Austin G. Stack

Hypertension is highly prevalent in chronic kidney disease (CKD), posing a significant but modifiable risk for adverse clinical outcomes. This study explored the prevalence, awareness, treatment, and control of hypertension in older Irish adults with CKD. Data were analysed from participants in Wave 1 of The Irish Longitudinal Study on Ageing (TILDA) who were aged 50 years and older. CKD was defined as eGFR 2, hypertension defined as systolic blood pressure (SBP) ≥140 mmHg and/or diastolic blood pressure (DBP) ≥90 mmHg and/or self-reported use of antihypertensive medication. Participant awareness and treatment of hypertension was based on self-report and SBP/DBP P < .001). Among hypertensive individuals, 70.1% (95% CI: 65.8–74.1) were aware, 83.5% (95% CI 80.0–86.6) were on treatment, yet blood pressure control <140/90 mmHg and SBP <120 mmHg were achieved in only 49.3% (CI 44.0–54.7%) and 17.9% (CI 14.4–22.1), respectively. In multivariable analysis, advancing age 1.05 (CI 1.01–1.10), obesity 6.23 (CI 2.51–15.5), diabetes 5.78 (CI 1.55–21.5), and cardiovascular disease 9.89 (CI 3.27–29.9) were associated with higher odds of treatment, while cardiovascular disease 2.35 (CI 1.39–3.99) and combination antihypertensive therapy 1.76 (CI 1.03–3.01) were associated with blood pressure control. The prevalence of hypertension is substantial in older Irish adults with CKD; however, control is poor. Approximately, one-third of participants were unaware of their hypertensive status and approximately one-fifth were untreated.

Key Points: The SAPPHIRE trial was designed to assess albuminuria-lowering effects of the urate transporter 1 inhibitor verinurad combined with allopurinol in patients with CKD. Verinurad 3, 7.5, and 12 mg in combination with allopurinol 300 mg did not reduce albuminuria during 34 weeks treatment compared with allopurinol alone or placebo. Verinurad/allopurinol combination dose-dependently reduced serum urate concentrations compared with placebo. Background: Hyperuricemia is associated with elevated risks of cardiovascular and chronic kidney disease (CKD). Since inhibition of urate transporter 1 has been suggested to be potentially nephroprotective, we performed a phase 2b study to assess albuminuria-lowering effects of the urate transporter 1 inhibitor verinurad combined with the xanthine oxidase inhibitor allopurinol in patients with CKD and hyperuricemia. Methods: In this randomized placebo and active controlled trial, we enrolled participants with serum urate concentrations ≥6.0 mg/dl, eGFR ≥25 ml/min per 1.73 m², and a urinary albumin-creatinine ratio (UACR) 30–5000 mg/g to one of five treatment arms: placebo, placebo+allopurinol 300 mg/day, verinurad 3 mg+allopurinol 300 mg/day, verinurad 7.5 mg+allopurinol 300 mg/day, or verinurad 12 mg+allopurinol 300 mg/day in a 1:1:1:1:1 ratio. The primary end point was the change in UACR from baseline to 34 weeks. Secondary end points were changes from baseline in UACR at week 60 and changes in serum urate and eGFR at weeks 34 and 60. Results: Between August 2019 and November 2021, 861 adults with CKD (mean age 65 years, 33.0% female, mean eGFR 48 ml/min per 1.73 m², median UACR 217 mg/g) were enrolled. At 34 weeks, the geometric mean percentage change in UACR from baseline did not differ among treatment groups (16.7%, 95% confidence interval [CI], −0.6 to 37.1 in the 3 mg group, 15.0% [95% CI, −1.85 to 34.6] in the 7.5 mg group, 14.0% [95% CI, −3.4 to 34.4] in the 12 mg group versus 9.9% [95% CI, −6.6 to 29.4] in the allopurinol group, and 37.3% [95% CI, 16.6 to 61.8] in the placebo group). UACR and eGFR change from baseline did not differ among treatment groups after 60 weeks. Verinurad/allopurinol combination dose-dependently reduced serum urate concentrations compared with placebo. The proportion of patients with adverse events and serious adverse events was balanced among treatment groups. Conclusions: Verinurad in combination with allopurinol did not decrease UACR or eGFR decline, but further reduced serum urate compared with allopurinol alone or placebo. Clinical Trial registry name and registration number: SAPPHIRE Trial registration number, NCT03990363.

Background: Anaemia is a common but treatable condition that predicts adverse clinical outcomes. However, standards of anaemia management vary considerably. Aim: To estimate the prevalence of anaemia and extent of screening for common underlying causes in the healthcare system in the Republic of Ireland. Design & setting: We conducted a retrospective cohort study of 112 181 adult patients, aged ≥18 years, who had a full blood count performed in 2013, using data from the National Kidney Disease Surveillance System. Method: The prevalence of anaemia was determined across demographic and clinical subgroups, according to World Health Organization (WHO) definitions. The proportion screened for iron, vitamin B12, and folate deficiency was determined within a 3-month follow-up period and the corresponding prevalence for each deficiency determined. Results: The overall prevalence of anaemia was 12.0% (95% confidence interval [CI] = 11.8% to 12.2%) and was higher in women than men (13.2% versus 10.5%, P 75 years) and worsening kidney function (8.2%, 10.9%, 33.2%, and 63.8% for each estimated glomerular filtration rate [eGFR] categories >90, 60–89, 30–59 and P <0.001). After 3-months' follow-up, the proportion screened for iron deficiency was 11.2% based on transferrin saturation and 33.7% using serum ferritin. Screening for folate and B12 deficiency was 17.6% and 19.8%, respectively. Among screened patients, the prevalence of iron deficiency, B12, and folate deficiency was 37.0%, 6.3%, and 5.8%, respectively. Conclusion: The burden of anaemia in the healthcare system is substantial especially for older patients and those with advanced kidney disease. Low screening rates for iron, B12, and folate deficiency are common and warrant quality improvement initiatives.

Background: Abnormalities of serum sodium are associated with increased mortality risk in hospitalised patients, but it is unclear whether, and to what extent other factors influence this relationship. We investigated the impact of dysnatraemia on total and cause-specific mortality in the Irish health system while exploring the concurrent impact of age, kidney function and designated clinical work-based settings. Methods: A retrospective cohort study of 32,666 participants was conducted using data from the National Kidney Disease Surveillance System. Hyponatraemia was defined as < 135 mmol/L and hypernatraemia as > 145 mmol/L with normal range 135–145 mmol/L. Multivariable Cox proportional hazards regression was used to estimate hazard ratios (HR’s) and 95% Confidence Intervals (CIs) while penalised spline models further examined patterns of risk. Results: There were 5,114 deaths (15.7%) over a median follow up of 5.5 years. Dysnatraemia was present in 8.5% of patients overall. In multivariable analysis, both baseline and time-dependent serum sodium concentrations exhibited a U-shaped association with mortality. Hyponatremia was significantly associated with increased risk for cardiovascular [HR 1.38 (1.18–1.61)], malignant [HR: 2.49 (2.23–2.78)] and non-cardiovascular/non-malignant causes of death [1.36 (1.17–1.58)], while hypernatremia was significantly associated with cardiovascular [HR: 2.16 (1.58–2.96)] and non-cardiovascular/ non-malignant deaths respectively [HR: 3.60 (2.87–4.52)]. The sodium-mortality relationship was significantly influenced by age, level of kidney function and the clinical setting at baseline (P < 0.001). For hyponatraemia, relative mortality risks were significantly higher for younger patients (interaction term P < 0.001), for patients with better kidney function, and for patients attending general practice [HR 2.70 (2.15–3.36)] than other clinical settings. For hypernatraemia, age and kidney function remained significant effect modifiers, with patients attending outpatient departments experiencing the greatest risk [HR 9.84 (4.88–18.62)] than patients who attended other clinical locations. Optimal serum sodium thresholds for mortality varied by level of kidney function with a flattening of mortality curve observed for patients with poorer kidney function. Conclusion: Serum sodium concentrations outside the standard normal range adversly impact mortality and are associated with specific causes of death. The thresholds at which these risks appear to vary by age, level of kidney function, and are modified in specific clinical settings within the health system.

Key Points: The study compares the effect of vascular access (arteriovenous fistula versus central venous catheter) on health-related quality of life. Arteriovenous fistula users were more satisfied with their access but dissatisfied with physical complications of access type, including bruising, bleeding, and pain. Central venous catheter users were more dissatisfied with social aspects of access care such as showering and bathing. Background: Arteriovenous fistulae (AVF) have superior clinical outcomes compared with central venous catheters (CVC) among patients undergoing hemodialysis (HD). Yet, there is increasing recognition that health-related quality of life (HRQoL) may be more important to patients than survival and that differences may exist between AVF and CVCs in this regard. This study compared HRQoL between AVF and CVC in an Irish cohort. Methods: We conducted a cross-sectional survey among prevalent patients undergoing hemodialysis (N=119) dialyzing with either an AVF or CVC at a regional program. The Short Form 36 (SF-36) and a validated Vascular Access Questionnaire (SF-VAQ) compared QoL between AVF and CVC in domains of physical functioning, social functioning, and dialysis complications. Multivariable logistic regression compared differences between groups for outcomes of physical functioning, social functioning, and dialysis complications expressed as adjusted odds ratios and 95% CI. Results: Mean age was 66.6 years; 52% were using an AVF and 48% had a CVC. Patients dialyzing with an AVF were more satisfied with their access when asked directly (6.2 versus 5.0; PP=0.001, P=0.001, and PPP=0.04) but more likely to report dialysis complications (OR=1.94; 95% CI, 0.69 to 5.87; P=0.22). Conclusions: Vascular access contributes to HRQoL in hemodialysis. CVCs are associated with fewer difficulties from bleeding and bruising but greater negative effect on social activities, including bathing and showering. Overall, patients with a CVC had lower dissatisfaction scores than patients with an AVF when all three domains were added. Innovation in vascular access design and engineering may confer benefits and improve patient comfort on HD.

Background: Although the arteriovenous fistula (AVF) confers superior benefits over central venous catheters (CVCs), utilization rates remain low among prevalent patients on hemodialysis (HD). The goal of this study was to determine the evolution of vascular access type in the first year of dialysis and identify factors associated with conversion from CVC to a functioning AVF. Methods: We studiedadult patients (n=610) who began HD between the January 1, 2015 and December 31, 2016 and were treated for at least 90 days, using data from the National Kidney Disease Clinical Patient Management System in the Irish health system. Prevalence of vascular access type was determined at days 90 and 360 after dialysis initiation and at 30-day intervals. Multivariable logistic regression explored factors associated with CVC at day 90, and Cox regression evaluated predictors of conversion from CVC to AVF on day 360. Results: CVC use was present in 77% of incident patients at day 90, with significant variation across HD centers (from 63% to 91%, P77 years versus referent, adjusted hazard ratio [HR], 0.43; 95% CI, 0.19 to 0.96), for patients with a lower BMI (per unit decrease in BMI, HR, 0.95; 95% CI, 0.93 to 0.98), and varied significantly across HD centers (from an HR of 0.25 [95% CI, 0.08 to 0.74] to 2.09 [95% CI, 1.04 to 4.18]). Conclusion: CVCs are the predominant type of vascular access observed during the first year of dialysis, with low conversion rates from CVC to AVF. There is substantial center variation in the Irish health system that is not explained by patient-related factors alone.