Shunt Nephritis

Shunt nephritis is an immune complex glomerulonephritis caused by chronic low grade infection of a ventriculoatrial cerebrospinal fluid shunt (inserted for hydrocephalus).

Coagulase negative staphylococci (Staphylococcus epidermidis) account for about 75% of cases. Staphylococcus aureus and Cutibacterium acnes make up most of the rest. The disease has also been reported with ventriculoperitoneal shunts and infected cardiac devices.

It develops in about 0.7 to 2% of patients with a ventriculoatrial shunt, usually after months to years (median about 3 to 4 years, rarely much later). It has become rare since ventriculoperitoneal shunts replaced ventriculoatrial shunts.

The characteristic lesion is membranoproliferative glomerulonephritis with low complement. Without removal of the infected shunt, kidney failure follows.

Pathophysiology. Bacterial antigen shed from biofilm on the catheter tip in the right atrium enters the circulation, forms immune complexes with host antibody and deposits in the glomerulus, often with cryoglobulin. Complement is consumed through the classical cascade.

• Chronic or intermittent low grade fever, malaise, weight loss, anaemia, hepatosplenomegaly, arthralgia and rash (purpura or urticaria); signs may be subtle.
• Kidney: haematuria (microscopic in most), proteinuria (nephrotic range in about 30 to 50%), hypertension, oedema, impaired kidney function with a rapidly progressive course in some.
• Low C3 and C4, positive rheumatoid factor, cryoglobulins in a proportion; ANCA (PR3) may be positive.
• Shunt related: headache, vomiting or drowsiness from shunt malfunction, tenderness along the tract.
• Pulmonary: recurrent pulmonary emboli and pulmonary hypertension from septic thromboemboli to the lungs.

Red flags

• Fever of unknown cause in a patient with a ventriculoatrial shunt.
• New nephrotic syndrome or nephritic sediment in a patient with a shunt.
• Rapid loss of kidney function, crescents or pulmonary haemorrhage (ANCA positive).
• Features of shunt malfunction or ventriculitis.

• Blood cultures: several sets (at least 3) over 24 to 48 hours, with prolonged incubation (up to 14 days) for slow growing organisms; yield is variable (about 70 to 80%).
• Shunt assessment by neurosurgery: cerebrospinal fluid culture and cell count from the shunt reservoir, and culture of the removed shunt.
• Echocardiography for atrial thrombus or vegetation on the catheter tip; chest imaging for pulmonary emboli.
• C3, C4, rheumatoid factor, cryoglobulins, ANCA, antinuclear antibodies; creatinine, urine protein:creatinine ratio, urine microscopy, albumin; haemoglobin, C-reactive protein.
• Kidney biopsy: membranoproliferative or diffuse proliferative glomerulonephritis with subendothelial and mesangial deposits (IgG, IgM, C3), tuft double contours, and sometimes crescents; electron microscopy shows subendothelial and mesangial electron dense deposits.

Differential diagnosis

• Infective endocarditis, hepatitis B or C associated glomerulonephritis, cryoglobulinaemic glomerulonephritis, lupus nephritis, C3 glomerulopathy, ANCA vasculitis, post-infectious glomerulonephritis, idiopathic membranoproliferative glomerulonephritis.

First line: remove the infected shunt and eradicate the infection (this is essential)

• Neurosurgical removal of the infected shunt with temporary external ventricular drainage. Immunosuppression without shunt removal fails.
• Intravenous antibiotics directed at the isolate.
• Methicillin resistant coagulase negative staphylococci: vancomycin loading 25 to 30 mg/kg then adjusted to trough 15 to 20 mg/L (levels before every dose in kidney impairment). Add rifampicin 300 to 600 mg twice daily when the infection involves foreign material.
• Susceptible strains: flucloxacillin 2 g every 4 hours (maximum 12 g daily).
• Intraventricular vancomycin 10 to 20 mg daily (adjusted to cerebrospinal fluid levels) when cerebrospinal fluid is infected or ventriculitis is present.
• Continue antibiotics for 10 to 14 days after cerebrospinal fluid cultures become negative, then insert a new shunt as a ventriculoperitoneal system, not atrial.
• Dose all antibiotics to current eGFR; avoid aminoglycosides and NSAIDs.

Treatment of the glomerulonephritis

• Complement and urine abnormalities improve within weeks of eradication. Kidney function recovers in about 60 to 70% of patients when treated early.
• Immunosuppression is reserved for crescentic or rapidly progressive disease after the infection is controlled. Give methylprednisolone 500 mg intravenously daily for 3 days, then prednisolone 1 mg/kg daily (maximum 60 mg) tapered over 3 to 6 months, with specialist input.
• Renoprotection once infection is controlled: ramipril 2.5 mg daily increased to 10 mg daily (stop if potassium exceeds 6.0 mmol/L); blood pressure below 130/80 mmHg; sodium under 2 g daily.
• Furosemide 40 to 80 mg for oedema; dapagliflozin 10 mg daily (eGFR at least 25) for persistent proteinuria.
• Pulmonary emboli or atrial thrombus: anticoagulation with specialist input; avoid when haemorrhage risk is high.
• Kidney replacement therapy at eGFR 5 to 10 with symptoms or complications, or for urgent indications (potassium above 6.5 mmol/L refractory, pH under 7.15, overload).

Monitoring. Cerebrospinal fluid cultures every 2 to 3 days during drainage. Blood cultures until negative. C3, C4, creatinine and urine protein:creatinine ratio at 2, 6 and 12 weeks, then every 3 months for a year. Recurrence is unusual after a new ventriculoperitoneal shunt, but recheck after any fever.

Referral and escalation. Neurosurgery, infectious diseases and nephrology together from diagnosis. Escalate urgently when function falls rapidly, there are signs of ventriculitis, or pulmonary haemorrhage occurs.

Special groups

• Children with hydrocephalus (the original at risk group): a high index of suspicion for any persistent fever.
• Adults with long standing shunts placed in childhood: shunt nephritis can present decades later.
• Pregnancy: avoid immunosuppressives where possible; antibiotics chosen for safety, with obstetric and neurosurgical input.