Papers by Olumide Rowaiye

Anti-ETAR and suPAR as markers of disease activity in renal ANCA-associated vasculitis
Advances in Medical Sciences, Mar 1, 2022
PURPOSE In anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), there is a la... more PURPOSE In anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), there is a lack of reliable biomarkers of disease activity. The aim of the study was to evaluate soluble urokinase plasminogen activator receptor (suPAR) and anti-endothelin-1 type A receptor (anti-ETAR) antibodies levels in active phase and remission of AAV. PATIENTS AND METHODS We enrolled 60 patients (median age 63.0 years) with renal AAV into this study. Plasma suPAR, urine suPAR (expressed as urine suPAR/creatinine ratio) and serum anti-ETAR antibodies were assayed by ELISA. Disease activity was assessed using Birmingham Vasculitis Activity Score (BVAS) and patients were divided into 2 subgroups based on their BVAS scores, namely: active AAV subgroup (BVAS≥1) and remission subgroup (BVAS = 0). Median follow-up was 12 months. RESULTS Patients with active AAV had higher levels of all candidate biomarkers in comparison to those in remission (p < 0.05). C-statistics for plasma suPAR, urine suPAR/creatinine ratio and serum anti-ETAR were 0.807, 0.713 and 0.783, respectively. In multivariable analysis, no clear associations were found between serum anti-ETAR and BVAS, while both plasma suPAR and serum anti-ETAR were independently influenced by estimated glomerular filtration rate (eGFR). CONCLUSIONS Plasma suPAR better discriminated between active AAV and remission in comparison to urine suPAR/creatinine ratio and serum anti-ETAR antibodies.
Cardiology Journal, Oct 3, 2013
Diabetes mellitus (DM) is a disease of increasing incidence and prevalence. Arterial baroreceptor... more Diabetes mellitus (DM) is a disease of increasing incidence and prevalence. Arterial baroreceptors are stretch-sensitive receptors, which in a reflex manner are involved in the homeostatic control of arterial blood pressure. Diabetic subjects have depressed baroreflex sensitivity (BRS), although the exact pathomechanisms are unclear. In this review, we discuss the features, clinical and prognostic implications of reduced BRS for diabetic patients and the potential involvement of cardiovascular autonomic neuropathy and atherosclerosis. Finally, we demonstrate evidence on interventions (e.g. pioglitazone, alpha-lipoic acid, leptin, fluvastatin, physical training etc.) which could improve BRS and ameliorate cardiovascular autonomic dysfunction in diabetic patients.
Nephrology Dialysis Transplantation, 2018

Nephrology Dialysis Transplantation, 2018
INTRODUCTION AND AIMS: ANCA-associated vasculitis (AAV) is an autoimmune inflammatory disease aff... more INTRODUCTION AND AIMS: ANCA-associated vasculitis (AAV) is an autoimmune inflammatory disease affecting small-sized vessels. In AAV, endothelial dysfunction occurs. Endothelial dysfunction has been identified as an early event in the process of atherogenesis. The aim of this study was to investigate the clinical characteristics and correlates of endothelial dysfunction in AAV. METHODS: Endothelial function was assessed in 48 renal AAV patients (25M, 23F; median age 60 yrs) by means of brachial artery flow-mediated dilation (FMD) using the ultrasound system according to standard protocols. Pts with procalcitonin >0.1 ng/ml, on antibiotic course or recent vascular episode were excluded. 26 patients were PR3-ANCA positive, 20 were MPO-ANCA positive while 2 were ANCA-negative. Patients were then divided into 2 groups based on FMD namely: the low FMD (FMD <10%) and normal FMD groups (FMD 10%). Disease activity and damage were assessed using the Birmingham Vasculitis Activity Score (BVAS) and the Vasculitis Damage Index (VDI) respectively. Other laboratory and clinical parameters (including Charlson Comorbidity Index, CCI) were also assessed (table ). RESULTS: Median AAV duration was 35 months. Patients in the low FMD group (i.e. those with endothelial dysfunction) had higher VDI and CCI scores than those in normal FMD group (table ). Using Pearson correlations, FMD was shown to correlate with age (r ¼ -0.29; p ¼0.03), CRP (r ¼ -0.30; p¼ 0.03) and CCI (r ¼-0.34; p¼0.01) but not with BVAS (r ¼ -0.07; P¼0.59) or eGFR (r ¼ 0.03; p¼0.81). Also no correlations were found between FMD and other tested parameters. CONCLUSIONS: Our study indicated that impaired FMD correlated with advanced age and the presence of comorbidites, but not with renal dysfunction in renal AAV patients. As we noticed weak correlation with CRP and only tendency between vasculitis activity and FMD, the latter parameter may help to better identify a subset of AAV patients with endothelial dysfunction and therefore at increased risk for cardiovascular disease. Such patients may benefit from the use of additional interventions known to ameliorate endothelial dysfunction (e.g. statins, physical activity program).

Advances in Medical Sciences, 2020
The aim of this study is to present the treatment modalities and associated side effects in a Pol... more The aim of this study is to present the treatment modalities and associated side effects in a Polish nation-wide ANCA-associated vasculitides (AAV) patients' cohort. Materials and methods: Retrospective analysis of patients diagnosed with AAV between 1990 and 2016, included in the POLVAS registry was performed. Standard descriptive statistic methods were used with an emphasis on the treatment modalities. Results: There were 625 patients diagnosed with AAV included in this study: 417 cases of granulomatosis with polyangiitis (GPA; 66.7%), 106 cases of microscopic polyangiitis (MPA; 17.0%) and 102 cases of eosinophilic granulomatosis with polyangiitis (EGPA; 16.3%). The mean age at the date of diagnosis was 50.4 ( ± 15.7) years and the median observational period amounted to 4.0 (2.0-8.0) years. Glucocorticosteroids (GCs) were the medicaments most frequently used for remission induction (593/622; 95.3%), followed by cyclophosphamide (487/622; 78.3%), rituximab (44/622; 7.1%), and methotrexate (39/ 622; 6.3%). GCs were also most frequently administered for maintenance therapy (499/592; 84.3%), followed by azathioprine (224/592; 37.8%), methotrexate (136/592; 23.0%) and mycophenolate mofetil (99/592; 16.7%). The median cumulative doses of cyclophosphamide and rituximab equalled 7.99 g (4.18-14.0) and 2000 mg (1500-2800), respectively. The most commonly observed adverse events included: infections -214/ 551 cases (38.8%), which were associated with the time of observation (OR = 1.05; 95% CI 1.01-1.10), the use

Clinical Rheumatology, 2019
Objective Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are rare small... more Objective Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are rare small to medium-size vessel systemic diseases. As their clinical picture, organ involvement, and factors influencing outcome may differ between countries and geographical areas, we decided to describe a large cohort of Polish AAV patients coming from several referral centers-members of the Scientific Consortium of the Polish Vasculitis Registry (POLVAS). Methods We conducted a systematic multicenter retrospective study of adult patients diagnosed with AAV between Jan 1990 and Dec 2016 to analyze their clinical picture, organ involvement, and factors influencing outcome. Patients were enrolled to the study by nine centers (14 clinical wards) from seven Voivodeships populated by 22.3 mln inhabitants (58.2% of the Polish population). Results Participating centers included 625 AAV patients into the registry. Their distribution was as follows: 417 patients (66.7%) with GPA, 106 (17.0%) with MPA, and 102 (16.3%) with EGPA. Male-to-female ratios were almost 1:1 for GPA (210/207) and MPA (54/52), but EGPA was twice more frequent among women (34/68). Clinical manifestations and organ involvement were analyzed by clinical phenotype. Their clinical manifestations seem very similar to other European countries, but interestingly, men with GPA appeared to follow a more severe course than the women. Fifty five patients died. In GPA, two variables were significantly associated with death: permanent renal replacement therapy (PRRT) and respiratory involvement (univariate analysis). In multivariate analysis, PRRT (OR = 5.3; 95% confidence Electronic supplementary material The online version of this article () contains supplementary material, which is available to authorized users.

Rheumatology, 2019
Background: Renal involvement in ANCA-associated vasculitis (AAV) is frequently characterized by ... more Background: Renal involvement in ANCA-associated vasculitis (AAV) is frequently characterized by a decline in renal function. Endothelin has been implicated in renal cell injury, inflammation and fibrosis. We hypothesized that the degree of endothelin-1 type A receptor (ETAR) expression in renal specimen can predict decline in estimated glomerular filtration (eGFR) in renal AAV patients. Methods: Immunohistochemical evaluation for ETAR expression was performed on the renal biopsies of patients with renal AAV using anti-ETAR antibody (rabbit polyclonal, Abcam, USA). Control reactions were performed on 5 normal kidneys. A composite ETAR expression score [EES] was calculated for each biopsy based on the intensity of expression (0 for negative, 3 for high) using the formula: Results: Cohort consisted of 8 patients with PR3-ANCA, 6 with MPO-ANCA and 2 ANCA-negative (10M, 6F); mean age 55 AE 10 years. Tubular epithelium revealed diffuse cytoplasmic pattern of ETAR expression in all analyzed patients [fig. A]. Renal vessels were negative for ETAR [fig. B]. In 3 patients immunoreactivity of ETAR was observed only in glomerular crescents [figs. C and D]. Composite EES was in range 1-6 for all patients. In general, patients with higher composite EES (>3) showed a decline in eGFR when compared to lower EES ( 3) after 24 (17 vs 47ml/min; p < 0.05) and 36 months (16,5 vs 44ml/min; p < 0.05). Conclusion: ETAR expression in kidney biopsies of renal AAV patients appears as the new prognostic marker in predicting renal function decline in the long term. Further studies are needed to fully elucidate the relevance of ETAR expression and its antibody presence in patients with AAV.

Nephrology Dialysis Transplantation, 2017
nephrotic syndrome and were followed-up for at least 1 year, excluding those with secondary membr... more nephrotic syndrome and were followed-up for at least 1 year, excluding those with secondary membranous nephropathy. We investigated the renal prognosis with respect to treatment methods, regarding end-stage renal disease (ESRD) or a 50% increase in the creatinine (Cre) level as an outcome. To analyze the rate of kidney hypofunction with respect to treatment methods, a log-rank test was performed using the Kaplan-Meier method. In addition, Cox's proportional hazard analysis was conducted using factors involved in kidney hypofunction as covariants. RESULTS: Concerning the background of the 160 subjects, the mean follow-up period was 11.3 years. They consisted of 91 males and 69 females. The mean age, blood pressure, urinary protein level, albumin (Alb) level, estimated glomerular filtration rate (eGFR), and total cholesterol (TCho) level were 53.8 years, 97.5 mmHg, 5.1 g/day, 2.6 g/dL, 72.0 mL/min/1.73 m 2 , and 314 mg/dL, respectively. Corticosteroid therapy was performed for 76 patients (P group), combination therapy with corticosteroid and cyclophosphamide for 58 (CPA group), and combination therapy with corticosteroid and cyclosporine for 26 (CyA group). RAS inhibitors were concurrently administered to 40 patients. When regarding ESRD as an outcome, the renal survival rates after 10 years in the P, CPA, and CyA groups were 96.1, 87.4, and 94.7%, respectively. Those after 20 years were 89.1, 69.1, and 94.7%, respectively. When regarding a 50% increase in the Cre level as an outcome, the rates after 10 years were 80.7, 76.8, and 69.5%, respectively; there were no significant differences among the 3 groups (log-rank, p=0.553). Cox's proportional hazard analysis involving adjustment with the sex, blood pressure, urinary protein level, Alb level, eGFR, and treatment methods showed that the hazard ratios of combination therapy with cyclosporine and monotherapy with corticosteroid were 1.11 (95%CI: 0.38-3.01) and 0.88 (95%CI: 0.43-1.81), respectively, regarding combination therapy with cyclophosphamide as a reference. There were no significant differences among the 3 groups. CONCLUSIONS: These results suggest that the effects of combination therapy with cyclosporine to prevent kidney function deterioration are similar to those of combination therapy with cyclophosphamide in idiopathic membranous nephropathy patients with nephrotic syndrome.
Postępy Higieny i Medycyny Doświadczalnej, 2016
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are a group of small ves... more Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are a group of small vessel vasculitides which commonly affect the kidneys, manifesting as rapidly progressive glomerulonephritis. In this review, we present different treatment methods (e.g. cyclophosphamide, rituximab, plasma exchange) used for remission induction and maintenance in renal AAV. We also discuss treatment options in relapsing and refractory disease and for patients with end-stage renal disease due to AAV. In addition, we enumerate the various risk factors associated with relapsing and refractory disease, quality of life impairment and decreased renal and patient survival in AAV. Finally we present information on new, potentially applicable agents which can further help modify the disease course, thereby leading to increased patient survival.

Clinical Kidney Journal, 2015
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are a group of pauciimmu... more Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are a group of pauciimmune small vessel vasculitides that often affect the kidneys manifesting as rapidly progressive glomerulonephritis. Although the exact pathogenesis of AAV is not fully known, evidence from in vitro, in vivo and clinical studies all point to the involvement of ANCA in the pathogenesis of AAV. In this review, we highlight the contributory roles played by various factors (e.g. genetics, environment, B and T-regulatory cells, toll-like receptors, etc.) in the pathogenesis of AAV. Furthermore, we discuss renal involvement in AAV in terms of clinical features and the various histopathological classification patterns, which are also known to be of prognostic importance. We also present information on useful imaging techniques for localizing kidney and other organ system involvement in AAV, and also on novel laboratory methods and assays useful for rapid and more specific determination of patients' ANCA status. Finally, we demonstrate evidence on novel serum biomarkers that have been shown to correlate with disease activity in AAV.
Cardiology Journal, 2013
Diabetes mellitus (DM) is a disease of increasing incidence and prevalence. Arterial baroreceptor... more Diabetes mellitus (DM) is a disease of increasing incidence and prevalence. Arterial baroreceptors are stretch-sensitive receptors, which in a reflex manner are involved in the homeostatic control of arterial blood pressure. Diabetic subjects have depressed baroreflex sensitivity (BRS), although the exact pathomechanisms are unclear. In this review, we discuss the features, clinical and prognostic implications of reduced BRS for diabetic patients and the potential involvement of cardiovascular autonomic neuropathy and atherosclerosis. Finally, we demonstrate evidence on interventions (e.g. pioglitazone, alpha-lipoic acid, leptin, fluvastatin, physical training etc.) which could improve BRS and ameliorate cardiovascular autonomic dysfunction in diabetic patients.

Anti-ETAR and suPAR as markers of disease activity in renal ANCA-associated vasculitis
Advances in Medical Sciences, 2022
PURPOSE In anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), there is a la... more PURPOSE In anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), there is a lack of reliable biomarkers of disease activity. The aim of the study was to evaluate soluble urokinase plasminogen activator receptor (suPAR) and anti-endothelin-1 type A receptor (anti-ETAR) antibodies levels in active phase and remission of AAV. PATIENTS AND METHODS We enrolled 60 patients (median age 63.0 years) with renal AAV into this study. Plasma suPAR, urine suPAR (expressed as urine suPAR/creatinine ratio) and serum anti-ETAR antibodies were assayed by ELISA. Disease activity was assessed using Birmingham Vasculitis Activity Score (BVAS) and patients were divided into 2 subgroups based on their BVAS scores, namely: active AAV subgroup (BVAS≥1) and remission subgroup (BVAS = 0). Median follow-up was 12 months. RESULTS Patients with active AAV had higher levels of all candidate biomarkers in comparison to those in remission (p < 0.05). C-statistics for plasma suPAR, urine suPAR/creatinine ratio and serum anti-ETAR were 0.807, 0.713 and 0.783, respectively. In multivariable analysis, no clear associations were found between serum anti-ETAR and BVAS, while both plasma suPAR and serum anti-ETAR were independently influenced by estimated glomerular filtration rate (eGFR). CONCLUSIONS Plasma suPAR better discriminated between active AAV and remission in comparison to urine suPAR/creatinine ratio and serum anti-ETAR antibodies.
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Papers by Olumide Rowaiye