Peroxiredoxins as Markers of Oxidative Stress in IgA Nephropathy, Membranous Nephropathy and Lupus Nephritis

IgA nephropathy (IgAN), membranous nephropathy (MN), and lupus nephritis (LN) represent important causes of chronic kidney disease. They belong to the immune-mediated glomerulonephritis (GNs), and have distinct pathogenesis, distinct clinical courses, and variable responses to treatment. Therefore, specific diagnostic procedures are necessary for more effective patient management. Recently, a role for oxidative stress has been proposed in various renal disorders. Thus, molecules related to oxidative stress, such as 2-Cys-peroxiredoxins (PRDXs), may represent plausible candidates for biomarkers in renal pathologies. The aim of this study was to assess whether there are differences between individual GNs and healthy controls in the context of PRDXs serum concentration. We enrolled 108 patients with biopsy-proven IgAN (47), MN (26), LN (35) and 30 healthy age- and sex-matched controls. The serum concentrations of PRDX 1–5 were measured with ELISA assays and correlated with demographic and clinical data. The PRDXs’ concentration varied depending on the GN type. We also observed an association of PRDXs with lower estimated glomerular filtration rates, complement, hemoglobin, and body mass index. Our study indicates that individual PRDX can play roles in pathophysiology of selected GNs and that their serum concentrations may become useful as a new supplementary diagnostic markers in IgAN, MN as well as LN. The results of this study open a new avenue for prospective research on PRDXs in renal diseases.

Chronic Kidney Disease and Heart Failure—Everyday Diagnostic Challenges

Is advanced chronic kidney disease (CKD) a cardiac “no man’s land”? Chronic heart failure (HF) is widely believed to be one of the most serious medical challenges of the 21st century. Moreover, the number of patients with CKD is increasing. To date, patients with estimated glomerular filtration rates <30 mL/min/1.73 m2 have frequently been excluded from large, randomized clinical trials. Although this situation is slowly changing, in everyday practice we continue to struggle with problems that are not clearly addressed in the guidelines. This literature review was conducted by an interdisciplinary group, which comprised a nephrologist, internal medicine specialists, and cardiologist. In this review, we discuss the difficulties in ruling out HF for patients with advanced CKD and issues regarding the cardiotoxicity of dialysis fistulas and the occurrence of pulmonary hypertension in patients with CKD. Due to the recent publication of the new HF guidelines by the European Society of Cardiology, this is a good time to address these difficult issues. Contrary to appearances, these are not niche issues, but problems that affect many patients.

AN69 Filter Membranes with High Ultrafiltration Rates during Continuous Venovenous Hemofiltration Reduce Mortality in Patients with Sepsis-Induced Multiorgan Dysfunction Syndrome

Polyacrylonitrile (AN69) filter membranes adsorb cytokines during continuous venovenous hemofiltration (CVVH). Although high-volume hemofiltration has shown limited benefits, the dose-effect relationship in CVVH with AN69 membranes on severe sepsis remains undetermined. This multi-centered study enrolled 266 patients with sepsis-induced multiorgan dysfunction syndrome (MODS) who underwent CVVH with AN69 membranes between 2014 and 2015. We investigated the effects of ultrafiltration rates (UFR) on mortality. We categorized patients that were treated with UFR of 20–25 mL/kg/h as the standard UFR group (n = 124) and those that were treated with a UFR >25 mL/kg/h as the high UFR group (n = 142). Among the patient characteristics, the baseline estimated glomerular filtration rates (eGFR) <60 mL/min/1.73 m2, hemoglobin levels <10 g/dL, and a sequential organ failure assessment (SOFA) score ≥15 at CVVH initiation were independently associated with in-hospital mortality. In the subgroup analysis, for patients with SOFA scores that were ≥15, the 90-day survival rate was higher in the high UFR group than in the standard UFR group (HR 0.54, CI: 0.36–0.79, p = 0.005). We concluded that in patients with sepsis-induced MODS, SOFA scores ≥15 predicted a poor rate of survival. High UFR setting >25 mL/kg/h in CVVH with AN69 membranes may reduce the mortality risk in these high-risk patients.

Diffusion tensor imaging for the study of early renal dysfunction in patients affected by bardet-biedl syndrome

Kidney structural abnormalities are common features of Bardet-Biedl syndrome (BBS) patients that lead to a progressive decline in renal function. Magnetic resonance diffusion tensor imaging (DTI) provides useful information on renal microstructures but it has not been applied to these patients. This study investigated using DTI to detect renal abnormalities in BBS patients with no overt renal dysfunction. Ten BBS subjects with estimated glomerular filtration rates over 60 ml/min/1.73m2 and 14 individuals matched for age, gender, body mass index and renal function were subjected to high-field DTI. Fractional anisotropy (FA), and mean, radial and axial diffusivity were evaluated from renal cortex and medulla. Moreover, the corticomedullary differentiation of each DTI parameter was compared between groups. Only cortical FA statistically differed between BBS patients and controls (p = 0.033), but all the medullary DTI parameters discriminated between the two groups with lower FA (p < 0.001) and axial diffusivity (p = 0.021) and higher mean diffusivity (p = 0.043) and radial diffusivity (p < 0.001) in BBS patients compared with controls. Corticomedullary differentiation values were significantly reduced in BBS patients. Thus, DTI is a valuable tool for investigating microstructural alterations in renal disorders when kidney functionality is preserved.

The Mediation Effects of Aluminum in Plasma and Dipeptidyl Peptidase Like Protein 6 (DPP6) Polymorphism on Renal Function via Genome-Wide Typing Association

Aluminum (Al) toxicity is related to renal failure and the failure of other systems. Although there were some genome-wide association studies (GWAS) in Australia and England, there were no GWAS about Han Chinese to our knowledge. Thus, this research focused on using whole genomic genotypes from the Taiwan Biobank for exploring the association between Al concentrations in plasma and renal function. Participants, who underwent questionnaire interviews, biomarkers, and genotyping, were from the Taiwan Biobank database. Then, we measured their plasma Al concentrations with ICP-MS in the laboratory at Kaohsiung Medical University. We used this data to link genome-wide association (GWA) tests while looking for candidate genes and associated plasma Al concentration to renal function. Furthermore, we examined the path relationship between Single Nucleotide Polymorphisms (SNPs), Al concentrations, and estimated glomerular filtration rates (eGFR) through the mediation analysis with 3000 replication bootstraps. Following the principles of GWAS, we focused on three SNPs within the dipeptidyl peptidase-like protein 6 (DPP6) gene in chromosome 7, rs10224371, rs2316242, and rs10268004, respectively. The results of the mediation analysis showed that all of the selected SNPs have indirectly affected eGFR through a mediation of Al concentrations. Our analysis revealed the association between DPP6 SNPs, plasma Al concentrations, and eGFR. However, further longitudinal studies and research on mechanism are in need. Our analysis was still be the first study that explored the association between the DPP6, SNPs, and Al in plasma affecting eGFR.

Prevalence of sickle cell trait and its association to renal dysfunction among blood donors at university of medical sciences teaching hospital, Ondo, Nigeria

Introduction: Prospective blood donors are routinely screened for blood borne infections but medical illnesses and haemo- globin genotype are overlooked despite a high prevalence of haemoglobin AS among Nigerian donors. Objective: To determine the prevalence of haemoglobin AS and its association to renal function, if any. Method: Apparently healthy donors were studied between February and December 2018. Their haemoglobin genotype and, estimated glomerular filtration rates were determined. Results: There were 96 males (94.1%) and 6 (5.9%) females with mean age of 26.7±4.5 years (range 19-44 years) and mean eGFR of 103.97±19.00ml/min/1.73m2. Eighty one (79.4%) and 21 (20.6%) subjects had haemoglobin AA and AS geno- types respectively. The mean eGFR for subjects with haemoglobin AA and AS were 105.2±18.6ml/min/1.73m2 and 99.9 ± 21.2ml/min/1.73m2 respectively (p value = 0.270). Eighty one (79.4%), 20 (19.6%) and 1 (1.0%) subjects had renal function at >90ml/min/1.73m2, 60-89ml/min/1.73m2 and 30-59ml/min/m2 respectively. There was no significant difference in the mean eGFR between subjects with haemoglobin AA and AS (mean difference 5.3, p = 0.265, 95%CI = -4.07 to 14.60). Conclusion: The prevalence of sickle cell trait among Nigerian blood donors is high. There is no significant difference in the renal function status of blood donors with SCT and normal haemoglobin genotype. Keywords: Haemoglobin genotype; sickle cell trait; renal function; blood donor; Nigeria.

Clinical Mass Spectrometry Discovered Human IgG Sialylation as a Potential Biosignature for Kidney Function

Immunoglobulin G (IgG) N-glycosylation was discovered to have an association with inflammation status, which has the potential to be a novel biomarker for kidney diseases. In this study, we applied an ultra-high performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS) method to plasma and urine samples from 57 individuals with different levels of kidney function. Natural abundances of total IgG, IgG1, IgG2, and IgG3 subclasses in plasma showed positive correlations to the estimated glomerular filtration rates (eGFRs). Eighteen IgG glycopeptides also showed positive correlations. In contrast, higher IgG amounts were found in urine samples from participants with lower eGFR values. After normalizing IgG glycopeptides from plasma to their respective protein amounts, H4N4F1S1-IgG1 (r = 0.37, p = 0.0047, significant) and H5N4F1S1-IgG1 (r = 0.25, p = 0.063, marginally significant) were the two glycopeptides that still had positive correlations with eGFRs. The results showed that the UHPLC-MS/MS method is capable of investigating IgG profiles, and monitoring IgG and glycosylation patterns is worthy of further clinical application for kidney disease.

Maintenance Therapy With Bortezomib and Dexamethasone for Transplant-ineligible Patients With Multiple Myeloma

Background/Aim: Here, we investigated whether bortezomib as a maintenance therapy affected outcomes in transplant-ineligible patients with multiple myeloma (MM). Patients and Methods: Following induction therapy with bortezomib, maintenance therapy with bortezomib (1.3 mg/m2) and dexamethasone (20 mg) was administered once or twice every 4 weeks until disease progression. The endpoints of this study were time to next treatment and overall survival. Results: Seventy-six newly diagnosed, transplant-ineligible patients were treated with a bortezomib-based regimen; 28 discontinued induction therapy, 27 did not receive maintenance therapy after induction therapy (the non-maintenance group), and 21 did (the maintenance group). In the three groups, the median times to the next required treatment were 3, 14, and 37 months, respectively. The 3-year overall survival rates were 55%, 69%, and 85%, respectively. There were no significant differences in patient characteristics between the non-maintenance and maintenance groups, except for poorer estimated glomerular filtration rates in the maintenance group. Conclusion: Bortezomib maintenance therapy may be a useful option for transplant-ineligible patients with MM.