Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers for adults with early (stage 1 to 3) non-diabetic chronic kidney disease

Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers for adults with early (stage 1 to 3) non-diabetic chronic kidney disease

Chronic kidney disease (CKD) is a long term condition that occurs as a result of damage to the kidneys. Early recognition of CKD is becoming increasingly common due to widespread laboratory estimated glomerular filtration rate (eGFR) reporting, raised clinical awareness, and international adoption of Kidney Disease Outcomes Quality Initiative (K/DOQI) classification.

Early recognition and management of CKD affords the opportunity not only to prepare for progressive kidney impairment and impending renal replacement therapy, but also for intervening to reduce the risk of progression and cardiovascular disease. Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) are two classes of antihypertensive drugs that act on the renin-angiotensin-aldosterone system.

Beneficial effects of ACEi and ARB

Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers for adults with early (stage 1 to 3) non-diabetic chronic kidney disease
Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers for adults with early (stage 1 to 3) non-diabetic chronic kidney disease

Beneficial effects of ACEi and ARB on renal outcomes and survival in people with a wide range of severity of renal impairment have been reported; however, their effectiveness in the subgroup of people with early CKD (stage 1 to 3) is less certain.OBJECTIVEThis review aimed to evaluate the benefits and harms of ACEi and ARB or both in the management of people with early (stage 1 to 3) CKD who do not have diabetes mellitus.METHODSIn March 2010 we searched

The Cochrane Library, including The Cochrane Renal Group’s specialised register and The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE. Reference lists of review articles and relevant studies were also checked. The search was conducted using the optimally sensitive strategy developed by the Cochrane Collaboration for the identification of randomised controlled trials (RCTs) with input from an expert in trial search strategy.METHODSAll RCTs reporting the effect of ACEi or ARB in people with early (stage 1 to 3) CKD who did not have diabetes mellitus were selected for inclusion.

Only studies of at least four weeks duration were selected. Authors, working in teams of two, independently assessed the retrieved titles and abstracts, and whenever necessary the full text of these studies were screened to determine which studies satisfied the inclusion criteria.

shows the cell viability results obtained for the four calcium hydroxide

ResultsTable 2 shows the cell viability results obtained for the four calcium hydroxide based materials. Application of a warm or hot air stream did not influence cell viability in the conventional calcium hydroxide cement Dycal, which presented higher viability rates than resin-mo-dified materials. Conversely, in all resin-based calcium hydroxide materials, the hot air stream enhanced cell viability at both 24 hours and 7 days. All tested materials presented lower rates of cell viability at 7 days compa-red to 24 hours.DiscussionLight-curing pulp-capping materials were developed with the goal of simplifying the operating technique by facilitating material application.

Due to their resin base, these materials are associated with increased mechanical resistance (4) and improved marginal seal as a result of lower dissolution rates (25). The present study showed that treatment of these materials with a jet of warm air just before their application resulted in cytotoxicity rates similar to those reported for chemically activated ce-ments, most widely used at present.

However, studies have shown that these cements, even when used for pulp capping, present a certain degree of cytotoxicity – a fact that becomes extremely relevant, as these cements are often used very close to dental pulp tissues.

studies have shown that these cements

METHODSData extraction was carried out by two authors, independently, using a standard data extraction form and cross checked by two other authors. Methodological quality of included studies was assessed using the Cochrane risk of bias tool. Data entry was carried out by one author and cross checked by another author. When more than one study reported similar outcomes, data were pooled using the random-effects model, but a fixed-effect model was also analysed to ensure the robustness of the model chosen and to check susceptibility to outliers. Heterogeneity was analysed using a Chi² test on N-1 degrees of freedom, with an alpha of 0.05 used for statistical significance and with the I² test. Where data permitted, subgroup analysis was used to explore possible sources of heterogeneity.

The quality of the evidence was analysed.RESULTSFour RCTs enrolling 2177 participants met our inclusion criteria. Of these, three compared ACEi with placebo and one compared ACEi with ARB. Two studies had an overall low risk of bias, and the other two were considered to be at moderate to high risk of bias. Low to moderate quality of evidence (from two studies representing 1906 patients) suggested that ACEi had no impact on all-cause mortality (RR 1.80, 95% CI 0.17 to 19.27, P = 0.63) or cardiovascular events (RR 0.87, 95% CI 0.66 to 1.14, P = 0.31) in people with stage 3 CKD.

The quality of the evidence was analysed

For all-cause mortality, there was substantial heterogeneity in the results. One study (quality assessment: low risk of bias) reported no difference in the risk of end-stage kidney disease in those with an eGFR>> 45 mL/min/1.74 m² treated with ACEi versus placebo (RR 1.00, 95% CI 0.09 to 1.11, P = 0.99). The (high risk of bias) study that compared ACEi with ARB reported little difference in effect between the treatments when urinary protein, blood pressure or creatinine clearance were compared. No published studies comparing ARB with placebo or ACEi and ARB with placebo were identified.

CONCLUSIONSOur review demonstrated that there is currently insufficient evidence to determine the effectiveness of ACEi or ARB in patients with stage 1 to 3 CKD who do not have diabetes mellitus. We have identified an area of significant uncertainty for a group of patients who account for most of those labelled as having CKD.

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