52 A potential explanation for our weak evidence could lie in our separate assessment of various mediating factors, instead of lumping them. For example, we found separate associations of LHL with knowledge of medication[45,54], lifestyle[7], disease[41], transplant[37,45] and cardiopulmonary resuscitation[50]. We think that these factors are too heterogeneous to combine validly. However, one could argue that these studies together offer strong evidence for an association of LHL with knowledge. CKD studies should further examine the role of mediation in high quality studies to unravel the mechanisms leading from LHL to health outcomes. In agreement with HL interventions in other populations[20,23,94] and general CKD educational interventions[95,96], our review gave weak evidence that CKD HL interventions were effective to improve knowledge[75–78], decision making[76,77] and self-care behaviors[78,79]. However, the included six interventions were unable to detect long-term behavior change and an effect on health outcomes, and mostly used online or digital intervention strategies. Since patients with LHL also have more problems with technology[97], the effectiveness of the current strategies remains questionable. Research in other populations concludes multi-component interventions are the most successful to support people with LHL and emphasize the importance of aiming at the health system[23,98]. Our included qualitative studies[71–74], in which patients explicitly requested easier, non-medical language in consultations and inclusion of the social network, indicate other promising intervention strategies. Health care organizations and researchers should therefore develop and test a broader range of CKD-interventions, targeting both patients and the health system, to bridge the barriers of LHL patients. We identified several important research gaps. Most studies focused on dialysis and transplant patients. There is very little evidence on the improvement of outcomes of LHL patients in earlier stages of CKD, and thus on the prevention of progression towards severe kidney disease. Moreover, most studies are from the United States. The results from these studies should be confirmed for other parts of the world, as findings may be influenced by culture and specific characteristics of the health system. Finally, interventions that target the capacities of health care professionals are totally lacking.
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