Kidney in Systemic Diseases

Systemic Diseases & Kidneys - Renal Rumble

• Systemic diseases frequently target kidneys, causing varied renal damage.
• Key injury patterns:
  • Glomerular: Immune complex deposition (e.g., lupus nephritis), podocytopathies, amyloidosis.
  • Tubulointerstitial: Acute Tubular Necrosis (ATN) from toxins/ischemia, drug-induced nephritis, infiltrative diseases (sarcoidosis).
  • Vascular: Hypertensive nephrosclerosis, renal artery stenosis, vasculitis (e.g., ANCA), thrombotic microangiopathies (TMA).
• Common pathogenic pathways:
  • Hemodynamic changes (e.g., ↓ renal perfusion in sepsis/heart failure).
  • Direct cellular injury (e.g., myeloma light chains).
  • Immune complex formation & deposition.

⭐ Diabetes Mellitus is the leading cause of End-Stage Renal Disease (ESRD) worldwide.

Diabetic Nephropathy - Sugar-Coated Kidneys

• Leading cause of CKD & ESRD; progressive damage from chronic hyperglycemia.
• Pathogenesis: Glomerular hyperfiltration, GBM thickening, mesangial expansion.
• Histo: Kimmelstiel-Wilson (KW) nodules (nodular glomerulosclerosis) pathognomonic. Diffuse form commoner.
• Screening: Annual urine Albumin-to-Creatinine Ratio (AER).
  • T2DM: At diagnosis.
  • T1DM: 5 yrs post-diagnosis.

⭐ Earliest detectable clinical sign: Persistent microalbuminuria (AER 30-300 mg/g).

DN Stages (KDIGO Albuminuria Categories)

Management:

• Glycemic control (HbA1c <7%).
• BP control: <130/80 mmHg.
• RAAS blockade (ACEi/ARB): If albuminuria.
• SGLT2 inhibitors: Renoprotective.
• Statins.

Lupus Nephritis - Lupus's Kidney PUNCH

• Immune complex glomerulonephritis in SLE; anti-dsDNA antibodies.
• "Full house" immunofluorescence: IgG, IgA, IgM, C3, C1q.
• Clinical: Proteinuria, hematuria, HTN, ↓ GFR.
• Treatment: Varies by class; immunosuppression (steroids, MMF, cyclophosphamide).

ISN/RPS Classification (2003/2018)

⭐ Class IV (Diffuse Proliferative) Lupus Nephritis is the most common and severe form, often presenting with nephrotic syndrome and rapidly progressive glomerulonephritis.

Renal Vasculitis - Vessel Villainy

• ANCA-associated vasculitides (AAV) cause pauci-immune GN, often RPGN.
• Symptoms: Hematuria, proteinuria, rapid ↓ renal function.
• Urgent diagnosis & immunosuppression vital.

AAV Comparison: GPA vs MPA vs EGPA

Diagnostic Approach for RPGN (Focus on AAV)

⭐ Exam Favourite: ANCA type correlates with disease & prognosis:

• c-ANCA/PR3: GPA, higher relapse rates.
• p-ANCA/MPO: MPA & EGPA, often linked to more severe renal involvement initially.

High‑Yield Points - ⚡ Biggest Takeaways

• Lupus Nephritis Class IV (diffuse proliferative) is most common; renal biopsy is crucial for staging.
• Diabetic Nephropathy: Microalbuminuria is the earliest detectable abnormality; Kimmelstiel-Wilson nodules are specific.
• ANCA-associated vasculitis (GPA, MPA) typically causes pauci-immune crescentic glomerulonephritis.
• Goodpasture's Syndrome: Anti-GBM antibodies lead to linear IgG deposition; presents as pulmonary-renal syndrome.
• Myeloma Kidney: Due to light chain cast nephropathy; characterized by Bence Jones proteinuria.
• Scleroderma Renal Crisis: Presents with abrupt severe hypertension and acute kidney injury; ACE inhibitors are vital.