What kind of kidney injury does Capecitabine cause?

Prerenal / Hemodynamic AKI — Renal hypoperfusion from capillary leak and cytokine storm — IL-2 and CAR-T cytokine release syndrome. Other reported patterns: Thrombotic Microangiopathy.

Is kidney injury from Capecitabine reversible?

Reversible. Typical onset: Acute, during cycles with GI toxicity; TMA delayed and rare..

How should kidney function be monitored during Capecitabine therapy?

Serum creatinine/CrCl at baseline and across cycles (drives dosing); Diarrhea grade and volume status each cycle; CBC, LDH/haptoglobin if TMA suspected; DPYD status where available.

How can kidney injury from Capecitabine be prevented?

Dose by creatinine clearance per labeling (75% dose for CrCl 30-50); avoid if CrCl <30 Early aggressive management of diarrhea and hydration Consider DPYD genotyping before starting capecitabine

Who is at higher risk of kidney injury from Capecitabine?

Reduced creatinine clearance (dose-adjust; avoid below CrCl 30 unless no alternative); Severe diarrhea/dehydration; Older age and DPD (DPYD) deficiency; Concurrent mitomycin (TMA risk).

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Printable monograph

Pyrimidine analog (oral 5-FU)

Capecitabine

Xeloda · Cape

Pyrimidine analog (oral 5-FU) · approved 1998 · 9 citations

Up to date· through 2025

Deeply sourced7/9 · 6 signals

Met: 9 citations
Not met: 12+ references
Met: Accrued over 10+ years (span: 24y)
Met: Beyond single case reports
Met: High-impact journal
Met: Landmark reference
Met: Current through 2025
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.

Oral 5-FU whose diarrhea, more than any tubular toxin, is what dents the kidney.

MildFluoropyrimidine antimetabolite (oral)

Colorectal cancerBreast cancerGastric/gastroesophageal cancer

§01

Signature kidney injury

Signature lesion

Prerenal / Hemodynamic AKI

Intrinsic nephrotoxicity is uncommon; the main renal issue is prerenal AKI from drug-induced diarrhea and volume depletion. Renal impairment increases toxicity - in the PK study, all patients with severe impairment (CrCl <30) had grade 3-4 adverse events - so labeling mandates dose adjustment by creatinine clearance and, below CrCl 30, establishes no dose (avoid unless no alternative).Source: Poole et al., Cancer Chemother Pharmacol 2002

Onset & rechallenge

Time to injuryAcute (~1–7 days)

Acute AKI during cycles with GI toxicity; TMA is delayed and rare.

Distilled from: “Acute, during cycles with GI toxicity; TMA delayed and rare.”

§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.

Prerenal / Hemodynamic AKI#1 · Signaturequalitative — no citable incidence
Renal hypoperfusion from capillary leak and cytokine storm — IL-2 and CAR-T cytokine release syndrome.
Thrombotic MicroangiopathyRarequalitative — no citable incidence
Endothelial injury with microvascular thrombi, hemolysis and thrombocytopenia — gemcitabine, mitomycin C, anti-VEGF.

§03

Kidney injury

Mechanism of kidney injury

Severe diarrhea, nausea and reduced intake cause volume depletion and prerenal azotemia; because the 5-FU catabolites are renally cleared, impaired kidney function increases systemic exposure and toxicity (the basis for CrCl-based dosing). Rare thrombotic microangiopathy/HUS can occur as with other fluoropyrimidines, particularly in mitomycin-containing or high-risk settings, and is occasionally managed with complement blockade. DPD (DPYD) deficiency markedly increases systemic toxicity.

Clinical presentation

Prerenal azotemia (elevated BUN:creatinine, low urine sodium) in the setting of diarrhea/dehydration; enhanced systemic toxicity (hand-foot syndrome, mucositis, cytopenias) when clearance is reduced. Rarely, microangiopathic hemolysis with thrombocytopenia and AKI.

Management

Hold drug and rehydrate for prerenal AKI and significant diarrhea; correct electrolytes and resume at an adjusted dose. For rare TMA, discontinue and provide supportive/complement-directed care. Prerenal injury reverses with volume restoration.Lesion-level management framework

Risk factors

Reduced creatinine clearance (dose-adjust; avoid below CrCl 30 unless no alternative)
Severe diarrhea/dehydration
Older age and DPD (DPYD) deficiency
Concurrent mitomycin (TMA risk)

Prevention

Dose by creatinine clearance per labeling (75% dose for CrCl 30-50); avoid if CrCl <30
Early aggressive management of diarrhea and hydration
Consider DPYD genotyping before starting capecitabine

Anticancer mechanism· how it treats cancer

Oral fluoropyrimidine prodrug converted in three enzymatic steps (carboxylesterase, cytidine deaminase, then tumor-enriched thymidine phosphorylase) to 5-fluorouracil, inhibiting thymidylate synthase. Used in colorectal, breast and gastric/gastroesophageal cancers.

Note · Renal dosing matters chiefly because reduced clearance amplifies systemic toxicity; direct tubular nephrotoxicity is not characteristic.

§04

Clinical depth

Renal dose adjustment

Per labeling/PK data: no adjustment for mild impairment (CrCl 51-80); reduce to 75% of starting dose for moderate impairment (CrCl 30-50). Below CrCl 30 the current XELODA label does NOT contraindicate - section 4 lists only severe hypersensitivity to fluorouracil or capecitabine - but states that experience is limited and a dosage has not been established, permitting administration on an individual basis if no treatment alternative exists, at a reduced starting dose with close clinical and biochemical monitoring. Treat that band as avoid-unless-no-alternative rather than an absolute bar: every patient with severe impairment in the PK study experienced grade 3-4 toxicity, and legacy pre-PLR generic labels still carry an outright CrCl <30 contraindication.

Dialyzability & ESKD dosing

Capecitabine and 5-FU have short half-lives and are not managed by dialysis; the renally cleared catabolites (e.g., fluoro-beta-alanine) accumulate in renal failure, which is why severe impairment is avoided rather than dialysis-supported - no dialysis dosing has been established.

Differential diagnosis

Prerenal azotemia from diarrhea (low FeNa, volume-responsive, BUN:Cr elevated) is the usual picture; distinguish from rare fluoropyrimidine TMA (microangiopathic hemolysis, thrombocytopenia) and from amplified systemic toxicity due to unrecognized renal impairment or DPD deficiency. Pseudo-AKI is not the issue here - it is real volume-driven prerenal injury.

Monitoring

Serum creatinine/CrCl at baseline and across cycles (drives dosing)
Diarrhea grade and volume status each cycle
CBC, LDH/haptoglobin if TMA suspected; DPYD status where available

Key trials & series

Poole Cancer Chemother Pharmacol 2002 - the renal-impairment PK study underpinning CrCl-based dosing and the <30 contraindication
Cassidy Ann Oncol 2002 - phase III safety supporting higher toxicity at CrCl 30-50
Henricks Lancet Oncol 2018 - DPYD genotype-guided dosing safety

Clinical pearls

The kidney lever for capecitabine is dosing, not toxicity surveillance: 75% dose at CrCl 30-50 and do not use below 30.
Most capecitabine AKI is prerenal from diarrhea - hydrate, hold, and it reverses.
Unexpectedly severe hand-foot syndrome/mucositis/cytopenias should prompt checks for occult renal impairment or DPD deficiency.

Where it strikes· nephron segments & injury signatures

Nephron segments

Vasculature / Endothelium

Glomerular & peritubular capillaries

Injury signatures

Prerenal / Hemodynamic AKI Thrombotic Microangiopathy

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

Class-level context for the major non-renal toxicities of the Pyrimidine analog (oral 5-FU) class.

Gastrointestinal

Diarrhea, colitis, mucositis, perforation

Mucositis and diarrhea

Hepatic / Liver

Transaminitis, hepatitis, VOD/SOS

Transaminitis (methotrexate)

Hematologic

Cytopenias, thrombosis, TMA

Myelosuppression

Pulmonary

Pneumonitis, ILD, effusions, hypertension

Methotrexate / gemcitabine pneumonitis

§05

References

7 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

7 references · 2001–2025 · 1 since 2023

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· 2

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 · ModerateCapecitabine-Related Thrombotic Microangiopathy.Mateo FJP et al. · J Gastrointest Cancer 2024 · PMID 38175385Biopsy-proven thrombotic microangiopathy with acute renal impairment attributed to capecitabine in an 82-year-old woman, reported as the first such case in the literature.CaseC · LimitedCapecitabine-induced severe diabetes and hypokalemia: a case report.Yang Q et al. · J Med Case Rep 2022 · PMID 35462530Severe hypokalemia (serum potassium 2.5 mmol/L) and glucose intolerance during long-term capecitabine therapy, resolving after drug discontinuation, illustrating a rare electrolyte disturbance.

FDA label — boxed warning & renal dosing· boxed warning · renal impairment

Quoted verbatim from this agent's current FDA label (Jul 2026) — not paraphrased or interpreted. Full label on DailyMed .

Boxed warning

WARNING: INCREASED RISK OF BLEEDING WITH CONCOMITANT USE OF VITAMIN K ANTAGONISTS Altered coagulation parameters and/or bleeding, including death, have been reported in patients taking capecitabine concomitantly with oral vitamin K antagonists, such as warfarin [see Warnings and Precautions (5.1) , Drug Interactions (7.2) ]. Clinically significant increases in prothrombin time (PT) and international normalized ratio (INR) have been reported in patients who were on stable doses of a vitamin K antagonist at the time capecitabine was introduced. These events occurred within several days and up to several months after initiating capecitabine and, in a few cases, within 1 month after stopping capecitabine. These events occurred in patients with and without liver metastases. Monitor INR more frequently and adjust the dose of the vitamin K antagonist as appropriate [see Drug Interactions (7.2) ]. WARNING: INCREASED RISK OF BLEEDING WITH CONCOMITANT USE OF VITAMIN K ANTAGONISTS See full prescribing information for complete boxed warning. Altered coagulation parameters and/or bleeding, including death, have been reported in patients taking capecitabine concomitantly with oral vitamin K antagonists. ( 5.1 , 7.2 ) Monitor international normalized ratio (INR) more frequently and adjust the dose of the vitamin K antagonist as appropriate. ( 7.2 )

Renal impairment — from the label

The exposure of capecitabine and its inactive metabolites (5-DFUR and FBAL) increases in patients with CLcr <50 mL/min as determined by Cockcroft-Gault [see Clinical Pharmacology (12.3) ]. Reduce the dosage for patients with CLcr of 30 to 50 mL/min [see Dosage and Administration (2.6) ]. There is limited experience with capecitabine in patients with CLcr <30 mL/min, and a dosage has not been established in those patients. If no treatment alternative exists, capecitabine could be administered to such patients on an individual basis applying a reduced starting dose, close monitoring of a patient's clinical and biochemical data and dose modifications guided by observed adverse reactions.

What gets reported — FAERS

Everything below is FAERS — adverse events someone chose to report, about 90,989 of them for this agent. Nobody counts the patients who were fine, so none of these numbers is an incidence, a risk, or a rate: they describe what gets reported, shaped by a drug's fame, its indication, and who was watching. How these numbers work.

Reporting odds ratio (ROR) — is kidney injury named in this agent's reports more often than in every other drug's? Above 1 means yes, disproportionately.
Renal phenotypes — the same question asked separately for each kind of kidney injury, so the ratios differ from the overall one and from each other.
Outcomes — a share of this agent's own reports, not of patients: how many were filed as involving a death or a hospitalization. Not a case-fatality rate.

FAERS reported renal phenotypes· 6 signals

Only significant signals appear (95% CI lower bound above 1) — a phenotype missing here was tested and did not reach significance, except Prerenal / Hemodynamic AKI, Pseudo-AKI, Renal Cysts, Chronic Interstitial Nephropathy — outside the clinician-reviewed MedDRA term map, never queried — and ATN and AIN, queried but biopsy-bound: real cases are filed as generic “acute kidney injury”, so their absence is not a negative. As of 2026-10-01.

What reporting says about this profile's documented lesions

Thrombotic Microangiopathycorroborated · ROR 2.46
Prerenal / Hemodynamic AKINot queried in FAERS — No MedDRA term set is defined for this phenotype, so FAERS was never asked about it.

Glomerular Injury / Proteinuria

ROR 3.6595% CI 3.33–4.01· 454 reports

Electrolyte Disturbance

ROR 2.6795% CI 2.56–2.79· 2,167 reports

Thrombotic Microangiopathy

ROR 2.4695% CI 2.11–2.87· 164 reports

SIADH / Hyponatremia

ROR 1.8795% CI 1.73–2.02· 650 reports

Hemorrhagic Cystitis

ROR 1.2195% CI 1.09–1.34· 364 reports

Crystal / Obstructive Nephropathy

ROR 1.1495% CI 1.01–1.29· 276 reports

FAERS outcomes & reporting trend· 20.1% of reports w/ death · 31.7% w/ hospitalization

20.1%

Reported with a death outcome

18,289 of 90,989 reports

31.7%

Reported with hospitalization

28,845 of 90,989 reports

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 7 systems · 90,989 reports

Bars rank systems by summed reaction-term mentions (a report counts once per term it names) — an ordinal “more vs less reported” cue, not a tally of distinct reports. Renal & urinary first. As of 2026-10-01.

Disproportionality (acute kidney injury):ROR 1.0295% CI 0.95–1.10· 677 AKI reports ·no disproportionate AKI reporting signal (CI spans 1).

Gastrointestinal

Diarrhoea13,623Nausea8,454Vomiting6,280Abdominal Pain2,266Stomatitis2,102

General / constitutional

Fatigue6,477Asthenia3,414Pyrexia2,460Pain2,194Weight Decreased2,043

Skin

Palmar-Plantar Erythrodysaesthesia Syndrome6,675Rash2,261

Blood & lymphatic

Neutropenia3,112Thrombocytopenia2,513Anaemia2,380

Metabolic & electrolyte

Decreased Appetite3,269Dehydration2,753

Nervous system

Neuropathy Peripheral2,897

Respiratory

Dyspnoea2,671

Guidelines & consensus· 14

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.

ADQIConventional cytotoxic chemotherapy-associated nephrotoxicity: consensus report of the 34th Acute Disease Quality Initiative (ADQI) WorkgroupKidney Int 2026 · PMID 41881107Cisplatin is identified as a leading cytotoxic nephrotoxin; the workgroup details preventive measures (adequate isotonic hydration, correction of volume depletion, avoidance of concurrent nephrotoxins, attention to electrolyte/magnesium wasting) and management of cisplatin-associated AKI, with a research agenda for knowledge gaps.

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 Capecitabine 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

5-Fluorouracil

Adrucil · Pyrimidine analog

Profile

Rare TMA, esp. with mitomycin; mostly renally safe.

TMAPRE

Mild#1 · 100% phenotype match

Docetaxel

Taxotere · Taxane

Profile

Fluid retention; low direct renal toxicity.

PRECYSTTMA

Mild#2 · 73% phenotype match

Ruxolitinib

Jakafi · JAK1/2 inhibitor

Profile

Tumor lysis in myelofibrosis; renally adjusted.

PRELYTETMA

Mild#3 · 71% phenotype match

Trifluridine/tipiracil

Lonsurf · Oral fluoropyrimidine + TP inhibitor

Profile

Tipiracil is renally cleared; reduced GFR raises exposure and early severe neutropenia; dose-reduce in renal impairment.

PRE

Moderate#4 · 68% phenotype match

Ponatinib

Iclusig · BCR-ABL TKI

Profile

Vascular toxicity and hypertension.

HTNPRETMA

Moderate#5 · 68% phenotype match

Doxifluridine

Furtulon · Antimetabolite (oral 5-FU prodrug)

Profile

5'-DFUR prodrug; class-level TMA risk plus a real renal-clearance component warranting caution in renal impairment.

TMALYTEPRE

Moderate#6 · 67% phenotype match

Compare Capecitabine 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 Antimetabolites

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.

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 Capecitabine’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 Capecitabine; 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 76 clinical records among all 99 PubMed matches, so counts are within-sample — bibliometric context, not an endorsement or a measure of clinical authority.