Objective . The present study aimed to compare key demographic and clinical parameters with morphological features defined by the Oxford MEST-C classification, supplemented by additional quantitative assessment, in order to identify the principal clinico-morphological phenotypes of IgA nephropathy (IgAN). Materials and Methods . This retrospective study included 2,679 patients with biopsy-proven IgAN. The mean age was 35.3±13 years. Clinical and laboratory variables (degree of hematuria, 24-hour proteinuria, and serum creatinine) were assessed at the time of biopsy. Morphological evaluation comprised Oxford MESTC scoring, quantitative assessment of of interstitial fibrosis/tubular atrophy (IFTA), global and segmental glomerulosclerosis, cellular/fibrocellular and fibrous crescents. Results . At the time of biopsy, median proteinuria was 2.1 g/day (IQR: 0.75-3.0), estimated glomerular filtration rate (eGFR) was 60.4 mL/min (IQR: 33.3-84.16). Hematuria was detected in 88% of patients. The distribution of Oxford MEST-C lesions was as follows: M1, 37%; E1, 21%; S, 73%; T1, 37%; T2, 16%; C1, 16.5%; C2, 2.5%. The severity of proteinuria correlated with E and C lesions, as well as the extent of IFTA and both global and segmental glomerulosclerosis. Correlation coefficients were higher when lesions C and S were quantified (% involvement): 0.17 vs 0.24 and 0.07 vs 0.23, respectively. Decline in eGFR were associated with the degree of IFTA and the presence of crescents. Based on clinicopathological correlations and morphological profiling, three distinct phenotypes of IgAN, likely reflecting different dominant mechanisms of disease progression, were identified: Phenotype 1: (Typical): Defined by mesangial proliferation and segmental glomerulosclerosis. Clinically characterized by persistent microhematuria, gradually increasing proteinuria, and arterial hypertension. Phenotype 2: (Aggressive): Defined by endocapillary hypercellularity with or without crescents. Clinically associated with acute nephritic syndrome, marked proteinuria – often at nephrotic range – and hematuria. Phenotype 3: (Macrohematuric): Defined by focal necrosis of capillary loops and crescent formation in the absence of endocapillary hypercellularity. Clinically manifests with episodes of macroscopic hematuria; during remission, urinary abnormalities are typically absent and renal function remains preserved. Conclusion . Identification of clinicopathological phenotypes in IgAN represents a promising strategy for personalizing therapy and refining prognostic assessment, thereby improving risk stratification for disease progression.
Background : the catabolism of aromatic amino acids is closely linked to the immune response. Their metabolites act as molecular messengers, facilitating communication between the microbiome and the immune system. Selected studies suggested that the pathogenesis of immunoglobulin A nephropathy (IgAN) may be associated with alterations in tryptophan (Trp) metabolic pathways. Aim : to test the hypothesis about probable changes in Trp metabolism in IgAN using untargeted and targeted metabolomics analyses. Materials and methods : the cohort study included 113 patients with a clinical and morphological diagnosis of primary IgAN, comprised two subgroups: with an active/progressive process who did not receive treatment (IgAN-A, n=85); with inactive IgAN/remission (IgAN-R, n=28). Control groups included healthy volunteers without kidney disease (K1, n=31) and patients with non-inflammatory glomerulopathies (K2, n=33). Untargeted and targeted metabolomics studies of serum were performed using high-resolution high-performance liquid chromatography with mass spectrometric detection (HPLC-MS) in positive and negative ionisation mode. Intergroup differences in Trp metabolites were assessed, and their associations with clinical parameters were analysed. Results : untargeted analysis of mass spectrometric data revealed that tryptophan synthesis and metabolism were enriched among other metabolic pathways in patients with IgAN. Significant differences were found in kynurenic acid (KynA), kynurenine (Kyn), 5-hydroxytryptophan (HTrp), 3-hydroxyanthranilic acid, tryptamine, and indole-3-lactic acid (ILA), suggesting alterations in the serotonin, kynurenine, and indole metabolic pathways. Targeted analyses showed that Trp and its metabolites’ levels differed significantly in patients with IgAN (overall group, n=113) compared to healthy controls. Compared with the IgA-R subgroup, subjects with IgAN-A had higher levels of KynA:Kyn, Kyn:Trp, KynA:Trp, and HTrp:Trp ratios, alongside decreased tryptophan and indoxyacetic acid (IAA). In the IgAN-A group, diverse associations of Trp and its metabolites with clinical parameters were revealed. Except for Trp and indole acetate, metabolites of the Trp pathway were negatively correlated with estimated glomerular filtration rate (eGFR), blood pressure, and age. Tryptophan and indole acetate had negative associations with proteinuria and positive associations with serum albumin levels. Tryptophan and IAA concentrations were inversely associated with proteinuria and directly with serum albumin levels; the associations of these clinical indicators and the ratios of HTrp, Kyn, KynA, NA and ILA to tryptophan were opposite. Conclusions : In IgAN patients, apparent alterations in tryptophan metabolic pathways are associated with clinical parameters and may contribute to the pathogenesis of the disease.
The Kidney Disease: Improving Global Outcomes (KDIGO) 2025 Clinical Practice Guideline for the Management of Immunoglobulin A Nephropathy (IgAN) and Immunoglobulin A Vasculitis (IgAV) represents a focused update of Chapter 2: Immunoglobulin A Nephropathy (IgAN) / Immunoglobulin A Vasculitis (IgAV) from the KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. The aim is to assist healthcare providers caring for people with IgAN or IgAV. The update takes into consideration evidence from randomized controlled trials published through April 2023 and updated in August 2024. As in 2021, this guideline provides guidance related to diagnosis, prognosis, treatment, and special situations. Based on the new evidence, this update is mostly related to the guidance relevant to IgAN. Development of this guideline followed an explicit process of evidence review and appraisal. Treatment approaches and guideline recommendations are based on systematic reviews of relevant studies, and appraisal of the certainty of the evidence and the strength of recommendations following the “Grading of Recommendations Assessment, Development and Evaluation” (GRADE) approach. Limitations of the evidence are discussed, and areas of future research are also presented.
Introduction. Atypical hemolytic uremic syndrome (aHUS) is a rare form of thrombotic microangiopathy (TMA) associated with dysregulation of the complement system. aHUS take an important place in the spectrum of kidney disease because of the high risk of kidney loss and damage to other vital organs. Objective. The evaluate the outcomes of follow-up and treatment of patients with aHUS receiving complement-blocking therapy (CBT), with assessment of overall and renal survival. Materials and methods . Medical records and outpatient charts of 25 patients with aHUS followed at the nephrology department of Yekaterinburg Regional Clinical Hospital No. 1 between 2014 and 2024 (10 years) were analyzed. Differential diagnostic methods, as well as morphological (kidney biopsy) and genetic studies (genetic testing of the complement system) studies, were performed. Treatment included plasma therapy (fresh frozen plasma (FFP) transfusions and/or plasma exchange) and/or CBT with eculizumab. Statistical analysis was performed using SPSS version 24. Descriptive statistics, Kaplan-Meier survival estimates with corresponding graphs, and Fisher's exact test for intergroup comparisons were used. Results. The identified triggers of aHUS included pregnancy and childbirth (32%), infections (16%), IgA nephropathy (8%), oral contraceptive use (8%), paint inhalation poisoning (4%), and kidney transplantation (4%). Genetic testing of the complement system was performed in 22 patients, and pathogenic variants associated with aHUS were identified in 12 (54.5%) of the examined patients. Overall patient survival rates were 96% at as: 1 year, and 89% at both 5 and 10 years. Renal survival was 100% at 1 year and 84% at 5years. Plasma therapy with FFP transfusions was administrated to 10 (40%) patients, and plasma exchange was performed in 16 (64%) patients. Specific CBT with eculizumab was used in 22 (88%) patients. Discontinuation of eculizumab was associated with a high risk of TMA recurrence (36%). Conclusion . Long-term follow-up of 25 patients with aHUS receiving specific CBT demonstrated satisfactory overall patient survival (96% at 1 year, 89% at 5 years) and renal survival (100% at 1year, and 84% 5 years).
The prevalence of chronic kidney disease (CKD) has not decreased over the past 50 years and is now comparable to that of major conditions as hypertension and diabetes mellitus. It is now well established that CKD may develop as a consequence of acute kidney injury (AKI). Recent studies indicate that AKI is among the most common complications following emergency abdominal surgery. However, this problem remains insufficiently represented in general surgical literature, partly due to limited scientific interaction between surgeons and nephrologists. In general surgical hospitals, the diagnosis of AKI is currently based mainly increases in serum creatinine and/or decreases in urine output. However, serum creatinine, as a marker of glomerular filtration rate, is relatively insensitive to acute changes in renal function. This limitation may contribute to delayed clinical diagnosis and underestimation of the severity tubular and glomerular injury. Circulatory collapse is a prominent clinical sign of the early stage of AKI, but in some cases it is so transient that it remains unnoticed. A detailed understanding of the dynamics of morphological and functional changes at the level of the renal microcirculation, renal corpuscles, and parenchymal microcirculation during endotoxicosis is essential, as these processes form the pathogenetic basis of AKI and the subsequent development of CKD even after apparent recovery. Without such knowledge, meaningful improvements in pathogenetically targeted therapy for complications of urgent abdominal surgical diseases and in the prevention of dependence on renal replacement therapy, both in the early and late postoperative periods, are unlikely. One objective criterion for assessing the severity of AKI and the effectiveness of its prevention and treatment in abdominal surgical diseases of the is the time factor. Its significance should be validated experimentally through models of acute strangulatory small intestinal obstruction and through the study of associated morphological and functional changes in the renal corpuscles.
Background . Chronic kidney disease (CKD) is associated with disturbances in calcium-phosphate homeostasis and vitamin D metabolism, leading in mineral and bone disorders (CKD-MBD). However, the pathogenetic features of these alterations at predialysis CKD stages and the effects of high-dose cholecalciferol therapy remain insufficiently characterized. Objective . To compare vitamin D metabolites and calcium-phosphate metabolism parameters in patients with predialysis CKD and individuals without impaired kidney function, and to assess their dynamics after a single bolus dose of 150,000 IU of cholecalciferol. Materials and Methods . The study included 58 participants: 23 patients with CKD stage C3, 14 with CKD stages C4-5, and 21 controls. Parameters of calcium-phosphate metabolism and vitamin D metabolites were assessed at baseline and 7 days after a single oral dose of aqueous cholecalciferol (150,000 IU). Vitamin D metabolites were measured using LC–MS/MS. Results . Data are presented as follows: control group, CKD C3, CKD C4-5. At baseline, CKD patients had higher parathyroid hormone (PTH) levels (51.3 [40.6; 62.7] vs 70.9 [49.0; 105.9] vs 101.0 [91.7; 120.1] pg/mL), lower calcitriol concentrations (40.9 [34.3; 59.4] vs 25.0 [19.8; 29.1] vs 26.4 [13.8; 30.6] pg/mL), a trend toward higher fibroblast growth factor 23 (FGF-23) levels (0.73 [0.43; 1.07] vs 1.08 [0.61; 2.52] vs 3.22 [1.78; 4.51] pmol/L), and a reduced 24,25 (OH) 2 D 3 /25(OH)D 3 ratio (0.06 [0.04; 0.08] vs 0.03 [0.01; 0.04] vs 0.03 [0.02; 0.04]), indicating impaired 24-hydroxylase activity. Total and free 25(OH)D levels and vitamin D-binding protein (VDBP) were comparable between groups. Seven days after cholecalciferol administration, a similar increase in total 25(OH)D 3 , 3-epi-25(OH)D 3 , and 24,25(OH) 2 D 3 was observed in all groups. However, the increase in free 25(OH)D was significantly smaller in CKD C3 and C4-5 compared with controls ( p =0.036 and p =0.028). PTH decreased in CKD C3 ( p =0.039), whereas FGF-23 increased in CKD C4-5 ( p =0.042). Serum calcium, phosphorus, calcitriol, and VDBP remained unchanged. Conclusion . Alterations in calcium-phosphate and vitamin D metabolism at predialysis CKD stages show a sequential pattern. Reduced vitamin D activation and inactivation, increased FGF-23 levels, and a blunted free 25(OH)D response to bolus cholecalciferol indicate specific regulatory features and limit the applicability of standard vitamin D correction regimens in this population.
IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis, diagnosed by the presence of dominant immunoglobulin A deposits in the mesangial matrix of the renal glomeruli. Overproduction of galactose-deficient IgA1, associated with lymphoid tissue of the intestinal mucosa, plays a central role in the disease pathogenesis. The state of the intestinal microbiota, as a major source of IgA1 production, is an important factor of shaping immune response diverse antigenic stimuli. Mucosal hyperreactivity, according to numerous studies, is crucial not only in the development but also in the progression of IgAN. The widespread introduction of metagenomic DNA sequencing has demonstrated reduced microbial diversity of the intestinal flora in patients with IgAN compared with the healthy individuals. Another important finding is the identification of genomic loci associated with impaired permeability of the intestinal mucosa and the increased susceptibility to inflammatory diseases in IgAN patients. In addition, a relationship has been reported the genetic predisposition to IgAN, which is believed to involve multilocus interaction of risk alleles, and the composition of the microbiota. In patients with IgAN, a direct correlation was observed between the abundance of specific bacterial families including Actinobacteriaceae, Ruminococcaceae and Bacteroidaceae, and clinical and laboratory parameters such as proteinuria, microhematuria and glomerular filtration rate. In intestinal dysbiosis, the production of key bacterial metabolites, particularly short-chain fatty acids (SCFA) are reduced. These metabolites regulate intestinal barrier permeability, immune response intensity, and antioxidant activity among other processes that may influence the course of the IgAN. Comprehensive analysis of the intestinal microbiome, including quantitative assessment of specific bacterial species and their metabolites, represents a promising direction for further research and may facilitate the development personalized therapeutic strategies for patients with IgAN.
Background . Chronic kidney disease-associated pruritus (CKD-aP) can significantly impair quality of life by negatively affecting patient psycho-emotional well-being and sleep quality, while also increasing the risk of hospitalizations and mortality. In Russia, this issue remains understudied. Objective: to assess the prevalence of pruritus and its impact on various aspects of quality of life in a Russian cohort of patients with CKD receiving maintenance hemodialysis. Methods . The cross-sectional study included 225 patients from two dialysis centers with who has been receiving hemodialysis for more than 3 months. The presence and severity of CKD-aP were assessed using the following validated instruments: WI-NRS, Skindex-16, Itch MOS, and the 5-D Itch Scale. Results. CKD-aP was identified in 52% of the patients, with 16% [95% CI: 11; 21] experiencing moderate-to-very severe pruritus (WI-NRS ≥4). The most commonly affected body areas were the back (53%), head (35%), shins (32%), and thighs (25%). Patients with CKD-aP, particularly those with moderate-to-severe pruritus, demonstrated more pronounced sleep disturbances. Sleep Problem Index II (SPI-II) scores were 13.3 [Q1-Q3: 0.0; 33.3] in patients without pruritus, 20 [6.7; 33.3] in those with mild pruritus, and 33.3 [20.0; 60.0] in those with moderate-to-severe pruritus (p=0.001). Patients with moderate-to-severe pruritus also had significantly higher Skindex-16 total and subscales score compared to those with mild pruritus: total score 20.7 [8.9; 35.3] vs. 7.4 [2.8; 15.5] (p<0.001), emotional subscale 14.3 [2.4; 47.6] vs. 5.2 [0.0; 16.7] (p<0.001), and symptomatic subscale 31.3 [12.5; 50.0] vs. 12.5 [4.2; 20.8] (p<0.001). The total score on the 5-D Itch Scale was also higher in patients with CKD-aP, particularly in the moderate-to-severe group: 6.0 [5.0; 8.0] in patients without pruritus, 10.0 [8.0; 11.0] in those with mild pruritus, and 13.0 [11.0; 15.0] in those with moderate-to-severe pruritus (p<0.001). Patients with pruritus had higher creatinine levels: 804.8 (217.4) μmol/L vs. 727.8 (197.8) μmol/L in patients without pruritus, p=0.0091. Conclusions . CKD-aP is highly prevalent in a Russian cohort of patients receiving maintenance hemodialysis. Patients with pruritus, particularly of severe pruritus, experience substantial impairment in overall quality of life and across multiple domains, including sleep, daily activities, and emotional well-being.
Dent disease and Lowe syndrome are hereditary tubulopathies characterized by low-molecular-weight proteinuria, hypercalciuria, and nephrocalcinosis. Proteinuria may reach high levels, necessitating differential diagnosis with steroid-resistant nephrotic syndrome. Materials and Methods : from 2010 to 2025, 41 children with Dent disease or Lowe syndrome were followed at the Nephrology Department of the National Medical Research Center for Children's Health. Dent disease type 1 was confirmed in 29 children (71%), type 2 in 3 children (7%), and type 3 in 3 children (7%). Lowe syndrome was diagnosed in 6 children (15%). Results : all children exhibited low-molecular-weight proteinuria, ranging from 139 to 3,653 mg/m 2 /day, with a median of 1,590 (952; 2248) mg/m 2 /day. Ultrasound signs of nephrocalcinosis were observed in 61% of patients, and hypercalciuria was detected in 66%. Molecular genetic testing identified causative variants in the CLCN5 and OCRL genes in all but three children. Nearly all detected pathogenic variants were unique; only one variant, CLCN5 c.2320C>T was found in two unrelated children. At the time of analysis (mean age 9 years 8 months, SD 5 years 1 months), decreased renal function was present in 41% of patients. Renal replacement therapy was required in only one child (2%). No correlations were found between decreased estimated GFR and maximum proteinuria level, presence of nephrocalcinosis, or growth retardation. However, a significant correlation was observed between growth Z-score and the daily proteinuria level ( ϱ =-0.451, p <0.01). Conclusions : Dent disease and Lowe syndrome can be clinically based on laboratory and instrumental findings, with molecular genetic testing confirming the diagnosis. Given the wide variety of variants identified in the CLCN5 and OCRL genes, establishing genotype-phenotypic correlations is challenging and requires further investigation in larger cohorts.
Sarcopenia is a syndrome characterized by the progressive and generalized loss of skeletal muscle mass, strength, and physical performance, leading to an increased risk of adverse outcomes, particularly in elderly individuals, including impaired quality of life, disability, and mortality. Chronic kidney disease (CKD) is a condition associated with accelerated aging that contributes to disturbances in nutritional and functional status, thereby predisposing patients, especially whose with end-stage kidney disease, to an increased risk of sarcopenia. Sarcopenia is considered one of the major geriatric syndromes, while CKD is recognized as an important risk factor for the development of metabolic disturbances and chronic systemic inflammation. The main pathogenetic mechanisms of sarcopenia include mitochondrial dysfunction, age-related degeneration of motor neuron end plates, excessive apoptosis, decreased nitric oxide production, androgen deficiency, reduced activity of satellite and stem cells, systemic inflammation, and glucocorticoid exposure. CKD is accompanied by multiple metabolic and hormonal abnormalities, including metabolic acidosis, uremia, hyperparathyroidism, and disturbances in increased insulin-like growth factor (IGF) signaling, all of which negatively affect muscle metabolism and increase the risk of sarcopenia. Intestinal dysbiosis is also considered as a potential mechanism contributing to CKD progression, and may indirectly influence muscle. Several studies have demonstrated an association between loss of muscle mass and deterioration of kidney function, including in patients with sarcopenic obesity. Muscle mass is an important determinant of longevity in the older adults, whereas sarcopenic obesity represent a significant risk factor for adverse health outcomes. However, the prevalence and clinical significance of sarcopenic obesity in patients with CKD remains insufficiently investigated. Systematic reviews have shown that sarcopenia in CKD patients is associated with multiple adverse clinical outcomes, including falls, fractures, and cardiovascular events. Despite the large number of studies examining these processes, the precise molecular pathways and interactions leading to muscular atrophy remain incompletely understood. Moreover, relatively few systematic reviews and meta-analyses have summarized the prevalence of sarcopenia in CKD, and most available data are limited to dialysis patients and kidney transplant recipients.
