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.

Development and validation of the prediction model for mortality in patients with diabetic kidney disease in intensive care unit: a study based on medical information Mart for intensive care.

We aimed to explore factors associated with mortality of diabetic kidney disease (DKD), and to establish a prediction model for predicting the mortality of DKD. This was a cohort study. In total, 1,357 DKD patients were identified from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database, with 505 DKD patients being identified from the MIMIC-III as the testing set. The outcome of the study was 1-year mortality. COX proportional hazard models were applied to screen the predictive factors. The prediction model was conducted based on the predictive factors. A receiver operating characteristic (ROC) curve with the area under the curve (AUC) was calculated to evaluate the performance of the prediction model. The median follow-up time was 365.00 (54.50,365.00) days, and 586 patients (43.18%) died within 1 year. The predictive factors for 1-year mortality in DKD included age, weight, sepsis, heart rate, temperature, Charlson Comorbidity Index (CCI), Simplified Acute Physiology Score (SAPS) II, and Sequential Organ Failure Assessment (SOFA), lymphocytes, red cell distribution width (RDW), serum albumin, and metformin. The AUC of the prediction model for predicting 1-year mortality in the training set was 0.771 [95% confidence interval (CI): 0.746-0.795] and the AUC of the prediction model in the testing set was 0.795 (95% CI: 0.756-0.834). This study establishes a prediction model for predicting mortality of DKD, providing a basis for clinical intervention and decision-making in time.

B-type natriuretic peptide levels and volume status in twice-weekly hemodialysis patients.

BACKGROUND: Twice-weekly hemodialysis (HD) could be regarded as an important part of incremental hemodialysis, volume status of this treatment model remains to be elucidated. METHODS: Patients undergoing regular twice-weekly or thrice-weekly hemodialysis in our unit on June 2015 were enrolled into the cohort study with an average of 2.02 years follow-up. Volume status of the subjects was evaluated by clinical characteristics, plasma B-type natriuretic peptide (BNP) levels and bioimpedance assessments with body composition monitor (BCM). Cox proportional hazards models and Kaplan-Meier analysis were used to compare patient survival between the two groups. RESULTS: Compared with patients on thrice-weekly HD, twice-weekly HD patients had significantly higher log-transformed BNP levels (2.54 ± 0.41 vs. 2.33 ± 0.49 pg/ml, p = 0.010). Overhydration (OH) and the ratio of overhydration to extracellular water (OH/ECW) in twice-weekly HD group were significantly higher than that of thrice-weekly HD (OH, 2.54 ± 1.42 vs. 1.88 ± 1.46, p = 0.033; OH/ECW, 0.17 ± 0.07 vs. 0.12 ± 0.08, p = 0.015). However, subgroup analysis of patients within 6 years HD vintage indicated that the two groups had similar hydration status. Multivariate Cox regression analysis showed that log-transformed BNP levels, serum albumin and diabetes status were predictors of mortality in hemodialysis patients. Kaplan-Meier survival analysis indicated that patients with BNP levels higher than 500 pg/ml had significantly worse survival compared with those with lower BNP levels (p = 0.014). CONCLUSIONS: Twice-weekly hemodialysis patients had worse volume status than that of thrice-weekly HD patients especially for those with long-term dialysis vintage, BNP level was a powerful predictor of mortality in HD patients.

A pilot study of thiamin and folic acid in hemodialysis patients with cognitive impairment.

OBJECTIVE: This study aimed to explore the effectiveness of thiamin and folic acid supplementation on the improvement of the cognitive function in patients with maintenance hemodialysis. METHOD: In the present study, we randomly assigned patients undergoing hemodialysis who had the Montreal Cognitive Assessment (MoCA) score lower than 26 to treatment group (n = 25, thiamin 90 mg/day combined with folic acid 30 mg/day) or control group (n = 25, nonintervention). All subjects were followed up for 96 weeks. The primary outcome was the improvement of the MoCA score. The secondary outcomes included homocysteine level, survival and safety. RESULTS: Patients in treatment group had an increase of the MoCA score from 21.95 ± 3.81 at baseline to 25.68 ± 1.96 at week 96 (p < 0.001, primary outcome), as compared with the MoCA score from 20.69 ± 3.40 to 19.62 ± 3.58 in control group. Thiamin combined with folic acid treatment also resulted in lower level of serum homocysteine in treatment group compare with control group at week 96 (p < 0.05, secondary outcome). 3 patients and 9 patients died during follow-up period in treatment and control group respectively (p = 0.048). The proportion of adverse events in treatment group was significantly lower than that in control group. CONCLUSION: Hemodialysis patients with cognitive impairment treated with thiamin and folic acid had a significant improvement in MoCA score.

Association of abdominal aortic calcification estimated by plain radiography with outcomes in haemodialysis patients: A 6-year follow-up study.

AIM: Vascular calcification has played a vital role in increasing the prevalence of cardiovascular disease (CVD) and mortality in maintenance haemodialysis (MHD) patients. This study is aimed at exploring the prognostic value of abdominal aortic calcification (AAC) estimated by plain lateral abdominal radiography in MHD patients. METHODS: Lateral abdominal radiography was used to determine the abdominal aortic calcification score (AACS). The serum level of fibroblast growth factor-23 was tested by enzyme-linked immunosorbent assay. Patients were divided into two groups: no or minor calcification group (AACS < 5) and moderate to severe calcification group (AACS ≥ 5). All patients were followed up to death or the end of the study (30 November 2016). RESULTS: A total of 114 patients were enrolled in this study, including 64 males (56.1%), and the mean age was 57.42 ± 13.48 years. Seventy-six patients (66.7%) exhibited AAC. Independent predictors for moderate to severe calcification were older age (odds ratio (OR) 1.06 (1.02-1.10), P = 0.003), longer dialysis vintage (OR 1.01 (1.00-1.02), P = 0.039), presence of smoking (OR 3.01 (1.18-7.70), P = 0.021) and higher Log fibroblast growth factor-23 serum levels (OR 2.83 (1.01-7.94), P = 0.048). During a median follow-up of 6.0 (5.6, 6.1) years, 22 patients (19.3%) died of all-cause death, and 17 cases (14.9%) died of CVD. Kaplan-Meier survival curves showed that patients in the moderate to severe calcification group had significantly higher all-cause (28.3 vs 11.5%, P = 0.028) and CVD mortality (22.6 vs 8.2%, P = 0.035) than that in the no or minor calcification group. A multivariate Cox regression showed that AACS (hazard ratio 1.08 (1.01-1.15), P = 0.022) was an independent predictor of CVD mortality. Compared with the no or minor calcification group, the risk of CVD mortality was increased by a factor of 3.14 in patients in the moderate to severe calcification group (hazard ratio 3.14 (1.04-9.44), P = 0.042). CONCLUSION: Our data suggest that AAC is prevalent in MHD patients and could provide potential predictive information for CVD mortality. Plain lateral abdominal radiography, which is simple and cheap and involves lower radiation, might represent an appropriate screening method for evaluating vascular calcification in daily clinical practice.

Early serum cystatin C-enhanced risk prediction for acute kidney injury post cardiac surgery: a prospective, observational, cohort study.

Background: Acute kidney injury (AKI) is a common post-cardiac surgery complication. It leads to increased morbidity and mortality. The aim of our study is to identify the prevalence and risk factors of AKI and to demonstrate if early postoperative serum cystatin C (sCyC) could accurately predict the development of AKI.Methods: We prospectively studied 628 patients undergoing elective cardiac surgery. Pre-morbid and operative variables known to be or potentially associated with AKI or other adverse outcomes were examined. AKI was defined according to Kidney Disease Improving Global Outcomes (KDIGO) creatinine criteria. Blood samples for biomarker measurement were collected at baseline, within 10 h of surgical completion and daily for three days. Logistic regression was used to assess predictive factors for AKI including 10 h sCyC. Model discrimination was assessed using receiver operator characteristic (ROC) curves.Results: AKI occurred in 178 (28.3%) patients, Stage 1 in 17.5%, Stage 2 in 8.6% and Stage 3 in 2.2%. Mortality rose progressively with increased AKI stage (non-AKI 0.2%, Stage 1 1.8%, Stage 2 11.1% and Stage 3 35.7%). Age > 75 years, baseline estimated glomerular filtration rate (eGFR), proteinuria, diabetes mellitus, hypertension, hyperuricaemia, NYHA classification >2, recent myocardial infarction were associated with AKI in univariate analysis. A multivariate logistic model with clinical factors (age, eGFR, hypertension, NYHA classification >2, combined surgery and operation time) demonstrated moderate discrimination for AKI (area under ROC curve [AUC] 0.75). The 10 h postoperative sCyC levels strongly associated with AKI. After multivariable adjustment, the highest quartile of sCyC was associated with 13.1 - higher odds of AKI, compared with the lowest quartile. Elevated 10 h sCyC levels associated with longer hospital stay, longer intensive care unit stay and duration of mechanical ventilation. The addition of 10 h sCyC improved model discrimination for AKI (AUC 0.81).Conclusions: AKI following cardiac surgery was identified using KDIGO criteria in around one fourth of the patients. These patients had significantly increased morbidity and mortality. When added to prediction model, 10 h sCyC may enhance the identification of patients at higher risk of AKI, providing a readily available prognostic marker.

Use of Both Serum Cystatin C and Creatinine as Diagnostic Criteria for Cardiac Surgery-Associated Acute Kidney Injury and Its Correlation with Long-Term Major Adverse Events.

BACKGROUND/AIMS: Cardiac surgery-associated acute kidney injury (CSA-AKI) was traditionally defined as an increase in serum creatinine (sCr) after cardiac surgery. Recently, serum cystatin C (sCyC) has been proposed to be a better biomarker in the prediction of AKI. The clinical utility and performance of combining sCyC and sCr in patients with AKI, particularly for the prediction of long-term outcomes, remain unknown. METHODS: We measured sCyC together with sCr in 628 patients undergoing cardiac surgery. sCyC and sCr were assessed at baseline and 24 and 48 h after surgery. CSA-AKI determined by sCr (CSA-AKIsCr) was defined as an sCr increase greater than 0.3 mg/dL or 50% from baseline. Major adverse events (MAEs; including death of any cause and dialysis) at 3 years were assessed. RESULTS: CSA-AKIsCr developed in 178 patients (28.3%). Three-year follow-up was available for 621 patients; MAEs occurred in 42 patients (6.8%). An increase in sCyC concentration ≥30% within 48 h after surgery was detected in 228 patients (36.3%). This was the best sCyC cutoff for CSA-AKIsCr detection (negative predictive value = 88.8%, positive predictive value = 58.3%). To evaluate the use of both sCyC and sCr as CSA-AKI diagnostic criteria, we stratified patients into 3 groups: non-CSA-AKI, CSA-AKI detected by a single marker, and CSA-AKI detected by both markers. By multivariable logistic regression analysis, the independent predictors of MAEs at 3 years were group 2 (non-CSA-AKI group as the reference, CSA-AKI detected by a single marker: odds ratio [OR] = 3.48, 95% confidence interval [CI]: 1.27-9.58, p = 0.016), group 3 (CSA-AKI detected by both markers: OR = 5.12, 95% CI: 2.01-13.09; p = 0.001), and baseline glomerular filtration rate (OR = 2.24; 95% CI: 1.27-3.95; p = 0.005). CONCLUSION: Combining sCyC and sCr to diagnose CSA-AKI would be beneficial for risk stratification and prognosis in patients after cardiac surgery.

A Clinical Score to Predict Severe Acute Kidney Injury in Chinese Patients after Cardiac Surgery.

BACKGROUND/AIMS: Cardiac surgery-associated severe acute kidney injury (SAKI) is associated with high mortality and poor quality of life. A prognostic score for SAKI may enable prevention of complications. METHODS: This observational study of 2,552 patients undergoing cardiac surgery from January 2006 to December 2011 in our institution established associations between predictor variables and postoperative SAKI from a cohort of 1,692 patients and developed a clinical score that was assessed in a validation cohort of 860 patients. RESULTS: Postoperative SAKI occurred in 262 -patients (10.3%). We identified 7 independent and significant risk factors in the derivation model (adjusted OR 95% CI): age ≥81 years (vs. age < 40 years, 4.30, 1.52-12.21), age 61-80 years (vs. age < 40 years, 2.84, 1.24-6.52), age 41-60 years (vs. age < 40 years, 1.62, 0.68-3.87), hypertension (1.65, 1.13-2.39), previous cardiac surgery (3.62, 1.27-10.32), -hyperuricemia (2.02, 1.40-2.92), prolonged operation time (1.32, 1.17-1.48), postoperative central venous pressure < 6 mm H2O (3.53, 2.38-5.23), and low postoperative cardiac output (4.78, 2.97-7.69). The 7-variable risk prediction model had acceptable performance characteristics in the validation cohort (C statistic 0.80, 95% CI 0.74-0.85). The difference in the C statistic was 0.21 (95% CI 0.12-0.29, p < 0.001) compared with the Cleveland Clinic score. CONCLUSION: We developed and validated a practical risk prediction model for SAKI after cardiac surgery based on routinely available perioperative clinical and laboratory data. The prediction model can be easily applied at the bedside and provides a simple and interpretable estimation of risk.

Clinical Outcome of Twice-Weekly Hemodialysis Patients with Long-Term Dialysis Vintage.

BACKGROUND/AIMS: Twice-weekly hemodialysis(HD) is prevalent in the developing countries, scarce data are available for this treatment in patients with long-term dialysis vintage. METHODS: 106 patients with more than 5 years HD vintage undergoing twice-weekly HD or thrice-weekly HD in a hemodialysis center in Shanghai between December 1, 2013 and December 31, 2013 were enrolled into the cohort study with 3 years follow-up. Kaplan-Meier analysis and Cox proportional hazards models were used to compare patient survival between the two groups. Subgroup analysis of 62 patients more than 10 years HD vintage was also performed according to their different dialysis frequency. RESULTS: Compared with patients on thrice-weekly HD, twice-weekly HD patients had significantly longer HD session time and higher single-pool Kt/V (spKt/V) (session time, 4.59±0.45 vs 4.14±0.31 hours/per session, P< 0.001; spKt/V, 2.12±0.31 vs 1.83±0.30, P< 0.001). Kaplan-Meier survival analysis indicated that the two groups had similar survival (P=0.983). Multivariate Cox regression analysis showed that age and time-dependent serum albumin were predictors of patient mortality. Subgroup analysis of 62 patients more than 10 years HD vintage also indicated that the two groups had similar survival. During the follow-up, 4 patients dropped out from the twice-weekly HD group and transferred to thrice-weekly HD. CONCLUSION: The similar survival between twice-weekly HD and thrice-weekly HD in patients with long-term dialysis vintage is likely relating to patient selection, individualized treatment for dialysis patients based on clinical features and socioeconomic factors remains a tough task for the clinicians.

Surgical intervention after catheter removal in a case of refractory peritoneal dialysis-related peritonitis.

Peritonitis is the most common infection in peritoneal dialysis (PD) and has been noted to be not only a cause of mortality but also the leading cause of technique failure in patients maintained on PD. Appropriate management of peritonitis to improve patient outcome has been the focus of clinical practice. We report a case of refractory PD-related peritonitis with surgical intervention intending to control ongoing peritoneal infection despite aggressive antibiotics and timely catheter removal. Exploratory laparotomy was performed in this case, and an encapsulated abscess in the peritoneal and pelvic cavity was obliterated. Adhesiolysis was done simultaneously. Continuous postoperative peritoneal lavage and drainage were implemented. Symptoms dramatically improved after operation, and indwelling tubes were removed several days later. Finally, the patient recovered and switched to permanent hemodialysis without intra-abdominal complications. Our case suggested that appropriate and timely surgical intervention in refractory peritonitis is necessary for saving lives in certain subgroups of patients. Clearly, well-designed studies with large samples are warranted to explore this issue in more detail.

Preoperative serum cystatin C combined with dipstick proteinuria predicts acute kidney injury after cardiac surgery.

BACKGROUND: Acute kidney injury (AKI) is common following cardiac surgery and is associated with poor outcomes. However, the detection of those preoperative patients who will develop AKI is still difficult. In this study, we compared serum cystatin C combined with dipstick proteinuria as early markers to predict AKI available before surgery. METHODS: We prospectively followed 616 patients undergoing cardiac surgery and identified 179 that developed AKI, defined as an increase in serum creatinine (SCr) of ≥ 0.3 mg/dL or ≥ 50% increase in creatinine level. Preoperative values for cystatin C were categorized into quartiles. We defined proteinuria, measured with a dipstick, as mild (trace to 1+) or heavy (2 + to 4+). Univariate as well as multivariate regression was performed. Cystatin C combined with dipstick proteinuria before surgery was assessed for its' predictive value of AKI using receiver operating characteristic (ROC) curves. RESULTS: The final cohort consisted of 616 patients aged 60.7 ± 13.2 years, and baseline SCr was 75.8 ± 26.4 µmol/L, estimated glomerular filtration rate (eGFR) 96.3 ± 29.0 mL/min/1.73 m(2) and cystatin C 1.05 ± 0.33 mg/L. Patients in higher cystatin C quartiles were older (p < 0.001), more often to have heavy proteinuria (p = 0.021), hyperuricemia (p < 0.001), heart failure (p < 0.001) and recent myocardial infarction (p = 0.002). Those with heavy proteinuria were more often to have diabetes mellitus (p = 0.010), hyperuricemia (p = 0.043), worse cardiac function (p < 0.05), higher creatinine levels (p < 0.001) and lower eGFR levels (p < 0.001). In a multiple logistic regression model, preoperative heavy proteinuria [OR: 3.14, 95% confidence interval (CI): 1.26-7.77] and preoperative cystatin C quartiles (Q2:OR: 1.60, 95% CI: 0.72-3.60; Q3:OR: 1.87, 95% CI: 0.85-4.14; Q4:OR: 3.10, 95% CI: 1.37-7.02) each associated with an increased odds of AKI, independent of advanced age (OR: 1.04, 95% CI: 1.01-1.06), hypertension (OR: 1.88, 95% CI: 1.13-3.12) and combined surgery (OR: 3.47, 95% CI: 1.35-8.89). The risk for adverse outcomes such as postoperative AKI, persistent AKI, severe AKI, dialysis and mortality were highest in patients with highest quartile of cystatin C (p < 0.05, respectively) and heavy proteinuria (p < 0.05, respectively). The area under the ROC curve for preoperative cystatin C combined with proteinuria to detect AKI, persistent AKI and severe AKI were 0.695 (p < 0.001; 95% CI = 0.637-0.754), 0.753 (p < 0.001; 95% CI = 0.693-0.812) and 0.718 (p < 0.001; 95% CI = 0.642-0.795), respectively. CONCLUSION: These data suggest that preoperative serum cystatin C combined with dipstick proteinuria may improve prediction of AKI among patients undergoing cardiac surgery.

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.

Urinary neutrophil gelatinase-associated lipocalin and L-type fatty acid binding protein as diagnostic markers of early acute kidney injury after liver transplantation.

OBJECTIVE: We examined the value of two potential novel urinary biomarkers, neutrophil gelatinase-associated lipocalin (NGAL) and L-type fatty acid binding protein (L-FABP), in diagnosing acute kidney injury (AKI) in liver transplant recipients. METHODS: NGAL and L-FABP in urinary sample from Twenty-five patients before surgery and at 2, 4, 6, 12, 24, 48, 72 and 120 h after the anhepatic phase were tested. Standard statistics were used along with receiver-operating characteristic (ROC) analysis to evaluate the diagnostic value of selected markers. RESULTS: Urinary NGAL was only slightly elevated at 2 h in the non-AKI group while rose and stayed high from 2-6 h in the AKI group. However, urinary L-FABP rose transiently in both groups 2-120 h following surgery. The level of urinary NGAL presented differences at 2-6 h (p < 0.05) and urinary L-FABP at 4 h (p < 0.05) between AKI and non-AKI groups. ROC analysis showed that area under the curves (AUCs) of NGAL were 0.766, 0.773, and 0.773 at 2, 4 and 6 h respectively while 0.760 of L-FABP at 4 h. CONCLUSION: Urinary NGAL rather than L-FABP appeared to be a sensitive and specific marker of AKI in liver transplant recipients.

Prevalence of acute kidney injury following cardiac surgery and related risk factors in Chinese patients.

BACKGROUND/AIMS: Acute kidney injury (AKI) following surgery is a major complication, but the prevalence and risk factors in the Asian population are unclear. Recently, a consensus definition of AKI (AKIN) was proposed. We studied a cohort of cardiac surgery patients and identified AKI by AKIN and associated risk factors. METHODS: We retrospectively evaluated 1,056 consecutive patients undergoing cardiac surgery in Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China from January 1, 2004 to June 30, 2007. We recorded AKIN stage, clinical characteristics, perioperative variables and complications, as well as clinical outcomes. Univariate and multivariate regression as well as survival analysis was performed. RESULTS: AKI occurred in 328 (31.1%) patients, stage 1 in 21.1%, stage 2 in 6.3% and stage 3 in 3.7%. Patients with AKI were older (65.8 vs. 53.5 years, p < 0.001), more often male (66.8 vs. 54.1%, p < 0.001), and had higher Charlson Comorbidity Index (CCI) (CCI >2: 22.6 vs. 7.8%, p < 0.001). In logistic regression, advanced age (OR 1.48 per decade, 95% CI 1.32-1.67), CCI >2 (OR 2.82, 95% CI 1.80-4.41), hypertension (OR 2.13, 95% CI 1.47-3.09), left ventricular ejection fraction (LVEF) <45% (OR 1.97, 95% CI 1.14-3.40), postoperative central venous pressure (CVP) <6 cm H(2)O (OR 13.28, 95% CI 8.72-20.14) and postoperative use of ACEI/ARB (OR 1.90, 95% CI 1.27-2.85) were risk factors of AKI. Mortality rose progressively with increased AKIN stage (non-AKI 0.7%, stage 1 4.9%, stage 2 12.1% and stage 3 48.7%). In ROC analysis, AKIN classification was identified to be associated with in-hospital mortality with an AUC of 0.865 (95% CI 0.801-0.929, sensitivity 0.884, specificity 0.714, p < 0.001). Finally, in a Cox proportional hazards model, AKIN stage (HR 2.40, p < 0.001), re-exploration (HR 6.30, p = 0.002) and multiple organ dysfunction syndrome (MODS) (HR 4.42, p = 0.001) were associated risk factors for in-hospital mortality. CONCLUSION: We evaluated AKIN as a marker of AKI and mortality risk in a large, unselected Chinese cohort of incident patients undergoing cardiac surgery. AKI following cardiac surgery was diagnosed by AKIN criteria in around one third of the patients, and AKI may be associated with outcome. The value of preventative strategies to reduce AKI and their effect on in-hospital mortality should be studied.

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-beta-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 micromol/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 microg/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 microg/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.

[Analysis of drug-induced acute renal failure in Shanghai].

OBJECTIVE: To investigate the incidence and prognosis of drug-induced acute renal failure (ARF) in Shanghai. METHODS: The registration forms of ARF patients admitted in 17 hospitals of and over the middle class in Shanghai from January 1, 2004 to December 31, 2006 were screened prospectively. The data, such as epidemiology, survival, mortality, and morbidity were analyzed. RESULTS: 347 of the 1200 ARF patients (28.9%), 224 males and 123 females, aged (58+/-20), suffered from drug-induced ARF. 51.0% of the 347 patients were older than 60. 60.2% of the drug-induced ARF in the non-surgical departments were community-acquired, while 55.7% of the drug-induced ARF in the surgical departments were hospital-acquired. Among the non-surgical departments, the incidence of hospital-acquired drug-induced ARF was the lowest in the department of nephrology (9.5%), while higher in the departments of hematology, cardiology, and neurology, and among the surgical departments, it was the lowest in department of renal surgery, while higher in the departments of liver transplantation, neurosurgery, and cardiovascular surgery. The most common complication was chronic kidney disease (CKD) (n=69, 19.9%), followed by cerebrovascular disease (n=59, 17.0%), diabetes mellitus (n=43, 12.4%), and hypertension (n=41, 11.8%). Renal biopsy showed acute tubular necrosis (18, 37.5%), acute interstitial nephritis (11, 22.9%), and acute infectious tubulo-interstitial nephritis (6, 12.5%). Antibiotics (47.8%) were the head causes of drug-induced ARF, especially aminoglycoside (17.0%) and cephalosporins (12.7%), followed by diuretics (22.2%) and radiocontrasts (13.3%). 22.5% of the drug-induced ARF patients had used two or more drugs. 119 patients (34.3%) needed renal replacement treatment. 100 of the 347 patients (28.8%) died. 188 of the surviving patients (54.2%) had their renal function recovered completely, the renal function of 42 of them (12.1%) was recovered partially, and 17 of then (4.9%) required dialysis when discharged. CONCLUSION: Drug-induced ARF is common with higher incidence in the patients with complications. Antibiotics, diuretic agents, and contrast medium are the main causes.

[Analysis of independent risk factor in patients with poor prognosis after liver transplantation].

OBJECTIVE: To investigate the prognosis after orthotopic liver transplantation (OLT), and to elucidate the risk factors of poor prognosis in these patients. METHODS: Adult recipients of OLT in Renji Hospital of Shanghai Jiaotong University were retrospectively analyzed. Data in pre-, intra- and post-OLT periods of these patients were collected. Acute kidney injury net (AKIN) criteria were used to analyze the post-OLT acute kidney injury (AKI). By following up all the patients for over a year, Kaplan-Meier survival analysis was used to evaluate the prognosis within 28 days and 1 year. Cox regression analysis was performed to evaluate risk factors of patient death, especially the influence of AKI on patient prognosis. RESULTS: There were 193 patients enrolled, the average age was (48.07+/-10.02) years old. The ratio of male to female was 4:1. One hundred and sixteen patients (60.1%) were found to have AKI after OLT. Twenty-eight-day mortality of post-OLT AKI patients was higher than that without AKI patients [15.5%(18/116) vs. 0, P<0.05], 1 year survival rate of post-OLT AKI patients was lower than that without AKI patients [(70.7% (82/116) vs. 90.9 (70/77), P<0.05). Kaplan-Meier survival analysis showed the survival rate of non-AKI (77 patients), AKI stage 1, 2 and 3 patients (58, 25 and 33 patients respectively) post-OLT were 90.9%, 81.0%, 84.0% and 42.4%, respectively. All the non-survivors were discovered to have AKI within 28 days post-OLT. Cox regression analysis showed pre-OLT hypertension [hazard ratio (HR)=4.398, 95% confidence interval (CI)ú 1.535-12.604, P=0.006], post-OLT AKI (HR=12.100, 95%CI: 1.565-93.540, P=0.017), infection (HR=4.709, 95%CI: 1.813-12.226, P=0.001) and acute physiology and chronic health evaluation II (APACHE II) score > or =10 (HR=3.627, 95%CI: 1.244-10.573, P=0.018) were risk factors of 1 year death. CONCLUSION: AKI is an independent risk factor of poor prognosis after liver transplantation. Prevention of AKI may improve the survival rate of OLT patients.