Pathophysiology

Pathophysiology

II-8. Causes and systemic consequences of acute renal failure

急性腰不全の原因と全身的影響

Types of Acute Renal Failure

  • Pre-renal (60%): sudden ↓renal blood supply — ↓total blood volume (shock, dehydration, edema) or inhibited supply (renal artery sclerosis, renal vein thrombosis).
  • Renal/intrinsic (35%): parenchymal damage — pre-glomerular (microangiopathies), glomerular, post-glomerular (tubular + interstitial).
  • Post-renal (5%): obstruction — anatomical (prostate, stone, tumor) or functional (bladder innervation disturbance).

Pre-glomerular Small Vessel Diseases

  • Embolus: cholesterol crystals from atherosclerotic plaques in afferent arterioles.
  • Thrombotic microangiopathy (TMA): systemic — HUS/TTP, DIC, HELLP.
  • Vasculitis (small vessel affects kidneys):
    • Pauci-immune (no immunocomplex): ANCA vasculitis — MPA, GPA (Wegener), EGPA (Churg-Strauss).
    • Immunocomplex: anti-GBM (glomerular capillaries); IgA most common.
  • IgA vasculitis (Henoch-Schönlein): overproduction of galactose-deficient IgA (Gd-IgA1) → immunocomplexes; after URT/GI infection → skin/GI/joint inflammation; glomerular deposition → IgA nephropathy.
  • IgA nephropathy (Berger’s): most common primary glomerulonephritis in adults; mesangial immunocomplex deposition → cytokines damage podocytes → proteinuria (mild) / hematuria (severe). Nephritic syndrome.
  • Malignant hypertension: afferent arteriole damage → intimal proliferation → vicious cycle; “flea-bite” kidney; fibrinoid necrosis, onion-peel arteriolitis.

Nephrotic Syndrome

  • Definition: edema + hypoproteinemia + severe proteinuria (>3.5 g/day).
  • Primary causes:
    • MCD (minimal change disease): most common in children; podocyte cytoskeleton damage → selective albuminuria; normal on light microscopy; ↑LDL/cholesterol; steroid-sensitive.
    • FSGS: mainly adults; podocyte damage → recovery (hypertrophy) or scarring (glomerulosclerosis); steroid-insensitive.
    • CNF (congenital Finnish type): severe, therapy-resistant; nephrin/podocin/WT1 mutations; needs transplant within 1–2 yrs.
  • Secondary: diabetes, hypertensive nephropathy, obesity-related (hyperfiltration/glomerulomegaly); infections (HIVAN → FSGS, HBV/HCV, malaria).

Nephritic Syndrome

  • Pre-glomerular/glomeruli attacked by immune system. Signs: edema, hematuria (Coke-colored, RBC casts — main sign), oliguria (↓GFR → BUN/creatinine retention).
  • Causes: immunocomplex + complement + cytokines → glomerular proliferation:
    • Endocapillary (in glomeruli, BM deposition) → MPGN.
    • Extracapillary (Bowman’s capsule, crescents) → RPGN.
  • PSGN (post-streptococcal): GAS (M-protein mimics GBM); 2–3 weeks post-infection; anti-streptolysin titer (ASO); needs nephritogenic strain + host predisposition. Affects myocardium, glomeruli, synovium, vessels.

Post-glomerular: Acute Tubular Necrosis (ATN)

  • Most common cause of ARF; tubular epithelial damage from ischemia or toxins.
  • Types: ischemic (shock → ↓flow), pigment-induced (Hb/myoglobin/Ca²⁺ precipitation → obstruction; crush syndrome/rhabdomyolysis), nephrotoxic (heavy metals, drugs, solvents).
  • Pathogenesis: inner tubules (lowest pO₂) most hypoxia-sensitive → loss of brush border/polarity (initiation) → de-differentiation (extension) → cell death/lumen obstruction (maintenance) → regeneration (if BM preserved).
  • Morphology: ischemic/pigment → “skip lesions,” BM fragmentation (50% lethality, bad prognosis); nephrotoxic → proximal convoluted tubule, BM preserved (better prognosis).

Acute Interstitial Nephritis (AIN)

  • Other common AKI cause; interstitium + tubules (TIN = bacterial; interstitial nephritis = non-bacterial).
  • Causes: drug-induced (acyclovir crystals, allergic to penicillin/NSAIDs/furosemide; WBC casts), CNI/contrast hypoxia, infections (Leptospira, CMV, EBV), systemic (lymphoma, leukemia, SLE, Sjögren), transplant rejection, idiopathic.
  • Morphology: flat tubular epithelium, dilated edematous interstitium with mononuclear infiltration (tubules far apart).

一問一答

▶What are the three types of acute renal failure and their approximate frequencies?

Pre-renal (60%), renal/intrinsic (35%), and post-renal (5%).

▶What causes pre-renal acute renal failure?

Sudden reduced renal blood supply — decreased total blood volume (shock, dehydration, edema) or inhibited supply (renal artery sclerosis, renal vein thrombosis).

▶What causes post-renal acute renal failure?

Obstruction — anatomical (prostate, stone, tumor) or functional (bladder innervation disturbance).

▶What is the most common cause of acute renal failure?

Acute tubular necrosis (ATN), from ischemia or toxins.

▶What are the types of acute tubular necrosis?

Ischemic (shock → low flow), pigment-induced (Hb/myoglobin/Ca²⁺ precipitation, e.g., crush syndrome/rhabdomyolysis), and nephrotoxic (heavy metals, drugs, solvents).

▶Why are inner tubules most vulnerable in ATN, and what are the phases?

Inner tubules have the lowest pO₂, so they are most hypoxia-sensitive; phases are initiation (loss of brush border/polarity), extension (de-differentiation), maintenance (cell death/lumen obstruction), and regeneration (if BM preserved).

▶How do ischemic and nephrotoxic ATN differ in morphology and prognosis?

Ischemic/pigment ATN causes 'skip lesions' and BM fragmentation (~50% lethality, bad prognosis); nephrotoxic ATN affects the proximal convoluted tubule with preserved BM (better prognosis).

▶How is nephrotic syndrome defined?

Edema + hypoproteinemia + severe proteinuria (>3.5 g/day).

▶What is minimal change disease (MCD)?

The most common nephrotic syndrome in children; podocyte cytoskeleton damage causing selective albuminuria, normal light microscopy, raised LDL/cholesterol, and steroid-sensitive.

▶What characterizes FSGS?

Mainly affects adults; podocyte damage with recovery (hypertrophy) or scarring (glomerulosclerosis); steroid-insensitive.

▶What are the signs of nephritic syndrome?

Edema, hematuria (Coke-colored urine with RBC casts — the main sign), and oliguria (low GFR with BUN/creatinine retention).

▶What distinguishes endocapillary from extracapillary glomerular proliferation?

Endocapillary (within glomeruli, BM deposition) leads to MPGN; extracapillary (Bowman's capsule, crescents) leads to RPGN.

▶What is post-streptococcal glomerulonephritis (PSGN)?

GAS infection (M-protein mimics GBM) causing nephritic syndrome 2–3 weeks post-infection, with raised anti-streptolysin O (ASO) titer; needs a nephritogenic strain and host predisposition.

▶What is IgA nephropathy (Berger's disease)?

The most common primary glomerulonephritis in adults; mesangial immunocomplex deposition → cytokine podocyte damage → proteinuria (mild)/hematuria (severe), a nephritic syndrome.

▶What is IgA vasculitis (Henoch-Schönlein)?

Overproduction of galactose-deficient IgA (Gd-IgA1) forming immunocomplexes after URT/GI infection, causing skin/GI/joint inflammation and glomerular deposition (IgA nephropathy).

▶What are the ANCA (pauci-immune) vasculitides affecting the kidney?

MPA, GPA (Wegener), and EGPA (Churg-Strauss).

▶What is thrombotic microangiopathy (TMA) and its systemic forms?

A pre-glomerular small vessel disease occurring systemically as HUS/TTP, DIC, and HELLP.

▶What characterizes malignant hypertension in the kidney?

Afferent arteriole damage → intimal proliferation (vicious cycle); 'flea-bite' kidney with fibrinoid necrosis and onion-peel arteriolitis.

▶What is acute interstitial nephritis (AIN) and its main causes?

An AKI affecting interstitium + tubules; causes include drug-induced (acyclovir crystals; allergic to penicillin/NSAIDs/furosemide with WBC casts), infections (Leptospira, CMV, EBV), systemic disease (lymphoma, SLE, Sjögren), and transplant rejection.

▶What are the secondary causes of nephrotic syndrome?

Diabetes, hypertensive nephropathy, obesity-related (hyperfiltration/glomerulomegaly), and infections (HIVAN → FSGS, HBV/HCV, malaria).