– 2021 Update

Polycystic kidney disease (PKD) is the most common inherited kidney disease affecting one in 800 people. There have been several advances in our understanding of PKD since our last blog. In a previous blog, we discussed the genetics of PKD and how genetic variants translate into a disease. In this blog, we will discuss recommendations for water, salt, and caffeine intake to reduce cyst growth. You will find out if ketogenic diet or intermittent fasting is the best diet for polycystic kidney disease.

Kidneys

PKD at the Cellular Level

To determine the best PKD diet and lifestyle recommendations, we must understand what is happening at the cellular level. In essence, abnormalities in PC1 or PC2 proteins will activate two pathways inside the cell. First, it activates the cAMP pathway which regulates fluid transport. Second, it changes the way cells make energy from sugar (called glycolysis). When PC1 or PC2 proteins don’t work well, they switch from aerobic (with oxygen) to anaerobic (without oxygen) glycolysis. This is similar to the shift that occurs in cancer cells. 
While anaerobic glycolysis produces less energy from glucose, it is faster than aerobic glycolysis. This faster energy production allows the cells to grow faster. However, it also leads to a critical dependence on glucose.1


 

How Much Water to Drink in PKD

Vasopressin, also called anti-diuretic hormone (ADH), is a hormone that is produced by the brain and excreted by the pituitary gland. It plays an important role in the body’s fluid and sodium balance, blood pressure, and kidney function. ADH was found in several studies to promote cyst growth by stimulating the production of cAMP. Further proving the role of ADH in polycystic kidney disease, cyst growth was inhibited in both forms of PKD by administering ADH receptor blockers (medications that block ADH)
Dehydration can increase ADH and make cysts worse. Drinking large amounts of water leads to a significant decrease in the progression of PKD. The optimal amount of water to drink in PKD patients depends on the amount of salt and food they eat. The simplest way to assess this is by checking a 24-hour urine osmolality. You can use our calculator to assess the amount of water you should drink daily based on your 24-hour urine osmolality. Alternatively, measuring first morning urine osmolality can be used. The target for that is keeping the level less than 280 mOsm/kg. 
In addition to dehydration, other factors that lead to the production of ADH include stress, pain, and surgery. These factors, therefore, can indirectly lead to cyst growth and further harm kidney function. 
 

Polycystic Kidney Disease and Caffeine 

In the laboratory, caffeine increased cAMP accumulation in the cells. Yet, in human clinical trials, caffeine intake was not directly associated with kidney size in patients with PKD. An analysis in one clinical trial found no significant association between the consumption of caffeine from coffee and tea on the progression of ADPKD.

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Calorie-restricted and Keto Diets for Polycystic Kidney Disease

Kidney cysts thrive on sugar or glucose, as discussed earlier. Therefore, calorie-restricted and ketogenic diets can be beneficial for patients with PKD. Ketogenic diets induce a state that resembles starvation by providing high fat content and low protein and carbohydrate content. Time-restricted feeding such as intermittent fasting can have similar effects. Studies on animals demonstrated that ketosis could decrease cyst growth in PKD. These effects were thought to be mediated by a strong inhibition of mTOR.2
It is worth mentioning here that metformin can activate AMPK and is currently being studied in PKD.
To our knowledge, there is no published human study to confirm the effect of ketogenic diets and intermittent fasting on PKD. However, given the strong benefit of ketosis on cyst growth, we generally recommend a plant-based ketogenic diet or intermittent fasting in addition to a large water intake for patients with PKD.
  

Dietary, Lifestyle, and Water Recommendations for PKD

The phrase “our genes are not our destiny” describes how nutrition and lifestyle factors can have a positive impact on genetic expression for certain diseases. Drinking large amounts of filtered water, restricting salt intake, a ketogenic diet, or intermittent fasting can have significant benefits in patients with PKD. So far, limiting caffeine is not necessary to improve PKD, but it has other health benefits. Finally, stress reduction techniques can help to lower ADH and reduce kidney cysts.
 

Ongoing Studies of Diet and Lifestyle PKD Treatments 

  1. PREVENT-ADPKD trial is looking at water intake and the progression of ADPKD. It should be released in late 2021. 
  2. DRINK trial is investigating water intake in ADPKD. It should also be released in late 2021 or early 2022.
  3. METROPOLIS trial is comparing Metformin and Tolvaptan for the treatment of ADPKD. It should be completed in early 2022.
  4. Time-restricted feeding in ADPKD is currently recruiting subjects and is estimated to be completed by end of 2022.
  5. Keto-ADPKD trial is looking at how the ketogenic diet affects the progression of ADPKD. It should be completed in mid-2022.
  6. Curcumin Therapy to treat vascular dysfunction in ADPKD was completed in late 2020. It should be released soon.

 


1 It is noteworthy that glycolysis is inhibited by a cellular messenger called AMP-activated protein kinase (AMPK). It is activated by another messenger called mTOR. Metformin activates AMPK.
2 Activation of AMPK and inhibition of mTOR can theoretically inhibit glycolysis in cells that line the cysts in PKD. However, studies that looked at medications that inhibit mTOR such as sirolimus, did not show any benefit in PKD