Group Of Chronic Kidney Disease Patients Research Articles

Effects of Yishenjiangzhuo granules on immunity and bone metabolism in patients with stage 3-4 chronic kidney disease

ObjectiveTo determine the effects of Yishenjiangzhuo granules (YJG) on bone metabolism and to explore the changes in levels of bone Gla protein (BGP), tartrate-resistant acid phosphatase (TRAP), as well as their relationships with levels of B cells, regulatory T cells (Treg) and interleukin (IL)-17 in patients with stage 3-4 chronic kidney disease (CKD) before and after treatment. MethodsFifty-three stage 3-4 CKD patients were divided randomly into two groups: YJG treatment and control. Peripheral blood was taken from two groups of CKD patients and 21 healthy subjects in the normal group. The parameters determined were the levels of CD4 +, CD19 +, CD19 + CD69 +, CD19 + AV, Treg (CD4 + CD25 + CD127l°), BGP, TRAP, IL-17, calcium, phosphate, blood urea nitrogen, serum creatinine (SCr), hemoglobin (Hb) in peripheral blood, and urinary creatinine. Calcium-phosphate products and endogenous creatinine clearance rate (CCr) were calculated according to standard protocols. ResultsIn YJG and control groups, SCr levels were lowered (P<0.01) after treatment, whereas CCr (P<0.05) as well as Hb and albumin levels (P< 0.01) were increased. The changes in levels of CCr and SCr in the YJG group were more significant. After treatment, CD19+CD69+ and Treg levels in the two groups varied (P<0.01) compared with those of the normal group; the level of CD19+ increased but the levels of CD4 + and CD19 + AV decreased (P< 0.01) in both groups. Compared with the control group, the changes of CD19+ and CD19+AV in the YJG group were more apparent (P<0.05). Compared with the normal group, levels of IL-17 in both groups increased significantly (P<0.01), and the difference in the control group was more significant (P<0.05). After treatment, the TRAP level increased (P<0.05), but the difference in BGP level (P>0.05) was not significant. ConclusionIn stage 3-4 CKD patients, B cells and IL-17 participated in the induction of osteoclast activation. YJG could also elevate the level of B cells and decrease their apoptosis, but showed no significant effects on active B cells, IL-17 or osteoclast activity.

Prolonged elevated postprandial sugar augments severity in kidney disease: a North Indian hospital-based study

Aim: Diabetes plays a major role in progression of renal failure. The risk-factor profile changes during the progression of chronic kidney disease (CKD) from mild/moderate to end-stage renal disease. The relationship between glycemic indices, blood pressure, body mass index (BMI) and age at diagnosis in Indians has been less investigated. We assessed association of these risk factors with CKD stages in Indian population. Methods: This study was carried out on patients (n = 162) who were diagnosed with CKD and normal control group (n = 155). For BMI, National Institutes for Health criteria were used to categorize the patients. Result: The mean age of CKD patients were significantly increased with the advancement of stage. BMI, systolic blood pressure (SBP), postprandial sugar level (PP), urea and creatinine were also significantly higher with elevated stages, whereas no differences were observed in diastolic blood pressure (DBP) and fasting blood sugar (FBS). The logistic regression study gave a significant result (p = 0.000) when we compared the group of CKD patients with established/prolonged postprandial blood sugar. It was independently associated with mild CKD [odds ratio (OR) = 5.213, 95% confidence interval (CI) = 2.06–13.21, p = 0.000], moderate CKD (OR = 7.724, 95% CI = 4.05–14.74, p = 0.000) and severe CKD (OR = 7.610, 95% CI = 4.03–14.36, p = 0.000). Conclusion: SBP and PP were the best predictors of prevalent nephropathy in this population, while DBP and FBS were found to be less effective. This may have implication for kidney disease risk stratification and protection.

Chronic Kidney Disease Progression to End Stage Renal Disease: A Single Center Experience of the Role of the Underlying Kidney Disease

Chronic kidney disease (CKD) is common and several factors affect its progression to end-stage renal disease (ESRD). The main goal of our study was to assess the influence of underlying kidney disease and some other important factors during the time of CKD progression to ESRD. A retrospective study of 91 patients (57 men, 34 women; average age 57.7 ± 13.2 years) was carried out. Patients were monitored at least one month before the first renal replacement treatment (RRT). Estimated glomerular filtration rate (eGFR) at first referral to nephrologist was determined by Modification of Diet in Renal Disease equation. Proteinuria was assessed semiquantitatively with dipsticks. Thirty-five patients (38.5%) had diabetic nephropathy (DN), 21 (23.1%) hypertensive nephrosclerosis (HN), 21 (23.1%) adult polycystic kidney disease (APKD) and 14 (15.4%) immunoglobulin A nephropathy (IgAN). Average eGFR at first referral for DN patients was 20.1, and then 23.4 for HN, 35.5 for APKD, and 36.4 mL/min per 1,73 m(2) for IgAN patients. Average time between first nephrological visit and first RRT was 28.4 months for DN patients, 41 for HN, 80.8 for APKD, and 70.1 for IgAN patients. Comparison of all four groups of CKD patients showed that in patients with APKD and IgAN impairment of kidney function to ESRD had progressed statistically significantly slower (P < 0.001). When eGFR at referral, proteinuria, smoking, and renin-angiontensin-aldosterone blockade treatment had been added into the model, patients with APKD and IgAN had a statistically significant longer period between first nephrological visit and first RRT (P < 0.026). In comparison with patients with other underlying causes of CKD, patients with APKD and IgAN had a statistically significant slower progression rate of CKD to ESRD.

High Population Frequencies of APOL1 Risk Variants Are Associated with Increased Prevalence of Non-Diabetic Chronic Kidney Disease in the Igbo People from South-Eastern Nigeria

Background: Continental Africa is facing an epidemic of chronic kidney disease (CKD). APOL1 risk variants have been shown to be strongly associated with an increased risk for non-diabetic kidney disease including HIV nephropathy, primary non-monogenic focal and segmental glomerulosclerosis, and hypertension-attributed nephropathy among African ancestry populations in the USA. The world's highest frequencies of APOL1 risk alleles have been reported in West African nations, overlapping regions with a high incidence of CKD and hypertension. One such region is south-eastern Nigeria, and therefore we sought to quantify the association of APOL1 risk alleles with CKD in this region. Methods: APOL1 risk variants were genotyped in a case-control sample set consisting of non-diabetic, CKD patients (n = 44) and control individuals (n = 43) from Enugu and Abakaliki, Nigeria. Results: We found a high frequency of two APOL1 risk alleles in the general population of Igbo people of south-eastern Nigeria (23.3%). The two APOL1 risk allele frequency in the CKD patient group was 66%. Logistic regression analysis under a recessive inheritance model showed a strong and significant association of APOL1 two-risk alleles with CKD, yielding an odds ratio of 6.4 (unadjusted p = 1.2E-4); following correction for age, gender, HIV and BMI, the odds ratio was 4.8 (adjusted p = 5.1E-03). Conclusion: APOL1 risk variants are common in the Igbo population of south-eastern Nigeria, and are also highly associated with non-diabetic CKD in this area. APOL1 may explain the increased prevalence of CKD in this region.

High density lipoprotein cholesterol levels are an independent predictor of the progression of chronic kidney disease

Patients with chronic kidney disease (CKD) often present with reduced plasma HDL cholesterol (HDL-C) levels. Whether this reduction in an epiphenomenon or is involved in disease progression is unclear. The aim of this study was to investigate the relation between HDL-C levels/function and CKD progression in patients with different degrees of disease. A total of 176 patients with CKD [glomerular filtration rate (GFR) 50.3 ± 29.1 mL min⁻¹] were recruited and followed for up to 84 months. Lipid profile, metabolic status and kidney function were evaluated at predetermined times. Age-matched control subjects were selected from the PLIC study (n = 453). Scavenger receptor class B member 1 (SR-BI) and ATP-binding cassette transporter A1 (ABCA-1)-dependent efflux of cholesterol were measured in CKD patients and in age-matched control subjects. Low HDL-C levels, diabetes and hypertension were associated with reduced GFR. At follow-up, low HDL-C levels were associated with earlier entry in dialysis or doubling of the plasma creatinine level (P = 0.017); HDL-C levels were the only lipid parameter that affected the progression of CKD (hazard ratio 0.951, 95% confidence interval 0.917-0.986, P = 0.007), independently of the presence of diabetes. Only SR-BI-mediated serum cholesterol efflux was significantly reduced in the group of CKD patients with low HDL-C levels compared to the control group. CKD patients with low levels of plasma HDL-C have a poor prognosis. HDL functionality is also impaired in renal dysfunction. These data support the relevance of HDL in influencing CKD progression.

A Study of Lipid Profile and Lipid Peroxidation in Chronic Kidney Disease with Special Reference to Hemodialysis,

Chronic Kidney Disease (CKD) exhibits dyslipidemia and oxidative stress which are well known traditional risk factors for vascular complications. Therefore this study was undertaken to assess the lipid profile and oxidative stress in CKD patients. The study comprised of 95 patients with evidence of CKD. These cases were further divided into 2 groups i.e. non dialysis and hemodialysis groups. There is a significant increase of serum triglycerides and Very Low Density Lipoprotein (VLDL) with a decrease in serum High Density Lipoprotein–Cholesterol (HDL-C) in both non dialysis and hemodialysis groups of CKD patients when compared with control. But there is no alteration in serum total cholesterol and Low Density Lipoprotein Cholesterol (LDL-C) in both groups. Serum Malondialdehyde (MDA) was significantly raised and serum Superoxide Dismutase (SOD) was significantly lowered in CKD patients both in non dialysis and hemodialysis groups when compared with control. The same changes in respect of serum Malondialdehyde (MDA) and Superoxide dismutase (SOD) were also noted in hemodialysis group when compared with non dialysis patients. In hemodialysis patients, the alteration was further aggravated after hemodialysis and these changes were found to be significant when compared with those patients before hemodialysis. All these factors are suggestive of abnormal lipid profile and enhanced lipid peroxidation with decreased antioxidant status. This study would be beneficial for patients with CKD especially those under hemodialysis for instituting antilipidemic drugs and antioxidant therapy which will improve the quality of their lives.

THE IMPACT OF BODY WEIGHT MANAGEMENT IN CHRONIC KIDNEY DISEASE PATIENTS WITH OBESITY

Chronic kidney disease (CKD) and obesity are important public health concerns. We examined the influence of dietary management and physical exercises on renal function, lipid profiles and exercise tolerance of a group of CKD patients. We enrolled 45 obese patients with CKD from stage 1 to 3b with tailored by regular dietitian consultation, recommendations of adequate daily protein and caloric intake, and physical exercises for body weight (BW) reduction. The target was BW reduction ≥ 3%. Thirty eight obese CKD patients completed the study and 24 patients reached the target. Patients who reached the target was significant larger in total body fat decrement than those who failed (3.0% vs 0.5%, p = 0.003). In addition, total muscle mass, especially on trunk and lower limbs (1.2% vs 0%, P = 0.026) was significant decreased in patients who reached the target compared to those who failed. The laboratory data disclosed the significant reduction of Chol (0.7% vs. -19.3%; P = 0.007), LDL-C ( 3.7% vs. -37.6%; P

Avaliação cardiológica de pacientes portadores de doença renal crônica: quais as lições?

Patients with chronic kidney disease (CKD) experiment a synergistic effect of the traditional and the emerging uremia-related risk factors for atherosclerosis. Draw the epidemiologic profile of a group of CKD patients who underwent cardiac evaluation. Symptomatic patients, patients with ischemia on myocardial scintigraphy and/or systolic dysfunction on echocardiography, patients older than 50 years and diabetes mellitus (DM) as a cause of CKD, and those with two or more risk factors underwent coronary angiography. Asymptomatic, non-diabetic patients and patients with no risk factors were investigated with echocardiography. Those with a single risk factor were investigated with echocardiography and scintigraphy. 46 patients (58.7% men) were enrolled. Their mean age was 50.7 ± 11.7 years. 91.3% were on dialysis, for 61.96 ± 55.1 months. Hypertension was the cause of CKD in 56.5%. Of the 28 patients (60.9%) who underwent angiography, 53.6% had coronary artery disease (CAD). The patients were divided into three groups: those with CAD (A), those without CAD (B) and those who didn't undergo coronary angiography (C). A significant difference occurred only between groups B and C, as regards an abnormal ABI (p = 0.026), with no ABI abnormality in group C, and as regards the mean age, which was higher in group B (p = 0.045). In group A, 53.3% of the patients were in the preoperative stage of parathyroidectomy. This study confirmed the high rate of cardiovascular disorders, including CAD, in patients with CKD, especially those on dialysis.

Low-Dose Treatment with Erythropoiesis-Stimulating Agents and Cardiovascular Geometry in Chronic Kidney Disease: Is Darbepoetin-α More Effective than Expected?

Introduction: Chronic kidney disease (CKD) is a widespread invalidating condition, leading to erythropoietin deficiency and decreased cardiovascular performance. Darbepoetin-α and epoetin-α are extensively used to correct renal anemia. The aim of this study was to evaluate cardiological outcomes in two groups of CKD patients treated with erythropoiesis-stimulating agents (ESA: 20 µg darbepoetin-α weekly vs. 2,000 IU epoetin-α thrice weekly) with an unconventional 1:300 conversion ratio. Methods: The study was designed as a single center, retrospective, observational study. One hundred stage IV CKD patients were selected. Hemoglobin (Hb), hematocrit, C-reactive protein, pro-brain natriuretic peptide (BNP) and basal echocardiograms were monitored every 3 months. Results: Darbepoetin-α was significantly more effective in increasing Hb levels after 3 (p < 0.0001), 6 (p < 0.0001), 9 (p < 0.01) and 12 months (p < 0.01) compared to epoetin-α. The optimal Hb target level (11 g/dl < Hb < 12 g/dl) was completely reached after 1 year of treatment with darbepoetin-α and in 70% of the patients treated with epoetin-α (p < 0.01). Cardiovascular performance (left ventricular end-diastolic volume, ejection fraction and pro-BNP) was significantly improved after darbepoetin-α treatment at the 6- and 12-month follow-ups compared to epoetin-α. Discussion: Despite the limitations of a retrospective observational study, these results encourage nephrologists to test the 1:300 darbepoetin/epoetin conversion ratio in ‘easy’ patients, and aggressive protocols for the treatment of anemia in CKD patients are avoided. Darbepoetin-α appeared effective in anemia correction, improving cardiovascular performance in a significantly higher proportion than epoetin. At low doses, on the other hand, it has to be borne in mind that a treatment regimen with only one submaximal administration per week may increase patient compliance and adherence to therapy, explaining in part the observed results.

Chronic Kidney Disease Progression and Outcome According to Serum Phosphorus in Mild-to-Moderate Kidney Dysfunction

Several factors might alter serum phosphate homeostasis and induce hyperhosphatemia in patients with chronic kidney disease (CKD) not requiring dialysis. However, whether and to what extent hyperphosphatemia is associated with a poor prognosis in different CKD patient groups remain to be elucidated. We utilized the "Prevenzione Insufficienza Renale Progressiva" (PIRP) database, a large project sponsored by the Emilia-Romagna Health Institute. PIRP is a collaborative network of nephrologists and general practitioners located in the Emilia-Romagna region, Italy, aimed at increasing awareness of CKD complications and optimizing CKD patient care. We identified 1716 patients who underwent a GFR and serum phosphorous assessment between 2004 and 2007. We tested whether phosphate levels ≥4.3 mg/dl are associated with the risk of CKD progression or all causes of death. Older age and male sex were associated with lower phosphate levels. Instead, higher phosphate levels were noted in patients with diabetes. Patients with phosphate levels ≥4.3 mg/dl were at an increased risk of starting dialysis or dying (hazard ratio 2.04; 95% confidence interval [1.44, 2.90]). Notably, subgroup analyses revealed that the magnitude of the risk associated with hyperphosphatemia varied depending on age, sex, diabetes, and different stages of CKD. These analyses lend support to the hypothesis that phosphorous abnormalities might have a negative effect on the residual renal function and prognosis in different groups of CKD patients. However, the risk associated with hyperphosphatemia might vary in specific CKD patient subgroups.

Natural History of Chronic Kidney Disease Stages 2-4

Introduction: Chronic kidney disease (CKD) is a worldwide problem. The majority of patients in stage 3-5 CKD progress relentlessly to end stage renal disease (ESRD). This study aimed to measure the rate of decline in kidney function among a group of CKD patients and to examine risk factors associated with disease progression. Methods: This is a retrospective study of 300 CKD patients in stages 2-4, that were randomly selected from patients who were on regular follow up in Sheffield kidney institute (SKI), Sheffield, UK, up to June 2007. Patients whose estimated glomerular filtration rate (GFR) declined by more than 1 ml/min/year according to the MDRD formula during a 5-year follow up period were classified as progressors. Baseline parameters that may be associated with a more rapid decline in GFR were evaluated. Results: Males constituted 57.7% of the study population, one third of patients were older than 65 years of age, 93% were white and 39.7% were diabetic. The study showed that 52.7% of patients had a progressive course of CKD. Gender, old age, ethnicity and diabetic status were not significantly different between progressors and non-progressors. Progressors tended to have higher 24-hour urinary protein excretion (2.6 ± 3.6 versus 1.8 ± 3.5 g/dl) and higher blood pressures measurements at baseline that did not reach statistical significance. The slope of reciprocal serum creatinine (1/S. Cr) was significantly and negatively correlated with systolic blood pressure (SBP). It was also significantly and negatively correlated to baseline serum creatinine. Conclusion: Almost half the patients had a rate of decline in estimated GFR that exceeded 1 ml/min/year and were classified as progressors. Key words: CKD progression; ESRD; progressors; non-progressors.

Relationship between Assays of Glycemia in Diabetic Subjects with Advanced Chronic Kidney Disease

Background: Relative to hemoglobin A_1c (HbA_1c), glycated albumin (GA) more accurately reflects recent glycemic control in diabetic patients on hemodialysis and peritoneal dialysis. These assays have yet to be compared in patients with advanced chronic kidney disease (CKD). Methods: HbA_1c and GA were simultaneously measured in 303 diabetic subjects: 70 with CKD prior to dialysis (CKD-stage 4), 184 with CKD after transplantation (TXP-stage 3) and 49 non-nephropathy controls. Results: Mean estimated GFR was 76, 46 and 26 ml/min in controls, TXP-3 and CKD-4 cases, respectively. Mean (SD) HbA_1c (%) and GA (%) concentrations were 7.30 (1.40) and 16.8 (4.9) in controls, 7.28 (1.66) and 21.5 (6.4) in CKD-4 cases, and 7.21 (1.62) and 21.2 (5.5) in TXP-3 cases, respectively. The GA:HbA_1c ratio differed significantly between non-nephropathy controls and both groups of CKD patients (both p < 0.001), but not between CKD-4 and TXP-3 cases (p = 0.92). The glucose:HbA_1c ratio was inversely associated with GFR in all 254 nephropathy cases (r = –0.13; p = 0.04), while glucose:GA did not vary significantly based upon GFR (r = –0.08; p = 0.24). Conclusions: The relationship between glycated albumin and HbA_1c is influenced by the presence of reduced GFR in diabetic patients with CKD. The accuracy of the HbA_1c assay in diabetic subjects with severe nephropathy requires further investigation, although HbA_1c performs relatively well with milder CKD.

Influence of Renal Function and Diet on Acid-Base Status in Chronic Kidney Disease Patients

We investigated the influence of potential renal acid load (PRAL) and renal function on the degree of metabolic acidosis in patients with chronic kidney disease (CKD). This was a cross-sectional study. This study was conducted at the Nephrology Outpatient Division of the Hospital Universitário Clementino Fraga Filho (Rio de Janeiro, Brazil). Thirty CKD patients undergoing conservative treatment were divided according to plasma HCO(3)(-) values into acidotic (HCO(3)(-) <or=22 mM, n = 15) and nonacidotic (HCO(3)(-) >22 mM, n = 15). Biochemical, nutritional, and anthropometric parameters and PRAL were measured. The mean of plasma HCO(3)(-) values was 17.7 +/- 2.8 mM in the acidotic group, and 25.1 +/- 2.2 mM in the nonacidotic group. There was no significant difference in mean PRAL values between the acidotic (9.8 +/- 6.4 mEq/day) and nonacidotic (12.7 +/- 10.0 mEq/day) groups, but there was a significant correlation between plasma HCO(3)(-) and creatinine clearance (r = 0.78, P < .0001). Based on the receiver operating characteristic curve, the level of creatinine clearance to begin detection of acidosis was 31.8 mL/min, with a sensitivity and specificity of 86.7%. The acid-base status of this group of CKD patients undergoing conservative treatment was mainly determined by degree of renal insufficiency rather than diet.

Abstract 809: Greater Fluid Retention is Associated with Increased Cardiovascular Mortality in Different Groups of CKD Patients on Hemodialysis

Patients with chronic kidney disease (CKD) who undergo hemodialysis (HD) treatment have striking similarities to heart failure (HF) patients, in that both populations retain fluid frequently, have excessively high mortality, and exhibit an obesity paradox. We hypothesized that in HD patients greater interdialytic fluid retention is associated with poor cardiovascular (CV) survival. We examined the 2-year (7/01– 6/03) mortality in 34,003 MHD patients across the United States, who had an average weight gain of at least 0.5 kg above their end-dialysis dry weight by the time the subsequent HD treatment started. The 3-month average interdialytic weight gain was dichotomized into two categories of 0.5 to 2.0 kg (reference) and &gt;=2.0 kg. After multivariate adjustment for demographics (case-mix) and laboratory surrogates of malnutrition and inflammation, higher weight gain &gt;=2.0 kg was significantly associated with increased death risk in most subgroups of patients particularly among Blacks (death hazard ratio [HD] and 95% confidence interval [CI]: 1.10 [1.01–1.20]), non-diabetics (1.07 [1.01–1.14]), those with 3 to 6 months on dialysis (1.23 [1.14–1.33]) and between 6 months and 2 years on dialysis (1.20 [1.09–1.33]), and those with albumin &gt;3.8 g/dL (1.08 [1.01–1.18]) (see Figure ): In MHD patients greater fluid retention of 2 kg or higher between two consecutive HD treatment sessions appears associated with higher death risk particularly among Blacks, non-diabetics, those with less than 2 years of HD treatment, and those with better nutritional status. The mechanisms by which fluid retention influences survival in HD may be similar to HF patients and warrants further research. This research has received full or partial funding support from the American Heart Association, AHA Western States Affiliate (California, Nevada &amp; Utah).

Cross-Talk between Inflammation, Coagulation/Fibrinolysis and Vascular access in Hemodialysis Patients

This work aimed to study the association between fibrinolytic/endothelial cell function and inflammatory markers in chronic kidney disease (CKD) patients undergoing hemodialysis (HD) and recombinant human erythropoietin (rhEPO) therapies, and its relationship with the type of vascular access (VA) used for the HD procedure. As fibrinolytic/endothelial cell function markers we evaluated plasminogen activator inhibitor type-1 (PAI-1), tissue plasminogen activator (tPA) and D-dimers, and as inflammatory markers; C-reactive protein (CRP), soluble interleukin (IL)-2 receptor (s-IL2R), IL-6 and serum albumin levels. The study was performed in 50 CKD patients undergoing regular HD, 11 with a central venous dialysis catheter (CVC) and 39 with an arteriovenous fistula (AVF), and in 25 healthy controls. Compared to controls, CKD patients presented with significantly higher levels of CRP, s-IL2R, IL-6 and D-dimers, and significantly lower levels of PAI-1. The tPA/PAI-1 ratio was significantly higher in CKD patients. We also found statistical significant correlations in CKD patients between D-dimers levels and inflammatory markers: CRP, albumin, s-IL2R and IL-6. When comparing the two groups of CKD patients, we found that those with a CVC presented statistically significant lower levels of hemoglobin concentration and albumin, and higher levels of CRP, IL-6, D-dimers and tPA. Our results showed an association between fibrinolytic/endothelial cell function and increased inflammatory markers in CKD patients. The increased levels of D-dimer, tPA and inflammatory markers in CKD patients using a CVC, led us to propose a relationship between the type of VA chosen for HD, and the risk of thrombogenesis.

MULTIDISCIPLINARY APPROACH FOR PRESCRIPTIVE MANAGEMENT OF MINERAL AND BONE METABOLISM IN CHRONIC KIDNEY DISEASE: DEVELOPMENT OF A DIETETIC LED PROTOCOL

A number of mineral metabolism abnormalities occur as kidney function declines, these include hyperphosphatemia, hyperparathyroidism and altered vitamin D metabolism. These derangements are associated with increased morbidity and mortality amongst the chronic kidney disease patient group. Treatment requires a multidisciplinary team approach in which the dietitian plays a pivotal role. The development of protocols to aid implementation of various international, national and local treatment strategies is described. Audit the protocol to evaluate their clinical effectiveness. A prescriptive Protocol for the management of mineral and bone metabolism abnormalities in chronic kidney disease was developed and implemented. Initial audit findings suggest the protocol has had a positive effect on the control of phosphate, corrected calcium and parathyroid (PTH) levels. The development and implementation of a dietetic-led prescriptive therapy protocol allows dietitians and clinicians to adopt an integrated approach for the diagnosis and timely management of these complicated conditions.

Associations between renal function, volume status and endotoxaemia in chronic kidney disease patients

Inflammation is an important predictor of increased cardiovascular morbidity and mortality in patients with chronic kidney disease (CKD), but the mechanisms behind the chronic activation of the immune system are not clearly understood. CKD patients develop fluid overload, which has been proposed to be a stimulus for inflammatory activation due to the translocation of macromolecules from the gut. We hypothesize that fluid overload is associated with signs of systemic inflammation and endotoxaemia in stages 1-5 CKD patients. The aim of this prospective study was to evaluate the associations between renal function, fluid status [evaluated by the inferior vena cava diameter (IVCD) and the collapsibility index (CI)], systemic inflammation [plasma levels of C-reactive protein (CRP), fibrinogen and albumin] and endotoxaemia (through the Limulus amebocyte lysate enzymatic assay) in a group of CKD patients in our out-patient clinic. The population consisted of 74 (mean of 57; range 23-83 years of age; 47% males) CKD patients with glomerular filtration rate (based on the mean of urea and creatinine clearances) of 34 ml/min. Both albumin (Rho = 0.25; P = 0.05) and fibrinogen (Rho= - 0.48; P < 0.0001) were significantly correlated to glomerular filtration rate (GFR). According to the IVCD, 84% of the patients were fluid overloaded, while 83% were considered overloaded by the CI. Signs of endotoxaemia were detected in all patients. Endotoxin levels were higher in patients with signs of fluid overload (0.85 +/- 0.11ng/l) when compared with patients with normal values of IVCD (0.61 +/- 0.05 ng/l; P < 0.05). Endotoxin levels correlated to both IVCD (Rho=0.33, P < 0.005) and CI (Rho = -0.25, P < 0.05). There was no correlation between endotoxin levels and GFR, CRP or fibrinogen. In summary, although most CKD patients presented signs of fluid overload that was associated with endotoxaemia, there was no association between endotoxaemia and systemic inflammation, suggesting the endotoxaemia may not be the main determinant of the inflammatory status in this group of patients.

Erythrocyte PAF-acetylhydrolase activity in various stages of chronic kidney disease: Effect of long-term therapy with erythropoietin

Erythrocytes represent an important component of the antioxidant capacity of blood, comprising, in particular, intracellular enzymes, including platelet-activating factor acetylhydrolase (PAF-AH) and glutathione peroxidase (Gpx). We evaluated the erythrocyte PAF-AH and Gpx activities in various stages of chronic kidney disease (CKD), and further investigated whether erythropoietin (EPO) administration in these patients has any influence on the enzyme activities. Thirty-six patients (19 men and 17 women) with CKD (stages 1 to 5) participated in the study. Thirteen of them presented with CKD stage 1 to 2 (group I), whereas 23 patients presented with CKD stage 3 to 5 and randomized into two groups (i.e., groups II and III). Patients of group II (N= 11) were administered EPO subcutaneously, 50 units per kg once per week. In group III (N= 12), EPO was initiated only when the hemoglobin (Hb) levels decreased during follow-up to less than 9 g/dL. All patients were seen on an outpatient basis at 2 and 4 months. Fifteen normolipidemic age- and sex-matched healthy volunteers also participated in the study and were used as controls. The PAF-AH and Gpx activities were determined in isolated washed erythrocytes. The erythrocyte-associated PAF-AH and Gpx activities were higher in all CKD patient groups at baseline compared to controls, the groups II and III exhibiting significantly higher enzyme activities compared with group I. In all studied populations, both enzyme activities were negatively correlated with the creatinine clearance values. Importantly, the PAF-AH and Gpx activities were progressively decreased during the follow-up in patients not treated with EPO (group III), a phenomenon not observed in patients receiving EPO (group II), or in patients of group I. This reduction in enzyme activities was positively correlated with the decrease in the creatinine clearance values in patients of group III. Significant alterations in the erythrocyte-associated PAF-AH and Gpx activities related to the disease stage are observed in CKD patients. Administration of EPO prevented the reduction in enzyme activities observed during the progression of the renal insufficiency, thus preserving the erythrocyte defense mechanisms against oxidative stress.

Reviews: Should the Target Hemoglobin for Patients with Chronic Kidney Disease Treated with Erythropoietic Replacement Therapy be Changed?

Recombinant human erythropoietin (rHuEPO, epoetin) revolutionized the treatment of anemia in patients with chronic kidney disease (CKD) when it was approved for use in the United States in 1989. Among dialysis patients, the mean hemoglobin (Hb) in patients undergoing dialysis rose from 7-8 g/dl prior to 1989 to 11-12 g/dl today. Among patients with CKD not on dialysis, epoetin use has not been as broadly applied as among dialysis patients, and although the mean Hb level in this patient population has increased, the impact has been less than in patients on dialysis. The optimal treatment target for epoetin remains controversial. Consistent with clinical practice guidelines, current practice in dialysis patients in the United States aims to maintain a target Hb of 11-12 g/dl, a level that is still well below the normal range. Debate centers on whether the current Hb target is too low and whether the target range is too narrow. Quality of life clearly improves in many individuals as Hb rises into the normal range from lower levels. In retrospective studies, higher Hb levels have been associated with lower risks of hospitalization and mortality. However, one large, prospective clinical trial has raised concern about normalizing Hb in hemodialysis patients with cardiac disease, and other prospective studies have not yet provided convincing evidence of significant benefits from normalizing Hb in dialysis-dependent and non-dialysis-dependent patients with CKD. A relative lack of information on non-dialysis-dependent patients with CKD and changes in fiscal policies regulating reimbursement for epoetin have contributed to uncertainty as to the best practices for anemia management in patients with CKD. There is increasing interest in the potential benefits of broadening the current target Hb range or eliminating an upper limit altogether and instead establishing a minimum Hb goal. While some extension of the upper limit of the currently recommended target Hb range might appear to be reasonable, the extent to which this should be extended, the benefits, risks, and costs of maintaining higher Hb levels in patients with CKD, and whether target Hb levels should be different in different CKD patient groups remains to be determined. Future efforts are likely to focus on selecting patient populations most likely to benefit from normalizing Hb, while adjusting the range of a subnormal Hb target for others.