Is Long-Term Low-Dose Aspirin Therapy Associated with Renal Dysfunction in Patients with Type 2 Diabetes? JPAD2 Cohort Study

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2016 Jan 26

PMID 26808136

Citations 10

Authors

Sadanori Okada

Takeshi Morimoto

Hisao Ogawa

Mio Sakuma

Hirofumi Soejima

Masafumi Nakayama

Hideaki Jinnouchi

Masako Waki

Yasuhiro Akai

Hitoshi Ishii

Yoshihiko Saito

Affiliations

Soon will be listed here.

Abstract

Background: Low-dose aspirin is widely recommended for patients at high risk for cardiovascular disease (CVD); however, it remains uncertain whether long-term treatment adversely affects renal function in patients with diabetes. We investigated whether long-term low-dose aspirin affects renal dysfunction in patients with diabetes.

Methods: We conducted a randomized controlled trial (RCT), the Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD) trial, to evaluate low-dose aspirin as primary prevention for CVD in patients with type 2 diabetes. We followed the patients with negative urine dipstick albumin of the JPAD trial in a cohort study after the RCT period was completed. Patients were randomly allocated to receive aspirin (81 mg or 100 mg daily, aspirin group) or no aspirin (no aspirin group). After the RCT, the treating physician decided whether to administer aspirin. We evaluated the incidence of positive urine dipstick albumin and annual changes in estimated glomerular filtration rate (eGFR).

Results: Positive urine dipstick albumin developed in 297 patients in the aspirin group (n = 1,075) and 270 patients in the no aspirin group (n = 1,098) during follow-up (median, 8.5 years). Intention-to-treat analysis showed low-dose aspirin did not increase the incidence of positive urine dipstick albumin (hazard ratio [HR], 1.17; 95% confidence interval [CI], 0.995-1.38). On-treatment analysis yielded similar results (HR, 1.08; 95% CI, 0.92-1.28). Multivariable analysis showed the incidence of positive urine dipstick albumin was higher among the elderly and those with elevated serum creatinine, high hemoglobin A1c, or high blood pressure; however, low-dose aspirin did not increase the risk of positive urine dipstick albumin. There were no significant differences in annual changes in eGFR between the groups (aspirin, -0.8 ± 2.9; no aspirin, -0.9 ± 2.5 ml/min/1.73 m(2)/year).

Conclusion: Long-term low-dose aspirin does not affect eGFR and positive urine dipstick albumin in patients with type 2 diabetes.

Citing Articles

NSAIDs, analgesics, antiplatelet drugs, and decline in renal function: a retrospective case-control study with SIDIAP database.

Bonet-Monne S, Vedia Urgell C, Saez M, Puertolas O, Baena-Diez J, Pascual J BMC Pharmacol Toxicol. 2024; 25(1):58.

PMID: 39198874 PMC: 11351315. DOI: 10.1186/s40360-024-00771-5.

The influence of cyclooxygenase inhibitors on kynurenic acid production in rat kidney: a novel path for kidney protection?.

Zakrocka I, Zaluska W Pharmacol Rep. 2023; 75(2):376-385.

PMID: 36788192 PMC: 10060280. DOI: 10.1007/s43440-023-00460-w.

Antiplatelet agents for chronic kidney disease.

Natale P, Palmer S, Saglimbene V, Ruospo M, Razavian M, Craig J Cochrane Database Syst Rev. 2022; 2:CD008834.

PMID: 35224730 PMC: 8883339. DOI: 10.1002/14651858.CD008834.pub4.

Discharge Prescription Patterns for Antiplatelet Therapy Following Lower Extremity Peripheral Vascular Intervention.

Singh N, Ding L, Magee G, Shavelle D, Kashyap V, Garg P Circ Cardiovasc Interv. 2020; 13(8):e008791.

PMID: 32791948 PMC: 7430046. DOI: 10.1161/CIRCINTERVENTIONS.119.008791.

Pros and Cons of Aspirin Prophylaxis for Prevention of Cardiovascular Events in Kidney Transplantation and Review of Evidence.

Khalil M, Khalil M, Ahmed Khamis S, Alam S, Daiwajna R, Rajput A Adv Prev Med. 2019; 2019:6139253.

PMID: 31223503 PMC: 6541935. DOI: 10.1155/2019/6139253.

References

. Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Heart Outcomes Prevention Evaluation Study Investigators. Lancet. 2000; 355(9200):253-9. View

Hansen H, Gaede P, Jensen B, Parving H . Lack of impact of low-dose acetylsalicylic acid on kidney function in type 1 diabetic patients with microalbuminuria. Diabetes Care. 2000; 23(12):1742-5. DOI: 10.2337/diacare.23.12.1742. View

Rexrode K, Buring J, Glynn R, Stampfer M, Youngman L, Gaziano J . Analgesic use and renal function in men. JAMA. 2001; 286(3):315-21. DOI: 10.1001/jama.286.3.315. View

Parving H, Lehnert H, Brochner-Mortensen J, Gomis R, Andersen S, Arner P . The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med. 2001; 345(12):870-8. DOI: 10.1056/NEJMoa011489. View

Fored C, Ejerblad E, Lindblad P, Fryzek J, Dickman P, Signorello L . Acetaminophen, aspirin, and chronic renal failure. N Engl J Med. 2001; 345(25):1801-8. DOI: 10.1056/NEJMoa010323. View

Adler A, Stevens R, Manley S, Bilous R, Cull C, Holman R . Development and progression of nephropathy in type 2 diabetes: the United Kingdom Prospective Diabetes Study (UKPDS 64). Kidney Int. 2002; 63(1):225-32. DOI: 10.1046/j.1523-1755.2003.00712.x. View

Gaede P, Post Hansen H, Parving H, Pedersen O . Impact of low-dose acetylsalicylic acid on kidney function in type 2 diabetic patients with elevated urinary albumin excretion rate. Nephrol Dial Transplant. 2003; 18(3):539-42. DOI: 10.1093/ndt/18.3.539. View

Kurth T, Glynn R, Walker A, Rexrode K, Buring J, Stampfer M . Analgesic use and change in kidney function in apparently healthy men. Am J Kidney Dis. 2003; 42(2):234-44. DOI: 10.1016/s0272-6386(03)00647-4. View

Curhan G, Knight E, Rosner B, Hankinson S, Stampfer M . Lifetime nonnarcotic analgesic use and decline in renal function in women. Arch Intern Med. 2004; 164(14):1519-24. DOI: 10.1001/archinte.164.14.1519. View

10.

Mogensen C, Christensen C . Predicting diabetic nephropathy in insulin-dependent patients. N Engl J Med. 1984; 311(2):89-93. DOI: 10.1056/NEJM198407123110204. View

11.

Sandler D, Smith J, Weinberg C, BUCKALEW Jr V, Dennis V, BLYTHE W . Analgesic use and chronic renal disease. N Engl J Med. 1989; 320(19):1238-43. DOI: 10.1056/NEJM198905113201903. View

12.

Hopper A, Tindall H, Davies J . Administration of aspirin-dipyridamole reduces proteinuria in diabetic nephropathy. Nephrol Dial Transplant. 1989; 4(2):140-3. View

13.

Morlans M, Laporte J, Vidal X, Cabeza D, STOLLEY P . End-stage renal disease and non-narcotic analgesics: a case-control study. Br J Clin Pharmacol. 1990; 30(5):717-23. PMC: 1368172. DOI: 10.1111/j.1365-2125.1990.tb03841.x. View

14.

Perneger T, Whelton P, Klag M . Risk of kidney failure associated with the use of acetaminophen, aspirin, and nonsteroidal antiinflammatory drugs. N Engl J Med. 1994; 331(25):1675-9. DOI: 10.1056/NEJM199412223312502. View

15.

Ibanez L, Morlans M, Vidal X, Martinez M, Laporte J . Case-control study of regular analgesic and nonsteroidal anti-inflammatory use and end-stage renal disease. Kidney Int. 2005; 67(6):2393-8. DOI: 10.1111/j.1523-1755.2005.00346.x. View

16.

Suleyman H, Demircan B, Karagoz Y . Anti-inflammatory and side effects of cyclooxygenase inhibitors. Pharmacol Rep. 2007; 59(3):247-58. View

17.

Agodoa L, Francis M, Eggers P . Association of analgesic use with prevalence of albuminuria and reduced GFR in US adults. Am J Kidney Dis. 2008; 51(4):573-83. DOI: 10.1053/j.ajkd.2007.12.014. View

18.

Ogawa H, Nakayama M, Morimoto T, Uemura S, Kanauchi M, Doi N . Low-dose aspirin for primary prevention of atherosclerotic events in patients with type 2 diabetes: a randomized controlled trial. JAMA. 2008; 300(18):2134-41. DOI: 10.1001/jama.2008.623. View

19.

Evans M, Fored C, Bellocco R, Fitzmaurice G, Fryzek J, McLaughlin J . Acetaminophen, aspirin and progression of advanced chronic kidney disease. Nephrol Dial Transplant. 2009; 24(6):1908-18. DOI: 10.1093/ndt/gfn745. View

20.

Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K . Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis. 2009; 53(6):982-92. DOI: 10.1053/j.ajkd.2008.12.034. View