Diuretic Use Directly Linked to End-Stage Renal Disease Rates in US

The rise in the incidence of end-stage renal disease (ESRD) that has taken place in the US in the last two decades coincides with an increase in population-wide diuretic use, according to a report in the American Journal of Hypertension for June.

At the same time ESRD rates were climbing, there was a fall in cardiovascular disease mortality. This led Dr. Ralph G. Hawkins and Dr. Mark C. Houston, from Vanderbilt University in Nashville, Tennessee, to look for a single factor that could explain these different trends.

The researchers hypothesized that increased diuretic use could explain both patterns. To investigate, they analyzed population-wide data from the National Vital Statistics Registry and from the US Renal Data Service.

From 1980 to 1998, all-cause cardiovascular disease mortality rates showed a strong inverse relationship with ESRD incidence (p < 0.0001), confirming previous reports. Moreover, based on diuretic distribution and expenditures, population-wide diuretic use was directly linked to the incidence of ESRD (p = 0.03).

"Until a randomized clinical trial designed to examine this hypothesis is undertaken, the data imply that diuretics appear to permit, induce, or possibly accelerate renal disease in a small but significant proportion of diuretic-treated patients," the authors state.

How should we interpret this study? First, I can only hypothesize unless I actually read the study. But that rarely inhibits me from speculating, so here goes!

One possibility is that decreasing cardiovascular mortality allows end stage renal disease to develop. Thus, an intervention that prolongs life in those with cardiovascular disease will functionally result in higher rates of ESRD.

Another possibility is that some patients are overdiuresed and thus susceptible to nephrotoxins. One of my repeated teaching points – the goal of diuretic therapy is to render the patient “not wet” not to make the patient dry. Volume contracted patients more often have renal complications (the importance of volume in preventing acute renal failure is well known).

Finally, diuretics may be renal toxic in rare patients. Given the large number of patients who receive diuretics, this relationship would still be hard to find.

Of course, this is one epidemiologic study. We should not overinterpret the results. Rather, we should hope that other investigators examine their patient databases to shed more light on this unexpected and interesting finding.

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