Fimasartan attenuates renal ischemia-reperfusion injury by modulating inflammation-related apoptosis

Fimasartan, a new angiotensin II receptor antagonist, reduces myocyte damage and stabilizes atherosclerotic plaque through its anti-inflammatory effect in animal studies. We investigated the protective effects of pretreatment with fimasartan on ischemia-reperfusion injury (IRI) in a mouse model of ischemic renal damage. C57BL/6 mice were pretreated with or without 5 (IR-F5) or 10 (IR-F10) mg/kg/day fimasartan for 3 days. Renal ischemia was induced by clamping bilateral renal vascular pedicles for 30 min. Histology, pro-inflammatory cytokines, and apoptosis assays were evaluated 24 h after IRI. Compared to the untreated group, blood urea nitrogen and serum creatinine levels were significantly lower in the IR-F10 group. IR-F10 kidneys showed less tubular necrosis and interstitial fibrosis than untreated kidneys. The expression of F4/80, a macrophage infiltration marker, and tumor necrosis factor (TNF)-α, decreased in the IR-F10 group. High-dose fimasartan treatment attenuated the upregulation of TNF-α, interleukin (IL)-1β, and IL-6 in ischemic kidneys. Fewer TUNEL positive cells were observed in IR-F10 compared to control mice. Fimasartan caused a significant decrease in caspase-3 activity and the level of Bax, and increased the Bcl-2 level. Fimasartan preserved renal function and tubular architecture from IRI in a mouse ischemic renal injury model. Fimasartan also attenuated upregulation of inflammatory cytokines and decreased apoptosis of renal tubular cells. Our results suggest that fimasartan inhibited the process of tubular injury by preventing apoptosis induced by the inflammatory pathway.

Vitamin D deficiency is associated with increased risk of bacterial infections after kidney transplantation

BACKGROUND/AIMS: There may be an association between vitamin D levels and allograft outcomes in kidney transplant recipients (KTRs). However, few studies have been conducted to determine the association between vitamin D levels and post-transplant infections. This study investigated the impact of vitamin D deficiency on the risk of infection after kidney transplantation. METHODS: We measured 25-hydroxyvitamin D (25(OH)D) levels prior to kidney transplantation. Vitamin D deficiency was defined as a serum 25(OH)D level < 20 ng/mL. We examined the incidence of various post-transplant infections during follow-up period. We used Cox proportional hazards regression analysis to determine factors associated with increased risk of post-transplant infections during the follow-up period. RESULTS: A total of 164 KTRs were followed up for a mean of 24.8 ± 10.7 months. Among them, 135 patients (82.3%) had vitamin D deficiency. Patients with vitamin D deficiency had a significantly higher incidence of urinary tract infection (p = 0.027) and any bacterial infection (p = 0.010) compared to those without vitamin D deficiency. Vitamin D deficiency was not significantly associated with incidence of viral or fungal infections. Cox proportional hazards regression analysis revealed that vitamin D deficiency (hazard ratio, 11.07; 95% confidence interval, 1.46 to 84.03; p = 0.020) was independent risk factor for post-transplant bacterial infections. CONCLUSIONS: Pre-transplant vitamin D deficiency was a significant risk factor for bacterial infections after kidney transplantation. Further studies are needed on possible benefits of vitamin D supplementation for preventing post-transplant bacterial infection.

Vitamin D deficiency is associated with increased risk of bacterial infections after kidney transplantation

BACKGROUND/AIMS: There may be an association between vitamin D levels and allograft outcomes in kidney transplant recipients (KTRs). However, few studies have been conducted to determine the association between vitamin D levels and post-transplant infections. This study investigated the impact of vitamin D deficiency on the risk of infection after kidney transplantation. METHODS: We measured 25-hydroxyvitamin D (25(OH)D) levels prior to kidney transplantation. Vitamin D deficiency was defined as a serum 25(OH)D level < 20 ng/mL. We examined the incidence of various post-transplant infections during follow-up period. We used Cox proportional hazards regression analysis to determine factors associated with increased risk of post-transplant infections during the follow-up period. RESULTS: A total of 164 KTRs were followed up for a mean of 24.8 ± 10.7 months. Among them, 135 patients (82.3%) had vitamin D deficiency. Patients with vitamin D deficiency had a significantly higher incidence of urinary tract infection (p = 0.027) and any bacterial infection (p = 0.010) compared to those without vitamin D deficiency. Vitamin D deficiency was not significantly associated with incidence of viral or fungal infections. Cox proportional hazards regression analysis revealed that vitamin D deficiency (hazard ratio, 11.07; 95% confidence interval, 1.46 to 84.03; p = 0.020) was independent risk factor for post-transplant bacterial infections. CONCLUSIONS: Pre-transplant vitamin D deficiency was a significant risk factor for bacterial infections after kidney transplantation. Further studies are needed on possible benefits of vitamin D supplementation for preventing post-transplant bacterial infection.

A Case of Transient Central Diabetes Insipidus after Aorto-Coronary Bypass Operation

Diabetes insipidus (DI) is characterized by excessive urination and thirst. This disease results from inadequate output of antidiuretic hormone (ADH) from the pituitary gland or the absence of the normal response to ADH in the kidney. We present a case of transient central DI in a patient who underwent a cardiopulmonary bypass (CPB) for coronary artery bypass grafting (CABG). A 44-yr-old male underwent a CABG operation. An hour after the operation, the patient developed polyuria and was diagnosed with central DI. The patient responded to desmopressin and completely recovered five days after surgery. It is probable that transient cerebral ischemia resulted in the dysfunction of osmotic receptors in the hypothalamus or hypothalamus-pituitary axis during CPB. It is also possible that cardiac standstill altered the left atrial non-osmotic receptor function and suppressed ADH release. Therefore, we suggest that central DI is a possible cause of polyuria after CPB.

A Validation of Dietary Self-Efficacy Questionnaire in Hemodialysis Patients

BACKGROUND: This study was performed to develop a dietary self-efficacy questionnaire and to determine how dietary self-efficacy is related to selected biochemical markers and health-related quality of life in hemodialysis patients. METHODS: Participants included 172 patients who had been participating in a dialysis program for at least 6 months at two teaching hospitals. A questionnaire was used to assess socio-demographic factors, dialysis-related factors, dietary self-efficacy, and kidney disease quality of life (KDQOL). Serum levels of potassium and phosphorus and interdialytic weight gain were also measured. RESULTS: The internal reliability of dietary self-efficacy was 0.944 (Cronbach's alpha). Principal component analysis resulted in two factors, situational self-efficacy of compliance with dietary guidelines and self-efficacy of food choice. The correlation analysis showed a significant association between situational self-efficacy of compliance with dietary guidelines and serum potassium and KIDQOL. The average scores of situational self-efficacy of compliance with dietary guidelines and self-efficacy of food choice in the participants were 3.52+/-0.72 and 3.61+/-0.71 respectively. Multiple linear regression analysis showed that the situational self-efficacy of compliance with dietary guidelines was significantly associated with serum potassium level and KDQOL and self-efficacy of food choice was significantly associated with KDQOL. CONCLUSIONS: Based on our results, the developed dietary self-efficacy questionnaire may be a suitable survey tool for hemodialysis patients, which can play a role in predicting clinical indicators of patient and health-related quality of life. We recommend further research into clarifying whether the positive effects of increased dietary self-efficacy is maintained in long-term dialysis patients.

Sustained Low-Efficiency Dialysis as an Alternative Therapy to Continuous Renal Replacement Therapy in Critically Ill Patients with Acute Kidney Injury / 대한신장학회지

PURPOSE: Although continuous renal replacement therapy (CRRT) is commonly used as a renal replacement therapy in critically ill patients with acute kidney injury, it has some disadvantages such as inconvenience, intensive labor, expensiveness and high bleeding risk. Recent studies have shown that sustained-low efficiency dialysis (SLED) can overcome these shortages of CRRT and also has the advantages of CRRT. We prospectively compared the efficiency, safety, cost and convenience between SLED and CRRT, and evaluated whether SLED could be a complementary substitute to traditional CRRT. METHODS: Forty-six critically ill patients with acute kidney injury (AKI) from 2003 to 2005 were treated with SLED (n=25) and CRRT (n=21). The modality was tended to be selected randomly and based largely on availability of equipments and not on the clinical status of patients. Mann-Whitney rank-sum test, Fisher's exact test and chi-square test were used for statistics, and data were described as median value, range from 25th to 75th. RESULTS: The Acute Physiology and Chronic Health Evaluation (APACHE) II score at the point of ICU admission was 27 for SLED (range 17-32, 25-75th percentile) and 26 for CRRT group (range 19-31) (p=NS). There were no significant differences between the two groups in mean arterial blood pressure when measured pre-dialysis (83 for SLED vs. 85 for CRRT; p=NS), mid-dialysis (90 vs. 84; p=NS) and at the end of treatment (88 vs. 80; p=NS). Incidences of hypotension also did not differ between the two groups (p=NS). Ultrafiltration volume per treatment day was similar in two treatment modalities (2,000 mL for SLED vs. 2,400 mL for CRRT; p=NS). Heparin was used to thirty-one patients (SLED: 18 patients, CRRT: 13 patients). The dosage of heparin tended to be lower in SLED (2,900 unit per day for SLED vs. 6,000 unit per day for in CRRT, p=0.065). Total clotting number was 4 for SLED and 11 for CRRT (p=NS). There was also no significant difference in hospital mortality between the two groups (56% for SLED vs. 42.9% for CRRT; p=NS). SLED was superior to CRRT in the aspect of cost and convenience. CONCLUSION: Our data suggest that SLED can be used as a useful substitute to traditional CRRT in critically ill patients with AKI.

Clinical Usefulness of Low Calcium Dialysate in CAPD Patients with High Risk of Low-turnover Bone Disease / 대한신장학회잡지

Hypercalcemia is a common complication in CAPD patients treated with calcium-containing phosphate binders and using the standard dialysate(Ca++ : 3.5 mEq/L). Furthermore, the high calcium concentration in standard dialysate may have a suppressive effect on parathyroid hormone(iPTH) level, contributing to the high prevalence of low-urnover bone disease. We studied the effect of low calcium dialysate(Ca++ : 2.5 mEq/L) for those patients with high risk of low- turnover bone disease. Among 386 patients(1996. 1.- 1999. 12.) who had been stable on CAPD for at least 3 months, 46 patients were included in this study. The patients were divided into 3 groups on the basis of the iPTH levels(10 mg/dL) before the conversion to low calcium dialysate. Group 1(n=29), iPTH 10 mg/dL; Group 2 (n=14), iPTH 150 pg/mL and Ca++ >10 mg/ dL. During a 2-month run-in period, those patients were treated with standard dialysate. After that, a 12-month therapy with low calcium dialysate was followed. Biochemical data including calcium, phosphorus, iPTH and alkaline phosphatase were measured regularly and daily phosphate binder and calcitriol intake(pill counting) were assessed during the run-in and therapy period. We obtained the following result: the prevalence of hypercalcemia(Ca++>10.5 mg/dL) was 5.7%(22/ 386 patients). Serum calcium levels decreased during the therapy period(12 months)(10.5+/-1.4 vs 9.4+/-1.3 mg/dL, p<0.05). Serum phosphorus levels remained unchanged. Mean serum alkaline phosphatase level increased(203.0+/-92.9 vs 257.2+/-103.4 U/L, p<0.05). Serum iPTH levels increased (92.7+/-128.8 vs 225.3+/-237.3 pg/mL,p<0.05). The mean intake of oral phosphate binders was not significantly different between run-in period and therapy period. But calcitriol doses increased 0.038+/-0.087 at run-in period to 0.158+/-0.288 tablets/person/day at therapy period(p<0.05). In the six patients, low calcium dialysate was converted to standard dialysate due to high iPTH level (n=3), symptomatic hypo calcemia(n=2), and uncontrolled edema(n=1). In conclusion, in the study of 46 patients over 12 month period, the usage of 2.5 mEq/L calcium dialysate resulted in a significant decrement in calcium levels and increased iPTH levels. Therefore, we propose that dialysis with a low calcium dialysate is an acceptable form of therapy for the patients with high risk of low-turnover bone disease showing hypercalcemia and low iPTH level. However, further study will be needed for evaluating the effect of low calcium dialysate in low-turnover bone disease.

The Influence of Changes in Preload on Tei index

BACKGROUND: Tei index is a Doppler-derived index of combined systolic and diastolic myocardial performance proposed to be a promising noninvasive measurement of overall cardiac function, calculated as the sum of isovolumic contraction (ICT) and isovolumic relaxation times (IRT) divided by ejection time (ET). This study aimed to investigate the effect of changes in preload on Tei index. SUBJECTS AND METHOD: The study population was 10 patients with chronic renal failure who are on regular hemodialysis (HD). They were 3 men and 7 women with a mean age of 45.3+/-12.4 years old. The complete 2-dimensional and Doppler echocardiography including recordings of mitral inflow and left ventricular outflow were performed using HP SONOS 1500 equipment before and after HD. Body weight was measured using electric scale before and after HD. Blood pressure and pulse rate were measured by an automated cuff measurement every 1 hour throughout HD. Hematocrit was monitored noninvasively and continuously using the Crit-Line instrument (In-Line Diagnostics, Riverdale, UT, USA) during HD. RESULTS: There were no significant changes in systolic and diastolic blood pressure, RR interval, left ventricular end-diastolic and end-systolic dimension, left atrial dimension, and left ventricular ejection fraction during HD. The mean body weight loss during HD was 2.1+/-0.65 kg. The percentage of reduction of body weight was 4.1+/-1.56%. Changes in total blood volume at the end of HD were compared with that of baseline -11.79+/-5.51%. The percent change in total blood volume during the HD correlated significantly with the amount of change in body weight (r=0.678, p<0.05) and percent change in body weight (r=0.835, p<0.01), respectively. ICT before HD and at the end of HD were 39+/-13.0, 42+/-24.1 msec (p=NS). IRT before HD and at the end of HD were 76+/-29.1, 95+/-28.5 msec (p<0.01) and , ET before HD and at the end of HD were 317+/-18.1, 289+/-9.0 msec (p<0.01), respectively. Tei index before HD was 0.36+/-0.10, and the index at the end of HD were 0.47+/-0.13 (p<0.001). CONCLUSION: When there is a change in preload during a short period, it seems that the effect of change in preload should be considered when using Tei index to assess ventricular function.