Forgotten compartment: Impact of tubulointerstitial inflammation and damage on renal outcomes in lupus nephritis from Saudi Arabia

doi:10.5493/wjem.v16.i2.119440

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World Journal of Experimental Medicine

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2220-315x

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Retrospective Study

Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Exp Med. Jun 20, 2026; 16(2): 119440
Published online Jun 20, 2026. doi: 10.5493/wjem.v16.i2.119440

Table 1 Baseline characteristics of the study population, mean ± SD/n (%)

Variable	TII/TID, n = 52	TII + TID, n = 48	Total, n = 100	P value
Age (year)	26.08 ± 14.89	29.79 ± 10.69	27.86 ± 13.12	0.158
Systolic BP (mmHg)	125.10 ± 24.87	133.74 ± 30.75	129.24 ± 28.03	0.132
Diastolic BP (mmHg)	74.30 ± 15.92	80.28 ± 17.65	77.17 ± 16.95	0.084
Urine protein (g)	3.35 ± 4.52	2.97 ± 2.71	3.17 ± 3.75	0.615
Serum creatinine (µmol/L)	121.27 ± 162.65	126.75 ± 120.38	123.92 ± 143.02	0.852
eGFR (mL/minute/1.73 m²)	98.21 ± 52.71	77.67 ± 37.37	88.35 ± 46.91	0.028
Hemoglobin (g/dL)	10.51 ± 2.05	13.87 ± 16.90	12.12 ± 11.85	0.161
WBC count (× 10⁹/L)	7.17 ± 3.89	7.04 ± 4.02	7.10 ± 3.93	0.888
Platelet count (× 10⁹/L)	230.67 ± 135.81	236.26 ± 150.98	233.53 ± 142.94	0.859
PTH (pmol/L)	8.09 ± 14.35	9.33 ± 10.09	8.72 ± 12.30	0.674
C3 (g/L)	0.70 ± 0.46	0.67 ± 0.30	0.69 ± 0.39	0.648
C4 (g/L)	0.17 ± 0.15	0.14 ± 0.09	0.16 ± 0.13	0.248
Total protein in serum (g/L)	52.37 ± 17.04	51.50 ± 16.02	51.93 ± 16.42	0.825
Albumin in serum (g/L)	28.50 ± 7.59	27.66 ± 7.06	28.09 ± 7.32	0.571
Total cholesterol (mmol/L)	4.75 ± 4.32	4.70 ± 2.36	4.72 ± 3.44	0.951
LDL-C (mmol/L)	1.78 ± 1.82	3.01 ± 1.88	2.40 ± 1.94	0.006
HDL-C (mmol/L)	0.91 ± 0.86	0.94 ± 0.56	0.93 ± 0.72	0.843
TG (mmol/L)	1.32 ± 0.96	1.57 ± 0.86	1.45 ± 0.91	0.253
HA1C at diagnosis (%)	3.74 ± 3.00	4.70 ± 1.61	4.19 ± 2.48	0.069
Sodium (mmol/L)	137.80 ± 4.06	135.53 ± 5.72	136.65 ± 5.07	0.058
Potassium (mmol/L)	4.23 ± 0.60	4.42 ± 0.70	4.32 ± 0.65	0.226
Calcium (mmol/L)	2.05 ± 0.49	2.09 ± 0.24	2.07 ± 0.39	0.626
Phosphorus (mmol/L)	1.30 ± 0.65	1.22 ± 0.38	1.26 ± 0.54	0.517
Uric acid (µmol/L)	313.23 ± 193.36	383.15 ± 178.02	349.14 ± 187.68	0.11
CRP (mg/L)	10.98 ± 17.35	12.85 ± 28.66	11.88 ± 23.40	0.703
ANA	1.20 ± 0.40	1.07 ± 0.26	1.14 ± 0.35	0.077
ANA titer or dilution	621.71 ± 584.77	687.78 ± 492.12	655.21 ± 536.93	0.608
Anti ds-DNA	1.24 ± 0.65	1.45 ± 0.54	1.34 ± 0.61	0.085
Anti ds-DNA titer	215.29 ± 512.00	125.32 ± 355.03	172.14 ± 443.78	0.319
Anti SM antibody	16.59 ± 81.41	1.92 ± 7.11	9.15 ± 57.43	0.285
Anti RNP antibody positivity	0.69 ± 4.06	0.00 ± 0.00	0.34 ± 2.85	0.314
Modified NIH Activity score	3.13 ± 3.18	6.17 ± 3.90	4.59 ± 3.84	0
Chronicity score	1.85 ± 2.44	4.21 ± 1.74	2.98 ± 2.43	0
Gender
Female	43 (82.7)	41 (85.4)	84 (84.0)	0.71
Male	9 (17.3)	7 (14.6)	16 (16.0)
Class
I/II	7 (13.5)	1 (2.1)	8 (8.0)	0.024^a
III	8 (15.4)	17 (35.4)	25 (25.0)
III and V	5 (9.6)	8 (16.7)	13 (13.0)
IV	11 (21.2)	7 (14.6)	18 (18.0)
IV and V	8 (15.4)	10 (20.8)	18 (18.0)
V/VI	13 (25.0)	5 (10.4)	18 (18.0)
Hypertension
Yes	33 (64.7)	38 (79.2)	71 (71.7)	0.11
No	18 (35.3)	10 (20.8)	28 (28.3)
DM
Yes	6 (12.0)	9 (19.1)	15 (15.5)	0.33
No	44 (88.0)	38 (80.9)	82 (84.5)
Induction drug: CYC	15 (28.8)	9 (18.8)	24 (24.0)	0.292
MMF	36 (69.2)	39 (81.3)	75 (75.0)
MMF + CYC	1 (1.9)	0 (0.0)	1 (1.0)
Maintenance (yes)	5 (9.6)	2 (4.2)	7 (7.0)	0.502
MMF (maintenance)	38 (73.1)	42 (87.5)	80 (80.0)
Azathioprine (AZA)	3 (5.8)	3 (6.3)	6 (6.0)
MMF + CNI	3 (5.8)	1 (2.1)	4 (4.0)
MMF or AZA	1 (1.9)	0 (0.0)	1 (1.0)
MMF+ AZA + CNI	1 (1.9)	0 (0.0)	1 (1.0)
Podocyte effacement ≥ 50	27 (52.9)	22 (46.8)	49 (50.0)	0.083
Podocyte effacement < 50	14 (27.5)	7 (14.9)	21 (21.4)
No comment or not done	10 (19.6)	18 (38.3)	28 (28.6)
EM mesangium deposits	3 (6.0)	14 (30.4)	17 (17.7)	0.007^a
EM
Yes	26 (52.0)	16 (34.8)	42 (43.8)
No	21 (42.0)	16 (34.8)	37 (38.5)
Full house	30 (63.8)	21 (52.5)	51 (58.6)	0.285
Partial	17 (36.2)	19 (47.5)	36 (41.4)
Statin
Yes	17 (34.0)	17 (36.2)	34 (35.1)	0.823
No	33 (66.0)	30 (63.8)	63 (64.9)
ACEI
Yes	24 (55.8)	27 (64.3)	51 (60.0)	0.425
No	19 (44.2)	15 (35.7)	34 (40.0)
ARB
Yes	22 (47.8)	23 (56.1)	45 (51.7)	0.441
No	24 (52.2)	18 (43.9)	42 (48.3)
SGLT-2
Yes	4 (7.8)	4 (8.5)	8 (8.2)	0.904
No	47 (92.2)	43 (91.5)	90 (91.8)

^aP < 0.05.

ACEI: Angiotensin-converting enzyme inhibitor; ANA: Antinuclear antibody; ds-DNA: Double-stranded DNA; RNP: Ribonucleoprotein; SM: Smith; ARB: Angiotensin receptor blocker; AZA: Azathioprine; BP: Blood pressure; CNI: Calcineurin inhibitor; CRP: C-reactive protein; DM: Diabetes mellitus; eGFR: Estimated glomerular filtration rate; EM: Electron microscopy; HDL-C: High-density lipoprotein cholesterol; LDL-C: Low-density lipoprotein cholesterol; MMF: Mycophenolate mofetil; NIH: National Institutes of Health; PTH: Parathyroid hormone; SGLT-2: Sodium-glucose cotransporter-2; TG: Triglycerides; TII: Tubulointerstitial inflammation; TID: Tubulointerstitial damage; WBC: White blood cell; CYC: Cyclophosphamide.

Full Size Table

Table 2 Multivariable logistic regression analyses to identify clinical predictors of coexisting tubulointerstitial inflammation and tubulointerstitial damage

Variable	OR (95%CI)	P value
Age at time of diagnosis	1.044 (0.984-1.109)	0.157
Class
III	150.420 (4.280-5285.889)	0.006^a
III and V	14.361 (0.744-277.264)	0.078
IV	8.181 (0.388-172.397)	0.177
IV and V	44.114 (1.445-1347.071)	0.03^a
V/VI	2.301 (0.139-38.101)	0.561
ANA	0.011 (0.001-0.199)	0.002^a
LDL-C	2.259 (1.288-3.963)	0.004^a
eGFR at zero	0.995 (0.979-1.012)	0.579
Endocapillary hypercellularity	0.461 (0.203-1.046)	0.064
Neutrophil and/or karyorrhexis	1.744 (0.720-4.225)	0.218
Fibrinoid necrosis × 2	2.293 (1.034-5.085)	0.041^a
Cellular/fibrocellular crescents score × 2	0.897 (0.584-1.378)	0.619
Hyaline deposit (wire loop and/or hyaline thrombi)	1.319 (0.530-3.285)	0.552
Interstitial inflammation (interstitial leukocytes)	73.287 (8.235-652.247)	< 0.001

^aP < 0.05.

ANA: Antinuclear antibody; eGFR: Estimated glomerular filtration rate; LDL-C: Low-density lipoprotein cholesterol.

Full Size Table

Table 3 Multivariable Cox-proportional regression analysis to identify predictors for the composite outcome in lupus nephritis patients with coexisting tubulointerstitial inflammation and tubulointerstitial damage, and all the patients

Variable	TII + TID		Total
Variable	HR (95%CI)	Sig.	HR (95%CI)	Sig.
Baseline characteristics
Age	1.123 (1.025-1.230)	0.013	1.037 (0.999-1.076)	0.055
Gender	0.641 (0.093-4.418)	0.652	1.460 (0.521-4.090)	0.472
Baseline urine protein (g)	0.969 (0.763-1.231)	0.796	0.916 (0.759-1.105)	0.359
Baseline serum creatinine	1.010 (1.003-1.018)	0.006	1.005 (1.002-1.007)	< 0.001
C3	0.001 (0.000-0.134)	0.007	0.260 (0.050-1.336)	0.107
CRP	1.062 (1.025-1.100)	0.001	1.018 (1.003-1.034)	0.022
ANA titer	0.998 (0.997-1.000)	0.051	0.999 (0.998-1.000)	0.205
Chronic pathological features
Total glomerulosclerosis	0.344 (0.135-0.874)	0.025	0.616 (0.323-1.174)	0.141
Fibrous crescents	3.112 (0.899-10.771)	0.073	3.091 (1.063-8.984)	0.038
Interstitial fibrosis	0.002 (approximately 0-approximately ∞)	0.961	0.798 (0.134-4.745)	0.804
Tubular atrophy	4155.207 (approximately 0-approximately ∞)	0.945	1.424 (0.222-9.131)	0.709
Acute pathological features
Endocapillary hypercellularity	0.318 (0.069-1.468)	0.142	1.192 (0.650-2.187)	0.57
Neutrophil and/or karyorrhexis	1.005 (0.338-2.989)	0.993	0.743 (0.366-1.507)	0.41
Fibrinoid necrosis	1.225 (0.737-2.038)	0.434	0.828 (0.554-1.237)	0.357
Cellular/fibrocellular crescents	0.928 (0.458-1.883)	0.837	1.401 (0.947-2.073)	0.091
Hyaline deposit	3.923 (1.197-12.853)	0.024	1.301 (0.573-2.953)	0.53
Interstitial inflammation	2.158 (0.678-6.868)	0.193	0.844 (0.447-1.593)	0.601

Sig.: Significance; TII: Tubulointerstitial inflammation; TID: Tubulointerstitial damage; CRP: C-reactive protein; ANA: Antinuclear antibody.

Full Size Table

Citation: Khalil MAM, Sadagah NM, Mahmood HHK, Alrowaie F, Almansour AM, Alghamdi RMH, Alghamdi L, A Al-Ghamdi R, Elgadi A, Al-Qurashi SH. Forgotten compartment: Impact of tubulointerstitial inflammation and damage on renal outcomes in lupus nephritis from Saudi Arabia. World J Exp Med 2026; 16(2): 119440
URL: https://www.wjgnet.com/2220-315x/full/v16/i2/119440.htm
DOI: https://dx.doi.org/10.5493/wjem.v16.i2.119440

Khalil MAM, Sadagah NM, Mahmood HHK, Alrowaie F, Almansour AM, Alghamdi RMH, Alghamdi L, A Al-Ghamdi R, Elgadi A, Al-Qurashi SH. Forgotten compartment: Impact of tubulointerstitial inflammation and damage on renal outcomes in lupus nephritis from Saudi Arabia. World J Exp Med 2026; 16(2): 119440 [DOI: 10.5493/wjem.v16.i2.119440]

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