Jiaqi Qian

Frequencies of hepatitis B and C infections among haemodialysis and peritoneal dialysis patients in Asia-Pacific countries: analysis of registry data

BACKGROUND The impact of dialysis modality on the rates and types of infectious complications has not been well studied. The aim of the present investigation was to evaluate the rates of hepatitis C virus (HCV) and hepatitis B virus (HBV) infections in peritoneal dialysis (PD) and haemodialysis (HD) patients in the Asia-Pacific region. METHODS The study included the most recent period-prevalent data recorded in the national or regional dialysis registries of the 10 Asia-Pacific countries/areas (Australia, New Zealand, Japan, China, Taiwan, Korea, Thailand, Hong Kong, Malaysia and India), where such data were available. Longitudinal data were also available for all incident Australian and New Zealand patients commencing dialysis between 1 April 1995 and 31 December 2005. Rates of HCV and HBV infections were compared by chi-square, Poisson regression and Kaplan-Meier survival analyses, as appropriate. RESULTS Data were obtained on 201,590 patients (HD 173,788; PD 27,802). HCV seroprevalences ranged between 0.7% and 18.1% across different countries and were generally higher in HD versus PD populations (7.9% +/- 5.5% versus 3.0% +/- 2.0%, P = 0.01). Seroconversion rates on dialysis were also significantly higher in HD patients (incidence rate ratio PD versus HD 0.33, 95% CI 0.13-0.75). HCV infection was highly predictive of mortality in Japan (relative risk 1.37, 95% CI 1.15-1.62, P = 0.003) and in Australia and New Zealand (adjusted hazards ratio 1.29, 95% CI 1.05-1.58). HBV infection data were limited, but less clearly influenced by dialysis modality. CONCLUSIONS Dialysis modality selection significantly influences the risk of HCV infection experienced by end-stage renal failure patients in the Asia-Pacific region. No such association could be identified for HBV infection.

Clinical usefulness of novel biomarkers for the detection of acute kidney injury following elective cardiac surgery.

Background/Aims: Acute kidney injury (AKI) is common following cardiac surgery and predicts a poor outcome. However, the early detection of AKI has proved elusive and most cases are diagnosed only following a significant rise in serum creatinine (SCr). We compared a panel of early biomarkers of AKI for the detection of AKI in patients undergoing heart surgery. This study included serum cystatin C (CyC) and urinary levels of neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), retinol-binding protein (RBP) and N-acetyl-β-D-glucosaminidase (NAG). Methods: We retrospectively identified 15 patients undergoing open cardiac surgery who developed AKI within 72 h postoperatively. For these, we identified 15 matched controls also having undergone surgery but without AKI. Serial serum and urine samples had prospectively been postoperatively obtained from all patients at 0, 2, 4, 6, 10, 24, 48 and 72 h after admission to the intensive care unit. AKI was defined as a >50% increase in SCr. CyC was measured by nephelometry, while NGAL, IL-18, and RBP were measured by ELISA and NAG was measured by spectrophotometry. The urinary biomarkers were normalized to urinary creatinine (UCr) concentration. Each marker was assessed at each time point for its predictive value using receiver operating characteristic curves to predict AKI. Results: Following the exclusion of 1 case due to a urinary tract infection, the final cohort consisted of 29 patients aged 62.9 ± 13.7 years with baseline SCr of 73.2 ± 11.9 µmol/l. While there were no differences in the demographics between cases and controls, the aortic clamp time was predictably higher in AKI cases than in controls (60.6 ± 13.9 vs. 43.0 ± 9.2 min, p < 0.05). Each biomarker differed significantly between cases and controls for at least one time point. The optimal area under the curve (AUC) was for CyC at 10 h (sensitivity 0.71, specificity 0.92, cutoff 1.31 mg/l), NGAL at 0 h (sensitivity 0.84, specificity 0.80, cutoff 49.15 µg/g UCr), IL-18 at 2 h (sensitivity 0.85, specificity 0.73, cutoff 285.65 ng/g UCr), RBP at 0 h (sensitivity 0.75, specificity 0.67, cutoff 2,934.65 µg/g UCr) and NAG at 4 h (sensitivity 0.86, specificity 0.67, cutoff 37.05 U/mg UCr). Using a combination of all 5 biomarkers analyzed at the optimal time point as above, we were able to obtain an AUC of 0.98 (0.93–1.02, p < 0.001) in this limited sample. Conclusion: The use of serum and urinary biomarkers for the prediction of AKI in patients undergoing cardiac surgery is highly dependent on the sampling time. Of the evaluated markers urinary NGAL had the best predictive profile. The previously unstudied marker of urinary RBP showed similar predictive power as more established markers. By combining all 5 studied biomarkers we were able to predict significantly more cases, suggesting that the use of more than one marker may be beneficial clinically.

Strong Impact of Acute Kidney Injury on Survival After Liver Transplantation

Acute kidney injury (AKI) is a major complication in orthotopic liver transplantation (OLT). In an evaluation of Acute Kidney Injury Network (AKIN) criteria in liver transplanted patients, we retrospectively analyzed the usefulness of these criteria to predict survival of 193 consecutive patients at a single center who underwent primary OLT for clinical parameters and peak AKI. Postoperative AKI according to AKIN occurred in 60.1% of the patients, namely, stages 1, 2, and 3 in 30%, 13% and 17.1% respectively. Using multivariate logistic regression, AKIN stage 1 and 2 AKI were independently associated with the pre-OLT Model for End-Stage Liver Disease (MELD) score and age, while stage 3 AKI was independently associated with MELD and Acute Physiology and Chronic Health Evaluation (APACHE) II scores. The 28-day and 1-year mortality post-OLT of AKI patients were 15.5% and 25.9% respectively compared with 0% and 3.9% among non-AKI patients (P < .05 for both). The survival rates of non-AKI and stages 1, 2, and 3 AKI subjects were 96%, 85.5%, 84%, and 45.3%, respectively. Cox regression analysis showed independent risk factors for mortality during the first year after transplantation to include post-OLT AKI (12.1; P < .05), post-OLT infection (HR 4.7; P < .01), pre-OLT hypertension (HR 4.4; P < .01) hazard ratio [HR] and post-OLT APACHE II ≥10 (HR 3.6; P < .05). We concluded that AKI as defined by the AKIN criteria is a major complication of OLT linked to a poor outcomes. It remains to be evaluated whether aggressive perioperative therapy to prevent AKI can improve survival among OLT patients.

Randomized Controlled Trial of Icodextrin versus Glucose Containing Peritoneal Dialysis Fluid

BACKGROUND AND OBJECTIVES While peritoneal dialysis with icodextrin is commonly used in patients with poor peritoneal membrane characteristics, the data on the usefulness of this solution in patients with lower transport characteristics are limited. The study was designed to compare icodextrin to glucose in Chinese prevalent peritoneal dialysis patients of different peritoneal transport characteristics (PET) categories. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This was a randomized, double-blind, perspective control study. Stable prevalent continuous ambulatory peritoneal dialysis (CAPD) patients were randomized to either 7.5% icodextrin (ICO) or 2.5% glucose (GLU) solution for 4 wk. Peritoneal membrane function was measured to define PET category in baseline. Creatinine clearance (Ccr), urea nitrogen clearance (C(BUN)), ultrafiltration (UF) during the long night dwell, dialysate, and metabolic biomarkers were measured at baseline, 2, and 4 wk. UF, Ccr, and C(BUN) were compared among different PET categories. RESULTS A total of 201 CAPD patients were enrolled in the study. There were no baseline differences between the groups. Following 2 and 4 wk of therapy, Ccr, C(BUN,) and UF were all significantly higher in the ICO versus the GLU group. Additionally, switching to ICO resulted in a significant increase in UF in high, high-average, and low-average transporters as compared with baseline. The extent of increased UF was more obvious in higher transporters. Blood cholesterol level in the ICO group decreased significantly than that in the GLU group. CONCLUSION Compared with glucose-based solution, 7.5% icodextrin significantly improved UF and small solute clearance, even in patients with low-average peritoneal transport.

Clinical Outcome of Twice-Weekly Hemodialysis Patients in Shanghai

Background: Twice-weekly hemodialysis (HD) is prevalent in the developing countries and the clinical outcome of this population remains to be elucidated. Methods: Data were collected from Shanghai Renal Registry. 2,572 patients undergoing regular HD in Shanghai on January 2007 were enrolled into the cohort study with 2 years’ follow-up. Clinical and HD parameters obtained from the network were utilized to compare twice-weekly with thrice-weekly HD. Results: Compared with patients on thrice-weekly HD, the twice-weekly HD patients were significantly younger and had significantly longer HD session time, higher single-pool Kt/V (spKt/V) but shorter HD vintage (p < 0.001). Kaplan-Meier survival analysis indicated that the two groups had similar survival. Multivariate Cox regression analysis showed that age, body mass index, serum albumin and weekly Kt/V were predictors of patient mortality. Conclusions: The similar survival between twice-weekly HD and thrice-weekly HD is likely relating to patient selection; dialysis adequacy of twice-weekly HD remains to be elucidated.

Urinary L-FABP and its combination with urinary NGAL in early diagnosis of acute kidney injury after cardiac surgery in adult patients

Background/Aim: The early detection of acute kidney injury (AKI) may be become possible by several promising early biomarkers which may facilitate the early detection, differentiation and prognosis prediction of AKI. In this study, we investigated the value of urinary liver-type fatty acid-binding protein (L-FABP), neutrophil gelatinase-associated lipocalin (NGAL) and their combination in predicting the occurrence and the severity of AKI following cardiac surgery. Methods: We prospectively followed 109 patients undergoing open heart surgery and identified 26 that developed AKI, defined as an increase in serum creatinine of ≥0.3 mg/dl or ≥150% of baseline creatinine. Serum creatinine (SCr), urinary L-FABP, and NGAL corrected by urine creatinine were tested pre-operation, at 0 hour and 2 hours post-operation. Each marker was assessed at each time point between patients with and without AKI. Receiver operating characteristic (ROC) curves and area under curves (AUC) were used to evaluate the diagnostic accuracy of urinary L-FABP, NGAL and their combination for predicting AKI. Results: Patients were aged 63.0 ± 11.3 years, 66.1% were male and baseline SCr was 70.5 ± 19.1 umol/L. Of 109 patients, 26(23.9%) developed AKI (AKIN stage I, II and III were 46.2%, 34.6% and 19.2% separately). The levels of urinary L-FABP and NGAL were significantly higher in AKI patients than non-AKI patients at 0 hour and 2 hours postoperative. AUCs for L-FABP was 0.844 (sensitivity (ST) 0.846, specificity (SP) 0.819, cut-off (CO) 2226.50 μg/g Ucr) at 0 hours and 0.832 at 2 hours (ST 0.808, SP 0.747, CO 673.09 μg/g Ucr) while 0.866 for NGAL at 0 hours (ST 0.769, SP 0.819, CO 131.12 μg/g Ucr) and 0.871 at 2 hours (ST 0.808, SP 0.831, CO 33.73 μg/g Ucr) to predict AKI occurrence. Using a combination of L-FABP and NGAL analyzed at the same timepoint as above, we were able to obtain an AUC of 0.911–0.927, p < 0.001. Similar AUCs of 0.81–0.87 were found to predict AKI stage II–III. Conclusions: Urinary L-FABP and NGAL increased at an early stage after cardiac surgery. The combination of the two biomarkers enhanced the accuracy of the early detection of postoperative AKI after cardiac surgery before a rise in SCr.

Circulating levels of asymmetric dimethylarginine are an independent risk factor for left ventricular hypertrophy and predict cardiovascular events in pre-dialysis patients with chronic kidney disease.

BACKGROUND Several studies have related the circulating level of asymmetric dimethylarginine (ADMA) to cardiac remodeling and cardiovascular (CV) events in end-stage renal disease (ESRD) patients. Studies investigating this relationship in patients with pre-dialysis chronic kidney disease (CKD) are lacking. METHODS We enrolled 76 CKD patients (age, 46.7+/-14.3 years, 39 females) and 15 controls (age, 40.1+/-18.5 years, 6 females). Clinical parameters, blood biochemistry and echocardiographic findings were recorded, and plasma ADMA concentrations measured by high-performance liquid chromatography-mass spectrometry (HPLC-MS). Patients were prospectively followed up for a median of 15 (range, 6-24) months. RESULTS Plasma ADMA was significantly elevated in CKD patients compared with controls (41.56+/-12.76 microg/mL vs 17.12+/-7.09 microg/mL, P<0.001), and correlated with the left ventricular mass index (LVMI) (r=0.597, P<0.001). During follow-up, 25 patients experienced new CV events and their plasma ADMA level was significantly elevated (48.27+/-13.70 vs 34.91+/-6.38 in CV event-free patients, P<0.001). Cox regression analysis further confirmed that ADMA was an independent risk factor for CVD (HR=1.175, 95%CI[1.070-1.290], P=0.001). CONCLUSION Similar to findings in ESRD patients, elevated circulating levels of ADMA may increase the risk of LVH and CV events in pre-dialysis CKD patients.

Better preservation of residual renal function in peritoneal dialysis patients treated with a low-protein diet supplemented with keto acids: a prospective, randomized trial

BACKGROUND While a low-protein diet may preserve residual renal function (RRF) in chronic kidney disease (CKD) patients before the start of dialysis, a high-protein intake is usually recommended in dialysis patients to prevent protein-energy wasting. Keto acids, which were often recommended to pre-dialysis CKD patients treated with a low-protein diet, had also been reported to be associated with both RRF and nutrition maintenance. We conducted a randomized trial to test whether a low-protein diet with or without keto acids would be safe and associated with a preserved RRF during peritoneal dialysis (PD). METHODS To assess the safety of low protein, we first conducted a nitrogen balance study in 34 incident PD patients randomized to receive in-centre diets containing 1.2, 0.9 or 0.6 g of protein/kg ideal body weight (IBW)/day for 10 days. Second, 60 stable PD patients [RRF 4.04 +/- 2.30 ml/ min/1.73 m(2), urine output 1226 +/- 449 ml/day, aged 53.6 +/- 12.8 years, PD duration 8.8 (1.5-17.8) months] were randomized to receive either a low- (LP: 0.6-0.8 g/kg IBW/day), keto acid-supplemented low- (sLP: 0.6-0.8 g/kg IBW/day with 0.12 g/kg IBW/day of keto acids) or high-protein (HP: 1.0-1.2 g/kg IBW/day) diet. The groups were followed for 1 year and RRF as well as nutritional status was evaluated serially. RESULTS A neutral or positive nitrogen balance was achieved in all three groups. RRF remained stable in group sLP (3.84 +/- 2.17 to 3.39 +/- 3.23 ml/min/1.73 m(2), P = ns) while it decreased in group LP (4.02 +/- 2.49 to 2.29 +/- 1.72 ml/min/1.73 m(2), P < 0.05) and HP (4.25 +/- 2.34 to 2.55 +/- 2.29 ml/min/1.73 m(2), P < 0.05). There was no change from baseline on nutritional status in any of the groups during follow-up. CONCLUSIONS A diet containing 0.6-0.8 g of protein/kg IBW/day is safe and, when combined with keto acids, is associated with an improved preservation of RRF in relatively new PD patients without significant malnutrition or inflammation.

Comparison of peritoneal dialysis practice patterns and outcomes between a Canadian and a Chinese centre

UNLABELLED Objective. We compared patient characteristics, dialysis practice patterns and outcomes of peritoneal dialysis (PD) patients between one Chinese centre and one Canadian centre to determine whether observed differences in demographics and practices are associated with patient and technique survival. METHODS This study included all patients who started on PD between 1 January 2000 and 31 December 2004 at the University Health Network, University of Toronto, Canada and Renji Hospital, Shanghai Jiao Tong University School of Medicine, China. They were followed up from the date of PD initiation until death, cessation of PD, transfer to other centres or to the end of the study (31 December 2006). RESULTS We studied 496 patients, 256 from the Canadian centre and 240 from the Chinese centre. Canadian patients were older and more likely to have diabetes and cardiovascular comorbidities at the initiation of PD, while the Chinese patients had lower residual renal function (RRF). More Canadian patients were treated with APD, whereas all Chinese patients were on CAPD with a lower PD volume. Crude patient survival rates at 1, 2, 3 and 5 years were similar between the two centres: 90%, 79%, 72% and 61% for Canadian and 90%, 79%, 71% and 64% for Chinese patients, respectively. After adjustment for demographic and clinical variables, there is no significant difference in mortality between Chinese patients and Canadian patients. Age, cardiovascular disease, diabetes, RRF and serum albumin were independent predictors of patient survival. The death-censored technique survival rates were significantly lower among the Canadian patients compared to Chinese patients. Chinese patients showed a lower risk of technique failure (HR 0.491, 95% CI 0.269-0.898, P = 0.021) after adjustment for patient characteristics. Chinese centre, BMI, serum albumin and gender were independent predictors of technique survival. The average peritonitis rate was one episode every 36.1 patient-months in Canadian patients and one episode every 60.6 patient-months in their Chinese counterparts. CONCLUSION Patient characteristics, dialysis practice patterns and outcomes vary between Canadian and Chinese patients. The variability in patient outcomes between these two centres indicates that further improvements may be possible in both centres. We have identified several areas for improving outcomes.

Autophagy Protects Renal Tubular Cells Against Ischemia / Reperfusion Injury in a Time-Dependent Manner

Background/Aims: Autophagy is a dynamic catabolic process that maintains cellular homeostasis. Whether it plays a role in promoting cell survival or cell death in the process of renal ischemia/reperfusion (I/R) remains controversial, partly because renal autophagy is usually examined at a certain time point. Therefore, monitoring of the whole time course of autophagy and apoptosis may help better understand the role of autophagy in renal I/R. Methods: Autophagy and apoptosis were detected after mice were subjected to bilateral renal ischemia followed by 0-h to 7-day reperfusion, exposure of TCMK-1 cells to 24-h hypoxia, and 2 to 24-h reoxygenation. The effect of autophagy on apoptosis was assessed in the presence of autophagy inhibitor 3-methyladenine (3-MA) and autophagy activator rapamycin. Results: Earlier than apoptosis, autophagy increased from 2-h reperfusion, reached the maximum at day 2, and then began declining from day 3 when renal damage had nearly recovered to normal. Exposure to 24-h hypoxia induced autophagy markedly, but it decreased drastically after 4 and 8-h reoxygenation, which was accompanied with increased cell apoptosis. Inhibition of autophagy with 3-MA increased the apoptosis of renal tubular cells during I/R in vivo and hypoxia/reoxygenation (H/R) in vitro. In contrast, activation of autophagy by rapamycin significantly alleviated renal tissue damage and tubular cell apoptosis in the two models. Conclusion: Autophagy was induced in a time-dependent manner and occurred earlier than the onset of cell apoptosis as an early response that played a renoprotective role during renal I/R and cell H/R. Up-regulation of autophagy may prove to be a potential strategy for the treatment of acute kidney injury.