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Statins and albuminuria

Systematic review

There are times when you just don't know what to think of evidence, especially when it comes on a topic that one's tired mind has not considered before. Is it overwhelming, underwhelming, or something in between? A systematic review [1] looking at the effects of statins on urinary albumin or protein excretion is a useful example of how to look at evidence, over and above being of interest in itself.

Systematic review

Many databases were searched for randomised studies in adults of statin compared with placebo, with urinary excretion of albumin or protein as an outcome. Information required was the mean baseline and final excretion rates for statin and placebo groups. Prior intent was to analyse according to the level of albumin or protein excretion, with below 30 mg/day as normal excretion, between 30 and 299 mg/day as microalbuminuria, and 300 mg/day or more being macroalbuminuria.


Fifteen trials with 1,384 participants were found. Three trials with 938 patients had normal urinary albumin excretion (based on average of all patients), six (171 patients) had microalbuminuria, and six (275 patients) had macroalbuminuria or proteinuria above 300 mg/day. Two of the trials were not double blind, and one had no clear eligibility criteria.

There was clinical heterogeneity between studies, with causes of raised albumin including diabetes, IgA nephropathy, hypertension, and complex kidney disease, or not being reported in one trial. There was one large trial, but most were small, with only eight patients treated with statins in two trials. Trial duration was three to 46 months, with most between three and 12 months.

The results of the statin treatment arms in individual trials are shown in Figure 1, using a logarithmic scale because baseline excretion varied between <10 mg/day and more than 5,000 mg/day.

Figure 1: Individual studies showing baseline and final urinary albumin excretion, by normal albumin excretion, and micro- and macroalbuminuria

With placebo, urinary albumin or protein excretion changed but little. No trial where baseline urinary albumin excretion was normal had any meaningful change in excretion with statin. Most trials where patients had raised baseline urinary albumin excretion showed substantial reductions with statin treatment.

The weighted mean percentage reduction was about 50% for both microalbuminuria and macroalbuminuria or raised protein excretion compared with placebo. The exceptions were two trials. One was neither double blind nor had clear eligibility criteria in 36 patients with type 2 diabetes and apparently a mean age of 24 years. The second was in 30 patients with complex renal problems.


The authors of the paper do a good job of making sense of their data, but perhaps miss the obvious problem when assessing an outcome of urinary albumin excretion. For instance, if an excretion is reported as 5,000 mg/day, with a standard deviation of 2,500 mg/day, the chances are that data used for these calculations are not normally distributed. Some individual urinary excretions could be very high, while many could be lower; in the circumstance an average may not be representative of urinary excretion values of most patients.

Is the mean meaningful, in that case? It probably is much less useful than a median, and the mean may mislead. The fact that we see means falling by 50% in most trials should therefore give us some confidence, because results are consistent. Moreover, the two trials not in overall agreement are one with the lowest quality, and the only one in complex kidney disease, quite different from the others.

However, this is an excellent example about how one could lose a potentially important effect by lumping together clinically heterogeneous groups. Almost 70% of participants had normal urine protein excretion, and here there was no change. Had the analysis lumped these together with those with increased urine protein excretion, the effect may have been missed. It emphasises that we need always to ask the question whether these patients in the trial are like ours, and always to ask for the most appropriate analysis of data.


  1. K Douglas et al. Meta-analysis: the effect of statins on albuminuria. Annals of Internal Medicine 2006 145: 117-124.

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