Probenecid (PB) to Treat Hereditary Nephrogenic Diabetes Insipidus (NDI), ADPKD Treated With Tolvaptan, and Severely Polyuric Patients With Previous Lithium Administration

Inclusion Criteria:

• Male or female, ≥ 18 years of age (inclusive) at time of screening

• Diagnosis of one of the following:

1. ADPKD(as delineated in cohort 1)

2. Congenital NDI (as delineated in cohort 1)

3. Lithium-induced NDI (as delineated in cohort 1)

• Glomerular filtration rate (GFR) ≥ 25 ml/min/1.73 m2 at time of screening visitcalculated as in cohort

• 24 hours urine volume in baseline 1 visit ≥ 5000 ml/ day

• If hypertensive, blood pressure controlled on antihypertensives (<130/80 mm Hg) atleast 30 days before day 1. Antihypertensives may be adjusted at time of baseline 2per PI discretion.

• Female participants (see details in cohort 1 inclusion criteria)

• Have read, understood, and provided written informed consent after the nature of thestudy has been fully explained and must be willing to comply with protocolrequirements and study-related procedures.

• Negative urinary pregnancy test (if applicable) at baseline 2

• Capable of providing urine samples as dictated by the protocol

Exclusion Criteria:

• Advanced diabetes (e.g., glycosylated hemoglobin [HgbA1c] >7.5%, and/or glycosuriaby dipstick, significant proteinuria [>300 mcg albumin/mg creatinine]), othersignificant kidney disease, kidney cancer, transplanted kidney, single kidney,kidney surgery within the past 6 months (including cyst drainage or fenestration) oracute kidney injury within 6 months prior to screening.

• Clinically significant incontinence, overactive bladder, or urinary retention (e.g.,benign prostatic hyperplasia).

• Other significant chronic medical disease (heart failure, diabetes mellitus, liverdisease, transient or persistent elevated transaminases)

• History of acute gout attack in the past 30 days

• History of clinically significant drug or alcohol abuse in the 2 years prior toscreening visit.

• Uncontrolled hyperuricemia or active gout

• History of hepatotoxicity related to tolvaptan; or clinically significant liverdisease or impairment; or alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total bilirubin values >1.2 x Upper Limit of Normal (ULN) duringscreening.

• Medical history or findings that preclude safe participation in the trial orparticipants who are likely to be non-compliant with trial procedures in the opinionof the investigator or medical monitor.

• Requirement for ongoing diuretic use.

• Participants who are currently taking, or are expected to be taking, strong ormoderate CYP3A4 or CYP2C8 inhibitors or inducers including regular use of grapefruitjuice, Seville oranges, or St. John's wort. If applicable, there should be a 14-daywashout of these treatments prior to Day 1.

• Prior use of a sodium-glucose cotransporter 2 inhibitor (SGLT2i) (e.g.,canagliflozin, dapagliflozin, empagliflozin, etc.) within the 2 months prior toscreening visit or expected need for initiation of treatment with a SGLT2i inhibitorduring the study. Current use of SGLT2i will be reviewed by PI and allow enrollmentif patient has been on stable dose for at least 2 months.

• Prior use of a hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor withinthe 2 months prior to screening visit or expected need for initiation of treatmentwith a HIF-PH inhibitor during the study;

• Participants who have taken any investigational drug or used an investigationaldevice within 30 days, or 5 half-lives, whichever is longer, prior to screeningvisit 1a or plan to participate in an interventional trial during the study.

• Allergy to probenecid

• History of persistent hyponatremia

• Positive test results for hepatitis B surface antigen (HBsAg).

• Positive test results for hepatitis C (HCV) antibody (Anti-HCV), with the exceptionof participants for whom the reflex HCV RNA titer test is negative.