Session Information
Session Type: Abstract Submissions (ACR)
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 10th day while serum levels showed partial fall at 14th 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 |
Disclosure:
A. Shukla,
None;
M. K. Rai,
None;
N. Prasad,
None;
V. Agarwal,
None.
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/