Influence Of Chronic Renal Failure Research Articles

Platelet reactivity in patients with impaired renal function receiving dual antiplatelet therapy with clopidogrel or ticagrelor

BackgroundSuboptimal platelet inhibition still represents an important challenge, especially for patients undergoing percutaneous coronary interventions (PCI). Chronic kidney disease (CKD) is a common comorbidity of patients with coronary artery disease, and may potentially influence platelet reactivity. So far only few studies have assessed the role of CKD on response to dual antiplatelet therapy (DAPT) with conflicting results. Therefore, the aim of our study was to evaluate the impact of CKD on platelet function in patients treated with DAPT after a recent acute coronary syndrome (ACS) or PCI. MethodsPatients treated with DAPT, acetylsalicylic acid (ASA)+adenosine diphosphate antagonist (ADP-antagonist) such as clopidogrel or ticagrelor, for ACS or elective patients undergoing PCI were scheduled for platelet function assessment at 30–90days post-discharge. Platelet function was assessed by whole blood impedance aggregometry (Multiplate®- Roche Diagnostics AG), high residual platelet reactivity (HRPR) was considered for ASPI test >862AU*min (for ASA) and ADP test values ≥417AU*min (for ADP-antagonists). Chronic renal failure was defined as an estimated glomerular filtration rate of 60mol/min/1.73m2 or less, calculated by applying MDRD (Modification of Diet in renal Disease) formula. ResultsOur population included a total of 537 patients of which 308 (57.3%) received ASA and clopidogrel and 229 (42.6%) received ASA and ticagrelor. Patients with renal failure at baseline (101 out of 537, 18.8%) were older, with higher prevalence of hypertension, previous myocardial infarction and coronary artery bypass graft surgery. Moreover, they had a lower ejection fraction at baseline and were more often in therapy with diuretics, but less often with statins at admission. They had lower haemoglobin and higher glycated haemoglobin. HRPR was observed in 1.5% of patients treated with ASA with no difference according to renal function (p=0.18). HRPR for ADP-antagonists was observed in 23.7% of patients, with no difference according to renal function (p=0.50). This result was confirmed either with clopidogrel (31.9% versus 38%, p=0.41) and ticagrelor (13.1% versus 10.8%, p=0.99), also after correction for all baseline confounders (clopidogrel: adjusted OR[95%CI]=1.26 [0.60–2.63], p=0.54) (ticagrelor: adjusted OR[95%CI]=0.95 [0.54–1.65], p=0.84). The absence of association between renal function and platelet reactivity was confirmed at linear regression analysis both with clopidogrel (r=−0.04, p=0.52) and ticagrelor (r=0.006, p=0.92). ConclusionIn patients receiving DAPT, chronic renal failure did not influence ADP-mediated platelet reactivity, with both ticagrelor or clopidogrel. No influence of chronic renal failure was found on the effectiveness of ASA.

Marcadores cardiacos en diferentes grados de enfermedad renal crónica: influencia de la inflamación y de la afectación cardiaca previa

Background and objectiveTroponin T (TnT), brain natriuretic peptide (BNP) and its precursor (NT-proBNP) are useful markers of acute coronary events and heart failure. The aim of this study was to analyze the influence of chronic renal failure, inflammation and heart disease in these biomarkers. Patients and methodsIn 266 patients with different stages of chronic renal diseases, the following parameters were measured: cardiac markers (TnT, BNP and NT-proBNP), renal function, inflammatory markers (hsCRP, fibrinogen, albumin, uric acid and white blood cells). We recorded the cardiovascular history. Ventricular dysfunction and left ventricular hypertrophy were assessed by echocardiography. ResultsA significant correlation between cardiac markers and inflammatory parameters such as fibrinogen, hsCRP and albumin was found. Age (OR 1.05, P = .021), serum albumin (OR: 0.06, P=.006), ischemic heart disease (OR: 8.17, P=.0092) and renal failure (OR: 1.67, P=.05) were predictors of higher BNP levels. Age (OR 1.05, P=.0097), serum albumin (OR: 0.12, P=.001), ischemic heart disease (OR: 3.43, P=.034), renal failure (OR: 1, 65, P=.036) and heart failure (OR: 4.33, P=.0312) were predictors of elevated NT-proBNP. Previous ischemic heart disease alone increased TnT levels (OR: 6.51, P=.0012). ConclusionsAge, previous cardiac disease and inflammation increase cardiac marker levels in patients with different stages of renal disease, but the degree of renal failure is an important factor influencing NT-proBNP levels. However, ischemic heart disease alone increases the levels of TnT.

The influence of chronic renal failure on the spectrum and antimicrobial susceptibility of uropathogens in community-acquired acute pyelonephritis presenting as a positive urine culture

BackgroundThe role of chronic renal failure (CRF) in the antimicrobial resistance of uropathogens in patients with community-acquired acute pyelonephritis (APN) remains poorly understood.MethodWe performed a retrospective analysis of 502 adults (54 men, 448 women; mean age 61.7 ± 16.0 years, range 18-98 years) who were treated for community-acquired APN at Kosin University Gospel Hospital (Busan, Republic of Korea) during a ten-year period (January 2000 to December 2009). We evaluated the spectra and antimicrobial susceptibility profiles of uropathogens in CRF and non-CRF patients with community-acquired APN that presented as a positive urine culture.ResultsThe 502 adult subjects were classified as either non-CRF APN patients (336 patients, 66.9%) or CRF APN patients (166 patients, 33.1%) according to their estimated glomerular filtration rate. No significant differences in the sensitivity of E. coli to a third cephalosporin, aminoglycoside (except gentamycin), or ciprofloxacin were observed between non-CRF and CRF patients.ConclusionsIn our series of patients with community-acquired APN that initially presented as a positive urine culture, CRF did not influence the isolation rates of different uropathogens or their patterns of susceptibility to antimicrobials.

The Influence of Chronic Renal Failure on Drug Metabolism and Transport

Chronic renal failure (CRF) has been shown, in animal models and clinical studies, to significantly reduce nonrenal clearance and to alter the bioavailability of predominantly metabolized drugs. Phase II reactions and drug transporters such as P-glycoprotein (P-gp) and organic anion transporting polypeptide (OATP) are also affected. High levels of parathyroid hormone (PTH), cytokines, and uremic toxins are implicated in some of these effects, which have a clinically significant impact on drug disposition and increase the risk of adverse drug reaction.

Miringosclerose em pacientes com insuficiência renal crônica: análise comparativa com um grupo controle

A miringoesclerose é uma alteração cicatricial da lâmina própria da membrana timpânica caracterizada por proliferação de fibras colágenas, seguida de hialinização, deposição de cálcio e fósforo, seguindo uma seqüência semelhante ao que ocorre em outros tipos de calcificação patológica comuns em pacientes com doença renal crônica. OBJETIVO: Verificar a influencia da insuficiência renal crônica (IRC) na prevalência da miringoesclerose. MÉTODO: Foi realizada otoscopia em 341 pacientes com IRC em hemodiálise e em 356 indivíduos de um grupo controle. Foi comparada a freqüência de otoscopia positiva entre os dois grupos, procurando-se relacionar com variáveis pessoais e relacionadas a IRC. RESULTADOS: O grupo de pacientes apresentou 11,7% de otoscopia positiva contra 5,1% do grupo controle. Não houve influência do sexo ou cor na freqüência da miringoesclerose. Porém, os grupos foram heterogêneos em relação à faixa etária. Também não houve diferença importante no tempo de diálise nem nos níveis séricos de minerais e do PTH entre os pacientes do grupo de estudo que apresentavam otoscopia positiva ou negativa. CONCLUSÃO: Os achados, embora apontem para uma maior ocorrência da miringoesclerose nos pacientes renais crônicos, não nos permitem concluir com certeza que exista alguma relação entre a IRC e as alterações timpânicas.

Myringosclerosis in patients with chronic renal failure: comparative analysis with a control group

SummaryMyringosclerosis is a scar of the tympanic membrane lamina propria, resulting from trauma or inflammation, characterized by proliferation of collagen, hyalinization, calcium and phosphate deposits and cartilaginous or osseous metaplasia of the middle ear mucosa, a sequence that is similar to that taking place in other types of pathologic calcification, common in chronic renal failure (CRF).AimTo verify the influence of chronic renal failure on the prevalence of myringosclerosis.MethodThe otoscopic examination was done in 341 chronic renal failure patients and in 356 normal control individuals. The frequency of positive otoscopies was compared between the two groups, based on individual variables and those pertaining to CRF.Results11.7% of the patients had a positive otoscopy in the CRF group, compared to 5.1% in the control group. There was no statistical diference in the frequency of myringosclerosis acording to gender, ethnic group, time of dialysis or serum minerals. The groups had a wide age range.ConclusionAlthough the findings of this study suggest a higher ocurrence of myringosclerosis in patients with renal disease, they do not provide a basis for stating that there is any relation between renal failure and tympanic alterations.

Influence of chronic renal failure on the heart rate response to dipyridamole in patients undergoing myocardial perfusion SPECT

Dipyridamole promotes a reduction in blood pressure and an increase in heart rate (HR), considered the normal hemodynamic response to the drug. Data suggest that patients with chronic renal failure (CRF) have an attenuation of this hemodynamic response. This study sought to evaluate the HR response to dipyridamole and its determinants in patients with or without CRF undergoing gated myocardial perfusion single photon emission computed tomography. Consecutive patients (n = 355, 9.6% with CRF) undergoing rest/dipyridamole myocardial perfusion single photon emission computed tomography were evaluated. The HR response to dipyridamole was considered to be reduced if the HR ratio (maximal HR/rest HR) was 1.20 or less. A logistic regression analysis determined independent predictors of a blunted HR response. A reduced HR response was found in 84.4% of patients with CRF and 40.6% of those without CRF (P < .0001). In patients without CRF the independent predictors of abnormal HR response were hypertension, rest and differential perfusion scores, and left ventricular ejection fraction. In contrast, in CRF patients there was no significant association of any of the studied variables with abnormal HR response. An abnormal HR response to dipyridamole is frequently found in patients with CRF. Different mechanisms may account for abnormal HR response in patients with or without CRF.

Influence of Chronic Renal Failure on Stereoselective Metoprolol Metabolism in Hypertensive Patients

The influence of chronic renal failure on the stereoselective metabolism of rac-metoprolol was investigated in 15 hypertensive patients, 7 of them with chronic renal failure and 8 with normal renal function. They were treated with rac-metoprolol (200 mg) for 7 days. The patients of both groups presented stereoselectivity in metoprolol metabolism, favoring the formation of 1'R-alpha-hydroxymetoprolol (AUC(1(')R/1(')S)(0-24) approximately 2.5) and (R)-metoprolol acidic metabolite (AUC((S)/(R))(0-24) = 0.8), the latter resulting in the plasma accumulation of (S)-metoprolol (AUC((S)/(R))(0-24) = 1.2). Patients with chronic renal failure presented plasma accumulation of the 4 alpha-hydroxymetoprolol isomers and of both metoprolol acidic metabolite enantiomers. A 50% reduction in Cl(R) does not explain the 3- to 4-fold plasma accumulation of metoprolol acidic metabolite in this group, suggesting that other pathways of metoprolol elimination are affected in chronic renal failure in addition to renal excretion. Chronic renal failure does not change the stereoselective kinetic disposition of metoprolol but modifies its stereoselective metabolism, inducing some of the CYP enzymes involved in the formation of the metoprolol acid metabolite.

Acute Ischemia/Reperfusion Injury After Isogeneic Kidney Transplantation Is Mitigated in a Rat Model of Chronic Renal Failure

The influence of chronic renal failure on renal susceptibility to an acute ischemic insult was evaluated. Recipient Lewis rats were randomly assigned to undergo 5/6 nephrectomy (chronic renal failure, CRF) or sham operation (normal renal function, NRF). After 11 weeks, normal kidneys of Lewis donor rats were transplanted in the recipients. The outcome of the isografts was assessed. Filtration capacity of the isografts in the CRF rats was preserved to approximately one-quarter of its normal capacity on the 1st day post-transplantation, whereas it fell to 0 in the NRF rats. This was reflected by a significantly higher increase in serum creatinine in the latter group. The isografts in the CRF rats had a significantly lower degree of acute tubular necrosis and no increase in the number of macrophages and T lymphocytes in the first 24 h in contrast to the NRF rats. Epithelial regeneration and repair started earlier in the CRF group. In conclusion, the present study indicated that CRF blunted ischemia/reperfusion injury of a transplanted kidney, and that its regeneration capacity was certainly not hampered by the presence of chronic uremia. These results will be the basis for studies on modulation of early leukocyte-endothelial interactions resulting from immunological disturbances inherent to the uremic environment.

Utility of tumor marker CA 72.4 in patients with chronic renal failure.

The tumor marker CA 72.4 is composed of two monoclonal antibodies, B 72.3 and cc49, which detect the glycoprotein TAG 72 present in tumor cells. The levels of CA 72.4 may be modified depending on the route of excretion of the antigen TAG 72. The objective of this study was to evaluate the behavior of CA 72.4 in healthy subjects and to assess the influence of chronic renal failure (CRF) on the levels of this tumor marker. Random serum samples were collected in 181 individuals (148 healthy volunteers and 33 patients with CRF) and 214 determinations of CA 72.4 were performed. We also performed 66 determinations of plasma creatinine. In healthy subjects the cutoff value of CA 72.4 was established at 3 U/mL, with a sensitivity of 53% and a specificity of 85.8%. In the CRF patients we found no statistically significant differences when we compared the values of CA 72.4 predialysis and postdialysis (p = 0.197). However, a statistically significant difference was found in the plasma creatinine levels (p < 0.001). Chronic renal failure does not affect the result of CA 72.4 determinations; this tumor marker may therefore be useful in the monitoring of patients with cancer, independent of their renal function.

11.6 Influence of chronic renal failure on the post-operative outcome after cardiac surgery

11.6 Influence of chronic renal failure on the post-operative outcome after cardiac surgery

Contributions to biorheology during hemodialysis

Thrombogenicity is the property of a foreign surface to induce clotting processes or formation of aggregates after contact with blood. Beside the sort of anticoagulation patient's prethrombotic state, rheological factors as well as physicochemical properties of foreign membranes decisively influence thrombogenicity. We examined the influence of chronic renal failure and different hemodialyzers and blood transfusion therapy during hemodialysis on hemorheological parameters. Different membranes cannot be discriminated by the used hemorheological parameters. We clearly could demonstrate the close relationship between the hemofiltration rate and an increase of viscosity. Blood transfusion therapy or elevated hematocrit in combination with increased hemofiltration rate have influence on the flow behaviour of blood, especially in disturbed microcirculation.

Plasma and pituitary content of growth hormone luteinizing hormone, and prolactin in uremic rats. Effects of chronic infusion of insulin.

The influence of chronic renal failure on pituitary content and on serum concentrations of growth hormone (GH), prolactin (PRL), and luteinizing hormone (LH) was studied in chronically uremic rats by comparison with control rats fed ad libitum and diet-restricted rats pair-fed with uremic rats. A decrease of pituitary GH content was found in uremic and diet-restricted rats, in association with a normal circulating GH level. A decrease of pituitary PRL and LH content with respectively high and normal serum values was observed in uremic but not in diet-restricted rats. These data strongly suggest that GH disturbances are related to malnutrition, whereas PRL and LH abnormalities are related to the uremic state per se. As hypoinsulinemia was observed in uremic rats, and as insulin is largely implicated in growth, we have investigated the effects of chronic infusion of insulin, using miniosmotic pumps, on pituitary hormone content. In spite of normalization of circulating insulin levels in uremic rats treated with insulin, pituitary GH, LH, and PRL contents were unaffected. Thus, insulin deficiency did not appear to be responsible for the diminished pituitary reserve of these hormones.

Influence of chronic renal failure on captopril pharmacokinetics and clinical and biological effects in hypertensive patients.

The pharmacokinetic parameters of unchanged plasma captopril and the kinetics of the drug effects on plasma converting enzyme activity (PCEA), plasma renin activity (PRA), plasma aldosterone (PA) and mean blood pressure (MBP) were studied over 24 h after oral administration in three groups of hypertensive patients: with normal renal function (group 1, plasma creatinine less than 110 mumol/l, n = 10), with moderate chronic renal failure (group 2, 135 less than plasma creatinine less than 450 mumol/l, n = 10) and with severe chronic renal failure (group 3, plasma creatinine greater than 500 mumol/l, n = 10). Renal impairment had no effect on plasma captopril Cmax, CLtot and relative bioavailability (AUC). In contrast, captopril kel decreased while T1/2 increased progressively from group 1 to group 3. PCEA blockade (T1/2 and AUC) was increased significantly and proportionally to the degree of renal impairment. However, there were no differences between the three groups regarding captopril-induced modifications of PRA and PA. Although the maximal reduction in MBP was identical in the three groups, the overall antihypertensive effect (AUC) of captopril increased significantly and progressively from group 1 to group 3, especially in duration. There was no correlation between basal plasma creatinine values and unchanged captopril relative bioavailability (AUC) and between unchanged captopril relative bioavailability (AUC) and the drug effects (AUC) on PCEA, PRA, PA and MBP. However there was a correlation between basal plasma creatinine values and plasma captopril T1/2, PCEA blockade (AUC) and overall antihypertensive effect (AUC). The apparent discrepancy between the lack of effects of chronic renal failure on plasma unchanged captopril bioavailability and its potentiating effects on PCEA blockade and MBP reduction may be accounted for by the renal impairment-induced accumulation of captopril metabolites.

Influence of chronic renal failure and hemodialysis on diflunisal plasma protein binding

Diflunisal protein binding was studied by equilibrium dialysis at 37 degrees in plasma from healthy, uremic, and geriatric subjects. Binding data were computer analyzed assuming 2 classes of independent binding sites (Scatchard model). K1, the primary association constant for the diflunisal-albumin interaction, was substantially lower in uremic plasma (2.39 +/- 0.29 x 10(5) M-1) than in normal plasma (6.86 +/- 0.59 x 10(5) M-1). No difference was found between the number of primary diflunisal binding sites (N1) in uremic and normal plasma. In geriatric plasma neither K1 nor N1 differed from the normal values, indicating that decreased diflunisal plasma protein binding in the elderly is a result of lower plasma albumin concentration. Binding studies with plasma from uremic patients during hemodialysis revealed that free diflunisal rose from 0.46 +/- 0.04% at the start to 0.61 +/- 0.06% at the end of dialysis. Plasma free fatty acid concentrations rose similarly. In vitro displacement studies showed that oleic acid is a competitive inhibitor for the binding of diflunisal to human serum albumin. This may explain the decrease in diflunisal plasma binding at the end of hemodialysis treatment.

Inhibition of Na+,K+-stimulated ATPase in the cochlea of the guinea pig. A potential cause of disturbed inner ear function in terminal renal failure.

The frequent occurrence of sensorineural hearing loss in patients with chronic renal insufficiency prompted us to study the influence of chronic renal failure upon Na+,K+-ATPase in the inner ear of guinea pigs. Na+,K+-activated ATPase was defined as the ouabain-sensitive part of total ATPase, the activity of which was obtained in the presence of sodium, potassium and magnesium. A significant reduction of Na+,K+-activated ATPase was found in the inner ear of uremic animals. Such inhibition could be demonstrated as early as 12 hours after subtotal nephrectomy. An inverse correlation was found between serum creatinine levels and Na+,K+-activated ATPase. A similar inhibition of Na+,K+-activated ATPase in uremia is also found in other tissues (erythrocytes, renal tubules, intestinal mucosal cells, sarcolemma). Na+,K+-ATPase in the cochlea plays a key role in the maintenance of cochlear cationic gradients. It is suggested that inhibition of this enzyme system may contribute to the inner ear dysfunction in uremia.

Hemmung der Na+-K+-stimulierten ATPase in der Cochlea des Meerschweinchens ? eine m�gliche Ursache der gest�rten Innenohrfunktion bei terminaler Niereninsuffizienz

The frequence occurence of sensorineural hearing loss in patients with chronic renal insufficiency prompted us to study the influence of chronic renal failure upon Na+-K+-ATPase in the inner ear of guinea pigs. Na+-K+-activated ATPase was measured as the difference between total ATPase (in the presence of Na+-K+) and basal ATPase (inhibition by ouabain). A significant reduction of Na+-K+-activated ATPase (given as fraction of total ATPase) was found in the inner ear. Such inhibition could be demonstrated even 12 h after subtotal nephrectomy. An inverse correlation was found between serum creatinine levels and Na+-K+-activated ATPase. A similar inhibition of Na+-K+-activated ATPase in uremia is also found in other tissues (erythrocytes, renal tubules, intestinal mucosal cells, sarcolemma). Na+-K+-ATPase in the cochlea plays a key role in the maintenance of cochlear cationic gradients. It is suggested that inhibition of this enzyme system may contribute to the inner ear dysfunction in uremia.

Influence of chronic renal failure on protein synthesis and albumin metabolism in rat liver.

Chronic renal failure in rats leads to changes in hepatic protein synthesis and albumin metabolism at both the cellular and molecular level. In rats with chronic uremia (blood urea nitrogen greater than 45 mg/100 ml 1 mo after surgical reduction in renal mass), cell-free protein synthesis is reduced 30--40% in liver membrane-bound polyribosomes. Albumin synthesis by membrane-bound polysomes in uremia is reduced even more than the reduction in total protein synthesis. Activity of free polysomes remains norma. There is also intracellular accumulation of albumin in liver of uremic rats and a concomitant decrease in serum albumin. In normal liver, most intracellular albumin is located in the microsomal fraction, whereas in liver from uremic animals the excess albumin is found in the free cytosol fraction. These results can be explained either by a defect in synthesis of albumin by membrane-bound polysomes with release of newly synthesized albumin into the cytosol or by a reduced ability of polysomes synthesizing albumin to associate with the membrane fraction in rats with chronic renal failure.

Uremic stomatitis: report of a case

A case report has been presented demonstrating the influence of chronic renal failure in the development of oral disease. Uremic stomatitis is a disease entity that requires both local and systemic therapy. The primary emphasis is directed toward the correction of the systemic pathology for proper resolution of the oral condition.