SIADH

SIADH / Hyponatremia

Inappropriate water retention at the collecting duct — high-dose cyclophosphamide.

16agents

Where it strikes

Distal Tubule / Collecting Duct

Fine-tuning of Na, K, Mg, acid & water

See it on the nephron

Severity mix

Moderate· 2Mild· 14

Reversibility

Reversible· 16

Signature offenders

Agents for which siadh / hyponatremia is the defining renal lesion.

SelinexorEarly — within the first cycle/few weeks; front-loaded.Hyponatremia is common and dose-limiting. In STORM it occurred in ~22% of patients and was predominantly grade >=3 — the most common grade >=3 non-hematologic toxicity. In BOSTON any-grade hyponatremia affected roughly a third of the selinexor arm (grade 3-4 ~8-9%); in SADAL grade 3-4 hyponatremia occurred in ~8%.Moderate CyclophosphamideHyponatremia within hours; cystitis acute.Dose-related hyponatremia (not reliably quantified); hemorrhagic cystitis ~5–20%, lower with mesna prophylaxis.Mild MelphalanDays 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. Notably, melphalan PK is not adversely affected by renal failure, so transplant in renal impairment is feasible with dose reduction.Mild TemozolomideDuring 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.Mild OsimertinibReported 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. Not quantified as a discrete renal endpoint in randomized data, where overall renal adverse events are uncommon.Mild VincristineDays 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.Mild VinblastineDays after administration, generally within the first cycles.As a vinca alkaloid, 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.Mild VinorelbineDays 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.Mild TamoxifenFlare 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.Mild LazertinibDuring 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.Mild SunvozertinibElectrolyte 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.Mild VismodegibMuscle 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.Mild ChlorambucilHyponatremia, 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

Agents that cause siadh / hyponatremia as a secondary pattern alongside a different signature lesion.

MitotaneAdrenal insufficiency and its electrolyte/volume consequences develop over weeks of therapy as adrenolytic effect accrues; cisplatin-associated AKI in EDP-M is acute, within days of chemotherapy cycles.Intrinsic mitotane nephrotoxicity is not characteristically quantified. Clinically important renal events are indirect (adrenal insufficiency-related electrolyte/volume disturbance) or attributable to co-administered cisplatin in EDP-M; incidence not reliably enumerated for mitotane alone.Moderate VinflunineElectrolyte/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.Mild OctreotideNot applicable for intrinsic injury; pharmacokinetic accumulation in renal failure is gradual.No characteristic intrinsic nephrotoxicity; octreotide is generally considered kidney-neutral. Renal events are rare, indirect, and not reliably quantified. Mild electrolyte disturbances are uncommon and not well enumerated.Mild

See these on the Toxic-Ties graph All 14 lesions