Commencement Of Renal Replacement Therapy Research Articles

A STUDY OF LIPID PROFILE IN ELDERLY PATIENTS WITH CHRONIC KIDNEY DISEASE

Context :Dyslipidemia is recognized common cardiovascular risk factor in the general population and CKD patients. This cardiovascular risk factor commonly occurs in patients with CKD. Dyslipidemia is linked to a fast decrease in renal function and commencement of Renal Replacement Therapy (RRT) in CKD patients. Methods & Material : This research was conducted on 50 CKD patients admitted to the IP unit of General Medicine. Around 100 patients got admitted into NRI Medical College during the study period in the General Medicine unit with various renal problems. 100 Statistical Population size: Statistical analysis : analysis was done using statistical software named Statistical Package for the Social Science version 23.0.0 (SPSS Inc., Chicago, Illinois, USA). All categorical variables are expressed in percentage. In the current study, we included 50 CKD patients with various stages of CKD aged above 60 years. Conclusions : Dyslipidemia is a common cardiovascular risk factor in CKD, especially in males and older CKD patients and recommends early evaluation in CKD and management with both lifestyle and therapeutic intervention

The relationship between obesity, hemoglobin A1c and the severity of COVID-19 at an urban tertiary care center in New York City: a retrospective cohort study

ObjectivesTo determine if obesity and diabetes are risk factors for severe outcomes in COVID-19 and to compare patient outcomes in those two conditions.DesignRetrospective cohort study.SettingUrban tertiary care center in New...

Sodium bicarbonate to improve physical function in patients over 60 years with advanced chronic kidney disease: the BiCARB RCT.

Advanced chronic kidney disease is common in older people and is frequently accompanied by metabolic acidosis. Oral sodium bicarbonate is used to treat this acidosis, but evidence is lacking on whether or not this provides a net gain in health or quality of life for older people. The objectives were to determine whether or not oral bicarbonate therapy improves physical function, quality of life, markers of renal function, bone turnover and vascular health compared with placebo in older people with chronic kidney disease and mild acidosis; to assess the safety of oral bicarbonate; and to establish whether or not oral bicarbonate therapy is cost-effective in this setting. A parallel-group, double-blind, placebo-controlled randomised trial. The setting was nephrology and geriatric medicine outpatient departments in 27 UK hospitals. Participants were adults aged ≥ 60 years with advanced chronic kidney disease (glomerular filtration rate category 4 or 5, not on dialysis) with a serum bicarbonate concentration of < 22 mmol/l. Eligible participants were randomised 1 : 1 to oral sodium bicarbonate or matching placebo. Dosing started at 500 mg three times daily, increasing to 1 g three times daily if the serum bicarbonate concentration was < 22 mmol/l at 3 months. The primary outcome was the between-group difference in the Short Physical Performance Battery score at 12 months, adjusted for baseline. Other outcome measures included generic and disease-specific health-related quality of life, anthropometry, 6-minute walk speed, grip strength, renal function, markers of bone turnover, blood pressure and brain natriuretic peptide. All adverse events were recorded, including commencement of renal replacement therapy. For the health economic analysis, the incremental cost per quality-adjusted life-year was the main outcome. In total, 300 participants were randomised, 152 to bicarbonate and 148 to placebo. The mean age of participants was 74 years and 86 (29%) were female. Adherence to study medication was 73% in both groups. A total of 220 (73%) participants were assessed at the 12-month visit. No significant treatment effect was evident for the primary outcome of the between-group difference in the Short Physical Performance Battery score at 12 months (-0.4 points, 95% confidence interval -0.9 to 0.1 points; p = 0.15). No significant treatment benefit was seen for any of the secondary outcomes. Adverse events were more frequent in the bicarbonate arm (457 vs. 400). Time to commencement of renal replacement therapy was similar in both groups (hazard ratio 1.22, 95% confidence interval 0.74 to 2.02; p = 0.43). Health economic analysis showed higher costs and lower quality of life in the bicarbonate arm at 1 year, with additional costs of £564 (95% confidence interval £88 to £1154) and a quality-adjusted life-year difference of -0.05 (95% confidence interval -0.08 to -0.01); placebo dominated bicarbonate under all sensitivity analyses for incremental cost-effectiveness. The trial population was predominantly white and male, limiting generalisability. The increment in serum bicarbonate concentrations achieved was small and a benefit from larger doses of bicarbonate cannot be excluded. Oral sodium bicarbonate did not improve a range of health measures in people aged ≥ 60 years with chronic kidney disease category 4 or 5 and mild acidosis, and is unlikely to be cost-effective for use in the NHS in this patient group. Once other current trials of bicarbonate therapy in chronic kidney disease are complete, an individual participant meta-analysis would be helpful to determine which subgroups, if any, are more likely to benefit and which treatment regimens are more beneficial. Current Controlled Trials ISRCTN09486651 and EudraCT 2011-005271-16. The systematic review is registered as PROSPERO CRD42018112908. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 27. See the NIHR Journals Library website for further project information.

P1852REGISTRATION WITH PATIENT-FACING ONLINE HEALTH RECORDS IN CHRONIC KIDNEY DISEASE IS ASSOCIATED WITH A LOWER INCIDENCE OF HYPERKALAEMIA

Abstract Background and Aims PatientView (https://patientview.org) is a web-based health record available throughout the United Kingdom which allows patients to review blood results and clinical communication from renal services. PatientView registration may differ across demographic groups and may be associated with improved clinical end points. We investigated the demographic factors associated with PatientView registration, and the association with incidence of severe hyperkalaemia. Method A retrospective analysis was performed of a prospectively-acquired database of adults with chronic kidney disease (CKD) stages 3 – 5 in a single Scottish health board attending 2006–2017. Individual start date was point of first clinic attendance; end date was date of death, commencement of renal replacement therapy or point of data extraction. Covariates included age, sex, biochemistry, socioeconomic status and co-morbidity. The Scottish Index of Multiple Deprivation (SIMD) was used as a measure of socioeconomic status, where quintile 1 is most deprived. A survival analysis of time to severe hyperkalaemia (&amp;gt;6.5mmol/L) was performed with PatientView registration as a time dependent covariate. Results Of 9935 patients, 967 (9.7%) were registered users of PatientView. The PatientView group had lower age in years (54.7 [42.7-65.6] vs 71.5 [62.1-78.4], p&amp;lt;0.001), estimated glomerular filtration rate (eGFR) (27.1 [18.6-38.8] vs 38.5 [28.3-51.8] ml/min/1.73m2, p&amp;lt;0.001), and higher SIMD (indicating lower levels of deprivation) (23 vs 13% in least deprived quintile, 25 vs 37% in most deprived quintile, p&amp;lt;0.001); fewer patients were female in the PatientView group (46 vs 51%, p&amp;lt;0.001). PatientView users had lower body mass index (29.1±7.6 vs 29.8±7.3 kg/m2, p&amp;lt;0.001), and lower prevalence of diabetes (28 vs 33%, p&amp;lt;0.001), heart failure (5 vs 7%, p&amp;lt;0.001), myocardial infarction (13 vs 22%, p&amp;lt;0.001) and stroke (3 vs 6%, p&amp;lt;0.001). On Cox regression, PatientView was associated with reduced risk of hyperkalaemia (HR 0.43, 95% CI 0.32,0.58) after adjustment for baseline eGFR, baseline serum potassium, SIMD, sex, diabetes and heart failure. Conclusion PatientView use is more prevalent amongst male, middle-aged patients with higher socioeconomic status. Registration with PatientView is associated with reduced likelihood of adverse clinical events including hyperkalaemia. Limitations include lack of ethnicity data, retrospective design and drug therapy. PatientView usage may associate with concordance to a low potassium diet, reflecting general health literacy. However, it is plausible that a causal relationship exists between Patientview usage and hyperkalaemia, by facilitating feedback on, and engagement with, lifestyle changes encouraged by healthcare providers. Whilst there remains a lack of PatientView registration in certain demographic groups, these should be targeted via quality improvement initiatives to enhance renal outcomes in underserved groups.

Abdominal aortic calcification in predialysis patients: Contribution of traditional and uremia-related risk factors.

Cardiovascular disease is the main cause of morbidity and mortality in end-stage renal disease (ESRD) patients. Recent population based epidemiological studies demonstrated a correlation between reduced renal function and risk for all causes and cardiovascular mortality, 50% of patients dying before the commencement of renal replacement therapy. Vascular calcifications (VC) and arterial stiffness are major contributors to cardiovascular disease and are independent predictors of cardiovascular mortality in ESRD patients. Scarce information is available on the risk factors and prognosis of predialysis patients with VC. The aim of this study was to evaluate the contribution of traditional and uremia related risk factors to abdominal aortic calcification in predialysis patients. A single center, retrospective study was performed on 305 adult patients monitored at the Bucharest University Emergency Hospital for at least 6 months. Our study reports an increased incidence of VC in predialysis chronic kidney disease (CKD) patients, higher in those with advanced age, history of cardiovascular disease, osteoporosis, and declining renal function.

SAT-201 ASSOCIATION BETWEEN SMOKING AND ALL-CAUSE AND CAUSE- SPECIFIC MORTALITY IN INCIDENT DIALYSIS PATIENTS-AN ANZDATA REGISTRY ANALYSIS

Smoking increases all-cause mortality and development of cardiovascular disease in patients with end-stage kidneydisease(1). No study to date has examined prevalence and outcomes amongst smokers in Australian and New Zealand dialysis patients. The aims of this study were to explore the prevalence of smoking in incident patients commencing dialysis and to evaluate the effect of smoking at commencement of dialysis on subsequent all-cause and cardiovascular mortality. We conducted a cohort study using the ANZDATA Registry (1990-2016) to explore the association of smoking status at commencement of renal replacement therapy (RT) with all cause and cardiovascular mortality in Australian and New Zealand. Inclusion criteria were adults (18 years or older) at commencement of renal replacement therapy (RRT) for >3 months. Patients who started with a transplant (pre-emptive) were excluded. Incidence of death was estimated by using survival analysis. In the final model of time to all-cause mortality, we adjusted for age, aboriginal, mode of dialysis, BMI, diabetes, history of chronic lung disease, history of coronary artery disease, history of perivascular disease and time dependent transplant status. The hazard ratios of death of current smokers versus non-smokers and former smokers and the 95% confidence interval was calculated from the adjusted model and a Kaplan Meier survival curves of commencement of dialysis until death were constructed. A total of 57838 patients commenced dialysis during 1990-2016, of whom 56512 individuals had data on smoking history: the mean age was 59.0 years, 45.6% reported they were non-smokers, 40.8% were former smokers and 13.6% current smokers. Forty-one % were female, 43% had diabetes, 29.2 % were obese, 38.5% were>65 years of age and 7.5% were Aboriginal and Torres Strait Islanders. During the median followup of 4.4 years with a mean of 6.1 years, 33547 died (59.4%), 13140 (23.3%) underwent a kidney transplant without lost to follow-up. Cardiovascular disease was the major cause of death, reported in 15174 (45.2% of deaths), 9.739 (17.2% of deaths ) died of a malignancy, 66 (0.1% of deaths) died of infection related cause and 301 (0.5% of deaths) died of respiratory failure and 5185 (9.2%) had a cancer diagnosis. Hazard ratio of all cause-mortality for smokers was 1.13 (95%CI :1.10-1.15, p<0.0001). Similarly smokers had a higher rate of death due to cardiovascular disease ( HR 1.16; 95% CI 1.12-1.20, p < 0.0001). In addition, smoking history was significantly associated with a higher rate of diagnosis of cancer (HR 1.26; 95% CI 1.19-1.33, p< 0.0001), infections ( HR 1.07; 95% CI 1.06-1.09, p<0.0001) and respiratory failure ( HR 1.06; 95% CI 1.05-1.07, p< 0.001). The death due to infections rate is higher for smokers but this is not significant ( HR 1.37; 95% CI 0.83,2.26, p=0.22) The cumulative incidence of death among smokers and non- smokers were 63.1% for smokers and 54.9% for non-smokers. Amongst patients commencing dialysis in Australia and New Zealand, 54% were either current or former smokers. Smoking history was an independent risk factor for all-cause mortality, cardiovascular mortality, diagnosis of cancer and respiratory failure. Smoking is an important risk factor and the patients should be encouraged to quit

104 Oral Sodium Bicarbonate Therapy for Older Patients with Chronic Kidney Disease and Low-Grade Acidosis: The BiCARB Randomised Controlled Trial

Abstract Background Oral sodium bicarbonate is often used to treat metabolic acidosis in older people with advanced chronic kidney disease, but evidence is lacking on whether this provides a net gain in health or quality of life. Methods We conducted a multicentre, parallel group, double-blind, placebo-controlled randomised trial. Adults aged 60 years and over with category 4 or 5 chronic kidney disease, not on dialysis, with serum bicarbonate concentrations &amp;lt;22 mmol/L were recruited from 27 UK centres. Participants were randomised 1:1 to oral sodium bicarbonate or matching placebo. The primary outcome was the between-group difference in the Short Physical Performance Battery at 12 months, adjusted for baseline. Other key outcome measures included generic and disease-specific health-related quality of life, anthropometry, physical performance, renal function, adverse events including commencement of renal replacement therapy, and health economic analysis. Results We randomised 300 participants, mean age 74 years; 86 (29%) were female. Mean baseline estimated GFR was 19 ml/min/1.73m2. Study medication adherence was 73% in both groups. No significant treatment effect was evident for the primary outcome of the between-group difference in the Short Physical Performance Battery at 12 months (-0.4 points; 95% CI -0.9 to 0.1, p=0.15). No significant treatment benefit was seen for any of the secondary outcomes. Adverse events were more frequent in the bicarbonate arm (457 versus 400). Time to commencing renal replacement therapy was similar in both groups (HR 1.22, 95% CI 0.74 to 2.02, p=0.43). Health economic analysis showed lower quality of life and higher costs in the bicarbonate arm at one year (£1234 vs £807); placebo dominated bicarbonate under all sensitivity analyses for incremental cost-effectiveness. Conclusions Oral sodium bicarbonate did not improve a wide range of health measures in this trial, and is unlikely to be cost-effective for use in the UK NHS in this patient group.

Correction and Control of Hyperammonemia in Acute Liver Failure: The Impact of Continuous Renal Replacement Timing, Intensity, and Duration.

Hyperammonemia is a key contributing factor for cerebral edema in acute liver failure. Continuous renal replacement therapy may help reduce ammonia levels. However, the optimal timing, mode, intensity, and duration of continuous renal replacement therapy in this setting are unknown. We aimed to study continuous renal replacement therapy use in acute liver failure patients and to assess its impact on hyperammonemia. Retrospective observational study. ICU within a specialized liver transplant hospital. Fifty-four patients with acute liver failure. Data were obtained from medical records and analyzed for patient characteristics, continuous renal replacement therapy use, ammonia dynamics, and outcomes. Forty-five patients (83%) had high grade encephalopathy. Median time to continuous renal replacement therapy commencement was 4 hours (interquartile range, 2-4.5) with 35 (78%) treated with continuous venovenous hemodiafiltration and 10 (22%) with continuous venovenous hemofiltration. Median hourly effluent flow rate was 43 mL/kg (interquartile range, 37-62). The median ammonia concentration decreased every day during treatment from 151 µmol/L (interquartile range, 110-204) to 107 µmol/L (interquartile range, 84-133) on day 2, 75 µmol/L (interquartile range, 63-95) on day 3, and 52 µmol/L (interquartile range, 42-70) (p < 0.0001) on day 5. The number of patients with an ammonia level greater than 150 µmol/L decreased on the same days from 26, to nine, then two, and finally none. Reductions in ammonia levels correlated best with the cumulative duration of therapy hours (p = 0.03), rather than hourly treatment intensity. Continuous renal replacement therapy is associated with reduced ammonia concentrations in acute liver failure patients. This effect is related to greater cumulative dose. These findings suggest that continuous renal replacement therapy initiated early and continued or longer may represent a useful approach to hyperammonemia control in acute liver failure patients.

Late referral and associated factors among chronic kidney disease outpatients in Southern Nigeria.

Background:Chronic kidney disease (CKD) is a recognized noncommunicable disease that contributes to the global disease burden. Studies on late referral (LR) of CKD patients to the nephrologist have reported incidence rates of 22%–58% according to the definition of LR used. CKD patients who present late to the nephrologist tend to have poorer outcomes with increased morbidity and mortality.Aim:The aim of the study is to determine the prevalence of LR and associated factors among CKD outpatients.Materials and Methods:A cross-sectional observational study, in which CKD patients attending the renal outpatient clinic of two tertiary hospitals over a period of 6 months, were recruited. LR was defined as commencement of renal replacement therapy within 3 months after the first presentation to a nephrologist.Results:A total of 181 participants were recruited during the period of study; 114 were men. One hundred and twelve participants (61.8%) had stage 5 CKD, of which 97 had commenced maintenance hemodialysis. The prevalence of LR was 44.8% (81/181) (95% confidence interval: 37.4%–51.9%). Lack of funds was the most frequent reason given by participants who delayed after formal referral to a nephrologist. Being a known diabetic was associated with LR. Age, gender, level of education, occupation, being a known hypertensive, or known diabetic were not significant predictors of LR.Conclusion:Prevalence of LR is high. Education of medical practitioners, patients, and the general public on early symptoms and physical signs of kidney disease is required. Initiation of all-encompassing health insurance scheme is necessary to solve the problem of lack of funds for medical consultation and treatment.

Vascular age is associated with the risk of dialysis or death in chronic kidney disease.

Increased arterial stiffness is associated with progressive renal deterioration and poor clinical outcomes in patients with chronic kidney disease (CKD). Assessment of vascular age as derived from arterial stiffness parameters might be an important clinical marker of cardiovascular risks. The aim of the present study is to evaluate whether the difference (△age) between vascular age and chronological age can predict the risk of reaching dialysis or death in patients with known CKD. This longitudinal study enrolled 94 male Chinese CKD patients, aged 40-62 years. Vascular age was calculated by brachial-ankle pulse wave velocity, and measured by an ankle-brachial index-form device. The study endpoints were the commencement of renal replacement therapy or death. After a stepwise multivariate analysis, △age was associated independently with increased urine protein-to-creatinine ratio (β = 0.32; P = 0.001) and decreased baseline estimated glomerular filtration rate (β = -0.24; P = 0.008). During a median follow-up period of 62 (interquartile range = 55-66) months, the 4-year cumulative incidence of reaching the study endpoint in patients with △age = 0 and △age > 0 year was 4.9% and 25%, respectively (log-rank test, P = 0.009). Multivariate forward Cox regression analysis identified that higher △age (hazard ratio (HR) = 1.05; P = 0.027), lower baseline estimated glomerular filtration rate (HR = 0.93; P < 0.001), and history of cardiovascular disease (HR = 5.90; P = 0.031) were independently associated with progression to commencement of dialysis or death. Thus, the assessment of the difference between vascular age and chronological age may provide an alternative method to identify CKD patients at a high risk of progression to dialysis or death.

Association of anthropometric measures with kidney disease progression and mortality: a retrospective cohort study of pre-dialysis chronic kidney disease patients referred to a specialist renal service.

BackgroundAlthough elevated body mass index (BMI) is a predictor of better clinical outcomes in dialysis patients, the evidence in pre-dialysis chronic kidney disease (CKD) is conflicting. Clinical measures of central obesity may be better prognostic indicators, although investigation has been limited. The aim of this study was to assess the predictive value of anthropometric measures for kidney failure progression and mortality in stage 3–4 CKD.MethodsThe study included newly referred stage 3–4 CKD patients at a single centre between 1/1/2008 and 31/12/2010. The associations between clinical measures of obesity (BMI, waist circumference [WC] and conicity index [ConI]) and time to a composite primary outcome of doubling of serum creatinine, commencement of renal replacement therapy or mortality were evaluated using the Kaplan-Meier method and multivariable Cox regression models.ResultsOver a median follow-up period of 3.3 years, 229 (25.4 %) patients of a total population of 903 experienced the composite primary renal outcome. When compared to normal BMI (18.5-24.9 kg/m2, n = 174), the risk of the composite primary outcome was significantly lower in both the overweight (BMI 25–29.9 kg/m2, n = 293; adjusted hazard ratio [HR] 0.50, 95 % CI 0.33-0.75) and obese class I/II groups (BMI 30–39.9 kg/m2, n = 288; HR 0.62, 95 % CI 0.41-0.93), but not in the obese class III group (BMI ≥40 kg/m2, n = 72; HR 0.94, 95 % CI 0.52-1.69). All-cause mortality was also lower in the overweight group (HR 0.50, 95 % CI 0.30-0.83). WC and ConI were not associated with either the composite primary outcome or mortality.ConclusionBMI in the overweight range is associated with reduced risks of kidney disease progression and all-cause mortality in stage 3–4 CKD. WC and ConI were not independent predictors of these outcomes in this population.Electronic supplementary materialThe online version of this article (doi:10.1186/s12882-016-0290-y) contains supplementary material, which is available to authorized users.

The Variability of Estimated Glomerular Filtration Rate Decline in Alport Syndrome.

Background:A progressive trajectory toward renal failure is common in patients with Alport syndrome. Genotype-phenotype correlations have been well described; however, the natural history of the trajectory toward renal failure is not well described.Objective:The objective of this study is to describe the natural history of renal function decline in a cohort of Alport syndrome patients.Design:Retrospective observational cohort study.Setting:British Columbia, Canada, chronic renal disease registry 1995-2012.Patients:37 biopsy proven Alport syndrome or hematuria with family history of Alport syndrome.Measurements:Serial estimated glomerular filtration rate (eGFR) Trajectory of renal decline described graphically by fitting a cubic smoothing spline to patient’s eGFR measures. Various time points within a trajectory were indexed, randomly sampled, and followed for 2 years to estimate portion of progressors (>5 mL/min/1.73 m2 /y decline), stable state (0-2 mL/min/1.73 m2 /y decline), and regressors (>2 mL/min/1.73 m2 /y incline).Methods:In this retrospective observational cohort study, participants were identified through a chronic renal disease registry in British Columbia, Canada, from 1995 to 2012. Inclusion criteria were biopsy proven or hematuria with a family history of Alport syndrome. Individual patients and family group members were studied. Trajectory of renal decline described graphically by fitting a cubic smoothing spline to patient’s serial estimated glomerular filtration rate (eGFR) measures. Various time points within a trajectory were indexed, randomly sampled, and followed for 2 years to estimate portion of progressors (>5 mL/min/1.73 m2/y decline), stable state (0-2 mL/min/1.73 m2/y decline), and regressors (>2 mL/min/1.73 m2/y incline).Limitations:Histological or genetic evidence of Alport syndrome is not available in all patients.Results:Median follow-up time was 48.2 months of 37 patients (78% male), with a median age of 36 (interquartile range [IQR], 18-47) and a median age of renal replacement therapy commencement (n = 23) of 38 (IQR = 20-52). Renal function changes were found to be heterogeneous overall, intra-individual and within families. Portion of progressors in eGFR 45-60 mL/min/1.73 m2 was 73.7% (SD, 10.3), whereas 23.6% (SD, 11.0) remained stable. Within eGFR 30-45 mL/min/1.73 m2, 45.6% (SD, 7.0) were progressors, whereas 53.4% (SD, 7.4) remained stable. A large portion of eGFR 15-30 mL/min/1.73 m2 patients were stable (54.8%; SD, 8.4), whereas 25.7% (SD, 7.1) progressed and 19.5% (SD, 5.6) regressed.Conclusions:The renal decline in Alport syndrome patients is heterogeneous which has implications for designing clinical trials of interventions.

Periodontal disease and chronic kidney disease among Aboriginal adults; an RCT.

BackgroundThis study will assess measures of vascular health and inflammation in Aboriginal Australian adults with chronic kidney disease (CKD), and determine if intensive periodontal intervention improves cardiovascular health, progression of renal disease and periodontal health over a 24-month follow-up.MethodsThe study will be a randomised controlled trial. All participants will receive the periodontal intervention benefits, with the delayed intervention group receiving periodontal treatment 24 months following baseline. Inclusion criteria include being an Aboriginal Australian, having CKD (a. on dialysis; b. eGFR levels of <60 mls/min/1.73 m2 (CKD Stages 3 to 5); c. ACR ≥30 mg/mmol irrespective of eGFR (CKD Stages 1 and 2); d. diabetes plus albuminuria (ACR ≥ 3 mg/mmol) irrespective of eGFR), having moderate or severe periodontal disease, having at least 12 teeth, and living in Central Australia for the 2-year study duration. The intervention involves intensive removal of dental plaque biofilms by scaling, root-planing and removal of teeth that cannot be saved. The intervention will occur in three visits; baseline, 3-month and 6-month follow-up. The primary outcome will be changes in carotid intima-media thickness (cIMT). Secondary outcomes will include progression of CKD or death as a consequence of CKD/cardiovascular disease. Progression of CKD will be defined by time to the development of the first of: (1) new development of macroalbuminuria; (2) 30 % loss of baseline eGFR; (3) progression to end stage kidney disease defined by eGFR <15 mLs/min/1.73 m2; (4) progression to end stage kidney disease defined by commencement of renal replacement therapy. A sample size of 472 is necessary to detect a difference in cIMT of 0.026 mm (SD 0.09) at the significance criterion of 0.05 and a power of 0.80. Allowing for 20 % attrition, 592 participants are necessary at baseline, rounded to 600 for convenience.DiscussionThis will be the first RCT evaluating the effect of periodontal therapy on progression of CKD and cardiovascular disease among Aboriginal patients with CKD. Demonstration of a significant attenuation of CKD progression and cardiovascular disease has the potential to inform clinicians of an important, new and widely available strategy for reducing CKD progression and cardiovascular disease for Australia’s most disadvantaged population.Trial registrationThis trial is registered with the Australian New Zealand Clinical Trial Registry ANZCTR12614001183673.

Does early-start renal replacement therapy improve outcomes for patients with acute kidney injury?

There is a paucity of high-quality evidence to guide clinicians on thresholds for commencement of renal replacement therapy (RRT) in critically ill patients with acute kidney injury (AKI), and wide international practice variation. Wald et al. report a pilot randomized trial examining accelerated use of RRT for moderate AKI in the intensive care unit, providing a workable design for a definitive trial examining the timing of RRT in critical illness.

Interventions for lowering plasma homocysteine levels in kidney transplant recipients.

Elevated homocysteine levels have been shown to be an independent risk factor for cardiovascular disease. However studies of homocysteine lowering in general and end-stage kidney disease (ESKD) populations have not demonstrated a reduction in cardiovascular event rates. Kidney transplant recipients have high homocysteine levels, high cardiovascular event rates and, unlike the ESKD population, may achieve normalisation of homocysteine levels with homocysteine lowering therapies. Thus may benefit from homocysteine lowering therapy. To evaluate the effects of established homocysteine lowering therapy on cardiovascular mortality in patients with functioning kidney transplants. We searched the Cochrane Renal Group's Specialised Register to 16 March 2015 through contact with the Trials' Search Co-ordinator using search terms relevant to this review. Randomised controlled trials of any therapy that has been shown to significantly lower homocysteine levels conducted in people with functioning kidney transplants. Studies were to be included if they compared homocysteine lowering therapy with placebo or usual care, or compare higher versus lower doses of homocysteine lowering therapy. Two authors independently assessed study quality and extracted data. Results were to be expressed as the risk ratio (RR) for dichotomous outcomes or mean difference (MD) for continuous outcomes with 95% confidence intervals (CI). Data was to be pooled using the random effects model. The literature search yielded 359 reports of which only one study was identified that met our inclusion criteria and reported relevant clinical endpoints. This study randomised 4110 adult participants with a functioning kidney transplant and elevated homocysteine levels to folic acid plus high dose B multivitamins or low dose multivitamins who were followed for a mean 4.0 years. Despite effectively lowering homocysteine levels) in homocysteine levels at follow-up (MD -4.40 μmol/L, 95% CI -5.98 to -2.82) there was no evidence the intervention impacted on any of the outcomes reported including cardiovascular mortality (RR 0.91, 95% CI 0.69 to 1.20), all-cause mortality (RR 1.04, 95% CI 0.88 to 1.22), myocardial infarction (RR 1.02, 95% CI 0.77 to 1.35), stroke (RR 1.08, 95% CI 0.69 to 1.71), commencement of renal replacement therapy (RR 1.12, 95% CI 0.91 to 1.37) or all reported adverse events (RR 1.02, 95% CI 0.87 to 1.20). There was no evidence the intervention impacted on the primary endpoint of the study, a cardiovascular event composite (RR 0.99, 95% CI 0.85 to 1.15). The study was of high quality. There is no current evidence to support the use of homocysteine lowering therapy for cardiovascular disease prevention in kidney transplant recipients.

Timing of Renal Replacement Therapy and Patient Outcomes in the Randomized Evaluation of Normal Versus Augmented Level of Replacement Therapy Study*

To explore the relationship between timing of continuous renal replacement therapy commencement and clinical outcomes in critically ill patients with acute kidney injury. The primary outcomes were all-cause mortality at 28 and 90 days. Nested observational cohort study using data from the Randomized Evaluation of Normal Versus Augmented Level Replacement Therapy Study. Twenty-three ICUs in Australia and New Zealand. Four hundred thirty-nine critically ill patients with acute kidney injury Risk, Injury, Failure, Loss, End-stage kidney disease-injury (RIFLE-I) criteria. None. The time between RIFLE-I acute kidney injury and randomization in the Randomized Evaluation of Normal Versus Augmented Level Replacement Therapy Study (proxy for continuous renal replacement therapy commencement) was the variable of interest. All baseline variables in the Randomized Evaluation of Normal Versus Augmented Level Replacement Therapy Study were assessed. Multivariable Cox, logistic, and linear regression models were used to assess the independent relationship of time of onset of RIFLE-I acute kidney injury and randomization and patient outcomes. The median time between RIFLE-I acute kidney injury and continuous renal replacement therapy commencement was 17.6 hours (interquartile range, 7.1-46 hr). Based on four groups of continuous renal replacement therapy commencement ([group 1; reference]: < 7.1, [group 2]: ≥ 7.1 to < 17.6, [group 3]: ≥ 17.6 to < 46.0, [group 4]: ≥ 46.0 hr), earlier commencement of continuous renal replacement therapy was not associated with a significantly lower risk of death at 28 days (hazard ratio for group 2: 1.06, 95% CI: 0.62-1.81; p = 0.83; hazard ratio for group 3: 1.23, 95% CI: 0.71-2.12; p = 0.46; hazard ratio for group 4: 1.33, 95% CI: 0.77-2.31; p = 0.31). Similar findings were observed for death at 90 days. In a subgroup of participants of the Randomized Evaluation of Normal Versus Augmented Level Replacement Therapy Study, earlier commencement of continuous renal replacement therapy relative to RIFLE-I acute kidney injury was not significantly associated with improved survival. Additional studies with larger sample sizes and broader commencement times are warranted.

Analysis of factors predicting mortality of new patients commencing renal replacement therapy 10 years of follow-up.

BackgroundThe natural history of patients commencing dialysis in East Yorkshire is not well characterised and there is little convincing evidence which has studied the impact of potential factors prior to commencement of renal replacement therapy (RRT) at predicting mortality during dialysis. The aim of this study was to examine the previously published 5-year data on end stage renal disease and co-morbid risk factors for mortality at 10 years.MethodsAn observational cohort study of subjects commencing dialysis in 2001/02 in East Yorkshire with a mean follow up from dialysis initiation of 8.8 years. Predictors of mortality were determined by univariate, multivariate analysis and survival via Kaplan-Meier analysis. Assessment of the utility of the Tangri risk calculator was carried out in addition to slope change in eGFR prior to dialysis commencement.ResultsBaseline characteristics and the preferred mode of dialysis remained concordant with the original trial. The mortality rate at the end of the study period was 60% (56/94) with 30% (29) of patients having been transplanted. Highlighted in the 5 year data a significant proportion of mortality was made up of vascular disease and sepsis (71%) but this proportion had decreased (57%) by 10 years. Cardiac disease was the commonest cause of death but notably in 18% of patients, death was related to dialysis or withdrawal of treatment. Vascular disease and diabetes remained independent risk factors and predicative of mortality. Calcium - phosphate product which was associated in the early years with mortality was not in later years. Use of the risk calculator was predictive of commencement of RRT but not mortality but slope change in eGFR was predictive of mortality.ConclusionsAlthough diabetes and vascular disease remained predictive of mortality, interestingly calcium-phosphate levels are no longer significant and may be a more specific predictor of early cardiac mortality. Slope eGFR changes prior to RRT are a predictor of mortality. We speculate that aggressive management of cardiac risk factors in addition to early transplantation may be key to influencing the impact of survival in this cohort in addition to possible measures to delay renal progression.

Variability in estimated glomerular filtration rate by area under the curve predicts renal outcomes in chronic kidney disease.

Greater variability in renal function is associated with mortality in patients with chronic kidney disease (CKD). However, few studies have demonstrated the predictive value of renal function variability in relation to renal outcomes. This study investigates the predictive ability of different methods of determining estimated glomerular filtration rate (eGFR) variability for progression to renal replacement therapy (RRT) in CKD patients. This was a prospective observational study, which enrolled 1,862 CKD patients. The renal end point was defined as commencement of RRT. The variability in eGFR was measured by the area under the eGFR curve (AUC)%. A significant improvement in model prediction was based on the −2 log likelihood ratio statistic. During a median 28.7-month follow-up, there were 564 (30.3%) patients receiving RRT. In an adjusted Cox model, a smaller initial eGFR AUC%_12M (P < 0.001), a smaller peak eGFR AUC%_12M (P < 0.001), and a larger negative eGFR slope_12M (P < 0.001) were associated with a higher risk of renal end point. Two calculated formulas: initial eGFR AUC%_12M and eGFR slope_12M were the best predictors. Our results demonstrate that the greater eGFR variability by AUC% is associated with the higher risk of progression to RRT.

Factors affecting growth and adult height in pediatric renal transplantation

Growth retardation is common in children with chronic kidney disease. Renal transplantation (TPL) resolves many endocrine, metabolic and uremic disturbances that contribute to growth retardation. However, growth continues to be suboptimal even after TPL. The aim of this study was to review factors affecting post-TPL growth and final adult height (FAH) in children who received kidney allografts.A retrospective chart review of 65 patients (44 male) who received renal TPL at Seoul National University hospital was done. Only patients less than 15 years of age at TPL with regular follow up for at least 3 years afterwards were included. Subjects with immediate graft failure or those receiving post-TPL growth hormone treatments were excluded. Height z-scores were recorded at diagnosis, commencement of renal replacement therapy (RRT), TPL and thereafter at 6 month intervals for 3 to 5 years. The delta height z-scores during 2 years and 5 years post TPL were calculated as the difference in height z-scores between those time points and height z-score at TPL.The mean age at TPL was 10.1 (1.8 – 14.4) years. The mean height z-score of recipients was -1.61±1.36 (-4.64 – 1.64). The mean delta height z-score at 2 years and 5 years were 0.61±0.89 (-1.03 – 2.41) and 0.38±0.88 (-0.98 – 2.04) respectively. Age at TPL (before or after age 10) had a significant correlation with both 2 and 5 year change in height z-score (p=0.001 and p=0.012, respectively). Multivariate linear regression analysis showed that age and height at the time of TPL were significant determinants of 2 and 5 year growth after TPL (r2=0.56, p=0.006). Further analysis showed that height at commencement of RRT and duration of RRT were significant factors in determining the pre-TPL height (r2=0.76, p<0.001). The mean FAH was -1.21±1.10 (-2.85 – 1.61, n=33) and the percentage of patients who attained a FAH z-score ≥-1.88 was 76%. FAH z-score correlated with height z-score at the time of TPL (p<0.001).This study suggests that age and height at the time of TPL are important factors affecting post-TPL growth and FAH. Maximizing growth before TPL by decreasing the duration of RRT and early preemptive TPL may lead to better attainment of expected adult height.

Empiricism or rationalism: how should we measure proteinuria?

Proteinuria is the cardinal sign of renal disease, therefore accurate identification of clinically significant proteinuria is essential to the diagnosis and management of kidney disease. Spot samples are now widely used, namely protein: creatinine ratio (uPCR) and albumin: creatinine ratio (uACR). In this article we review the evidence comparing uPCR and uACR including clinical, laboratory and financial arguments. uPCR has a superior performance to uACR to predict 24-hour total proteinuria, the measurement on which the evidence for interventions in chronic kidney disease is based. Furthermore a retrospective study comparing uPCR and uACR as predictors of renal outcome found comparable performance to predict all-cause mortality, commencement of renal replacement therapy and doubling of serum creatinine. Only uPCR takes account of non-albumin proteinuria which has been shown to have prognostic significance. uACR was been thought to be superior at low levels (where there is less 'noise' from physiological urinary proteins), but uPCR has recently been shown to perform well at levels equivalent to <0.5 g/day (and even within the reference range) as a predictor of outcomes. uACR is measured using an immunoassay that may be technically superior, but is not without shortcomings (such as antigen excess) and is 2-10 times more expensive than uPCR. The theories explaining the superiority of albumin are appealing. However, the available comparative data do not seem to support the theory. We cannot explain the disparity, but in science, if the data do not fit the existing theory, then maybe it's time for a new theory.