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.

Dysregulation of immunity in COVID-19 and SLE.

The immune response plays a crucial role in preventing diseases, such as infections. There are two types of immune responses, specific and innate immunity, each of which consists of two components: cellular immunity and humoral immunity. Dysfunction in any immune system component increases the risk of developing certain diseases. Systemic lupus erythematosus (SLE), an autoimmune disease in the human body, develops an immune response against its own components. In these patients, due to underlying immune system disorders and receipt of immunosuppressive drugs, the susceptibility to infections is higher than in the general population and is the single largest cause of mortality in this group. COVID-19 infection, which first appeared in late 2019, has caused several concerns in patients with SLE. However, there is no strong proof of additional risk of developing COVID-19 in patients with SLE, and in some cases, studies have shown less severity of the disease in these individuals. This review paper discusses the immune disorders in SLE and COVID-19.

Prevalence of SARS-CoV-2 Specific Antibodies in Asymptomatic Hemodialysis Patients.

BACKGROUND: Since the outbreak of the new coronavirus pandemic, the importance of carrying out an infection check to prevent acquisition and transmission among end-stage renal disease patients (ESRD) under maintenance hemodialysis (MHD) has become a major concern in the health care system. Applying serology screening tests could enlighten the view with regards to disease prevalence in dialysis wards. METHODS: We subjected 328 end-stage renal disease patients to maintenance hemodialysis. After dividing patients into suspicious and non-suspicious groups for COVID-19 infection based on their clinical manifestation, they were investigated for SARS-CoV-2 specific IgM and IgG screening against nucleoprotein (NP), spike protein (SP), and receptor-binding domain (RBD), utilizing our recently developed ELISA tests. RESULTS: We found that approximately 10.1% of asymptomatically tested cases were antibody positive. Although IgG positivity showed a higher prevalence than IgM across all three virus antigen subunits, there were no significant differences among mentioned immunoglobulins of the studied groups. The most prevalent antibody was from the IgG subtype against virus nucleoprotein (NP), while the lowest prevalence was attributed to receptor-binding domain (RBD) IgM. CONCLUSION: High seropositive rate among asymptomatic end-stage renal disease patients, as a sample of high-risk population, reflected the importance of considering SARS-CoV-2 specific antibody screening for disease containment.

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.

Association Between Matrix Metalloproteinase-3 Activity and Glomerular Filtration Rate and Albuminuria Status in Patients With Type 2 Diabetes Mellitus.

INTRODUCTION: Diabetic nephropathy is pictured as matrix accumulation and thickening of glomerular basal membrane. Matrix metalloproteinases (MMPs) are major proteases involved in extracellular matrix degradation. Moreover, plasminogen activator inhibitor-1 (PAI-1) primarily regulates plasmin dependent proteolysis. It plays a role in renal fibrosis causing extracellular matrix accumulation through inhibition of plasmin-dependent extracellular matrix degradation. This study investigated PAI-1 serum level and MMP-3 activity and their correlation with glomerular filtration rate in patients with diabetes mellitus. MATERIALS AND METHODS: In a case-control design, serum PAI-1 concentrations and MMP-3 activity were measured in 80 patients with normoalbuminuria, microalbuminuria, and macroalbuminuria. Receiver operating characteristics curve analysis was used to assess the diagnostic accuracy of MMP-3 activity in discriminating albuminuria. RESULTS: In the patients with microalbuminuria, serum PAI-1 levels were higher compared with macroalbuminuric patients (P < .001). The patients with macroalbuminuria exhibited a significantly lower MMP-3 activity than the patients with microalbuminuria and normoalbuminuria (P < .001). No significant correlation was found between serum MMP-3 activity and serum PAI-1 levels in those with normoalbuminuria, microalbuminuria, and macroalbuminuria. The MMP-3 activity had a strong positive correlation with estimated glomerular filtration (r = 0.853, P < .001). CONCLUSIONS: We found that there was a positive correlation between glomerular filtration rate and MMP-3 activity in diabetic patients. This concludes that MMP-3 may have a role in the pathogenesis of diabetic nephropathy progressions towards macroalbuminuria, and therefore, MMP-3 activity may be used in evaluating albuminuria status.

Role of plasma neutrophil gelatinase-associated lipocalin as an emerging biomarker of acute renal failure following kidney transplantation and its correlation with plasma creatinine.

INTRODUCTION: Graft function early after kidney transplantation is an important parameter in determining the outcome of operation. Urinary and plasma neutrophil gelatinase-associated lipocalin (NGAL), a member of the lipocalin protein family, has been advocated as a sensitive, early biomarker for predicting early renal graft after transplantation. The functions of NGAL appears to be expressed in stress conditions and in tissues undergoing involution. It rapidly accumulates in the kidney tubules and urine after nephrotoxic and ischemic insults. OBJECTIVES: This study aimed to examine the prognostic role of NGAL early after renal transplantation. PATIENTS AND METHODS: A total of 37 kidney recipients were enrolled from a teaching centre in Tabriz within a 6-month period of time. Plasma NGAL was measured immediately before and at 6 and 12 hours post-transplantation. Changes of serum creatinine were documented daily within the first week post-operation. Acute kidney injury (AKI)/graft rejection during the first week after transplantation was the outcome variable. RESULTS: There were 22 males (59.5%) and 15 females (40.5%) with the mean age of 34.93 ± 14.97 years (range: 12-59) in the study group. AKI/graft rejection developed in 12 patients (32.4%). The mean post-transplantation plasma NGAL levels and serum creatinine at all time points were significantly higher in patients with AKI/graft rejection. The best prognostic role was found for plasma NGAL at 12 hours (sensitivity = 100%, specificity = 92%; cut-off value = 309 ng/ml), far better than the prognostic accuracy of corresponding serum creatinine (sensitivity = 66.7%, specificity = 61.9%). CONCLUSION: Plasma NGAL, particularly 12 hours after transplantation, is a very sensitive and specific biomarker for predicting acute renal injury.

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.

Renal vascular Doppler ultrasonographic indices and carotid artery intima-media thickness in diabetic nephropathy.

INTRODUCTION: Diabetes is one of the common causes of renal insufficiency and is responsible for about one third of cases requiring renal transplantation. Conventional sonography provides limited information regarding the severity and prognosis of disease. The present study was carried out to evaluate the renal vascular Doppler indices role in determining renal dysfunction and carotid artery atherosclerosis. METHODS: Fifty five patients with diabetic nephropathy (albuminuria more than 300mg/24 hours) were enrolled into this cross-sectional study. Renal interlobar arterioles were studied using resistive (RI) and pulsatility (PI) indices of Doppler ultrasonography, in addition to conventional kidney length and renal parenchyma thickness. Intima-media thickness of common carotid artery (CCIMT) was also assessed just before the bifurcation. Serum creatinine (sCr), urine albumin and lipid profile were measured using standard methods. Estimated glomerular filtration rate (eGFR) was calculated by the Modification of Diet in Renal Disease formula. RESULTS: The renal interlobar arterioles' RI was positively and linearly correlated with the sCr and albuminuria levels (P<0.039 r= +0.320 and P=0.047, r= +0.287). There were negative linear correlations between eGFR and the renal interlobar arterioles' RI (P<0.001, r=-0.539) and PI (P<0.045, r= -0.328). The mean CCIMT was more than 0.7 mm in 90% of the studied patients. No correlation was found between CCIMT and renal ultrasonographic and Doppler findings. CONCLUSION: Although Doppler ultrasonographic indices of renal interlobar arteriols show the severity of renal dysfunction in patients with diabetic nephropathy, these indices do not have any advantage over the simple and cost effective biochemical parameters.

Brain hemodynamics in patients with end-stage renal disease between hemodialysis sessions.

INTRODUCTION: End-stage renal disease has been associated with premature atherosclerosis of the cerebral circulation. The risk of stroke, a frequent complication of uremia as a result of cerebral blood flow reduction, is high in dialysis patients. This study aimed to assess brain hemodynamics between hemodialysis interval periods by transcranial Doppler ultrasonography. MATERIALS AND METHODS: In a case-control study, to evaluate cerebral circulation homodynamics, 20 hemodialysis patients and 20 age- gender-matched healthy control subjects underwent transcranial Doppler ultrasonography. Blood parameters were also measured simultaneously. Among hemodialysis patients, these studies were performed 48 hours after a dialysis session. RESULTS: The mean blood flow velocity (MV) values were significantly higher in the middle cerebral artery (P = .007), anterior cerebral artery (P = .003), posterior cerebral artery-segment 2 (P = .03), basilar artery (P = .05) in hemodialysis patients compared to the controls. The MV had a negative meaningful correlation with hemoglobin and hematocrit in most intracranial arteries of the patients, but no significant correlation was observed between these variables and MV of the arteries in the control group. CONCLUSIONS: The MV of the cerebral arteries significantly increases in hemodialysis patients, which could be due to the decrease in hemoglobin levels in these patients.