Creatinine Clearance Levels Research Articles

Angiostatin overexpression is associated with an improvement in chronic kidney injury by an anti-inflammatory mechanism.

Angiostatin, a proteolytic fragment of plasminogen, is a potent anti-angiogenic factor recently shown also to have an inhibitory effect on leukocyte recruitment and macrophage migration. Because both angiogenesis and inflammation play key roles in the progression of chronic kidney disease, we evaluated the effect of angiostatin treatment in the rat remnant kidney model. Rats were pretreated for 4 wk with recombinant adeno-associated viruses expressing either angiostatin or green fluorescence protein. Chronic renal disease was then induced by a subtotal nephrectomy, and rats were killed 8 wk later for analysis. Angiostatin treatment was associated with significantly less proteinuria but no alterations in serum creatinine, creatinine clearance, and blood urea nitrogen levels. Treatment with angiostatin reduced renal peritubular capillary number and decreased urinary nitric oxide levels. Despite reducing capillary density, angiostatin diminished interstitial fibrosis in association with reduced macrophage and T-cell infiltration and renal monocyte chemoattractant protein-1 mRNA levels. In conclusion, angiostatin overexpression was associated with attenuated renal disease progression in a model of chronic kidney injury, likely because of its anti-inflammatory actions. However, its anti-angiogenic actions suggest countering effects that could partially offset its benefit in chronic kidney diseases.

Impact of Mild or Moderate Renal Insufficiency on the Intravascular Ultrasonic Analysis of Chronic Vascular Response to Paclitaxel-Eluting and Bare-Metal Stents (from the TAXUS IV, V, and VI Trials)

The presence of even mild renal insufficiency is usually associated with an increased rate of cardiovascular events after coronary stenting. The aim of this study was to evaluate the impact of mild to moderate renal insufficiency on the chronic vascular responses to the implantation of paclitaxel-eluting stents (PES; Taxus) and bare-metal stents (BMS). In the TAXUS IV, TAXUS V, and TAXUS VI trials, patients with serum creatinine levels >2.0 mg/dl were excluded. In the present analysis, 816 patients with serum creatinine levels <or=2.0 mg/dl had intravascular ultrasound images acquired after the procedures and/or at 9-month follow-up (406 with PES, 410 with BMS). Patients were stratified by level of creatinine clearance (Ccr; group 1: Ccr <40; group 2: 40 <or=Ccr <60; group 3: 60 or/=Ccr <80; group 4: Ccr >or=80 ml/min/1.73 m(2)). For all levels of Ccr, patients with PES compared with those with BMS had less intimal hyperplasia area (group 1: 0.97 +/- 0.98 vs 2.94 +/- 1.89; group 2: 0.94 +/- 0.86 vs 2.30 +/- 1.21; group 3: 0.99 +/- 1.02 vs 2.53 +/- 1.29; group 4: 0.87 +/- 0.95 vs 2.12 +/- 1.29 mm(2), all p values <0.0001) and greater increases in peristent plaque and media area (group 1: 0.90 +/- 0.98 vs -0.02 +/- 0.98 mm(2), p = 0.03; group 2: 0.57 +/- 1.43 vs 0.20 +/- 1.14 mm(2), p = 0.11; group 3: 1.20 +/- 1.95 vs 0.02 +/- 1.17, p <0.0001; group 4: 0.35 +/- 1.44 vs -0.19 +/- 1.08 mm(2), p = 0.08). Neointimal growth and vessel remodeling were not affected by variations in Ccr after either BMS or PES implantation over the range studied. The incidence of incomplete stent apposition at follow-up was lowest in patients with the greatest renal impairment after BMS and PES implantation. In conclusion, neointimal proliferation was less prominent and expansive vessel remodeling was more prominent after PES than BMS implantation, independent of the severity of renal dysfunction.

Impact of moderate or severe renal insufficiency on long-term outcomes in patients undergoing drug-eluting stent based coronary intervention

Aims We sought to examine the impact of moderate or severe renal insufficiency (RI) on long-term clinical outcomes after successful percutaneous coronary intervention (PCI) with drug-eluting stent implantation. Methods All-cause mortality and major adverse cardiac events were prospectively determined for 1174 patients after successful PCI with drug-eluting stent implantation. Based on estimated creatinine clearance (CrCl) levels, long-term outcomes were compared between patients with CrCl < 60 ml/min (RI group; n = 460) and those with CrCl ≥ 60 ml/min (control group; n = 714). Hazard ratio for mortality and myocardial infarction was further evaluated for patients with severe (CrCl < 30 ml/min), moderate (CrCl 30–59 ml/min), mild RI (CrCl 60–89 ml/min) and normal renal function (CrCl ≥ 90 ml/min). Results Patients in RI group were older, lower body weight and hemoglobin, more female gender, and less cigarette smokers than those in control group. During follow-up (averaged 19.2 months) after successful PCI, all-cause death (8.3% vs. 1.5%, P < 0.001), cardiac death (5.7% vs. 1.1%, P < 0.001) and occurrence of non-fatal myocardial infarction (2.2% vs. 0.4%, P = 0.005) were significantly higher, but rate of target vessel revascularization (TVR) was lower (5.7% vs. 9.6%, P = 0.017) in RI group than in control group. Multivariate analysis revealed that CrCl < 60 ml/min, diabetes, left ventricular ejection fraction < 0.50 and anemia were independent risk factors for mortality and non-fatal myocardial infarction. Compared with patients with normal renal function, hazard ratio for a composite of mortality and myocardial infarction was 1.079 ( P = 0.907), 5.067 ( P = 0.007) and 8.828 ( P = 0.002) in patents with mild, moderate and severe RI, respectively. Conclusions Irrespective of whether drug-eluting stent implantation reduces TVR, the presence of moderate or severe RI is still associated with unfavorable long-term outcomes.

Tamoxifen is safe and effective in gynecological cancer patients with renal dysfunction

Tamoxifen has been found to be safe and effective in gynecological cancer patients with normal renal function. However, to our knowledge, no data exist regarding its effectiveness and toxicity in gynecological cancer patients with chronic kidney disease (CKD). Therefore, we retrospectively evaluated the effects of tamoxifen in patients with recurrent gynecological cancer and CKD. We collected clinical and demographic data for all patients. CKD was defined as a creatinine clearance (CrCl) level of less than 90 mL/min/1.73 m2, in accordance with the National Kidney Foundation Kidney and Dialysis Outcomes Quality Initiative, and further categorized as mild, moderate, or severe (CrCl levels of 60–89, 30–59, and &lt; 30 mL/min/1.73 m2, respectively). Twenty-nine patients were included in the study— 22 with epithelial ovarian cancer, 4 with peritoneal cancer, and 3 with fallopian tube cancer. Thirteen patients had mild CKD, 13 had moderate, and 3 had severe. Most patients had been treated with 20 mg/day of tamoxifen every 4 weeks. The median duration of treatment was 5 months (range, 1–52 months). The overall complete response, partial response, stable disease, and disease progression rates were 0%, 10%, 41%, and 48%, respectively. Twenty-one percent of patients experienced hot flashes, and 7% experienced nausea. No major adverse reactions occurred. These findings were similar to those for gynecological cancer patients with normal renal function. In conclusion, 20 mg/day of tamoxifen is safe and effective in gynecological cancer patients with CKD.

Determinants of Target Organ Damage in Black Hypertensive Patients Attending Primary Health Care Services in Cape Town: The Hi-Hi Study

In South Africa (SA) cardiovascular disease (CVD) is the second leading cause of death, with hypertension (HTN) being the predominant contributor to morbidity and mortality associated with this disease. We examined the prevalence and determinants of target organ damage (TOD) among urban black hypertensive South Africans attending primary health-care (PHC) services in Cape Town. Patients on HTN treatment, 35-65 years of age, participated in this cross-sectional study. Data relating to sociodemographic factors, medical history, lifestyle patterns, and HTN care regimens were obtained. Blood and urine samples were analyzed and electrocardiographs (ECGs) were recorded. Sokolow-Lyon and Minnesota Code (MC) criteria were used for identifying left ventricular hypertrophy (LVH). Reduced creatinine clearance (Cockroft-Gault), microalbuminuria, proteinuria, and elevated serum creatinine levels were used for identifying "renal impairment by any criteria" (RIC). Ischemic ECG patterns were classified in terms of MC criteria. Multivariate logistic regression analyses were carried out to identify variables independently associated with TOD. The study sample comprised 403 participants. RIC was identified in 26%, LVH in 35%, and ischemic ECG patterns in 49% of the participants. Uncontrolled HTN and an absence of diabetes were associated with LVH as per Sokolow-Lyon criteria. Older age, the presence of diabetes, and the use of beta-blockers were associated with RIC. Ischemic ECG patterns were associated with uncontrolled HTN, older age, male gender, the consumption of less alcohol, and higher levels of low-density lipoprotein cholesterol (LDL-C). TOD is common in this group of black hypertensive patients attending PHC sites. Uncontrolled HTN and older age were most often associated with TOD. Reducing the burden of TOD will require improving the quality of HTN care in PHC settings.

An Underappreciated Problem in Renal Transplant Recipients: Anemia

Purpose Posttransplant anemia (PTA) is associated with a higher risk of cardiac mortality, which is the most frequent cause of death among renal transplant recipients. In this study, we sought to determine the prevalence and causes of PTA among Turkish patients. Patients and methods The study included 75 (52 male, 23 female) adults. Anemia was defined as an hemoglobin (Hb) level ≤ 13 g/dL for men and ≤ 12 g/dL for women. Results The prevalence of PTA was 49.3% at a mean duration of 60.45 months after renal transplantation. The most frequent causes of PTA were erythropoietin (EPO) and iron deficiency. The mean Hb level of 12.76 ± 2.31 g/dL was significantly higher in male compared to female patients (13.26 ± 2.31 g/dL vs 11.64 ± 1.93 g/dL, P = .005). The Hb value was positively correlated with creatinine clearance and serum albumin level, and negatively correlated with serum creatinine level, the amount of proteinuria, and cyclosporine level. Creatinine clearance and serum albumin level were found to be an independent risk factors for PTA upon multivariate analysis. Only 12 of 37 anemic patients received treatment for anemia: 5 (13.5%) with EPO and 7 (18.9%) with iron preparations. Conclusion PTA a common complication was unfortunately neglected in this setting. Impaired renal allograft function and decreased serum albumin were major risk factors for PTA. Increased cyclosporine levels were also correlated with decreased Hb concentrations.

Medication Dosing and Renal Insufficiency in a Pediatric Cardiac Intensive Unit

Appropriate drug dosing in renal insufficiency is an important consideration to optimize therapeutic outcomes and to minimize toxicity. In this issue of the journal, Moffett and colleagues [4] remind health care providers of the clinical benefits of pharmacist involvement on drug dosing for patients with renal insufficiency in a pediatric cardiac intensive care unit. The authors adapted a wellknown list of drugs primarily excreted by the kidneys for patients with renal impairment. They noted that patients who required medication adjustments were significantly younger compared to those who did not require medication adjustment. Moffett et al. also report that clinical pharmacist consultation for prescribing drugs in the pediatric intensive care setting would be associated with shorter length of stay, lower costs, and lower rate of medication errors. Clinical pharmacist services in the hospital setting are proven to be beneficial. Such services are labor-intensive and require collecting patient data, calculating a creatinine clearance (CrCl) level, and contacting a physician to change the order to increase the likelihood of accurate medication selection and dosing based on an estimated CrCl. A rational approach to drug dosing in patients with renal impairment begins with a thorough history and physical examination. Particularly important is the history of previous drug allergy or toxicity and the use of concurrently prescribed or nonprescription drugs. Physical assessment should include estimating the extracellular fluid volume (ECFV); the presence of edema or dehydration alters drug dose. Body weight and height need to be measured, and the ideal body weight should be calculated and drug doses estimated accordingly. The renal excretion of drugs depends on glomerular filtration and renal tubular secretion and reabsorption. The glomerular elimination of drugs also depends on the molecular size and protein binding of the agent. Although protein binding decreases the filtration of drugs, it may increase the amount that the renal tubule secretes. When glomerular filtration is impaired by renal disease, the clearance of drugs that are eliminated primarily by this mechanism will be decreased and the plasma half-life of the drugs prolonged. The secretion of drugs eliminated by active transport systems in the renal tubule also will be affected in patients with renal disease. As the rate of CrCl decreases, drugs dependent on renal tubular excretion for elimination will be excreted more slowly. Furthermore, because the proximal tubular secretion of some agents is carrier mediated and capacity limited, concurrent use of multiple drugs eliminated by renal tubular secretion may saturate the transport system. Renal insufficiency alters both the disposition of drugs in the body (pharmacokinetics) and tissue responses to drugs (pharmacodynamics). If drugs or their metabolites are excreted by the kidneys, they can accumulate in patients with renal insufficiency and cause adverse effects. When the necessity for drug therapy has been established, renal function should be measured. Because the rate of elimination of drug excreted by the kidneys is proportional to the glomerular filtration rate (GFR), the serum creatinine or CrCl should be used to estimate renal function. The Schwartz equation can be used to estimate CrCl in children and adolescents [5]. However, estimating GFR from the serum creatinine assumes that renal function is stable and that the serum creatinine measurement is constant. With changing renal function, the serum creatinine level will no F. Assadi (&) Rush University Medical Center, Chicago, IL, USA e-mail: Ra-Id_Abdulla@rush.edu

Reducing Preventable Medication Safety Events by Recognizing Renal Risk

Evidence suggests that medication safety may be improved through more accurate assessment of renal function and appropriate dosing of renally cleared medications. The purpose of this article is to describe patient renal risk groups, associated medication errors, and ways that nurses can improve renal assessment. Medication safety data were collected through voluntary reporting, computerized triggers, pharmacist surveillance, and retrospective chart review. Data were analyzed across 3 renal risk groups. Findings indicated that regarding the detected medication errors, elderly women were more likely to have hidden renal risk and that prescribing errors involving a wrong dose occurred more often in patients with high and hidden renal risk. Antibiotic and diabetic medications were the primary drug categories involved in these medication errors. Results indicated that identification of patients with hidden renal risk can be improved by routinely assessing serum creatinine and estimated creatinine clearance levels during renal assessments. Clinical nurse specialists can use this evidence to promote safer nursing care of renal patients.

Short-Term Efficacy of Enzyme Replacement Therapy in Korean Patients with Fabry Disease

Fabrazyme has been widely used for treatment of Fabry disease since its approval by the U.S. Food and Drug Administration in 2003. This study was undertaken to assess the short-term efficacy and safety of enzyme replacement therapy (ERT) for Fabry disease in Korea. Eight male patients and three female symptomatic carriers aged 13 to 48 yr were included. Fabrazyme was administered by intravenous infusion at a dose of 1 mg/kg every 2 weeks. Plasma and urine globotriaosylceramide (GL-3) levels, serum creatinine, creatinine clearance, and 24-hr urine protein levels were measured every 3 months. Kidney biopsies, ophthalmologic exams, and pure tone audiometry were performed before and 1 yr after ERT. Kidney function, including serum creatinine, creatinine clearance, and the 24-hr urine protein level, remained stable during ERT. Plasma and urine GL-3 levels were reduced within 3 to 6 months of ERT initiation. Microvascular endothelial deposits of GL-3 were decreased from renal biopsy specimens after 1 yr of treatment. The severity of sensorineural hearing loss and tinnitus did not improve after ERT. ERT is safe and effective in stabilizing renal function and clearing microvascular endothelial GL-3 from kidney biopsy specimen in Korean patients with Fabry disease.

塩酸バンコマイシン注初回投与設計における血清シスタチンＣの有用性に関する検討

In clinical practice,the glomerular filtration rate (GFR) is often estimated from serum creatinine (Scr).However,several recent studies have shown that serum cystatin C (SCysC) is a better parameter for the diagnosis of early impaired renal function than Scr.In this study,we measured SCysC and 24 hour creatinine clearance (CLcr) levels in 102 in-hospital patients to determine if there was a relationship between the 2 parameters,finding that 1/SCysC was significantly positively correlated with CLcr.From the results,we derived the simple formula CLcr=65.45/SCysC-3.36(r=0.79,p<0.01).Using a formula including the one above we predicted vancomycin concentrations based on SCysC and compared them with actual vancomycin concentrations in 17 patients.Our analysis of the results showed that the formula had greater prediction accuracy for vancomycin concentrations than the Cockcroft&Gault equation which is based on Scr.These results suggest that SCysC is a better marker of renal function for setting initial doses of vancomycin and other drugs that are renally excreted.

The Effect of Sirolimus in the Development of Chronic Allograft Nephropathy

Purpose The effect of sirolimus (SRL) in renal function was studied in renal transplant recipients. Patients and Methods We studied 20 patients who underwent live related kidney transplantation 1 to 2 years prior under cyclosporine (CsA) treatment and displayed serum creatinine values between 2 and 3 mg/dL. The patients were randomized into 2 groups prospectively. The calcineurin inhibitors (CNI) group continued taking CsA; the SRL group underwent a switch from CsA to SRL. Biopsies were performed to assess chronic allograft nephropathy (CAN) findings and TGFβ1 in the transplanted kidneys at the beginning and the end of the study. Creatinine clearance, serum creatinine, and proteinuria values were detected in the beginning as well as at 1, 3, 6, and 12 months later. Results At the beginning of the study, the creatinine clearance and serum creatinine levels were 52.21 mL/min and 2.05 mg/dL in the CNI group and 47.76 mL/min and 2.13 mg/dL in the SRL group, respectively. At 12 months, these values were 48.11 mL/min and 2.57 mg/dL in the CNI group and 50.45 mL/min and 2.12 mg/dL in the SRL group, respectively. Creatinine clearance values between the 2 groups at 12 months were statistically different. Although it was not significant, there was a tendency toward decreases inflammatory infiltration and TGFβ1 levels in the SRL group compared with the CNI group on the second biopsies. Conclusion Pathologic findings of CAN development, serum creatinine, and creatinine clearance values were ameliorated in the SRL group. We concluded that SRL positively affected long-term graft survival.

Clinical Aspects and Risk Factors of Nosocomial Stenotrophomonas maltophilia Bacteremia Episodes in a Turkish Intensive Care Unit

Stenotrophomonas maltophilia is an important nosocomial pathogen with increasing frequency in recent years, especially in immunocompromised and clinically debilitated patients. The aim of this study is to describe the characteristics of 35 episodes of S. maltophilia bacteremia at Celal Bayar University hospital in Turkey over a 3-year period from January 2003 to December 2005. Cases were identified with microbiology laboratory records and clinical data were collected from the medical record of each patient. The source of bacteremia was central venous catheter (CVC) in 65.7% (23) and respiratory tract infection in 2.9% (1) of episodes while the source of bacteremia was unknown in 11 (31.4%) episodes of bacteremia. Factors significantly associated with mortality were age of ≥65 years, APACHE score of ≥16, the presence of the total parenteral nutrition, anemia, low creatinine clearance level and shock. The most sensitive antibiotic was found as trimethoprim-sulfamethoxazole (91.4%) in antibiotic susceptibility testing of the isolates. Susceptibilities of piperacillin-tazobactam and netilmicin which frequently used antibiotics as an empirical therapy were 62.8% and 68.6%, respectively.

Efficacy and Safety of Colistin for the Treatment of Infections Caused by Multidrug-Resistant Isolates of Pseudomonas Aeruginosa Sensitive to Colistin in Patients with Haematological Malignancy; a Matched-Pair Analysis.

Infections due to multidrug-resistant (MDR) Gram-negative bacteria have been increasing and they are an important cause of nosocomial morbidity and mortality, especially in immunocompromised patients. In order to determine efficacy and safety of colistin (colistimethate sodium) use in the treatment of MDR Pseudomonas aeruginosa sensitive to colistin, a comparison of renal function, other toxicities, and outcome of therapy was done between a group of patients treated with colistin and patients treated with other antipseudomonas drugs as control group. A group of 26 patients that was hospitalized in our institution between February 2002 and December 2006 and treated with intravenous colistin for an infection caused by MDR P.aeruginosa was compared in a matched-pair analysis to a group of 26 patients treated with other antipseudomonas drugs. Patients were 52% male and 48% female; mean age was 37 years (range 17–63). All of the patients were treated for haematological malignancy, most received intensive chemotherapy regimens (44%), 19% received allogeneic and 31% autologous transplants. Groups of patients did not differ in age, sex, disease, or kind of treatment received. All of the patients in both groups had clinical signs of sepsis; in 69% of patients from colistin group and 84% from control group P.aeruginosa was isolated from blood, and in 27% and 12% it was isolated from skin lesions that had clinical presentation of echtyma gangrenosum, respectively. Patients treated with colistin received 3 MU of colistin every 8 hours for a mean (± SD) duration of 12.5 (± 5.4) days. Due to nature of their disease, and severity of infections, all of the patients received more than two other possibly nephrotoxic drugs; in colistin group 4 other concomitant drugs, on control group 3; most frequently vancomycin, cefepime, amikacine, garamycine and amphotericine B deoxycholate was used. Of 26 patients receiving colistin, 76.9% of patients had the drug discontinued after successful clearance of infection, while in control group 65.4% of patients had the drug discontinued due to same reason. Only one patient had displayed neurological toxicity (Jacksons attack with secondary generalisation), but the drug was not discontinued, dose was modified, patient had no further attacks. There was no statistically significant difference in the level of serum creatinine, creatinine clearance (calculated), or potassium levels between prior to therapy and after treatment discontinuation between groups. One patient treated with colistin developed renal failure and was subjected to continuous venovenous hemodiafiltration; of note is that at the time colistin introduction patient already had impaired renal function. In one patient drug was discontinued due to suspected allergic reaction. No other adverse events of colistin therapy were noted. Colistin is an effective antimicrobial drug for the treatment of severe infections caused by MDR P.aeruginosa in haematological patients. The safety profile observed is acceptable in these severe life-threatening infections, in matched-pair analysis it did not display greater toxicity than other antipseudomonas drugs. Further studies are needed to better address the treatment of MDR P. aeruginosa, naimely the optimal dose and schedule, also route of administration of colistin, as well as drug-to-drug interactions.

Assessment of Individual Characteristics on the Pharmacokinetics of Oral Busulfan in Adults Patients Undergoing Hematopoietic Stem-Cell Transplantation.

Introduction Busulfan is one of the most commonly used drugs in preparative regimens for hematopoietic stem-cell transplantation. Administration of accurate doses of busulfan is critical to limit toxicity while ensuring maximum efficacy. Indeed, busulfan pharmacokinetics exhibit important interpatient variability and its therapeutic interval is narrow.Objective To determine the impact of glutathione-S-transferase (GST) genotype and individual characteristics on the pharmacokinetics of oral busulfan in adult patients.Methods An observational retrospective study was performed. Individual characteristics were obtained from the medical charts of adult patients who received oral busulfan between June 2003 and May 2007. Genotype for the enzyme GST A1 was determined in patients for whom consent was available. Linear regression analysis was used to identify the variables that have significant impact on oral clearance of the first dose of busulfan. Oral and intravenous pharmacokinetics were also compared in patients presenting between November 2006 and May 2007.Results Oral clearance on the first dose of busulfan was available for 104 of the 106 eligible patients. Lean body weight (LBW) was used to determine the dose and was a significant predictor of oral clearance (r = 0,61; r2 = 0,37). No added precision was obtained with the addition of age, bilirubin and hepatic transaminase levels (r = 0,62; r2 = 0,38). GST genotype was determined for 87 patients and an increase in precision is obtained when adding GST genotype to LBW for prediction of oral clearance (r = 0,65; r2 = 0,43). The impact of GST genotype was found to be independent of all other variables considered. The model that includes LBW, GST genotype, age, bilirubin and hepatic transaminase levels provides little further precision (r = 0,67; r2 = 0,45). No significant impact was identified when considering the following variables: gender, creatinine clearance, albumin, lactate deshydrogenase and alkaline phosphatase levels, prior history of chemotherapy and/or radiotherapy, concomitant use of acetaminophen or antifungal drugs. The impact of GST genotype (*A wild-type allele, *B variant allele with reduced activity) on oral clearance was also evaluated. A significant difference in busulfan clearance between individuals with the *A/*A genotype and individuals with the *B/*B genotype was observed (p = 0,003; ANOVA and Bonferroni). In the prospective study, eight patients agreed to receive their second dose of busulfan via the intravenous route. Oral clearance was a good estimation of absolute clearance (Student's t-test for mean difference p = 0,573; r = 0,963). Volume of distribution of busulfan was an excellent predictor of oral clearance for the 8 patients (r = 0,96; r2 = 0,93) and LBW was an adequate predictor of volume of distribution (r = 0,94; r2 = 0,88).Conclusion An increase in precision could be obtained by adjusting the busulfan dose with LBW and GST genotype rather than LBW alone. No other individual patient characteristic was identified that influences significantly the pharmacokinetics of oral busulfan. More than 50% of intersubject variability in busulfan oral pharmacokinetics remains unexplained even after considering all above variables. Estimation of volume of distribution may represent a very innovative and promising avenue to more closely predict busulfan dosage.

Potential adverse effects of a low-dose aspirin-diuretic combination on kidney function

Low-dose aspirin and diuretics are commonly co-utilized in patients with cardiovascular diseases. The objective of this study was to investigate the effects of a low-dose aspirin-diuretic drug combination on renal function. In this cross-sectional retrospective study, all patients, excluding those on renal dialysis, admitted to the Internal Medicine Department of the Al-Watani Hospital, Nablus, Palestine, were included in the study. Medical data were obtained from patients' medical files. Estimation of creatinine clearance was carried out using the Cockcroft-Gault equation. Patients on the target drug combination were compared with patients who were not receiving the target drug combination. An independent paired t-test and 1-way ANOVA were used to test for significance between groups. Statistics were carried out using the Statistical Package for Social Sciences (SPSS), version 13. A total of 340 subjects (54.4% men) were included in the study. There were 90 patients on the target drug combination and designated as the study group. Of the remaining 250 patients comprising the control group, 114 received none of the target drugs and 136 received only one target medication. There was a significant (p < 0.001) difference in the levels of creatinine clearance between the two groups. Patients on the target drug combination had significantly lower creatinine clearance levels than those in the control group. Men in the study group had lower creatinine clearances than men in the control group and similar results were found for women. Patients in the study group with > or = 2 chronic diseases, had lower creatinine clearances than patients in the control group with > or = 2 chronic diseases. Similar results were found in patients with < 2 chronic diseases. Administration of a low-dose aspirin-diuretic drug combination was associated with significantly lower creatinine clearance levels. This finding was independent of gender and the number of chronic diseases present. Monitoring kidney function in patients receiving this drug combination is recommended.

Role of N-Acetylcysteine on Renal Function in Patients After Orthotopic Heart Transplantation Undergoing Coronary Angiography

Introduction The aim of this study was to assess nephroprotective influence of intravenous N-acetylcysteine (NAC) on renal function after radiocontrast use in calcineurin inhibitor–treated patients after orthotopic heart transplantation (OHT). Materials and Methods We analyzed the results of 112 consecutive coronary angiography examinations (CAG). All patients received intravenous 500 mL multielectrolyte fluid (PWE) before catheterization. Group I of 55 randomly selected cases in addition were treated with 300 mg of NAC. The other 57 cases (group II) received only hydration. After catheterization, we administered 500 mL 0.9% saline with 20 mg furosemide. A nonionic, low-osmolality contrast agent (OPTIRAY) was used for all catheterizations. All patients underwent measurements of serum creatinine and creatinine clearance levels before and after the procedure (CREA0, CREA1, CC0, and CC1, respectively). We assessed the influence of NAC on CREA1 and the relative change of CREA1/CREA0 and CC1/CC0 ratios. Results In groups I and II we noticed decreased CC0 in 17 versus 22 cases (31% vs 39%), a relative change of CREA1/CREA0 ratio of 0% versus −3.95% and of CC1/CC0 ratio 0% versus 4, 11%, respectively. CIN was not recognized in any patient. None of the differences was significant. Conclusion Intravenous NAC (300 mg) along with hydration before radiocontrast use had no impact on renal function in OHT patients undergoing CAG. It seems that there is no need for an additional preventive strategy apart from hydration and a small volume of low osmolar contrast in the majority of patients.

Protective Effect of Heat-Processed American Ginseng against Diabetic Renal Damage in Rats

We investigated the effects of American ginseng (AG) and heat-processed American ginseng (H-AG) on diabetic renal damage using streptozotocin (STZ)-induced diabetic rats in this study. The diabetic rats showed a loss of body weight gain, and increases in kidney weight, food intake, water intake, and urine volume, whereas the oral administration of H-AG at a dose of 100 mg/kg of body weight per day for 20 days attenuated these diabetes-induced physiological abnormalities. Among the renal function parameters, the elevated urinary protein levels in diabetic control rats were significantly decreased by the AG or H-AG administrations, and the decreased creatinine clearance level was significantly increased in H-AG-administered rats. In addition, the markedly high serum levels of glucose and glycosylated protein in diabetic control rats were significantly decreased by the administration of H-AG, implying that H-AG might prevent the pathogenesis of diabetic complications caused by impaired glucose metabolism and glycosylation of serum proteins. Although no significant ameliorations were shown in overexpressed protein expressions related to diabetic oxidative stress by the AG or H-AG administrations, the accumulation of N (epsilon)-(carboxymethyl)lysine and receptors for advanced glycation endproduct (AGE) expressions were significantly reduced by the administration of H-AG. On the basis of these results, we found that AG and H-AG inhibit AGE accumulation in diabetic rat kidney by their hypoglycemic and renal function ameliorating effects, and this effect was stronger in the H-AG-administered group than in the AG-administered group. These findings indicate that H-AG may have beneficial effect on pathological conditions associated with diabetic nephropathy.

Tamoxifen is safe and effective in gynecological cancer patients with renal dysfunction

Tamoxifen has been found to be safe and effective in gynecological cancer patients with normal renal function. However, to our knowledge, no data exist regarding its effectiveness and toxicity in gynecological cancer patients with chronic kidney disease (CKD). Therefore, we retrospectively evaluated the effects of tamoxifen in patients with recurrent gynecological cancer and CKD. We collected clinical and demographic data for all patients. CKD was defined as a creatinine clearance (CrCl) level of less than 90 mL/min/1.73 m(2), in accordance with the National Kidney Foundation Kidney and Dialysis Outcomes Quality Initiative, and further categorized as mild, moderate, or severe (CrCl levels of 60-89, 30-59, and <30 mL/min/1.73 m(2), respectively). Twenty-nine patients were included in the study--22 with epithelial ovarian cancer, 4 with peritoneal cancer, and 3 with fallopian tube cancer. Thirteen patients had mild CKD, 13 had moderate, and 3 had severe. Most patients had been treated with 20 mg/day of tamoxifen every 4 weeks. The median duration of treatment was 5 months (range, 1-52 months). The overall complete response, partial response, stable disease, and disease progression rates were 0%, 10%, 41%, and 48%, respectively. Twenty-one percent of patients experienced hot flashes, and 7% experienced nausea. No major adverse reactions occurred. These findings were similar to those for gynecological cancer patients with normal renal function. In conclusion, 20 mg/day of tamoxifen is safe and effective in gynecological cancer patients with CKD.

Rhabdomyolysis and Unilateral Renal Infarction After a Motor Vehicle Crash

A 46-year-old man with no previous history of abnormal urinalysis findings or renal dysfunction was admitted to a local hospital because of a motor vehicle crash. An open laparotomy was performed to treat a perforation of the small intestine. After operation, oliguria and renal dysfunction developed, and he was admitted to our hospital because of acute renal failure after trauma. Acute renal failure was assumed to be due to rhabdomyolysis with elevated serum creatinine, blood urea nitrogen, and creatine kinase levels and myoglobinemia. Left flank pain occurred several days after admission, and the serum alkaline phosphatase level increased between days 5 and 12 following admission. Although hemodialysis was performed 9 times and the urine output was satisfactory, the creatinine clearance levels increased only to about 50 mL/min/1.73 m2 (0.84 mL/s/m2) at 6 weeks following admission. As a result, a diagnosis of renal infarction due to acute renal artery occlusion was considered. The left kidney was atrophic on an abdominal computed tomographic scan and was nonfunctioning on a renogram. This case shows the importance of not overlooking the possibility of a renal infarction associated with rhabdomyolysis after a motor vehicle crash. In particular, the changes in the serum alkaline phosphatase levels were important in making a correct diagnosis in this case.

Long-term follow-up of renal transplant patients with renal artery stenosis treated by percutaneous angioplasty

Purpose of the study To evaluate if renal angioplasty (PTRA) in patients with transplanted kidney and renal artery stenosis (TRAS) can have long-term effect on hypertension and renal function. Materials and methods Within a 24-year time period, 58 PTRAs in 55 adults (three times Re-PTRA) with transplanted kidney were performed. The group included 34 males and 21 females, average age 41 ± 10.6 (18–72) years. After exclusion of 7 technical failures, 51 PTRAs were followed at 1 week, 6 months and 1–3 years after PTRA. Hypertension improvement was defined as mean arterial pressure (MAP) decrease of at least 15% from the pre-PTRA value. Graft function was evaluated by serum creatinine (Scr) and creatinine clearance (Ccr) levels, and the improvement was defined as a 20% change. Clinical FU was 3 years. Results PTRA technical success was 88.4%. In 51 kidney recipients at the end of FU, blood pressure improved in 65.2% of patients (MAP decreased from 123 ± 13.1 to 107 ± 12.1 mmHg), but no patient remained normotensive medication free. Graft function improved in 44.8% of patients and was stabilized in 20.7% of them (average Ccr before PTRA: 0.48 ± 0.29, after PTRA: 0.78 ± 47 ml/s). PTRA complications were observed in 25.5% of procedures, most often with no clinical sequel. Thirty days mortality was 1.8% (one patient). Conclusions PTRA results in kidney recipients are valuable mainly in preserving graft function.