The Injury Atlas See it on the nephron Does the kidney recover? Cross-drug outcomes
SIADH
SIADH / Hyponatremia
Inappropriate water retention at the collecting duct — high-dose cyclophosphamide.
24agents
Where it strikes
Distal Tubule / Collecting Duct
Fine-tuning of Na, K, Mg, acid & water
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· 1Moderate· 8Mild· 15
Agents’ overall reversibility
Partially reversible· 4Reversible· 20
Agents’ onset window
How soon each agent’s kidney toxicity typically appears — a whole-drug tempo, not specific to this lesion.
Hyperacute (<24 h)· 1Acute (days)· 8Subacute (weeks)· 3Delayed (weeks–months)· 4Variable· 8
Real-world reporting for this lesion
FAERS across all lesions →Agents with a disproportionate FAERS reporting signal for siadh / hyponatremia (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.
19Corroborated
Documented in the atlas profile and carrying a FAERS signal — the strongest claim the atlas makes.
1Documented, 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.
67Not 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.
27Reported 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.
5-FluorouracilAcalabrutinibAfatinibAlpelisibAtezolizumabAxitinibAzacitidineBelzutifanBevacizumabBicalutamideBinimetinibBleomycinBortezomibBrentuximab vedotinBusulfanCabazitaxelCabozantinibCapecitabineCapmatinibCarboplatinCeritinibCetuximabChlorambucilCisplatinCobimetinibCrizotinibCyclophosphamideCytarabineDabrafenibDacarbazineDarolutamideDasatinibDinutuximabDocetaxelDoxorubicinDurvalumabEncorafenibEnfortumab vedotinEpcoritamabErdafitinibErlotinibEtoposideEverolimusFludarabineFutibatinibGefitinibGemcitabineGemtuzumab ozogamicinGlasdegibHydroxyureaIbritumomab tiuxetanIbrutinibIfosfamideImlunestrantInavolisibInotuzumab ozogamicinInterleukin-2 (high-dose)IpilimumabIrinotecanLanreotideLenvatinibLifileucelLomustine (CCNU)LurbinectedinMelphalanMitotaneNaxitamabNelarabineNiraparibNivolumabOctreotideOxaliplatinPaclitaxelPamidronatePanitumumabPazopanibPegaspargasePembrolizumabPemetrexedPentostatinPolatuzumab vedotinPralatrexatePralsetinibRamucirumabRegorafenibRelacorilantRibociclibRituximabSelinexorSorafenibSunitinibTalazoparibTamoxifenTemozolomideTemsirolimusTepotinibThalidomideThiotepaTislelizumabTopotecanTrabectedinTrametinibTrastuzumab deruxtecanTrastuzumab emtansine (T-DM1)TucatinibVandetanibVemurafenibVinblastineVincristineVinorelbineVismodegibZolbetuximabZoledronic acid
113 agents with a significant SIADH reporting signal.
Management approach
Full framework →Manage the hyponatremia (fluid restriction, careful correction); avoid over-hydration around dosing.
Drug-level levers
- Avoid the large hypotonic fluid loads historically given with cyclophosphamide.
- Adjust dose timing and hydration strategy.
Pharmacologic toolkit
- Fluid restriction — First line for euvolemic hyponatremia.
- Careful sodium correction — Correct slowly to avoid osmotic demyelination syndrome.
When to biopsy
Not indicated — a water-handling disorder, not structural injury.
Monitoring
- · Serum sodium around dosing
- · Fluid balance
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
Signature offenders
12Agents for which siadh / hyponatremia is the defining renal lesion.
SelinexorEarly — within the first cycle/few weeks; front-loaded.Hyponatremia is common and dose-limiting. All-grade hyponatremia affected 39% of the selinexor-dexamethasone patients tabulated in the FDA label's STORM adverse-reaction table, reaching grade 3-4 in 22% — making it the leading grade >=3 non-hematologic toxicity, and one of the six grade 3-4 laboratory abnormalities the label lists at >=10%. Both rates come from the trial's safety tables rather than its abstract, which does not mention hyponatremia; a separate phase 1 dose-escalation cohort reported grade >=3 hyponatremia at a concordant 23%. Combination regimens run lower: in BOSTON grade 3-4 hyponatremia was ~8-9%, and in SADAL ~8%.ModerateCyclophosphamideHyponatremia 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).MildMelphalanDays after high-dose administration.High-dose intravenous melphalan can cause hyponatremia/SIADH; in a small high-dose series most patients showed declining sodium, but this is reported at case/series level rather than as a large quantified rate. Melphalan PK is not adversely affected by renal failure, so transplant in renal impairment is feasible.MildTemozolomideDuring cycles of therapy; variable.Generally renally well tolerated; renal clearance of the parent drug is a minor elimination pathway and dedicated PubMed searches for temozolomide nephrotoxicity/SIADH return essentially no indexed series. Hyponatremia/SIADH is an occasional, case/toxicity-table-level event, and rare acute interstitial nephritis has been reported in combination contexts.MildOsimertinibReported within roughly the first weeks to a few months of therapy (around two months in several published cases).Syndrome of inappropriate antidiuretic hormone (SIADH)-type hyponatremia is described at the case level; occasional acute kidney injury and rare proteinuria are reported. True structural kidney injury is not quantified as a discrete endpoint in randomized data, where overall renal adverse events are uncommon. The common osimertinib renal finding is instead a pseudo-decrease in creatinine-based eGFR from inhibited tubular creatinine secretion, quantified for osimertinib specifically by Ilyas et al. (Kidney Med 2026) and, at the cohort level, in the AMBORA real-world analysis: among 238 patients on 38 oral antitumor agents likely to cause pseudo-worsening, mean eGFR fell 6.8 mL/min within 30 days and by >=20 mL/min in 17.2% — a whole-group figure, not an osimertinib-specific rate.MildVincristineDays after dosing, often within the first 1-2 cycles; resolves after the drug is withheld.Vincristine-associated SIADH with hyponatremia is a recognized but uncommon, largely case-level adverse effect; a global pharmacovigilance analysis estimated a reporting rate of about 1.3 per 100,000 treated patients, with a possible over-representation in Asian patients. FAERS disproportionality analysis also flags inappropriate ADH secretion as a vinca-class signal.MildVinblastineDays after administration, generally within the first cycles.Vinblastine can cause SIADH with hyponatremia; this is a recognized class effect reported at case level rather than as a quantified rate. Rare Raynaud phenomenon and other vascular events (especially in germ-cell regimens) are also described.MildVinorelbineDays after dosing, sometimes after several cycles (one report after three cycles).SIADH with hyponatremia is reported with vinorelbine at case level; FAERS pharmacovigilance analysis of vinca alkaloids flags inappropriate ADH secretion as a shared signal. Quantitative incidence is not established.MildTamoxifenFlare hypercalcemia within the first days to weeks; hyponatremia case-level and variable.Direct nephrotoxicity is not a feature. Tumor-flare hypercalcemia occurs early in patients with osteolytic bone metastases (about 13% — 12 of 93 — in one hypercalcemic breast-cancer series). Euvolemic hyponatremia (SIADH-type) is reported only at the case level.MildLazertinibDuring therapy; case-level and variable.Hyponatremia is a recognized signal of third-generation EGFR TKIs (an osimertinib-class effect); for lazertinib specifically the renal/sodium data are limited and not well quantified. EGFR blockade also causes electrolyte wasting (hypomagnesemia, hypokalemia), and combination with amivantamab adds to these effects.MildVismodegibMuscle spasms within the first weeks-to-months; hyponatremia is sporadic and variable in timing.Muscle spasms are near-universal (~64-71%), with dysgeusia and alopecia close behind; hyponatremia is reported but uncommon and not precisely quantified for an SIADH mechanism. Direct kidney injury is rare.MildChlorambucilHyponatremia, when reported, has occurred during ongoing dosing, including with low doses; timing is variable.Chlorambucil has minimal direct nephrotoxicity. Drug-associated SIADH with hyponatremia is reported only rarely, in isolated case reports; tumor lysis is uncommon given its indolent-disease indications and gradual cytoreduction. No reliable incidence figure exists.Mild
Also associated
12Agents that cause siadh / hyponatremia 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%.SeverePemetrexedDelayed / cumulative; risk rises after ~10 cycles.Clinically relevant eGFR decline (≥25%) in ~21%; ~8% discontinue for nephrotoxicity. Cumulative-dose dependent.ModerateInterleukin-2 (high-dose)Acute — during the treatment cycle.Oliguria / prerenal AKI is very common during therapy at high dose — but reversible.ModerateCytarabineHours to days after initiating therapy in high-burden disease.Intrinsic tubular nephrotoxicity is uncommon; the major renal risk is AKI from tumor lysis syndrome during leukemia/lymphoma cytoreduction, reported at case and series level including fatal TLS. Direct cytarabine-nephrotoxicity primary literature is genuinely sparse.ModerateAtezolizumabTypically 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.ModerateSelpercatinibHypertension within the first weeks to months; creatinine changes early.Hypertension is among the most common adverse events in LIBRETTO-001 (a frequent grade >=3 event), and a reversible serum-creatinine increase is also recognized. A single-center hereditary-MTC series found hypertension in ~26% on selective RET inhibitors. Reported rate: grade >=3 hypertension in 19.7% — 837 patients with RET-activated advanced/metastatic solid tumors receiving selpercatinib monotherapy (20 mg QD to 240… (Raez 2024, PMID 39471424).ModeratePentostatinDuring or after dosing cycles; generally reversible with dose reduction or discontinuation.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.ModerateNivolumabCharacteristically delayed compared with other drug-induced AIN: median time from ICI initiation to AKI was about 14 weeks (IQR 6-37) in a 138-patient multicenter cohort, and 91 days in the original series; onset ranges from weeks to many months and can follow drug discontinuation.Clinically significant ICI-attributed AKI is uncommon but not rare. A 2023 systematic review/meta-analysis of real-world data (18 studies, ~12,000 ICI-treated patients) found a pooled incidence of all-cause AKI during ICI therapy of about 16%, but AKI specifically attributed to the ICI of roughly 3.5%. Risk is higher with combination ICI regimens (e.g., nivolumab-ipilimumab) than with PD-1 monotherapy. Among biopsied ICI-AKI, acute tubulointerstitial nephritis is the dominant lesion (>90%); glomerular lesions and thrombotic microangiopathy are reported but uncommon.ModerateCarboplatinAcute when it occurs (high-dose regimens).Clinically significant nephrotoxicity uncommon at standard doses; emerges mainly at high/myeloablative doses.MildSunvozertinibElectrolyte changes can appear within the first weeks to months of therapy; hypomagnesemia risk rises with treatment duration.No established AKI rate. As with the EGFR-inhibitor class, the renal-relevant signal is electrolyte disturbance — particularly hypomagnesemia (renal Mg wasting) and diarrhea-driven losses, with a hyponatremia/SIADH-like pattern possible — rather than structural nephron injury. WU-KONG6 reported diarrhea and skin/EGFR-pathway toxicities as dominant; renal-specific events are not quantified.MildVinflunineElectrolyte/prerenal effects can appear within days of a cycle; PK accumulation in renal impairment is immediate but mitigated by protocol dose reduction.No strong direct nephrotoxic signal. Vinflunine is given to renally impaired, cisplatin-unfit patients with a defined dose-reduction schema, and tolerability in renal impairment mirrors that of patients with normal renal function once dose-banded. SIADH/hyponatremia is a class-level vinca-alkaloid effect rather than a quantified vinflunine-specific rate. Reported rate: grade >=3 hyponatremia in 12% — 51 patients with relapse-sensitive or relapse-refractory small cell lung cancer treated with single-agent vinflunine… (Spigel 2010, PMID 20521355).MildDabrafenibVariable and biphasic. Pyrexia-associated AKI clusters early, in the first weeks to months of therapy and coincides with febrile episodes. Biopsy-proven granulomatous/acute interstitial nephritis has appeared anywhere from a few weeks to as late as ~5 years into treatment.AKI is relatively common on dabrafenib-based therapy but usually mild and reversible. In the largest cohort, 42/199 (21%) of patients on dabrafenib/trametinib developed AKI within 12 months, and roughly 24% of those episodes occurred during the drug-induced febrile (pyrexia) syndrome (Seethapathy 2022). Pharmacovigilance places dabrafenib well below vemurafenib: FAERS acute-kidney-injury reporting-odds-ratio approximately 1.35 (95% CI 1.15–1.60) for dabrafenib versus approximately 3.28 for vemurafenib (Sanagawa 2021). Biopsy-proven granulomatous/acute interstitial nephritis and clinically significant electrolyte disorders (hyponatremia, hypokalemia, hypophosphatemia) are each individually rare — documented mainly in case reports and small FAERS counts. Registrational trials did not flag renal toxicity; the signal emerged post-marketing.Mild