[Clinical significance of the determination of antibodies to thrombospondin type 1 containing domain 7A (THSD7A) in membranous nephropathy].

BACKGROUND: Membranous nephropathy (MN) is an immunocomplex glomerular disease, which is the most common cause of nephrotic syndrome in adults. Numerous studies have established that autoantibodies against the target podocyte autoantigens, including the thrombospondin type 1 domain containing 7A (THSD7A), play a leading role in the development of idiopathic MN. AIM: To evaluate the prevalence of anti-THSD7A autoantibodies (anti-THSD7A AB) in a group of Russian patients with MN. MATERIALS AND METHODS: Serum titers of anti-THSD7A AB were tested in 61 patients with biopsy-proven MN and 12 healthy controls. RESULTS: The prevalence of anti-THSD7A AB was not differing significantly in patients with MN and in the control group (110.9 [71.63; 210.62] and 159.25 [125.64; 231.97] pg/ml, respectively; p=0.111). When comparing subgroups of anti-PLA2R-negative patients and patients who did not receive immunosuppressive therapy with the control group, there were also no statistically significant differences in the Anti-THSD7A AB levels (p>0.05). In the MN group, 1 (1.6%) patient was anti-THSD7A-positive: a 60-year-old man with anti-PLA2R-negative MN and the presence of hormonally inactive adenomas of both adrenal glands and colon polyps (villous adenoma with focal moderate dysplasia, tubulo-villous and tubular adenoma with focal moderate severe dysplasia). CONCLUSION: THSD7-associated MN is a rare variant of MN and is usually detected in PLA2R-negative patients. Screening for malignancies in THSD7A-positive MN patients is proposed.

[Frailty and chronic kidney disease - the real problem of modern nephrology: A review].

The article deals with the syndrome of frailty or senile asthenia in patients with chronic kidney disease. The questions of prevalence, diagnosis, pathogenesis of this syndrome and its clinical consequences in chronic kidney disease are discussed.

[Changes in metabolic parameters and glomerular filtration rate in patients with morbid obesity after bariatric surgery].

AIM: To study the effect of weight loss in the short term after bariatric surgery (BO) on metabolic parameters and glomerular filtration rate (GFR) in patients with morbid obesity. MATERIALS AND METHODS: We studied 40 adult (over 18 years) patients with morbid obesity who underwent bariatric surgery. Metabolic indices and calculated GFR according to the CKD-EPI formula in patients before and after bariatric surgery were compared. RESULTS: In the whole group of operated patients, the average body mass index (BMI) after surgery decreased from 45.8 to 30.5 kg/m2. In 11 (92%) patients with impaired carbohydrate metabolism, remission of diabetes mellitus was achieved and sugar-lowering drugs were canceled. In patients with baseline GFR90 ml/min/1.73 m2 after surgery, there is a tendency towards a decrease in GFR, probably due to a decrease in hyperfiltration. In patients with baseline GFR90 ml/min/1.73 m2 after surgery, a statistically significant increase in the level of GFR was noted. The greater metabolic efficacy of combined operations (mini-gastric bypass, biliopancreatic diversion) in relation to the correction of carbohydrate and fat metabolism was revealed. CONCLUSION: Obesity is a modifiable risk factor for decreased kidney function and the progression of chronic kidney disease. Bariatric surgery is an effective treatment for morbid obesity. The study proved the positive effect of weight loss after BO on renal function, including by improving the course of diseases associated with obesity.

[Successful treatment of a rare variant of mesangioproliferative glomerulonephritis with IgM deposits with Cyclosporin A].

We present a case with a rare variant of glomerulonephritis, IgM nephropathy, which occurs mainly with nephrotic syndrome. The clinical features of this variant of kidney damage are characterized; the pathogenetic and the transformation of this form of nephritis into focal segmental glomerulosclerosis are discussed. The development of severe nephrotic syndrome at the beginning of the disease, the formation of secondary steroid resistance have confirmed this hypothesis and have justified the treatment with cyclosporin A aimed at the recovery of the function of the podocyte with remission of nephritis.

[Modern approaches to conservative therapy of polycystic kidney disease].

Polycystic kidney disease (PKD) is a genetically determined pathological process associated with the formation and growth of cysts originating from the epithelial cells of the tubules and/or collecting tubes. PBP is represented by two main types - autosomal dominant (ADPKD) and autosomal recessive PKD (ARPKD), which are different diseases. The main causes of ADPKD are mutations of the PKD1 and PKD2 genes, which encode the formation of polycystin-1 and polycystin-2 proteins. ARPKD-linked mutation in the gene PKHD1, leads to total absence or defective synthesis of receptor protein primary cilia - fibrocystin. There are relationships between the structural and functional defects in the primary cilia and PBP. Mechanisms of cysts formation and growth include a) mutations of polycystines genes located on the cilia; b) increased activity of renal intracellular cAMP; c) vasopressin V2 receptors activation; d) violation of the tubular epithelium polarity (translocation of Na,K-ATPasa from basolateral to apical membrane); e) increased mTOR activity in epithelial cells lining renal cyst. The most promising directions of ADPKD therapy are blockade of vasopressin V2 receptors activation, inhibition of mTOR signaling pathways and reduction of intracellular cAMP level. The review presents clinical studies that assessed the effectiveness of named drugs in ADPKD.

Nephrological aspects of surgical weight correction in morbid obesity.

Obesity, including morbid obesity, is a growing worldwide problem. The adverse effect of obesity on the kidneys is associated with the development of comorbid conditions, such as insulin resistance (IR), metabolic syndrome (MS), diabetes mellitus (DM), arterial hypertension (AH), which are the recognized risk factors of chronic kidney disease (СKD). Obesity also causes direct kidney damage with the development of non-immune focal segmental glomerulosclerosis. The leading pathophysiological mechanisms of kidney damage in obesity are intrarenal hemodynamic disorders with the formation of hyperfiltration and damaging effects of adipokines produced by adipose tissue. Bariatric surgery (BS) has taken a leading position in the treatment of morbid obesity, demonstrating its effectiveness not only in long-term weight loss, but also in the correction of IR, MS, DM, AH. Nephroprotective effect of significant and persistent weight loss is caused by the elimination of hyperfiltration and damaging effect of adipokines. Results of the observational studies of the immediate and long-term effects of BS have demonstrated positive renal outcomes, in particular, the decrease in albuminuria/proteinuria, the improvement or stabilization of glomerular filtration rate, the delay of end-stage renal failure development; surgical correction of body weight in dialysis patients with morbid obesity lets them realize subsequent kidney transplantation. Large, randomized prospective studies with a longer follow-up are needed; analysis of the long-term renal consequences of BS in obesity patients with pre-existing renal impairment, including dialysis patients, is required; stratification of the BS risk of renal complications (acute kidney damage, nephrolithiasis, nephrocalcinosis) and effective strategy for managing these risks need to be developed.

[Idiopathic membranous nephropathy: Evolution in understanding the problem].

The review highlights the evolution of ideas on the. mechanisms responsible for the 'development of membranous nephropathy(MN), glomerulopathy that is the most common cause of nephrotic syndrome in adults. Primary emphasis is placed on the primary form of MN. The important step to understanding the nature of this clinical and morphological form of glomerulonephritis is to create its animal model (Heymann nephritis), then to decipher the mechanisms of immune complex damage (complement activation,a role of cellular immunity), and to identify autoantigens responsible for the development of idiopathic MN in man (podocyteneutral endopeptidase, transmembrane M-type phospholipase A2 receptor, thrombospondin type-1 domain-containing 7A. The findings constituted the basis for developing current methods for the diagnosis and treatment of MN, including the pathogenetically sound inhibition of autoantibody production, as well as a molecular orientation effect on podocyte dysfunction.