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Abstract

Background:

Although extramusculoskeletal manifestations, such as uveitis and psoriasis, in patients with axial spondyloarthritis (SpA) are well-documented, studies on the occurrence of glomerulonephritis in this population are scarce.

Objectives:

This study aimed to assess the incidence rate and risk factors for glomerulonephritis in patients with axial SpA using a nationwide population-based cohort in Korea.

Design:

Nationwide population-based study.

Methods:

This study included patients diagnosed with axial SpA between 2016 and 2019 from Korea’s National Health Insurance Database. Patients with a diagnosis of preexisting kidney disease prior to their axial SpA diagnosis and those diagnosed with glomerulonephritis within 1 year of their axial SpA diagnosis were excluded. For the remaining patients, the incidence rates of glomerulonephritis and Cox proportional hazard ratios were analyzed.

Results:

Among the 11,796 patients, 58 had glomerulonephritis, resulting in an incidence rate of 1.82 per 1000 person-years. After adjusting for age and sex, the hazard ratio for patients with a Charlson Comorbidity Index score of ⩾1 was 2.03 (confidence interval (CI), 1.14–3.63; p = 0.017). When adjusting for age, sex, and comorbidities, the hazard ratio for patients with hypertension was 2.37 (CI, 1.20–4.69; p = 0.014). Among the 58 patients, 4 (6.9%) were diagnosed with glomerulonephritis, as confirmed via kidney biopsy.

Conclusion:

The incidence rate of glomerulonephritis in Korean patients with axial SpA is lower than that in patients with other musculoskeletal manifestations. In addition, the presence of comorbidities, including hypertension, is a significant risk factor for glomerulonephritis in patients with axial SpA. Despite the low occurrence, careful monitoring for glomerulonephritis in patients with axial SpA is essential.

Keywords

glomerulonephritis kidney disease spondyloarthritis

Introduction

Axial spondyloarthritis (SpA) is a chronic inflammatory disease that primarily affects the spine and sacroiliac joints. In addition to musculoskeletal symptoms, patients often experience extramusculoskeletal manifestations, such as uveitis, psoriasis, and inflammatory enteritis. Furthermore, cardiovascular, lung, and kidney diseases can occur as less common extramusculoskeletal manifestations.^1,2

Kidney disease in axial SpA is rare but has been documented in various studies.^3
–5 Among kidney-related conditions associated with axial SpA, those related to medication use are the most common. Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to manage axial SpA; however, long-term use of NSAIDs can negatively affect kidney function.^6
-8 These drugs can reduce blood flow to the kidneys, potentially leading to kidney damage over time. Chronic inflammation related to axial SpA can lead to amyloidosis, a condition characterized by the accumulation of amyloid proteins in the kidneys, which impairs their function. In addition, there is a potential association between axial SpA and immunoglobulin A (IgA) nephropathy, a kidney disease in which IgA antibodies are deposited in the glomeruli, causing inflammation and subsequent kidney damage.⁹

Glomerulonephritis (GN) is rarely reported in patients with axial SpA. GN is a disease in which inflammation occurs in the glomeruli because of infection and autoimmune disease, and it can be affected by axial SpA and tumor necrosis factor (TNF) inhibitors.^10,11 However, because it is relatively rare compared with amyloidosis or IgA nephropathy, there have been no reports on its incidence rate or risk factors. This study aimed to determine the incidence rate and risk factors for GN in patients with axial SpA using a nationwide population-based cohort in Korea.

Methods

Materials and methods

Patients and study design

This retrospective study used health insurance data obtained from the Korea Review and Assessment Service. The inclusion criteria for this study specified patients diagnosed with axial SpA between May 1, 2016, and December 31, 2019 (Figure 1). However, patients with concurrent rheumatic diseases, such as psoriatic arthritis, Behçet’s disease, rheumatoid arthritis, inflammatory bowel disease, and systemic lupus erythematosus, were excluded. In addition, patients aged <20 years and those who did not visit a medical institution after axial SpA diagnosis were excluded from the analysis.

Figure 1.

Flowchart of the study.

Furthermore, to identify patients diagnosed with GN, inclusion criteria were defined as patients assigned primary and secondary diagnosis codes for GN (N00, N01, N02, N03, N04, N05, N06, N085, and N391). Patients registered with renal dialysis (Z992) or rare intractable disease (hemodialysis V001 and peritoneal dialysis V003) before the index date or patients who received dialysis for at least 3 months (Health Insurance Review and Assessment Service (HIRA) procedure codes) 7072, O9991, O7005) were excluded. To determine the relationship with axial SpA, patients diagnosed with GN within 1 year of the axial SpA diagnosis were excluded (diagnosis codes for axial SpA, GN, and comorbidities are shown in Supplemental Table 1). Subsequently, a detailed treatment history was confirmed in patients who underwent biopsy using the HIRA procedure code (needle biopsy code: C8513).

Patient information

Information on age group, sex, comorbidities, and medications at 5-year intervals was obtained from the classified patient claims data. The Charlson Comorbidity Index (CCI) score was calculated using diagnosis codes. The dosage of NSAIDs was calculated using the Assessment of SpondyloArthritis International Society (ASAS) NSAID Intake Score¹² from the intake history for 1 year after axial SpA diagnosis (NSAID codes for calculation of the ASAS NSAID intake score are shown in Supplemental Table 2). The presence or absence of the remaining drugs was confirmed (other medication codes are shown in Supplemental Table 3). If a patient had previously been prescribed oral, injection, or topical corticosteroids for treating peripheral arthritis or extramusculoskeletal manifestations of SpA, they were defined as users of corticosteroids.

Statistical analyses

Continuous variables are reported as means and standard deviations, whereas categorical variables are presented as counts and percentages. The incidence rate of GN events among patients with axial SpA was calculated per 1000 person-years. The risk of GN was calculated using Cox proportional hazard ratios. Variables deemed significant in the crude hazard ratio were included in the multivariate analysis. p-Value <0.05 was considered statistically significant. Finally, among patients classified as having GN, those diagnosed via biopsy had additional descriptions of their basic characteristics and treatment methods at the time of diagnosis.

The SAS Enterprise Guide (version 6.1, SAS Institute, Inc., Cary, NC, USA) and Project R (version 3.5.2, R Foundation for Statistical Computing, Vienna, Austria) software packages were used for statistical evaluations.

Results

Baseline characteristics and incidence rate

The baseline characteristics are shown in Table 1. There were 11,796 patients with axial SpA, 68% of whom were aged <50 years. Of these, 72.8% were male, and 61.3% had a comorbidity index of 0. The most common comorbidity was dyslipidemia, followed by hypertension and diabetes. Among the medications prescribed for 1 year after axial SpA diagnosis, 52.5% of the patients had an ASAS NSAID Index Score of ⩾ 33.3. Corticosteroids (67%), sulfasalazine (54.8%), and TNF inhibitors (20.8%) were mainly prescribed.

Table 1.

Baseline characteristics of the study population.

Variable	N (%)
Age group, year
<30	3082 (26.1)
30–39	2611 (22.1)
40–49	2339 (19.8)
50–59	1998 (16.9)
60+	1766 (15.1)
Sex
Female	3237 (27.4)
Charlson Comorbidity Index score
0	7236 (61.3)
1–2	3526 (29.9)
3–4	1034 (8.8)
Comorbidities (1 year prior to the index date)
Dyslipidemia	2681 (22.7)
Hypertension	2204 (18.7)
Diabetes mellitus	1190 (10.1)
COPD	627 (5.3)
Ischemic heart disease	455 (3.9)
Psoriasis	103 (0.9)
Stroke	221 (1.9)
Renal failure	77 (0.7)
Asthma	113 (1.0)
Concomitant drugs*
NSAID Index Score = 0	269 (2.3)
NSAID Index Score (0, 33.3)	5335 (45.2)
NSAID Index Score (33.3, 66.6)	5697 (48.3)
NSAID Index Score ⩾ 66.6	495 (4.2)
Corticosteroid	7928 (67.2)
Immune-modulating agents	6715 (56.9)
Sulfasalazine	6468 (54.8)
Methotrexate	1136 (9.6)
Cyclosporine	108 (0.9)
Azathioprine	81 (0.7)
Mycophenolate mofetil	21 (0.2)
Cyclophosphamide	7 (0.1)
TNF inhibitor	2453 (20.8)
IL-17 inhibitor	33 (0.3)

One year after axial SpA diagnosis.

COPD, chronic obstructive pulmonary disease; IL, interleukin; NSAIDs, nonsteroidal anti-inflammatory drugs; TNF, tumor necrosis factor.

Incidence rate and crude hazard ratio for glomerulonephritis (GN)

Table 2 shows the characteristics and crude hazard ratio (HR) of the patients with GN. Among the 11,796 patients, 58 were diagnosed with GN. Their incidence rate was 1.82 per 1000 person-years. Crude HR increased with age, and those aged ⩾60 years had a crude HR of 5.34 (95% confidence interval (CI), 2.13–13.38). Patients with a CCI score of ⩾1 had a higher risk compared with those with a CCI score of 0 (crude HR, 2.79; 95% CI, 1.63–4.77). Among comorbidities, dyslipidemia (crude HR, 2.21; 95% CI, 1.31–2.75), hypertension (crude HR, 3.68; 95% CI, 2.2–6.17), diabetes mellitus (crude HR, 2.78; 95% CI, 1.52–5.07), chronic obstructive pulmonary disease (crude HR, 2.44; 95% CI, 1.11–5.38), and renal failure (crude HR, 5.84; 95% CI, 1.42–23.93) showed a significant increase in crude HR. However, medication prescriptions, including NSAIDs, during the first year after axial SpA diagnosis were not associated with GN.

Table 2.

Risk of glomerulonephritis.

Variable	Total N	Event	Sum of person-years	Incidence rate (/1000 person-years)	Crude HR (95% CI)	p-Value
Total	11,796	58	31802.1	1.82
Age group, year
<30	3082	6	8127.2	0.74	Ref.	0.002
30–39	2611	10	7041.3	1.42	1.90 (0.69–5.24)	0.213
40–49	2339	10	6331.2	1.58	2.12 (0.77–5.83)	0.146
50–59	1998	13	5535.9	2.35	3.13 (1.19–8.23)	0.021
⩽60	1766	19	4766.4	3.99	5.34 (2.13–13.38)	0.000
Sex
Female	3237	20	8965.0	2.23	1.32 (0.77–2.27)	0.313
Charlson Comorbidity Index score
0	7236	21	19485.1	1.08	Ref.
1+	4560	37	12316.9	3.00	2.79 (1.63–4.77)	<0.001
Comorbidities (1 year prior to the index date)
Dyslipidemia	2681	23	7281.8	3.16	2.21 (1.31–3.75)	0.003
Hypertension	2204	27	6047.0	4.47	3.68 (2.20–6.17)	<0.001
Diabetes mellitus	1190	14	3254.4	4.30	2.78 (1.52–5.07)	0.001
COPD	627	7	1692.9	4.13	2.44 (1.11–5.38)	0.027
Ischemic heart disease	455	4	1247.8	3.21	1.81 (0.65–4.98)	0.254
Psoriasis	103	1	292.5	3.42	1.85 (0.26–13.35)	0.542
Stroke	221	1	618.1	1.62	0.87 (0.12–6.30)	0.892
Renal failure	77	2	17270.8	0.12	5.84 (1.42–23.93)	0.014
Asthma	113	1	263.3	3.80	1.92 (0.27–13.87)	0.517
Concomitant drug*
NSAID Index Score = 0	269	1	697.8	1.43	Ref.	0.854
NSAID Index Score (0, 33.3)	5335	28	14442.6	1.94	1.35 (0.18–9.89)	0.771
NSAID Index Score (33.3, 66.6)	5697	28	15369.1	1.82	1.27 (0.17–9.36)	0.813
NSAID Index Score ⩾ 66.6	495	1	1292.6	0.77	0.55 (0.03–8.72)	0.668
Corticosteroid	7928	44	21023.5	2.09	1.42 (0.78–2.59)	0.252
Immune-modulating agents	6715	28	18261.0	1.53	0.69 (0.41–1.15)	0.155
Sulfasalazine	6468	28	17591.3	1.59	0.75 (0.45–1.26)	0.274
Methotrexate	1136	3	3175.0	0.94	0.49 (0.15–1.56)	0.225
Cyclosporine	108	1	291.4	3.43	1.90 (0.26–13.72)	0.524
Azathioprine	81	0	215.7	0.00	NA	NA
Mycophenolate mofetil	21	0	50.5	0.00	NA	NA
Cyclophosphamide	7	0	15.5	0.00	NA	NA
TNF inhibitor	2453	12	6611.3	1.82	1.00 (0.53–1.89)	0.998
IL-17 inhibitor	33	1	86.6	11.55	6.51 (0.90–47.04)	0.063

One year after AS diagnosis.

COPD, chronic obstructive pulmonary disease; HR, hazard ratio; IL, interleukin; NA, not available; NSAIDs, nonsteroidal anti-inflammatory drugs; TNF, tumor necrosis factor.

Risk of GN by multivariate analysis

The multivariate analyses, including age, sex, and comorbidities, are shown in Table 3. Model 1 included age, sex, and CCI score. Compared with those aged <30 years, those aged ⩾60 years had an adjusted HR of 3.59 (95% CI, 1.36–9.46), and those with a CCI score of ⩾ 1 increased to 2.03 (95% CI, 1.14–3.63) compared with those with a CCI score of 0. Model 2 included age, sex, and other comorbidities. Hypertension was the only significant factor with an adjusted HR of 2.37 (95% CI, 1.20–4.69). Model 3 included age, sex, CCI score, and comorbidities. In this model, hypertension was the only significant, with an adjusted HR of 2.26 (95% CI, 1.14–4.46).

Table 3.

Risk for glomerulonephritis (multivariate analysis).

Variable	Univariate		Model 1		Model 2		Model 3
	Crude HR (95% CI)	p-Value	Adjusted HR (95% CI)	p-Value	Adjusted HR (95% CI)	p-Value	Adjusted HR (95% CI)	p-Value
Total
Age group, year
<30	Ref.	0.002	Ref.	0.095	Ref.	0.645	Ref.	0.752
30–39	1.90 (0.69–5.24)	0.213	1.76 (0.64–4.86)	0.274	1.75 (0.64–4.84)	0.278	1.70 (0.62–4.70)	0.307
40–49	2.12 (0.77–5.83)	0.146	1.80 (0.65–5.01)	0.259	1.65 (0.59–4.63)	0.345	1.54 (0.55–4.36)	0.415
50–59	3.13 (1.19–8.23)	0.021	2.38 (0.88–6.43)	0.087	1.96 (0.70–5.51)	0.204	1.78 (0.63–5.06)	0.279
<60	5.34 (2.13–13.38)	0.000	3.59 (1.36–9.46)	0.010	2.33 (0.80–6.77)	0.121	2.09 (0.71–6.12)	0.181
Sex
Female	1.32 (0.77–2.27)	0.313	1.10 (0.64–1.90)	0.728	1.18 (0.68–2.04)	0.561	1.16 (0.67–2.01)	0.604
Charlson Comorbidity Index score
0	Ref.		Ref.				Ref.
1+	2.79 (1.63–4.77)	<.001	2.03 (1.14–3.63)	0.017			1.59 (0.82–3.07)	0.172
Comorbidities
Dyslipidemia	2.21 (1.31–3.75)	0.003			0.99 (0.52–1.89)	0.978	0.92 (0.48–1.75)	0.796
Hypertension	3.68 (2.20–6.17)	<0.001			2.37 (1.20–4.69)	0.014	2.26 (1.14–4.46)	0.019
Diabetes mellitus	2.78 (1.52–5.07)	0.001			1.38 (0.69–2.78)	0.369	1.20 (0.59–2.45)	0.613
COPD	2.44 (1.11–5.38)	0.027			1.59 (0.71–3.60)	0.263	1.38 (0.60–3.17)	0.447
Ischemic heart disease	1.81 (0.65–4.98)	0.254
Psoriasis	1.85 (0.26–13.35)	0.542
Stroke	0.87 (0.12–6.30)	0.892
Renal failure	5.84 (1.42–23.93)	0.014			2.40 (0.56–10.23)	0.236	2.29 (0.54–9.73)	0.263
Asthma	1.92 (0.27–13.87)	0.517

COPD, chronic obstructive pulmonary disease.

Characteristics of patients with GN diagnosed by kidney biopsy

Among the 58 patients diagnosed with GN, four were found to have undergone kidney biopsy (Table 4). These patients were diagnosed with unspecified nephritic syndrome with focal and segmental glomerular lesions (N051), unspecified nephrotic syndrome (N049), isolated proteinuria with specified morphological lesions and diffuse membranous GN (N062), or other recurrent and persistent hematuria with proliferative GN (N028). All patients were male, and diagnosis codes for hypertension, diabetes, and dyslipidemia were found in three, two, and two patients, respectively. It took 1.80–2.36 years from axial SpA diagnosis to GN diagnosis. Of these, only one patient was diagnosed with chronic kidney disease before the diagnosis of GN. None of the patients underwent dialysis. Two patients were treated with glucocorticoids after diagnosis, and none received immunosuppressant treatment. In clinical practice, kidney biopsy is typically performed in cases of nephrotic-range proteinuria or rapidly declining renal function, and glomerulonephritis is diagnosed based on histopathological confirmation. Considering these characteristics of glomerulonephritis, renal failure was observed in two of the remaining 54 patients. No other distinguishable baseline characteristics were observed in the four patients who underwent biopsy.

Table 4.

Characteristics of patients with glomerulonephritis and axial spondyloarthritis.

Patient number	Age at AS diagnosis (years)	Sex	GN diagnosis code	Other comorbidities	Time since AS to GN diagnosis (year)	CKD diagnosis before and after GN	Dialysis before and after GN	Cumulative dose of NSAIDs from AS to GN diagnosis (NSAID index)	Concomitant drugs (from AS to GN diagnosis)	Medication use after GN diagnosis (time since GN diagnosis (day), cumulative dose)
Patient number	Age at AS diagnosis (years)	Sex	GN diagnosis code	Other comorbidities	Time since AS to GN diagnosis (year)	CKD diagnosis before and after GN	Dialysis before and after GN		Concomitant drugs (from AS to GN diagnosis)	Steroid (PO, IV)	Cyclophosphamide (PO, IV)CyclosporinAzathioprineMycophenolate mofetil
#1	35–39	Male	N051	Hypertension	1.97	No	No	43.8	Yes (other indication, short-term use)	Prednisolone 391 days use (after 40 days of GN diagnosis)	No
#2	50–54	Male	N049	Hypertension, diabetes mellitus	2.36	No	No	45.6			No
#3	65–69	Male	N062	Hypertension, dyslipidemia, diabetes mellitus	1.80	CKD diagnosis before GN: 6.98 months	No	60.8	Yes (prednisolone, 24 days) 43 days before GN dx	Methylprednisolone 35 days (after 23 days of GN diagnosis)	No
#4	20–24	Male	N028	Dyslipidemia	2.34	No	No	28.8	Yes (other indication, short-term use)		No

CKD, chronic kidney disease; GN, glomerulonephritis; N028, other recurrent and persistent hematuria with proliferative glomerulonephritis; N049, unspecified nephrotic syndrome; N051, unspecified nephritic syndrome with focal and segmental glomerular lesions; N062, isolated proteinuria with specified morphological lesions and diffuse membranous glomerulonephritis; NSAID, nonsteroidal anti-inflammatory disease.

Discussion

Using the national insurance claims data, we investigated the incidence rate and risk factors for GN in patients with axial SpA. The incidence rate of GN in this study was 1.82 per 1000 person-years. The occurrence of GN was significantly associated with comorbidities, including hypertension, but no significant association was observed with the use of medications. Among the patients, four were diagnosed through kidney biopsy, and none appeared to have experienced sufficient kidney function deterioration requiring dialysis. This study is the first to examine the incidence rate and risk factors for GN in patients with axial SpA using nationwide health insurance claims data.

The extramusculoskeletal manifestations of axial SpA vary. Uveitis, psoriasis, and inflammatory bowel disease are the primary manifestations. In a population-based matched cohort study in the UK from 1987 to 2012, the proportions of uveitis, psoriasis, and inflammatory bowel disease were 11.4%, 4.4%, and 3.7%, respectively, and the incidence rates were 8.9/1000 person-years, 3.4/1000 person-years, and 2.4/1000 person-years, respectively.² Based on a population-based study conducted in Korea using health insurance data from 2003 to 2013, the prevalence rates of uveitis, psoriasis, and inflammatory bowel disease were 20%, 7%, and 4%, respectively.¹³ However, there are limited reports on kidney disease as an extramusculoskeletal manifestation in patients with ankylosing spondylitis.

In the International ASAS-COMOSPA Study, 5.2% of patients with SpA had renal impairment (Modification of Diet in Renal Disease-based estimated glomerular filtration rate <60 ml/min/1.73 m²).¹⁴ In a retrospective cohort study in Canada, renal complications were found in 3.2% of men and 2.1% of women, including chronic kidney disease, acute kidney disease, amyloidosis, and hypertensive kidney disease.¹⁵ A retrospective study on axial SpA kidney was conducted at a single center in Korea. Of the 681 patients, 8% had proteinuria or hematuria. Of these, six underwent kidney biopsy: two had GN, two had IgA nephropathy, and one had a thin glomerular basement membrane. These studies have shown that kidney-related extramusculoskeletal symptoms in patients with axial SpA are not as common as uveitis but can be found to be as prevalent as psoriasis or inflammatory bowel disease. However, GN is a rare kidney disease, and its diagnosis, such as through renal biopsy, is difficult, making it difficult to prove its relationship with axial SpA.

The incidence rate of kidney biopsy in Denmark was 46.5 patients per million inhabitants from 2005 to 2014.¹⁶ In Korea, the incidence rate of kidney biopsy from 2010 to 2018 was 24.26 patients per million population.¹⁷ In our study, the incidence rate of biopsy among patients with axial SpA was 4 out of 11,796 (33.91 patients per million population) from 2016 to 2019. Although it is difficult to compare the incidence of GN in the general population owing to differences in study timing and methods, the incidence rate of renal biopsy in patients with axial SpA in our study appears to be slightly higher than that in the general population of Korea. In addition, there were 54 patients diagnosed with GN without a renal biopsy; therefore, the incidence rate of GN may be higher than that in the general population of Korea.

In our study, many patients were diagnosed with GN without renal biopsy. We assumed that many patients were diagnosed with GN based on characteristic clinical findings or those with relatively mild GN findings such as transient proteinuria, normal renal function, or mild symptoms.^18,19 Notably, among the patients who underwent biopsy in our study, IgA nephropathy, which is highly prevalent in patients with axial SpA, was not observed. Patients with IgA nephropathy were assumed to belong to the group of patients who did not undergo renal biopsy. Furthermore, as none of the four patients who underwent renal biopsy required dialysis, it can be inferred that their renal prognosis was relatively favorable.

The pathogenesis of GN involves infectious organisms, immune responses, and activation of the complement system, all of which can cause glomerular injury, leading to the leakage of albumin, blood cells, and other proteins into the urine. Depending on the severity of the immune response, GN can present as a chronic, subacute, or acute illness. Infectious or autoimmune triggers can cause excessive complement activation and neutrophil extracellular trap release, leading to glomerular capillary necrosis and impaired filtration, resulting in a rapid decline in kidney function. Conditions such as hypertension, diabetes mellitus, and obesity further exacerbate glomerular injury by increasing filtration pressure and promoting barrier dysfunction, thereby worsening GN-related symptoms.¹⁰ In our study, CCI score ⩾1 and hypertension were associated with GN development. This also suggests that other comorbidities, mainly hypertension, are correlated with GN development. Although many patients with axial SpA are relatively young, if they have concomitant diseases, such as high blood pressure, they may need to pay attention to kidney diseases, such as GN.

NSAIDs are commonly prescribed for the treatment of axial SpA,^20
–22 but they have potential adverse effects on kidney function.^14,22,23 We analyzed the correlation between the 1-year cumulative dose of NSAIDs and the incidence of GN using the ASAS NSAID intake score. However, our analysis revealed no significant association between any level of NSAID exposure and GN occurrence. In addition, case reports have suggested that TNF inhibitors may be associated with GN development.^11,24 However, in our study, the use of TNF inhibitors was not significantly associated with GN. Notably, the duration of drug use associated with axial SpA was relatively short in our study population. In addition, there is a possibility of selection bias in drug administration, where medications may have been selectively administered to patients deemed unlikely to experience adverse effects from these treatments.^8,23 Well-designed prospective studies are warranted to draw definitive conclusions about the relationship between these drugs and GN.

This study has some limitations. First, GN may have been undervalued because various autoimmune diseases were excluded from the initial patient selection. The actual incidence rate of GN is likely to be higher than the numbers we present, as it likely shares codes not only with axial SpA but also with other rheumatic diseases. Second, most GN cases were diagnosed without a kidney biopsy. The accuracy of GN diagnosis must be proven through various claims data studies. Third, it was difficult to determine the effect of drugs on GN in this retrospective study owing to bias. Although our study was based on nationwide health insurance claims data, the bias toward drug treatment is a limitation that is difficult to improve. Fourth, we used disease codes to investigate the association between SpA and GN. However, we did not exclude patients with GN who used immunosuppressants because renal disease and rheumatic diseases share immunosuppressant treatment. The study includes patients who were undergoing treatment with immunosuppressive agents, and they may potentially have had underlying renal disease at baseline. However, excluding such patients from the analysis may contradict the primary objective of our study, which is to observe the occurrence of renal disease in real-world clinical settings. Our study aims to better reflect the diverse spectrum of clinical scenarios encountered in practice, thereby enhancing the generalizability and clinical relevance of our findings. Fifth, we excluded all rheumatic diseases other than GN and axial SpA at baseline. However, patients who used immunosuppressants were included in less than 1% of each drug. This is likely to have been used to treat extramusculoskeletal manifestations such as uveitis or psoriasis that do not respond to general treatment rather than for the treatment of renal disease. In Korea, the use of TNF inhibitors to treat extra-articular manifestations such as uveitis or psoriasis is not readily accessible due to high barriers within the national insurance system. Sixth, some patients with renal failure may have GN. The spectrum of renal failure is broad, ranging from acute kidney injury to chronic kidney disease and end-stage kidney disease. In this study, disease classification was based on diagnostic codes, which made it challenging to distinguish between these conditions. Since GN is one of the causes of various renal failures, we included renal failure as a comorbidity.

Conclusion

The incidence of kidney disease in patients with axial SpA appears to be lower compared with that in patients with extra-articular symptoms, such as uveitis, psoriasis, and inflammatory bowel disease. GN is considered a rare disease; however, its incidence has been observed in patients with axial SpA. Comorbidities, including hypertension, are associated with a higher incidence of GN. Notably, in the first year after AS diagnosis, the use of medications, including NSAIDs, did not show a significant association with GN development. These findings suggest the importance of monitoring comorbid conditions, particularly hypertension when managing the long-term renal health of patients with axial SpA. Further studies are required to explore the underlying mechanisms and potential preventive strategies for GN in patients with SpA.

Supplemental Material

sj-docx-1-tab-10.1177_1759720X251320328 – Supplemental material for Incidence rate of and risk factors for glomerulonephritis in patients with axial spondyloarthritis: a nationwide population-based study

Supplemental material, sj-docx-1-tab-10.1177_1759720X251320328 for Incidence rate of and risk factors for glomerulonephritis in patients with axial spondyloarthritis: a nationwide population-based study by Subin Hwang, Ye-Jee Kim, Soo Min Ahn and Bon San Koo in Therapeutic Advances in Musculoskeletal Disease

Supplemental Material

sj-docx-2-tab-10.1177_1759720X251320328 – Supplemental material for Incidence rate of and risk factors for glomerulonephritis in patients with axial spondyloarthritis: a nationwide population-based study

Supplemental material, sj-docx-2-tab-10.1177_1759720X251320328 for Incidence rate of and risk factors for glomerulonephritis in patients with axial spondyloarthritis: a nationwide population-based study by Subin Hwang, Ye-Jee Kim, Soo Min Ahn and Bon San Koo in Therapeutic Advances in Musculoskeletal Disease

Footnotes

Acknowledgements

I would like to thank the members of the Department of Rheumatology at Seoul Asan Medical Center for their help in this study.

Declarations

ORCID iDs

Subin Hwang

Ye-Jee Kim

Soo Min Ahn

Bon San Koo

Supplemental material

Supplemental material for this article is available online.

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