Chih-Yang Hsu

The clinical impact of bacteremia in complicated acute pyelonephritis.

Background: Bacteremia has been considered as a surrogate marker of severe infection in several infectious diseases. However, it remains uncertain whether the presence of bacteremia correlates with severe infection in patients with complicated acute pyelonephritis (APN). Methods: We performed a retrospective study to investigate the relationship between the presence of bacteremia and disease severity in complicated APN. To do this, we reviewed medical records from 128 patients diagnosed with complicated APN admitted to Kaohsiung Veterans General Hospital, Taiwan between January, 2003 and December, 2003. In our analysis, we compared clinical presentation, treatment response, and outcome in patients with and without bacteremia. Results: Fifty-four of 128 patients (42%) were bacteremic. This group of patients presented more frequently with severe sepsis or septic shock (P < 0.001), compared with nonbacteremic patients. Other factors that correlated with the presence of bacteremia were older age, diabetes mellitus, more band forms in neutrophil cell counts, impaired renal function, and a lower level of serum albumin. Using a multivariate logistic regression analysis, we show that lower levels of serum albumin (odds ratio, 0.18; 95% CI, 0.05–0.65; P = 0.008) and presence of severe sepsis (odds ratio, 4.76; 95% CI, 1.43–15.84; P = 0.011) were independent factors associated with bacteremia. Following treatment, the bacteremic group took a longer time to become defervescent than the nonbacteremic group (5.1 ± 2.3 vs. 4.2 ± 1.6 days, P = 0.023). Also, the bacteremic group had a greater mean duration of intravenous antibiotics administration and longer hospital stays (P < 0.001). Multiple logistic regression analysis shows that non-Escherichia coli bacteremia, presence of urolithiasis or hydronephrosis, shorter duration of antibiotics administration, and being male were significantly associated with recurrence of urinary tract infection within 6 months. Conclusion: Bacteremia in cases of complicated APN indicates a severe disease, which is more likely to recur in patients with non-E coli bacteremia. Our study showed that bacteremia is indeed a useful clinical indicator of severe disease and, if found, should influence patient management. Therefore, we recommend that blood culture samples should be taken in all patients with complicated APN.

An Open-Label, Prospective Pilot Clinical Study of Denosumab for Severe Hyperparathyroidism in Patients With Low Bone Mass Undergoing Dialysis

CONTEXT Denosumab is widely used for bone diseases with increased bone resorption. Its effectiveness in patients with severe secondary hyperparathyroidism on dialysis is unclear. OBJECTIVE This study aimed to evaluate the efficacy and safety of denosumab in patients with severe secondary hyperparathyroidism who are on dialysis. DESIGN This 6-month prospective, open-labeled study evaluated 12 patients (five women, seven men; mean age 53.5 ± 3.8 y). All had intact PTH (iPTH; > 1000 pg/mL), low bone mass (T-score < -1.0 SD), and bone pain and were poor surgical candidates. Serum calcium, phosphorus, alkaline phosphatase (AP), and iPTH levels were assessed at baseline and every month thereafter. Vertebral spine x-rays and bone mineral densities (BMDs) (lumbar spine and femoral neck) were assessed at the start and end of the study. All patients received denosumab (60 mg), calcitriol, phosphate binders, and dialysate calcium that were adjusted according to the biochemistry data. RESULTS The BMD increased in both the femoral neck (mean increase 23.7% ± 4.0%) and lumbar spine (17.1% ± 2.6%) after 6 months. In the first month, most patients had increased iPTH levels, which dramatically decreased from 1702.1 ± 181.9 to 518.8 ± 126.8 pg/mL by the end of the study after increasing the calcitriol dose. All patients had significant decreases in AP, calcium × phosphorus, and bone pain. Changes in femoral neck BMD correlated only with AP and iPTH levels. CONCLUSIONS Denosumab is effective in restoring bone mass and reducing bone pain in patients on dialysis with secondary hyperparathyroidism. It also allows for a more aggressive use of calcitriol to control hyperparathyroidism.

Mechanisms of star fruit-induced acute renal failure.

We have previously discovered that star fruit can induce oliguric acute renal failure. To investigate the mechanisms of star fruit-associated acute oxalate nephropathy, the nephrotoxic effect of star fruit was examined in both cellular experiments and animal models. We evaluated renal function, pathological changes in kidney tissues and apoptotic effects using terminal deoxynucleotidyl transferase nick-end labeling (TUNEL) assay in four groups of rats -- a control group (CG), fed with tap water (1); a star fruit group (SG), fed with star fruit juice naturally containing 0.2M oxalate (2); and oxalate groups (OxG), fed with 0.2M (3) or 0.4M (4) oxalate solution. The effects of both star fruit juice and oxalate on MDCK cells were also analyzed by flow cytometry. We found that the mean creatinine clearance was significantly lower in the SG, 0.2M OxG and 0.4M OxG. Dose-dependent apoptotic effects were evident from the TUNEL assay, and flow cytometry analysis of treated MDCK cells showed dose- and time-dependent effects. Our findings suggest that star fruit juice produces acute renal injury, not only through the obstructive effect of calcium oxalate crystals, but also by inducing apoptosis of renal epithelial cells, which may be caused by the levels of oxalate in the fruit.

Parathyroidectomy improves cardiovascular outcome in nondiabetic dialysis patients with secondary hyperparathyroidism

Secondary hyperparathyroidism and its associated abnormalities in mineral metabolism and haemodynamic changes increase the cardiovascular risk in patients with end‐stage renal disease (ESRD). Our objective was to determine the association of parathyroidectomy (PTX) with major cardiovascular events in nondiabetic dialysis patients with severe secondary hyperparathyroidism (SHPTH).

Erythropoietin suppresses epithelial to mesenchymal transition and intercepts Smad signal transduction through a MEK-dependent mechanism in pig kidney (LLC-PK1) cell lines

PURPOSE Tumor growth factor-beta1 (TGF-beta1) plays a pivotal role in processes like kidney epithelial-mesenchymal transition (EMT) and interstitial fibrosis, which correlate well with progression of renal disease. Little is known about underlying mechanisms that regulate EMT. Based on the anatomical relationship between erythropoietin (EPO)-producing interstitial fibroblasts and adjacent tubular cells, we investigated the role of EPO in TGF-beta1-mediated EMT and fibrosis in kidney injury. METHODS We examined apoptosis and EMT in TGF-beta1-treated LLC-PK1 cells in the presence or absence of EPO. We examined the effect of EPO on TGF-beta1-mediated Smad signaling. Apoptosis and cell proliferation were assessed with flow cytometry and hemocytometry. We used Western blotting and indirect immunofluorescence to evaluate expression levels of TGF-beta1 signal pathway proteins and EMT markers. RESULTS We demonstrated that ZVAD-FMK (a caspase inhibitor) inhibited TGF-beta1-induced apoptosis but did not inhibit EMT. In contrast, EPO reversed TGF-beta1-mediated apoptosis and also partially inhibited TGF-beta1-mediated EMT. We showed that EPO treatment suppressed TGF-beta1-mediated signaling by inhibiting the phosphorylation and nuclear translocation of Smad 3. Inhibition of mitogen-activated protein kinase kinase 1 (MEK 1) either directly with PD98059 or with MEK 1 siRNA resulted in inhibition of EPO-mediated suppression of EMT and Smad signal transduction in TGF-beta1-treated cells. CONCLUSIONS EPO inhibited apoptosis and EMT in TGF-beta1-treated LLC-PK1 cells. This effect of EPO was partially mediated by a mitogen-activated protein kinase-dependent inhibition of Smad signal transduction.

Low-Dose Heparin Retention in Temporary Hemodialysis Double-Lumen Catheter Does Not Increase Catheter Occlusion and Might Reduce Risk of Bleeding

Background: The objective of this study was to assess the impact of heparin concentration retained in temporary double-lumen catheters on bleeding risk. Methods: Activated partial thromboplastin time (aPTT) was measured in patients hemodialyzed via double-lumen catheters. Heparin solutions of 5,000 U/ml (group 1, n = 95) and 1,000 U/ml (group 2, n = 89) were randomly retained in catheters after placement and each hemodialysis (HD) session. Blood transfusion, bleeding episodes, and changes of hematocrit were recorded. Results: The aPTT at the beginning of HD or 10 min after heparin lock was significantly prolonged, which was more prominent in the 5,000 U/ml group, whereas the aPTT declined to baseline values at the end of HD or before the next dialysis session in both groups. Infection and occlusion rates were similar in both groups. More patients suffered from major bleeding and prominent decline of hematocrit in the 5,000 U/ml group. Conclusions: Low-dose heparin (1,000 U/ml) retention in double-lumen catheters for temporary HD maintains comparable catheter patency and might reduce the bleeding risk.

Effects of Denosumab and Calcitriol on Severe Secondary Hyperparathyroidism in Dialysis Patients With Low Bone Mass

CONTEXT Secondary hyperparathyroidism (SHPT) may worsen with administration of denosumab in chronic renal failure patients with low bone mass. OBJECTIVE This study aimed to evaluate the short-term effect of coadministration of calcitriol and denosumab on PTH secretion and parathyroid structure and the incidence of adverse effects in patients with SHPT and low bone mass. DESIGN AND SETTING This was a 24-week, open-label study at Kaohsiung Veterans General Hospital in Kaohsiung, Taiwan. PATIENTS Dialysis patients with SHPT (intact parathyroid hormone [iPTH] > 800 pg/mL) and low bone mass (T score < -2.5) were enrolled. INTERVENTION Patients received denosumab (60 mg) and doses of calcitriol adjusted to achieve iPTH < 300 pg/mL. MAIN OUTCOME MEASURES Parathyroid gland volume was assessed upon study initiation and completion. Serum calcium, phosphate, alkaline phosphatase, iPTH, and adverse effects were assessed at each visit (Day 7, 14, and 21, and every month thereafter). RESULTS iPTH significantly decreased (mean decrease, 58.28 ± 6.12%) with denosumab/calcitriol administration (P < .01) but not in the controls (patients not receiving denosumab). Parathyroid gland volume decreased (mean decrease, 21.98 ± 5.54%) with denosumab/calcitriol administration (P < .01) and progressively increased (20.58 ± 4.48%) in the controls (P < .05). Serum alkaline phosphatase and iPTH levels were significantly correlated to decreased iPTH and regression of parathyroid hyperplasia (P < .05). The most common adverse events were hypocalcemia (33.33%) and respiratory tract infection (4.17%). Hypocalcemia rapidly resolved with calcium and calcitriol supplements. CONCLUSIONS Denosumab allows for supra-physiologic doses of calcitriol resulting in decreased parathyroid secretion and parathyroid hyperplasia. Supervised administration and weekly laboratory and clinical monitoring of serum calcium are recommended during the first month to prevent hypocalcemia.

Effect of Ultrafiltration versus Intravenous Furosemide for Decompensated Heart Failure in Cardiorenal Syndrome: A Systematic Review with Meta-Analysis of Randomized Controlled Trials

Background: Ultrafiltration is an adjunctive treatment for decompensated heart failure patients with cardiorenal syndrome. The efficacy and safety of ultrafiltration in the patient cohort are still unknown. Methods: We systematically reviewed and evaluated randomized controlled trials, comparing diuretics with ultrafiltration in adult patients with decompensated heart failure and cardiorenal syndrome through January 2014. The primary outcomes were body weight loss and total fluid removal. Results: We identified 8 trials including 608 patients. In a random-effects model, the pooled difference of body weight loss was 1.44 kg between patients receiving ultrafiltration and diuretics (95% CI, 0.29-2.59; p = 0.01). The difference of fluid removal was 1.28 l between groups (95% CI, 0.43-2.12; p = 0.003). The RR for mortality was 0.90 for ultrafiltration compared with diuretics (95% CI, 0.61-1.33; p = 0.60) and the RR for renal function deterioration was 1.29 (95% CI, 0.90-1.85; p = 0.17). There is a trend toward reducing readmission rate in ultrafiltration group. Conclusions: Ultrafiltration is a safe and effective strategy in the treatment of cardiorenal syndrome without increasing the risk of renal deterioration.

The Strategy to Prevent and Regress the Vascular Calcification in Dialysis Patients

The high prevalence of arterial calcification in end-stage renal disease (ESRD) is far beyond the explanation by common cardiovascular risk factors such as aging, diabetes, hypertension, and dyslipidemia. The finding relies on the fact that vascular and valvular calcifications are predictors of cardiovascular diseases and mortality in persons with chronic renal failure. In addition to traditional cardiovascular risk factors such as diabetes mellitus and blood pressure control, other ESRD-related risks such as phosphate retention, excess calcium, and prolonged dialysis time also contribute to the development of vascular calcification. The strategies are to reverse “calcium paradox” and lower vascular calcification by decreasing procalcific factors including minimization of inflammation (through adequate dialysis and by avoiding malnutrition, intravenous labile iron, and positive calcium and phosphate balance), correction of high and low bone turnover, and restoration of anticalcification factor balance such as correction of vitamin D and K deficiency; parathyroid intervention is reserved for severe hyperparathyroidism. The role of bone antiresorption therapy such as bisphosphonates and denosumab in vascular calcification in high-bone-turnover disease remains unclear. The limited data on sodium thiosulfate are promising. However, if calcification is to be targeted, ensure that bone health is not compromised by the treatments.

Low Potassium Dialysate as a Protective Factor of Sudden Cardiac Death in Hemodialysis Patients with Hyperkalemia

Aim Hyperkalemia increases the risk of sudden cardiac death (SCD) in hemodialysis patients. Our objective was to determine the association between administering low potassium dialysate to hyperkalemic hemodialysis patients and SCD. Methods We conducted a retrospective cohort study with patients undergoing maintenance hemodialysis from May 1, 2006, through December 31, 2013. The dialysate composition was adjusted over time according to monthly laboratory results. A 1.0 mEq/L potassium dialysate was applied in patients with predialysis hyperkalemia (>5.5 mEq/L) and was included as a time-dependent confounding factor. The clinical characteristics of enrolled patients, the incidence and timing of SCD and risk factors for all-cause mortality and SCD were analyzed. Results There were 312 patients on maintenance hemodialysis during the study period. One hundred and fifty-seven patients had been dialyzed against a 1.0 mEq/L potassium dialysate at least once. The rates of all-cause mortality and SCD were 48.17 and 20.74 per 1000 patient-years, respectively. A 1.12-fold increase in the risk of SCD in the 24-hour period starting with the hemodialysis procedure and a 1.36-fold increase in the 24 hours preceding a weekly cycle were found (p = 0.017). Multivariate Cox proportional hazards models showed that age, diabetes mellitus and predialysis hyperkalemia (>5.0 mEq/L) were significant predictors of all-cause mortality and SCD. Exposure to 1.0 mEq/L potassium dialysate, Kt/V, and serum albumin were independent protective factors against all-cause mortality. Only exposure to 1.0 mEq/L potassium dialysate significantly prevented SCD (hazard ratio = 0.33, 95% CI = 0.13–0.85). Conclusions Using low potassium dialysate in hyperkalemic hemodialysis patients may prevent SCD.