Does Drinking More Water Improve Kidney Function?

Hello. I am Lynda Szczech, a practicing nephrologist in Durham, North Carolina. I'm coming to you from my front porch where, with two kids and three terriers in the house, sometimes it is the quietest place to record, even in a thunderstorm. Today I want to summarize the report of a clinical trial published recently in JAMA.^[1] This trial looked at the effect of increasing a patient's water intake on kidney function over time.

Often, we hear patients say that they need to increase their water intake to flush the kidneys. As a nephrologist, when I hear that, I always wonder whether it really works, given the concentration gradient of urea and other things as the urine passes through the medulla. What is the physiologic significance of that? The authors lay this out in the introduction. They discuss previous work in humans as well as their own pilot study, which suggested that increasing the patient's water intake lowers vasopressin levels, which could, in turn, benefit kidney function.

Effect of Fluid Intake on eGFR and Other Outcomes

These investigators randomly assigned 631 patients with stage 3 kidney disease—estimated glomerular filtration rate (eGFR) between 30 and 60 mL/min/1.73m²—to one of two water intake arms. Patients in the hydration arm were coached to increase their water intake by 0.5 to 1.5 L per day. Patients in the maintenance or control arm were told to maintain or perhaps even lower their water intake by 0.5 L.

Both groups were followed for 1 year to assess the effect of water intake on their kidney function over time. After a year, the mean separation of water intake between the groups was about 0.6 L; thus, the hydration group drank about half a liter more than the maintenance group. That was the difference between the two arms.

The primary outcome was the change in the eGFR. Of interest, the mean decline in eGFR in the hydration group at 1 year was a decrement of 2.2 mL/min/1.73m² versus 1.9 mL/min/1.73m² in the control group; this did not reach statistical significance. Other outcomes that were assessed included change in urine osmolality, change in creatinine clearance, and change in plasma copeptin concentration (part of the pre-pro-vasopressin hormone that is excreted). As one would expect, urine osmolality fell dramatically in the hydration group. Of interest, there was a statistically significant difference in change in creatinine clearance over time that the authors hypothesized could be related urine flow and its effect on the tubules.

From the safety standpoint, there were no concerns. Only three people in the hydration group had significant hyponatremia compared with one in the control group; all three episodes of hyponatremia in the hydration group returned to baseline the next time it was measured.

In a very interesting discussion, the authors examine the reasons why this study may not have demonstrated a statistically significant difference in the primary endpoint, including the possibility that the difference in water intake wasn't enough. They posit that increasing water intake may work but it requires an increase in intake greater than the 0.6 L between the two groups.

They also suggest that it may require a larger sample size and that this study didn't have the power to show an effect. Finally, they suggest the obvious: that despite demonstrating that water intake did lower vasopressin levels (confirmed in the analysis by showing a decrease in the copeptin levels), perhaps this just doesn't have a significant effect on kidney function.

The Bottom Line

Judging by this study, increasing the urine output by half a liter to a liter does not necessarily lead to a positive effect on declining kidney function over time. That is unfortunate because it would be a nice low-tech, low-risk intervention to address what is becoming a global problem.

I am encouraged that a high-level journal such as JAMA decided to publish this study, for a number of reasons. The use of eGFR as a continuous outcome is something that the National Kidney Foundation and the US Food and Drug Administration are currently pursuing to help accelerate time to approval of various therapies meant to slow the progression of kidney disease.

Kidney disease is on the radar screen—not only of nephrologists who passionately care for our patients, but also of the regulatory agencies. Looking at alternative endpoints (other than doubling of creatinine or time to dialysis) is something that everyone is interested in trying to validate so that we can make trials easier to accomplish, more feasible, and potentially shorter, so that we can test more therapies.

Although we have a lot of hope for therapies down the road, an increase in water intake, administered this way, did not appear to have a benefit. It also did not appear to cause harm. As the authors suggest, will there be subgroups that will continue to be explored? Will additional protocols continue to be explored?

I hope the answer is yes. Potentially, there will be a benefit. But for now, increasing water intake will not join the armamentarium to slow kidney disease.

I hope you all have a great day. Thank you so much for watching.

Follow Medscape Nephrology on Twitter for more nephrology news: @MedscapeKidney.

Comments

Commenting is limited to medical professionals. To comment please Log-in.

Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.