Background/Aims: We aimed to investigate the effects of glomerular IgM and C3 deposition on outcomes of adult patients with primary focal segmental glomerulosclerosis (FSGS). Methods: In this retrospective analysis, 86 consecutive adult patients with biopsy-proven primary FSGS were stratified into 3 groups according to their histopathological features: IgM– C3–, IgM+ C3–, and IgM+ C3+. Primary outcome was defined as at least a 50% reduction in baseline estimated glomerular filtration rate (eGFR) or development of kidney failure, while complete or partial remission rates were secondary outcomes. Results: Glomerular IgM deposits were found in 44 (51.1%) patients, 22 (25.5%) of which presented with accompanying C3 deposition. Patients in IgM+ C3+ group had higher level of proteinuria (5.6 g/24 h [3.77–8.5], p = 0.073), higher percentage of segmental glomerulosclerosis (20% [12.3–27.2], p = 0.001), and lower levels of eGFR (69 ± 37.2 mL/min/1.73 m2, p = 0.029) and serum albumin (2.71 ± 0.85 g/dL, p = 0.045) at the time of diagnosis. Despite 86.3% of patients in IgM+ C3+ group (19/22) received immunosuppressive treatment, the primary outcome was more common in patients in the IgM+ C3+ group compared with patients in IgM+ C3– and IgM– C3– groups (11 [50%] vs. 2 [9%] and 11 [26.1%] respectively [p = 0.010]). Complete or partial remission rates were lower in patients in the IgM+ C3+ group (5/22, 22.7%), as well (p = 0.043). Multivariate Cox regression analysis revealed that IgM and C3 co-deposition was an independent risk factor associated with primary outcome (hazard ratio 3.355, 95% CI 1.349–8.344, p = 0.009). Conclusions: Glomerular IgM and C3 co-deposition is a predictor of unfavorable renal outcomes in adult patients with primary FSGS.
Objective: Angiotensin II promotes growth and angiogenesis via type 1 receptors (AGTR1) in certain tumors. In this study, we examine the bone marrow AGTR1 expression in multiple myeloma (MM) and its relationship with the regulation of angiogenesis and prognostic factors. Materials and Methods: Bone marrow AGTR1 mRNA levels of 39 MM patients and 15 healthy controls were analyzed with quantitative RT-PCR. Immunohistochemical staining of the tissue vascular endothelial growth factor (VEGF), CD34, and factor VIIIrAg (fVIIIrAg) was used to assess bone marrow angiogenesis. Results: Bone marrow samples of the patients showed increased VEGF, fVIIIrAg, and CD34 staining and higher AGTR1 expression levels when compared to controls. Patients with severe-diffuse bone marrow infiltration showed higher bone marrow VEGF, fVIIIrAg, CD34, and AGTR1 mRNA levels when compared to other patients. Conclusion: AGTR1 expression was found positively correlated with plasma β2-microglobulin level and patients with increased AGTR1 expression showed increased bone marrow CD34 levels.
Background Galactose-deficient IgA1 (Gd-IgA1) has an increased tendency to form immunocomplexes with IgG in the serum, contributing to IgAN pathogenesis by accumulating in the glomerular mesangium. Several studies showed that glomerular IgG deposition in IgAN is an important cause of mesangial proliferation and glomerular damage. This study aims to determine the association of the positivity of IgG and the intensity of IgG staining with a poor renal prognosis. Methods A total of 943 IgAN patients were included in the study. Glomerular IgG staining negative and positive patients were compared using Oxford classification scores, histopathological evaluations, proteinuria, eGFR, albumin, blood pressures. IgG positive patients were classified as (+), (++), (+++) based on their staining intensity, and the association with the prognostic criteria was also evaluated. Results 81% (n = 764) of the patients were detected as IgG negative, while 19% (n = 179) were positive. Age, gender, body mass index, blood pressure, proteinuria, eGFR, uric acid values were similar in IgG positive and negative patients who underwent biopsy (p > 0.05). Intensity of glomerular IgG positivity was not found to be associated with diastolic and systolic blood pressure, urea, uric acid, age, eGFR, albumin, proteinuria (p > 0.05 for all, r = − 0.084, r = − 0.102, r = − 0.006, r = 0.062, r = 0.014, r = − 0.044, r = − 0.061, r = − 0.066, r = 0.150, respectively). There was no difference for histopathological findings between IgG (+), IgG (++), IgG (+++) groups (for all, p > 0.05). Conclusion Glomerular IgG negativity and positivity detected by routine IFM in IgAN patients is not associated with poor renal prognostic risk factors.
Background In this study, we evaluated hepatobiliary involvement in inflammatory bowel disease (IBD) with FibroScan® (transient elastography) and examined drug effects on liver fibrosis and steatosis. We particularly focused on the effect of azathioprine (AZT) on spleen stiffness (SS). Methods A total of 352 subjects were included in this study, including 298 IBD patients and 54 healthy controls. LSM (liver stiffness measurement), SS, and CAP™ (controlled attenuation parameter) scores were measured by FibroScan®. In addition to disease and patient characteristics; laboratory tests, and effect of the drugs were evaluated and compared within the groups. Results The patient and control groups were similar in terms of age and gender. The characteristics of the groups are shown in Table 1. Mean LSM (5.2±3.1kPa vs 4.5±1,1kPa), mean SS (22.69±13,10kPa vs 17.96±7,44kPa), CAP™ score (hepatosteatosis) (233±56dB/m vs 224±47dB/m) were significantly higher in the patients with IBD than in the control group (p<0.05). Liver fibrosis and steatosis grades are shown in Figure 1. A positive correlation was found between CAP™ score and male gender, hypertension, diabetes, BMI, smoking, penetrating disease, GGT, triglyceride, LSM, and SS (p<0.05). LSM (5.7±3,1kPa vs 5.0±3,1kPa) was significantly higher in patients with extraintestinal involvement (p<0.05). In patients with significant liver fibrosis (F2-3-4), the frequency of anti-TNF treatment was lower (44,4% vs 69,5%; p=0,008) (Figure 2). In patients who use alcohol regularly compared to nondrinkers (25.54±14,83kPa vs 21.05±11,24kPa) SS was significantly higher (p<0.05). Additionally, in patients using AZT≥100 mg/day compared to those using AZT<100 mg/day (23.48±14,61kPa vs 19.99±11,84kPa; p<0,05) SS was significantly higher (Figure 3). AZT dose was positively correlated with SS (Spearman analysis; r=0.182 and p=0.013); however, no correlation was found with the duration or cumulative dose of AZT. The mean level of platelets was significantly higher in patients with IBD than in controls (300±104x10³/µL vs 251±52x10³/µL, p=0,001); however, there was no correlation between SS and trombosit level (p>0,05). 83% of patients were in clinical remission (Mayo score≤2/CDAI<150). No positive correlation was found between disease activity and SS in IBD patients. AZT-associated non-cirrhotic portal hypertension was detected in only one patient. Conclusion In this study, fatty liver, liver fibrosis, and SS were found to be significantly higher in IBD patients than in healthy controls. Although there is no relationship with the duration of AZT therapy, AZT dose was positively correlated with SS. We recommend that spleen stiffness should be evaluated in patients who use high doses of AZT (≥100 mg/day).
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