Obesity promises to be the No. 1 problem of the new millennium. The prevalence of this pathology and the many triggers, with which it is associated are increasing in every age group. And there is increasing evidence that along with the cardiovascular system, other organs become vulnerable even in the absence of arterial hypertension or type 2 diabetes mellitus. For example, extra pounds can appear against the background of a decrease in the rate of glomerular filtration. You will learn why the kidneys are also involved in the obesity process in this article.
- Leptin as a mediator of target organ damage.
- Pathogenesis of leptin kidney disease.
Leptin as a mediator of target organ damage
Abdominal obesity activates the synthesis of adipokines in adipose tissue. These are active mediating biochemicals that also damage renal tissue, which automatically forms obesity-associated chronic kidney disease and contributes to its progression.
Such mediators, affecting target organs include leptin. Patients who are overweight develop resistance to this bioactive substance. And this automatically causes his hypersynthesis. As a result, the excess hormone injures the vascular wall, myocardium and nephrons. It is leptin that is the trigger of renal fibrogenesis, which develops as a result of the activation of growth factor and receptors to it, localized in the membranes of endothelial mesengial cells.
The endothelium rather rapidly acquires the ability to express growth factor, a component of leptin-initiated dysfunction of the inner lining of blood vessels. In obese patients, such dysfunction becomes generalized, which is of great importance in the pathogenesis of kidney damage.
Critically, such pathogenesis is asymptomatic and exists for quite a long time. At the same time, chronic kidney disease against the background of obesity provokes the development of the terminal stage of renal failure and becomes the cause of disability. In this case, leptin becomes a kind of biomarker that can detect kidney damage at early stages.
Pathogenesis of leptin kidney disease
Based on clinical studies, which involved 110 obese patients totaled clinically and laboratory examination. Lipid, glucose, creatinine, urea, and C-reactive protein levels in the bloodstream were determined in a standard biochemical manner. BMI was calculated by Ketle formula: body weight in kilograms divided by height squared. Insulin resistance index, glomerular filtration rate by a special formula were also calculated.
Microalbuminuria concentration was measured in the morning portion of urine. Levels of insulin and leptin were calculated by enzyme immunoassay. All obese patients had no data for kidney damage.
The formation and progression of obesity-associated chronic kidney disease may be due to the damaging effect of leptin on renal tissue structures. In this study, a significant correlation of high leptin concentration with low glomerular filtration rate was found. It is a negative correlation fixing pathological association between these parameters.
At the same time, minimum glomerular filtration rate was found to correlate with increased microalbuminuria. Namely, MAU serves as a reliable marker of renal dysfunction and generalized microvascular lesion in combination with cardiovascular risk.
It turns out that microalbuminuria in first- or second-degree arterial hypertension is about 20%, and in combination with overweight it doubles. Thus, the assumption that there is a direct link between hyperleptinemia and high values of microalbuminuria and decrease in glomerular filtration rate is confirmed. In obesity, leptin can provoke collagen synthesis by mesangial cells and fibrogenesis in renal nephrons. In addition, at the same time there is a stimulation of proliferation of endothelial cells and smooth muscles, which also indirectly provokes glomerular hypertrophy.
They established the relationship between microalbuminuria and glomerular filtration rate, which proved the presence of endothelial dysfunction, stimulation of fibrogenesis in the renal glomerules and the associated criminal decline in renal function. It turns out that in obese patients microalbuminuria is completely controlled by hyperlipidemia and hyperleptinemia.
The inverse relationship of leptin concentration with an increase in urinary microalbuminuria suggests a traumatic effect of adipokines on the glomerular apparatus of the kidney. It should be emphasized that a marker of nephron damage, which is considered to be microalbuminuria, is also revealed in patients with optimal level of glomerular filtration.
Thus, if we talk about stages of chronic kidney disease with projection on glomerular filtration rate, an inverse correlation between these indices will be noticeable. That is, the higher the patient’s body weight, the lower the stages of chronic kidney disease.
According to the results of the study we can say that:
- Early in the development of obesity, patients without clinical renal symptomatology have an increase in microalbuminuria in 30% of cases and a low glomerular filtration rate, which is associated with hyperleptinemiaю
- Obesity is accompanied by high microalbuminuria, hyperleptinemia and low glomerular filtration rate, which is explained by increased fibrogenesis and endothelial dysfunction, which has a traumatic effect on the glomeruli of the kidneysюю
- The use of lipid and carbohydrate metabolism levels as biomarkers of kidney damage in obesity in the early stages of the pathological process in combination with the index of insulin resistance, serum leptin indices are promising for the diagnosis of kidney damage in overweight.
Today, research on the role of leptin in nephron damage and the development of chronic renal disease is at a very early stage. There is not enough data to draw global conclusions. But for pharmacologists it is valuable information in the light of the synthesis of new drugs capable of balancing leptin levels, and thus correcting its negative effect on target organs.