Patiromer Acetate Induced Hypercalcemia: An Unreported Adverse Effect

Hindawi Case Reports in Nephrology Volume 2019, Article ID 3507407, 4 pages https://doi.org/10.1155/2019/3507407 Case Report Patiromer Acetate Induced Hypercalcemia: An Unreported Adverse Effect Shreeyukta Bhattarai ,1,2 Stephen Pupillo,1,2 Gulshan Man Singh Dangol ,1,2 and Erdal Sarac 1,2,3,4 1 Northeast Ohio Medical University, Department of Medicine, Rootstown, Ohio, USA St. Elizabeth Youngstown Hospital, Department of Internal Medicine, Youngstown, Ohio, USA 3 Lake Erie College of Osteopathic Medicine, Erie, Pennsylvania, USA 4 Ohio University Heritage College of Osteopathic Medicine, Athens, Ohio, USA 2 Correspondence should be addressed to Shreeyukta Bhattarai; Received 22 October 2018; Accepted 9 December 2018; Published 4 February 2019 Academic Editor: Yoshihide Fujigaki Copyright © 2019 Shreeyukta Bhattarai et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Hyperkalemia, a potential life threating condition, is a commonly encountered problem in chronic kidney disease (CKD) patients. Patiromer acetate, a nonabsorbable cation exchange polymer, is a gastrointestinal agent for chronic therapy in patients with persistent hyperkalemia. Patiromer is generally well tolerated in patients; common side effects are gastrointestinal, such as diarrhea, constipation, flatulence, and vomiting. Hypercalcemia, although a theoretical possibility, has not been reported in any major clinical trials. We present a case of hypercalcemia associated with patiromer acetate used for treatment of hyperkalemia in a stage IV CKD patient. Clinicians should be aware of the possibility of hypercalcemia while taking patiromer. 1. Introduction Patiromer acetate, a nonabsorbable cation exchange polymer, was recently approved for chronic management of hyperkalemia. Patiromer acetate decreases serum potassium by exchanging calcium for potassium in the intestine, especially the colon, resulting in gastrointestinal loss of potassium. It is considered safe and well tolerated; gastrointestinal side effects include diarrhea, constipation, flatulence, and vomiting. Other potential side effects include hypomagnesemia and hypokalemia. We present a case of a seventy-year-old man with diabetes, CKD stage IV, and hypertension with hypercalcemia on patiromer acetate for consistently elevated potassium. 2. Case During routine follow-up, a 70-year-old Caucasian male with past medical history of type 2 diabetes mellitus, gout, chronic kidney disease (CKD) stage IV, anemia of chronic disease, vitamin D deficiency, and hypertension, managed with patiromer acetate for persistent hyperkalemia secondary to CKD, presented with hypercalcemia. Home medications included metformin, allopurinol, weekly erythropoietin, and vitamin D supplementation. Serum potassium was persistently above 5.5 mmol/L prior to treatment initiation. Estimated glomerular filtration rate (eGFR) was 24 ml/min/1.73 m2 , blood urea nitrogen (BUN) was 86 mg/dl, and creatinine was 2.6 mg/dl. Other labs included calcium (Ca), 9.2 mg/dl; potassium (K), 5.7 mmol/L; and parathyroid hormone (PTH), 86 pg/ml. BUN and creatinine were similar over the last year. Initial patiromer acetate dosing was 8.5 mg nightly. Symptomatically, the patient tolerated the medication very well. However, calcium at 30-day follow-up increased to 10.2 mg/dl, and potassium level decreased to 5.1 mmol/L. Since the patient was asymptomatic, he was advised to continue patiromer acetate and discontinue vitamin D supplementation. Repeat lab values after two months demonstrated higher calcium, 10.7 mg/dl, and unchanged potassium, 5.1 mmol/L. At this point, secondary causes of hypercalcemia were investigated. See Table 1. Mild hyperparathyroidism of 2 Case Reports in Nephrology Table 1 Potassium, mmol/L eGFR, ml/min/m2 BUN, mg/dL Creatinine, mg/dL Calcium, mg/dL PTH, pg/ml 25 OH vitamin D, ng/mL Day 1 5.7 24 86 2.6 9.2 86 31 Day 30 5.1 23 92 2.7 10.2 86pg/ml before the initiation of therapy (normal 15-65pg/ml) was considered secondary to vitamin D deficiency. 25hydroxy (OH) Vitamin D was 31 ng/ml (normal: 30100ng/ml), and 1, 25-OH Vitamin D was 10.2 pg/ml (normal: 19.9-79.3pg/ml), suggesting insufficient 1-alpha hydroxylase enzyme secondary to CKD. Parathyroid hormone related peptide (PTHrP) was within the normal limit, 2.1 pmol/L (normal: 0.0-2.3pmol/L). Normal bone density was observed on dual energy X-ray absorptiometry (DEXA) scan; the lowest T score (– 1.2), was femoral. Urinalysis was negative for proteinuria; urine immunofixation demonstrated no light chains. Thyroid stimulating hormone (TSH) level was 0.874 uIU/mL (normal 0.27-4.2uIU/mL). Chest computed tomography (CT) scan showed multiple bilateral 2-3 mm calcified and noncalcified pulmonary nodules. Nodules were stable in size, compared to scan seven years before, and considered noncontributory to hypercalcemia. Angiotensin converting enzyme (ACE) level was 53 U/L (normal 9-67 U/L). With no obvious secondary causes of hypercalcemia on laboratory assessment and imaging, patiromer was discontinued. Despite discontinuation, he continued the medication because of misunderstanding. On follow-up after an additional 30 days, calcium returned even higher, 11.6 mg/dL (Figure 1), and potassium even lower, 4.6 mmol/L (Figures 2 and 3). After additional patient education, he was advised again to stop taking patiromer acetate. One month after stopping medication, calcium normalized to 8.4 mg/dL. PTH level, suppressed at 10 pg/ml during the hypercalcemic state, returned to 66 pg/ml after calcium normalization and patiromer acetate cessation. BUN, 80 mg/dl; creatinine, 2.8 mg/dl; and GFR, 22 mL/min/1.73 m2 remained stable. Potassium trended upward, 5.3 mmol/L. Day 90 5.1 31 65 2.1 10.7 Calcium 12.36 11.44 10.52 9.6 8.68 7.76 6.84 5.92 5 Day 120 4.6 25 87 2.5 11.6 10 Day 150 5.3 22 80 2.8 8.4 204 34 11.6 10.2 10.2 10.7 9.5 9.2 8.4 Apr 16 Jun 16 Aug 16 Oct 16 Dec 16 Feb 17 Apr 17 Figure 1: Trend in calcium level during the course of treatment with patiromer acetate. Potassium 6.68 5.7 5.97 5.3 5.3 5.2 5.1 5.1 5.26 4.6 4.55 3.84 3.13 2.42 1.71 1 Apr 16 Jun 16 Aug 16 Oct 16 Dec 16 Feb 17 Apr 17 Figure 2: Trend in potassium level during the course of treatment with patiromer acetate. 14 12 10 8 3. Discussion Prevalence of hyperkalemia in CKD patients is directly proportional to the residual renal function and increases from 13% in CKD stage II to 34% in CKD stage IV.[1] Gastrointestinal tract and renal systems are important regulators of potassium homeostasis. In patients with intact renal function, approximately 90 percent of potassium is excreted through the kidneys, the remaining 10 percent excreted through the gastrointestinal tract, especially the colon.[2] Renal potassium excretion is controlled by different physiologic signals, such as aldost (...truncated)