Nejvíce citovaný článek - PubMed ID 32723805
Developments in the Histopathological Classification of ANCA-Associated Glomerulonephritis
INTRODUCTION: The histopathological classification for antineutrophil cytoplasmic autoantibody (ANCA)-associated glomerulonephritis (ANCA-GN) is a well-established tool to reflect the variety of patterns and severity of lesions that can occur in kidney biopsies. It was demonstrated previously that deep learning (DL) approaches can aid in identifying histopathological classes of kidney diseases; for example, of diabetic kidney disease. These models can potentially be used as decision support tools for kidney pathologists. Although they reach high prediction accuracies, their "black box" structure makes them nontransparent. Explainable (X) artificial intelligence (AI) techniques can be used to make the AI model decisions accessible for human experts. We have developed a DL-based model, which detects and classifies the glomerular lesions according to the Berden classification. METHODS: Kidney biopsy slides of 80 patients with ANCA-GN from 3 European centers, who underwent a diagnostic kidney biopsy between 1991 and 2011, were included. We also investigated the explainability of our model using Gradient-weighted Class Activation Mapping (Grad-CAM) heatmaps. These maps were analyzed by pathologists to compare the decision-making criteria of humans and the DL model and assess the impact of different training settings. RESULTS: The DL model shows a prediction accuracy of 93% for classifying lesions. The heatmaps from our trained DL models showed that the most predictive areas in the image correlated well with the areas deemed to be important by the pathologist. CONCLUSION: We present the first DL-based computational pipeline for classifying ANCA-GN kidney biopsies as per the Berden classification. XAI techniques helped us to make the decision-making criteria of the DL accessible for renal pathologists, potentially improving clinical decision-making.
- Klíčová slova
- ANCA, artificial intelligence, histopathology, machine learning, vasculitis,
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Kidney involvement is common in anti-neutrophil cytoplasm antibody-associated vasculitis (AAV) and the prognosis is determined by the severity of kidney damage. This study focused on long-term kidney outcomes, defining possible risk factors and comparing the performance of three different histological classifications to predict outcomes for patients with AAV. METHODS: The dataset included 848 patients with newly diagnosed AAV who participated in seven randomized controlled trials (RCTs) (1995-2012). Follow-up information was obtained from questionnaires sent to the principal investigators of the original RCTs. RESULTS: The cumulative incidence of end-stage kidney disease (ESKD) at 5 and 10 years was 17% and 22%, respectively. Patients who developed ESKD had reduced patient survival compared with those with preserved kidney function (hazard ratio 2.8, P < .001). Comparing patients with AAV and kidney involvement with a matched general population, patients with AAV had poor survival outcomes, even in early stages of chronic kidney disease. The main cause of death was infection followed by cardiovascular disease in patients developing ESKD and malignancy in those who did not. Some 34% of patients with initial need for dialysis recovered kidney function after treatment. Thirty-five out of 175 in need of kidney replacement therapy (KRT) during follow-up received a kidney transplant with good outcome; there was 86% patient survival at 10 years.In the subcohort of 214 patients with available kidney biopsies, three scoring systems were tested: the Berden classification, the Renal Risk Score and the Mayo Clinic Score. The scores highlighted the importance of normal glomeruli and severe glomerulosclerosis on kidney survival (P < .001 and P = .001, respectively). The Renal Risk Score demonstrated a moderate prediction of kidney survival (area under the curve 0.79; standard error 0.03, 95% confidence interval 0.71-0.83). CONCLUSIONS: Early diagnosis of AAV is extremely important. Even milder forms of kidney involvement have an impact on the prognosis. Patients in need of KRT had the lowest survival rates, but kidney transplantation has shown favorable outcomes for eligible AAV patients. The three histologic scoring systems were all identified as independent prognostic factors for kidney outcome.
- Klíčová slova
- ANCA-associated vasculitis, end-stage kidney disease, kidney histology scores, prognosis, transplantation,
- MeSH
- ANCA-asociované vaskulitidy * komplikace mortalita terapie MeSH
- chronické selhání ledvin * mortalita terapie etiologie MeSH
- dospělí MeSH
- hodnoty glomerulární filtrace MeSH
- lidé středního věku MeSH
- lidé MeSH
- míra přežití MeSH
- následné studie MeSH
- prognóza MeSH
- rizikové faktory MeSH
- senioři MeSH
- vyšetření funkce ledvin MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
SIGNIFICANCE STATEMENT: Reliable prediction tools are needed to personalize treatment in ANCA-associated GN. More than 1500 patients were collated in an international longitudinal study to revise the ANCA kidney risk score. The score showed satisfactory performance, mimicking the original study (Harrell's C=0.779). In the development cohort of 959 patients, no additional parameters aiding the tool were detected, but replacing the GFR with creatinine identified an additional cutoff. The parameter interstitial fibrosis and tubular atrophy was modified to allow wider access, risk points were reweighted, and a fourth risk group was created, improving predictive ability (C=0.831). In the validation, the new model performed similarly well with excellent calibration and discrimination ( n =480, C=0.821). The revised score optimizes prognostication for clinical practice and trials. BACKGROUND: Reliable prediction tools are needed to personalize treatment in ANCA-associated GN. A retrospective international longitudinal cohort was collated to revise the ANCA renal risk score. METHODS: The primary end point was ESKD with patients censored at last follow-up. Cox proportional hazards were used to reweight risk factors. Kaplan-Meier curves, Harrell's C statistic, receiver operating characteristics, and calibration plots were used to assess model performance. RESULTS: Of 1591 patients, 1439 were included in the final analyses, 2:1 randomly allocated per center to development and validation cohorts (52% male, median age 64 years). In the development cohort ( n =959), the ANCA renal risk score was validated and calibrated, and parameters were reinvestigated modifying interstitial fibrosis and tubular atrophy allowing semiquantitative reporting. An additional cutoff for kidney function (K) was identified, and serum creatinine replaced GFR (K0: <250 µ mol/L=0, K1: 250-450 µ mol/L=4, K2: >450 µ mol/L=11 points). The risk points for the percentage of normal glomeruli (N) and interstitial fibrosis and tubular atrophy (T) were reweighted (N0: >25%=0, N1: 10%-25%=4, N2: <10%=7, T0: none/mild or <25%=0, T1: ≥ mild-moderate or ≥25%=3 points), and four risk groups created: low (0-4 points), moderate (5-11), high (12-18), and very high (21). Discrimination was C=0.831, and the 3-year kidney survival was 96%, 79%, 54%, and 19%, respectively. The revised score performed similarly well in the validation cohort with excellent calibration and discrimination ( n =480, C=0.821). CONCLUSIONS: The updated score optimizes clinicopathologic prognostication for clinical practice and trials.
- MeSH
- ANCA-asociované vaskulitidy * diagnóza MeSH
- atrofie MeSH
- fibróza MeSH
- kreatinin MeSH
- ledviny MeSH
- lidé středního věku MeSH
- lidé MeSH
- longitudinální studie MeSH
- protilátky proti cytoplazmě neutrofilů * MeSH
- retrospektivní studie MeSH
- rizikové faktory MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- kreatinin MeSH
- protilátky proti cytoplazmě neutrofilů * MeSH
Years of standing still have ended, and the field of nephrology has seen a plethora of clinical trials, changing the therapeutic landscape of chronic kidney disease (CKD) and immune-mediated kidney disease management [...].
