Table 2.
Randomized controlled trials on treatments of uremic pruritus
| Study | Design | Country | Population | No. of patients | Treatment duration (wk) | Treatment | Pruritus assessment | Results |
|---|---|---|---|---|---|---|---|---|
| Topical treatment | ||||||||
| Capsaicin | ||||||||
| Tarng et al., 1996 [42] | Crossover | Taiwan | HD | 19 | 4 | Capsaicin 0.025% cream vs. placebo | 4-Point scale | 82.4% of participants experienced relief of pruritus after receiving capsaicin cream; capsaicin cream was more effective in improving itching score than placebo (p < 0.001). |
| Cho et al., 1997 [43] | Crossover | Taiwan | HD | 22 | 4 | Capsaicin 0.025% cream vs. placebo | 4-Point scale | 86.4% of participants experienced relief of pruritus after receiving capsaicin cream; 22.7% experienced relief of pruritus after placebo treatment (p < 0.001). |
| Calcineurin inhibitors | ||||||||
| Duque et al., 2005 [44] | Parallel | United States | HD | 22 | 4 | 0.1% Tacrolimus ointment vs. placebo | VAS | Percentage of reduction in VAS was not different between tacrolimus (77%) and placebo groups (79%). |
| Ghorbani et al., 2011 [45] | Parallel | Iran | HD | 60 | 8 | Topical pimecrolimus 1% vs. placebo | VAS | Change in VAS was not different between pimecrolimus (–6) and placebo groups (–7). |
| Pramoxine | ||||||||
| Young et al., 2009 [46] | Parallel | United States | HD | 28 | 4 | 1% Pramoxine lotion vs. placebo | VAS | Percentage of reduction in VAS was higher in the pramoxine group (61%) than in the placebo group (12%) (p = 0.0072). |
| Gamma-linolenic acid | ||||||||
| Chen et al., 2006 [47] | Crossover | Taiwan | HD, PD | 17 | 2 | 2.2% Gamma-linolenic acid cream vs. placebo | VAS, QPS | More reduction of VAS in the gamma-linolenic acid group (–4.5) than the placebo group (–0.5) (p < 0.01). |
| Treatment of underlying disease | ||||||||
| Dialysis modality | ||||||||
| Chen et al., 2009 [48] | Parallel | China | HD | 116 | 12 | High-flux HD vs. low-flux HD | VAS | More reduction of VAS in the high-flux group (–3.99) than the low-flux group (–0.71). |
| Jiang et al., 2016 [49] | Parallel | China | HD | 51 | 12 | High-flux HD vs. hemodiafiltration | VAS, QPS | More reduction of VAS in the high-flux HD group (–7.2) than the hemodiafiltration group (–5.6) (p < 0.05). |
| Lim et al., 2020 [50] | Parallel | South Korea | HD | 50 | 12 | MCO dialyzer vs. high-flux dialyzer | VAS, QPS | MCO group had lower scores for morning pruritus distribution and frequency of scratching during sleep at week 12. Between-group differences for VAS were not significant. |
| Cinacalcet | ||||||||
| El-Shafey et al., 2011 [51] | Parallel | Kuwait, Saudi Arabia | HD | 82 | 36 | Cinacalcet vs. vitamin D + phosphate binder | QPS | Pruritus intensity decreased from 3.38 at baseline to 1.74 at week 36 in the cinacalcet group. |
| Phototherapy | ||||||||
| Gilchrest et al., 1977 [52] | Parallel | United States | HD | 24 | 4 | Broadband UVB vs. UVA | 4-Point scale | 90% of participants in the UVB group and 25% in UVA group showed improvement of pruritus (p < 0.01). |
| Ko et al., 2011 [53] | Parallel | Taiwan | CKD, HD, PD | 21 | 6 | Narrowband UVB vs. UVA | VAS | Change in VAS was not different between the UVB (–3.53) and UVA groups (–3.38) (p = 0.92). |
| Systemic treatment | ||||||||
| Gabapentinoids | ||||||||
| Gunal et al., 2004 [54] | Crossover | Turkey | HD | 25 | 4 | Gabapentin vs. placebo | VAS | More reduction of VAS in the gabapentin group (–6.7) than the placebo group (–0.8) (p < 0.001). |
| Naini et al., 2007 [55] | Parallel | Iran | HD | 34 | 4 | Gabapentin vs. placebo | VAS | More reduction of VAS in the gabapentin group (–6.7) than the placebo group (–1.5) (p < 0.001). |
| Solak et al., 2012 [56] | Crossover | Turkey | HD | 29 | 6 | Gabapentin vs. pregabalin | VAS | Change in VAS was not different between the gabapentin (–4.41) and the pregabalin groups (–4.43) (p = 0.844). |
| Yue et al., 2015 [57] | Parallel | China | HD | 188 | 12 | Pregabalin vs. ondansetron vs. placebo | VAS, QPS | More reduction of VAS in the pregabalin group (–6.6) than the ondansetron (–2.5) or placebo (–2.0) groups (p < 0.05). |
| Nofal et al., 2016 [58] | Parallel | Egypt | HD | 54 | 3 | Gabapentin vs. placebo | VAS, QPS | More reduction of VAS in the gabapentin group (–5.82) than the placebo group (–0.1) (p < 0.001). |
| Foroutan et al., 2017 [59] | Parallel | Iran | HD | 90 | 4 | Pregabalin vs. doxepin | VAS | More reduction of VAS in the pregabalin group (–5.4) than the doxepin group (–2.9) (p < 0.001). |
| Gobo-Oliveira et al., 2018 [60] | Parallel | Brazil | HD | 60 | 3 | Gabapentin vs. dexchlorpheniramine | VAS, QPS | Change in VAS was not different between the gabapentin (–4) and the dexchlorpheniramine groups (–4) (p > 0.7). |
| Rossi et al., 2019 [61] | Parallel | Italy | HD | 25 | 2 | Gabapentin 300 mg vs. gabapentin 100 mg vs. placebo | VAS, QPS | Compared with the placebo group (–11.1%), there was a higher percentage of VAS reduction in both the gabapentin 300 mg group (–81.6%, p = 0.0121) and gabapentin 100 mg group (–48.3%, p = 0.0379). |
| Haber et al., 2020 [62] | Crossover | Lebanon | HD | 16 | 4 | Gabapentin vs. doxepin | VAS, QPS | More reduction of VAS in the gabapentin group (–6.14) than the doxepin group (–3.78) (p < 0.001). |
| Opioid antagonists and agonists | ||||||||
| Peer et al., 1996 [63] | Crossover | Israel | HD | 15 | 1 | Naltrexone vs. placebo | VAS | More reduction of VAS in the naltrexone group (–8.3) than the placebo group (–1.1). |
| Pauli-Magnus et al., 2000 [64] | Crossover | Germany | HD, PD | 23 | 4 | Naltrexone vs. placebo | VAS, QPS | Percentage of reduction in VAS was not different between the naltrexone (29.2%) and placebo groups (16.9%) (p = 0.095). |
| Wikström et al., 2005 [65] | Parallel | Sweden, Denmark, Norway, Finland | HD | 79 | 4 | Nalfurafine vs. placebo | VAS | Change in VAS was not different between the nalfurafine (–2.5) and placebo groups (–1.27) (p = 0.0649). |
| Wikström et al., 2005 [65] | Crossover | Poland | HD | 34 | 2 | Nalfurafine vs. placebo | VAS | Change in VAS was not different between the nalfurafine (–2.21) and placebo groups (–1.35) (p = 0.0863). |
| Kumagai et al., 2010 [66] | Parallel | Japan | HD | 339 | 2 | Nalfurafine 5 μg vs. nalfurafine 2.5 μg vs. placebo | VAS | Compared with placebo group (–1.3), there was a greater reduction of VAS in the nalfurafine 5 μg group (–2.2, p = 0.0002) and nalfurafine 2.5 μg group (–2.3, p = 0.0001). |
| Mathur et al., 2017 [67] | Parallel | United States | HD | 373 | 8 | Nalbuphine 120 mg vs. nalbuphine 60 mg vs. placebo | 11-Point NRS, QPS | A greater reduction of NRS occurred in the nalbuphine 120 mg group (–3.5) than the placebo group (–2.8) (p = 0.017). |
| Fishbane et al., 2020 [40] | Parallel | United States | HD | 378 | 12 | Difelikefalin vs. placebo | 11-Point NRS, QPS | 49.1% of the difelikefalin group and 27.9% of the placebo group exhibited improvement in pruritus intensity (p < 0.001). |
| Fishbane et al., 2020 [68] | Parallel | United States | HD | 175 | 8 | Difelikefalin (0.5, 1.0, or 1.5 μg/kg) vs. placebo | 11-Point NRS, QPS | A greater reduction of NRS in all difelikefalin groups combined (–3.2) compared with the placebo group (–1.9) (p = 0.002). |
| Mast cell stabilizers & leukotriene receptor antagonists | ||||||||
| Vessal et al., 2010 [69] | Parallel | Iran | HD | 62 | 8 | Cromolyn sodium vs. placebo | VAS | A greater reduction of VAS in the cromolyn sodium group (–7.78) than the placebo group (–2.90) (p < 0.001). |
| Mahmudpour et al., 2017 [70] | Parallel | Iran | HD | 80 | 4 | Montelukast vs. placebo | VAS, QPS | A greater reduction of VAS in the montelukast group (–2.73) than the placebo group (–5.47) (p < 0.001). |
| Oral activated charcoal | ||||||||
| Pederson et al., 1980 [71] | Crossover | United States | HD | 11 | 8 | Activated charcoal vs. placebo | QPS | A greater reduction of pruritus intensity in the activated charcoal group than the placebo group (p = 0.01 in the first crossover period; p = 0.05 in the second crossover period). |
| Cholestyramine | ||||||||
| Silverberg et al., 1977 [72] | Parallel | Israel | HD | 10 | 4 | Cholestyramine vs. placebo | 4-Point scale | Pruritus improved considerably in 80% of the cromolyn sodium group and 20% of the placebo group. |
| Biologics | ||||||||
| Kinugasa et al., 2021 [73] | Parallel | Japan | HD | 56 | 4 | Nemolizumab (0.125, 0.5, or 2.0 mg/kg) vs. placebo | VAS, QPS | Reduction in VAS was not different between each nemolizumab group and the placebo group. |
| Thalidomide | ||||||||
| Silva et al., 1994 [74] | Crossover | Brazil | HD | 29 | 1 | Thalidomide vs. placebo | 4-Point scale | Pruritus improved in 55.6% of the thalidomide group and 13.3% of the placebo group (p < 0.05). |
| Sertraline | ||||||||
| Pakfetrat et al., 2018 [75] | Parallel | Iran | HD | 50 | 8 | Sertraline vs. placebo | VAS, QPS | Reduction in VAS showed a borderline difference between the sertraline group (–5.5) and the placebo group (–3.7) (p = 0.07). |
CKD, chronic kidney disease; HD, hemodialysis; MCO, medium cut-off; NRS, numerical rating scale; PD, peritoneal dialysis; QPS, questionnaire pruritus score; UVA, ultraviolet A; UVB, ultraviolet B; VAS, visual analog scale.