Zbigniew Heleniak

BACKGROUND: Immunoglobulin A nephropathy (IgAN), the most frequent cause of primary glomerulonephritis worldwide, is an autoimmune disease with complex pathogenesis. In this review, we focus on T cells and summarize knowledge about their involvement in pathophysiology and treatment of IgAN METHODS: We reviewed the literature for (1) alterations of T cell subpopulations in IgAN, (2) experimental and clinical proofs for T cells' participation in IgAN pathogenesis, (3) clinical correlations with T cell-associated alterations, and (4) influence of drugs used in IgAN therapy on T cell subpopulations. RESULTS: We found that IgAN is characterized by higher proportions of circulatory Th2, Tfh, Th17, Th22 and γδ T cells, but lower Th1 and Treg cells. We discuss genetic and epigenetic makeup that may contribute to this immunological phenotype. We found that Th2, Th17 and Tfh-type interleukins contribute to elevated synthesis of galactose-deficient IgA1 (Gd-IgA1) and that the production of anti-Gd-IgA1 autoantibodies may be stimulated by Tfh cells. We described the roles of Th2, Th17, Th22 and Treg cells in the renal injury and summarized correlations between T cell-associated alterations and clinical features of IgAN (proteinuria, reduced GFR, hematuria). We detailed the impact of immunosuppressive drugs on T cell subpopulations and found that the majority of drugs have nonoptimal influence on T cells in IgAN patients. CONCLUSIONS: T cells play an important role in IgAN pathogenesis and are correlated with its clinical severity. Clinical trials with the drugs targeting the reported alterations of the T-cell compartment are highly desirable.

CD4(+) T lymphocytes of patients with chronic kidney disease (CKD) are characterized by reduced levels of crucial surface antigens and changes in the cell cycle parameters. Recombinant human erythropoietin (rhEPO) normalizes their altered phenotype and proliferative capacity. Mechanisms leading to the deficient responses of T lymphocytes are still not clear but it is postulated that immunological changes are deepened by hemodialysis (HD). Study of activation parameters of CD4(+) T lymphocytes in hemodialyzed and predialysis CKD patients could bring insight into this problem. Two groups of patients, treated conservatively (predialysis, PD) and hemodialyzed (HD), as well as healthy controls, were included into the study; neither had received rhEPO. Proportions of main CD4(+)CD28(+), CD4(+)CD25(+), CD4(+)CD69(+), CD4(+)CD95(+), and CD4(+)HLA-DR(+) lymphocyte subpopulations and proliferation kinetic parameters were measured with flow cytometry, both ex vivo and in vitro. No differences were seen in the proportions of main CD4(+) lymphocyte subpopulations (CD4(+)CD28(+), CD4(+)CD25(+), CD4(+)HLA-DR(+), CD4(+)CD69(+), CD4(+)CD95(+)) between all examined groups ex vivo. CD4(+) T lymphocytes of HD patients exhibited significantly decreased expression of co-stimulatory molecule CD28 and activation markers CD25 and CD69 after stimulation in vitro when compared with PD patients and healthy controls. HD patients showed also decreased percentage of CD4(+)CD28(+) lymphocytes proliferating in vitro; these cells presented decreased numbers of finished divisions after 72 h of stimulation in vitro and had longer G0→G1 time when compared to healthy controls. CD4(+) T lymphocytes of PD patients and healthy controls were characterized by similar cell cycle parameters. Our study shows that repeated hemodialysis procedure influences phenotype and proliferation parameters of CD4(+) T lymphocytes.

AIMS: Nonsteroidal anti-inflammatory drugs (NSAIDs) are the cornerstone of pain management. There are no detailed data on NSAIDs use in Poland, especially in patients with chronic kidney disease (CKD). The aim of this study was to evaluate the frequency, circumstances, and causes of NSAIDs use as well as knowledge of their side-effects in patients with CKD. METHOD: This cross-sectional study was conducted in 972 individuals with CKD, enrolled in a written survey originally developed by the authors. There were 574 patients with CKD stage I-IV, 414 patients after renal transplantation stage II-IV (CKDT) and 84 dialyzed patients (44 peritoneal, 40 hemodialysis). RESULTS: Among the entire study group, 16.9 % of patients used NSAIDs every day, or several times a week. The average number of tablets taken within a month was 21.8. Subgroup analysis revealed that NSAIDs were taken most often by patients on hemodialysis: 35 % of them used NSAIDs every day or several times a week (43.15 pills per month). The most common reason for using NSAIDs were bone-joint pain (29.3 %) and headache (26.2 %). Side effects of painkillers such as renal function deterioration and the possible promotion of stomach ulcers were experienced by 43.6 and 37.6 % of respondents, respectively. CONCLUSION: Patients with CKD often take NSAIDs. This applies especially to the group of people undergoing hemodialysis, which is mainly associated with chronic osteo-articular pain. The results also show a low awareness of painkillers' adverse effects.

INTRODUCTION: Patients after SARS-CoV-2 infection frequently face "Post-COVID-19 Syndrome", defined by symptoms that develop during or after COVID-19, continue for more than 12 weeks, and are not explained by an alternative diagnosis. We aimed to evaluate the presence of post-COVID-19 syndrome and its predictors in kidney transplant recipients (KTR) 6 months after the disease. MATERIALS AND METHODS: A total of 67 KTR (38 m) with a mean age of 53.6 ± 14 years, 7.3 ± 6.4 years post-transplant were included in the cohort longitudinal study. Thirty-nine (58.2%) of them were hospitalized, but not one required invasive ventilation therapy. They were interviewed 6 months after being infected, with a series of standardized questionnaires: a self-reported symptoms questionnaire, the modified British Medical Research Council (mMRC) dyspnea scale, EQ-5D-5L questionnaire, and EQ-VAS scale. RESULTS: Post-COVID-19 syndrome was diagnosed in 70.1% of KTR and 26.9% of them reported at least three persistent symptoms. The most common symptoms were fatigue (43.3%), hair loss (31.3%), memory impairment (11.9%), muscle aches, and headaches (11.9%). Dyspnea with an mMRC scale grade of at least 1 was reported by 34.3% patients vs. 14.9% before infection; 47.8% stated that they still feel worse than before the disease. Mean EQ-VAS scores were 64.83 vs. 73.34 before infection. The persistent symptoms are more frequent in older patients and those with greater comorbidity. CONCLUSIONS: Persistent symptoms of post-COVID-19 syndrome are present in the majority of KTR, which highlights the need for long-term follow-up as well as diagnostic and rehabilitation programs.