Cerebral blood flow changes in maintenance hemodialysis patients with restless legs syndrome and their clinical significance:a cross-sectional case-control study.

OBJECTIVE: Restless legs syndrome (RLS) stands as a prevalent neurological complication within maintenance hemodialysis (MHD) patients. However, the alterations in cerebral blood flow (CBF) among MHD-RLS patients remain uncharted. Through the utilization of the arterial spin labeling (ASL) technique, we evaluated the fluctuations in CBF within distinct brain regions and analyzed the risk factors for the development of RLS in MHD patients in the context of the clinic. METHODS: Thirty-one MHD patients with concomitant RLS (MHD-RLS group) and thirty-one non-RLS patients matched based on age, gender, as well as cognitive function (MHD-nRLS group) were included. Through image preprocessing and data analysis, the changes in CBF values in distinct brain regions were obtained, and the CBF values of brain regions with substantial differences between the two groups were correlated with the RLS scores. Furthermore, the differences in baseline data were compared, and through the utilization of multifactorial logistic regression, the independent risk factors for the development of RLS were examined. RESULTS: Compared with the MHD-nRLS group, the MHD-RLS group had increased CBF in the right superior temporal gyrus, reduced CBF in the right hippocampus, left middle frontal gyrus, inferior frontal gyrus of right triangle, middle frontal gyrus of left orbit, left precentral gyrus, and left precuneus. Only left precentral gyrus CBF were negatively correlated with RLS scores after correction for dialysis duration(r = -0.436, P = 0.016). Accordingly, multifactorial regression analysis by stepwise method yielded that the left precentral gyrus CBF values(OR: 0.968, 95%CI: 0.944-0.993, P = 0.012) remained an independent risk factor for RLS in MHD patients. In addition, the results showed that hemodialysis duration (OR: 1.055, 95%CI: 1.014-1.098, P = 0.008) and serum iron levels (OR: 0.685, 95%CI: 0.551-0.852, P = 0.001) were also risk factors for the development of RLS. CONCLUSION: Patients afflicted with MHD-RLS exhibit alterations in CBF across several brain regions. Notably, the left precentral gyrus might serve as a pivotal region influencing the onset of RLS among MHD patients. Furthermore, extended hemodialysis duration and a relative insufficiency in serum iron levels independently contribute as risk factors for RLS development within the MHD patient population.

Improvement of restless leg syndrome in maintenance hemodialysis patients with limb ischemic preconditioning: a single-center randomized controlled clinical trial.

OBJECTIVE: This study evaluated the efficacy and safety of limb ischemic preconditioning (LIPC) in treating restless leg syndrome (RLS) in maintenance hemodialysis (MHD) patients. METHODS: A total number of 45 patients participated in the study. They were randomly divided into LIPC group and control group. The LIPC was performed by inflating the limb ischemic preconditioning training device in the patient's thigh to 200 mmHg to create transient ischemia, whereas control group inflated the device to 20 mmHg. International Restless Legs Syndrome (IRLS), Clinical Global Impression Scale (CGI-S), and Medical Outputs Study Sleep Scale were employed to evaluate LIPC effectiveness. The primary endpoint was the 'rate of clinical improvement in RLS severity', defined as the percentage of patients who had an IRLS score decrease of ≥5 points in each group. RESULTS: After intervention, the rate of clinical improvement in RLS severity was 56.5% in the LIPC group and 13.6% in the control group (13 (56.5) vs 3 (13.6), p = 0.003). In addition, the LIPC group's IRLS, CGI-S scores, the sleep disturbance and somnolence scores showed a significant downward trend compared to the control group (-5.5 ± 5.3 vs - 1.0 ± 3.8, p = 0.002; -1.7 ± 1.2 vs - 0.5 ± 1.4, p = 0.003; -15.5 ± 17.8 vs 3.7 ± 12.0, p < 0.001; -9.9 ± 18.8 vs - 2.4 ± 8.6, p = 0.003). During the study, there were no serious adverse event in any of the patients. CONCLUSIONS: LIPC could be employed to effectively and safely alleviate the RLS symptoms in MHD patients.

Application Value of Limb Ischemic Preconditioning in Preventing Intradialytic Hypotension during Maintenance Hemodialysis.

INTRODUCTION: The aim of this study was to investigate the efficacy and safety of limb ischemia preconditioning (LIPC) in the treatment of intradialytic hypotension (IDH) in patients with maintenance hemodialysis (MHD). METHODS: This was a single-center, prospective, and randomized controlled case study. A total of 38 patients with MHD who met the inclusion criteria from September 2021 to August 2022 were selected from the Blood Purification Center of our hospital. They were randomly divided into the LIPC group (n = 19) and the control group (n = 19). For patients in the LIPC group, the femoral artery blood flow was blocked with an LIPC instrument for 5 min (pressurized to 200 mm Hg) before each dialysis, and they were reperfused for 5 min. The cycle was repeated five times, with a total of 50 min for 12 weeks. The control group was pressurized to 20 mm Hg with an LIPC instrument, and the rest was the same as the LIPC group. The blood pressure of 0 h, 1 h, 2 h, 3 h, 4 h, and body weight before and after hemodialysis were measured in the two groups during hemodialysis, the incidence of IDH and the changes of serum troponin I (TNI) and creatine kinase isoenzyme MB (CK-MB) levels before and after the intervention were observed, and the ultrafiltration volume and ultrafiltration rate were recorded. RESULTS: At the 8th and 12th week after intervention, the MAP in the LIPC group was higher than that in the control group (103.28 ± 12.19 mm Hg vs. 93.18 ± 11.11 mm Hg, p = 0.04; 101.81 ± 11.36 mm Hg vs. 91.81 ± 11.92 mm Hg, p = 0.047). The incidence of IDH in the LIPC group was lower than that in the control group (36.5% vs. 43.1%, p = 0.01). The incidence of clinical treatment in IDH patients in the LIPC group was lower than that in the control group (6.3% vs. 12.4%, p = 0.00). The incidence of early termination of hemodialysis in the LIPC group was lower than that in the control group (1.6% vs. 3.8%, p = 0.01). The levels of TNI and CK-MB in the LIPC group after the intervention were lower than those in the control group (322.30 ± 13.72 ng/dL vs. 438.50 ± 24.72 ng/dL, p = 0.00; 159.78 ± 8.48 U/dL vs. 207.00 ± 8.70 U/dL, p = 0.00). The changes of MAP before and after the intervention were negatively correlated with the changes of TNI and CK-MB before and after the intervention (r = -0.473, p = 0.04; r = -0.469, p = 0.04). There were no differences in dry body mass and ultrafiltration rate between the two groups before and after the LIPC intervention (p > 0.05). Multiple linear regression analysis shows that TNI is the main influencing factor of ΔMAP. No LIPC-related adverse events were found during the study period. CONCLUSION: LIPC can effectively reduce the incidence of IDH in patients with MHD and may be associated with the alleviation of myocardial damage.

Acute Kidney Injury after Multiple Cycles of Cisplatin Chemotherapy: A Nomogram for Risk Assessment.

INTRODUCTION: Acute kidney injury (AKI) caused by cisplatin is common and has a higher incidence of multiple use, resulting in a poor short- and long-term prognosis for patients. There is currently no good premedication AKI risk assessment tool. The aim of this study was to establish an AKI risk assessment nomogram for patients with multiple cisplatin applications. METHODS: This study was a retrospective analysis of patients who were treated with non-first-time cisplatin chemotherapy regimen at Changzhou Second People's Hospital affiliated to Nanjing Medical University from January 2016 to January 2022. All data from the development group were used to screen the impact factors of AKI via univariate and multivariate analyses. A nomogram was developed based on these impact factors and verified with verification group. The area under the curve (AUC) of receiver operating characteristic (ROC) curve, calibration curves, and decision curve analyses (DCAs) were used to evaluate the nomogram. RESULTS: Among the 256 patients enrolled in 450 cycles of chemotherapy, 282 were in the development cohort (97 AKI), and 168 were in the validation cohort (61 AKI). Multivariate logistic regression revealed that age, hypertension, diabetes, serum cystatin C (sCysC), urinary kidney injury molecule-1 (uKim1), and a single dose of cisplatin were independently associated with AKI. The results showed that our model yielded satisfied diagnostic performance with an AUC value of 0.887 and 0.906 using the development group and on verification group. The calibration plots and DCA showed the superior clinical applicability of the nomogram. These results were verified in the validation cohort. CONCLUSION: A nomogram combining functional (sCysC) and tubular (uKim1) injury biomarkers with conventional clinical factors might assess the risk of AKI after multiple cycles of cisplatin chemotherapy.

Left ventricular hypertrophy, carotid atherosclerosis, and cognitive impairment in peritoneal dialysis patients.

BACKGROUND: Left ventricular hypertrophy (LVH) and carotid atherosclerosis (CAS) have been identified as factors associated with cognitive impairment (CI) but have not been studied in patients undergoing peritoneal dialysis (PD). This study investigated the relationship between LVH and CAS and cognitive function in patients undergoing PD. METHODS: In this single-center cross-sectional study, the clinically stable patients who were over 18 years of age and had undergone PD for at least 3 months were enrolled. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA), which included seven areas: visuospatial/executive function, naming, attention, language, abstraction, delayed recall, and orientation. LVH was defined as LVMI > 46.7 g/m2.7 in women and LVMI > 49.2 g/m2.7 in men. CAS was defined as carotid intima-media thickness ≥ 1.0 mm and/or the presence of plaque. RESULTS: A total of 207 patients undergoing PD were recruited, with an average age of 52.14 ± 14.93 years and a median PD duration of 8 months (5-19 months). The CI rate was 56%, and the prevalence of CAS was 53.6%. LVH occurred in 110 patients (53.1%). Patients in the LVH group tended to be older, and had a higher body mass index, a higher pulse pressure, a higher male proportion, a lower ejection fraction, a higher prevalence of cardiovascular disease and CI, and a lower MoCA scores.Multivariate logistic regression analysis was conducted to analyze the association between LVH and CI (OR, 10.087; 95% confidence interval, 2.966-34.307). And the association between LVH and CI was still supported after propensity matching scores. CAS was not significantly associated with CI. CONCLUSION: LVH is independently associated with CI in patients undergoing PD, while CAS is not significantly associated with CI.

The Effects of Febuxostat on Urine NGAL and Urine KIM-1 in Patients with Hyperuricemia.

Retrospective analysis of the effects of febuxostat on urine neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) in patients with hyperuricemia was performed. From January 2018 to June 2018, there were 45 patients with asymptomatic hyperuricemia in the outpatient or inpatient of Changzhou Second People's Hospital, which were divided into the febuxostat group (25 cases) and the control group (20 cases). We collected the patients' baseline indicators and testing indicators after three months of treatment, including blood urea nitrogen, blood creatinine, blood uric acid, urine microalbumin, urine NGAL, urine KIM-1, and other indicators. The subjects in both groups were given lifestyle intervention, instructed to drink more water, and given a low-purine diet. The patients in the febuxostat group took febuxostat 40 mg/D or 80 mg/D. We used SPSS 25.0 statistical software for statistical analysis. Baseline indexes between the febuxostat group and the control group and indexes after treatment between two groups were both performed by independent sample t-test, and paired t-test was used for self-comparison between the groups before and after treatment. There was no significant difference in age, sex, body mass index (BMI), urea nitrogen, creatinine, uric acid, urine microalbumin/creatinine, urine NGAL/creatinine, and urine KIM-1/creatinine between the two groups before treatment (P > 0.05). Compared with before treatment, after 3 months of intervention, the levels of serum uric acid, urine microalbumin/creatinine, urine NGAL/creatinine, and urine KIM-1/creatinine were significantly decreased in the febuxostat group (P < 0.05), while the changes of blood urea nitrogen, serum creatinine, and epidermal growth factor receptor (eGFR) were not statistically significant (P > 0.05). After 3 months of intervention, the control group had no significant changes in blood urea nitrogen, creatinine, eGFR, uric acid, microalbumin/creatinine, urine NGAL/creatinine, and urine KIM-1/creatinine (P > 0.05). After 3 months of intervention, compared with the control group, the serum uric acid, microalbumin/creatinine, urine NGAL/creatinine, and urine KIM-1/creatinine were significantly decreased in the febuxostat group (P < 0.05), but there was no significant difference in blood urea nitrogen, creatinine, and eGFR (P > 0.05). Febuxostat can reduce urine NGAL/creatinine and urine KIM-1/creatinine levels in patients with hyperuricemia and has the protective effects on renal tubular injury caused by hyperuricemia, which can provide evidences for the early prevention and treatment of asymptomatic hyperuricemia.

miR-155-5p Implicates in the Pathogenesis of Renal Fibrosis via Targeting SOCS1 and SOCS6.

Renal fibrosis is associated with the reduction in the functional renal parenchyma and in most cases progresses to end-stage kidney failure, a devastating condition that requires lifelong dialysis or kidney transplantation. However, due to the extreme complexity in the pathogenesis of renal fibrosis and our limited knowledge, therapeutic options for renal fibrosis in the clinical setting are still scarce and often ineffective. Hence, further studies on the molecular mechanisms underlying renal fibrosis are compellingly needed. Multiple miRNAs have demonstrated to participate in kidney diseases in a TGF-ß dependent or independent manner, but there is very little known about miR-155-5p on renal fibrosis. In the present study, we firstly explored the expression level and functions of miR-155-5p in the setting of renal fibrosis. Our research revealed that miR-155-5p is highly expressed in kidney tissues from patients and unilateral ureteral obstruction (UUO) rat models, and miR-155-5p knockdown significantly blocks renal fibrosis both in vivo and in vitro. In mechanism, our data demonstrate that miR-155-5p promotes renal fibrosis by increasing the phosphorylated activation of STAT3 via targeting SOCS1/6. Altogether, our findings highlight a miR-155-5p/SOCS/STAT3 axis in the pathogenesis of renal fibrosis, which may provide promising therapeutic targets for clinical prevention of this disease.

Limb ischemic preconditioning ameliorates renal microcirculation through activation of PI3K/Akt/eNOS signaling pathway after acute kidney injury.

PURPOSE: Contrast-induced acute kidney injury (CI-AKI) resulting from administration of iodinated contrast media (CM) is the third leading cause of hospital-acquired acute kidney injury and is associated with substantial morbidity and mortality. Deteriorated renal microcirculation plays an important role in CI-AKI. Limb ischemic preconditioning (LIPC), where brief and non-injurious ischemia/reperfusion is applied to a limb prior to the administration of the contrast agent, is emerging as a promising strategy for CI-AKI prevention. However, it is not known whether the renal protection of LIPC against CI-AKI is mediated by regulation of renal microcirculation and the molecular mechanisms remain largely unknown. METHODS: In this study, we examined the renal cortical and medullary blood flow in a stable CI-AKI model using 5/6-nephrectomized (NE) rat. The LIPC and sham procedures were performed prior to the injection of CM. Furthermore, we analyzed renal medulla hypoxia using in vivo labeling of hypoxyprobe. Pharmacological inhibitions and western blotting were used to determine the underlying molecular mechanisms. RESULTS: In this study, we found LIPC significantly ameliorated CM-induced reduction of medullary blood flow and attenuated CM-induced hypoxia. PI3K inhibitor (wortmannin) treatment blocked the regulation of medullary blood flow and the attenuation of hypoxia of LIPC. Phosphorylation of Akt/eNOS was significantly decreased via wortmannin treatment compared with LIPC. Nitric oxide synthase-inhibitor [Nω-nitro-L-arginine methyl ester (L-NAME)] treatment abolished the above effects and decreased phosphorylation of eNOS, but not Akt. CONCLUSIONS: Collectively, the results demonstrate that LIPC ameliorates CM-induced renal vasocontraction and is mediated by activation of PI3K/Akt/eNOS signaling pathway.

Hydration Strategies for Preventing Contrast-Induced Acute Kidney Injury: A Systematic Review and Bayesian Network Meta-Analysis.

AIMS: Many previous studies have examined the effect of different hydration strategies on prevention of contrast-induced acute kidney injury (CI-AKI), but the optimal strategy is unknown. We performed a network meta-analysis (NWM) of these previous studies to identify the optimal strategy. METHODS AND RESULTS: Web of Science, PubMed, OVID Medline, and Cochrane Library were searched from their inception dates to September 30, 2018. Randomized controlled trials (RCTs) were selected based on strict inclusion criteria, and a Bayesian NWM was performed using WinBUGS V.1.4.3. We finally analyzed 60 eligible RCTs, which examined 21,293 patients and 2232 CI-AKI events. Compared to intravenous 0.9% sodium chloride (reference), intravenous sodium bicarbonate (OR [95% CI]: 0.74 [0.57, 0.93]), hemodynamic guided hydration (0.41 [0.18, 0.93]), and RenalGuard guided hydration (0.32 [0.14, 0.70]) significantly reduced the occurrence of CI-AKI. Oral hydration and intravenous 0.9% sodium chloride were each noninferior to no hydration in preventing CI-AKI. Intravenous 0.9% sodium chloride, sodium bicarbonate, and hemodynamic guided hydration were each noninferior to oral hydration in preventing CI-AKI. Based on surface under the cumulative ranking curve values, the RenalGuard system was best (0.974) and hemodynamic guided hydration was second best (0.849). CONCLUSION: There was substantial evidence to support the use of RenalGuard or hemodynamic guided hydration for preventing CI-AKI in high-risk patients, especially those with chronic kidney disease or cardiac dysfunction.