Background/Purpose

NSAIDs are the first-line therapy for spondyloarthritis (SpA) patients and are associated with the risk of kidney injury. Long-term NSAID use is known to cause poor urine concentrating abilities. Short-term NSAID induced subclinical-kidney-injury is not well studied. Herein, we studied the effect of short-term NSAID use on kidney injury by measuring serum and urine biomarkers.

Methods

In cross-sectional study, 40 healthy controls with minimal-NSAID-exposure (cohort-A) and 40 SpA patients on regular-NSAIDs for >3 months (cohort-B) were included. In another cohort, 17 SpA-patients with minimal baseline NSAID-exposure (cohort-C) were treated with regular-NSAIDs for 6 weeks. Urine and serum samples were collected at 0, 1 and 6 weeks. In addition, 6 healthy volunteers (cohort-D) were treated with 7 days of daily NSAID. Daily urine and weekly blood samples were collected for 14 days; including 7 days after the drug was stopped. Biomarkers like NGAL, KIM1, cystatin-C and micro-albumin (ELISA) were measured. Creatinine (Jaffe’s method) was measured in all samples.

Minimal-NSAID-exposure was defined as nil in last week, <15 tablets in last month, <2 tablets/week in last year or <1000 tablets lifetime exposure. Normal-renal-function was ensured in all subjects as eGFR ≥90ml/min, <1+dipstick proteinuria and inactive urine sediments.

Results

Median age of cohort-A and B was 27 (IQR 26-35) and 30 (IQR 24-38) years respectively with male to female ratio of 3:1. Duration of NSAID use in cohort-B was 7 (IQR 5-12.5) months. There was no significant difference in serum creatinine and eGFR in both cohorts while biomarker levels were raised in cohort-B compared to cohort A (Mann-Whitney test, table).

Median age of cohort-C was 35 (IQR 28-40) years and male to female ratio of 9:8. Urine biomarker levels showed a significant rise on treatment with NSAIDs at 1 week, (Wilcoxon test) cystatin C p=0.01, NGAL p=0.02, KIM1 p=0.08 and micro-albumin p=0.1. There was a further significant rise in urine and serum levels at 6 weeks (Friedman test, table). Cohort-D showed a rise in urine and serum levels of biomarkers at 7 days followed by a fall to baseline in urine levels at 10^th day while serum levels showed partial fall at 14^th day.

Conclusion

Short-term NSAID use may induce subclinical-kidney-injury represented by rise of urine and serum biomarkers, even in absence of changes in serum creatinine or eGFR. These levels start rising as early as 7 days of NSAID use.

Table 

Changes in urine and serum levels of Kidney-Injury Biomarkers

U=urine, S=serum, Cr=creatinine, results represented as median with inter-quartile range, Estimated GFR (eGFR) calculated by Cockcroft-Gault Equation

Biomarkers	Cohort-A N=40	Cohort-B N=40	p value	Cohort-C Baseline N=17	Cohort-C 1-week N=17	Cohort-C 6-week N=17	p value
S Creatinine mg/dl	0.79 (0.7-0.9)	0.78 (0.7-0.85)	0.56	0.85 (0.7-1.0)	–	0.85 (0.77-0.95)	0.74
eGFR ml/min	117 (100-137)	108 (95-139)	0.37	107 (101-121)	–	123 (105-134)	0.59
U KIM1/Cr ng/mg	0.07 (0.05 to 0.1)	0.2 (0.01-0.28)	<0.0001	0.03 (0.02-0.12)	0.08 (0.04-0.14)	0.18 (0.10-0.54)	<0.0001
U NGAL/Cr ng/mg	7.1 (4.2 to 15.6)	22.22 (10.35-48.31)	<0.0001	4 (3.2-7.4)	6.8 (5.2-11.6)	37 (20.6-72.6)	<0.0001
U Cystatin-C/Cr ng/mg	71.6 (63.2-102.7)	136.6 (64-216)	0.03	50 (40.7-86)	74 (51-94.3)	123 (93.3-208)	0.0007
Micro-albumin/Cr μg/mg	7.7 (4.3-12)	8.4 (3.6-19.5)	0.55	5.4 (3.4-8.2)	5.5 (5-9.5)	9 (7.6-36.3)	0.003
S KIM1 pg/ml	230 (123-412)	391 (296-494)	0.001	221 (166-248)	–	397 (321-449)	<0.0001
S NGAL ng/ml	137 (90-170)	187 (132-214)	0.001	101 (45.5-130)	–	140 (86-171)	<0.0001
S Cystatin-C mg/ml	0.15 (0.13-0.16)	0.18 (0.12-0.28)	0.07	0.07 (0.06-0.08)	–	0.09 (0.08-0.1)	<0.0001

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/short-term-non-steroidal-anti-inflammatory-drug-nsaid-use-induces-subclinical-kidney-injury-in-spondyloarthritis-patients-urinary-biomarker-study/