OVERVIEW
Obesity-related glomerulopathy (ORG) refers to kidney disease caused by obesity. In patients with proteinuria due to obesity, renal biopsy reveals glomerular hypertrophy and focal segmental glomerulosclerosis (FSGS) lesions. Changes in renal function are characterized by increased renal blood flow and glomerular filtration rate.ORG requires comprehensive treatment, mainly weight loss, correction of insulin resistance, correction of local hemodynamic abnormalities in the kidneys, and the application of weight loss medications, or even surgical treatment, if necessary.
Etiology
The etiology of obesity-associated glomerulopathy is related to insulin resistance, renal hemodynamic changes, adipocytokines, lipotoxicity, oxidative stress, genetic background and environmental factors.
1. Insulin resistance
Obesity, hypertension, hyperlipidemia, hyperuricemia and hypercoagulability constitute the clinical syndrome of insulin resistance.
2. Hemodynamic abnormalities
Due to the activation of the renin-angiotensin system (RAS) and sympathetic nerves, angiotensin II contributes directly or indirectly to renal structural and functional impairment through hypertension, inflammation and abnormal lipid metabolism.
3. Adipocyte factors
Adipocytes secrete a series of inflammatory factors, which have toxic effects on glomerular podocytes, pericytes and endothelial cells; induce insulin resistance and promote the formation of atherosclerosis, thus directly or indirectly affecting the structure and function of the kidney.
4.Lipotoxicity
Hyperlipidemia is involved in the development of glomerulosclerosis by oxidizing low-density lipoprotein; it disrupts the dynamic balance of prostaglandins and thromboxanes in the kidney, affects glomerular hemodynamics and vascular permeability, and indirectly participates in glomerular injury. Hyperlipidemia also has a direct toxic effect on podocytes and promotes the production of proteinuria.
5. Heredity
Among ORG patients, 56.0% have a family history of obesity, 41.7% have a family history of hypertension, and 17.9% have a family history of diabetes mellitus.
6.Environment
Changes in dietary structure and living habits have led to a sudden increase in the incidence of obesity.
Symptoms
Patients with obesity, the onset of kidney disease is relatively insidious. 54.4% of the patients have no obvious clinical symptoms, mostly found in the physical examination of the urine test abnormalities. Clinical manifestations of proteinuria, mostly light and moderate proteinuria, large proteinuria (>3.5g/24h) only accounted for 10.0%. The amount of urinary protein in patients was correlated with the degree of obesity. In patients with body mass index (BMI) ≥35kg/m2, the incidence of massive proteinuria could be up to 30.8%. ORG patients had clinically massive proteinuria but hypoproteinemia was not obvious, and patients showing typical nephrotic syndrome (edema, hypoproteinemia) accounted for only 2.22%. About 44% of patients were associated with abnormal renal tubular function. Renal tubular damage is associated with renal ischemia due to the combined presence of hypertension and atherosclerosis.
Hypoxemia associated with sleep apnea can impair renal tubular function. Some patients have renal insufficiency, which progresses to end-stage renal insufficiency, and the vast majority of patients with ORG have one or more metabolic disorders. 87.8% have insulin resistance, and 76.7% have impaired glucose tolerance, with 68% having hypertriglyceridemia and 64.4% having reduced HDL levels.
Screening
BMI measurement, blood biochemical tests such as lipids, blood glucose, uric acid, urine routine, liver and kidney function, and renal biopsy.
Diagnosis
1. Meet the criteria of obesity, our standard is BMI>28kg/m2;
2. Urine routine for proteinuria with or without a small amount of microscopic hematuria, some patients may have renal insufficiency, often not accompanied by hypoproteinemia. Renal biopsy pathology suggests glomerular hypertrophy, focal segmental glomerulosclerosis or glomerulosclerosis. Other primary and secondary glomerular diseases are excluded.
Treatment
The main insulin sensitizers currently in clinical use are thiazolidinediones and biguanides (metformin).
Angiotensin-converting enzyme inhibitors (ACEI)/angiotensin II receptor antagonists (ARB) inhibit the activity of the renin-angiotensin system is an effective measure for controlling hypertension, correcting local hemodynamic abnormalities in the kidneys, decreasing proteinuria, attenuating inflammatory responses, and protecting renal function.
Central diet drugs can increase the utilization of central nervous system anorexia neurotransmitters, such as norepinephrine, 5-hydroxytryptamine, dopamine, etc., and inhibit the feeding center. Non-central weight loss drugs (e.g., orlistat) are selective gastrointestinal lipase inhibitors.
For those with a BMI ≥40 kg/m2, vertical taped plication and gastric bypass surgery are used to reduce gastric volume in order to control food intake and reduce weight.