Predialysis Patients Research Articles

Lipid status association with 25-hydroxy vitamin D: Cross sectional study of end stage renal disease patients.

Some observational studies indicate an association of 25-hydroxy vitamin D (25(OH)D) insufficiency and atherogenic cholesterol concentrations. The aim of this study was to investigate relationship between 25(OH)D concentrations and lipid parameters in end stage renal disease (ESRD) patients, separately for predialysis, hemodialysis and peritoneal dialysis patients. We have adjusted 25(OH)D concentrations for seasonal variability with cosinor analysis, and performed all further analysis using these corrected 25(OH)D concentrations. Concentrations of 25(OH)D and the lipid parameters were determined in 214 ESRD patients and 50 control group participants. The analysis included the measurement of 25(OH)D by HPLC, apolipoprotein (Apo) AI, ApoB and Lp(a) by nephelometry, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) by spectrophotometry and manually calculated ApoB/ApoAI and LDL-C/HDL-C ratio. ESRD patients with adjusted 25(OH)D concentrations of 50 nmol/L had significantly higher TC (P = 0.005) and ApoAI (P = 0.049). Significantly higher HDLC (P = 0.011) and ApoAI (P = 0.020) were found in hemodialysis patients with the 25(OH)D concentrations of 50 nmol/L. The other analyzed lipid parameters differed significantly between predialysis, hemodialysis and peritoneal dialysis patients with 25(OH)D concentrations of < 50 nmol/L. Our study indicate the significant relationship between 25(OH)D repletion and optimal concentrations of lipid parameters in ESRD patients. Further research is necessary to explain whether joint evaluation of vitamin D status and lipid abnormalities could improve cardiovascular outcome in ESRD patients.

SUN-291 PREDICTIVE FACTORS OF ESA HYPORESPONSIVENESS IN PRE-DIALYSIS CKD PATIENTS: SECONDARY ANALYSIS OF THE RADIANCE-CKD STUDY

Erythropoiesis-Stimulating Agents [ESA] hyporesponsiveness is related to poor renal outcome in management of renal anemia; however, it is difficult to predict which patients will be hyporesponsive. We previously reported on the RADIANCE-CKD study, a multicenter, open-label, randomized controlled study to evaluate renal outcome by different target hemoglobin [Hb] levels using epoetin beta pegol [CERA] in pre-dialysis CKD patients with poor response to ESA (ASN 2018). The aim of the present study was to predict the patients with ESA hyporesponsiveness among pre-dialysis CKD patients. Pre-dialysis CKD patients (362 patients) with poor response to ESA were randomly assigned to an intensive treatment group (I-group; target Hb level of ≥11 g/dl) or a conservative treatment group (C-group; target Hb level of baseline Hb ±1g/dl). The primary renal composite endpoint was a transition to renal replacement therapy, reduction of eGFR to <6 ml/min/1.73 m2, or >30% reduction of eGFR. In the 3-month landmark analysis, the incidence of renal outcome was evaluated in 3 categories of Hb levels (<10, 10 to <11, ≥11 g/dl) according to tertiles of ESA dose. ESA hyporesponsiveness patients (HYPO) were defined as achieved Hb level <11 g/dl with high tertile and achieved Hb level <10 g/dl with mid-tertile in I-group. The predictive factors of hyporesponsiveness patients were then assessed using a logistic regression model and estimated area under the receiver operating characteristic (ROC) curve. Mean age was 74.7 years and 58.6% of patients were male. Mean baseline eGFR in I-group and C-group were 15.3 and 15.9 ml/min/1.73 m2, respectively. Kaplan-Meier analysis and Cox proportional hazards analysis showed no significant difference in the primary end point between the two groups (99 and 109 events) during the 21-month observation period. In the 3-month landmark analysis, achieved Hb level and required ESA dose were higher in I-group. The incidence of the renal composite endpoint had a tendency to increase in accordance with decrease of Hb levels regardless of the ESA dose in both groups. A total of 30 (54.5%) HYPO patients had the renal composite endpoint, as compared with 54 (50.9%) non-HYPO. Based on the logistic regression analysis, 19 background characteristics (age, BW, eGFR, Alb, ferritin, Hb, CRP, etc.) and 14 biomarkers (IL-6, Hepcidin, TGFβ, CD147, PTH, 25Vitamin-D, etc.) were evaluated as predictive factors of HYPO. The obtained area under the ROC curve (AUC) was 0.88, with sensitivity of 84% and specificity of 84%. Using a branch-and-bound algorithm to find the highest likelihood score statistic for 6 variables, the selected variables were age, Hb, Hepcidin, TGFβ, CD147, and PTH; then, the estimated AUC was 0.82. The patients with ESA hyporesponsiveness among Japanese CKD patients can be predicted based on clinical characteristics and biomarkers in pre-dialysis.

MON-318 A PHASE II TRIAL TO ASSESS SAFETY, TOLERABILITY AND EFFICACY OF PHD-2 INHIBITOR (DESIDUSTAT-ZYAN1) IN THE TREATMENT OF ANEMIA IN PRE-DIALYSIS CHRONIC KIDNEY DISEASE PATIENTS

Anemia is a condition of decrease in red blood cells (RBCs) or/and haemoglobin, which can be caused by a range of serious medical conditions, like chronic kidney disease (CKD), chemotherapy induced anemia (CIA), and anemia of chronic disease (ACD). Erythropoiesis, the production of RBCs in the bone marrow, is a dynamic, multifaceted process requiring precise coordination to meet the demands of the body for oxygen. Hypoxia-inducible factor (HIF) orchestrates this process by mediating genes involved in erythropoiesis. Erythropoiesis is often suppressed in chronic inflammatory diseases due to expression of hepcidin, a regulatory hormone that limits the availability of iron for erythropoiesis even when dietary iron intake is sufficient whereas HIF inhibits the expression of hepcidin. So, selective activation of the erythropoietic cascade using HIF-PHI (hypoxia-inducible factor prolyl hydroxylase inhibitors) has the potential to induce the full complement of factors necessary for erythropoiesis including Erythropoetin (EPO), EPO-Receptor, and iron regulatory genes. Induction of HIF-mediated erythropoiesis, HIF-PHI offer potential advantages over current anemia therapy. So the Phase II study was design to evaluate the safety, efficacy and pharmacokinetic of ZYAN1 versus placebo in pre-dialysis chronic kidney disease patients with anemia The study was a multi-center, prospective, randomized, double-blind, and parallel group phase II study planned in 120 subjects. Subjects were assigned randomly in a ratio of 1:1:1:1 treatment groups i.e. ZYAN1 group 100 mg, 150 mg and 200 mg and placebo group. Subjects received the study drug orally once every alternate day in fasting condition for six weeks. Efficacy criteria such as change from baseline in hemoglobin (Hb), Hepcidin and CRP were assessed. A total of 117 subjects were enrolled and out of them 103 subjects completed the study. Responder subjects were defined as at least 1 gm/dL increase in Hb during the study. Greater than 80% responders were observed in ZYAN1 200 mg and >60% responders were observed in ZYAN1 100 mg and 150 mg treatment groups in both mITT and PP populations during the study. Hepcidin levels significantly decreased at Week 2 in ZYAN1 150 and 200 mg treatment groups compared to placebo. At Week 6, the change from baseline in hepcidin levels was statistically significant in ZYAN1 100 mg, 150 mg and 200 mg treatment groups. Trend similar to mITT population was observed in PP population. A total of 31 AEs were reported from 18 (15.38%) subjects during the study. In total, the most commonly reported TEAEs (PTs) during the study were abdominal pain, vomiting and headache. These TEAEs were observed in total approximately 4% of subjects. The phase 2 clinical trial results obtained led to the conclusion of ZYAN1 (100 mg, 150 mg and 200 mg) effectively treating CKD-related anemia in pre-dialysis Indian patient. More than 60% of the ZYAN1-treated (100 mg, 150 mg and 200 mg) pre-dialysis-CKD subjects responded to the treatment and experienced >1 gm/dL increase in Hb levels within the short period of 6 weeks of dosing. In this study, ZYAN1 increased Hb levels in dose dependent manner.

MON-265 ANAEMIA, MEAN CORPUSCULAR VOLUME AND MORTALITY AMONG A BLACK CKD POPULATION IN SOUTH AFRICA

The burden of chronic kidney disease is increasing globally and prompt identification; coupled with improved management of CKD patients have increased the population of pre-dialysis patients. However, CKD patients in less resourced countries may not have optimal care and the current survival pattern of pre-dialysis CKD patients is not well characterized. We, therefore, aimed to evaluate the predictors of survival among black pre-dialysis CKD patients in Johannesburg. We conducted a cohort study of 256 consecutive consenting Black non-dialysis requiring CKD patients attending the renal outpatient clinic of Charlotte Maxeke Academic Hospital from 1st June 2016 to 1st December 2016 and were followed up till 31 December 2017. Socio-demographic and clinical information of the participants were obtained using a self -administered pro forma, and participants were followed up at clinic visits every one to three months or by telephone. Descriptive statistics, Kaplan-Meier curves and Cox proportional hazard regression analyses were conducted to evaluate factors affecting the survival of the participants. The mean age of the participants was 52.8±14.3 years and 49.5% were females, and 51.9% were males. During a median follow up of 18 months, the mortality rate was 1.12 per 100 person-years. The death rate increased with worsening haemoglobin level from 0.96 among patients with mild anaemia to 4.29 per 100-person-years among patients with severe anaemia. Anaemic patients with GFR < 30mls/min had significantly increased risk of death (HR 11.51, 95% CI 1.62–78.32, P < 0.001). Participants with hyperphosphatemia had about 2.6-fold increased hazard of death (HR, 2.60; 95%CI, 1.09-6.20, P =0.02). Tabled 1VariableAll (n=256)Alive (n=216)Dead (n=40)P-valueAge (years)52.8±14.352.7±14.653.4±12.90.79Gender n (%)Male133 (52.0)110 (50.9)23 (57.5)0.27Female123 (48.0)106 (49.1)17 (42.5)Hb (g/dl)12.2± 2.712.6± 2.59.7± 2.7<0.0001Median MCV (fl)88 (83-92)88 (84-93)85 (82-89)0.009Ferritin ng/mL104 (57-198)99 (56-179)211 (100-394)<0.0001BMI (kg/m2)29.9±6.430.0±6.529.1± 6.50.43 Open table in a new tab Mortality in pre-dialysis CKD patients was associated with anaemia and hyperphosphatemia. Clinical interventions targeted at preventing these conditions may improve outcomes among this group of CKD patients

Assessment of Pulmonary Function in End Stage Renal Disease Patients on Regular Hemodialysis

Background: end-stage renal disease (ESRD), is the last stage of chronic kidney disease. When your kidneys fail, it means they have stopped working well enough for you to survive without dialysis or a kidney transplant. Objective: it was to assess the pulmonary function in patients with ESRD after hemodialysis. Patients and Methods: Prospective study which was done in tertiary level care center.Thirty ESRD patients who were on hemodialysis regularly were studied. Results: The mean FEV1/FVC% which was observed in the patients of this study was 67.8±20.8% of the predicted value, after hemodialysis, the mean FEV1/FVC% increased up to 82.3±20.1% of the predicted value, and this increase was statistically significant with P value <0.006. The mean of the forced expiratory flow 25-75% (FEF 25-75%) of the studied patients pre-dialysis was 53.1±33% of the predicted value, after hemodialysis, the mean of the FEF 25-75% increased up to 58.3±34.6% of the predicted value and that was statistically significant with P value <0.05. The mean of the peaked expiratory flow rate (PEFR) was 47.8±31.7% of the predicted value and after hemodialysis, the mean PEFR increased to 52.1±30.9% of the predicted value and that was statistically significant with P value <0.05). Conclusions: pulmonary function tests decrease significantly among ESRD patients who undergo hemodialysis regularly pre and after the sessions of hemodialysis. Most ESRD patients were with abnormal pulmonary functions, mainly of a restrictive pattern.

Fracture risk in chronic kidney disease: A Korean population-based cohort study.

BackgroundChronic kidney disease (CKD)-mineral and bone disorder (MBD) and fracture risk are both closely related to declining renal function. Controlling hyperphosphatemia with phosphate binders is a basic principle of CKD-MBD treatment. The aim of this study was to identify differences in fracture risk between pre-dialysis CKD patients and end-stage renal disease (ESRD) on dialysis, and to evaluate the effects of phosphate binders on fracture risk in ESRD patients.MethodsData from a total of 89,533 CKD patients comprising CKD diagnosis, dialysis, fracture history, and phosphate binder prescription history from 2012 to 2016 were retrieved from the Health Insurance Review and Assessment Service Database. Multivariate Cox regression analyses were performed to identify whether dialysis or phosphate binders were associated with an increased fracture risk.ResultsOverall, the rate of fractures in pre-dialysis CKD patients was 74 per 1,000 patient-years, while that in dialysis patients was 84 per 1,000 patient-years. The risk of fracture in ESRD patients was higher than pre-dialysis CKD patients (hazard ratio, 1.16; 95% confidence interval, 1.12–1.21; P < 0.001) after adjusting for confounding variables. In addition, the fracture risk in patients who were not taking phosphate binders was 20.0% higher compared to ESRD patients taking phosphate binders.ConclusionFractures were more prevalent in ESRD patients on dialysis than pre-dialysis CKD patients. Use of phosphate binders was associated with a lower fracture risk in ESRD patients.

Validity and internal consistency of EQ-5D-3L quality of life tool among pre-dialysis patients with chronic kidney disease in Sri Lanka, a lower middle-income country.

ObjectiveEQ-5D-3L is a generic QOL tool used mainly in economic evaluations. Burden of Chronic Kidney Disease (CKD) is rising in Sri Lanka. Assessing the validity of generic QOL tools creates new opportunities of their utilization among patients with CKD.MethodsA cross-sectional study was conducted among 1036 CKD patients, selected using the simple random sampling technique. The validity was tested with six a-priori hypotheses. These included construct validity assessments, evaluating convergent validity and performing known group comparisons. EQ-5D-3L, Short Form-36 (SF-36) were used to assess QOL. Center for Epidemiological Studies Depression Scale (CES-D-20) and General Health Questionnaire-12 (GHQ-12) were used to assess the presence of depression and psychological distress respectively. Internal consistency of the whole tool and when each item is removed was assessed by Cronbach alpha.ResultsThe response rate was 99.2%. Majority of participants were males (n = 646,62.4%) in the age category of 41–60 (n = 530; 51.2%). Most were in either stage 4 or 5 of CKD (n = 646,75.1%). The summary measures of SF-36, positively and significantly correlated with the EQ-5D-3L index and VAS scores (p<0.001). EQ-5D-3L QOL scores were significantly different between the group with depression and without as measured by CES-D-20 (p<0.001). Assessed using GHQ-12, similar significance was detected between the group with psychological distress and without (p<0.001). The Cronbach alpha was 0.834 and when each item was removed, ranged from 0.782 to 0.832.ConclusionEQ-5D-3L is a valid generic QOL tool with satisfactory internal consistency to be used among CKD patients in the pre-dialysis stage.

Specific risk factors for cerebrovascular disorders in patients with chronic kidney disease in the pre-dialysis period

Cerebral vascular disorders are one of the leading causes of disability and mortality in patients with chronic kidney disease (CKD). The article presents the currently available data on risk factors (RF) for the development of cerebrovascular disorders in pre-dialysis patients with CKD. Two groups of RF are identified: traditional and non-traditional (specific). Traditional RF, which include arterial hypertension, diabetes mellitus and hypercholesterolemia, independently affect the cerebral vascular bed and get worse against the background of CKD. Specific RF is associated with features of the CKD pathogenesis. It includes increased blood levels of homocysteine, β2-microglobulin, impaired calcium-phosphorus metabolism, accumulation of uremic toxins and toxins of intestinal bacteria, anemia and other factors. In the present review, special attention is paid to specific RF and pathogenetic mechanisms of the development of cerebrovascular disorders in predialysis patients with CKD. Timely detection of cerebral risk factors may lead to the improvement of early diagnosis and prevention of cerebral vascular disorders, optimization of therapy for patients with CKD.

Does aspirin for cardiovascular disease prevention improve outcomes in predialysis patients with chronic kidney disease?

Department of Family and Community Medicine, University of Missouri, Columbia, MO The authors declare no conflicts of interest.

An increased mortality risk is associated with abnormal iron status in diabetic and non-diabetic Veterans with predialysis chronic kidney disease

Iron parameters have not been well characterized in pre-dialysis patients with chronic kidney disease (CKD), and it remains unclear if abnormal iron balance is associated with increased mortality. Therefore, we performed a historical cohort study using data from the Veterans Affairs Corporate Data Warehouse to evaluate the relationship between iron status and mortality. We identified a pre-dialysis CKD cohort with at least one set of iron indices between 2006-2015. The cohort was divided into four iron groups based on the joint quartiles of serum transferrin saturation (percent) and ferritin concentration (ng/ml): reference (16-28%, 55-205 ng/ml), low iron (0.4-16%, 0.4-55 ng/ml), high iron (28-99.6%, 205-4941 ng/ml), and function iron deficiency (0.8-16%, 109-2783 ng/ml). We compared mortality risk between the iron groups using matching weights based on multinomial propensity score models and Poisson rate-based regression. We also evaluated if the association between iron groups and mortality differs between the diabetic and non-diabetic subgroups. Of the 80,067 eligible veterans, 32,489 were successfully matched. During the mean follow-up period of 4.0 years, adjusted relative rate (95% confidence interval) for all-cause mortality in three abnormal iron groups were increased compared to the reference: functional iron deficiency [1.21 (1.17, 1.25)], low iron [1.10 (1.07, 1.14)], and high iron [1.09 (1.06, 1.13)]. The mortality risk was similar between diabetic and non-diabetic subgroups for each iron group. Thus, an abnormal iron balance, particularly functional iron deficiency, is associated with increased mortality in CKD.

Oral mucosa and salivary findings in non-diabetic patients with chronic kidney disease

IntroductionChronic kidney disease (CKD) and dialysis treatment could affect oral mucosa and cause qualitative or quantitative changes of saliva. ObjectiveThe aim of the study was to investigate oral manifestations, unstimulated salivary flow rate (USFR), salivary pH value and biochemical composition of saliva in non-diabetic patients with CKD. DesignThe study group (PD) consisted of 50 pre-dialysis patients diagnosed with CKD, positive control group (HD) of 25 haemodialysis patients and negative control (H) of 25 age and gender-matched healthy persons. Creatinine clearance rate (CrCl) was calculated from the blood creatinine using the Cockcroft-Gault formula. After a detailed intraoral examination, whole unstimulated saliva samples were collected to determine salivary pH value, and biochemical composition using a spectrophotometric method. ResultsStatistical analysis revealed that PD subjects had more oral lesions (p < 0.05) and symptoms (p < 0.001) than controls. The mean CrCl was significantly lower (p < 0.05) in CKD subjects with pale mucosa, xerostomia, dysgeusia, and uremic odour, comparing to those without listed symptoms. PD subjects had significantly decreased USFR and increased pH, urea and creatinine than H controls (p < 0.05). A moderately strong positive correlation between serum and salivary creatinine in both PD (p < 0.05) and HD (p < 0.05) groups was found. ConclusionThis study confirmed that xerostomia and dysgeusia are major symptoms among pre-dialysis patients. Their presence along with uremic odour and pale mucosa is directly related to decreased kidney function. On the diagnostic point, decreased USFR, especially hyposalivation and increased salivary creatinine, should be considered a significant indicator of CKD in stages before dialysis therapy.

Abstract No. 477 Endovascular arteriovenous dialysis fistula intervention: outcomes and factors contributing to fistula failure

To determine post-intervention patency rates and contributing factors for fistula failure in pre-dialysis patients with arteriovenous (AV) dialysis fistulas. Institutional review board approval was obtained for this single-institution retrospective study. All pre-dialysis patients who underwent upper extremity AV fistula creation for anticipated dialysis between October 1995 and January 2015 and who required subsequent endovascular therapy to maintain patency were reviewed. A total of 210 patients were identified. The medical record was queried for patient demographics, procedural details and outcomes. Multiple AV fistula configurations were reviewed: 138 brachiocephalic, 39 radiocephalic, 30 brachiobasilic, 2 ulnocephalic and 1 radiobasilic. Median post-intervention primary patency was 2.7 years, median post-intervention primary-assisted patency was 3.2 years, and median post-intervention secondary patency was 3.6 years. There were 293 initial stenosis treated. This included 5 stenosis in the inflow artery, 50 at the anastomosis, 71 in the juxta-anastomotic segment, 71 in the cannulation zone of the outflow vein, 16 in the noncannulation zone, 10 at the swing point of basilic vein transpositions, 57 in the cephalic arch, and 13 in the central veins. Stenoses in the non-cannulation zone of the outflow vein had the highest rate of target lesion revascularization (TLR) (76.7%), whereas central venous stenosis had the lowest rate of TLR (7.7%). The radiocephalic fistula configuration had better post-intervention primary patency (hazard ratio [HR] 0.58; 95% confidence interval [CI] 0.35-0.96; p=0.034). Conversely, brachiocephalic fistulas had higher risk for loss of post-intervention primary patency (HR 1.90; 95% CI 1.13-3.20; p=0.015). Among predialysis patients who undergo initial endovascular therapy to maintain patency of the AV fistula, the radiocephalic configuration was found to have the best post-intervention primary patency compared to other configurations. While the majority of hemodynamically significant lesions occurred at the anastomosis, lesions in the non-cannulation zone of the outflow vein had the highest rates of TLR.

Acceptance, choice and empowerment (ACE) for pre-dialysis patients: a peer educator-based community project that aims to improve choice and quality of life for patients with kidney failure

To improve patients’ acceptance of their kidney failure diagnosis and to empower them regarding their dialysis treatment choices. In partnership with patients and clinical staff (a consultant and two–three senior nurses were involved), they worked collaboratively to facilitate acceptance and decision making. The project had a four-pronged approach:

SCREENING DIAGNOSTICS OF FABRIC DISEASE AMONG PATIENTS WITH CHRONIC KIDNEY DISEASE IN THE NORTH-WESTERN REGION OF RUSSIA

Fabry disease (FD) is a progressive multi-organ disease leading to the development of cardiovascular and cerebrovascular complications and progression of renal failure. Nonspecificity of clinical signs often leads to late diagnosis of the FD that causes high diagnostic relevance of screening in high risk groups, particularly among patients with chronic kidney disease (CKD). According to the results of screening programs in many countries, the average prevalence of FD among patients with CKD is about 0.26%. THE AIM of this study was to investigate the prevalence of FD in patients with CKD in the northern west region of Russian Federation. PATIENTS AND METHODS. This prospective study assessed α-galactosidase A (α-Gal A) activity in dried blood spots in 1835 stage 1-5 CKD (85% – dialysis, 15% – pre-dialysis) patients, 74% males, mean age 55±12 years. The survey was carried out regardless of gender, age and primary diagnosis leading to CKD. The activity of α-Gal A more than 1.89 umol/l/hr was considered as normal. In the case of identifying the decreased activity of the enzyme the diagnosis was confirmed by GLA gene mutation analysis. RESULTS. The average level of α-Gal A was 5.39±2.69 umol/l/h. The level of α-Gal A was significantly higher in patients with pre-dialysis stages of CKD compared with patients receiving dialysis (7.5±3 vs 4.3±2.3 umol/l/h, p&lt;0.001) as well as in males higher than in females (5.9±3.4 vs 3.4±2.3 umol/l/h, p &lt;0.001). The decrease in α-Gal A activity was detected in 6 patients, of which 3 had the GLA gene mutations (c.427G&gt;A, с.818Т&gt;С, c.895G&gt;C). One patient (p.508G&gt; T) had a confirmed FD and received an enzyme-replacement therapy at the time of screening. All patients with identified FD were males treated by hemodialysis. Thus, the prevalence of FD in patients with CKD C5d was 1:392 (0.26%). A survey of relatives revealed the disease in two additional cases. CONCLUSION. The prevalence of Fabry disease in selected CKD patients of northern west region of Russian Federation is in the mean worldwide range. In all cases, the FD was not timely diagnosed, leading to serious organ damage and delaying the onset of enzyme replacement therapy. Thus, the screening of FD is necessary at the early stages of CKD.

The association between vitamin D/calcium deficiency and cardiovascular events.

According to some case reports, extreme hypocalcemia induced by vitamin D and calcium deficiency leads to heart failure. This rare clinical entity "Hypocalcemic cardiomyopathy" is also reported in elderly patients as well as infants. In patients with chronic kidney disease and heart failure, hypocalcemia is reported to predict worse outcome. Prescription of active vitamin D or its analogues is associated with lower rates of cardiovascular events in predialysis and dialysis patients, however indication biases often seen in observational studies cannot preclude the possibility that the benefit of these agents is limited to patients with high parathyroid hormone(PTH)levels. In fact, J-DAVID study, a randomized controlled trial from Japan, clearly showed that oral administration of alfacalcidol of 0.5 μg/day did not reduce cardiovascular events in hemodialysis patients with intact PTH<180 pg/mL.

Chronic kidney disease progression in kidney transplant recipients: A focus on traditional risk factors.

Kidney transplant recipients are a subset of patients with chronic kidney disease (CKD) that remain at high risk for progression to dialysis and mortality. Recent advances in immunosuppression have only partially improved long-term graft and patient survival. Discovery of new immunosuppressive regimens is a slow and resource-intensive process. Hence, recognition and management of modifiable allogeneic and non-allogeneic risk factors for progression to CKD among kidney transplant recipients is of major interest for improving long-term outcomes. Graft survival is mainly determined by the quality of the allograft and by the patient's alloimmune response, which is influenced by human leukocyte antigen matching and the presence of donor-specific antibodies. Alloimmune responses manifest as acute and chronic forms of cell- and antibody-mediated rejection, which can be worsened by patient non-adherence or under-immunosuppression. However, donor and patient ages, glomerular disease recurrence, time on dialysis, pre-existing cardiovascular burden, medication side-effects and traditional risk factors, such as hypertension, proteinuria, anaemia, dyslipidaemia, diabetes and bone mineral disorder, which can ultimately lead to severe endothelial derangement, also contribute to graft loss and mortality. These traditional risk factors, common to pre-dialysis patients, often are considered of secondary importance when compared to alloimmunity and immunosuppression concerns. In this review article, we focus on the epidemiological, pathophysiological and therapeutic features of non-allogeneic traditional risk factors for CKD. We also discuss the benefit of adopting a multidisciplinary approach to pursue the same therapeutic targets recommended for pre-dialysis patients.

High prevalence of occult hepatitis C infection in predialysis patients.

BACKGROUNDOccult hepatitis C virus (HCV) infection (OCI) may be associated with extrahepatic diseases and it is known that the patients with chronic kidney disease (CKD) who are on hemodialysis (HD) present a higher prevalence of this type of infection than the general population, with a worse clinical outcome. However, there are no data in the literature to assess the presence of OCI in patients prior to the initiation of renal replacement therapy (RRT). Therefore, this study aimed to evaluate the occurrence and epidemiological aspects of OCI in patients with Predialysis CKD. We hypothesize that this infection could occur before RRT initiation.AIMTo research the status in predialysis patients when HD patients have high prevalence of OCI.METHODSA cross-sectional study was conducted between 2015 and 2017. Adults with creatinine clearance < 60 mL/min·1.73 m2 (predialysis patients) were recruited to the study. Pregnant and postpartum women, patients with glomerulopathies, and patients showing positivity for serological markers of hepatitis B virus (HBV), HCV or human immunodeficiency virus infection were excluded. Patients were diagnosed with OCI according to test results of anti-HCV antibody negativity and HCV RNA positivity in either ultracentrifuged serum or, if serum-negative, in peripheral blood mononuclear cells.RESULTSAmong the 91 total patients included in the study, the prevalence of OCI was 16.5%. Among these 15 total OCI patients, 1 was diagnosed by 14 ultracentrifuged serum results and 14 were diagnosed by peripheral blood mononuclear cell results. Compared to the non-OCI group, the OCI patients presented higher frequency of older age (P = 0.002), patients with CKD of mixed etiology (P = 0.019), and patients with markers of previous HBV infection (i.e., combined positivity for anti-hepatitis B core protein antibody and anti-hepatitis B surface protein antibody) (P = 0.001).CONCLUSIONAmong predialysis patients, OCI involved the elderly, patients with CKD of mixed etiology, and patients with previous HBV infection.

Relationship Between SCUBE1 Levels and Echocardiography and Electrocardiography Findings and Epicardial Adipose Tissue/Carotid Intima-Media Thickness in Patients Receiving Renal Replacement Therapy.

In patients with advanced-stage chronic kidney disease, renal insufficiency, arterial stiffness, and vascular calcification are strong predictors of cardiovascular risk. Signal peptide-CUB-EGF-like protein-1 (SCUBE1) levels increase during platelet activation and acute ischemic events. Here, we evaluated associations between SCUBE1 levels and electrocardiographic/echocardiographic findings, epicardial adipose tissue thickness, and carotid intimamedia thickness in patients with chronic kidney disease. Our study included 21 renal transplant recipients, 20 peritoneal dialysis patients, 20 hemodialysis patients, 20 predialysis patients with glomerular filtration rate < 30 mL/min, and 16 healthy volunteers. We found no differences in SCUBE1 levels between patient groups and healthy volunteers, regardless of history of diabetes mellitus, myocardial infarction, cerebrovascular events, and hypertension. SCUBE1 levels correlated with C-reactive protein in renal transplant recipients; magnesium in peritoneal dialysis patients; erythrocyte sedimentation rate in predialysis patients; and parathyroid hormone, platelet count, calcium-phosphate product, and calcium in hemo dialysis patients. No associations were shown between SCUBE1 levels and electrocardiographic/echocardiographic findings. Elevated C-reactive protein in predialysis patients was associated with cardiac valvular pathologies. In hemodialysis patients, SCUBE1 levels increased after hemodialysis (P = .007). Levels were higher in healthy individuals with normal echocardiography and predialysis patients with left ventricular diastolic dysfunction. Positive correlations were found between carotid intima-media thickness and SCUBE1 levels in dialysis patients (P < .05), but no study groups showed correlations regarding epicardial adipose tissue thickness. Hemodialysis may contribute to cardiovascular events because of increased SCUBE1 levels after hemodialysis; however, no association was shown between SCUBE1 and electrocardiography/echocardiography findings. We found no correlations between epicardial adipose tissue thickness and SCUBE1 levels, and levels were significantly higher in healthy patients and in predialysis patients without left ventricular diastolic dysfunction. However, correlations were shown between SCUBE1 levels and carotid intima-media thickness and secondary hyperparathyroidism markers, indicating associations with atherosclerosis and bone mineral disease in dialysis patients.

Statin therapy and erythropoiesis-stimulating agent hyporesponsiveness in patients with nondialysis chronic kidney disease: A retrospective study in Beijing, China.

Erythropoiesis-stimulating agents (ESAs) are frequently used among patients with renal anemia, while a significant proportion of patients exhibit ESA hyporesponsiveness despite adequate dosing. Previous studies have suggested an inverse association between ESA hyporesponsiveness and statin use among patients receiving dialysis therapy. However, studies based on predialysis patients are extremely limited.Based on electronic medical records of a tertiary hospital in Beijing, China between April 2010 and April 2015, we investigated the association between statin use and ESA hyporesponsiveness among patients with predialysis-chronic kidney disease (CKD).Altogether 232 patients with CKD initiating ESA therapy and with hemoglobin levels monitored for at least 6 months were included in our analyses. Among them, 77 (38.5%) were long-term statin users (regular statin treatment for more than 3 months) before ESA initiation. Overall, 6.5% of the statin users and 17.1% of nonusers were considered to have ESA hyporesponsiveness. Long-term statin therapy was significantly associated with a lower proportion of ESA hyporesponsiveness in fully adjusted model (odds ratio 0.15, 95% confidence interval: 0.03–0.64).We found that long-term statin therapy was inversely associated with ESA hyporesponsiveness among predialysis patients with CKD. Further studies are needed to validate our observations, and to explore the potential mechanisms between ESA resistance and statin therapy.

Assessment of abdominal aortic calcification by computed tomography for prediction of latent left ventricular stiffness and future cardiovascular risk in pre-dialysis patients with chronic kidney disease: A single center cross-sectional study

Introduction: There is general interest in finding clinical markers for left ventricular diastolic dysfunction (LVDD), a major cause of cardiorenal syndrome leading to heart failure in chronic kidney disease (CKD) patients. The aim was to assess the utility of computed tomography (CT)-based abdominal aortic calcification (AAC) for the prediction of LVDD and prognosis of asymptomatic pre-dialysis CKD patients.Materials and methods: We prospectively evaluated 218 pre-dialysis CKD patients [median estimated glomerular filtration rate (eGFR); 40.9 mL/min/1.73m²]. Non-contrast CT scan and echocardiography were performed to determine the aortic calcification index (ACI) as a semi-quantitative measure of AAC.Results: The median ACI was 11.4. AAC and LVDD were diagnosed in 193 patients (89%) and 75 patients (34%), respectively. Using receiver operating characteristic curve analysis for the estimation of LVDD, ACI of 20 showed optimal sensitivity (52.0%) and specificity (62.8 %) (AUC = 0.664, p < .001). High ACI group included more patients with LVDD-related factors, such as old age, hypertension, diabetes, and more severe CKD. LVDD was significantly more common in patients with high ACI group [39 (50%) and 36 (26%), respectively, p<0.001]. Multivariate analysis showed that ACI correlated significantly with E/A (β=-0.993, p=0.003), E/e' (β=0.077, p<0.001), and cardio-ankle vascular index (β=0.209, p=0.001). Correspondingly, E/e' correlated with logBNP and log(ACI+1), and increased proportionately and significantly with the quartiles of ACI values. Cox proportional hazard models showed that ACI was an independent predictor of CV outcome (hazard ratio 1.03, 95% confidence interval 1.00-1.06, p=0.029).Conclusion: The results would suggest the usefulness of AAC assessment by CT to predict latent LVDD and future CV risk in asymptomatic pre-dialysis CKD patients.