Objective To analyze the efficacy and safety of nalfurafine hydrochloride in treating chronic kidney disease-associated pruritus (CKD-aP) in hemodialysis (HD) patients. Methods This study adopted a multicenter, prospective, single-arm, self-controlled before-after design. The clinical data of HD patients with CKD-aP at 13 blood purification centers, including the First Affiliated Hospital of Zhengzhou University, from December 2024 to May 2025 were collected. All patients received nalfurafine hydrochloride orally disintegrating tablets (2.5 μg qd) for 14 days, followed by a 14-day follow-up without the medication. The visual analogue scale (VAS) was used to assess the daily severity of pruritus, and adverse events were closely monitored. Paired t-test was performed to compare the daily VAS scores during treatment with baseline, and Kaplan-Meier survival analysis was used to assess the onset time of drug. Results A total of 61 HD patients were enrolled in this study, including 38 males (62.30%), with age of (62.07±12.29) years, and a dialysis vintage of (64.18±40.31) months. At baseline, 14 patients (22.95%), 22 patients (36.07%) and 25 patients (40.98%) had moderate, severe, and extremely severe pruritus, respectively. During treatment, one patient withdrew from the study due to a severe rash, and VAS data of 60 patients were collected. The VAS scores decreased most significantly in the first week of treatment [(64.90±14.43) mm vs. (83.72±13.98) mm, t=22.214, P<0.001]. Although slight fluctuations occurred in the second week of treatment, VAS scores remained significantly lower than baseline [(55.88±16.64) mm vs. (83.72±13.98) mm, t=18.544, P<0.001]. The overall response rate reached 68.33% (41/60) after 14 days of treatment. The VAS value during the follow-up period was slightly higher than that at the second week of the treatment period, but remained significantly lower than the baseline level by the end of the follow-up [(68.38±13.56) mm vs. (83.72±13.98) mm, t=17.755, P<0.001]. Kaplan-Meier survival analysis showed that the median onset time of nalfurafine hydrochloride for CKD-aP in HD patients was 4 days. The incidence of adverse events was 9.84% (6/61), of which 4 patients with mild to moderate adverse reaction were transient and self-limiting, and 2 patients with severe adverse reactions improved after symptomatic treatment. Conclusion Nalfurafine hydrochloride can effectively relieve pruritus symptoms in HD patients with CKD-aP and has a good safety profile.
Objective To investigate the association of intradialytic cerebral blood flow changes with the progression of cerebral small vessel disease (CSVD) in middle-aged and elderly maintenance hemodialysis (MHD) patients. Methods This prospective cohort study enrolled MHD patients aged ≥50 years from January 2023 to June 2023 at Beijing Shijitan Hospital, Capital Medical University. General clinical data were collected. Transcranial Doppler (TCD) was used to monitor the mean flow velocity (MFV) of the cerebral artery at various time points during dialysis, and MFV decline rate during dialysis was calculated. The number of cerebral microbleed (CMB), white matter hyperintensity (WMH), lacunar, and the degree of brain atrophy on brain magnetic resonance imaging (MRI) were assessed at baseline and at the 12-month follow-up. Spearman correlation analysis and multivariate linear regression model were used to analyze the relationship between MFV decline rate and the progression of CSVD. Results A total of 102 MHD patients were included in this study, with age of (63.79±7.83) years (50-85 years old) and 80 males (78.43%). The median dialysis age was 32.00 (16.00, 106.00) months. TCD indicated a downward trend in MFV during dialysis (P<0.05). A total of 86 patients completed two brain MRI examinations at baseline and 12-months of follow-up. Compared with baseline, significant progression was observed in CMB, WMH and lacunar at the 12-month follow-up, while brain volume (including white matter and gray matter) and brain parenchymal fraction were significantly reduced, and the differences were statistically significant (all P<0.05). Multivariate linear regression analysis showed that MFV decline rate was an independent risk factor for CMB and WMH progression [β=13.898, 95% confidence interval (CI) 2.372-25.425, P=0.019; β=0.894, 95% CI 0.207-1.582, P=0.011]. Conclusion The decrease of cerebral blood flow during hemodialysis is an independent risk factor for the progression of CSVD in middle-aged and elderly MHD patients.
Objective To investigate the effects of multi-component exercise training on frailty, physical function, quality of life, and serum albumin levels in patients undergoing maintenance hemodialysis (MHD). Methods This study was a single-center, parallel-group, prospective randomized controlled trial with a 1∶1 allocation ratio. Patients receiving MHD treatment at the First Affiliated Hospital of Zhejiang University School of Medicine between November 2024 and February 2025, who met the criteria for pre-frailty, were included. Participants were randomly assigned to either the multi-component exercise group or the control group by means of a computer-generated random number sequence. The multi-component exercise group received a 12-week exercise intervention in addition to routine dialysis treatment, which included resistance exercises on dialysis days and aerobic exercises on non-dialysis days, along with flexibility training prior to each exercise session. The control group received only hemodialysis treatment. The primary outcome was the frailty score, while secondary outcomes included physical function score, quality of life score, and serum albumin level. These parameters were assessed at baseline and at 4, 8, and 12 weeks of intervention, and the effectiveness of the intervention was analyzed using a linear mixed-effects model. In the linear mixed-effects model, time, group, and their interaction were specified as fixed effects, with subject ID included as a random intercept. The time-by-group interaction was assessed using an F-test to evaluate the overall intervention effect. For each outcome, between-group comparisons at 4, 8, and 12 weeks were performed using Bonferroni correction for multiple testing. Results A total of 60 patients were enrolled and assigned to a multi-component exercise group (n=30) and a control group (n=30). The baseline characteristics of the two groups showed no statistically significant differences (all P>0.05). Linear mixed-effects model analysis showed a significant time-by-group interaction for frailty score (F=7.521, P<0.001). The multi-component exercise group had significantly lower frailty scores than the control group at 4 weeks (t=-4.440, adjusted P<0.001), 8 weeks (t=-3.946, adjusted P<0.001), and 12 weeks (t=-5.591, adjusted P<0.001). The interaction between time and group for the short physical performance battery score was also significant (F=3.894, P=0.010), with the multi-component exercise group achieving significantly higher scores than the control group at 8 weeks (t=2.867, adjusted P=0.015) and 12 weeks (t=3.734, adjusted P<0.001). The interaction for the 36-item short form health survey score was not statistically significant (F=0.139, P=0.937), and no significant differences were found at each time point (adjusted all P>0.05). The interaction for serum albumin was not significant (F=2.337, P=0.076), with serum albumin level in the multi-component exercise group being significantly higher than that in the control group at 12 weeks (t=3.496, adjusted P=0.002). No adverse events, such as falls, occurred during the study period. Conclusion Multi-component exercise training can effectively improve the frailty status and body function of MHD patients and help maintain the stability of serum albumin.
Objective To evaluate the efficacy and safety of limb ischemic preconditioning (LIPC) in improving left ventricular function in maintenance hemodialysis (MHD) patients. Methods This was a single-center, prospective, randomized controlled trial. MHD patients with impaired left ventricular systolic function from the Blood Purification Center of the Third Affiliated Hospital of Nanjing Medical University between March 2022 and April 2023 were recruited and randomly divided into LIPC group and control group according to the randomly generated sequence of numbers by the computer. In the LIPC group, a LIPC training cuff was placed around the thigh near the knee joint, inflated to 200 mmHg for 5 minutes, then deflated to 0 mmHg for 5 minutes, for 5 consecutive cycles (total 50 minutes), once daily. The control group received sham stimulation (cuff inflated to 20 mmHg), while all other procedures were the same as those for the LIPC group. Left ventricular systolic function indices, including left ventricular ejection fraction (LVEF), left ventricular global longitudinal strain (LVGLS), and left ventricular peak strain dispersion (LVPSD), were measured by two-dimensional speckle tracking echocardiography before intervention (week 0), at week 6 and week 12 of intervention. Myocardial injury markers, cardiac troponin I (cTnI) and creatine kinase isoenzyme (CK-MB), were detected by enzyme-linked immunosorbent assay (ELISA). The differences between the two groups of the obove indicator were compared. Results A total of 37 patients completed the study, 18 in the LIPC group and 19 in the control group. Intra-group comparison: at week 6 of intervention, LVEF and absolute LVGLS values in the LIPC group were significantly increased compared with baseline (LVEF: t=2.438, P=0.020; LVGLS: t=4.674, P<0.001), and LVPSD value was decreased compared with baseline (t=-2.030, P=0.001); at week 12 of intervention, LVEF and absolute LVGLS values in the LIPC group remained significantly higher than baseline (LVEF: t=3.236, P=0.001; LVGLS: t=5.467, P<0.001), but the difference in LVPSD value was not statistically significant (t=1.682, P=0.101). No significant changes in the above indices were observed in the control group at any time point (all P>0.05). Inter-group comparison: at week 6 of intervention, LVEF and absolute LVGLS values in the LIPC group were significantly higher than those in the control group (LVEF: t=2.945, P=0.009; LVGLS: t=4.115, P<0.001), and LVPSD was significantly lower than that in the control group (t=-3.290, P=0.002); at week 12 of intervention, LVEF and absolute LVGLS values in the LIPC group remained significantly higher than those in the control group (LVEF: t=3.572, P=0.001; LVGLS: t=6.245, P<0.001), and LVPSD was significantly lower than that in the control group (t=-3.333, P=0.002). Myocardial injury marker test results showed that at 12 weeks of intervention, the cTnI level in the LIPC group was significantly lower than that in the control group (t=-2.580, P=0.013); the change in cTnI in the LIPC group was negatively correlated with the change in absolute LVGLS value (r=-0.63, P=0.005). No serous LIPC-related adverse events occurred during the study period. Conclusions LIPC can improve left ventricular systolic function in MHD patients, and has good safety. Its mechanism of action may be related to reducing myocardial injury.
Objective To explore the factors associated with hyperphosphatemia in patients undergoing maintenance hemodialysis (MHD), and to provide a theoretical basis for the clinical management of hyperphosphatemia. Methods This was a multicenter cross-sectional study. Demographic data, medication use over the past 3 months, and laboratory test results were collected from MHD patients at four blood purification centers in Jiangsu and Shandong Provinces from January 2025 to March 2025. Patients were divided into a hyperphosphatemia group (serum phosphorus >1.45 mmol/L) and a non-hyperphosphatemia group (serum phosphorus ≤1.45 mmol/L) according to their serum phosphorus levels. Patients were randomly assigned to a training set and a validation set at a ratio of 7:3. In the training set, univariate logistic regression was performed to screen potential associated factors (P<0.05). Variables meeting this criterion were then entered into a multivariate logistic regression model to identify independent associated factors, after which a nomogram prediction model was constructed. Using data from the training and validation sets, receiver-operating characteristic (ROC) curves were plotted and the area under the curve (AUC) was calculated to evaluate model performance, and the Hosmer-Lemeshow goodness-of-fit test was used to assess model calibration and goodness of fit. Results A total of 1 597 MHD patients were enrolled in this study, with age of (58.06±12.98) years, including 966 males (60.49%). The incidence of hyperphosphatemia was 79.65% (1 272/1 597), and the rate of achieving target serum phosphorus control in MHD patients was 30.93% (494/1 597). Multivariate logistic regression analysis showed that age [odds ratio (OR)=0.99, 95% confidence interval (CI) 0.97-0.99, P=0.033], use of phosphate binders (OR=1.44, 95% CI 1.03-2.01, P=0.032), serum potassium (OR=3.70, 95% CI 2.87-4.78, P<0.001), and parathyroid hormone (OR=1.01, 95% CI 1.01-1.01, P<0.001) were independent factors associated with hyperphosphatemia in MHD patients. The established nomogram model exhibited favorable discrimination and consistency. The AUC of the ROC curve in the training set was 0.77 (95% CI 0.74-0.81), with a Hosmer-Lemeshow goodness-of-fit test result of χ2=10.96, P=0.204. The AUC in the validation set was 0.79 (95% CI 0.74-0.84), with a Hosmer-Lemeshow test result of χ2=8.78, P=0.361. Conclusion The incidence of hyperphosphatemia is relatively high among MHD patients. Age, use of phosphate binders, serum potassium, and parathyroid hormone are the independent factors associated with hyperphosphatemia in this population.
Objective To investigate the role and mechanism of succinyl-CoA: 3-oxoacid CoA transferase 1 (OXCT1), the rate?limiting enzyme of ketone body catabolism, in renal tubular injury of diabetic kidney disease. Methods Human kidney?2 (HK?2) cells were treated with 60 mmol/L glucose for 48 hours to establish a high glucose injury model. Lentiviral transduction was used to construct stable cell lines overexpressing or knocking down OXCT1. An additional group was established with high glucose combined with OXCT1 overexpression and 2 μmol/L rotenone, an inhibitor of mitochondrial respiratory chain complex Ⅰ. Quantitative real?time PCR and Western blotting were performed to detect the expression levels of OXCT1, hydroxy methylglutaryl?CoA synthase 1 (HMGCS1), and acetyl?CoA acetyltransferase 1 (ACAT1). Cell counting kit?8 and ethynyl?deoxyuridine staining were used to assess the cell proliferation, and TUNEL staining was used to evaluate the cell apoptosis. JC?1, MitoTracker, and MitoSOX probes were used to measure mitochondrial membrane potential, biomass, and reactive oxygen species, respectively. Adenosine triphosphate (ATP) content and the activities of mitochondrial respiratory chain complexes Ⅰ-Ⅳ were determined. Renal tissue samples from 42 patients undergoing partial nephrectomy for renal cancer were prospectively enrolled, and these patients were divided into the renal injury group (n=25) and the control group (n=17) based on the presence or absence of renal tubular injury. Immunohistochemistry was used to detect OXCT1, HMGCS1 and ACAT1 protein expression levels. Results After high-glucose treatment in HK-2 cells, mRNA and protein expression levels of OXCT1and ACAT1 were decreased, mRNA and protein expression levels of HMGCS1 were increased; cell proliferation activity was decreased, while the apoptosis rate was increased; ATP content, mitochondrial membrane potential, activity of mitochondrial respiratory chain complexes Ⅰ?Ⅳ, and mitochondrial biomass were reduced, whereas reactive oxygen species level was elevated (all P<0.05). Overexpression of OXCT1 reversed these changes, whereas knockdown of OXCT1 aggravated those injury (all P<0.05). In the presence of rotenone, OXCT1 overexpression still partially restored ATP content and complex Ⅰactivity under high glucose condition (both P<0.05). The immunohistochemical analysis of clinical samples showed lower OXCT1 protein expression but higher HMGCS1 and ACAT1 protein expression in the renal injury group compared with the control group (all P<0.05). Conclusions Downregulation of OXCT1 is a key factor in high glucose?induced ketone body metabolic disorder, mitochondrial dysfunction, and cell injury in HK?2 cells. Overexpression of OXCT1 exerts protective effects by improving mitochondrial oxidative phosphorylation and ketone body-metabolic homeostasis, and this effect is partially independent of intact mitochondrial respiratory chain function.
Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a form of hereditary nephropathy characterized primarily by renal tubular and interstitial injury. The subtype caused by point mutations or deletions involving the entire HNF1B gene, located on chromosome 17q12, is collectively termed ADTKD-HNF1B. The authors report 3 patients with ADTKD-HNF1B: case 1 resulted from a de novo point mutation, with clinical manifestations including elevated serum creatinine, hyperuricemia, hypomagnesemia, and hypercalcemia. Treatment included magnesium supplementation, losartan (50 mg qd) for blood pressure control, and correction of electrolyte disturbance, with renal function remaining stable after 2 years of follow-up. Cases 2 and 3 were two patients with 17q12 region deletions within the same family, presenting with bilateral renal cysts and hyperuricemia. They received symptomatic urate-lowering therapy and correction of electrolyte disturbance, and were still under follow-up. Through clinical and genetic testing, this article analyzes the genotypes and phenotypes of 3 cases, deepens understanding of ADTKD-HNF1B, and provides a reference for the diagnosis, management and follow-up of such rare diseases in China.
Drug-induced hypersensitivity syndrome (DiHS), also known as drug reaction with eosinophilia and systemic symptoms(DRESS), is a rare, potentially life-threatening adverse drug reaction, often accompanied by fever, rash, hematologic abnormalities, and multi-organ involvement. Polyarteritis nodosa (PAN) is a systemic necrotizing vasculitis that can affect the kidneys, but simultaneous occurrence of PAN and DiHS is extremely rare. This paper reports a case of a 58-year-old female patient who was admitted with fever, rash, and acute kidney injury. She was initially diagnosed with DiHS, and renal biopsy later confirmed kidney involvement of polyarteritis nodosa. During the disease course, the patient experienced recurrent deterioration of renal function, severe rash, coagulation dysfunction, pulmonary hemorrhage, and multi-organ failure. Despite combined treatment with glucocorticoids, intravenous immunoglobulin, cyclophosphamide, and rituximab, the patient ultimately died from infection, bleeding, and multi-organ failure. DiHS and PAN can occur concurrently, presenting with complex clinical manifestations and severe disease. Early recognition, timely immunosuppressive therapy, and close monitoring of complications are crucial for improving prognosis.
This article reports a case of a 23?year?old female patient with systemic lupus erythematosus who initially presented with classⅡlupus nephritis and developed new?onset incomplete intestinal obstruction during treatment with belimumab combined with immunosuppressive agents. The patient presented with abdominal pain, vomiting, and diarrhea, and imaging revealed signs of small bowel obstruction. Differential diagnosis included mesenteric vasculitis, infectious enteropathy, intestinal adhesions, and drug?induced gastrointestinal injury. Based on the presence of hypocomplementemia, positive anti?dsDNA antibodies, and ANCA positivity, along with the exclusion of infection and other causes, the condition was finally diagnosed as incomplete intestinal obstruction secondary to lupus?related intestinal involvement. Treatment with a combination of methylprednisolone, cyclophosphamide, and telitacicept led to symptomatic relief, resolution of obstructive signs, and stabilization of the disease. Incomplete intestinal obstruction is a rare but severe gastrointestinal complication of systemic lupus erythematosus. Timely recognition of lupus activity and adjustment of immunosuppressive therapy are crucial. Telitacicept may offer a new therapeutic option for refractory cases, although its efficacy and safety require further validation.
This study aims to analyze the influencing factors of tolvaptan's therapeutic effect, an arginine vasopressin V2 receptor antagonist, in patients with chronic kidney disease (CKD) complicated by edema. It was a retrospective observational study. A total of 32 patients with CKD hospitalized at the Second Affiliated Hospital of Dalian Medical University from December 2023 to December 2024 were included. Demographic data, such as sex and age, were collected alongside clinical data, including free water clearance, urine osmolality, serum creatinine, blood urea, estimated glomerular filtration rate, urine urea/serum urea ratio, and fractional excretion of urea. Univariate logistic regression analysis was used to screen the factors influencing the efficacy of tolvaptan in treating renal edema, and receiver operating characteristic (ROC) curves were plotted to evaluate the predictive value of each indicator. Univariate logistic regression showed that higher urine osmolality [odds ratio (OR)=1.010, 95% confidence interval (CI) 1.002-1.018, P=0.011], more negative free water clearance (OR=0.052, 95% CI 0.004-0.717, P=0.027), higher estimated glomerular filtration rate (OR=1.048, 95% CI 1.007-1.092, P=0.023), higher urine urea/serum urea ratio (OR=1.112, 95%CI 1.021-1.212, P=0.015), and lower fractional excretion of urea (OR=0.917, 95% CI 0.850-0.989, P=0.025) were significantly associated with tolvaptan efficacy. ROC curve analysis identified the following predictors: more negative free water clearance: AUC 0.787, optimal cutoff value-0.79 ml/min (specificity 100%, sensitivity 47.8%); higher urine osmolality: AUC 0.870, optimal cutoff value 439.5 mmol/L (specificity 87.0%, sensitivity 77.8%); higher estimated glomerular filtration rate: AUC 0.783, optimal cutoff value 83.3 ml·min?1·(1.73 m2)?1 (specificity 88.9%, sensitivity 60.9%); lower fractional excretion of urea: AUC 0.827, optimal cutoff value 35.27% (specificity 75.0%, sensitivity 90.5%); higher urine urea/serum urea ratio: AUC 0.792, optimal cutoff value 16.66 (specificity 75.0%, sensitivity 95.2%). The study suggests that the above indicators may assist in personalizing tolvaptan treatment for CKD patients with renal edema.
Diabetic kidney disease ( DKD ) is a common micro vascular complication of diabetes and the most leading cause of chronic kidney disease and end-stage renal disease. Its pathogenesis is complex, involving various metabolic disorders and cellular damage. Increasing evidence suggests that lipid metabolism disorders, in conjunction with mitochondrial dysfunction, play a critical role in the development of DKD, creating a vicious cycle of mutual reinforcement. Therefore, a deeper understanding of the interplay between these two key pathological processes may provide new insights and potential targets for the treatment of DKD. This article systematically reviews the mechanism of lipid metabolism disorder and mitochondrial damage in DKD, explores their interaction and impact on disease progression, discusses potential therapeutic strategies targeting lipid metabolism and mitochondrial function, and looks forward to future research directions.
Fibrosis is a common pathological endpoint in the progression of kidney disease, driven by complex signaling networks. Epigenetic modifications, particularly histone modifications, play a pivotal role in renal pathophysiology and disease progression, offering new insights into the mechanisms underlying renal fibrosis. This review systematically summarizes recent advances elucidating the involvement of histone acetylation, methylation, and the dysregulation of their corresponding modifying enzymes in renal fibrogenesis. We aim to refine the current understanding of the pathological framework of renal fibrosis, identify critical therapeutic targets, and propose potential intervention strategies. Furthermore, we discuss future directions in precision targeting, combinatorial epigenetic strategies, and clinical translation, with the goal of providing novel insights for the development of targeted antifibrotic therapies.
Dialysis patients generally experience a heavy symptom burden and poor quality of life, which are not fully captured by traditional clinical indicators. The application of patient-reported outcome (PRO) and patient-reported outcome measure (PROM) in clinical practice facilitates the early identification of patients' symptom burden, functional status, and self-efficacy. This enables targeted early interventions, thereby enhancing quality of life and improving prognosis. The implementation of PRO is a crucial pathway to realizing a person-centered medical and care model. This review summarizes the definitions of PRO and PROM in dialysis population, commonly used instruments, the development of electronic PROM, and the applications of PRO in symptom burden and health-related quality of life assessment, health management and clinical practice, as well as clinical trials, and further discusses future directions for their implementation and development.
