Non-steroidal anti-inflammatories and the development of analgesic nephropathy: a systematic review

Figures & data

Figure 1. Flow diagram of search strategy.

Table 1. Characteristics of observational studies included in this review.

Study	Design	Population	Intervention Group	Control Group	Adjustment for Confounders	Definition of Outcome	Relative Risk of Renal Impairment	Relationship Identified	GRADE Study Quality
Agodoa et al.^12	Cohort	305 study patients, 6191 control patients	Random civilians reporting daily ibuprofen ingestion for at least 1 month at any time previously	Random civilians reporting maximum consecutive daily ibuprofen ingestion of less than 1 month	Age, ethnicity, sex, education, diabetes, hypertension, cardiovascular disease, other analgesic agents	GFR <60 mL/min/1.73m^2, albuminuria with uACR >30 mg/g	OR 1.21 (95% CI: 0.7–2.1), OR 0.65 (95% CI: 0.4–1.2)	No	Low
Curhan et al.^13	Cohort	840 study patients, 790 controls	Female registered nurses reporting lifetime consumption of 100–499 g NSAIDs, 500–2999 g NSAIDs, or ≥3000g NSAIDs	Female registered nurses reporting lifetime consumption of <100g NSAIDs	Age, weight, smoking, hypertension, diabetes, hypercholesterolemia	Decline in GFR from baseline ≥30 mL/min/1.73m^2 over 11 years, decline in GFR from baseline ≥30% over 11 years	100–499g NSAIDs: GFR decline ≥30 mL/min/1.73m^2 OR 1.33 (0.79–2.24), GFR decline ≥30% OR 1.28 (0.75–2.19) 500–2999g NSAIDs: GFR decline ≥30 mL/min/1.73m^2 OR 1.10 (0.70–1.92), GFR decline ≥30% OR 1.20 (0.77–1.85) ≥3000g NSAIDs: GFR decline ≥30 mL/min/1.73m^2 OR 1.08 (0.67–1.76), GFR decline ≥30% OR 1.21 (0.75–1.93)	No	Moderate
Ibanez et al.^14	Case–control	520 study patients, 982 controls	Consecutive patients enrolled in a metropolitan dialysis registry between June 1995 and November 1997	Randomly selected age-matched hospital inpatients	Smoking, kidney stones, gout, aspirin use, cardiovascular disease, gender, “serious” medical comorbidities	Daily or second-daily use of an NSAID for 1 month at any time prior to kidney disease diagnosis	OR 0.94 (0.57–1.56)	No	Low
Ingrasciotta et al.^15	Case–control	1989 study patients, 7906 controls	Primary care network patients with a coded diagnosis of CKD	Age-matched controls randomly selected from the primary care network database	Gender, cardiovascular disease, cancer, liver disease, autoimmune disease	Any NSAID consumption in the previous 90 days, 91–180 days, and before 180 days ago	OR 1.10 (0.96–1.25), OR 1.00 (0.89–1.12), OR 0.94 (0.84–1.05)	No	Low
Kohlhagen et al.^16	Cohort	69 study patients, 69 controls	Consecutive rheumatology outpatient attendees reporting lifetime consumption of greater than 500 NSAID tablets	Consecutive age-matched medical inpatients with lifetime consumption of less than 100 NSAID tablets	Gender, weight, hypertension, aspirin consumption, combination analgesic consumption, known renal diagnoses	Reduced GFR, defined as estimated GFR less than expected for patient age using the Cockcroft–Gault equation	OR 1.24 (95% CI: 0.49–3.10)	No	Low
Moller et al.^17	Cohort	2739 study patients, 1362 controls	Health registry patients with rheumatoid arthritis and at least one filled prescription for NSAIDs over a study duration of 3.2 years	Health registry patients with rheumatoid arthritis and no filled prescription for NSAIDs over a study duration of 3.2 years	Gender, age, cardiovascular disease, known renal diagnoses, non-NSAID anti-rheumatic therapy	Difference in mean reduction of GFR from baseline after follow-up	NSAID-user mean GFR decline 0.87 mL/min/1.73m^2 (95% CI: 0.59–1.15), non-users mean GFR decline 0.67 mL/min/1.73m^2 (95% CI: 0.09–1.26), p = 0.63	No	Low
Perneger et al.^18	Case–control	716 study patients, 361 controls	All patients enlisted in an interstate regional dialysis registry, excluding those logistically unable to participate or whose kidney function had recovered	Age-matched random civilian residents within the dialysis registry jurisdiction who were not included on the registry	Gender, ethnicity, other analgesic drugs	Lifetime consumption of <1000 NSAID tablets, 1000–4999 NSAID tablets, or ≥5000 NSAID tablets	OR 1.0, OR 0.6 (95% CI: 0.3–1.1), OR 8.8 (1.1–71.8)	No	Moderate
Rexrode et al.^19	Cohort	4686 study patients, 5700 controls	Male physicians reporting lifetime consumption of 12–1499 NSAID tablets, 1500–2499 tablets, or ≥2500 tablets	Male physicians reporting lifetime consumption of <12 NSAID tablets	Age, weight, cardiovascular disease, physical activity, use of other analgesic drugs	Creatinine >1.5 mg/dL, GFR ≤55 mL/min/1.73m^2	12–1499 NSAID tablets: creatinine >1.5 mg/dL RR 1.01 (95% CI: 0.78–1.30), GFR ≤55 mL/min/1.73m^2 RR 1.01 (0.84–1.23) 1500–2499 NSAID tablets: creatinine >1.5 mg/dL RR 0.87 (0.46–1.63), GFR ≤55 mL/min/1.73m^2 RR 1.06 (0.66–1.72) ≥2500 NSAID tablets: creatinine >1.5 mg/dL RR 1.07 (0.71–1.64), GFR ≤55 mL/min/1.73m^2 RR 1.01 (0.73–1.41)	No	Moderate
Sandler et al.^20	Case–control	554 study patients, 516 controls	Consecutive patients discharged following hospital admission with a discharge diagnosis of CKD and with serum creatinine ≥1.5 mg/dL	Randomly matched civilians residing in the local postcodes of the relevant hospitals	Age, gender, ethnicity, financial income	Daily ingestion of NSAIDs for a minimum 360 consecutive days at any time previously	OR 2.1 (1.1–4.1) overall, effect limited to men aged greater than 65 years of age (OR 10.0, 95% CI: 1.2–82.7)	Yes	Very low

Table

Underlying methodology	Quality rating
Randomized trials; or double-upgraded observational studies	High
Downgraded randomized trials; or upgraded observational studies	Moderate
Double-downgraded randomized trials; or observational studies	Low
Triple-downgraded randomized trials; or downgraded observational studies; or case series/case reports	Very low

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