Assessment of glomerular morphological patterns by deep learning algorithms

Background Compilation of different morphological lesion signatures is characteristic of renal pathology. Previous studies have documented the potential value of artificial intelligence (AI) in recognizing relatively clear-cut glomerular structures and patterns, such as segmental or global sclerosis or mesangial hypercellularity. This study aimed to test the capacity of deep learning algorithms to recognize complex glomerular structural changes that reflect common diagnostic dilemmas in nephropathology. Methods For this purpose, we defined nine classes of glomerular morphological patterns and trained twelve convolutional neuronal network (CNN) models on these. The two-step training process was done on a first dataset defined by an expert nephropathologist (12,253 images) and a second consensus dataset (11,142 images) defined by three experts in the field. Results The efficacy of CNN training was evaluated using another set with 180 consensus images, showing convincingly good classification results (kappa-values 0.838–0.938). Furthermore, we elucidated the image areas decisive for CNN-based decision making by class activation maps. Finally, we demonstrated that the algorithm could decipher glomerular disease patterns coinciding in a single glomerulus (e.g. necrosis along with mesangial and endocapillary hypercellularity). Conclusions In summary, our model, focusing on glomerular lesions detectable by conventional microscopy, is the first sui generis to deploy deep learning as a reliable and promising tool in recognition of even discrete and/or overlapping morphological changes. Our results provide a stimulus for ongoing projects that integrate further input levels next to morphology (such as immunohistochemistry, electron microscopy, and clinical information) to develop a novel tool applicable for routine diagnostic nephropathology.

Lupus Nephritis Correlates with B-Cell Interferon-β, Anti-Smith, and Anti-DNA: A Retrospective Study

Background: In systemic lupus erythematosus (SLE), detection of interferon-β (IFNβ)in B cells was found to be most prominent in patients with high anti-Smith (Sm) and renal disease, but a mechanistic connection was not clear. The objective of the present study is to determine the association of IFNβ in peripheral blood naïve B cells with the histopathological features of lupus nephritis (LN).Methods: The percentage of IFNβ+ cells in IgD+CD27− naïve CD19+ B cells (B-cell IFNβ) among peripheral blood mononuclear cells (PBMCs) from 80 SLE patients were analyzed using flow cytometry. Serological and clinical data were collected. The correlations of B-cell IFNβ with LN classification and with histopathological findings (light, electron and immunofluorescence [IF] microscopic analyses for deposition of IgM, IgG, IgA, C1q, and C3) were determined in 23 available biopsy specimens.Results: B-cell IFNβ is positively associated with anti-Sm (p = 0.001), anti-DNA (p = 0.010), and LN (p = 0.001), but was negatively associated with oral/nasal ulcer (p = 0.003) and photosensitivity (p = 0.045). B-cell IFNβ positively correlated with immune complex (IC) deposit in the glomerular basement membrane (GBM) (p = 0.002) but not in the mesangial (p = 0.107) or tubular region (p = 0.313). Patients with high B-cell IFNβ had statistically increased development of the proliferative LN (Classes III, IV and/or V), compared to patients with low B-cell IFNβ (p < 0.0001). Histopathological features positively associated with increased B-cell IFNβ included active glomerular lesions as determined by fibrocellular crescents (p = 0.023), chronic glomerular lesions indicated by segmental sclerosis (p = 0.033), and a membranous pattern of renal damage indicated by spike/holes (p = 0.015).Conclusion: B-cell IFNβ correlates with severe LN, glomerular basement membrane (GBM) IC deposition, and anatomical features of both active and chronic glomerular lesions.

AN UNUSUAL CASE OF NEW ONSET NEPHROPATHY IN A PATIENT OF PSORIASIS: CASE REPORT AND REVIEW OF LITERATURE

Psoriasis is known to cause chronic inammatory disorder of the skin through an immune mediated mechanism, it may be complicated by different types of glomerular lesions. Three different mechanisms have been implicated by which psoriasis can cause renal damage: immune-mediated renal damage, drug-related renal damage and chronic renal damage. This report presents a case of 35 years old male patient with extensive psoriasis, who presented to our hospital with nephrotic syndrome

Alpha-1 Acid Glycoprotein and Podocin mRNA as Novel Biomarkers for Early Glomerular Injury in Obese Children

Introduction: Obesity, which is a serious problem in children, has a negative impact on many organs, including kidneys, and obesity-related glomerulopathy (ORG) is an increasingly common cause of ESKD (end-stage kidney disease) in adults. Early-detected and -treated glomerular lesions are reversible, so it is important to find a useful marker of early damage. The study aimed to evaluate the albumin-to-creatinine ratio (ACR), urinary alpha-1-acid glycoprotein (α1-AGP), and mRNA of podocyte-specific proteins as indicators of glomerular injury and their relationship with the degree of obesity and metabolic disorders. Materials and Methods: A total of 125 obese children and 33 healthy peers were enrolled. Patients were divided into two groups, depending on SDS BMI values. ACR, α1-AGP, mRNA expression of nephrin, synaptopodin, podocin, and C2AP protein in urine sediment were measured. Results: ACR values did not differ between groups and were within the normal range. α1-AGP and mRNA expression were significantly higher in obese children compared with controls. mRNA expression of the remaining podocyte proteins was similar in both groups. No significant differences concerning all examined parameters were found depending on the degree of obesity. There was a positive significant correlation between α1-AGP and ACR. Conclusions: Increased α1-AGP before the onset of albuminuria suggests its usefulness as a biomarker of early glomerular damage in obese children. An increased podocin mRNA expression also indicates podocyte damage and may be linked to ORG development. The lack of increase in expression of other podocyte proteins suggests that podocin mRNA may be a more specific and sensitive biomarker. The degree of obesity has no impact on the tested parameters, but further studies are needed to confirm it.

Acute tubulointerstitial nephritis associated with antineutrophil cytoplasmic antibody following cimetidine treatment: a case report

Background Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis usually induces rapidly progressive glomerulonephritis, including pauci-immune necrotizing crescentic glomerulonephritis. Acute tubulointerstitial nephritis (ATIN), which is often drug-induced, is a frequent cause of kidney injury. However, ATIN associated with ANCA without any glomerular lesions has been rarely reported, and drug-induced ATIN associated with ANCA is not well recognized. Here we present a case of an older woman with ATIN associated with myeloperoxidase-ANCA (MPO-ANCA) following cimetidine treatment. Case presentation A 70-year-old woman was admitted to our hospital due to acute kidney injury and mild proteinuria. She had a one-year history of chronic thyroiditis and dyslipidemia, for which she was taking levothyroxine sodium and atorvastatin, respectively. Two weeks before admission she had started cimetidine, methylmethionine sulfonium chloride, and itopride hydrochloride for gastric discomfort persistent since a month. She had experienced fatigue for two weeks and later appetite loss. The patient demonstrated a positive titer for MPO-ANCA (192 IU/mL) and a positive drug-induced lymphocyte stimulation test for cimetidine. She underwent two kidney biopsies that revealed ATIN without any glomerular lesions. Despite discontinuation of cimetidine on admission, renal injury continued with the presence of high MPO-ANCA titer. Oral steroid treatment was closely related with the recovery of her renal function and disappearance of MPO-ANCA. Conclusions In this case, ATIN presented as sustained renal insufficiency and high MPO-ANCA titer despite withdrawal of cimetidine. Therefore, we reason that the development of ANCA-associated ATIN was caused by cimetidine. Serologic follow-up with measurement of MPO-ANCA titers and renal biopsy are recommended when the clinical history is inconsistent with the relatively benign course of drug-induced ATIN.

Systematic Scoring of Tubular Injury Patterns Reveals Interplay between Distinct Tubular and Glomerular Lesions in ANCA-Associated Glomerulonephritis

Background: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a small vessel vasculitis, most frequently presenting as microscopic polyangiitis (MPA) or granulomatosis with polyangiitis (GPA). Acute tubular injury with the presence of tubulitis was previously reported to be of prognostic value in ANCA glomerulonephritis (GN). In particular, distinct tubular injury lesions were associated with the deterioration of kidney function at AAV disease onset, as well as renal resistance to treatment, and higher risk of progression to composite outcome in patients with AAV. To expand our knowledge regarding distinct tubular lesions in AAV, we aimed to describe acute tubular injury patterns in association with glomerular lesions in ANCA GN by systematic histological scoring. Methods: A total number of 48 renal biopsies with confirmed renal involvement of AAV admitted to the University Medical Center Göttingen from 2015 to 2020 were retrospectively examined. By systematic scoring of tubular injury lesions, the association between clinical parameters, laboratory markers, and histopathological findings was explored. Results: We have shown that cellular casts in renal biopsies were frequently observed in the majority of cases with ANCA GN. Furthermore, we showed that tubular epithelial simplification with dilatation correlated with MPA and MPO subtypes, C3c hypocomplementemia, severe renal involvement, and uACR. Red blood cell (RBC) casts were associated with increased levels of C-reactive protein (CRP), leukocyturia, and hematuria. Finally, we found that hyaline casts were associated with an increased fraction of glomeruli with global glomerular sclerosis. Conclusions: Acute tubular injury patterns were correlated with active ANCA GN, whereas tubular injury lesions reflecting the later stages of kidney disease correlated with chronic glomerular lesions. These results suggest an interplay between different renal compartments.

Membranoproliferative glomerulonephritis: A rare presentation of occult filariasis

Parasitic infections do not usually present with rapidly progressive renal failure but can provoke glomerular lesions which are mostly proliferative. In filarial infection, glomerular involvement is usually mild and transient, and presentation with renal failure is rare. We report occult filariasis presenting as rapidly progressive renal failure due to immune-complex mediated membranoproliferative glomerulonephritis. Our patient responded to treatment with diethylcarbamazine and a short course of steroid. This case highlights the importance of thorough workup to identify the cause and consideration of filariasis in an endemic area.

Lupus Nephritis: Renal Biopsy Guiding the Clinician

Systemic lupus erythematosus is a chronic autoimmune disease that affects mostly women. The kidneys are involved in 50% of patients causing a high degree of disease morbidity and mortality with poor prognosis. Early diagnosis of lupus nephritis with prompt therapy correlates with a better outcome. The renal biopsy provides important informations to clinicians to monitor the patients. The patterns of glomerular lesion, degree of activity and chronicity of the disease and extent of lesions to the tubulointerstitial and vascular compartments are fundamental information for the clinician to decide the most appropriate treatment. In order to correlate the kidney disease with clinical manifestations and patient outcome the glomerular lesions are classified according to International Society of Nephrology and Renal Pathology Society Classification (ISN/RPS). The definition of active and chronic lesions was introduced by studies conducted at National Institute of Health (NIH). The ISN/RPS classification and NIH indices have recently been revised by a series of retrospective validation studies to improve and minimize the controversial aspects.

C3 glomerulonephritis associated with ANCA positivity: a case report

Background C3 glomerulopathy (C3G) is a recent disease classification that is characterized by the presence of glomerular deposits (composed of C3) in the absence of significant amounts of immunoglobulin and comprises dense deposit disease and C3 glomerulonephritis (C3GN). Most C3GN manifests as membranoproliferative, mesangial proliferative glomerulonephritis patterns via light microscopy. Pure membranous nephropathy (MN)-like glomerular lesions are rare manifestations of C3GN. Anti-neutrophil cytoplasmic antibodies (ANCAs) are also seldomly reported to be positive in C3GN. Herein, we report the case of a C3GN patient presenting with an MN-like glomerular pattern with ANCA positivity. Case presentation A 68-year-old woman was admitted to a local hospital with elevated serum creatinine for two weeks. Laboratory tests showed a hemoglobin level of 85 g/L. Urinalysis was positive for 2 + protein and 360 RBCs/HPF. Blood biochemistry analysis revealed the following concentrations: albumin, 30.3 g/L; globulin, 46.2 g/L; blood urea nitrogen, 19.9 mmol/L; and serum creatinine, 234 µmol/L. The serum C3 level was 0.4950 g/L, and the serum C4 level was 0.1050 g/L. The direct Coombs test was positive. Serologic testing for ANCA revealed the presence of p-ANCA (1:10) by indirect immunofluorescence microscopy assay, as well as the presence of PR3 1.2 (normal range < 1) and MPO 3.5 (normal range < 1) by enzyme immunoassay. Renal biopsy sample pathology showed 2/6 cellular crescents and thickened glomerular basement membranes. Immunofluorescence testing revealed only diffuse, finely granular depositions of C3 along the glomerular capillary walls in frozen and paraffin-embedded tissue sections. Electron microscopy demonstrated the presence of subepithelial electron-dense deposits, similar to those that are observed in membranous nephropathy. Corticosteroid and cyclophosphamide were administered, with a subsequent improvement in renal function. Conclusions We present the rare case of a patient with MN-like C3GN with ANCA positivity. C3GN with ANCA positivity may be represented by more crescents, severe renal dysfunction and more extrarenal manifestations. More cases are needed to elucidate the clinicopathologic features and optimal treatments of these patients.