Robert MacGinley

Dietary salt loading impairs arterial vascular reactivity

BACKGROUND Studies of sodium have shown improvements in vascular function and blood pressure (BP). The effect of chronic sodium loading from a low-sodium diet to a Western diet on vascular function and BP has been less well studied. OBJECTIVE The objective was to examine the effects of dietary salt intake on vascular function and BP. DESIGN Thirty-five hypertensive volunteers met the inclusion criteria. After a 2-wk run-in with a low-sodium diet (60 mmol/d), the participants maintained their diets and were randomly assigned to receive sequentially 1 of 3 interventions for 4 wk, with a 2-wk washout between interventions: sodium-free tomato juice (A), tomato juice containing 90 mmol Na (B), and tomato juice containing 140 mmol Na (C). The outcomes were changes in pulse wave velocity (PWV), systolic BP (SBP), and diastolic BP (DBP). RESULTS The difference in PWV between interventions B and A was 0.39 m/s (95% CI: 0.18, 0.60 m/s; P < or = 0.001) and between C and A was 0.35 m/s (95% CI: 0.13, 0.57 m/s; P < or = 0.01). Differences in SBP and DBP between interventions B and A were 4.4 mm Hg (95% CI: 1.2, 7.8 mm Hg; P < or = 0.01) and 2.4 mm Hg (95% CI: 0.8, 4.1 mm Hg; P < or = 0.001), respectively, and between interventions C and A were 5.6 mm Hg (95% CI: 2.7, 8.4 mm Hg; P < or = 0.01) and 3.3 mm Hg (95% CI: 1.5, 5.0 mm Hg; P < or = 0.001), respectively. Changes in PWV correlated with changes in SBP (r = 0.52) and DBP (r = 0.58). CONCLUSIONS Dietary salt loading produced significant increases in PWV and BP in hypertensive volunteers. Correlations between BP and PWV suggest that salt loading may have a BP-independent effect on vascular wall function. This further supports the importance of dietary sodium restriction in the management of hypertension. This trial was registered with the Australian and New Zealand Clinical Trials Registry as ACTRN12609000161224.

KHA‐CARI Guideline: Vascular access – central venous catheters, arteriovenous fistulae and arteriovenous grafts

Department of Nephrology, Monash Medical Centre, Department of Medicine, Monash University, Department of Radiology, Austin Health, Melbourne, Victoria, Department of Renal Medicine, Fremantle Hospital, Fremantle, Western Australia, Department of Nephrology, Royal Adelaide Hospital, Adelaide, South Australia, Department of Renal Medicine, The Canberra Hospital, Canberra, Australian Capital Territory, and Centre for Kidney Research, The Children’s Hospital at Westmead, Sydney, New South Wales, Australia

Dietary sodium loading in normotensive healthy volunteers does not increase arterial vascular reactivity or blood pressure

Background:  Studies of dietary sodium on vascular function and blood pressure in normotensive volunteers have shown conflicting results. There are very limited data available on the effect of chronic sodium loading from a low‐sodium diet to a high‐sodium diet on vascular function and blood pressure in normotensive volunteers.

KHA-CARI guideline: use of iron in chronic kidney disease patients

a. That therapeutic iron be used to correct diagnosed iron deficiency (1D). b. Parenteral iron (intravenous) is administered in preference to oral iron to correct iron deficiency. As it is more likely to: • achieve target haemoglobin (Hb) levels (1B), • maintain ferritin and transferrin saturation (%TSAT) at target ranges (1C), • reduce erythropoiesis stimulating agent (ESA) dose requirements (1C) and • have fewer adverse reactions (1C).

KHA-CARI guideline: biochemical and haematological targets: haemoglobin concentrations in patients using erythropoietin-stimulating agents.

GUIDELINE RECOMMENDATIONS • We recommend against haemoglobin targets above 130 g/L due to the strong association with increased morbidity and mortality in chronic kidney disease (CKD) (1A).* • For many anaemic patients with CKD, we suggest a haemoglobin target of between 100 and 115 g/L, balancing risks and benefits for each patient treated, in order to alleviate symptoms and reduce the risk of blood transfusion (2A).* • We suggest that in dialysis patients with anaemia due to CKD, an erythropoiesis-stimulating agent (ESA) can be used to prevent the haemoglobin falling below 95 g/L in order to avoid the need for blood transfusion (2B)* and to improve quality of life (2D).* • We suggest that ESA are indicated for the partial correction of the anaemia of CKD in patients who are symptomatic or who may otherwise require blood transfusion (2A).*

Role of distal protection devices

Date written: November 2008

International treatment guidelines for anaemia in chronic kidney disease — what has changed?

ne ea no five stages O in nine Australians has chronic kidney disse (CKD),1 although the condition may often t be recognised in primary care.2 There are of CKD, ranging from Stage 1, in which patients have normal renal function but urinary abnormalities, structural abnormalities or genetic traits pointing to kidney disease, through to Stage 5, in which patients have end-stage disease.1 Although anaemia in patients with CKD is multifactorial in origin, it is primarily associated with relative erythropoietin production deficiency3 as the glomerular filtration rate (GFR) falls. Once the estimated GFR trends below 60 mL/min/1.73 m2 (Stage 3a CKD), erythropoietin production by the kidneys falls, and anaemia may develop. The history of anaemia management in CKD and associated clinical practice guidelines has been one of contradiction and perceived industry influence.4 The publication in August 2012 by the Kidney Disease: Improving Global Outcomes (KDIGO) group (an international collaboration of nephrologists) of a guideline that updates and informs clinical practice in this area5 was therefore welcome. The KDIGO guideline contains 47 recommendations with varying grades of evidence (Box).5 It is noteworthy that the conclusions, recommendations and ungraded suggestions for clinical practice in the KDIGO guideline are largely consistent with those currently provided in the Kidney Health Australia–Caring for Australasians with Renal Impairment (KHA-CARI) guidelines.6,7 Of particular note, the KDIGO guideline takes into account the importance of balancing the risks and benefits of erythropoietin-stimulating agents (ESAs) and iron therapy. A key aspect of the KDIGO guideline is that it recommends more caution in the use of erythropoietin. poietin 30 years ago was t led to the clinical develerythropoietin and thus anaemia in patients with l studies suggested that haemoglobin levels had ith higher targets.4 This conclusion was supported by the clinical consequences of anaemia (including fatigue, exercise intolerance, cognitive impairment and exacerbation of cardiovascular disease)3 and led clinicians to virtually demand ESAs for the treatment of CKD-associated anaemia. It was therefore ironic that the first randomised controlled trials to evaluate the outcomes of higher versus lower haemoglobin targets, using recombinant human erythropoietin, found the unexpected reverse outcome of negative effects (increased cardiovascular events and mortality) in patients randomly assigned to the higher targets.8,9 The evidence now seems to suggest that haemoglobin target levels between 100 and 115 g/L should be the aim for patients with CKD, and certainly not levels > 130 g/L,10 which have the potential to cause harm. In fact, the KDIGO guideline reaffirms the very strong (Grade 1A) KHA-CARI recommendation of not targeting haemoglobin concentrations > 130 g/L.7,10 There are also newer cautionary recommendations, not covered by the KHACARI guidelines, regarding ESA use in patients with active malignancy (1B), a history of stroke (1B) or a history of malignancy (2C), where there is greater potential for harm. The recommendations in the KDIGO guideline relating to the use of iron supplementation are similar to those in the KHA-CARI guidelines.6 They include the recommendation that oral iron supplementation is inadequate compared with injectable iron. This is problematic for most general practitioners, as intravenous iron cannot be administered in general practice, due to the need for monitoring. However, intravenous iron therapy may sometimes be arranged for the patient at a local hospital. Further, the KDIGO guideline recommends the use of iron indices to help guide therapy, with considerations of infection risk from excess iron and suboptimal ESA responsiveness.

Inhibition of the renin–angiotensin system

Date written: December 2008

Efficacy and Safety of Oral Methazolamide in Patients With Type 2 Diabetes: A 24-Week, Placebo-Controlled, Double-Blind Study

OBJECTIVE To evaluate the safety and efficacy of methazolamide as a potential therapy for type 2 diabetes. RESEARCH DESIGN AND METHODS This double-blind, placebo-controlled study randomized 76 patients to oral methazolamide (40 mg b.i.d.) or placebo for 24 weeks. The primary efficacy end point for methazolamide treatment was a placebo-corrected reduction in HbA1c from baseline after 24 weeks (ΔHbA1c). RESULTS Mean ± SD baseline HbA1c was 7.1 ± 0.7% (54 ± 5 mmol/mol; n = 37) and 7.4 ± 0.6% (57 ± 5 mmol/mol; n = 39) in the methazolamide and placebo groups, respectively. Methazolamide treatment was associated with a ΔHbA1c of –0.39% (95% CI –0.82, 0.04; P < 0.05) (–4.3 mmol/mol [–9.0, 0.4]), an increase in the proportion of patients achieving HbA1c ≤6.5% (48 mmol/mol) from 8 to 33%, a rapid reduction in alanine aminotransferase (∼10 units/L), and weight loss (2%) in metformin-cotreated patients. CONCLUSIONS Methazolamide is the archetype for a new intervention in type 2 diabetes with clinical benefits beyond glucose control.

Screening tests for diagnosis of renal artery stenosis

Date written: December 2008