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Table 2 Efficacy outcome reporting of gout flare prophylaxis and therapy use with renal function stratification

From: Efficacy and safety of gout flare prophylaxis and therapy use in people with chronic kidney disease: a Gout, Hyperuricemia and Crystal-Associated Disease Network (G-CAN)-initiated literature review

First Author (Year)

(Trial Name)

Study Design

Renal Function Exclusion Criteria or Baseline Renal Function – eGFR/CrCl (mL/min/1.73m2) or Serum Creatinine Level

Clinical Indication for Gout Flare

Actual/Mean Gout Flare Prophylaxis and Therapy Dose

Number of Participants by eGFR/CrCl at Baseline (mL/min/1.73m2)

Total, n

Efficacy Data with Renal Function Stratification

≥90

60–90

30–60

< 30

COLCHICINE

 AKDAG 2006 [17]

Case report

eGFR of 22 (serum creatinine of 3.1 mg/dL)

Gout flare prophylaxis

0.5 mg PO twice daily (for at least 15 years)

   

1

1

Efficacy data not available. Renal function deteriorated (serum creatinine peaked at 7.6 mg/dL) during an episode of pneumonia requiring antibiotics (clarithromycin and cefepime).

 ALAYLI 2005 [18]

Case report

eGFR of 44 (serum creatinine of 1.3 mg/dL)

Gout flare treatment

1.5 mg PO daily (for few days)

  

1

 

1

Gout flare resolution was achieved without worsening renal function (serum creatinine of 1.1 mg/dL – baseline of 1.3 mg/dL)

 ALTMAN 2007 [20]

Case report

eGFR of 34 (serum creatinine of 2 mg/dL)

Gout flare treatment

1.5 mg PO daily (for at least 1 week)

  

1

 

1

Efficacy data not available. Renal function deteriorated (serum creatinine peaked at 2.56 mg/dL).

 BONNEL 2002 [22]

Case series

eGFR of 29 (serum creatinine of 2.3 mg/dL)

Gout flare treatment

2 mg IV loading dose, followed by 0.5 mg IV every 2 h until diarrhoea developed (total dose of 5.5 mg in 5 h)

   

1

1

Efficacy data not available. Renal function deteriorated rapidly (serum creatinine peaked at 4.9 mg/dL).

 BOUQUIÉ 2011 [24]

Case report

eGFR of 32 (serum creatinine of 216 μmol/l)

Gout flare treatment

1 mg PO three times daily on day 1, 1 mg twice daily on day 2 and 3, and 1 mg once daily for 3 days

  

1

 

1

Efficacy data not available (colchicine was self-ceased after day 6). Renal function deteriorated on day 8 (serum creatinine peaked at 370 μmol/l).

 ELEFTHERIOU 2008 [28]

Case report

ESRD with eGFR of 6–8

Gout flare treatment

1 mg PO daily (for at least 6 days)

   

1

1

Efficacy data not available. Renal function was stable.

 GARROUSTE 2012 [29]

Case report

Renal transplant with eGFR of 41 (serum creatinine of 160 μmol/l)

Gout flare treatment

3 mg PO daily for 7 days

   

1

1

Efficacy data not available. Renal function deteriorated (serum creatinine peaked at 512 μmol/l), but gradually recovered on day 34 (serum creatinine of 188 μmol/l).

 HUH 2013 [31]

Case report

Renal transplant with eGFR of 34 (serum creatinine of 1.65 mg/dL)

Gout flare treatment

0.3 mg PO twice daily (for at least 3 weeks)

  

1

 

1

Efficacy data not available. Renal function deteriorated but returned to baseline 2 weeks after colchicine cessation.

 JUSTINIANO 2007 [32]

Case report

eGFR of 57 (serum creatinine of 1.6 mg/dL)

Gout flare treatment

0.6 mg PO twice daily (for at least 2 weeks)

  

1

 

1

Efficacy data not available. Renal function deteriorated (serum creatinine peaked at 1.7 mg/dL).

 KUBLER 2000 [33]

Case report

eGFR of 26 (serum creatinine of 160 μmol/l)

Gout flare treatment

0.5 mg PO three times daily (for at least 12 days)

   

1

1

Gout flare resolution was achieved within 48 h, but ARF developed (serum creatinine peaked at 450 μmol/l) in the context of ongoing colchicine use (same dose and frequency).

 LAI 2006 [35]

Case report

eGFR of 9 (serum creatinine of 565.8 μmol/l)

Gout flare treatment

0.5 mg PO three times daily for 3 days on a monthly basis (for at least 1 year); recent gout flare treatment with 0.5 mg PO twice daily (for at least 2 weeks)

   

1

1

Efficacy data not available. Renal function deteriorated (serum creatinine peaked at 680.7 μmol/l).

 LEE 1997 [36]

Case report

Renal transplant with eGFR of 49 (serum creatinine of 1.6 mg/dL)

Gout flare treatment

0.5 mg PO twice daily for 3 days

  

1

 

1

Efficacy data not available. Renal function deteriorated (serum creatinine peaked at 2.7 mg/dL) but returned to baseline upon colchicine cessation.

 LY 2007 [37]

Audit (single centre)

Patients with CKD (defined as serum creatinine of ≥0.17 mmol/L or CrCl of < 0.83)

Gout flare treatment

2.5 mg PO over 24 h or less

 

22

22

Efficacy data not available.

 MEDANI 2016 [39]

Case series

CKD Stage 3b-4 (serum creatinine of 300 μmol/l in patient 1 and 200 μmol/l in patient 2)

Gout flare treatment

Patient 1: 0.5 mg PO three times daily for 6 weeks

Patient 2: 0.5 mg PO once daily for at least 6 months

  

1

1

2

Efficacy data not available. Renal function deteriorated for both patients (serum creatinine peaked at 526 μmol/l in patient 1 and 255 μmol/l in patient 2).

 NEUSS 1986 [44]

Case report

eGFR of 23 (serum creatinine of 2.3 mg/dL)

Gout flare prophylaxis

0.6 mg PO twice daily (long term)

   

1

1

No gout flare during therapy, but with multi-organ failure, including AKI (serum creatinine peaked at 3 mg/dL).

 PATEL 2016 [46]

Case report

eGFR of 32 (serum creatinine of 1.87 mg/dL)

Gout flare prophylaxis

0.6 mg PO once daily (for > 5 years)

  

1

 

1

Efficacy data not available. Renal function deteriorated (serum creatinine peaked at 2.5 mg/dL) but returned to baseline upon colchicine cessation.

 RIEGER 1990 [49]

Case report

ESRD with eGFR of < 30 on haemodialysis and underlying renal transplant

Gout flare prophylaxis

0.6 mg PO twice daily

   

1

1

Efficacy data not available.

 WILBUR 2004 [53]

Case series

Patient 1: ESRD on peritoneal dialysis

Patient 2: CKD Stage 3

Gout flare treatment

0.6 mg PO (variable frequency)

  

1

1

2

Patient 1: ongoing treatment due to recurrent flare (despite 0.6 mg PO three times daily for the first 3 days). Renal function worsened.

Patient 2: ongoing treatment due to recurrent gout flare for at least 2 weeks (dosing was increased from 0.6 mg PO once daily to three times daily). Renal function was stable.

 YOON 2001 [55]

Case report

eGFR of 39 (serum creatinine of 134 μmol/l)

Gout flare treatment

0.5 mg PO three times daily (total dose of 4.5 mg)

  

1

 

1

Gout flare persisted. Renal function deteriorated (CrCl peaked at 30 mL/min/1.73m2).

 ZAGLER 2009 [57]

Case report

eGFR of 34

Gout flare treatment

1 mg PO once off dosing

  

1

 

1

Efficacy data not available. However, renal function deteriorated (serum creatinine increased from 2.4 to 5.2 mg/dL).

IL-1 INHIBITORS

 ADLER 2007 [67]

Case report

eGFR of 27–30

Gout flare treatment

Anakinra 100 mg/d for 3 days

   

1

1

Complete clinical remission with stable renal function.

 AOUBA 2015 [68]

Case series (single-centre)

eGFR of 20–40

Gout flare treatment

Anakinra 100 mg/d (up to 6 days)

1

1

1

 

3

2 patients achieved complete clinical remission after 5 days of treatment. 1 patient who received initial 3-day treatment required a second course (5-day period) due to recurrent gout flare. Renal function remained stable.

 BARTOV 2013 [69]

Case report

eGFR of < 20

Gout flare treatment

Anakinra 100 mg every other day for 1 week

   

1

1

Complete clinical remission with no worsening renal function.

 DIREZ 2012 [71]

Case report

CrCl of 14 mL/min/1.73m2

Gout flare treatment

Anakinra 100 mg/d for 5 days, followed by re-dosing of alternate-daily 100 mg dosing for 2 months (commenced 1 week after the first therapy)

   

1

1

Partial responder for the first course of treatment. During the second treatment, renal function deteriorated after 2 months (CrCl declined to 6 mL/min/1.73m2).

 LOUSTAU 2018 [76]

Case series (multi-centre)

CKD stage 4–5 (mean eGFR 22 ± 6.6) and history of renal transplant (mean eGFR 41 ± 22.8)

Gout flare treatment

Anakinra 100 mg/d (except in 5 patients who had 100 mg every 48–72 h) for less than a week; in 10 patients, dose was maintained for > 15 days (up to 14 months) with progressive dose spacing due to frequent gout flare

  

6

25

31

Pooled efficacy outcome: complete clinical remission with a mean of 46 days (range 4–90 days). Decrease in pain VAS from 69.6 ± 13.4 mm to 10.4 ± 15.3 mm and CRP level from 160 ± 133 mg/mL to 11 ± 11 mg/mL. No significant change in eGFR (26.3 pre-treatment vs 26.9 post-treatment).

 MAROTTO 2018 [77]

Case report

CKD stage 3 (CrCl of 56.47 mL/min/1.73m2)

Gout flare treatment

Canakinumab 100 mg single dose

  

1

 

1

Rapid clinical response 12 h after canakinumab administration. No worsening renal function.

 PEREZ-RUIZ 2013 [81]

Case series (single centre)

EULAR abstract

CKD stage 3–4

Gout flare treatment

Anakinra 100 mg/d (varying duration)

2

 

6

 

8

Pooled efficacy outcome: reduction in hsCRP level from 5.7 ± 7.3 to 0.56 ± 1.07 at 6 months post-treatment. Renal function remained stable (baseline CrCl 68 ± 28 vs 74 ± 43 at 6th month).

 TRAN 2011 [83]

Case series

eGFR of 57 (serum creatinine of 118 μmol/l)

Gout flare treatment

Anakinra 100 mg/d

  

1

 

1

Clinical remission was achieved with CRP reduction. Renal function remained stable.

NON-STEROIDAL ANTI-INFLAMMATORY DRUGS

 KAHL 1989 [84]

Case series

Patient 1: eGFR of 32 (serum creatinine of 2.4 mg/dL)

Patient 2: eGFR of 21 (serum creatinine of 3.3)

Gout flare treatment

Sulindac 200 mg twice daily and indomethacin 50 mg three times daily

  

1

1

2

No improvement in gout flare. Acute kidney injury developed in both patients.

 SCHLONDORFF 1993 [86]

Case report

Creatinine clearance of 70 (serum creatinine of 1.8 mg/dL)

Gout flare treatment

Indomethacin 50 mg three times daily

 

1

  

1

Gout flare improved rapidly. Acute kidney injury ensued.

 ZAGLER 2009 [57]

Case report

eGFR of 34

Gout flare treatment

Diclofenac 100 mg/d

  

1

 

1

No improvement in gout flare. However, renal function deteriorated (serum creatinine increased from 2.4 to 5.2 mg/dL).

GLUCOCORTICOIDS

 TAUSCHE 2011 [95]

Case report

eGFR of 30

Gout flare prophylaxis

Prednisone 10 mg/d

  

1

 

1

Improvement in frequency of gout flare (in combination with regular low-dose colchicine use and low-dose NSAID as required; the duration for the gout flare prophylaxis use was not known). Renal function remained stable.

 ZAGLER 2009 [57]

Case report

eGFR of 34

Gout flare treatment

Prednisone 40 mg/d

  

1

 

1

Gout flare treatment was effective. However, renal function deteriorated (serum creatinine increased from 2.4 to 5.2 mg/dL).

  1. AKI acute kidney injury, CKD chronic kidney disease, CRP C-reactive protein, CrCl creatinine clearance, eGFR estimated glomerular filtration rate, ESRD end-stage renal disease, hsCRP highly sensitive C-reactive protein, IV intravenous, PO per os (by mouth), VAS visual analogue score