Kidney lesions in the form of focal segmental glomerulosclerosis (FSGS) and glomerulopathy associated with obesity are found in very obese patients. Weight loss has favorable effects on this disease (3).

In obese patients, kidneys show various nonspecific structural changes. The main characteristic of glomerulopathy associated with obesity is glomerulomegaly, which precedes the occurrence of pronounced proteinuria, i.e. before CKD. Besides glomerulomegaly, mesangial matrix proliferation, podocyte hypertrophy and glomerulosclerosis are also observed (4, 5). In this secondary form of FSGS, CKD progression follows slower course as compared with CKD progression in idiopathic forms of FSGS. Inflammatory response to initial lesions leads to development of secondary focal glomerulosclerosis and CKD progression. This ‘hyperfiltration theory’ leaves numerous dilemmas related to the fact that not all obese patients develop kidney disease and that there is no correlation between the degree of obesity and extension of glomerular structural alterations. Metabolically healthy obese individuals generally do not develop glomerulopathy associated with obesity (6). Accordingly, besides obesity, some genetic and environmental factors may also be involved in the onset and progression of CKD.

Adipose tissue is an endocrine organ involved in the pathogenic mechanisms that influence insulin resistance and vascular injury (7, 8).

Leptin is mostly a product of adipose tissue. In obese individuals, both the level of and resistance to leptin are increased. Leptin receptors are members of class I cytokine receptors, thus being considered responsible for triggering inflammatory process in the kidneys. Leptin action on kidney tubules leads to increased tubular sodium reabsorption and increased glomerular filtration (9). Glomerular hyperfiltration then influences insulin, angiotensin II and aldosterone. The leptin to adiponectin imbalance is associated with insulin resistance, cardiovascular disease, and glomerular injury. Decreased adiponectin level is the result of fetuin-A activity. Significant weight loss leads to leptin level decrease and adiponectin level increase with consequential albuminuria reduction (10, 11). In obese patients, the level of aldosterone is also elevated, independently of the rennin-angiotensin system. Activation of the rennin-angiotensin-aldosterone system results in glomerular hyperfiltration and increased tubular water and sodium reabsorption, pre-glomerular vasodilatation, and consequential hypertension.

Elevation of aldosterone level via various mechanisms results in podocyte injury. Central type obesity is associated with insulin resistance and hyperinsulinemia, as well as an increased prevalence of diabetes mellitus. The interleukin-6 production in visceral adipose tissue is increased, leading to the state of systemic inflammation (12).

Obese persons suffer from intestinal microflora impairments that result in the release of inflammatory factors into the intestine, impaired intestinal homeostasis, and increased inflammatory response in patients with CKD (13). In CKD, inflammation acts directly on the migration and activation of immune cells in adipose tissue, along with proinflammatory adipocyte activation. The presence and function of intestinal flora are to be regulated by restriction diet, drugs and other potential modes of obesity treatment.

Obesity research has instigated interest in ectopic lipids accumulated in non-adipose tissue. Ectopic lipids have been related to structural and functional changes in mesangial cells, podocytes and proximal tubular cells, and thus to the development of kidney disease associated with obesity (14). Recent studies have been focused on developing appropriate methods to monitor ectopic lipid metabolism and their influence on obesity complications.

Obesity poses a major problem in the world today. Public health systems have created various programs for obesity prevention and healthy lifestyle promotion. Obesity is a chronic disease that is difficult to treat. In CKD patients, weight loss results in decreased glomerular hyperfiltration and proteinuria, while acting favorably on arterial hypertension, lipid metabolism impairments, insulin resistance, and inflammation (15, 16). Low-calorie diet has been demonstrated to reduce fetuin-A level, along with increasing the level of adiponectin and preventing podocyte injury.

With low-calorie diet, a major problem is maintaining body weight reduction. Using drugs such as orlistat or sibutramine in combination with low-calorie diet and enhanced physical activity may lead to a number of complications, in particular in patients at a high cardiovascular risk. In patients undergoing operative procedures for the treatment of obesity, it can improve their kidney function and slow down progression of the existing CKD. Although surgical approach reduces the risk of diseases associated with obesity, the procedure itself is associated with an increased risk of acute renal failure (17, 18).

Drugs acting on the rennin-angiotensin-aldosterone system can also be used in the treatment of obesity in CKD patients.

Inhibitors of the rennin-angiotensin system decrease intraglomerular pressure and thus podocyte injury. Since hyperaldosteronism favors development of hyperfiltration, podocyte injury and inflammatory response, aldosterone inhibitors have a renoprotective effect. Aldosterone induced fibrosis is suppressed by aldosterone inhibitors. Aldosterone inhibitors with angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers result in proteinuria reduction but do not improve kidney function. There are experimental studies investigating the potential modes of acting on the intracellular lipid metabolism because reduced lipid accumulation decreases glomerular injury (19).

In spite of numerous studies, the key factor (process) influencing kidney function in obese patients has not yet been identified.

The aim of future research is establishment of novel non-pharmacological procedures to improve kidney function. Previous epidemiological studies have demonstrated significant gender and ethnic differences in the incidence and prevalence of obesity, CKD and end-stage chronic renal failure, which can be explained by genetic and environmental factors.

Additional explanations are needed concerning the action of probiotics, postbiotics and diet on inflammation and metabolic impairments, and so are studies of the association of sleep apnea, hypoxia and CKD (20). These patients require individualized therapeutic approach.

As prevention is better than cure, favorable lifestyle modifications in children to prevent development of obesity should come first.