Renal Pathology

1. Renal Deposits & Glomerular Anatomy

Diabetic Nephropathy / Diabetic Glomerulosclerosis

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Sweet stain

• Stain Reticulin fibres of liver
• Type 3 collagen

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Type IV Collagen Pathologies

Disorder	Chr	Gene/Target	Pattern
Goodpasture	2	• Anti GBM antibody • Type 1 RPGN • Type 2 Hypersensitivity • α3 chain of Type 4 collagen (COL4A3)	Linear IF
Thin BM disease	2	• COL4A4 • Benign familial Hematuria	ㅤ
Alport	XLD	• COL4A5 >> COL4A3/4 (AR/AD) Triad 1. SNHL 2. Hematuria 3. Anterior Lenticonus	Basket weave pattern

Goodpasture Syndrome

• Kidneys
• Type I RPGN → Hematuria

• Lung manifestation
• Diffuse Alveolar Hemorrhage

• Management
• Plasmapheresis
• Removes circulating Anti-GBM antibodies
• Immunosuppressive therapy
• Prevents further antibody production

Lenticonus:

Type	Cause
Posterior	• Lowe syndrome ↳ Oculo Cerebro Renal syndrome • Opacity at posterior capsule center
Anterior	SAW Spina bifida Alport syndrome Waardenburg syndrome

2. Nephritic Syndrome

Classic Triad:

• Hematuria

• Oliguria

• Hypertension

PSGN vs IgA Nephritis

Hematuria + URTI

Diagnostic Criteria for Glomerular Hematuria

• Dysmorphic RBCs > 40%

• Acanthocytes > 5%

• RBC casts > 1

NOTE: Acute Interstitial Nephritis (AIN):

• Triad: Fever + Rash + Eosinophilia

• M/c: NSAIDs.

• Other causes
• Beta-lactam antibiotics
• Rifampicin
• Proton pump inhibitors.
• Sulfonamide derivatives.

• Treatment
• Stop the offending drug
• Severe: High-dose prednisolone

Rapidly Progressive Glomerulonephritis (RPGN)

 

• Histology: Crescents

• Composition of Crescents:
• WBCs
• Fibrin
• Parietal Epithelial Cells

• Prognosis:
• More crescents → poorer prognosis.

• EM: 
• Rupture and wrinkling of the basement membrane 

• Mnemonic:
• Moon ruptured () while watching in the wrinkling () Full (Fibrin) and Partial (Parietal bowman) moon

Treatment

• Sparsentan:
• ARB + Endothelin-antagonist.
• Mnemonic: Sparse → Burger

Nephrotic vs. Nephritic Syndrome

3. Nephrotic Syndrome

• Definition:
• Proteinuria > 3g/d
• Edema
• Frothy urine

Etiologies and Characteristics

Congenital Nephrotic Syndrome

• Finnish type: Nephrin (NPHS1) mutation.

Serum protein electrophoresis in nephrotic syndrome

MCD Treatment Protocol

• Oral prednisolone 2 mg/kg/day (Upto 60 mg).
• Duration: 6 weeks.
• Taper and stop over another 6 weeks
• Total duration of therapy : 12 weeks.

• Steroid Resistant NS:
• No response by 4 weeks
• Boys > girls
• Biopsy needed
• If biopsy shows FSGS → evaluate for genetic causes of FSGS
• DOC:
• Tacrolimus > Cyclosporin (gum hyperplasia) > Levamisole
• Last choice: 
• Rituximab (Anti-CD20)

• Steroid Dependent NS:
• Avoid steroids (can lead to toxicity).
• MMF

1. Levamisole

2. Cyclophosphamide

3. Inj. Mycophenolate

4. Cyclosporine
ANS
Steroid-Sparing Agents in Nephrotic Syndrome
In given scenario:
• Cyclophosphamide (option 2) better than MMF (option 3).

4. Renal Pathology (Gross & Specifics)

Gross Kidney Appearances

• Putty Kidney:
• TB 
• Clinically: sterile pyuria

• Waxy kidneys:
• Amyloidosis.
• M/C organ affected: Kidneys.
• AL Amyloid → Bence-Jones proteinuria.

• Flea Bitten kidney:
• D/D
• Wegener's granulomatosis
• HSP/HUS
• PAN/PSGN
• SLE/SBE
• Malignant hypertension
• Onion-peel appearance:
• Hyperplastic Arteriolosclerosis
• Hus () Sleepan (SLE) poyapo Vegetable (wegner) Panil (PAN) vachu → flea vann (flea btten) irunn → kandapo BP (HTN) kuudi

• Leather Grain appearance:
• Benign Hypertension
• Hyaline Arteriolosclerosis:
• A/w DM / Benign HTN.

• Thyroidisation of Tubules (Microscopy)
• Chronic Pyelonephritis.
• URE - WBC Cast

Polycystic Kidneys:

5. AKI vs CKD (Acute vs Chronic Kidney Injury)

• Specific AKI Points

New Markers	Early Markers for AKI
• Cystatin C ↳ For Patients with extremes of muscle mass ↳ Non-specifically elevated in inflammation	• Kidney Injury Molecule 1 (KIM-D) • Neutrophil Gelatinase Associated Lipocalin (NGAL) • Liver Fatty Acid Binding Protein (LFABP) • TIMP2, IGFBP7.

• Papillary Necrosis Causes
• NSAIDs Mnemonic
• NSAIDS
• Sickle cell disease/trait
• Acute pyelonephritis
• Infections
• Diabetes mellitus

Urinary Casts & Associations

Cast Type	Composition / Appearance	Clinical Association / Notes
Hyaline Cast	Made of  Tamm-Horsfall protein	Dehydration/fever
RBC Cast	Hyaline cast + red cells	Glomerulonephritis IgA Nephropathy
WBC Cast	Hyaline cast + white blood cells	Pyelonephritis Allergic Interstitial nephritis  (↑ eosinophils) PSGN
Granular Cast	Degenerated cast	Non-specific
Muddy Brown Cast	Brown color	Acute Tubular Necrosis (ATN)  (e.g., mercury, ethylene glycol poisoning).
Broad Waxy Cast (Broad Cast)	Very broad	Chronic Renal Failure (CRF)
Maltase Cross Cast	ㅤ	Fabrys disease, Nephrotic syndrome
Lipid of Fatty cast	ㅤ	Nephrotic Syndrome
Pigmented fine granular cast	ㅤ	Hemolysis Rhabdomyolysis
Fractured cast	Not a urine cast	Appearance of biopsy tissue after fixation in Multiple myeloma

6. AKI Types & Staging

Pre-Renal vs Acute Tubular Necrosis (ATN)

AKI Staging (RIFLE / KDIGO / AKIN)

Atheroembolic Disease:

• History:
• Patient underwent Balloon Angioplasty
• 1 week later presents with "Blue toe" / Livedo Reticularis.

• Hollenhost plaques
• Cholesterol microemboli in Retina

• Livido reticularis also seen in Amantadine

7. Chronic Kidney Disease (CKD)

CKD - KDIGO Guidelines

Stage	GFR (ml/min/1.73 m²)	Notes
Stage 1	>90	Reversible
Stage 2	60 to 89	Reversible
Stage 3a	45 to 59	Treat complications
Stage 3b	30 to 44	Treat complications
Stage 4	15 to 29	Prepare for Renal Replacement
Stage 5	< 15 (ESRD)	Renal Replacement Therapy

Drugs Safe in AKI

• Paracetamol

• Warfarin

• Statins

• Aspirin

• B-blockers

• Clopidogrel

 

Complications & Management

• M/c/c of Death:
• Accelerated Atherosclerosis → CVS

• Anemia:
• Erythropoietin Deficiency.
• EPO secreted by Peritubular cells
• Target Hb: 10–11.5.
• Rx: EPO supplements (Side effect: HTN).

• Bone Disease:
• No 1 α OH → ↓ Ca → ↑ PTH → ↑ PO4 & ALP
• Osteopenia
• Rugger jersey spine

• Acid-Base:
• NAGMA → HAGMA.

• Calciphylaxis:
• Ca-PO4 deposits causing necrosis

Rugger Jersey Spine: 

• Alternating sclerotic and lucent bands,

• [Resemble stripes on a rugby jersey]

• Seen in
• Osteopetrosis
• Renal osteodystrophy - Secondary hyperparathyroidism

• Mnemonic:
• Mnemonic: Rugger jersey → look like rods → ROD → Renal osteodystrophy
• Rugby Jersey ittond marble (Osteopetrosis/marble bone ds) panikk poi → Got CKD ()

Criteria for Urgent Dialysis

• Ph < 7.2 (Acidosis)

• K > 6.5

• Uremia Symptoms
• Encephalopathy
• Pericarditis
• Pulmonary Edema

Dialysis Disequilibrium Syndrome

• DOC: Mannitol.

Lupus Nephritis

• Kidney involvement in Systemic Lupus Erythematosus (SLE).

• Complement system involvement in SLE:
• Can cause complement-mediated vasculitis.
• Results in multiple organ affection.

• Lupus nephritis:
• Proteinuria.
• Urinary protein: Urinary creatinine ratio >0.5.
• RBC casts present due to glomerular damage.

• Histopathological subtypes (ISN classification):
• 6 classes of lupus nephritis.
• Class 4: Diffuse lupus nephritis (most common and most severe).

• High mortality risk.

• Progression to end-stage renal disease (ESRD).

• Requires
• hemodialysis (3 times/week) or
• kidney transplantation.
• Kidney transplantation recommended.
• Prognosis improving with advancements

Severity of Lupus Nephritis:

• Best Determined by kidney biopsy

• Best antibody to detect severity
• Anti-C1q antibody titres
• indicate progression and severity compared to previous years

Histological Findings

• Loopus → Wire Loop

• Wire loop lesion:
• Thickening of glomerular capillary loops
• due to subendothelial immune deposits.
• Often seen in Grade II, III, IV.
• Its presence is maximum in Grade IV.
• Deposit: Subendothelial.

Grades of Lupus Nephritis (ISN/RPS Classification)

Grade	Disease	Features
Grade I	Minimal mesangial	-
Grade II	Mesangio-proliferative	• Increased cellularity in mesangium
Grade III	Focal proliferative	• Increased cellularity: <50% of glomeruli
Grade IV	Diffuse proliferative	• Increased cellularity: >50% of glomeruli.  • Most common type. • Displays wire loop lesion  (maximum severity).
Grade V	Membranous LN	-
Grade VI	Dense sclerosing	-

Immunofluorescence

• Also known as "Full house effect".

• Shows global deposition of:
• All immunoglobulins (IgM, IgG, IgA).
• All complement components (C1q, C3, C4).

Electron Microscopy

• Characterized by Thumb print lesion.

• Mnemonic: SLE → Antibodies ellaam kude oru House Party nadathi → Full Wire () okke vach → but a murder occurred → Solved by Thumb print