Open-label Safety and Efficacy of Sodium Zirconium Cyclosilicate for up to 12 Months

Subjects with 2 consecutive i STAT potassium values 5.1 mmol/L will enter the Acute Phase and
receive ZS 10 g tid for 24 to 72 hours, depending on potassium values. Once normokalemia (i
STAT potassium between 3.5 and 5.0 mmol/L, inclusive) is restored (whether after 24, 48 or 72
hours), subjects will be enrolled in the Maintenance Phase to be dosed with ZS at a starting
dose of 5 g qd. Potassium (i STAT and central laboratory) will be measured weekly throughout
the first month of study and every 4 weeks thereafter through Month 12. During the
Maintenance Phase, the ZS dose may be increased or decreased in increments/decrements of 5 g
qd up to a maximum of 15 g qd or a minimum of 5 g every other day based on i STAT potassium
measurements as outlined below:

• > 5.0 mmol/L while receiving 5 g qd or 5 g every other day or > 5.5 mmol/L while receiving
10 g qd: increase ZS dose in 5 g qd increments to a maximum dose of 15 g qd

.• Between 3.0 and 3.4 mmol/L, inclusive: decrease ZS dose in 5 g qd decrements to a minimum
dose of 5 g every other day; if a subject's i STAT potassium value remains between 3.0 and
3.4 mmol/L, inclusive, on the ZS 5 g every other day dose, the subject will be withdrawn from
the study and receive standard of care treatment.

There is no limit to the number of dose titrations allowed. Subjects will receive up to 12
months of treatment with open-label ZS.

Inclusion Criteria:

- Provision of written informed consent.

- Over 18 years of age.

- Two consecutive i STAT potassium values, measured 60 (+/- 15) minutes apart, both >/=
5.1 mmol/L and measured within 1 day before the first dose of ZS on Acute Phase Study
Day 1.

- Ability to have repeated blood draws or effective venous catheterization.

- Women of childbearing potential must be using 2 forms of medically acceptable
contraception (at least 1 barrier method) and have a negative pregnancy test at Acute
Phase Study Day 1. Women who are surgically sterile or those who are postmenopausal
for at least 2 years are not considered to be of childbearing potential.

- Controlled diabetic subjects.

Exclusion Criteria:

- Pseudohyperkalemia signs and symptoms, such as hemolyzed blood specimen due to
excessive fist clenching to make veins prominent, difficult or traumatic venipuncture,
or history of severe leukocytosis or thrombocytosis.

- Subjects treated with lactulose, rifaximin, or other non-absorbed antibiotics for
hyperammonemia within 7 days prior to first dose of ZS on Acute Phase Study Day 1.

- Subjects treated with sodium polystyrene sulfonate (SPS; eg, Kayexalate®) or calcium
polystyrene sulfonate (eg, Resonium®) within 3 days prior to first dose of ZS on Acute
Phase Study Day 1.

- Subjects with a life expectancy of less than 12 months.

- Subjects who are severely physically or mentally incapacitated and who, in the opinion
of investigator, are unable to perform the subjects' tasks associated with the
protocol.

- Women who are pregnant, lactating, or planning to become pregnant.

- Subjects with diabetic ketoacidosis.

- Presence of any condition which, in the opinion of the investigator, places the
subject at undue risk or potentially jeopardizes the quality of the data to be
generated.

- Known hypersensitivity or previous anaphylaxis to ZS or to components thereof.

- Treatment with a drug or device within the last 30 days that has not received
regulatory approval at the time of study entry.

- Subjects with cardiac arrhythmias that require immediate treatment.

- Subjects on dialysis.

- Subjects randomized into the previous ZS-002, ZS-003, ZS-004, or ZS-004E studies.

- Documented GFR <15 mL/min within 90 days prior to study entry.