Hemodiafiltration with endogenous reinfusion for uremic toxin removal in patients undergoing maintenance hemodialysis: a pilot study.

OBJECTIVE: To delineate the efficacy and safety profile of hemodiafiltration with endogenous reinfusion (HFR) for uremic toxin removal in patients undergoing maintenance hemodialysis (MHD). METHODS: Patients who have been on MHD for a period of at least 3 months were enrolled. Each subject underwent one HFR and one hemodiafiltration (HDF) treatment. Blood samples were collected before and after a single HFR or HDF treatment to test uremic toxin levels and to calculate clearance rate. The primary efficacy endpoint was to compare uremic toxin levels of indoxyl sulfate (IS), λ-free light chains (λFLC), and ß2-microglobulin (ß2-MG) before and after HFR treatment. Secondary efficacy endpoints was to compare the levels of urea, interleukin-6 (IL-6), P-cresol, chitinase-3-like protein 1 (YKL-40), leptin (LEP), hippuric acid (HPA), trimethylamine N-oxide (TMAO), asymmetric dimethylarginine (ADMA), tumor necrosis factor-α (TNF-α), fibroblast growth factor 23 (FGF23) before and after HFR treatment. The study also undertook a comparative analysis of uremic toxin clearance between a single HFR and HDF treatment. Meanwhile, the lever of serum albumin and branched-chain amino acids before and after a single HFR or HDF treatment were compared. In terms of safety, the study was meticulous in recording vital signs and the incidence of adverse events throughout its duration. RESULTS: The study enrolled 20 patients. After a single HFR treatment, levels of IS, λFLC, ß2-MG, IL-6, P-cresol, YKL-40, LEP, HPA, TMAO, ADMA, TNF-α, and FGF23 significantly decreased (p < 0.001 for all). The clearance rates of λFLC, ß2-MG, IL-6, LEP, and TNF-α were significantly higher in HFR compared to HDF (p values: 0.036, 0.042, 0.041, 0.019, and 0.036, respectively). Compared with pre-HFR and post-HFR treatment, levels of serum albumin, valine, and isoleucine showed no significant difference (p > 0.05), while post-HDF, levels of serum albumin significantly decreased (p = 0.000). CONCLUSION: HFR treatment effectively eliminates uremic toxins from the bloodstream of patients undergoing MHD, especially protein-bound toxins and large middle-molecule toxins. Additionally, it retains essential physiological compounds like albumin and branched-chain amino acids, underscoring its commendable safety profile.

The relationship between thiamin, folic acid and cognitive function in a rat model of uremia.

End-stage renal disease is a worldwide health burden, but the pathogenesis of uremia-associated cognitive impairment (CI) is poorly recognized. We hypothesized that uremia brings about deficiency of thiamin and folic acid and causes CI by inducing oxidative stress. Therefore, 24 Sprague-Dawley rats were randomly divided into two groups: a 5/6 nephrectomy group (n = 12) and a sham-operated group (n = 12). The Morris water maze was used to assess the cognitive function eight weeks post-surgery, and serum levels of thiamin, folic acid and homocysteine were detected subsequently. Brain and kidney tissues were collected for pathological examination and 8-Hydroxy-2'-deoxyguanosine (8-OHdG) immunochemistry staining. Results showed that the escape latency on training days 1-2 was longer, and the time in quadrant IV on experimental day 6 was significantly shorter in 5/6 nephrectomy group. Meanwhile, the uremic rats showed decreased thiamin, folic acid and increased homocysteine. We also found the time in quadrant IV was positively correlated with thiamin and folic acid level, while negatively correlated with the blood urea nitrogen and 8-OHdG positive cell proportion. Furthermore, in 5/6 nephrectomy group, the hippocampal neuron count was significantly reduced, and a greater proportion of 8-OHdG positive cells were detected. Pretreating LPS-stimulated rat microglial cells with thiamin or folic acid in vitro alleviated the inflammatory impairment in terms of cell viability and oxidative stress. In summary, we applied a uremic rat model and proved that uremia causes serum thiamin and folic acid deficiency, homocysteine elevation, along with neuron reduction and severe oxidative stress in hippocampus, finally leading to CI.

The presence of exudative thickening of Bowman's capsule predict poor prognosis in diabetic kidney disease.

BACKGROUND: The relationship between Bowman's capsule thickening and progression of diabetic kidney disease (DKD) remains uncertain. METHODS: Renal biopsy specimens from 145 DKD patients and 20 control subjects were evaluated for Bowman's capsule thickness. Immunohistochemical staining assessed col4α2, laminin ß1, and albumin expression. In a discovery cohort of 111 DKD patients with eGFR ≥ 30 ml/min/1.73 m2, thickening was classified as fibrotic or exudative. The composite endpoint included CKD stage 5, dialysis initiation, and renal disease-related death. Prognosis was analyzed using Kaplan-Meier and Cox regression analyses. Two validation cohorts were included. RESULTS: Three types of thickening were observed: fibrotic, exudative, and periglomerular fibrosis. Parietal epithelial cell matrix protein accumulation contributed to fibrotic thickening, while albumin was present in exudative thickening. Bowman's capsule was significantly thicker in DKD patients (5.74 ± 2.09 µm) compared to controls (3.38 ± 0.43 µm, P < 0.01). In discovery cohort, the group of exudative thickning had a poorer prognosis(median time 20 months vs 57 months, P = 0.000). Cox multivariate analysis revealed that exudative thickening of Bowman's capsule were associated with a poor prognosis. The validation cohorts confirmed the result. CONCLUSIONS: Various mechanisms contribute to Bowman's capsule thickening in DKD. The proportion of exudative thickening may serve as a valuable prognostic indicator for DKD patients.

Fractal Analysis of Left Ventricular Trabeculae in Patients with End-Stage Renal Disease: A Random Survival Tree Analysis.

BACKGROUND: The complexity of left ventricular (LV) trabeculae is related to the prognosis of several cardiovascular diseases. PURPOSE: To evaluate the prognostic value of LV trabecular complexity in patients with end-stage renal disease (ESRD). STUDY TYPE: Prospective outcome study. POPULATION: 207 participants on maintenance dialysis, divided into development (160 patients from 2 centers) and external validation (47 patients from a third center) cohorts, and 72 healthy controls. FIELD STRENGTH: 3.0T, steady-state free precession (SSFP) and modified Look-Locker imaging sequences. ASSESSMENT: All participants had their trabecular complexity quantified by fractal analysis using cine SSFP images. Patients were followed up every 2 weeks until April 2023, or endpoint events happened. Random Forest (RF) and Cox regression models including age, diabetes, LV mass index, mean basal fractal dimension (FD), and left atrial volume index, were developed to predict major adverse cardiac events (MACE). Patients were divided into low- and high-risk groups based on scores derived from the RF model and survival compared. STATISTICAL TESTS: Receiver operating characteristic curve analysis; Kaplan-Meier survival analysis with log rank tests; Harrel's C-index to assess model performance. A P value <0.05 was considered statistically significant. RESULTS: Fifty-five patients (26.57%) experienced MACE during a median follow-up time of 21.83 months. An increased mean basal FD (≥1.324) was associated with a significantly higher risk of MACE. The RF model (C-index: 0.81) had significantly better discrimination than the Cox regression model (C-index: 0.74). Participants of the external validation dataset classified into the high-risk group had a hazard of experiencing MACE increased by 12.29 times compared to those in the low-risk group. DATA CONCLUSION: LV basal FD was an independent predictor for MACE in patients with ESRD. Reliable risk stratification models could be generated based on LV basal FD and other MRI variables using RF analysis. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Left Ventricular Vertical Run-Length Nonuniformity MRI Adds Prognostic Value to MACE in Patients with End-Stage Renal Disease.

BACKGROUND: Vertical run-length nonuniformity (VRLN) is a texture feature representing heterogeneity within native T1 images and reflects the extent of cardiac fibrosis. In uremic cardiomyopathy, interstitial fibrosis was the major histological alteration. The prognostic value of VRLN in patients with end-stage renal disease (ESRD) remains unclear. PURPOSE: To evaluate the prognostic value of VRLN MRI in patients with ESRD. STUDY TYPE: Prospective. POPULATION: A total of 127 ESRD patients (30 participants in the major adverse cardiac events, MACE group). FIELD STRENGTH/SEQUENCE: 3.0 T/steady-state free precession sequence, modified Look-Locker imaging. ASSESSMENT: MRI image qualities were assessed by three independent radiologists. VRLN values were measured in the myocardium on the mid-ventricular short-axis slice of T1 mapping. Left ventricular (LV) mass, LV end-diastolic and end-systolic volume, as well as LV global strain cardiac parameters were measured. STATISTICAL TESTS: The primary endpoint was the incident of MACE from enrollment time to January 2023. MACE is a composite endpoint consisting of all-cause mortality, acute myocardial infarction, stroke, heart failure hospitalization, and life-threatening arrhythmia. Cox proportional-hazards regression was performed to test whether VRLN independently correlated with MACE. The intraclass correlation coefficients of VRLN were calculated to evaluate intraobserver and interobserver reproducibility. The C-index was computed to examine the prognostic value of VRLN. P-value <0.05 were considered statistically significant. RESULTS: Participants were followed for a median of 26 months. VRLN, age, LV end-systolic volume index, and global longitudinal strain remained significantly associated with MACE in the multivariable model. Adding VRLN to a baseline model containing clinical and conventional cardiac MRI parameters significantly improved the accuracy of the predictive model (C-index of the baseline model: 0.781 vs. the model added VRLN: 0.814). DATA CONCLUSION: VRLN is a novel marker for risk stratification toward MACE in patients with ESRD, superior to native T1 mapping and LV ejection fraction. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY STAGE: 2.

Assessment of the Prognostic Value of MRI Left Ventricular Global Function Index (LVGFI) in Patients With End-Stage Renal Disease Under Maintenance Dialysis.

BACKGROUND: Left ventricular global function index (LVGFI) integrates LV volumetric and functional parameters. In patients with end-stage renal disease (ESRD), cardiac injury manifests as LV hypertrophy and dysfunction. However, the prognostic value of LVGFI in this population remains unclear. PURPOSE: To investigate the association of LVGFI with major adverse cardiac events (MACE) in patients with ESRD. STUDY TYPE: Prospective. POPULATION: One hundred fifty-eight ESRD patients (mean age: 54.1 ± 14.4 years; 105 male) on maintenance dialysis. FILED STRENGTH/SEQUENCE: 3.0 T, balanced steady-state free precession (bSSFP) cine and modified Look-Locker inversion recovery (MOLLI) sequences. ASSESSMENT: LV volumetric and functional parameters were determined from bSSFP images. LVGFI was calculated as the ratio of stroke volume to global volume and native T1 was determined from MOLLI T1 maps. MACE was recorded on follow up. Models were developed to predict MACE from conventional risk factors combined with LVGFI, GLS, native T1, and LV mass index (LVMI), respectively. Subgroup analyses were further performed in participants with LVEF above median. STATISTICAL TESTS: Cox proportional hazard regression and log-rank test were used to investigate the association between LVGFI and MACE. The predictive models were evaluated and compared using Harrell's C-statistics and DeLong tests. A P value <0.05 was considered statistically significant. RESULTS: Thirty-four MACE occurred during the median follow-up period of 26 months. The hazard of MACE increased by 114% for each 10% decrease in LVGFI in univariable analysis. The predictive model consisting of LVGFI (C-statistic: 0.724) had significantly better predictive performance than the others (all P < 0.001). These results were consistent in patients (N = 79) with LVEF > median (63.54%). DATA CONCLUSION: LVGFI is a novel marker for MACE risk stratification in patients with ESRD and was better able to predict MACE than native T1 mapping and GLS. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 3.

Pharmacokinetics of Henagliflozin in Dialysis Patients with Diabetes.

AIM: This study aimed to assess the pharmacokinetics of henagliflozin in dialysis patients with diabetes. METHODS: In this prospective, randomized, open-label study where 10 hemodialysis and 10 peritoneal dialysis patients with diabetes were randomized in a 1:1:1:1 ratio to oral administration of henagliflozin in doses of 5 and 10 mg/day. The pharmacokinetics of a single dose of henagliflozin on Days 1 and 2, the minimum plasma concentration (Cmin) of the steady state on Day 10, and single hemodialysis clearance of henagliflozin were measured. RESULTS: The mean values of Cmax were 70.2-77.0 ng/mL and 105-143 ng/mL in the 5 mg and 10 mg henagliflozin groups, respectively; the mean values of AUCinf were 777-811 h*ng/mL and 1290-1730 h*ng/mL in the 5 mg and 10 mg henagliflozin groups, respectively. The median Tmax values ranged from 1 to 3 h across the dose range. The mean values of T1/2 of henagliflozin were 14.1-14.5 and 16.2-21.0 h in the 5 mg and 10 mg groups, respectively. The Cmin values of the steady state in dialysis patients taking 5 mg and 10 mg of henagliflozin were 15.0 ± 4.4 ng/mL and 26.8 ± 16.3 ng/mL, respectively, which were 123.8% and 131.0% higher than those in diabetic patients with normal renal function, respectively. Henagliflozin concentration was decreased by 1.1% after hemodialysis treatment. No treatment-related serious adverse events or discontinuations occurred. CONCLUSIONS: Henagliflozin at the current recommended dosage may be safe, although it is possible to result in slight accumulation in patients on dialysis. REGISTRATION: Chinese Clinical Trial Registry number ChiCTR2200062872. The date of registration: August 22, 2022.

Fractal analysis: Left ventricular trabecular complexity cardiac MRI adds independent risks for heart failure with preserved ejection fraction in participants with end-stage renal disease.

PURPOSE: To measure left ventricular (LV) trabecular complexity by fractal dimension (FD) in patients with end-stage renal disease (ESRD), and assess whether FD was an independent risk factor for heart failure with preserved ejection fraction (HFpEF), or a significant predictor for adverse outcome in this population. METHODS: The study retrospectively enrolled 104 participants with ESRD who underwent 3.0 T cardiac magnetic resonance imaging (MRI) from June 2018 to November 2020. LV trabeculation was quantified with fractal analysis of short-axis cine slices to estimate the FD. Logistic regression analyses were used to evaluate FD and cardiac MRI parameters and to find independent risk predictors. Cox proportional hazard regression was used to investigate the association between FD and MACE. RESULTS: LV FD was higher in in the HFpEF group than those in the non-HFpEF group, with the greatest difference near the base of the ventricle. Age, minimum left atrial volume index, and LV mean basal FD were independent predictors for HFpEF in patients with ESRD. Combining the mean basal FD with typical predictive factors resulted in a C-index (0.902 vs 0.921), which was not significantly higher. Same improvements were found for net reclassification improvement [0.642; 95% confidence interval (CI), 0.254-1.029] and integrated discrimination index (0.026; 95% CI, 0.008-0.061). Participants with a LV global FD above the cutoff value (1.278) had higher risks of MACE in ESRD patients. CONCLUSIONS: LV trabecular complexity measured by FD was an independent risk factor for HFpEF, and a significant predictor for MACE among patients with ESRD.

Hyperkalaemia prevalence and dialysis patterns in Chinese patients on haemodialysis: an interim analysis of a prospective cohort study (PRECEDE-K).

BACKGROUND: Hyperkalaemia is a known risk factor for cardiac arrhythmia and mortality in patients on haemodialysis. Despite standard adequate haemodialysis, hyperkalaemia is common in patients with end-stage renal disease (ESRD) at interdialytic intervals. Data on hyperkalaemia burden and its effects on dialysis patterns and serum potassium (sK) fluctuations in patients on haemodialysis in China remain limited. The prospective, observational cohort study (PRECEDE-K; NCT04799067) investigated the prevalence, recurrence, and treatment patterns of hyperkalaemia in Chinese patients with ESRD on haemodialysis. METHODS: Six hundred adult patients were consecutively enrolled from 15 secondary and tertiary hospitals in China. In this interim analysis, we report the baseline characteristics of the cohort, the prevalence of predialysis hyperkalaemia (sK > 5.0 mmol/L), and the trends in serum-dialysate potassium gradient and intradialytic sK shift at Visit 1 (following a long interdialytic interval [LIDI]). RESULTS: At baseline, most patients (85.6%) received three-times weekly dialysis; mean duration was 4.0 h. Mean urea reduction ratio was 68.0% and Kt/V was 1.45; 60.0% of patients had prior hyperkalaemia (previous 6 months). At Visit 1, mean predialysis sK was 4.83 mmol/L, and 39.6% of patients had hyperkalaemia. Most patients (97.7%) received a dialysate potassium concentration of 2.0 mmol/L. The serum-dialysate potassium gradient was greater than 3 mmol/L for over 40% of the cohort (1- < 2, 2- < 3, 3- < 4, and ≥ 4 mmol/L in 13.6%, 45.1%, 35.7%, and 5.2% of patients, respectively; mean: 2.8 mmol/L). The intradialytic sK reduction was 1- < 3 mmol/L for most patients (0- < 1, 1- < 2, 2- < 3, and ≥ 3 mmol/L in 24.2%, 62.2%, 12.8%, and 0.9% of patients, respectively; mean: 1.4 mmol/L). CONCLUSIONS: Hyperkalaemia after a LIDI was common in this real-world cohort of Chinese patients despite standard adequate haemodialysis, and led to large serum-dialysate potassium gradients and intradialytic sK shifts. Previous studies have shown hyperkalaemia and sK fluctuations are highly correlated with poor prognosis. Effective potassium-lowering treatments should be evaluated for the improvement of long-term prognosis through the control of hyperkalaemia and sK fluctuations. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04799067.

DIALIZE China: A Phase IIIb, Randomized, Placebo-Controlled Study to Reduce Predialysis Hyperkalemia With Sodium Zirconium Cyclosilicate in Chinese Patients.

PURPOSE: The DIALIZE China study (Reduce Incidence of Pre-Dialysis Hyperkalaemia With Sodium Zirconium Cyclosilicate in Chinese Subjects) (NCT04217590) evaluated sodium zirconium cyclosilicate (SZC) for the management of hyperkalemia in Chinese patients undergoing hemodialysis. METHODS: In the double-blind, Phase IIIb DIALIZE China study, Chinese adults with kidney failure and predialysis hyperkalemia (predialysis serum potassium [sK+] concentration >5.4 mmol/L after the long interdialytic interval [LIDI] and >5.0 mmol/L after ≥1 short interdialytic interval) who were receiving hemodialysis 3 times weekly were randomized to placebo or SZC 5 g once daily on nondialysis days. Doses were titrated towards maintaining normokalemia for 4 weeks (titration period) in 5-g increments up to 15 g. Primary efficacy was the proportion of responders during the 4-week evaluation period following the titration period (ie, those with a predialysis sK+ of 4.0-5.0 mmol/L for at least 3 of 4 hemodialysis visits following the LIDI) who did not require urgent rescue therapy. FINDINGS: Overall, 134 adults (mean [SD] age, 55 [11.3] years) were randomized to SZC or placebo (n = 67 each). There were significantly more responders with SZC (37.3%) versus placebo (10.4%; estimated odds ratio [OR] = 5.10; 95% CI, 1.90-15.12; P < 0.001). The probability of all predialysis sK+ concentrations being 3.5 to 5.5 mmol/L was significantly higher with SZC versus placebo (estimated OR = 6.41; 95% CI, 2.71-15.12; P < 0.001). A greater proportion of patients achieved an sK+ of 3.5 to 5.5 mmol/L on at least 3 of 4 LIDI visits during evaluation with SZC (73.1%) versus placebo (29.9%). Serious adverse events occurred in 9.1% and 11.9% of patients in the SZC and placebo groups, respectively. IMPLICATIONS: SZC treatment for predialysis hyperkalemia is effective and well tolerated in Chinese patients with kidney failure receiving hemodialysis. CLINICALTRIALS: gov identifier: NCT04217590.

P2X7R/AKT/mTOR signaling mediates high glucose-induced decrease in podocyte autophagy.

Diabetic nephropathy is one of the leading causes of end-stage renal disease worldwide. In our study we found that Adenosine triphosphate (ATP) content was significantly increased in the urine of diabetic mice. We examined the expression of all purinergic receptors in the renal cortex and found that only purinergic P2X7 receptor (P2X7R) expression was significantly increased in the renal cortex of wild-type diabetic mice and that the P2X7R protein partially co-localized with podocytes. Compared with P2X7R(-/-) non-diabetic mice, P2X7R(-/-) diabetic mice showed stable expression of the podocyte marker protein podocin in the renal cortex. The renal expression of microtubule associated protein light chain 3 (LC-3II) in wild-type diabetic mice was significantly lower than in wild-type controls, whereas the expression of LC-3II in the kidneys of P2X7R(-/-) diabetic mice was not significantly different from that of P2X7R(-/-) non-diabetic mice. In vitro, high glucose induced an increase in p-Akt/Akt, p-mTOR/mTOR and p62 protein expression along with a decrease in LC-3II levels in podocytes, whereas after transfection with P2X7R siRNA, Phosphorylated protein kinase B (p-Akt)/Akt, Phosphorylated mammalian target of rapamycin (p-mTOR)/mTOR, and p62 expression were restored and LC-3II expression was increased. In addition, LC-3II expression was also restored after inhibition of Akt and mTOR signaling with MK2206 and rapamycin, respectively. Our results suggest that P2X7R expression is increased in podocytes in diabetes, and that P2X7R is involved in the inhibition of podocyte autophagy by high glucose, at least in part through the Akt-mTOR pathway, thereby exacerbating podocyte damage and promoting the onset of diabetic nephropathy. Targeting P2X7R may be a potential treatment for diabetic nephropathy.

Texture analysis of native T1 images as a novel method for non-invasive assessment of heart failure with preserved ejection fraction in end-stage renal disease patients.

OBJECTIVES: To explore the diagnostic potential of texture analysis applied to native T1 maps obtained from cardiac magnetic resonance (CMR) images for the assessment of heart failure with preserved ejection fraction (HFpEF) among patients with end-stage renal disease (ESRD). METHODS: This study, conducted from June 2018 to November 2020, included 119 patients (35 on hemodialysis, 55 on peritoneal dialysis, and 29 with kidney transplants) in Renji Hospital. Native T1 maps were assessed with texture analysis, using a freely available software package, in participants who underwent cardiac MRI at 3.0 T. Four texture features, selected by dimension reduction specific to the diagnosis of HFpEF, were analyzed. Multivariate logistic regression was performed to examine the independent association between the selected features and HFpEF in ESRD patients. RESULTS: Seventy-six of 119 patients were diagnosed with HFpEF. Demographic, laboratory, cardiac MRI, and echocardiogram characteristics were compared between HFpEF and non-HFpEF groups. The four texture features that were analyzed showed statistically significant differences between groups. In multivariate analysis, age, left atrial volume index (LAVI), and sum average 4 (SA4) turned out to be independent predictors for HFpEF in ESRD patients. Combining the texture feature, SA4, with typical predictive factors resulted in higher C-index (0.923 vs. 0.898, p = 0.045) and a sensitivity and specificity of 79.2% and 95.2%, respectively. CONCLUSIONS: Texture analysis of T1 maps adds diagnostic value to typical clinical parameters for the assessment of heart failure with preserved ejection fraction in patients with end-stage renal disease. KEY POINTS: • Non-invasive assessment of HFpEF can help predict prognosis in ESRD patients and help them take timely preventative measures. • Texture analysis of native T1 maps adds diagnostic value to the typical clinical parameters for the assessment of HFpEF in patients with ESRD.

The initial attempt at home hemodialysis in mainland China.

BACKGROUND: Observational studies have shown home hemodialysis (HHD) to be associated with better survival than facility hemodialysis (HD) and peritoneal dialysis (PD). Patients on HHD have reported higher quality of life and independence. HHD is considered to be an economical way to manage end-stage kidney disease (ESKD). The coronavirus disease 2019 pandemic has had a significant impact on patients with ESKD. Patients on HHD may have an advantage over in-center HD patients because of a lower risk of exposure to infection. PARTICIPANTS AND METHODS: We enrolled HD patients from our dialysis center. We first established the HHD training center. The training center was approved by the Chinese government. Doctors, nurses and engineers train and assess patients separately. There are three forms of patient monitoring: home visits, internet remote monitoring, and outpatient services. Demographic and medical data included age, sex, blood pressure, and dialysis-related data. Laboratory tests were conducted in our central testing laboratory, including hemoglobin (Hgb), serum creatinine (Cr), urea nitrogen (BUN), uric acid (UA), albumin (Alb), calcium (Ca), phosphorus (P), parathyroid hormone (PTH), and brain natriuretic peptide (BNP) levels. RESULTS: Six patients who underwent regular dialysis in the HD center of our hospital were selected for HHD training. We enrolled 6 patients, including 4 males and 2 females. The mean age of the patients was 47.5 (34.7-55.7) years, and the mean dialysis age was 33.5 (11.2-41.5) months. After an average of 16.0 (11.2-25.5) months of training, Alb, P and BNP levels were improved compared with the baseline values. After training, three patients returned home to begin independent HD. During the follow-up, there were no serious adverse events leading to hospitalization or death, but there were several adverse events. They were solved quickly by extra home visits of the technicians or online by remote monitoring. During the follow-up time, the laboratory indicators of all the patients, including Hgb, Alb, Ca, P, PTH, BNP, and ß2-MG levels, remained stable before and after HHD treatment. CONCLUSION: HHD is feasible and safe for ESKD in China, but larger-scale and longer-term studies are needed for further confirmation.

Automated peritoneal dialysis as a cost-effective urgent-start dialysis option for ESRD patients: A prospective cohort study.

BACKGROUND: Several studies have reported the feasibility of urgent-start peritoneal dialysis (PD) as an alternative to hemodialysis (HD) using a central venous catheter (CVC). However, the cost-effectiveness of automated peritoneal dialysis (APD) as an urgent-start dialysis modality has not been directly evaluated, especially in China. METHODS: We prospectively enrolled patients with end-stage renal disease (ESRD) who required urgent-start dialysis at a single center from March 2019 to November 2020. Patients were grouped according to their urgent-start dialysis modality (APD and HD). Urgent-start dialysis conducted until 14 days after PD catheter insertion. Then, PD was maintained. Each patient was followed until July 2021 or death or loss to follow-up. The primary outcome was the incidence of short-term dialysis-related complications. The secondary outcome was the cost and duration of the initial hospitalization. Technique survival, peritonitis-free or bacteriamia-free survival and patient survival were also compared. RESULTS: Sixty-eight patients were included in the study, of whom 36 (52.9%) patients were in APD group. Mean follow-up duration was 20.1 months. Compared with the HD group, the APD group had significantly fewer short-term dialysis-related complications. The cost of initial hospitalization was also significantly lower in APD patients. There was no significant difference between APD and HD patients with respect to duration of the initial hospitalization, technique survival rate, peritonitis-free or bacteriemia-free survival rate, and patient survival rate. CONCLUSION: Among ESRD patients with an urgent need for dialysis, APD as urgent-start dialysis modality, compared with HD using a CVC, resulted in fewer short-term dialysis-related complications and lower cost.

Incremental diagnostic value of CMR-derived LA strain and strain rate in dialysis patients with HFpEF.

OBJECTIVES: To test whether left atrial (LA) strain and strain rate add incremental value in the diagnosis of heart failure with preserved ejection fraction (HFpEF) in dialysis patients over clinical and conventional parameters only. BACKGROUND: HFpEF frequently occurs in dialysis patients, however, the diagnosis of HFpEF is difficult. Although HFpEF is always companied with LA dysfunction, the performance of novel LA parameters, LA strain, and strain rate, in the diagnosis of HFpEF among dialysis patients remains unknown. METHODS: In the study, 153 dialysis patients (57 without HFpEF and 96 with HFpEF) and 52 healthy controls underwent cardiovascular magnetic imaging (CMR). Three components of LA strain and strain rate, including reservoir, contractile, and booster pump, were assessed via the CMR feature tracking module. Extra diagnostic value was examined by Harrell's C-statistic. RESULTS: Compared with healthy controls and dialysis patients without HFpEF, dialysis patients with HFpEF had significantly impaired LA reservoir (εs) and contractile (εe) strain and strain rate (SRs, SRe), all p < 0.0001. Among these parameters, εs, εe, and SRe showed relatively high accuracy in diagnosing HFpEF among dialysis patients (areas under the curve: 0.84, 0.91, and 0.90, respectively). Reduction of εs, εe, and SRs provided incremental diagnostic value over conventional clinical and echocardiogram parameters. Combined with εs, εe or SRs, the diagnostic performance was further improved (Harrell's C-statistic: 0.83 vs. 0.96, 0.97, and 0.97, respectively, all p < 0.0001). CONCLUSIONS: CMR-derived εs, εe, and SRs might add incremental diagnostic value over conventional indexes in diagnosing HFpEF among dialysis patients.

Magnetic Resonance Imaging Quantification of Accumulation of Epicardial Adipose Tissue Adds Independent Risks for Diastolic Dysfunction among Dialysis Patients.

BACKGROUND: Diastolic dysfunction (DD) frequently occurs in dialysis patients; however, the risk factors of DD remain to be further explored in such a population. Epicardial adipose tissue (EAT) volume has proven to be an independent clinical risk factor for multiple cardiac disorders. PURPOSE: To assess whether EAT volume is an independent risk factor for DD in dialysis patients. STUDY TYPE: Case-control study. POPULATION: A total of 113 patients (mean age: 54.5 ± 14.4 years; 41 women) who had underwent dialysis for at least 3 months due to uremia. FIELD STRENGTH: A 3 T, steady-state free precession (SSFP) sequence for cine imaging, modified Look-Locker imaging (MOLLI) for T1 mapping and gradient-recalled-echo for T2*. ASSESSMENT: All participants were performed cardiac magnetic resonance imaging (MRI) and echocardiogram. For MRI images analysis, borders of the EAT were manually delineated, as well as, pericardial adipose tissue (PeAT) and paracardial adipose tissue (PaAT), T1 mapping, T2* mapping, global longitudinal strain (GLS), and left atrial strain. For echocardiogram assessments, the thickness of PaAT, e' velocity, E velocity, E/e ratio, A velocity, and deceleration time were measured. STATISTICAL TESTS: Univariate and multivariate logistic regressions were performed to explore the independent risk factors for DD. P value less than 0.05 was considered as significant. RESULTS: Compared with the DD(-) group, the DD(+) group had significantly more epicardial tissue fat (18.5 ± 1.3 vs. 30.9 ± 2.3) In addition, EAT volumes increased significantly with the grades of DD (grade 1 vs. grade 2 and 3: 27.9 ± 15.9 vs. 35.4 ± 13.1). Moreover, EAT had significant correlations with T1 mapping, T2* mapping, GLS, left atrial strain, e' velocity, and E/e ratio. EAT accumulation added an independent risk for DD (Odds Ratio = 1.03) over conventional clinical risk factors including age, diabetes mellitus, and hemodialysis. DATA CONCLUSION: EAT was associated with diastolic function, and its accumulation may be an independent risk factor for DD among dialysis patients. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Protocol for thiamine and folic acid in the treatment of cognitive impairment in maintenance haemodialysis patients: a prospective, randomised, placebo-controlled, double-blind, multicentre study.

INTRODUCTION: Cognitive impairment (CI) is the common complications in maintenance haemodialysis (MHD) patients. Recently, the pathogenesis of CI has been discussed and oxidative stress is one of the main mechanisms in these patients. Thiamine and folic acid, which play an important role in relieving the production of reactive oxygen species, reducing homocysteine levels, improving oxidative stress in the nervous system. In pilot study, cognitive function was significantly improved in the group with thiamine and folic supplementation. Based on this result, we hypothesise that thiamine combined with folic acid supplementation may improve cognitive function in patients with MHD. METHODS AND ANALYSIS: In this prospective, randomised, placebo-controlled, double-blind, multicentre study, we will enrol patients undergoing haemodialysis who has the Montreal Cognitive Assessment score lower than 26 to treatment group (thiamine 90 mg/day combined with folic acid 30 mg/day) or control group (thiamine placebo 90 mg/day combined with folic acid placebo 30 mg/day). All subjects will be followed up for 96 weeks. The primary endpoint is the comparison of Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) score between treatment group and control group at 96 weeks of follow-up. The secondary endpoints include serum thiamine, folate, homocysteine levels, cranial functional MRI and survival. The central randomisation method will be adopted and the principles of placebo-controlled, double-blind randomised control will be followed. The comparisons among ADAS-Cog scores and other secondary endpoints over time within subjects is conducted by using repeated measure analysis of variance (ANOVA) or generalised estimating equations (GEE). Pairwise t-test with Bonferroni adjustment is performed for multiple comparisons. On the other hand, for comparisons between treatment and control group, simple one-way ANOVA, GEE or Wilcoxon rank sum test is used. The χ2 method is used for statistical analysis of the categorical data. Kaplan-Meier survival curve is used for survival analysis. A p<0.05 is considered statistically significant difference. ETHICS AND DISSEMINATION: This trial has been approved by Shanghai Jiao Tong University School of Medicine, Renji Hospital Ethics Committee (KY2019-199). After publication of study results, trial report will be published in peer-reviewed journals and/or in national or international conferences. TRIAL REGISTRATION NUMBER: ChiCTR2000029297.

Hyperkalaemia prevalence, recurrence and treatment in patients on haemodialysis in China: protocol for a prospective multicentre cohort study (PRECEDE-K).

INTRODUCTION: Hyperkalaemia (HK) is a potentially life-threatening electrolyte imbalance associated with several adverse clinical outcomes and is common in patients with kidney failure. However, there is no evidence on the occurrence, recurrence and treatment of HK in patients on haemodialysis (HD) in China. METHODS AND ANALYSIS: The HK Prevalence, Recurrence, and Treatment in Haemodialysis Study is a prospective, multicentre, observational, cohort study being conducted across 15-18 sites in China. Approximately 600 patients with end-stage kidney disease on HD are anticipated to be enrolled and will be followed up for 24 weeks. Patients will be in the long interdialytic interval (LIDI) at enrolment and will receive follow-up care every 4 weeks in LIDI for pre-dialysis and post-dialysis (at enrolment only) serum potassium measurements. To obtain pre-dialysis serum potassium levels in the short interdialytic interval (SIDI), a follow-up visit will be performed in the SIDI during the first week. Information on concomitant medications, blood gas analysis and biochemistry measurements will be obtained at enrolment and at each follow-up visit. The primary endpoint will be the proportion of patients experiencing HK (defined as serum potassium level >5.0 mmol/L) at the study enrolment or during the 24-week follow-up. The key secondary endpoint will be the proportion of patients experiencing HK recurrence (defined as any HK event after the first HK event) within 1-6 months (if applicable) during the 24-week follow-up, including enrolment assessment. ETHICS AND DISSEMINATION: This study has been approved by Shanghai Jiaotong University School of Medicine, Renji Hospital Ethics Committee (2020-040). Other participating subcentres must also obtain ethics committee approval prior to the start of the study. The Good Clinical Practice regulations shall be strictly followed during the test implementation. Amendments to the protocol will be reviewed by the ethics committees. Written informed consent will be obtained from all participants before collection of any patient data and patient information. The findings of this study will be disseminated through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT04799067).

Efficacy and safety of polysaccharide iron complex capsules compared with iron sucrose in hemodialysis patients: study protocol for a randomized, open-label, positive control, multicenter trial (IHOPE).

BACKGROUND: Anemia is one of the main complications of chronic kidney disease especially kidney failure, which includes treatment with erythropoiesis-stimulating agents and iron supplementation, including intravenous and oral iron. However, intravenous iron may pose limitations, such as potential infusion reactions. Oral iron is mainly composed of divalent iron, which can excessively stimulate the gastrointestinal tract. Iron polysaccharide complex capsules are a novel oral iron trivalent supplement with higher iron content and lower gastrointestinal irritation. However, since high-quality evidence-based medicinal support is lacking, it is necessary to conduct clinical studies to further evaluate the effectiveness and safety of oral iron polysaccharide complex in chronic kidney disease patients. METHODS: This randomized controlled trial uses an open-label, parallel group design, where the efficacy and safety of maintenance hemodialysis (MHD) participants is evaluated. The experimental group is assigned erythropoietins and iron polysaccharide complex (two capsules each time, bid), and the control group is assigned erythropoietin and sucrose iron (100mg, 2w) injection. Participants (aged 18-75 years) undergoing maintenance hemodialysis were considered for screening. Inclusion criteria included hemoglobin (Hb) ≥110g/L and < 130g/L, transferrin saturation (TSAT) > 20% and < 50%, and serum ferritin (SF) > 200µg/L and < 500µg/L. Exclusion criteria included acute or chronic bleeding, serum albumin < 35g/L, hypersensitive C-reactive protein (HsCRP) > 10 mg/L, and severe secondary hyperparathyroidism (iPTH ≥ 800 pg/mL). Full inclusion and exclusion criteria are described in the "Methods" section. The primary endpoint is TSAT of the participants at week 12. Secondary endpoints include Hb, SF, hematocrit (Hct), HsCRP, pharmacoeconomic evaluation, drug costs, quality of life, and indicators of oxidative stress. The treatment will last for 24 weeks with a follow-up visit at baseline (within 7 days prior to initial treatment) and weeks 4, 8, 12, 16, 20, and 24 after initial treatment. This clinical research includes 9 hemodialysis centers in mainland China and plans to enroll 186 participants. DISCUSSION: It is expected that it will provide strong evidence to reveal the clinical efficacy and safety of oral iron in the treatment of chronic CKD-related anemia in MHD patients through this clinical trial. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000031166 . Registered on March 23, 2020.

Intelligent "Internet Plus" services in the first case of home hemodialysis in mainland China.

BACKGROUND: Many studies have shown that compared with those who use other dialysis modalities, patients using home hemodialysis (HHD) have an increased rate of survival and better quality of life. It was noted in 2006 that there was opportunity for significant expansion of the use of HHD in many countries. China covers a vast area and has a large amount of end-stage renal failure patients. But in mainland China, all dialysis treatments are in-center, and the number of HHD patients is zero. In 2018, our hospital received the permission of the Shanghai government to carry out HHD. CASE PRESENTATION: We initiated four incident hemodialysis patients on an HHD regimen, one patient has been dialyzed in the home safely for 8 months. The biochemical parameters of the first patient remained stable on the regimen and he achieved standard Kt/V urea targets. Treatment-related adverse events were not reported during the follow-up. We combined HHD with intelligent "Internet Plus" real-time remote monitoring and introduced the Internet, especially visualization software, to replace traditional telephone and home visit methods. It is more intuitive and quicker to assist patients in performing home hemodialysis and improve the safety of treatment. CONCLUSIONS: HHD can be performed by selected trained patients in mainland China. Combined with the internet, visualization software, and traditional telephone and home visits, it is intuitive and quick to assist patients in carrying out HHD and improve the safety of treatment. HHD broadens the choices for uremia patients in China.