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Case Report: PRaG 3.0 therapy for advanced cervical cancer with severe comorbidities
The Injury Atlas
CYST

Hemorrhagic Cystitis

Bleeding inflammation of the bladder urothelium — classically acrolein injury from the oxazaphosphorines (prevented by mesna), but also reported as immune-related, intravesical-chemical, or radiation-recall injury.

15agents

Where it strikes

Bladder / Urothelium

Urine storage (outflow, not a nephron segment)

See it on the nephron

Agents’ overall severity

Each agent’s whole-drug severity grade, not the severity of this lesion specifically — an agent whose signature injury is elsewhere can still be graded severe here.

Severe· 4Moderate· 2Mild· 9

Agents’ overall reversibility

Often irreversible· 2Partially reversible· 3Variable· 2Reversible· 8
Does the kidney recover? Cross-drug outcomes

Agents’ onset window

How soon each agent’s kidney toxicity typically appears — a whole-drug tempo, not specific to this lesion.

Hyperacute (<24 h)· 2Acute (days)· 3Subacute (weeks)· 2Delayed (weeks–months)· 5Variable· 3

Real-world reporting for this lesion

FAERS across all lesions →

Agents with a disproportionate FAERS reporting signal for hemorrhagic cystitis (reporting odds ratio with a 95% CI lower bound above 1) — a spontaneous-reporting signal, not incidence or proven causation. FAERS carries reporting and indication biases and has no denominator.

15Corroborated

Documented in the atlas profile and carrying a FAERS signal — the strongest claim the atlas makes.

0Documented, FAERS-silent

Documented in a profile with no reporting signal. Mostly expected: naming this lesion on a report can require a biopsy, and silence is not evidence against the literature.

44Not attributable

A real reporting signal that is not evidence for this drug-lesion pair: no MedDRA term names it, the naming subset asked alone came back flat, or the 2026-08 review attributed the reporting to the population, co-therapy, or class-level literature.

21Reported by name

The terms that name this lesion are disproportionate, but no profile documents it for that agent. Most are echoed by a sibling agent in the same class. Leads for review, never lesions the atlas claims.

AbirateroneAtezolizumabAzacitidineBendamustineBevacizumabBicalutamideBortezomibBrigatinibBusulfanCabazitaxelCapecitabineCarboplatinCarmustine (BCNU)CisplatinCladribineClofarabineCyclophosphamideCytarabineDactinomycin (actinomycin D)DarolutamideDenosumabDocetaxelDoxorubicinEnfortumab vedotinEnzalutamideEribulinEtoposideEverolimusFludarabineGefitinibGemcitabineGemtuzumab ozogamicinHydroxyureaIbandronateIbrutinibIfosfamideImatinibInotuzumab ozogamicinLenvatinibLeuprolideMelphalanMethotrexate (high-dose)Mitomycin CMitotaneMitoxantroneNelarabineNilotinibNintedanibNiraparibObinutuzumabOctreotideOxaliplatinPaclitaxelPazopanibPegaspargasePembrolizumabPenpulimabPentostatinPolatuzumab vedotinPralatrexateRadium-223 dichlorideRegorafenibRelacorilantRibociclibRituximabRuxolitinibSirolimusSonidegibSorafenibSunitinibTalazoparibTamoxifenTemsirolimusThalidomideThiotepaTisotumab vedotinTopotecanTrifluridine/tipiracilVincristineZoledronic acid

80 agents with a significant CYST reporting signal.

Management approach

Full framework →

Prevent with mesna and hydration; this is an outflow (bladder) toxicity, not nephron injury.

Drug-level levers

  • Hold further dosing for significant hemorrhagic cystitis.
  • Co-administer mesna with ifosfamide and high-dose cyclophosphamide.

Pharmacologic toolkit

  • Mesna — Binds acrolein in the urine; standard prophylaxis with the oxazaphosphorines.
  • Hydration / bladder irrigation — Forced diuresis; continuous bladder irrigation for established hemorrhagic cystitis.

When to biopsy

Not a kidney-biopsy lesion; cystoscopy for severe or refractory bladder bleeding.

Monitoring

  • · Urinalysis for hematuria
  • · Symptoms of cystitis

Grounding

Educational use only. Educational synthesis of the published literature — not a treatment protocol, dosing guide, or medical advice. Regimens and agents shown are illustrative of what the literature describes; verify against current guidelines (ASON / KDIGO / ASCO / NCCN) and individualize to the patient. Using this site creates no clinician–patient relationship.

Offending agents

Any agent15Primary (#1) only1

Signature offenders

1

Agents for which hemorrhagic cystitis is the defining renal lesion.

ThiotepaEarly HC during/after conditioning; later HC with viral (BK/JC) reactivation.Hemorrhagic cystitis is a recognized complication of alkylator-based conditioning, but no thiotepa-attributable rate exists. Post-transplant HC is reported at roughly 12-37% ACROSS conditioning regimens; in a 134-patient allogeneic cohort on uniform cyclophosphamide-based GVHD prophylaxis, overall HC was 23%, with TBF (thiotepa-busulfan-fludarabine) conditioning an independent risk factor at OR 1.32 alongside HLA mismatch and comorbidity score (Galli 2024). These are cohort-wide incidences confounded by concurrent cyclophosphamide and by BK/JC reactivation — thiotepa's own contribution is quantified as a relative risk, not an incidence.Mild

Also associated

14

Agents that cause hemorrhagic cystitis as a secondary pattern alongside a different signature lesion.

CisplatinAcute — creatinine peaks ~day 4–7; magnesium wasting can persist for months.AKI in ~20–35% per cycle (classic teaching: ~1 in 3). Hypomagnesemia in 40–100%.SevereIfosfamideAcute tubulopathy during therapy; chronic Fanconi/CKD can emerge months–years later.Subclinical tubular dysfunction is common while overt Fanconi is not, and the gap is the point. In 183 children investigated prospectively at least 5 years out — none of whom received any platinum, so the toxicity is attributable — the tubular threshold for phosphate was reduced in 24% and glycosuria detected in 37%, yet glycosuria exceeded 0.5 g/24 h in only 5%, bicarbonate and calcium were normal in every patient, and 89.5% had normal tubular function overall at a median 10 years. GFR was abnormal in 21.5%. Ifosfamide dose and time since therapy both predicted tubulopathy. Rates elsewhere span 0% to 84% depending on the definition and cohort used, so a single figure is only meaningful with its threshold attached.SevereGemcitabineDelayed — months of cumulative exposure.Estimates span three orders of magnitude by ascertainment. The only figure with a real denominator is the manufacturer safety-database review: 12 cases against 78,800 patient exposures, a crude 0.015% (range 0.008–0.078%). The product characteristics give 0.01%. Against that, a single center reported 2.7% — four of its five cases on nab-paclitaxel/gemcitabine, where a pharmacokinetic interaction is suspected. Historically high mortality: of 23 cases with reported outcome in the literature tally, 11 died within a few weeks, death directly attributed to HUS in two.SevereMitomycin CDelayed — after cumulative dosing, sometimes after therapy ends.Dose-dependent, generally 4–15%; nearly every case in the landmark 85-patient registry had received a cumulative total dose above 60 mg. >50% historical mortality.SevereAtezolizumabTypically weeks to a few months after initiation (median time to checkpoint-inhibitor AKI is on the order of 3-4 months, characteristically later than classic drug AIN).Across the checkpoint-inhibitor class, any acute kidney injury occurs in roughly 15-17% of treated patients in cohort studies, while clinically significant immune-related AKI (most often acute interstitial nephritis) affects a smaller subset (commonly a few percent). Meta-analysis suggests anti-PD-L1 agents like atezolizumab carry somewhat lower AKI risk than anti-PD-1 agents; PD-L1-specific rates are not precisely separated. A separate real-world cohort of 1,037 ICI-treated patients supplies the drug-attributable denominator this class otherwise lacks: 18.2% developed AKI of any cause, but only 3.6% (37 patients) had AKI attributed to the checkpoint inhibitor itself — a class figure, not an atezolizumab-specific one.ModeratePembrolizumabDelayed and highly variable, typically weeks to months after initiation; multicenter cohorts reported median onsets around 14-16 weeks. Can occur after a single dose or after many months, and may recur on rechallenge.In real-world cohorts of patients receiving immune checkpoint inhibitors, any AKI is common (roughly 16-18%), but AKI attributable to the checkpoint inhibitor itself (ICPi-AKI) is less frequent. A single-center cohort reported AKI in 16.5% of ICI-treated patients with checkpoint-attributable nephrotoxicity in a minority, while a larger real-world study found ICPi-AKI in about 3.6%. Acute interstitial nephritis is the dominant biopsy lesion (>80% in the largest multicenter series). These figures are pooled across PD-1/PD-L1/CTLA-4 agents rather than pembrolizumab-specific.ModerateCarboplatinAcute when it occurs (high-dose regimens).Clinically significant nephrotoxicity uncommon at standard doses; emerges mainly at high/myeloablative doses.MildCyclophosphamideHyponatremia within hours; cystitis acute.Dose-related hyponatremia (not reliably quantified); hemorrhagic cystitis ~5–20%, lower with mesna prophylaxis. Reported rate: hyponatremia in 52% — 69 adults who received high-dose cyclophosphamide therapy at a single center 2010-2014 (retrospective cohort (Bonella 2017, PMID 29890094).MildDoxorubicinSubacute in models (over weeks); clinical events rare and variable.Adriamycin nephropathy is the canonical rodent model of podocyte injury and focal segmental glomerulosclerosis (FSGS); clinically significant glomerular disease from therapeutic dosing in patients is rare and largely case-level. Separately, doxorubicin — especially the pegylated liposomal formulation — is an increasingly recognized but underreported cause of kidney-limited thrombotic microangiopathy (a vascular/endothelial lesion), described in biopsy-proven case reports and drug-induced-TMA series.MildGefitinibWeeks to months after initiation in reported cases; proteinuria resolves over weeks to months after stopping the drug.Nephrotic syndrome (minimal-change disease and secondary membranous nephropathy patterns) and rare acute renal failure are reported only as isolated cases; not quantified in clinical-trial datasets.MildPaclitaxelInfusion reactions occur during or shortly after administration (typically first/second exposure); any prerenal AKI follows the hemodynamic instability.Paclitaxel has low direct nephrotoxicity. Hypersensitivity/infusion reactions - historically attributed to the Cremophor EL (polyoxyethylated castor oil) vehicle via complement activation, with newer evidence for IgE-mediated reactions - and associated fluid shifts can transiently compromise renal perfusion, but structural kidney injury is uncommon and not well quantified.MildDocetaxelFluid retention develops cumulatively (often after several cycles / cumulative dose); hypersensitivity reactions occur during infusion.Docetaxel has low direct renal toxicity. Its characteristic fluid-retention syndrome (peripheral edema, effusions, weight gain) reflects increased capillary permeability rather than tubular injury; AKI directly attributable to docetaxel is uncommon and not well quantified, and the drug has been used successfully even in kidney-transplant recipients.MildCabazitaxelAKI follows intercurrent gastrointestinal or infectious complications during treatment cycles.Cabazitaxel has low direct nephrotoxicity; AKI is uncommon and usually mediated by gastrointestinal losses (diarrhea, occurring in a substantial minority), neutropenic sepsis, or hemodynamic instability rather than direct tubular toxicity. In real-world safety data, grade >=3 diarrhea and febrile neutropenia each occur in roughly 5% of patients. A drug-specific renal AKI rate is not well established.MildMitoxantroneTumor lysis hours to days post-infusion.Direct nephrotoxicity is low and not quantified; the principal renal risk is tumor lysis syndrome when used in bulky/rapidly proliferating hematologic malignancies. Benign blue-green discoloration of urine/sclera is expected (the anthracenedione chromophore), not injury.Mild
See these on the Toxic-Ties graphAll 14 lesions