Chronic Pyelonephritis

Chronic pyelonephritis is a chronic tubulointerstitial kidney disease with scarring and deformity of the calyces and pelvis. It is caused by recurrent or persistent bacterial infection in the presence of an anatomical or functional predisposing factor. It accounts for 1 to 2% of kidney failure in adults (higher in low resource settings). In children it is the same entity as reflux nephropathy.

Predisposing factors:

• Vesicoureteric reflux.
• Urinary tract obstruction (stones, strictures, posterior urethral valves, prostatic enlargement).
• Neurogenic bladder, urinary diversion, instrumentation.
• Diabetes, pregnancy or immunosuppression.

Infection alone in a normal urinary tract rarely causes chronic scarring in adults. Two variants are important.

• Xanthogranulomatous pyelonephritis is a destructive, mass forming infection of an obstructed kidney, usually with a staghorn calculus and Proteus or Escherichia coli. It affects middle aged women and people with diabetes. It presents as a non-functioning, enlarged kidney.
• Emphysematous pyelonephritis is a necrotising gas forming infection (Escherichia coli, Klebsiella) in people with poorly controlled diabetes or obstruction. Mortality is high (10 to 40%).

Pathophysiology. Persistent infection with an impaired host or drainage causes neutrophilic and then lymphocytic and plasma cell inflammation. This leads to papillary necrosis, fibrosis, tubular atrophy and calyceal clubbing, with secondary glomerulosclerosis.

• Recurrent loin pain, fever, dysuria and urinary frequency; many patients have few symptoms.
• Hypertension (in up to 50%), proteinuria (usually under 2 g daily), polyuria and salt wasting, distal acidosis, hyperkalaemia, slowly progressive loss of function.
• Xanthogranulomatous pyelonephritis: flank mass, fever, weight loss, anaemia, recurrent infections, staghorn stone.
• Emphysematous pyelonephritis: fever, sepsis, flank pain, hyperglycaemia, shock.
• Complications: pyonephrosis, perinephric abscess, sepsis, papillary necrosis, renal stones.

Red flags

• Sepsis or shock with flank pain (obstructed infected kidney).
• Diabetes with severe infection and gas on imaging.
• Rapid loss of kidney function or anuria.
• A palpable renal mass with fever and weight loss.
• Pregnancy with bacteriuria.

• Urine microscopy and culture (before antibiotics), blood cultures when febrile, full blood count, C-reactive protein, creatinine, eGFR, electrolytes, bicarbonate, glucose and HbA1c, urine protein:creatinine ratio.
• Ultrasound: small, irregular kidney with cortical scars; hydronephrosis; stones; residual urine.
• CT of the abdomen (contrast when eGFR is at least 30 and the patient is stable; non-contrast CT for stones): calyceal clubbing with overlying scars, parenchymal thinning, staghorn calculi, gas (emphysematous), a mass with calyceal replacement ("bear paw" pattern in xanthogranulomatous disease).
• Technetium-99m dimercaptosuccinic acid scan for scars; micturating cystourethrography to exclude reflux in children and young adults; cystoscopy and urodynamics for bladder abnormalities.
• Tuberculosis screen in sterile pyuria (three early morning urine samples).
• Biopsy not usually needed; histology after nephrectomy confirms foamy macrophages in xanthogranulomatous disease.

Differential diagnosis

• Reflux nephropathy, obstructive uropathy, renal tuberculosis, papillary necrosis (analgesic, diabetes, sickle cell), renal cell carcinoma, lymphoma, chronic interstitial nephritis from drugs or toxins, hypertensive nephrosclerosis, renal artery stenosis with small kidney.

First line: treat infection, relieve obstruction, remove stones

• Mild pyelonephritis (outpatient): ciprofloxacin 500 mg twice daily for 7 days, or co-trimoxazole 960 mg twice daily for 14 days, or cefalexin 500 mg three times daily for 10 to 14 days. Adjust for eGFR and direct by culture.
• Moderate or severe (sepsis, vomiting, obstruction): ceftriaxone 1 to 2 g intravenously daily, or piperacillin-tazobactam 4.5 g three times daily (adjust to eGFR). Switch to oral therapy once afebrile for 48 hours. Total duration 7 to 14 days (14 days for men and for complicated disease).
• Extended spectrum beta lactamase producers: ertapenem 1 g intravenously daily (500 mg when eGFR is under 30) or meropenem 1 g three times daily (adjust to eGFR).
• For lower tract infection where susceptible, use fosfomycin 3 g orally every 48 to 72 hours.
• Avoid aminoglycosides, NSAIDs and contrast where possible in impaired function.
• Obstructed infected system: urgent decompression by nephrostomy or ureteric stent within hours. Then perform definitive stone removal (ureteroscopy, percutaneous nephrolithotomy) once sepsis is controlled.

Variants

• Emphysematous pyelonephritis: intravenous broad spectrum antibiotics, glucose control with insulin infusion, percutaneous drainage for localised gas or abscess. Nephrectomy when there is extensive gas, shock or no response in 48 to 72 hours.
• Xanthogranulomatous pyelonephritis: antibiotics, then nephrectomy for non-functioning kidney with a stone; partial nephrectomy for focal disease.

Prevention of recurrence

• Correct the cause: stone clearance, relief of obstruction, correction of reflux, urethral stricture or valve treatment, catheter removal where possible, glucose control (HbA1c below 53 mmol/mol where safe).
• Prophylaxis for 3 to 12 months in recurrent infection (3 or more in 12 months): nitrofurantoin 50 to 100 mg at night when eGFR is at least 45, or trimethoprim 100 mg at night (potassium check), or cefalexin 250 mg at night.
• Alternatively use methenamine hippurate 1 g twice daily where eGFR is at least 30. Give vaginal oestrogen in postmenopausal women. Advise fluids of at least 2.5 litres daily.

Chronic kidney disease and complications

• Blood pressure below 130/80 mmHg. Use ramipril 2.5 mg daily increased to 10 mg daily, with creatinine and potassium checks at 1 to 2 weeks. Accept a rise up to 30%; stop if potassium exceeds 6.0 mmol/L.
• Dapagliflozin 10 mg daily (eGFR at least 25) increases genital mycotic infection risk; use with caution in recurrent infection.
• Metabolic acidosis: sodium bicarbonate 500 mg to 1 g two to three times daily to bicarbonate at least 22 mmol/L.
• Anaemia, mineral and bone disorder at the usual thresholds.
• Kidney failure: dialysis at eGFR 5 to 10 with symptoms. Transplantation after eradication of infection (nephrectomy of infected native kidneys if needed).

Monitoring. Urine culture at every symptomatic episode and 1 to 2 weeks after treatment in high risk patients. Creatinine and blood pressure every 3 to 6 months. Imaging for stones every 6 to 12 months. Yearly cystoscopy in neurogenic bladder.

Referral and escalation. Urology for obstruction, stones or abnormalities. Nephrology when eGFR is under 45 or falling. Escalate urgently for sepsis, gas on imaging or anuria.

Special groups

• Pregnancy: screen for bacteriuria monthly. Treat for 7 days (cefalexin 500 mg four times daily or nitrofurantoin 100 mg modified release twice daily in the second trimester when eGFR is at least 45) and give prophylaxis with cefalexin 250 mg at night. Avoid fluoroquinolones and trimethoprim in the first trimester.
• Diabetes: low threshold for imaging in severe infection.
• Spinal cord injury and neurogenic bladder: intermittent catheterisation and prophylaxis review.
• Children: reflux and dysplasia are the main causes; refer early to a paediatric urologist.