If you have chronic kidney disease or impaired kidney function, ask a doctor before buying painkillers such as ibuprofen for long-term use; also avoid star fruit and its juice

No cost. Ask a doctor or pharmacist before buying a painkiller. Tell them if you take a diuretic and an ACE inhibitor or ARB for blood pressure. Avoid both star fruit and star fruit juice.

These painkillers are called nonsteroidal anti-inflammatory drugs (NSAIDs), commonly including ibuprofen, naproxen, and diclofenac. Acute kidney injury refers to an abrupt decline in kidney function within a few days. A systematic review pooled observational studies without control groups in community populations. In the general population currently taking these drugs, the odds ratio (OR) for acute kidney injury was 1.73 (95% CI 1.44–2.07). The odds ratio was somewhat higher in individuals aged 50 and older; the abstract reported an OR of 2.51, while the subgroup analysis and Figure 4 in the main text reported an OR of 2.01 (both cited a 95% CI of 1.52–2.68, reflecting an internal inconsistency in the original paper). Among those with pre-existing chronic kidney disease, pooled results from 5 studies showed an OR of 1.63 (1.22–2.19). The authors noted that none of the studies reported baseline incidence rates, precluding absolute risk calculations. A UK study followed 487,372 individuals taking antihypertensive medications for an average of 5.9 years. Combining a diuretic, an ACE inhibitor or ARB, and an NSAID is referred to as "triple therapy." Under triple therapy, the incidence rate ratio for acute kidney injury was 1.31 (95% CI 1.12–1.53), about 31% higher. The risk peaked during the first 30 days of concurrent use, with an incidence rate ratio of 1.82 (1.35–2.46). Dual combinations of just one antihypertensive drug and an NSAID showed no increased risk. The KDIGO 2024 Clinical Practice Guideline for chronic kidney disease states that individuals with chronic kidney disease may be more susceptible to drug-induced nephrotoxicity. Practice Point 4.1.3 recommends reviewing and restricting potentially nephrotoxic over-the-counter medications and herbal remedies. The guideline notes that indiscriminate, long-term self-administration of these drugs is associated with an increased risk of kidney failure and should be discouraged. U.S. regulations mandate that over-the-counter labels for these medications state: ask a doctor before use if you have hypertension, heart disease, liver cirrhosis, or kidney disease, or if you are taking a diuretic. Evidence regarding starfruit comes from case series. A review evaluated 126 patients from 33 reports published between 1993 and 2016. The most common symptom was intractable hiccups (65%). Confusion and seizures were most frequently associated with death. No deaths occurred among patients with previously normal kidney function. Mortality was 36% among non-dialysis chronic kidney disease patients and 27% among dialysis patients. In individuals with normal kidney function who developed toxicity, the quantity of starfruit consumed was substantially higher. Another review of 136 patients found that 69.1% had pre-existing renal impairment. Renal biopsies showed oxalate-induced acute kidney injury, with authors concluding that oxalate and a neurotoxin called caramboxin are the primary toxic agents. Over a 10-year period, one hospital admitted 20 patients with kidney failure who developed illness after consuming starfruit or starfruit juice; 8 died, all within 5 days, including 1 who had not yet initiated dialysis. In a Brazilian cohort of 32 uremic patients, all those who received prompt hemodialysis—including severe cases—recovered without sequelae. Severe cases that were untreated or treated only with peritoneal dialysis did not survive. The KDIGO guideline lists starfruit among herbal remedies and dietary supplements with evidence of potential nephrotoxicity.

Zhang X, Donnan PT, Bell S, Guthrie B (2017). Non-steroidal anti-inflammatory drug induced acute kidney injury in the community dwelling general population and people with chronic kidney disease: systematic review and meta-analysis. BMC Nephrology, 18(1):256. https://doi.org/10.1186/s12882-017-0673-8；Lapi F, Azoulay L, Yin H, Nessim SJ, Suissa S (2013). Concurrent use of diuretics, angiotensin converting enzyme inhibitors, and angiotensin receptor blockers with non-steroidal anti-inflammatory drugs and risk of acute kidney injury: nested case-control study. BMJ, 346:e8525. https://doi.org/10.1136/bmj.e8525；Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group (2024). KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney International, 105(4S):S117-S314，Practice Point 4.1.1、4.1.3 与 Figure 45. https://doi.org/10.1016/j.kint.2023.10.018；21 CFR 201.326(a)(2)(iii)(B). https://www.ecfr.gov/current/title-21/chapter-I/subchapter-C/part-201/subpart-G/section-201.326；Nderitu P, Doos L, Jones PW, Davies SJ, Kadam UT (2013). Non-steroidal anti-inflammatory drugs and chronic kidney disease progression: a systematic review. Family Practice, 30(3):247-255. https://doi.org/10.1093/fampra/cms086；Chua CB, Sun CK, Tsui HW, et al. (2017). Association of renal function and symptoms with mortality in star fruit (Averrhoa carambola) intoxication. Clinical Toxicology, 55(7):624-628. https://doi.org/10.1080/15563650.2017.1314490；Yasawardene P, Jayarajah U, De Zoysa I, Seneviratne SL (2021). Nephrotoxicity and neurotoxicity following star fruit (Averrhoa carambola) ingestion: a narrative review. Transactions of the Royal Society of Tropical Medicine and Hygiene, 115(9):947-955. https://doi.org/10.1093/trstmh/trab026；Chang JM, Hwang SJ, Kuo HT, et al. (2000). Fatal outcome after ingestion of star fruit (Averrhoa carambola) in uremic patients. American Journal of Kidney Diseases, 35(2):189-193. https://doi.org/10.1016/s0272-6386(00)70325-8；Neto MM, da Costa JA, Garcia-Cairasco N, et al. (2003). Intoxication by star fruit (Averrhoa carambola) in 32 uraemic patients: treatment and outcome. Nephrology Dialysis Transplantation, 18(1):120-125. https://doi.org/10.1093/ndt/18.1.120

Disputed: studies disagree on kidney harm from occasional use at the labeled dose. A 2013 systematic review concerned people aged 45 and older with moderate to severe chronic kidney disease. Standard doses were not significantly associated with faster kidney function decline: OR 0.96 (0.86–1.07). High doses were associated: OR 1.26 (1.06–1.50). KDIGO also says judicious use under a nephrologist’s supervision may be preferable to switching to opioid painkillers. The action is to ask a doctor first; this does not mean you can never take a single tablet. Your doctor should choose the painkiller and dose according to your kidney function; do not choose by yourself based on whether a medicine is metabolized in the liver or kidneys. Many combination cold remedies also contain NSAIDs; check the ingredients first. Many people with hypertension or diabetes have kidney disease without knowing it. If you have not been tested, get checked; see Section 16, Item 13 (detect chronic kidney disease early). For the maximum daily dose of paracetamol, see Item 1 in this section (paracetamol). For people at high risk of stomach harm from NSAIDs, see Item 3 in this section (painkillers such as ibuprofen). Star fruit cases were reported retrospectively, and severe cases are more likely to be published, so the roughly 30% mortality proportion may be inflated. These reports also cannot tell us what proportion of kidney patients who eat star fruit become ill. If persistent hiccups or confusion occur after eating star fruit, go to hospital the same day and tell the staff you ate it. The evidence grade is B because the NSAID figures come from observational studies without assigned interventions, and star fruit evidence consists only of case reviews. The benefit is rated medium as a judgment: acute kidney injury and star fruit poisoning have serious consequences but occur infrequently, and the studies cannot quantify how much following this advice reduces them. The main beneficiary is you. Site editorial note: the abstract of Zhang et al. (2017) reports a pooled odds ratio for acute kidney injury in older people of OR 2.51 (95% CI 1.52–2.68), but the subgroup analysis in the main text and Figure 4 both report OR 2.01 (1.52–2.68). The paper defines this age subgroup as older than 50 years. The abstract’s figure is therefore not consistent throughout the paper. An OR is an odds ratio, not a ratio of probabilities; it must not be read directly as a 2.51-fold or 2.01-fold probability of illness. Original paper: https://doi.org/10.1186/s12882-017-0673-8 .