Citation: Tangri, N., Peach, E. J., Franzén, S., Barone, S., & Kushner, P. R. (2023). Patient management and clinical outcomes associated with a recorded diagnosis of stage 3 chronic kidney disease: the REVEAL-CKD study. Advances in Therapy, 40(6), 2869-2885.
Introduction
Chronic kidney disease (CKD) is a major public health concern [1], and its prevalence is rising due to risk factors such as type 2 diabetes and hypertension [2]. Despite the high prevalence and the associated risks of complications and mortality, research studies related to the associations between CKD diagnosis, patient management, and their clinical outcomes remain limited.
The purpose of this study was to investigate the prevalence and consequences of undiagnosed stage 3 CKD in large populations across several countries. Here, they investigated associations between a recorded diagnosis of CKD and the medical management of, and clinical outcomes in, adult patients in the USA with estimated glomerular filtration rate (eGFR) measurements indicative of stage 3 CKD.
This multinational retrospective cohort study was conducted across 35 healthcare organizations in the USA using data extracted from the TriNetX database, which integrates electronic medical records. The inclusion criteria for this study were patients aged over 18 years with two consecutive eGFR measurements indicative of stage 3a/3b CKD, recorded 90 days apart (up to a maximum of 730 days), between 1 January 2015 and 31 December 2020. All patients had at least 12 months of continuous data in the database prior to the first qualifying eGFR measurement. Patients with a history of solid organ transplant, renal replacement therapy (RRT), or evidence of advanced CKD (stages 4, 5, or end-stage renal disease) recorded before the second qualifying eGFR measurement were excluded from the study.
Demographic and clinical characteristics of the patients were presented descriptively. The incidence of CKD management practices and treatment patterns was reported as events per person-year with exact Poisson confidence intervals (CIs) and compared between the 180 days pre- and post-diagnosis using a Poisson regression model. The annual eGFR decline before and after CKD diagnosis was estimated by fitting linear regression models with time to diagnosis as the only independent variable for the 2-year period before and up to the 2-year period after CKD diagnosis. Estimated annual eGFR decline was summarized using medians and compared before and after CKD diagnosis using the Wilcoxon rank test. Moreover, associations between diagnostic delay and post-diagnosis event rates were assessed using a Cox regression model, with diagnostic delay defined as the time from 6 months after the second qualifying eGFR measurement to CKD diagnosis. All statistical analyses were performed in R version 4.0.2, with the significance level at 0.05.
The study included data from 26,851 patients. Following diagnosis, significant increases were observed in the prescribing rates of recommended medications, including angiotensin-converting enzyme (ACE) inhibitors (rate ratio [95% confidence interval]: 1.87 [1.82–1.93]), angiotensin receptor blockers (ARBs) (1.91 [1.85–1.97]), and mineralocorticoid receptor antagonists (MRAs) (2.23 [2.13–2.34]). The annual eGFR decline significantly reduced after CKD diagnosis, from 3.20 ml/min/1.73 m² before diagnosis to 0.74 ml/min/1.73 m² after diagnosis. Additionally, delayed diagnosis (by 1-year increments) was associated with an increased risk of CKD progression to stages 4/5 (hazard ratio [95% confidence interval]: 1.40 [1.31–1.49]) and kidney failure (1.63 [1.23–2.18]).
This study found that a recorded CKD diagnosis was associated with significant improvements in CKD management and monitoring practices, as well as reduced eGFR decline. This represents an important first step in reducing the risk of CKD disease progression and minimizing its adverse clinical outcomes.
Critique
This study provides valuable insights into the importance of early CKD diagnosis and its impact on patient management and outcomes. A major strength is its large, multinational sample size, collecting data from 26,851 patients across 35 healthcare organizations, which enhances the generalizability of the findings. The use of a robust database (TriNetX) and standardized inclusion criteria ensures consistency and reliability in the data. Additionally, the study employs complex statistical methods, such as Poisson regression and Cox regression models, to assess associations and event rates, providing comprehensive analyses. The observed improvements in prescribing rates of recommended medications and the reduced annual eGFR decline highlight the potential positive outcomes of timely CKD diagnosis and relevant intervention.
However, the study has some limitations. First, it is a retrospective study, which inherently limits the ability to establish cause-and-effect links. Second, despite the large sample size, the study is restricted to healthcare organizations within the USA, which may limit its applicability to other healthcare systems with different management practices and patient populations. Third, the reliance on electronic medical records like TriNetX could introduce biases or inaccuracies if data were incomplete or incorrectly recorded. Additionally, while the study highlights the association between delayed diagnosis and adverse outcomes, it does not explore in detail the underlying reasons for diagnostic delays, which could have practical implications for improving early detection of CKD. Finally, the study lacks consideration of patient adherence to prescribed treatments, which could influence their observed overall clinical outcomes. Despite these limitations, the study serves as a critical step toward understanding CKD management and underscores the importance of timely diagnosis in improving clinical outcomes among CKD patients.
Recommendations
Future studies should consider conducting prospective studies to better establish cause-and-effect relationships between early CKD diagnosis and improved patient outcomes. Additionally, expanding the study population to include healthcare systems outside the USA would enhance the generalizability of the findings and allow for comparisons across diverse healthcare settings in different ethnic backgrounds. It would also be valuable for future research to explore the underlying reasons for diagnostic delays, such as healthcare access, provider awareness, and patient behaviour, as these factors could inform strategies for improving early detection. Furthermore, investigating patient adherence to prescribed treatments and its impact on clinical outcomes would provide a more comprehensive understanding of how management practices influence CKD progression. These steps would provide deeper insights into CKD management and offer actionable strategies to reduce disease progression and improve patient outcomes in the future.
Conclusion
In conclusion, this study highlights the significant impact of early CKD diagnosis on patient management and clinical outcomes. The findings underscore the importance of timely diagnosis in improving medication prescribing practices, slowing eGFR decline, and reducing the risk of CKD progression and related complications. While the study has some limitations, iit provides valuable insights into CKD management. Future research, particularly prospective studies and those exploring factors contributing to diagnostic delays and patient adherence, will be essential in refining strategies for early detection and treatment of CKD, eventually leading to better patient outcomes and more effective management of the disease.
References
1. Jager, K. J., Kovesdy, C., Langham, R., Rosenberg, M., Jha, V., & Zoccali, C. (2019). A single number for advocacy and communication—worldwide more than 850 million individuals have kidney diseases. Nephrology Dialysis Transplantation, 34(11), 1803-1805.
2. Gansevoort, R. T., Correa-Rotter, R., Hemmelgarn, B. R., Jafar, T. H., Heerspink, H. J. L., Mann, J. F., … & Wen, C. P. (2013). Chronic kidney disease and cardiovascular risk: epidemiology, mechanisms, and prevention. The Lancet, 382(9889), 339-352.
