The gut microbiota is an essential part of the human organism, which plays a crucial role in maintaining its homeostasis. Peaceful coexistence with trillions of microorganisms mainly depends on the normal functioning of cellular and extracellular components of the intestinal mucosa, often called the "intestinal barrier". This barrier protects the organism against pathogenic infections while and at the same time satisfying its requirements for digestion and absorption of nutrients. It is not surprising that structural and functional intestinal barrier abnormalities are involved in the pathogenesis of many diseases including various nephropathies. The pathogenetic interconnection between the intestine and the kidneys is bidirectional. On the one hand, uremia affects the microbiota composition and the integrity of the intestinal epithelium. On the other hand, uremic toxins translocation, formed as a result of abnormal microbial metabolism, from the intestine into circulation through the ultra-permeable barrier contributes to the progression of renal dysfunction. Furthermore, according to a number of researchers, dysbiosis and the leaky gut syndrome are considered as one of the possible causes of anemia, nutritional disorders, cardiovascular and many other complications, often diagnosed in patients with chronic renal disease. The first part of the review reflects modern data about normal intestinal barrier structure and physiology, as well as methods for studying the intestinal wall integrity and permeability. The significant role of microbiota in the regulation of the barrier properties of the intestinal mucous and epithelial layer is emphasizing. The main differences between the intestinal microflora of patients with nephropathies from healthy people are presented, possible causes of their occurrence are discussed.
Background and Aims It is well established that cardiovascular pathology is the leading cause of increased morbidity and mortality in chronic kidney disease patients, especially in the terminal stage. This is explained by high prevalence of both traditional and non-traditional cardiovascular risk factors, among which inflammation, intestinal dysbiosis and microbe-derived uremic toxins such as indoxyl sulfate, p-cresyl sulfate, trimethylamine-N-oxide (TMAO) are recently considered the most significant. However, the potential underlying mechanisms of these findings have not been fully elucidated. Here we aimed to investigate the association of serum TMAO with echocardiographic parameters of cardiac remodeling in patients receiving hemodialysis treatment. Method One hundred and forty (85M, 55F) clinically stable patients on dialysis were studied. The median (interquartile range) age was 56,5 (46,2-60,5) years, median duration of dialysis treatment – 48 (14,5-97) months, 39 (27,9%) were diabetic, 109 (77,9%) had high blood pressure, 39 (27,9%) – previous history of ischemic heart disease, including 8 (5,7%) suffered a myocardial infarction. All patients underwent transthoracic echocardiography (General Electric Vivid E95 device) with the registration of standard parameters. The determination of TMAO in serum was performed by LC/MS using a Shimadzu-8060 system combined with a Shimadzu LC-20AD liquid chromatograph. Statistical analysis was performed with STATISTICA 14.0 program. Non-parametric Spearman's rank correlation method was used to evaluate the associations between serum TMAO level and echocardiographic parameters. Value of p<0.05 was considered statistically significant in all analyses. Results Median serum TMAO was 5244 (3588-8701) ng/ml. Echocardiography data: end-systolic left ventricular (LV) size is 38,2±0,6 mm, end-systolic LV volume – 62,0±4,4 ml, end-diastolic LV size – 55,8 ±1,3 mm, end-diastolic LV volume – 111,5±19,7 ml, ejection fraction (according to Simpson method) – 53,2±7,2%, shortening fraction – 28,9±4,4%, inter-ventricular septum thickness – 11,6±0,2 mm, posterior wall thickness – 11,9 ± 0,1 mm, LV mass index – 142,8±4,6 g/m2, LV mass – 298,6±8,8 g, relative wall thickness – 0,43±0,3, number of patients with LV remodeling or hypertrophy – 98 (70%). LV diastolic function parameters (n = 113): E – 0,69±0,2 m/s, A – 0,79±0,2 m/s, E/A (early (E) to late (A) ventricular filling ratio) – 0,89±0,2, deceleration time (DT) – 211±52 ms, number of patients with diastolic disfunction – 104 (74,3%). Statistically significant correlation was fount between TMAO concentration and end-diastolic LV volume (r = 0,315; р = 0,028), LV mass (r = 0,409; р = 0,011) and DT (r = 0,272; р = 0,041). TMAO levels in individuals with LV myocardial hypertrophy and diastolic dysfunction was significantly higher than without these abnormalities (Mann–Whitney U-test р = 0,037 and р = 0,043, correspondingly). Conclusion Our results suggest that elevated TMAO may contribute to cardiac remodeling in hemodialysis patients through the myocardial fibrosis and hypertrophy. The pathophysiological mechanisms of TMAO must be investigated further for a better understanding of its role in cardiovascular disease progression and to develop therapeutic interventions against uremic toxicity.
IgG4-related disease (IgG4-RD) currently is considered as a chronic fibroinflammatory immune-mediated multisystemic condition of unidentified etiology, which can imitate a wide range of malignant, infectious, rheumatologic, and other diseases. It can affect almost any organ system in the body synchronously or sequentially, but the most often affected are the pancreas, hepatobiliary tract, periorbital structures, salivary glands, kidneys, and lymph nodes. The most frequent renal manifestations of IgG4-RD is IgG4-related tubulointerstitial nephritis. Membranous nephropathy is the most common glomerular disease accompanied by IgG4-RD. Regardless of the organ localization, patients with IgG4-RD are characterized by elevated serum IgG4, but this laboratory abnormality is not specific and can be changed in other diseases. In all suspected cases of IgG4-RD the diagnosis should be confirmed by histological examination. Characteristic pathologic features include diffuse or focal lymphoplasmacytic infiltration with prominent IgG4+ plasma cells, storiform fibrosis, and obliterative phlebitis. Patients with IgG4- RD usually have an excellent clinical response to glucocorticoids, but relapse rates after steroid withdrawal are high, which may require additional use of immunosuppressants or rituximab. Due to the low prevalence and multitude of clinical manifestations the disease often remains underdiagnosed on time. This case report describes middle-aged patients with a history of chronic recurrent pancreatitis complicated by the nephrotic syndrome. Kidney biopsy showed membranous nephropathy and diagnosis IgG4-RD with multiorgan involvement was made. Partial remission was achieved on corticosteroid therapy. The presented case clearly demonstrates the difficulties of diagnosis and treatment of IgG4-RD. IgG4-related membranous nephropathy should be included in the differential diagnosis for patients with nephrotic syndrome accompanied by multiorgan dysfunction.
Fibronectin glomerulopathy (FNGP) is an extremely rare glomerulopathy with an autosomal dominant pattern of inheritance. Sporadic cases of the disease are also described. Currently, several types of FN1 gene mutations are known that underlie conformational changes in the fibronectin molecule and lead to its deposition in the renal tissue. The clinical manifestations of FNGP may be very heterogeneous, but in most cases are characterized by proteinuria, microscopic hematuria, arterial hypertension, and long-term progressive renal failure. Renal biopsy is the main method for diagnosing the disease. Histologically, GFND is characterized by a lobular glomerular architecture with mesangial expansion and obliteration of capillary loops due to the accumulation of an acellular, periodic acid–Schiff positive, silver Jones-negative material. Immunofluorescence is usually negative. Electron microscopy shows finely granular or fibrillary mesangial and subendothelial electron-dense deposits. At higher magnifications, the fibrils have a diameter of 12-16 nm and are randomly arranged. Standard protocols for the etiopathogenetic therapy of FNGP are not currently developed. Improvement of clinical status and prognosis can be achieved by optimizing blood pressure and proteinuria control by renin–angiotensin–aldosterone system blockers. The recurrence risk of FNGP after renal transplantation remains uncertain due to the rare prevalence of the pathology. In this article, we report a 25-year-old man with nephrotic syndrome, which occurred after a previous upper respiratory tract infection. Histological changes specific to FNGP were found in the kidney biopsy. Genetic analysis was not performed. The absence of a family history of kidney disease suggests that this is a sporadic case of FNGP.
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