Background Acute kidney injury (AKI) is a frequent and serious complication among patients with multiple myeloma (MM), occurring due to various mechanisms such as light chain cast nephropathy, hypercalcemia, sepsis, dehydration, and the nephrotoxic effects of anti-myeloma therapies including chemotherapy and novel agents like proteasome inhibitors. AKI not only complicates the clinical management of MM but may also delay or limit the use of effective treatments, contributing to poorer outcomes. Despite the recognized importance of renal complications in MM, data on the contemporary burden of AKI and its association with short-term hospital outcomes in real-world inpatient settings are limited.

Methods We conducted a retrospective cohort study using the 2020–2022 National Inpatient Sample (NIS), a nationally representative, all-payer hospital database in the United States. Adult hospitalizations (age ≥18) with a diagnosis of MM were identified using ICD-10-CM codes. The primary exposure was a co-diagnosis of AKI during the same admission, identified by validated ICD-10 codes. Primary outcome was in-hospital mortality; secondary outcomes included length of stay (LOS) and total hospital charges (inflation-adjusted to 2022 USD).

Multivariable regression models accounted for survey design and weights. Logistic regression was used for mortality, negative binomial regression for LOS, and gamma generalized linear models with log-link for cost. All models adjusted for age, sex, race/ethnicity, primary insurance payer, ZIP-code-based income quartile, comorbidity burden (Elixhauser Index), hospital region, teaching status, and urban/rural location.

Results A total of 55,010 unweighted hospitalizations for MM were identified, representing an estimated ~270,000 hospitalizations nationally. AKI was present in 24% of MM hospitalizations. Patients with AKI were older on average and had a higher burden of comorbid conditions.

In adjusted analyses, AKI was independently associated withnearly double the odds of in-hospital mortality (adjusted odds ratio [aOR] 1.95; 95% CI 1.81–2.10; p<0.001), a 20% longer length of stay (incidence rate ratio [IRR] 1.20; 95% CI 1.17–1.22; p<0.001), and a 20% increase in total hospital charges (cost ratio 1.20; 95% CI 1.17–1.23; p<0.001), indicating substantial clinical and economic burden.

Beyond AKI, other predictors of worse outcomes emerged. Older age, Black and Hispanic race/ethnicity, and non-Medicare insurance types—particularly Medicaid and other government programs—were associated with significantly higher odds of in-hospital mortality. Conversely, female sex and residence in higher-income ZIP codes were associated with reduced mortality risk. Patients from higher-income communities also experienced slightly shorter LOS, though their hospital charges were modestly higher, possibly reflecting greater access to high-cost interventions or more aggressive supportive care.

Hospital-level factors were also significant. Admissions to urban teaching hospitals, which likely serve more complex cases and offer advanced interventions, were associated with a 35% longer LOS and more than double the hospitalization costs compared to non-teaching, rural hospitals (both p<0.001), even after adjusting for patient- and region-level factors.

Conclusions In this large, contemporary, nationally representative cohort of hospitalized patients with multiple myeloma, AKI was a common complication and was strongly associated with increased in-hospital mortality, prolonged hospital stays, and elevated healthcare costs. These findings underscore the need for early recognition, prevention, and aggressive management of AKI in MM patients—particularly in the inpatient setting where these complications can rapidly worsen.

Additionally, our analysis highlights significant disparities in outcomes based on race, insurance status, and hospital type, suggesting that socioeconomic and structural factors continue to impact the care and prognosis of MM patients. Targeted interventions addressing both clinical and systemic contributors—such as improving access to nephrology consultation, expanding care pathways for high-risk groups, and standardizing renal protective strategies—may help mitigate these disparities and improve overall outcomes in this vulnerable population.

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