Imaging modality: Histopathology, brightfield light microscopy of hematoxylin and eosin–stained renal tissue from a kidney biopsy. The primary subject is intravascular large B-cell lymphoma (IVLBCL) involving the kidney, with conspicuous localization of neoplastic lymphocytes within glomerular capillaries. The glomerulus shows densely packed, round to irregular lymphoid cells occupying intravascular lumina, often compressing capillary loops. The surrounding glomerular tuft is variably preserved; endothelial cells may be reactive, without overt basement membrane destruction. Nuclear morphology is pleomorphic with prominent nucleoli and scant cytoplasm; mitotic figures may be present. Extracapillary invasion is limited in this field. This intravascular pattern argues for IVLBCL over typical glomerulonephritis and may be associated with minimal change disease clinically. Immunohistochemical confirmation (not shown) would demonstrate CD20 positivity and B-cell markers, with relative absence of T-cell markers, supporting a B-cell neoplasm. Diagnostic significance rests on recognizing renal involvement as part of systemic IVLBCL; confirms disease and informs staging and chemoimmunotherapy (R-CHOP). Clinical correlation includes possible renal dysfunction, nephrotic syndrome, or minimal change disease, with cutaneous, CNS, pulmonary, hepatic, and adrenal involvement reported in IVLBCL. Potential use cases include differential diagnosis of nephrotic-range proteinuria with atypical histology and guiding targeted therapy. This image exemplifies diagnostic pathology guiding timely therapy decisively.

Summary : This flowchart outlines the recommended immunosuppressive treatment strategies for patients with Class I or Class II lupus nephritis, based on kidney biopsy findings and clinical presentation (low-level proteinuria vs. nephrotic syndrome). flowchart: # Nodes : • Kidney biopsy showing Class I/II lupus nephritis (rounded rectangle, top node) • Low-level proteinuria (rounded rectangle, left branch) • Nephrotic syndrome (rounded rectangle, right branch) • Immunosuppressive treatment guided by extrarenal manifestations of systemic lupus erythematosus (rounded rectangle, leftmost bottom node) • Evaluate for lupus podocytopathy (electron microscopy would be useful) (rounded rectangle, right branch, intermediate node) • Treat as minimal change disease (Chapter 5) (rounded rectangle, right branch, intermediate node) • Consider maintenance combination therapy with low-dose glucocorticoid and another immunosuppressive agent (rounded rectangle, rightmost bottom node, bolded text) # Connectors : • Downward arrows from the top node to "Low-level proteinuria" and "Nephrotic syndrome" (branching into two paths). • "Low-level proteinuria" leads directly down to "Immunosuppressive treatment guided by extrarenal manifestations of systemic lupus erythematosus". • "Nephrotic syndrome" leads down to "Evaluate for lupus podocytopathy (electron microscopy would be useful)". • "Evaluate for lupus podocytopathy" leads down to "Treat as minimal change disease (Chapter 5)". • "Treat as minimal change disease" leads down to "Consider maintenance combination therapy with low-dose glucocorticoid and another immunosuppressive agent". # Layout : • Vertical flow, starting from a single top node, splitting into two parallel branches (left: low-level proteinuria, right: nephrotic syndrome). • Left branch is a single-step path; right branch is a multi-step path with three nodes. • All nodes are rounded rectangles; the final rightmost node uses bold text for emphasis. # Analysis : • The flowchart distinguishes treatment approaches based on proteinuria severity in lupus nephritis. • Patients with low-level proteinuria receive immunosuppression based on extrarenal lupus activity. • Patients with nephrotic syndrome are evaluated for lupus podocytopathy and treated as minimal change disease, with consideration for maintenance combination therapy (low-dose glucocorticoid plus another immunosuppressive agent). • The right branch is more complex, reflecting additional diagnostic and therapeutic steps for nephrotic syndrome. • The chart references Chapter 5 of the KDIGO Guideline for further details on minimal change disease management.

Summary : This flowchart outlines the immunosuppressive treatment approach for patients with Class I or Class II lupus nephritis, based on kidney biopsy findings and clinical presentation (low-level proteinuria vs. nephrotic syndrome). flowchart: # Nodes : • Kidney biopsy showing Class I/II lupus nephritis (rounded rectangle, top/starting node) • Low-level proteinuria (rounded rectangle, left branch) • Immunosuppressive treatment guided by extrarenal manifestations of systemic lupus erythematosus (rounded rectangle, leftmost terminal node) • Nephrotic syndrome (rounded rectangle, right branch) • Evaluate for lupus podocytopathy (electron microscopy would be useful) (rounded rectangle, right branch, intermediate node) • Treat as minimal change disease (Chapter 5) (rounded rectangle, right branch, intermediate node) • Consider maintenance combination therapy with low-dose glucocorticoid and another immunosuppressive agent (rounded rectangle, rightmost terminal node) # Connectors : • The starting node splits into two branches: one to "Low-level proteinuria" (left), one to "Nephrotic syndrome" (right). • "Low-level proteinuria" leads directly to "Immunosuppressive treatment guided by extrarenal manifestations of systemic lupus erythematosus". • "Nephrotic syndrome" leads to "Evaluate for lupus podocytopathy (electron microscopy would be useful)". • "Evaluate for lupus podocytopathy" leads to "Treat as minimal change disease (Chapter 5)". • "Treat as minimal change disease" leads to "Consider maintenance combination therapy with low-dose glucocorticoid and another immunosuppressive agent". # Layout : • Top-down hierarchical structure. • Two main branches (left: low-level proteinuria, right: nephrotic syndrome). • Right branch has additional sequential steps before reaching the terminal node. • All nodes are rounded rectangles; connectors are straight arrows. # Analysis : • The flowchart distinguishes treatment pathways based on the presence of low-level proteinuria versus nephrotic syndrome in patients with Class I/II lupus nephritis. • For low-level proteinuria, treatment is guided by extrarenal lupus manifestations. • For nephrotic syndrome, further evaluation for lupus podocytopathy is recommended, with subsequent treatment as minimal change disease and consideration of maintenance combination therapy. • The right branch is more complex, indicating a need for additional diagnostic steps and combination therapy.

Summary : This flowchart outlines the immunosuppressive treatment approach for patients with Class I or Class II lupus nephritis (LN) based on kidney biopsy findings, differentiating management according to the presence of low-level proteinuria or nephrotic syndrome. flowchart: # Nodes : • Kidney biopsy showing Class I/II lupus nephritis (rounded rectangle, top/starting node) • Low-level proteinuria (rectangle, left branch) • Nephrotic syndrome (rectangle, right branch) • Immunosuppressive treatment guided by extrarenal manifestations of systemic lupus erythematosus (rectangle, leftmost terminal node) • Evaluate for lupus podocytopathy (electron microscopy would be useful) (rectangle, right branch, intermediate node) • Treat as minimal change disease (Chapter 5) (rectangle, right branch, intermediate node) • Consider maintenance combination therapy with low-dose glucocorticoid and another immunosuppressive agent (rectangle, rightmost terminal node) # Connectors : • Downward arrows from the starting node to two branches: "Low-level proteinuria" and "Nephrotic syndrome". • From "Low-level proteinuria" → arrow to "Immunosuppressive treatment guided by extrarenal manifestations of systemic lupus erythematosus". • From "Nephrotic syndrome" → arrow to "Evaluate for lupus podocytopathy (electron microscopy would be useful)". • From "Evaluate for lupus podocytopathy" → arrow to "Treat as minimal change disease (Chapter 5)". • From "Treat as minimal change disease" → arrow to "Consider maintenance combination therapy with low-dose glucocorticoid and another immunosuppressive agent". # Layout : • Top-down hierarchical structure. • Initial node at the top, splitting into two parallel branches (left: low-level proteinuria; right: nephrotic syndrome). • Left branch is a single-step pathway; right branch is a multi-step pathway with three sequential nodes. • Terminal nodes at the bottom of each branch. # Analysis : • The flowchart distinguishes treatment based on proteinuria severity: low-level proteinuria leads to immunosuppression guided by extrarenal lupus activity, while nephrotic syndrome prompts evaluation for lupus podocytopathy, treatment as minimal change disease, and consideration of maintenance combination therapy. • The right branch (nephrotic syndrome) involves more diagnostic and therapeutic steps, reflecting greater disease severity. • The chart emphasizes the importance of extrarenal manifestations in guiding therapy for milder renal involvement.

Summary : This figure presents a proposed classification scheme for focal segmental glomerulosclerosis (FSGS) based on the nature and cause of lesions observed on light microscopy. It divides FSGS into four main categories: primary, genetic, secondary, and undetermined cause, with defining features for each. flowchart: # Nodes : • FSGS lesions on light microscopy (rectangle, top central node) • Primary FSGS (rectangle) – FSGS with diffuse foot process effacement and nephrotic syndrome (often sudden onset, amenable to therapy) • Genetic FSGS (rectangle) – Familial – Syndromic – Sporadic • Secondary FSGS (rectangle) – Viral – Drug-induced – Adaptive changes to glomerular hyperfiltration (normal or reduced nephron mass; segmental foot process effacement; proteinuria without nephrotic syndrome) • FSGS of undetermined cause (FSGS-UC) (rectangle) – Segmental foot process effacement – Proteinuria without nephrotic syndrome – No evidence of secondary cause # Connectors : • Single downward arrows from "FSGS lesions on light microscopy" to each of the four category nodes (Primary FSGS, Genetic FSGS, Secondary FSGS, FSGS-UC). • No further branching or merging. # Layout : • Hierarchical, top-down arrangement. • Central top node ("FSGS lesions on light microscopy") branches downward to four horizontally aligned category nodes. # Analysis : • The classification distinguishes FSGS types by etiology and clinical features, separating primary (diffuse effacement, nephrotic syndrome), genetic (familial/syndromic/sporadic), secondary (viral, drug, adaptive hyperfiltration), and undetermined cause (segmental effacement, proteinuria without nephrotic syndrome, no secondary cause). • The scheme emphasizes both pathological findings (foot process effacement) and clinical presentation (nephrotic syndrome, proteinuria), aiding differential diagnosis and guiding therapy.

Summary : This flowchart outlines the immunosuppressive treatment approach for patients with Class I or Class II lupus nephritis (LN) based on kidney biopsy findings, differentiating management according to the presence of low-level proteinuria or nephrotic syndrome. flowchart: # Nodes : • Kidney biopsy showing Class I/II lupus nephritis (rounded rectangle, top/starting node) • Low-level proteinuria (rectangle, left branch) • Nephrotic syndrome (rectangle, right branch) • Immunosuppressive treatment guided by extrarenal manifestations of systemic lupus erythematosus (rectangle, leftmost terminal node) • Evaluate for lupus podocytopathy (electron microscopy would be useful) (rectangle, right branch, intermediate node) • Treat as minimal change disease (Chapter 5) (rectangle, right branch, intermediate node) • Consider maintenance combination therapy with low-dose glucocorticoid and another immunosuppressive agent (rectangle, rightmost terminal node) # Connectors : • Downward arrows from the starting node to two branches: "Low-level proteinuria" and "Nephrotic syndrome". • From "Low-level proteinuria" → arrow to "Immunosuppressive treatment guided by extrarenal manifestations of systemic lupus erythematosus". • From "Nephrotic syndrome" → arrow to "Evaluate for lupus podocytopathy (electron microscopy would be useful)". • From "Evaluate for lupus podocytopathy" → arrow to "Treat as minimal change disease (Chapter 5)". • From "Treat as minimal change disease" → arrow to "Consider maintenance combination therapy with low-dose glucocorticoid and another immunosuppressive agent". # Layout : • Top-down hierarchical structure. • Initial node at the top, splitting into two parallel branches (left: low-level proteinuria; right: nephrotic syndrome). • Left branch is a single-step pathway; right branch is a multi-step pathway with three sequential nodes. • Terminal nodes at the bottom of each branch. # Analysis : • The flowchart distinguishes treatment based on proteinuria severity: low-level proteinuria leads to immunosuppression guided by extrarenal lupus activity, while nephrotic syndrome prompts evaluation for lupus podocytopathy, treatment as minimal change disease, and consideration of maintenance combination therapy. • The right branch (nephrotic syndrome) involves more diagnostic and therapeutic steps, reflecting greater disease severity. • The chart emphasizes the importance of extrarenal manifestations in guiding therapy for milder renal involvement.

This Transmission Electron Microscopy (TEM) image of a renal glomerulus demonstrates diffuse thickening of the glomerular basement membrane (GBM), an ultrastructural hallmark of diabetic nephropathy. The sample is a renal biopsy from a patient with type 1 diabetes mellitus, illustrating early intraglomerular microangiopathy within approximately two years of disease onset. In TEM, the GBM appears markedly thickened, with increased electron density and reduced capillary luminal space; podocyte foot processes may show effacement, though not clearly identifiable in this static field. The specimen is oriented in the glomerular capillary loops within the renal cortex; scale bar indicates 5 μm, reflecting ultrastructural resolution. Clinically, GBM thickening correlates with progression to overt proteinuria and chronic kidney disease; however, nodular sclerosis (Kimmelstiel-Wilson lesions) and overt glomerulosclerosis develop later. This image underscores the value of electron microscopy for early detection of diabetic microangiopathy when light microscopy may be less sensitive. Diagnostic significance lies in confirming diabetic nephropathy in the appropriate clinical context, differentiating from other glomerulopathies where GBM thickening may occur, such as membranous nephropathy or hypertensive nephrosclerosis. Potential uses include educational illustration of early diabetic kidney disease, research into ultrastructural changes in diabetes, and aiding pathology concordance with clinical diabetes management and nephrology planning.

<table><thead><tr><th>Nephrotic syndrome</th><th>Nephrotic-range proteinuria</th><th>Non-nephrotic-range proteinuria</th></tr></thead><tbody><tr><td>Proteinuria (adults)*<br>• ≥3.5 g per 24 h<br>• PCR ≥3000 mg/g<br>(≥300 mg/mmol)</td><td>Proteinuria (adults)<br>• ≥3.5 g per 24 h<br>• PCR ≥3000 mg/g<br>(≥300 mg/mmol)</td><td>Variable levels of proteinuria<br>• 0.3–3.4 g per 24 h<br>• PCR <300 mg/g (<30 mg/mmol)</td></tr><tr><td>Proteinuria (children)*<br>• ≥40 mg/m²/h<br>• ≥300 mg/dl<br>• 3+ on urine dipstick<br>• PCR ≥2000 mg/g (≥200 mg/mmol)</td><td>Proteinuria (children)<br>• ≥40 mg/m²/h<br>• ≥300 mg/dl<br>• 3+ on urine dipstick<br>• PCR ≥2000 mg/g (≥200 mg/mmol)</td><td>• Serum albumin normal<br>• No clinical symptoms</td></tr><tr><td>• Hypoalbuminemia†<br>• Edema†<br>• Hyperlipidemia‡</td><td>• Serum albumin usually normal<br>• Edema is usually absent or minor<br>• Serum lipids usually normal or<br> only mildly elevated</td><td></td></tr></tbody></table>

Summary : This flowchart outlines the management of Class V lupus nephritis based on kidney biopsy findings, stratified by the level of proteinuria (low-level vs. nephrotic syndrome), and details recommended treatments and monitoring steps. flowchart: # Nodes : • Start (rectangle): "Kidney biopsy showing Class V lupus nephritis" • Decision (split into two rectangles): "Low-level proteinuria" and "Nephrotic syndrome" • Process (rectangle, shared): "Monitor the level of proteinuria and prevent or treat complications (e.g., thrombosis, dyslipidemia, edema)" • Treatment (rectangle, left branch for low-level proteinuria): 1. "Renin-angiotensin system blockade and blood pressure control" 2. "Immunosuppressive treatment guided by extrarenal manifestations of systemic lupus erythematosus" 3. "Hydroxychloroquine" • Treatment (rectangle, right branch for nephrotic syndrome): 1. "Renin-angiotensin system blockade and blood pressure control" 2. "Combined immunosuppressive treatment with glucocorticoid and one other agent (e.g., mycophenolic acid analogs, cyclophosphamide, calcineurin inhibitor, rituximab, azathioprine)" 3. "Hydroxychloroquine" • Conditional (rectangle, bottom): "If proteinuria worsens and/or complications of proteinuria develop (e.g., thrombosis, dyslipidemia, edema), consider immunosuppressive therapy" # Connectors : • Downward arrows from "Kidney biopsy showing Class V lupus nephritis" to both "Low-level proteinuria" and "Nephrotic syndrome" • Downward arrows from both "Low-level proteinuria" and "Nephrotic syndrome" to the shared monitoring node • Downward arrows from the monitoring node to each respective treatment node (left and right) • Downward arrows from both treatment nodes to the conditional node at the bottom # Layout : • Top-down hierarchical structure • Initial node at the top, branching into two parallel pathways (left: low-level proteinuria, right: nephrotic syndrome) • Both pathways converge at the bottom conditional node • All nodes are rectangles; no diamonds or ellipses # Analysis : • The flowchart provides a clear decision-making pathway for managing Class V lupus nephritis based on proteinuria severity. • Both pathways include renin-angiotensin system blockade, blood pressure control, and hydroxychloroquine. • Immunosuppressive therapy is tailored: guided by extrarenal manifestations for low-level proteinuria, and combined with glucocorticoid plus another agent for nephrotic syndrome. • Monitoring for complications is emphasized, with escalation to immunosuppressive therapy if proteinuria worsens or complications arise. • The structure supports individualized treatment escalation based on clinical progression.

Summary : This flowchart outlines the management of patients with pure Class V lupus nephritis (LN) based on kidney biopsy findings, stratified by the level of proteinuria (low-level vs. nephrotic syndrome), and details the recommended monitoring and treatment steps for each scenario. flowchart: # Nodes : • Start node: "Kidney biopsy showing Class V lupus nephritis" (rectangle, top center) • Decision node: splits into "Low-level proteinuria" (left) and "Nephrotic syndrome" (right) (rounded rectangles) • Common process node: "Monitor the level of proteinuria and prevent or treat complications (e.g., thrombosis, dyslipidemia, edema)" (rectangle, center) • Left treatment node (for low-level proteinuria): 1. "Renin-angiotensin system blockade and blood pressure control" 2. "Immunosuppressive treatment guided by extrarenal manifestations of systemic lupus erythematosus" 3. "Hydroxychloroquine" • Right treatment node (for nephrotic syndrome): 1. "Renin-angiotensin system blockade and blood pressure control" 2. "Combined immunosuppressive treatment with glucocorticoid and one other agent (e.g., mycophenolic acid analogs, cyclophosphamide, calcineurin inhibitor, rituximab, azathioprine)" 3. "Hydroxychloroquine" • Bottom process node: "If proteinuria worsens and/or complications of proteinuria develop (e.g., thrombosis, dyslipidemia, edema), consider immunosuppressive therapy" (rectangle, bottom center) # Connectors : • Downward arrow from "Kidney biopsy showing Class V lupus nephritis" to both "Low-level proteinuria" and "Nephrotic syndrome" • Both "Low-level proteinuria" and "Nephrotic syndrome" connect downward to the shared node: "Monitor the level of proteinuria and prevent or treat complications..." • From the shared monitoring node, left arrow to the left treatment node (low-level proteinuria), right arrow to the right treatment node (nephrotic syndrome) • Both treatment nodes have downward arrows merging into the bottom process node about worsening proteinuria/complications # Layout : • Vertical, top-down flow with a split into two parallel branches (left: low-level proteinuria, right: nephrotic syndrome), then reconverging at the bottom for escalation of therapy if needed. • All nodes are rectangular or rounded rectangles; no diamonds or ellipses. # Analysis : • The flowchart provides a clear, stepwise approach to managing Class V lupus nephritis, emphasizing initial stratification by proteinuria level. • Both pathways include renin-angiotensin system blockade, blood pressure control, and hydroxychloroquine, but differ in the intensity and type of immunosuppressive therapy. • The chart highlights the importance of monitoring for complications and escalating immunosuppression if proteinuria worsens or complications arise. • The structure supports individualized treatment based on disease severity and response.