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Idea#198

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Alkali therapy to slow down progression of CKD

Recent studies in experimental animals and clinical studies suggest that alkali therapy may be a powerful suppressor of CKD progression. There is a need for well controlled studies and using alkali formulations that are more palatable than existing ones to enhance patient compliance.

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Submitted by Daniel Batlle 3 years ago

Comments (9)

  1. For such powerful reported effects (through such a simple intervention) to have gone this long with so few human trials is a research oversight clearly needing correction.

    NIH and other governmental direct funding will be crucial, since industry will not pay for this particular avenue of research.

    Without *substantially* more direct support, studies will continue to be small and isolated, and definitive answers to the alkali question will continue to languish.

    3 years ago
  2. Has this therapy been shown to have any benefit for genetically-based CKD such as PKD?

    3 years ago
  3. Yes, PKD community has been studying this, (more often potassium citrate, sodium citrate.) Promising animal (PKD rats) results since around 2000 (Tanner). Also for prevention of kidney stones in PKD.

    3 years ago
  4. I was aware that citrate salts had shown promise in delaying CKD progression in PKD rats. I guess I was thrown off by use of the word "alkali" in the title. Potassium and sodium citrate are not alkaline salts as citrate is the conjugate base of citric acid, a weak acid. A citrate buffer is used to maintain pH 3-6, well in the acid range. Sodium bicarbonate and calcium carbonate, however, are alkaline salts.

    3 years ago
  5. These citrates are metabolized to corresponding bicarbonates, so act as systemic alkalizers.

    Potassium salts advocated by some due to excess sodium "concerns" (despite surprisingly few reported problems in these recent studies - a finding contrary to expectations) Total amounts of actual sodium arguably modest regardless.

    3 years ago
  6. Perspective: For the first time in nearly a generation, it looks like we might have found a truly "new" weapon against CKD. Not just refinement of upon previous strategies--something different.

    If this effect is confirmed and sustainable (plausible), CKD becomes a far more "manageable" disease for many, or even most patients. ESRD or dialysis delayed not by a few years, but perhaps a decade or more.

    (“Powerful suppressor” as described by Daniel Batlle refers to recent studies showing relative impacts ranging from 30%-80%, even for early CKD). The alkali question MATTERS, not just for the sake of scientific curiosity, but for today’s patients--not just future generations. We can’t let the alkali question languish yet another 25 years.

    Thank you very much Dr. Batlle for posting on this highly important topic.

    3 years ago
  7. Daniel Batlle Idea Submitter

    Thank you for your support of this concept and kind words, Dr. Carter. As you are probably aware, most of the recent work in this area comes from studies led by Dr. Don Wesson. Both in the rat model of renal ablation and in patients with CKD associated with hypertensive nephropathy, there has been a remarkable effect in terms of disease progression. I concur with your sense of urgency to undertake such studies in CKD patients, but I would propose including patients with diabetic nephropathy or even study them separately as this population was not included in Dr. Wesson's clinical studies. Given the importance of diabetic nephropathy, it seems that studies in such patients are warranted and perhaps this should be a separate proposal altogether. Before I propose it as a separate idea on this website, I will wait to see if there are any comments in this regard.

    3 years ago
  8. Based on Wesson and others' hypothesis that this involves endothelin-1 and other inflammatory mechanisms(results are disproportionate to what can be explained just in terms of acid-base), I concur there seems reasonable probability of equal or greater relevance to diabetic nephropathy.

    However, I would not recommend diluting this topic as a separate post. Diabetics should definitely be included within future research cohorts, which would expand, rather than limit our knowledge of relevant patient populations. However, it does not seem that diabetic nephropathies’ response to alkali therapy would arise through fundamentally *unrelated* mechanisms. (Therefore, it seems that they represent one aspect of the alkali question, rather than comprising a truly separate question.) Sub-analysis should be relatively straightforward.

    Phase II of KRND will provide opportunity to refine research strategies.

    3 years ago
  9. Daniel Batlle Idea Submitter

    Thanks again for your comment and support Dr. Carter. Since our last communication of about 2-3 weeks ago, no one has offered comments regarding the need of a separate study in diabetic nephropathy. Therefore, I agree with you that for now, the focus should be on prevention of CKD progression in general using alkali-based therapies and that in phase II of the KRND, the issue of diabetic nephropathy can then be addressed.

    3 years ago

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