Screening for chronic kidney disease

In the linked study (doi:10.1136/bmj.c5869), Manns and colleagues assess the cost effectiveness of using the estimated glomerular filtration rate (GFR) to screen the general population for chronic kidney disease.1 Screening to prevent disease is a topic that consistently generates debate, with mammography being a prime example.2 Screening recommendations pit clinical epidemiologists who specialise in screening evaluation against special interest groups and their key opinion leaders, with health policy makers and sometimes even the law making the decisions. Ironically, debates become the most heated when the net benefits are the smallest. Although screening for kidney disease has lacked the publicity of breast cancer screening, the principles and arguments are similar but the impact may be greater⇓.

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Axis-Shield UK

Preventing the progression of kidney disease may reduce the expense and clinical consequences of end stage renal disease and prevent premature death from cardiovascular disease. Several recent articles have highlighted independent and significant relative risks associated with albuminuria and low estimated glomerular filtration rate for both end stage renal disease and mortality.3 4 These reports have already generated renewed interest in screening, especially because even small amounts of albuminuria are associated with risk.

Routine screening for chronic kidney disease in diabetes and as part of the initial evaluation of hypertension are well established, but some have argued that the screening criteria are nearly met by the entire population.5 Manns and colleagues’ study relies mainly on a Canadian provincial database and predicts that the costs of screening the general population are too high for the benefit (about seven hours of quality adjusted life per person screened) to warrant implementation in a population free of diabetes.

Intuitively, screening should be beneficial. For the increased risk of morbidity and mortality associated with chronic kidney disease, multiplied by fixed reduction of risk by an intervention (angiotensin blockade in the current study) and examined over time the accrued benefits should be substantial. However, on the basis of their interpretation of the evidence on angiotensin blockade, Manns and colleagues do not conclude that it reduces progression in non-proteinuric chronic kidney disease or reduces mortality in chronic kidney disease without diabetes. However they do assume in the model that the intervention reduces progression in proteinuric chronic kidney disease and reduces mortality in chronic kidney disease with diabetes.

In addition, Manns and colleagues use estimated GFR as the screening tool, but many argue that proteinuria should be used in the initial screen.6 7 This is important because about 40% of chronic kidney disease is defined by proteinuria, and proteinuria predicts cardiovascular events.8 Manns and colleagues justify their choice of screening tool with the argument that many patients with low estimated GFR have no proteinuria and low estimated GFR is a prerequisite for end stage renal disease. These proteinuria studies find that screening patients with hypertension is cost effective and screening populations without diabetes or hypertension marginally cost effective in selected scenarios because they attribute a 23% reduction in mortality to angiotensin blockade for all treated patients.6 7 The overall conclusions between reports would not differ substantially, despite the differences in approach, if they agreed on the effects of angiotensin blockade.

Most of the evidence for reduced mortality with angiotensin blockade is in large trials of people with cardiac disease or diabetes. The evidence in other populations is less convincing. One randomised controlled trial looked at a community based cohort of 864 people who were screened for chronic kidney disease (defined by albuminuria) (PREVEND IT).9 The overall event rate in the study was low and compared with placebo, angiotensin blockade had no significant effect on the composite end point of mortality and cardiovascular events over about four years. The study was also too small to detect differences in end stage renal disease. Proponents of angiotensin blockade could argue that a larger and longer study would prove the obvious. In the PREVEND IT trial some subjects had diabetes, hypertension, or established cardiovascular disease that already warranted angiotensin blockade. Studies in patients at lower risk, such as those with prediabetes, have not shown expected benefits, and a large study with combined angiotensin receptor blockade and angiotensin converting enzyme inhibition (possibly excessive angiotensin blockade) showed evidence of harm (ON-TARGET study).10 Manns and colleagues were conservative in their assessment of the effect of angiotensin blockade, and they may or may not be correct.

Even for an effective intervention the benefits gained will be small if the absolute event rates are small.2 When the benefits are small, adverse effects may dominate. Currently, we have insufficient evidence to support screening for chronic kidney disease in otherwise healthy people. Without conclusive evidence from a large randomised trial that the benefits significantly outweigh harms, agencies such as the Canadian Task Force, the US Preventative Health Care Service, and a UK consensus group are not likely to recommend general population screening for chronic kidney disease.11 Rather, efforts should be intensified to achieve recommended blood pressure, lipid targets, and glucose control targets in relevant patient groups, and this includes angiotensin blockade where appropriate and primary prevention with diet and lifestyle change in the entire population.