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

Soliman, Saeed; Ahmed, Rabab Mahmoud; Ahmed, Marwa Mostafa; Attia, Abeer; Soliman, Amin Roshdy

doi:10.2478/rjim-2024-0029

Figures & Tables

Geographical distribution of studied populations.

Forest plot of pooled ORs with subgroup analysis by age.

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

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

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

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

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

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
IBAÂ´ 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)

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

Figures & Tables

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Characteristics of included studies

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