Initiation of sodium polystyrene sulphonate and the risk of gastrointestinal adverse events in advanced chronic kidney disease: a nationwide study

Paola Laureati, Yang Xu, Marco Trevisan, Lovisa Schalin, Illaria Mariani, Rino Bellocco, Manish M Sood, Peter Barany, Arvid Sjölander, Marie Evans, Juan J Carrero, Paola Laureati, Yang Xu, Marco Trevisan, Lovisa Schalin, Illaria Mariani, Rino Bellocco, Manish M Sood, Peter Barany, Arvid Sjölander, Marie Evans, Juan J Carrero

Abstract

Background: Despite long-standing clinical use of sodium polystyrene sulphonate (SPS) for hyperkalaemia management in chronic kidney disease (CKD), its safety profile remains poorly investigated.

Methods: We undertook an observational analysis of nephrology-referred adults with incident CKD Stage 4+ in Sweden during 2006-16 and with no previous SPS use. We studied patterns of use and adverse events associated to SPS initiation during follow-up. Patterns of SPS use were defined by chronicity of treatment and by prescribed dose. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) associated with SPS initiation (time-varying exposure) for the risk of severe (intestinal ischaemia, thrombosis or ulceration/perforation) and minor (de novo dispensation of laxatives or anti-diarrheal drugs) gastrointestinal (GI) events.

Results: Of 19 530 SPS-naïve patients with CKD, 3690 initiated SPS during follow-up. A total of 59% took SPS chronically, with an average of three dispensations/year. The majority (85%) were prescribed lower dosages than specified on the product label. During follow-up, 202 severe and 1149 minor GI events were recorded. SPS initiation was associated with a higher incidence of severe adverse events [adjusted HR 1.25 95% CI 1.05-1.49)], particularly in those receiving per label doses [1.54 (1.09-2.17)] and mainly attributed to ulcers and perforations. SPS initiation was also associated with higher incidence of minor GI events [adjusted HR 1.11 (95% CI 1.03-1.19)], regardless of dose, and mainly accounted for by de novo dispensation of laxatives.

Conclusions: Initiation of SPS in patients with advanced CKD is associated with a higher risk of severe GI complications as well as the initiation of GI-related medications, particularly when prescribed at per label doses.

Keywords: CKD; chronic haemodialysis; chronic renal failure; epidemiology; hyperkalaemia.

© The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA.

Figures

FIGURE 1
FIGURE 1
Flow chart of patient selection to the study.
FIGURE 2
FIGURE 2
Distribution of (A) the number of days between the first and second SPS dispensation and (B) the percentage of patients dispensing a single SPS package or receiving chronic treatment, as well as dosages used. In (A), the dashed line represents the median number of days between dispensations, which was 70 days.
FIGURE 3
FIGURE 3
Forest plot for the severe and minor GI adverse events associated with SPS initiation in advanced CKD.

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