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Vascular calcification (VC) is an active process, resulting from the disturbance of balance between inhibitors and promoters of calcification, in favor of the latter. Matrix Gla Protein, a powerful inhibitor of VC, needs vitamin K to become active. In vitamin K depletion, plasma levels of the inactive form of MGP, dephosphorylated, uncarboxylated MGP (dp-ucMGP) are increased and associated with VC and cardiovascular (CV) outcomes. End Stage Renal Disease (ESRD) patients have increased circulating dp-ucMGP levels and accelerated VC. VItamin K In PEritoneal DIAlysis (VIKIPEDIA) is a prospective, randomized, open label, placebo-controlled trial, evaluating the effect of vitamin K2 supplementation on arterial stiffness and CV events in ESRD patients undergoing peritoneal dialysis (PD). Forty-four PD patients will be included in the study. At baseline, dp-ucMGP and pulse-wave velocity (PWV) will be assessed and then patients will be randomized (1:1 ratio) to vitamin K (1000 μg MK-7/day) or placebo for 1.5 years. The primary endpoint of this trial is the change in PWV in the placebo group as compared to the treatment group. Secondary endpoints are the occurrence of CV events, mortality, changes in PD adequacy, change in 24-hour ambulatory blood pressure indexes and aortic systolic blood pressure and changes in calcium/phosphorus/parathormone metabolism. VIKIPEDIA is a new superiority randomized, open label, placebo-controlled trial aiming to determine the effect of vitamin K2 supplementation on VC, CV disease and calcium/phosphorus metabolism, in PD patients. Trial registration: The protocol of this study is registered at ClinicalTrials.gov with identification number NCT04900610 (25 May 2021).

Background: Fibroblast growth factor 23 (FGF-23) and α-Klotho protein appear to have an important role in the pathogenesis of CKD-mineral and bone disorders. The aim of this study was to investigate the association of FGF-23 and α-Klotho levels with adverse clinical outcomes in patients with non-dialysis CKD. Materials and Methods: We conducted a prospective cohort study, enrolling participants with non-dialysis CKD from a single center in Greece. At enrollment, glomerular filtration rate (GFR) was measured (mGFR) and plasma levels of carboxyl terminal FGF-23 (cFGF-23) and soluble α-Klotho (sKlotho) were determined by enzyme-linked immunoassay. Participants were followed for up to 5 years or until the occurrence of the primary endpoint of initiation of renal replacement therapy or death. Multivariate regression tree analysis was used to identify informative baseline parameters in order to categorize participants. Also, using median values of cFGF-23 and sKlotho, participants were categorized into 4 groups, in whom survival was compared using Kaplan-Meier and Cox regression analysis. Results: 128 participants were enrolled with a median mGFR of 41.5 mL/min/1.73 m 2 (IQR = 28.2). Baseline mGFR correlated with cFGF-23 and sKlotho (r = −0.54 and r = 0.49, respectively; p < 0.0001 for both). cFGF-23 and sKlotho levels correlated negatively (r = −0.24, p = 0.006). Multivariate regression tree analysis resulted in 3 groups defined by cutoff values of mGFR (60.9 mL/min/1.73 m 2 ) and phosphate (3.7 mg/dL). These groups correlated with CKD stage, cFGF-23, and sKlotho (p < 0.0001 for all). During a median follow-up of 36 months (IQR = 22), 40 (31.2%) participants reached the primary endpoint (31 initiated renal replacement therapy, 9 died). Survival to primary endpoint differed among the 4 groups formed using median values of both biomarkers, with the low FGF-23/high Klotho and high FGF-23/low Klotho having the longest and shortest survival, respectively. High FGF-23/low Klotho group, compared to the opposite one, had a significantly elevated risk of the primary outcome (HR, 6.8; 95% CI, 2.3–19.6; p = 0.0004). Conclusions: In patients with CKD stages 1–5, the combination of higher cFGF-23 and lower sKlotho levels along with mGFR and serum phosphate was associated with adverse clinical outcomes. The utility of combinations of traditional and novel biomarkers to predict outcomes warrants further study.

Contrast-induced nephropathy (CIN) is a frequent, potentially lethal complication of percutaneous coronary interventions (PCIs). We prospectively validated the diagnostic performance of a simple CIN risk score in a large multicenter international cohort of patients who underwent PCI. About 2,882 consecutive patients treated with elective or urgent PCI were enrolled. A simple CIN risk score was calculated for all patients by allocating points according to a prespecified scale (pre-existing renal disease = 2; metformin use = 2; previous PCI = 1; peripheral arterial disease = 2; and injected volume of contrast medium ≥300 ml = 1). CIN was defined as an increase, compared with baseline, of serum creatinine by ≥25%, or by ≥0.5 mg/dl, 48 hours after PCI. CIN occurred in 15.7% of the study population. The predictive accuracy of the CIN risk score was good (c-statistic 0.741, 95% confidence interval 0.713 to 0.769). Receiver-operating characteristic analysis identified a score of ≥3 as having the best diagnostic accuracy. Examination of the performance of the proposed risk score using different definitions of CIN yielded a robust predictive ability. The score exhibited good discrimination (area under the curve ≥0.700) across all predefined subgroups of the study population. Compared with 2 previously published risk scores for CIN, our score demonstrated higher discriminative ability and resulted in a net reclassification improvement and an integrated discrimination improvement (p <0.001). In conclusion, the new risk score can easily be applied in the setting of urgent or elective PCI, allows for robust risk assessment and offers the potential to improve the peri-interventional management of patients at risk for CIN.

The gut microbiome is known as an important predictive tool for perceiving characteristic shifts in disease states. Multiple renal diseases and pathologies seem to be associated with gut dysbiosis which directly affects host homeostasis. The gastrointestinal-kidney dialogue confers interesting information about the pathogenesis of multiple kidney diseases. Moreover, aging is followed by specific shifts in the human microbiome, and gradual elimination of physiological functions predisposes the microbiome to inflammaging, sarcopenia, and disease. Aging is characterized by a microbiota with an abundance of disease-associated pathobionts. Multiple factors such as the immune system, environment, medication, diet, and genetic endowment are involved in determining the age of the microbiome in health and disease. Our present review promotes recently acquired knowledge and is expected to inspire researchers to advance studies and investigations on the involved pathways of the gut microbiota and kidney axis.

Background and objectives Chronic kidney disease (CKD) and its management can adversely affect patients' quality of life and mental health. Many patients are often inadequately informed about their condition and the available treatment options. A considerable number of people with advanced kidney disease have insufficient knowledge about their condition and the available treatment options. This study aims to investigate the impact of an educational intervention on quality of life, psychological resilience, anxiety, and depression. This study specifically aims to evaluate the effectiveness of this intervention on variables such as quality of life, psychological resilience, anxiety, and depression. Methods A prospective randomized study was conducted on patients with CKD stage 4-5 to evaluate the effectiveness of an educational intervention in improving the aforementioned parameters. Furthermore, the correlation between these outcomes and the level of satisfaction with the intervention was analyzed. Participants were randomized (3:1) into two groups: an educational intervention group (33 patients) and a control group (12 patients). In the intervention group, we performed educational presentations accompanied by a relevant video. Participants completed the questionnaires both before and after the intervention. Participants in the control group were only asked to complete the questionnaires again after the same time period as the intervention group. Results Higher satisfaction with the intervention was significantly associated with a reduction in anxiety (r = -0.38, p = 0.03) and depression scores (r = -0.44, p = 0.01), along with a notable improvement in social functioning (r = 0.40, p = 0.02). Furthermore, a marginally significant positive correlation was observed between the satisfaction scale and psychological resilience (r = 0.32, p = 0.07). Conclusion The level of satisfaction with the intervention is a critical factor in determining its effectiveness. Tailoring the intervention to address the unique needs of each patient may significantly enhance its impact.

Vascular calcification (VC) is an active process, resulting from the disturbance of balance between inhibitors and promoters of calcification, in favor of the latter. Matrix Gla Protein, a powerful inhibitor of VC, needs vitamin K to become active. In vitamin K depletion, plasma levels of the inactive form of MGP, dephosphorylated, uncarboxylated MGP (dp-ucMGP) are increased and associated with VC and cardiovascular (CV) outcomes. End Stage Renal Disease (ESRD) patients have increased circulating dp-ucMGP levels and accelerated VC. VItamin K In PEritoneal DIAlysis (VIKIPEDIA) is a prospective, randomized, open label, placebo-controlled trial, evaluating the effect of vitamin K2 supplementation on arterial stiffness and CV events in ESRD patients undergoing peritoneal dialysis (PD). Forty-four PD patients will be included in the study. At baseline, dp-ucMGP and pulse-wave velocity (PWV) will be assessed and then patients will be randomized (1:1 ratio) to vitamin K (1000 [mu]g MK-7/day) or placebo for 1.5 years. The primary endpoint of this trial is the change in PWV in the placebo group as compared to the treatment group. Secondary endpoints are the occurrence of CV events, mortality, changes in PD adequacy, change in 24-hour ambulatory blood pressure indexes and aortic systolic blood pressure and changes in calcium/phosphorus/parathormone metabolism. VIKIPEDIA is a new superiority randomized, open label, placebo-controlled trial aiming to determine the effect of vitamin K2 supplementation on VC, CV disease and calcium/phosphorus metabolism, in PD patients.

BackgroundMyasthenia gravis (MG) is a rare autoimmune disorder affecting the neuromuscular junction (NMJ). Here, we investigate the genetic architecture of MG via a genome-wide association study (GWAS) of the largest MG data set analysed to date.MethodsWe performed GWAS meta-analysis integrating three different data sets (total of 1401 cases and 3508 controls). We carried out human leucocyte antigen (HLA) fine-mapping, gene-based and tissue enrichment analyses and investigated genetic correlation with 13 other autoimmune disorders as well as pleiotropy across MG and correlated disorders.ResultsWe confirmed the previously reported MG association with TNFRSF11A (rs4369774; p=1.09×10−13, OR=1.4). Furthermore, gene-based analysis revealed AGRN as a novel MG susceptibility gene. HLA fine-mapping pointed to two independent MG loci: HLA-DRB1 and HLA-B. MG onset-specific analysis reveals differences in the genetic architecture of early-onset MG (EOMG) versus late-onset MG (LOMG). Furthermore, we find MG to be genetically correlated with type 1 diabetes (T1D), rheumatoid arthritis (RA), late-onset vitiligo and autoimmune thyroid disease (ATD). Cross-disorder meta-analysis reveals multiple risk loci that appear pleiotropic across MG and correlated disorders.DiscussionOur gene-based analysis identifies AGRN as a novel MG susceptibility gene, implicating for the first time a locus encoding a protein (agrin) that is directly relevant to NMJ activation. Mutations in AGRN have been found to underlie congenital myasthenic syndrome. Our results are also consistent with previous studies highlighting the role of HLA and TNFRSF11A in MG aetiology and the different risk genes in EOMG versus LOMG. Finally, we uncover the genetic correlation of MG with T1D, RA, ATD and late-onset vitiligo, pointing to shared underlying genetic mechanisms.

Background: The aim of this study was to evaluate the prognostic value of automated office blood pressure (AOBP) measurement in patients with hypertension and chronic kidney disease (CKD) stage 3–5 not on dialysis. Methods: At baseline, 140 patients were recruited, and blood pressure (BP) measurements with 3 different methods, namely, office blood pressure (OBP), AOBP, and ambulatory blood pressure measurement (ABPM), were recorded. All patients were prospectively followed for a median period of 3.4 years. The primary outcome of this study was a composite outcome of cardiovascular (CV) events (both fatal and nonfatal) or a doubling of serum creatine or progression to end-stage kidney disease (ESKD), whichever occurred first. Results: At baseline, the median age of patients was 65.2 years; 36.4% had diabetes; 21.4% had a history of CV disease; the mean of estimated glomerular filtration rate (eGFR) was 33 mL/min/1.73 m2; and the means of OBP, AOBP, and daytime ABPM were 151/84 mm Hg, 134/77 mm Hg, and 132/77 mm Hg, respectively. During the follow-up, 18 patients had a CV event, and 37 patients had a renal event. In the univariate cox regression analysis, systolic AOBP was found to be predictive of the primary outcome (HR per 1 mm Hg increase in BP, 1.019, 95% CI 1.003–1.035), and after adjustment for eGFR, smoking status, diabetes, and a history of CV disease and systolic and diastolic AOBP were also found to be predictive of the primary outcome (HR per 1 mm Hg increase in BP, 1.017, 95% CI 1.002–1.032 and 1.033, 95% CI 1.009–1.058, respectively). Conclusions: In patients with CKD, AOBP appears to be prognostic of CV risk or risk for kidney disease progression and could, therefore, be considered a reliable means for recording BP in the office setting.

Background: Insufficient evidenced-based information is available for the treatment of osteoporosis in hemodialysis (HD) patients. Methods: In 102 HD patients, bone mineral density (BMD) was measured twice 16 ± 3 months apart. In the second BMD measurement 66 of them had a femoral neck (FN) T-score <–2.5. Of these 66 patients, 38 consented to a bone biopsy. Depending on both the bone biopsy findings and parathyroid hormone levels, patients were assigned to treatment groups. Eleven patients with osteitis fibrosa and iPTH >300 pg/ml received cinacalcet, 11 with osteitis fibrosa and iPTH <300 pg/ml received ibandronate, 9 with adynamic bone disease received teriparatide, and 7 with mild abnormalities received no treatment. A third BMD measurement was done after an average treatment period of 13–16 months. We compared the annual percent change of FN and lumbar spine (LS) BMD before and during treatment. Results: FN and LS BMD decreased significantly in the cinacalcet group, with an annual change of 3.6 and 3.4% before treatment to –4.2% (p = 0.04) and –7.7% (p = 0.02) during treatment, respectively. In the teriparatide group, FN and LS BMD increased, although not significantly, with an annual change of –5.4 and –2.6% before treatment to 2.7 and 4.9% during treatment, respectively. In both the ibandronate and the no treatment groups, BMD change rate remained negative during the whole study. Conclusions: Teriparatide administration improved BMD in HD patients with adynamic bone disease, although these results did not reach statistical significance. In HD patients with osteitis fibrosa, ibandronate did not improve BMD while cinacalcet reduced BMD.

PurposeReversing the connection mode of permanent dual-lumen dialysis catheters results in higher access recirculation that may compromise the dialysis adequacy. The purpose of this study is to investigate the effect of reversed-connected dialysis with a higher versus a standard blood flow rate (Qb) on adequacy parameters and access recirculation.Materials and methodsIn a cross-over design, 46 prevalent dialysis patients with a properly functioning cuffed, tunneled, dual-lumen catheter were evaluated in three consecutive mid-week dialysis sessions. At baseline, participants were evaluated under standardized conditions (correct connection, Qb = 300 ml/min). In Phase A, dialysis was performed with reversed connection and Qb = 300 ml/min. In Phase B, dialysis was performed with reversed connection and Qb = 400 ml/min. The sequence of evaluations (Phase A and B or vise verse) was randomized. All other dialysis-related parameters were unchanged in all three occasions.ResultsAs expected, compared with baseline, reversed-connected dialysis in Phase A resulted in lower URR and spKt/V, and in a higher recirculation rate. Compared with baseline, reversed-connected dialysis with a higher Qb in Phase B resulted in an even higher recirculation rate, but the parameters of dialysis adequacy were not different. Increase in Qb from 300 to 400 ml/min resulted in an improvement of the dialysis adequacy (URR: 64.1 ± 7.8% vs. 70.6 ± 8.2%, P < 0.001; spKt/V: 1.22 ± 0.3 vs. 1.45 ± 0.3, P < 0.001) despite the higher recirculation rate.ConclusionThis study suggests that reversed-connected dialysis with increasing Qb maintains the adequacy of the delivered dialysis despite the compensatory increase in recirculation.