Moderate Chronic Renal Failure Research Articles

#4154 CIRCULATING BETA-TRACE PROTEIN VERSUS CREATININE AS MARKERS OF EARLY KIDNEY (DYS)FUNCTION IN THE NX-INDUCED RAT MODEL OF CHRONIC KIDNEY DISEASE

Abstract Background and Aims Beta trace protein (BTP) is a low molecular weight protein that has been proposed as an earlier biomarker of decreased glomerular filtration rate (GFR) and renal damage, than the traditional biomarkers, particularly in the creatinine blind range. Early biomarkers of renal (dys)function are needed to allow, in due time, the detection and treatment, to prevent worsening of the disease. To the authors’ knowledge, neither urine nor serum BTP has been assessed in animals with kidney disease. In the present study, we aimed to concomitantly evaluate BTP and creatinine circulating levels, to compare their value as early biomarkers of renal dysfunction, by performing the studies in rat models of mild and moderate chronic renal failure (CRF) induced by nephrectomy. Method Male Wistar rats, 12 weeks old, were randomly divided in three groups: Sham (n = 8, subjected to surgical process without kidney mass reduction), Mild CRF (n = 8, subjected to 1/2 nephrectomy), and Moderate CRF (n = 7, subjected to 5/6 nephrectomy). After five weeks, rats were sacrificed, blood and kidneys were collected. We analysed the circulating levels of BTP and creatinine and studied the association of BTP concentration with the glomerular and tubulointerstitial lesions, and with the traditional biomarkers of renal (dys)function, eGFR and creatinine. Results The serum levels of BTP were correlated with serum levels of creatinine (r = 0.575, p = 0.004) and also with eGFR (r = -0.453, p = 0.030); additionally, we found positive correlations with the total score of mild and advanced tubular lesions (r = 0.610, p = 0.02 and r = 0.517, p = 0.011, respectively), observed in kidney sections. The circulating levels of BTP increased with disease severity; Mild CRF showed a higher value of BTP than Sham group, although without statistical significance that was reached in Moderate CRF group, as observed for serum creatinine. The combined use of BTP and creatinine did not improve the discriminatory power in early disease detection. Though, the combination showed stronger correlations with the total score of tubular lesions (r = 0.849, p < 0.001 for mild tubular lesions and r = 0.774, p < 0.01 for advanced tubular lesions). Conclusion In rat models of mild and moderate CRF induced by nephrectomy, serum BTP levels increased with kidney function worsening, and correlated with disease severity, assessed by GFR and the degree of histopathological alterations. However, the earlier diagnostic value of BTP does not outperform serum creatinine in this model.

POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME: DIVERSE ETIOLOGIES

Objective: Posterior Reversible Encephalopathy, called PRES, is a clinico-radiological entity individualized for the first time in 1996 as a special form of hypertensive encephalopathy. Design and method: We collected retrospectively 8 cases of PRES Syndrome either on-specific or followed in Internal Medicine service. All patients had a confirmed diagnosis by brain MRI. Results: There were 5 women and 3 men, mean age was 30 years (range 16–66 years). Three patients had a past history of arterial hypertension. Two patients had moderate chronic renal failure, three had a chronic renal failure on hemodialysis, one had normal renal function and the two others were transplanted. Hypertension with diastolic blood pressure greater than 120 mmHg was noted in two patients. For the others, it was an acute and sudden increase of blood pressure usually well balanced. Neurological manifestations are on-specific, such as confusion, a prolonged critical post coma or seizure initially focal (Braved-Jacksonian) limited to brain lobe affected by the PRES which become generalized secondarily. All patients had seizures, one presented a status epilepticus. They all underwent magnetic resonance imaging (MRI). Typical imaging findings characteristically involve the white matter bilaterally in the parieto-occipital regions. Involvement of the white matter is constant. To equilibrate the systemic blood pressure, we used calcium channel blockers in all cases (nicardipine in the electric syringe pump in one case). The therapeutic goal was to maintain a mean arterial pressure between 105 and 125 mmHg. Conclusions: PRES is highly diverse in terms of etiologies. Our series is particular by the large number of cases of PRES compared to the literature but especially by the diversity of the etiologies of PRES. All our patients had chronic renal failure and / or underlying nephropathy.

Alveolar hemorrhage linked to Evans syndrome

Evans syndrome associates thrombocytopenia, autoimmune hemolytic anemia, and/or neutropenia with a positive direct antihuman globulin test. It is an autoimmune entity. We report here a case of a 71-year-old patient followed up for Evans syndrome, arterial hypertension, diabetes mellitus, and moderate chronic renal failure. He was hospitalized for massive hemoptysis and decline of platelet blood count to under 40 000 cells/mm3. Alveolar hemorrhage was so extended in computed tomography scan. The acute respiratory failure was followed by a systemic shock and then death. This disease has no consensual treatment but some therapies are effective. Preventive management should be considered to avoid cataclysmic complications.

Q Kidney Risk Calculator- Useful Tool in Hospitals and Community

A kidney health check was conducted over a day in two private hospitals (Peninsula Private Hospital and Beleura Hospital) in 2017. 243 participants enrolled in this study. The study population were mobile inpatients, members from the public and health workers (nurses, doctors, allied health workers and administrative staff). Method: A Q risk calculator was used to assess the risk of developing moderate and severe chronic kidney disease (eGFR <60 mls/min) and end stage renal failure over the next 5 years. All participants consented prior to being involved in the study. Results: The majority was aged 65 to 75 years old (aged population). 18% of the participants were diabetic, 18% had cardiovascular disease, 37% were hypertensive, 5% were smokers, 28% of the participants were overweight and obesity was seen in 25%. Diabetic females are five times higher risk than non-diabetic females in developing chronic kidney disease stage 3 and 4. Male diabetics are three times more at risk than non-diabetic men in developing moderate to severe chronic kidney disease. However diabetic men are five times higher risk than normoglycaemic men in progressing into end stage renal failure Females with cardiovascular disease are five times higher risk than women with no cardiovascular disease in developing moderate to severe chronic kidney disease. Men with cardiovascular disease are three times higher risk than men with no cardiovascular disease in developing moderate to severe chronic kidney disease. Hypertensive women are ten times higher risk than normotensive women in developing moderate to severe chronic kidney disease. Interestingly hypertensive men are four times higher risk than normotensive male in developing end stage renal failure Obese men are three times higher risk than normal weight men in developing moderate to severe chronic kidney disease. Underweight females are three times at risk than normal weight females in developing moderate and severe chronic kidney disease. Summary: Qrisk questionaire is a quick and easy tool to assess risk of developing chronic kidney disease. Participants with diabetes, hypertension and cardiovascular disease have a higher risk of developing moderate and severe chronic kidney disease over the next 5 years. Overweight (body mass index 25 to 29.99), obese patients (body mass index more than 30) and interestingly underweight females with body mass index 18.5 or less have a higher risk of developing moderate and severe chronic kidney disease.

Anxiété et dépression au cours de l’insuffisance rénale chronique avant le stade terminal au centre hospitalier universitaire Yalgado Ouédraogo de Ouagadougou (Burkina Faso)

AimWe wanted to know the prevalence of depression and anxiety, as well as the associated factors in patients with chronic renal failure in Burkina Faso. Patients and methodsThis was an analytical cross-sectional study conducted from February to May 2016. We included all adult patients with moderate or severe chronic renal failure. The diagnosis of anxiety and depression was made using the Hamilton scales. Identification of factors associated with both conditions required bi- and multivariate analyzes. ResultsThe study involved 191 patients, with a mean age of 53.2±14.2 years and a sex ratio of 1.4. The prevalence of anxiety and depression was 42.4% and 66.5%, respectively. In 37.7% of cases, both anxiety and depression were noted. The mean age was 52.2±13.1 years for anxious patients and 53.5±13.3 years for the depressed. After multivariate analysis, female sex (odds ratio 2.2; adjusted P=0.014) was significantly associated with anxiety, and anxiety itself at depression (odds ratio 7.5; adjusted P<0.001). ConclusionAnxiety and depression are very common during moderate or severe chronic renal failure in Burkina Faso. In view of their potentially serious consequences, there is a definite interest in their early detection by the nephrologist, especially in the female patient, and for early management.

Study of comparative evaluation of Atorvastatin and Salicinol (salacia roxburghii) on GFR and carotid intima media thickness in diabetic and non-diabetic CKD patients with hypertension

Background: Most of the newer concepts in Nephrology developed in the 19th and 20th centuries. Progression of renal failure is an area of Nephrology where our understanding has improved appreciably in the last century, but still, our knowledge is like a drop in the ocean. We have ample evidence that the progression of renal failure can be slowed down, but we still need more definite information on whether established renal failure can be reversed. This pilot clinical study was planned to explore the therapeutic potential of salicinol in retardation of chronic kidney disease progression and anti-atherosclerotic property by looking for if a reduction in CIMT is possible. Objectives: To study of comparative evaluation of atorvastatin and salicinol (salacia roxburghii) on GFR and CIMT in diabetic and non-diabetic CKD patients with hypertension. Methods: The present study was conducted in the Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi. Eighty patients of mild to moderate stable chronic renal failure with hypertension attending Nephrology OPD or admitted in the Nephrology ward from May 2014 to June 2015 were included in the study. Patient with acute MI, congestive heart failure, unstable angina, myopathy. Subsequently, patients were allocated to one of the two groups, the first group consisted of Diabetic patient treated with atorvastatin salicinol, and second group was of non-diabetic treated patients. Results: Among total patients included in study, 35 were non-diabetic, and 45 were diabetic. Mean serum creatinine at baseline study in the diabetic and non-diabetic group were 4.3 ± 2.0, and 5.0 ± 1.6, and changes were statistically significant intragroup. Mean CIMT in diabetic and non-diabetic at baseline were 0.92 ± 0.07 and 0.90±0.07, and when comparing both changes were statistically significant at three months and 6 months suggesting CIMT regression more in diabetic groups compared to non-diabetics. Mean GFR in a diabetic and non-diabetic group at baseline was 23.4 ± 15.6 and 17.8±13.7. On intergroup comparison, changes were statistically significant at 3 months and at 6-month. Conclusion: The male to female ratio was 2:1. Age of the patient ranged from 20years onwards. No significant effect of the drug was seen on 24hrs urinary protein, blood pressure, hemoglobin and GFR. On comparison of non-diabetic and diabetic significant decreases (0.05) in GFR were observed at the end of the study. On comparison of non-diabetic and diabetic highly significant decrease (0.001) in CIMT were observed at three months and at the end of the study.

Chronic kidney disease and periodontal disease. Case report

Chronic renal disease promotes a decrease on kidneys filterability and nitrogen products accumulation on blood, electrolyte and system endocrine functions imbalance. Among the many clinical manifestations of chronic renal failure (CRF) in the oral cavity, there are: dry mouth, uremic stomatitis, radiographic changes in maxillary and jaw bones and accumulation of calculus on the teeth that increases levels of periodonto pathogenic microorganisms able to lead a periodontal tissue destruction and also have the potential to act from a distance on other organs, e.g. the kidneys. Thus, it becomes evident that a periodontal treatment of patients suffering from chronic renal failure is crucial for maintaining their general health conditions and a subsequent successful organ transplant.Thus, the objectives of this case report were to highlight how important the periodontal treatment is for chronic renal failure patients and to demonstrate improvements in their clinical condition through the treatment plan proposed herein. A patient with 43 years old carrier generalized moderate chronic periodontitis and CRF was submitted to scaling and root planning sessions, and later surgical access for scaling where the basic treatment not resulted in a resolution of the inflammatory periodontal process. The results obtained from a well-developed periodontal treatment and an effective cooperation of patient showed satisfactory results with periodontal disease process resolution or stabilization.Thus, periodontal treatment and patient compliance were crucial for the improvement of periodontal clinical conditions enabling a future successful renal transplantation.KeywordsDental care; Periodontal diseases; Renal insufficiency.

A Rare Cause of Intestinal Volvulus: Spontaneous Intramural Hematoma of Small Intestine

Introduction: Anticoagulation therapy is widely used for curative and prophylactic purposes. The most serious complication is bleeding, which presents as an intramural hematoma of the small intestine; however, it is uncommon, seen in 1 in 2,500 patients. We report an unusual case of a warfarin overdose that resulted in spontaneous intramural hematoma of the small intestine with intestinal volvulus. Observation: A 60-year-old patient was admitted to the emergency department with diffuse abdominal pain and anuria that had started several hours earlier. The patient had a long history of complicated diabetes, marked by moderate chronic renal failure as well as arterial hypertension and atrial fibrillation, which was managed with the oral anticoagulant acenocoumarol. Respiratory and cardiovascular exams revealed no abnormality except for an irregular rhythm in cardiac auscultation. His abdomen was mildly distended and there was tenderness with Blumberg’s sign in the periumbilical region, which was associated with signs of peritoneal irritation. Laboratory tests showed incoagulable plasma, an inflammatory syndrome, and renal failure. The Computed tomography (CT) scan without intravenous injection revealed a spontaneous intramural hematoma of the small intestine with intestinal volvulus; moderate hemoperitoneum was also documented. Initial patient management consisted of the cessation of oral anticoagulation therapy, gentle gastric aspiration, correction of the coagulopathy with fresh frozen plasma, and the administration of parenteral Vitamin K. The patient’s condition began to decline, marked by a worsening of clinical and laboratory parameters, and the patient ultimately died from acute cardio-circulatory failure while on ventricular fibrillation. Conclusion: Spontaneous small intestine hematoma is an uncommon clinical complication, but it should be taken into consideration for any patient on long-term anticoagulation therapy who presents with acute abdomen. Abdominal CT is the key for diagnosis. Early diagnosis is crucial because most patients can be treated nonoperatively with a good outcome.

English

BACKGROUND: Chronic Renal Failure (CRF) is one of the common conditions which a physician comes across in day to day practice. Chronic Renal Failure affects every aspect of the lives of the patients who suffer it and involves all systems of body & results in various abnormalities. Today, cardiovascular complications are a major clinical problem in ureamic patients accounting for 44% of all deaths in this population. Left Ventricular Hypertrophy (LVH) is a major Echocardiographic finding in Chronic Renal Failure (CRF). Prevalence of LVH increases with decline of renal function. Left ventricular hypertrophy is an independent predictor of survival, present in approximately 70% of patients at the initiation of dialysis. MATERIALS AND METHODS: The data for this study was collected from the one hundred subjects fulfilling the inclusion /exclusion criteria admitted and patients visiting OPD and patients undergoing dialysis in dialysis unit of VIMS Hospital during the period from Jan 2010 To June 2011. RESULTS: LVH is a major echocardiographic finding in uremic patients. In the present study, 12 (17%) patients of mild, 18(26%) patients of moderate and 39(57%) patients of severe Chronic Renal Failure group had Left Ventricular Hypertrophy. In the present study, the most common cause of CRF in the Severe CRF group was Diabetes plus Hypertension in 47% followed by Diabetes alone in 33% as compared to Moderate CRF group where in Diabetes plus Hypertension accounted for 47%, followed by Diabetes in 47%, whereas in Mild CRF group Diabetes was the cause 38%, followed by Diabetes plus Hypertension in 33% of cases. Pericardial effusion was seen in 25% of cases (15 cases had mild and 10 cases had moderate pericardial effusion. CONCLUSIONS: The high prevalence of Left ventricular hypertrophy in these populations on echocardiography implies that these patients require detailed cardiovascular evaluation despite absence of symptoms and control of hypertension, anemia should be considered in earlier stages.

Qual o efeito da redução da hiperuricemia nos eventos cardiovasculares? Revisão baseada na evidência

IntroductionHigh levels of uric acid (UA) have been associated with cardiovascular (CV) disease, but its role as an independent risk factor is the subject of debate. Treating hyperuricemia may be useful in reducing CV risk. ObjectiveTo review the evidence on the effect of treatment with allopurinol in patients with hyperuricemia on reducing CV events. MethodsWe searched medical databases for randomized controlled trials (RCT), cohort studies (CS) and case‐control studies (CCS), meta‐analyses, systematic reviews and guidelines, published between January 2002 and December 2013 in Portuguese and English. Level of evidence (LE) and strength of recommendation were graded according to the definitions used by the European Society of Cardiology. ResultsOut of 46 articles, one RCT, three CS and one CCS were included. In the RCT, treatment with allopurinol decreased CV events in patients with moderate chronic renal failure by 71% compared to controls (LE B). In one CS, patients treated with high doses had a greater reduction in CV events compared to low doses (LE B). The other two CS, in patients with heart failure (HF), found similar benefits in patients treated with high doses of allopurinol (LE B). In the CCS, in patients with HF and a history of gout, treatment with allopurinol reduced HF admission and all‐cause mortality (LE B). Discussion and ConclusionsProlonged treatment with high doses of allopurinol may be associated with a reduction in morbidity and mortality in high CV risk populations (class of recommendation IIa). More studies evaluating the effect of therapy with allopurinol in reducing CV events in patients with and without risk are needed.

What is the effect on cardiovascular events of reducing hyperuricemia with allopurinol? An evidence-based review

IntroductionHigh levels of uric acid (UA) have been associated with cardiovascular (CV) disease, but its role as an independent risk factor is the subject of debate. Treating hyperuricemia may be useful in reducing CV risk. ObjectiveTo review the evidence on the effect of treatment with allopurinol in patients with hyperuricemia on reducing CV events. MethodsWe searched medical databases for randomized controlled trials (RCT), cohort studies (CS) and case-control studies (CCS), meta-analyses, systematic reviews and guidelines, published between January 2002 and December 2013 in Portuguese and English. Level of evidence (LE) and strength of recommendation were graded according to the definitions used by the European Society of Cardiology. ResultsOut of 46 articles, one RCT, three CS and one CCS were included. In the RCT, treatment with allopurinol decreased CV events in patients with moderate chronic renal failure by 71% compared to controls (LE B). In one CS, patients treated with high doses had a greater reduction in CV events compared to low doses (LE B). The other two CS, in patients with heart failure (HF), found similar benefits in patients treated with high doses of allopurinol (LE B). In the CCS, in patients with HF and a history of gout, treatment with allopurinol reduced HF admission and all-cause mortality (LE B). Discussion and ConclusionsProlonged treatment with high doses of allopurinol may be associated with a reduction in morbidity and mortality in high CV risk populations (class of recommendation IIa). More studies evaluating the effect of therapy with allopurinol in reducing CV events in patients with and without risk are needed.

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

Echocardiography and right ventricular function in NKF stage III cronic kidney disease: Ultrasound nephrologists' role

TAPSE measurement during echocardiography is a well known measure of right heart systo-diastolic function. Low TAPSE means reduced cranio-caudal excursion of tricuspidal annulus, sign of both reduced ejection fraction and reduced distensibility of right ventricle. It is a good prognostic index for cardiac mortality risk in CHF patients, adding significant prognostic information to NYHA stadiation.Nephrologists do not always fully aware of right ventricular function in their patients affected by chronic renal failure (CRF), even if this datum is probably crucial in vascular access policy.Our study was designed to study right ventricle function and TAPSE on 202 patients affected by moderate chronic renal failure, free from overt pulmonary hypertension. TAPSE, PAPs, right chambers diameters, classical Framingham factors, estimated glomerular filtration rate were recorded.TAPSE was reduced (<23 mm) in 43% of patients enrolled, while dilated right chambers were present in 24%. PAPs exceeded 30 mmHg in 29% of patients. Echocardiographic signs of left ventricular hypertrophy were found in 36% of patients. The ejection fraction was normal in all patients. Statistical analysis showed a significant indirect correlation between TAPSE and PAPs and between TAPSE and tele-diastolic diameters and volumes of the right ventricle, while a direct correlation was observed between TAPSE and Framingham score.TAPSE showed a bimodal distribution, with a subpopulation “low TAPSE – high PAPs”, next to a population characterized by normal values ??for both parameters.A reduction in compliance and systolic function of the right heart chambers is quite early and frequent in course of CKD, a fact that the nephrologist should take in due consideration, managing blood volume or planning vascular access for hemodialysis.

Junctional bradycardia with verapamil in renal failure - care required even with mild hyperkalaemia

Treatment for hypertension with verapamil has a favourable renoprotective effect and is generally considered safe in patients with mild to moderate renal failure. In this report, we highlight the vulnerability of patients with mild to moderate renal failure to verapamil side effects especially in the presence of hyperkalaemia. We report two cases of junctional bradycardia with slow release (SR) verapamil therapy in the presence of mild hyperkalaemia in patients with mild to moderate chronic renal failure. Verapamil and hyperkalaemia may synergistically increase the vulnerability to atrioventricular conduction delay. Renal failure patients with baseline mild hyperkalaemia are particularly liable to bradyarrhythmias with SR verapamil. In such cases, we would recommend verapamil dose reduction and avoidance of SR formulation. In cases of verapamil toxicity, actively treating any level of hyperkalaemia is recommended.

A Randomized Controlled Trial of Two Schedules of Hepatitis B Vaccination in Predialysed Chronic Renal Failure Patients

Patients with chronic renal disease should be vaccinated as soon as dialysis is forestalled, and this could improve the seroconversion of hepatitis B vaccination. In this study, we aimed to compare seroconversion and immune response rates using 4 doses of 40 μg and 3 doses of 20 μg Euvax B recombinant Hepatitis B surface Antigen (HBs Ag) vaccine administered to predialysis patients with chronic kidney disease (CKD). In an open, randomized clinical trial, we compared seroconversion rates in 51 predialysis patients with mild and moderate chronic renal failure who received either 4 doses of 40 μg or 3 doses of 20 μg of Euvax B recombinant hepatitis B vaccine administered at 0, 1, 2, 6 and 0, 1, 6 months, respectively. Differences in seroconversion rates after 4 doses of 40 μg (80.88%) compared to 3 doses of 20 μg (92%) were not significant (P = 0.4124). The mean HBs antibody level after 4 doses of 40 μg at 0, 1, 2, and 6 months (182.2 ± 286.7) was significantly higher than that after 3 doses of 40 μg at 0,1, and 6 months (96.9 ± 192.1) (P = 0.004). Seroconversion after 4 doses of 40 μg (80.8%) was also significantly higher than that after 3 doses of 40 μg (77%) (P = 0.004). Multivariable analysis showed that none of the variables contributed to seroconversion. We found that 4 doses of 40 μg did not lead to significantly more seroconversion than 3 doses of 20 μg.

Cardiac antiapoptotic and proproliferative effect of recombinant human erythropoietin in a moderate stage of chronic renal failure in the rat

Objective:Recombinant human erythropoietin (rhEPO) therapy under circumstances of moderate chronic renal failure (CRF), with yet lower kidney and heart lesion, may have a protective cardiac effect beyond the correction of anemia, whose mechanism deserves better elucidation, namely by clarifying the impact on gene expression profile of markers of apoptosis, inflammation, proliferation, angiogenesis, and lesion/stress in the heart.Materials and Methods:Four groups of rats were studied over a period of 15 weeks (n=7 each): control—without surgery and without drug treatment; rhEPO—treated with 50 IU/kg/week of rhEPO—beta; CRF—submitted to partial nephrectomy (3/4); CRF + rhEPO—CRF with rhEPO treatment after the 3rd week of surgery. The heart was collected in order to evaluate the gene expression, by real-time qPCR, of markers of apoptotic machinery, inflammation/immunology, proliferation/angiogenesis, and lesion/stress.Results:The main findings obtained were (a) CRF rats have demonstrated overexpression of EPO-R in the heart without changes on EPO expression, together with overexpression of Bax/Bcl2 ratio, PCNA, and IL-2; (b) rhEPO therapy on the heart of the rats with CRF induced by partial 3/4 nephrectomy promoted nonhematopoietic protection, demonstrated by the apoptosis prevention, viewed by the Bax/Bcl2 balance, by the promotion of proliferation, due to PCNA increment, and by the immunomodulatory action, expressed by a trend to prevent the IL-2 increment.Conclusion:In this model of moderate CRF, rhEPO treatment showed important cardiac nonhematopoietic effects, expressed mainly by the antiapoptotic and the proproliferative action, suggesting that early rhEPO therapy in moderate stages of CRF might have further therapeutic benefits.

Incremental Value of Arterial Stiffness Over Traditional Risk Factors in Predicting Subclinical Cardiovascular Remodeling in Patients With Moderate Chronic Renal Failure

Cardiovascular remodeling in chronic kidney disease (CKD) is responsible for the high mortality found in this condition. A total of 89 consecutive outpatients with stage III CKD and 52 patients with stage II CKD with similar degree of traditional atherosclerotic risk factors underwent routine echocardiographic and carotid Doppler examination, evaluating vascular and cardiac remodeling (intima-media thickness [IMT] and left ventricular mass index [LVMi]), and its relation with arterial stiffness, determined in the same examination, using an echo-tracking technique. Also the absolute values of LVMi and IMT were statistically similar between the 2 groups, their determinants were completely different, only in stage III the markers of renal impairment and arterial stiffness being independent predictors of cardiac and vascular modifications. We concluded that macroanatomical measurements do not fully describe cardiovascular remodeling in this setting. Arterial stiffness echo-tracking derived could add valuable information, being an easy-to-perform parameter during a routine examination.

Early Sympathetic Activation in the Initial Clinical Stages of Chronic Renal Failure

Direct and indirect indices of neuroadrenergic function have shown that end-stage renal disease is characterized by a marked sympathetic overdrive. It is unknown, however, whether this phenomenon represents a peculiar feature of end-stage renal disease or whether it is also detectable in the early clinical phases of the disease. The study has been performed in 73 hypertensive patients, of which there were 42 (age: 60.7±1.8 years, mean±SEM) with a stable moderate chronic renal failure (mean estimated glomerular filtration rate: 40.7 mL/min per 1.73 m2, MDRD formula) and 31 age-matched controls with a preserved renal function. Measurements included anthropometric variables, sphygmomanometric and beat-to-beat blood pressure, heart rate (ECG), venous plasma norepinephrine (high-performance liquid chromatography), and efferent postganglionic muscle sympathetic nerve activity (microneurography, peroneal nerve). For similar anthropometric and hemodynamic values, renal failure patients displayed muscle sympathetic nerve activity values significantly and markedly greater than controls (60.0±2.1 versus 45.7±2.0 bursts per 100 heartbeats; P<0.001). Muscle sympathetic nerve activity showed a progressive and significant increase from the first to the fourth quartile of the estimated glomerular filtration rate values (first: 41.0±2.7; second: 51.9±1.7; third: 59.8±3.0; fourth: 61.9±3.3 bursts per 100 heartbeats), the statistical significance (P<0.05) between groups being maintained after adjustment for confounders. In the population as a whole, muscle sympathetic nerve activity was significantly and inversely correlated with the estimated glomerular filtration rate (r=-0.59; P<0.0001). Thus, adrenergic activation is a phenomenon not confined to advanced renal failure but already detectable in the initial phases of the disease. The sympathetic overdrive parallels the severity of the renal failure, state and, thus, it might participate, in conjunction with other factors, at the disease progression.

Recombinant human erythropoietin treatment protects the cardio-renal axis in a model of moderate chronic renal failure

Chronic kidney disease (CKD) patients develop anemia because of the low kidney erythropoietin (EPO) production, thus promoting cardiovascular complications. The degree of renal insufficiency might determine the moment to start recombinant human erythropoietin (rhEPO) therapy, but the molecular basis for these options deserves better elucidation. This study aimed to clarify the cardio-renal effects of earlier rhEPO therapy in rats with moderate chronic renal failure (CRF). Four groups of rats were evaluated for 15 weeks (control; rhEPO − 50 IU/kg/week; CRF − 3/4 nephrectomy; CRF + rhEPO) to assess renal and hematology data, EPO levels, blood pressure, heart rate, peripheral catecholamines contents, serum-transforming growth factor-β1 (TGF-β1), kidney gene expression of EPO, Caspase 9 (Casp9), and vascular endothelial growth factor (Vegf). This model of moderate CRF showed moderate and corrected anemia, hypertension, tachycardia, sympathetic overactivity, and increased serum TGF-β1 content. The remnant kidney showed a proliferative profile, with hypertrophy, downregulated gene expression of EPO, and upregulated gene expression of Vegf and Casp9. rhEPO treatment promoted erythrocytosis and prevented tachycardia and catecholamines increment, with a rise of serum TGF-β1. Furthermore, the decreased kidney gene expression of EPO and the overexpression of Casp9 were prevented, demonstrating a renoprotective action on the remnant kidney. In conclusion, rhEPO therapy promotes a protective effect on the cardio-renal axis, which might be mainly attributed to its pro-proliferative and anti-apoptotic properties. These findings might recommend its use in earlier stages of CRF, acting as an erythropoiesis stimulating agent, to efficiently correct not only the anemia, one of the major complications in these patients, but also the succeeding adverse cardio-renal effects.