Navigating the Challenges of Evidence-based Chronic Kidney Disease Care


Nutrition Examination Survey (NHANES) 1999–2004 show that adults with CKD are less likely to have awareness, treatment and control of BP than those without evidence of CKD.5


One RCT of 52 patients with


non-diabetic proteinuric CKD comparing dual versus single RAAS blockade followed by low and regular sodium diets was remarkable not only for its result (which was that low sodium diet plus single RAAS blockade reduced BP and attenuated proteinuria significantly more effectively than dual RAAS blockade), but also for addressing a question highly relevant to achieving BP targets with multiple interventions in this population.12


Table 1: Methods of Blood Pressure Measurement Method


Advantages Office/clinic blood pressure measurement and observational studies


Disadvantages Most commonly used in RCTs Highly variable,


observer bias, white-coat HTN


Self/home blood pressure Improves patient compliance Requires training monitoring (HBPM)


Multiple interventions are the mainstay of CKD care, but are rarely addressed by RCTs and are a source of uncertainty for the clinician. Comparative effectiveness research may be helpful with respect to multidrug therapy, but clinical practice guidelines are probably the most useful resource for the busy clinician.


Given this background of uncertainty and some controversy regarding the exact BP target, wide achievement of the conservative clinical practice guideline and evidence-based BP target of <140/90 mmHg would arguably have an effect greater than that of any blockbuster drug in slowing CKD progression and reducing both cardiovascular events and cardiovascular mortality. The cost savings obtained from reduced adverse outcomes and gained quality-of-life years would be estimated by pharmacoeconomic modelling to be more than worth the considerable downsides in clinician visits, cost, and drug side effects.


Diabetes Control


Tight glycaemic control in patients with both type 1 and type 2 diabetes reduces the risk of them developing incident microalbuminuria as well as progression to macroalbuminuria, based on RCTs such as the Diabetes control and complications trial (DCCT),13 diabetes study (UKPDS),14


the UK prospective the Action in diabetes and vascular disease:


preterax and diamicron modified release controlled evaluation (ADVANCE) study,15


cardiovascular risk in diabetes (ACCORD) study.16


and, to some extent, the Action to control These results support


maintaining glycated haemoglobin (HbA1c) concentrations as close to 7 % as safely possible, in order to attenuate albuminuria progression in


CKD. Only observational studies suggest that this target is associated with a reduced risk of loss of kidney function in CKD stages 3 to 5.17


When diabetes is complicated by kidney disease, the effect of tight glycaemic control on macrovascular disease remains less clear. Data from the DCCT in type 1 diabetes suggest that the risk of cardiovascular events is reduced with intensive insulin therapy,18


yet


other studies have not consistently shown a protective effect of tight glycaemic control with regard to macrovascular complications. Data from the ACCORD study suggest that intensive glycaemic control


(HbA1c <6.0 %) to prevent cardiovascular disease results in excess mortality in type 2 diabetes patients,19


confirmed by the similarly designed ADVANCE study.15


although this was not Therefore,


consensus guidelines recommend an HbA1c level <7 % to prevent macrovascular complications in the diabetes population with CKD.20,21


Lipid Management


CKD is well established as a major cardiovascular risk factor, with comorbidity and mortality markedly higher than in the general population but generally lower than in chronic kidney failure patients.22 The available evidence in this area has focused primarily on statin therapy, a drug class generally safe and efficacious in reducing low-density lipoprotein (LDL) cholesterol in CKD to the target of


EUROPEAN NEPHROLOGY


and hypertension control rates and device Detection of white-coat and calibration masked HTN Wide availability and low cost


Ambulatory blood pressure monitoring (ABPM)


Only way to assess non-dipping Not reimbursed blood pressure (common in CKD)


by all health insurers


Detection of white-coat and Limited availability masked HTN


CKD = chronic kidney disease; HTN = hypertension; RCT = randomised controlled trial.


<100 mg/dl suggested by the current evidence, with the achievement of a more aggressive target of <70 mg/dl as a therapeutic option.23


The


statin effect on kidney function loss is inconsistent in published trials, making the primary indication for therapy atherosclerotic event risk reduction. Perhaps the strongest data in patients with early CKD (primarily stage 3a) come from the Pravastatin Pooling Project, a post hoc analysis of three trials that compared 40 mg pravastatin with placebo and showed that the primary composite outcome (myocardial infarction, coronary death, or coronary revascularization) was reduced by 23 % in patients with CKD, versus 22 % in those without CKD in the general study population.24


A post hoc analysis of the CKD


(predominantly stage 3a) population with cardiovascular disease at enrollment in the Treating to new targets (TNT) trial showed a benefit from atorvastatin 80 mg versus 10 mg in reducing major cardiovascular events by 32 % without any significant difference in side effects.25


The Study of heart and renal protection (SHARP) trial randomised 9,270 patients with CKD stage 4 to 5d (dialysis) without a history of myocardial infarction or coronary revascularization to a combination of simvastatin 20 mg and ezetimibe 10 mg daily versus placebo, demonstrating a statistically significant 17 % proportional reduction in major atherosclerotic events in the intervention group.26


This is an


important trial, since it supports dyslipidemia drug therapy in patients with CKD stage 3b to 5, who were sparsely enrolled or excluded in all other published trials to date.


Metabolic Acidosis


In experimental results in animals, clinical observational data and small non-randomised trials suggest that metabolic acidosis either directly or indirectly promotes progression of loss of kidney function.27


Interestingly,


a diet rich in fruits and vegetables may be as effective as oral sodium bicarbonate, with the obvious advantages of a reduced sodium load and potential antioxidant effects. Titration of therapy to approximately 24 mmol/l serum bicarbonate is a reasonable recommendation.28


Anaemia


The safety signals from the Correction of hemoglobin and outcomes in renal insufficiency (CHOIR) trial,29


by early anaemia treatment with epoetin-β (CREATE) trial,30


the Cardiovascular risk reduction and the


Trial to reduce cardiovascular events with aranesp therapy (TREAT),31 which all study erythropoietin-stimulating agent (ESA), have resulted in a shift in the haemoglobin target of therapy in CKD patients, especially in those with ESA hyporesponsiveness and pre-existing


11


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