Acute and chronic pyelonephritis

1. Tubulointerstitial Nephritis (TIN) — Overview

• TIN = group of inflammatory diseases involving interstitium + tubules.
• When bacterial + renal pelvis involved → pyelonephritis (pyelo = pelvis).
• When non-bacterial (drugs, viral, metabolic, immune, physical) → interstitial nephritis.

2. Acute Pyelonephritis

Definition

• Suppurative inflammation of kidney + renal pelvis from bacterial infection.
• Manifestation of UTI (lower: cystitis, urethritis; upper: pyelonephritis).

Pathogenesis — Two Routes

A) Ascending infection (most common)

• Gram-negative rods: E. coli (#1), Proteus, Klebsiella, Enterobacter, Pseudomonas.
• Steps:
  1. Adhesion to urothelium (P-fimbriae).
  2. Colonization of distal urethra.
  3. Ascent: urethra → bladder → ureter → renal pelvis → interstitium.
• Predisposing factors:
  • Catheterization
  • DM, immunodeficiency
  • Urinary obstruction: BPH, calculi, tumor, pregnancy
  • Female sex: short urethra near rectum; “honeymoon cystitis”
  • Vesicoureteral reflux (VUR) — incompetent vesicoureteral orifice → retrograde urine flow → bacteria ascend

B) Hematogenous spread

• Via bloodstream from septicemia or infective endocarditis emboli.
• Organisms: non-enteric — Staphylococcus, fungi.

Morphology

• Yellowish raised abscesses on cortical surface.
• Composition: PMNs + cell debris + necrotic tissue.
• Healing → fibrosis + contraction → “flowerbed” scars.
• Papillary necrosis — special form; classic in diabetics + analgesic nephropathy + sickle cell.

Clinical course

• Sudden onset — costovertebral angle pain + systemic infection signs (chills, fever, malaise).
• Urine: pyuria (WBCs) + bacteriuria + WBC casts (pathognomonic) + dysuria + frequency.
• May progress to sepsis or perinephric abscess.
• Usually benign + self-limiting with antibiotics.

3. Chronic Pyelonephritis

Definition

• Tubulointerstitial inflammation + scarring with grossly visible deformity of pelvicalyceal system.
• Important cause of chronic renal failure.

Two Types

A) Chronic obstructive pyelonephritis

• Obstruction (calculi, BPH, tumor) → urine stasis → recurrent infections → inflammation + scarring → chronic pyelonephritis.

B) Chronic reflux-associated pyelonephritis (more common)

• Congenital VUR + superimposed UTI.
• Ureter doesn’t reach bladder at correct angle → reflux → chronic damage.
• Often bilateral → chronic renal failure.

Morphology

• Uneven cortical scarring with pelvic + calyceal deformities (blunting/clubbing).
• Necrotic areas → fibroblast invasion → interstitial fibrosis → parenchymal contraction.
• “Flowerbed” scars on kidney surface.
• “Thyroidization” of tubules (eosinophilic colloid casts in atrophic tubules).

Clinical course

• Diagnosed late — gradual onset of renal insufficiency.
• Polyuria early (tubular dysfunction) → later renal failure.
• Often accompanied by HTN.

4. Drug-Induced Tubulointerstitial Nephritis

Pathogenesis

• Type I or IV hypersensitivity to drugs:
  • Antibiotics — penicillin, rifampin, sulfonamides, methicillin
  • Diuretics — thiazides
  • NSAIDs
  • PPIs, allopurinol
• Drugs act as haptens: during tubular secretion → bind tubular components → become immunogenic.

Morphology

• Interstitial edema + lymphocyte / macrophage / eosinophil / neutrophil infiltration.
• Sometimes granuloma + giant cells.

Clinical course

• Onset ~15 days after exposure.
• Classic triad: fever + eosinophilia + rash.
• Renal abnormalities: hematuria, eosinophiluria, proteinuria, leukocyturia, renal failure.
• Drug withdrawal → good chance of full recovery.

5. Acute vs Chronic Pyelonephritis

Feature	Acute	Chronic
Inflammation	Suppurative (PMNs, abscess)	Tubulointerstitial fibrosis + lymphocytes
Pelvis/calyces	Normal	Deformed (blunted, clubbed)
Scarring	None or focal	Coarse “flowerbed” scars
Tubules	Normal/mild damage	Thyroidization of atrophic tubules
Sx	Acute fever, CVA pain, pyuria	Insidious, polyuria → renal failure, HTN
Outcome	Self-limiting	Chronic renal failure

💡 High-yield: Acute pyelonephritis = suppurative, E. coli ascending from UTI, CVA pain + pyuria + WBC casts, abscesses. Risk: catheterization, female sex (short urethra), VUR, DM, obstruction. Papillary necrosis in DM, analgesic nephropathy, sickle cell. Chronic pyelonephritis = obstructive or reflux-associated (VUR), flowerbed scars + calyceal deformity + thyroidization of tubules → chronic renal failure + HTN. Drug-induced TIN = hapten/HSR → fever + eosinophilia + rash, ~15 d after drug.