Antibody response to two doses of inactivated SARS-CoV-2 vaccine (CoronaVac) in kidney transplant recipients.

BACKGROUND: Coronavirus Disease-19 (COVID-19) has high mortality in kidney transplant recipients (KTR), and vaccination against severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) is vital for this population. Although the humoral response to messenger RNA vaccines was shown to be impaired in KTR, there is a lack of data regarding the antibody response to inactivated vaccines. We investigated the antibody response to two consequent doses of the inactivated SARS-CoV-2 vaccine (CoronaVac; Sinovac Biotech, China). METHODS: A total of 118 patients from two centers were included. The levels of anti-SARS-CoV-2 immunoglobulin-G antibodies against the nucleocapsid and spike antigens were determined with enzyme immunoassay (DIA.PRO; Milano, Italy) before the vaccine and one month after the second dose of the vaccine. Thirty-three patients were excluded due to antibody positivity in the serum samples obtained before vaccination. RESULTS: Eighty-five patients, 47 of whom were female, with a mean age of 46 ± 12, were included in the statistical analysis. The maintenance immunosuppressive therapy comprised tacrolimus (88.2%), mycophenolate (63.6%), and low-dose steroids (95.3%) in the majority of the patients. After a median of 31 days following the second dose of the vaccine, only 16 (18.8%) patients developed an antibody response. The median (IQR) antibody level was 52.5 IU/ml (21.5-96). Age (48 vs. 38, p = .005) and serum creatinine levels (1.14 vs. 0.91, p = .04) were higher in non-responders and were also found to be independently associated with the antibody response (odds ratio (OR): 0.93, p = 0.012 and 0.15, p = 0.045, respectively) in multivariate analysis. CONCLUSION: In this study, we found the antibody response to the inactivated vaccine to be considerably low (18.8%) in KTR. Increased age and impaired renal function were associated with worse antibody response. Based on the knowledge that mRNA vaccines yield better humoral responses, this special population might be considered for additional doses of mRNA vaccination.

A multicenter study of the clinical, laboratory characteristics, and potential prognostic factors in patients with amyloid A amyloidosis on hemodialysis.

INTRODUCTION: While light chain (AL) amyloidosis is more common in western countries, the most common type of amyloidosis is amyloid A (AA) amyloidosis in Eastern Mediterranean Region, including Turkey. Although worse prognosis has been attributed to the AL amyloidosis, AA amyloidosis can be related to higher mortality under renal replacement therapies. However, there are no sufficient data regarding etiology, clinical presentation, and prognostic factors of AA amyloidosis. The objective of our study is to evaluate the clinical, laboratory characteristics, and possible predictive factors related to mortality in patients with AA amyloidosis undergoing hemodialysis (HD). METHODS: This multicenter, cross-sectional study was a retrospective analysis of 2100 patients on HD. It was carried out in 14 selected HD centers throughout Turkey. Thirty-two patients with biopsy-proven AA amyloidosis and thirty-two control patients without AA amyloidosis undergoing HD were included between October 2018 and October 2019. There was no significant difference between the groups in terms of age and dialysis vintage. Causes of AA amyloidosis, treatment (colchicine and/or anti-interleukin 1 [IL] treatment), and the number of familial Mediterranean fever (FMF) attacks in the last year in case of FMF, systolic and diastolic blood pressures, biochemical values such as mean CRP, hemoglobin, serum albumin, phosphorus, calcium, PTH, ferritin, transferrin saturation, total cholesterol levels, EPO dose, erythropoietin-stimulating agents resistance index, interdialytic fluid intake, body mass indexes, heparin dosage, UF volume, and Kt/V data in the last year were collected by retrospective review of medical records. FINDINGS: Prevalence of AA amyloidosis was found to be 1.87% in HD centers. In amyloidosis and control groups, 56% and 53% were male, mean age was 54 ± 11 and 53 ± 11 years, and mean dialysis vintage was 104 ± 94 and 107 ± 95 months, respectively. FMF was the most common cause of AA amyloidosis (59.5%). All FMF patients received colchicine and the mean colchicine dose was 0.70 ± 0.30 mg/day. 26.3% of FMF patients were unresponsive to colchicine and anti-IL-1 treatment was used in these patients. In AA amyloid and control groups, erythropoietin-stimulating agents resistance index were 7.88 ± 3.78 and 5.41 ± 3.06 IU/kg/week/g/dl, respectively (p = 0.008). Additionally, higher CRP values (18.78 ± 18.74 and 10.61 ± 10.47 mg/L, p = 0.037), lower phosphorus (4.68 ± 0.73 vs. 5.25 ± 1.04 mg/dl, p = 0.014), total cholesterol (135 ± 42 vs. 174 ± 39 mg/dl, p < 0.01), and serum albumin (3.67 ± 0.49 mg/dl, 4.03 ± 0.22, p < 0.01) were observed in patients with AA amyloidosis compared to the control group. DISCUSSION: In this study, we found that long-term prognostic factors including higher inflammation, malnutritional parameters, and higher erythropoietin-stimulating agents resistance index were more frequent in AA amyloidosis patients under HD treatment.

Potential drug-drug interactions of immunosuppressants in kidney transplant recipients: comparison of drug interaction resources.

Background Drug-drug interactions are frequently observed in kidney transplant recipients due to polypharmacy and use of immunosuppressants. However, there is only one study evaluating clinically relevant potential drug-drug interactions of immunosuppressants specially in kidney transplant recipients by means of online databases and Stockleys Drug Interactions, as a gold standard. Aim This study aimed to compare four online databases used frequently to determined clinically relevant potential drug-drug interactions of immunosuppressants in kidney transplant recipients according to the Renal Drug Handbook. Method This was a descriptive cross-sectional study conducted between October 1, 2019, and March 18, 2020, in the nephrology ward of Ankara University School of the Medicine, Ibn-i Sina Hospital. In total, 52 adult patients' discharge prescriptions were retrieved from their medical records and analyzed retrospectively. Micromedex®, Lexicomp®, Medscape, and Drugs.com databases were used to evaluate drug interactions. The Renal Drug Handbook was used as a gold standard to do specificity and sensitivity analysis. Results A total of 127 potential drug-drug interactions between the immunosuppressants and co-medications were detected by at least one online database. 32 (25.2%) of these were approved as clinically relevant potential drug-drug interactions by the Renal Drug Handbook. Lexicomp® and Drugs.com have exhibited the highest sensitivity (0.72 and 0.75) while Micromedex® has shown the highest specifity (0.83). Furthermore, the highest positive predictive value has been observed in Micromedex® (0.53). Micromedex® and Medscape had the highest negative predictive value (0.83 and 0.82). However, the kappa value of all was low. The values of inter-rater agreement (Kappa index) between online databases and the Renal Drug Handbook were weak (range 0.05-0.36). In addition, only 11 (8.7%) of potential drug-drug interactions were identified by all online databases. Conclusion This study showed that there was a weak compatibility between each database examined and the Renal Drug Handbook to detect clinically relevant potential drug-drug interactions for immunosuppressants in kidney transplant recipients. Therefore, we suggest that although databases might be practical to take a quick glance in detection of potential drug-drug interactions between immunosuppressants and co-medications, the data should be evaluated in detail and interpreted with caution in combination with a reference book like Renal Drug Handbook.

Cytomegalovirus infection in patients with glomerular diseases treated with cyclophosphamide: a single-center prospective study.

PURPOSE: Cytomegalovirus infection is an important complication in immunocompromised patients. As few studies have shown that cyclophosphamide treatment is a risk factor for cytomegalovirus infection in patients with glomerulonephritis, we aimed to describe the frequency and risk factors of cytomegalovirus infection in glomerulonephritis patients treated with cyclophosphamide. METHODS: We prospectively recruited 43 cytomegalovirus seropositive patients with glomerulonephritis treated with cyclophosphamide. We screened all patients for viral DNA monthly during treatment. Patients were compared for age, sex, glomerular pathology, renal function and clinical status regarding development of cytomegalovirus infection before and after the treatment. RESULTS: Cytomegalovirus infection was detected in 10 (23.3%) patients, most commonly within the first 2 months of cyclophosphamide treatment. All patients recovered without any cytomegalovirus-related complications. Patients with cytomegalovirus infection had higher serum creatinine (4.2 ± 3.2 vs. 1.9 ± 1.8 mg/dl, p = 0.006) and lower estimated glomerular filtration rate (29 ± 11 vs. 65 ± 8 ml/min/1.73 m2, p = 0.016) at diagnosis compared with cytomegalovirus infection non-occurred patients. In addition, number of patients presented with rapidly progressive glomerulonephritis were higher in cytomegalovirus infection group (80.0% vs. 27.3%, p = 0.007). Moreover, cytomegalovirus infection was associated with prolonged hospital stay (54 ± 7 vs. 29 ± 6 days, p = 0.027). CONCLUSION: Cytomegalovirus infection is a common complication in glomerulonephritis patients treated with cyclophosphamide in this prospective study. Routine monitoring and prophylaxis should be considered for these high-risk patients.

Two patients, two viruses and multiple sites of injury in the kidney.

Viral nephropathy is a term defines glomerular, tubular and/or vascular injury in kidney caused by viruses itself or virus-induced immune mechanisms. It is difficult to prove causality between the renal disease and the viral infection, however, renal biopsy findings can help in this regard. Several viruses such as hepatitis B and C, Human immun deficiciency virus (HIV), Hantavirus, Cytomegalovirus (CMV), an recently Coronavirus are shown to affect the kidney. Treatment of viral nephropathies are unique regarding the diagnosis which can be made only with renal biopsy in most of the situations. We present two patients presented with acute kidney injury and thrombocytopenia caused by different viruses (Hantavirus and HIV) that affect multiple areas in kidney that revealed with kidney biopsy. Supportive treatment in the patient with Hantavirus nephropathy and HIV treatment along with eculizumab and supportive treatment in the patient with HIVAN were successfully implemented.

Infectious Complications in Patients with Primary Glomerulonephritis over 10 Years: A Single-Center Experience in Turkey.

INTRODUCTION: Infections can play an important role in the mortality and morbidity of patients with glomerulonephritis. However, the frequency of infectious complications in primary glomerulonephritis and their burden to the healthcare managements are not clear. METHODS: We evaluated the infectious complications in patients with biopsy-proven focal segmental glomerulosclerosis, membranous glomerulonephritis, IgA nephropathy, minimal change disease, membranoproliferative glomerulonephritis, and chronic glomerulonephritis during the last 10 years in a single center. We recorded the demographic, clinical, and laboratory characteristics; treatment modalities; infectious episodes; and infection-related mortality and morbidity of the patients. RESULTS: Of the patients, 154 (63.6%) received immunosuppressive treatment and 88 (34.4%) were followed up under conservative treatment. Overall, 118 infectious episodes were noted in 64 patients, with an infection rate of 0.20 per patient-year. Total infectious complications were higher in the immunosuppressive group than in the conservative group (42.1 vs. 23.3%, p = 0.005). Infection-related hospitalizations were also higher in the immunosuppressive group (p = 0.01). The most frequently infected area was the lungs (15.7%). Although bacterial infections were the most common in both groups, 14.9% of the immunosuppressive group had cytomegalovirus (CMV) replication. Age >50 years (OR 2.19, p = 0.03), basal serum albumin <2.5 g/dL (OR 2.28, p = 0.02), cyclophosphamide (OR 2.43, p = 0.02), and cyclosporine (OR 2.30, p = 0.03) were independently associated with experiencing infectious episodes. CONCLUSIONS: Because of high seropositivity for CMV in Turkey, it might be a wise approach to use prophylactic antiviral drugs in patients treated with immunosuppressive treatments. Close monitoring of patients with primary glomerulonephritis, especially those treated with immunosuppressive therapy, is important for reducing infection-related morbidity and mortality.

Pre-transplant sTIM-3 levels may have a predictive impact on transplant outcome in acute leukemia patients.

Objectives: T-cell immunoglobulin and mucin domain-containing protein-3 (TIM-3) is considered as a negative regulator of T-cell driven immune response. This study is planned to investigate the prognostic role of pre-transplant soluble TIM-3 (sTIM-3) levels in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Methods: Pre-transplant serum sTIM-3 levels were measured in 177 allo-HSCT recipients [median age: 36(16-66) years; male/female: 111/66]. Results: Pre-transplant sTIM-3 levels were significantly higher in acute myeloid leukemia (AML) patients compared to acute lymphoblastic leukemia (ALL) patients (p = 0.01). Pre-transplant sTIM-3 levels were significantly lower in patients with abnormal cytogenetics (p = 0.017). Pre-transplant sTIM-3 levels were significantly higher in patients who developed viral hemorrhagic cystitis (p = 0.034). A positive correlation was demonstrated between sTIM-3 levels and acute graft versus host disease (GvHD) grade (p = 0.013; r = 0.299). Overall survival (OS) was not statistically different between low- and high-TIM-3 groups (%35.2 vs %20.4; p > 0.05). Primary diagnosis (p = 0.042), sinusoidal obstruction syndrome (p < 0.001), acute GvHD (p = 0.001), chronic GvHD (p = 0.009) and post-transplant relapse (p = 0.003) represented significant impact on OS. Discussion: Increased sTIM-3 levels in AML patients seem to be compatible with the previous reports. The inhibitor role of TIM-3 in cellular immune response may be a possible explanation for the association of sTIM-3 with viral infections and GvHD. However, the main challenge remains to be the ambiguous association of pre-transplant sTIM-3 levels and post-transplant complications, as allo-HSCT recipients are expected to represent donor genetic features in the post-transplant setting. Conclusion: Further studies are warranted to clarify the particular role of sTIM-3 in the allo-HSCT setting.