Sodium Zirconium Cyclosilicate; A Novel Potassium-Binding Agent for Hyperkalemia in Advanced Chronic Kidney Disease: A First Use Case Report in India

Hyperkalemia is a commonly seen electrolyte disturbance in patients with chronic kidney disease stage 5 (CKD 5), due to the altered ability of excreting potassium through urine [1]. The incidence of hyperkalemia in CKD 5 patients increases with declining glomerular filtration rate [2]. Supplementing this information is that severe hyperkalemia (K? >6.0 mEq/L) is extremely dangerous to the cardiovascular system, causing arrhythmias, conduction abnormalities and hemodynamic instability preventing the patient from surgery whether it's elective or emergency until the electrolyte abnormality corrects [1][3].

The general treatment of hyperkalemia includes calcium gluconate for cardio protection, insulin with dextrose, beta-agonists, and potassium binders such as sodium polystyrene sulphonate (Kayexalate) and calcium polystyrene sulphonate (K-Bind) [1][4]. However, these agents have different and fluctuating efficacies and may not always provide adequate potassium reduction in patients, particularly those with severe baseline elevations or resistant hyperkalemia [2][4].

Sodium Zirconium Cyclosilicate (SZC) sold under the brand name LOKELMA is a novel class of non-absorbed, selective potassium binder that selectively exchanges potassium for hydrogen and sodium in the gastrointestinal tract [5]. With the gathered extensive clinical trial data on this drug, it has shown to have rapid onset of potassium reduction within one hour of administration, with dose-dependent efficacy across varying severity levels of hyperkalemia [5][6]. Despite FDA approval in 2018, Sodium Zirconium Cyclosilicate has had limited use in Indian clinical practice, as it was only officially launched in India in December 2025 [7].

We present a case of a 76-year-old male with CKD Stage 5 not on dialysis, who developed subdural hemorrhage after suffering a fall at home and needed surgical intervention. In attempts to correct hyperkalemia, all necessary standard protocol management was given to the patient, showing no effect, delaying the need for a necessary surgery, necessitating escalation to newly launched drug, SZC which lead to the desired reduction in potassium required with this agent allowing the patient for timely surgical intervention that was previously contraindicated due to the severe electrolyte imbalance.

CASE REPORT

We observed a 76-year-old male patient who presented to the Max Super Specialty Hospital, Mohali, Punjab with the history of a fall one month ago with head trauma and bleeding on the day of the fall. The patient had gone to a local hospital a 2 day after the fall, for which he was given with the necessary medications and discharged. Then, about 1 week prior to the current admission, the patient had developed fresh symptoms like forgetfulness and confusion, after which the patient’s family went for a CT Head Scan which showed a chronic subdural hematoma with significant mass effect, after which the patient was referred and admitted for further surgical intervention. The patient's past medical history included a Coronary Artery Bypass Grafting (CABG) performed in 2013, along with comorbidities like hypertension, hypothyroidism and CKD for last one and half years (not on dialysis). The patient's regular medications prior to admission included Amlodipine 5 mg daily, Metoprolol XR 50 mg daily, and Atorvastatin 20 mg at night. Physical examination on the day of admission showed; Blood Pressure- 135/80 mmHg, Pulse Rate- 74 beats /min, Respiratory Rate- 22/min, SPO2- 98%, Temperature- 97.2°F. Upon admission the patient was planned for a burr hole craniotomy for hematoma evacuation. However, preoperative clearance for surgery was based upon achieving acceptable electrolyte stability, particularly normalized serum potassium levels (target <5.0 mEq/L). The laboratory reports of serum showed the following electrolyte levels; Sodium- 132 mEq/L, Potassium- 5.36 mEq/L, Chloride- 104 mEq/L and Urea 121 mg/dL and was started on pharmacotherapy of, Amlodipine 5mg, Cap. Tab. Metoprolol XR 25mg BD and Tab. Atorvastatin 20mg at Night.

On Day 2, the patients laboratory electrolyte serum values showed: Sodium- 136 mEq/L, Potassium 5.76 mEq/L, Chloride- 106 mEq/L and Urea- 137 mg/dL. Given the elevated potassium level, corrective therapeutic measures were initiated; Inj. Calcium gluconate 10 mL intravenously over 10 minutes, Neb. Asthalin (salbutamol), Calcium Polystyrene Sulphonate (K-Bind) 1 sachet in 15 mL lactulose twice daily, along with a strict K+- Free diet.

On Day 3, Despite continuation of K-Bind BD therapy combined with all other potassium-lowering measures, serum potassium paradoxically had escalated to 5.85 mEq/L on Day 3 and further to 6.06 mEq/L on Day 4, demonstrating the poor-response of calcium polystyrene sulphonate regimen under the patient’s physiology. These highly elevated potassium levels made the patient unsuitable for surgical intervention, as hyperkalemia of this magnitude carried a substantial risk of intraoperative arrhythmias and hemodynamic compromise, delaying a necessary surgery.

The option of dialysis was available and presented to the patient and the caretakers but was refused due to beliefs that if the patient was started on dialysis for this treatment will be needed for all future treatments, as the patient is a CKD 5 not on dialysis. Fortunately, on the last hopes despite having tried all possible potassium-lowering methods, one more attempt was available. SZC which was launched only a few days prior in the Indian market, was ordered by the physician to reduce and correct the serum potassium imbalance.

SZC was initiated to the patient at a dose of 5mg three times daily as an alternative. This represented one of the first uses of SZC not only in our institution but also in India, due to its very fresh release to the Indian market. Approximately 12 hours after the first dose and following administration of the second dose of SZC, repeat laboratory testing revealed a reduction in serum potassium from 6.06 mEq/L to 4.39 mEq/L, a decrement of 1.67 mEq/L within half a day. This rapid normalization of potassium allowed for the patient to proceed with the planned burr hole craniectomy. On Day 5, following a successful burr hole craniotomy for evacuation of the chronic subdural hematoma, the serum electrolyte panel showed potassium to be controlled at 4.71 mEq/L with sodium and chloride remaining within normal ranges (136 and 107 mEq/L, respectively).

The rapid and effective control of hyperkalemia with SZC allowed the healthcare team to perform surgical intervention in a timely manner that was delayed due to the electrolyte instability. The patient tolerated the procedure well without intraoperative complications related to hyperkalemia or electrolyte imbalances and following the surgery was kept under observation in the ICU for 1 more day and then shifted to a private room for post-op recovery.

On Day 6, the patient was recovering well without any new complaints, showing improvement, Although there was a slight increase in the serum potassium levels, it hadn’t exceeded 5.0 mEq/L, showing the efficacy of SZC in maintaining potassium levels within a safe range, even in such hemodynamically compromised patients at high risk of electrolyte fluctuations due to the advanced CKD. The prescription of Lokelma (SZC) which was written for the patient had been completed, in which the patient received 6 total doses of Lokelma 5mg TDS for 2 days. Resulting in the successful reduction of serum potassium from a highly elevated range to one that was safe allowed to proceed for the surgery which was required and continued post-op Aswell. This trend in recovery from the surgery and subsequent decreases in serum potassium (4.47, 4.61, 4.0) continued for the remainder of the days (Day 7,8,9) respectively, the patient stayed in the hospital until the completion of the post-op care and other discharge criteria required.

TABLE 1:  Serial electrolyte and serum urea panel demonstrating the progressive hyperkalemia in the patient despite on-going measure to decrease potassium level and response to LOKELMA.

DISCUSSION

This case represents one of the documented uses of SZC in Indian clinical practice for management of hyperkalemia since its launch to the public, as it isn’t widely available across hospitals, the case report aims to document its first Real-World use. Sodium Zirconium Cyclosilicate is a non-absorbed, microporous, inorganic compound that selectively binds to potassium ions in the gastrointestinal lumen through preferential ion exchange of potassium for hydrogen and sodium [5]. Unlike older potassium binders such as sodium or calcium polystyrene sulphonate, which follow non-selective ion exchange, Sodium Zirconium Cyclosilicate demonstrates a higher affinity for potassium, resulting in superior efficacy and reduced sodium/calcium loading [5][6]. It reaches maximal efficacy within 24-48 hours but shows onset of action as early as one hour after administration [5]. In Phase 2/3 clinical trials, Sodium Zirconium Cyclosilicate 10 mg administered three times daily achieved a mean serum potassium reduction of 0.7 mEq/L over 48 hours in patients with baseline hyperkalemia [6]. In the present case, a dose of 5 mg TDS achieved reduction of 1.67 mEq/L within 12 hours exceeding the efficacy typically observed in published trials, but can also be attributed to other factors like strict diet control, Neb. Asthalin and aswell as the patient's highly elevated baseline potassium (6.06 mEq/L), as clinical pharmacology data indicate that patients with higher baseline potassium concentrations demonstrate greater absolute and proportional reductions with SZC [5][6]. The inefficacy of Calcium Polystyrene Sulphonate (K-Bind) in this patient, despite optimal dosing, raises important questions regarding the efficacy of older potassium binders in advanced CKD patients. Multiple factors may contribute to reduced effectiveness of polystyrene sulphonates in CKD Stage 5, including: Reduced gastrointestinal transit time and reduced GI surface contact time resulting from uremic alterations in motility [8]. Impaired colonic bioavailability due to altered microbiota composition in advanced CKD [8]. Ion selectivity limitations of non-selective polystyrene exchange resins in high-potassium environments [5]. Individual genetic variation in sulphonate resin efficacy [9]. The higher affinity of sodium zirconium cyclosilicate’s potassium-binding capacity may have overcome these limitations, as evidenced by the rapid clinical response observed in this case. The hyperkalemia leading to delays in the surgical intervention carried a highly relevant risk regarding morbidity and mortality for the patient [1][3]. But, due to this ability to rapidly normalize serum potassium with SZC any such events were prevented.

In this case all options to reduce hyperkalemia had been exhausted before considering the use of SZC aside from one, known as Paritomer [10]. It is a sodium?free, non?absorbed cation?exchange polymer approved for the treatment of hyperkalemia, especially in patients with CKD, diabetes, heart failure, or those on RAAS inhibitors, but the limitations of this drug come in its high cost and the fact that it isn’t currently available for use in India [11][12].

TABLE 2: Treatment options for correcting Hyperkalemia: Class, Mechanism, and Clinical Profile