The relationship between glomerular IgG staining and poor prognostic findings in patients with IgA nephropathy: the data from TSN-GOLD working group.

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.

Co-Deposition of IgM and C3 May Indicate Unfavorable Renal Outcomes in Adult Patients with Primary Focal Segmental Glomerulosclerosis.

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.

Diagnosis and Treatment of Autoimmune Hepatitis: Questions, Answers, and Illustrative Cases: Endorsed by Autoimmune Liver Diseases Special Interest Group, Turkish Association for the Study of Liver.

Autoimmune hepatitis (AIH) is a rare, immune-mediated liver disease. It has a heterogeneous nature with varied clinical presentations. The management of patients with AIH is challenging in many ways. The main difficulties are inexperience due to the rarity of the disease, diagnostic confusion in controversial areas such as variant/overlap cases, acute presentations, the presence of non-alcoholic fatty liver disease or drug-induced liver injury features, and the long and complex course of treatment. Here, we provide a clear, concise, and visualized review regarding the diagnosis and treatment of AIH, including illustrative cases.

Efficacy and Safety of Sofosbuvir and Ledipasvir for Hepatitis C in Kidney Transplant Recipients: A Single-center Retrospective Observational Study

Background: Treatment using direct-acting antivirals provides high rates of sustained virologic response and a favorable safety profile for patients with chronic hepatitis C virus infection. However, data on the efficacy of direct-acting antivirals in kidney transplant recipients are still limited. Aims: To evaluate the safety and efficacy of fixed-dose sofosbuvir/ledipasvir combination in kidney transplant recipients. Study Design: Retrospective, observational, single-center study. Methods: Data of 29 kidney transplant recipients who received a fixed-dose safety and efficacy of fixed-dose sofosbuvir/ledipasvir combination for 12 or 24 weeks with or without ribavirin were analyzed. The primary outcome was SVR12, which was defined as undetectable HCV-RNA levels 12 weeks after the treatment. Secondary outcomes were graft function, proteinuria, and calcineurin inhibitor trough level variability. Results: The predominant hepatitis C virus genotype was 1b (n = 19, 65.6%). All patients achieved SVR12. No graft failures nor deaths were reported during the study period. Throughout and after the treatment, the levels of aspartate aminotransferase [21 (range: 18-29.5) to 16 (range: 14-20) U/l, p < 0.001] and alanine aminotransferase [22 (range: 15-34) to 14 (range: 12-17.5) U/l, p < 0.001] improved significantly, unlike bilirubin, hemoglobin, and platelet levels. Renal function remained stable. Dose adjustments for calcineurin inhibitors were required. Serious adverse events were not observed. Conclusion: Safety and efficacy of fixed-dose sofosbuvir/ledipasvir combination was effective and safe in kidney transplant recipients with hepatitis C virus. However, cautious monitoring of trough levels of calcineurin inhibitorss is needed due to potential drug-drug interactions during the treatment episode.

Demographic, clinical and laboratory characteristics of adult-onset minimal change disease in Turkey: Turkish Society of Nephrology-Glomerular Diseases (TSN-GOLD) Working Group.

PURPOSE: In our study, diagnostic and demographic characteristics of patients diagnosed with minimal change disease (MCD) by biopsy, clinical and laboratory findings in our country were investigated. METHODS: Data were obtained from the Turkish Society of Nephrology Glomerular Diseases (TSN-GOLD) Working Group database. Demographic characteristics, indications for biopsy, diagnosis of the glomerular diseases, comorbidities, laboratory and biopsy findings of all patients were recorded. The data presented are cross-sectional and includes application data for the biopsy period. RESULTS: Of 3875 patients, 233 patients with MCD (median age 35.0 years) were included in the study, which constitutes 6.0% of the total glomerulonephritis database. Renal biopsy was performed in 196 (84.1%) patients due to nephrotic syndrome. Median serum creatinine was 0.7 (0.6-1.0) mg/dl, mean eGFR was 104 ± 33 ml/min/1.73 m2 and median proteinuria 6000 mg/day. The number of patients under the age of 40 years was 139 (59.7%) (Group A), and the number of patients aged 40 years and over was 94 (40.3%) (Group B). Compared to Group A, global sclerotic glomeruli (24 vs. 43, p < 0.001) interstitial inflammation (15 vs. 34, p < 0.001), interstitial fibrosis (20 vs. 31, p = 0.001, vascular changes (10 vs. 25, p < 0.001) and tubular atrophy (18 vs. 30, p < 0.001) were found to be significantly higher in Group B. There was no difference in immunofluorescent staining properties between the two groups. CONCLUSION: Our data are generally compatible with the literature. Chronic histopathological changes were more common in patients aged 40 years and older than younger patients. Studies investigating the effects of these different features on renal survival are needed.

Optimal testosterone level to improve symptoms of hypogonadism without causing dopa-testotoxicosis in male macroprolactinoma.

BACKGROUND: Male prolactinoma treatment by dopamine agonists (DA) restores sexual function. However, excessive DA dose can lead to impulse control disorder. OBJECTIVES: The aim of this retrospective study was to determine the level of testosterone that eliminates symptoms and provides fertility in male macroprolactinoma, without causing these adverse effects. MATERIALS AND METHODS: Twenty-seven male patients with macroprolactinoma were included. There were 16 macro (≥1-2.8cm), 7 large macro (≥2.9-3.9cm) and 4 giant (≥4cm) adenomas. Prolactin (PRL) and testosterone (T) levels were evaluated. A timeline was created to analyze improvement in symptoms of hypogonadism and infertility. Testosterone levels were compared with age-matched controls. RESULTS: Mean PRL, basal tumor diameter and shrinkage were 2846±3415ng/mL, 27.2±10.2mm and 63.4%, respectively. Basal T levels were 1.6±1.0ng/mL for patients and 4.4±1.5ng/mL for controls (P<0.001). Mean T level in the asymptomatic period was significantly lower than in controls (3.2±0.4ng/mL vs. 4.4±1.5ng/mL, respectively; P=0.002), while mean PRL was 27.2ng/mL. Fertility was achieved in 6 of the patients seeking fertility, and there was no difference in T level between these patients and controls (3.7±0.8ng/mL and 4.4±1.5ng/mL, respectively; P=0.14); when fertility was achieved, mean PRL was 26.9±23ng/mL. CONCLUSION: Patients should be carefully questioned regarding complaints at each consultation, and DA dose should not be increased unnecessarily, to avoid possible serious adverse effects.

Characteristics of primary glomerular diseases patients with hematuria in Turkey: the data from TSN-GOLD Working Group.

PURPOSE: Hematuria is one of the most common laboratory findings in nephrology practice. To date, there is no enough data regarding the clinical and histopathologic characteristics of primary glomerular disease (PGD) patients with hematuria in our country. METHODS: Data were obtained from national multicenter (47 centers) data entered into the Turkish Society of Nephrology Glomerular Diseases (TSN-GOLD) database between May 2009 and June 2019. The data of all PGD patients over the age of 16 years who were diagnosed with renal biopsy and had hematuria data were included in the study. Demographic characteristics, laboratory and biopsy findings were also recorded. RESULTS: Data of 3394 PGD patients were included in the study. While 1699 (50.1%) patients had hematuria, 1695 (49.9%) patients did not have hematuria. Patients with hematuria had statistically higher systolic blood pressure, serum blood urea nitrogen, creatinine, albumin, levels and urine pyuria. However, these patients had statistically lower age, body mass index, presence of hypertension and diabetes, eGFR, 24-h proteinuria, serum total, HDL and LDL cholesterol, and C3 levels when compared with patients without hematuria. Hematuria was present 609 of 1733 patients (35.8%) among the patients presenting with nephrotic syndrome, while it was presented in 1090 of 1661 (64.2%) patients in non-nephrotics (p < 0.001). CONCLUSION: This is the first multicenter national report regarding the demographic and histopathologic data of PGD patients with or without hematuria. Hematuria, a feature of nephritic syndrome, was found at a higher than expected in the PGDs presenting with nephrotic syndrome in our national database.

The Role of the Local Bone Marrow Renin-Angiotensin System in Multiple Myeloma

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 ß2-microglobulin level and patients with increased AGTR1 expression showed increased bone marrow CD34 levels.