The annual ERA-EDTA congress was held in Copenhagen, in this, its 55th year. The conference covers all fields of nephrology, but here the COMPACT RENAL team have selected and summarised the most significant talks relating to CKD-MBD. Features of this year included real-world data on the use of sucroferric oxyhydroxide (SFOH) and trial results regarding nicotinamide.
New data on available therapies
ERA-EDTA 2018 featured several presentations with new, real-world data on SFOH. Interim analysis of the first 18 months of the VERIFIE trial suggests real-life use of SFOH lowers phosphate levels in dialysis patients, regardless of dialysis vintage, prior phosphate binder (PB) treatment, or concomitant PB use.[FO047]Interim safety analysis of the same trial found SFOH to be well-tolerated, with the majority of adverse drug reactions being GI-related and with no new safety risks in this real-world study. [FP593]
Analyses of data from a European clinical database of dialysis patients (EuCliD5) showed that SFOH therapy can significantly improve control of serum phosphate with a reduced pill burden (from 5.1 at baseline to 3.9 pills/day in months 4-6 in patients switched from another PB) [FP611]. In previously PB-naive patients treated with SFOH monotherapy, the mean number of pills was 2.6 pills/day in months 4-6. [FP603]
During the late-breaking trial session, Geoffrey A Block, USA presented the Phosphate Normalisation Trial of fixed-dose ferric citrate compared to standard of care in patients with progressive CKD. Results from this pilot study showed that, regardless of baseline, ferric citrate significantly increased iron stores and haemoglobin, and decreased phosphate and intact FGF-23. After adjusting for baseline characteristics, the results suggested a benefit in time to death, dialysis or transplant for those assigned to ferric citrate in the total cohort (HR 0.44, p=0.006) and among the diabetic patient sub-group (HR 0.41, p=0.02). [LB05]
Conflicting results for nicotinamide
By inhibiting the sodium phosphate transporter 2b (NaP2b) in the intestine, initial studies with nicotinamide have indicated its potential for treating hyperphosphataemia. However, studies presented at this year’s ERA-EDTA have produced conflicting results.
In a late-breaking poster, the COMBINE study (N=205) reported no significant reduction in serum phosphate or FGF23 in CKD Stage 3-4 patients treated with lanthanum carbonate and nicotinamide as monotherapy or in combination. Treatment was poorly tolerated, mainly due to GI side effects, with high rates of discontinuation. [FP803]
A symposium sponsored by Medice Arzneimittel Pütter outlined the rationale behind the use of nicotinamide to treat hyperphosphataemia, and its potential role in ameliorating the increase in NaP2b expression seen with oral PBs. Andrzej Wiecek, Poland went on to present results from the NOPHOS trial (N=358) designed to investigate the efficacy of concomitant nicotinamide use in dialysis patients with persistent hyperphosphataemia despite PB therapy. At 12 weeks the mean reduction in serum phosphate was 0.67 mg/dL in the nicotinamide group vs 0.10 mg/dL reduction in the control group, although the long-term efficacy of nicotinamide may be affected by patient non-adherence to therapy.
Treatment practices – the challenges
Data from the Dialysis Outcomes and Practice Patterns Study (DOPPS) reinforced the understanding that non-adherence to PBs was strongly correlated with dissatisfaction, difficulties and inconvenience in taking PBs, and that poor adherence led to increased serum phosphorus levels. [FP610] Another poster based on data from the Chronic Kidney Disease DOPPS (CKDOPPS) found that, while assessment of MBD markers was generally consistent with KDIGO recommendations, prescription of vitamin D for PTH was significantly greater in Germany than Brazil or USA. Most important,however, was the consistent lack of use of PBs across countries, even at high serum phosphate levels; up to 85% of CKD non-dialysis patients in the US with phosphorus ≥5.5 mg/dL were not receiving any phosphate binders. [FP386]
Identifying the ‘at-risk’ patient
Luca Neri, Italy, presented data from the EUCLID study of CKD-MBD phenotypes in dialysis patients and associated 5-year mortality and hospitalization risk. From an international sample (N=35,763) the investigators found that isolated hyperphosphataemia occurred in 15% of patients and accounted for 55% of the excess, CKD-MBD related deaths, while parathyroid hormone (PTH) levels <130 pg/mL accounted for 45%. [SAO030].
As part of the ‘Treatment of CKD-MBD’ session, Joao M Frazao, Portugal discussed the importance of managing phosphate levels to reduce all-cause and cardiovascular mortality. Dr Frazao highlighted studies into the risks of increased calcification with calcium-based binders, and the impact of a switch from sevelamer to SFOH on pill-burden and adherence.
Within the same session was a talk on treating secondary hyperparathyroidism (sHPT) by John Cunningham, UK, highlighting the greater improvement in risk profile with calcimimetics vs active vitamin D.