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PA27.8-10 | Tubulointerstitial Diseases, ATN & Pyelonephritis — SDL Guide (Part 3)

Chronic Pyelonephritis and Reflux Nephropathy

Chronic pyelonephritis (CPN) is the result of repeated or persistent bacterial infections producing progressive renal scarring, tubular atrophy, and interstitial fibrosis. It is a morphological diagnosis — scarring is the defining feature, not bacterial cultures.

Two types:

1. Reflux nephropathy (most common form of CPN):
High-grade vesicoureteric reflux allows infected urine to enter the collecting system under pressure. Intrarenal reflux (compound papillae at the poles allow urine to enter collecting ducts) generates polar scars disproportionately affecting the upper and lower poles. Even sterile reflux in children can cause progressive scarring.

2. Obstructive CPN:
Repeated infections in the context of fixed obstruction (stones, strictures) cause diffuse symmetric scarring.

Gross morphology (hallmark):
- Coarse, irregular, corticomedullary scars overlying deformed, dilated, blunted calyces. This calyceal blunting distinguishes CPN from other causes of renal scarring (glomerulosclerosis produces a granular contracted surface without calyceal change).
- Polar distribution in reflux nephropathy.

Microscopic morphology:
- Tubular atrophy with inspissated colloid casts — thyroidisation (the dilated tubules filled with homogeneous eosinophilic material resemble thyroid follicles).
- Periglomerular fibrosis; glomerulosclerosis in advanced cases.
- Chronic interstitial inflammation (lymphocytes, plasma cells).

Clinical consequence: hypertension (RAAS activation from scars) and proteinuria; may progress to ESRD.

A labelled three-panel diagram compares a chronic pyelonephritis kidney with polar corticomedullary scars and blunted calyces against normal renal calyceal architecture. — **Panel A:** Chronic pyelonephritis kidney with upper and lower pole coarse corticomedullary scars, deformed blunted calyces, dilated calyces beneath scars, renal pelvis, cortex, medulla, and adjacent normal-appearing parenchyma.. **Panel B:** Normal kidney coronal section showing smooth renal contour, cortex, medulla, sharp renal papillae, normal minor calyces, major calyces, and renal pelvis.. **Panel C:** Magnified comparison of normal pointed papilla with narrow calyx versus fibrotic polar scar overlying a clubbed dilated blunted calyx..

A four-panel medical illustration shows chronic pyelonephritis with thyroidisation, periglomerular fibrosis, chronic lymphocytic infiltrate, and reflux-associated polar renal scarring. — **Panel A:** Low-power H&E 100x field showing dilated atrophic tubules, homogeneous pink colloid-like casts, interstitial fibrosis, chronic lymphocytic infiltrate, and scarred glomeruli.. **Panel B:** Higher-magnification thyroidisation showing dilated tubules lined by flattened epithelium and filled with eosinophilic colloid-like casts.. **Panel C:** Periglomerular fibrosis surrounding a scarred glomerulus with adjacent chronic lymphocytic infiltrate in the interstitium.. **Panel D:** Simplified kidney schematic showing reflux nephropathy with polar cortical scars and reflux entering collecting ducts..

SELF-CHECK

A 35-year-old woman with a childhood history of recurrent UTIs presents with hypertension. Renal ultrasound shows asymmetric kidneys with focal corticomedullary scars at both poles and dilated calyces underneath the scars. Renal biopsy shows dilated tubules filled with homogeneous eosinophilic material. What is the most likely diagnosis?

A. Focal segmental glomerulosclerosis

B. Chronic obstructive pyelonephritis

C. Reflux nephropathy (chronic pyelonephritis)

D. Analgesic nephropathy with papillary necrosis

Reveal Answer

Answer: C. Reflux nephropathy (chronic pyelonephritis)

The polar distribution of coarse corticomedullary scars overlying deformed blunted calyces, combined with a history of childhood UTIs and thyroidisation on biopsy, is the classical picture of reflux nephropathy (the commonest form of chronic pyelonephritis). Obstructive CPN produces diffuse symmetric scarring, not polar. FSGS causes nephrotic syndrome without calyceal change. Analgesic nephropathy targets papillae and presents with papillary necrosis.

Drug-Induced Allergic Interstitial Nephritis

Drug-induced (allergic) interstitial nephritis represents a type-IV hypersensitivity reaction in the renal interstitium, most commonly triggered by:
- β-lactam antibiotics (methicillin — classic teaching example; ampicillin, amoxicillin)
- NSAIDs (especially with concurrent minimal change disease)
- Proton pump inhibitors (a growing cause in clinical practice)
- Sulfonamides, rifampicin, allopurinol

Onset: typically 2 weeks after exposure (range days to months); may recur on re-exposure.

Morphology:
- Diffuse interstitial oedema and infiltration by lymphocytes, plasma cells, and — characteristically — eosinophils.
- Tubulitis (inflammatory cells between tubular epithelial cells).
- Non-caseating interstitial granulomas in some cases (methicillin, sarcoidosis-like).
- Glomeruli and vessels: spared in most cases.

Clinically: fever, rash, eosinophilia (the classic allergy triad) + rising creatinine. Urine shows sterile pyuria, eosinophiluria (Hansel stain), mild proteinuria. Responds to withdrawal of offending drug ± short-course corticosteroids.

Analgesic nephropathy (mention here as a metabolic/toxic overlap): chronic NSAID/phenacetin use causes papillary necrosis + CPN-like cortical scarring. Classic triad: bilateral papillary necrosis + interstitial nephritis + cortical scarring. Sloughed papillae may calcify.

Papillary Necrosis — A Unifying Lesion

A four-panel medical diagram shows renal papillary necrosis as grey-white necrosis of papillary tips, its vulnerable vasa recta blood supply, POSTCARDS causes, and a sloughed papilla causing a urinary filling defect. — **Panel A:** Coronal kidney section showing renal cortex, medulla, renal pelvis, minor calyces, grey-white necrotic papillary tips, and a sloughed papilla.. **Panel B:** Magnified medullary blood supply showing vasa recta, absence of collateral supply, reduced medullary blood flow, ischaemia, and hypoxic inner medulla/papilla.. **Panel C:** POSTCARDS causes and pathogenesis flow showing pyelonephritis, obstruction, sickle cell disease/trait, tuberculosis, cirrhosis, analgesic nephropathy, renal vein thrombosis, diabetes mellitus, and sepsis leading to ischaemic coagulative papillary necrosis.. **Panel D:** CT urogram or IVU-style collecting system illustration showing calyx, renal pelvis, ureter, filling defect, sloughed papilla, calcified papillary fragment, haematuria, and colicky flank pain..

Renal papillary necrosis (RPN) is ischaemic coagulative necrosis of the inner medulla and papillae. It deserves a dedicated section because it cuts across multiple tubulointerstitial diseases as a life-threatening complication.

Causes — the mnemonic POSTCARDS:
- Pyelonephritis (diabetics especially)
- Obstruction
- Sickle cell disease/trait
- Tuberculosis (less common)
- Cirrhosis
- Analgesic nephropathy (NSAIDs, phenacetin)
- Renal vein thrombosis
- Diabetes mellitus
- Sepsis

Pathogenesis: the vasa recta supplying the medulla and papillae are the only blood supply — there is no collateral. Any condition that reduces medullary blood flow (DM vasculopathy) or increases oxygen demand (infection) can trigger ischaemic papillary necrosis.

Gross: grey-white wedge-shaped area of necrosis at papillary tips; may slough and appear as a filling defect on IVU/CT urogram.

Clinical:
- Acute: colicky flank pain (sloughed papilla in ureter), haematuria, fever
- Chronic: slowly progressive CKD

Three-panel pathology diagram showing renal papillary necrosis with grey-white necrotic papillary tips, a sloughed calcified papilla in the renal pelvis, and a CT urogram filling defect. — **Panel A:** Gross coronal kidney section showing renal cortex, medullary pyramids, papillae, minor and major calyces, renal pelvis, grey-white necrotic papillary tips, and calcified sloughed papilla.. **Panel B:** CT urogram-style collecting system showing contrast-filled calyces and renal pelvis with a filling defect caused by a sloughed necrotic papilla.. **Panel C:** Magnified papillary tip showing renal cortex, medulla, calyx, necrotic zone of papilla, and direction of sloughing into the renal pelvis..

SELF-CHECK

A 55-year-old woman with poorly controlled diabetes presents with sudden right-flank pain and haematuria. CT urogram shows a filling defect in the right renal pelvis. Which pathological mechanism best explains this finding?

A. Clot formation from glomerular haematuria due to IgA nephropathy

B. Sloughed necrotic papilla causing a filling defect in the pelvis

C. Transitional cell carcinoma arising in the renal pelvis

D. Uric acid stone formed secondary to chronic dehydration

Reveal Answer

Answer: B. Sloughed necrotic papilla causing a filling defect in the pelvis

Papillary necrosis in a diabetic patient produces ischaemic coagulative necrosis of the medullary papillae. The necrotic papillary tip detaches and passes into the renal pelvis, creating a 'ring shadow' or filling defect on imaging — classically described on IVU. The diabetes predisposes via medullary ischaemia (vasculopathy) and impaired neutrophil function (coexistent pyelonephritis). IgA nephropathy causes haematuria but not a filling defect; TCC and uric acid stones are possible differentials but the diabetic context strongly favours papillary necrosis.

Distinguishing Features at a Glance

Five-panel comparison diagram showing key sites of injury, inflammatory cells, and casts in ischaemic ATN, nephrotoxic ATN, acute pyelonephritis, chronic pyelonephritis, and drug-induced tubulointerstitial nephritis. — **Panel A:** Ischaemic ATN: PCT S3 segment injury, thick ascending limb injury, muddy-brown granular casts, minimal inflammatory cells. **Panel B:** Nephrotoxic ATN: diffuse proximal convoluted tubule injury, muddy-brown granular casts, minimal inflammatory cells. **Panel C:** Acute pyelonephritis: tubules and interstitium involved, neutrophilic infiltrate, WBC casts, acute suppurative inflammation. **Panel D:** Chronic pyelonephritis / reflux nephropathy: corticomedullary scarring, tubular atrophy, thyroidization, lymphocytes, plasma cells, irregular reflux scars. **Panel E:** Drug-induced TIN: interstitial edema, eosinophils, lymphocytes, tubulitis, drug-triggered immune injury.

This comparison table consolidates the key discriminating features examined most often in MBBS theory and OSPE:

Feature	Ischaemic ATN	Nephrotoxic ATN	Acute PN	Chronic PN / Reflux	Drug-induced TIN
Primary injury site	PCT (S3) + thick asc. limb	Entire PCT	Tubules + interstitium	Corticomedullary	Interstitium
Inflammatory cells	None significant	None significant	Neutrophils	Lymphocytes + PC	Eosinophils + lymphocytes
Casts	Granular (muddy-brown)	Granular (muddy-brown)	WBC casts	Colloid / hyaline	Sterile pyuria (no casts)
Basement membrane	Ruptured (tubulorrhexis)	Intact	Intact	Thickened/fibrosed	Intact
Reversibility	Yes (if insult removed)	Yes (if insult removed)	Yes (antibiotics)	Partial (fibrosis)	Yes (withdraw drug ± steroids)
Gross kidney	Normal/slightly swollen	Normal/slightly swollen	Enlarged, abscesses	Small, scarred	Normal/slightly swollen
Key hallmark	Patchy tubular necrosis	Diffuse PCT necrosis	Microabscesses + WBC casts	Thyroidisation + calyceal blunting	Eosinophilic interstitial infiltrate