Is kidney injury from mTOR Inhibitors reversible?

Reversible. Typical onset: Weeks–months..

How should kidney function be monitored during mTOR Inhibitors therapy?

Quantify proteinuria at baseline and serially (spot urine protein/creatinine or albumin/creatinine ratio) — mTOR-inhibitor proteinuria can be heavy/nephrotic and is the dominant renal signal; Check serum creatinine/eGFR before starting and periodically; an unexpected rise should prompt evaluation rather than a level-driven dose increase; Screen for thrombotic microangiopathy when creatinine rises with new anemia or thrombocytopenia — order CBC with smear (schistocytes), LDH, and haptoglobin, especially in combination with calcineurin inhibitors or VEGF-pathway agents; Monitor sirolimus/everolimus trough levels in transplant recipients to keep exposure in target range and limit dose-dependent glomerular injury; Reassess proteinuria and renal function after any dose change or after switching from a calcineurin inhibitor, since de novo or worsening proteinuria often emerges after conversion.

How can kidney injury from mTOR Inhibitors be prevented?

Check a baseline urine protein/creatinine ratio before starting or converting from a calcineurin inhibitor — the baseline gates initiation and anchors later attribution

Who is at higher risk of kidney injury from mTOR Inhibitors?

Pre-existing CKD / proteinuria.

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Printable monograph

mTOR inhibitor

mTOR Inhibitors

Afinitor · Torisel · mTORi

mTOR inhibitor · approved 2009 · 8 citations

Dated evidence· through 2019

Fairly sourced6/9 · 5 signals

Met: 8 citations
Not met: 12+ references
Met: Accrued over 10+ years (span: 14y)
Met: Beyond single case reports
Met: High-impact journal
Met: Landmark reference
Not met: Current through 2019
Not met: Real-world FAERS signal

Describes how this page is sourced, not how dangerous the drug is. Thinly sourced means fewer of the sourcing signals are met — not that the agent is kidney-safe. A rule-based summary, not a formal certainty appraisal.

Disrupt the podocyte's maintenance program and protein slips through.

MildmTOR inhibitor

Renal cellNeuroendocrineBreast

§01

Signature kidney injury

Signature lesion

Glomerular Injury / Proteinuria

Everolimus commonly causes all-grade proteinuria, with high-grade uncommon; mTOR-inhibitor proteinuria/FSGS is well described. Temsirolimus case-level only.Source: Vollenbröker et al., Am J Physiol Renal Physiol 2008; Letavernier et al., 2008

Onset & rechallenge

Time to injurySubacute (~1–6 weeks)

Develops over weeks to months of therapy.

Distilled from: “Weeks–months.”

§02

Renal toxicities, ranked

This agent's kidney lesions ordered by prominence — the #1 signature lesion first, then secondary and rare patterns. Cited incidence is shown where a citable figure exists; otherwise the tier stands qualitatively.

Glomerular Injury / Proteinuria#1 · Signature96%PMID 25505255 (opens PubMed in a new tab)
Proteinuria in 96% (44/46) of everolimus-treated first-line metastatic RCC patients (overall 81% across VEGF/mTOR agents), the great majority grade 1-2 and managed by continued monitoring; reflects mTOR-inhibitor podocyte/slit-diaphragm injury. High-grade (grade 3-4) proteinuria is uncommon.
Acute Tubular NecrosisSecondaryqualitative — no citable incidence
Direct death of tubular epithelial cells — the dose-limiting lesion of the platinums and zoledronate.
Thrombotic MicroangiopathyRarequalitative — no citable incidence
Endothelial injury with microvascular thrombi, hemolysis and thrombocytopenia — gemcitabine, mitomycin C, anti-VEGF.

Toxicity fingerprint

Tap a signature to trace where it strikes the nephron.

Incidence not quantified

SeverityMild

ReversibilityReversible

Evidence8 citations

Nephron map

GlomerulusFiltration barrier (podocytes + endothelium)

Vasculature / Endothelium

Proximal Tubule

Distal Tubule / Collecting Duct

Glomerular Injury / Proteinuria

Damage to the filtration barrier — podocyte injury, FSGS and protein leak from VEGF and mTOR blockade.

§03

Kidney injury

Mechanism of kidney injury

mTOR inhibition down-regulates slit-diaphragm proteins (nephrin, TRPC6) and disrupts the podocyte cytoskeleton, impairing autophagy/repair and downstream VEGF signaling — producing proteinuria and FSGS.

Clinical presentation

Proteinuria (sometimes nephrotic range), occasionally a rising creatinine.

Management

ACEi/ARB, dose reduction or hold.Lesion-level management framework

Risk factors

Pre-existing CKD / proteinuria

Prevention

Check a baseline urine protein/creatinine ratio before starting or converting from a calcineurin inhibitor — the baseline gates initiation and anchors later attribution

Anticancer mechanism· how it treats cancer

Everolimus and temsirolimus inhibit mTORC1 to block cell growth, proliferation and angiogenesis. Renal cell, neuroendocrine and breast cancer.

Note · Same drug class used in transplant (sirolimus). Temsirolimus incidence is not firmly quantified.

§04

Clinical depth

Renal dose adjustment

No mandatory renal dose adjustment for sirolimus, everolimus, or temsirolimus by CrCl — these are hepatically (CYP3A4) metabolized, and renal excretion of parent drug is minimal, so labels do not specify creatinine-based reductions. Dosing is instead driven by trough levels (sirolimus/everolimus in transplant) or fixed mg dosing (oncology). In practice, dose is reduced or the drug held when proteinuria worsens or new-onset TMA appears, since toxicity is not a clearance problem but a podocyte/endothelial effect.

Dialyzability & ESKD dosing

Not appreciably dialyzable — large molecules with very high protein binding (~92% sirolimus, ~74% everolimus) and very large volumes of distribution, so hemodialysis does not meaningfully remove them and no post-HD supplemental dose is needed. There is no separate ESKD dose recommendation; level-guided or standard fixed dosing applies, with limited formal pharmacokinetic data in dialysis patients.

Differential diagnosis

The hallmark is glomerular proteinuria (often FSGS-pattern podocyte injury) rather than the tubular/interstitial picture of calcineurin inhibitors — useful when distinguishing toxicity in a patient on combined immunosuppression. New proteinuria plus a creatinine rise with hemolysis (schistocytes, low haptoglobin, high LDH, thrombocytopenia) points to drug-associated thrombotic microangiopathy rather than simple acute tubular necrosis or rejection. Recovery or stabilization of proteinuria after dose reduction or withdrawal supports a drug effect over an intrinsic or recurrent glomerulonephritis.

Monitoring

Quantify proteinuria at baseline and serially (spot urine protein/creatinine or albumin/creatinine ratio) — mTOR-inhibitor proteinuria can be heavy/nephrotic and is the dominant renal signal
Check serum creatinine/eGFR before starting and periodically; an unexpected rise should prompt evaluation rather than a level-driven dose increase
Screen for thrombotic microangiopathy when creatinine rises with new anemia or thrombocytopenia — order CBC with smear (schistocytes), LDH, and haptoglobin, especially in combination with calcineurin inhibitors or VEGF-pathway agents
Monitor sirolimus/everolimus trough levels in transplant recipients to keep exposure in target range and limit dose-dependent glomerular injury
Reassess proteinuria and renal function after any dose change or after switching from a calcineurin inhibitor, since de novo or worsening proteinuria often emerges after conversion

Key trials & series

ZEUS — early conversion from cyclosporine to everolimus after kidney transplant improved measured GFR at 12 months, but the everolimus arm showed more proteinuria, illustrating the trade-off between escaping CNI nephrotoxicity and incurring mTOR-inhibitor glomerular effects.
RECORD-1 — registrational placebo-controlled phase 3 of everolimus in VEGF-refractory metastatic RCC; established efficacy and characterized the class adverse-event profile including proteinuria.
Global ARCC trial (Hudes et al.) — temsirolimus vs interferon-alfa in poor-prognosis advanced RCC, the registrational study for temsirolimus that defined its tolerability/toxicity profile.
Sirolimus conversion/de novo series in kidney transplantation — multiple cohorts linked sirolimus to new-onset or worsening proteinuria and biopsy-proven FSGS-pattern podocyte injury, anchoring the mechanistic glomerular signal of the class.

Clinical pearls

The dominant renal toxicity is proteinuria from podocyte injury (FSGS-pattern), not a filtration/clearance problem — so the class is generally mild and reversible, and management is dose reduction or withdrawal, not renal dose-capping.
Proteinuria is frequently unmasked or worsened when patients are converted from a calcineurin inhibitor to an mTOR inhibitor, a classic transplant scenario — check a baseline UPCR before and after conversion.
mTOR inhibitors can also impair tubular recovery and have been associated with delayed graft function and acute tubular injury, so they are usually avoided early post-transplant while tubules are healing.
Thrombotic microangiopathy is an uncommon but serious class effect, with risk amplified by concurrent calcineurin inhibitors or VEGF-pathway agents — keep it on the differential for any creatinine rise plus cytopenias.

Beyond the kidney — non-renal toxicities· 4 organ systems

Class-level context for the major non-renal toxicities of the mTOR inhibitor class.

Pulmonary

Pneumonitis, ILD, effusions, hypertension

Non-infectious pneumonitis

Endocrine

Thyroiditis, hypophysitis, diabetes

Hyperglycemia, hyperlipidemia

Gastrointestinal

Diarrhea, colitis, mucositis, perforation

Stomatitis

Immune / Infusion

CRS, infusion reactions, irAEs, anaphylaxis

Immunosuppression / infection

§05

References

5 primary references — trials, cohorts, mechanism, and reviews. Single-patient case reports are listed separately below, graded by strength. Citation metadata via PubMed / NLM.

Evidence accrual

5 references · 2008–2019 · 1 since 2017

Primary (non–case-report) references per year — a proxy for how actively the agent's renal literature is accruing. Recent years are highlighted. Reflects curation depth, not a systematic bibliometric count.

Case reports — ranked by strength· 3

Single-patient and small-series reports, graded by evidentiary strength — A Strong (biopsy-proven plus a series and/or positive rechallenge), B Moderate, and C Limited (a single clinically-diagnosed case). Strongest first. Grades are inferred automatically from each report's abstract and journal — a heuristic ranking aid, not a formal quality appraisal.

CaseB · ModerateTemsirolimus-induced glomerulopathy.Izzedine H et al. · Oncology 2009 · PMID 19212144A man with renal cell carcinoma developed grade 3 nephrotic-range proteinuria (8.5 g/24h) with biopsy-proven focal segmental glomerulosclerosis five days after temsirolimus, reversing on withdrawal.CaseB · ModerateThrombotic microangiopathy in marginal kidneys after sirolimus use.Pellé G et al. · Am J Kidney Dis 2005 · PMID 16310579Three recipients of marginal donor kidneys developed de novo biopsy-proven renal thrombotic microangiopathy on sirolimus without prior calcineurin inhibitor exposure.CaseC · LimitedEverolimus worsening chronic proteinuria in patient with diabetic nephropathy post liver transplantation.Hanna RM et al. · Saudi J Kidney Dis Transpl 2019 · PMID 31464262Everolimus markedly worsened proteinuria (0.46 to 2.2 g/g) in a liver transplant patient with diabetic glomerulosclerosis, with improvement after drug discontinuation, illustrating mTOR-inhibitor podocyte/glomerular injury.

Guidelines & consensus· 13

Each recommendation below is this atlas's faithful summary of the source, not a quotation from it — follow the PubMed link for the wording the society published. Summaries may be superseded; consult the current full text and individualize to the patient.

General onco-nephrology references

ADQIThe nephrotoxic effects of anti-cancer therapies: consensus report of the 34th Acute Disease Quality Initiative workgroupNat Rev Nephrol 2026 · PMID 41361704Provides 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.SIRMSIRM-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)Radiol Med 2022 · PMID 35303246Recommends 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.KDIGOKDIGO Controversies Conference on onco-nephrology: understanding kidney impairment and solid-organ malignancies, and managing kidney cancerKidney Int 2020 · PMID 33126977Identifies 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.KDIGOKDIGO Controversies Conference on onco-nephrology: kidney disease in hematological malignancies and the burden of cancer after kidney transplantationKidney Int 2020 · PMID 33276867Addresses 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.ADDIKDIntegrating International Consensus Guidelines for Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD) into everyday practiceEClinicalMedicine 2025 · PMID 40290844Provides 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.ADDIKDAligning kidney function assessment in patients with cancer to global practices in internal medicineEClinicalMedicine 2025 · PMID 40290845Three 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.ADDIKDA methodology for determining dosing recommendations for anticancer drugs in patients with reduced kidney functionEClinicalMedicine 2025 · PMID 40290846Establishes 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.KDIGODiagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (Part 1)Crit Care 2013 · PMID 23394211Defines/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.KDIGOExecutive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknownsKidney Int 2024 · PMID 38519239Evaluate and risk-stratify CKD, manage to delay progression and its complications, and practise explicit medication management and drug stewardship — the framework the atlas's G1–G5 eGFR banding and every renal dose-adjustment recommendation sit inside. Because the guideline excludes dialysis and transplant recipients by its own statement of scope, its recommendations do not carry to those settings, where this atlas's dialyzability and post-transplant guidance rests on other sources.KDIGOExecutive summary of the KDIGO 2021 Guideline for the Management of Glomerular DiseasesKidney Int 2021 · PMID 34556300Provides 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.KDIGOExecutive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of ANCA-Associated VasculitisKidney Int 2024 · PMID 38388147Updates 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.KDIGOExecutive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of Lupus NephritisKidney Int 2024 · PMID 38182299Updates 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.KDIGOExecutive summary of the KDIGO 2025 Clinical Practice Guideline for the Management of Immunoglobulin A Nephropathy (IgAN) and Immunoglobulin A Vasculitis (IgAV)Kidney Int 2025 · PMID 40975525Encourages 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.

Where mTOR Inhibitors sits in nephrotoxicity space — each dot is an anti-cancer agent, positioned so neighbors share a kidney-injury phenotype. Its 6 closest are filled and lead to a numbered marker, matching the numbered cards below.

Position is a 2-D projection (MDS) of each agent's injury signature, nephron target, severity, and class, so two dots can sit close on the page while differing on an axis the projection flattened — the numbered ranking is computed from the full metric, not from the distance you see. Open the full map.

Phenotype-similar agents· the numbered markers on the map above

Sirolimus

Rapamune · mTOR inhibitor

Profile

Proteinuria, cast nephropathy, delayed graft recovery.

GLOMATN

Moderate#1 · 79% phenotype match

Erlotinib

Tarceva · EGFR TKI

Profile

Rare minimal-change disease and AKI.

GLOMATNPRE

Mild#2 · 77% phenotype match

Temsirolimus

Torisel · mTOR inhibitor

Profile

Proteinuria and glomerular effects; less firmly quantified than everolimus.

GLOMLYTE

Mild#3 · 62% phenotype match

Everolimus

Afinitor · mTOR inhibitor

Profile

Podocyte injury with proteinuria/FSGS; occasional thrombotic microangiopathy.

GLOMTMALYTE

Moderate#4 · 61% phenotype match

Oxaliplatin

Eloxatin · Platinum agent

Profile

Least nephrotoxic platinum; rare immune hemolysis.

TMAATN

Mild#5 · 58% phenotype match

Ibandronate

Boniva · Bisphosphonate

Profile

Lower renal risk than zoledronate.

ATNLYTEGLOM

Mild#6 · 54% phenotype match

Compare mTOR Inhibitors with its nearest agents

Nearest agents by kidney-injury phenotype (shared injuries, nephron target, severity, class) — a similarity approximation, not a claim of shared drug identity or mechanism.

Kidney risk across mTOR inhibitors

Same-class agents ordered by their documented kidney-injury profile — atlas severity, an acute-kidney-injury FAERS signal, and how many injury types each is documented to cause. Agents nearer the top carry the lighter documented renal profile.

1TemsirolimusGLOM — Glomerular Injury / ProteinuriaMild
2mTOR Inhibitors· this agentGLOM — Glomerular Injury / ProteinuriaMild
3SirolimusGLOM — Glomerular Injury / ProteinuriaFAERS AKIModerate
4EverolimusGLOM — Glomerular Injury / ProteinuriaFAERS AKIModerate

A comparison of documented kidney-injury data within one drug class — not a substitution recommendation. Efficacy, indication, and non-renal toxicity differ between these agents and are out of scope here. Educational only, not medical advice.

Who studies this

The leading contributors to mTOR Inhibitors’s clinical kidney literature on PubMed, ranked by a blend of publication volume and citation impact — filtered toward clinical work via the PubMed Humans heading and clinical publication types (trials, cohorts, case reports, guidelines, reviews). Names link to that author’s work on mTOR Inhibitors; the PMIDs beside each name are up to three of their most recent papers on it, not the full count.

Ranked by a 50/50 blend of publication volume and a position-weighted, capped Relative Citation Ratio (NIH iCite) on this agent’s renal literature; the citation count shown is the raw total, not the ranking score — counted over the 171 clinical records among all 245 PubMed matches, so counts are within-sample — bibliometric context, not an endorsement or a measure of clinical authority.