Kwan-Dun Wu

Long-Term Risk of Coronary Events after AKI

The incidence rate of AKI in hospitalized patients is increasing. However, relatively little attention has been paid to the association of AKI with long-term risk of adverse coronary events. Our study investigated hospitalized patients who recovered from de novo dialysis-requiring AKI between 1999 and 2008 using patient data collected from inpatient claims from Taiwan National Health Insurance. We used Cox regression with time-varying covariates to adjust for subsequent CKD and ESRD after discharge. Results were further validated by analysis of a prospectively constructed database. Among 17,106 acute dialysis patients who were discharged, 4869 patients recovered from dialysis-requiring AKI (AKI recovery group) and were matched with 4869 patients without AKI (non-AKI group). The incidence rates of coronary events were 19.8 and 10.3 per 1000 person-years in the AKI recovery and non-AKI groups, respectively. AKI recovery associated with higher risk of coronary events (hazard ratio [HR], 1.67; 95% confidence interval [95% CI], 1.36 to 2.04) and all-cause mortality (HR, 1.67; 95% CI, 1.57 to 1.79) independent of the effects of subsequent progression to CKD and ESRD. The risk levels of de novo coronary events after hospital discharge were similar in patients with diabetes alone and patients with AKI alone (P=0.23). Our results reveal that AKI with recovery associated with higher long-term risks of coronary events and death in this cohort, suggesting that AKI may identify patients with high risk of future coronary events. Enhanced postdischarge follow-up of renal function of patients who have recovered from temporary dialysis may be warranted.

Multistate Outbreak of Listeriosis Linked to Turkey Deli Meat and Subsequent Changes in US Regulatory Policy

BACKGROUND Data about the efficacy and tolerability of linezolid for the treatment of gram-positive bacterial infections in patients with end-stage renal disease (ESRD) are lacking. METHODS This retrospective case-control study compared the tolerability and efficacy of linezolid therapy for patients with ESRD and patients with non-end-stage renal disease (NESRD), all of whom had gram-positive bacterial infections. RESULTS There were 58 men and 33 women enrolled in the study, with a mean age of 61.5 years (range, 45.4-81.2 years). Among these patients, 28 (30.8%) were receiving hemodialysis at the start of linezolid treatment. The ESRD group had a higher percentage of patients with diabetes mellitus (57.1% vs. 33.3%; P = .029) and an older mean age (+/-SD) (72.1 +/- 10.8 years vs. 56.8 +/- 20.4 years; P < .001), compared with the NESRD group. Severe thrombocytopenia (platelet count, < 100 x 10(9) platelets/L) and anemia were significantly more frequent in the ESRD group, compared with the NESRD group (78.6% vs. 42.9% [P = .003] and 71.4% vs. 36.5% [P = .003], respectively). The independent risk factors for thrombocytopenia identified by logistic regression analysis were pretreatment disease severity score (odds ratio [OR], 1.34; 95%, confidence interval [CI], 1.13-1.60; P = .001), central catheter-related infection (OR, 4.96; 95% CI, 1.08-22.73; P = .046), and ESRD (OR, 6.14; 95% CI, 1.63-23.26; P = .007). ESRD was the only independent risk factor for anemia (OR, 4; 95% CI, 1.50-10.64; P = .006). Survival analysis for the development of thrombocytopenia or death showed significant differences between patients with ESRD and patients with NESRD (P < .001). CONCLUSIONS The lower tolerability of linezolid in patients with ESRD, compared with those with NESRD, is evidenced by the higher rates of thrombocytopenia and anemia in the former group. The severity of these conditions necessitates treatment discontinuation for patients with ESRD more often than for patients with NESRD.

Comparative effectiveness of renin-angiotensin system blockers and other antihypertensive drugs in patients with diabetes: systematic review and bayesian network meta-analysis

Objective To assess the effects of different classes of antihypertensive treatments, including monotherapy and combination therapy, on survival and major renal outcomes in patients with diabetes. Design Systematic review and bayesian network meta-analysis of randomised clinical trials. Data sources Electronic literature search of PubMed, Medline, Scopus, and the Cochrane Library for studies published up to December 2011. Study selection Randomised clinical trials of antihypertensive therapy (angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), α blockers, β blockers, calcium channel blockers, diuretics, and their combinations) in patients with diabetes with a follow-up of at least 12 months, reporting all cause mortality, requirement for dialysis, or doubling of serum creatinine levels. Data extraction Bayesian network meta-analysis combined direct and indirect evidence to estimate the relative effects between treatments as well as the probabilities of ranking for treatments based on their protective effects. Results 63 trials with 36 917 participants were identified, including 2400 deaths, 766 patients who required dialysis, and 1099 patients whose serum creatinine level had doubled. Compared with placebo, only ACE inhibitors significantly reduced the doubling of serum creatinine levels (odds ratio 0.58, 95% credible interval 0.32 to 0.90), and only β blockers showed a significant difference in mortality (odds ratio 7.13, 95% credible interval 1.37 to 41.39). Comparisons among all treatments showed no statistical significance in the outcome of dialysis. Although the beneficial effects of ACE inhibitors compared with ARBs did not reach statistical significance, ACE inhibitors consistently showed higher probabilities of being in the superior ranking positions among all three outcomes. Although the protective effect of an ACE inhibitor plus calcium channel blocker compared with placebo was not statistically significant, the treatment ranking identified this combination therapy to have the greatest probability (73.9%) for being the best treatment on reducing mortality, followed by ACE inhibitor plus diuretic (12.5%), ACE inhibitors (2.0%), calcium channel blockers (1.2%), and ARBs (0.4%). Conclusions Our analyses show the renoprotective effects and superiority of using ACE inhibitors in patients with diabetes, and available evidence is not able to show a better effect for ARBs compared with ACE inhibitors. Considering the cost of drugs, our findings support the use of ACE inhibitors as the first line antihypertensive agent in patients with diabetes. Calcium channel blockers might be the preferred treatment in combination with ACE inhibitors if adequate blood pressure control cannot be achieved by ACE inhibitors alone.

Acute-on-chronic kidney injury at hospital discharge is associated with long-term dialysis and mortality

Existing chronic kidney disease (CKD) is among the most potent predictors of postoperative acute kidney injury (AKI). Here we quantified this risk in a multicenter, observational study of 9425 patients who survived to hospital discharge after major surgery. CKD was defined as a baseline estimated glomerular filtration rate <45 ml/min per 1.73 m(2). AKI was stratified according to the maximum simplified RIFLE classification at hospitalization and unresolved AKI defined as a persistent increase in serum creatinine of more than half above the baseline or the need for dialysis at discharge. A Cox proportional hazard model showed that patients with AKI-on-CKD during hospitalization had significantly worse long-term survival over a median follow-up of 4.8 years (hazard ratio, 1.7) [corrected] than patients with AKI but without CKD.The incidence of long-term dialysis was 22.4 and 0.17 per 100 person-years among patients with and without existing CKD, respectively. The adjusted hazard ratio for long-term dialysis in patients with AKI-on-CKD was 19.8 compared to patients who developed AKI without existing CKD. Furthermore, AKI-on-CKD but without kidney recovery at discharge had a worse outcome (hazard ratios of 4.6 and 213, respectively) for mortality and long-term dialysis as compared to patients without CKD or AKI. Thus, in a large cohort of postoperative patients who developed AKI, those with existing CKD were at higher risk for long-term mortality and dialysis after hospital discharge than those without. These outcomes were significantly worse in those with unresolved AKI at discharge.

Pentoxifylline Attenuates Tubulointerstitial Fibrosis by Blocking Smad3/4-Activated Transcription and Profibrogenic Effects of Connective Tissue Growth Factor

Pentoxifylline (PTX) is a potent inhibitor of connective tissue growth factor (CTGF), but its underlying mechanism is poorly understood. Here, it was demonstrated that PTX inhibited not only TGF-beta1-induced CTGF expression but also CTGF-induced collagen I (alpha1) [Col I (alpha1)] expression in normal rat kidney fibroblasts (NRK-49F) and alpha-smooth muscle actin expression in normal rat kidney proximal tubular epithelial cells (NRK-52E). Furthermore, PTX attenuated tubulointerstitial fibrosis, myofibroblasts accumulation, and expression of CTGF and Col I (alpha1) in unilateral ureteral obstruction kidneys. The mechanism by which PTX reduced CTGF in NRK-49F and NRK-52E was investigated. Activation of Smad3/4 was essential for TGF-beta1-induced CTGF transcription, but PTX did not interfere with TGF-beta1 signaling to Smad2/3 activation and association with Smad4 and their nuclear translocation. However, PTX was capable of blocking activation of TGF-beta1-induced Smad3/4-dependent reporter as well as CTGF promoter, suggesting that PTX affects a factor that acts cooperatively with Smad3/4 to execute transcriptional activation. It was found that PTX increased intracellular cAMP and caused cAMP response element binding protein phosphorylation. The protein kinase A antagonist H89 abolished the inhibitory effect of PTX on Smad3/4-dependent CTGF transcription, whereas dibutyryl cAMP and forskolin recapitulated the inhibitory effect. In conclusion, these results indicate that PTX inhibits CTGF expression by interfering with Smad3/4-dependent CTGF transcription through protein kinase A and blocks the profibrogenic effects of CTGF on renal cells. Because of the dual blockade, PTX potently attenuates the tubulointerstitial fibrosis in unilateral ureteral obstruction kidneys.

Rate of decline of residual renal function is associated with all-cause mortality and technique failure in patients on long-term peritoneal dialysis

BACKGROUND Residual renal function (RRF) at the initiation of peritoneal dialysis (PD) therapy can predict patient outcome. However, RRF declines with time at variable rates in different patients. This study was performed to compare the impact of baseline RRF and the rate of RRF decline on patient survival and on death-censored technique survival after initiation of long-term PD. METHODS We enrolled 270 patients with sufficient urine amount (daily urine volume >100 mL) from a medical centre in North Taiwan who began PD between January 1996 and December 2005 and followed them until December 2007. The study population was stratified by the decline rate of RRF into a fast, intermediate and slow decline group. The Kaplan-Meier survival analysis was used to determine patient survival and technique survival. The Cox regression model was used to identify factors associated with patient outcome. The proportional odds polychotomous logistic regression model was used to identify variables associated with rapid decline of RRF. RESULTS During an average follow-up period of 45 months, 50 (18.5%) deaths, 67 (24.8%) death-censored technique failures (transfer to haemodialysis) and 43 (15.9%) renal transplantations occurred. The median rate of RRF decline was 0.885 mL/min/1.73 m(2) per year. Survival analysis showed that patients with fast RRF decline had worse survival and increased risk of technique failure. The multivariate Cox regression model confirmed that the rate of RRF decline was an independent factor associated with patient and technique survival and was a more powerful prognostic factor than basal RRF. Variables associated with a rapid decline of RRF were larger body mass index, presence of diabetes, prior history of congestive heart failure, use of diuretics, peritonitis episodes and hypotensive events. CONCLUSIONS Our data indicate that the rate of decline of RRF is a more powerful prognostic factor than baseline RRF associated with all-cause mortality and technique failure in patients on long-term PD. To prevent accelerated loss of RRF, it is imperative that every effort be made to avoid overdiuresis, peritonitis and hypotensive episodes, especially in those with diabetes, obesity and congestive heart failure.

Sexual dysfunction in female hemodialysis patients: A multicenter study

BACKGROUND Sexual function is one aspect of physical functioning. Sexual dysfunction, no matter the etiology, could cause distress. In female hemodialysis patients, sexual problems have often been neglected in clinical performance and research. METHODS We conducted this study by use of self-reported questionnaires. A total of 578 female hemodialysis patients in northern Taiwan were included in this study. Demographic data, comorbid diseases, medications in use, biochemical, and hematologic parameters were analyzed. All patients were asked to complete by themselves three questionnaires: (1) the Index of Female Sexual Function (IFSF) to assess sexual function; (2) the Beck Depression Inventory (BDI) (Chinese version) to rate the severity of depressive symptoms; and (3) the 36-item Short Form Health Survey Questionnaire (SF-36, Taiwan Standard Version 1.0) to survey their quality of life. RESULTS A total of 138 female patients were enrolled into further analysis. The mean age was 48.7 +/- 11.2 years old. The mean IFSF score was 24.5 +/- 9.3. Age, BDI score, and serum triglyceride levels were the independent factors of dysfunction in each sexual functional dimension. Patients with higher IFSF scores had significantly higher scores in physical functioning and mental health (P= 0.007 and 0.018, respectively). Patients with higher intercourse satisfaction had significantly higher general health scores (P= 0.001). CONCLUSION Sexual dysfunction is frequent in the female hemodialysis population. It is strongly associated with increasing age, dyslipidemia, and depression. The subjects with sexual dysfunction had poorer quality of life. The diagnosis and treatment of sexual dysfunction should be included in the clinical assessment.

Impact of timing of renal replacement therapy initiation on outcome of septic acute kidney injury

IntroductionSepsis is the leading cause of acute kidney injury (AKI) in critical patients. The optimal timing of initiating renal replacement therapy (RRT) in septic AKI patients remains controversial. The objective of this study is to determine the impact of early or late initiation of RRT, as defined using the simplified RIFLE (risk, injury, failure, loss of kidney function, and end-stage renal failure) classification (sRIFLE), on hospital mortality among septic AKI patients.MethodsPatient with sepsis and AKI requiring RRT in surgical intensive care units were enrolled between January 2002 and October 2009. The patients were divided into early (sRIFLE-0 or -Risk) or late (sRIFLE-Injury or -Failure) initiation of RRT by sRIFLE criteria. Cox proportional hazard ratios for in hospital mortality were determined to assess the impact of timing of RRT.ResultsAmong the 370 patients, 192 (51.9%) underwent early RRT and 259 (70.0%) died during hospitalization. The mortality rate in early and late RRT groups were 70.8% and 69.7% respectively (P > 0.05). Early dialysis did not relate to hospital mortality by Cox proportional hazard model (P > 0.05). Patients with heart failure, male gender, higher admission creatinine, and operation were more likely to be in the late RRT group. Cox proportional hazard model, after adjustment with propensity score including all patients based on the probability of late RRT, showed early dialysis was not related to hospital mortality. Further model matched patients by 1:1 fashion according to each patients propensity to late RRT showed no differences in hospital mortality according to head-to-head comparison of demographic data (P > 0.05).ConclusionsUse of sRIFLE classification as a marker poorly predicted the benefits of early or late RRT in the context of septic AKI. In the future, more physiologically meaningful markers with which to determine the optimal timing of RRT initiation should be identified.

131I-6β-Iodomethyl-19-Norcholesterol SPECT/CT for Primary Aldosteronism Patients with Inconclusive Adrenal Venous Sampling and CT Results

The 2 main causes of primary aldosteronism (PA) are aldosterone-producing adenoma (APA) and idiopathic adrenal hyperplasia (IAH). Dexamethasone-suppression 131I-6β-iodomethyl-19-norcholesterol (NP-59) adrenal scintigraphy can assess the functioning of the adrenal cortex. This study evaluated the diagnostic usefulness of NP-59 SPECT/CT in differentiating APA from IAH and in predicting postadrenalectomy clinical outcome for PA patients who had inconclusive adrenal venous sampling (AVS) and CT results. Methods: We retrospectively reviewed the 31 adrenal lesions of 27 patients (age range, 33–71 y; mean age ± SD, 50.4 ± 10.9 y) who had been clinically confirmed (by saline infusion and captopril tests) to have PA, had inconclusive CT and AVS test results, and had undergone NP-59 imaging before adrenalectomy. The accuracy of NP-59 imaging was determined by comparison with histopathologic findings. Results: NP-59 SPECT/CT gave us 18 true-positive, 3 false-positive, 6 true-negative, and 4 false-negative results. Compared with planar imaging, SPECT/CT significantly improved diagnostic accuracy and prognostic predicting ability (P = 0.0390 and P = 0.0141, respectively). The NP-59 results were negative for 7 of the 23 patients with unilateral adrenal lesions, and none of these 7 patients had shown postsurgical clinical improvement. Conclusion: NP-59 SPECT/CT is an effective imaging tool for differentiating APA from IAH in PA patients whose CT and AVS results are inconclusive. Our results suggest that patients with presurgically negative NP-59 results should be treated medically and that noninvasive NP-59 SPECT/CT may be suited for use as the first lateralization modality after CT in patients with clinically confirmed PA.

Association of Kidney Function With Residual Hypertension After Treatment of Aldosterone-Producing Adenoma

BACKGROUND Autonomous secretion of aldosterone in patients with primary aldosteronism increases glomerular filtration rate and causes kidney damage. The influence of a mild decrease in kidney function on residual hypertension after adrenalectomy is unexplored. STUDY DESIGN Nonconcurrent prospective study. SETTING & PARTICIPANTS The study was based on the Taiwan Primary Aldosteronism Investigation (TAIPAI) database. 150 patients (61 men; overall mean age, 47.2 +/- 11.6 years) with a diagnosis of aldosterone-producing adenoma had undergone unilateral adrenalectomy at National Taiwan University Hospital from July 1999 to January 2007. PREDICTOR Presurgery estimated glomerular filtration rate (eGFR). OUTCOMES & MEASUREMENTS Residual hypertension after adrenalectomy, defined either as less than 75% of recorded blood pressure measurements with systolic blood pressure less than 140 mm Hg and diastolic blood pressure less than 90 mm Hg or requiring antihypertensive medications during the first year after surgery. RESULTS Before surgery, 27 (18%), 72 (48%), and 51 (34%) patients had moderately to severely decreased (<60 mL/min/1.73 m(2)), mildly decreased (60 <or= eGFR < 90 mL/min/1.73 m(2)), or nondecreased eGFR (>or=90 mL/min/1.73 m(2)), respectively. After surgery, 16 (59.3%), 29 (40.3%), and 10 (19.3%) patients in each category had postsurgery residual hypertension. Compared with patients without decreased eGFR before surgery, adjusted odds ratios for postsurgery residual hypertension were 2.7 (95% confidence interval, 1.03 to 7.0; P = 0.04) and 2.8 (95% confidence interval, 1.05 to 9.3) for mildly and moderately to severely decreased eGFR, respectively. LIMITATIONS Arbitrary definition for residual hypertension. CONCLUSIONS Two-thirds of patients with aldosterone-producing adenoma were cured of hypertension by means of unilateral adrenalectomy. Kidney function impairment, even mild, appears to be associated with a high incidence of postsurgery residual hypertension.