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Non-steroidal anti-inflammatory drugs: what is the actual risk of chronic kidney disease? A systematic review and meta-analysis

Saeed Soliman

Saeed Soliman

Associate Professor of Family Medicine – Kasr Alainy Faculty of Medicine, Cairo UniversityCairo, Egypt
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Soliman, Saeed
, 
Rabab Mahmoud Ahmed

Rabab Mahmoud Ahmed

Associate Professor of Internal Medicine and Nephrology – Kasr Alainy Faculty of Medicine, Cairo UniversityCairo, Egypt
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Ahmed, Rabab Mahmoud
, 
Marwa Mostafa Ahmed

Marwa Mostafa Ahmed

Professor of Family Medicine – Kasr Alainy Faculty of Medicine, Cairo UniversityCairo, Egypt
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Ahmed, Marwa Mostafa
, 
Abeer Attia

Abeer Attia

Department of Public Health and Community Medicine – Kasr Alainy Faculty of Medicine, Cairo UniversityCairo, Egypt
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Attia, Abeer
 e 
Amin Roshdy Soliman

Amin Roshdy Soliman

Professor of Internal Medicine and Nephrology – Kasr Alainy Faculty of Medicine, Cairo UniversityCairo, Egypt
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Soliman, Amin Roshdy
  
31 mar 2025
Non-steroidal anti-inflammatory drugs: what is the actual risk of chronic kidney disease? A systematic review and meta-analysis's Cover Image
INFORMAZIONI SU QUESTO ARTICOLO
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Categoria dell'articolo: Review Articles
Pubblicato online: 31 mar 2025
Pagine: 3 - 27
Ricevuto: 30 lug 2024
DOI: https://doi.org/10.2478/rjim-2024-0029
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© 2025 Saeed Soliman et al., published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Figure 1.

PRISMA flowchart of study selection.
PRISMA flowchart of study selection.

Figure 2.

Geographical distribution of studied populations.
Geographical distribution of studied populations.

Figure 3.

Forest plot of pooled ORs.
Forest plot of pooled ORs.

Figure 4.

Forest plot of pooled HRs.
Forest plot of pooled HRs.

Figure 5.

Forest plot of pooled ORs with subgroup analysis by age.
Forest plot of pooled ORs with subgroup analysis by age.

Figure 6.

Forest plot of pooled ORs with subgroup analysis by chronic kidney disease outcome measurement methods.
Forest plot of pooled ORs with subgroup analysis by chronic kidney disease outcome measurement methods.

Figure 7.

Forest plot of pooled ORs with subgroup analysis by method of NSAID assessment.
Forest plot of pooled ORs with subgroup analysis by method of NSAID assessment.

Figure 8.

Forest plot of pooled HRs with subgroup analysis by chronic kidney disease status.
Forest plot of pooled HRs with subgroup analysis by chronic kidney disease status.

Figure 9.

Forest plot for studies with HR by subgrouping by chronic disease other than CKD.
Forest plot for studies with HR by subgrouping by chronic disease other than CKD.

Figure 10.

Forest plot for studies with HR by subgrouping with Method of NSAID assessment.
Forest plot for studies with HR by subgrouping with Method of NSAID assessment.

Figure 11.

Risk of bias (by study and by domain).
Risk of bias (by study and by domain).

Source/database Search term 1: NSAIDs Use Search Term 2: (AND) Search TERM 3: (OR) Number of entries found
Pubmed (((NSAID*[Title/Abstract]) OR (non-steroidal[Title/Abstract] AND anti-inflammatory[Title/Abstract] AND drugs[Title/Abstract])) OR (nonsteroidal[Title/Abstract] AND antiinflammatory[Title/Abstract] AND drugs[Title/Abstract])) OR (((ANTI-INFLAMMATORY AGENT [Title/Abstract]) OR (ANTI-INFLAMMATORY AGENTS[Title/Abstract])) OR (ANALGESICS[Title/Abstract])) ((((CKD[Title/Abstract]) OR (Chronic[Title/Abstract] AND Kidney[Title/Abstract] AND Disease[Title/Abstract])) OR (KIDNEY DISEASES[Title/Abstract])) OR (KIDNEY FAILURE[Title/Abstract])) OR (Nephropathy[Title/Abstract]) OR 2490
Chocrane database (nonsteroidal OR non-steroidal OR NSAID*):ti,ab,kw AND (((Long-term OR Chronic OR prolonged OR extended OR continuous) AND use) OR "Long-term effect" OR "long-term toxicity" OR "drug toxicity"OR "adverse effect"):ti,ab,kw ("Renal function" OR "kidney function" OR "glomerular filtration rate" OR creatinine OR albuminuria OR proteinuria OR EGFR):ti,ab,kw) 784
Scopus through Egyptian Knowledge bank ((((((AB=(CKD)) OR AB=(chronic kidney disease)) OR AB=(chronic renal )) OR AB=(e-GFR)) OR AB=(eGFR)) OR AB=(glomerular AND filtration)) OR AB=(nephropathy) (((AB=(nsaid*)) OR AB=( non-steroidal OR nonsteroidal)) OR AB=(anti-inflammatory )) OR AB=( anti-inflammatory ) 784
Science direct (nsaids OR non-steroidal OR nonsteroidal OR analgesics ((((CKD) OR (Chronic AND Kidney AND Disease)) OR (KIDNEY DISEASES)) OR (KIDNEY FAILURE)) 504

Characteristics of included studies

Study ID Population numbers Country Year of publication Aim of study: to determine Setting Study design Start date-End date of the study Population characteristics How NSAIDs exposure was assessed Outcome Outcome assessment methods
Agodoa 45 2008 996 United States 2008 Habitual analgesic use with decreased kidney function community based Cross sectional 1999–2002 civilian population 20 years or older standardized interview ACR≥ 30 mg/g and/or eGFR< 60 mL/min/1.73 m2 Creatinine, eGFR (MDRD), ACR
Amatruda 14 2021 2999 United States 2021 NSAID use with kidney damage in older adults community based Cross sectional 1997–1998 older adults 70–79 years with preserved physical function structured interview ACR≥ 30 mg/g and/or eGFR< 60 mL/min/1.73 m2 cysC-based CKD-EPI equation; ACR
Battelli 44 2015 33227 Republic of San Marino 2015 prevalence of NSAID use in patients with kidney damage in year 2013 compared to the general population community based Case-control 2013–2013 whole population under national health care Medical records Non severe renal damage Vs severe Creatinine; e GFR (CKD-EPI)
Chiu 22 2015 17376 Taiwan 2015 concomitant drugs of psoriasis and the risk of CKD community based Cohort 2001–2005 newly diagnosed with psoriasis and psoriatic arthritis Health Insurance Database new-onset CKD, ESRD secondary claim data
Chiu 23 2015 50316 Taiwan 2015 Risk of developing CKD in patients with RA community based Cohort 2001–2005 newly diagnosed with RA Health Insurance Database new-onset CKD, ESRD secondary claim data
Curhan 19 2004 1697 United States 2004 association between lifetime use of aspirin, and NSAIDs and renal function community based Cohort 1989–2000 Female aged 30–55 years with high life-time use of analgesic a mailed questionnaire change in eGFR in 11 years Estimated creatinine clearance(Cockcroft-Gault formula); e GFR (MDRD)
Field 15 1999 4999 United States 1999 NSAIDs use in older people and kidney function community based Cross sectional 1981–1989 older adults aged 70 y or more by interview Increased BUN and creatinine Creatinine, BUN BUN:creatinine ratio
Flores 46 2017 121 United States 2017 associations to CKD in an urban adult population A population-based Cross sectional 2015–2015 adult urban residents questionnaire Low eGFR e GFR (MDRD), spot proteinuria (semiquanitative reagent strip)
Gooch 16 2007 13523 Canada 2007 NSAID use and the progression of CKD in an elderly people community based Cross sectional 2001–2003 older adults aged 66 years with ≥ 2 serum creatinine measurements healthcare database decrease in eGFR of 15 mL/min/1.732 Creatinine; e GFR (MDRD)
Guh 41 2007 1740 Taiwan 2007 Herbal Vs NSAIDs therapy and CKD community based Cross sectional 1993–1996 adults in Nutrition and Health Survey in Taiwan by interview eGFR< 60 mL/min/1.73 m2 e GFR(Cockcroft-Gault)
Hanaoka 24 2022 423 Japan 2022 CKD in patients with RA and factors that influence CKD progression community based Cross sectional 2000–2016 patients diagnosed with RA who treated with one bDMARD for >5 years medical records eGFR< 60 mL/min/1.73 m2 or >25% decrease in eGFR from baseline e GFR(MDRD)
Hemmelgarn 17 2007 10148 Canada 2007 predict rapid progression of kidney dysfunction in elderly community based Cohort 2001–2003 elderly ≥66 years with ≥2 serum creatinine measurements provincial administrative data ≥25% decrease in eGFR from baseline Creatinine, e GFR (MDRD)
Hsu 31 2015 94541 Taiwan 2015 NSAID use on the development of CKD in hypertensive patients community based Cohort 2007–2011 Hypertensive patients aged 20 or more, had 1 admission or 2 outpatient visits and free of CKD Health Insurance Database newly diagnosed CKD medical claims data
Hsu 37 2019 456 Taiwan 2019 chronic pain and CKD progression in pre-dialysis CKD community based Cohort 2006–2007 18–80 y with stable CKD by interview CKD stage progression BUN, Creatinine; eGFR(CKD-EPI) and Proteinuria
IBA´ NEZ 32 2005 1302 Spain 2005 risk of ESRD associated with the chronic use of NSAID community based Case-control 1995–1997 advanced CKD patients by interview using a standardized questionnaire Entering dialysis Unclear
Ingrasciotta 42 2015 10034 Italy 2015 NSAIDs and risk of CKD in a general population community based Case-control 2006 to 2011 general populations who were registered in the Arianna database healthcare database Incident CKD By using ICD9-CM codes
Kaewput 13 2016 184 Thailand 2016 COX-2 inhibitors and CKD progression community based Cohort 2009–2014 >18 years with a diagnosis of CKD Medical records Any decrease in eGFR Creatinine, e GFR (CKD-EPI), spot proteinuria (semiquanitative reagent strip
Kang 18 2019 24219 Korea 2019 polypharmacy and kidney dysfunction among older patients. community based Case-control 2009–2013 older adults 65–84 medical records decline rate of ≥ 10% compared to the baseline eGFR e GFR (CKD-EPI)
Kuo 38 2010 19163 Taiwan 2010 Analgesic use in CKD patients hospital based Cohort 1997–2006 newly diagnosed CKD healthcare database increased risk for ESRD By using ICD9-CM codes
Kurth 21 2003 4494 United States 2003 aspirin and chronic kidney disease community based Cohort 1982–1996 apparently healthy males questionnaire Increase creatinine ≥0.3 mg/dl or decrease in eGFR of 29 mL/min/1.732 Creatinine, e GFR (MDRD)
Mackinnon 50 2003 7827 UK 2003 the rate of decline in renal function and risk of death or dialysis hospital based Cohort 1989–2003 Patients diagnosed with AAN by interview rate of change of ECC per year ESTIMATED Creatinine clearance (ECC)
Möller 25 2015 4101 Switzerland 2013 prolonged NSAID exposure on renal function in (RA) patient community based Cohort 1996–2007 RA patients annual visit & phone calls change of eGFR e GFR(Cockroft– Gault formula)
Mori 26 2017 1908 Japan 2017 prevalence of renal dysfunction in rheumatoid arthritis patients hospital based Cross sectional 2014–2015 Patients with RA medical records change of eGFR e GFR(Cockroft– Gault formula)
Morlans 20 1990 1305 Spain 1990 risk of ESRD with the regular use of analgesics Hospital based Case-control 1980–1983 female patients on dialysis by interview ESRD Unclear
Murray 40 1990 1908 United States 1990 incidence of renal impairment among patients NSAIDs community based Cohort 1975–1986 general population medical records >10% increase of BUN,Creatinine BUN,Creatinine
Nderitu 47 2014 3566 UK 2014 the effect of different dose NSAIDs on eGFR decline community based Cohort 2009–2010 general population healthcare database >5mL/min/1.73 m2/year eGFR decrease e GFR(MDRD)
Nelson 49 2019 764228 United States 2019 NSAIDs and incident chronic kidney disease community based Cohort 2011–2014 active-duty US Army soldiers medical records Incident CKD By using ICD9-CM codes
Pan 48 2014 50316 China 2014 NSAIDs intake and presence of (CKD) community based Cross sectional 2009–2010 general population by questionnaire eGFR< 60 mL/min per 1.73 m2 e GFR (Cockroft– Gault formula), ACR
Perneger 33 1994 1900 United States 1994 cumulative intake (in pills) with ESRD community based Case-control 1991–1991 20 to 64 y, with advanced CKD by telephone interview ESRD unclear
Plantinga 43 2011 12065 United States 2011 patterns of NSAID use in CKD patients community based Cross sectional 1999–2004 adult aged 20 years or older by questionnaire eGFR< 60 mL/min per 1.73 m2 e GFR (MDRD)
Sandler 34 1989 1070 United States 1989 analgesics and chronic renal disease community based Case-control 1980–1982 age 30–70 y with newly diagnosed CKD and matched controls By telephone interview Renal disease ICD9-CM codes
Sandler 35 1991 1070 United States 1991 risk for CKD with regular use of (NSAIDs). hospital based Case-control 1980–1982 newly diagnosed CKD and matched controls by telephone interview Renal disease ICD9-CM codes
Shigidi 29 2021 736 Sudan 2021 factors that promote the development and progression of DKD hospital based Case-control 2019–2019 aged 35 years or above, with T2DM for more than 10 years Direct interview eGFR< 60 mL/min per 1.73 m2 e GFR
Sturmer 27 2001 802 Germany 2001 effects of NSAID half-life and dosing intervals on renal function hospital based Cross sectional 1995–1996 patients undergoing total joint replacement because of osteoarthritis under the age of 76 years Standardized interview eGFR< 60 mL/min per 1.73 m2 Creatinine, estimate creatinine clearance
Tokoroyama 28 2017 107746 Japan 2017 prevalence of CKD hospital based Cohort 2004–2014 RA patients medical records eGFR< 60 mL/min per 1.73 m2 Proteinuria ≥ +1, e GFR (Cockroft– Gault formula)
Tsai 30 2015 48715 Taiwan 2015 relationship between NSAIDs and the development of CKD in people with Type 2 diabetes mellitus hospital based Cohort 2007–2011 adult population with Type 2 diabetes Healthcare database CKD development ICD9-CM codes
vanderWoude 36 2007 3286 Germany 2007 relation between phenacetin-free analgesics and nephropathy community based Case-control 2001–2004 advanced CKD under the age of 50 by Standardized interview ESRD unclear
WanEYF 51 2021 419506 Hong kong 2021 NSAIDs exposure and eGFR hospital based Cohort not mentioned All individuals with eGFR above or equal 60 ml/min by interview incident eGFR, 60 ml/min per 1.73 m2, eGFR decline $30% e GFR (MDRD)
Yarger 12 2011 34,295 United States 2011 NSAID use and CKD progression in elderly community based Cohort 2006–2008 CKD stage 2 or 3 who were elderly (67 years of age) received treatment at a military facility Healthcare database CKD progression of stage 2 or 3 e GFR
Zhan 39 2020 3939 United States 2020 opioid and NSAID use in patients with CKD hospital based Cohort 2003–2006 21–74 years of age with eGFR 20–70 mL/min by interview 50% reduction of baseline eGFR or requiring kidney replacement therapy e GFR(MDRD)
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