scholarly journals Comparative Histological Subtyping of Immune Cell Infiltrates in MPO-ANCA and PR3-ANCA Glomerulonephritis

2021 ◽  
Vol 12 ◽  
Author(s):  
Samy Hakroush ◽  
Désirée Tampe ◽  
Philipp Ströbel ◽  
Peter Korsten ◽  
Björn Tampe
Keyword(s):  
Mononuclear Cell ◽  
Plasma Cells ◽  
Immune Cell ◽  
Interstitial Fibrosis ◽  
Kidney Injury ◽  
Tubular Atrophy ◽  
Interstitial Inflammation ◽  
Tubulointerstitial Lesions ◽  
Mononuclear Cell Infiltrates ◽  
Immune Cell Infiltrates

BackgroundAcute kidney injury (AKI) is a common and severe complication of anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV), potentially leading to chronic kidney disease (CKD), end-stage renal disease (ESRD), or death. Pathogenic ANCAs, in particular proteinase 3 (PR3) and myeloperoxidase (MPO), trigger a deleterious immune response with intrarenal immune cell infiltration resulting in a pauci-immune necrotizing and crescentic glomerulonephritis (GN). However, a systematic analysis of intrarenal immune cell subtypes concerning neutrophils, eosinophils, plasma cells, and mononuclear cell infiltrates (macrophages, lymphocytes) in ANCA GN remains elusive. Therefore, we aimed to compare distinct immune cell infiltrates in association with clinicopathological findings in ANCA GN.MethodsA total of 53 kidney biopsies with ANCA GN at the University Medical Center Göttingen were retrospectively analyzed. Histological infiltrates of neutrophils, eosinophils, plasma cells, and mononucleated cells (macrophages, lymphocytes) were quantified as a fraction of the total area of inflammation.ResultsNeutrophilic infiltrates were associated with glomerular necrosis and severe kidney injury in ANCA GN. Among tubulointerstitial lesions, intrarenal neutrophils correlated with interstitial inflammation, tubulitis, and inflammation in areas of interstitial fibrosis/tubular atrophy (IFTA), representing active inflammatory lesions. Concerning eosinophils, infiltrates were associated with severe kidney injury, interstitial inflammation, and cellular casts independent of glomerular lesions, implicating a distinct role in inflammation and damage in ANCA GN. Plasma cell infiltrates correlated with tubulitis and interstitial fibrosis and were associated with renal replacement therapy during the short-term disease course. Finally, mononuclear cell infiltrates correlated with severe kidney injury and active histopathological lesions (glomerular crescents, interstitial inflammation, tubulitis, inflammation, and tubulitis in areas of IFTA) besides chronic lesions (interstitial fibrosis and tubular atrophy) in ANCA GN. Interestingly, intrarenal subtypes of immune cell infiltrates differed in MPO-ANCA versus PR3-ANCA GN and were associated with distinct glomerular and tubulointerstitial lesions, implicating different pathogenic mechanisms of kidney injury in ANCA subtypes.ConclusionOur observations imply distinct pathomechanisms contributing to inflammation and renal injury in MPO vs. PR3-associated ANCA GN and potentially contribute to new therapeutic targets in specific ANCA subtypes.

scholarly journals POS0247 INTERSTITIAL ANCA-ASSOCIATED VASCULITIS ASSOCIATES WITH SEVERE KIDNEY INJURY INDEPENDENT OF GLOMERULONEPHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 345.2-345
Author(s):  
S. Hakroush ◽  
B. Tampe
Keyword(s):  
Kidney Function ◽  
Current Knowledge ◽  
Interstitial Fibrosis ◽  
Kidney Injury ◽  
Small Vessel ◽  
Small Vessel Vasculitis ◽  
Tubular Atrophy ◽  
Anca Associated Vasculitis ◽  
Tubulointerstitial Lesions ◽  
Peritubular Capillaritis

Background:Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a small vessel vasculitis affecting multiple organ systems, including the kidney. Small vessels in the kidney include small-sized arteries (interlobular artery, afferent and efferent arteriole), capillaries (glomerular and peritubular capillary) and venules.Objectives:Although crescentic ANCA glomerulonephritis (GN) is a common histological finding reflecting glomerular small vessel vasculitis, it is reasonable that manifestation of AAV could also contribute to interstitial small vessel vasculitis. Therefore, we here aimed to expand our current knowledge focusing on interstitial vasculitis in ANCA GN by systematic histological scoring of vascular lesions analogous to Banff.Methods:A total number of 49 kidney biopsies with confirmed renal involvement of AAV at the University Medical Center Göttingen were retrospectively included between 2015 till 2020. A renal pathologist (SH) evaluated all biopsies and was blinded to clinical data collection and analysis. A detailed methological section is provided in the Supplementary material and methods section.Results:Since previous studies established that crescentic ANCA GN associates with severe kidney injury and acute deterioration of kidney function in AAV, we first systematically scored interstitial vasculitis in association with requirement of renal replacement therapy (RRT). Among all active and chronic tubulointerstitial lesions analogous to the Banff scoring system, the only association between severe kidney injury requiring RRT was observed for interstitial vasculitis in AAV reflected by peritubular capillaritis (ptc, p=0.0002) and arteritis (v, p=0.0069), affecting 5/49 (10.2%) and 11/49 (22.4%) of renal biopsies, respectively. Since it is known that severe deterioration of kidney function also correlates with crescentic ANCA GN, we next directly compared glomerular and tubulointerstitial lesions. The fraction of normal glomeruli was inversely associated with interstitial fibrosis (ci), total (ti) and inflammation in IFTA (i-IFTA), whereas glomerular crescents were associated with interstitial inflammation (i), tubulitis (t) and total inflammation (ti). In contrast, global glomerular sclerosis associated with less interstitial inflammation (i) but correlated with interstitial fibrosis (ci) and tubular atrophy (ct), confirming established mechansim that chronic glomerular injury leads to tubular atrophy and interstitial fibrosis. Interestingly, no association between interstitial vasculitis (ptc and v correlating with severe kidney injury) and any glomerular lesion in ANCA GN (also correlating with severe kidney injury) was observed, thereby confirming that interstitial vasculitis contributes to severe kidney injury independent of ANCA GN. By contrast, short-term renal recovery from RRT was equal in both groups, suggesting a distinct association with acute decline of kidney function at disease onset.Conclusion:Taken together, by using the Banff scoring system we here expand our current knowledge of renal interstitial lesions in AAV revealing peritubular capillaritis and arteritis as important histological alterations associated with severe kidney injury in a considerable subset of AAV. Furthermore, our findings that interstitial vasculitis did not correlate with crescentic ANCA GN implicate that the characteristics of each vasculitis manifestation are independent and could further improve our understanding of mechanisms contributing to renal injury. These observations suggest that interstitial vasculitis in AAV may also affect long-term prognosis requiring further investigation.Disclosure of Interests:None declared

scholarly journals Cellular Mechanisms of Tissue Fibrosis. 3. Novel mechanisms of kidney fibrosis

2013 ◽  
Vol 304 (7) ◽  
pp. C591-C603 ◽  
Author(s):  
Gabriela Campanholle ◽  
Giovanni Ligresti ◽  
Sina A. Gharib ◽  
Jeremy S. Duffield
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Interstitial Fibrosis ◽  
Kidney Injury ◽  
Innate Immune ◽  
Cellular Mechanisms ◽  
Tubular Atrophy ◽  
Kidney Fibrosis ◽  
Capillary Rarefaction ◽  
Peritubular Capillaries

Chronic kidney disease, defined as loss of kidney function for more than three months, is characterized pathologically by glomerulosclerosis, interstitial fibrosis, tubular atrophy, peritubular capillary rarefaction, and inflammation. Recent studies have identified a previously poorly appreciated, yet extensive population of mesenchymal cells, called either pericytes when attached to peritubular capillaries or resident fibroblasts when embedded in matrix, as the progenitors of scar-forming cells known as myofibroblasts. In response to sustained kidney injury, pericytes detach from the vasculature and differentiate into myofibroblasts, a process not only causing fibrosis, but also directly contributing to capillary rarefaction and inflammation. The interrelationship of these three detrimental processes makes myofibroblasts and their pericyte progenitors an attractive target in chronic kidney disease. In this review, we describe current understanding of the mechanisms of pericyte-to-myofibroblast differentiation during chronic kidney disease, draw parallels with disease processes in the glomerulus, and highlight promising new therapeutic strategies that target pericytes or myofibroblasts. In addition, we describe the critical paracrine roles of epithelial, endothelial, and innate immune cells in the fibrogenic process.

scholarly journals Neutrophils associate with Bowman’s capsule rupture specifically in PR3-ANCA glomerulonephritis

2021 ◽  
Author(s):  
Samy Hakroush ◽  
Björn Tampe
Keyword(s):  
Plasma Cells ◽  
Immune Cell ◽  
Renal Involvement ◽  
Kidney Injury ◽  
Antineutrophil Cytoplasmic Antibody ◽  
Stage Renal Disease ◽  
End Stage ◽  
Bowman's Capsule ◽  
Tubulointerstitial Inflammation ◽  
Capsule Rupture

Abstract Background Renal involvement is a common and severe complication of ANCA (antineutrophil cytoplasmic antibody) associated vasculitis (AAV) potentially resulting in a pauci-immune necrotizing and crescentic antineutrophil cytoplasmic antibody (ANCA) glomerulonephritis (GN) with acute kidney injury (AKI), end-stage renal disease (ESRD) or death. We recently described that Bowman’s capsule rupture links glomerular damage to tubulointerstitial inflammation in ANCA-associated glomerulonephritis. Herein we provide a comprehensive histological subtyping of immune cell infiltrates in association with Bowman’s capsule rupture in ANCA GN. Methods A total of 44 kidney biopsies with ANCA GN were retrospectively included in a single-center observational study. Within a renal biopsy specimen, each glomerulus was scored separately for the presence of extensive and focal Bowman’s capsule rupture in injured glomeruli. Infiltrates of neutrophils, eosinophils, plasma cells, and mononucleated cells (macrophages, lymphocytes) were quantified as a fraction of the area of total cortical inflammation. Results Extensive Bowman’s capsule rupture was associated with tubulointerstitial inflammation containing infiltrates of neutrophils, eosinophils and plasma cells. A similar association was observed for the presence of focal Bowman’s capsule rupture, correlating with tubulointerstitial inflammation containing neutrophils, eosinophils and plasma cells. Multiple logistic regression confirmed that extensive Bowman’s capsule rupture correlated with tubulointerstitial inflammation containing neutrophils, and focal Bowman’s capsule rupture correlated with neutrophil and plasma cell infiltration. Furthermore, this association was specifically observed in PR3-ANCA GN. Conclusion To our knowledge, this is the first report linking Bowman’s capsule rupture directly to tubulointerstitial inflammation by immune cell subtypes. This underscores a pathomechanistic link between tubulointerstitial and glomerular lesions in ANCA GN and needs further investigation. Graphical abstract

P0661DIAGNOSTIC VALUE OF FULL AGE SPECTRUM EQUATION AS A PREDICTOR OF MORPHOLOGICAL LESIONS IN PATIENTS WITH GLOMERULONEPHRITIS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Saganova Elena ◽  
Olga Galkina ◽  
Vasiliy Sipovskii ◽  
Ivan Kayukov, ◽  
Alexei Smirnov
Keyword(s):  
Serum Creatinine ◽  
Interstitial Fibrosis ◽  
Severe Heart Failure ◽  
Kidney Injury ◽  
Roc Curves ◽  
Diagnostic Value ◽  
Tubular Atrophy ◽  
Mild Degree ◽  
Severe Group ◽  
Global Glomerulosclerosis

Abstract Background and Aims Glomerular filtration rate (GFR) is generally accepted as a best overall index of kidney function. However, it remains controversial to choose the optimal equation to estimate GFR in patients with glomerulonephritis (GN). Recent studies have reported that newly developed full age spectrum equation based on normalized serum creatinine (FASsCr) showed improved validity and was less biased, more accurate than currently recommended sCr-based eGFR equations. Our aim was to assess FASsCr equation as a predictor of various morphological lesions in patients with GN. Method 100 patients [48 female, age Me 39 (27; 54) years] with biopsy proven primary GN and without acute kidney injury, infectious diseases, severe heart failure, respiratory insufficiency, cancer were included in the study. Minimal change disease was diagnosed in 9% of cases based on the results of kidney biopsy, in 28% – focal segmental glomerulosclerosis, in 26% – membranous nephropathy and in 37% – IgA-nephropathy. Serum creatinine (sCr) level was measured by enzymatic method (Uni Cel DxC 800 PRO, «Beckman Coulter»,USA). eGFR was calculated using FASsCr equation. The extent of global glomerulosclerosis (GS) was assessed quantitatively as a sum of full and focal sclerotic glomeruli. Tubulo-interstitial fibrosis (TIF) and tubular atrophy (TA) were assessed semi-quantitatively (0-lesions absent; 1-mild focal tubular and interstitial lesions; 2-moderate tubular and interstitial lesions; 3 - diffuse tubular and interstitial lesions). All patients consistently were separated into 2 groups according to the degree of each morphological lesion (GS, TIF or TA): “mild” (GS<25% or TIF/TA grade 0 or 1) and “severe” (GS ≥ than 25% or TIF/TA grade 2-3). Results eGFR using FASsCr equation positively correlated (p<0,001 in all cases) with GS (r=0,44), TIF (r=0,64) and TA (r=0,61) and was significantly higher in patients with “mild” GS, TIF and TA (p<0,001) in comparison with “severe” group. Using ROC-analysis all patients were separated (p<0.001) in 2 groups using FASsCr equation according to the degree of morphological lesions (“mild” or “severe”): GS (Sn – 48.8%, Sp – 88.1%, ACC – 72.0%, AUC – 0.696, cut-off value – 47 ml/min/1.73m2), TIF (Sn - 75.4%, Sp – 76.9%, ACC – 76.0%, AUC – 0.815, cut-off value – 72 ml/min/1.73m2), TA (Sn – 65.9%, Sp – 88.8%, ACC – 70.0%, AUC – 0.798, cut-off value – 74 ml/min/1.73m2), (Figure). Conclusion Our results show that FASsCr equation is a significant marker of various morphological lesions in patients with GN. FASsCr equation predominantly can be used as a predictor of mild degree of interstitial sclerosis and tubular atrophy with high diagnostic value. Figure: ROC curves with 95% CI of BM panel for A – GS; B – TIF; C – TA

scholarly journals Cisplatin-induced renal toxicity in elderly people

2020 ◽  
Vol 12 ◽  
pp. 175883592092343 ◽  
Author(s):  
ZhiYu Duan ◽  
GuangYan Cai ◽  
JiJun Li ◽  
XiangMei Chen
Keyword(s):  
Elderly Patients ◽  
Elderly People ◽  
Renal Toxicity ◽  
Enzyme Inhibitor ◽  
Interstitial Fibrosis ◽  
Angiotensin Receptor Blockers ◽  
Young Patients ◽  
Kidney Injury ◽  
The Elderly ◽  
Tubular Atrophy

Despite available prevention and treatment measures, such as hydration, diuresis, magnesium supplementation, and amifostine, renal toxicity is still one of the major dose-limiting side effects of cisplatin. The aim of this review is to discuss the issue of cisplatin-induced nephrotoxicity in the elderly. Compared with young patients, the incidences of cisplatin-induced nephrotoxicity and acute kidney injury (AKI) in elderly patients are significantly increased, and survival time may be decreased. Following cisplatin treatment of elderly patients, tubulointerstitial injuries will be significantly aggravated based on their original age, both for acute injuries due to cell necrosis and exfoliation and chronic injuries due to interstitial fibrosis, tubular atrophy, and dilatation. The high incidence of cisplatin-induced nephrotoxicity in elderly patients may be associated with renal hypoperfusion; increased comorbidities, such as chronic kidney disease (CKD), cardiovascular disease, and diabetes mellitus; increased use of combined drugs [especially non-steroidal anti-inflammatory drugs, angiotensin-converting enzyme inhibitor and angiotensin receptor blockers (ACEI/ARB), and antibiotics]; decreased clearance of cisplatin; and high plasma ultrafilterable cisplatin. Considering hemodynamic stability and water balance, short duration and low volume hydration may be more suitable for treating elderly people. With the increasing popularity of low-dose daily/weekly regimens, we do not recommend routine diuretic treatment for elderly patients. We recommend using a less nephrotoxic platinum if large doses of cisplatin (100mg/m2) are needed.

scholarly journals Automated Computational Detection of Interstitial Fibrosis, Tubular Atrophy, and Glomerulosclerosis

2021 ◽  
Vol 32 (4) ◽  
pp. 837-850 ◽  
Author(s):  
Brandon Ginley ◽  
Kuang-Yu Jen ◽  
Seung Seok Han ◽  
Luís Rodrigues ◽  
Sanjay Jain ◽  
...  
Keyword(s):  
Patient Outcome ◽  
Interstitial Fibrosis ◽  
Kidney Injury ◽  
Automated Identification ◽  
Statistical Tools ◽  
Tubular Atrophy ◽  
Biopsy Specimens ◽  
Chronic Kidney Injury ◽  
Modern Machine ◽  
Whole Slide Images

BackgroundInterstitial fibrosis, tubular atrophy (IFTA), and glomerulosclerosis are indicators of irrecoverable kidney injury. Modern machine learning (ML) tools have enabled robust, automated identification of image structures that can be comparable with analysis by human experts. ML algorithms were developed and tested for the ability to replicate the detection and quantification of IFTA and glomerulosclerosis that renal pathologists perform.MethodsA renal pathologist annotated renal biopsy specimens from 116 whole-slide images (WSIs) for IFTA and glomerulosclerosis. A total of 79 WSIs were used for training different configurations of a convolutional neural network (CNN), and 17 and 20 WSIs were used as internal and external testing cases, respectively. The best model was compared against the input of four renal pathologists on 20 new testing slides. Further, for 87 testing biopsy specimens, IFTA and glomerulosclerosis measurements made by pathologists and the CNN were correlated to patient outcome using classic statistical tools.ResultsThe best average performance across all image classes came from a DeepLab version 2 network trained at 40× magnification. IFTA and glomerulosclerosis percentages derived from this CNN achieved high levels of agreement with four renal pathologists. The pathologist- and CNN-based analyses of IFTA and glomerulosclerosis showed statistically significant and equivalent correlation with all patient-outcome variables.ConclusionsML algorithms can be trained to replicate the IFTA and glomerulosclerosis assessment performed by renal pathologists. This suggests computational methods may be able to provide a standardized approach to evaluate the extent of chronic kidney injury in situations in which renal-pathologist time is restricted or unavailable.

scholarly journals Histopathological Findings in Cynomolgus Macaques (Macaca fascicularis) Consistent with Secondary Immunological Reaction to Biotherapeutics with an Emphasis on the CNS and Eye

2019 ◽  
Vol 47 (2) ◽  
pp. 165-173 ◽  
Author(s):  
Stuart W. Naylor ◽  
Melissa Czajkowski ◽  
Warren Harvey ◽  
Matt Smith ◽  
Alys E. Bradley ◽  
...  
Keyword(s):  
Mononuclear Cell ◽  
Macaca Fascicularis ◽  
Plasma Cells ◽  
Cynomolgus Macaque ◽  
Pharmaceutical Products ◽  
Test Facility ◽  
Mononuclear Cell Infiltrates ◽  
The Brain ◽  
Microscopic Findings ◽  
Good Agreement

Biotherapeutics are pharmaceutical products derived from or synthesized by biological systems. Such molecules carry the potential for immunogenicity which may lead to adverse immune responses. The cynomolgus macaque ( Macaca fascicularis) is the species of choice in nonclinical safety assessment of biotherapeutics. The main aim of this study was to confirm whether mononuclear cell infiltrates at specific locations represent a generic effect of biotherapeutics, and therefore the result of their immunogenicity. Following a review of microscopic findings in studies conducted over a 10-year period at one test facility, 15% of biotherapeutics were reported to have such findings. The most commonly affected site was the choroid plexus and less frequently the meninges and ciliary body. The reporting of such findings as test article–related becomes more subjective as the severity and incidence decreases. To assess the accuracy of such associations, a mathematical approach was employed to determine the probability of obtaining the observed results by chance. There was good agreement between this approach and the original findings. In addition to an increased number and size of mononuclear cell infiltrates in the brain, biotherapeutic administration was strongly associated with the presence of plasma cells and eosinophils.

scholarly journals Complement Inhibition Therapy and Dialytic Strategies in Paroxysmal Nocturnal Hemoglobinuria: The Nephrologist’s Opinion

2020 ◽  
Vol 9 (5) ◽  
pp. 1261 ◽  
Author(s):  
Guido Gembillo ◽  
Rossella Siligato ◽  
Valeria Cernaro ◽  
Domenico Santoro
Keyword(s):  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Multidisciplinary Approach ◽  
Interstitial Fibrosis ◽  
Kidney Injury ◽  
Surface Proteins ◽  
Tubular Atrophy ◽  
Class A ◽  
Complement Inhibitors ◽  
Chronic Hemolysis ◽  
Epithelium Cells

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal disease that presents an estimated incidence of 1.3 cases per million per year, with a prevalence of 15.9 cases per million. It is characterized by hemolysis, bone marrow dysfunction with peripheral blood cytopenia, hypercoagulability, thrombosis, renal impairment and arterial and pulmonary hypertension. Hemolysis and subsequent hemosiderin accumulation in tubular epithelium cells induce tubular atrophy and interstitial fibrosis. The origin of PNH is the somatic mutation in the X-linked phosphatidylinositol glycan class A (PIG-A) gene located on Xp22: this condition leads to the production of clonal blood cells with a deficiency in those surface proteins that protect against the lytic action of the activated complement system. Despite the increased knowledge of this syndrome, therapies for PNH were still only experimental and symptomatic, until the introduction of the C5 complement blockade agent Eculizumab. A second generation of anti-complement agents is currently under investigation, representing future promising therapeutic strategies for patients affected by PNH. In the case of chronic hemolysis and renal iron deposition, a multidisciplinary approach should be considered to avoid or treat acute tubular injury or acute kidney injury (AKI). New promising perspectives derive from complement inhibitors and iron chelators, as well as more invasive treatments such as immunoadsorption or the use of dedicated hemodialysis filters in the presence of AKI.

Composite urinary biomarkers to predict pathological tubulointerstitial lesions in lupus nephritis

Lupus ◽  
2018 ◽  
Vol 27 (11) ◽  
pp. 1778-1789 ◽  
Author(s):  
Y Ding ◽  
L-M Nie ◽  
Y Pang ◽  
W-J Wu ◽  
Y Tan ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Cox Regression ◽  
Kidney Injury ◽  
Urinary Biomarkers ◽  
Clinical Value ◽  
Tubular Atrophy ◽  
Monocyte Chemoattractant Protein 1 ◽  
Renal Outcomes ◽  
Tubulointerstitial Lesions ◽  
Normal Controls

Objective This study aimed to evaluate the clinical value of urinary biomarkers including kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and monocyte chemoattractant protein-1 (MCP-1) in lupus nephritis. Methods A total of 109 biopsy-proven lupus nephritis patients were included and 50 healthy individuals were used as normal controls. Urinary KIM-1, NGAL, and MCP-1 levels were measured by ELISA and their correlations with clinical and histological features were assessed. Receiver operating characteristic curves were performed and the Cox regression model was applied to identify prognostic factors associated with renal outcomes. Results Active lupus nephritis patients exhibited elevated urinary levels of KIM-1, NGAL, and MCP-1 compared with lupus nephritis patients in remission ( P < 0.001) and normal controls ( P < 0.001). The urinary KIM-1 level was correlated with pathological tubular atrophy ( r = 0.208, P < 0.05) and increased significantly in the presence of interstitial inflammatory lesions ( P = 0.031). Urinary KIM-1, NGAL, and MCP-1 levels were higher in patients with active tubulointerstitial lesions than in those with only chronic lesions ( P = 0.015, P = 0.230, and P = 0.086, respectively). A combination of KIM-1, NGAL, and MCP-1 was a good indicator for diagnosing active tubulointerstitial lesions (area under the curve: 0.796). The combination of KIM-1 and NGAL was identified as an independent risk factor for renal outcomes (hazard ratio = 7.491, P < 0.05). Conclusion Urinary KIM-1, NGAL, and MCP-1 levels were associated with kidney injury indices in lupus nephritis. The combination of the three biomarkers showed increased power in predicting tubulointerstitial lesions and renal outcomes.

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