Introduction
The increasing prevalence of obesity has been a major global public health threat. The National Institutes of Health and World Health Organization guidelines define individuals with body mass index (BMI) ≥25 kg/m2 as overweight and those with BMI ≥30 kg/m2 as obese. Worldwide, more than 1.9 billion 18 years and older population were overweight and among these, over 650 million were obese in 2016 (1). In the United State, the prevalence of obesity was 39.8% and affected about 93.3 million of adults in 2016 according to the Centers for Disease Control and Prevention (2). Obesity is a well-known risk factor for mortality, morbidity, and disability, and has been linked to a rising number of metabolic and cardiovascular comorbidities, such as diabetes mellitus and hypertension (3). It also has a direct impact on the development of chronic kidney disease (CKD) and end-stage renal disease (ESRD).
Chronic kidney disease (CKD) is a condition identified as the gradual loss of kidney function over time. CKD refers to all 5 stages of kidney damage, from very mild damage in Stage 1 to complete kidney failure (ESRD) in Stage 5. The stages of kidney disease are based on the eGFR level, which is a blood test that measures the efficiency of kidneys filter waste from the blood. In addition, microalbuminuria and proteinuria are also markers of CKD and they are used to predict the progression of CKD. Currently, CKD affects 30 million people in the U.S. (15% of the adult population). Moreover, more than 660,000 Americans are being treated for kidney failure, or ESRD (4).
The association between obesity and the rising rates of diabetes and hypertension is well-understood and the pathways that draw the connection between obesity and these two conditions are well-established. This is important since diabetes and hypertension are the leading causes of CKD. Moreover, a number of observational studies suggest that obesity is an independent risk factor for CKD patients with or without those comorbidities. Compared with patients with body mass indexes (BMIs) <25 kg/m2, patients with severe obesity have a 341% increased risk of developing ESRD (5).
Weight loss is an effective tool in the treatment of cardiovascular disease and type 2 diabetes. However, the consequence of intentional weight loss for patients with established renal damage, independently of diabetes and hypertension control, remains unknown. This review will provide a summary of the pathophysiology, review of literature, discussion of important findings, existing controversies about the effect of weight loss in patients with chronic kidney disease.
Background
Pathophysiology
Numerous observational studies have shown that there is an association between obesity and both the development and the progression of CKD (6). Excessive body fat leads to a series of metabolic changes which negatively affect different body systems including the kidney. The exact mechanisms underlying how obesity may cause or aggravate CKD remain unclear. Current scientific evidence suggests that the pathophysiology associated with obesity-related kidney disease may be multifactorial. Several contributing factors of kidney damage have been proposed (6).
The main contributing factors are metabolic effects, which may directly or indirectly affect renal structure and function These include inflammation, insulin resistance, and adipokine dysregulation. Some of the detrimental renal consequences of obesity may be mediated by downstream comorbidities such as diabetes mellitus or hypertension. However, adipose tissue may impact the kidney function directly. Specifically, the endocrine activity of the adipose tissue can affect renal function through the production of adiponectin, leptin, and resistin. Adipokine dysregulation induces the development of inflammation, oxidative stress, abnormal lipid metabolism, activation of the renin-angiotensin-aldosterone system, and increased production of insulin and insulin resistance (6).
These negative consequences of metabolic changes led to specific disorders in the kidneys, including “ectopic lipid accumulation and increased deposition of renal sinus fat, the development of glomerular hypertension and increased glomerular permeability caused by hyperfiltration-related glomerular filtration barrier injury, and ultimately the development of glomerulomegaly, and focal or segmental glomerulosclerosis” described by Kovesdy et al. All these disorders underlie the higher risk of CKD reported in the observational studies (6).
Another theory is that chronic kidney damage may be caused by renal lipotoxicity, which is the increased influx of lipids into the kidney. The hypothesis states that the adipose tissue has a limited expansion capability, and once this limit is reached, the adipose tissue cannot store any more lipids and will thus release them into the bloodstream. The intracellular accumulation of free fatty acids and triglycerides in renal glomerular and tubulointerstitial cells results in chronic kidney injuries (7).
