Severity Of Chronic Renal Failure Research Articles

Study of some biochemical and hematological parameters in continuously hemodialysis patients in Kirkuk city

Introduction: The severity of chronic renal failure (CRF) classified by professional guidelines in five stages, stage 5 is a severe illness often called end stage kidney failure or end stage renal disease (ESRD), dialysis may be used for this stage. Dialysis treatments replace some of these functions through diffusion (waste removal) and ultrafiltration (fluid removal). Hemodialysis, is a process of purifying the blood, when the kidneys are not working normally. It is one of three renal replacement therapies (the other two being peritoneal dialysis and renal transplant).
 Materials and Methods: The samples of this study consists of 80 patients (42 males, 38 females) and 85 healthy individuals (43 males, 42 females) from (20 - 70) years old of age. Serum paraoxonase-1 (PON1), `5-nucleatidase, blood urea ( BU), serum creatinine Cr, serum iron (Fe), serum total iron binding capacity (TIBC), Serum feritin, serum amylase activity and serum lipase activity were determined. Some hematological parameters includes packed cell volume (PCV), hemoglobin (Hb), white blood cells count (WBCs), red blood cell count (RBCs) were measured, the erythrocyte sedimentation rate (ESR), Body mass index (BMI) and creatinine clearance Ccl were also measured.
 Results: Decreased levels of some enzymes activity and some biochemical and hematological parameters and increased others in continuous and regular hemodialysis patients in Kirkuk city. Blood urea and serum creatinine showed significant increased (P˂0.05) in their levels, while the creatinine clearance was significantly decreased (P˂0.05) in patients with continuous hemodialysis patients when compared to those of controls. In the present study; there was significant decreased (P˂0.05) in PON-1 in patients when compared to those of controls. However, the serum`5-NT, amylase and lipase activities were significantly increased (P ˂ 0.05) in these patients when compared with serum of normal individuals. In the present study; there was significant decreased in Fe and TIBC concentrations in the serum of patients when compared to those of healthy control individuals (P˂0.05). While the serum ferritin was significantly increased (P˂0.05) in these patients as compared to the controls. In the present study; there was significant decreased (P ˂ 0.05) in Hb and PCV and RBCs concentrations inthese patients when compared to those of controls. While WBCs and ESR was significantly increased (P˂0.05) in these patients as compared to the controls.
 Conclusion: Serum paraoxonase PON -1 activity is the most commonly affected than other biochemical parameters in continuous hemodialysis patients. Anemia, pancreatitis are the common and often an early complication of chronic renal diseases

Impact of Treatment Strategies and Hemodynamics on Kidney Function After Heart Transplantation

<h3>Purpose</h3> Renal failure is a common finding in patients with end stage heart failure. While some patients show stable or even improved kidney function after orthotopic heart transplantation (OHT), progressive kidney dysfunction is a common, severe comorbidity after OHT. We quantified changes in kidney function after OHT and determined predictors of persistent kidney dysfunction in a uniformly phenotyped, contemporary cohort treated in our center. <h3>Methods</h3> We analysed data of consecutive OHT recipients being transplanted between 2020 and 2021. Clinical characteristics including hemodynamic data and diuretic regimen were assessed. We performed regression analyses to identify predictors of short-term renal outcome defined as a change of renal function after seven days and one month. <h3>Results</h3> The cohort consisted of 42 OHT recipients (33 men, 78%), median age 54 (IQR 8), ejection fraction of 21% (IQR 8), TAPSE 13 mm (IQR 4), cardiac index of 1.8 L/min/m² (IQR 0.3). Right heart failure was present 16 patients (38 %). 13 patients (33 %) were on mechanical circulatory support prior to OHT and 22 (52%) patients required inotropes. Median pre-operative Creatinine was 1.72 mg/dL (IQR 0.80). Creatinine increased to a maximum of 2.90 mg/dL (IQR 1.51) 10 days after OHT but stabilized on day 30 with 2.25 mg/dL (IQR 1.23). Higher baseline creatinine (p = 0.002) and higher central venous pressure on the first day after OHT (p = 0.025) were associated with more severe kidney disease one month after OHT. Furthermore, right heart failure was associated with stage II/III kidney disease one month after OHT (p = 0.037, OR 5.7, 95% CI 1.3-25.9). Other pre-operative hemodynamic parameters and diuretic drug management had no impact on renal outcome. <h3>Conclusion</h3> In our study, high baseline creatinine and high CVP on the first day after OHT were associated with a more severe decrease of renal function after OHT pointing out the importance of an optimized fluid management in OHT candidates to clear high CVP in favour of good renal outcome. Further studies are needed to determine the optimal treatment regime for this topic with high impact on severity of chronic renal failure and survival after OHT.

IMPACT OF GLOMERULAR FILTRATION RATE ON LONG-TERM SURVIVAL AFTER OFF-PUMP CORONARY ARTERY BYPASS SURGERY

Chronic renal failure (CRF) is a marker of poor long-term survival after coronary surgery. Off-pump coronary artery bypass (OPCAB) surgery has been thought to decrease prevalence of post-operative renal failure. The objective of this study is to assess the influence of preoperative CRF stage on survival rates and major adverse cardiac event (MACE) after OPCAB surgery. Data on 1400 consecutive patients who underwent off-pump isolated OPCAB between September 1996 and April 2007 were prospectively collected. Preoperative creatinine clearance (CrCl) was estimated according to Cockcroft and Gault equation. Patients were divided in 4 groups according to preoperative CrCl (ml/min): Gr 1: >90; Gr 2: >60 and ≤90; Gr 3: >30 and ≤60; and Gr 4: ≤30. Kaplan-Meier and Cox regression analysis were performed to assess long term and MACE-free survival rates and to identify their risk factors. Severity of CRF correlated with age (p < 0.001), female sex (p < 0.001), diabetes (p < 0.001), cerebrovascular disease (p < 0.001), lower ventricular ejection fraction (p < 0.001), hypertension (p < 0.001), chronic heart failure (p < 0.001), preoperative atrial fibrillation (p=0.04), peripheral and cerebral vascular disease (p < 0.001), and previous myocardial infarction (p=0.02). Hypercholesterolemia, smoking habit, and obesity negatively correlated with CRF. Kaplan-Meier overall survival decreased with severity of CRF but after correcting for demographics and risk factors only Gr 4 had a lower overall and MACE-free 10-year survival (Cox regression analysis; p=0.01 and p=0.03 respectively). Among the MACE, cardiac death, rehospitalization for congestive heart failure (CHF), and repeat revascularization were more frequent in Gr 4. Severe (CrCl < 30 ml/min) CRF is a significant risk factor for overall and MACE-free survival after OPCAB surgery. It is associated to cardiac death, CHF and repeat revascularization.

Effect of gum arabic on the stomach of uraemic rat

Background Gastrointestinal dysfunction is inevitable with chronic renal failure (CRF). Gum arabic (GA) has previously been shown to ameliorate the severity of CRF in humans and rodents. However, to our knowledge, unbiased quantitative studies on the effect of GA on the stomach in experimentally induced CRF have not been carried out. Aim This study was designed to investigate the gastroprotective effects of GA against gastric injury in uraemic rats. Material and methods A total of 60 adult male albino rats were randomly divided into control, sham control, GA, uraemic and protected groups. After 5 weeks, blood and stomach samples were collected from the rats and the following studies were carried out to assess tissue injury: histological studies (light, scanning and transmission microscopy), immunohistochemical studies to detect the expression of caspase-3 and smoothelin-A, and biochemical studies to measure serum concentrations of creatinine and urea and detect the presence of biomarkers such as superoxide dismutase, catalase, interleukin (IL)-1β and IL-6 and tumour necrosis factor-α. Results Compared with the uraemic group of rats, the microscopic images of the stomachs of GA-protected rats yielded a significantly ameliorated appearance, and showed downregulated expression of oxidative, inflammatory and apoptotic markers. Conclusion Uraemia is confirmed to induce gastroparesis and cause inflammation and oxidation- related tissue injury as well as increase the risk for neoplasia. GA probably protects against gastroparesis-induced epithelial injury in uraemic rat stomachs through antioxidant, anti-inflammatory and antiapoptotic mechanisms.

Abstract 17072: Disruption of mTORC2 Integrity Underlies Increased Myocardial Susceptibility to Ischemia/reperfusion Injury in Chronic Renal Failure

Objective: Chronic renal failure (CRF) worsens prognosis after myocardial infarction, but its impact on myocardial injury remains unclear. We recently found that mTORC2, a kinase complex promoting phosphorylation of Akt at Ser473, plays a pivotal role in cardioprotection. Here, we tested the hypothesis that CRF increases myocardial susceptibility to ischemia/reperfusion injury by disrupting mTORC2 activation. Methods and results: Rats underwent 5/6 nephrectomy (subtotal nephrectomy, SNx) or a sham operation (Sham). Levels of serum creatinine at 4 weeks after the operation were higher in SNx (n=7) than in Sham (n=8) (0.72±0.05 vs. 0.33±0.05 mg/dl, p&lt;0.05), confirming the development of CRF in SNx. Infarct size after 20-min coronary occlusion/2-hr reperfusion was larger in SNx than in Sham (53.2±5.8 vs. 41.1±2.4% of risk area, p&lt;0.05) and was positively correlated with serum creatinine levels (r=0.54, p=0.01), indicating that severity of CRF is a determinant of infarct size. Using separate groups of rats, the effect of CRF on cellular signaling was examined by immunoblotting. Reperfusion-induced phosphorylation of Akt-Ser473 was significantly lower by 32% in SNx than in Sham, with attenuated phosphorylation of p70S6 kinase and GSK3β, downstream substrates of Akt. On the other hand, phosphorylation levels of Jak2, Akt-Thr308, and ERK were comparable between the two groups. Although expression levels of mTORC2 components (mTOR, Rictor, Sin1, and Deptor) and PTEN, a negative regulator of Akt activity, were similar in SNx and Sham, interaction of mTOR and Sin1 determined by immunoprecipitation was 17% less in SNx than in Sham, indicating partial disruption of mTORC2 integrity in CRF. In neonatal cardiomyocytes, mTOR-Sin1 interaction was reduced by treatment with H2O2 (100 μM). Conclusion: Taken together with previous reports that CRF up-regulates oxidative stress level in the myocardium, the present results suggest that oxidative stress-mediated disruption of mTOC2 integrity, leading to impaired phosphorylation of Akt at Ser473 upon reperfusion, underlies the increased myocardial susceptibility to ischemia/reperfusion injury in CRF.

New model for adenine-induced chronic renal failure in mice, and the effect of gum acacia treatment thereon: Comparison with rats

IntroductionThis study aimed at comparing the effects of feeding mice and rats with adenine to induce a state of chronic renal failure (CRF), and to assess the effect of treatment with gum acacia (GA) thereon. MethodsWe compared the outcome, in mice, of feeding adenine at three different doses (0.75%, 0.3%, and 0.2%, w/w). Biochemical and histopathological studies were conducted in plasma, urine and renal homogenates from both species. ResultsWhen mice and rats were fed adenine (0.75%, w/w), all treated rats survived the treatment, but all treated mice died within 1–2days. The dosage in mice was reduced to 0.3%, w/w, for 4weeks, but again all treated mice died within 3–4days. A further reduction in the dosage in mice to 0.2%, w/w, for 4weeks resulted in no mortality, and produced alterations similar to those observed in rats fed adenine at a dose of 0.75%,w/w, for 4weeks. Plasma creatinine, urea and urinary protein were significantly increased (P<0.001) in adenine-treated mice and rats, and this action was incompletely, but significantly (P<0.05), reversed by GA. Adenine significantly (P<0.001) reduced superoxide dismutase (SOD) activity and reduced glutathione (GSH) concentration in renal homogenates from both species, and these reductions were significantly (P<0.05) ameliorated by GA. DiscussionOur data suggest that mice are more sensitive to adenine than rats, and that a dose of adenine of 0.2%, w/w, for 4weeks in mice is suggested as a model for CRF. In both models, GA (15%, w/v, in the drinking water for 4weeks) given concomitantly with adenine ameliorated the severity of CRF to a similar extent.

Relationship of Hemoglobin, Packed Cell Volume and Total Count of RBC with the Severity of Chronic Renal Failure

Background: Anemia is one of the most consistent and severe hematological complication in chronic renal failure (CRF) patients. Lowered Hb concentration, packed cell volume (PCV) and total count (TC) of red blood cell (RBC) in such patients and the relation of changes of these values with the severity of renal failure is important to detect anemia earlier.. Subjects and Methods: The present study has been designed to observe hemoglobin concentration, PCV and TC of RBC in different stages of CRF patients suffering from anemia. For this purpose, 65 male CRF patients with anemia and 25 healthy male (control) subjects, age ranged from 30–50 years were selected randomly from BSMMU outpatient department. Hb concentration, PCV, TC of RBC and creatinine clearance were estimated by usual laboratory technique. Data were analyzed statistically by ANOVA and Pearson’s correlation coefficient test. Among 65 CRF patients, 15 were mild, 25 were moderate and 25 were severe with renal failure associated with anemia. Results: In this study, the mean Hb concentration, PCV and total count of RBCs were significantly lower in three stages of CRF patients with anemia compared to those of healthy subjects. Again, these hematological values were significantly ( P < 0.001) lower in moderate and severe CRF patients compared to mild cases and also in severe cases than those of moderate CRF cases with anemia. All the hematological parameters showed positive correlation with creatinine clearance in three stages of CRF and it was statistically significant in moderate and severe group. Conclusion: From the present study it may be concluded that CRF patients with anemia had lower Hb concentration, PCV and TC of RBC and the degree of changes depend on severity of renal failure. DOI: http://dx.doi.org/10.11566/cmoshmcj.v12i2.36 Chatt Maa Shi Hosp Med Coll J 2013; 12(2): 31-34

Iron Status in Chronic Renal Failure with Anemia

Background: Chronic renal failure (CRF) is a major public health hazard. Anemia is an accompaniment and independent risk factor for the development of cardiac dysfunction and responsible for 40% to 50% deaths in CRF patients. For this reason, effective erythropoiesis to correct anemia by erythropoietin therapy and mainte­nance of target iron level is very much important. Subjects and Methods: The present study has been designed to observe iron status in different stages of CRF patients suffering from anemia. For this purpose, 65 male CRF patients with anemia and 25 healthy male (control) subjects, in the age group of 30–50 years were selected randomly from BSMMU outpatient department. Iron level, hemoglobin and creati­nine clearance were estimated by usual laboratory technique. Data were analyzed statistically by ANOVA and Pearson’s correlation coefficient test. Among 65 CRF patients, 15 were mild, 25 were moderate and 25 were reported severe renal failure with anemia. Results: The mean serum iron, transferrin saturation and ferritin were significantly ( P < 0.001) lower in moderate but severe in CRF patients with anemia compared to those of healthy subjects and these values were also significantly ( P < 0.001) lower in severe CRF than those of mild and moderate groups of patients. On the other hand, total iron binding capacity was significantly ( P < 0.001) higher only in severe group of CRF patients compared to healthy, mild and moderate group of CRF patients. In addition, 72% severe group of CRF patients had serum ferritin and 28% had transferrin saturation below the target level (≥100 ng/ml serum ferritin & ≥20% transferrin saturation). Decreasing iron status which is more marked in severe CRF patients are suggestive of iron deficiency and iron status below the target level in severe CRF patients indicate inadequate iron store. Also, a significantly ( P < 0.001) decreasing hemoglobin concentration is observed in severe CRF case compared to those of mild and moderate CRF patients with anemia. Conclusion: From the present study it may be concluded that changes in iron status occur in CRF patients with anemia and these changes vary along with severity of CRF. DOI: http://dx.doi.org/10.11566/cmoshmcj.v12i1.21 Chatt Maa Shi Hosp Med Coll J 2013; 12(1): 12-17

Effect of Acacia gum on blood pressure in rats with adenine-induced chronic renal failure

Chronic renal failure (CRF) occurring naturally in patients or induced by subtotal nephrectomy in rats induces several alterations in the cardiovascular system (CVS). However, the effect of chemically induced CRF in rats on the CVS is less well known. We induced CRF in rats by feeding adenine (0.75%, w/w, four weeks) and investigated the effect of the ensuing CRF on the systolic and diastolic blood pressure (BP) and heart rate (HR). Further, we investigated the effect of giving acacia gum (AG, 10%, w/v) in the drinking water concomitantly with adenine on the above parameters. AG has been previously shown to ameliorate the severity of CRF in humans and rats. We confirmed here that adenine-induced CRF significantly increased the plasma concentrations of urea and creatinine, and reduced creatinine clearance. Additionally, it significantly increased both systolic and diastolic BP, with no significant effect on HR. Both of these actions were significantly mitigated by AG treatment. The antihypertensive angiotenisn-converting enzyme inhibitor lisinopril (10 mg/kg) was given by gavage to rats concomitantly with adenine, significantly reduced the rise in blood pressure induced by adenine. In conclusion, adenine-induced CRF in rats significantly increased BP, and this was significantly mitigated by administration of AG. Possible mechanisms of these changes and the protective effect of AG will be investigated.

Effect of Acacia Gum on blood pressure in Rats with Adenine‐Induced Chronic Renal Failure

Chronic renal failure (CRF) occurring naturally in patients or induced by subtotal nephrectomy in rats induces several alterations in the cardiovascular system (CVS). However, the effect of chemically-induced CRF in rats on the CVS is less well known. We induced CRF in rats by feeding adenine (0.75%w/w, four weeks) and investigated the effect of the ensuing CRF on the systolic and diastolic blood pressure (BP) and heart rate (HR). Further, we investigated the effect of giving acacia gum (10%w/v) in the drinking water concomitantly with adenine on the above parameters. AG has been previously shown to ameliorate the severity of CRF in humans and rats. We confirmed here that adenine-induced CRF significantly increased the plasma concentrations of urea and creatinine, and reduced creatinine clearance. Additionally, it significantly increased both systolic and diastolic BP, with no significant effect on HR. Both of these actions were significantly mitigated by AG treatment. The antihypertensive angiotenisn- converting enzyme inhibitor lisinopril (10mg/kg) was given by gavage to rats concomitantly with adenine significantly reduced the rise in blood pressure induced by adenine. In conclusion, adenine CRF in rats significantly increased BP, and this was significantly mitigated by administration of AG.

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.

Chronic Kidney Disease, Thrombotic Microangiopathy, and Hypertension Following T Cell-Depleted Hematopoietic Stem Cell Transplantation

Chronic kidney disease (CKD) is now an accepted long-term complication of allogeneic hematopoietic stem cell transplantation. Calcineurin inhibitors (CNI), which are used for prophylaxis and treatment of graft-versus-host disease (GVHD), have been associated with the development of nephrotoxicity. Hypertension (HTN) and thrombotic microangiopathy (TMA) are 2 comorbidities linked to CKD. T cell depletion (TCD) of stem cell grafts can obviate the need for the use of CNI. We conducted a retrospective analysis of 100 patients who underwent TCD transplantation: 30 in group A were conditioned without total-body radiation (TBI) and 70 in group B received a TBI containing regimen. None of the patients received CNI. The median age was 55.5 and 45 years for groups A and B, respectively. Eleven patients developed TMA, all in group B. The 2-year cumulative incidence of sustained CKD was 29.2% and 48.8% in group A and group B, respectively, with a mean follow-up of at least 21 months. CKD free survival was better in the non-TBI group (P = .046). Multivariable survival analysis revealed that exposure to TBI, older age, and TMA were risk factors for CKD. The incidence of new onset or worsening HTN was 6.7% and 25.7% (P = .03) in group A and B, respectively. The use of TBI (P = .0182) and diagnosis of TMA (P = .0006) predisposed patients to the development of HTN using univariable logistic regression models. Thus, despite the absence of CNI, a proportion of these older patients in both groups developed CKD and HTN.

Mechanisms of Aortic and Cardiac Dysfunction in Uremic Mice With Aortic Calcification

Chronic renal failure (CRF) is associated with cardiac dysfunction and increased aortic stiffness. The mechanisms involved are not clearly understood. We examined changes over time in cardiac and aortic function in a murine CRF model. Eight-week-old mice were randomly assigned to 1 of 4 groups: wild-type non-CRF, wild-type CRF, apolipoprotein E knockout non-CRF, and apolipoprotein E knockout CRF. Echocardiography was performed and blood samples were taken at baseline and after 6 and 10 weeks of CRF. Vascular reactivity and adhesion molecule expression were studied after 6 and 10 weeks of CRF. Left ventricular hypertrophy, altered left ventricular relaxation, and increased aortic stiffness were observed after 6 weeks of CRF and persisted after 10 weeks. The 4 groups of mice did not significantly differ in terms of arterial blood pressure and aortic structure. The degree of vascular calcification and serum total cholesterol concentration were higher in the CRF groups than in the non-CRF groups. These changes, however, could not explain the cardiac and vascular differences seen in the 2 CRF groups. In contrast, alterations in vascular reactivity, the upregulation of adhesion molecule expression, and CRF status were significantly associated with these changes. In a mouse model of CRF, left ventricular hypertrophy, cardiac diastolic dysfunction, and increased aortic stiffness were not related to structural changes in the aorta (including aortic calcification) or high serum cholesterol levels. However, cardiac and aortic abnormalities were associated with the extent of subendothelial dysfunction and the severity of CRF.

Urinary Excretion of Creatol, an In Vivo Biomarker of Hydroxyl Radical, in Patients with Chronic Renal Failure

Creatol (CTL) is a hydroxyl radical adduct of creatinine (Cr). The serum methylguanidine (MG) level and the MG/Cr molar ratio are reported to be biomarkers for oxidative stress. The aim of this study was to examine whether urinary excretion of CTL, another oxidative stress-related marker, is increased in patients with chronic renal failure (CRF). One hundred twenty-four non-dialyzed patients with chronic renal failure (serum Cr level, 1.3–10.0 mg/dL) were recruited from our hospitals. Urine and serum levels of CTL and MG were determined by high-performance liquid chromatography with the use of 9, 10- phenanthrenequinone as a fluorogenic reagent. The CTL/Cr and (CTL+MG)/Cr molar ratios in spot urine samples were also compared with those in 24-h urine samples. The urinary CTL/Cr and (CTL+MG)/Cr molar ratios increased with decreases in Cr clearance in patients with CRF. Correlations between serum and spot urine (CTL+MG)/Cr and between serum and spot urine CTL/Cr were quite similar to those in 24-h urine samples. CTL/Cr and (CTL+MG)/Cr molar ratios in both 24-h urine and spot urine samples appear to be useful indices of the severity of CRF.

The Importance of Age, Fludarabine, and Total Body Irradiation in the Incidence and Severity of Chronic Renal Failure after Allogeneic Hematopoietic Cell Transplantation

Nonmalignant late effects, including chronic renal failure (CRF), impair the quality of life of long-term survivors after allogeneic hematopoietic cell transplantation. One of the major risk factors is the use of total body irradiation (TBI) in the preparative regimen; TBI is currently fractionated in an attempt to reduce toxicity. We analyzed 241 patients who had TBI-based preparative regimens for allogeneic hematopoietic cell transplantation. TBI was delivered as a single fraction of 7.5 Gy (7.5S group), 12 Gy in 6 fractions (12F group), or 14.4 Gy in 8 fractions (14.4F group). The cumulative incidence of CRF at 2 years was 12%. Statistical analysis revealed that older age ( P < .001) and fludarabine administration ( P = .016) had a significant effect on the incidence of CRF. Furthermore, single-fraction TBI was also significantly associated with CRF severity, because 7 (6.3%) of 111 patients in the 7.5S group developed severe CRF, as opposed to 1 (0.8%) of 130 patients in the 12F and 14.4F groups combined ( P = .044). However, these conclusions should be regarded as preliminary in view of the retrospective and nonrandomized nature of this study.

Polyamine Oxidase and Acrolein as Novel Biochemical Markers for Diagnosis of Cerebral Stroke

We found previously that plasma levels of acrolein (CH2=CHCHO) and spermine oxidase (SMO) were well correlated with the degree of severity of chronic renal failure. The aim of this study was to test whether the levels of these 2 markers and of acetylpolyamine oxidase (AcPAO) were increased in the plasma of stroke patients. The activity of AcPAO and SMO and the level of protein-conjugated acrolein in plasma of the stroke patients and normal subjects were measured by high-performance liquid chromatography and ELISA, respectively. Focal infarcts were estimated by MRI or computed tomography (CT). The levels of AcPAO, SMO, and acrolein were significantly increased in the plasma of stroke patients. The size of stroke was nearly parallel with the multiplied value of acrolein and total polyamine oxidase (AcPAO plus SMO). After the onset of stroke, an increase in AcPAO first occurred, followed by increased levels of SMO and finally acrolein. In 1 case, an increase in AcPAO and SMO preceded focal damage as detected by MRI or CT. Furthermore, stroke was confirmed by MRI in a number of mildly symptomatic patients (11 cases) who had increased levels of total polyamine oxidase and acrolein. Among apparently normal subjects (8 cases) who had high values of acroleinxtotal polyamine oxidase, stroke was found in 4 cases by MRI. The results indicate that increased levels of AcPAO, SMO, and acrolein are good markers of stroke.

The Importance of Age, Fludarabine and Total Body Irradiation in the Incidence and Severity of Chronic Renal Failure Following Allogeneic Hematopoietic Stem Cell Transplantation.

Nonmalignant late effects significantly impair the quality of life of long-term survivors following hematopoietic stem cell transplantation (HSCT), the major risk factors being chronic graft-versus-host disease (GVHD) and the use of total body irradiation (TBI) in the preparative regime. There has been a shift towards the use of fractionated, as opposed to single-dose TBI, in an attempt to reduce toxicity. Few reports exist on the renal consequences of HSCT, although many warn about the potential toxicity that eventually leads to chronic renal failure (CRF). However, the exact incidence of HSCT nephropathy is unknown, as there is a lack of well-designed analyses to provide cumulative incidence rates and descriptions of risk factors. The aim of this study was to assess retrospectively the risk and severity of CRF following TBI-based preparative regimes and the contribution of other patient, disease and post-transplant factors. From February 1996 to April 2004, 274 patients had TBI-based preparative regimes for allogeneic HSCT at our institution. Chemotherapy mainly consisted of cyclophosphamide (120 mg/kg) alone or in combination with fludarabine (90 mg/m2). TBI was started the day after completion of chemotherapy and was delivered as a single dose of 7.5 Gy (7.5S), 12 Gy in 6 fractions (12F), or 14.4 Gy in 8 fractions (14.4F). Fludarabine and high-dose TBI (14.4 Gy) were administered preferentially to those patients receiving T-cell depleted (TCD) grafts. GVHD prophylaxis was with a combination of cyclosporin (CSA) + methotrexate in unmanipulated transplants and with CSA alone or nothing in case of TCD grafts. CRF was defined as a persistent increase of serum creatinine (SCr) to greater than 120 μmol/l in males and 97 μmol/l in females (upper limits at our institution) over a period of at least six months. The cumulative incidence of CRF was 11% for the whole group. Renal tissue was available for review in 9 patients. All except one had histologic features suggestive of thrombotic microangiopathy ± radiation nephropathy. Kaplan-Meier analysis revealed a significant association between the incidence of CRF and older age at transplantation (>30 years; P = 0.0043), administration of fludarabine (P = 0.0014), high-dose/unfractionated TBI (14.4F > 7.5S > 12F; P = 0.0005) and TCD (P = 0.0031). Since fludarabine was usually associated to TCD grafts and high-dose TBI, we investigated whether the use of fludarabine was masking the effect of these other factors. Only older age at transplant (HR = 2.97; 95% CI, 1.32–6.68; P = 0.008) and fludarabine administration (HR = 3.22; 95% CI, 1.47–7.04; P = 0.003) remained significant in a multivariate Cox regression analysis. Of note, although TBI dose/fractionation did not fit in the multivariate model, CRF severity was significantly different as 38% of the patients in the 7.5S group currently require or have required permanent dialysis as opposed to 7% in both 12F and 14.4F groups combined. In conclusion, the incidence and severity of CRF post-transplant is associated with age, fludarabine administration and TBI dose/fractionation and, therefore, these factors should be kept in mind in order to prevent this late effect and devise new preparative regimens for HSCT.

Bone mineral density and bone turnover markers in children with chronic renal failure

Bone mineral density (BMD) at lumbar spine (L2-L4) was measured by dual-energy X-ray absorptiometry (DEXA) in 21 children with predialysis chronic renal failure (CRF) and 44 children with end-stage renal failure (ESRF) on regular hemodialysis. BMD results were expressed as Z-scores. Osteopenia was documented in 13 predialysis patients (61.9%) and 26 patients (59.1%) with ESRF. No significant correlation was observed between Z-scores and the duration of CRF or estimated creatinine clearance. In osteopenic children there was a negative correlation between Z-scores and serum phosphorus (r=-0.61, P=0.004), intact parathyroid hormone (iPTH) (r=-0.47, P=0.03), and bone-specific alkaline phosphatase (r=-0.52, P=0.02) and a positive correlation with total calcium (r=0.41, P=0.07) and 25-hydroxycholecalciferol (r=0.53, P=0.02). Osteopenic children who had iPTH values > or = 200 pg/ml were more osteopenic than those who had lower iPTH levels (P=0.006). In conclusion, osteopenia, assessed by DEXA, is frequent in children with CRF. It occurs early irrespective of the duration or the severity of CRF. In children with ESRF the degree of osteopenia is correlated with laboratory markers of renal osteodystrophy and patients with biochemical findings of secondary hyperparathyroidism are more osteopenic than the others.

Activation of receptor for advanced glycation end products: a mechanism for monocyte-mediated inflammation in chronic renal failure

To investigate the expression of receptor for advanced glycation end products (RAGE) in chronic renal failure (CRF) and its role in monocyte-mediated inflammation associated with chronic renal failure (CRF). Peripheral monocytes (PMC) were isolated from 96 non-diabetic patients with varying severity of CRF. RAGE expression on monocytes was quantitated by flow cytometry. The binding capacity of monocytes with advanced glycation end products (AGE) was determined by 125I-AGEs-HSA binding assay. The plasma level of pentosidine, a marker of AGE, was determined by competitive ELISA. Commercially available kits were used for measuring the plasma levels of neopterin, TNF-alpha and C-reactive protein (CRP), a systemic acute phase reactant. Flow cytometry showed that the RAGE expression at the PMC surface of CRF patients was 8.02 +/- 0.43, significantly higher than that of the normal controls (P < 0.001). The number of functional sites to bind 125I-AGEs-HSA at the surface of PMC of CRF patients was increased in comparison with the normal control group. The biding capacity (Ka) at the surface of PMC of CRF patients was 2 times that of normal control group. Stimulated by AGEs-HAS, the TNF-alpha level in the supernatant of PMC increased dose-dependently in both the normal control and CRF patients, especially in the latter (P < 0.01). After pretreatment of anti-RAGE or non-immune rabbit IgG and then by AGEs-HAS the levels of TNF-alpha in the PMC supernatants of CRF patients and normal controls decreased form 90.52 pg/(10(5) cell) +/- 2.82 pg/(10(5) cell) to 17.86 pg/(10(5) cell) +/- 1.05 pg/(10(5) cell) and from 26.38 pg/(10(5) cell) +/- 1.54 pg/(10(5) cell) to 6.76 pg/(10(5) cell) +/- 0.20 pg/(10(5) cell). HAS not modified by AGEs and non-immune rabbit IgG showed no influence on the secretion of TNF-alpha. The plasma levels of TNF-alpha, neopterin, and CRP increased along with the worsening of renal function. The RAGE expression and pentosidine level at the surface of PMC in CPR patients without hemodialysis were positively correlated with plasma neopterin, TNF-alpha, and CRP levels, even after correction of creatine clearance rate (r = 0.53, P < 0.001; r = 0.58, P < 0.001; r = 0.40, P = 0.001). The expression of RAGE in CRF patients with hemodialysis was positively correlated with the plasma TNF-alpha level (r = 0.33, P = 0.029, n = 36), however, not correlated with neopterin or CRP. Enhanced RAGE may trigger a positive feed back loop of AGEs-induced monocyte perturbation, and may contribute to the monocyte-mediated systemic inflammation in CRF.

Parathyroid hormone and its fragments in children with chronic renal failure.

Parathyroid hormone (PTH) immunoradiometric assays (IRMA) exhibit cross-reactivity between 1-84 PTH and long carboxyl-terminal-PTH (C-PTH) molecules. C-PTH antagonizes the biological actions of 1-84 PTH and circulates in excess in chronic renal failure (CRF), partially explaining why supra-physiological PTH levels are recommended to maintain bone turnover. Furthermore, the ratio 1-84 PTH/C-PTH may be related to bone turnover. This study characterizes the 1-84 PTH/C-PTH ratio in children with varying severity of CRF and levels of PTH. Two hundred and forty-one children with CRF, managed with the aim of preventing the development of hyperparathyroidism, had PTH measured by 'intact' IRMA and a new more specific Cyclase-Activating-PTH (CAP) IRMA. C-PTH levels were calculated by subtracting CAP-IRMA from 'intact' IRMA. Fifty-three controls with normal renal function were also recruited. Mean 'intact' IRMA correlated with CAP-IRMA ( r=0.98), but was higher ( P<0.001). The mean 1-84 PTH/C-PTH ratio was lower than controls in dialysis patients ( P=0.022) and those with a glomerular filtration rate <30 ml/min per m(2 )( P=0.033). This ratio was comparable to controls when the PTH level was normal, but was lower with PTH levels outside the normal range ( P<0.01). These data suggest that CAP-IRMA gives a more accurate assessment of actual PTH levels than 'intact' IRMA in CRF. Maintenance of normal PTH levels throughout the course of CRF permits the maintenance of a normal 1-84 PTH/C-PTH ratio, the clinical significance of which requires further investigation in children.