Clinical manifestations and outcomes in tubulointerstitial nephritis and uveitis syndrome: a case report and a systematic review in China.

PURPOSE: Tubulointerstitial nephritis and uveitis (TINU) syndrome is an uncommon disease. We present a confirmed case of TINU syndrome, and a systematic review of epidemiological characteristics, clinical manifestations, management, and outcomes in Chinese patients. METHODS: A systematic search was carried out using defined terms and updated up to September 2022, in PubMed, Web of Science, Wanfang, CNKI, and VIP, to identify reported cases of TINU in China, according to PRISMA guidelines. RESULTS: An 18-year-old boy presented with elevated serum creatinine and 24-h urine protein level of > 2 g. Inspection result revealed acute tubulointerstitial nephritis, and bilateral uveitis. The patient was diagnosed with TINU syndrome and received treatment with methylprednisolone sodium succinate, which resulted in a significant decrease in creatinine and urinary protein levels. Systematic review identified 35 publications that met the inclusion criteria. A total of 71 cases were included in this article, of which 70 were from publications and 1 was from our hospital. The median age at onset was 42 years and was significantly lower in males than females (P < 0.05). The symptoms of uveitis often occurred after kidney injury (54%) and most uveitis was anterior (55%) and bilateral (75%). Among the 51 patients who were followed up for more than 6 months, 24 had recurrent ocular symptoms or progression to chronic uveitis. Twenty patients experienced chronic or progressive kidney disease. CONCLUSION: TINU syndrome is prone to misdiagnosis because kidney damage may not occur simultaneously with uveitis. The incidence of kidney sequelae in children is lower than that in adults, and glucocorticoids are the preferred treatment. INPLASY REGISTRATION NUMBER: INPLASY202350050.

Extracorporeal membrane oxygenation combined with minimally invasive surgery for acute respiratory failure and sudden cardiac arrest: A case report.

Acute respiratory failure and sudden cardiac arrest caused by acute intrathoracic infection is a fatal clinical condition with a low resuscitation success rate. The present study describes the case of a patient with acute empyema secondary to an acute lung abscess rupture, complicated by acute respiratory failure and sudden cardiac arrest caused by severe hypoxemia. The patient recovered well through the administration of multiple therapeutic measures, including medication and closed chest drainage, cardiopulmonary resuscitation, extracorporeal membrane oxygenation combined with continuous renal replacement therapy, and minimally invasive surgical resection of the lung lesion with persistent alveolar fistula as the clinical manifestation. To the best of our knowledge, the treatment of such a severe condition combined with thoracoscopic surgery has rarely been reported before, and the present study may provide insight regarding therapeutic schedules for acute respiratory failure by intrathoracic infection, and excision of ruptured lung abscess.

Evaluation of safety, effectiveness and treatment patterns of sodium zirconium cyclosilicate in management of hyperkalaemia in China: a real-world study protocol.

INTRODUCTION: Hyperkalaemia (HK) is a potentially life-threatening electrolyte imbalance associated with several adverse clinical outcomes. The efficacy and negative effects of currently existing treatment options have made HK management questionable. Sodium zirconium cyclosilicate (SZC), a novel highly selective potassium binder, is approved for the treatment of HK. The present study will be aimed to assess the safety, effectiveness and treatment patterns of SZC in Chinese patients with HK in a real-world clinical setting as it is required by China's drug review and approval process. METHODS AND ANALYSIS: This is a multicentre, prospective cohort study which plans to enrol 1000 patients taking SZC or willing to take SZC from approximately 40 sites in China. Patients ≥18 years of age at the time of signing the written informed consent and with documented serum potassium levels ≥5.0 mmol/L within 1 year before study enrolment day will be included. Eligible patients will receive SZC treatment and will be followed up for 6 months from enrolment day. The primary objective will be to evaluate the safety of SZC for the management of HK in Chinese patients in terms of adverse events (AEs), serious AEs as well as discontinuation of SZC. The secondary objectives will include understanding the SZC dosage information in terms of its effectiveness and treatment patterns under real-world clinical practice and assessing effectiveness of SZC during the observational period. ETHICS AND DISSEMINATION: This study protocol was approved by the Ethics Committee of the First Affiliated Hospital of Dalian Medical University (approval number: YJ-JG-YW-2020). All the participating sites have received the ethics approval. Results will be disseminated through national and international presentations and peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT05271266.

Effectiveness and Tolerability of Nifedipine GITS in Patients with Chronic Kidney Disease and Uncontrolled Hypertension: A Prospective, Multicenter, Observational Study (ADRENAL).

INTRODUCTION: Achieving target blood pressure (BP) goals in patients with chronic kidney disease (CKD) and uncontrolled hypertension is a challenge. Various studies have shown the efficacy of nifedipine gastrointestinal therapeutic system (GITS) 60 mg in patients with hypertension. However, there is a paucity of clinical studies in patients with CKD. Hence, we conducted this study to evaluate the effectiveness and tolerability of nifedipine GITS 60 mg in Chinese patients with CKD and uncontrolled hypertension in real-world clinical settings. METHODS: In a prospective, multicenter, observational study, Chinese patients with CKD and uncontrolled hypertension were given nifedipine GITS 60 mg with a primary endpoint of change in office systolic BP (SBP) at 12 weeks. The secondary endpoints included changes at 12 weeks in office diastolic BP (DBP), office SBP and DBP in SBP subgroups (140-160 mmHg and ≥ 160 mmHg) and CKD stages subgroups, SBP and DBP control rate, and the adverse events (AEs). Statistical analysis was performed using SAS® version 9.4. RESULTS: In total, 871 and 622 patients were included in the safety analysis set and efficacy analysis set respectively. The mean office SBP and DBP at baseline were 162.9 and 97.3 mmHg, respectively. At week 12, the mean change in SBP was - 24.0 mmHg (95% confidence interval [CI] - 25.32, - 22.65 mmHg); after missing data were accounted for, it was - 23.9 mmHg (95% CI - 25.25, - 22.60 mmHg). Marked decreases in DBP, and office SBP and DBP in baseline SBP subgroups as well as CKD stages were observed at week 12. The BP control rate at week 12 was 50.0%. Twenty-three (2.6%) patients reported at least one drug-related AEs. No event of hypotension or death occurred during the study. CONCLUSION: Nifedipine GITS 60 mg showed effectiveness and tolerability in reducing office SBP and DBP in Chinese patients with CKD and uncontrolled hypertension. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03194633.

Time spent outside of the hospital, CKD progression, and mortality: a prospective cohort study.

PURPOSE: Home time-being out of any healthcare facility-has been proposed as a patient-centered outcome. This novel measure has not been investigated in patients with chronic kidney disease (CKD). The aim of this study is to determine whether there was an association between home time and occurrence of end-stage renal disease (ESRD) or all-cause mortality during 1 year of follow-up. METHODS: We assembled a prospective cohort of patients with CKD not requiring dialysis at the Nephrology Center of First Affiliated Hospital of Jiaxing University between May 2014 and April 2017 and followed up for 1 year. Home time was calculated as the number of days spent out of a hospital, rehabilitation facility, or skilled nursing facility. Outcomes included progression to ESRD and all-cause mortality. RESULTS: Among 943 patients, 882 (93.5%) had complete follow-up through 1 year. Mean home time was 246.9 ± 126.7 days. In regression analysis, several patient characteristics were associated with significantly reduced home time, including diabetes mellitus, cardiovascular disease, and albuminuria. Home time was strongly correlated with time-to-event endpoints of ESRD (τ=0.324) and all-cause mortality (τ=0.785). CONCLUSIONS: Home time is significantly reduced for patients with CKD not requiring dialysis and is highly correlated with traditional time-to-event endpoints. Home time serves as a novel, easily calculated, patient-centered outcome that may reflect effect of interventions on future CKD research.

Dysregulation of microRNA-181b and TIMP3 is functionally involved in the pathogenesis of diabetic nephropathy.

This study aimed to study the roleof microRNA (miR)-181b and its target TIMP3 in the development of diabetic nephropathy (DMN) via inhibiting the apoptosis of mesangial cells. Real-time polymerase chain reaction (RT-PCR) was adopted to compare the miR-181b expression between subjects with diabetic nephropathy (DN) and normal control. In addition, luciferase assays were utilized to explore the regulatory relationship between TIMP3 and miR-181b. Real-time PCR and densitometry analysis were conducted to measure the levels of TIMP3 mRNA/protein in DMN or in cells treated by miR-181b inhibitors, miR-181b mimics, and TIMP3 siRNA. And the 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was adopted to study the effect of miR-181b on cell survival and apoptosis. miR-181b expression was much higher in the DN group, and the results of computational analysis identified TIMP3 as a miR-181b target. The luciferase activity of cells transfected with wild-type TIMP3 and mutant2 TIMP3 was significantly reduced, whereas the luciferase activity of cells transfected with mutant1 TIMP3 was evidently higher. Furthermore, a negative regulatory relationship was established between TIMP3 and miR-181b expression with a correlation efficient of -0.5351. The levels of TIMP3 mRNA/protein expression were apparently increased in the DN group. In addition, the treatment of cells with miR-181b mimics and TIMP3 siRNA remarkably lowered the levels of TIMP3 mRNA/protein, whereas the transfection of cells with miR-181b inhibitors notably elevated the expression of TIMP3 mRNA/protein. miR-181b promoted the survival of cells and inhibited their apoptosis. The miR-181b expression was related to the development of DMN and could be used as a prognosis biomarker of DMN in the patients with DM.

MiR-208a-3p functions as an oncogene in colorectal cancer by targeting PDCD4.

Accumulating evidences have shown microRNAs (miRNAs) play important roles in the progression of human cancers including colorectal cancer (CRC). However, the biological function and molecular mechanism of miRNAs in CRC still remains to be further investigated. Using microarray, we found and confirmed that miR-208a-3p was up-regulated in CRC tissues. Its high expression was statistically associated with distant metastasis and TNM stage. Functional assays revealed inhibition of miR-208a-3p suppressed proliferation, invasion and migration, and induced cell apoptosis of CRC cells. Moreover, we identified programmed cell death protein 4 (PDCD4), a well-known tumor suppressor, is a direct target of miR-208a-3p. We also found that overexpression of PDCD4 suppressed cell proliferation, invasion, and migration. Importantly, silencing of PDCD4 efficiently abrogated the promoting effects on CRC cells proliferation, invasion, and migration caused by inhibition of miR-208a-3p. Our findings confirmed the oncogenic role of miR-208a-3p via targeting PDCD4 in CRC, identifying miR-208a-3p as a potential diagnosis and therapeutic biomarker for CRC.

Association between Serum Vitamin D Levels and Sleep Disturbance in Hemodialysis Patients.

Sleep disturbance is a frequent and serious complication of hemodialysis (HD). Low serum vitamin D levels have been associated with sleep quality in non-HD subjects. Our aim was to examine the possible association between serum vitamin D levels and the presence of sleep disturbance in HD patients. We recruited 141 HD patients at the HD center of the First Affiliated Hospital of Jiaxing University during 2014-2015. Serum levels of 25-hydroxyvitamin D (25(OH)D) were determined by the competitive protein-binding assay. Sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI). Demographic, clinical and laboratory data were recorded. Meanwhile, 117 healthy control subjects were also recruited and underwent measurement of 25(OH)D. Eighty-eight patients (62.4%) had sleep disturbance (PSQI scores ≥ 5). Patients with sleep disturbance showed lower levels of 25(OH)D as compared to those without sleep disturbance (85.6 ± 37.4 vs. 39.1 ± 29.1 nmol/L, p < 0.001). In multivariate analyses, serum levels of 25(OH)D (≤48.0 nmol/L) were independently associated with sleep disturbance in HD patients (OR 9.897, 95% CI 3.356-29.187, p < 0.001) after adjustment for possible variables. Our study demonstrates that low serum levels of vitamin D are independently associated with sleep disturbance in HD patients, but the finding needs to be confirmed in future experimental and clinical studies.

Serum levels of copeptin are associated with type 2 diabetes and diabetic complications in Chinese population.

PURPOSE: The aim of this study was to investigate copeptin levels in serum, and assess their associations with type 2 diabetes (T2DM) and diabetic complications. METHODS: In this post hoc analysis, serum levels of copeptin were tested in 306 patients with T2DM. Clinical information including diabetic retinopathy (DR) and diabetic nephropathy (DN) were collected. The relation of serum copeptin with DR and DN were investigated with the use of logistic regression models according to equal quartiles of the distributions of serum copeptin. RESULTS: We found that serum copeptin levels were significantly higher in diabetes as compared to normal controls [9.4(IQR, 7.4-12.5) pmol/L vs. 4.1(IQR, 2.5-6.2) pmol/L; P<0.0001]. In multivariate analysis, there was an increased risk of T2DM associated with copeptin levels (OR 1.312, 95% CI: 1.204-1.403; P<0.0001) after adjusting for possible confounders. After adjustment for possible confounders, serum copeptin levels were positively associated with the DR (odds ratio [OR], 1.117; 95% confidence interval [CI], 1.072-1.241; P<0.001) and DN (OR, 1.259; 95% CI, 1.198-1.323; P<0.001). Compared with the first quartile of serum copeptin levels, the ORs for DR and DN were as follows: second quartile, 1.19 (95% CI, 0.94-1.51, P=0.12) and 1.37 (95% CI, 0.78-2.37, P=0.28); third quartile, 1.61 (95% CI, 1.18-2.43, P=0.005) and 2.12 (95% CI, 1.32-3.27, P=0.003); fourth quartile, 2.83 (95% CI, 2.04-4.93; P<0.001) and 3.48 (95% CI, 1.77-7.03; P<0.001), respectively. CONCLUSIONS: Using a post-hoc analysis our data show that elevated serum levels of copeptin are associated with type 2 diabetes and diabetic complications in Chinese population, suggesting a potential role of the AVP system (copeptin) in the pathophysiology of diabetes.

Acute renal failure in hospitalized patients in China: a prospective study.

Acute renal failure (ARF) is a common complication in hospitalized patients, but little is known about the epidemiology of ARF in China. In this study, we performed a prospective examination of the cause, prognosis, and risk factors associated with ARF at a hospital in Shanghai, China. We considered all ARF patients who were admitted to our hospital from December 2003 to December 2006. Among the 320 ARF patients, 135 (42.2%) were over the age of 60. Sepsis, heart failure, and nephrotoxic drug use were the leading causes of ARF. The overall mortality rate was 31.9%, and mortality rate was significantly higher among the elderly. Logistic regression indicated that heart failure, respiratory failure, and malignant cancer were risk factors independently associated with poor prognosis. In this Shanghai hospital, there was a high incidence and mortality rate of patients hospitalized with ARF. The prognosis of patients who underwent renal replacement therapy was better than those who were treated more conservatively.