Clinical and pathologic features of primary membranous nephropathy in Turkey: a multicenter study by the Turkish Society of Nephrology Glomerular Diseases Working Group.

BACKGROUND: We aimed to evaluate the features of primary membranous nephropathy (MNP) in Turkish people. METHODS: This is a retrospective analysis of patients with biopsy-proven primary MNP. We obtained the data collected between 2009 and 2019 in the primary glomerulonephritis registry of the Turkish Society of Nephrology Glomerular Diseases Study Group (TSN-GOLD). Patients with a secondary cause for MNP were excluded. Clinical, demographic, laboratory, and histopathological findings were analyzed. RESULTS: A total of 995 patients with primary MNP were included in the analyses. Males constituted the majority (58.8%). The mean age was 48.4 ± 13.9 years. The most common presentation was the presence of nephrotic syndrome (81.7%) and sub nephrotic proteinuria (10.3%). Microscopic hematuria was detected in one-third of patients. The median estimated glomerular filtration rate (eGFR) was 100.6 mL/min/1.73 m2 (IQR, 75.4-116.3), and median proteinuria was 6000 mg/d (IQR, 3656-9457). Serum C3 and C4 complement levels were decreased in 3.7 and 1.7% of patients, respectively. Twenty-four (2.4%) patients had glomerular crescents in their kidney biopsy samples. Basal membrane thickening was detected in 93.8% of cases under light microscopy. Mesangial proliferation and interstitial inflammation were evident in 32.8 and 55.9% of the patients, respectively. The most commonly detected depositions were IgG (93%), C3 complement (68.8%), and kappa and lambda immunoglobulin light chains (70%). Although renal functions were normal at presentation, vascular, interstitial, and glomerular findings were more prominent on biopsy in hypertensive patients. No significant effect of BMI on biopsy findings was observed. CONCLUSIONS: Despite some atypical findings, the main features of primary MNP in Turkey were similar to the published literature. This is the largest MNP study to date conducted in Turkish people.

COVID-19 in chronic kidney disease: a retrospective, propensity score-matched cohort study.

BACKGROUND: The prognostic factors for COVID-19 in patients with chronic kidney disease (CKD) are uncertain. We conducted a study to compare clinical and prognostic features between hospitalized COVID-19 patients with and without CKD. METHODS: Fifty-six patients with stage 3-5 CKD and propensity score-matched fifty-six patients without CKD were included in the study. Patients were followed-up at least fifteen days or until death after COVID-19 diagnosis. The endpoints were death from all causes, development of acute kidney injury (AKI) or cytokine release syndrome or respiratory failure, or admission to the intensive care unit (ICU). RESULTS: All patients were reviewed retrospectively over a median follow-up of 44 days (IQR, 36-52) after diagnosis of COVID-19. Patients with CKD had higher intensive care unit admission and mortality rates than the patients without CKD, but these results did not reach statistical significance (16 vs. 19; p = 0.54 and 11 vs. 16, p = 0.269, respectively). The frequency of AKI development was significantly higher in predialysis patients with CKD compared to the other group (8 vs. 5; p < 0.001), but there was no significant difference between the groups in terms of cytokine release syndrome (13 vs. 8; p = 0.226), follow-up in the ICU (19 vs. 16; p = 0.541), and respiratory failure (25 vs. 22, p = 0.566). Multivariate logistic regression analysis revealed that respiratory failure and AKI were independent risk factors for mortality. CONCLUSION: The mortality rates of COVID-19 patients with CKD had higher than COVID-19 patients without CKD. Also, AKI and respiratory failure were independently related to mortality.

Clinical significance of glomerular C3 deposition in primary membranous nephropathy.

BACKGROUND: We aimed to investigate the effects of glomerular C3 deposition on clinical, histopathological features, and outcomes of patients with primary membranous nephropathy (MN). METHODS: A total of 261 patients with biopsy-proven primary MN, who were on follow up for at least 6 months, were included in the study. The patients were grouped according to their C3 immunostaining in kidney biopsy samples at the time of diagnosis: Low intensity [LI; (C3 1 +)] and high intensity [HI; (C3 2 + or C3 3 +)]. The primary outcome was the development of kidney failure. Complete (CR) or partial remission (PR) was defined as secondary outcome. RESULTS: Sixteen patients reached the primary outcome after a median follow-up of 33.8 months. Patients in the high intensity group (119 cases) had lower eGFR and higher proteinuria at admission and last follow-up compared to patients in the low intensity group (142 cases). Also, more patients in the high intensity group reached the primary outcome compared to patients in the low intensity group: twelve patients (10.1%) in the high intensity group and four patients (2.8%) in the low intensity group reached the primary outcome (p = 0.015). Kaplan-Meier analysis demonstrated that patients in the high intensity group had a higher risk for kidney failure (p = 0.02). In multivariate logistic regression analysis, high intensity C3 deposition and initial estimated glomerular filtration rate (eGFR) indepenently predicted primary outcome. CONCLUSION: Extensive glomerular C3 deposition is a predictor of kidney failure in patients with MN.

COVID-19 in kidney transplant recipients: A multicenter experience in Istanbul.

INTRODUCTION: Management of COVID-19 in kidney transplant recipients should include treatment of the infection, regulation of immunosuppression, and supportive therapy. However, there is no consensus on this issue yet. This study aimed to our experiences with kidney transplant recipients diagnosed with COVID-19. MATERIAL AND METHODS: Kidney transplant recipients diagnosed with COVID-19 from five major transplant centers in Istanbul, Turkey, were included in this retrospective cohort study. Patients were classified as having moderate or severe pneumonia for the analysis. The primary endpoint was all-cause mortality. The secondary endpoints were acute kidney injury, the average length of hospital stay, admission to intensive care, and mechanical ventilation. RESULTS: Forty patients were reviewed retrospectively over a follow-up period of 32 days after being diagnosed with COVID-19. Cough, fever, and dyspnea were the most frequent symptoms in all patients. The frequency of previous induction and rejection therapy was significantly higher in the group with severe pneumonia compared to the moderate pneumonia group. None of the patients using cyclosporine A developed severe pneumonia. Five patients died during follow-up in the intensive care unit. None of the patients developed graft loss during follow-up. DISCUSSION: COVID-19 has been seen to more commonly cause moderate or severe pneumonia in kidney transplant recipients. Immunosuppression should be carefully reduced in these patients. Induction therapy with lymphocyte-depleting agents should be carefully avoided in kidney transplant recipients during the pandemic period.

Fatal SARS-CoV-2 infection in a renal transplant recipient.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV 2) caused a pandemic that first discovered in Wuhan, China. While 10% of the patients have asymptomatic infection, 15-20% have lung involvement, 5-10% have multiple organ failure, and macrophage activation syndrome. Chronic respiratory diseases, diabetes mellitus, hypertension, and cancer are risk factors for mortality. Prognosis or optimal treatment strategy for renal transplant recipients in SARS-CoV-2 infection is still unknown. Besides fatal cases, there were also milder case reports. In addition, COVID-19 treatment and the maintenance immunosuppression strategy is still under debate. Antiviral therapies and drug interactions are special topics for these patients. To the best of our knowledge, favipiravir and anti-cytokine treatments have not been previously reported in a kidney transplant recipient with SARS-CoV-2 infection before. We report a case of SARS-CoV-2 infection in a kidney transplant recipient with fatal outcomes.

Infectious Complications of Induction Therapies in Kidney Transplantation.

BACKGROUND Cytomegalovirus (CMV) and BK virus (BKV) are post-transplant opportunistic viral infections that affect patient and graft survival. This study was designed to evaluate the risk of BKV nephropathy and CMV disease in kidney transplant recipients who received induction therapy with ATG or basiliximab. MATERIAL AND METHODS We retrospectively analyzed information on 257 adult patients who underwent kidney transplantation between January 2007 and 2017. Patients were categorized into 3 groups according to the induction therapies. The primary endpoint was the onset of CMV disease or biopsy-confirmed BKV nephropathy. The secondary endpoints were biopsy-proven rejection episodes, graft loss, loss to follow-up, and death. RESULTS We followed 257 patients for a median of 55.5 months. The incidence of CMV disease was significantly higher in the only ATG group compared to the group without induction treatment (p<0.001). There was no significant difference in the incidence of BKV nephropathy among groups (p>0.05). The dosage of ATG (OR, 10.685; 95% CI, 1.343 5 to 85.009; P=0.025) was independent risk factor for death. CONCLUSIONS This study demonstrated that a higher dosage of ATG in high-risk patients is associated with an increased risk of CMV disease and patient death, also, reducing the dosage may be a rational strategy for increasing graft and patient's survival.

Fabry Disease Prevalence in Renal Replacement Therapy in Turkey.

BACKGROUND: Fabry disease (FD) is an X-linked lysosomal storage disorder resulting from lack of alpha-galactosidase A (AGALA) activity in lysosomes. OBJECTIVE: In this multicenter study, we aimed to evaluate the prevalence of FD in renal transplant (Tx) recipients in Turkey. We also screened dialysis patients as a control group. METHODS: All Tx and dialysis patients were screened regardless of the presence of a primary disease. We measured the AGALA activity in all male patients as initial analysis. Mutation analysis was performed in male patients with decreased AGALA activity and in female patients as the initial diagnostic assay. RESULTS: We screened 5,657 patients. A total of 17 mutations were identified. No significant difference was observed between the groups regarding the prevalence of patients with mutation. We found FD even in patients with presumed primary kidney diseases. Seventy-one relatives were analyzed and mutation was detected in 43 of them. We detected a patient with a new, unknown mutation (p.Cys223) in the GLA gene. CONCLUSIONS: There are important implications of the screening. First, detection of the undiagnosed patients leads to starting appropriate therapies for these patients. Second, the transmission of the disease to future generations may be prevented by prenatal screening after appropriate genetic counseling. In conclusion, we suggest screening of kidney Tx candidates for FD, regardless of etiologies of chronic kidney disease.

Acute renal infarction in Turkey: a review of 121 cases.

PURPOSE: Renal infarction is a clinical condition which is caused by renal artery occlusion and leads to permanent renal parenchymal damage. In the literature, there are generally case reports on this subject, and few studies that include a large group of patients. Therefore, we aimed to present the data of a large group of patients who were diagnosed with acute renal infarction in our country in this retrospective study. METHODS: The data of patients who were diagnosed with acute renal infarction according to clinical and radiological findings in Turkey in the last 3 years were examined. For this purpose, we contacted with more than 40 centers in 7 regions and obtained support from clinically responsible persons. Demographic data of patients, laboratory data at the time of diagnosis, tests performed for etiologic evaluation, given medications, and patients' clinical status during follow-up were obtained from databases and statistical analysis was performed. RESULTS: One-hundred and twenty-one patients were included in the study. The mean age was 53 ± 1.4 (19-91) years. Seventy-one (58.7%) patients were male, 18 (14.9%) had diabetes, 53 (43.8%) had hypertension, 36 (30%) had atrial fibrillation (AF), and 6 had a history of lupus + antiphospholipid syndrome (APS). Forty-five patients had right renal infarction, 50 patients had left renal infarction, and 26 (21.5%) patients had bilateral renal infarction. The examinations for the ethiologies revealed that, 36 patients had thromboemboli due to atrial fibrillation, 10 patients had genetic anomalies leading to thrombosis, 9 patients had trauma, 6 patients had lupus + APS, 2 patients had hematologic diseases, and 1 patient had a substance abuse problem. Fifty-seven (57%) patients had unknown. The mean follow-up period was 14 ± 2 months. The mean creatinine and glomerular filtration rate (GFR) values at 3 months were found to be 1.65 ± 0.16 mg/dl and 62 ± 3 ml/min, respectively. The final mean creatinine and GFR values were found to be 1.69 ± 0.16 mg/dl and 62 ± 3 ml/min, respectively. CONCLUSIONS: Our study is the second largest series published on renal infarction in the literature. More detailed studies are needed to determine the etiological causes of acute renal infarction occurring in patients.

Transplant Patients With Failing Renal Allografts.

Progress in patient care and immunosuppressive medications has resulted in improved allograft survival in the early posttransplant period; however, substantial graft loss continues in the long term. Therefore, the number of dialysis patients with failed allografts is increasing progressively. These patients have a worse prognosis than naive dialysis patients. Cardiovascular causes are the leading cause of death, followed by infections and malignancies. Delay in return to dialysis, a chronic inflammatory state, infections, and cancer are contributing factors to mortality, whereas type of dialysis modality does not have a significant effect on outcomes. Graft nephrectomy is a risky operation; therefore, it should not be a routine procedure and rather should be performed only when indicated. Overall, most grafts are left in place, whereas graft nephrectomy is performed in atients with graft intolerance syndrome. Management of immunosuppressive drugs after graft failure is controversial. In the case of maintaining immunosuppression, there is increased risk of infections, cardiovascular diseases, and malignancies and also steroid-related adverse effects. On the other hand, discontinuation of immunosuppressants may result in loss of residual allograft function and also acute graft inflammation. Together, immunosuppressive drugs are almost always discontinued in these patients because of their inherent adverse effects. Considering the sequence of cessation, first antiproliferative drugs are stopped, followed by calcineurin inhibitors, and finally steroids. Because many studies show a clear survival benefit, every attempt should be made for a retransplant in patients with failed renal allografts.

Inflammatory myofibroblastic tumor mimicking a relapse in a patient with Hodgkin's lymphoma: report of an unusual case and review of the literature.

New PET-positive lesions in previously treated patients with lymphomatous malignancies need further investigations. Relapse, sarcoidosis and secondary malignancies are the most important differential diagnosis. Inflammatory myofibroblastic tumors (IMT) is a rare complication after treatment of Hodgkin's disease and every PET-positive lesion should be biopsied to prevent unnecessary intervention.