Bidirectional association between depression and diabetic nephropathy by meta-analysis

PLOS ONE RESEARCH ARTICLE Bidirectional association between depression and diabetic nephropathy by meta-analysis Tingting Fang ID1,2*, Qiuling Zhang3, Zhiguo Wang1, Jun-Ping Liu1,4,5* 1 Institute of Ageing Research, Hangzhou Normal University, School of Basic Medicine, Hangzhou, Zhejiang Province, China, 2 School of Public Health, Hangzhou Normal University, Hangzhou, Zhejiang Province, China, 3 Department of Endocrinology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang Province, China, 4 Monash University Department of Immunology and Pathology, Central Clinical School, Faculty of Medicine, Prahran, Victoria, Australia, 5 Hudson Institute of Medical Research, Clayton, Victoria, Australia a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 * (TF); (JPL) Abstract Background OPEN ACCESS Citation: Fang T, Zhang Q, Wang Z, Liu J-P (2022) Bidirectional association between depression and diabetic nephropathy by meta-analysis. PLoS ONE 17(12): e0278489. https://doi.org/10.1371/journal. pone.0278489 Editor: Donovan Anthony McGrowder, The University of the West Indies, JAMAICA Received: June 6, 2022 Accepted: November 16, 2022 Published: December 20, 2022 Copyright: © 2022 Fang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: If the paper is accepted, we can provide data extracted from the included literature. Funding: This work was supported by grants from the National Key Research and Development Program of China (2018YFC2000100, and 2021ZD0202402), the National Natural Science Foundation of China (91949207, 82130044, 92149302, 91849124, and 81871112), and the Victorian Government’s Operational Infrastructure Support Program of Australia. Studies suggested that the association between depression and diabetic nephropathy may be bi-directional, but this hypothesis remains investigating. In this meta-analysis, the bidirectional relationship between depression and diabetic nephropathy was investigated. Methods A search for the publications on depression and diabetic nephropathy in the databases of PubMed, Web of science, and Embase from the earliest available to August 2022 was conducted. Two sets of pooled risk estimates were calculated using random effects models: diabetic nephropathy predicting depression and depression predicting diabetic nephropathy. Cross-sectional studies were assessed using Agency for Healthcare Research and Quality (AHRQ), cohort and case-control studies were assessed using Newcastle-Ottawa Scale (NOS). Result Of the 974,121 patients in 30 clinical studies, 24 studies met eligibility for diabetic nephropathy predicting onset of depression, representing 28,438 incident cases. The other 6 studies met criteria for depression predicting onset of diabetic nephropathy, representing 945,683 incident cases. The pooled odds ratio (OR) of diabetic nephropathy predicting depression was 1.46 (95% CI 1.27–1.67). The OR of depression predicting diabetic nephropathy was 1.22 (95% CI 1.13–1.31). Conclusion This meta-analysis shows that the relationship between depression and diabetic nephropathy may be bidirectional. Diabetic nephropathy may be a predictor of depression, and depression may also be an indicator of diabetic nephropathy. The mechanisms underlying PLOS ONE | https://doi.org/10.1371/journal.pone.0278489 December 20, 2022 1 / 15 PLOS ONE Competing interests: Authors declare no conflict of interest. Bidirectional association between depression and diabetic nephropathy the bidirectional relationship need to be further investigated and interventions of the comorbidity of depression and diabetic nephropathy need be studied in clinical practice. Introduction The global disease diabetes imposes threat to many aspects of public health. From 2005 to 2015, the cases of diabetes increased from 333 million to 435 million, predicting 439 million diabetics worldwide by 2030 [1, 2]. Of a variety of microvascular and macrovascular complications, including blindness, kidney disease, and lower limb amputation, diabetic nephropathy (DN) is the most common microvascular complication of diabetes. In the United States, the number of patients with end-stage renal failure (ESRD) due to DN increased from 40,000 to 50,000 between 2000 and 2014 [3]. Compared with the developed countries, greater burden of chronic kidney disease due to diabetes was in developing countries [4]. In the past decades, the occurrence of DN in China increased dramatically, with 24.3 million patients suffering from diabetic kidney disease in 2016 [5]. Studies showed that 95% of diabetics developed kidney injury after 10 years, 35% progressed to end-stage kidney disease after 5 years, and 18% died of kidney failure after 20 years [6]. In addition to the organic complications, diabetes underpins severe mental disorders such as depression and anxiety, the prevalence of depression was doubled in type 2 diabetics compared with subjects without diabetes [7]. Depression is a most common mental disorders, recently dramatically increased worldwide [1]. Depression is associated with unhealthy behaviors such as smoking, lack of exercise, and calorie intake, reducing life quality and diabetes self-care ability [8–10]. Depression-related pathophysiological mechanisms include dysregulation of hypothalamic-pituitary-adrenalimmune (HPAI) axis and activation of pro-inflammatory cytokines, potentially resulting in insulin resistance and increased risk of diabetes [9, 11]. The present study was undertaken to systematically review the reported data on DN and depression by performing meta-analysis. We found that DN and depression coexist as comorbidity developing shared risk of intimately influencing each other [12]. Research question • Whether diabetic nephropathy is a risk factor of depression? • Whether depression is a risk factor of diabetic nephropathy? • Is there a bidirectional relationship between diabetic nephropathy and depression? Methods We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) checklist (S1 Checklist) [13], and registered in the international prospective register of systematic reviews (PROSPERO) under the registration number CRD42022357342. Inclusion and exclusion criteria Included in the analysis were those that met the following criteria: (1) the study design was a cohort, case-control, cross-sectional study; (2) contained DN and depression (depressive disorders and symptoms, not only the syndrome of major depression); (3) reported odds ratios PLOS ONE | https://doi.org/10.1371/journal.pone.0278489 December 20, 2022 2 / 15 PLOS ONE Bidirectional association between depression and diabetic nephropathy (ORs), relative risks (RRs) or hazard ratios (HRs) with corresponding 95% confidence (...truncated)