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