Mean Increase In Serum Creatinine Research Articles

A prospective study to estimate the incidence and pattern of adverse drug reactions to first-line antiretroviral therapy (tenofovir, efavirenz, and lamivudine).

Antiretroviral drugs are efficacious but are associated with long-term toxicities, drug interactions, and emergence of drug resistance. To study the incidence and pattern of adverse drug reactions in human immunodeficiency virus (HIV) patients receiving first-line antiretroviral therapy (ART) (tenofovir, efavirenz, and lamivudine (TEL) which was introduced by NACO in 2013. A prospective, single-center observational study that included 135 treatment-naive HIV patients who were started on fixed drug once-daily regimen (TEL). At baseline, detailed clinical history, body weight, waist-hip ratio, complete blood count, liver and renal function test, CD4 cell count were performed. Clinical monitoring for cutaneous, neuropsychiatric, and gastrointestinal side effects was done every month along with laboratory monitoring and anthropometric measurement for every 6 months. CD4 counts were measured at baseline and end of the study at 12 months. Out of 135 participants, 89 (65.9%) were males and 46 (34%) were females. The mean age and the mean duration of illness at inclusion were 35.10 ± 8.97 years and 1.2 ± 0.6 years, respectively. The mean increase in weight at baseline and at 12 months (57.55 ± 6.56 to 64.04 ± 8.2) was statistically significant (95% confidence interval [CI]: 4.35-8.62, P < 0.001). The mean CD4 counts at baseline were 309.73 ± 118.44 and increased after 12 months of treatment to 421 ± 129.4 which was statistically significant (95% CI: 81.54-140.99, P < 0.001). The mean difference in platelet count was statistically significant between baseline and 12 months (95% CI: 10.32-46.13, P = 0.002). The mean difference in serum urea levels at baseline and at 6 months (95% CI: 0.60-1.61, P < 0.001) as well as 12 months were statistically significant (95% CI: 0.08-1.03, P = 0.02). The mean increase in serum creatinine at baseline (0.75 ± 0.12) and at 12 months (0.97 ± 0.16) was also significant (95% CI: 0.21-0.28, P < 0.001). There was a significant difference between mean creatinine clearance at baseline and at 12 months (109.9 ± 13.75 to 99.33 ± 12.52, P < 0.0001). One patient discontinued treatment due to adverse effects while two patients were shifted to second-line antiretroviral treatment. Small sample size, single-center study and short follow-up period, long-term toxicities were not appreciated. Fixed drug combination with TEL as a first-line ART for HIV is a safe regime as we observed minimal side effects with current regimen.

Recurrent Urinary Tract Infection in Living Donor Renal Transplant Recipients and the Role of Behavioral Education Program in Management: A Single-Center Experience

Urinary tract infections (UTIs) are the most prevalent type of kidney transplant (KT) recipients. We aimed to investigate the incidence, causes, and clinical impact of early recurrent UTI post-living donor KT and to examine the role of behavioral education program in management. This retrospective cohort chart-review study included all KT recipients with recurrent UTI necessitating hospital admission between September 2017 and August 2021. All patients with recurrent UTI were subjected to behavioral education for a month. UTI was found in 14 of 145 patients (9.6%), with recurrent UTI in 11 (7.6%). A total of 93% of UTIs occurred during the first 6 months post-transplant and represented 52% of KT readmissions during the same period. A total of 64.3% of patients were older than 50 years. The mean (SD) length of hospital stay was 5 (2.5) days, with an equal incidence in both sexes. The most common bacterial isolates in early recurrent UTI were Escherichia coli in 80.9%. Both Extended-spectrum beta-lactamases and multidrug-resistant organisms (resistance in ≥3 drugs) were seen in 82.4% of isolates. Furthermore, the most effective antibiotic was meropenem, with 86.7% effectiveness. A total of 65% of UTIs were managed with a single antibacterial course. A total of 64.3% of patients were older than 50 years. In patients who developed UTI, the mean (SD) serum creatinine was 1.31 (0.52) mg/dL, with a mean increase in serum creatinine of 0.19 mg/dL on having the episodes; at 1 year post-transplant, serum creatinine declined to 1.23 (0.43) mg/dL. Four patients (36%) had no recurrence of UTI after behavioral education. The multidrug-resistant bacterial isolates account for 82.4% of the UTIs. Therefore, antibiotic prescription should follow the antimicrobial stewardship guidelines. Behavioral education significantly reduced the incidence of recurrent UTI.

Transarterial embolization of T1b and T2a renal cell carcinoma prior to percutaneous cryoablation: a retrospective comparative study.

To compare outcomes in patients with T1b and T2a renal cell carcinoma (RCC) treated with percutaneous cryoablation (PCA) who underwent transarterial embolization (TAE) of the RCC prior to PCA (TAE + PCA) to patients who were treated with PCA alone. Retrospective review of all adult patients with T1b (4.1-7cm) and T2a (7.1-10cm) RCC treated with PCA from 2008 to 2021. Data collected included age, sex, tumor diameter, RENAL nephrometry score, technical success, adverse events (AEs), changes in serum creatinine, local control, and recurrence rates. A p value of 0.05 was considered the threshold for statistical significance. 13 patients with 13 RCCs (mean age: 72.7 ± 10.4; 54% male) and 35 patients with 37 RCCs (mean age: 66.7 ± 10.6; 60% male) were included in the TAE + PCA and PCA groups, respectively. The TAE + PCA group had larger mean tumor diameter (5.7 ± 1.1cm vs. 4.7 ± 0.6cm; p < 0.0001) and higher mean RENAL nephrometry score (8.9 ± 1.1 vs. 7.8 ± 1.5; p = 0.02). There were no differences between the groups with respect to technical success of PCA (p = 0.46), local tumor control (p = 0.3), or mean number of procedures to achieve local tumor control (p = 0.85). Mean increase in serum creatinine was not significantly different between the two groups (p = .63). Major AEs were similar between the groups (p = 1); however, the TAE + PCA group had no major hemorrhagic AEs while the PCA alone group had three (8.3%). TAE + PCA in patients with T1b or T2 RCC is technically feasible without significant added detriment to renal function. This combined approach may help to reduce hemorrhagic AEs but larger patient cohorts are needed.

The role of serum creatinine in the early detection of ureteral injury after gynecological and obstetric surgery

Objective: Ureteral injury is a typical complication in pelvic surgery even though occurring not frequently. The goal of this study was to classify the importance of perioperative assessment of serum creatinine with clinical symptoms concerning the early detection of ureteral lesions after surgery. Patients and methods: The postoperative course of 7 gynecological and 2 obstetric patients raising doubt on ureteral integrity was analyzed, retrospectively, using medical records. Clinical symptoms (urinary production, flank pain), and the temporary changes of serum creatinine (µmol/L) as well as interdisciplinary diagnostic and interventional procedures were recorded. Glomerular filtration rate (GRF) was calculated using CKD-EPI formula (mL/min/1.73m2). Data analysis was done using descriptive statistics, Fisher’s exact test, non-parametric tests, and regression analysis (SPSS). Results: 6/9 patients presented with ureteral impairment. In 5/6 patients unilateral (n=2) and bilateral (n=3) obstructions were detected all deriving from anterior colporrhaphy. 1 patient exhibited ureteral kinking healing spontaneously. In patients affected by ureteral obstruction diminishing of urinary outflow occurred significantly earlier than flank pain (2.8±1.0 vs. 28.8±9.2 hours, p=0.03). Mean increase in serum creatinine and decrease of GFR was from 72±16 before surgery up to 160±34 and from 79±18 down to 30±6 (p=0.07), respectively, within 8–48 hours after surgery being significantly different from respective values in patients without obstruction (p=0.03). The increase in creatinine in patients with unilateral obstruction followed a logarithmic graph indicating interference between deteriorated ipsilateral and functionally compensating contralateral kidney after 24 hours. Conclusion: Perioperative measurement of serum creatinine is useful in testing ureteral integrity. However, the negative predictive value is superior to the positive predictive value. According to decreasing GFR highly important is a contemporary registration of the urine outflow in the first hours after surgery.

Associated Biochemical Changes and Outcome of Acute Kidney Injury in ICU Patients and Impact on Rifle Classes

Background: Acute Kidney Injury (AKI) has an independent impact on outcome, even after correction of all other variables in critically ill patients . AKI in ICU is often associated with different biochemical metabolic derrangements as a result of sepsis and non-renal organ system failure. Adequate informations are essential to develop effective measures to prevent and control morbidity and mortality. This study was done to detect AKI with their associated biochemical abnormalities and outcome among admitted patients in intensive care unit of BSMMU.&#x0D; Materials and methods: This prospective observational study was carried out in the Department of Nephrology, Bangabandhu Sheikh Mujib Medical University (BSMMU) Dhaka, during the period of September 2015 to October 2016. A total of 105 patients who were admitted in the Department of Anesthesia, Analgesia and intensive care medicine, BSMMU were included in this study. Patients who had pre-existing CKD, those on maintenance dialysis, with history of renal transplantation, Feature suggestive of chronic kidney disease were excluded. Baseline data were recorded accordingly. The study population was divided initially into two group (No AKI and AKI) then sub groups into risk, injury, failure and followed up till discharge or death.&#x0D; Results: Incidence of AKI was 37.14%. Mean increase in Serum creatinine was 64.53%, 132.87% and 375.01% from baseline for risk, injury and failure respectively. Subgroup analysis revealed risk (20%) injury (6.67%) and failure (10.47%). Associated acid base disorder, electrolytes imbalance, hepatic dysfunction, haemotogical disorder and hypoalbuminemia were found statistically significant between two groups. Logistic regression analysis showed that associated haematological abnormalities were positively correlated to the development of AKI. But among these no variables showed significant effect on RIFLE class population. Our study revealed overall morality is (53.8%). Mortality was highest in Failure class and most patients from risk class achieved renal recovery.&#x0D; Conclusion: The incidence of AKI in critically ill patient is high. Associated biochemical changes should be addressed properly to minimize fatality. RIFLE classification for AKI might help in recruitment of patients for predicting prognosis.&#x0D; JCMCTA 2021 ; 32 (2) : 53-58

Tenofovir Disoproxil Fumarate Is Superior to Entecavir in Reducing Hepatitis B Surface Antigen for Chronic Hepatitis B in China: 2-Year Comprehensive Comparative Result of a Matched Comparative Study.

Aim: Tenofovir disoproxil fumarate (TDF) and entecavir (ETV) are equally recommended as the first-line antiviral treatments for chronic hepatitis B (CHB) at present. We aimed to compare the long-term efficacy and safety between ETV and TDF therapy in CHB patients who had not received nucleoside analog treatment.Method: In this single-center retrospective study, 414 patients who received ETV (290 patients) or TDF (124 patients) therapy at our center from January 2017 to May 2019 were included. To reduce the imbalance of baseline variables, propensity score matching (PSM) was employed to yield 124 pairs of patients at a ratio of 1:1 based on the treatment regimen.Result: After PSM, the cumulative rate of patients who achieved complete virological response (CVR) was not different by drug therapy at each inspection time (1, 3, 6, 12, 18, and 24 months). Subgroup analysis on HBeAg status and level of HBV DNA demonstrated that evolution of proportion of achieving CVR was not significantly different between groups. Despite the insignificant incidence of HBsAg seroclearance in either group, patients in TDF group achieved higher on-treatment HBsAg decline at each inspection time (1, 3, 6, 9, 12, 18, and 24 months), 0.39, 0.51, 0.61, 0.64, 0.68, 0.76, and 0.91 log IU/mL, respectively; while the corresponding reduction were 0.27, 0.37, 0.40, 0.45, 0.48, 0.55, and 0.66 log IU/mL in ETV group (p < 0.05). In subgroup analysis, we found that the significant difference still existed in patients with high baseline HBsAg level (>3 log IU/mL). Additionally, the proportion of patients who achieved on-treatment HBsAg decline >1 log IU/mL in TDF and ETV group was 33.3 and 17.1% (p < 0.01) at the 12th month, 44.4 and 29.5% (p = 0.03) at the 24th month, respectively. Mean increase in serum creatinine from baseline was 0.10 and 0.08 mg/dL in TDF and ETV group (p = 0.11), with no patient experienced acute kidney injury.Conclusions: TDF has higher potency in reducing HBsAg than ETV in this study. Considering the effect still existed in patients with high HBsAg level (>3 log IU/mL), TDF might be a superior therapeutic regimen combining with its relatively safety.

Diarrhea in kidney transplant recipients: Etiology and outcome.

Diarrhea in kidney transplant recipients influences outcome of transplantation. Data from India in this regard are sparse and do not address the differential outcome of infective and non-infective diarrhea. We studied the demographic data, laboratory findings, treatment response, disease duration, and outcome of diarrhea in kidney transplant recipients, and the differential outcome between infective and non-infective diarrhea, if any. All kidney transplant recipients who were referred to the Division of Gastroenterology with diarrhea between June 2015 and February 2017 were prospectively included. Demographic, clinical and laboratory data, graft function, treatment administered, and outcome were noted, and the patients were followed up for 3months. Forty-seven patients (median age 45years, range 16-78; 34 men) with 64 episodes of diarrhea were studied. Thirty-three (51.5%) episodes were attributed to infections. Eleven (17%) were immunosuppressant-induced (mycophenolate 8, tacrolimus 2, cyclosporine 1). Twenty (31%) were due to other causes (antibiotics 6, laxatives 3, irritable bowel syndrome 3, sepsis 8). Fifty-three episodes (82%) had graft dysfunction during the diarrheal episodes. Mean increase in serum creatinine was 45% in the infectious diarrhea group and 95% in the non-infectious diarrhea group (p < 0.05). Median time to resolution of diarrhea was 3days. With improvement in diarrhea, return to pre-diarrhea creatinine levels occurred in 87% of episodes at 3months. One-half of episodes of diarrhea in kidney transplant recipients were non-infectious in origin. Seventeen percent were attributed to immunosuppressants, requiring dose modification. More than 80% were associated with worsening of graft function. Recovery of graft function to baseline was seen in a majority of cases with the resolution of diarrhea.

What are the maternal risks and pregnancy outcomes after kidney transplantation?

Background: Pregnancy after kidney transplantation should be considered as a major concern. Women with transplanted kidney were able to conceive for more than 50 years. Little studies are available highlighting the effects of transplantation on fetal and neonatal health.Purpose: This study was conducted with the purpose of identifying the maternal risks and pregnancy outcomes after kidney transplantation.Methods: Research design: A descriptive (non-experimental) design was used in conducting this study. Tools: Three tools were used during the course of this study, the interviewing questionnaire sheet, maternal risks assessment sheet and pregnancy outcomes sheet.Results: Regarding the maternal risks, there was a significant increase in mean serum creatinine, decrease in estimated glomerular filtration rate, increase in proteinuria, reported abortion rate was 16.3%, pregnancy induced hypertension rate was 20.9%; Among acquired infections, primary herpes simplex was very common with a rate of 18.6% while urinary tract infection rate was 39.5%. Among pregnancy outcomes, the mean gestational age was 35.4 ± 3, mean birth weight was 2,107.8 ± 567.7 and 74.4% of women delivered by C.s. 30.2% of delivered infants experienced incubator admission.Conclusions: The current findings succeeded in answering both study questions.Recommendation: Pregnant women with kidney transplantation should be followed-up more frequent than normal women for early detection of any risks and for obtaining favorable pregnancy outcomes. Women should be monitored frequently for kidney functions, early signs of pregnancy induced hypertension, acquired infections and other maternal risks reported by this study.

Effect of Gestational Age and Birth Weight on Serum Creatinine in the First Week of Newborn Life

ABSTRACT Introduction Serum creatinine concentration in health is essentially a function of muscle mass. We designed a prospective study to know the influence of gestational age and birth weight on creatinine in the first week of life. Materials and methods A total of 218 neonates were enrolled during a 2-year study period (May 2014—April 2016) at Kamineni Hospitals, Hyderabad, India. The study group was categorized based on gestational age [very preterm (VPT), preterm (PT), and term] and birth weight [very low birth weight (VLBW), low birth weight (LBW), and normal birth weight (NBW)]. The serum creatinine was assayed on the day of delivery in the mother and on days 0, 3, 5, and 7 in the neonates. The method of estimation of serum creatinine was by the modified kinetic Jaffe's reaction. Results Serum creatinine was high in the VPT neonates (28—33 weeks of gestational age) and VLBW neonates (&lt;1.5 kg) on day 0. An increase in mean serum creatinine was recorded on day 3 in VPT and VLBW neonates. Mean neonatal serum creatinine in all the subgroups based either on gestational age or birth weight decreased on day 7. Conclusion The serum creatinine in the first week of a newborn should be interpreted cautiously as the kidneys are in the process of maturation. High serum creatinine in neonates with insignificant muscle mass is a reflection of maternal serum creatinine coupled with an immature kidney. How to cite this article Ayyala VL, Devabathina N, Gurappagari P. Effect of Gestational Age and Birth Weight on Serum Creatinine in the First Week of Newborn Life. Indian J Med Biochem 2017;21(2):131-135.

A pilot goal-directed perfusion initiative is associated with less acute kidney injury after cardiac surgery

BackgroundWe sought to determine whether a pilot goal-directed perfusion initiative could reduce the incidence of acute kidney injury after cardiac surgery. MethodsOn the basis of the available literature, we identified goals to achieve during cardiopulmonary bypass (including maintenance of oxygen delivery >300 mL O2/min/m2 and reduction in vasopressor use) that were combined into a goal-directed perfusion initiative and implemented as a quality improvement measure in patients undergoing cardiac surgery at Johns Hopkins during 2015. Goal-directed perfusion initiative patients were matched to controls who underwent cardiac surgery between 2010 and 2015 using propensity scoring across 15 variables. The primary and secondary outcomes were the incidence of acute kidney injury and the mean increase in serum creatinine within the first 72 hours after cardiac surgery. ResultsWe used the goal-directed perfusion initiative in 88 patients and matched these to 88 control patients who were similar across all variables, including mean age (61 years in controls vs 64 years in goal-directed perfusion initiative patients, P = .12) and preoperative glomerular filtration rate (90 vs 83 mL/min, P = .34). Controls received more phenylephrine on cardiopulmonary bypass (mean 2.1 vs 1.4 mg, P < .001) and had lower nadir oxygen delivery (mean 241 vs 301 mL O2/min/m2, P < .001). Acute kidney injury incidence was 23.9% in controls and 9.1% in goal-directed perfusion initiative patients (P = .008); incidences of acute kidney injury stage 1, 2, and 3 were 19.3%, 3.4%, and 1.1% in controls, and 5.7%, 3.4%, and 0% in goal-directed perfusion initiative patients, respectively. Control patients exhibited a larger median percent increase in creatinine from baseline (27% vs 10%, P < .001). ConclusionsThe goal-directed perfusion initiative was associated with reduced acute kidney injury incidence after cardiac surgery in this pilot study.

Zonisamide-induced acute kidney injury.

Zonisamide is a new generation anticonvulsant indicated for the adjunctive management of partial seizures in adults [1]. The anticonvulsant activity of zonisamide is predominantly related to the inhibition of voltage-gated sodium action potentials and reduction of T-type calcium-channel currents. Because of its broad mechanism of action, zonisamide is used for many types of epilepsy and in patients whose epilepsy is resistant to other antiepileptic drugs (AEDs) [2,3]. There is insufficient evidence to demonstrate the superior clinical effectiveness of zonisamide compared to other adjunctive AEDs; however, its long half-life of 63 h supports convenient once- or twice-daily dosing. In vitro studies have demonstrated antioxidant and neuroprotective properties at therapeutic doses, suggesting that zonisamide may protect against ischemic damage and recurrent seizure activity [4]. Therapy is generally well tolerated; the most common reported adverse events include somnolence in 17% of patients and dizziness and anorexia in 13% of patients. Zonisamide may be an alternative in some patients over agents associated with weight gain, such as valproate or pregabalin [5,6]. Zonisamide is metabolized by acetylation to N-acetyl zonisamide and reduction to 2-sulfamoylacetyl phenol (SMAP) by cytochrome P450 isoenzyme 3A4. Zonisamide primarily undergoes renal excretion with 62% recovered from urine and 3% from feces following multiple doses [1,7]. The package insert was recently updated to reflect a risk of hyperchloremic, nonanion gap metabolic acidosis due to weak inhibition of carbonic anhydrase and increased renal excretion of bicarbonate. Furthermore, according to the manufacturer's label, zonisamide is not recommended for use in patients with renal failure (defined by the manufacturer as an estimated GFR < 50 mL/min); use of this agent in patients with renal insufficiency, defined as having a GFR < 60 mL/min according to the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative, requires slower titration and more frequent clinical monitoring for toxicities and adverse effects. Avoidance of use of zonisamide in individuals with end-stage kidney disease (e.g., GFR < 15 mL/min or on dialysis) is prudent based on manufacturer recommendations. Zonisamide has been associated with a statistically significant 8% mean increase in serum creatinine and blood urea nitrogen in clinical trials; however, this effect dissipated after therapy was discontinued. Of note, a case report has demonstrated hypersensitivity syndrome with acute kidney injury due to zonisamide; however; acute kidney injury has not been previously reported as an adverse event of zonisamide [7]. We present a case report that suggests that such an association exists as demonstrated by acute kidney injury in a patient on two separate occasions.

Comparison Of Renal Changes with Lopinavir/Ritonavir Plus Raltegravir or Tenofovir/Emtricitabine in c PROGRESS Study

ABSTRACT Aim: To assess renal function changes among 172 treatment-naive subjects treated with lopinavir/ritonavir (LPV/r) plus raltegravir (RAL) or LPV/r plus tenofovir/emtricitabine in the PROGRESS study, a prospective, randomized controlled trial. Patients &amp; methods: Serum creatinine, creatinine clearance and chronic kidney disease category were compared between groups. Results: Mean change from baseline to week 96 in creatinine clearance was smaller with LPV/r plus RAL versus LPV/r plus tenofovir/emtricitabine (-1.4 vs -7.3 ml/min; p = 0.035). Chronic kidney disease category improvement was more frequent and the mean increase in serum creatinine was smaller for the LPV/r plus RAL group. Differences in estimated renal function were also detected when the analysis was performed according to baseline demographics. Conclusion: Smaller renal function declines were observed with LPV/r plus RAL. The results from this study warrant further evaluation of the renal safety profile of nucleotide reverse transcriptase inhibitor-sparing regimens.

Evaluation of the Efficacy and Safety of a Hydrochlorothiazide to Chlorthalidone Medication Change in Veterans With Hypertension

BackgroundThere are few data available examining the clinical impact of switching patients from hydrochlorothiazide (HCTZ) to chlorthalidone for blood pressure management. ObjectivesThe goal of this study was to compare within-patient clinic blood pressure readings, serum electrolyte levels, and renal function markers before and after a medication change from HCTZ to chlorthalidone in a veteran population. MethodsThis was a retrospective, pre- and postmeasure, self-controlled study. Veterans Affairs Ann Arbor Healthcare System patients switched from HCTZ to chlorthalidone between January 1, 2001, and January 31, 2012, who had at least 1 follow-up clinic blood pressure reading recorded between 2 and 8 weeks from the date of the medication change were included in the study. Mean pre- and postmeasure values for systolic and diastolic clinic blood pressures, serum potassium, serum sodium, serum calcium, serum creatinine, and blood urea nitrogen were compared by using a 2-tailed, paired t test with a significance level (α) of 0.05. ResultsOf the 40 patients included in the study 95% were male, 65% were white, and the mean age was 64.9 (10.8) years. Both mean systolic (–15.8 mm Hg [95% CI, 8.9 to 22.6], P < 0.0001) and mean diastolic (–4.2 mm Hg [95% CI, 1.5 to 6.9], P = 0.0035) blood pressures showed statistically and clinically significant reductions after the medication change. A statistically significant decrease in mean sodium (–1.1 mmol/L [95% CI, 0.4 to 1.9], P = 0.003) and an increase in mean serum creatinine (0.06 mg/dL [95% CI, –0.09 to –0.02], P = 0.002) was observed; however, these changes may not be viewed as clinically significant by many practitioners. No statistically significant changes were observed in any of the other outcomes examined. Most patients (38 of 40) were taking at least 1 additional antihypertensive agent; 73% of patients were using ≥3 antihypertensive agents at the time of the medication change. ConclusionsIn patients with hypertension already taking HCTZ, switching to chlorthalidone seems to further reduce systolic and diastolic blood pressures without any clinically significant changes in renal function or electrolyte levels.

Increased Spironolactone in Advanced Heart Failure: Effect of Doses Greater than 25 mg/Day on Plasma Potassium Concentration

Background: Daily doses of spironolactone higher than 25 mg are rarely used in heart failure (HF) patients, presumably due to the concern for hyperkalemia. However, in advanced HF, doses ≥50 mg have been found to be necessary to produce natriuresis. The aim of the present study was to examine the safety of natriuretic doses of spironolactone (50–200 mg) on serum potassium concentration in New York Heart Association (NYHA) class III/IV HF patients over several weeks. Methods: 18 patients with advanced HF received 50–200 mg of spironolactone in addition to standard treatment. Serum electrolytes, BUN and serum creatinine were assessed at baseline, during increased doses of spironolactone and at the 1-month follow-up. Results: During a total of 738 patient-weeks, there was no significant increase in mean serum potassium (4.0 vs. 4.2 mEq/l) or serum creatinine (1.3 vs. 1.4 mg/dl). However, in 3 patients, spironolactone treatment was stopped due to a mean increase in serum creatinine (1.9 vs. 2.6 mg/dl) and in one of them, an increase in serum potassium (4.4 vs. 5.2 mEq/l) was noted. Conclusion: Increased doses of spironolactone are generally safe during outpatient follow-up in selected patients with advanced HF, who are receiving treatment with ACE inhibitors, beta-blockers, and loop diuretics.

Safety and tolerability of an immediate-release formulation of the oral direct thrombin inhibitor AZD0837 in the prevention of stroke and systemic embolism in patients with atrial fibrillation

AZD0837 is an investigational oral anticoagulant which is converted to the active form, AR-H067637, a selective direct thrombin inhibitor. The present study, a multicentre, randomised, parallel-group, dose-guiding study, assessed the safety and tolerability of an immediate-release formulation of AZD0837 compared with dose-adjusted warfarin in the prevention of stroke and systemic embolic events in atrial fibrillation (AF) patients. Two hundred fifty AF patients with at least one additional risk factor for stroke were randomised to receive either immediate-release AZD0837 (150mg twice daily [bid] or 350mg bid, blinded treatment) or dose-adjusted warfarin (international normalised ratio 2.0-3.0, open treatment) for three months. The safety and tolerability of 150mg bid AZD0837 appeared to be as good as that of warfarin. Total bleeding events were six with 150mg bid AZD0837, 15 with 350mg bid AZD0837 and eight with warfarin. Alanine aminotransferase elevations (>3xupper limit of normal) were infrequent, without apparent differences between treatment groups. A numerically higher incidence of serious adverse events was observed with 350mg bid AZD0837 compared with 150mg bid, with six of 13 being cardiac related, all with different diagnoses. An increase in mean serum creatinine of approximately 10% was observed in both AZD0837 groups, which returned to baseline after completion of therapy. There were no strokes, transient ischaemic attacks or cerebral haemorrhages with any of the treatments. In conclusion, the safety and tolerability of 150mg bid immediate-release AZD0837 appeared to be as good as that of dose-adjusted warfarin. However, larger studies will be needed to define the safety profile of AZD0837.

Comparison of Iodixanol and Ioversol for the Prevention of Contrast-Induced Nephropathy in Diabetic Patients After Coronary Angiography or Angioplasty

This study was designed to compare differences in the incidence of contrast-induced nephropathy (CIN) and changes in serum creatinine (SCr) level following iso-osmolar iodixanol or low-osmolar ioversol administration in diabetic patients undergoing coronary angiography, with or without percutaneous coronary intervention (PCI). A number of studies have indicated that iodixanol reduces the risk of CIN in patients with renal impairment, with or without diabetes. Diabetic patients may have some degree of renal dysfunction despite having a normal SCr level. The study included 250 consecutive diabetic patients undergoing coronary angiography with or without PCI. Those enrolled during the first 7 months of the study received ioversol and those enrolled during the following 11 months received iodixanol. The primary study endpoint was the incidence of CIN. Secondary objectives were to identify independent predictors of CIN and to determine the mean increase in SCr 72 hours after contrast injection. The overall incidence of CIN was 5.6%. The incidence of CIN was significantly lower with iodixanol than with ioversol (2.5% vs. 8.3%, respectively; odds ratio [OR]=0.255; 95% confidence interval [CI], 0.068-0.952; P=.047). A low estimated glomerular filtration rate (60.8+/-29 mL/min per 1.73 m2 in those with CIN vs. 75.3+/-25 mL/min per 1.73 m2 in those without; OR=0.975; 95% CI, 0.952-0.997; P=.03) and ioversol use were independent predictors of CIN. In diabetic patients undergoing diagnostic coronary angiography with or without PCI, the iso-osmolar contrast medium iodixanol was associated with a lower incidence of CIN than low-osmolar ioversol.

Prevalence and Predictors of Acute Renal Injury in Liver Transplant Recipients

Renal failure is a major factor impacting liver transplant outcomes. Renal functional impairment predicts decreased survival, leading to increased morbidity and mortality. The aim of this study was to estimate the incidence, risk factors, and resolution of acute kidney injury (AKI) among liver transplant recipients during the operative hospital stay. We analyzed data from 99 orthotopic liver transplantations (OLT) performed at our center in 2008. Posttransplantation occurrence of AKI was defined as an increase in serum creatinine (SCr) concentration of 0.3 mg/dL or more, namely, 1.5-fold from baseline. AKI was observed among 31.31% of liver transplant recipients (n = 31). The mean increase in SCr was 2.49 ± 0.78-fold from baseline. The mean posttransplant SCr level was 2.59 ± 0.92 mg/dL. Renal replacement therapy was introduced to 16.12% (n = 5) liver recipients developing AKI. Among them, 2 subjects (6.45%) died. The mean SCr level at the time of discharge from the hospital was 1.17 ± 0.57 mg/dL among the AKI group compared with 0.77 ± 0.32 mg/dL among the group without AKI. Pretransplant renal impairment expressed by an elevated SCr concentration (relative risk [RR] = 1.25; P = .0386) and treatment with exogenous vasoconstrictors during the operation (RR = 2.27; P = .016) were identified as risk factors for developing AKI after liver transplantation.

Prevalence, predictors and prognostic value of acute impairment in renal function during intensive unloading therapy in a community population hospitalized for decompensated heart failure

Chronic heart failure (CHF) is often associated with impaired renal function. Diuretics and vasodilators may lead to aggravated renal dysfunction (ARD), particularly among patients with decompensated CHF. Although the prevalence of ARD has been evaluated in patients awaiting heart transplantation, little is known about ARD in the community sample of CHF patients. Accordingly, we prospectively assessed the prevalence, predictors and prognostic value of ARD in 79 consecutive patients admitted to our general community hospital for decompensated CHF undergoing intensive unloading therapy (intravenous nitroprusside and furosemide). ARD was defined as a >or= 25% increase in serum creatinine between admission and maximal value of >or= 2 mg/dl. Sixteen patients (20%) developed ARD with a mean increase in serum creatinine of 31% (from 1.74 +/- 0.6 to 2.27 +/- 0.9 mg/dl). ARD persisted at 8-day evaluation in seven of 16 subjects (44%) whereas it was reversible in nine (56%). Lower creatinine clearance at baseline [exp beta = 0.93, 95% confidence interval (CI)=0.87-0.99] and the higher dose of furosemide (exp beta=1.02, 95% CI=1.01-1.03) emerged as independent predictors of ARD. During a follow-up of 11 +/- 8 months, death and hospitalization for worsening CHF occurred more frequently in ARD than non-ARD patients (69% versus 17%, P=0.0001; 69% versus 29%, P=0.003, respectively). Persistent ARD was a powerful independent predictor of long-term adverse outcome (odds ratio=11.1; 95% CI=1.12-36.1; P=0.04). Intensive unloading therapy is associated with the development of ARD in one-fifth of the community population hospitalized for decompensated CHF. The magnitude of this phenomenon is not greater than that observed in younger selected populations with advanced CHF, and depends on baseline renal function and increased diuretic dosage. ARD persisting after 8 days from starting intensive unloading is a powerful predictor of subsequent worsened clinical outcome.

Amphotericin B-related nephrotoxicity in low-risk patients

Amphotericin B (AmphoB) is the drug of choice for treatment of severe fungal illnesses; however, it is very nephrotoxic. Modified (less toxic) amphotericins are very expensive. In low-risk patients, saline loading would be enough to prevent significant loss of renal function. Patients with normal renal function and within the first 24 hours of treatment with AmphoB were prospectively enrolled in the study. Patients in intensive care units or who were using vasoactive drugs were excluded. Saline loads were infused before and after the AmphoB treatment. Blood and urine analyses were made at the beginning and at the end of the treatment. Serum creatinine was repeated 30 days after the end of the AmphoB treatment. The mean increase in serum creatinine in the 48 patients was 0.3 (0.18-0.41) mg/dL, due to a mean decrease of 25 (12.8-36.9) mL/min of creatinine clearance (CrCl). Acute renal failure, defined as an increase of more than 50% of the baseline creatinine, occurred in 15 patients (31%). Patients that were on antibiotics, in post-chemotherapy status or those submitted to bone marrow transplantation had the highest risk. Mean serum creatinine and the CrCl levels were no different from baseline values after 30 days. In low-risk patients, the use of AmphoB with prophylactic sodium chloride loading was associated with a small and reversible decrease in renal function. Due to its high cost the use of more expensive therapies for this type of patient does not seem to be justified.

Two-year results of multicenter phase III trials on the effect of the addition of sirolimus to Cyclosporine-based immunosuppressive regimens in renal transplantation

Randomized clinical trials conducted over 24 months and including nearly 1300 renal transplant patients compared the efficacy and safety of two dose levels of sirolimus versus azathioprine (United States) or placebo (Global) comparators administered with a cyclosporine (CsA) and prednisone (Pred) baseline regimen. Analysis of 24-month data revealed that patients in the 5 mg/d sirolimus groups experienced a significant delay in the onset and reduction in the incidence of acute rejection episodes compared with azathioprine (Aza) or placebo groups ( P = .02/ P = .001). Graft and patient survival rates and also the occurrence of transplant-related infections, lymphoproliferative disorders, or malignancies were similar among all treatment arms. Between 12 and 24 months, patients treated with 2 mg/d sirolimus displayed relatively stable mean serum creatinine values, namely 1.9–1.8 mg/dL for the US and 1.8–1.8 mg/dL for the Global ( P = NS) studies, which remained higher than those of the comparators. Both 5 mg/d groups showed an increase in mean serum creatinine during this interval, which was significantly higher than the value in both comparators at 24 months. Both sirolimus groups showed persistently elevated triglyceride levels compared with Aza-treated patients at month 24. The Global trial showed a less-pronounced difference in mean fasting triglyceride values compared with placebo. Data from both trials demonstrate that the addition of sirolimus to a CsA-Pred treatment regimen yielded a durable immunosuppressive effect associated with a progressive resolution of adverse side effects over time except for hyperlipidemia, which required continued countermeasure therapy.