Meta-analysis Suggests Vitamin C Protective Against Acute Kidney Injury
Vitamin C appears to reduce the risk of contrast-induced acute kidney injury (AKI) by one-third in patients undergoing coronary angiography, reports a meta-analysis published online August 28, 2013, in the Journal of the American College of Cardiology. However, additional research is required to determine optimal dose and administration route.
Investigators led by Umar Sadat, MD, PhD, of Addenbrooke’s Hospital (Cambridge, United Kingdom), identified 9 randomized controlled trials reporting on contrast-induced AKI in 1,536 patients that were published between 2004 and 2013. Patients were assigned to ascorbic acid (with or without saline hydration; n = 740) vs. saline hydration, placebo, or other nephroprotective agents such as N-acetylcysteine (n = 796).
Ascorbic acid was administered intravenously or orally and given before, during, and after treatment. Doses varied. AKI (defined as an absolute increase in serum creatinine ≥ 0.5 mg/dL or a relative increase ≥ 25% from baseline following contrast administration) was assessed anywhere from 24 hours to 5 days after angiography.
Consistently Lower Risk
The incidence of contrast-induced AKI was lower for patients who received ascorbic acid compared with those given placebo, saline alone, or an alternate pharmacological treatment (9.59% vs. 16.83%).
Using a random effects model, Dr. Sadat and colleagues calculated that the ascorbic acid group had a lower risk of developing AKI (RR 0.672; 95% CI 0.466-0.969; P = 0.034). Heterogeneity among studies was low and did not reach statistical significance. Additional analyses including a fixed effects model and removal of individual studies from the pool showed consistent benefit with ascorbic acid. Publication bias was deemed unlikely.
Best Dose, Administration Route Unclear
According to the investigators, the meta-analysis “provides robust evidence that ascorbic acid reduces the risk of [contrast-induced] AKI, albeit by somewhat small magnitude, in patients undergoing coronary angiography compared to alternate treatment strategies. As participants of these studies had documented preexisting renal insufficiency, this indicates that ascorbic acid is effective in offering nephroprotection in this patient group.”
Vitamin C has traditionally been used as a dietary supplement, they note. “Today there is strong evidence that it acts as a potent antioxidant by scavenging physiologically relevant reactive oxygen species. As oxidative stress has been implicated in the etiology of [contrast-induced] AKI, use of ascorbic acid as a nephroprotective agent is therefore logical.”
The preferred route of administration for ascorbic acid is yet unknown, Dr. Sadat and colleagues say, noting that IV administration achieves higher plasma concentrations than does oral intake. Much as smokers and others with higher oxidative stress require more vitamin C, they explain, “it is possible that higher plasma concentration of ascorbic acid which is achievable with higher intravenous doses may be more beneficial in individuals with preexisting renal insufficiency.”
Further research is required to determine optimal dosing, they conclude.
Antidotes Merely a ‘Workaround’
Peter A. McCullough, MD, MPH, of Providence Hospital and Medical Center (Novi, MI) and Krittapoom Akrawinthawong, MD, of St. John Hospital and Medical Center (Detroit, MI), write in an accompanying editorial that “this paper has helped the field advance and appropriately framed ascorbic acid, perhaps in the higher doses and possibly for a longer duration of time, as a potential therapy to be tested in large-scale clinical trials.”
However, they ask, ultimately, “if we prevent or lessen [contrast-induced] AKI as determined by serum creatinine, will we reduce the rates of clinical outcomes including end-stage renal disease, mortality, and more secondary events . . . ?”
In a telephone interview with TCTMD, Dr. McCullough said he was “skeptical that giving [vitamin C] in high doses for very short durations really does anything to the human body,” noting that contrast-induced kidney damage takes approximately 1 week to fully develop.
Ascorbic acid must be studied to the same degree as N-acetylcysteine, Dr. McCullough emphasized. Several other nephroprotective agents are also being evaluated including atorvastatin as well as anti-inflammatories, stem cells, and other experimental drugs. “The real question,” he said, “is whether this is enough to position [ascorbic acid] in line for a big trial [costing] millions and millions of dollars, or should we pass and move on to novel agents?”
The idea of developing an antidote to contrast media is “a workaround,” Dr. McCullough stressed. “What we need are better and safer contrast agents. . . . That’s really what the community wants to see.”
Both Drs. Sadat and McCullough said that vitamin C for AKI is primarily a research question at this point and is rarely, if ever, used in a clinical setting. Overall, the adjunctive therapy appears safe, they commented, noting that urine acidification is not an issue. However, Dr. Sadat cautioned against using the treatment in patients with hemochromatosis, who might suffer worse kidney damage with ascorbic acid.
Sources:1. Sadat U, Usman A, Gillard JH, Boyle JR. Does ascorbic acid protect against contrast-induced acute kidney injury in patients undergoing coronary angiography: A systematic review with meta-analysis of randomized controlled trials. J Am Coll Cardiol. 2013;Epub ahead of print.
2. McCullough PA, Akrawinthawong K. Ascorbic acid for the prevention of contrast-induced acute kidney injury [editorial]. J Am Coll Cardiol. 2013;Epub ahead of print.
- Drs. Sadat, McCullough, and Akrawinthawong report no relevant conflicts of interest.