Management of Chronic Gout in Chronic Kidney Disease (CKD)

Chronic Gout: Pharmacologic strategies

First line: Xanthine Oxidase Inhibitors (XOI)
Allopurinol or Febuxostat

Starting dose: not greater than 100 mg/d and in CKD stage 4 or worse, no greater than 50 mg/d.
Doses can be increased up to 300 mg/d in CKD patients for as long appropriate parameters are closely monitored. The ACR does not recommend the traditional dosing methods for CKD patients but rather to start therapy with lower dose and gradually titrate upward every 2-5 weeks from the maintenance dose to the maximum dose needed to achieve serum rate target. This regimen may reduce occurrences of Allopurinol-induced hypersensitivity reactions (AHS).

AHS may lead to Steven-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) as well as systemic abnormalities like vasculitis, rash, end organ disease and eoisonophilia.
A combination of CKD and Thiazide diuretics can increase risk if AHS.

Creatinine Clearance (ml/min)	Dose
10- 20	200 mg daily
3- 10	Maximum of 100 mg daily
< 3	100 mg at intervals of > 24 h may be necessary

Table 1: Dose of Allopurinol in CKD.

Because oxypurinol is excreted primarily by the kidneys, accumulation may occur in patients with renal failure. Patients receiving dialysis may require therapeutic doses of Allopurinol. For patients not receiving dialysis, creatinine clearance as above [Table 1] may be used as guide but is limited by the unreliability of creatinine of this low order.

First line: Uricosuric Agent
Probenecid 
It is not recommended for patients with creatine clearance (CrCL) < 50 ml/min.

Alternatives: Uricosuric Agents
Fenofibrate or Losartan
Consider urine alkalisation, urine pH monitoring and increased fluid intake to reduce risk of urolithiasis.

*If disease is refractory to monotherapy with either XOI options, then a uricosuric agent can be as a second line approach.

Prophylaxis for Gout Flares When Initiating Urate Lowering Therapy (ULT): 
Rapid drop in serum rate levels can trigger gout flares.

First line: Low dose Colchicine 0.6 mg OD-BD, with lower doses for moderate to severe CKD [eGFR: 15-59 mL/ min/ 1.73 m2) and potential drug-drug interaction.
Although low dose NSAIDS is recommended by ACR, they should generally be avoided in CKD. Additionally, a stronger level of evidence exists for using Colchicine over NSAIDS.

For patients with severe CKD (CrCL <30 ml/ min): Recommended starting dose of Colchicine is 0.3 mg/d.
For patients on dialysis, the starting dose is 0.3 mg twice a week. In CKD, even a lower dose of Colchicine may result in neuromyopathy and bone marrow suppression.

CAUTIONS: 
Colchicine + Macrolides: Toxicity in CKD.
Colchicine + Clarithromycin: Fatal Interactions in CKD.
Colchicine + elderly: Creatinine clearance may appear normal despite renal impairment.

AVOIDED NSAIDS IN:
PATIENTS WITH GFR < 30 ml/ min/ 1.73 m2.
GFR < 60 ml/ min/ 1.73 m2 when using it as a prolonged therapy.
Patients on Lithium and RAAS blocking agents.

*Second line agent when first line is contraindicated or ineffective: Low dose Prednisolone (<10 mg daily). 

Monitoring parameters:
Allopurinol:
-CBC, Serum uric acid levels every 2-5 weeks during dose titration until desired level is achieved; every 6 months thereafter, fluid input-output, hepatic and renal function, signs and symptoms of hypersensitivity.

Colchicine:
-CBC, Renal and hepatic function tests. Obtain baseline CBC and monitor while on long term therapy to observe for blood dyscrasias. Monitor for GI side effects.


Reference:
1. https://www.kidney.org/sites/default/files/02-10-6446_ABE_Gout_Bulletin_SINGLE_PAGES.pdf
2. Lexicomp