Absence of coronary thrombosis in Navajo Indians

No proved case of coronary thrombosis was present among 10,267 admissions of full-blooded Navajos at the Navajo Medical Center in the years 1949-52. There were 125 cases of gallbladder disease in the same period.Questioning of 100 patients elicited that the diets of many had an average or even high amount of cholesterol in them. It was concluded that heredity is probably the most important factor in the prevention of coronary thrombosis in this select group.     

The Risk of Peripheral Arterial Disease after Parathyroidectomy in Patients with End-Stage Renal Disease

PurposeThe changes of the risk of peripheral arterial disease (PAD) in patients with end-stage renal disease after parathyroidectomy are scant.MethodsWe used a nationwide health insurance claims database to select all dialysis-dependent patients with end-stage renal disease aged 18 years and older for the study population in 2000 to 2006. Of the patients with end-stage renal disease, we selected 947 patients who had undergone parathyroidectomy as the parathyroidectomy group and frequency matched 3746 patients with end-stage renal disease by sex, age, years since the disease diagnosis, and the year of index date as the non-parathyroidectomy group. We used a multivariate Cox proportional hazards regression analysis with the use of a robust sandwich covariance matrix estimate, accounting for the intra-cluster dependence of hospitals or clinics, to measure the risk of peripheral arterial disease for the parathyroidectomy group compared with the non-parathyroidectomy group after adjusting for sex, age, premium-based income, urbanization, and comorbidity.ResultsThe mean post-op follow-up periods were 5.08 and 4.52 years for the parathyroidectomy and non-parathyroidectomy groups, respectively; the incidence density rate of PAD in the PTX group was 12.26 per 1000 person-years, significantly lower than the data in the non-PTX group (24.09 per 1000 person-years, adjusted HR = 0.66, 95% CI = 0.46–0.94).ConclusionParathyroidectomy is associated with reduced risk of peripheral arterial disease in patients with end-stage renal disease complicated with severe secondary hyperparathyroidism.     

Aberrant Functional Connectome in Neurologically Asymptomatic Patients with End-Stage Renal Disease

Purpose

This study aimed to investigate the topological organization of intrinsic functional brain networks in patients with end-stage renal disease (ESRD).

Materials and Methods

Resting-state functional MRI data were collected from 22 patients with ESRD (16 men, 18–61 years) and 29age- and gender-matched healthy controls (HCs, 19 men, 32–61 years). Whole-brain functional networks were obtained by calculating the interregional correlation of low-frequency fluctuations in spontaneous brain activity among 1,024 parcels that cover the entire cerebrum. Weighted graph-based models were then employed to topologically characterize these networks at different global, modular and nodal levels.

Results

Compared to HCs, the patients exhibited significant disruption in parallel information processing over the whole networks (P< 0.05). The disruption was present in all the functional modules (default mode, executive control, sensorimotor and visual networks) although decreased functional connectivity was observed only within the default mode network. Regional analysis showed that the disease disproportionately weakened nodal efficiency of the default mode components and tended to preferentially affect central or hub-like regions. Intriguingly, the network abnormalities correlated with biochemical hemoglobin and serum calcium levels in the patients. Finally, the functional changes were substantively unchanged after correcting for gray matter atrophy in the patients.

Conclusion

Our findings provide evidence for the disconnection nature of ESRD’s brain and therefore have important implications for understanding the neuropathologic substrate of the disease from disrupted network organization perspective.     

Association of RAC1 Gene Polymorphisms with Primary End-Stage Renal Disease in Chinese Renal Recipients

Background/Objective

RAC1 gene could influence susceptibility to renal failure by altering the activity and expression of Rac1, which is a member of the Rho family of small GTP-binding proteins. In clinical practice, renal transplantation provides the optimal treatment for people with end-stage renal disease (ESRD). The objective of this present study was to determine whether the RAC1 gene polymorphisms were associated with primary ESRD susceptibility in Chinese renal recipients.

Methods

Six single nucleotide polymorphisms (SNPs) of RAC1 gene, including rs836488 T>C, rs702482 A>T, rs10951982 G>A, rs702483 A>G, rs6954996 G>A, and rs9374 G>A, were genotyped in 300 renal transplant recipients (cases) and 998 healthy Chinese subjects (controls) by using TaqMan SNP genotyping assay. Allele, genotype, and haplotype frequencies of the six SNPs were compared between cases and controls. Odds ratios (OR) and 95% confidence intervals (CI) were calculated in logistic regression models to evaluate the associations of the six SNPs with ESRD risk.

Results

The genotype distributions for the six SNPs in controls were consistent with Hardy-Weinberg equilibrium (P > 0.05). Association analysis revealed that three SNPs were significantly associated with ESRD risk. Positive associations with ESRD risk were found for the rs836488, rs702482, and rs702483 in the co-dominant model (minor allele homozygotes versus major allele homozygotes); specifically, the frequencies of the minor allele homozygotes and the minor allele for the three SNPs were higher in the cases than in the controls. In addition, these three SNPs also had associations with increased ESRD risk under the additive model (P < 0.05), and positive associations were also found for the rs836488 in the dominant model (P < 0.05) and for the rs702483 in the recessive model (P < 0.05). All these associations were independent of confounding factors. The other three SNPs (rs10951982, rs6954996, and rs9374), in all comparison models, were not associated with ESRD risk (P > 0.05). In haplotype analysis, carriers with "C-T-G-G-G-G" haplotype had a significantly higher risk of ESRD compared with the most common haplotype "T-A-G-A-G-G" (P = 0.011, OR = 1.46, 95% CI = 1.09–1.94).

Conclusion

This study suggested that polymorphisms of RAC1 gene might influence the susceptibility to ESRD in Chinese Han population. Further studies are necessary to confirm our findings.     

B-Type Natriuretic Peptide and Prognosis of End-Stage Renal Disease: A Meta-Analysis

Background

The prognostic importance of B-type natriuretic peptide (BNP) or N-terminal pro BNP (NT-proBNP) in patients with end-stage renal disease (ESRD) remains controversial.

Methodology/Principal Findings

We conducted an unrestricted search from the MEDLINE and EMBASE in all languages that were published between 1966 and Augest2013. Twenty-seven long-term prospective studies met our inclusion criterias. From the pooled analysis, elevated BNP/NT-proBNP was significantly associated with increased all cause mortality [odds ratio (OR), 3.85; 95% CI, 3.11 to 4.75], cardiovascular mortality (OR, 4.05; 95% CI, 2.53 to 6.84), and cardiovascular events (OR, 7.02; 95% CI, 2.21 to 22.33). The funnel plot showed no evidence of publication bias. The corresponding pooled positive and negative likelihood ratio for prediction of all cause mortality were 1.86 (95% CI, 1.66 to 2.08) and 0.48 (95% CI, 0.42 to 0.55), respectively.

Conclusions/Significance

BNP/NT-proBNP is a promising prognostic tool to risk-stratify the patients with ESRD. Further investigations are warranted to elucidate the specific pathogenic mechanisms and the impact of other potential prognostic factors.     

Comparative craniofacial variation in Navajo Indians and North American Caucasians

Landmarks digitized from lateral cephalometric radiographs of 107 Navajo Indians between 10 and 12 years of age were analyzed to determine coefficients of variation or standard deviations for 38 cephalometric measurements. These values were compared with the same measures of variation for identical measurements on North American whites derived from the Michigan and Philadelphia Growth Studies. For the majority of variables, there were no differences between groups. Variation for the genetically and environmentally isolated Navajo Indians was the same as that of the highly diverse Caucasian samples. However, measurements of upper, lower, and total anterior facial height (N-ANS, ANS-Me, and N-Me, respectively) indicate that these features are substantially less variable in Navajo Indians relative to the Michigan and Philadelphia populations.     

The Gap between Estimated Incidence of End-Stage Renal Disease and Use of Therapy

Background

Relatively few data exist on the burden of end-stage renal disease (ESRD) and use of renal replacement therapy (RRT)–a life-saving therapy–in developing regions. No study has quantified the proportion of patients who develop ESRD but are unable to access RRT.

Methods

We performed a comprehensive literature search to estimate use and annual initiation of RRT worldwide, and present these estimates according to World Bank regions. We also present estimates of survival and of etiology of diseases in patients undergoing RRT. Using data on prevalence of diabetes and hypertension, we modeled the incidence of ESRD related to these risk factors in order to quantify the gap between ESRD and use of RRT in developing regions.

Results

We find that 1.9 million patients are undergoing RRT worldwide, with continued use and annual initiation at 316 and 73 per million population respectively. RRT use correlates directly (Pearson’s r = 0.94) with regional income. Hemodialysis remains the dominant form of RRT but there is wide regional variation in its use. With the exception of the Latin American and Caribbean region, it appears that initiation of RRT in developing regions is restricted to fewer than a quarter of patients projected to develop ESRD. This results in at least 1.2 million premature deaths each year due to lack of access to RRT as a result of diabetes and elevated blood pressure and as many as 3.2 million premature deaths due to all causes of ESRD.

Conclusion

Thus, the majority of patients projected to reach ESRD due to diabetes or hypertension in developing regions are unable to access RRT; this gap will increase with rising prevalence of these risk factors worldwide.     

Influence of Socio-Economic Inequalities on Access to Renal Transplantation and Survival of Patients with End-Stage Renal Disease

BackgroundPublic and scientific concerns about the social gradient of end-stage renal disease and access to renal replacement therapies are increasing. This study investigated the influence of social inequalities on the (i) access to renal transplant waiting list, (ii) access to renal transplantation and (iii) patients’ survival.MethodsAll incident adult patients with end-stage renal disease who lived in Bretagne, a French region, and started dialysis during the 2004–2009 period were geocoded in census-blocks. To each census-block was assigned a level of neighborhood deprivation and a degree of urbanization. Cox proportional hazards models were used to identify factors associated with each study outcome.ResultsPatients living in neighborhoods with low level of deprivation had more chance to be placed on the waiting list and less risk of death (HR = 1.40 95%CI: [1.1–1.7]; HR = 0.82 95%CI: [0.7–0.98]), but this association did not remain after adjustment for the patients’ clinical features. The likelihood of receiving renal transplantation after being waitlisted was not associated with neighborhood deprivation in univariate and multivariate analyses.ConclusionsIn a mixed rural and urban French region, patients living in deprived or advantaged neighborhoods had the same chance to be placed on the waiting list and to undergo renal transplantation. They also showed the same mortality risk, when their clinical features were taken into account.     

Lipoprotein X Causes Renal Disease in LCAT Deficiency

Human familial lecithin:cholesterol acyltransferase (LCAT) deficiency (FLD) is characterized by low HDL, accumulation of an abnormal cholesterol-rich multilamellar particle called lipoprotein-X (LpX) in plasma, and renal disease. The aim of our study was to determine if LpX is nephrotoxic and to gain insight into the pathogenesis of FLD renal disease. We administered a synthetic LpX, nearly identical to endogenous LpX in its physical, chemical and biologic characteristics, to wild-type and Lcat^-/- mice. Our in vitro and in vivo studies demonstrated an apoA-I and LCAT-dependent pathway for LpX conversion to HDL-like particles, which likely mediates normal plasma clearance of LpX. Plasma clearance of exogenous LpX was markedly delayed in Lcat^-/- mice, which have low HDL, but only minimal amounts of endogenous LpX and do not spontaneously develop renal disease. Chronically administered exogenous LpX deposited in all renal glomerular cellular and matrical compartments of Lcat^-/- mice, and induced proteinuria and nephrotoxic gene changes, as well as all of the hallmarks of FLD renal disease as assessed by histological, TEM, and SEM analyses. Extensive in vivo EM studies revealed LpX uptake by macropinocytosis into mouse glomerular endothelial cells, podocytes, and mesangial cells and delivery to lysosomes where it was degraded. Endocytosed LpX appeared to be degraded by both human podocyte and mesangial cell lysosomal PLA₂ and induced podocyte secretion of pro-inflammatory IL-6 in vitro and renal Cxl10 expression in Lcat^-/- mice. In conclusion, LpX is a nephrotoxic particle that in the absence of Lcat induces all of the histological and functional hallmarks of FLD and hence may serve as a biomarker for monitoring recombinant LCAT therapy. In addition, our studies suggest that LpX-induced loss of endothelial barrier function and release of cytokines by renal glomerular cells likely plays a role in the initiation and progression of FLD nephrosis.     

The Growth Attainment,Hematological, Iron Status and Inflammatory Profile of Guatemalan Juvenile End-Stage Renal Disease Patients

BackgroundStunting, anemia and inflammation are frequently observed in children with end-stage renal disease (ESRD).ObjectivesTo assess anthropometric, hematological and inflammatory data and to study their potential interrelationship in Guatemalan juveniles undergoing hemodialysis (HD) and peritoneal dialysis (PD).Methods54 juveniles 7–20 years of age were recruited in FUNDANIER, Guatemala City: 27 on HD and 27 PD. Hemoglobin, serum iron, transferrin, serum transferrin receptor (sTfR), serum ferritin, transferrin saturation and iron-binding capacity, white blood cell count (WBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), as well as IL-6, IL-1 and TNF-α, weight and height were determined by standard methods. Hepcidin–25 (Hep-25) was assessed by weak cation exchange time-of-flight mass-spectrometry.Results92% and 55% of HD and PD children, respectively, were stunted and 95% and 85% were anemic. Among iron status biomarkers, serum ferritin was massively increased and significantly higher in the HD group compared to the PD group. Hep-25 was also greatly elevated in both groups. 41% of HD patients showed increments in three or more inflammatory biomarkers, while it was 2 or less in all PD subjects.ConclusionsThe degree of stunting, the prevalence and severity of anemia in Guatemalan juvenile ESRD far exceed the national statistics for this low-income Central American country. Ferritin and Hep-25 concentrations were elevated, with the latter to an extraordinary magnitude. Additional biomarkers of inflammation not directly related to iron status were elevated as well. The role of both disease- and environment-related factors in combination best explains the magnitude of the biomarker abnormalities.     

Risk of End-Stage Renal Disease after Cancer Nephrectomy in Taiwan: A Nationwide Population-Based Study

BackgroundThe conclusions of population-based studies examining the risk of developing end-stage renal disease (ESRD) after nephrectomy among patients with renal cell carcinoma (RCC) remain inconclusive. In this study, we sought to examine whether patients with RCC undergoing radical nephrectomy (RN) have higher risk of ESRD compared to those undergoing partial nephrectomy (PN).MethodsNationwide population-based retrospective cohort of 7670 patients with RCC who underwent RN or PN between 2000 and 2011 as recorded in the Taiwan National Health Insurance in-patient claims data were analyzed. The primary outcome of interest was the occurrence of ESRD requiring regular renal hemodialysis. Multivariable Cox proportional hazard regression model was performed to assess the risk.FindingsThe median follow-up for the post-propensity matched cohort (1212 PN and 2424 RN) was 48 months. Seventy patients (2.9%) developed ESRD among those who underwent RN, for an incidence rate of 6.9 cases per 1000 person-years. In contrast, only 23 patients (1.9%) developed ESRD among patients who underwent PN, for an incidence rate of 5.5 cases per 1000 person-years. Despite the higher incidence rate of ESRD among RN, the aIRR (RN/PN) was 1.26 (95% CI 0.78-2.01), which was not statistically significant.ConclusionsThis Taiwan nationwide population-based study suggests that patients with RCC undergoing RN do not have significantly higher risk of developing ESRD compared to those undergoing PN.     

Serum Vascular Adhesion Protein-1 Predicts End-Stage Renal Disease in Patients with Type 2 Diabetes

Background

Diabetes is the leading cause of end-stage renal disease (ESRD) worldwide. Vascular adhesion protein-1 (VAP-1) participates in inflammation and catalyzes the deamination of primary amines into aldehydes, hydrogen peroxide, and ammonia, both of which are involved in the pathogenesis of diabetic complications. We have shown that serum VAP-1 is higher in patients with diabetes and in patients with chronic kidney disease (CKD), and can predict cardiovascular mortality in subjects with diabetes. In this study, we investigated if serum VAP-1 can predict ESRD in diabetic subjects.

Methods

In this prospective cohort study, a total of 604 type 2 diabetic subjects were enrolled between 1996 to 2003 at National Taiwan University Hospital, Taiwan, and were followed for a median of 12.36 years. The development of ESRD was ascertained by linking our database with the nationally comprehensive Taiwan Society Nephrology registry. Serum VAP-1 concentrations at enrollment were measured by time-resolved immunofluorometric assay.

Results

Subjects with serum VAP-1 in the highest tertile had the highest incidence of ESRD (p<0.001). Every 1-SD increase in serum VAP-1 was associated with a hazard ratio of 1.55 (95%CI 1.12–2.14, p<0.01) for the risk of ESRD, adjusted for smoking, history of cardiovascular disease, body mass index, hypertension, HbA1c, duration of diabetes, total cholesterol, use of statins, ankle-brachial index, estimated GFR, and proteinuria. We developed a risk score comprising serum VAP-1, HbA1c, estimated GFR, and proteinuria, which could predict ESRD with good performance (area under the ROC curve = 0.9406, 95%CI 0.8871–0.9941, sensitivity = 77.3%, and specificity = 92.8%). We also developed an algorithm based on the stage of CKD and a risk score including serum VAP-1, which can stratify these subjects into 3 categories with an ESRD risk of 0.101%/year, 0.131%/year, and 2.427%/year, respectively.

Conclusions

In conclusion, serum VAP-1 can predict ESRD and is a useful biomarker to improve risk stratification in type 2 diabetic subjects.     

Predictive Parameters of Arteriovenous Fistula Functional Maturation in a Population of Patients with End-Stage Renal Disease

Introduction

With increasing numbers of patients diagnosed with ESRD, arteriovenous fistula (AVF) maturation has become a major factor in improving both dialysis related outcomes and quality of life of those patients. Compared to other types of access it has been established that a functional AVF access is the least likely to be associated with thrombosis, infection, hospital admissions, secondary interventions to maintain patency and death.

Aim

Study of demographic factors implicated in the functional maturation of arteriovenous fistulas. Also, to explore any possible association between preoperative haematological investigations and functional maturation.

Methods

We performed a retrospective chart review of all patients with ESRD who were referred to the vascular service in the University Hospital of Limerick for creation of vascular access for HD. We included patients with primary AVFs; and excluded those who underwent secondary procedures.

Results

Overall AVF functional maturation rate in our study was 53.7% (52/97). Female gender showed significant association with nonmaturation (P = 0.004) and was the only predictor for non-maturation in a logistic regression model (P = 0.011). Patients who had history of renal transplant (P = 0.036), had relatively lower haemoglobin levels (P = 0.01) and were on calcium channel blockers (P = 0.001) showed better functional maturation rates.

Conclusion

Female gender was found to be associated with functional non-maturation, while a history kidney transplant, calcium channel-blocker agents and low haemoglobin levels were all associated with successful functional maturation. In view of the conflicting evidence in the literature, large prospective multi-centre registry-based studies with well-defined outcomes are needed.     

A Meta-Analysis of Mortality in End-Stage Renal Disease Patients Receiving Implantable Cardioverter Defibrillators (ICDs)

Data on the effectiveness of implantable implantable cardioverter defibrillators (ICDs) with respect to reducing mortality in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD) are lacking. The purpose of this meta-analysis was to compare the mortality of patients with ESRD who have received and not received an ICD. A search was conducted on January 31, 2013 of Medline, Cochrane, EMBASE, and Google Scholar. Studies were selected for inclusion based on the following criteria. 1) Randomized controlled trial. 2) ESRD patients with heart failure. 3) Device therapy (ICD, CRT-defibrillator [CRT-D]) used to treat heart failure. 4) Primary outcome is survival analysis. 5) Retrospective study if survival analysis was performed. The primary outcome was overall survival (OS), and the secondary outcome was 2-year survival. Odds ratios (ORs) with 95% confidence intervals (CI) were calculated, and a χ²-based test of homogeneity was performed. Three studies were included in the analysis. The combined OR for OS was 2.245 (95% CI 1.871 to 2.685, P<0.001), indicating that patients with an ICD had a significantly higher OS than those without an ICD. The combined OR for 2-year survival was 2.312 (95% CI 1.921 to 2.784, P<0.001), indicating that patients with an ICD had a significantly higher 2-year survival rate than those without an ICD. The use of ICD in patients with ESRD is associated with an increase in the OS and the 2-year survival rate.     

Effectiveness of Influenza Vaccination in Patients with End-Stage Renal Disease Receiving Hemodialysis: A Population-Based Study

Background

Little is known on the effectiveness of influenza vaccine in ESRD patients. This study compared the incidence of hospitalization, morbidity, and mortality in end-stage renal disease (ESRD) patients undergoing hemodialysis (HD) between cohorts with and without influenza vaccination.

Methods

We used the insurance claims data from 1998 to 2009 in Taiwan to determine the incidence of these events within one year after influenza vaccination in the vaccine (N = 831) and the non-vaccine (N = 3187) cohorts. The vaccine cohort to the non-vaccine cohort incidence rate ratio and hazard ratio (HR) of morbidities and mortality were measured.

Results

The age-specific analysis showed that the elderly in the vaccine cohort had lower hospitalization rate (100.8 vs. 133.9 per 100 person-years), contributing to an overall HR of 0.81 (95% confidence interval (CI) 0.72–0.90). The vaccine cohort also had an adjusted HR of 0.85 [95% CI 0.75–0.96] for heart disease. The corresponding incidence of pneumonia and influenza was 22.4 versus 17.2 per 100 person-years, but with an adjusted HR of 0.80 (95% CI 0.64–1.02). The vaccine cohort had lowered risks than the non-vaccine cohort for intensive care unit (ICU) admission (adjusted HR 0.20, 95% CI 0.12–0.33) and mortality (adjusted HR 0.50, 95% CI 0.41–0.60). The time-dependent Cox model revealed an overall adjusted HR for mortality of 0.30 (95% CI 0.26–0.35) after counting vaccination for multi-years.

Conclusions

ESRD patients with HD receiving the influenza vaccination could have reduced risks of pneumonia/influenza and other morbidities, ICU stay, hospitalization and death, particularly for the elderly.     

Correlations of MTHFR 677C>T Polymorphism with Cardiovascular Disease in Patients with End-Stage Renal Disease: A Meta-Analysis

ObjectiveThis meta-analysis was conducted to evaluate the correlations of a common polymorphism (677C>T) in the methylenetetrahydrofolate reductase (MTHFR) gene with risk of cardiovascular disease (CVD) in patients with end-stage renal disease (ESRD).MethodThe following electronic databases were searched without language restrictions: Web of Science (1945∼2013), the Cochrane Library Database (Issue 12, 2013), MEDLINE (1966∼2013), EMBASE (1980∼2013), CINAHL (1982∼2013) and the Chinese Biomedical Database (CBM) (1982∼2013). Meta-analysis was performed using STATA statistical software. Odds ratios (ORs) with their 95% confidence intervals (95%CIs) were calculated.ResultsEight cohort studies met all inclusion criteria and were included in this meta-analysis. A total of 2,292 ESRD patients with CVD were involved in this meta-analysis. Our meta-analysis results revealed that the MTHFR 677C>T polymorphism might increase the risk of CVD in ESRD patients (TT vs. CC: OR = 2.75, 95%CI = 1.35∼5.59, P = 0.005; CT+TT vs. CC: OR = 1.39, 95%CI = 1.09∼1.78, P = 0.008; TT vs. CC+CT: OR = 2.52, 95%CI = 1.25∼5.09, P = 0.010; respectively). Further subgroup analysis by ethnicity suggested that the MTHFR 677C>T polymorphism was associated with an elevated risk for CVD in ESRD patients among Asians (TT vs. CC: OR = 3.38, 95%CI = 1.11∼10.28, P = 0.032; CT+TT vs. CC: OR = 1.44, 95%CI = 1.05∼1.97, P = 0.022; TT vs. CC+CT: OR = 3.15, 95%CI = 1.02∼9.72, P = 0.046; respectively), but not among Africans or Caucasians (all P>0.05).ConclusionOur findings indicate that the MTHFR 677C>T polymorphism may be associated with an elevated risk for CVD in ESRD patients, especially among Asians.