An Analysis of Vascular Access Thrombosis Events From the Proactive IV irOn Therapy in hemodiALysis Patients Trial.

Introduction: Treatment of anemia in dialysis patients has been associated with increased risk of vascular access thrombosis (VAT). Proactive IV irOn Therapy in hemodiALysis Patients (PIVOTAL) was a clinical trial of proactive compared with reactive i.v. iron therapy in patients requiring hemodialysis. We analyzed the trial data to determine whether randomized treatment arm, alongside other clinical and laboratory variables, independently associated with VAT. Methods: In PIVOTAL, 2141 adult patients were randomized. The type of vascular access (arteriovenous fistula [AVF], arteriovenous graft [AVG], or central venous catheter [CVC]) was recorded at baseline and every month after randomization. The associations between clinical and laboratory data and first VAT were evaluated in a multivariate analysis. Results: A total of 480 (22.4%) participants experienced VAT in a median of 2.1 years of follow-up. In multivariable analyses, treatment arm (proactive vs. reactive) was not an independent predictor of VAT (hazard ratio [HR] 1.13, P = 0.18). Diabetic kidney disease (HR 1.45, P < 0.001), AVG use (HR 2.29, P < 0.001), digoxin use (HR 2.48, P < 0.001), diuretic use (HR 1.25, P = 0.02), female sex (HR 1.33, P = 0.002), and previous/current smoker (HR 1.47, P = 0.004) were independently associated with a higher risk of VAT. Angiotensin receptor blocker (ARB) use (HR 0.66, P = 0.01) was independently associated with a lower risk of VAT. Conclusion: In PIVOTAL, VAT occurred in nearly 1 quarter of participants in a median of just >2 years. In this post hoc analysis, randomization to proactive i.v. iron treatment arms did not increase the risk of VAT.

Dialysis Patients' Preferences on Resuscitation: A Cross-Sectional Study Design.

Background: End-stage kidney disease is associated with a 10- to 100-fold increase in cardiovascular mortality compared with age-, sex-, and race-matched population. Cardiopulmonary resuscitation (CPR) in this cohort has poor outcomes and leads to increased functional morbidity. Objective: The aim of this study is to assess patients' preferences toward CPR and advance care planning (ACP). Design: cross-sectional study design. Setting: Two outpatient dialysis units. Patients: Adults undergoing dialysis for more than 3 months were included. Exclusion criteria were severe cognitive impairment or non-English-speaking patients. Measurements: A structured interview with the use of Willingness to Accept Life-Sustaining Treatment (WALT) tool. Methods: Demographic data were collected, and baseline Montreal Cognitive Assessment, Patient Health Questionnaire-9, Duke Activity Status Index, Charlson comorbidity index, and WALT instruments were used. Descriptive analysis, chi-square, and t test were performed along with probability plot for testing hypotheses. Results: Seventy participants were included in this analysis representing a 62.5% response rate. There was a clear association between treatment burden, anticipated clinical outcome, and the likelihood of that outcome with patient preferences. Low-burden treatment with expected return to baseline was associated with 98.5% willingness to accept treatment, whereas high-burden treatment with expected return to baseline was associated with 94.2% willingness. When the outcome was severe functional or cognitive impairment, then 45.7% and 28.5% would accept low-burden treatment, respectively. The response changed based on the likelihood of the outcome. In terms of resuscitation, more than 75% of the participants would be in favor of receiving CPR and mechanical ventilation at their current health state. Over 94% of patients stated they had never discussed ACP, whereas 59.4% expressed their wish to discuss this with their primary nephrologist. Limitations: Limited generalizability due to lack of diversity. Unclear decision stability due to changes in health status and patients' priorities. Conclusions: ACP should be incorporated in managing chronic kidney disease (CKD) to improve communication and encourage patient involvement.

Mise en contexte: Les patients atteints d'insuffisance rénale terminale voient leur taux de mortalité cardiovasculaire augmenté de 10 à 100 fois par rapport à une population appariée selon l'âge, le sexe et l'origine ethnique. La réanimation cardiorespiratoire (RCR) donne de mauvais résultats dans cette cohorte de patients et conduit à une morbidité fonctionnelle accrue. Objectif de l'étude: Évaluer les préférences des patients en matière de RCR et de planification préalable des soins (PPS). Conception: Étude transversale. Cadre et type d'étude: Deux unités de dialyse pour patients ambulatoires. Patients: Ont été inclus les adultes suivant des traitements de dialyse pendant plus de trois mois. Les patients non anglophones ou ayant des troubles cognitifs graves ont été exclus. Mesures: Une entrevue structurée réalisée à l'aide de l'outil WALT (Willingness to Accept Life-Sustaining Treatment). Méthodologie: Des données démographiques ont été recueillies et les outils d'évaluation suivants ont été utilisés à l'inclusion: le Montreal Cognitive Assessment, le questionnaire sur la santé des patients (PHQ-9), le Duke Activity Status Index, l'indice de comorbidité de Charlson et l'outil WALT. Des analyses descriptives, tests de chi carré et tests de t ont été effectués, ainsi que des graphiques de probabilité pour tester les hypothèses. Résultats: Soixante-dix participants ont été inclus dans l'analyse, soit un taux de réponse de 62.5%. On a observé une association claire entre les préférences du patient et le fardeau du traitement, le résultat clinique attendu et la probabilité de ce résultat. La probabilité qu'un patient accepte un traitement représentant un faible fardeau, avec un retour à l'état initial prévu, s'établissait à 98.5%; cette probabilité était de 94.2% pour un traitement avec retour à l'état initial, mais représentant un lourd fardeau. Lorsqu'un traitement de faible fardeau était susceptible d'entraîner une déficience fonctionnelle ou cognitive grave, cette probabilité passait respectivement à 45.7% et 28.5%. La réponse variait en fonction de la probabilité du résultat. En ce qui concerne la réanimation, plus de 75% des participants seraient favorables à la RCR et à la ventilation mécanique dans leur état de santé actuel. Plus de 94% des patients n'avaient jamais discuté de PPS avec leur néphrologue principal, alors que 59.4% ont exprimé leur souhait de le faire. Limites de l'étude: Généralisabilité limitée en raison du manque de diversité. Stabilité incertaine des décisions en raison de l'évolution de l'état de santé et des priorités des patients. Conclusion: La PPS devrait être intégrée à la prise en charge de l'insuffisance rénale chronique afin d'améliorer la communication avec les patients et d'encourager leur participation.

Cutaneous Absidia corymbifera in a Lupus Nephritis Patient.

A 28-year-old farmer with class IV lupus nephritis presented with a two-week history of a right shin lesion. The lesion was purple in color, fungating, and indurated with a focus of deep ulceration at the inferior pole and punctate, bleeding from its surface. Three months earlier, he was started on induction immunosuppression for a relapse of his lupus nephritis. Since the diagnosis of lupus nephritis, nine years previously, he had had six flares of his disease and had been treated at different time points with cyclophosphamide, rituximab, and high-dose corticosteroids, without adverse events. Laboratory investigations showed improving kidney function (chronic kidney disease [CKD] stage IV) with reducing proteinuria, on his current immunosuppressive regimen. The differential diagnosis for this lesion was calciphylaxis, pyoderma gangrenosum, vasculitic lesion, or an infection. Histology and microbiological analysis confirmed the presence of Absidia corymbifera. He was treated with a combination of isavuconazole, reduction of his immunosuppressive agents, excision of the lesion, and skin grafting.

Burden of chronic kidney disease and rapid decline in renal function among adults attending a hospital-based diabetes center in Northern Europe.

INTRODUCTION: This study aimed to determine the prevalence of diabetic kidney disease (DKD) and rapid renal function decline and to identify indices associated with this decline among adults attending a diabetes center in Northern Europe. RESEARCH DESIGN AND METHODS: This is a retrospective cohort study of 4606 patients who attended a diabetes center in Ireland between June 2012 and December 2016. Definition/staging of chronic kidney disease used the Kidney Disease: Improving Global Outcomes (KDIGO) 2012 classification based on data from the most recently attended appointment. Relevant longitudinal trends and variabilities were derived from serial records prior to index visit. Rapid renal function decline was defined based on per cent and absolute rates of estimated glomerular filtration rate (eGFR) change. Multiple linear regression was used to explore the relationships between explanatory variables and per cent eGFR change. RESULTS: 42.0% (total), 23.4% (type 1 diabetes), 47.9% (type 2 diabetes) and 32.6% (other diabetes) had DKD. Rapid decline based on per cent change was more frequent in type 2 than in type 1 diabetes (32.8% vs 14.0%, p<0.001). Indices independently associated with rapid eGFR decline included older age, greater number of antihypertensives, higher log-normalized urine albumin to creatinine ratio (LNuACR), serum alkaline phosphatase, thyroid stimulating hormone, variability in systolic blood pressure and variability in LNuACR, lower glycated hemoglobin, high-density lipoprotein cholesterol and diastolic blood pressure, and lack of ACE inhibitor/angiotensin receptor blocker prescription. CONCLUSIONS: DKD (using the KDIGO 2012 classification) and rapid eGFR decline were highly prevalent among adults attending a hospital-based diabetes clinic in a predominantly Caucasian Northern European country. The burden was greater for adults with type 2 diabetes. Expected as well as potentially novel clinical predictors were identified.

Pilot Randomized Controlled Trial of a Standard Versus a Modified Low-Phosphorus Diet in Hemodialysis Patients.

INTRODUCTION: The standard low-phosphorus diet restricts pulses, nuts, and whole grains and other high phosphorus foods to control hyperphosphatemia. We conducted a randomized controlled trial to evaluate the effectiveness, safety, and tolerability of the modified diet, which introduced some pulses and nuts, increased the use of whole grains, increased focus on the avoidance of phosphate additives, and introduced the prescription of low-biological-value protein such as bread. METHODS: We conducted a multicenter, pragmatic, parallel-arm, open-label, randomized controlled trial of modified versus standard diet in 74 adults on hemodialysis with hyperphosphatemia over 1 month. Biochemistry was assessed using monthly laboratory tests. Dietary intake was assessed using a 2-day record of weighed intake of food, and tolerability was assessed using a patient questionnaire. RESULTS: There was no significant difference in the change in serum phosphate between the standard and modified diets. Although total dietary phosphorus intake was similar, phytate-bound phosphorus, found in pulses, nuts, and whole grains, was significantly higher in the modified diet (P < 0.001). Dietary fiber intake was also significantly higher (P < 0.003), as was the percentage of patients reporting an increase in bowel movements while following the modified diet (P = 0.008). There was no significant difference in the change in serum potassium or in reported protein intake between the 2 diets. Both diets were similarly well tolerated. CONCLUSION: The modified low phosphorus diet was well tolerated and was associated with similar phosphate and potassium control but with a wider food choice and greater fiber intake than the standard diet.

Acute interstitial nephritis with podocyte foot-process effacement complicating Plasmodium falciparum infection.

BACKGROUND: Malarial acute renal failure (MARF) is a component of the severe malaria syndrome, and complicates 1-5% of malaria infections. This form of renal failure has not been well characterized by histopathology. CASE PRESENTATION: A 44 year-old male presented to the emergency department with a 5-day history of fever and malaise after returning from Nigeria. A blood film was positive for Plasmodium falciparum. His creatinine was 616 µmol/L coming from a normal baseline of 89 µmol/L. He had a urine protein:creatinine ratio of 346 mg/mmol (4.4 g/L). He required dialysis. A renal biopsy showed acute interstitial nephritis with podocyte foot-process effacement. He was treated with artesunate and his renal function improved. At 1 year follow-up his creatinine had plateaued at 120 µmol/L with persistent low-grade proteinuria. CONCLUSION: Acute interstitial nephritis and podocyte foot-process effacement might be under-recognized lesions in MARF. Studying the mechanisms of MARF could give insight into the immunopathology of severe malaria.

Trends in the treatment of chronic kidney disease-associated anaemia in a cohort of haemodialysis patients: the Irish experience.

BACKGROUND: Anaemia among haemodialysis patients is treated with iron and erythropoietin-stimulating agents (ESAs). ESAs reduce requirements for blood transfusions but are also expensive and overzealous use may be associated with adverse outcomes. Recent international trends have been characterised by reduced ESA doses and a greater reliance on intravenous (IV) iron. We determined trends in prescribing patterns of ESAs and IV iron for the treatment of anaemia in two representative Irish dialysis centres and correlated with current guidelines and international trends. METHODS: Patient data was accessed from the Kidney Disease Clinical Patient Management System (KDCPMS) for the period 2012 to 2014. We generated reports on ESA and iron doses, lab data (haemoglobin (Hb), transferrin saturation (TSAT) and ferritin) and patient population characteristics. We mapped the trends in ESA, iron dosing and lab parameters achieved. A linear mixed model determined the significance of these trends over time. RESULTS: ESA dosing became lower in the second, third and fourth quarters of 2014. Dosing of iron increased throughout but a large increase was seen in the third and fourth quarters of 2014. Ferritin levels decreased and TSAT and haemoglobin levels increased. Changes in iron dosing were significant with p value of < 0.05. CONCLUSIONS: Our findings are consistent with recent global trends toward increasing iron use. Such trends may have economic implications given the high cost of ESAs and the relative affordability of iron. In addition, the potential harm of excessive iron dosing may need to be considered.

Increased Weight Gain During the Long Interdialytic Period Is Associated with Minor Effects on Blood Pressure Control in Clinically Stable In-Centre Haemodialysis Patients.

BACKGROUND/AIMS: Three-day-a-week chronic haemodialysis (cHD) involves 1 long (72 h) and 2 short (48 h) inter-dialytic periods (IDPs). We aimed to determine whether BP control following the long IDP is inferior to the short IDPs. METHODS: All pre- and post-dialysis BP and weight measurements over a 4-week period were retrospectively analyzed among 135 clinically stable cHD patients at 2 academic centres with comparisons between measurements recorded following short and long IDPs. Subsequently, 23 clinically stable cHD patients underwent 24-h ambulatory blood pressure monitoring (ABPM) during the final day/night cycle of the long IDP and 1 short IDP within the same week. RESULTS: In combined and separate analyses of the 2 retrospective cohorts, pre-dialysis BP parameters were not different following long and short IDPs despite greater inter-dialytic weight gain (IDWG) during the long IDP. Subgroup analyses of the total cohort showed no evidence for inferior BP control during the long IDP among those with high %IDWG. In the ABPM study, nocturnal hypertension and loss of nocturnal dipping were frequent. Furthermore, daytime systolic blood pressure (SBP) and pulse pressure were modestly higher during the last day/night cycle of the long compared with short IDP. CONCLUSION: In stable cHD patients, the greater IDWG that occurred during the long IDP was not associated with overtly inferior BP control as reflected in pre-dialysis BP measurements. However, modestly higher daytime SBP was evident towards the end of the long IDP by 24 h ABPM. Thus, while fluid gain has well-documented associations with hypertension and adverse cardiovascular outcomes, the excess IDWG that occurs during the long IDP exerts relatively minor effects on BP control in patients on well-established dialysis regimens that are better identified by ambulatory monitoring.

Quality of care and practice patterns in anaemia management at specialist kidney clinics in Ireland: a national study.

BACKGROUND: Although anaemia is a common complication of advanced chronic kidney disease (CKD), knowledge of quality of care and management practices in specialist clinics varies. We examined anaemia practices at specialist nephrology clinics within the Irish health system and evaluated the opinions of practicing nephrologists. METHODS: A multicentre cross-sectional study was conducted at specialist nephrology clinics across six geographic regions in Ireland. Clinical characteristics and treatment practices were evaluated in a sample of 530 patients with CKD. An accompanying national survey questionnaire captured opinions and treatment strategies of nephrologists on anaemia management. RESULTS: The prevalence of anaemia [defined as haemoglobin (Hb) <12.0 g/dL] was 37.8%, which increased significantly with advancing CKD (from 21% to 63%; P < 0.01) and varied across clinical sites (from 36% to 62%; P < 0.026). Iron deficiency (ID) was present in 46% of all patients tested and 86% of them were not on treatment. More than 45% of anaemic patients were not tested for ID. Respondents differed in their selection of clinical guidelines, threshold targets for erythropoiesis-stimulating agent (ESA) and intravenous iron therapy and anaemia management algorithms were absent in 47% of the clinics. The unexpectedly low rates of ESA use (4.7%) and iron therapy (10.2%) in clinical practice were in contrast to survey responses where 63% of nephrologists indicated ESA therapy initiation when Hb was <10.0 g/dL and 46% indicated commencement of iron therapy for ferritin <150 ng/mL. CONCLUSION: This study highlights substantial variability in the management of anaemia and ID at specialist nephrology clinics with low testing rates for ID, high rates of anaemia and ID and underutilization of effective treatments. Variability in the adoption and implementation of different clinical guidelines was evident.

Diet and Major Renal Outcomes: A Prospective Cohort Study. The NIH-AARP Diet and Health Study.

BACKGROUND: Chronic kidney disease (CKD) is prevalent and associated with significant morbidity and mortality. Dietary modification may be an approach to reducing CKD. DESIGN: In this prospective cohort study, we evaluated the association between diet quality, sodium and potassium intakes, and major renal outcomes. A total of 544,635 community-dwelling adults, aged 51 to 70 years, living in 6 states and 2 urban areas in the United States, from the National Institutes of Health-American Association of Retired Persons Diet and Health Study. Using a food frequency questionnaire completed at baseline, we assessed diet quality using the Alternate Healthy Eating Index (AHEI), Healthy Eating Index (HEI), Mediterranean Diet Score (MDS), Recommended Food Score, and Dietary Approaches to Stop Hypertension (DASH) scores. This was also used to estimate daily sodium and potassium intakes. MAIN OUTCOME MEASURES: Multivariable adjusted competing risks regression calculated sub-hazard ratios (sHRs) for a composite of death due to a renal cause and dialysis, with death due to a nonrenal cause as the competing event. RESULTS: During a mean of 14.3-year follow-up, a total of 4,848 participants died from a renal cause or initiated dialysis. Four diet quality scores (AHEI, HEI, MDS, and DASH) were significantly associated with the composite renal outcome; the Recommended Food Score was not. Compared to the lowest score quintile, the highest quintiles of AHEI (sHR 0.71; 95% confidence interval [CI] 0.65-0.79), HEI (sHR 0.82; 95% CI 0.74-0.91), MDS (sHR 0.84; 95% CI 0.74-0.95), and DASH (sHR 0.85; 95% CI 0.77-0.94) were associated with a reduced hazard of the composite. The highest sodium quintile (sHR 1.17; 95% CI 1.02-1.33 for sodium intake > 3.6 g/day) was associated with an increased hazard, whereas the highest potassium quintile (sHR 0.83 [0.73-0.95]) with a reduced hazard. CONCLUSIONS: Our findings support an association between healthy dietary patterns and reduced risk of major renal outcomes and provide observational evidence to inform dietary guideline recommendations for CKD prevention.

Sodium intake and renal outcomes: a systematic review.

BACKGROUND: Sodium intake is an important determinant of blood pressure; therefore, reduction of intake may be an attractive population-based target for chronic kidney disease (CKD) prevention. Most guidelines recommend sodium intake of < 2.3 g/day, based on limited evidence. We reviewed the association between sodium intake and renal outcomes. METHODS: We reviewed cohort studies and clinical trials, which were retrieved by searching electronic databases, that evaluated the association between sodium intake/excretion and measures of renal function, proteinuria, or new need for dialysis. RESULTS: Of 4,337 reviewed citations, seven (n = 8,129) were eligible, including six cohort studies (n = 7,942) and one clinical trial (n = 187). Four studies (n = 1,787) included patients with CKD. All four cohort studies reported that high intake (> 4.6 g/day) was associated with adverse outcomes (vs. moderate/low), while none reported an increased risk with moderate intake (vs. low). Three studies (n = 6,342) included patients without CKD. Two cohort studies (n = 6,155) reported opposing directions of association between low (vs. moderate) sodium intake and renal outcomes, and one clinical trial (n = 187) reported a benefit from low intake (vs. moderate) on proteinuria but an adverse effect on serum creatinine. CONCLUSIONS: Available, but limited, evidence supports an association between high sodium intake (> 4.6g/day) and adverse outcomes. However, the association with low intake (vs. moderate) is uncertain, with inconsistent findings from cohort studies. There is urgent need to clarify the long-term efficacy and safety of currently recommended low sodium intake in patients with CKD.

Cardiovascular toxicity of epoetin-alfa in patients with chronic kidney disease.

BACKGROUND: Recombinant erythropoietin has become a routine component of care of patients with chronic kidney disease reducing the need for blood transfusions but raising the risks for cardiovascular events. We undertook this secondary analysis of subjects enrolled in the Correction of Hemoglobin and Outcomes in Renal Insufficiency (CHOIR) trial to examine the interrelationships between epoetin-alfa maintenance doses utilized and achieved hemoglobin (Hb) irrespective of treatment target and randomized allocation. METHODS: We performed a post hoc analysis from the CHOIR trial. Inclusion criteria were Hb <11.0 g/dl and estimated glomerular filtration rates of 15-50 ml/min/1.73 m(2). To be included in the present analysis, subjects needed to be free of the composite event at 4 months, receive epoetin-alfa, and have ≥1 postbaseline Hb measurement. The mean weekly dose of epoetin-alfa received up to the time of first event or censure was the main exposure variable, while the achieved Hb at month 4 was the confounder representing the subject's underlying response to treatment. The primary outcome was the composite of death, heart failure hospitalization, stroke, or myocardial infarction. A Cox proportional hazard regression model was used in time-to-event analysis. RESULTS: Among 1,244 subjects with complete data, the average weekly dose of epoetin-alfa ranged 143.3-fold from 133 to 19,106 units/week at the time of first event or censure. Cox proportional hazard analysis found that those in the middle tertile of Hb achieved (>11.5 to <12.7 g/dl) and the lowest tertile of epoetin-alfa dose exposure level (<5,164 units/week) had the lowest risk. Irrespective of Hb achieved, the relative risk in the highest tertile (>10,095 units/week) of epoetin-alfa dose exposure level was significantly escalated (hazard ratios ranged from 2.536 to 3.572, p < 0.05, when compared to the group of middle Hb tertile and lowered dose tertile). In a multivariable model that adjusted for achieved Hb, albumin, cholesterol, age, prior heart failure, prior stroke, prior deep venous thrombosis, atrial fibrillation or malignancy, the average weekly dose had a significant (p = 0.005) relative risk of 1.067 per 1,000 units of epoetin-alfa for the primary end point. CONCLUSIONS: In the CHOIR trial, average epoetin-alfa doses >10,095 units/week were associated with increased risks for cardiovascular events irrespective of the Hb achieved within the first 4 months of treatment. These data suggest the weekly epoetin-alfa dose and not the Hb achieved was a principal determinant in the primary outcome observed implicating a cardiovascular toxicity of this erythrocyte-stimulating agent.

Blood pressure measurement in peritoneal dialysis: which method is best?

BACKGROUND: The optimal approach to monitoring blood pressure (BP) in the peritoneal dialysis (PD) population is unclear. Ambulatory BP monitoring reliably predicts prognosis, but can be inconvenient. The accuracy of home BP monitoring in this population is unproven. The automated BpTRU device (BpTRU Medical Devices, Coquitlam, BC, Canada), which provides an average of up to 6 successive in-office BP measurements, has not been studied in this patient group. METHODS: We studied 17 patients (average age: 54 ± 12 years; 12 men, 5 women; 94% on automated PD) attending a single center. All patients underwent office, home, BpTRU, and ambulatory BP measurement. The reference standard for analysis was daytime ambulatory BP. Correlation between the referent method and each comparator method was determined (Pearson correlation coefficient), and Bland-Altman scatter plots depicting the differences in the BP measurements were constructed. RESULTS: Mean office BP (126.4 ± 16.9/78.8 ± 11.6 mmHg) and BpTRU BP (123.8 ± 13.7/80.7 ± 11.1 mmHg) closely approximated mean daytime ambulatory BP (129.3 ± 14.8/78.2 ± 7.9 mmHg). Mean home BP (143.8 ± 15.0/89.9 ± 28.1 mmHg) significantly overestimated mean daytime systolic BP by 14.2 mmHg (95% confidence interval: 4.3 mmHg to 24.1 mmHg; p = 0.008). Bland-Altman plots demonstrated poorest agreement between home BP and daytime ambulatory BP. No patient had "white-coat hypertension," and only 1 patient had false-resistant hypertension. Most patients showed abnormal nocturnal dipping patterns (non-dipping: n = 11; reverse-dipping: n = 5; normal dipping: n = 1). CONCLUSIONS: We report a novel finding that BP measurement using the BpTRU device is more accurate than home BP measurement in a PD population. Potential explanations for this observation include poor home BP measurement technique, use of poorly validated home BP measurement devices, or a reduced prevalence of white-coat effect among PD patients. Our study also confirms that, in the PD population, BP measurements vary considerably with patient location, time of day, and measurement technique.

Mild chronic kidney disease and functional impairment in community-dwelling older adults.

BACKGROUND: chronic kidney disease (CKD) has been associated with an increased risk of death and cardiovascular events, but its relationship with non-vascular outcomes, including functional impairment (FI), is less well understood. OBJECTIVE: in this study, we review the association between CKD and FI, adjusting for potential confounders and risk factors, with a primary outcome of impairment in any instrumental ADL (IADL) or basic ADL (BADL). DESIGN: the Cardiovascular Multimorbidity in Primary Care Study (CLARITY) is a cross-sectional study of community-dwelling adults. SETTING: participants were adults living in the West of Ireland attending university-affiliated general practices. SUBJECTS: all participants were adults aged ≥50 years living in the community. METHODS: CKD was defined as an estimated glomerular filtration rate (eGFR) ≤60 ml/min/1.73 m(2). A standardised self-reported health questionnaire to measure activities of daily living (ADL) was completed by participants. Logistic regression analyses were used to determine the independent association between CKD and FI. RESULTS: a total of 3,499 patients were included with a mean age of 66.2 ± 10.3 years. 18.0% (n = 630) had CKD (mean eGFR 50.2 ± 9.2 ml/min/1.73m(2)), 21.9% (n = 138) of which had a diagnosis of CKD documented in medical records. 40.4% (n = 1,413) reported FI and multivariable adjustment showed CKD to be independently associated with FI (OR: 1.43, 1.15-1.78), impairment in IADL (OR: 1.43, 1.15-1.78) and impairment in BADL (OR: 1.39, 1.11-1.75). CONCLUSION: our study shows even mild CKD is associated with FI, independent of age, gender, co-morbidities, traditional vascular risk factors and cardiovascular events.

Impact of higher hemoglobin targets on blood pressure and clinical outcomes: a secondary analysis of CHOIR.

BACKGROUND: Targeting a higher hemoglobin in patients with chronic kidney disease leads to adverse cardiovascular outcomes, yet the reasons remain unclear. Herein, we sought to determine whether changes in erythropoiesis-stimulating agent (ESA) dose and in hemoglobin were predictive of changes in blood pressure (BP) and whether these changes were associated with cardiovascular outcomes. METHODS: In this secondary analysis of 1421 Correction of Hemoglobin and Outcomes in Renal Disease (CHOIR) participants, mixed model analyses were used to describe monthly changes in ESA dose and hemoglobin with changes in diastolic BP (DBP) and systolic BP (SBP). Poisson modeling was performed to determine whether changes in hemoglobin and BP were associated with the composite end point of death or cardiovascular outcomes. RESULTS: Monthly average DBP, but not SBP, was higher in participants in the higher hemoglobin arm. Increases in ESA doses and in hemoglobin were significantly associated with linear increases in DBP, but not consistently with increases in SBP. In models adjusted for demographics and comorbid conditions, increases in ESA dose (>0 U) and larger increases in hemoglobin (>1.0 g/dL/month) were associated with poorer outcomes [event rate ratio per 1000 U weekly dose per month increase 1.05, (1.02-1.08), P = 0.002 and event rate ratio 1.70 (1.02-2.85), P = 0.05, respectively]. However, increasing DBP was not associated with adverse outcomes [event rate ratio 1.01 (0.98-1.03), P = 0.7]. CONCLUSION: Among CHOIR participants, higher hemoglobin targets, increases in ESA dose and in hemoglobin were associated both with increases in DBP and with higher event rates; however, increasing DBP was not associated with adverse outcomes.

Effect of hemoglobin target on progression of kidney disease: a secondary analysis of the CHOIR (Correction of Hemoglobin and Outcomes in Renal Insufficiency) trial.

BACKGROUND: Conflicting relationships have been described between anemia correction using erythropoiesis-stimulating agents and progression of chronic kidney disease (CKD). This study was undertaken to examine the impact of target hemoglobin level on progression of kidney disease in the CHOIR (Correction of Hemoglobin and Outcomes in Renal Insufficiency) trial. STUDY DESIGN: Secondary analysis of a randomized controlled trial. SETTING & PARTICIPANTS: 1,432 participants with CKD and anemia. INTERVENTION: Participants were randomly assigned to target hemoglobin levels of 13.5 versus 11.3 g/dL with the use of epoetin alfa. OUTCOMES & MEASUREMENTS: Cox regression was used to estimate HRs for progression of CKD (a composite of doubling of creatinine level, initiation of renal replacement therapy, or death). Interactions between hemoglobin target and select baseline variables (estimated glomerular filtration rate, proteinuria, diabetes, heart failure, and smoking history) also were examined. RESULTS: Participants randomly assigned to higher hemoglobin targets experienced shorter time to progression of kidney disease in both univariate (HR, 1.25; 95% CI, 1.03-1.52; P = 0.02) and multivariable models (HR, 1.22; 95% CI, 1.00-1.48; P = 0.05). These differences were attributable to higher rates of renal replacement therapy and death for participants in the high hemoglobin arm. Hemoglobin target did not interact with estimated glomerular filtration rate, proteinuria, diabetes, or heart failure (P > 0.05 for all). In the multivariable model, hemoglobin target interacted with tobacco use (P = 0.04) such that the higher target had a greater risk of CKD progression for participants who currently smoked (HR, 2.50; 95% CI, 1.23-5.09; P = 0.01), which was not present for those who did not currently smoke (HR, 1.15; 95% CI, 0.93-1.41; P = 0.2). LIMITATIONS: A post hoc analysis; thus, cause and effect cannot be determined. CONCLUSIONS: These results suggest that a high hemoglobin target is associated with a greater risk of progression of CKD. This risk may be augmented by concurrent smoking. Further defining the mechanism of injury may provide insight into methods to optimize outcomes in anemia management.

Sudden cardiac death in dialysis: do current guidelines for implantable cardioverter defibrillator therapy apply to patients with end-stage kidney disease?

Arrhythmic mechanisms account for one in four deaths in end-stage kidney disease. Large-scale randomized controlled trials have demonstrated a mortality benefit from implantable cardioverter defibrillator therapy in carefully selected patient groups at high risk for sudden cardiac death. Unfortunately, patients with end-stage kidney disease were systematically excluded from these trials. Consequently, the applicability of American College of Cardiology (ACC)/American Heart Association (AHA)/Heart Rhythm Society (HRS) guidelines on implantable cardioverter defibrillator therapy to dialysis patients remains uncertain. Observational data suggest that secondary preventative implantable cardioverter defibrillator therapy following resuscitated cardiac arrest prolongs the lives of dialysis patients. This intervention may also offer a survival advantage as a primary preventative strategy in end-stage kidney disease. However, competing risk from co-morbidity can negate any perceived benefit. Device-related complications also negatively impact outcome. The recommendation that primary preventative device implantation be reserved for patients with severely impaired left ventricular function may be excessively restrictive in this high-risk population. Trials of implantable cardioverter defibrillator therapy that include dialysis patients are required to validate existing device eligibility criteria in this unique population. Novel indications for this intervention in dialysis patients should also be identified.

A novel hybrid CFH/CFHR3 gene generated by a microhomology-mediated deletion in familial atypical hemolytic uremic syndrome.

Genomic disorders affecting the genes encoding factor H (fH) and the 5 factor H related proteins have been described in association with atypical hemolytic uremic syndrome. These include deletions of CFHR3, CFHR1, and CFHR4 in association with fH autoantibodies and the formation of a hybrid CFH/CFHR1 gene. These occur through nonallelic homologous recombination secondary to the presence of large segmental duplications (macrohomology) in this region. Using multiplex ligation-dependent probe amplification to screen for such genomic disorders, we have identified a large atypical hemolytic uremic syndrome family where a deletion has occurred through microhomology-mediated end joining rather than nonallelic homologous recombination. In the 3 affected persons of this family, we have shown that the deletion results in formation of a CFH/CFHR3 gene. We have shown that the protein product of this is a 24 SCR protein that is secreted with normal fluid-phase activity but marked loss of complement regulation at cell surfaces despite increased heparin binding. In this study, we have therefore shown that microhomology in this area of chromosome 1 predisposes to disease associated genomic disorders and that the complement regulatory function of fH at the cell surface is critically dependent on the structural integrity of the whole molecule.

In-office assessment of blood pressure in chronic kidney disease: usual measurement versus automated BpTRU measurement.

OBJECTIVES: The automated BpTRU device has been shown to improve the accuracy of in-office blood pressure assessment in hypertensive populations. We aimed to determine whether this was also true for patients with chronic kidney disease. MATERIALS AND METHODS: We recorded the blood pressure of 80 hypertensive outpatients with chronic kidney disease by usual automated measurement and BpTRU automated measurement. We established whether there were any statistically significant differences in the absolute blood pressure values measured by either method and whether these differences had any impact on the assessment of blood pressure control. RESULTS: Systolic and diastolic blood pressures were significantly lower by BpTRU measurement than by usual measurement, by 10.1±12.2 mmHg (95% confidence interval: 7.4-12.8 mmHg, P<0.001) and 2.8±10.6 mmHg (95% confidence interval: 0.4-5.1 mmHg, P=0.02), respectively. Significantly, more patients achieved their blood pressure target of 130/80 mmHg or less by BpTRU measurement than by usual measurement (72.5 vs. 48.8% for systolic blood pressure, P<0.001; 68.8 vs. 61.3% for diastolic blood pressure, P=0.02). Systolic blood pressures remained significantly lower by BpTRU measurement than by usual measurement in all predefined study subgroups (estimated glomerular filtration rate <30 vs ≥30 ml/min/1.73m; transplant vs. nontransplant). We detected more hypotension by BpTRU measurement than by usual measurement. CONCLUSION: Our study suggests that the BpTRU device can negate white coat effect in patients with chronic kidney disease. The use of this device in routine clinical practice could improve the overall accuracy of in-office blood pressure assessment in this high-risk population, minimizing the potential for undertreatment and overtreatment of hypertension.