Acute kidney injury associated with immune checkpoint inhibitor therapy: incidence, risk factors and outcomes

BackgroundImmune checkpoint inhibitors (ICPi) are a novel and promising anti-cancer therapy. There are limited data on the incidence, risk factors and outcomes of acute kidney injury (AKI) in patients receiving ICPi.MethodsWe conducted a cohort study of patients receiving ICPi at our center between 2010 and 2017 via electronic health record. The primary outcome was AKI (increase of >50% from baseline serum creatinine (sCr)). Risk factors for AKI were assessed using logistic regression. Survival among those with and without AKI was compared using the Kaplan-Meier method.ResultsAmong 309 patients on ICPi, 51 (16.5%) developed AKI (Kidney Disease Improving Global Outcomes (KDIGO) stages 1: 53%, 2: 22%, 3: 25%). AKI was associated with other immune-related adverse events (IRAE) (OR 3.2, 95% CI 1.6 to 6; p<0.001), hypertension (OR 4.3, 95% CI 1.8 to 6.1; p<0.001) and cerebrovascular disease (OR 9.2; 95% CI 2.1 to 40; p<0.001). Baseline sCr, cancer, and ICPi type was not associated with AKI. Use of angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers (OR 2.9; 95% CI 1.5 to 5.7; p=0.002), diuretics (OR 4.3; 95% CI 1.9 to 9.8; p<0.001), and corticosteroid treatment (OR 1.9; 95% CI 1.1 to 3.6; p=0.03) were associated with AKI. In the multivariable analysis, AKI was associated only with other IRAE (OR 2.82; 95% CI 1.45 to 5.48; p=0.002) and hypertension (OR 2.96; 95% CI 1.33 to 6.59; p=0.008). AKI was not associated with increased risk of mortality (HR 1.1; 95% CI: 0.8 to 1.6; p=0.67). ICPi nephrotoxicity was attributed via biopsy or nephrologist assessment in 12 patients (six interstitial nephritis, two membranous nephropathy, two minimal change disease, and two thrombotic microangiopathy). Subsequent doses of ICPi were administered to 12 patients with prior AKI, with one (8.3%) having recurrent AKI.ConclusionAKI is a common complication in patients receiving ICPi treatment. The development of other IRAE and previous diagnosis of hypertension were associated with increased AKI risk. AKI was not associated with worse survival. Distinguishing kidney IRAE from other causes of AKI will present a frequent challenge to oncology and nephrology practitioners. Kidney biopsy should be considered to characterize kidney lesions and guide potential therapy.

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Risk factors for emergency room and hospital care for patients with advanced solid tumors on immune checkpoint inhibitor therapy.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e15142 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e15142-e15142

Author(s):

Anish B Parikh ◽

George Mellgard ◽

Qian Qin ◽

Vaibhav G. Patel ◽

Bo Wang ◽

...

Keyword(s):

Risk Factors ◽

Emergency Room ◽

Solid Tumors ◽

Immune Checkpoint ◽

Checkpoint Inhibitors ◽

Multivariable Analysis ◽

Advanced Solid Tumors ◽

Significance Level ◽

Exact Test ◽

Increased Risk

e15142 Background: Immune checkpoint inhibitors (ICIs) are increasingly utilized across cancer types. Risk factors for emergency room (ER) and inpatient (IP) care in this patient (pt) population remain poorly defined. Methods: We retrospectively reviewed charts for pts with (w/) advanced solid tumors who received more than 1 ICI dose at Mount Sinai from 1/1/11 – 4/28/17. Demographics, medical history, cancer diagnosis and therapy (tx) details, and outcomes were recorded. Descriptive data detailing ER/IP care during ICI tx (from first dose to 3 months after last dose) were collected. Fisher’s exact test and multivariable regression analyses were used to study differences between pts w/ versus w/out ER/IP care during ICI tx. Significance level was set at 0.05 for all tests. Results: 345 patients met the inclusion criteria for this study. Mean age was 64 years. Common tumor types were non-small cell lung cancer (n = 87), melanoma (n = 78), hepatocellular carcinoma (n = 53), and urothelial carcinoma (n = 38). 83% of patients had metastatic disease. Median duration of ICI tx was 2 months. During ICI tx, 50% received ER care and 43% received IP care, resulting in 369 total episodes of ER and/or IP care. 12% of episodes were attributed to ICI toxicity; 6% required intensive care. Median time to ER/IP care was 111 days. Median IP length of stay was 2 days. Several factors were found to be significant predictors of risk for ER or IP care on multivariable analysis (Table). African-American race and Hispanic ethnicity were each predictive of increased risk for both ER and IP care. Conclusions: ER/IP care is common among pts w/ advanced solid tumors on ICI tx. Understanding demographic and clinical risk factors can help prospectively identify higher-risk pts to inform preventive programs aimed at reducing such care. [Table: see text]

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Immune checkpoint inhibitor-associated acute kidney injury and mortality: An observational study

PLoS ONE ◽

10.1371/journal.pone.0252978 ◽

2021 ◽

Vol 16 (6) ◽

pp. e0252978

Author(s):

Marije S. Koks ◽

Gurbey Ocak ◽

Britt B. M. Suelmann ◽

Cornelia A. R. Hulsbergen-Veelken ◽

Saskia Haitjema ◽

...

Keyword(s):

Risk Factors ◽

Acute Kidney Injury ◽

Serum Creatinine ◽

Renal Dysfunction ◽

Immune Checkpoint ◽

Enzyme Inhibitor ◽

Checkpoint Inhibitor ◽

Checkpoint Inhibitors ◽

Kidney Injury ◽

Low Grade

Background Immune checkpoint inhibitors, approved for the treatment of various types of cancer, are known to cause a unique spectrum of side effects, including acute kidney injury (AKI). The aim of this study was to describe the incidence, risk factors, renal outcomes, and mortality of AKI in patients receiving checkpoint inhibitors. Methods Patients receiving checkpoint inhibitors between January 2013 and May 2020 at the University Medical Center Utrecht, the Netherlands, were identified using the Utrecht Patient Oriented Database. AKI was defined as an increase in serum creatinine of ≥1.5 times the baseline value, based on the Kidney Disease: Improving Global Outcomes criteria. Cox proportional hazard regression analysis was used to assess risk factors for AKI and to evaluate the relationship between AKI and mortality. Persistent renal dysfunction was diagnosed in AKI patients with a final serum creatinine measurement of >1.3 times the baseline value. Results Among 676 patients receiving checkpoint inhibitors, the overall incidence of AKI was 14.2%. Baseline variables independently associated with AKI were a gynecologic malignancy, monotherapy with ipilimumab, and the use of a diuretic, angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker, or proton pump inhibitor at baseline. AKI was checkpoint inhibitor-associated in one third of all patients with AKI. Checkpoint inhibitor-associated AKI was mostly low-grade, occurred a median of 15 weeks after checkpoint inhibitor initiation, and resulted in persistent renal dysfunction in approximately 40% of the patients. Patients with all-cause AKI had a twofold increased mortality risk, but checkpoint inhibitor-associated AKI was not associated with increased mortality. Conclusions In this study, patients receiving checkpoint inhibitors frequently developed AKI due to various etiologies. AKI directly related to the effect of checkpoint inhibitor toxicity did not increase mortality. However, AKI not related to the effect of checkpoint inhibitor toxicity was associated with increased mortality.

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MO363CHECKPOINT-INHIBITOR-ASSOCIATED ACUTE KIDNEY INJURY AND MORTALITY: AN OBSERVATIONAL STUDY

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab082.0017 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Marije Koks ◽

Gurbey Ocak ◽

Britt Suelmann ◽

Cornelia Hulsbergen-Veelken ◽

Saskia Haitjema ◽

...

Keyword(s):

Risk Factors ◽

Acute Kidney Injury ◽

Mortality Risk ◽

Enzyme Inhibitor ◽

Checkpoint Inhibitor ◽

Checkpoint Inhibitors ◽

Kidney Injury ◽

Gynecological Malignancy ◽

Incidence Risk ◽

Cox Proportional Hazard Regression

Abstract Background and Aims Immune checkpoint inhibitors, approved for the treatment of various types of cancer, are known to cause a unique spectrum of autoimmune-related side effects, including acute kidney injury (AKI). The aim of this study was to describe the incidence, risk factors, renal outcomes, and mortality of AKI in patients receiving checkpoint inhibitors. Method Patients receiving checkpoint inhibitors between January 2013 and May 2020 were identified using the Utrecht Patient Oriented Database. AKI was defined as an increase in creatinine of ≥1.5 times the baseline value. Cox proportional hazard regression analysis was used to assess risk factors for AKI and to evaluate the relationship between AKI and mortality. Persistent kidney injury was diagnosed in AKI patients with a final creatinine measurement of >1.3 times the baseline value. Results Out of 676 patients receiving checkpoint inhibitors, AKI occurred in 96 (14.2%) patients. Chart review showed that AKI was checkpoint inhibitor-associated in 32 (4.7%) patients. Baseline variables associated with AKI were a primary gynecological malignancy (HR 3.91, 95% CI 1.55 to 9.85), treatment with checkpoint inhibitor ipilimumab (HR 2.31, 95% CI 1.03 to 5.20), and pre-existent use of a diuretic (HR 2.61, 95% CI 1.21 to 5.60), an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker (HR 2.49, 95% CI 1.10 to 5.60), and a proton pump inhibitor (HR 1.69, 95% CI 1.04 to 2.75). In 35.4% of the patients who had developed AKI, persistent kidney dysfunction was observed at the end of follow-up. Patients who developed AKI had a 2.13-fold (95% CI 1.58 to 2.87) increased mortality risk compared to patients who did not develop AKI. Mortality risk was not increased by checkpoint inhibitor-associated AKI (HR 1.11, 95% CI 0.64 to 1.92), but only by AKI related to other causes (HR 2.87, 95% CI 2.04 to 4.04). Conclusion Patients receiving checkpoint inhibitors frequently develop AKI, however, checkpoint inhibitor-associated AKI does not seem to increase mortality.

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Contrast Associated Acute Kidney Injury and Mortality in Older Adults with Acute Coronary Syndrome: A Pooled Analysis of the FRASER and HULK Studies

Journal of Clinical Medicine ◽

10.3390/jcm10102151 ◽

2021 ◽

Vol 10 (10) ◽

pp. 2151

Author(s):

Rita Pavasini ◽

Matteo Tebaldi ◽

Giulia Bugani ◽

Elisabetta Tonet ◽

Roberta Campana ◽

...

Keyword(s):

Acute Kidney Injury ◽

Renal Function ◽

Multivariable Analysis ◽

Kidney Injury ◽

Coronary Intervention ◽

Pooled Analysis ◽

Coronary Syndrome ◽

Risk Of Mortality ◽

Increased Risk ◽

Short Term Mortality

Whether contrast-associated acute kidney injury (CA-AKI) is only a bystander or a risk factor for mortality in older patients undergoing percutaneous coronary intervention (PCI) is not well understood. Data from FRASER (NCT02386124) and HULK (NCT03021044) studies have been analysed. All patients enrolled underwent coronary angiography. The occurrence of CA-AKI was defined based on KDIGO criteria. The primary outcome of the study was to test the relation between CA-AKI and 3-month mortality. Overall, 870 older ACS adults were included in the analysis (mean age 78 ± 5 years; 28% females). CA-AKI occurred in 136 (16%) patients. At 3 months, 13 (9.6%) patients with CA-AKI died as compared with 13 (1.8%) without it (p < 0.001). At multivariable analysis, CA-AKI emerged as independent predictor of 3-month mortality (HR 3.51, 95%CI 1.05–7.01). After 3 months, renal function returned to the baseline value in 78 (63%) with CA-AKI. Those without recovered renal function (n = 45, 37%) showed an increased risk of mortality as compared to recovered renal function and no CA-AKI subgroups (HR 2.01, 95%CI 1.55–2.59, p = 0.009 and HR 2.71, 95%CI 1.45–5.89, p < 0.001, respectively). In conclusion, CA-AKI occurs in a not negligible portion of older MI patients undergoing invasive strategy and it is associated with short-term mortality.

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Does deeper hypothermia reduce the risk of acute kidney injury after circulatory arrest for aortic arch surgery?

European Journal of Cardio-Thoracic Surgery ◽

10.1093/ejcts/ezab044 ◽

2021 ◽

Author(s):

Andrew M Vekstein ◽

Babtunde A Yerokun ◽

Oliver K Jawitz ◽

Julie W Doberne ◽

Jatin Anand ◽

...

Keyword(s):

Acute Kidney Injury ◽

Circulatory Arrest ◽

Aortic Surgery ◽

Multivariable Analysis ◽

Kidney Injury ◽

Deep Hypothermia ◽

Moderate Hypothermia ◽

Bladder Temperature ◽

Increased Risk ◽

The Impact

Abstract OBJECTIVES The impact of hypothermic circulatory arrest (HCA) temperature on postoperative acute kidney injury (AKI) has not been evaluated. This study examined the association between circulatory arrest temperatures and AKI in patients undergoing proximal aortic surgery with HCA. METHODS A total of 759 consecutive patients who underwent proximal aortic surgery (ascending ± valve ± root) including arch replacement requiring HCA between July 2005 and December 2016 were identified from a prospectively maintained institutional aortic surgery database. The primary outcome was AKI as defined by Risk, Injury, Failure, Loss, End Stage Renal Disease (ESRD) criteria. The association between minimum nasopharyngeal (NP) and bladder temperatures during HCA and postoperative AKI was assessed, adjusting for patient-level factors using multivariable logistic regression. RESULTS A total of 85% (n = 645) of patients underwent deep hypothermia (14.1–20.0°C), 11% (n = 83) low-moderate hypothermia (20.1–24.0°C) and 4% (n = 31) high-moderate hypothermia (24.1–28.0°C) as classified by NP temperature. When analysed by bladder temperature, 59% (n = 447) underwent deep hypothermia, 22% (n = 170) low-moderate, 16% (n = 118) high-moderate and 3% mild (n = 24) (28.1–34.0°C) hypothermia. The median systemic circulatory arrest time was 17 min. The incidence of AKI did not differ between hypothermia groups, whether analysed using minimum NP or bladder temperature. In the multivariable analysis, the association between degree of hypothermia and AKI remained non-significant whether analysed as a categorical variable (hypothermia group) or as a continuous variable (minimum NP or bladder temperature) (all P > 0.05). CONCLUSIONS In patients undergoing proximal aortic surgery including arch replacement requiring HCA, degree of systemic hypothermia was not associated with the risk of AKI. These data suggest that moderate hypothermia does not confer increased risk of AKI for patients requiring circulatory arrest, although additional prospective data are needed.

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