Victoria Socha

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Because phosphate excretion becomes impaired as kidney function declines, patients with chronic kidney disease (CKD) commonly develop hyperphosphatemia, defined as elevated serum phosphate levels &gt;4.5 mg/dL. An analysis of data from a US health care system estimated the prevalence of hyperphosphatemia at approximately 7% among patients with estimated glomerular filtration rates of 30 to 39 mL/min/1.73 m2 (CKD stage 3b), approximately 21% among those with eGFR 20 to 29 mL/min/1.73 m2 (CKD stage 4), and more than 80% in patients with eGFR &lt;20 mL/min/1.73 m2 (CKD stage 4/5).Patients with hyperphosphatemia face increased risks for mortality. The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend that serum phosphate in patients with CKD stage 3 and above should be&nbsp; lowered to within 2.5 to 4.5 mg/dl (normal range). Recommended treatment for lowering serum phosphate in patients with hyperphosphatemia includes use of phosphate binders. However, the KDIGO guidelines call for caution when managing serum phosphate in patients with CKD not on dialysis, and suggest consideration of the risk-benefit ratio of phosphate lowering therapies. Phosphate binders are not approved for the treatment of patients with CKD not on dialysis in the United States.Patiromer, a nonabsorbed, sodium-free potassium binder, uses calcium as the exchange ion and may also reduce serum phosphate. Three clinical trials (AMETHYST-DN, OPAL-HK, and TOURMALINE) have shown the efficacy of patiromer for hyperkalemia in patients who are eligible for treatment with renin-angiotensin-aldosterone system (RAAS) inhibitors.David A. Bushinsky, MD, and colleagues conducted a post hoc pooled analysis of individual-level data from the three trials of patiromer to characterize the effect of patiromer on serum phosphate in patients with CKD, hyperkalemia, and hyperphosphatemia. Results were reported in the American Journal of Kidney Diseases.The study cohorts included patients with CKD and hyperkalemia who were treated with patiromer (8.4-33.6 g/day). The analysis outcome of interest was mean changes from baseline in serum phosphate, serum potassium, serum calcium, and serum magnesium after 2 to 4 weeks of treatment. Descriptive statistics were used to summarize pooled data on the study outcomes from the three studies.The analysis included 578 patients: 61.8% (n=357) were male, mean age was 65.6 years, 80.1% (n=463) had diabetes, mean eGFR was 39.1 mL/min/1.73 m2, and 37.7% (n=218) had stage 4/5 CKD. At baseline, mean serum potassium was 5.4 mEq/L and mean serum phosphate was 3.9 mg/dL.A total of 492 patients (85.1%) had baseline serum phosphate levels of &le;4.5 mg/dL, and 86 patients (14.9%) had a baseline serum phosphate level of &gt;4.5 mg/dL (above the threshold for hyperphosphatemia). Of the 86 patients with baseline serum phosphate level &gt;4.5 mg/dL, 50 (58.1%) had a baseline serum phosphate level &gt;4.8 mg/dL, and 24 (27.9%) had a baseline serum phosphate level &nbsp;&gt;5.1 mg/dL. Of the patients with baseline serum phosphate level &gt;4.5 mg/dL, mean baseline serum potassium level was 5.5 mEq/L and mean baseline serum phosphate level was 5.0 mg/dL. Those with baseline serum phosphate level &le;4.5 mg/dL had a mean baseline serum potassium of 5.4 mEq/L and baseline serum phosphate of 3.6 mg/dL.The proportion of patients with CKD stage 4.5 was higher among those with baseline serum phosphate level &gt;4.5 mg/dL than among patients with baseline serum phosphate level &le;4.5 mg/dL (75.6% vs 31.1%). The proportion of patients with CKD stage 4/5 increased with increasing baseline serum phosphate level.Following 4 weeks of treatment, reductions from baseline in serum potassium were similar in patients with serum phosphate &gt;4.5 mg/dL and those with serum phosphate &le;4.5 mg/dL: mean &ndash;0.71 (95% CI, &ndash;0.83 to &ndash;0.59) mEq/L and mean &ndash;0.84 (95% CI, &ndash;0.90 to &ndash;0.78) mEq/L, respectively.In patients with concomitant hyperphosphatemia treated with patiromer, mean serum phosphate decreased into the normal range within 2 weeks. At 4 weeks of treatment, mean reduction in serum phosphate was &ndash;0.62 (95% CI, &ndash;0.87 to &ndash;0.36) mg/dL. Patients with serum phospahte &le;4.5 mg/dl had a mean reduction in serum phospahte of &ndash;0.07 (95% CI, &ndash;0.13 to &ndash;0.00). Among those with baseline serum phosphate &gt;4.2 mg/dL, &gt;4.5 mg/dL, &gt;4.8 mg/dL, and&nbsp; &gt;5.1 mg/dL, the reductions after 4 weeks of treatment with patiromer were &ndash;0.48 mg/dL, &ndash;0.62 mg/dL, &ndash;0.73 mg/dL, and &ndash;0.83 mg/dL, respectively. Reductions in serum phosphate over 4 weeks of treatment with patiromer were typically greater in patients with higher baseline serum phosphate.At week 4, treatment with patiromer reduced serum phosphate compared with baseline in both patients with serum phosphate &le;4.5 mg/dL and those with serums phosphate &gt;4.5 mg/dL. Serum phosphate remained in the normal levels in patients with baseline serum phosphate &lt;4.2 mg/dL while levels of serum potassium declined.There were also reductions in serum magnesium across 4 weeks of treatment with patiromer compared with baseline. Irrespective of baseline serum phosphate, mean serum magnesium remained within the normal range. Over the 4 weeks of treatment with patiromer, mean serum calcium remained at similar concentrations in patients with serum phosphate &gt;4.5 mg/dL and serum phosphate &le;4.5 mg/dL, with mean changes form baseline to week 4 of 0.04 and 0.00 mg/dL, respectively.Treatment-emergent adverse events (TEAEs) were reported in 32.4% of patients (n=187). The most common TEAEs reported by preferred term were constipation (5.7%, n=33) and diarrhea (2.9%, n=17). Most of the reported TEAEs were mild or moderate. For nine patients, the TEAEs were severe. All severe TEAES occurred in patients with serum phosphate &le;4.5 mg/dL. Seventy-six patients (13.1%) had TEAEs determined to be related to patiromer. There were no severe TEAEs considered related to patiromer. Thirteen serious TEAEs were reported in nine patients, and 20 patients discontinued treatment due to TEAEs.In citing limitations to the analysis results, the researchers noted that due to the post hoc nature of the analyses, the findings should be considered exploratory in nature. In addition, the findings were only considered in patients treated with patiromer with no comparisons made with placebo.The researchers said, &ldquo;In conclusion, in this post hoc analysis of these three clinical trials evaluating patiromer for the treatment of hyperkalemia in patients with NDD-CKD [nondialysis-dependent CKD], 14.9% of patients also had hyperphosphatemia (serum phosphate &gt;4.5 mg/dL) at baseline. In patients treated with patiromer, there was a reduction in both serum potassium and serum phosphate levels to within the normal range after 2 weeks, which was sustained for up to 4 weeks. Patiromer was well tolerated in patients with hyperkalemia and NDD-CKD, and the most common adverse events were mild or moderate gastrointestinal events. Future placebo-controlled trials in both NDD-CKD and stage 5 CKD are needed to assess the ability of patiromer to concomitantly normalize serum phosphate in hyperkalemic patients with CKD to manage hyperphosphatemia.&rdquo;Takeaway Points<ol>
<li>Researchers reported results of a post hoc analysis of data from three trials of patiromer in patients with nondialysis-dependent chronic kidney disease, hyperkalemia, and hyperphosphatemia.</li>
<li>After 2 weeks of treatment with patiromer, there were reductions in serum phosphate levels from baseline, and the reduction was sustained during 4 weeks of treatment.</li>
<li>There were also reductions in serum potassium from baseline at 2 weeks of treatment, sustained during the 4-week treatment period.</li>
</ol>Source: <a href="https://www.ajkd.org/article/S0272-6386(23)00576-0/fulltext" target="_blank" rel="noopener">American Journal of Kidney Diseases</a>

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In patients with concomitant hyperphosphatemia treated with patiromer, the mean serum phosphate decreased into the normal range within 2 weeks.