Associations between intercurrent events and cardiorenal clinical outcomes in non-diabetic chronic kidney disease: a real-world retrospective cohort study in the United States
Abstract Background Chronic kidney disease (CKD) is a global public health concern, with 50–70% of the burden attributed to non-diabetic aetiology. To expand CKD research, there is a need to identify novel surrogate endpoints preceding cardiorenal outcomes that are commonly used in CKD trials. This...
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2025-04-01
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| Series: | BMC Nephrology |
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| Online Access: | https://doi.org/10.1186/s12882-025-04021-6 |
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| author | Christoph Wanner Johannes Schuchhardt Chris Bauer Meike Brinker Frank Kleinjung Tatsiana Vaitsiakhovich |
| author_facet | Christoph Wanner Johannes Schuchhardt Chris Bauer Meike Brinker Frank Kleinjung Tatsiana Vaitsiakhovich |
| author_sort | Christoph Wanner |
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| description | Abstract Background Chronic kidney disease (CKD) is a global public health concern, with 50–70% of the burden attributed to non-diabetic aetiology. To expand CKD research, there is a need to identify novel surrogate endpoints preceding cardiorenal outcomes that are commonly used in CKD trials. This study explored and quantified associations between intercurrent events and clinical outcomes in patients with non-diabetic CKD to inform potential surrogate endpoints. Methods In this retrospective observational cohort study, adults with non-diabetic, moderate-to-severe CKD (stage 3/4) were identified in the US Optum Clinformatics® Data Mart healthcare claims database. Key outcomes were hospitalization for heart failure, kidney failure/need for dialysis, and worsening of CKD stage from baseline. Intercurrent events were defined as events observed in patient medical or pharmacy claims after the cohort inclusion date that either precluded a clinical outcome of interest or were associated with a modified risk of the respective outcome. Intercurrent events were selected a priori or by a data-driven exploratory approach. Associations between intercurrent events and clinical outcomes were explored and quantified using a Cox proportional hazards regression model. Results The study cohort included 504,924 patients. An outpatient heart failure diagnosis code was associated with an increased risk of consequent hospitalization for heart failure (hazard ratio [HR]: 12.92, 95% confidence interval [CI]: 12.67–13.17). CKD stage 4 diagnosis code was associated with an increased risk of kidney failure/need for dialysis (HR: 3.75, 95% CI: 3.69–3.81). Dispensation of potassium-removing resins and potassium-binding agents as an intercurrent event was associated with an increased risk of consequent worsening of CKD stage (HR: 4.83, 95% CI: 4.51–5.17). The estimated glomerular filtration rate decline in 295,174 patients with available laboratory data was associated with progressively increased risk of hospitalization for heart failure and kidney failure/need for dialysis. Conclusions Associations between intercurrent events and clinical outcomes in patients with non-diabetic CKD were investigated, quantified, and ranked using a large set of routinely collected data from a US claims database. Our approach may help identify novel surrogate endpoints that occur earlier in the disease course and could be leveraged as indicators of clinical outcomes in CKD research. |
| format | Article |
| id | doaj-art-bb9c8990548b40f68d095e30198d6035 |
| institution | OA Journals |
| issn | 1471-2369 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Nephrology |
| spelling | doaj-art-bb9c8990548b40f68d095e30198d60352025-08-20T02:17:01ZengBMCBMC Nephrology1471-23692025-04-0126111110.1186/s12882-025-04021-6Associations between intercurrent events and cardiorenal clinical outcomes in non-diabetic chronic kidney disease: a real-world retrospective cohort study in the United StatesChristoph Wanner0Johannes Schuchhardt1Chris Bauer2Meike Brinker3Frank Kleinjung4Tatsiana Vaitsiakhovich5Department of Clinical Research and Epidemiology, Comprehensive Heart Failure Center, University Hospital WürzburgMicroDiscovery GmbHMicroDiscovery GmbHBayer AG, Research & Development, Pharmaceuticals, Clinical DevelopmentAt the time of the study: Bayer AG, Medical Affairs & Pharmacovigilance, Pharmaceuticals, Integrated Evidence Generation & Business InnovationAt the time of the study: Bayer AG, Medical Affairs & Pharmacovigilance, Pharmaceuticals, Integrated Evidence Generation & Business InnovationAbstract Background Chronic kidney disease (CKD) is a global public health concern, with 50–70% of the burden attributed to non-diabetic aetiology. To expand CKD research, there is a need to identify novel surrogate endpoints preceding cardiorenal outcomes that are commonly used in CKD trials. This study explored and quantified associations between intercurrent events and clinical outcomes in patients with non-diabetic CKD to inform potential surrogate endpoints. Methods In this retrospective observational cohort study, adults with non-diabetic, moderate-to-severe CKD (stage 3/4) were identified in the US Optum Clinformatics® Data Mart healthcare claims database. Key outcomes were hospitalization for heart failure, kidney failure/need for dialysis, and worsening of CKD stage from baseline. Intercurrent events were defined as events observed in patient medical or pharmacy claims after the cohort inclusion date that either precluded a clinical outcome of interest or were associated with a modified risk of the respective outcome. Intercurrent events were selected a priori or by a data-driven exploratory approach. Associations between intercurrent events and clinical outcomes were explored and quantified using a Cox proportional hazards regression model. Results The study cohort included 504,924 patients. An outpatient heart failure diagnosis code was associated with an increased risk of consequent hospitalization for heart failure (hazard ratio [HR]: 12.92, 95% confidence interval [CI]: 12.67–13.17). CKD stage 4 diagnosis code was associated with an increased risk of kidney failure/need for dialysis (HR: 3.75, 95% CI: 3.69–3.81). Dispensation of potassium-removing resins and potassium-binding agents as an intercurrent event was associated with an increased risk of consequent worsening of CKD stage (HR: 4.83, 95% CI: 4.51–5.17). The estimated glomerular filtration rate decline in 295,174 patients with available laboratory data was associated with progressively increased risk of hospitalization for heart failure and kidney failure/need for dialysis. Conclusions Associations between intercurrent events and clinical outcomes in patients with non-diabetic CKD were investigated, quantified, and ranked using a large set of routinely collected data from a US claims database. Our approach may help identify novel surrogate endpoints that occur earlier in the disease course and could be leveraged as indicators of clinical outcomes in CKD research.https://doi.org/10.1186/s12882-025-04021-6Non-diabetic chronic kidney diseaseEnd-stage kidney diseaseKidney failureCardiovascularHeart failure hospitalizationIntercurrent event |
| spellingShingle | Christoph Wanner Johannes Schuchhardt Chris Bauer Meike Brinker Frank Kleinjung Tatsiana Vaitsiakhovich Associations between intercurrent events and cardiorenal clinical outcomes in non-diabetic chronic kidney disease: a real-world retrospective cohort study in the United States BMC Nephrology Non-diabetic chronic kidney disease End-stage kidney disease Kidney failure Cardiovascular Heart failure hospitalization Intercurrent event |
| title | Associations between intercurrent events and cardiorenal clinical outcomes in non-diabetic chronic kidney disease: a real-world retrospective cohort study in the United States |
| title_full | Associations between intercurrent events and cardiorenal clinical outcomes in non-diabetic chronic kidney disease: a real-world retrospective cohort study in the United States |
| title_fullStr | Associations between intercurrent events and cardiorenal clinical outcomes in non-diabetic chronic kidney disease: a real-world retrospective cohort study in the United States |
| title_full_unstemmed | Associations between intercurrent events and cardiorenal clinical outcomes in non-diabetic chronic kidney disease: a real-world retrospective cohort study in the United States |
| title_short | Associations between intercurrent events and cardiorenal clinical outcomes in non-diabetic chronic kidney disease: a real-world retrospective cohort study in the United States |
| title_sort | associations between intercurrent events and cardiorenal clinical outcomes in non diabetic chronic kidney disease a real world retrospective cohort study in the united states |
| topic | Non-diabetic chronic kidney disease End-stage kidney disease Kidney failure Cardiovascular Heart failure hospitalization Intercurrent event |
| url | https://doi.org/10.1186/s12882-025-04021-6 |
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