What is the role of prednisone in treating kidney disease in patients undergoing hemodialysis (HD)?

Prednisone for Kidney Disease in Hemodialysis Patients

Prednisone should generally be avoided in patients already on hemodialysis for most glomerular diseases, as the evidence supporting immunosuppression is limited to patients with earlier-stage CKD, and the risks of infection and other complications substantially outweigh potential benefits once patients reach end-stage renal disease requiring dialysis. 1

Key Pharmacokinetic Considerations

• Prednisone does not require dose adjustment in hemodialysis patients because it undergoes hepatic metabolism with minimal renal excretion, allowing standard dosing protocols even in CKD stage 5. 2
• However, the lack of need for dose adjustment does not justify its use when the underlying disease is unlikely to respond.

Disease-Specific Guidance

Glomerular Diseases in Dialysis Patients

The KDIGO 2021 guidelines do not recommend immunosuppressive therapy for most glomerular diseases once patients have progressed to advanced CKD or dialysis. 1

• Patients with advanced chronic kidney disease, severe tubulointerstitial fibrosis, or findings consistent with chronic inactive disease should not be treated with immunosuppression. 1
• The intensity of immunosuppression must be predicated on the severity of presenting symptoms, type of glomerulonephritis, and level of GFR. 1

Membranous Nephropathy

• In the pre-dialysis setting, prednisone combined with cyclophosphamide has shown benefit for membranous nephropathy with impaired renal function. 3, 4
• However, once patients reach dialysis, the evidence does not support initiating or continuing prednisone, as the controlled trial data showing benefit were in patients with preserved renal function (creatinine <5 mg/dL). 5, 4

HIV-Associated Nephropathy (HIVAN)

HIVAN represents a notable exception where prednisone may be beneficial even in advanced renal failure:

• Prednisone at 60 mg/day (or 1 mg/kg/day) has demonstrated improvement in renal function and reduction in proteinuria in HIV-infected patients with advanced renal failure. 2, 6
• One case report documented successful discontinuation of hemodialysis in an AIDS patient with membranous nephropathy treated with prednisone, with creatinine declining from 10.1 mg/dL to 1.9 mg/dL. 7
• However, this should only be considered in patients without active infection, not actively using injection drugs, and who are potential transplant candidates. 1
• The recommended regimen is prednisone 1 mg/kg/day (maximum 80 mg/day) for 2 months, followed by a 2-4 month taper. 1

Critical Safety Considerations

Infection Risk

The risk of serious infection is substantially elevated in dialysis patients receiving prednisone:

• Hemodialysis patients are already at greater risk for infections due to their immunocompromised status. 1
• In HIV-associated nephropathy studies, 6 of 20 patients developed serious infections while on prednisone, including Mycobacterium avium-complex and CMV retinitis. 6
• Prophylactic trimethoprim-sulfamethoxazole should be considered in patients receiving high-dose prednisone or other immunosuppressive agents. 1
• Screen for tuberculosis, hepatitis B, hepatitis C, HIV, and syphilis before initiating therapy. 1

Metabolic Complications

• All corticosteroids increase calcium excretion, which is particularly concerning in dialysis patients who already have disturbed calcium metabolism. 2
• Monitor serum creatinine and potassium levels regularly, with weekly monitoring recommended during active treatment. 2

Cardiovascular Risk

• A controlled trial in nephrotic syndrome showed a significantly higher number of deaths from cardiovascular disease in the prednisone group compared to controls. 5
• This is particularly relevant given the already elevated cardiovascular risk in dialysis patients.

Practical Algorithm for Decision-Making

For a hemodialysis patient being considered for prednisone:

1. Identify the underlying kidney disease - Most glomerular diseases on dialysis should NOT receive prednisone. 1

2. If HIVAN is confirmed by biopsy:

   • Rule out active infections (tuberculosis, opportunistic infections). 1
   • Confirm patient is not actively using injection drugs. 1
   • Consider only if patient is a potential transplant candidate. 1
   • If criteria met, use prednisone 1 mg/kg/day (max 80 mg) for 2 months, then taper over 2-4 months. 1

3. If membranous nephropathy in HIV-positive patient:

   • Consider prednisone trial only if recent progression to dialysis and biopsy-proven disease. 7
   • Monitor closely for response within 4-8 weeks.

4. For all other glomerular diseases on dialysis:

   • Do not initiate prednisone - the risks outweigh benefits. 1

Common Pitfalls to Avoid

• Do not combine prednisone with NSAIDs in dialysis patients, as this combination may further impair residual renal function. 2
• Do not use prednisone for IgA-dominant postinfectious glomerulonephritis, as it needs to be distinguished from idiopathic IgA nephropathy to avoid inappropriate steroid treatment. 1
• Avoid initiating immunosuppression in patients with chronic inactive disease, severe tubulointerstitial fibrosis, or small kidney size on imaging. 1