Assessment of renal involvement in an Iraqi cohort of rheumatoid arthritis

Bzhar Abdullah Abubaker; Hussein Yousif Sinjari

doi:10.4103/MJBL.MJBL_29_20

ORIGINAL ARTICLE

Year : 2020 | Volume : 17 | Issue : 4 | Page : 353-357

Assessment of renal involvement in an Iraqi cohort of rheumatoid arthritis

Bzhar Abdullah Abubaker¹, Hussein Yousif Sinjari²
¹ Department of Internal Medicine, KBMS, Erbil, Iraq
² Department of Internal Medicine, College of Medicine, HMU, Erbil, Iraq

Date of Submission	23-Apr-2020
Date of Acceptance	23-Aug-2020
Date of Web Publication	14-Dec-2020

Correspondence Address:
Bzhar Abdullah Abubaker
Department of Internal Medicine, KBMS, Erbil
Iraq

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/MJBL.MJBL_29_20

Abstract

Background: Rheumatoid arthritis (RA) is an autoimmune chronic systemic inflammatory disease involves synovial joints but may involve extra-articular organ as well. Objectives: to determine the prevalence of indicators of renal involvement in patients with RA with implications of impact of related drugs on the kidney. Materials and Methods: This cross-sectional study was conducted from May 1, 2019, to November 1, 2019, in the Outpatient Rheumatology Clinic of Hawler teaching hospital, Erbil, Iraq. One hundred and seventy-six patients with seropositive RA were enrolled, other 13 were dropped because of missing data. Participant's characteristics and data regarding drug history were collected. Body mass index (BMI), erythrocyte sedimentation rate (ESR), and serum creatinine were measured; renal function was assessed from the estimated glomerular filtration rate (eGFR) using the modification of diet in renal disease formula. Urine examined for proteinuria, microscopic hematuria, and noninfectious leucocyturia. When eGFR <60 ml/min/1.73 m² regarded as renal impairment, impact of RA medications non-steroidal anti-inflammatory drug, disease-modifying anti-rheumatic drugs, and biological agents on renal function and urine sediments were studied. Results: Out of a total 176 RA patients, 56.8% were females, their mean age 50.4 (±10.4) years, BMI 28.7 (±3.6) kg/m², with disease duration 8.3(±4.5) years. Renal impairment was detected in 20 (11.4%) participants. Proteinuria, hematuria, and uninfectious leucocyturia were observed in 10.2%, 23.9%, and 25%, respectively. Renal dysfunction was significantly associated with old ages, BMI ≥30, long duration of disease and proteinuria (P = 0.004, 0.002, 0.014, and 0.009, respectively). Renal impairment was not significantly associated with sex, smoking status, ESR level, RA medications, hematuria, and uninfectious leucocyturia (P > 0.5). Conclusions: Renal disorder is common in RA patients. Regular monitoring of renal involvement by using eGFR and urinary dipstick is crucial, especially in the elderly obese RA patients with a long duration of the disease and proteinuria. Early identification of renal disease can facilitate the early intervention and achieve the better management of RA patients.

Keywords: Disease-modifying anti-rheumatic drugs, estimated glomerular filtration rate, proteinuria, renal involvement, rheumatoid arthritis

How to cite this article:
Abubaker BA, Sinjari HY. Assessment of renal involvement in an Iraqi cohort of rheumatoid arthritis. Med J Babylon 2020;17:353-7

How to cite this URL:
Abubaker BA, Sinjari HY. Assessment of renal involvement in an Iraqi cohort of rheumatoid arthritis. Med J Babylon [serial online] 2020 [cited 2021 Feb 28];17:353-7. Available from: https://www.medjbabylon.org/text.asp?2020/17/4/353/303252

Introduction

Rheumatic diseases are autoimmune diseases affecting joints and soft tissue with some time extra articular involvement that affects solid organs such as kidneys.^[1] There are number of rheumatic diseases can present with renal involvement with different presentations varies from mild to severe, screening of serum and urine parameters for assessing of renal function is mandatory for patients with rheumatic diseases.^[2] Renal disease and rheumatic disease are both commonly seen in outpatients, about 18% of rheumatology clinics were reported to have estimated glomerular filtration rate (eGFR) ≤60 ml/min/1.73 m² in comparison with the general population which is 5%.^[3] Rheumatoid arthritis (RA) is an autoimmune chronic systemic inflammatory disease involves synovial joints but may involve extraarticular organ as well, affects 0.5%–1% population worldwide.^[4] Renal involvement in RA patients are caused by either renal toxicity of medications used in RA such as nonsteroidal anti-inflammatory drugs (NSAIDs), cyclosporine, and methotrexate or secondary renal involvement by the chronic inflammatory process of RA such as renal amyloidosis or various types of glomerulonephritis.^[5] Despite the presence of various causes of renal involvement in RA patients, the prevalence of renal disorders in RA are too small and the incidence of renal involvement vary depending on the criteria used and the patients population examined, they might present with isolated hematuria or proteinuria or combined hematuria and proteinuria or decrease in eGFR.^[6],[7],[8] Proper management of RA and judicious use of RA medications could help to reduce other related diseases by reducing shared risk factors and prevalence of systemic manifestations like renal impairment which is serious health problem but treatable disease if caught in the early stages.^[9]

The current study designed to determine the indicators of renal involvement in RA patients with implications of impact of RA medications on the kidney.

Materials and Methods

Study design and patients

This cross-sectional study was conducted in the Outpatient Rheumatology Clinic at Hawler teaching hospital, Erbil, Iraq, from May 1, 2019, to November 1, 2019. All patients with confirmed seropositive RA for either or both (rheumatoid factor and Anti CCP antibody) were enrolled in this study, unless they met any of the following exclusion criteria: <18 years of age, those with comorbidities such as diabetes mellitus, hypertension, heart failure, chronic liver disease, history of organ transplant, acute renal failure in past 3 months, receiving renal replacement therapy, having other rheumatic disorders, and being pregnant.

Out of 189 patients met the inclusion criteria, 176 of them enrolled in the study other dropped because of unwillingness or missing data. All participants underwent detailed history and proper physical examination. For each participant, the following data were recorded: age, gender, obesity (body mass index [BMI]: kg/m²), smoking status, duration of the disease, and medication use in the treatment course; disease modifying antirheumatic drugs (DMARDs), biological agents, and intake of NSAIDs during the last 3 months. Laboratory tests include erythrocyte sedimentation rate (ESR) as a parameter of inflammation, serum creatinine (sample was analyzed on COBS-111 machine) as a marker of excretory renal function, for calculation the mean of 2 readings 1 week apart was used. At enrolment, all patients were screened for renal disorder by urine dipstick and urine analysis, kidney damage was suggested by the presence of proteinuria ≥1+, hematuria ≥5 RBC/high-power field or uninfectious leucocyturia ≥1+ without nitrite on two occasions 1 week apart. Calculation of eGFR was done by using the modification of diet in renal disease formula which is widely used formula in clinical practice.^[10] In our study, if eGFR <60 ml/min/1.73 m² regarded as renal impairment. All patients with abnormal urine sediment underwent renal ultrasonography study to exclude local anatomical cause.

Statistical analysis

Data were analyzed using the Statistical Package for the Social Sciences software version 24 (SPSS, IBM company, USA). The Chi-square test of association was used to compare the proportions. P < 0.05 was considered statistically significant.

Ethical consideration

The study was approved by the scientific and ethical committee of Kurdistan Board for Medical Specialties in accordance with the Helsinki's declaration guideline for the involvement of humans in research. All participants gave their written and informed consent.

Results

Out of 189 RA patients, 13 (6.8%) were dropped because of unwillingness or missing data. A total of 176 participants were analyzed, including 100 (56.8%) women, the mean age of the study subjects was 50 ± 10 years, 46 (26.1%) smokers, disease duration 8.3 ± 4.5 years, and BMI 28.7 ± 3.6 kg/m², renal impairment was detected in 20 patients (11.4%) with eGFR 60 mL/min/1.73 m² [Table 1].

Table 1: Demographic characteristics of the participants

Click here to view

The association between renal impairment and basic characteristics of the participants shows that, renal impairment was strongly associated with age >45 years, BMI ≥30, and longer disease duration >5 years (P = 0.004, 0.002, and 0.014, respectively), but not associated with gender, smoking status, and ESR level, (P = 0.062, 0.477, and 0.611, respectively). Almost all participants were on DMARDs, 112 (63.6%) of them were on one or more of the following DMARDs: methotrexate, leflunomide, hydroxychloroquine, and sulfasalazine, whereas 62 (35.2%) were on a biological agent (etanercept, adalimumab, or infliximab) in addition to a conventional DMARDs, 80 patients (45.5%) were on self-use or clinician prescription NSAIDs, the association of these medications with renal dysfunction were statistically not significant (P = 0.229, 0.261, and 0.137, respectively) [Table 2].

Table 2: Association of studied parameters with impaired renal function

Click here to view

Proteinuria was detected in 18 participants (10.2%) and strongly associated with renal impairment (P = 0.009). Microscopic hematuria was recorded in 42 (23.9%) and uninfectious leucocyturia in 44 (25%) of the respondents, although their prevalence is a bit higher in patients with low eGFR but the association is statically not significant (P = 0.074 and 0.078, respectively) [Table 3].

Table 3: Association of estimated glomerular filtration rate with urine sediments of participants

Click here to view

The impact of RA medications on urine sediment shows no significant association between NSAIDs and DMARDs with proteinuria (P = 0.949 and 0.178, respectively). The prevalence of proteinuria was significantly less among patients using biological agent plus DMARDs P = 0.009. On the other hand, no statistically significant association detected between NSAIDs, DMARDs, and biological agent with hematuria (P = 218, 0.741 and 0.170, respectively) [Table 4] and [Table 5]

Table 4: The association of rheumatoid arthritis medications with proteinuria

Click here to view

Table 5: The association of rheumatoid arthritis medications with hematuria

Click here to view

Discussion

RA is an autoimmune chronic systemic inflammatory disease involves the joints with extraarticular manifestations. Renal involvement in RA may be caused by disease process and the medications for control, it increases the morbidity and mortality by increasing the cardiovascular events.^[11],[12] In the current study, out of 176 RA patients, 11.4% of them had eGFR 60 ml/min/1.73 m². On comparing our results with related studies, it is a bit higher than that recorded in multicenter COMEDRA French study (8.8%),^[13] but it is lower than that reported in recent study conducted in Pakistan (14.8%), in MATRIX study in UK (15%), in a nationwide database study in Japan, (18.5%) and in a study from Ethiopia (22.4%).^{[14],[15],[16]} This variation could be explained by the exclusion criteria depended in this study, which excluded patients with comorbidities that might be an additional risk factor for kidney disease. The finding of the present study revealed that older age of participants was one of the strong predictors associated with renal insufficiency, this is similar to many other related studies.^{[13],[14],[16],[17]} This is possibly explained by the inverse relationship of advancing age and eGFR calculation in addition to the fact that with increasing age there is gradual decrease in nephrons number and concomitant decline in GFR. The present study shows that obesity (BMI ≥30) was significantly associated with renal impairment, this is consistent with Hickson et al. study^[18] but inconsistent with several studies which used BMI >25 as cut off value for calculations.^{[12],[14],[19]} Our results revealed that RA duration was significantly associated with renal dysfunction, similar to the data obtained in other studies^[14],[19] and inconsistent with COMEDRA study.^[13] In the current study, there was no significant association of renal dysfunction with sex, smoking history, ESR level, or RA-related medications. Similarly, Couderc et al. revealed that there was no significant association between renal impairment and sex, disease activity (as assessed by DAS28-ESR), NSAIDs, and biological and conventional DMARDs.^[7] Jima et al. found that Smoking and NSAIDs associated with renal impairment but sex and DMARDS not.^[16] Two recently published study reported that the use of biological DMARDs may lower the risk of decreasing renal function in RA patients.^[20],[21] Proteinuria is associated with increased cardiovascular mortality in the general population^[22] and in RA patients.^[8] In the present study, proteinuria was associated significantly with renal impairment similar to Jima et al.'s study^[16] and was less prevalent in patients using biological agents with DMARDs. Proteinuria, hematuria, and uninfectious leucocyturia were observed in 10.2%, 23.9%, and 25% of the study participants, respectively; our results is near to that reported in MATRIX study 16.2%, 17.2%, and 20.2% of the patients, respectively.^[5] Mori et al. in a large cross-sectional study identified proteinuria in 8.1% (155 out of 1908 patients), and hematuria in 7.5% (143 out of 1908 patients), both were more prevalent in the renal dysfunction group.^[19] Koseki et al. in a prospective study of renal disease with early RA, noted persistent proteinuria in 7% mostly drug-related (Gold and D-Penicillamine but not Methotrexate), and isolated hematuria in 17% which was associated with disease activity rather than treatment.^[23]

Limitations of the study

First, it was a cross-sectional study, which cannot establish cause-effect relationship. Second sample size was small. However, it has few strong points, like it was the first study carried out on local population in Kurdistan, Iraq, about renal involvement in RA patients.

Conclusions

Renal disorder is common in RA patients. Regular monitoring of renal involvement by using eGFR and urinary dipstick is crucial, especially in elderly obese RA patients with a long duration of the disease and proteinuria. Early identification of renal disease can facilitate early intervention and achieve better management of RA patients.

Acknowledgment

We would like to thank the staffs of rheumatology clinic and laboratory for their unreserved support and patients who participated in the study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1.	Anders HJ, Vielhauer V. Renal co-morbidity in patients with rheumatic diseases. Arthritis Res Ther 2011;13:222.
2.	Horak P, Smrzova A, Krejci K, Tichy T, Zadrazil J, Skacelova M. Renal manifestations of rheumatic diseases. A review. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2013;157:98-104.
3.	Hill AJ, Thomson RJ, Hunter JA, Traynor JP. The prevalence of chronic kidney disease in rheumatology outpatients. Scott Med J 2009;54:9-12.
4.	Kelly's Text Book of Rheumatology. 9^th ed.. St Louis: WB Saunders; 2012. p. 1132-3.
5.	Karie S, Launay-Vacher V, Gandjbakhch F, Janus N, Rozenberg S, Bourgeois P, et al. Comment on: Kidney disease in RA patients: Prevalence and implication on RA-related drugs management: The MATRIX study: Reply. Rheumatology 2008;47:1259-60.
6.	Karstila K, Korpela M, Sihvonen S, Mustonen J. Prognosis of clinical renal disease and incidence of new renal findings in patients with rheumatoid arthritis: Follow-up of a population-based study. Clin Rheumatol 2007;26:2089-95.
7.	Couderc M, Tatar Z, Pereira B, Tiple A, Gilson M, Fautrel B, et al. Prevalence of renal impairment in patients with rheumatoid arthritis: Results from a cross-sectional multicenter study. Arthritis Care Res (Hoboken) 2016;68:638-44.
8.	Sihvonen S, Korpela M, Mustonen J, Laippala P, Pasternack A. Renal disease as a predictor of increased mortality among patients with rheumatoid arthritis. Nephron Clin Pract 2004;96:c107-14.
9.	Hajivandi A, Amiri M. World kidney day 2014: Kidney disease and elderly. J Parathyroid Dis 2014;2:3-4.
10.	Stevens PE, Levin A, Kidney Disease: Improving Global Outcomes Chronic Kidney Disease Guideline Development Work Group Members. Evaluation and management of chronic kidney disease: Synopsis of the kidney disease: Improving global outcomes 2012 clinical practice guideline. Ann Intern Med 2013;158:825-30.
11.	Sijl A, Oever A, Peters M, Boers M, Dijkmans B, Halm V, et al. Subclinical renal dysfunction is independently associated with cardiovascular events in rheumatoid arthritis: CARRE study. Ann Rheum Dis 2012;71:341-4.
12.	Hsien-Yi C, Hui-Ling H, Chien-Hsun L, Hung-An C, Chia-Lun Y, Shih-Hsiang C, et al. Increased risk of chronic kidney disease in rheumatoid arthritis associated with cardiovascular complications– A national population cohort study. PLoS One 2015;10:e0136508.
13.	Marion C, Zuzana T, Bruno P, Aurelien T, Melanie G, Bruno F, et al. Prevalence of renal impairment in patients with rheumatoid arthritis: Results from a multicenter study. Arthritis Care Res 2016;68:638-44.
14.	Wagan AA, Nasir S, Rahim A, Khan D. Impaired renal functions in Pakistani cohort of rheumatoid arthritis. Pak J Med Sci 2019;35:905-10.
15.	Saisho K, Yoshikawa N, Sugata K, Hamada H, Tohma S. Prevalence of chronic kidney disease and administration of RA-related drugs in patients with RA: The NinJa 2012 study in Japan. Mod Rheumatol 2016;26:331-5.
16.	Jima B, Dejene G, Hailemariam T. Prevalence and risk factors of renal impairment among rheumatoid arthritis patients attending outpatient department of Tikur Anbessa specialized hospital. Intern Med 2016;6;230.
17.	Daoussis D, Panoulas VF, Antonopoulos I, John H, Toms TE, Wong P, et al. Cardiovascular risk factors and not disease activity, severity or therapy associate with renal dysfunction in patients with rheumatoid arthritis. Ann Rheum Dis 2010;69:517-21.
18.	Hickson LJ, Crowson CS, Gabriel SE, McCarthy JT, Matteson EL. Development of reduced kidney function in rheumatoid arthritis. Am J Kidney Dis 2014;63:206-13.
19.	Mori S, Yoshitama T, Hirakata N, Ueki Y. Prevalence of and factors associated with renal dysfunction in rheumatoid arthritis patients: A cross-sectional study in community hospitals. Clin Rheumatol 2017;36:2673-82.
20.	Yusuke M, Yajima N, Isojima S, Yanai R, Hatano M, Miura Y, et al. Treatment of rheumatoid arthritis with combination therapy using a biological agent and Methotrexate lowers the risk of decreasing kidney function compared to Methotrexate monotherapy. Ann Rheum Dis 2019;78:331-2.
21.	Sumida K, Molnar M, Potukuchi P, Hassan F, Thomas F, Yamagata K, et al. Treatment of rheumatoid arthritis with biologic agents lowers the risk of incident chronic kidney disease. Kidney Inter 2018;93:1207-16.
22.	Irie F, Iso H, Sairenchi T, Fukasawa N, Yamagishi K, Ikehara S, et al. The relationships of proteinuria, serum creatinine, glomerular filtration rate with cardiovascular disease mortality in Japanese general population. Kidney Int 2006;69:1264-71.
23.	Koseki Y, Terai C, Moriguchi M, Uesato M, Kamatani N. A prospective study of renal disease in patients with early rheumatoid arthritis. Ann Rheum Dis 2001;60:327-31.