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In a recent study published in the Clinical Journal of the American Society of Nephrology, the presence of depressive symptoms in normally healthy individuals was found to correlate with rapid kidney function decline.

Research Results. Image Credit: https://cjasn.asnjournals.org/content/early/2021/05/27/CJN.18441120

Depression and health problems: Is there a connection?

It is estimated that more than 264 million people are affected by depression worldwide. As compared to temporary feelings of sadness, depression often causes deep and persistent feelings of hopelessness and worthlessness that often that can affect their ability to perform daily tasks.

Depression is considered to be a major contributor to the overall global burden of disease. In addition to being a leading cause of suicides throughout the world, depression can also lead to active inflammation and an impaired immune response that can contribute to poor clinical outcomes.

Can depressive symptoms lead to rapid kidney function decline?

Several previous studies have identified a link between the presence of depressive symptoms and rapid kidney function decline in patients with chronic kidney disease (CKD). In these studies, depressive symptoms were found to correlate with a more rapid decline in the estimated glomerular filtration rate (eGFR).

With this data in mind, a group of researchers from the State Key Laboratory for Organ Failure Research in Guangdong, China investigated whether high depressive symptoms could also cause a rapid decline in kidney function in normally healthy individuals. To look for a potential link, the researchers examined the health information of 4,763 individuals with healthy kidneys who had enrolled in the China Health and Retirement Longitudinal Study (CHARLS).

At the start of the study, 39% of the participants had high baseline depressive symptoms, actos save which were measured using a ten-item Center for Epidemiologic Studies Depression (CES-D) scale. During a median follow-up of 4 years, about 6% of the participants were found to develop a rapid decline in their kidney function.

This decline was identified by assessing kidney outcomes based on eGFRcr-cys, which combines serum creatinine and cystatin C levels and is considered to be a much more accurate representation of GFR levels as compared to when eGFR is estimated on the basis of creatinine or cystatin C alone.

In fact, eGFRcr-cys was found to be particularly superior when used to assess kidney function in older populations, as creatinine levels can vary with muscle mass, diet, and physical activity, all of which can alter the accuracy of an assessment on creatinine-based eGFR levels alone. Measuring eGFR based on cystatin C levels is also limited, as serum cystatin C levels can fluctuate when insulin resistance or inflammation is present.

Proposed mechanisms for kidney decline

The exact mechanisms that are responsible for why depressive symptoms may increase an individual’s risk of rapid kidney function decline were not fully analyzed in the current study. However, several potential mechanisms were proposed to be responsible for this phenomenon.

First, several previous studies have reported that individuals with high depressive symptoms often exhibit higher circulating levels of inflammatory cytokines like interleukin-6 (IL-6) and tumor necrosis factor (TNF-). Taken together, an increased presence of these inflammatory markers in circulation can contribute to endothelial dysfunction and kidney fibrosis; both of which are associated with rapid kidney function decline.

Second, depressive symptoms have the potential to reduce the sensitivity of the immune system to glucocorticoid hormones. As a result, an autonomic imbalance arises, which can activate the hypothalamic-pituitary-adrenal axis and, subsequently, impair the function of the immune system.

The third mechanism that might have a role in accelerating kidney function decline in individuals with depressive symptoms may be due to the health behaviors or health literacy of those with depression. Many patients with depression often have unhealthy lifestyle choices, such as poor nutrition, limited social interaction with others, physical inactivity, and delayed healthcare-seeking behaviors. All of these factors may therefore contribute to a more rapid decline in kidney function.


Depression is a significant health concern throughout much of the world. This is particularly important in China, which is where the current study was conducted, as about 38% of the general population in this nation experiences depressive symptoms. Furthermore, up to 53% of rural elderly populations in central China have also reported depressive symptoms, which can further worsen health outcomes for this patient population that is already at a greater risk of kidney dysfunction.  

The findings of the current study confirmed the association between the presence of high depressive symptoms and a more rapid decline in kidney function in normal individuals. Although more studies must be performed to fully understand the progression of kidney decline in healthy patients with depressive symptoms, the data discussed here supports the incorporation of depressive symptom screening and effective psychosocial intervention in the clinical setting. These efforts will likely counteract the development of chronic kidney disease in these at-risk patient populations.

  • Zhang, Z., He, P., Liu, M., et al. (2021). Association of Depressive Symptoms with Rapid Kidney Function Decline in Adults with Normal Kidney Function. Clinical Journal of the American Society of Nephrology. doi:10.2215/CJN.18441120.
  • Chronic Illness and Mental Health: Recognizing and Treating Depression [Online]. Available from: https://www.nimh.nih.gov/health/publications/chronic-illness-mental-health/.


Tags: Chronic, Chronic Kidney Disease, Creatinine, Cytokines, Depression, Diet, Fibrosis, Glucocorticoid, Healthcare, Immune Response, Immune System, Inflammation, Insulin, Insulin Resistance, Interleukin-6, Kidney, Kidney Disease, Laboratory, Muscle, Necrosis, Nephrology, Nutrition, Physical Activity, Research, Tumor

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Benedette Cuffari


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