Citrate Preparation Prior to Angiography Reduces Contrast Nephropathy


Patients undergoing coronary angiography who receive sodium potassium (Na/K) citrate experience lower rates of contrast-induced nephropathy (CIN), according to a study published online January 24, 2013, ahead of print in the European Heart Journal. This appears especially true in patients with higher urine pH immediately before cardiac catheterization.

Researchers led by Ivica Markota, MD, of University Clinical Hospital Mostar (Mostar, Bosnia and Herzegovina), randomized 202 patients scheduled to undergo coronary angiography at their institution to hydration with (n = 100) or without (n = 102) Na/K citrate. The theory is that alkalinization of urine via the citrate preparation may prevent CIN by suppressing the generation of oxygen free radicals, which are mainly created in an acid medium.

The incidence of CIN 2 days after angiography was decreased in citrate patients, as were other measures of change in creatinine and eGFR (table 1).

Table 1. Measures of Creatinine and eGFR 2 Days After Angiography

 

Citrate Group
(n = 100)

Control Group
(n = 102)

P Value

CINa

4%

20%

0.0001

Absolute Change in Creatinine, µmol/L

1.470

9.451

0.0004

Absolute Change in eGFR, mL/min/1.73 m2

-0.055

-8.828

0.0078

a CIN was defined as an increase in serum creatinine of greater than 25% and/or a decrease in eGFR of greater than 25% and/or an absolute increase in serum creatinine of greater than 44 µmol/L from baseline within 48 hours after contrast exposure.

Immediately before coronary angiography (an hour after Na/K citrate administration), average urine pH was higher in patients who did not develop CIN (5.89 vs. 5.54; P = 0.009). Urine pH was also higher in citrate patients vs. controls immediately before angiography (6.93 vs. 5.96; P < 0.0001).

There was a significant correlation between urine pH immediately prior to coronary angiography and change in creatinine 48 hours after the procedure (P < 0.0001) such that increase in creatinine after angiography was higher in patients whose pre-angiography pH was less than 6 (15.6 µmol/L) vs. greater than 6 (0.396 µmol/L; P < 0.0001).

In addition, CIN incidence was lower in patients whose urine pH was greater than 6.0 immediately before angiography compared with patients whose urine pH was lower than 6.0 (2.2% vs. 32.8%; P < 0.0001).

Overall, Na/K citrate increased urine pH by an average of 1 unit compared with baseline.

Urine pH Threshold Key

“Undoubtedly, adequate hydration, accurate indication of contrast medium, and volume of administered contrast medium remain the basis of CIN prevention,” the authors note. “In addition, however, the results of our study document that oral administration of citrates is an efficient, simple, and economical strategy to prevent CIN.”

In particular, they point out that when urine pH was greater than 6 prior to angiography, the incidence of CIN was tenfold lower compared with the patients whose baseline urine pH was lower than 6. “Such correlation supports the hypothesis that a low urine pH is a risk factor that predisposes to the development of contrast nephropathy,” Dr. Markota and colleagues observe. They added that contrary to previous research which identified a critical urine pH of 7 above which CIN is less likely to occur, the current study lowers that threshold to 6.

Richard Solomon, MD, of the University of Vermont (Burlington, VT), noted that the theorized mechanism of alkalinization of urine makes sense. “There’s been a lot of trials with bicarbonates and some trials show positive effect and some don’t, so it’s not clear whether bicarbonates and alkalinization work, and why some trials seem to show some benefit and some don’t,” he told TCTMD in a telephone interview. “But a hypothesis is that the trials in which bicarbonate did not work did not adequately alkalinize the urine, and that’s what’s key about this paper.”

In particular, “the really important finding is the relationship between urine pH immediately before contrast exposure and the incidence of rise in creatinine,” Dr. Solomon added. “That supports the hypothesis that urinary alkalinization may be protective if you can get the urine pH up.”

Caution Urged After Failure of Other CIN Strategies

Hitinder S. Gurm, MD, of the University of Michigan Medical Center (Ann Arbor, MI), called the strategy “a very smart idea,” since sodium citrate is often used in patients with kidney stones. “It’s an old treatment to keep the urine alkaline,” he told TCTMD in a telephone interview.

Still, he cautioned, the study by itself will not change practice. “We’ve seen too many studies with CIN where one is dramatically positive and then others are all negative,” Dr. Gurm said. “Small studies have a way of being positive. The challenge is, how do you apply this to a larger group of patients that are more germane to our practice?”

He explained that most of the patients in the study had normal GFR levels. “These are not the people who develop renal failure,” Dr. Gurm said. “We have to use it in people who have abnormal renal function.”

In addition, Dr. Solomon noted that patients with an eGFR < 60 mL/min/1.73 m2 were hydrated with IV saline, while those with an eGFR > 60 mL/min/1.73 m2 received water orally. “The protocol is a little weird,” he said. “I’m not sure in the truly high-risk group, which are the people with chronic kidney disease, that one can conclude that this therapy works [due to the difference in hydration regimens], and if it works in the low-risk group, that’s nice, but that’s not going to go too far.”

In addition, the exact Na/K citrate preparation used in the study (hexakalium-hexanatrium-trihydrogen-pentacitrat, 5 granules diluted in 200 mL of water; Uralyt-U, Madaus granulat, Germany) is not available in the United States, making it difficult to determine the level of potassium exposure. “We have to use it in people who have abnormal renal function,” Dr. Gurm said, “and in these people you have to be careful with giving them potassium salts because they’ll get hyperkalemia, and then they can’t get catheterized and they get other problems.”

 


Source:
Markota D, Markota I, Starčević B, et al. Prevention of contrast-induced nephropathy with Na/K citrate. Eur Heart J. 2013;Epub ahead of print.

 

 

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Disclosures
  • Drs. Markota, Solomon, and Gurm report no relevant conflicts of interest.

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