Delay Diabetic Kidney Disease

Treatment Research/Cure
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Up to 40% of diabetics may develop kidney disease, and since the patient’s genetics are an important causal factor, controlling blood sugar is a less effective way to prevent diabetic nephropathy than it is for preventing other complications. (A. McKnight, et al., “Genetics of Diabetic Nephropathy: A Long Road of Discovery,” Current Diabetes Reports, 15 (7) 41 (2015))

There is, however, one adjunctive therapy that can delay the progression of diabetic nephropathy, and that is a form of modified charcoal, AST-120 (Kremezin) that has been used in Japan, Korea, and the Philippines as a standard treatment for this condition since the 1990s. There have been numerous scientific studies of its effects, and it seems to work by absorbing the toxins left circulating in the body because of declining renal function, which in turn worsen the health of the kidneys, in a vicious cycle which accelerates their decline. Because the chemically modified charcoal in AST-120 absorbs these toxins, the vicious cycle is interrupted. Here is an example of one study of its effects:

Diabetes Res Clin Pract. 2008 Sep;81(3):310-5. doi: 10.1016/j.diabres.2008.04.024. Epub 2008 Jun 11.
AST-120 (Kremezin) initiated in early stage chronic kidney disease stunts the progression of renal dysfunction in type 2 diabetic subjects.
Konishi K1, Nakano S, Tsuda S, Nakagawa A, Kigoshi T, Koya D.

Abstract
There is little clinical evidence when AST-120 should be prescribed for subjects with early stage overt diabetic nephropathy. We therefore designed a prospective, randomized, controlled study for subjects with type 2 diabetes (serum creatinine <1.5mg/dl and urinary protein >0.5g/day) in November, 2001. The primary end point was defined as exceeding 2mg/dl of serum creatinine, and the secondary end point was defined as introducing a hemodialysis. Twenty-two subjects were selected, and after excluding 6 drop-out subjects, 16 subjects (10 in the control group; 6 in the KRM group) finally entered the study. Mean follow-up periods were 37 and 34 months in the control and KRM groups, respectively. There was no difference in clinical characteristics including renal dysfunction at baseline between the two groups. There was a significant reduction in urinary indoxyl sulfate at month 12 in the KRM group than in the control group. A significant difference was observed in changes in mean levels of serum creatinine versus time between the two groups. The primary end points were counted in 7 (70%) of the control subjects, while only 1 (17%) of the KRM group, and the Kaplan-Meier analysis was statistically significant. Although 4 (40%) of the control group and 1 (17%) of the KRM group were initiated hemodialysis as the secondary end point, the difference did not reach a statistical significance. Thus, we concluded that administration of AST-120 initiated in early stage overt diabetic nephropathy stunts the progression of renal dysfunction.

Although AST-120 is available only with a doctor’s prescription in Japan, outside Japan it can be ordered without a prescription. It seems to be effective in slowing all forms of renal disease, since by absorbing the toxins associated with declining renal function it interrupts the accelerative process by which all renal diseases cause kidney failure.

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I wonder how lower carb/higher protein diets might be dangerous for kidneys. Can anyone give feedback on that?

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At the later stages of renal decline patients are usually advised to follow a protein restriction diet, since the loss of protein in the urine itself accelerates the decline of renal function.

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The primary end points were counted in 7 (70%) of the control subjects, while only 1 (17%) of the KRM group, and the Kaplan-Meier analysis was statistically significant. Although 4 (40%) of the control group and 1 (17%) of the KRM group were initiated hemodialysis as the secondary end point, the difference did not reach a statistical significance. Thus, we concluded that administration of AST-120 initiated in early stage overt diabetic nephropathy stunts the progression of renal dysfunction.

Sorry, but these results are worthless for clinical practice decisions. The sample size (10 controls, 6 treatment) does not even meet the criteria for a decent pilot study, let alone a study by which anyone should make treatment decisions. The study question is a good one and one wonders why it the study has not been done, if it hasn’t, with a larger, representative sample.
Eat charcoal if you want but not based on this as a scientific reason for it. I am sure there are members here who are still in the research field. I only worked at NIH, quite a few years back but I do know the requirements for a sound research study. The author could have concluded: warrants further study, maybe.

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I agree that further studies are always useful to confirm early indications, but for patients whose kidneys are now in accelerative decline waiting to try something which may slow the loss of function until its benefits are fully established may not be a sensible option. As I said initially, there have now been 20 published peer-reviewed studies of the benefits of AST-120 in chronic renal disease, of which I gave an example of one which was particularly relevant to diabetics. Other studies, such as the one whose abstract is copied below, are larger-scale and more convincing:

Heart Vessels. 2016 Oct;31(10):1625-32. doi: 10.1007/s00380-015-0785-7. Epub 2015 Dec 23.
Long-term effects of AST-120 on the progression and prognosis of pre-dialysis chronic kidney disease: a 5-year retrospective study.
Sato E1, Tanaka A2, Oyama J3, Yamasaki A2, Shimomura M2, Hiwatashi A2, Ueda Y4, Amaha M1, Nomura M1, Matsumura D1, Nakamura T1, Node K5.

Abstract
AST-120 has been used widely in Japan to slow the deterioration of renal function in patients with chronic kidney disease (CKD) by decreasing uremic toxins. The heart and the kidney are closely related, with cardiorenal interaction being very important. This retrospective study examined whether AST-120 influences the prevalence of dialysis induction, mortality, and cardiac and stroke events in CKD patients. The study included 278 patients diagnosed with chronic renal failure (CKD stage: III-V) in 2006. Of these patients, 128 received AST-120 (6 g/day), while the remaining 150 patients did not. A log-rank test was performed to compare dialysis induction, mortality, and cardiac and stroke events in the two groups. Univariate and multivariate Cox proportional hazard regression analyses were used to identify the potential factors that contributed to dialysis induction, mortality, and cardiac and stroke events over the next 5 years. Patient profiles before the study were almost the same other than age, primary disease (DM or non-DM) and urine volume. The prevalence of dialysis induction, mortality, and cardiac and stroke events in patients treated with AST-120 was significantly lower after 3 and 5 years (p < 0.0001) compared with the prevalence observed in the untreated patients. The absence of AST-120 treatment was associated independently with a high risk of dialysis induction (hazard ratio 4.979, 95 % CI 3.502-7.079, p < 0.0001), mortality (4.536, 2.666-7.720, p < 0.0001), cardiac event (3.590, 2.572-5.011, p < 0.001) and stroke (1.949, 1.342-2.829, p = 0.0005). The results of this retrospective analysis suggest that long-term treatment with AST-120 may improve the prognosis of CKD patients in the pre-dialysis stage. Long-term (i.e., >5 years) prospective randomized studies are needed to confirm the findings of the current study.

So what is the reasonable recommendation? Simply sit back and wait for the natural progression of chronic diabetic renal disease to put you on dialysis or try something which has been found in a five-year study of 278 patients to be associated with a lower risk of dialysis induction? It is worth noting that this product is not just charcoal, but is a modified charcoal which better absorbs uremic toxins than ordinary charcoal.

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Dogs and cats are routinely treated with activated charcoal in cases of ingested toxins (such as grapes or raisins). This has been practiced for many years. The NIH has several formal abstracts on the use of activated charcoal (AST-120), the most recent of which is this: https://www.ncbi.nlm.nih.gov/pubmed/23689670

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@Seydlitz, I remember reading in one of your posts stating that you had renal issues. Are you going to use AST-120 to help you prevent further deterioration of your kidneys? Will AST-120 help diabetics with unhealthy kidneys, and start AST-120 regimen? What is the typical daily dosage?

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No, I don’t take AST-120. The normal dose of AST-120 is 2 grams three times a day. It is difficult to dose correctly, however, since just as it absorbs uremic toxins, it can also interfere with the metabolism of any medicines you might be taking. For example, when it was used to combat chronic allograft nephropathy in patients with renal transplants, it was found, surprisingly, to increase the amount of the immunosuppressive drug they were taking, cyclosporine, in the bloodstream to dangerously high levels. Eventually it was determined that AST-120 does not interact with cyclosporine in an olive oil emulsion, which is one form in which the drug is available, but it does interfere in the more normal, encapsulated form of the drug. The olive oil emulsion had to be substituted for the encapsulated form, but since the emulsified form of the drug was not dose-equivalent to the encapsulated form, an extended period of testing of the drug levels in each patient was necessary to determine the correct dosing. So, it’s complicated.

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Seydlitz, you neglect to mention that a huge huge risk factor for kidney disease on top of diabetes, is high blood pressure.

For the good of your kidneys, make sure your blood pressure is under control. Many of us are on super-aggressive low blood pressure targets and I think there’s good reason.

ACE and ARB inhibitors are another powerful tool for kidney protection.

I really hope folks are keeping their blood pressure controlled and using ACE inhibitors before they do bonkers stuff like charcoal.

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I never purported to be providing a full guide to preventing diabetic kidney failure, a subject to which entire books have been devoted! Of course a healthy blood pressure is always important to preserving renal health, though to some extent the association between worsening blood pressure and renal decline can be explained by the kidneys themselves losing their ability to contribute to normalizing blood pressure, so hypertension is both cause and effect. ACE inhibitors are especially useful, since they help not only by reducing blood pressure, but they also seem to have some effect in promoting renal health even apart from that.

But, unfortunately, all these measures can at most delay the decline in renal function, but not stop it. Thus the reason for looking further afield to alternatives to slow the progress even more than conventional treatments can do. It is important to note that since the 1990s AST-120 has been used as a first-line conventional treatment for patients with declining renal function in Japan, South Korea, and the Philippines, so there is no reason to let social and institutional factors such as national borders and medical cultures deprive people of a few extra years delay in initiating dialysis. Renadyl has also been confirmed to delay dialysis initiation, so since it consists just of a few microbiota which have been raised to feed on uremic toxins and so do a good job of cleansing these toxins in the intestines, there is no reason for patients with declining renal function not to try it, unless they are terrified of that type of yoghurt.

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Diabetics are at risk of renal problems. What do I watch out for to keep my kidneys healthy? In my last blood test I keep an eye on my eGFR results. This will show how my kidneys’ filtration function is performing. Then I also watch for the albumin and creatinin counts.

What other tests should diabetics watch for to help monitor their kidney’s health?

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Glomerular filtration rate, or GFR, is the basic measure of renal health. Alternatively, creatinine levels are sometimes measured, which provide another look at the same function. A normal creatinine level should be around 80. Albumin really just provides an indication of how good your nutrition is, so it is not much used as a measure of renal function, though urinary albumin can show whether protein is leaking into the urine, which is a sign that something is wrong with the kidneys. An indirect measure of declining renal health is a lower hemoglobin value, since healthy kidneys help you avoid anemia.

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I have never had blood pressure issues, but because of my age, and the fact that I’m T1D, my doctor has had me take an ACE inhibitor for years. It’s a tiny pill that I take once a day. Easy enough, and my kidney function tests have been normal for years as well.

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Diabetic nephropathy is the most heavily genetically driven complication of diabetes. Years ago, back in the late 1970s, I remember looking at a chart of the time after diagnosis when diabetics developed end-stage renal failure, and there was an extreme peak at 17.5 years after onset. My first thought was, this must be genetic, since why else would it occur after almost the same number of years in so many different patients with such different lifetime blood sugar profiles, and why else would the number of new onsets decline as the patients got past the 17.5 year peak, even though they must have suffered a much greater exposure to hyperglycemia over their many more years of diabetes? I discussed my idea at the time with someone from New York Medical College, but all he said was that it was ‘very interesting.’ Only much later did research confirming the genetic hypothesis start appearing.

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I have had T1 diabetes for 52 years since I was 16. I got a kidney transplant 6 mos ago.

You should mostly watch your creatine level as it tests the health of your kidney.

Unfortunately for the first 15 years I had diabetes I virtually ignored my diabetes. As a result I am sure my BG was mostly in the 300s and occasionally in the 200s. I think that was the principal cause of my kidney failure. My veins, arteries and organs also calcified so they are virtually turning to bone. When they opened me up for a transplant I was told they may not transplant me if I was too calcified. Luckily they found a spot they were not considering And I woke to find I had a new kidney.

So it is important to mange you BG in the early years. I did manage my BG pretty well as an adult, A1C of 5.1, but it is important to do it early as that was my downfall.

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Well, rcarli, you shouldn’t blame yourself too much for having developed cardiovascular and renal disease, since in diabetics these conditions are both closely associated and heavily driven by genetic factors rather than by blood sugar control. Consider this study:

"Curr Diab Rep. 2015 Jul;15(7):41

Genetics of diabetic nephropathy: a long road of discovery.

McKnight AJ, et al.

Abstract

The global prevalence of diabetic nephropathy is rising in parallel with the increasing incidence of diabetes in most countries. Unfortunately, up to 40 % of persons diagnosed with diabetes may develop kidney complications. Diabetic nephropathy is associated with substantially increased risks of cardiovascular disease and premature mortality. An inherited susceptibility to diabetic nephropathy exists, and progress is being made unravelling the genetic basis for nephropathy thanks to international research collaborations, shared biological resources and new analytical approaches. Multiple epidemiological studies have highlighted the clinical heterogeneity of nephropathy and the need for better phenotyping to help define important subgroups for analysis and increase the power of genetic studies. Collaborative genome-wide association studies for nephropathy have reported unique genes, highlighted novel biological pathways and suggested new disease mechanisms, but progress towards clinically relevant risk prediction models for diabetic nephropathy has been slow. This review summarises the current status, recent developments and ongoing challenges elucidating the genetics of diabetic nephropathy."

Because genetics has such a profound influence on the development of diabetic complications, the value of strict blood sugar control has to be in part discounted by the degree to which complications are driven by inherited factors. In my case, for example, both my paternal grandmother and I developed type 1 diabetes, but even though my blood sugar control was infinitely better than hers, since I was diagnosed almost 20 years after her, I developed exactly the same type of complications to exactly the same degree and after exactly the same number of years after onset as she did, so I have to ask, what difference did my strict blood sugar control make?

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(Experienced & knowledgeable but NOT a doctor) A lot of studies that examine history cases, not active trials, have found 3 deficiencies in diabetics with neuropathy & nephropathy. The main and important ones are magnesium, zinc and mangangese. A prenatal birth defect I have of being born with only 1 kidney, I’m “on top” of protecting the only one I have. Compared to non-diabetic family members, I’m pretty much right there with them and have increased my gfr above past rates by replenishing these nutrients.

Due to a ~4-year undx adrenal insufficiency, a nephrologist at one point said I was going into kidney failure. (Had a ~long discussion with him when I was in hospital and he walked out, apologized for the fight I’ve had and said I was probably right). Anyways, these improved my gfr above my baseline and also, if you’re able and doctor has no objections, get checked (magnesium they can’t really check) and vitamin c helps prevent hemoglobin from becoming glycated, thus it’ll slow down any damage and also lowers your A1C, for me about .5%. With us, our “higher” glucose levels, the body will urinate these nutrients away, even when endo is happy with our A1C, and causes us to be deficient even if we eat the healthiest of diets and get more than enough of them. (Presuming an A1C of >=6%)

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I applaud your initiative in trying to think and act ‘outside the box.’ The usual approach of conventional medicine is to say we will only apply treatments that have been exhaustively tested scientifically for safety and effectiveness, even if we know that these are inadequate to restore you to adequate health and cannot prevent you from getting much sicker, and indeed, even if we know that there is as yet only partially tested research showing that there are other things you could try which might save your life. These options we will never discuss with you, reveal to you, use on you, or make available to you, because they have been proved to save patients’ lives only in adequately sized studies or only over inadequately long studies or because some potential statistical flaw can be found in the work that has been done or because the evidence supporting their efficacy is merely anecdotal.

But the idiocy of medicine in this argument is that what is scientifically right is not the same as what is existentially right, since we are patients whose health and lives are threatened today and many of us feel we must try to save our health and life today because we cannot afford to wait 20 or 30 years for adequate scientific studies to be undertaken. This is especially a problem with supplements, because expensive, large-scale scientific studies will never be undertaken to prove their efficacy, since they can’t be patented and thus cannot be sufficiently profitable to repay the cost of such studies. Oftentimes to live you have to try things which are not scientifically proven, and it should be up to you how much of a risk you want to take with unproven treatments to save your life. Unfortunately, for many treatments, the FDA and similar regulatory agencies elsewhere say that this is not your personal right, but that it is the right of government bureaucrats to block your freedom to decide for yourself how you will try to save your life.

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Visit to treatment and find the well clinic.

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I wonder about the genetic factor. Since type 1 and type 2 diabetes are very different, is it possible that the correlation between diabetes and genetic predisposition to nephropathy is much more pronounced in one type but not in the other? Intuitively I’d guess that predisposition to type 2 diabetes is more likely to have this correlation, since T2 is a metabolic disease, while T1 is autoimmune. Also, T2 - more specificially, insulin resistance - is often accompanied by high blood pressure and form the metabolic syndrome (and high blood pressure, as was mentioned in this thread, is bad for your kidneys), while T1 doesn’t correlate with high BP as far as I know.