PKD - Water a Cure for PKD?

                                                                     WATER A TREATMENT FOR PKD?  PROBABLY,  YES           


PKD Clinical trials for water are beginning in New York City. For the PKD water clinical trial click here. In Tokyo, Japan doctors there are looking at water as a treatment for PKD. There is a second clinical trial involving water in Kansas City USA. Short excerpts taken from these interesting papers are written beside each article. For some interesting information on bottled water click here  

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Here is some information on city water supplies in the USA

Water a possible treatment for PKD? Recently published PKD medical research points to the possibility that by increasing water intake, we can slow down kidney decline and cyst growth. In the PKD model, this has resulted in a reduction in plasma vasopressin levels; renal cyst cell proliferation decreased; and in the rats who increased their water intake, they slowed PKD progression; diminished kidney cyst growth; and these PKD models developed smaller cystic kidneys with a lower number of kidney cysts. Sustained hydration might be beneficial to PKD’rs especially early in the disease by limiting the detrimental effects of vasopressin. The rats drank the equivalent of 20 liters of water per day. Human clinical trials have yet to begin but are certainly warranted. This works in both ADPKD and ARPKD. No one can give an answer as to how much water should PKD’rs drink, but common sense says sufficient water intake would be to keep plasma vasopressin levels near a point that renders urine osmolality equal to or modestly lower than that of plasma. To know for certain how much of the water cure is prudent therapy, a carefully controlled clinical trial seems justified. Some of us have tried 3 liters/ day. Others have tried about 8 liters/day. We have yet to see if this makes a difference. It is not known if this helps liver cysts or kidney cysts, but we are willing to give it a try. Send an email. One suggestion was to calculate daily urine output – if it is 1500 cc, then drinking twice this amount or about 3000 cc of water might be sufficient to shut down vasopressin or to take urine osmolality equal to that of plasma.

Increased Water Intake Decreases Progression Polycystic Kidney Disease PCK Rat
Wallace D 2006 J Am Soc Nephrol 17: 2220–2227, 2006. doi: 10.1681/ASN.2006030251
Arginine vasopressin (AVP) is an important antidiuretic hormone that mediates its effect through the activation of vasopressin V2 receptors (AVPV2R) and the subsequent stimulation of adenylyl cyclase and synthesis of cAMP (10). . .Normally, urine is concentrated to an osmolality that is greater than plasma. Day-to-day maintenance of urine output depends on appropriate plasma AVP levels to regulate osmotic water reabsorption by distal tubules and collecting ducts. Relatively normal plasma levels of AVP may be sufficient to stimulate cyst epithelial cell growth and renal enlargement in patients with PKD. Some patients have an intrinsic defect in the capacity to concentrate urine maximally, potentially leading to even greater levels of plasma AVP than normal (11–13). . .Increased water intake sufficient to cause a reduction in plasma (arginine vasopressin) AVP levels decreased renal cell proliferation, and slowed PKD progression in PCK rats. We propose that sustained hydration by increased water intake may be beneficial to some patients with PKD by limiting the detrimental effects of (arginine vasopressin) AVP on renal cyst growth.

Water for ADPKD? Probably, Yes    
Torres V E 2006        Am Soc Nephrol 17: 2089–2091, 2006. doi: 10.168 1/ASN 2006060 60 3
Increased fluid intake may be beneficial to some patients with ADPKD, at least in early stages of the disease, , , , If increased fluid intake, either by itself or together with the administration of V2 receptor antagonists, is proved to slow the rate of growth of polycystic kidneys, then its long-term safety will need to be considered. . . .A number of studies of other possible treatments for PKD have been published during 2005 to 2006. Long-acting octreotide may inhibit cAMP production. . .Rapamycin, an inhibitor of mammalian target of rapamycin (32–34), have been effective in animal models of cystic disease. The pace of development of new potential therapies for ADPKD raises the hope that its inexorable clinical course soon may be modified. .Caffeinated beverages should be discouraged because caffeine inhibits phosphodiesterase; enhances cAMP accumulation; and potentates the effects of vasopressin on chloride secretion, cell proliferation, and cyst growth, at least in vitro . . Calorically sweetened beverages and fruit drinks are major contributors to the epidemic of obesity in the United States and should be avoided (28). Because drinking tap water has been associated in some studies with a slightly increased risk for bladder cancer in men, whereas non-tap water has not, high-quality or bottled water may be preferable . . .A retrospective analysis of the MDRD study (139 participants with and 442 without ADPKD; GFR at entry 25 to 55 ml/min per 1.73 m2) was performed to examine the relationship between fluid intake (reflected by 24-h urine volume and urine osmolality) and renal disease progression. Higher urine volumes and lower urine osmolality is associated with faster GFR decline regardless if the patient had ADPKD. The authors considered two possible explanations. The first was that excessive fluid intake and high urine volume cause faster renal disease progression and possibly cyst growth in ADPKD. The second was that high urine volume with low urine osmolality is the result and not the cause of faster renal disease progression (19). The results by Nagao et al. (18) do not support the first explanation; on the contrary, they suggest that increased fluid intake may be beneficial to some patients with ADPKD, at least in early stages of the disease. . .Long-acting octreotide may inhibit cAMP production, and a pilot study of patients with ADPKD has shown promising results (30). PD184352, an inhibitor of mitogen-activated protein kinase/ extracellular signal–regulated kinase (31), and rapamycin, an inhibitor of mammalian target of rapamycin (32–34), have been effective in animal models of cystic disease. The pace of development of new potential therapies for ADPKD raises the hope that its inexorable clinical course soon may be modified.

Vasopressin Directly Regulates Cyst Growth in Polycystic Kidney
Torres V E 2008  Am Soc Nephrol. 2008 Jan;19(1):102-8. Epub 2007 Nov 21.
These observations indicate that AVP is a powerful modulator of cystogenesis and provide further support for clinical trials of V2 receptor antagonists in PKD.

Therapy for Polycystic Kidney Disease? It’s Water  
Grantham JJ 2008 J Am Soc Nephrol 19: 1–2, 2008. doi: 10.1681/ASN.2007101100
Now we are confronted by the bizarre prospect that water is the“cure” for hereditary diseases that grotesquely bloat the kidneys with . . . water. . .Cysts arise in renal tubules when epithelial cells focally proliferate, leading to tiny outpouchings, that progressively expand, upstream fluid from glomerular filtrate fills the budding cyst cavity. Later, after they separate from the parent tubules. Two ordinarily quiescent renal processes, epithelial cell proliferation and solute-driven fluid secretion, come storming out of hiding and push a relatively small number of cystic segments to take over eventually the parenchymal landscape, driving functional glomeruli and tubules into oblivion. .We knew this much about PKD for more than a decade. . .Although studies clearly implicate a central role for vasopressin and cAMP in promoting kidney enlargement and reducing renal function in PKD, a study from the Mayo laboratory in this issue of the JASN9 provides definitive proof. The dramatic results in this report are consonant with the view that epithelial cell growth is of paramount importance to the formation of the cyst as well to the overall increase of renal size in ARPKD. . .Of the hormones capable of increasing cAMP production in collecting ducts, only AVP (arginine vasopressin) is persistently elevated in the plasma of humans. Where do the cysts form in ARPKD? In collecting ducts. Land based animals are normally antidiuretic for most hours of the day and night, except for short periods when relatively large volumes of water are imbibed. Therefore, plasma AVP levels are usually high enough to activate adenylyl cyclase, generate cAMP, activate aquaporin-2, increase collecting duct permeability to water, and concentrate urinary osmolality above that of plasma. Thus, cyst growth is “clamped” by vasopressin. . .How much water should I drink now? Patients have already figured out that if extra water decreases vasopressin and cAMP levels, then why isn’t plain old water a useful therapy? No one can give an informed, definitive answer to that question, but common sense leads me to think that sufficient water should be drunk to keep plasma vasopressin levels near a point that renders urine osmolality equal to or modestly lower than that of plasma. To know for certain how much of the “water cure” is prudent therapy, a carefully controlled clinical trial seems justified.

Sirolimus Reduces Polycystic Liver Volume in ADPKD Patients After Renal Transplantation
Torres V E 2008 J Am Soc Nephrol. 2008 Mar;19(3):631-8. Epub 2008 Jan 16
Treatment with sirolimus was associated with decreased polycystic liver volume, perhaps by preventing aberrant activation of mTOR in epithelial cells lining the cysts.

Sirolimus ameliorates the enhanced expression of metalloproteinases in a rat model of autosomal dominant polycystic kidney disease.
Berthier CC 2007 Nephrol Dial Transplant. 2008 Mar;23(3):880-9. Epub 2007 Nov 27.
Sirolimus treatment was associated with a marked improvement of MMP-2 and MMP-14 overexpression, and this
correlated also with less matrix and TBM alterations and milder cystic disease.

Therapeutic intervention for autosomal dominant polycystic kidney disease.
Edelstein CL 2008 Nephrol News Issues. 2008 Mar; 22(3):25-6
Water Prescription for PKD
Clin J Am Soc Nephrol. 2011 Jan;6(1):192-7. Epub 2010 Sep 28.
Design, setting, participants, & measurements In eight ADPKD patients eating typical diets, osmolality and volume were measured in 24-hour urine collections. The amount of additional ingested water required daily to achieve a mean urine osmolality of 285 ± 45 mosm/kg was determined. Participants were instructed to distribute the prescribed water over waking hours for each of 5 days. Blood chemistries, 24-hour urine collections, BP, and weight were measured before and after the period of supplemental water intake. Results Five patients achieved the 285 mosm/kg urine target without difficulty. Mean urine osmolality decreased and mean urine volume increased; serum sodium, weight, and BP were unchanged. Daily osmolar excretion remained constant, indicating a stable ad lib dietary intake of solutes and protein over the 2-week study period. Conclusions The amount of additional water needed to achieve a urine osmolality target can be approximated from the urine osmolar excretion in ADPKD patients eating typical diets, providing a quantitative method to prescribe supplemental water for such individuals.


Here is some information on water from the EWG. The city water from Honolulu and Minneapolis tastes unusually sweet and delicious. Both cities are listed among the top ten (10) city water supplies. polycystic kidney disease polycystic liver diseasecontact us
last updated: Saturday, September 7, 2013 7:54 AM