PKD DIET
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Tolvaptan (Jynarque)

How Does Tolvaptan Work?

Tolvaptan showed an improvement in kidney functioning by decreasing kidney weight as well as kidney cyst volume. In clinical trials, tolvaptan slowed the rate of decline of kidney functioning from 5% per year to 3% per year. Once PKD kidneys start to decline, they decline at the rate of about 5% per year. The greatest results were seen from tolvaptan in the first year of treatment.

Tolvaptan is a vasopressin inhibitor; a V2 Receptor blocker or a V2 drug. Surrounding kidney cysts is vasopressin and cyclic AMP. Vasopressin triggers kidney cysts to fill with fluid, thus triggering kidney cyst expansion and growth. It is this kidney cyst expansion and growth that decreases PKD kidney functioning. Kidney cysts replace functioning kidney tissue. While taking tolvaptan be sure and drink copious amounts of water. This may result in walking up during the night to empty your bladder of urine.

Caution with Jynarque

Tolvaptan is a drug used to treat ADPKD. Common side effects from OPC 31260 (the mother drug) now called Tolvaptan (OPC-41061) are:
dry mouth, thirst, and increased urination. Possible research projects with tolvaptan might include:

Otsuka's JYNARQUE (tolvaptan) Approved by U.S.A. FDA approved as the First Treatment to Slow Kidney Function Decline in Adults at Risk of Rapidly Progressing (ADPKD)

It can affect liver functioning. Get liver function tests before beginning Tolvaptan and 6 weeks afterwards, In PKD patients taking Jynarque the increase was decreased. Tolvaptan Risks ~ Increases in blood sugar and diabetes were also noted.

Otsuka the maker of Jynarque (tolvaptan) is committed to helping ADPKD. Help with a $10 copay in the USA.

Tolvaptan (Jynarque)

Tolvaptan impedes the action of proteins in the kidney called vasopressin V2 receptors. These molecules respond to the hormone vasopressin, which signals cells to take up water.

Blocking V2 receptors

This prevents fluid from accumulating within cysts. In addition to keeping patients on the dry side, tolvaptan also appears to stabilize salt imbalances, or produce some hyponatremia (low sodium).

What is Vasopressin?

Vasopressin directly regulates cyst growth in Polycystic Kidney Disease PKD. Use of vasopressin antagonists such as tolvaptan can help delay cyst growth. Drinking copious amounts of water may also help to shut down vasopressin.

cAMP, What Stimulates It?

What stimulates cyclic AMP to start this process that causes kidney cysts to expand, fill with fluid and to multiply in numbers? Caffeine can start the process; caffeine from chocolate, decaf coffee, decaf tea, black tea, green tea, white tea, coffee in all its forms and all other products containing caffeine stimulants increase cyclic AMP. Increases in cyclic AMP and increases in vasopressin makes PKD kidney cysts multiply, expand and grow.

With congestive heart failure, diuretics are useful but in PKD diuretics can lead to kidney stones. Tolvaptan reduces fluid buildup, but works differently from diuretics. With alcoholics, tolvaptan treatment corrects low sodium. Low sodium is useful in decreasing cyst growth.

A year after FDA rejected Tolvaptan for ADPKD treatment

Otsuka the drug manufacturer of tolvaptan in the USA, (Jynarque) was not approved by the FDA for the treatment of ADPKD in the USA until recently, The FDA issued a warning that it should not be used to treat anyone with liver disease as Tolvaptan may result in further liver damage or even death. A new trial is underway to access this.
In April 2018 the FDA approved Tolvaptan for ADPKD in the USA.

Other Countries Approve Tolvaptan

Japan has approved (tolvaptan) JINARCŪ in March 2014 for the treatment of PKD. In Feb 27, 2015 a tolvaptan like drug has been approved for the treatment of ADPKD in Canada.
In May 2015, JINARCŪ (tolvaptan) became the first approved pharmaceutical therapy available in Europe for patients with autosomal dominant polycystic kidney disease (ADPKD).

Efficacy and Safety of Tolvaptan in Subjects With Chronic Kidney Disease Between Late Stage 2 to Early Stage 4 Due to Autosomal Dominant Polycystic Kidney Disease

A 2014 clinical trial recruiting participants within the USA. Tolvaptan (Jynarque) took a long time to be approved in the USA due to liver problems. In patients with autosomal dominant polycystic kidney disease (ADPKD), long-term treatment with tolvaptan can rarely cause severe and potentially life-threatening liver injury. This injury is typically hepatocellular, occurs between 3 and 18 months after starting tolvaptan, and it resolves within 4 months after stopping the drug. Clinical Pattern of Tolvaptan-Associated Liver Injury in Subjects with Autosomal Dominant Polycystic Kidney Disease: Analysis of Clinical Trials Database

FDA Warns of Liver Injury Risk with (Jynarque) Tolvaptan

Three cases of serious but reversible increases in hepatic enzymes in a clinical trial involving tolvaptan (Jynarque) have prompted the FDA to warn of potential liver injury with the drug. These three patients improved was the drug was stopped. Also of concern was that the incidence of seriously elevated serum alanine aminotransferase (ALT) three times above normal and elevated serum total bilirubin, twice above normal.

Tolvaptan"s side effects include increased thirst and increased urine output 4-5 liters (quarts) per day. Individuals taking tolvaptan must keep up with this fluid loss. It has been found safe and effective in congestive heart failure and cirrhosis of the liver. TEMPO Phase II (2) the open label study, (every participant receives tolvaptan) is well underway. In the double blind study, phase III (3) some individuals receive tolvaptan others do not. Additional Tolvaptan trials have begun, including one by DaVita.

Tolvaptan Inclusion - exclusion from first trial

Tolvaptan met its primary endpoint of demonstrating a statistically significant (p= less than 0.001) reduction (nearly 50% reduction) in the rate of increase in Total Kidney Volume (TKV) over the 3-year study period as compared to placebo among patients with ADPKD.

NEJM Aquaretic Tolvaptan Effects

A considerable number of patients discontinued tolvaptan owing to its aquaretic side effects such as:

thirst
polydipsia
polyuria
nocturia

Tolvaptan treatment was also associated with: 
elevated liver-enzyme levels
hypernatremia
increased level of uric acid
gout

However, as compared with patients who received placebo, significantly fewer patients who received tolvaptan had adverse events related to ADPKD, such as kidney and back pain, hematuria, and urinary tract infection.

Tolvaptan looks promising as a treatment for ADPKD, though it remains in clinical trials in the USA. Tolvaptan reduces the rate of increasing kidney size. With any drug, the side effects need to be balanced against the benefits. Perhaps if this is coupled with the alkaline diet for PKD and PLD there will be a resultant overall beneficial effect?

Tolvaptan Slows Kidney Disease Progress

"Thirst, polyuria, and related adverse events may affect the ability of some patients to take effective doses of tolvaptan," Torres and colleagues wrote. "The potential effects on liver-enzyme levels and plasma levels of sodium and uric acid require monitoring."

The study was limited because the researchers could not detect any of the drug's effects on hypertension, and because all patients were asked to maintain good hydration and avoid thirst, which may have underestimated the drug's effects on the disease.

In an accompanying editorial, Rudolf Wuthrich, MD, of University Hospital Zurich, and Changlin Mei, MD, of Changzheng Hospital in Shanghai, noted that there were no effects on the "worsening trajectories of hypertension and albuminuria."

"Assuming that tolvaptan causes structural rather than functional improvements, one would have expected beneficial effects on urinary protein excretion and blood pressure," they wrote. Nonetheless, they said the trial "represents a major advancement in the quest for a cure for ADPKD," adding that clinicians will need to balance the risks and benefits of an aquaretic drug with its impact on delays in dialysis and transplantation, as well as diminished pain.

Advanced ADPKD Renal Dysfunction Treated With Tolvaptan

Japanese physicians successfully treated two ADPKD patients with tolvaptan.

Open-label Trial to Evaluate the Long Term Safety of Titrated Immediate-release Tolvaptan

There is an open label study by invitation only for Tolvaptan.

Tolvaptan + Octreotide

A 2014 study in the PKD animal model shows Tolvaptan + Octreotide has a synergistic effect on cyst formation, better than either drug given alone. This holds true both for liver cysts and kidney cysts. Read about some of the advances for PKD.

We are  sharing our experiences with PKD/PLD Diet, an adjunct diet envisioning it complementing a physician's prescribed medical therapy. Consider testing this with your doctor's prior knowledge, who can  adjust it according to your own uniqueness by adding it to your current  treatment.

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