What are the risk factors, clinical presentation, diagnostic work‑up, and management of renal papillary necrosis?

Renal Papillary Necrosis: Clinical Overview

Definition and Pathophysiology

Renal papillary necrosis (RPN) is ischemic coagulative necrosis of the renal medullary pyramids and papillae, resulting from the vulnerable blood supply and hypertonic environment of this region. 1, 2

The renal medulla and papillae are particularly susceptible to ischemic injury due to their unique vascular arrangement and the metabolic demands of the hypertonic medullary environment. 1

Risk Factors

The classic mnemonic POSTCARDS identifies the major risk factors: 2

• Pyelonephritis (chronic or acute)
• Obstructive uropathy
• Sickle cell disease/hemoglobinopathy
• Tuberculosis
• Cirrhosis
• Analgesic abuse/overuse (NSAIDs, phenacetin)
• Renal vein thrombosis
• Diabetes mellitus
• Systemic vasculitis

Most patients with RPN have at least two contributing risk factors present simultaneously. 2

In African populations specifically, additional risk factors include genetic factors, iatrogenic causes, viral infections, antimicrobial therapy, schistosomiasis, substance abuse, and hypertension (GIVASSH). 2 Oxidative stress appears central to the pathogenesis across all risk factor categories. 2

Clinical Presentation

Patients typically present with:

• Acute pyelonephritis or urosepsis that fails to respond to standard intravenous antibiotic therapy 3
• Flank pain (acute or chronic)
• Hematuria (gross or microscopic)
• Fever and systemic signs of infection
• Acute kidney injury or worsening chronic kidney disease 3
• Passage of tissue fragments in urine (sloughed papillae)

In diabetic patients with compromised renal function presenting with urosepsis, RPN should be strongly suspected, particularly when standard antibiotic therapy fails. 3

Diagnostic Work-Up

Imaging Modalities

Contrast-enhanced multi-detector CT is the gold standard for diagnosing RPN, offering superior visualization compared to intravenous urography or ultrasound. 1

CT Findings (in order of diagnostic importance):

• Contrast-filled clefts extending into the renal medulla 1, 4
• "Ring shadows" - nonenhanced lesions surrounded by rings of excreted contrast material in the medullae 1, 4
• Hyperattenuated medullary calcifications 1
• Filling defects in the renal pelvis or ureter (sloughed papillae) 1, 4
• Hydronephrosis (present in 67.3% of diabetic RPN cases) 3
• Blunted, epithelialized papillary tips (chronic/healing phase) 1
• Renal shrinkage (late sequela) 1

Multi-detector row CT with thin sections and multiplanar reformation identifies RPN at earlier stages when treatment can reverse the ischemic process. 1

Endoscopic Evaluation

Retrograde pyelography (RGP) is essential when CT contrast studies are contraindicated due to compromised renal function. 3

• RGP directly visualizes filling defects in the pelvicaliceal system representing necrosed papillae 3
• Should be performed in diabetic patients with acute pyelonephritis who fail to respond to antibiotics within 48-72 hours 3

Laboratory Assessment

• Serum creatinine and estimated GFR (mean creatinine 2.7 mg/dL in diabetic RPN series) 3
• Urinalysis (hematuria, pyuria, proteinuria)
• Urine and blood cultures
• Hemoglobin electrophoresis (if sickle cell disease suspected)
• Toxicology screen for analgesic abuse

Management Algorithm

Acute Phase Management

For patients presenting with acute pyelonephritis/urosepsis:

1. Initiate broad-spectrum intravenous antibiotics immediately 3

2. If no clinical response within 48-72 hours: Perform RGP and place Double-J (DJ) ureteral stent for drainage 3

3. After 3 weeks (at time of DJ stent removal): Perform retrograde intrarenal surgery (RIRS) if filling defects persist on RGP 3

Definitive Endoscopic Management

RIRS with retrieval of necrosed papillae is the preferred definitive treatment for diabetic RPN with filling defects in the pelvicaliceal system. 3

• 46.1% of diabetic patients with RPN have retrievable necrosed papillae requiring RIRS 3
• Papillae can be present even without hydronephrosis (41% of non-obstructed cases) 3
• Retrieving necrosed papillae prevents ureteric obstruction, recurrent urosepsis, and future pyelonephritis episodes 3

Conservative Management

For patients without obstructing papillae or filling defects:

• Address underlying risk factors (optimize diabetes control, discontinue nephrotoxic analgesics, treat infection) 2
• Monitor renal function closely with serial creatinine and GFR measurements
• Antioxidant therapy may have a role given the central role of oxidative stress 2

Surgical Intervention

Open surgical intervention or nephrectomy is reserved for:

• Massive uncontrolled hemorrhage
• Complete renal parenchymal destruction
• Failed endoscopic management with ongoing sepsis

Prognosis and Follow-Up

Early diagnosis through imaging is critical to improve prognosis and reduce morbidity. 5

• Recurrent pyelonephritis occurs in 3.8% of patients after RIRS 3
• Minimum 6-month follow-up is recommended after endoscopic intervention 3
• Serial imaging and renal function monitoring to detect progressive kidney shrinkage 1

Critical Pitfall

RPN is significantly underdiagnosed in clinical practice, often with fatal outcomes, particularly in African populations and diabetic patients with compromised renal function where contrast studies are limited. 2 Maintain high clinical suspicion in patients with multiple risk factors presenting with treatment-refractory pyelonephritis.