Assessment of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker on the split renal function in the patients with primary hypertension.

ABSTRACT: Bilateral kidney damage in hypertensive patients is not parallel. Angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB), as a commonly used antihypertensive drug, could protect kidney function and delay its deterioration. Most studies focused on overall renal function, but the researches on split renal function (SRF) are rare. We investigated the effects of ACEI/ARB on the SRF in patients with primary hypertension.Patients with primary hypertension (n = 429; male: 213; female: 216) admitted to our department between January 2014 and December 2016 were included in this study. The glomerular filtration rate (GFR) of split and total renal function were determined using diethylenetriaminepentaacetic acid tagged with 99mTc renal dynamic imaging method. For the same patient, the side with high GFR was considered as higher GFR kidney, whereas that with a low GFR was considered as lower GFR kidney. The split function score (Q value) was utilized to evaluate the differences of bilateral renal function. The patients were divided into 3 groups based on the Q values (Group 1, Q value <5%; Group 2, Q value of 5%-10%; Group 3, Q value ≥10%). All the patients received antihypertensive therapy based on ACEI/ARB. The renal dynamic imaging was performed in the 1-year follow-up to investigate the changes of the SRF.Compared with the baseline level, significant decline was noticed in the serum creatinine (Scr) in Group 2 and Group 3 (P < .05). The cystatin C in Group 3 showed significant decline (P < .05). Compared with the baseline, there was significant decline in the Q value in Group 2, whereas the GFR of lower GFR kidney showed significant increase (P < .05). No statistical differences were noticed in the Q value and split GFR in Group 1 and Group 3 (P > .05).In primary hypertension patients, ACEI/ARB therapy could improve the SRF of lower GFR kidney in the presence of certain differences between the SRF. As a result, the SRF difference was reduced. In case of Q value in a range of 5% to 10%, ACEI/ARB could improve the renal function effectively. It may be significant for the design of antihypertensive drugs.

Therapeutic Drug Monitoring Coupled With Bayesian Forecasting Could Prevent Vancomycin-Associated Nephrotoxicity in Renal Insufficiency Patients: A Prospective Study and Pharmacoeconomic Analysis.

BACKGROUND: Vancomycin is a critical antibiotic used in important infections, and therapeutic drug monitoring (TDM) is recommended. Bayesian forecasting is demonstrated to provide an approach that can improve trough concentration monitoring for dose adjustment. The objective of this study was to determine whether TDM coupled with a Bayesian approach could increase trough concentration target attainment and prevent vancomycin-associated nephrotoxicity in patients with renal insufficiency. METHODS: A prospective study was performed using propensity score matching to provide covariate balance in renal insufficiency patients with gram-positive bacterial infections treated with vancomycin. Patients were divided into non-TDM (84 cases) and TDM (84 cases) groups, and their clinical outcomes were compared. The primary endpoints were probability of trough concentration target attainment and incidence of vancomycin-associated nephrotoxicity. A decision-tree model was developed to assess the cost effectiveness of TDM to prevent vancomycin-associated nephrotoxicity. RESULTS: Of the 168 eligible patients, 69 from each group (non-TDM and TDM) were matched based on propensity scores. In the matched cohort, trough concentration target attainment was higher with TDM (P = 0.003). Furthermore, reaching toxic trough concentrations was avoided (P = 0.027) in the TDM group. Multivariate logistic regression analysis confirmed that TDM practice independently reduced the incidence of vancomycin-associated nephrotoxicity in renal insufficiency patients (P = 0.021). According to this reduced nephrotoxicity, the incremental cost-effectiveness ratios of ¥22,638 per nephrotoxic episode prevented was found for vancomycin TDM. CONCLUSIONS: TDM coupled with Bayesian forecasting led to an increase in trough concentration target attainment and a decrease in the incidence of vancomycin-associated nephrotoxicity in renal insufficiency patients. In this high-risk population, TDM was demonstrated to be a cost-effective procedure.

Evaluation of the geographical utility of Eastern Russell's viper (Daboia siamensis) antivenom from Thailand and an assessment of its protective effects against venom-induced nephrotoxicity.

BACKGROUND: Daboia siamensis (Eastern Russell's viper) is a medically important snake species found widely distributed across Southeast Asia. Envenomings by this species can result in systemic coagulopathy, local tissue injury and/or renal failure. While administration of specific antivenom is an effective treatment for Russell's viper envenomings, the availability of, and access to, geographically-appropriate antivenom remains problematic in many rural areas. In this study, we determined the binding and neutralizing capability of antivenoms manufactured by the Thai Red Cross in Thailand against D. siamensis venoms from four geographical locales: Myanmar, Taiwan, China and Thailand. METHODOLOGY/PRINCIPLE FINDINGS: The D. siamensis monovalent antivenom displayed extensive recognition and binding to proteins found in D. siamensis venom, irrespective of the geographical origin of those venoms. Similar immunological characteristics were observed with the Hemato Polyvalent antivenom, which also uses D. siamensis venom as an immunogen, but binding levels were dramatically reduced when using comparator monovalent antivenoms manufactured against different snake species. A similar pattern was observed when investigating neutralization of coagulopathy, with the procoagulant action of all four geographical venom variants neutralized by both the D. siamensis monovalent and the Hemato Polyvalent antivenoms, while the comparator monovalent antivenoms were ineffective. These in vitro findings translated into therapeutic efficacy in vivo, as the D. siamensis monovalent antivenom was found to effectively protect against the lethal effects of all four geographical venom variants preclinically. Assessments of in vivo nephrotoxicity revealed that D. siamensis venom (700 µg/kg) significantly increased plasma creatinine and blood urea nitrogen levels in anaesthetised rats. The intravenous administration of D. siamensis monovalent antivenom at three times higher than the recommended scaled therapeutic dose, prior to and 1 h after the injection of venom, resulted in reduced levels of markers of nephrotoxicity and prevented renal morphological changes, although lower doses had no therapeutic effect. CONCLUSIONS/SIGNIFICANCE: This study highlights the potential broad geographical utility of the Thai D. siamensis monovalent antivenom for treating envenomings by the Eastern Russell's viper. However, only the early delivery of high antivenom doses appears to be capable of preventing venom-induced nephrotoxicity.

Assessment of Glomerular Filtration Rate and End-Stage Kidney Disease Risk in Living Kidney Donor Candidates: A Paradigm for Evaluation, Selection, and Counseling.

Living donor kidney transplantation is the preferred treatment option for ESRD. However, recent data suggest a small increase in the long-term risk of kidney failure in living kidney donors when compared to healthy nondonors. These data have led to a need for reconsideration of how donor candidates are evaluated and selected for donation. A Kidney Disease: Improving Global Outcomes (KDIGO) work group completed a comprehensive clinical practice guideline for evaluation of living kidney donor candidates in 2017, based on systematic evidence review, de novo evidence generation, and expert opinion. Central to the evaluation framework is assessment of glomerular filtration rate (GFR), which is used to screen for kidney disease and aid the prediction of long-term kidney failure risk after donation. Accurate estimation of the level of GFR and risk of kidney failure, and communication of estimated risks, can support evidence-based donor selection and shared decision-making. In this review, we discuss approaches to optimal GFR estimation in the donor evaluation process, long-term risk projection, and risk communication to donor candidates, integrating recommendations from the new KDIGO guideline, other recent literature, and experience from our own research and practice. We conclude by highlighting topics for further research in this important area of transplant medicine.

Prevention of renal failure in Chinese patients with newly diagnosed type 2 diabetes: A cost-effectiveness analysis.

AIMS/INTRODUCTION: Diabetic kidney disease (DKD) is the second leading cause (16.4%) of end-stage renal disease in China. The current study assessed the cost-effectiveness of preventing DKD in patients with newly diagnosed type 2 diabetes from the Chinese healthcare perspective. MATERIALS AND METHODS: A lifetime Markov decision model was developed according to the disease course of DKD. Patients with newly diagnosed type 2 diabetes might receive treatment according to one of the following three strategies: (i) "do nothing" strategy (control strategy); (ii) treatment with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers (universal strategy); (iii) or screening for microalbuminuria followed by angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker treatment (screening strategy). Clinical and utility data were obtained from the published literature. Direct medical costs and resource utilization in the Chinese healthcare setting were considered. Sensitivity analyses were undertaken to test the impact of a range of variables and assumptions on the results. RESULTS: Compared with the control strategy, both the screening and universal strategies were cost-saving options that showed lower costs and better health benefits. The incremental cost-effectiveness ratio of the universal strategy over the screening strategy was US $30,087 per quality-adjusted life-year, which was higher than the cost-effectiveness threshold of China. The sensitivity analyses showed robust results, except for the probability of developing macroalbuminuria from microalbuminuria. CONCLUSIONS: Screening for microalbuminuria could be a cost-saving option for the prevention of DKD in the Chinese setting.

Rice bran protein hydrolysates attenuate diabetic nephropathy in diabetic animal model.

INTRODUCTION: Diabetic nephropathy (DN) is an important microvascular complication of uncontrolled diabetes. The features of DN include albuminuria, extracellular matrix alterations, and progressive renal insufficiency. Rice bran protein hydrolysates (RBPs) have been reported to have antihyperglycemic, lipid-lowering, and anti-inflammatory effects in diabetic rats. Our study was to investigate the renoprotective effects of RBP in diabetic animals and mesangial cultured cells. METHODS: Eight-week-old male db/m and db/db mice were orally treated with tap water or RBP (100 or 500 mg/kg/day) for 8 weeks. At the end of the experiment, diabetic nephropathy in kidney tissues was investigated for histological, ultrastructural, and clinical chemistry changes, and biomarkers of angiogenesis, fibrosis, inflammation, and antioxidant in kidney were analyzed by Western blotting. Protection against proangiogenic proteins and induction of cytoprotection by RBP in cultured mesangial cells was evaluated. RESULTS: RBP treatment improved insulin sensitivity, decreased elevated fasting serum glucose levels, and improved serum lipid levels and urinary albumin/creatinine ratios in diabetic mice. RBP ameliorated the decreases in podocyte slit pore numbers, thickening of glomerular basement membranes, and mesangial matrix expansion and suppressed elevation of MCP-1, ICAM-1, HIF-1α, VEGF, TGF-ß, p-Smad2/3, and type IV collagen expression. Moreover, RBP restored suppressed antioxidant Nrf2 and HO-1 expression. In cultured mesangial cells, RBP inhibited high glucose-induced angiogenic protein expression and induced the expression of Nrf2 and HO-1. CONCLUSION: RBP attenuates the progression of diabetic nephropathy and restored renal function by suppressing the expression of proangiogenic and profibrotic proteins, inhibiting proinflammatory mediators, and restoring the antioxidant and cytoprotective system.

Low-protein diet for the prevention of renal failure.

The prevalence of chronic kidney disease (CKD) is estimated to be 8-16% worldwide, and it is increasing. CKD is a risk factor for heart attack and stroke, and it can progress to kidney failure requiring dialysis or transplantation. Recently, diabetic nephropathy has become the most common cause of CKD. In Japan, the cumulative probability of requiring hemodialysis by the age 80 years is 1/50 in males and 1/100 in females. The number of patients under hemodialysis in Japan exceeded 320,000 in 2014, among which 38,000 were newcomers and 27,000 died.The annual medical costs of hemodialysis are 1.25 trillion yen in Japan, representing 4% of the total national medical expenditures in 2014. A low-protein diet (less than 0.5 g/kg b.wt.) is a very effective intervention. Low-protein rice (1/10 to 1/25 of the normal protein contents) is helpful to control the consumption of proteins, decreasing at the same time the intake of potassium and phosphate.Protein restriction is indicated as soon as the eGFR becomes lower than 60 ml/min/1.73 m2 body surface, in order, to slow disease progression. The newly developed low-protein Indica rice is expected to help many CKD patients in China and Southeast Asia.

The role of the Kidney Foundation of Bangladesh in promoting kidney care in a resource-limited environment.

BACKGROUND: Prior to 2003 in Bangladesh, ~ 80% of kidney-failure patients could not afford treatment. The Kidney Foundation Bangladesh (KFB) was formed in 2003 with an aim to create awareness, to promote prevention of kidney disease to families and population, at risk as well as offer treatment to those afflicted with kidney failure. METHODS: KFB runs a 150-bed hospital for treatment of kidney disease, dialysis, and transplantation at an affordable price. New patients visiting the OPD pay only US$ 5.00 to consult a specialist, and dialysis and transplant patients pay US$1 for each consultation. All laboratory tests are discounted by 30% for all patients except patients with dialysis and transplantation who enjoy a 50% discount. Patients on HD pay only US$ 20.00 per session, and a renal transplant surgery costs US$ 3,000.00. RESULTS: From October 2004 to December 2014, there were 102,578 patients who received treatment in OPD in KFB at an affordable price. Similarly, more than 40,000 people per year benefited from various laboratory tests. A total of 11,099 patients were admitted in KFB hospital from January 2010 to December 2014. Of them, 2,409 (22%) were diagnosed as ESRD, and all of them were initially managed with dialysis either through a noncuffed catheter (82%) or by an AV fistula (8%); of the 388 continued on HD, 300 underwent transplantation, 289 agreed to shift to CAPD treatment, and rest of the patients were shifted to other HD centers. Simultaneously, a total of 3,600 patients were screened in rural, urban, and disadvantaged populations from 2004 to 2007 for detection of CKD. CONCLUSION: KFB is offering treatment for patients with kidney disease and kidney failure, not only at an affordable price, but also without compromising quality.

Vitamin E supplementation ameliorates aflatoxin B1-induced nephrotoxicity in rats.

Fungal toxins in nutrition can cause organ dysfunction or even failure. Aflatoxin B1 (AFB1)-induced renal impairment is not sufficiently studied regarding its extent and prevention. The aim of this experiment was to study the effect of AFB1 on renal cortical tissue and whether its possible harmful effect could be prevented by the conventional economical antioxidant, vitamin E. Forty rats were divided into four groups; I-IV. Group I represented the control while the others received vitamin E (Vit E), AFB1 and AFB1+Vit E, respectively. Renal cortex specimens were taken from each group after 25 days. Then, specimens were prepared for histological study by hematoxlyin and eosin (H&E), Masson's trichrome, caspase-3 as well as for ultrastructural examination and oxidative stress parameters evaluation. Data were morphometrically and statistically analyzed. In AFB1-treated group, focal tubulo-interstitial affection in the form of tubular cytoplasmic vacuolation, mitochondrial disruption, numerous lysosomes, marked increase in collagen deposition and in caspase-3 expression were observed. Glomerular impairment in the form of fusion of podocytes enlarged foot processes and thickening of the glomerular basement membrane (GBM) with loss of its trilaminar appearance were detected. In the group treated by AFB1+Vit E, there were minimal affection of the histological structure of the renal cortex as well as significant increase in the anti-oxidative parameters which were significantly decreased in the AFB1-treated group. Therefore, Vit E could be considered in wide experimental studies to be a first choice antioxidant of high cost-effectiveness in prevention of fungal toxins pro-oxidant-induced renal impairment.

Robot-assisted surgery for kidney cancer increased access to a procedure that can reduce mortality and renal failure.

Surgeons increasingly use robot-assisted minimally invasive surgery for a variety of medical conditions. For hospitals, the acquisition and maintenance of a robot requires a significant investment, but financial returns are not linked to any improvement in long-term patient outcomes in the current reimbursement environment. Kidney cancer provides a useful case study for evaluating the long-term value that this innovation can provide. Kidney cancer is generally treated through partial or radical nephrectomy, with evidence favoring the former procedure for appropriate patients. We found that robot-assisted surgery increased access to partial nephrectomy and that partial nephrectomy reduced mortality and renal failure. The value of the benefits of robot-assisted minimally invasive surgery to patients, in terms of quality-adjusted life-years gained, outweighed the health care and surgical costs to patients and payers by a ratio of five to one. In addition, we found no evidence that the availability of robot-assisted minimally invasive surgery increased the likelihood that inappropriate patients received partial nephrectomy.

Renal function after low central venous pressure-assisted liver resection: assessment of 2116 cases.

OBJECTIVES: Low central venous pressure (LCVP)-assisted hepatectomy is associated with decreased blood loss and lower transfusion rates. Concerns about its impact on renal function have prevented widespread application. This study was conducted to review the dynamics of renal function after LCVP-assisted hepatectomy. METHODS: A retrospective analysis of a prospective surgical database was carried out. Estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease (MDRD) equation. The RIFLE (risk-injury-failure-loss-end-stage) criteria were used to define postoperative biochemical acute kidney injury (bAKI). Occurrences of clinically relevant AKI (cAKI) were identified in the study center postoperative database. RESULTS: During the period 2003-2012, 2116 LCVP-assisted hepatectomies were performed. The median patient age was 61 years [interquartile range (IQR): 51-70 years] and 51% of patients were male. The median number of resected segments was two; resections involved from one to four segments. Median estimated blood loss was 300 ml (IQR: 200-600 ml). Rates of morbidity and 90-day mortality were 21% and 2%, respectively. Low baseline eGFR (<90 ml/min) was seen in 84% of patients; 29% of patients had eGFR of <30 ml/min. Postoperative bAKI was seen in 17% (n = 350) of patients. Biochemical AKI with low eGFR was seen in 336 patients, representing 16% of the whole cohort; 13% of patients had been at risk, 2% experienced injury and 1% experienced failure. Kidney function had normalized at discharge in 159 of these patients. Nine patients (<1%) developed postoperative cAKI. CONCLUSIONS: The majority of patients in the study cohort had low baseline eGFR. Biochemical alterations in eGFR are transient in the vast majority of patients after LCVP-assisted hepatectomy and their clinical impact is limited. The present data suggest that clinically relevant renal dysfunction is a very uncommon event in patients undergoing LCVP-assisted liver resection.

Astaxanthin from shrimp by-products ameliorates nephropathy in diabetic rats.

AIM: This study investigated the hypoglycemic and antioxidant effects of shrimp astaxanthin on the kidney of alloxan-induced diabetic rats. METHODS: Animals were distributed into four groups of six rats each: a control group (C), a diabetic group (D), a diabetic group supplemented with Astaxanthin (D+As) dissolved in olive oil and a diabetic group supplemented with olive oil (D+OO). In vitro antidiabetic effect was tested in plasma and kidney tissue. RESULTS: The group D of rats showed significant (P < 0.05) increase of glycemia, creatinine, urea and uric acid levels compared to those of the control group (C). Moreover, plasma and kidney malondialdehyde (MDA) and protein carbonyl (PCO) levels for the rats of the group D were significantly increased compared to the control group. Contrariwise, antioxidant enzyme activities, such as catalase (EC 1.11.1.6), superoxide dismutase (EC 1.15.1.1) and non-enzymatic levels of reduced glutathione, were significantly (P < 0.05) decreased in the plasma and kidney of diabetic rats compared to the control ones. The astaxanthin supplementation in rats diet improved the antioxidant enzyme activities and significantly decreased the MDA and PCO levels compared to diabetic rats. Indeed, no significant (P ≥ 0.05) improvement was observed for the fourth group (D+OO) compared to the control group (C). Histological analysis of kidney showed glomerular hypertrophy and tubular dilatation for the diabetic rats. For D+As rats, these histopathological changes were less prominent. CONCLUSIONS: Our results suggest that shrimp astaxanthin may play an important role in reduction of oxidative damage and could prevent pathological changes in diabetic rats suggesting promising application of shrimp astaxanthin in diabet treatment.

Second-line agents for glycemic control for type 2 diabetes: are newer agents better?

OBJECTIVE: While metformin is generally accepted as the first-line agent in treatment of type 2 diabetes, there are insufficient evidence and extensive debate about the best second-line agent. We aimed to assess the benefits and harms of four commonly used antihyperglycemia treatment regimens considering clinical effectiveness, quality of life, and cost. RESEARCH DESIGN AND METHODS: We developed and validated a new population-based glycemic control Markov model that simulates natural variation in HbA1c progression. The model was calibrated using a U.S. data set of privately insured individuals diagnosed with type 2 diabetes. We compared treatment intensification of metformin monotherapy with sulfonylurea, dipeptidyl peptidase-4 inhibitor, glucagon-like peptide-1 receptor agonist, or insulin. Outcome measures included life-years (LYs), quality-adjusted life-years (QALYs), mean time to insulin dependence, and expected medication cost per QALY from diagnosis to first diabetes complication (ischemic heart disease, myocardial infarction, congestive heart failure, stroke, blindness, renal failure, amputation) or death. RESULTS: According to our model, all regimens resulted in similar LYs and QALYs regardless of glycemic control goal, but the regimen with sulfonylurea incurred significantly lower cost per QALY and resulted in the longest time to insulin dependence. An HbA1c goal of 7% (53 mmol/mol) produced higher QALYs compared with a goal of 8% (64 mmol/mol) for all regimens. CONCLUSIONS: Use of sulfonylurea as second-line therapy for type 2 diabetes generated glycemic control and QALYs comparable with those associated with other agents but at lower cost. A model that incorporates HbA1c and diabetes complications can serve as a useful clinical decision tool for selection of treatment options.

Role of toxicogenomics in the development of safe, efficacious and novel anti-microbial therapies.

Over the last two decades, occurrence of bacterial resistance to commonly used antibiotics has necessitated the development of safer and more potent anti-microbial drugs. However, the development of novel antibiotics is severely hampered by adverse side effects, such as drug-induced liver toxicity. Several antibacterial drugs are known to have the potential to cause severe liver damage. The major challenge in developing novel anti-microbial drugs is to predict, with certain amount of probability, the drug-induced toxicity during the pre-clinical stages, thus optimizing and reducing the time and cost of drug development. Toxicogenomics approach is generally used to harness the potential of genomic tools and to understand the physiological basis of drug-induced toxicity based on the in-depth analysis of Metagenomic data sets, i.e., transcriptional, translational or metabolomic profiles. Toxicogenomics, therefore, represents a new paradigm in the drug development process, and is anticipated to play an invaluable role in future to develop safe and efficacious medicines, by predicting the toxic potential of a new chemical entity (NCE) in early stages of drug discovery. This review examines the toxicogenomic approach in predicting the safety/toxicity of novel anti-microbial drugs, and analyses the promises, pitfalls and challenges of applying this powerful technology to the drug development process.

[Side effects and risk profile of lithium: critical assessment of a systematic review and meta-analysis]. / Nebenwirkungs- und Risikoprofil von Lithium : Kritische Bewertung einer systematischen Übersicht und Metaanalyse.

Lithium is the only drug that obtained the highest level of recommendation for maintenance therapy in the recent German S3 guidelines on bipolar disorders. In addition it is the only drug with proven efficacy for the prevention of manic as well as depressive episodes in studies with a non-enriched design. Therefore, it is highly welcomed that The Lancet recently published a systematic review and meta-analysis on the risks and side effects of lithium. This is the most comprehensive review on this topic so far.The glomerular filtration rate and maximum urinary concentration ability are slightly reduced under lithium. More patients suffered from renal failure compared to controls; however, renal failure remains a very rare event. The review confirmed the well known suppressive effects of lithium on the thyroid. An increase of serum calcium could be observed relatively frequently, therefore, regular control of serum calcium under lithium therapy is recommended. A relevant increase in body weight is more frequent under lithium than under placebo but less frequent than under olanzapine. No statistically significant increase could be found for hair loss, skin disorders or major congenital abnormalities.Lithium treatment is a safe therapy when clinicians follow the established recommendations. Data indicate that a risk for renal failure exists especially in patients without regular monitoring or with too high lithium serum levels. A (subclinical) hypothyroidism is not an indication to stop administration of lithium but is an indication for l-thyroxin substitution therapy. In pregnancy the risks of continuing lithium should be balanced against the risks of stopping lithium together with the patient.

Clinical experience with low-dose continuous infusion of furosemide in acute heart failure: assessment of efficacy and safety.

INTRODUCTION: Clinical data are scarce for furosemide administered as a low-dose (<160 mg/24 hours) continuous intravenous infusion in acute heart failure (HF). Our purpose was to evaluate the efficacy and safety of low-dose continuous infusion of furosemide on diuretic response, renal function, and patient outcomes. METHODS: A retrospective study of patients with acute HF who received furosemide administered as a continuous infusion after initial therapy with intermittent boluses (usually 40-80 mg every 12 hours). End points included mean hourly urine output, incidence of acute renal injury, and outcome disparities of patients who developed acute renal injury. Comparison of patients with preserved and reduced left ventricular ejection fraction (LVEF) was also performed. RESULTS: The study included 150 patients (age 57 ± 13 years, male gender 61%, admission weight 87 ± 32 kg, LVEF 37 ± 15%, 28% preserved LVEF). Mean initial and maximum furosemide doses were 5.1 ± 1.1 mg/h and 6.2 ± 2.2 mg/h, respectively. Mean duration of therapy was 51.4 ± 67.5 hours. Continuous infusion of furosemide was associated with a significant increase in mean hourly urine output compared to baseline (150 ± 77 mL/h vs 116 ± 69 mL/h, P < .001). Acute renal injury developed in 19% of patients, with 70% of those occurring within the first 48 hours of therapy. Mean serum creatinine (baseline 1.55 ± 1.50 mg/dL vs at discharge 1.64 ± 1.61 mg/dL, P = .20) and estimated glomerular filtration rate (baseline 67 ± 39 mL/min vs at discharge 67 ± 43 mL/min, P = .89) did not significantly change over the course of the hospitalization. Development of acute renal injury was associated with poorer outcomes, higher furosemide dose, and longer duration of furosemide therapy. Diuretic response and safety were not different between patients with preserved or reduced LVEF. CONCLUSIONS: In patients with acute HF, furosemide administered as a low-dose continuous infusion was effective in achieving diuresis and was not associated with a detectable effect on renal function. This diuretic approach appeared to be similarly effective and safe in patients with preserved LVEF.

Valsartan plus hydrochlorothiazide: a review of its use since its introduction.

INTRODUCTION: This review focuses on the role of the fixed-dose combination (FDC) drug valsartan/hydrochlorothiazide (HCTZ) in the treatment of hypertension. Effective blood pressure control often is not achieved with monotherapy and, instead, requires combinations of drugs with different mechanisms of action to produce additive or synergistic effects. AREAS COVERED: FDC valsartan/HCTZ enhances not only efficacy for blood pressure control but also provides beneficial effects on target organs beyond that expected from arterial pressure reduction alone. Data describe key clinical trial experiences with the FDC, with particular attention to efficacy and tolerability. Literature searches of these various topics were conducted in January 2011. There is evidence of potential benefits with this combination associated with left ventricular hypertrophy, left ventricular dysfunction and renal disease. The FDC is an effective treatment for patients with hypertension and is superior to monotherapy than either drug alone. EXPERT OPINION: In addition to the benefits of each drug, valsartan/HCTZ's metabolic interactions reduce some of the negative effects of both compounds. With its increased simplicity, minimal side-effect profile and efficacy without a significant cost penalty, valsartan/HCTZ represents an excellent choice for antihypertensive therapy.