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Renal Impairment (renal + impairment)
Kinds of Renal Impairment Selected AbstractsRENAL IMPAIRMENT AND HYPERSENSITIVITY REACTION DUE TO EFAVIRENZNEPHROLOGY, Issue 6 2008ELIZABETH CURRY [source] ATHEROSCLEROTIC RISK FACTORS AND VASCULAR DISEASE IN CHRONIC RENAL IMPAIRMENTNEPHROLOGY, Issue 1 2002Dr J Kohlhagen [source] Serum and 24-hour Urine Analysis in Adult Cyanotic and Noncyanotic Congenital Heart Disease PatientsCONGENITAL HEART DISEASE, Issue 3 2009Efrén Martínez-Quintana MD ABSTRACT Introduction., Glomerulopathy is a complication of congenital heart disease patients. The risk of developing renal impairment is particularly high in cyanotic patients. Objective., The aim of this study was to determine the prevalence of renal dysfunction and microalbumiuria in adult cyanotic and non cyanotic congenital heart disease patients. Methods., Fourteen cyanotic and 22 noncyanotic congenital heart disease patients were studied in the Adult Congenital Heart Disease Unit at the Complejo Hospitalario Universitario Insular-Materno Infantil. Demographic characteristics, complete blood count, and 24-hour urianalysis were obtained, including abdominal ultrasound in those with cyanosis. Results., No differences were seen between age (years) (27.4 ± 8.2; 26.4 ± 8.3; P = .71), sex, size, weight, or glomerular filtration rate (mL/min/1.73 m2) (81.1 ± 22.9 vs. 84.9 ± 9.2, P = .482) between cyanotic and noncyanotic patients. However, Eisenmenger patients had significantly impaired renal function when compared with noncyanotic patients (73.0 ± 17.3 vs. 84.9 ± 9.2 mL/min/1.73 m2, P = .023). Significant differences were obtained in oxygen saturation (%) (83.8 ± 5.8 vs. 97.8 ± 0.8; P = .000), hematocrit (%) (59.3 ± 8.1 vs. 40.9 ± 8.5; P = .000), platelets (103/µL) (161.5 ± 70.5 vs. 277.9 ± 57.6; P = .000), serum uric acid (mg/dL) (7.5 ± 2.3 vs. 5.6 ± 1.5; P = .008) and microalbuminuria (mg/24 hours) (12.8 [0, 700.2] vs. 2.4 [0, 18.9]; P = .000) between cyanotic and noncyanotic patients. Five cyanotic patients (35.7%) had microalbuminuria (>30 mg/24 hours) and three of them (21.4%) proteinuria (>1 g/24 hours). No significant differences were seen between serum and urine parameters between cyanotic patients who had microalbuminuria (>30 mg/24 hours) and those cyanotic patients who did not have it (<30 mg/24 hours). Conclusions., Renal impairment is frequently seen in congenital heart disease patients, being associated occasionally with proteinuria and microalbuminuria in cyanotic ones. [source] Establishing pragmatic estimated GFR thresholds to guide metformin prescribingDIABETIC MEDICINE, Issue 10 2007J. S. Shaw Abstract Aims, Renal impairment is a contraindication to metformin treatment because of the perceived increased risk of lactic acidosis. Current guidelines define renal impairment according to the serum creatinine of the individual, but this measure is being supplanted by the use of estimated glomerular filtration rate (eGFR) as it gives a closer estimate to true GFR. This study aimed to establish pragmatic eGFR limits for use in patients being considered for metformin treatment. Methods, Estimated GFR measurements corresponding to currently used metformin creatinine limits of 130 and 150 µmol/l were derived and then applied to 12 482 patients with diabetes in Hull and East Yorkshire. Results, Few patients with a serum creatinine of 130 or 150 µmol/l have an eGFR of < 30 ml/min/1.73 m2[chronic kidney disease (CKD) stage 4 or greater], while most are between 30 and 59 ml/min/1.73 m2 (CKD stage 3). When applied to the 12 482 patients (median age 67 years, interquartile range 56,75), males predominated when using creatinine cut-offs (13.6% of males and 8.3% of females had creatinine > 130 µmol/l; 8.2% males and 5.2% females > 150 µmol/l), but not using eGFR CKD thresholds (3.3% males and 4.7% females < 30 ml/min/1.73 m2; 20.8% males and 28.1% females eGFR 30,59 ml/min/1.73 m2). Similar proportions of patients as currently would have metformin withheld if using eGFR cut-offs between 30 and 49 ml/min/1.73 m2. Conclusions, We have proposed pragmatic eGFR limits to guide metformin prescribing in patients with renal impairment. CKD stage 4 or greater should be an absolute contraindication to metformin, while CKD stage 3 should alert clinicians to consider other risk factors before initiating or continuing treatment. [source] Response of refractory colitis to intravenous or oral tacrolimus (FK506)INFLAMMATORY BOWEL DISEASES, Issue 5 2002Dr. Klaus Fellermann Abstract Intravenous cyclosporine has proven to be an alternative to emergency colectomy in steroid-refractory ulcerative colitis, whereas the experience with FK506 is limited. In this report we compare intravenous to oral FK506 treatment in 38 patients with refractory ulcerative (n = 33) or indeterminate (n = 5) colitis. FK506 was started intravenously in the first group (n = 18) at a dose of 0.01 to 0.02 mg/kg up to 14 days, followed by 0.1 to 0.2 mg/kg orally, or was started orally at this dose in a second group (n = 20). Additional azathioprine/6-mercaptopurine was given and steroids were tapered in responding patients, followed by a dose reduction of FK506. Clinical disease activity and laboratory parameters were assessed to evaluate efficacy and safety. Primary objectives were the induction of remission (Truelove index of mild) and colectomy-free survival. Treatment lasted for a mean of 7.6 months, and the mean observation period was 16.2 months. Eighteen of 38 patients improved within 14 days, and a complete remission was achieved in 13 patients after 1 month. A colectomy within 1 month was performed in 3 of 38 patients. The overall colectomy rate was 34%. One-half of the patients with a minimum follow-up of 2 years required a colectomy. Intravenous and per oral administration were equally safe and effective. The most frequent adverse events included tremor, hyperglycemia, hypertension, and infection, but none were severe. Renal impairment was rare and subsided upon drug withdrawal. In conclusion, FK506 is effective in the treatment of refractory colitis with per oral dosing being equivalent to intravenous administration. [source] Pilot study: Gelafundin (polygeline) 4% plus antibiotics in the treatment of high-risk cirrhotic patients with spontaneous bacterial peritonitisALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2010M. Cartier Aliment Pharmacol Ther 2010; 32: 43,48 Summary Background, Cirrhotic patients with spontaneous bacterial peritonitis (SBP) have elevated rates of renal impairment and mortality. It has been shown that cefotaxime plus albumin infusion decrease renal impairment compared with antibiotic treatment alone, in patients with serum bilirubin >4 mg/dL or creatinine >1 mg/dL. Aim, To assess clinical outcomes of high-risk cirrhotic patients with SBP who were treated with antibiotics associated with Gelafundin (polygeline) 4%. Methods, Twenty nine cirrhotic patients with SBP and serum bilirubin >4 mg/dL or creatinine >1 mg/dL were enrolled. Ceftriaxone was administered in doses of 2 g/day and Gelafundin 4% was given intravenously at 1.5 g/kg of body weight at the time of the diagnosis, followed by 1 g/kg on day 3. Renal impairment was defined as nonreversible deterioration of renal function during hospitalization. Results, Eight patients (27.5%) had basal renal failure. Infection resolved in 28 (96.6%) patients. Renal impairment occurred in four patients (13.8%), and three patients (10.4%) died during hospitalization. Mortality within 90 days after discharge was 34.5% (10 patients). Conclusion, The rates of renal impairment and mortality in high-risk patients with SBP suggest that Gelafundin 4% administration given with ceftriaxone may be a less expensive therapeutic alternative to albumin. [source] Preemptive treatment of fungal infection: has its time arrived in liver transplantation?LIVER TRANSPLANTATION, Issue 3 2008James D. Perkins M.D. Special Editor Background Invasive fungal infection remains a major challenge in liver transplantation and the mortality rate is high. Early diagnosis and treatment are required for better results. Patients We prospectively measured plasma (1 , 3),-d glucan (BDG) levels in 180 living donor liver transplant recipients for 1 year after surgery. Fungal infection was defined as proposed by the European Organization for Research and Treatment of Cancer/Mycoses Study Group. Preemptive treatment (intravenous fluconazole and trimethoprim-sulfamethoxazole) was started when the BDG level was greater than 40 pg/ml. Results Twenty-four patients (13%) were diagnosed with invasive fungal infection. The responsible pathogens included Candida spp. in 14 cases, Aspergillus fumigatus in 5, Cryptococcus neoformans in 3, and Pneumocystis jiroveci in 2. Preemptive treatment was performed in 22% of patients (n = 40). Renal impairment and mild gastrointestinal intolerance due to the drugs were observed in 28% (11/40) of patients during treatment. Among them 14 patients were diagnosed with fungal infection including seven candidiasis, five aspergillosis, and two Pneumocystis jiroveci pneumonia. The sensitivity and specificity of BDG for overall fungal infection was 58% and 83%, respectively, with a positive predictive value of 35% and a negative predictive value of 93%, and a positive likelihood ratio of 3.41 and a negative likelihood ratio of 1.98. The overall mortality for fungal infection in our series was 0.6%. Conclusion Although the sensitivity and positive predictive value were low, the low mortality rate after fungal infection and the mild side effects of the preemptive treatment might justify our therapeutic strategy. Based on the effectiveness, this strategy warrants further investigation. [source] Role of cytokine gene polymorphisms in acute rejection and renal impairment after liver transplantationLIVER TRANSPLANTATION, Issue 3 2001Julie R. Jonsson Although immunosuppressive regimens are effective, rejection occurs in up to 50% of patients after orthotopic liver transplantation (OLT), and there is concern about side effects from long-term therapy. Knowledge of clinical and immunogenetic variables may allow tailoring of immunosuppressive therapy to patients according to their potential risks. We studied the association between transforming growth factor-,, interleukin-10, and tumor necrosis factor , (TNF-,) gene polymorphisms and graft rejection and renal impairment in 121 white liver transplant recipients. Clinical variables were collected retrospectively, and creatinine clearance was estimated using the formula of Cockcroft and Gault. Biallelic polymorphisms were detected using polymerase chain reaction-based methods. Thirty-seven of 121 patients (30.6%) developed at least 1 episode of rejection. Multivariate analysis showed that Child-Pugh score (P = .001), immune-mediated liver disease (P = .018), normal pre-OLT creatinine clearance (P = .037), and fewer HLA class 1 mismatches (P = .038) were independently associated with rejection. Renal impairment occurred in 80% of patients and was moderate or severe in 39%. Clinical variables independently associated with renal impairment were female sex (P = .001), pre-OLT renal dysfunction (P = .0001), and a diagnosis of viral hepatitis (P = .0008). There was a significant difference in the frequency of TNF-,-308 alleles among the primary liver diseases. After adjustment for potential confounders and a Bonferroni correction, the association between the TNF-,-308 polymorphism and graft rejection approached significance (P = .06). Recipient cytokine genotypes do not have a major independent role in graft rejection or renal impairment after OLT. Additional studies of immunogenetic factors require analysis of large numbers of patients with appropriate phenotypic information to avoid population stratification, which may lead to inappropriate conclusions. [source] Renal impairment in deoxycorticosterone acetate-salt hypertensive ratsNEPHROLOGY, Issue 4 2000Catherine Dallemagne Summary: This study has compared renal function in deoxycorticosterone (DOCA)-salt hypertensive Wistar rats (uninephrectomy followed by administration of DOCA 25 mg subcutaneously every fourth day and 1% NaCl in the drinking water) with various control rats using the isolated perfused kidney preparation. The systolic blood pressure of DOCA-salt hypertensive rats was 180 ± 10 mmHg (uninephrectomy controls: 136 ± 9 mmHg) while normalization of calcium intake (DOCA-Ca rats, 1% CaCl2 in water) attenuated this increase (systolic blood pressure, 146 ± 5 mmHg). Renal mass corrected for body weight increased by 25% after uninephrectomy, 55% in uninephrectomized rats given NaCl, 152% in DOCA-salt rats and 147% in DOCA-Ca rats. At a renal perfusion pressure of 135 mmHg, isolated perfused kidneys from DOCA-salt rats showed decreases of 48% in glomerular filtration rate and 69% in sodium excretion with an increase of 44% in renal vascular resistance compared with uninephrectomized rats. There were no significant differences in renal function between DOCA-salt and DOCA-Ca rats. Histological assessment of renal pathology showed proximal tubular hypertrophy and hyperplasia, marked focal distal tubular atrophy, interstitial fibrosis and glomerular hypercellularity in DOCA rats compared with UNX rats. Lesions were less obvious in UNX-salt or DOCA-Ca rats. The lack of direct correlation between alterations in function and pathology may be explained by the compensatory effect of remaining healthy or hypertrophied nephrons. Thus, the DOCA-salt model of hypertension in rats is associated with marked structural kidney damage and severely decreased kidney function. Marked attenuation of systemic hypertension by normalizing calcium intake in DOCA-salt rats did not prevent impairment of kidney function. [source] Outcomes Following De Novo CNI-Free Immunosuppression After Heart Transplantation: A Single-Center ExperienceAMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2009A. S. Leet Renal impairment at the time of heart transplantation complicates the choice of subsequent immunosuppressive therapy. Calcineurin (CNI)-free regimens utilizing proliferation signal inhibitors (PSI) may mitigate against nephrotoxicity in this group; however, their effectiveness remains unclear. We present our 7-year experience with de novo CNI-free, PSI-based immunosuppression after heart transplantation. Of the 152 patients transplanted between July 1999 and July 2006, de novo immunosuppression regimens were 49 CNI-free, PSI-based, 88 CNI, 15 combination of CNI+PSI. Pretransplant creatinine clearance improved within 6 months in the PSI group (0.69 ± 0.34 mL/s vs. 1.00 ± 0.54 mL/s, p < 0.05) but not the CNI (1.32 ± 0.54 mL/s vs. 1.36 ± 0.53 mL/s, p = ns) or CNI+PSI (1.20 ± 0.24 mL/s vs. 1.20 ± 0.41 mL/s, p = ns) groups. The PSI group had more episodes of early (,6 months) acute rejection, bacterial or fungal infections and pleural effusions but less CMV infection (p < 0.05 for all comparisons). Early CNI addition occurred in 37% of the PSI group for acute rejection. 33% of the entire cohort changed immunosuppression regimens over 3.6 ± 2.2 years follow-up. De novo CNI-free, PSI-based immunosuppression in patients with significant renal dysfunction allowed significant posttransplantation renal recovery but with increased early acute rejection, bacterial and fungal infections and pleural effusions. [source] An analysis of renal dysfunction in 1511 patients with fractured neck of femur: the implications for peri-operative analgesiaANAESTHESIA, Issue 10 2009S. M. White Summary Following two deaths from respiratory failure secondary to opioid toxicity in patients admitted for surgical repair of fractured neck of femur, we retrospectively studied the serum urea and electrolyte concentrations of 1511 consecutive patients requiring surgery for proximal femoral fracture, and calculated their glomerular filtration rate. Five hundred and forty-five (36.1%) patients had renal dysfunction on admission (glomerular filtration rate < 60 ml.min,1.1.73 m,2); 435 (28.8%) had grade 3 chronic kidney disease (moderate; glomerular filtration rate 30,59 ml.min,1.1.73 m,2), 82 (5.4%) had grade 4 disease (severe; glomerular filtration rate 15,29 ml.min,1.1.73 m,2) and 28 (1.9%) had grade 5 (renal failure; glomerular filtration rate < 15 ml min,1.1.73 m,2). The 30-day mortality for patients with renal dysfunction (62/536; 11.6%) was significantly greater (p = 0.004) than for patients with normal renal function (68/958; 7.1%), although median (IQR [range]) postoperative lengths of stay were similar 15 (10,22 [1,125]) vs 14 (9,22 [1,120]) days respectively; p = 0.06). Renal impairment is common in patients admitted for fixation of fractured neck of femur, who are consequently at risk of opioid toxicity. [source] The risk of renal impairment in hormone-refractory prostate cancer patients with bone metastases treated with zoledronic acid,CANCER, Issue 6 2007William K. Oh MD Abstract BACKGROUND Bisphosphonates have been used to treat bone metastases in hormone-refractory prostate cancer (HRPC), but certain agents have been associated with renal toxicity. For this observational study, the authors assessed the risk of renal impairment in patients with HRPC who received zoledronic acid from December 1999 to April 2005. METHODS A comprehensive medical records review was performed in a major tertiary oncology center (n = 122 patients). The primary outcome of renal impairment was defined as an increase ,0.5 mg/dL or ,1.0 mg/dL over baseline creatinine value if the baseline value was <1.4 mg/dL or ,1.4 mg/dL, respectively. A risk factor analysis was conducted using the Andersen-Gill extension to the Cox proportional hazards model. RESULTS Renal impairment was observed in 23.8% of patients. The risk of renal impairment increased with an extended duration of zoledronic acid therapy (<6 months, 11.1%; ,24 months, 26.3%) and previous pamidronate treatment (45.5% vs 19.0% for patients with no prior pamidronate). A significantly greater risk of renal impairment was associated with increasing age at zoledronic acid initiation, prior pamidronate use, and a history of renal disease, hypertension, or smoking (P , 0.05). CONCLUSIONS In an outpatient clinic setting, the risk of renal impairment among patients with HRPC who received zoledronic acid was greater than the risk reported previously in clinical trials. Cancer 2007 © 2007 American Cancer Society. [source] Bridging of Chronic Oral Anticoagulation with Enoxaparin in Patients with Atrial Fibrillation: Results from the Prospective BRAVE RegistryCARDIOVASCULAR THERAPEUTICS, Issue 4 2009C. Hammerstingl Current American College of Chest Physicians (ACCP) guidelines on the perioperative management of oral anticoagulation (OAC) suggest bridging therapy with therapeutic doses of low-molecular-weight heparin (LMWH) in patients with atrial fibrillation (AF) if at high or moderate thromboembolic (TE) risk, and with reduced doses in patients with low TE risk. Our objective was to assess the efficacy and safety of bridging OAC with enoxaparin in AF patients. These are the results of an open, prospective monocenter register. Hospitalized and ambulatory patients with AF requiring bridging therapy at high or moderate TE risk and normal renal function were treated with therapeutic LMWH doses; all other patients received reduced doses. A total of 703 patients were enrolled, of whom 358 (50.9%) were at moderate-to-high and 345 (49.1%) at low TE risk. Renal impairment was detected in 308 patients (43.8%). One hundred ninety patients (27.1%) were treated with therapeutic LMWH doses and 513 (72.9%) with reduced doses. No TE events were observed during the follow-up period (0%; 95% confidence interval [CI] 0.0,0.52). Three major bleeds (0.4%; 0.1,1.2) and 60 minor bleeds were noted (8.9%; 6.6,10.9). Age and total LMWH doses were risk factors for bleeding in the multivariate analysis. The study, under conditions of everyday clinical care, supports a predefined bridging regimen based on the individual patient's TE risk and renal function. Patients with low TE risk or with impaired renal function can be bridged effectively and safely with reduced LMWH doses. [source] Serum and 24-hour Urine Analysis in Adult Cyanotic and Noncyanotic Congenital Heart Disease PatientsCONGENITAL HEART DISEASE, Issue 3 2009Efrén Martínez-Quintana MD ABSTRACT Introduction., Glomerulopathy is a complication of congenital heart disease patients. The risk of developing renal impairment is particularly high in cyanotic patients. Objective., The aim of this study was to determine the prevalence of renal dysfunction and microalbumiuria in adult cyanotic and non cyanotic congenital heart disease patients. Methods., Fourteen cyanotic and 22 noncyanotic congenital heart disease patients were studied in the Adult Congenital Heart Disease Unit at the Complejo Hospitalario Universitario Insular-Materno Infantil. Demographic characteristics, complete blood count, and 24-hour urianalysis were obtained, including abdominal ultrasound in those with cyanosis. Results., No differences were seen between age (years) (27.4 ± 8.2; 26.4 ± 8.3; P = .71), sex, size, weight, or glomerular filtration rate (mL/min/1.73 m2) (81.1 ± 22.9 vs. 84.9 ± 9.2, P = .482) between cyanotic and noncyanotic patients. However, Eisenmenger patients had significantly impaired renal function when compared with noncyanotic patients (73.0 ± 17.3 vs. 84.9 ± 9.2 mL/min/1.73 m2, P = .023). Significant differences were obtained in oxygen saturation (%) (83.8 ± 5.8 vs. 97.8 ± 0.8; P = .000), hematocrit (%) (59.3 ± 8.1 vs. 40.9 ± 8.5; P = .000), platelets (103/µL) (161.5 ± 70.5 vs. 277.9 ± 57.6; P = .000), serum uric acid (mg/dL) (7.5 ± 2.3 vs. 5.6 ± 1.5; P = .008) and microalbuminuria (mg/24 hours) (12.8 [0, 700.2] vs. 2.4 [0, 18.9]; P = .000) between cyanotic and noncyanotic patients. Five cyanotic patients (35.7%) had microalbuminuria (>30 mg/24 hours) and three of them (21.4%) proteinuria (>1 g/24 hours). No significant differences were seen between serum and urine parameters between cyanotic patients who had microalbuminuria (>30 mg/24 hours) and those cyanotic patients who did not have it (<30 mg/24 hours). Conclusions., Renal impairment is frequently seen in congenital heart disease patients, being associated occasionally with proteinuria and microalbuminuria in cyanotic ones. [source] Pharmacokinetics of dipeptidylpeptidase-4 inhibitorsDIABETES OBESITY & METABOLISM, Issue 8 2010A. J. Scheen Type 2 diabetes (T2DM) is a complex disease combining defects in insulin secretion and insulin action. New compounds have been developed for improving glucose-induced insulin secretion and glucose control, without inducing hypoglycaemia or weight gain. Dipeptidylpeptidase-4 (DPP-4) inhibitors are new oral glucose-lowering agents, so-called incretin enhancers, which may be used as monotherapy or in combination with other antidiabetic compounds. Sitagliptin, vildaglipin and saxagliptin are already on the market in many countries, either as single agents or in fixed-dose combined formulations with metformin. Other DPP-4 inhibitors, such as alogliptin and linagliptin, are currently in late phase of development. The present paper summarizes and compares the main pharmacokinetics (PK) properties, that is, absorption, distribution, metabolism and elimination, of these five DPP-4 inhibitors. Available data were obtained in clinical trials performed in healthy young male subjects, patients with T2DM, and patients with either renal insufficiency or hepatic impairment. PK characteristics were generally similar in young healthy subjects and in middle-aged overweight patients with diabetes. All together gliptins have a good oral bioavailability which is not significantly influenced by food intake. PK/pharmacodynamics characteristics, that is, sufficiently prolonged half-life and sustained DPP-4 enzyme inactivation, generally allow one single oral administration per day for the management of T2DM; the only exception is vildagliptin for which a twice-daily administration is recommended because of a shorter half-life. DPP-4 inhibitors are in general not substrates for cytochrome P450 (except saxagliptin that is metabolized via CYP 3A4/A5) and do not act as inducers or inhibitors of this system. Several metabolites have been documented but most of them are inactive; however, the main metabolite of saxagliptin also exerts a significant DPP-4 inhibition and is half as potent as the parent compound. Renal excretion is the most important elimination pathway, except for linagliptin whose metabolism in the liver appears to be predominant. PK properties of gliptins, combined with their good safety profile, explain why no dose adjustment is necessary in elderly patients or in patients with mild to moderate hepatic impairment. As far as patients with renal impairment are concerned, significant increases in drug exposure for sitagliptin and saxagliptin have been reported so that appropriate reductions in daily dosages are recommended according to estimated glomerular filtration rate. The PK characteristics of DPP-4 inhibitors suggest that these compounds are not exposed to a high risk of drug,drug interactions. However, the daily dose of saxagliptin should be reduced when coadministered with potent CYP 3A4 inhibitors. In conclusion, besides their pharmacodynamic properties leading to effective glucose-lowering effect without inducing hypoglycaemia or weight gain, DPP-4 inhibitors show favourable PK properties, which contribute to a good efficacy/safety ratio for the management of T2DM in clinical practice. [source] Establishing pragmatic estimated GFR thresholds to guide metformin prescribingDIABETIC MEDICINE, Issue 10 2007J. S. Shaw Abstract Aims, Renal impairment is a contraindication to metformin treatment because of the perceived increased risk of lactic acidosis. Current guidelines define renal impairment according to the serum creatinine of the individual, but this measure is being supplanted by the use of estimated glomerular filtration rate (eGFR) as it gives a closer estimate to true GFR. This study aimed to establish pragmatic eGFR limits for use in patients being considered for metformin treatment. Methods, Estimated GFR measurements corresponding to currently used metformin creatinine limits of 130 and 150 µmol/l were derived and then applied to 12 482 patients with diabetes in Hull and East Yorkshire. Results, Few patients with a serum creatinine of 130 or 150 µmol/l have an eGFR of < 30 ml/min/1.73 m2[chronic kidney disease (CKD) stage 4 or greater], while most are between 30 and 59 ml/min/1.73 m2 (CKD stage 3). When applied to the 12 482 patients (median age 67 years, interquartile range 56,75), males predominated when using creatinine cut-offs (13.6% of males and 8.3% of females had creatinine > 130 µmol/l; 8.2% males and 5.2% females > 150 µmol/l), but not using eGFR CKD thresholds (3.3% males and 4.7% females < 30 ml/min/1.73 m2; 20.8% males and 28.1% females eGFR 30,59 ml/min/1.73 m2). Similar proportions of patients as currently would have metformin withheld if using eGFR cut-offs between 30 and 49 ml/min/1.73 m2. Conclusions, We have proposed pragmatic eGFR limits to guide metformin prescribing in patients with renal impairment. CKD stage 4 or greater should be an absolute contraindication to metformin, while CKD stage 3 should alert clinicians to consider other risk factors before initiating or continuing treatment. [source] Oxford experience with neoadjuvant chemotherapy and surgical resection for esophageal adenocarcinomas and squamous cell tumorsDISEASES OF THE ESOPHAGUS, Issue 3 2008P. M. Safranek SUMMARY., The Medical Research Council trial for oesophageal cancer (OEO2) trial demonstrated a clear survival benefit from neoadjuvant chemotherapy in resectable esophageal carcinoma. Since February 2000 it has been our practice to offer this chemotherapy regime to patients with T2 and T3 or T1N1 tumors. We analyzed prospectively collected data of patients who received neoadjuvant chemotherapy prior to esophageal resection under the care of a single surgeon. Complications of treatment and overall outcomes were evaluated. A total of 194 patients had cisplatin and 5-fluorouracil prior to esophageal resection. Six patients (5.7%) had progressive disease and were inoperable (discovered in four at surgery). During chemotherapy one patient died and one perforated (operated immediately). Complications including severe neutropenia, coronary artery spasm, renal impairment and pulmonary edema led to the premature cessation of chemotherapy in 12 patients (6.2%). A total of 182 patients with a median age of 63 (range 30,80), 41 squamous and 141 adenocarcinomas underwent surgery. Operations were 91 left thoracoabdominal (50%), 45 radical transhiatal (25%), 40 Ivor-Lewis (22%) and six stage three (3%), and 78.6% had microscopically complete (R0) resections. Median survival was 28 months with 77.3% surviving for 1 year and 57.7% for 2 year. In hospital mortality was 5.5% and anastomotic leak rate 7.7%. A radical surgical approach to the primary tumor in combination with OEO2 neoadjuvant chemotherapy has led to a high R0 resection rate and good survival with acceptable morbidity and mortality. [source] Lenalidomide and dexamethasone for the treatment of refractory/relapsed multiple myeloma: dosing of lenalidomide according to renal function and effect on renal impairmentEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 1 2010Meletios A. Dimopoulos Abstract Objectives:, Lenalidomide and dexamethasone (LenDex) is an active regimen for relapsed/refractory multiple myeloma (MM). However, there is limited data for the effect of LenDex on renal impairment (RI) and on renal reversibility. Patients & Methods:, Fifty consecutive patients with relapsed/refractory MM received LenDex in 28-d cycles. Median lines of previous therapies were 2 (range: 1,6). Lenalidomide was administered on days 1,21 according to creatinine clearance (CrCl), while dexamethasone was given at a dose of 40 mg on days 1,4 and 15,18 for the first four cycles and only on days 1,4 thereafter. Results:, Twelve patients (24%) had RI at baseline, defined as CrCl < 50 mL/min. Most patients were pretreated with either thalidomide or bortezomib and > 50% of them were refractory to both drugs. At least partial response was documented in 60.5% and 58% of patients with and without RI. Median progression-free survival (PFS) and overall survival (OS) for all patients was 9 and 16 months, respectively. RI was not associated with an inferior PFS or OS. There were no differences in the incidence of adverse events among patients with and without RI. Three of 12 patients with RI (25%) achieved complete renal response and two (16%) achieved minor renal response with LenDex. Conclusions:, We conclude that LenDex is an active treatment even in heavily pretreated MM. With dosing of lenalidomide according to renal function, LenDex can be administered to patients with RI (who may not have other treatment options) without excessive toxicity. Furthermore, LenDex may improve the renal function in approximately 40% of patients with RI. [source] Clinical Pharmacokinetics of FrovatriptanHEADACHE, Issue 2002P. Buchan PhD Objective.,To review available data on the clinical pharmacokinetics of frovatriptan. Background.,Preclinical data suggest that the pharmacokinetic profile of frovatriptan may differ from that of the currently available triptans. Methods.,Studies of healthy volunteers, subjects with renal or hepatic impairment, elderly subjects, and patients with migraine during and between attacks were reviewed. Results.,Oral bioavailability of frovatriptan is 22% to 30%, and although the time to maximum concentration is typically 2 to 3 hours, approximately 60% to 70% of plasma maximum concentration is achieved within 1 hour of dosing. Frovatriptan distributes into erythrocytes, with binding reversible and time dependent. The relatively long terminal elimination half-life (about 26 hours) confers good systemic exposure and may produce a long duration of therapeutic action, thus reducing migraine recurrence and the need for redosing. Systemic exposure to frovatriptan generally correlates with dose between 1 and 100 mg. Blood and plasma frovatriptan concentrations are consistently higher in females, but there is no need to adjust dose according to gender. Pharmacokinetics are essentially unaffected by food and were predictable after repeat dosing; steady state is approached in about 4 to 5 days. Pharmacokinetics were changed only slightly in subjects with renal impairment or mild-to-moderate hepatic impairment, elderly individuals, and during migraine attacks. Frovatriptan is principally metabolized by the CYP1A2 isoenzyme of cytochrome P-450 and is cleared by the kidney and liver, each having sufficient capacity to compensate for impairment of the other. Conclusions.,Frovatriptan can be taken without regard for food intake, and because of the large therapeutic margin and shallow dose-response curve, there is no need for dosage adjustment in the elderly, in women taking a combined oral contraceptive, in patients with mild-to-severe renal impairment, mild-to-moderate hepatic impairment, or according to gender. The long duration of exposure may reduce the likelihood of early migraine recurrence. [source] Effects of clonidine on diuretic response in ascitic patients with cirrhosis and activation of sympathetic nervous system,,HEPATOLOGY, Issue 4 2006Anne Lenaerts The effects of the addition of clonidine to diuretics on the mobilization of ascites in the short term (diuretic response and requirement of diuretics) and the long term (readmissions for tense ascites and requirement of diuretics) were examined in patients with cirrhosis and with increased sympathetic nervous system (SNS) activity. We also studied neurohormonal, hemodynamic effects and side effects of clonidine and diuretics. Patients were randomized to receive placebo (group1, n = 32) or clonidine (0.075 mg) twice daily (group 2, n = 32) for 3 months. After 8 days and for 10 days duration, spironolactone (200 mg/day) was added in both groups. After this period, the dosages of diuretics were individually increased until diuretic response. Responding patients were discharged and followed at the outpatient clinic. During the first hospitalization, the time needed for diuretic response was shorter in group 2 than in group 1. The mean requirement for diuretics was significantly higher in group 1 than in group 2, and the diuretic complications (hyperkalemia and renal impairment) were significantly lower in group 2. Clonidine induced a permanent decrease in SNS activity and delayed decrease in renin/aldosterone levels. During the follow-up, the time to the first readmission for tense ascites was shorter in group 1 than in group 2. Readmissions related to tense ascites or diuretic complications were significantly lower in group 2. The mean requirement for diuretics was significantly higher in group 1 than in group 2. In conclusion, the additional administration of clonidine to diuretics induced an earlier diuretic response associated with fewer diuretic requirements and complications. (HEPATOLOGY 2006;44:844,849.) [source] Mycophenolate mofetil substitution for cyclosporine-dependent myasthenia gravis and nephrotoxicityINTERNAL MEDICINE JOURNAL, Issue 1 2007A. K. H. Lim Abstract Severe autoimmune myasthenia gravis is difficult to manage and may require immunosuppression with cyclosporine. However, cyclosporine dependency is associated with the risk of nephrotoxicity. Mycophenolate mofetil is a non-nephrotoxic alternative which should be considered to rescue cyclosporine-dependent, severe myasthenia gravis sufferers with renal impairment from progression to end-stage renal failure. However, the evidence is limited and studies have not assessed the outcome of a direct substitution in these cyclosporine-dependent patients. We study three such patients who successfully converted to mycophenolate mofetil, and briefly examine the evidence behind this option. We believe that total cyclosporine withdrawal is feasible, but strongly recommend overlapping mycophenolate mofetil treatment with cyclosporine. [source] The role of methadone in cancer pain treatment , a reviewINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 7 2009W. Leppert Summary Background:, Methadone is an opioid analgesic of step 3 of the World Health Organization (WHO) analgesic ladder. Aim and Methods:, To outline pharmacodynamics, pharmacokinetics, drug interactions, equianalgesic dose ratio with other opioids, dosing rules, adverse effects and methadone clinical studies in patients with cancer pain. A review of relevant literature on methadone use in cancer pain was conducted. Results:, Methadone is used in opioid rotation and administered to patients with cancer pain not responsive to morphine or other strong opioids when intractable opioid adverse effects appear. Methadone is considered as the first strong opioid analgesic and in patients with renal impairment. Methadone possesses different pharmacodynamics and pharmacokinetics in comparison to other opioids. The advantages of methadone include multimode analgesic activity, high oral and rectal bioavailability, long lasting analgesia, lack of active metabolites, excretion mainly with faeces, low cost and a weak immunosuppressive effect. The disadvantages include long and changeable plasma half-life, high bound to serum proteins, metabolism through P450 system, numerous drug interactions, lack of clear equianalgesic dose ratio to other opioids, QT interval prolongation, local reactions when administered subcutaneously. Conclusions:, Methadone is an important opioid analgesic at step 3 of the WHO analgesic ladder. Future controlled studies may focus on establishment of methadone equianalgesic dose ratio with other opioids and its role as the first strong opioid in comparative studies with analgesia, adverse effects and quality of life taken into consideration. [source] Lactate levels in Asian patients with type 2 diabetes mellitus on metformin and its association with dose of metformin and renal functionINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 11 2007Vivien C. C. Lim Summary Aim:, Our aims are to discover the average fasting plasma lactate level (FPL) in Asian patients with type 2 diabetes mellitus on metformin, with or without renal impairment and whether FPL is associated with the total daily dose of metformin (Tmet) and the degree of renal impairment in these patients. Methods:, We conducted an observational cross-sectional study of Asian patients with type 2 diabetes, using measurements of FPL levels and glomerular filtration rate (GFR) calculated, using the abbreviated modification of diet in renal disease (MDRD) formula. The association between FPL, Tmet, GFR and other potential predictors was analysed. Results:, A total of 97 subjects were recruited from our diabetes centre between July 2005 and February 2006. Sixty (61.9%) of the subjects were males; 69 (71.1%) Chinese, 21 (21.6%) Malays and 6 (6.2%) Indians. The mean (SD) age was 58.8 years (10.7) and the mean body mass index was 27.1 kg/m2 (5.3). The mean FPL was 1.8 mmol/l (0.9) with 20 (20.6%) of subjects having an FPL beyond the upper limit of our reference range of 2.2 mmol/l. The mean FPL (two SE) of subjects with Tmet of , 1000, 1001,2000 and > 2000 mg were 1.7 mmol/l (0.2), 1.6 mmol/l (0.2) and 2.1 mmol/l (0.5) respectively, (p = 0.119). The mean FPL of subjects with GFR of < 60, 60,90 and > 90 ml/min/1.73 m2 was 1.7 mmol/l (0.3), 1.8 mmol/l (0.3) and 1.8 mmol/l (0.4) respectively, p = 0.757. Among the potential predictors analysed, aspartate transaminase (p = 0.001) was found to be significantly associated with FPL. Conclusions:, Our study shows no correlation between Tmet and GFR with FPL in Asian type 2 diabetic patients on metformin. [source] Does prolonged systemic glucocorticoid use increase risk of tophus formation among gouty arthritis patients?INTERNATIONAL JOURNAL OF RHEUMATIC DISEASES, Issue 3 2009Anne-Annette P. RASO Abstract Aim:, To determine the relationship of steroid use with tophus formation and other comorbid conditions among male gout patients. Methods:, Review of medical records of Filipino gout patients under the care of rheumatologists was conducted. Univariate analysis (chi-square, Student's t -test) and multiple logistic regression analysis were performed to establish the risk for tophus formation among glucocorticoid users. Bivariate analysis was separately done to determine the confounding effect of steroid use in the association of comorbidities and tophi formation. Results:, There were 295 Filipino men with a mean age of 56 years and a mean duration of 12 years of gouty arthritis who were included in the study. Multivariate analysis showed a five times higher likelihood (OR 4.81 95% CI 1.92,12.04, P < 0.001) for tophus formation among prolonged steroid users. Confounders identified were disease duration of gout (, 10 years), presence of chronic kidney disease (CKD) and elevated serum creatinine level (SCr). Bivariate analysis of comorbidities showed that steroid use introduced a considerable bias in the relationship of hypertension, elevated SCr, CKD and dyslipidemia. Conclusion:, Patients with equivalent prednisone intake of at least 15 mg/week for , 3 months is associated with tophi formation. In the presence of hypertension, renal impairment, and elevated serum creatinine level, use of steroids confounds the individual risk that each factor carries. [source] Thrombotic thrombocytopenic purpura: 24 years of experience at the American University of Beirut Medical CenterJOURNAL OF CLINICAL APHERESIS, Issue 3 2004Ali Shamseddine Abstract Thrombotic thrombocytopenic purpura (TTP) is a hematological syndrome defined by the presence of thrombocytopenia and microangiopathic hemolytic anemia without a clinically apparent etiology. Patients may also suffer from fever in addition to neurological and renal impairment. Treatment should be initiated as soon as possible, otherwise this rare disease can be fatal. The main treatment options include therapeutic plasma exchange, fresh frozen plasma infusion, and adjuvant agents such as steroids and antiplatelet drugs. A search of patient records was carried out at the American University of Beirut Medical Center looking for patients who developed TTP over a 24-year period extending from 1980 to 2003. Relevant information was collected and analyzed. A total of 47 records were found. All presented with anemia and thrombocytopenia, 83% had neurological symptoms, 61.7% had fever and 34% had renal impairment. All patients were treated with a multimodality regimen including therapeutic plasma exchange, FFP infusion, steroids, antiplatelet agents, vincristine and others. 38 (81%) cases achieved complete remission. Out of these, 12 (31.6%) relapsed and responded to treatment. Patients who did not receive plasma exchange were more likely to relapse (P = 0.032). A second relapse was observed in 6 cases. The overall mortality rate from TTP over 24 years was 21.3%. TTP remains a fatal disease. A high index of suspicion should, therefore, always be present. Treatment options should be further developed and patients should directly be referred to tertiary care centers. J. Clin. Apheresis 19:119,124, 2004. © 2004 Wiley-Liss, Inc. [source] Clinical value of urinary kidney biomarkers for estimation of renal impairment in elderly Chinese with essential hypertensionJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 1 2008XunHui Xu Abstract The purpose of this work was to observe the excretion of specific types of urinary proteins and urinary enzymes in elderly essential hypertension patients, for early detection and targeted treatment of hypertensive nephropathy in the elderly. A total of 120 elderly essential hypertensive patients and 38 healthy elderly volunteers were involved. The urinary excretion rate of retinal-binding protein (RBP), transferrin (Tf), albumin (Alb), and urinary enzyme N-acetyl-beta-D-glucosaminidase (NAG) activity were determined. Patients were divided into two groups according to their creatinine clearance (Cockroft-Gault formula). There were 88 patients in group A, whose glomerular filtration rate (GFR) was ,80,mL/min, and 32 patients in group B with a GFR <80,mL/min. Among the essential hypertensive patients, urinary excretion rates of RBP, Alb, Tf, and NAG were increased in both groups compared with the healthy controls. But the amount of urinary protein differed between group A and group B. The excretion rate of specific urinary protein and urinary enzyme had a positive relationship with the duration of course of hypertension. We believe that specific types of urinary proteins and urinary enzymes may be useful markers for early diagnosis of hypertensive nephropathy; they can also be regarded as a clinical indicator of the progression of hypertensive nephropathy, serving in the assessment of therapeutic effects. J. Clin. Lab. Anal. 22:86,90, 2008. © 2008 Wiley-Liss, Inc. [source] ,-trace protein, a new marker of GFR, may predict the early prognostic stages of patients with type 2 diabetic nephropathyJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 4 2004Mami Kobata Abstract The relationship between serum levels of ,-trace protein (BTP) or serum creatinine (s-Cr) and the prognostic stages of type 2 diabetic nephropathy was determined. Serum samples from 174 patients with type 2 diabetes were obtained from Juntendo University Hospital, Tokyo, and Juntendo Urayasu Hospital, Chiba, Japan. They were classified into four groups according to the Report of the Ministry of Health and Welfare of Japan (1991, p 251,256) as follows: Stage I (normoalbuminuric stage), Stage II (microalbuminuric stage), Stage IIIA (macroalbuminuric stage without renal dysfunction), Stage IIIB (macroalbuminuric stage with renal dysfunction), and Stage IV (renal failure stage). Among these patients, 68 were Stage I, 29 Stage II, 32 Stage IIIA, 17 Stage IIIB, and 28 Stage IV. Levels of serum BTP were measured using the nephelometric assay on a BNA II analyzer (Dade Behring Diagnostics, Marburg, Germany). The mean levels of serum BTP in Stage IIIA were significantly higher than those in Stage I or II (P<0.00001, P<0.002, respectively). However, the mean levels of s-Cr in Stage IIIA were not significantly higher than that in Stage I or II. In conclusion, serum BTP was a good marker for the identification of early renal impairment in type 2 diabetes. J. Clin. Lab. Anal. 18:237,239, 2004. © 2004 Wiley-Liss, Inc. [source] Role of additional angiography and chemoembolization in patients with hepatocellular carcinoma who achieved complete necrosis following transarterial chemoembolizationJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 9 2004MYOUNG KUK JANG Abstract Background and Aims:, Although transarterial chemoembolization (TACE) has been reported to have antitumor effects in patients with hepatocellular carcinoma (HCC), optimal time schedules and follow-up methods have not yet been determined. We therefore prospectively analyzed the effects of additional angiography and chemoembolization on HCC recurrence and survival in patients who underwent TACE and achieved complete necrosis (CN). Methods:, A total of 68 patients who achieved CN after TACE, as assessed using dynamic computed tomography (CT), were randomized into two groups. Patients in the CT group (n = 34) were followed using dynamic CT every 3 months without any further intervention, whereas patients in the angiography group (n = 34) received additional angiography 1 month after achievement of CN. We compared overall survival and disease-free survival between the two groups and analyzed the benefit of additional angiography. Results:, The cumulative recurrence rate did not differ between the angiography and CT groups (55%vs 48% at 12 months and 66%vs 67% at 24 months, P = 0.92). The overall survival rates at 12 and 24 months were 88% and 84% in the angiography group, and 88% and 70% in the CT group, respectively (P = 0.57). Of the 34 patients in the angiography group, 27 (79%) suffered from adverse reactions of additional angiography and subsequent chemoembolization, seven (20.6%) experienced serum bilirubin increases of ,1 mg/dL over baseline, and two (5.9%) developed renal impairment. Conclusion:, Additional angiography and chemoembolization did not reduce tumor recurrence or improve patient survival in HCC patients who achieved CN, as assessed using dynamic CT, following TACE. © 2004 Blackwell Publishing Asia Pty Ltd [source] Two-Year Clinical Registry Follow-up of Endothelial Progenitor Cell Capture Stent Versus Sirolimus-Eluting Bioabsorbable Polymer-Coated Stent Versus Bare Metal Stents in Patients Undergoing Primary Percutaneous Coronary Intervention for ST Elevation Myocardial InfarctionJOURNAL OF INTERVENTIONAL CARDIOLOGY, Issue 2 2010ERIC CHONG M.B.B.S., F.A.M.S., M.R.C.P. Background: Endothelial progenitor cell (EPC) capture stent is designed to promote rapid endothelization and healing and is potentially useful in patients undergoing primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). We studied the intermediate-term efficacy and safety of EPC stent and compared that with sirolimus-eluting bioabsorbable polymer stent (CURA) and bare metal stent (BMS) in AMI patients. Methodology: Patients presenting with AMI who underwent primary PCI with the respective stents between January 2004 and June 2006 were enrolled in the single-center clinical registry. The study end-points were major adverse cardiac events (MACE) and stent thrombosis. Results: A total of 366 patients (EPC = 95, CURA = 53, BMS 218) were enrolled. Baseline demographics including age, gender, diabetes, renal impairment, predischarge left ventricular ejection fraction, and creatinine kinase level were comparable among the groups. Procedural success rate was 99.5%. Post-procedural thrombolysis in myocardial infarction (TIMI) 3 flow was achieved in EPC 91.6%, CURA 96.2%, and BMS 88.5% (P = 0.209). At 2 years, the MACE rate was EPC 13.7%, CURA 15.1%, and BMS 19.7% (P = 0.383). Target vessel revascularizations (TVR) were EPC 4.2%, CURA 9.4%, and BMS 6.0% (P = 0.439). Nonfatal myocardial infarctions were EPC 1.1%, CURA 3.8%, and BMS 4.1% (P = 0.364). One patient in the EPC group had acute stent thrombosis. There was no late stent thrombosis in the EPC group. Conclusion: EPC stent appeared to be safe and had comparable clinical efficacy with a BMS when used in the AMI setting. At 2-year follow-up, the EPC group showed favorable, single-digit TVR rate and stent thrombosis remained a low-event occurrence. (J Interven Cardiol 2010;23:101-108) [source] Gadolinium-based contrast agents and their potential role in the pathogenesis of nephrogenic systemic fibrosis: The role of excess ligandJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 5 2008Martin A. Sieber PhD Abstract Purpose To investigate the role of excess ligand present in gadolinium (Gd) -based contrast agents in the development of nephrogenic systemic fibrosis (NSF). Using a dosing regimen to simulate the exposure seen in patients with severe renal impairment, we investigated the effect of excess ligand on Gd-deposition and the depletion of endogenous ions. Materials and Methods Gadodiamide and gadoversetamide were formulated with 0%, 5%, and 10% excess ligand. Forty-two, healthy, male Hannover Wistar rats received daily intravenous injections of each formulation over a period of 20 days. At the end of the study, histopathological analysis of the skin was performed and the concentrations of Gd, Zn, and Cu were measured in several tissues. The levels of Zn in the urine were also measured. Results The most severe skin lesions were observed after injection of formulations containing 0% free ligand and in those animals with the highest Gd concentrations in the skin. There were no significant reductions in the levels of Zn or Cu observed in the skin; however, the levels of Zn in the urine were elevated following administration of formulations with the highest amount of excess ligand. Conclusion Our findings suggest that there is an inverse correlation between the amount of excess ligand present in Gd-containing contrast agents and the amount of Gd in the tissue, and further underline the importance of the inherent stability of these agents in the development of NSF. J. Magn. Reson. Imaging 2008;27:955,962. © 2008 Wiley-Liss, Inc. [source] | |||||||||||||||||||||||||||||||||||||