and renal-specific proteinuria was not systematically captured
• Phase 3 mantle-cell-lymphoma program — higher 175/75 mg dosing with a different, mostly hematologic/GI safety profile (Bouabdallah et al., Curr Opin Oncol 2013)

• Temsirolimus is the IV ester prodrug of sirolimus — its renal footprint is inferred mainly from the sirolimus/everolimus class literature rather than temsirolimus-specific trials.
• Proteinuria (podocyte slit-diaphragm down-regulation plus autophagy disruption, with FSGS in some cases) is the signature mTOR-inhibitor renal signal, but the temsirolimus-specific incidence is not firmly quantified — hedge.
• The pivotal ARCC trial foregrounded hyperglycemia, hyperlipidemia and hypophosphatemia; frank nephrotoxicity was uncommon and creatinine changes modest.
• No renal dose adjustment is required (hepatic metabolism and biliary excretion); hepatic impairment drives dose changes instead.
• An ACEi/ARB plus dose reduction usually controls proteinuria; nephrotic-range proteinuria or a rising creatinine warrants holding the drug and nephrology input.
• Watch for additive glomerular injury when temsirolimus is sequenced with VEGF-pathway agents in RCC.

• 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