Acute kidney injury (RAKI) caused by radioactive contrast media is a common complication in angiography and is more common in patients with pre-existing chronic kidney disease (CKD). At present, there are preliminary studies showing that sodium bicarbonate can reduce the incidence and hospitalization rate of RAKI and the incidence of short-term adverse prognostic events. However, there is no relevant study to show whether the long-term prognosis of RAKI patients improves.
Recently, the GOAL study in the United States mainly evaluated the effect of sodium bicarbonate on the prognosis of RAKI patients in short-term (1 year) and long-term (5 years). The findings of the study showed that sodium bicarbonate had a limited effect on patients with RAKI compared to normal saline¹.
A study design¹
The PRIMARY study was a forward-looking, single-center, randomized, double-blind study in which patients with stage CKD3 to 4 (GFR between 15 and 59 ml/min/1.73 m2) underwent angiography. The exclusion criteria are as follows:
(1) Age < 20 years;
(2) Pregnant or CKD stage 2 or 5 patients;
(3) Severe valvular heart disease;
(4) Undergo vascular regeneration after angiography;
(5) With heart failure, acute respiratory failure, sepsis or septic shock, acute kidney injury caused by non-angiography agents occurred within 30 days before admission.
Patients were randomly grouped into the sodium bicarbonate group (n=192) or the saline group (n=190). The incidence of RAKI between the two groups was mainly compared with the need for renal replacement therapy (RRT), the number of days in hospital stay, and the 1- and 5-year mortality rates.
II. Findings¹
The sodium bicarbonate group enrolled 192 patients, with an average age of 67 (±13 years), 53% of whom were male, with an average creatinine level of 2.0±0.4 mg/dL, an average eGFR value of 38.6 ± 19.3 ml/min/1.73㎡. The saline group enrolled 190 patients, with an average age of 68 (±10 years), 51% of whom were male, with an average creatinine level of 1.9 ± 0.3 mg/dL, and an average eGFR value of 41.3± 17.2 ml/min/1.73㎡.
01 Incidence of RAKI
A total of 56 patients developed RAKI after angiography, 25 (13.02%) cases in the sodium bicarbonate group and 31 (16.32%) cases in the saline group, with no significant difference between the two groups (P=0.89).
02 RRT
Eight (4.17%) patients in the sodium bicarbonate group received RRT treatment, compared with 6 (3.16%) in the saline group, with no significant difference (P=0.88). 4 (2.08%) patients in the sodium bicarbonate group and 5 (2.63%) in the saline group discontinued RRT therapy after 1 year (P=0.68), but 4 (2.08%) patients in the sodium bicarbonate group and 1 (0.53%) patients in the saline group required permanent RRT treatment (P=0.67).
After 5 years, a total of 41 (10.7%) of the 2 groups of patients with CKD required RRT treatment. There were 19 (9.90%) cases in the sodium bicarbonate group and 22 (11.58%) cases in the saline group, and there was no significant difference in the need for RRT therapy (P=0.91). Kaplan-Meir analysis showed a similar trend of no RRT treatment in the two groups after 5 years (P=0.710).
03 Risk of death
In terms of the 1-year risk of death, there were 5 (2.60%) deaths in the sodium bicarbonate group and 4 (2.11%) in the saline group, with no significant difference between the two (P=0.53). In terms of the 5-year risk of death, there were 31 (16.15%) deaths in the sodium bicarbonate group and 26 (13.68%) deaths in the saline group, and there was no significant difference (P=0.83).
In other aspects, such as non-fatal stroke, new-onset heart failure, and the number of days in hospital, sodium bicarbonate differed little from normal saline, with p-values > 0.10.
Three
discuss
It is reported that this is the first study to follow up RAKI patients for 5 years. The results of the study showed that for patients undergoing angiography stage 3-4 of CKD, the use of sodium bicarbonate had a limited impact on preventing RAKI, reducing RRT use, and reducing the risk of death¹.
In June, the Journal of Nephrology published a meta-analysis of 1.21 million people in 134 articles. The analysis showed that the incidence of RAKI was 12.8%, and the mortality rate of RAKI was higher, reaching 20.2%. More notably, the incidence and mortality rates of RAKI have not changed significantly over time². So, in addition to normal saline and sodium bicarbonate, what other interventions are there?
01 Expert consensus³
The "Chinese Expert Consensus on the Prevention and Treatment of Iodine-containing Contrast Agent-related Adverse Reactions in transarterial cardiovascular interventional diagnosis and treatment" issued in 2021 clearly states that there are the following 5 measures for the prevention of contrast nephropathy:
(1) Risk stratification
Patient eGFR was calculated and the risk of acute kidney injury after the use of contrast media was assessed, and the risk stratification was carried out to implement corresponding management (Figure 1).
Figure 1 Procedures for the administration of patients using iodine-containing contrast media
Note: eGFR is an estimated glomerular filtration rate, PC-AKI is acute kidney injury after the use of contrast media, NSAIDs are nonsteroidal anti-inflammatory drugs, and sCr is serum creatinine.
(2) Hydration:
The standard hydration regimen recommends intravenous 0.9% sodium chloride solution 1.0-1.5 ml/kg/h for 3-12 hours before surgery and 12-24 hours postoperatively. Hydration has a definite effect on the prevention of acute kidney injury after contrast media, but in patients with left-sided insufficiency, volume overload needs to be prevented.
(3) Limit the amount of contrast medium applied
The study found that the ratio of contrast medium dose to eGFR was < 1 when the contrast medium was the lowest risk of acute kidney injury, especially in patients with CKD; it is recommended that the ratio of contrast agent dose to eGFR in patients with moderate to severe renal insufficiency should not be greater than 3.7. In clinical work, for patients with severe renal insufficiency, contrast agent allergy, and severe thyroid dysfunction, zero or ultra-low doses of contrast medium are recommended to prevent adverse events.
(4) Preventive drugs
For patients who have not received statin therapy, high-dose statin (rosuvastatin 40/20 mg or atorvastatin 80 mg) is recommended to prevent acute kidney injury after contrast agents. Because Chinese populations are poorly tolerated with high-intensity statins, moderate-dose statins are recommended for prophylaxis prior to intervention.
(5) Surgical methods
Patients with radial approach have been shown to have a significantly lower risk of developing acute kidney injury after contrast media than patients with femoral artery approach. The recommended surgical method is the radial approach.
02 Domestic related research
In China, some scholars believe that compared with sodium chloride, sodium bicarbonate combined with vitamin C can effectively reduce the risk of RAKI in patients with early diabetic nephropathy, and can better protect the kidneys. The creatinine clearance and glomerular filtration rate in the combination therapy (sodium bicarbonate + vitamin C) group were significantly higher than those in the sodium chloride group (P<0.01), while the serum creatinine levels and urea nitrogen levels in the combination treatment group were also lower than those in the sodium chloride group (P<0.01) ⁴.
In a meta-analysis of 11 studies and 1810 patients, 11 vitamin groups significantly reduced the incidence of RAKI (RR =0.54, 95% CI: 0.39–0.73), and the symmetry of the points was well observed by the funnel plot, and most of the studies were evenly distributed left and right, and it was believed that there was a small possibility of publication bias in this meta-analysis. In addition, subgroup analysis showed that six vitamin C groups reduced the incidence of RAKI by 42% (RR =0.58, 95% CI=0.37–0.90); The 3 vitamin E groups reduced the incidence of RAKI by 52% (RR=0.48, 95% CI: 0.30–0.77)⁵.
bibliography:
1.BoccalandroF, Shreyder K, Harmon L, et al. Five-Year Follow-Up of Patients WithRadio-Contrast-Induced Acute Renal Injury: Can Intravenous Sodium BicarbonateImprove Long-Term Outcomes? Cardiovasc Revasc Med. 2021 Oct;31:61-68.
2.LunZ, Liu L, Chen G, et al. The global incidence and mortality ofcontrast-associated acute kidney injury following coronary angiography: ameta-analysis of 1.2 million patients. J Nephrol. 2021 Oct;34(5):1479-1489.
3. Chinese Expert Consensus on the Prevention and Treatment of Iodine-containing Contrast Medium-related Adverse Reactions in the Diagnosis and Treatment of Transarterial Cardiovascular Intervention (2021). Chinese Journal of Cardiovascular Diseases.2021,49(10): 972-985.
4. ZHANG Peng, ZHANG Reni, LI Fei, et al. Effect of sodium bicarbonate combined with vitamin C on PCI contrast nephropathy in patients with early diabetic nephropathy[J]. Journal of Cardiovascular Rehabilitation Medicine, 2019, 28(3):4.
5. Tang Geng. Meta-analysis of vitamins on the prevention of nephropathy by contrast agents after coronary angiography[D]. Southeast University.