Part 3:Association Between Multimorbidity And Kidney Function Among Patients With Non-Dialysis-Dependent CKD

Contact: emily.li@wecistanche.com

Cistanche can improve Kidney Function

Discussion

The FKR study is an observational cohort study of Japanese patients with non-dialysis-dependent CKD under nephrologist care. This cohort includes approximately 4,500 outpatients with CKD stages

Abbreviations: eGFR, estimated glomerular filtration rate; CI, confidence interval.

Major comorbid conditions included hypertension, diabetes, dyslipidemia, prior cardiovascular disease, cancer, and bone fracture.

Adjusted using the final selected model, which included age, sex, underlying kidney disease, hypertension, diabetes mellitus, dyslipidemia, history of cardiovascular disease, body mass index, and urinary protein excretion, Variables relevant to the categories were excluded from each model.

Abbreviations: eGFR, estimated glomerular filtration rate; CI, confidence interval.

Adjusted using the final selected model, which included age, sex, underlying kidney disease, hypertension, diabetes mellitus, dyslipidemia, history of cardiovascular disease, body mass index, and urinary protein excretion.

G1-G5. A multivariable analysis revealed that lifestyle-related diseases, such as hypertension, diabetes mellitus, dyslipidemia, and a history of CVD, were independent factors associated with reduced kidney function. Interestingly, an independent linear association between the cumulative number of comorbidities and eGFR reduction was observed. The findings from this study provide a comprehensive understanding of demographics and highlight the importance of managing multimorbidity among patients with CKD under nephrologist care in Japan.

Cistanche can improve Kidney Function

Patients with advanced CKD stages were older, more likely to have diabetes mellitus and cancer, and more likely to have high blood pressure levels, coronary artery disease, heart failure, and PAD. These data demonstrate the high disease burden of chronic diseases among older adults with comorbidities associated with CKD. Comorbidities, including CVD, are a major source of morbidity and healthcare costs for hospitalized elderly patients21. Furthermore,

CKD influences diagnosis and treatment decisions for these other comorbidities22). Thus, early detection of CKD and appropriate management of chronic diseases may be a useful strategy to prevent adverse outcomes caused by these comorbidities.

A multivariable analysis revealed an independent association between reduced kidney function and comorbidities, including lifestyle-related disease and CVD risk factors. The high prevalence of cardiovascular risk factors in patients with advanced CKD suggests that the underlying cause of CKD may be a form of diffuse atherosclerotic vascular disease, as well as cardiac and other vascular diseases. This hypothesis is consistent with prior pathophysiological and epidemiological studies23,24. The strong association between CKD and CVD suggests not only that both conditions share risks but also that CKD itself may promote a complex cardiovascular risk condition5,25,26. Longitudinal investigations are needed to more fully explore this hypothesis.

Tonelli et al. assessed medical complexity using nine markers(including the number of comorbidities, number of prescription medications, presence of psychiatric disorders, number of types of physicians involved in each patient's care, and number of physicians involved in each patient's care) and found that patients with CKD had the highest complexity, leading to an increased risk of death. The authors concluded that intensive risk management is recommended for patients with CKD at high risk for comorbid CVD. However, such intensive management has a negative aspect, which may lead to complexity of care because of the increased number of medications. An increase in the number of medications can lead to adverse effects and reduced kidney function due to poor adherence12. Indeed, in our study, we found a significant dose-response relationship between the cumulative number of complications(especially cardiovascular complications) and reduced eGFR. These findings suggest that complications in patients with impaired kidney function are mainly due to increased cardiovascular burden, and therefore, an increase in the number of medications may have an unfavorable impact on kidney function through adverse effects and reduced adherence. A longitudinal study of our cohort needs to be further investigated to determine what practice patterns regarding medication use are protective formoutcomes.

Ethnic differences exist in terms of susceptibility to CVD. Previous epidemiological studies have found that Western populations have a higher incidence of ischemic heart diseases, such as myocardial infarction and angina pectoris27-29. The crude prevalence of prior ischemic heart disease in our cohort was 10.8%, similar to the 13.4% observed in the CKD-JACstudy in Japan but less than the 26.0% observed in the Chronic Renal Insufficiency Cohort study in the United States30,31). The previous stroke was found in 11.1% of patients in our cohort, similar to the CKD-JAC study(11.5%), but the prevalence of stroke in individuals with an eGFR 30-60 mL/min/1.73 m² in the German CKD cohort deviated significantly to 37.2%32). The incidence of CVD, including stroke, may be less common in Japanese patients with CKD compared with Caucasians. A prospective survey of our cohort will also provide new insights into ethnic differences in CVD burden among CKD populations.

Multivariable-adjusted models showed an inverse association between diabetes and reduced kidney function （eGFR<60 mL/min/1.73 m²）.To address multicollinearity, we performed a sensitivity analysis excluding diabetic nephropathy from the model, but the OR of diabetes for reduced GFR was not significant(OR,1.05,95% CI,0.85-1.30). We speculate that a possible explanation for these findings observed in this cross-sectional study is that the influence of diabetes may have been diluted by the uniqueness of the participants in this cohort, which was restricted to patients with CKD. Future longitudinal studies of this cohort will reveal the definitive association between diabetes and kidney function.

Our study has several limitations. First, we did not perform Cr clearance measurements or urine protein measurements through 24 h urine collection. However, given that routine practice is based on spot urinalysis, evidence-based opportunistic testing may be useful in real-world practice. Second, there is the possibility of misclassification of underlying kidney disease. Nevertheless, the biopsy diagnosis rate in our cohort was relatively high (37%); thus, a highly accurate estimate could be expected. Finally, this study is cross-sectional and cannot address causality. A longitudinal study of this cohort should elucidate the association between comorbidities and the prognosis of Japanese patients with CKD.

Cistanche can improve Kidney Function

Conclusions

In conclusion, CKD is associated with a higher prevalence of comorbid conditions. Importantly, patients with CKD are at a higher risk of comorbid CVD and require intensive monitoring and risk management. Based on these findings, emphasis should be placed on preventing adverse outcomes in patients with CKD through comprehensive multimorbidity risk management. We believe that this study could provide a better knowledge of demographics and multimorbidity among patients with CKD under nephrologist care in Japan.

Authors'Contributions

S.T. and T.N.contributed to the study design, acquisition of data, statistical analysis, interpretation of data, and drafting of the manuscript. H.H contributed to the study design, statistical analysis, interpretation of data, and drafting of the manuscript. K. T.and T.K. contributed to the critical revision of the manuscript and study supervision. All authors provided critical reviews of the manuscript and approved the final version.

Acknowledgments

The authors thank the participants in the FKR study, the members of the FKR Study Group, and all personnel at participating institutions involved in the study.

We thank Satoru Fujimi (Fukuoka Renal Clinic), Hideki Hirakata (Fukuoka Renal Clinic), Tadashi Hirano (Hakujyuji Hospital), Tetsuhiko Yoshida (Hamanomachi Hospital),Takashi Deguchi (Hamanomachi Hospital), Hideki Yotsueda (Harasanshin Hospital), Kiichiro Fujisaki (Iizuka Hospital), Keita Takae(apanese Red Cross Fukuoka Hospital), Koji Mitsuiki(Japanese Red Cross Fukuoka Hospital), Akinori Nagashima (Japanese Red Cross Karatsu Hospital),Ritsuko Katafuchi (Kano Hospital),Hidetoshi Kanai(Kokura Memorial Hospital), Kenji Harada(Kokura Memorial Hospital), Tohru Mizumasa (Kyushu Central Hospital), Takanari Kitazono (Kyushu University),Toshiaki Nakano (Kyushu University), Toshiharu Ninomiya(Kyushu University),Kumiko Torisu (Kyushu University), Akihiro Tsuchimoto (Kyushu University), Shunsuke Yamada (Kyushu University), Hiroto Hiyamuta (Kyushu University), Shigeru Tanaka (Kyushu University), Dai Matsuo(Munakata Medical Association Hospital),Yusuke Kuroki (National Fukuoka-Higashi Medical Center), Hiroshi Nagae (National Fukuoka-Higashi Medical Center), Masaru Nakayama (National Kyushu Medical Center), Kazuhiko Tsuruya (Nara Medical University), Masaharu Nagata(Shin-eikai Hospital),Taihei Yanagida(Steel Memorial Yawata Hospital), Shotaro Onaka (Tagawa Municipal Hospital). We thank Emily Woodhouse, Ph.D., from Edanz Group (https://en-author-services.edanz.com/ac)for editing a draft of this manuscript.

Cistanche can improve Kidney Function

Conflict of Interest

The authors declare that they have no relevant

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