Glucocorticoid Receptor Polymorphisms and Avascular Osteonecrosis After Kidney Transplantation.

INTRODUCTION: Glucocorticoids (GCs) are commonly prescribed as immunosuppressive agents after kidney transplantation and their most common non-traumatic adverse effect is Avascular Necrosis (AVN) of the femoral head. In this regard, this study aimed to evaluate the glucocorticoid receptor (GR) polymorphisms among kidney transplant recipients and their potential role as a risk factor for the incidence of AVN. METHODS: In this study, 99 renal transplant recipients were evaluated for the correlations of GR polymorphisms including N363S (rs6195), BclI (rs41423247), ER22/23EK (rs6189/rs6190), and A3669G (rs6198) with AVN after renal transplantation. RESULTS: Results showed that none of the renal-transplanted patients neither with GC hypersensitive polymorphisms (N363S and BclI) nor with GC-resistant polymorphisms (A3669G and ER22/23EK) developed AVN (P > .05). In addition, the medications of the renal recipients with AVN were significantly different from the nonAVN patients (P < .001). CONCLUSION: The study results indicate that the GR polymorphisms have no critical roles in the susceptibility to AVN after renal transplantation. However, further studies to confirm the results are recommended.  DOI: 10.52547/ijkd.7221.

Association between Serum α-Klotho Levels and Behçet Disease.

BACKGROUND: Endothelial dysfunction (ED) has a well-known role in promoting vascular inflammation in Behçet disease (BD). α-klotho is involved in regulation of endothelial function, and its reduction has been reported to be associated with ED. OBJECTIVE: To assess serum α-klotho in patients with BD, compared with healthy control individuals. METHODS: In a cross-sectional study, 55 patients with BD and 30 age- and sex-matched healthy controls were enrolled, and their serum levels of α-klotho were measured. RESULTS: Common clinical symptoms in patients with BD were oral aphthous ulcers, uveitis, and genital ulcers. Median (IQR) serum α-klotho levels in the BD and control groups were 0.30 (0.20-0.70) and 1.00 (0.70-2.52) ng/mL, respectively. The difference was statistically significant (P = .005). No significant correlation was observed between serum α-klotho and age (r = 0.194; P = .14). Serum α-klotho levels in patients with uveitis were significantly lower. CONCLUSION: α-klotho may have a role in the pathogenesis of ED and is a potential biomarker for uveitis in BD.

Clinical characteristics and long-term outcome of Takayasu arteritis in Iran: a multicentre study

Background/aim: This study aimed to evaluate the demographic, clinical, angiographic and prognostic characteristics of Takayasu arteritis (TA) in Iran. Materials and methods: A total of 75 patients with TA based on the American College of Rheumatology 1990 criteria for TA classification referred to the Rheumatology Centres, were followed-up from 1989 to 2019. Demographic, clinical, angiographic and prognostic characteristics were collected at baseline and last visit. Results: The mean age was 31.9 ± 9.8 years at the disease onset. Female to male ratio was 14. The median latency in diagnosis was 24 months. Pulse discrepancy in the arms, blood pressure discrepancy in the arms, limb claudication, hypertension and constitutional symptoms were the most common clinical features. The most common angiographic type at the time of diagnosis was Type I (42.7%). The most frequent arterial lesion was stenosis (89.4%). Subclavian, carotid and aortic arteries were the most commonly involved arteries. New lesions developed in 28.6% of patients during the 5.25-year follow-up. Vasculitis-induced chronic damage was observed in all patients. Disease activity decreased and vascular damage remained stable throughout the follow-up period. Conclusions: The clinical features and angiographic type of TA in Iran are different from most Asian countries. Differences in angiographic and clinical features may lead to delayed diagnosis. The issue of delay in diagnosis should create awareness among health care providers that TA is not a very rare disease in Iranians and failure to pay attention to warning symptoms may delay the diagnosis.

Serum YKL-40 levels and disease characteristics in patients with rheumatoid arthritis.

BACKGROUND: The present study aimed to evaluate serum YKL-40 levels in patients with rheumatoid arthritis (RA) compared to healthy subjects and to search whether there is an association between YKL-40 levels and disease characteristics in RA. METHODS: In this cross-sectional study, 60 RA patients based on the ACR/EULAR 2010 criteria and 30 age- and sex-matched healthy controls were included. In patients, clinical examination was performed and disease activity score 28 (DAS-28) measure of disease activity was assessed. Serum YKL-40 level was measured using ELISA kit. RESULTS: The mean±SD age of patients and controls was 54.86±11.65 and 50.71±3.72 years, respectively). Serum YKL-40 level was significantly higher in RA patients (951.63±639.98 pg/mL) compared to healthy controls (444.92±150.37 pg/mL) (P<0.001). There was no significant difference in serum YKL-40 level according to the activity of disease (p>0.05). There were significant positive correlations between serum YKL-40 level with disease activity (r=0.347, P=0.007) and rheumatoid factor (r=0.396, P=0.002). There were no significant correlations between serum YKL-40 level with demographic characteristics as well as biochemical measurements including serum creatinine, blood urea nitrogen, erythrocyte sedimentation rate, C-reactive protein and anti-cyclic citrullinated peptide. CONCLUSION: Our study revealed higher serum YKL-40 levels in RA patients compared to healthy controls, which correlated positively with disease activity. Therefore, YKL-40 can be considered as a novel biomarker for disease activity estimation in RA.

Relationship between serum-soluble receptor for advanced glycation end products (sRAGE) and disease activity in rheumatoid arthritis patients.

Objective: Considering the important role of serum soluble receptor for advanced glycation end product (sRAGE/RAGE)-ligand system in rheumatoid arthritis (RA), this study aimed to evaluate serum sRAGE levels in RA patients compared to healthy subjects and to assess whether there is an association between sRAGE levels and disease characteristics in RA.Methods: In this cross-sectional study, 60 RA patients according to the ACR/EULAR 2010 criteria and 30 age- and sex-matched healthy controls were included. In patients, clinical examination was performed and disease activity score 28 (DAS-28) measure of disease activity was assessed. Serum sRAGE level was measured using ELISA kit.Results: The mean ± SD age of patients and controls was 54.86 ± 11.65 and 50.71 ± 3.72 years, respectively). Serum sRAGE level was significantly higher in RA patients (median [25th and 75th percentiles], 1000.3 [792.00, 1486.8]) compared to healthy controls (median [25th and 75th percentiles], 293.25 [220.35, 364.24]) (p < .001). There was significant difference in serum sRAGE level according to the activity of disease (p < .001). There were significant positive correlations between serum sRAGE level with disease activity (r = 0.67, p < .001), ESR (r = 0.411, p = .001) and CRP (r = 0.273, p = .035). There were no significant correlations between serum sRAGE level with demographic characteristics as well as biochemical measurements including serum creatinine, BUN, RF, and Anti-CCP (p > .05).Conclusions: Our study revealed higher serum sRAGE levels in RA patients compared to healthy controls, which correlated positively with disease activity.

Efficacy and Safety of Mycophenolate Mofetil Versus Intravenous Pulse Cyclophosphamide as Induction Therapy in Proliferative Lupus Nephritis.

INTRODUCTION: Lupus nephritis is a common and severe manifestation of systemic lupus erythematosus that can lead to end-stage renal disease and death. The aim of this study was to compare the efficacy and safety of mycophenolate mofetil (MMF) and cyclophosphamide as induction therapy and subsequently as maintenance therapy for lupus nephritis. MATERIALS AND METHODS: In this retrospective case-control study, 67 patients with proliferative lupus nephritis who were treated with MMF (n = 45) and pulse of intravenous cyclophosphamide (n = 22) were included. Remission of the kidney disease, mortality, and adverse events were evaluated and compared between the two groups. RESULTS: The 45 patients treated with MMF had a mean age of 33.8 ± 10.6 years and 17.1% of them were males. The 22 patients treated with pulse of intravenous cyclophosphamide had a mean age of  38.1 ± 11.1 years and 18.2% of them were males. Complete and partial kidney remission occurred in 40% and 42.2% of the patients treated with MMF and in 31.8% and 59.1% of the patients treated with cyclophosphamide, respectively. No significant differences were observed in complete and partial remission between the two groups. No mortality was reported in the studied patients. There were no significant differences in the frequency of adverse events between the two groups. CONCLUSIONS: The efficacy of MMF in long-term treatment of lupus nephritis was comparable to that of cyclophosphamide, and there is no significant differences in the rate of side effects between the two regimens.

Long-term follow-up of 76 Iranian patients with idiopathic inflammatory myopathies.

AIM: This study aimed to follow up patients with polymyositis (PM) and/or dermatomyositis (DM) to determine survival rate, pattern of disease, response to treatment, malignancy incidence and poor prognostic factors (PPFs). METHOD: A total of 76 patients with PM (n = 47) and/or DM (n = 29) based on Bohan and Peter diagnostic criteria referred to the Imam-Reza Hospital were followed up from 2004 to 2016. The follow-up period was considered from diagnosis to patient's death or last visit. All patients underwent physical examinations and data including age, sex, disease duration, disease subtype, pattern of disease, PPFs and malignancy incidence were collected. RESULTS: Mean age at diagnosis was 45.49 ± 10.88 years and women were predominant (84.2%). Course of disease in the majority of patients (52.6%) was polyphasic, followed by monophasic (31.6%) and chronic-progressive (5.3%). The 1-, 5- and 10-year survival rates were 96%, 93% and 92%, respectively. Delay in treatment and dysphagia were common PPFs in the present study. The majority of patients responded to treatment (88.2%) and there were significant differences in cancer and dysphagia between responders and non-responders to treatment (P < 0.05). The most common cause of death was cancer in four of eight deaths. There was significant difference in survival rates between patients with and without pulmonary involvement (P = 0.001). Moreover, the survival rates were significantly lower in patients with malignancy (P = 0.001). CONCLUSION: Presence of dysphagia and cancer were associated with poor response to treatment. Pulmonary involvement and cancer incidence significantly affect survival rate. Furthermore, since cancer is the most common cause of death, so this study emphasizes the importance of careful cancer screening in these patients.

Correlation of plasma interleukin-18 concentration and severity of renal involvement and disease activity in systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by activation of T and polyclonal B lymphocytes. IL-18 was originally identified as a factor which enhances IFN-γ production and is a potent inducer of the inflammatory mediators by T cells, causing severe inflammatory disorders in SLE. OBJECTIVES: This study aimed to evaluate the association of plasma interlukine-18 (IL-18) concentration and severity of lupus nephritis (LN) and disease activity in SLE patients. PATIENTS AND METHODS: In this cross-sectional study, 113 patients with SLE and 50 healthy individuals were examined. Serum level of IL-18 was measured. The severity and activity of the disease was determined by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score. The severity of kidney involvement was studied by renal biopsy, serum creatinine and 24 hours urine protein level. RESULTS: The mean level of serum IL-18 was significantly higher in the patients than controls (577.67 ± 649.95 versus 60.48 ± 19.53 pg/ml; P < 0.001). In SLE patients with active disease level of serum IL-18 was significantly higher than chronic disease (622.77 ± 716.54 versus 182 ± 184.37 pg/ml; P < 0.001). The serum level of IL-18 was significantly higher in stage IV (P < 0.001) and V (P < 0.001) of patients with LN, than other stages. CONCLUSIONS: The current study showed that the serum IL-18 is significantly higher in the patients than controls and it significantly correlated with sever renal involvement and disease activity in SLE patients.

Effects of Lactobacillus casei supplementation on disease activity and inflammatory cytokines in rheumatoid arthritis patients: a randomized double-blind clinical trial.

AIM: The present study aimed at investigating the effects of Lactobacillus casei 01 supplementation on symptoms and inflammatory biomarkers of rheumatoid arthritis (RA) in women. METHOD: In this randomized double-blind clinical trial, female patients with established RA for more than 1 year, 20-80 years of age and body mass index (BMI) lower than 40, who followed stable medication for 3 months prior to the supplementation, were randomly allocated to receive either one capsule containing 10(8) colony forming units (CFU) of L. casei 01, or a placebo for 8 weeks; allocation was stratified by BMI and menopausal status. Disease activity score-28 (DAS28) was calculated, European League Against Rheumatism (EULAR) response was evaluated and the cytokines, interleukin (IL)-1ß, IL-6, IL-10, IL-12 and tumor necrosis factor (TNF)-α were measured. RESULTS: Thirty patients were recruited in each group; 22 and 24 patients were analyzed in the probiotic and placebo groups, respectively. L. casei 01 supplementation decreased serum high-sensitivity C-reactive protein (hs-CRP) levels, tender and swollen joint counts, global health (GH) score and DAS28 (P < 0.05). More patients in the L. casei 01 group had moderate response to the treatment, based on the EULAR criteria, at the end of the study (P < 0.01). At the end of the study, a significant difference was observed between the two groups for IL-10, IL-12 and TNF-α changes through the study course (P < 0.05), in favor of the probiotic group. No adverse effects were reported for the intervention. CONCLUSION: Probiotic supplementation may be an appropriate adjunct therapy for RA patients and help alleviate symptoms and improve inflammatory cytokines.

Stronger Correlation between Interleukin 18 and Soluble Fas in Lupus Nephritis Compared with Mild Lupus.

Lupus nephritis (LN) is a major cause of morbidity in patients with systemic lupus erythematosus (SLE). Several cytokines and apoptotic markers such as IL-18 and soluble Fas (sFas) have been assumed to play a role in the pathogenesis of LN. Previous studies confirmed that serum concentrations of sFas and IL-18 are increased in SLE. However, only a few studies have suggested a possible correlation between IL-18 and sFas. This study was planned to continue our previous study on the correlation between those markers to evaluate this correlation in LN. Thirty-two patients with only LN and 46 patients without any major organ involvement participated in this study. SLEDAI score (except for scores related to nephritis) was the same in these two groups. In both groups, patients with any other major organ involvement were excluded. We found a significant rise in the serum concentrations of sFas (P = 0.03) and IL-18 (P = 0.02) in patients with proteinuria compared to those without it. This study showed that the correlation between sFas and IL-18 in LN (P < 0.001, r p = 0.5) is significantly stronger than it is in mild SLE (P < 0.001, r p = 0.4) with similar nonrenal SLEDAI score (P = 0.032, z = 1.85). Between these two serum markers, sFas is the only predictor of proteinuria.