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 Fibrosis regression is induced by AdhMMP8 in a murine model of chronic kidney injury

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0243307
Author(s):  
Homero Contreras-Salinas ◽  
Alejandra Meza-Rios ◽  
Jesús García-Bañuelos ◽  
Ana Sandoval-Rodriguez ◽  
Laura Sanchez-Orozco ◽  
...  
Keyword(s):  
Serum Creatinine ◽  
Interstitial Fibrosis ◽  
Left Kidney ◽  
Kidney Injury ◽  
Protein Detection ◽  
Experimental Models ◽  
Chronic Injury ◽  
Tubular Atrophy ◽  
Kidney Fibrosis ◽  
Ischemic Period

Adenoviral vector AdhMMP8 (human Metalloproteinase-8 cDNA) administration has been proven beneficial in various experimental models of liver injury improving liver function and decreasing fibrosis. In this study, we evaluated the potential therapeutic AdhMMP8 effect in a chronic kidney damage experimental model. Chronic injury was induced by orogastric adenine administration (100mg/kg/day) to Wistar rats for 4 weeks. AdhMMP8 (3x1011vp/kg) was administrated in renal vein during an induced-ligation-ischemic period to facilitate kidney transduction causing no-additional kidney injury as determined by histology and serum creatinine. Animals were sacrificed at 7- and 14-days post-Ad injection. Fibrosis, histopathological features, serum creatinine (sCr), BUN, and renal mRNA expression of αSMA, Col-1α, TGF-β1, CTGF, BMP7, IL-1, TNFα, VEGF and PAX2 were analyzed. Interestingly, AdhMMP8 administration resulted in cognate human MMP8 protein detection in both kidneys, whereas hMMP8 mRNA was detected only in the left kidney. AdhMMP8 significantly reduced kidney tubule-interstitial fibrosis and glomerulosclerosis. Also, tubular atrophy and interstitial inflammation were clearly decreased rendering improved histopathology, and down regulation of profibrogenic genes expression. Functionally, sCr and BUN were positively modified. The results showed that AdhMMP8 decreased renal fibrosis, suggesting that MMP8 could be a possible therapeutic candidate for kidney fibrosis treatment.

MO266URINARY TRANSFERRIN AND IGG EXCRETIONS PREDICT TUBULOINTERSTITIAL LESIONS IN PATIENTS WITH IGA NEPHROPATHY

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Saganova Elena ◽  
Olga Galkina ◽  
Vasiliy Sipovskii ◽  
Alexei Smirnov
Keyword(s):  
Iga Nephropathy ◽  
Roc Analysis ◽  
Severe Heart Failure ◽  
Kidney Injury ◽  
Diagnostic Value ◽  
Tubular Atrophy ◽  
Protein Excretion ◽  
Tubulointerstitial Lesions ◽  
Noninvasive Biomarkers ◽  
Stage Renal Disease

Abstract Background and Aims IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide and is a frequent cause of end-stage renal disease. The best predictors of progression are histologic parameters. Nevertheless, there is a pressing need to identify suitable noninvasive biomarkers in IgAN, to aid with diagnosis, treatment decisions, and prediction of the disease progression. Our aim was to assess diagnostic value of urinary excretions of transferrin and IgG in prediction of morphological lesions in patients with IgAN. Method 37 patients [19 female, age Me 33 (25; 48) years] with biopsy proven IgAN and without acute kidney injury, infectious diseases, severe heart failure, respiratory insufficiency, cancer were included in the study. 24-hour urinary excretions of transferrin (uTr), IgG (uIgG) were measured by immunoturbidimetric method (Furuno CA-90, Furuno Electric Co., Ltd., Japan). Tubulointerstitial 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 two groups according to the degree of each morphological lesion (TIF or TA): “mild” (TIF or TA grade 0 or 1) and “severe” (TIF/TA grade 2-3). Results uTr, uIgG positively correlated (p<0,05) with TIF (r=0,38, r=0,43) and TA (r=0,38, r=0,45), respectively. We did not find correlations between uTr, uIgG and glomerulosclerosis. Using ROC-analysis all patients were separated in two groups using uTr or uIgG according to the degree of morphological lesions (“mild” or “severe) (Table 1,2; Figure 1). According to the results of ROC-analysis we also found that all cut-off values of uTr, uIgG corresponded to the level of urinary protein excretion not more than 1,25 g/24hour. Conclusion Our results show that uTr and uIgG can be used as markers of early tubulointerstitial lesions in patients with IgA nephropathy with mild protein excretion.

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.

FC 044THE LONG-TERM EFFECTS OF ACUTE KIDNEY INJURY ON INTESTINAL OXALATE-DEGRADING BACTERIA IN RATS

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Natalia Stepanova ◽  
Ganna Tolstanova ◽  
Valentyn Nepomnyashchii ◽  
Iryna Akulenko ◽  
Svitlana Savchenko ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Serum Creatinine ◽  
Interstitial Fibrosis ◽  
Kidney Injury ◽  
Fecal Microbiota ◽  
Long Term Effects ◽  
Renal Interstitial Fibrosis ◽  
Degrading Bacteria ◽  
Group 1

Abstract Background and Aims Gut microbiota is considered an important factor affecting oxalate handling in the intestine. It has been demonstrated that intestinal oxalate secretion provides a complementary route of excretion, and it becomes more evident when kidney function declines. A diversity of gut oxalate-degrading bacteria (ODB) has been hypothesized to play a role in this process. However, there is a general lack of research on the long-term effects of acute kidney injury (AKI) on ODB and their total oxalate-degrading activity (ODA) in fecal microbiota. In this study, we evaluated whether renal dysfunction could affect intestinal ODB and their total ODA in a rat model of glycerol-induced AKI. Method The Male Wistar rats (200-300 g, n=20) on oxalate-free diet were randomly divided into 2 groups. After 24-h of water deprivation, Group 1 (n=10) received an intramuscular injection of 50% glycerol (10 ml/kg of body weight), and Group 2 (n=10) served as control. The numbers of ODB (incubated in a highly selective Oxalate Medium and determined using culture method) and total fecal ODA were measured after injection on days 7 and 70. The method of redoximetric titration with a KMnO4 solution was adopted to evaluate total ODA in fecal microbiota; the results were expressed as % of oxalate degradation per 0.01 g of feces. Renal injury was assessed by histopathological examination, serum creatinine and daily proteinuria levels after removing the animals from the experiment on day 70. Cortical interstitial fibrosis was measured by computerized image analysis on sections stained with picrosirius red. The median (Me) and the interquartile ranges (Q25; Q75) were calculated and compared using the nonparametric Mann-Whitney test. The Spearman correlation coefficient was used to evaluate association between the examined parameters. Results The obtained results demonstrated: 1) after glycerol injection on day 7, no differences were found in the numbers of ODB and total fecal ODA between the experimental and control groups: 5.9 (5.4-6.0) vs 6.0 (5.4-6.4) CFU/g, p=0.65 and 2.0 (0.1-5.0) vs 2.5 (2.0-9.0) %/0.01g, p=0.24, respectively; 2) after AKI initiation on day 70, the numbers of ODB and total fecal ODA were significantly lower in Group I compared with control Group II (Fig. 1); 3) the higher percentage of renal interstitial fibrosis was, the higher total fecal ODA occurred in the experimental rats (Fig. 2). In addition, the number of ODB in feces in Group 1 had an inverse association with serum creatinine (r=-0.52, p=0.006) and 24-h proteinuria levels (r=-0.86, p<0.0001). Conclusion AKI had the long-term negative effects on the quantitative and qualitative characteristics of ODB in fecal microbiota in rats. Moreover, the results of our study confirmed an increasing trend in total fecal ODA according to the aggravation of renal interstitial fibrosis in rats.

Gene of the month: GLIS1-3

2020 ◽  
Vol 73 (9) ◽  
pp. 527-530
Author(s):  
Karen Pinto ◽  
Runjan Chetty
Keyword(s):  
Autosomal Recessive ◽  
Interstitial Fibrosis ◽  
Neonatal Diabetes ◽  
Diagnostic Value ◽  
Cystic Kidney Disease ◽  
Cystic Kidney ◽  
Facial Dysmorphism ◽  
Loss Of Function ◽  
Tubular Atrophy ◽  
Colon Cancers

The GLIS 1–3 genes belong to a family of transcription factors, the Krüppel-like zinc finger proteins. The GLIS proteins function primarily as activators of transcription (GLIS 1 and 3), while GLIS 2 functions as a repressor. Collectively, the GLIS proteins are involved in a variety of diseases in several organs ranging from Alzheimer’s disease, facial dysmorphism, neonatal diabetes mellitus, breast and colon cancers and leukaemia. In particular, loss-of-function mutations in GLIS2 are responsible for an autosomal recessive cystic kidney disease called nephronophthisis, which is characterised by tubular atrophy, interstitial fibrosis and corticomedullary cysts.Of diagnostic value in current practice are the presence of GLIS 3 and 1 fusions with PAX8 in almost 100% of hyalinising trabecular tumours of the thyroid gland. This enables its separation from papillary thyroid cancer.

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 Renal Allograft Dysfunction Possibly Caused by Amiodarone Nephrotoxicity: a Case-Report

2017 ◽  
Vol 15 (1) ◽  
pp. 39-40
Author(s):  
Nikolina Basic-Jukic ◽  
Lea Katalinic ◽  
Marijana Coric ◽  
Monika Kocman ◽  
Branimir Krtalic ◽  
...  
Keyword(s):  
Renal Allograft ◽  
Potent Inhibitor ◽  
Interstitial Fibrosis ◽  
Deceased Donor ◽  
Immunosuppressive Drugs ◽  
Tubular Atrophy ◽  
Careful Revision ◽  
Global Glomerulosclerosis ◽  
Trough Levels ◽  
Important Drug

AbstractAmiodarone is a potent inhibitor of CYP3A4 and can increase serum concentrations of drugs that are substrates of this enzyme system. Immunosuppressive drugs are also metabolized through the cytochrome metabolic pathway what may lead to important drug-drug interactions. A 60-year-old female received her second allograft from the deceased donor and was treated with tacrolimus, mycophenolate mofetil and steroids. Amiodarone was introduced for treatment of paroxysmal atrial fibrillation four days after the transplantation. One month after the discharge she was readmitted to hospital for evaluation of the creeping creatinine. Biopsy showed borderline acute rejection. She received 3 boluses of 6- methilprednisolone but creatinine continued to rise. Repeated biopsy was without signs of rejection with mild interstitial fibrosis/tubular atrophy, mild global glomerulosclerosis and moderate arterial sclerosis. However, tubular vacuolization was prominent. After careful revision of her therapy we decided to replace amiodarone with sotalol. One week later her creatinine fell from 350 to 220 μmol/l and remained stable. This case illustrates possible amiodarone nephrotoxicity in a renal transplant recipient. We suggest that patients who need amiodarone in combination with tacrolimus be closely monitored by both cardiologists and nephrologists, with frequent determinations of tacrolimus trough levels and serum creatinine measurements.

scholarly journals Lithium Nephrotoxicity

2000 ◽  
Vol 11 (8) ◽  
pp. 1439-1448 ◽  
Author(s):  
GLEN S. MARKOWITZ ◽  
JAI RADHAKRISHNAN ◽  
NEERAJA KAMBHAM ◽  
ANTHONY M. VALERI ◽  
WILLIAM H. HINES ◽  
...  
Keyword(s):  
Serum Creatinine ◽  
Focal Segmental Glomerulosclerosis ◽  
Interstitial Fibrosis ◽  
Renal Cysts ◽  
Significant Degree ◽  
Fisher Exact Test ◽  
Tubular Atrophy ◽  
Segmental Glomerulosclerosis ◽  
Tubulointerstitial Nephropathy ◽  
Collecting Tubules

Abstract. This study examines the clinical features, pathologic findings, and outcome of 24 patients with biopsy-proven lithium toxicity. The patient population was 50% male, 87.5% Caucasian, and had a mean age of 42.5 yr (range, 26 to 57). Mean duration of lithium therapy for bipolar disorder was 13.6 yr (range, 2 to 25). All patients were biopsied for renal insufficiency (mean serum creatinine 2.8 mg/dl; range, 1.3 to 8.0), with associated proteinuria >1.0 g/d in 41.7%. Nephrotic proteinuria (>3.0 g/d) was present in 25%. Other features included nephrogenic diabetes insipidus in 87% and hypertension in 33.3%. Renal biopsy revealed a chronic tubulointerstitial nephropathy in 100%, with associated cortical and medullary tubular cysts (62.5%) or dilatation (33.3%). All of the renal cysts stained for epithelial membrane antigen, while 51.4% stained with lectin Arachis hypogaea, and only 3.8% stained with Tetragonolobus purpureas, indicating they originated from distal and collecting tubules. The degree of tubular atrophy and interstitial fibrosis was graded as severe in 58.3%, moderate in 37.5%, and mild in 4.2% of cases. There was a surprisingly high prevalence of focal segmental glomerulosclerosis (50%) and global glomerulosclerosis (100%), sometimes of equivalent severity to the chronic tubulointerstitial disease. The significant degree of foot process effacement (mean 34%, five of 14 cases with >50%) suggests a potential direct glomerular toxicity. Focal segmental glomerulosclerosis correlated with proteinuria >1.0 g/d (P= 0.0014, Fisher exact test). Despite discontinuation of lithium, seven of nine patients with initial serum creatinine values >2.5 mg/dl progressed to end-stage renal disease (ESRD). Only three patients, all with initial serum creatinine <2.1 mg/dl, had subsequent improvement in renal function. By Kaplan-Meier survival analysis, the only significant predictor of progression to ESRD was serum creatinine >2.5 mg/dl at biopsy (P= 0.008). In conclusion, lithium nephrotoxicity primarily targets distal and collecting tubules, with a higher incidence of proteinuria and associated glomerular pathology than recognized previously. Renal dysfunction is often irreversible despite lithium withdrawal, and early detection is essential to prevent progression to ESRD.

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 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.

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