Effect Of Patiromer Research Articles

Effects of Patiromer and Sodium Zirconium Cyclosilicate on Blood Pressure in Rats with Chronic Kidney Disease.

Potassium-binders patiromer and sodium zirconium cyclosilicate (SZC) are approved to treat hyperkalaemia, which is frequently observed in chronic kidney disease (CKD). Elevated blood pressure (BP) is common in CKD, due in part to impaired sodium excretion. The effect of patiromer, which exchanges calcium for potassium and SZC, which exchanges sodium or hydrogen for potassium, on BP was assessed in a CKD rat model. Thirty-six Sprague Dawley rats with 5/6 nephrectomy were randomised to three groups (n = 12/group) to receive 4 g/kg/day patiromer or SZC, or vehicle treatment, for 8 weeks. BP was determined by radiotelemetry and urinary protein and electrolytes were measured. At Week 8, systolic BP (sBP) increased in all groups; however, patiromer led to a lower mean (standard deviation) sBP than vehicle or SZC (141 [2.9] vs 158 [5.2] or 162 [6.1] mm Hg, respectively, both p < 0.001), with no difference in sBP between vehicle and SZC (p = 0.08). Similar results were observed for diastolic BP. Serum potassium levels fell with SZC (p < 0.02), but not vehicle or patiromer. Urine potassium decreased with both patiromer and SZC versus vehicle (p < 0.01); urine sodium increased with SZC (p < 0.01); and urine calcium increased with patiromer (p < 0.01). Urine phosphorus decreased with patiromer (p < 0.01) but increased with SZC (p < 0.01). Patiromer resulted in less proteinuria than vehicle or SZC (both p < 0.017). After 8 weeks, treatment with patiromer resulted in lower BP in rats than vehicle or SZC. Further studies are needed to determine the mechanism of the differential effect of potassium binders on rat BP.

Patiromer Treatment in Patients With CKD, Hyperkalemia, and Hyperphosphatemia: A Post Hoc Analysis of 3 Clinical Trials

Patients with chronic kidney disease (CKD), hyperkalemia (serum potassium [sK+]>5.0 mEq/L), and hyperphosphatemia experience poor clinical outcomes. Patiromer, a potassium binder that uses calcium as the exchange ion, may also reduce serum phosphorus (sP). We characterized the effect ofpatiromer on sP in patients with CKD, hyperkalemia, and hyperphosphatemia. A post hoc pooled analysis of individual-level data from the AMETHYST-DN, OPAL-HK, and TOURMALINE trials of patiromer. Patients with CKD and hyperkalemia. Patients treated with patiromer (8.4-33.6 g/day). Mean changes from baseline in sP, sK+, serum calcium (sCa2+), and serum magnesium (sMg2+) after 2 and 4 weeks of treatment. Descriptive statistics to summarize pooled data on the study outcomes from the 3 studies. We included 578 patients in the analysis. Of these participants, 86 patients (14.9%) had baseline hyperphosphatemia of whom 75.6% (65 of 86) had CKD stage 4/5 and 31.1% (153 of 492) with sP≤4.5mg/dL had CKD stage4/5. Among the patients with elevated sPand sK+at baseline, the mean±SD reduction insP and sK+after 4 weeks of patiromer treatment was-0.62±1.09mg/dL and-0.71± 0.51mEq/L,respectively. Additionally, the mean±SDreduction in sMg2+in these patients was -0.25±0.23mg/dL while sCa2+remained unchanged. Both sMg2+and sCa2+remained within the normal range. Patiromer was generally well tolerated, and no serious adverse events were considered related to patiromer. These were post hoc analyses, no placebo comparison was performed due to the design of the original studies, and the follow-up period was limited to 4 weeks. Reductions in sP and sK+to the normal range were observed after 2 weeks of patiromer treatment, and the reduction was sustained during 4 weeks of treatment among patients with non-dialysis-dependent CKD, hyperkalemia, and hyperphosphatemia. Future controlled trials are needed to establish if patiromer is useful to reduce both sK+and sP in hyperkalemic patients with CKD and hyperphosphatemia.

1118-P: Effect of Patiromer in Patients 75 Years or Older with Diabetic Kidney Disease and Hyperkalemia Receiving a RAAS Inhibitor

Background: Patiromer (PAT) is a sodium-free, non-absorbed potassium (K+) binder approved for the treatment of hyperkalemia (HK). HK is common in older patients (pts) with cardiorenal comorbidities and often limits the use of guideline recommended renin-angiotensin-aldosterone system inhibitor (RAASi) medications. We previously reported the design and results for AMETHYST-DN, a phase 2 multicenter, open-label, 52 week randomized clinical trial in a large cohort of adult pts (n=306; 30-80 years of age). Methods: Here we report the results in a subgroup ≥75 years of age with type 2 DM, chronic kidney disease (CKD) (eGFR 15 to &amp;lt;60 mL/min/1.73 m2), hypertension and serum (s) K+ &amp;gt;5.0 mEq/L (n=60). All pts received a RAASi before and during the study treatment and PAT was titrated to maintain sK+ in the normal range. Results: Two days after the first dose, mean sK+ was reduced to 4.89 mEq/L from a baseline (BL) mean of 5.19 mEq/L (p&amp;lt;0.001). The least square mean reduction in sK+ from BL to week 4 was -0.65 mEq/L (p&amp;lt;0.001) and -0.61 mEq/L (p&amp;lt;0.001) at 52 weeks (end of treatment). The % of pts with sK+ in the normal range (3.8-5.0 mEq/L) between weeks 12-52 ranged from 88-98%. At the end of treatment, 92% of pts had sK+ in the normal range. The most common GI-related adverse event (AE) was constipation observed in 2 pts (3.3%). Serum magnesium levels of &amp;lt;1.2 mg/dL were seen in 3 pts (5%). Hypokalemia (sK+ &amp;lt;3.5 mEq/L) did not occur in this older population. Serious AEs were reported for 9 pts (15%); none attributed to PAT by investigator. Study limitations include a lack of blinding, a lack of comparator, and a lack of diversity. Conclusions: In this subgroup of pts ≥75 years with diabetic CKD receiving a RAASi medication, PAT reduced and maintained control of sK+ for up to 1 year. PAT was well tolerated over 52 weeks with no serious AEs attributed to its use. These results suggest that PAT may facilitate the use of RAASi medications in older pts likely to benefit from their cardiorenal protective effects. Disclosure G.L. Bakris: Consultant; Self; Merck &amp; Co., Inc., Novo Nordisk Inc., Relypsa, Inc. Research Support; Self; Bayer AG, Janssen Pharmaceuticals, Inc. S.D. Woods: Employee; Self; Relypsa, Inc. P.J. Alvarez: Employee; Self; Relypsa, Inc. J. Fogli: Employee; Self; Relypsa, Inc. S. Arthur: Employee; Self; Relypsa, Inc. M.R. Mayo: Employee; Self; Relypsa, Inc. R. Kumar: None. Funding Relypsa, Inc.

164 Leucocytoclastic Vasculitis as a Potential Side Effect of Patiromer in CKD Patients

164 Leucocytoclastic Vasculitis as a Potential Side Effect of Patiromer in CKD Patients

Effect of Patiromer on Hyperkalemia Recurrence in Older Chronic Kidney Disease Patients Taking RAAS Inhibitors

BackgroundOlder people are predisposed to hyperkalemia because of impaired renal function, comorbid conditions, and polypharmacy. Renin–angiotensin–aldosterone system inhibitors (RAASi), which are recommended to treat chronic kidney disease and heart failure augment the risk. Patiromer, a nonabsorbed potassium binder, was shown in the phase 3 OPAL-HK study to decrease serum potassium in patients with chronic kidney disease taking RAASi. We studied the efficacy and safety of patiromer in a prespecified subgroup of patients aged ≥65 years from OPAL-HK. MethodsChronic kidney disease patients with mild or moderate-to-severe hyperkalemia received patiromer, initially 8.4 g/d or 16.8 g/d, respectively, for 4 weeks (treatment phase, part A). Eligible patients entered an 8-week randomized withdrawal phase (part B) and continued patiromer or switched to placebo. ResultsMean ± standard error change in serum potassium from baseline to week 4 of part A (primary endpoint) in patients aged ≥65 years was −1.01 ± 0.05 mEq/L (P < .001); 97% achieved serum potassium 3.8-<5.1 mEq/L. The serum potassium increase during the first 4 weeks of part B was greater in patients taking placebo than in those taking patiromer (P < .001). Fewer patients taking patiromer (30%) than placebo (92%) developed recurrent hyperkalemia (serum potassium ≥5.1 mEq/L). Mild-to-moderate constipation occurred in 15% (part A) and 7% (part B) of patients aged ≥65 years. Serum potassium <3.5 mEq/L and serum magnesium <1.4 mg/dL were infrequent (4% each in patients aged ≥65 years in part A). ConclusionsPatiromer reduced recurrent hyperkalemia and was well tolerated in older chronic kidney disease patients taking RAASi.

Patiromer Decreases Serum Potassium and Phosphate Levels in Patients on Hemodialysis

Background: Persistent hyperkalemia (serum potassium (K) ≥5.5 mEq/l) is a common condition in hemodialysis (HD) patients, is associated with increased mortality, and treatment options are limited. The effect of patiromer, a gastrointestinal K binder, on serum K was examined in HD patients. Methods: Six hyperkalemic HD patients (5 anuric) were admitted to clinical research units for 15 days (1 pretreatment week and 1 patiromer treatment week) and they received a controlled diet with identical meals on corresponding days of pretreatment and treatment weeks. Phosphate (P) binders were discontinued on admission. Patiromer, 12.6 g daily (divided 4.2 g TID with meals), was started on the Monday morning following the last pretreatment week blood sampling. Serum and 24-hour stool samples were collected daily. Results: Mean ± SE serum K decreased (maximum change per corresponding day, 0.6 ± 0.2 mEq/l, p = 0.009) and fecal K increased 58% on patiromer compared with the pretreatment week. During the pretreatment week, 69.0, 47.6, and 11.9% of patients' serum K values were ≥5.5, ≥6.0, and ≥6.5 mEq/l, respectively. This was reduced to 38.1% (p = 0.009), 11.9% (p < 0.001), and 2.4% (p = 0.2) on patiromer. Following P binder discontinuation, the long interdialytic interval mean ± SE serum P numerically increased from 5.8 ± 0.4 to 7.0 ± 0.5 mg/dl (p = 0.06). On patiromer, P decreased from 7.0 ± 0.5 to 6.2 ± 0.5 mg/dl (p = 0.04). While on patiromer, fecal P numerically increased by 112 ± 72 mg/day (17%; p = 0.1792; range -148 to 344 mg/day). No patient discontinued patiromer because of adverse events (AEs); none had serious AEs. Conclusions: In 6 hyperkalemic HD patients, patiromer decreased serum K and P levels and increased fecal K.

Effect of Patiromer on Urine Calcium and Phosphate Excretion in Healthy Adults

Effect of Patiromer on Urine Calcium and Phosphate Excretion in Healthy Adults

Abstract P602: Patiromer Decreased Aldosterone, Urine Albumin/Creatinine Ratio, and Blood Pressure in Patients with Chronic Kidney Disease and Hyperkalemia on RAAS Inhibitors: Results from OPAL-HK

Introduction: Elevated aldosterone (ALD) is associated with chronic kidney disease (CKD) and cardiovascular (CV) complications. Patiromer, a nonabsorbed potassium (K + )-binding polymer, decreases serum K + (sK + ) and may allow increased use of RAAS inhibitors (RAASi) in patients (pts) with CKD and hyperkalemia (HK). This analysis examined the effect of patiromer on ALD, urinary albumin/creatinine ratio (ACR), and blood pressure (BP) in pts with CKD on RAASi. Methods: OPAL-HK was a 2-part, phase 3 study in 243 CKD pts with sK + 5.1–&lt;6.5 mEq/L on RAASi. Pts received patiromer for 4 wks (Part A); pts with moderate-severe HK at baseline (sK + ≥5.5 mEq/L) and sK + 3.8–&lt;5.1 at Part A wk 4 continued on patiromer (n=55) or switched to placebo (n=52) in the 8-wk withdrawal phase (Part B). RAASi were stable prior to and during Part A. Changes in ALD, ACR, and systolic BP/diastolic BP (SBP/DBP) were analyzed. Results: After 4 wks of patiromer sK + , serum ALD and urine ALD/creatinine decreased, while plasma renin activity (PRA) was unchanged; SBP, DBP, and ACR also declined (Table). Mean±SE changes (ng/dL) in serum ALD from Part A wk 4 to Part B wk 4 and to Part B wk 8 were 4.6±1.6 (p&lt;0.01) and 5.7±1.8 (p&lt;0.01) in the placebo and 0.9±1.0 (p=NS) and 0.2±0.8 (p=NS) in the patiromer groups, respectively. Compared with Part A wk 4, SBP (mm Hg) was further reduced at Part B wk 4 (3.1±2.1, p=NS) and Part B wk 8 (5.4±1.9, p&lt;0.01) with maintained improvement in ACR in patiromer pts. Conclusions: Patiromer reduced both sK + and ALD (independent of PRA) in CKD pts with HK on RAASi. ALD reductions correlated with lower BP and ACR. Reduction in sK + may have lowered ALD possibly improving BP and ACR.

Effect of Patiromer on Serum Potassium Level in Patients With Hyperkalemia and Diabetic Kidney Disease

ImportanceHyperkalemia is a potentially life-threatening condition predominantly seen in patients treated with renin-angiotensin-aldosterone system (RAAS) inhibitors with stage 3 or greater chronic kidney disease (CKD) who may also have diabetes, heart failure, or both.ObjectivesTo select starting doses for a phase 3 study and to evaluate the long-term safety and efficacy of a potassium-binding polymer, patiromer, in outpatients with hyperkalemia.Design, Setting, and ParticipantsPhase 2, multicenter, open-label, dose-ranging, randomized clinical trial (AMETHYST-DN), conducted at 48 sites in Europe from June 2011 to June 2013 evaluating patiromer in 306 outpatients with type 2 diabetes (estimated glomerular filtration rate, 15 to <60 mL/min/1.73 m2 and serum potassium level >5.0 mEq/L). All patients received RAAS inhibitors prior to and during study treatment.InterventionsPatients were stratified by baseline serum potassium level into mild or moderate hyperkalemia groups and received 1 of 3 randomized starting doses of patiromer (4.2 g [n = 74], 8.4 g [n = 74], or 12.6 g [n = 74] twice daily [mild hyperkalemia] or 8.4 g [n = 26], 12.6 g [n = 28], or 16.8 g [n = 30] twice daily [moderate hyperkalemia]). Patiromer was titrated to achieve and maintain serum potassium level 5.0 mEq/L or lower.Main Outcomes and MeasuresThe primary efficacy end point was mean change in serum potassium level from baseline to week 4 or prior to initiation of dose titration. The primary safety end point was adverse events through 52 weeks. Secondary efficacy end points included mean change in serum potassium level through 52 weeks.ResultsA total of 306 patients were randomized. The least squares mean reduction from baseline in serum potassium level at week 4 or time of first dose titration in patients with mild hyperkalemia was 0.35 (95% CI, 0.22-0.48) mEq/L for the 4.2 g twice daily starting-dose group, 0.51 (95% CI, 0.38-0.64) mEq/L for the 8.4 g twice daily starting-dose group, and 0.55 (95% CI, 0.42-0.68) mEq/L for the 12.6 g twice daily starting-dose group. In those with moderate hyperkalemia, the reduction was 0.87 (95% CI, 0.60-1.14) mEq/L for the 8.4 g twice daily starting-dose group, 0.97 (95% CI, 0.70-1.23) mEq/L for the 12.6 g twice daily starting-dose group, and 0.92 (95% CI, 0.67-1.17) mEq/L for the 16.8 g twice daily starting-dose group (P < .001 for all changes vs baseline by hyperkalemia starting-dose groups within strata). From week 4 through week 52, statistically significant mean decreases in serum potassium levels were observed at each monthly point in patients with mild and moderate hyperkalemia. Over the 52 weeks, hypomagnesemia (7.2%) was the most common treatment-related adverse event, mild to moderate constipation (6.3%) was the most common gastrointestinal adverse event, and hypokalemia (<3.5 mEq/L) occurred in 5.6% of patients.Conclusions and RelevanceAmong patients with hyperkalemia and diabetic kidney disease, patiromer starting doses of 4.2 to 16.8 g twice daily resulted in statistically significant decreases in serum potassium level after 4 weeks of treatment, lasting through 52 weeks.Trial Registrationclinicaltrials.gov Identifier: NCT01371747