Renal Vascular Disease Research Articles

4119Predictors of progression of preclinical left ventricular diastolic dysfunction to clinical heart failure in patients with malignancy

Abstract Background Preclinical diastolic dysfunction PDD is a well-known but poorly understood risk factor for clinical heart failure CHF. Preclinical diastolic dysfunction and predictors of progression of PDD to CHF in patients with malignancy has never been studied. Purpose The purpose of our study was to determine the incidence of CHF in cancer patients who have preexisting preclinical diastolic dysfunction, with a particular focus on identifying the risk factors contributing to progression of PDD to CHF. Study design We retrospectively sought all the patients who underwent echocardiography from 2003 to 2008 and were found to have preclinical diastolic dysfunction at our institution. PDD was defined as presence of grade I diastolic dysfunction, LVEF ≥50%, and free of clinical diagnosis of heart failure. Of these, only the patients who had a confirmed histopathological diagnosis of malignancy were included in the study. The end point was incidence of clinical heart failure, HFrEF and HFpEF. Multivariable adjusted Cox proportional hazards regression were performed to study the predictors of CHF. Results Out of 1086 patients with PDD and a histopathological diagnosis of malignancy, 208 patients were diagnosed with new onset CHF during the 10 years follow-up. Incidence of CHF, HFpEF and HFrEF was found to be 32.1 per 1,000 person-year, 13.9 per 1,000 person-year and 2.93 per 1,000 person-year respectively. Patients who developed clinical heart failure were found to have more hypertension, diabetes, myocardial infarction, peripheral vascular disease, pulmonary disease, renal disease, hematological malignancies and metastatic disease when compared to patients who did not develop heart failure. In multivariable adjusted Cox regression analysis, age at index date (HR 1.02, 95% CI 1.01–1.04, p=0.001), diabetes (HR 1.74, 95% CI 1.28–2.35, p<0.001), myocardial infarction (HR 2.19, 95% CI 1.49–3.20, p<0.001), lung disease (HR 1.53, 95% CI 1.14–2.06, p=0.004) and renal disease (HR 2.03, 95% CI 1.45–2.84, p<0.001) were independent predictors of CHF in patients with PDD and malignancy. Among chemotherapy agents, Vincristine, Ifosfamide, transtuzumab and Bortezomib were found to be associated with CHF. Conclusion This is the first study ever to report the incidence of CHF, HFrEF and HFpEF and identify a distinct set of predictors of heart failure in patients with PDD and malignancy. We estimated a much higher incidence of CHF (19%) in our study population, when compared to the general population with malignancy. Our study also depicted a significantly high incidence of HFpEF compared to HFrEF (8.3% vs 1.75%). Our study shows that patients with malignancy are at a significantly higher risk of developing heart failure if they have preexisting diastolic dysfunction. This emphasizes the importance of identifying patients with diastolic dysfunction and a more rigorous cardiovascular surveillance to prevent them from potential heart failure. Acknowledgement/Funding None

The Origin of Present-on-admission Pressure Ulcers/Injuries Among Patients Admitted from the Community: Results of a Retrospective Study

The aim of this descriptive, retrospective study was to quantify the number of patients with pressure ulcers/injuries (PU/Is) present on admission (POA), with particular attention to patient residence (home or skilled/long-term care facility [SNF]). Data from the electronic medical records (EMR) and the incident reporting system of a 620-bed integrated health system in northern California from January 1, 2017, to December 31, 2017, were examined and used to create a registry that included patient demographics, length of stay (LOS), source of admission (home versus SNF), co-existing conditions, and documentation on end of life and death. A manual chart review was conducted to confirm the accuracy of data entered into the registry. All patients at least 18 years old and with a nurse-reported incident and EMR-documented PU/I that was listed as POA were included; pediatric, pregnant, or incarcerated patients were excluded. Extracted variables included demographic data, stage of PU/I on admission, and major diagnosis (or co-existing condition) by groups (spinal cord injuries [tetraplegia, paraplegia], neurological conditions, end-stage renal disease, cardiac and vascular disease, end of life [EOL], and death while in hospital during the year 2017). Descriptive analysis was used to examine the data. Of the 2340 records of patients with an PU/I POA, 477 were complete and analyzed. The majority (336, 70.4%) originated from home. Patients admitted from home were younger than those admitted from SNF (average age 62.9 and 71.5 years, respectively) and had a higher proportion of co-existing paraplegia/tetraplegia (24.4% vs 12.8%). More than 60% of all patients had a stage 3, stage 4, or unstageable PU/I. The majority of patients with a PU/I POA were admitted from home. Additional research and improved efforts to help high-risk individuals living at home prevent and manage PU/Is are needed.

SAT-243 THE CKD.QLD REGISTRY: CHARACTERISTICS AND COURSE OF CHRONIC KIDNEY DISEASE (CKD) PATIENTS IN PUBLIC NEPHROLOGY CARE IN QUEENSLAND, AUSTRALIA

Stemming the rise of end stage kidney failure (ESKF) depends on understanding, preventing and modifying its preterminal stages of CKD. We describe people with CKD in public renal practices in Queensland, Australia, who have enrolled in the CKD.QLD registry. Queensland has a vast area of 1,730,648 km2, a population of over 5 million, both of great diversity, and an excellent public health system - Queensland Health. CKD patients enrol in the registry with informed consent and are followed until death, start of renal replacement therapy (RRT), discharge or specified censor dates. Enrolment started in 2011, and has embraced adult nephrology services across Queensland Health Hospital and Health Services. Through a data-linkage collaboration, Queensland Health has supplied data on all hospital admissions, public and private, of CKD.QLD patients for five years retrospective from mid 2017. 9,005 patients have enrolled, with a total follow up of about 30,000 person years. Median age at enrolment was 68 years, 54% were male, and most had CKD stages 3A to 5. 50.8% were obese, compared with 20.8% of the Australian population, and, within the CKD cohort, obesity was powerfully associated with several serious complications. Dominant primary renal diseases were glomerulonephritis (GN) and genetic disease (GRD) in younger subjects, and diabetic disease (DN) and renal vascular (RV) disease in older people. 48% of subjects had multiple renal diagnosis. There was >2-fold variation in frequency of GN, DN and RV among some sites, and a >6-fold variation in proportions with diagnoses of uncertain or unknown etiology. Proportions of diagnoses also differed by socioeconomic status and by ethnic group, including Indigenous status. Older subjects more often had advanced renal disease, multiple renal diagnoses and more comorbidities. Renal function deteriorated over one and two years in 25%, but was stable or improved in 75%. CKD stages 4 and 5, overt proteinuria/albuminuria, diabetic nephropathy, male gender and acute kidney injury (AKI) were significant predictors of progression. Up to June 2016, the incidence per 100 person years of RRT was 2.79 (CI 3.4-4.0), and of death without RRT was 5.2 (CI 4.8-5.5). Mean (SD) age at start of RRT was 58.5 (15 years) and of death without RRT was 76.7 (10.6 years). Among the first 1,083 persons who died without receiving RRT, 19% were due to ESKF, while chronic renal failure and CKD were documented in an additional 50%. Cardiovascular events were recorded in 69% of these deaths, with other conditions also prominent. 10% of CKD.QLD patients were responsible for 60% of hospital admissions and 70% of expenditures, exclusive of dialysis. Underlying diabetic nephropathy and superimposed AKI were especially associated with such “high end” usage. There is great variation in CKD by age and in CKD cause by region. Progression over the short term is not inevitable. Subjects who start RRT and those who die without RRT are different populations. These data underline need for several pathways of care. Associations of obesity with CKD prevalence and complications, and of AKI with hospitalisations and progression in CKD patients, indicate major opportunities for prevention and better management.

The Effect of Ginkgo Biloba Dropping Pills on Hemorheology and Blood Lipid: A Systematic Review of Randomized Trials.

Objective A systematic review of randomized trials was performed to assess the effect of Ginkgo Biloba Dropping Pills (GBDP) on clinical hemorheology and blood lipid indicators. Methods The data of the Embase, Cochrane Library, PubMed, Clinical Trials, China National Knowledge Infrastructure, the Wanfang database, the VIP database, and the Sinomed were retrieved by computers from the establishment of the database to March 27, 2018, and screened and extracted by two researchers according to inclusion and exclusion criteria. Cochrane 5.0 recommended bias risk assessment tool was used to evaluate the methodological quality of the included literature, and Revman 5.3 software were used for meta-analysis. Results 10 literatures were finally selected in accordance with the standard. There were a total of 1201 cases, 608 cases in ginkgo biloba dropping pill group and 593 in routine treatment group. Compared with control group, GBDP significantly improved plasma viscosity [N=383, RR= - 0.45, 95%CI=(-0.86,-0.04), P=0.03], whole blood high shear [N=232, RR= - 0.92,95%CI=(-1.69, -0.16), P =0.02], whole blood low shear [N = 232, RR = - 2.22, 95% CI = (- 3.74, -0.7), P = 0.004], red blood cell specific volume [N =132, RR = - 4.55, 95% CI = (- 6.36, 2.73), P < 0.000 01], fibrinogen [N=243, RR=-0.60,95%CI=(-0.82,-0.39), P<0.00001], triglyceride [N=912, RR=-0.60,95%CI=(-1.12, -0.07), P =0.03], cholesterol [N=912, RR=-0.97,95%CI=(-1.41, -0.52), P <0.0001], low-density cholesterol [N=1100, RR=-0.72,95%CI=(-1.19, -0.25), P =0.003], and sensitivity analysis before and after of high-density cholesterol [N=1020, RR=0.08,95%CI=(-0.17,0.34), P =0.52] and [N=683, RR=0.27,95%CI=(0.13,0.42), P =0.0003]. And seven adverse reactions were reported. Conclusion GBDP can improve hemorheology indexes, which is to reduce the blood viscosity, to improve blood lipid status, and to prevent and treat cardiocerebral and renal vascular diseases to a certain extent, with slight clinical adverse reactions. But our results were based on small amount of clinical studies with poor quality and insufficient evidence, which may lead to low credibility of conclusions. Therefore, more large-sample, multiple-center, randomized controlled clinical trials and related mechanisms researches are needed to obtain better clinical trial evidence in order to verify the further effectiveness and safety of GBDP on hemorheology.

Cardiac structure and function after revascularization versus medical therapy for renal artery stenosis: the ASTRAL heart echocardiographic sub-study

BackgroundThe ASTRAL trial showed no difference in clinical outcomes between medical therapy and revascularization for atherosclerotic renal vascular disease (ARVD). Here we report a sub-study using echocardiography to assess differences in cardiac structure and function at 12 months.MethodsASTRAL patients from 7 participating centres underwent echocardiography at baseline and 12 months after randomisation. Changes in left ventricular ejection fraction (LVEF), left ventricular mass (LVM), left atrial diameter (LAD), aortic root diameter (AoRD), E:A, and E deceleration time (EDT) were compared between study arms. Analyses were performed using t-tests and multivariate linear regression.ResultsNinety two patients were included (50 medical versus 42 revascularization). There was no difference between arms in any baseline echocardiographic parameter. Comparisons of longitudinal changes in echocardiographic measurements were: δLVEF medical 0.8 ± 8.7% versus revascularization − 2.8 ± 6.8% (p = 0.05), δLVM − 2.9 ± 33 versus − 1.7 ± 39 g (p = 0.9), δLAD 0.1 ± 0.4 versus 0.01 ± 0.5 cm (p = 0.3), δAoRD 0.002 ± 0.3 versus 0.06 ± 0.3 cm (p = 0.4), δE:A − 0.0005 ± 0.6 versus 0.03 ± 0.7 (p = 0.8), δEDT − 1.1 ± 55.5 versus − 9.0 ± 70.2 ms (p = 0.6). In multivariate models, there were no differences between treatment groups for any parameter at 12 months. Likewise, change in blood pressure did not differ between arms (mean δsystolic blood pressure medical 0 mmHg [range − 56 to + 54], revascularization − 3 mmHg [− 61 to + 59], p = 0.60).ConclusionsThis sub-study did not show any significant differences in cardiac structure and function accompanying renal revascularization in ASTRAL. Limitations include the small sample size, the relative insensitivity of echocardiography, and the fact that a large proportion of ASTRAL patient population had only modest renal artery stenosis as described in the main study.

Connective Tissue Growth Factor Is Related to All-cause Mortality in Hemodialysis Patients and Is Lowered by On-line Hemodiafiltration: Results from the Convective Transport Study.

Connective tissue growth factor (CTGF) plays a key role in the pathogenesis of tissue fibrosis. The aminoterminal fragment of CTGF is a middle molecule that accumulates in chronic kidney disease. The aims of this study are to explore determinants of plasma CTGF in hemodialysis (HD) patients, investigate whether CTGF relates to all-cause mortality in HD patients, and investigate whether online-hemodiafiltration (HDF) lowers CTGF. Data from 404 patients participating in the CONvective TRAnsport STudy (CONTRAST) were analyzed. Patients were randomized to low-flux HD or HDF. Pre-dialysis CTGF was measured by sandwich ELISA at baseline, after six and 12 months. CTGF was inversely related in multivariable analysis to glomerular filtration rate (GFR) (p < 0.001) and positively to cardiovascular disease (CVD) (p = 0.006), dialysis vintage (p < 0.001), interleukin-6 (p < 0.001), beta-2-microglobulin (p = 0.045), polycystic kidney disease (p < 0.001), tubulointerstitial nephritis (p = 0.002), and renal vascular disease (p = 0.041). Patients in the highest quartile had a higher mortality risk compared to those in the lowest quartile (HR 1.7, 95% CI: 1.02–2.88, p = 0.043). HDF lowered CTGF with 4.8% between baseline and six months, whereas during HD, CTGF increased with 4.9% (p < 0.001). In conclusion, in HD patients, CTGF is related to GFR, CVD and underlying renal disease and increased the risk of all-cause mortality. HDF reduces CTGF.

Hypertension secondary to renal hypoplasia presenting as acute heart failure in a newborn

IntroductionNeonatal hypertension is defined as persistent systolic and/or diastolic blood pressures above the 95th percentile compared to other infants of similar gestational age and size. Neonatal hypertension is a rare condition, occurring in only 0.2–3.0% of neonates. The most common etiology of neonatal hypertension is renal vascular or parenchymal disease, and it is usually detected on routine examination in an asymptomatic child. However, it may present in a variety of manners, including acute heart failure, renal dysfunction, feeding difficulties, failure to thrive, tachypnea, apnea, lethargy, irritability, or seizures.Case presentationA term female was born via repeat caesarean section with vacuum extraction. On day of life (DOL) 3, the baby presented to the emergency department with poor feeding and lethargy. Initial laboratory tests indicated severe metabolic acidosis and the patient was transferred to our neonatal intensive care unit (NICU). During the hospital stay, the patient had intermittently high blood pressures. An echocardiogram was ordered, which demonstrated a severely decreased ejection fraction of 33%, but no signs of coarctation of the aorta. The low ejection fraction and constellation of symptoms were consistent with the diagnosis of acute heart failure, so treatment with milrinone was initiated. Further labs demonstrated elevated renin and aldosterone, and a computed tomography scan showed right kidney hypoplasia with reduced perfusion. This suggested a renovascular etiology of hypertension causing the initial presentation of acute heart failure. The patient was started on enalapril and clonidine for blood pressure control and was discharged with a home blood pressure monitoring system. At 5 months of life, this patient was still on enalapril and amlodipine as well as home blood pressure monitoring.ConclusionsAcute heart failure is a rare presentation of neonatal hypertension, and prompt recognition and treatment for the underlying systemic hypertension is necessary to provide the best possible outcomes for patients. Due to the lack of sufficient evidence, treatment of hypertension in newborns is often anecdotal in nature. Further awareness of neonatal hypertension and research determining ideal methods of diagnosis and treatment would benefit physicians and their affected patients.

CT Imaging of Renovascular Abnormalities

Abnormalities of the renal vasculature can manifest clinically as renal ischemia, renal insufficiency, and secondary hypertension. It is crucial to inspect the renal vessels not only for intrinsic or direct causes of vascular disease, but also for the enhancement pattern of the renal parenchyma as an indirect sign for vascular compromise. Although atherosclerotic renal artery stenosis is the most common renal vascular disease, fibromuscular dysplasia of the renal artery is the second most common and has characteristic imaging findings. Some vasculitides may affect the renal artery, and these need to be considered when there is abnormal soft tissue surrounding the artery or the kidney has a striated nephrogram. Arteriovenous abnormalities are divided into arteriovenous fistulas and arteriovenous malformations. A prominent renal artery in communication with a renal vein or a tangle of vessels associated with a prominent and early filling renal vein is very suggestive of a renal arteriovenous abnormality. Intraparenchymal renal artery aneurysms are not as common as main renal artery aneurysms, but the former can mimic a tumor, and a high index of suspicion is required to make the correct diagnosis. Many of these pathologies, in addition to renal trauma, can result in reduced perfusion or infarction of part of or all of the kidney.

Prevalence and Factors Associated with Hepatitis B Virus Surface Antigen and Human Immunodeficiency Virus Antibodies in Chronic Hemodialysis Patients Followed-Up in Lom&amp;#233;, Togo

Introduction: In haemodialysis patients, the risk of acquiring blood-borne viral infections is an important cause of the dialysis’s process. Indeed, viral infections are quite common in chronic haemodialysis patients including those due to viral hepatitis B and HIV. Objective: Determine the prevalence of HIV infection and hepatitis B infection among chronic hemodialysis patients of Togo. Methods: A cross-sectional study was conducted in chronic hemodialysis patients of Togo from January 1st to December 31st, 2016. Sociodemographic and clinical data were collected. Antigen HBs was screened by a rapid immunochromatographic test (SD BIOLINE® HBsAg), and HIV antibodies were detected using a combination of 2 rapid diagnostic test, SD BIOLINE® HIV-1/2 (first step) and TRIDOT test (second step). Results: During the study period, 95 subjects were included. Patient’s age was ranking from 13 to 80 years with a mean of 46.6 years. The sex-ratio (M/F) was 1.8 and a duration average of dialysis was 51.7 months. The aetiologies of the chronic endstage kidney failure were related respectively to a vascular renal disease for 42.1% of the patients, glomerular nephropaty for 34.74%, interstitial nephropaty for 9.47% and hereditary for 3.16%. For 10.53% of the patients, the initial renal disease remained indefinite. Prevalence of antigen HBs and HIV antibodies were respectively 10.5% and 7.4%. The frequency of co-infection HBV and HIV was 1.1%. Conclusion: The rates of HBV infection and HIV infection remain high in chronic hemodialysis in Togo, somewhat which is linked to an endemic aspect of these two viruses in the country. The type of initial renal disease (glomerular) and the vascular way (the central catheters) established the risk factors for the HIV infection while for the infection of HVB no factor was incriminated.

Renal vein aneurysm

Renal vein aneurysm (RVA) is a rare disease. Only a few cases have been reported in the past. With Institutional Research Board approval (IRB 201600376B0D001), we reported the case of a 51-year-old female without symptoms and incidental finding of a right renal lesion by renal echo during health examination. Computed tomography (CT) angiography showed a large aneurysm connecting to the right renal vein. Thus, a right RVA was diagnosed. Embolization was not performed due to extremely high probability of untargeted embolization, and the patient preferred outpatient follow-up. CT angiography follow-up was done 6 months later and revealed no obvious enlargement of the aneurysm but an arteriovenous fistula was suspected. The main objective of this report is to differentiate between renal vascular disease and malignant renal neoplasms by reviewing and discussing the available literature.

Estimated Glomerular Filtration Rate is not Associated with Alzheimer's Disease in a Northern Ireland Cohort.

Alzheimer's disease (AD) prevalence is increasing globally and typically progresses for several years prior to clinical presentation of dementia. Renal dysfunction and vascular disease have been reported in association with dementia in several cross-sectional and longitudinal studies, and may contribute to AD risk. Experimental and observational studies suggest amyloid-β (Aβ) clearance may be impaired in chronic kidney disease (CKD) indicating a mechanism for increased AD risk. The objective of this study was to compare estimated glomerular filtration rate (eGFR) between individuals with AD and cognitively intact controls, controlling for potential confounding factors. A cross-sectional, case-control study was carried out in 317 cognitively normal participants and 253 cases with a clinical diagnosis of AD in a UK tertiary care dementia clinic. Associations were considered using logistic regression adjusting for confounding variables (age, APOEɛ4 genotype, systolic blood pressure, education (left school at 14), and smoking status). AD cases were older than cognitively intact controls, had lower MMSE scores, were more likely to have at least one APOEɛ4 allele, had higher rates of smoking, were more likely to be taking aspirin and/or clopidogrel, and had lower blood pressure. We found no significant association between eGFR and AD both before and following adjustment for appropriate confounders. This study failed to find an association between eGFR and AD in a cross-sectional sample study of elderly white individuals.

A Retrospective Review of Risk Factors and Conversion Rate of Transmetatarsal Amputations to Below or Above Knee Amputation

Category: Diabetes Introduction/Purpose: Despite the presence of several studies examining the conversion from transmetatarsal amputation (TMA) to a more proximal amputation, few studies identified the possible predictors of failure. The objective of this study is to examine the rate of conversion of transmetatarsal amputation to below or above knee amputation, and to identify the risk factors for conversion. Methods: A retrospective cohort study was performed examining 71 transmetatarsal amputations performed by a single group of foot and ankle subspecialists within a single specialty group between October 1 2005 and August 25 2015. Demographic information and comorbidities were recorded, as were complications, readmission rate, and rate of conversion to a more proximal amputation. Results: Of the 71 patients who underwent transmetatarsal amputation during the study period, 74.7% progressed to a revision amputation or more proximal amputation at a mean of 9.7 months, but a median of only 3.2 months. 87.3% progressed to below knee amputation, 9.9% underwent revision transmetatarsal amputation, and 2.8% received an above knee amputation. Of the patients who progressed to more proximal amputation, 88.2% had diabetes mellitus, 72.4% had a pre-operative ulceration, and 81.7% had peripheral neuropathy. Only 52.7% had diagnosed peripheral vascular disease, 38.1% had a history of renal disease, and 35% were smokers. Conclusion: Transmetatarsal amputation has an extremely high short-term reamputation rate with the vast progressing to a below knee amputation. Comorbidities such as diabetes mellitus, neuropathy, and history of ulceration are often found in these patients, while renal and peripheral vascular disease as well as tobacco abuse are not necessarily present. This high rate of reamputation may bring into question the efficacy of performing transmetatarsal amputation as opposed to a more proximal amputation as a definitive procedure when lower extremity amputation is required.

Renal auto-transplantation promotes cortical microvascular network remodeling in a preclinical porcine model.

The vascular network is a major target of ischemia-reperfusion, but has been poorly investigated in renal transplantation. The aim of this study was to characterize the remodeling of the renal vascular network that follows ischemia-reperfusion along with the most highly affected cortex section in a preclinical renal transplantation model. There were two experimental groups. The first was a grafted kidney group consisting of large white pigs for which the left kidney was harvested, cold flushed, preserved for 24 h in the University of Wisconsin’s preservation solution, and then auto-transplanted (n = 5); the right kidney was removed to mimic the situation of human kidney transplantation. The second group (uni-nephrectomized kidney group) consisted of animals that underwent only right nephrectomy, but not left renal transplantation (n = 5). Three months after autotransplantation, the kidneys were studied by X-ray microcomputed tomography. Vessel morphology and density and tortuosity of the network were analyzed using a 3D image analysis method. Cortical blood flow was determined by laser doppler analysis and renal function and tissue injury assessed by plasma creatinine levels and histological analysis. Renal ischemia-reperfusion led to decreased vascular segment volume associated with fewer vessels of less than 30 μm, particularly in the inner cortex:0.79 ± 0.54% in grafted kidneys vs. 7.06 ± 1.44% in uni-nephrectomized kidneys, p < 0.05. Vessels showed higher connectivity throughout the cortex (the arborescence factor of the whole cortex was less in grafted than uni-nephrectomized kidneys 0.90 ± 0.04 vs. 1.07 ± 0.05, p < 0.05, with an increase in the number of bifurcations). Furthermore, cortical blood flow decreased early in kidney grafts and remained low three months after auto-transplantation. The decrease in microvasculature correlated with a deterioration of renal function, proteinuria, and tubular dysfunction, and was associated with the development of fibrous tissue. This work provides new evidence concerning the impact of ischemia-reperfusion injuries on the spectrum of renal vascular diseases and could potentially guide future therapy to preserve microvessels in transplantation ischemia-reperfusion injury.

Etiology of End-Stage Renal Disease and Arterial Stiffness among Hemodialysis Patients.

Background. Prior studies have demonstrated that conventional and emerging CV risk factors are associated with worsening arterial stiffness among end-stage renal disease (ESRD) patients on hemodialysis. The present cross-sectional study evaluates the association between the etiology of ESRD and arterial stiffness among a cohort of hemodialysis patients. Methods. Etiology of ESRD was identified from patients' medical records and classified as either vascular renal disease, diabetic nephropathy, nondiabetic glomerulopathy, tubular interstitial nephropathy, hereditary nephropathy, or ESRD of unconfirmed etiology. Results. A total of 82 subjects were enrolled. cfPWV was independently associated with the composite of either diabetic nephropathy or vascular renal disease (p = 0.022), pulse pressure (p = 0.001), and a history of CV events (p = 0.025), but not history of hypertension or diabetes mellitus alone. The median cfPWVs in diabetic nephropathy and vascular renal disease were comparable and significantly higher than median cfPWVs in other etiologies of ESRD. Conclusion. The study suggests that the etiology of ESRD is independently associated with arterial stiffness among hemodialysis patients. Furthermore, arterial stiffness was higher among patients who developed renal sequelae of either diabetes mellitus or hypertension as compared with those who have a history of either diabetes mellitus or hypertension alone.

Impact of hepatitis C virus therapy on metabolism and public health.

Chronic hepatitis C virus (HCV) is associated with insulin resistance (IR) and leads to type 2 diabetes mellitus (T2DM) and hepatic steatosis in many patients. These metabolic complications of HCV have been shown to accelerate the progression of fibrosis to cirrhosis and increase the risk of hepatocellular carcinoma. The metabolic syndrome is a common disorder that also includes IR, T2DM and hepatic steatosis. Approximately 20%-30% of patients with chronic HCV also have co-existent metabolic syndrome. The cause of steatosis in patients with the features of both the metabolic syndrome and chronic HCV is sometime difficult to determine. Patients with metabolic syndrome and chronic HCV are also at risk of developing renal, cardiovascular and cerebrovascular disease. Recent data suggest that HCV is an independent risk factor for renal, coronary and cerebral vascular disease, and may increase mortality associated with these disorders. The treatment of HCV can now result in a sustained virological response and cure nearly all patients with chronic HCV. The eradication of HCV reduces the risk of developing IR and T2DM, improves IR and 2TDM, reduces the risk of developing chronic kidney disease, end-stage renal disease, acute cardiac syndrome and stroke in patients with 2TDM. Thus, treatment of chronic HCV can provide a significant public health benefit, but only if all patients with chronic HCV are identified and universally treated.

Indoxyl Sulfate-Review of Toxicity and Therapeutic Strategies.

Indoxyl sulfate is an extensively studied uremic solute. It is a small molecule that is more than 90% bound to plasma proteins. Indoxyl sulfate is derived from the breakdown of tryptophan by colon microbes. The kidneys achieve high clearances of indoxyl sulfate by tubular secretion, a function not replicated by hemodialysis. Clearance by hemodialysis is limited by protein binding since only the free, unbound solute can diffuse across the membrane. Since the dialytic clearance is much lower than the kidney clearance, indoxyl sulfate accumulates to relatively high plasma levels in hemodialysis patients. Indoxyl sulfate has been most frequently implicated as a contributor to renal disease progression and vascular disease. Studies have suggested that indoxyl sulfate also has adverse effects on bones and the central nervous system. The majority of studies have assessed toxicity in cultured cells and animal models. The toxicity in humans has not yet been proven, as most data have been from association studies. Such toxicity data, albeit inconclusive, have prompted efforts to lower the plasma levels of indoxyl sulfate through dialytic and non-dialytic means. The largest randomized trial showed no benefit in renal disease progression with AST-120. No trials have yet tested cardiovascular or mortality benefit. Without such trials, the toxicity of indoxyl sulfate cannot be firmly established.

Aetiology, imaging features, and evolution of spontaneous perirenal haemorrhage

To evaluate the aetiology, imaging features, and the evolution of spontaneous perirenal haemorrhage detected by imaging. In this retrospective study, the hospital database was searched for all cases of spontaneous perinephric haemorrhage detected by imaging between January 2000 and December 2012. Imaging examinations were reviewed and the following parameters were recorded: the location, extension, and total volume of the haematoma, presence of active extravasation, the haematocrit effect, and highest density. The resolution time was calculated using follow-up imaging. The final aetiology for all cases was assessed via clinical, radiological, and histopathological data. Differences in imaging features of haemorrhage according to aetiology group were analysed with independent samples test and Fisher's exact test. Eighty-one haematomas were identified in 78 patients during this 13-year period. Causes of perirenal haemorrhage included coagulation disorders (22/81, 27.1%), ruptured renal cyst (11/81, 13.6%), rupture of abdominal aortic aneurysm (9/81, 11.1%), renal cell carcinoma (9/81, 11.1%), adrenal masses (9/81, 11.1%), polycystic kidney disease (7/81, 8.6%), angiomyolipoma (6/81, 7.4%), renal vascular diseases (2/81, 2.4%), and recurrent pyelonephritis (1/81, 1.2%). Haematomas associated with coagulation abnormalities and vascular diseases presented with larger volumes and were more likely to extent to the pararenal space more so than other groups; ruptured renal cyst and renal cell carcinomas tended to be more associated with subcapsular haematomas. The haematocrit effect and haemorrhage involving renal parenchyma were more often observed in the group with coagulation abnormalities. Imaging features, such as location and extension, could help radiologists identify possible aetiologies of spontaneous perirenal haemorrhage.

The Urinary Phosphate to Serum Fibroblast Growth Factor 23 Ratio Is a Useful Marker of Atherosclerosis in Early-Stage Chronic Kidney Disease.

BackgroundFibroblast growth factor 23 (FGF23) regulates mineral homeostasis. In developed renal dysfunction, FGF23 levels increase to maintain the phosphate excretion capacity. However, in diabetic patients with early-stage renal impairment, the FGF23 elevation is not very sensitive. We hypothesized that urinary phosphate (U-P)/serum FGF23 ratio would theoretically be an index that reflects the number of nephrons (nephron index). In this study, we determined whether the nephron index would be associated with renal function and vascular diseases in diabetic patients.MethodsIn total, 142 patients with diabetes mellitus were enrolled. The nephron index was calculated using the following formula: U-P (mg/day)/ serum FGF23 (pg/ml).ResultsThe mean age was 63 ± 11 years and eGFR levels were 79.5 ± 25.4 ml/min/1.73 m2, respectively. Thirty patients had a medical history of macroangiopathy. The Nephron index was significantly decreased in subjects with macroangiopathy compared with those without macroangiopathy. A multivariate analysis of risk factors for macroangiopathy revealed that duration of diabetes, eGFR, and nephron index were significantly associated with a higher frequency of arteriosclerotic disease.ConclusionThese findings suggest that a decrease in nephron index reflects early-stage renal impairment and is an independent risk factor of macroangiopathy in diabetic patients.

Relationship of childhood weight status to morbidity in adults.

A cohort of white males who had attended elementary schools in Hagerstown, Md., between 1923 and 1928, and whose height-weight records for those years were available, was examined during 1961-63. A study of their childhood relative weight at ages 9-13, and of their adult relative weight 35-40 years later, was made in relation to selected physiological variables and diagnosed morbidity.Essential findings were as follows: Childhood relative weight at ages 9-13 had no significant relationship to adult levels of fasting blood sugar, serum cholesterol, beta-lipoprotein, or blood pressure, or to cardiovascular renal disease.Childhood relative weight at ages 9-13 was significantly related to hypertensive vascular disease. The below average weight group experienced a higher prevalence than observed in either average or moderately overweight childhood groups.Approximately 30 percent of the below average weight children became average weight adults and 21 percent became overweight adults. Of the average weight children, approximately 40 percent became overweight adults. Overweight children tended to remain overweight as adults.Adult relative weight of the same cohort, viewed 35-40 years later, was significantly associated with fasting blood sugar, beta-lipoprotein, and systolic and diastolic blood pressure. Elevated levels of each of these variables occurred with greater frequency in the overweight child.Adult relative weight was significantly associated with hypertensive vascular disease and cardiovascular renal disease; the higher prevalence occurred in the overweight adults.The highest risk for hypertensive vascular and cardiovascular renal disease was associated with the persons who acquired their overweight status as adults. The higher prevalence of these diseases among the overweight adults was largely attributable to the adults who moved from a below average childhood weight category to an overweight adult group. The moderately or markedly overweight adults who was similarly classified as a child did not appear to be at greater risk than the average weight adult who had been an average weight child.

PO-60 - Renal tumors with extensive vascular disease: management challenges in a pediatric series from the Hospital for Sick Children

Venous thrombotic events (VTE) are becoming more and more common in children, particularly in the hospital setting. To date, 1 in 200 children admitted to tertiary pediatric hospitals are now being recognized to develop VTE. Amongst those patients with an identified thrombotic occlusion, pediatric patients diagnosed with renal tumors have long been recognized, but their ideal management in the instances of vascular invasion remains controversial. We describe the clinical behavior of patients diagnosed with renal tumors and extra renal vascular involvement at The Hospital for Sick Children in Toronto, Canada. A retrospective analysis was conducted in patients diagnosed from 1990 to 2012. Data collected included: age, gender, symptoms at presentation, staging, pathology report, radiological evidence of intravascular thrombus [i.e. renal veins (RV), inferior vena cava (IVC) and right atrium (RA)], intraoperative findings, therapeutic protocol implemented and anticoagulation; for outcomes, tumor and/or thrombus recurrence, thromboembolic phenomena [i.e. pulmonary embolism (PE)] and survival. Of 299 patients with renal tumors identified, 292 were included: Wilms (219), Renal Cell Carcinoma (RCC, 29), Clear Cell Sarcoma of the Kidney (CCSK, 12), others (32). The median age of the group was 4.53years (4days - 18 years). Extra renal vascular disease was identified in 29 patients, with a median age 7.05years (0.6-16 years; p=0.03), including Wilms tumors (22/219, 10%), RCC (2/29, 7%), CCSK (1/12, 8.3%) and others (4/32, 12.5%; p=0.01). Vascular involvement comprised exclusive evidence of RV disease (7), IVC disease (19; 15 infra-hepatic), RA disease (3) and PE (5).Treatment escalation because of vascular disease included neo-adjuvant chemotherapy (12; Wilms [11], RCC [1]), intraoperative cavectomy/ thrombectomy (1; Wilms), and cavotomies (11 Wilms [7], RCC [1], CCSK [1], PNET [1], sarcoma [1]). Four patients were placed under cardiopulmonary bypass. Anticoagulation was administered in 9/29 patients for their tumor-related thrombus, and one had a minor bleeding complications (oozing from the central venous line insertion site). Renal tumors with vascular invasion are a rare and challenging entity. Treatment included mostly cancer-related therapies and the role of vascular surgical approaches and/or systemic anticoagulation remains to be clarified.