Yihong Zhong

Acute Kidney Injury in a Chinese Hospitalized Population

Objectives: This study’s objective was to determine the incidence and mortality rate of acute kidney injury (AKI) among hospitalized adult patients in a tertiary metropolitan hospital of China, and to evaluate the impact of AKI on in-hospital mortality, cost and length of stay (LOS). Methods: Patients who were admitted to Zhongshan Hospital, Fudan University, Shanghai, China between September 1st, 2004 and June 30th, 2008 were involved. The presence and severity of AKI were assessed using absolute and relative increases from baseline to peak serum creatinine concentration during hospitalization. AKI was defined as a relative 50% increase or an absolute increment of 0.3 mg/dl (26.5 µmol/l) in serum creatinine within 48 h. After screening the computer-based data on kidney function, patients with AKI were identified and further history reviews were performed to obtain information regarding patients’ demography, prognosis, severity of kidney injury and causes of AKI. Results: There were 176,155 admissions during the study period and 5,619 met the diagnostic criteria of AKI. The overall incidence rate of AKI was 3.19%. Cardiovascular diseases followed by urogenital diseases and malignancy were the most common admission diagnoses. In-hospital mortality rate was 2.84% in all discharges and 19.68% in patients with AKI. Of AKI patients, old age, intensive care unit admission, Acute Kidney Injury Network score, need for renal replacement therapy and organ system failure number were independent predictors of hospital mortality according to forward conditional logistic regression. Conclusions: AKI is prevalent in the Chinese hospitalized patients. Slight elevations of serum creatinine are associated with significantly increased mortality, LOS and hospital cost. Moreover, outcomes are related directly to the severity of AKI characterized by percent changes in serum creatinine.

Transient hypoxia-inducible factor activation in rat renal ablation and reduced fibrosis with L-mimosine

Aim:  Hypoxia‐inducible factor (HIF) activity during the course of chronic kidney disease (CKD) development is poorly defined, and the effect of HIF activation on CKD is still controversial. The purpose of the present study was to characterize HIF expression during the course of CKD development, and to investigate the effect of HIF activation on CKD by using prolyl hydroxylase (PHD) inhibitor L‐mimosine.

Association of Indoxyl Sulfate with Heart Failure among Patients on Hemodialysis

BACKGROUND AND OBJECTIVES Indoxyl sulfate, a protein-bound uremic toxin, may be associated with cardiovascular events and mortality in patients with CKD. This study aimed to investigate the relationship between indoxyl sulfate and heart failure in patients on hemodialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Patients on hemodialysis for >6 months were enrolled within 6 months. Patients with congestive heart failure, angina pectoris, acute myocardial infarction, cerebral infarction, or cerebral hemorrhage within 3 months before the study or those <18 years old were excluded. The primary end point was first heart failure event during follow-up. RESULTS In total, 258 patients (145 men) with a mean age of 57.0 ± 14.6 years old were enrolled. Median plasma indoxyl sulfate level was used to categorize patients into two groups: the low-indoxyl sulfate group (indoxyl sulfate ≤ 2.35 μg/ml) and the high-indoxyl sulfate group (indoxyl sulfate >32.35 μg/ml). Then, patients were prospectively followed up for a median of 48.0 (interquartile range: 33.5-48.0) months. During follow-up, 68 patients experienced episodes of first heart failure. Kaplan-Meier analysis revealed the incidence of first heart failure event in the high-indoxyl sulfate group was significantly higher than in the low-indoxyl sulfate group (log rank P<0.001). Cox regression analysis showed indoxyl sulfate was significantly associated with first heart failure event (indoxyl sulfate as the continuous variable: hazard ratio, 1.02; 95% confidence interval [95% CI], 1.01 to 1.03; P=0.001; indoxyl sulfate as the dichotomous variable: hazard ratio, 3.49; 95% CI, 1.97 to 6.20; P<0.001). After adjustment for other confounding factors, the results remained significant (indoxyl sulfate as the continuous variable: hazard ratio, 1.04; 95% CI, 1.02 to 1.06; P<0.001; indoxyl sulfate as the dichotomous variable: hazard ratio, 5.31; 95% CI, 2.43 to 11.58; P<0.001). CONCLUSIONS Plasma indoxyl sulfate was associated with first heart failure event in patients on hemodialysis. Whether indoxyl sulfate is only a biomarker or involved in the pathogenesis of heart failure in hemodialysis warrants additional study.

Effectiveness and Safety of Patient-Initiated Single-Dose versus Continuous Low-Dose Antibiotic Prophylaxis for Recurrent Urinary Tract Infections in Postmenopausal Women: A Randomized Controlled Study:

This study evaluated patient-initiated single-dose antibiotic prophylaxis and continuous long-term low-dose daily antibiotic use for the prevention of recurrent urinary tract infections (UTI) in 68 postmenopausal women. The women were randomized to take a low-dose antibiotic each night (continuous group, n = 37) or a single-dose antibiotic each time they experienced conditions predisposing to UTI (intermittent group, n = 31). During the 12-month study, 1.4 and 1.9 UTIs/patient developed in the continuous and the intermittent groups, respectively, which was significantly lower than the incidence of UTIs in the previous 12 months in these patients (4.7 and 5.1 UTIs/patient, respectively). The incidence of gastrointestinal adverse events was significantly lower in the intermittent group compared with the continuous group (9.1% versus 30.0%). In conclusion, patient-initiated single-dose intermittent antibiotic prophylaxis was as effective as low-dose daily antibiotic prophylaxis in the treatment of recurrent UTIs in postmenopausal women and was associated with fewer gastrointestinal adverse events.

Serum Uric Acid Is Inversely Related to Acute Ischemic Stroke Morbidity in Hemodialysis Patients

Aim: Elevated serum uric acid (sUA) is usually associated with a high occurrence of acute ischemic stroke (AIS) in the general population. The aim of this study is to evaluate the role of sUA in AIS among hemodialysis (HD) patients. Methods: We followed up the occurrence of AIS in 226 HD patients for 18 months from January 2009 to June 2010. The parameters included demographic characteristics, duration of HD, sUA, serum albumin, and other parameters. Logistic regression was performed to evaluate the function of SUC levels in the occurrence of AIS. Results: A total of 43 patients suffered from AIS. By univariate logistic regression analysis an inverse association was observed in sUA level with the risk of AIS (p = 0.005), but the significance of this inverse association was attenuated while adjusted for age, gender and pulse pressure (PP) (p = 0.029), and even weakened while adjusted for age, gender, PP and diabetes nephropathy (DN) (p = 0.065), and finally abolished after adjustment for age, gender, PP, DN, hsCRP and pre-albumin. Conclusion: This study indicates an inverse association between sUC and the occurrence of AIS in HD patients. Demographic characteristics and malnutrition-microinflammation syndrome seem to play a significant role in this association.

Prolyl hydroxylase 2 (PHD2) inhibition protects human renal epithelial cells and mice kidney from hypoxia injury

Prolyl hydroxylase domain protein 2 (PHD2) is a key oxygen sensor, setting low steady-state level of hypoxia-inducible factor-α (HIF-α). Here, we showed that treatment of cobalt chloride (CoCl2), a hypoxia mimic, in HK-2 tubular epithelial cells induced PHD2 and HIF-1/2α expression as well as cell apoptosis and autophagy activation. Three methyladenine (3-MA), the autophagy inhibitor, blocked autophagy and protected HK-2 cells from CoCl2. Significantly, siRNA knockdown of PHD2 also protected HK-2 cells from CoCl2, possibly via increasing HIF-1α expression. Reversely, HIF-1α siRNA knockdown almost abolished cytoprotection by PHD2 siRNA in CoCl2-treated HK-2 cells. In vivo, pretreatment with a PHD inhibitor L-mimosine remarkably attenuated mice renal ischemia-reperfusion injuries. Molecularly, L-mimosine inhibited apoptosis and inflammatory responses in injured mice kidneys. Together, our results suggest that PHD2 silence or inhibition protects human renal epithelial cells and mice kidney from hypoxia injuries.

BMI, spKt/V, and SBP but Not DBP Are Related to LVH in Chinese Maintenance Hemodialysis Patients

Objective: Left ventricular hypertrophy (LVH) is the strongest predictor of cardiovascular mortality, the leading cause of death in hemodialysis (HD) patients. This study aims to identify the potential risk factors for LVH in HD patients. Methods: Exactly, 164 patients (84 men and 80 women) who had been on HD treatment for at least 6 months were enrolled. Clinical data were collected. Anthropometric measurements, biochemical analyses, and echocardiography were performed. The risk factors were determined by multivariate linear and logistic regression. Results: In all the patients, the prevalence of LVH was 66.5%. The patients with LVH had higher body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure, and lower single-pool kt/V (spKt/V) compared with those without LVH. Multivariate linear regression showed that BMI (β = 7.608, p = 0.014), SBP (β = 9.462, p = 0.001), and spKt/V (β = –14.226, p = 0.024) were independently correlated with left ventricular mass index (LVMI). Multivariate logistic regression showed the same results that BMI (β = 7.193, p = 0.032), SBP (β = 9.382, p = 0.02), and spKt/V (β = –12.535, p = 0.001) were independently correlated with LVH. Conclusions: In Chinese maintenance hemodialysis patients, BMI, single-pool Kt/V (spKt/V), and SBP were independently correlated with left ventricular mass index and were independent risk factors for LVH.

Clinical Factors Associated with Sodium Removal in Peritoneal Dialysis Patients

A cross-sectional study was conducted in 156 clinically-stable peritoneal dialysis patients to identify the factors associated with sodium removal. Serum biochemistry, peritoneal function (modified peritoneal equilibration test [PET]) and the adequacy of dialysis were analysed in relation to sodium removal using multivariate linear regression. Factors significantly affecting peritoneal sodium removal included infusion volume and ultrafiltration volume per 24 h, sodium dip in the first hour of PET and sodium difference between serum and fresh dialysate. Factors significantly affecting total sodium removal included ultrafiltration and urine volume per 24 h, sodium dip in the first hour of PET and sodium difference between serum and fresh dialysate. With traditional dialysate, adequate fluid removal is required to ensure sufficient sodium removal, but a low-sodium dialysate may prevent sodium retention. Sodium removal should be included in evaluation of the adequacy of dialysis.

Silencing HIF-1α aggravates growth inhibition and necrosis of proximal renal tubular epithelial cell under hypoxia

Abstract The kidney is particularly susceptible to ischemia/hypoxia insult while dysfunction of proximal tubular epithelial cells (PTEC) is a primary pathologic hallmark in acute kidney injury. Hypoxia-inducible factor-1 (HIF-1) is a key regulator responsible for cellular hypoxic responses. Therefore, we investigated the effects of HIF-1 suppression, using small interference RNA (siRNA), upon the cell fate of PTEC under hypoxia, and explored the underlying possible molecular mechanism. Hypoxia was induced with hypoxia mimetic cobalt chloride. Our data showed that, in HIF-1α siRNA group, the HK-2 cells growth inhibition and necrosis became worse than those in hypoxia group. However, for apoptosis, no significant difference was observed between them. Consistent with the downregulation of HIF-1α in HIF-1α siRNA group, both mRNA and protein expression of glucose transporter-1 (Glut-1) and vascular endothelial growth factor (VEGF) also reduced more significantly than those in hypoxia group. In conclusion, silencing HIF-1α gene could aggravate growth inhibition and necrosis of PTEC under hypoxia. We provide evidence, from the opposite direction, that HIF-1 activation under hypoxia may facilitate adaptation and survival of proximal renal tubular cells, and the beneficial effects may be related to its downstream genes, such as Glut-1 and VEGF.