Reduced Creatinine Clearance Research Articles

Pharmacological therapies for the prevention of acute kidney injury following cardiac surgery: a systematic review.

Post-cardiac surgery acute kidney injury (AKI) is common and is associated with a significant increase in morbidity and mortality. We aimed to systematically review randomised trials that assessed the renoprotective utility of pharmacological agents in patients undergoing cardiac surgery. We searched PubMed, Embase and the Cochrane Central Register of Controlled Trials for randomised controlled trials comparing renoprotective pharmacological interventions with control in adult patients undergoing cardiac surgery with cardiopulmonary bypass. We extracted data for mortality, need for renal replacement therapy (RRT), incidence of AKI, and creatinine clearance at 24-48 h. About 49 randomised controlled trials involving 4605 patients were included. Pharmacological interventions included dopamine, fenoldopam, calcium channel antagonists, natriuretic peptides, diuretics, and N-acetylcysteine. Most trials were of poor quality, with small sample sizes, under-reporting of randomisation procedure, allocation concealment and method of blinding. No pharmacological intervention significantly reduced mortality. Fenoldopam and Atrial Natriuretic Peptide (ANP) reduced the need for renal replacement therapy by 5% (NNT 20, 95% CI 11.3, 83.0) and 3.5% (NNT 29, 95% CI 17.1, 84.4), respectively. Brain Natriuretic Peptide resulted in a 10% reduction in the incidence of AKI (NNT 11, 95% CI 6.2, 32.0). Dopamine caused a significant reduction in creatinine clearance (-4.26 ml/min, 95% CI -7.14, -1.39). The quality of studies that have assessed pharmacological renoprotective agents in cardiac surgery is generally poor. Fenoldopam, ANP and BNP show evidence of renoprotection. Randomised studies evaluating the effect of novel renoprotective agents that are powered to detect clinically relevant differences in outcomes are required.

Antinuclear Antibodies and Clinical Associations in a British Cohort with Limited Cutaneous Systemic Sclerosis

To assess the prevalence of disease-specific autoantibodies in patients with limited cutaneous systemic sclerosis (lcSSc). Sera from 180 patients with lcSSc were analyzed for antinuclear antibody (ANA). Clinical characteristics were compared in the presence or absence of specific autoantibodies. SSc-specific antibodies were detected in 135 patients (75%). Associations were found between anticentromere antibody and age at lcSSc diagnosis, telangiectasia, reduced creatinine clearance, and selective reduction in DLCO, and between antitopoisomerase-I and pulmonary fibrosis. The majority of patients with lcSSc belong to distinctive serologic subsets, potentially with prognostic significance.

Motor and behavioral changes in rats with adenine-induced chronic renal failure: influence of acacia gum treatment

Chronic renal failure (CRF) either occurring naturally in humans or induced surgically in rats causes alterations in behavior and motor functions. However, the effect of chemically induced CRF in rats on behavior is not known. We induced CRF in rats by feeding adenine (0.75% w/w, four weeks) and investigated the effect of the ensuing CRF on a depression model (forced swimming test, FST), analgesia (mechanical nociception), neuromuscular coordination (Rota-rod test) and motor activity (activity meter test). Further, we investigated the effect of giving acacia gum (AG, 10% w/v) in the drinking water concomitantly with adenine using the above models. AG has been previously shown to ameliorate the severity of CRF in humans and rats. Adenine-induced CRF significantly increased the plasma concentrations of urea and creatinine, and reduced creatinine clearance. Additionally, it significantly reduced motor activity and increased immobility time in the FST, suggesting a depressant-like effect. Both of these actions were significantly antagonized by AG treatment. Adenine insignificantly reduced the mechanical nociceptive threshold by 15%. The results of the tests for neuromuscular coordination were inconclusive. In conclusion, adenine-induced CRF caused motor and behavioral alterations, and these were significantly mitigated by administration of AG.

Inflammatory Mediators Release in Urine from Mice Injected withCrotalus durissus terrificusVenom

In this study, we investigated in groups of female BALB/c mice injected with Crotalus durissus terrificus venom (Cdt) the renal function based on creatinine clearance, percentage of fractional excretion cytokines and histological examination of renal tissue. Cdt caused renal alterations that induced proteinuria during the initial hours post-venom and reduced creatinine clearance 15 min. up to 2 hours post-venom administration. In urine from mice injected with Cdt induced a decrease in IL-4 levels. More pronounced increments of IL-5, IL-6 and IFN-γ were observed after 15 and 30 min, respectively. The highest levels of TNF and IL-10 were observed at 1 and 4 hs, respectively. The ratios of pro- and anti-inflammatory cytokines in animals injected with Cdt, which may be manifested in the inflammatory status during the envenoming. In groups of animals treated with Cdt were observed a decreasing in creatinine clearance and its effect on glomerular filtration rate was accompanied by decreased fractional excretion of cytokines and morphologic disturbances. This loss of change selectively in envenomation could thus explain why the relatively excretion of cytokines is reduced while of total proteins increases. In conclusion the fractional excretion of cytokines is significantly reduced in mice injected with Cdt, despite proteinuria.

Acute ischemic injury to the renal microvasculature in human kidney transplantation

Increased understanding of the pathophysiology of ischemic acute kidney injury in renal transplantation may lead to novel therapies that improve early graft function. Therefore, we studied the renal microcirculation in ischemically injured kidneys from donors after cardiac death (DCD) and in living donor kidneys with minimal ischemia. During transplant surgery, peritubular capillaries were visualized by sidestream darkfield imaging. Despite a profound reduction in creatinine clearance, total renovascular resistance of DCD kidneys was similar to that of living donor kidneys. In contrast, renal microvascular perfusion in the early reperfusion period was 42% lower in DCD kidneys compared with living donor kidneys, which was accounted for by smaller blood vessel diameters in DCD kidneys. Furthermore, DCD kidneys were characterized by smaller red blood cell exclusion zones in peritubular capillaries and by greater production of syndecan-1 and heparan sulfate (main constituents of the endothelial glycocalyx) compared with living donor kidneys, providing strong evidence for glycocalyx degradation in these kidneys. We conclude that renal ischemia and reperfusion is associated with reduced capillary blood flow and loss of glycocalyx integrity. These findings form the basis for development of novel interventions to prevent ischemic acute kidney injury.

Contrasting effects of intervention with ETA and ETB receptor antagonists in hypertension induced by angiotensin II and high-salt dietThis article is one of a selection of papers published in the two-part special issue entitled 20 Years of Endothelin Research.

Endothelin (ET) receptor antagonists are antihypertensive and renoprotective in angiotensin II (AngII)-induced hypertension if administered when AngII infusion commences, but their effects on established hypertension are poorly understood. We therefore tested the effects of intervening with an ETA (ABT-627) or ETB (A-192621) receptor antagonist after establishing hypertension with AngII (65 ng/min s.c.) plus 8% NaCl diet (AngII–HS) in rats. Prior to administration of ABT-627, AngII–HS and AngII–HS plus ABT-627 groups displayed robust hypertension (mean arterial pressure (MAP), 170 ± 5 and 165 ± 5 mm Hg versus 110 ± 3 mm Hg in normal salt control rats at day 7, P < 0.05). Administering ABT-627 from day 8 of AngII–HS treatment prevented further rises in MAP (168 ± 5 and 191 ± 3 mm Hg at day 13 in AngII–HS plus ABT-627 and AngII–HS, P < 0.001), without blunting the significant increases in urinary protein (19-fold), albumin (25-fold), or MCP-1 excretion (6- to 8-fold) or the reduction in creatinine clearance. Administering A-192621 from day 8 mildly exacerbated AngII–HS induced hypertension (P < 0.05 for AngII–HS versus AngII–HS plus A-192621 on days 11 and 12 only) and reduced plasma nitrite/nitrate concentration (P < 0.05), without affecting proteinuria, albuminuria, or creatinine clearance. These results confirm the importance of ETA receptor signaling in maintaining AngII–HS hypertension and suggest that including ETB receptor blockade in therapeutic approaches to treating hypertension would be ineffective or even counterproductive.

Novel Superoxide Dismutase Mimetics for Protection against Paraquat-induced Acute Renal Injury

Paraquat-induced nephrotoxicity involves severe renal damage caused by reactive oxygen species (ROS), specifically by increasing superoxide (O2●-) generation in the kidney. While proven to be of benefit in animal models of organ injury involving O2●-, superoxide dismutase (SOD) and superoxide dismutase mimetics (SODm) can suffer problems regarding their bioavailability and toxicity. Since ROS has been incriminated in the pathogenesis of several disease conditions including acute kidney injury, the search for ideal SODm therefore continues unabated. Thus, the current study aims at investigating the therapeutic potential of Manganese (II) complexes of ethylenebis (oxyethylenenitrilo) tetraacetic acid (EGTA) and ethylenebis hydroxyphenylglycine (EHPG), novel SODm, against paraquat-induced nephrotoxicity using an in vivo rodent model. Administration of a single intraperitoneal dose of 10-50 or 100 mg/kg paraquat to male Wistar rats (200-250g) produced acute kidney injury within 48 and 24 hours respectively; as evidenced by a significant increase in serum creatinine, fractional excretion of sodium and a reduction in creatinine clearance. Unlike Mn (II)-EGTA (2mg/kg), Mn (II)-EHPG (4mg/kg) was able to significantly attenuate the acute kidney injury induced by 10-50 mg/kg paraquat. These complexes were not toxic at the doses examined unlike SOD or conventional SODm which can display pro-oxidant actions at higher concentrations. Since the clinical toxicity profiles of EGTA and EHPG are already known, these novel SODm particularly Mn (II)-EHPG could be beneficial in attenuating disease conditions involving ROS generation. Keywords: Acute kidney injury, Oxidative stress, Paraquat, Superoxide anion, Superoxide dismutase mimetics

Nephroprotection of lacidipine against gentamycin-induced nephrotoxicity in albino rats.

Gentamycin, a widely-used aminoglycoside antibiotic, is recognized as possessing significant nephrotoxic potential in human beings. Gentamycin-induced nephrotoxicity is suggested to be mediated via reactive oxygen species. The present study investigated the possible antioxidant nephroprotective effect of lacidipine as a calcium-channel blocker in a gentamycin-induced nephrotoxicity model in albino rats. Albino rats were divided into 3 groups. Group 1 received normal saline. Group 2 received gentamycin 80 mg/kg intraperitoneally for 14 days. Group 3 received lacidipine 1 mg/kg intraperitoneally 3 days before and 14 days concurrently with gentamycin. This dose does not affect the blood pressure of rats, as evidenced in the pilot study. Gentamycin-induced nephrotoxicity was evidenced by a marked reduction in creatinine clearance. Treatment with lacidipine improved creatinine clearance compared to the gentamycin-treated group. In addition, it reduced thiobarbituric acid reactive substance, as an index of lipid peroxidation, with significant increases in superoxide dismutase enzyme in erythrocyte lysates and kidney catalase enzyme activities. This study recommends the use of lacidipine in prophylaxis against gentamycin-induced nephrotoxicity.

ASSESSMENT OF RENAL FUNCTION IN DETECTION OF SUBCLINICAL ORGAN DAMAGE AND RISK STRATIFICATION IN HYPERTENSIVE PATIENTS: PP.35.464

Objective: Reduction in glomerular filtration rate (GFR) and microalbuminuria (MAU) are independent predictors of cardiovascular morbidity and mortality. ESH-ESC guidelines (2007) list a slight reduction of creatinine clearance by Cockroft-Gault formula (ClCr) or GFR-MDRD among signs of subclinical organ damage. The aim of study was to evaluate the impact of various methods of renal function assessment on detection of subclinical organ damage and risk stratification. Methods: In 576 non-diabetic hypertensive pts without established cardiovascular or renal disease (291 male, 53.0 ± 10.1 years (M ± SD), BMI 29.4 ± 4.4 kg/m2, 38% smokers, BP 156 ± 13/99 ± 8 mmHg, Cr 94.3 ± 17.4 μmol/l, FPG 5.2 ± 0.6 mmol/l) and in 158 hypertensive treatment-naive type 2 diabetes mellitus (T2DM) pts (82 male, 56.2 ± 8.2 years, BMI 31.5 ± 4.4 kg/m2, 30% smokers, BP 138 ± 14/82 ± 7 mmHg, Cr 81.5 ± 15.1 μmol/l, FPG 9.1 ± 2.4 mmol/l) MAU by albumin/creatinine urine ratio, ClCr and GFR-MDRD were assessed. Results: In non-diabetic pts ClCr was 96.7 ± 15.5 ml/min, GFR-MDRD 69.4 ± 20.1 ml/min/1.73m2. Prevalence of slight Cr increase, ClCr <60 ml/min, GFR-MDRD <60 ml/min/1.73m2 and MAU was 15.6, 5.9, 28.1 and 7.1%. Subclinical kidney damage and high/very high risk was detected in 15.6 and 30.7% of pts based on Cr increase and reduced ClCr or GFR-MDRD. Based on Cr increase, MAU and reduced ClCr or GFR-MDRD kidney damage was revealed in 22.4 and 37.5%. In T2DM pts ClCr was 104.3 ± 29.1 ml/min, GFR-MDRD 81.7 ± 15.6 ml/min/1.73m2, cystatin C 0.91 ± 0.12 mg/l. Prevalence of ClCr <60 ml/min, GFR-MDRD <60 ml/min/1.73m2, MAU and cystatin C >0.9 mg/l was 4.4, 8.2, 7.6 and 37.3%, respectively. MAU and reduced GFR-MDRD coexist within 7 (3.4%) and 2 (8%) of non-diabetic and T2DM pts. Conclusions: Combined assessment of GFR-MDRD and MAU improves the detection of subclinical kidney damage in hypertensive pts. Due availability, low cost and high predictive value it should be the first step in assessment of subclinical organ damage for cardiovascular risk assessment. Cystatin C, the novel alternative marker of renal function, is high sensitive in detection of renal damage in pts with T2DM.

The effect of creatinine clearance on the short-term outcome of neuropathic diabetic foot ulcers

Reduced creatinine clearance is related to an increased risk for diabetic foot ulcer development. Wound healing has been reported to be worse in diabetic patients with impaired kidney functions than general diabetic population. This study aimed to investigate the effect of creatinine clearance on the short-term outcome of neuropathic diabetic foot ulcers. Data from 147 neuropathic diabetic foot ulcer episodes were included in this observational study. Patients were admitted to Dokuz Eylul University Hospital between January 2003 and June 2008. Patients were excluded if they had limb ischemia. Diabetic nephropathy was investigated by 24 h urinary albumin excretion and serum creatinine levels. Creatinine clearance was calculated according to Cockcroft–Gault formula. Foot ulcers were followed up for 6 months to determine the outcome. Our short-term follow-up revealed that neuropathic diabetic ulcers healed worse in patients with decreased creatinine clearance than in those who had normal creatinine clearance. Amputation rates were also found to be higher. Our results suggest that creatinine clearance is an important factor affecting wound healing in patients with neuropathic diabetic foot ulcers.

Landmark Publication from The American Journal of the Medical Sciences: The Clinical Pharmacology of Digitalis Glycosides: A Review

The metabolic half-times and excretion rates of labeled cardiac glycosides are related to pharmacologic or therapeutic activity. Digoxin, a short-acting glycoside, is excreted primarily in the urine and has a serum half-time of 34hours. This function is related primarily to digoxin excretion. Digitoxin, a long-acting glycoside, has a serum half-time of 50+ hours and a physiologic half-time of 51/2 days. It is excreted primarily in the urine as metabolites of the parent compound. Renal failure compromises digoxin excretion and prolongs the digoxin serum half-time and thereby the pharmacologic activity of the drug. As excretion is related to creatinine clearance, dosage should be reduced in proportion to reduction in creatinine clearance in renal insufficiency. Hyper-thyroid patients have lower digoxin serum levels and hypothyroid patients higher digoxin serum levels when compared to euthyroid patients. This finding confirms the clinical impression of digitalis resistance in hyperthyoidism and sensitivity in myxe-dema. Appropriate alterations in digoxin dosage in thyroid disease are justified. Patients with liver disease and cor pulmonale have normal digoxin serum levels, half-times and excretion rates. Increased digitalis sensitivity in these patients is related to other factors. Knowledge of the serum half-time, route of excretion, and rate of excretion of the cardiac glycosides is now available. Application of this information to the patient receiving digitalis assists in avoiding over- and under-digitalization—both common clinical problems. If doubt exists regarding digitalis dosage, smaller, rather than larger, doses are suggested to avoid toxicity.

752 EVALUATION OF RENAL MORPHOLOGY AND FUNCTION AFTER ORTHOTOPIC BLADDER REPLACEMENT USING Z-SHAPED ILEAL NEOBLADDER: A SERIES OF 321 PATIENTS

You have accessJournal of UrologyUrinary Diversion: Bladder Reconstruction, Augmentation, Substitution, Diversion I1 Apr 2010752 EVALUATION OF RENAL MORPHOLOGY AND FUNCTION AFTER ORTHOTOPIC BLADDER REPLACEMENT USING Z-SHAPED ILEAL NEOBLADDER: A SERIES OF 321 PATIENTS Yann Neuzillet, Laurent Yonneau, Thierry Lebret, Jean-Marie Herve, Pierre-Marie Lugagne, and Henry Botto Yann NeuzilletYann Neuzillet More articles by this author , Laurent YonneauLaurent Yonneau More articles by this author , Thierry LebretThierry Lebret More articles by this author , Jean-Marie HerveJean-Marie Herve More articles by this author , Pierre-Marie LugagnePierre-Marie Lugagne More articles by this author , and Henry BottoHenry Botto More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.1304AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES To evaluate the results in terms of preservation of renal morphology and function with Z-shaped ileal neobladder performed at our center. METHODS 321 consecutive patients, 27 women (8%) and 294 men (92%) who had an orthotopic bladder replacement using Z-shaped ileal neobladder between May 1990 and January 2009. The techniques used for uretero-neobladder anastomosis were those of Camey-Leduc, a direct anastomosis or anastomosis “in trunk” respectively in 3, 252 and 66 cases. Renal function was assessed by creatinine clearance (MDRD) and renal morphology was assessed by IVP and/or by CT-scan. RESULTS The mean age of the patients was 63.4±11.8 years. The mean follow-up was 59.4 ± 55.5 months. The surgical indications were bladder tumors in 315 (98.2%) cases and non-oncological in 6 (1.8%) cases. Three (1%) patients had a creatinine clearance (MDRD) below 30 ml / min. before cystectomy, including one with a abnormal upper urinary tract (UUT) morphology. Ten (3.1%) patients required a surgical procedure for uretero-neobladder anastomosis stenosis. The preservation of the upper tract morphology, and necessity of a surgical procedure was independent of the techniques used for uretero-neobladder anastomosis. At the end of follow-up, renal function was reduced by 11 ml/min. on average. Creatinine clearance was 79±21 ml/min and 68±30 ml/min respectively before cystectomy and at the end of the follow-up (p <0.0001). After cystectomy, fourteen (4.3%) patients had creatinine clearance which is now below 30 ml/min. Forty five patients (14%) developed metabolic acidosis, easily controlled by oral treatment with bicarbonate. CONCLUSIONS In our series of 321 patients, Z-shaped ileal neobladder allowed the preservation of the morphology and function of the upper tract in more than 89% despite reduction of creatinine clearance. Figure 1. Modification of UUT morphology. Table. Change in creatinine clearance according to the morphology of the upper tract: Normal morphology AFTER cystectectomy (n= 287) Pathological morphology AFTER cystectectomy (n= 34) p= Normal morphology BEFORE cystectectomy (n= 277) -11,54 ± 36,19 (lost of 14% of initial value) -28,03 ± 32,98 (lost of 35% of initial value) 0,04 Pathological morphology BEFORE cystectectomy (n= 44) 0,16 ± 46,47 (lost of 0% of initial value) -13,54 ± 26,13 (lost of 18% of initial value) 0,46 p= 0,15 0,29 Suresnes, France© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e294 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yann Neuzillet More articles by this author Laurent Yonneau More articles by this author Thierry Lebret More articles by this author Jean-Marie Herve More articles by this author Pierre-Marie Lugagne More articles by this author Henry Botto More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...

Comparative protective effect of N‐acetyl cysteine and tetramethylpyrazine in rats with gentamicin nephrotoxicity

Gentamicin (GM) is used against serious and life‐threatening infections, but its use is limited by the occurrence of nephrotoxicity, which involves the generation of free radicals. In this work we tested the effect of a compound with antioxidant properties, tertamethylpyrazine (TMP), on GM‐induced nephrotoxicity, and compared it with an established anti‐oxidant compound N‐acetyl cysteine (NAC). Six groups of rats were studied: (1) control, treated orally (p.o.) and intraperitoneally (i.p.) with saline; (2) treated i.p. with GM (80 mg kg‐1 per day for 6 days); (3) TMP, given p.o. (100 mg kg‐1 per day for 10 days) + GM (same dose as above during the last 6 days); (4) NAC, given i.p. (500 mg kg‐1 per day for 10 days) + GM as above; (5) TMP (100 mg kg‐1 per day for 10 days) + saline; (6) NAC (500 mg kg‐1 per day for 10 days) + saline. GM nephrotoxicity was characterized by reduced creatinine clearance, increased creatinine and urea concentrations in plasma. These functional and structural alterations were prevented or ameliorated by NAC treatment, while TMP had only a slight mitigating effect. The concentration of GM in the renal cortex of the rats given GM + NAC (but not TMP) was lower than that found in rats treated with GM alone. The mechanism by which NAC and, to a lesser extent TMP, protected against GM‐induced nephrotoxicity may be related, at least in part, to the decrease in oxidative stress in renal cortex.

1974 ROLE OF TOTAL ANGIOTENSIN BLOCKADE ON RECOVERABILITY OF RENAL FUNCTION AFTER RELIEF OF CHRONIC PARTIAL UNILATERAL URETERAL OBSTRUCTION

You have accessJournal of UrologyStone Disease: Basic Research1 Apr 20101974 ROLE OF TOTAL ANGIOTENSIN BLOCKADE ON RECOVERABILITY OF RENAL FUNCTION AFTER RELIEF OF CHRONIC PARTIAL UNILATERAL URETERAL OBSTRUCTION Shady Soliman, Ahmed Shokeir, Ahmed Mosbah, Hassan Abol-Enein, Nashwa Barakat, Essam Abou-Bieh, and Ehab Wafa Shady SolimanShady Soliman More articles by this author , Ahmed ShokeirAhmed Shokeir More articles by this author , Ahmed MosbahAhmed Mosbah More articles by this author , Hassan Abol-EneinHassan Abol-Enein More articles by this author , Nashwa BarakatNashwa Barakat More articles by this author , Essam Abou-BiehEssam Abou-Bieh More articles by this author , and Ehab WafaEhab Wafa More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.1984AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES To evaluate of the effect of total angiotensin blockade (ACEI (enalapril) + angiotensin receptor blocker losartan) on prevention of deterioration of renal function during partial unilateral ureteral obstruction (PUO) and to study their impact on enhancement of recoverability of renal function after relief of obstruction. METHODS Fifty six male mongrel dogs were classified into 5 groups: sham (8; sham surgery + no medications), control (12; left PUO + no medications), and 3 study groups; 12 dogs each; left PUO + either enalapril; losartan or combination. The study and control groups were subjected to 4 weeks PUO. After that, dogs of the control and study groups were reopened and subjected to Lich-Grigoir ureterovesical re-implantation. Dogs of the control and the study groups were sacrificed by the 8th week after relief of obstruction after being evaluated at basal condition, by the end of the 4th week of obstruction and at 4 and 8 weeks after relief of obstruction by measurement of selective endogenous creatinine clearance, selective renographic clearance and renal resistive index (RI). Dogs of the sham group underwent sham surgery at basal, 4 and 8 weeks and were subjected to same evaluation. RESULTS Sham surgery showed no significant impact on any of the evaluated parameters. Compared with the control, combination therapy saved reduction of creatinine clearance by 13% of the basal value and saved reduction of the renographic clearance by 20 % of the basal value by the end of the 4th week of obstruction. During PUO, combination therapy adds no significant benefit compared with the use of either drug alone. The renoprotective effect after 4- week obstruction was 18 % for the losartan, 12% for the enalapril and 20 %for the combination. Moreover, compared with the control, combination therapy enhanced regain of creatinine clearance by 18 % of the basal value and enhanced regain of renographic clearance by 34 %. Combined therapy significantly enhanced recoverability of renal function compared with either drug alone. Compared with the controls, enhancement of the recoverability of renal function after 8 -week relief of 4- week obstruction was 24 % for the losartan, 23% for the enalapril and 34 %for the combination (P<0.001). In addition, the increase of RI was significantly less in the three study groups. CONCLUSIONS Total angiotensin blockade decreases deterioration of renal function in partial UUO and enhances recoverability of renal function after relief of obstruction. The effect was more pronounced during recoverability phase. Mansoura, Egypt© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e766 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Shady Soliman More articles by this author Ahmed Shokeir More articles by this author Ahmed Mosbah More articles by this author Hassan Abol-Enein More articles by this author Nashwa Barakat More articles by this author Essam Abou-Bieh More articles by this author Ehab Wafa More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Unfavourable interaction of microalbuminuria and mildly reduced creatinine clearance on aortic stiffness in essential hypertension

The aim of our study was to assess the independent relationships of urinary albumin excretion rate (AER), of creatinine clearance (CrCl) and of their interaction with aortic stiffness in hypertensive patients without overt renal insufficiency. We studied 222 untreated nondiabetic essential hypertensives. In patients with reliable 24-h urine collections, AER and CrCl were determined. Microalbuminuria (MAU) was defined as an AER of 20 to 200 µg/min. Aortic stiffness was assessed by measurement of carotid-femoral pulse wave velocity (c-f PWV). C-f PWV was higher in subjects with MAU than in those without it (p<0.001, even after adjustment for age, sex and mean arterial pressure) and in subjects with CrCl below 90 ml/min/1.73 m(2) when compared to those with greater values of CrCl (p=0.04 after correction for age, sex and mean arterial pressure). There was a significant interaction of MAU and reduced CrCl regarding c-f PWV (p=0.04). In multiple regression analysis, AER and CrCl remained independently associated with aortic stiffness (β=0.22; p<0.001 and β=-0.13; p=0.02, respectively). In essential hypertensive patients microalbuminuria and mildly reduced CrCl are related independently of each other with increased c-f PWV and exert a synergistic unfavourable effect on aortic stiffness.

Safety Considerations of Fluoroquinolones in the Elderly

The fluoroquinolones ciprofloxacin, levofloxacin, moxifloxacin and gemifloxacin are widely used for the treatment of various types of bacterial infections. Overall, these antibacterial agents can be considered safe and well tolerated drugs. Comparative studies have evaluated the use of quinolones in elderly and younger populations. Although age per se does not seem to decrease their tolerability, specific adverse effects of the quinolones must be considered when they are chosen for antibacterial treatment. Renal function declines consistently with age and doses of renally excreted quinolones (e.g. ofloxacin, levofloxacin, gatifloxacin) need to be adjusted if a clinically relevant reduction of creatinine clearance is identified. Reactions of the gastrointestinal tract, such as nausea, dyspepsia, vomiting or diarrhoea, are among the most often registered adverse drug reactions during therapy with fluoroquinolones. Treatment with a quinolone causes diarrhoea less frequently than treatment with other classes of antimicrobials. Conflicting data have been published with respect to the incidence of Clostridium difficile-associated diarrhoea in quinolone-treated patients. Hypersensitivity reactions, often manifested on the skin, occur less commonly during therapy with quinolones than, for example, during therapy with beta-lactam antibacterials. Adverse reactions of the CNS are of particular concern in the elderly population. Given the CNS excitatory effects of quinolones, elderly patients should be monitored carefully for such symptoms. It is likely that many signs of possible adverse reactions, such as confusion, weakness, loss of appetite, tremor or depression, are often mistakenly attributed to old age and remain unreported. Quinolones should be used with caution in patients with known or suspected CNS disorders that predispose to seizures (e.g. severe cerebral arteriosclerosis or epilepsy). Quinolones can cause QT interval prolongation. They should be avoided in patients with known prolongation of the QT interval, patients with uncorrected hypokalaemia or hypomagnesaemia and patients receiving class IA (e.g. quinidine, procainamide) or class III (e.g. amiodarone, sotalol) antiarrhythmic agents. Tendinitis and tendon ruptures are recognized as quinolone-induced adverse effects that can occur during treatment or as late as several months after treatment. Chronic renal diseases, concomitant use of corticosteroids and age >60 years are known risk factors for quinolone-induced tendopathies. Overall, the specific adverse-effect profile of quinolones must be considered when they are chosen for treatment of bacterial infections. Because of physiological changes in renal function and when certain co-morbidities are present, some special considerations are necessary when elderly patients are treated with these drugs.

A Gender Comparison of Postobstructive Injury in the Rat Kidney

Background/Aims: Unilateral ureteral obstruction (UUO) results in renal injury. Studies report increased injury indices in male rats following UUO. Our study examined whether this gender-based renal response to UUO was reflected in sustained differences following relief of obstruction. Methods: Adult male/female rats (200–400 g) were subjected to either sham surgery (S/RN) or UUO (UUO/RN). At 24 h, obstruc- tion was relieved and all animals underwent contralateral nephrectomy. Five days after initial surgery, animals were placed in metabolic cages and given water ad libitum for 24 h followed by a 24-hour period of complete water restriction. On day 7, animals were euthanized and samples harvested. Tubular injury, urinary volume/osmolality, creatinine clearance, plasma arginine vasopressin, renal medullary V2 receptor and aquaporin 2 (AQP2) expression were measured. Results: Male UUO/RN rats showed increased renal apoptotic injury and reduced creatinine clearance rates (glomerular filtration rate) vs. females. No gender-dependent differences were observed in urinary osmolality or concentrating ability. AQP2 expression increased post-obstruction. Conclusion: Increased injury in males following UUO remains manifest during early recovery after release of obstruction. Despite this, the grade of postobstructive diuresis is not significantly altered between sexes. This may reflect reduced glomerular filtration rate and elevated AQP2 in male rats.

Determination of Spatial Distribution of Melamine−Cyanuric Acid Crystals in Rat Kidney Tissue by Histology and Imaging Matrix-Assisted Laser Desorption/Ionization Quadrupole Time-of-Flight Mass Spectrometry

After the outbreak of acute renal failure associated with melamine-contaminated pet food, many attempts have been made to uncover the mechanism underlying the renal toxicity caused by melamine and melamine-related compounds. Using rat models, we investigated the renal crystal formation following the ingestion of a melamine-cyanuric acid mixture (M+CA, 1:1) to gain insight into the M+CA-induced renal toxicity. M+CA did not induce toxicity in precision-cut kidney slices, suggesting that M+CA does not have a direct nephrotoxicity. On the contrary, oral administration of M+CA for 3 days induced nephrotoxicity as determined by increased serum blood urea nitrogen and creatinine, reduced creatinine clearance, and enlarged kidneys in the animals treated with 50 mg/kg M+CA (melamine, 25 mg/kg, and cyanuric acid, 25 mg/kg; 2 of 10 animals) and 100 mg/kg M+CA (9 of 9 animals). While urine crystals were found in all animals treated with M+CA (25-100 mg/kg), histological examination revealed that renal crystals could be observed only in the kidneys of animals showing signs of nephrotoxicity. Remarkably, at 50 mg/kg M+CA, crystals were observed mainly in the medulla region of the kidney, while at 100 mg/kg, crystals were disseminated throughout the cortex and medulla regions. To further investigate the crystal formation by M+CA, matrix-assisted laser desorption/ionization quadrupole time-of-flight (MALDI-Q-TOF) imaging mass spectrometry detecting melamine distribution through monitoring the product ion (m/z 85, M + H) from melamine (m/z 127, M + H) was developed to directly obtain the image of melamine distribution in the kidney. The distribution image of melamine in kidney tissue confirmed that dense points of melamine were located only in the medulla region at 50 mg/kg M+CA, while at 100 mg/kg, they were disseminated widely from the cortex to medulla. These results demonstrated that M+CA ingestion could lead to crystal formation in kidney tubules along the osmotic gradient and that renal crystal formation is closely linked with M+CA-induced nephrotoxicity.

Occurrence of adverse, often preventable, events in community hospitals involving nephrotoxic drugs or those excreted by the kidney

Medication errors in patients with reduced creatinine clearance are harmful and costly; however, most studies have been conducted in large academic hospitals. As there are few studies regarding this issue in smaller community hospitals, we conducted a multicenter, retrospective cohort study in six community hospitals (100 to 300 beds) to assess the incidence and severity of adverse drug events (ADEs) in patients with reduced creatinine clearance. A chart review was performed on adult patients hospitalized during a 20-month study period with serum creatinine over 1.5 mg/dl who were exposed to drugs that are nephrotoxic or cleared by the kidney. Among 109,641 patients, 17,614 had reduced creatinine clearance, and in a random sample of 900 of these patients, there were 498 potential ADEs and 90 ADEs. Among these ADEs, 91% were preventable, 51% were serious, 44% were significant, and 4.5% were life threatening. Of the potential ADEs, 54% were serious, 44% were significant, 1.6% were life threatening, and 96.6% were not intercepted. All 82 preventable events could have been intercepted by renal dose checking. Our study shows that ADEs were common in patients with impaired kidney function in community hospitals, and many appear potentially preventable with renal dose checking.

Recoverability of Renal Function After Relief of Chronic Partial Unilateral Ureteral Obstruction: Study of the Effect of Angiotensin Receptor Blocker (Losartan)

To evaluate the effect of angiotensin receptor blocker (losartan) on renal function during and after relief of partial unilateral ureteral obstruction (PUO). A total of 32 male mongrel dogs were classified into 3 groups: sham (8), control (12; left PUO + no medications), and study (12; left PUO + losartan). Dogs of the study and control groups were subjected to 4 weeks of PUO. After that, they were reopened and subjected to Lich-Grigoir ureterovesical reimplantation and then were killed by the end of 32 weeks after relief of obstruction after being evaluated at basal condition; fourth week of obstruction; and at 4, 8, and 32 weeks after relief of obstruction by measurement of selective creatinine clearance (CCr), selective renographic clearance (RC), and renal resistive index. Sham group underwent sham surgery at 4 and 32 weeks and evaluated as the other 2 groups. Sham surgery showed no significant effect on any of the evaluated parameters. Compared with the control, losartan saved reduction in CCr by 11% and RC by 20% of the basal value by the end of the fourth week of obstruction, respectively. Moreover, compared with the control, losartan enhanced regain of CCr by 26% and RC by 26% also of the basal value at 32 weeks after relief of fourth week obstruction, respectively. In addition, the increase in renal resistive index was significantly less in the losartan group. Losartan decreases the deterioration of renal function in PUO and enhances recoverability of renal function after relief of obstruction.