BLOGS | World Kidney Day: Promoting Awareness of the Link Between Obesity & Kidney Disease
World Kidney Day: Promoting Awareness of the Link Between Obesity & Kidney Disease
Authors: Connie Rhee and Kamyar Kalantar-Zadeh
University of California
Irvine Division of Nephrology and Hypertension
March 9th, 2017 commemorates World Kidney Day, a global campaign to promote awareness of the critical importance of healthy kidneys. The theme of this year’s World Kidney Day is “Kidney Disease and Obesity: Healthy Lifestyle for Healthy Kidneys.”
It is commonly accepted that obesity is associated with many comorbidities, including cardiovascular disease, type 2 diabetes, hypertension, liver disease and a number of cancers. Less well-known is the link with renal health, yet obesity is a major risk factor for the development of de novo chronic kidney disease (CKD), which affects approximately 10% of the global population, and leads to heightened risk of cardiovascular disease and early death. Left untreated, CKD patients may eventually progress to end-stage renal disease (ESRD), which is associated with a 7-to-10 fold higher mortality risk compared to the general population.
There are multiple pathways by which obesity contributes to the development of CKD. Excess fat mass may indirectly lead to kidney damage by augmenting risk of type 2 diabetes, hypertension, and atherosclerosis, all of which are major risk factors for CKD. Obesity may also have direct pathophysiological effects on kidneys by altering (i) renal hemodynamics, (ii) inflammatory milieu, and (iii) adipokine (i.e., cytokines secreted by adipose tissue) and growth factor production. First, obesity may lead to increased expansion of the kidneys’ mesangial matrix and metabolic demand, resulting in glomerular hyperfiltration, hypertrophy, and hypertension and subsequent glomerulosclerosis and proteinuria (i.e., markers of kidney scarring and damage). Second, adipocytes may directly synthesize pro-inflammatory and pro-atherogenic cytokines such as tumor necrosis factor-alpha and interleukin-6 that may be implicated in the development of CKD. Third, obesity also leads to greater production of the adipokine, leptin, which has been shown to increase oxidative stress, sympathetic nervous system activity, glomerulosclerosis, renal fibrosis, and proteinuria. In contrast, lower levels of another adipokine, adiponectin, shown to reduce podocyte dysfunction and permeability to albumin, are typically observed in obesity. Fourth, excess fat may stimulate production of growth and hormonal factors that promote kidney damage, such as transforming growth factor-beta and renin-angiotensin.
Epidemiologic data also support a strong link between obesity and kidney disease. In the US, long-term follow up of 2585 participants in the Framingham Offspring Study cohort without pre-existing kidney disease showed that incrementally higher levels of body mass index (BMI) (i.e., +1-standard deviation of BMI) were associated with a 23% higher risk of developing CKD (defined as an estimated glomerular filtration rate [eGFR] <59 and <64 ml/min/1.73m2 in men and women, respectively) after a mean follow-up of 19 years. Data from over 300,000 patients in the Northern California Kaiser Permanente system has also shown that those with overweight status or class I, II, and III obesity had a 1.9, 3.6, 6.1, and 7.1-times higher risk of developing ESRD respectively, compared to those of normal weight. Finally, in a large population-based study of 3.4 million US veterans with normal baseline kidney function, those with obesity experienced a faster decline in kidney function, particularly among those of older age.
Large population-based studies of international cohorts also corroborate a potent association between obesity and kidney disease. In a study of over 105,000 Japanese adults with normal kidney function, incrementally higher BMI levels were associated with an increasingly higher risk of new-onset CKD, albeit at different BMI thresholds among men vs. women (>23.0 and >27.0 kg/m2, respectively). Among approximately 1.2 million Israeli adolescents (i.e., age 17 years) who underwent examination for military service fitness, those who were overweight or had obesity (85th to 95th and ≥95th percentiles of BMI, respectively) had respectively a 3-fold and 7-fold higher risk of developing ESRD after a mean follow up 26 years. While a study of >185,000 Austrian participants did not confirm an association between overweight/obesity status with development of ESRD, a meta-analysis comprised of 25 cohorts, 3 cross-sectional studies, and 19 case-control studies showed that individuals who were overweight or had obesity had respectively a 40% and 83% higher risk of developing CKD identified by clinical diagnostic codes. In another meta-analysis of patients with stage 3 to 5 CKD, re-analysis of the largest available study showed a graded association between higher BMI classes with risk of progression to ESRD.
By the time that kidney disease is identified, the sequelae of many causes of CKD cannot be reversed. However, as a potentially modifiable risk factor, reducing obesity may be a major target for preventing CKD and its ensuing complications. For example, in a study of 233 patients with severe obesity who underwent bariatric surgery, there was a statistically significant improvement in kidney function among those with obesity and CKD approximately one year after surgery. In another study of 255 patients with morbid obesity and type 2 diabetes, one year after bariatric surgery, those who experienced reductions in BMI experienced normalization of urine protein levels. However, further research including clinical trials studying the causal impact of both surgical and non-surgical interventions upon risk of CKD and ESRD is needed.
In summary, a large body of evidence has shown that obesity is a major risk factor for kidney disease and its complications. World Kidney Day provides us with a needed platform and opportunity to catalyze further awareness, education, policy change, and research on how obesity leads to CKD, and how this risk can be ameliorated. By targeting obesity and CKD as two of the dominant public health problems in contemporary society, we have the opportunity to improve the health and survival of a large proportion of the world’s population.
An earlier version of this article appeared in Rhee CM, Ahmadi SF, Kalantar-Zadeh K. The dual roles of obesity in chronic kidney disease: a review of the current literature. Current opinion in nephrology and hypertension. May 2016;25(3):208-216.
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