Mark Canney

Single Agent Antihypertensive Therapy and Orthostatic Blood Pressure Behaviour in Older Adults Using Beat-to-Beat Measurements: The Irish Longitudinal Study on Ageing.

Background Impaired blood pressure (BP) stabilisation after standing, defined using beat-to-beat measurements, has been shown to predict important health outcomes. We aimed to define the relationship between individual classes of antihypertensive agent and BP stabilisation among hypertensive older adults. Methods Cross-sectional analysis from The Irish Longitudinal Study on Ageing, a cohort study of Irish adults aged 50 years and over. Beat-to-beat BP was recorded in participants undergoing an active stand test. We defined grade 1 hypertension according to European Society of Cardiology criteria (systolic BP [SBP] 140-159mmHg ± diastolic BP [DBP] 90-99mmHg). Outcomes were: (i) initial orthostatic hypotension (IOH) (SBP drop ≥40mmHg ± DBP drop ≥20mmHg within 15 seconds [s] of standing accompanied by symptoms); (ii) sustained OH (SBP drop ≥20mmHg ± DBP drop ≥10mmHg from 60 to 110s inclusive); (iii) impaired BP stabilisation (SBP drop ≥20mmHg ± DBP drop ≥10mmHg at any 10s interval during the test). Outcomes were assessed using multivariable-adjusted logistic regression. Results A total of 536 hypertensive participants were receiving monotherapy with a renin-angiotensin-aldosterone-system inhibitor (n = 317, 59.1%), beta-blocker (n = 89, 16.6%), calcium channel blocker (n = 89, 16.6%) or diuretic (n = 41, 7.6%). A further 783 untreated participants met criteria for grade 1 hypertension. Beta-blockers were associated with increased odds of initial OH (OR 2.05, 95% CI 1.31–3.21) and sustained OH (OR 3.36, 95% CI 1.87–6.03) versus untreated grade 1 hypertension. Multivariable adjustment did not attenuate the results. Impaired BP stabilisation was evident at 20s (OR 2.59, 95% CI 1.58–4.25) and persisted at 110s (OR 2.90, 95% CI 1.64–5.11). No association was found between the other agents and any study outcome. Conclusion Beta-blocker monotherapy was associated with a >2-fold increased odds of initial OH and a >3-fold increased odds of sustained OH and impaired BP stabilisation, compared to untreated grade 1 hypertension. These findings support existing literature questioning the role of beta-blockers as first line agents for essential hypertension.

Posterior Reversible Encephalopathy Syndrome in End-Stage Kidney Disease: Not Strictly Posterior or Reversible

Posterior reversible encephalopathy syndrome (PRES) is an uncommon clinico-radiological condition that can result in severe brain injury. The pathogenesis of cerebral vasogenic edema, the hallmark of PRES, is not fully understood. Despite its name, there is substantial heterogeneity both in terms of imaging findings and outcome. Relatively little is known about PRES in kidney disease despite the clustering of risk factors including hypertension, autoimmune disease and immunosuppression. In a retrospective observational study of incident end-stage kidney disease patients in Southwest Ireland over a ten year period, we discovered five cases of PRES representing an incidence of 0.84% in this patient population. These five cases highlight the variability in clinical presentation and the potentially life-threatening nature of this condition. We provide an in-depth review of the existing literature regarding PRES in terms of its pathogenesis and heterogeneity, as well as the experience of PRES in ESKD patients. PRES appears to be rare in the ESKD population but could be under-recognized. Marked hypertension is a cardinal risk factor in this population, associated with extracellular fluid volume expansion. Neuroimaging findings can be diverse involving both anterior and posterior circulation territories. Three of the five patients described had commenced haemodialysis within four weeks of their presentation. These patients may be particularly vulnerable to microvascular brain injury, which can be devastating. This emphasises the need for clinicians to pay meticulous attention to extracellular fluid volume control during this potentially hazardous period.

Injurious Falls and Syncope in Older Community-Dwelling Adults Meeting Inclusion Criteria for SPRINT

Injurious Falls and Syncope in Older Community-Dwelling Adults Meeting Inclusion Criteria for SPRINT The Systolic Blood Pressure Intervention Trial (SPRINT) demonstrated that treating adults 75 years of age or older with hypertension to reach a systolic blood pressure target of less than 120 mm Hg compared with a systolic blood pressure target of less than 140 mm Hg reduced the numbers of cardiovascular events and death without a significant increase in the number of injurious falls or syncope.1 However, prior to the adoption of an intensive strategy to lower systolic blood pressure in the oldest segment of the population, it is prudent to determine if individuals meeting inclusion criteria for SPRINT outside the clinical trial context are similar to trial participants, especially with regard to risk for adverse outcomes. We used The Irish Longitudinal Study on Ageing2,3 (TILDA) to compare baseline rates of injurious falls and syncope in community-dwelling older adults with the rates in the standard care group of SPRINT.

Spatial and Temporal Clustering of Anti-Glomerular Basement Membrane Disease

BACKGROUND AND OBJECTIVES An environmental trigger has been proposed as an inciting factor in the development of anti-GBM disease. This multicenter, observational study sought to define the national incidence of anti-GBM disease during an 11-year period (2003-2014) in Ireland, investigate clustering of cases in time and space, and assess the effect of spatial variability in incidence on outcome. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We ascertained cases by screening immunology laboratories for instances of positivity for anti-GBM antibody and the national renal histopathology registry for biopsy-proven cases. The population at risk was defined from national census data. We used a variable-window scan statistic to detect temporal clustering. A Bayesian spatial model was used to calculate standardized incidence ratios (SIRs) for each of the 26 counties. RESULTS Seventy-nine cases were included. National incidence was 1.64 (95% confidence interval [95% CI], 0.82 to 3.35) per million population per year. A temporal cluster (n=10) was identified during a 3-month period; six cases were resident in four rural counties in the southeast. Spatial analysis revealed wide regional variation in SIRs and a cluster (n=7) in the northwest (SIR, 1.71; 95% CI, 1.02 to 3.06). There were 29 deaths and 57 cases of ESRD during a mean follow-up of 2.9 years. Greater distance from diagnosis site to treating center, stratified by median distance traveled, did not significantly affect patient (hazard ratio, 1.80; 95% CI, 0.87 to 3.77) or renal (hazard ratio, 0.76; 95% CI, 0.40 to 1.13) survival. CONCLUSIONS To our knowledge, this is the first study to report national incidence rates of anti-GBM disease and formally investigate patterns of incidence. Clustering of cases in time and space supports the hypothesis of an environmental trigger for disease onset. The substantial variability in regional incidence highlights the need for comprehensive country-wide studies to improve our understanding of the etiology of anti-GBM disease.

Mortality in Relation to Changes in a Healthy Aging Index: The Health, Aging, and Body Composition Study

Background Baseline scores on a Healthy Aging Index (HAI), including 5 key physiological domains, strongly predict health outcomes. This study aimed to characterize 9-year changes in a HAI and explore their relationship to subsequent mortality. Methods Data are from the Health, Aging and Body Composition study of well-functioning adults aged 70-79. A HAI, which ranges from 0-10, was constructed at year 1 and year 10 of the study including systolic blood pressure, forced expiratory volume, digit symbol substitution test, cystatin C and fasting glucose. The relationships between the HAI at year 1 and year 10 and the change between years and subsequent mortality until year 17 were estimated from Cox proportional hazards models. Results 2264 participants had complete data on a HAI at year 1, of these 1122 had complete data at year 10. HAI scores tended to increase (i.e., get worse) over 9-year follow-up, from (mean (SD)) 4.3 (2.1) to 5.7 (2.1); mean within person change 1.5 (1.6). After multivariable adjustment HAI score was related to mortality from year 1 (Hazard Ratio (95% Confidence Interval) =1.17 (1.13 - 1.21) per unit) and year 10 (1.20 (1.14 - 1.27) per unit). The change between years was also related to mortality (1.08 (1.02 - 1.15) per unit change). Conclusions HAI scores tended to increase with advancing age and stratified mortality rates among participants remaining at year 10. The HAI may prove useful to understand changes in health with aging.

Kidney Function Estimated From Cystatin C, But Not Creatinine, Is Related to Objective Tests of Physical Performance in Community-Dwelling Older Adults

Background The burden of chronic kidney disease is highest among older adults but the significance of a diminished level of kidney function in this heterogeneous population is poorly understood. We sought to examine the relationship between estimated glomerular filtration rate (eGFR) and objective physical performance in older adults. Methods Cross-sectional analysis of 4,562 participants from The Irish Longitudinal Study on Ageing, a national cohort of community-dwelling adults aged ≥50 years. We used multivariable linear or quantile regression to model the association between categories of cystatin C (eGFRcys) or creatinine eGFR (eGFRcr) and the following outcomes: gait speed, timed-up-and-go (TUG) and grip strength. Relationships were further explored using natural eGFR splines. We examined effect modification by age in the relationship between eGFR and gait speed. Results Mean (SD) age was 61.8 (8.3) years, 53.6% were female and median (IQR) eGFRcys was 82 (70-94) mL/min/1.73m2. In multivariable-adjusted models, participants in the lowest eGFRcys category (< 45 mL/min/1.73m2) had 3.32 cm/s (95% confidence interval [95%CI] 0.02-6.62) slower mean gait speed, 1.32 kg (95%CI 0.20-2.44) lower mean grip strength, and 0.31 seconds (95% CI -0.04 to 0.65) longer median TUG versus the reference group (eGFRcys ≥ 90 mL/min/1.73m2). The relationship between eGFRcys and outcomes appeared linear but varied by age. The association between eGFRcr and outcomes tended towards a U-shape. Conclusions Cystatin C eGFR was linearly related to poorer physical performance beyond middle age among community-dwelling adults. The non-linear relationships observed with eGFRcr underscore the limitations of creatinine as a predictor of frailty outcomes in older individuals.

Graded Association Between Kidney Function and Impaired Orthostatic Blood Pressure Stabilization in Older Adults

Background Impaired orthostatic blood pressure (BP) stabilization is highly prevalent in older adults and is a predictor of end‐organ injury, falls, and mortality. We sought to characterize the relationship between postural BP responses and the kidney. Methods and Results We performed a cross‐sectional analysis of 4204 participants from The Irish Longitudinal Study on Ageing, a national cohort of community‐dwelling adults aged ≥50 years. Beat‐to‐beat systolic and diastolic BP were measured during a 2‐minute active stand test. The primary predictor was cystatin C estimated glomerular filtration rate (eGFR) categorized as follows (mL/min per 1.73 m2): ≥90 (reference, n=1414); 75 to 89 (n=1379); 60 to 74 (n=942); 45 to 59 (n=337); <45 (n=132). We examined the association between eGFR categories and (1) sustained orthostatic hypotension, defined as a BP drop exceeding consensus thresholds (systolic BP drop ≥20 mm Hg±diastolic BP drop ≥10 mm Hg) at each 10‐second interval from 60 to 110 seconds inclusive; (2) pattern of BP stabilization, characterized as the difference from baseline in mean systolic BP/diastolic BP at 10‐second intervals. The mean age of subjects was 61.6 years; 47% of subjects were male, and the median eGFR was 82 mL/min per 1.73 m2. After multivariable adjustment, participants with eGFR <60 mL/min per 1.73 m2 were approximately twice as likely to have sustained orthostatic hypotension (P=0.008 for trend across eGFR categories). We observed a graded association between eGFR categories and impaired orthostatic BP stabilization, particularly within the first minute of standing. Conclusions We report a novel, graded relationship between diminished eGFR and impaired orthostatic BP stabilization. Mapping the postural BP response merits further study in kidney disease as a potential means of identifying those at risk of hypotension‐related events.

Nephrotic syndrome and hepatitis due to acquired syphilis: an uncommon presentation of a re-emerging disease.

The association between secondary syphilis and nephrotic syndrome has been documented in the distant past but is particularly rare in modern times. We report the diagnostic dilemma that was the case of a 41-year-old gentleman who presented to hospital with a profound nephrotic syndrome, rash and simultaneous hepatitis. After extensive investigation, a unifying diagnosis of secondary syphilis was made. Treatment with penicillin resulted in complete resolution of his multi-systemic illness. A summary of the patient’s presentation and progress is provided as well as a concise review of the relevant literature and important teaching points from this challenging case.

The relationship between kidney function and quality of life among community-dwelling adults varies by age and filtration marker

Abstract Background The impact of a diminished level of kidney function on the well-being of an older individual is poorly understood. We sought to determine the association between estimated glomerular filtration rate (eGFR) and overall quality of life (QoL) among older adults. Methods Cross-sectional analysis of 4293 participants from the Irish Longitudinal Study on Ageing, a population-based study of community-dwelling adults ≥50 years of age. We used multivariable negative binomial regression to model the relationship between categories of cystatin C eGFR (eGFRcys) or creatinine eGFR (eGFRcr) and the number of QoL deficits from the Control, Autonomy, Self-realization and Pleasure (CASP-19) scale, a holistic measure of QoL among older adults (range 0–57). We further explored this relationship across age strata. Results Median age was 61 [interquartile range (IQR) 55–68] years, 53% were female, mean (SD) CASP-19 score was 44.8 (7.4) and median eGFRcys was 81 (IQR 68–93) mL/min/1.73 m2. After multivariable adjustment, participants with eGFRcys <45 mL/min/1.73 m2 had 14% greater QoL deficits {incidence rate ratio 1.14 (95% confidence interval 1.03–1.25)] relative to the reference group (eGFRcys ≥90 mL/min/1.73 m2). This relationship appeared linear across eGFRcys categories and was more pronounced in younger (50–64 years) compared with older participants (65–74 or ≥75 years). There was no substantive relationship between eGFRcr and CASP-19. Conclusions Cystatin C but not creatinine eGFR was associated with clinically modest declines in QoL among a large sample of community-dwelling older adults. This relationship varied by age, suggesting that a diminished eGFR contributes little to overall QoL beyond middle age in this population.

Examining the utility of cystatin C as a confirmatory test of chronic kidney disease across the age range in middle-aged and older community-dwelling adults

Background Cystatin C has been proposed as a confirmatory test of chronic kidney disease (CKD). This is most applicable to older individuals with CKD, the majority of whom have a creatinine-based estimated glomerular filtration rate (eGFR) of 45–59 mL/min/1.73 m2 (CKD stage 3a). We sought to examine the utility of cystatin C as a confirmatory test of CKD across the age range in the general population of older adults. Methods Cross-sectional analysis of 5386 participants from The Irish Longitudinal Study on Ageing, a cluster-sampled national cohort of community-dwelling adults aged ≥50 years. Cystatin C and creatinine were measured simultaneously using standardised assays. Using generalised additive models, we modelled the distributions of creatinine and cystatin C per year of age from four distributional parameters: location, dispersion, skewness, kurtosis. Among participants with CKD stage 3a, we estimated the predicted probability of cystatin C eGFR <60 mL/min/1.73 m2 (‘confirmed CKD’) as a function of age. Results Median age was 62 years, 53% were female and median cystatin C eGFR was 80 mL/min/1.73 m2. We observed progressive variability in cystatin C with increasing age. Compared with creatinine, cystatin C levels rose sharply beyond the age of 65. Among participants with CKD stage 3a (n=463), the predicted probability of ‘confirmed CKD’ increased steadily with age, from 15% at age 50 to 80% at age 80. Conclusions The clinical utility of cystatin C may be maximised in middle-aged individuals, in whom the distribution of cystatin C is less variable than older adults, and the pretest probability of confirming CKD is lower.