How should kidney function be monitored during Pentostatin therapy?

CBC (myelosuppression) and LFTs; Urate/electrolytes (tumor-lysis screen); Infection surveillance (durable CD4 lymphopenia — PJP, CMV).

How can kidney injury from Pentostatin be prevented?

CrCl-based dosing using measured renal function Tumor-lysis prophylaxis in bulky disease Do not combine with fludarabine (severe/fatal pulmonary toxicity)

Who is at higher risk of kidney injury from Pentostatin?

Pre-existing renal impairment; High-dose schedules and overestimated GFR (Cockcroft-Gault) in the critically ill; Volume depletion and concurrent nephrotoxins; High tumor burden.

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Printable monograph

Purine analog (ADA inhibitor)

Pentostatin

Nipent · PENT

Purine analog (ADA inhibitor) · approved 1991 · 11 citations

Dated evidence· through 2013

Fairly sourced6/9 · 5 signals

Met: 11 citations
Not met: 12+ references
Met: Accrued over 10+ years (span: 29y)
Met: Beyond single case reports
Met: High-impact journal
Met: Landmark reference
Not met: Current through 2013
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.

A renally cleared, dialyzable ADA inhibitor with dose-related AKI — dose strictly by measured CrCl.

ModeratePurine analog (ADA inhibitor)

Alpha-interferon-refractory hairy-cell leukemiaOff-label: chronic lymphocytic leukemia, cutaneous/peripheral T-cell lymphoma, graft-versus-host disease

§01

Signature kidney injury

Signature lesion

Acute Tubular Necrosis

At modern low doses clinically significant nephrotoxicity is uncommon and a precise contemporary incidence is not quantified; serious dose-related AKI was historically tied to higher-dose regimens. Tumor lysis can add a secondary AKI mechanism in bulky disease.Source: Grever et al., J Clin Oncol 1995

Onset & rechallenge

Time to injuryVariable / unpredictable

Occurs during or after dosing cycles and is generally reversible with dose reduction or discontinuation.

Distilled from: “During or after dosing cycles; generally reversible with dose reduction or discontinuation.”

§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.

Acute Tubular Necrosis#1 · Signatureno population incidence denominator
Dose-related acute renal failure reported; high-dose regimens historically nephrotoxic PMID 11219485 (opens PubMed in a new tab)
Electrolyte DisturbanceSecondaryqualitative — no citable incidence
Renal electrolyte derangement — magnesium/potassium/calcium wasting (cisplatin, anti-EGFR antibodies) or retention (FGFR-inhibitor hyperphosphatemia, tumor-lysis hyperkalemia/hyperphosphatemia).
SIADH / HyponatremiaRarequalitative — no citable incidence
A single case report of mixed SIADH/extrarenal sodium loss after first-cycle monotherapy.

Toxicity fingerprint

Tap a signature to trace where it strikes the nephron.

Incidence not quantified

SeverityModerate

ReversibilityReversible

Evidence11 citations

Nephron map

Proximal TubuleBulk reabsorption + drug uptake (OCT2, OATs)

Distal Tubule / Collecting DuctFine-tuning of Na, K, Mg, acid & water

Acute Tubular Necrosis

Direct death of tubular epithelial cells — the dose-limiting lesion of the platinums and zoledronate.

§03

Kidney injury

Mechanism of kidney injury

Pentostatin is renally cleared and can cause dose-related intrinsic tubular nephrotoxicity and acute renal failure; the precise segment-level human histology is not well characterized but a proximal-tubular ATN pattern is described. Overexposure (from inadequate renal dose reduction) is the main driver, with tumor lysis a secondary contributor.

Clinical presentation

A rising creatinine and uremia, dose-related, emerging during dosing cycles (every 1-2 weeks); watch for concurrent tumor-lysis derangements. Profound, durable T-cell/CD4 lymphopenia predisposes to opportunistic infection.

Management

Hold or reduce the dose for a rising creatinine; provide supportive care and hydration. In ESKD, deliberate post-infusion hemodialysis has been used to limit exposure. Manage tumor lysis with standard measures.Lesion-level management framework

Risk factors

Pre-existing renal impairment
High-dose schedules and overestimated GFR (Cockcroft-Gault) in the critically ill
Volume depletion and concurrent nephrotoxins
High tumor burden

Prevention

CrCl-based dosing using measured renal function
Tumor-lysis prophylaxis in bulky disease
Do not combine with fludarabine (severe/fatal pulmonary toxicity)

Anticancer mechanism· how it treats cancer

Tight-binding, essentially irreversible adenosine deaminase (ADA) inhibitor. ADA blockade causes intracellular accumulation of (deoxy)adenosine and dATP, which inhibits ribonucleotide reductase, depletes the dNTP pool, and blocks DNA synthesis and repair while depleting ATP — lymphotoxic to dividing and resting lymphocytes (especially T cells).

Note · Established (1991) agent; modern low-dose nephrotoxicity is uncommon and not quantified, while CrCl-based dosing and dialyzability are well documented.

§04

Clinical depth

Renal dose adjustment

Renally adjusted: CrCl >60 mL/min ~4 mg/m2 every 14 days (standard); CrCl 41-60 ~3 mg/m2; CrCl 21-40 ~2 mg/m2; CrCl <20-30/severe generally avoid (insufficient data). Even these reductions may overexpose critically ill patients (Cockcroft-Gault overestimates function) — interpret cautiously.

Dialyzability & ESKD dosing

Dialyzable — deliberate post-infusion hemodialysis has been used to limit exposure and permit cautious dosing in ESKD.

Differential diagnosis

Tumor-lysis AKI, prerenal states, concurrent nephrotoxins, combination-therapy toxicity, leukemic infiltration and sepsis-related ATN — versus dose-related intrinsic pentostatin nephrotoxicity from overexposure.

Monitoring

CBC (myelosuppression) and LFTs
Urate/electrolytes (tumor-lysis screen)
Infection surveillance (durable CD4 lymphopenia — PJP, CMV)

Key trials & series

Grever NCI intergroup RCT (J Clin Oncol 1995) — pentostatin superior to interferon in HCL
Lathia renal PK study (Cancer Chemother Pharmacol 2002) — CrCl-stratified dose reductions

Clinical pearls

Dose strictly by measured CrCl — Cockcroft-Gault overestimates function in the critically ill and leads to overexposure.
Pentostatin is dialyzable — deliberate post-infusion hemodialysis allows cautious use in ESKD.
Do not combine with fludarabine (severe/fatal pulmonary toxicity); avoid high-dose regimens.
Profound durable T-cell depletion mandates PJP/CMV vigilance beyond the dosing period.
A single case report describes life-threatening hyponatremia (mixed SIADH and extrarenal sodium loss) after first-cycle pentostatin monotherapy; the authors hedge the attribution as 'possible'.

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

Class-level context for the major non-renal toxicities of the Purine analog (ADA inhibitor) 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

8 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

8 references · 1989–2013 · 1 since 2011

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.

CaseC · LimitedIntraglomerular thrombosis with deoxycoformycin--reversible acute renal failure.Harris DC et al. · Clin Nephrol 1984 · PMID 6608428Case report of reversible acute renal failure with intraglomerular thrombosis attributed to deoxycoformycin (pentostatin).CaseC · LimitedThrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) following treatment with deoxycoformycin in a patient with cutaneous T-cell lymphoma (Sezary syndrome): A case report.Leach JW et al. · Am J Hematol 1999 · PMID 10440915Pentostatin-induced TTP-HUS with oliguric acute renal failure requiring hemodialysis, suggesting dose-dependent renal toxicity.CaseC · LimitedHemolytic-uremic syndrome due to deoxycoformycin: a report of the second case.Sakai C et al. · Intern Med 1995 · PMID 7549151Fatal hemolytic-uremic syndrome with renal failure and glomerular damage (endothelial swelling, mesangiolysis) on kidney necropsy after pentostatin.

FDA label — boxed warning & renal dosing· boxed warning

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

Boxed warning

WARNING NIPENT should be administered under the supervision of a physician qualified and experienced in the use of cancer chemotherapeutic agents. The use of higher doses than those specified (see DOSAGE AND ADMINISTRATION ) is not recommended. Dose-limiting severe renal, liver, pulmonary, and CNS toxicities occurred in Phase 1 studies that used NIPENT at higher doses (20-50 mg/m 2 in divided doses over 5 days) than recommended. In a clinical investigation in patients with refractory chronic lymphocytic leukemia using NIPENT at the recommended dose in combination with fludarabine phosphate, 4 of 6 patients entered in the study had severe or fatal pulmonary toxicity. The use of NIPENT in combination with fludarabine phosphate is not recommended.

What gets reported — FAERS

Everything below is FAERS — adverse events someone chose to report, about 1,048 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· 5 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

SIADH / Hyponatremiacorroborated · ROR 6.34 — on the terms that name the lesion (ROR 5.91)
Electrolyte Disturbancecorroborated · ROR 3.2 — but the naming terms alone are not disproportionate, so this rests on terms merely consistent with the lesion
Acute Tubular NecrosisNot measurable in reporting — Reporters cannot reliably name this lesion, so its absence from FAERS is expected and is not evidence against the documented injury.

Thrombotic Microangiopathy

ROR 39.9695% CI 27.78–57.47· 30 reports

Hemorrhagic Cystitis

ROR 11.6695% CI 8.47–16.06· 39 reports

SIADH / Hyponatremia

ROR 6.3495% CI 4.26–9.43· 25 reports

Glomerular Injury / Proteinuria

ROR 5.5495% CI 2.76–11.10· 8 reports

Electrolyte Disturbance

ROR 3.2095% CI 2.23–4.61· 30 reports

FAERS outcomes & reporting trend· 24.3% of reports w/ death · 40.9% w/ hospitalization

24.3%

Reported with a death outcome

255 of 1,048 reports

40.9%

Reported with hospitalization

429 of 1,048 reports

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 8 systems · 1,048 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 1.1895% CI 0.61–2.28· 9 AKI reports ·no disproportionate AKI reporting signal (CI spans 1).

Renal & urinary

Renal Failure47

Blood & lymphatic

Neutropenia76Anaemia54Thrombocytopenia54Febrile Neutropenia47Neutrophil Count Decreased42

General / constitutional

Pyrexia74Fatigue45Chills38Asthenia31

Gastrointestinal

Diarrhoea62Nausea55Vomiting37

Immune / infection

Pneumonia58Sepsis57Bk Virus Infection32

Respiratory

Dyspnoea71Cough33Pleural Effusion27

Metabolic & electrolyte

Dehydration31Tumour Lysis Syndrome30

Vascular

Hypotension47

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 Pentostatin 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

Pemetrexed

Alimta · Antifolate

Profile

Cumulative chronic tubulointerstitial injury; RTA and nephrogenic DI.

CINATNLYTE

Moderate#1 · 76% phenotype match

Nedaplatin

Aqupla · Platinum agent

Profile

Second-gen platinum with reduced renal toxicity vs cisplatin.

ATNLYTE

Moderate#2 · 73% phenotype match

Carboplatin

Paraplatin · Platinum agent

Profile

Kidney-sparing; GFR-dosed by the Calvert formula.

ATNLYTECYST

Mild#3 · 71% phenotype match

Azacitidine

Vidaza · Hypomethylating agent

Profile

Proximal (type 2) RTA / Fanconi-like tubulopathy; overt AKI uncommon.

FANCATNLYTE

Moderate#4 · 71% phenotype match

Melphalan flufenamide (melflufen)

Pepaxto · Peptide-conjugated alkylator

Profile

Delivers melphalan intracellularly; BRIDGE supports a reduced 30 mg dose in moderate renal impairment.

ATNLYTE

Moderate#5 · 70% phenotype match

Telisotuzumab vedotin (Teliso-V)

Emrelis · c-Met ADC (MMAE)

Profile

c-Met MMAE antibody-drug conjugate; proximal tubular ATN risk extrapolated from the ADC/MMAE class.

ATNLYTE

Moderate#6 · 70% phenotype match

Compare Pentostatin 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.