25(OH)D3 is not active D3. It is only parent compound. 1alpha hydroxylase is strictly controlled by several factors. So giving 25(OH)D3 let's the organism the ability to form the active hormone, if useful. On the contrary we should not give the active form (1,25 OH D3) bypassing many leading feedback mechanisms

Yes there are reccomendations. Please see the results of various working groups.

Please read http://www.european-renal-best-practice.org/content/jorge-b-cannata-andia

Vitamin D deficiency is not uncommon in dialysis patients who aren't taking an adequate amount of vitamin D. This could impact on non skeletal effects of vitamin D such as on the immune system. It is desirable to maintain a serum 25OHD level of 30 ng/ml or more with supplementation although some investigators believe 20 ng/ml is sufficient. Since dialysis patients can not maintain a normal serum 1,25(OH)D level even in the presence of adequate 25OHD, calcitriol in physiologic doses is commonly given to try to maintain normal mineral metabolism.

To begin with .. Vitamin D is dosed in routine hemodialysis?

the international literature overebounds of publications about this topic, which remains one of the most discussed topic of nephrology interest . It is sufficient to insert the key words " renal failure, vitamin D " in Pub Med or in other similar sites to obtain so many citations sufficient to read during some years.

The genetic variants in the vitamin D binding protein (DBP) gene are able to influence both endocrine and intracrine function of vitamin D. The low affinity or low DBP facilitating improved availability of 25OH at target cells (free hormone hypothesis). So, the bioavailable vitamin D is more important than total vitamin D. In this way, caution is required when we use vitamin D supplements.

Here is a review of >120 papers on Kidney and vitamin D

http://vitamindwiki.com/tiki-index.php?page_id=813

agree to suppement viamin D if the level is low. This is due to pleiotropic actions of

vitamind D beyond bone and calcium metabolism.

Vit D and PTH are inversely related so hyperparathyroidism is the consequence of a bad vit D control ; in this condition calcitriol or paricalcitol given n vein can control PTH concentration and then the catastrophic effects of hyperparathyroidism

pls read http://clinicaltrials.gov/ct2/results?term=NCT00977080&Search=Search

Great question, Bandana. I have long held that the Vitamin D campaign we are now on is an erroneous and half-thought out approach. A true vitamin D that is biocompatible to the human body does not exist in pharmacopia or at the health food store. It is a synthesis process by the human body--what I call a "Super D" that is immensely more complex and potent yet less toxic than what we call Vit D2 or D3. It is made with adequate nutrition, sunlight, and exercise--and to me, those key factors are what we need to be promoting with the public. Amazingly, when our clinic advise patients, particularly females, to take a high grade B-Complex, to stop microwaving their food and also to go >50% of their daily diet consisting of fresh fruits and vegetables, and to get about an hour of sunshine three times a week, those with low vitamin D go back to normal and bones start to repair (among other obvious benetits). They have to abstain from high caffeine (very hard thing for most people to do today--we are killing ourselves with caffeine and the health professions are as guilty as the public), tobacco, alcohol, drugs, reducing medication to only that which is essential. Nothing really exotic about this approach, but change to better health is stunning in every case seen to-date.,

Dear Bandana

These abstracts my be helpful for you

1) Vitamin D in chronic kidney disease.

Contrib Nephrol. 2013;180:98-109.

Li YC.

Abstract

Vitamin D deficiency is highly prevalent in patients with chronic kidney disease (CKD). The low vitamin D status is, to a large extent, caused by dysregulation of vitamin D metabolism as a result of renal insufficiency. Recent studies indicate that vitamin D-deficiency may promote or accelerate the progression of CKD, whereas treatment with low calcemic vitamin D analogs can reduce proteinuria and ameliorate renal damage in animal models of kidney disease and in patients with CKD. The renoprotective activity of vitamin D regulates multiple signaling pathways known to play important roles in renal injury. These findings underscore the importance of correcting vitamin D deficiency with vitamin D supplementation or with activated vitamin D analogs in the management of CKD

2) Nutrition prescription to achieve positive outcomes in chronic kidney disease: a systematic review.

Nutrients. 2014 Jan 22;6(1):416-51.

Ash S1, Campbell KL2, Bogard J3, Millichamp A4.

Abstract

In Chronic Kidney Disease (CKD), management of diet is important in prevention of disease progression and symptom management, however evidence on nutrition prescription is limited. Recent international CKD guidelines and literature was reviewed to address the following question "What is the appropriate nutrition prescription to achieve positive outcomes in adult patients with chronic kidney disease?" Databases included in the search were Medline and CINAHL using EBSCOhost search engine, Embase and the Cochrane Database of Systematic Reviews published from 2000 to 2009. International guidelines pertaining to nutrition prescription in CKD were also reviewed from 2000 to 2013. Three hundred and eleven papers and eight guidelines were reviewed by three reviewers. Evidence was graded as per the National Health and Medical Research Council of Australia criteria. The evidence from thirty six papers was tabulated under the following headings: protein, weight loss, enteral support, vitamin D, sodium, fat, fibre, oral nutrition supplements, nutrition counselling, including protein and phosphate, nutrients in peritoneal dialysis solution and intradialytic parenteral nutrition, and was compared to international guidelines. While more evidence based studies are warranted, the customary nutrition prescription remains satisfactory with the exception of Vitamin D and phosphate. In these two areas, additional research is urgently needed given the potential of adve

I agree that the use dela vitamin D needs to be standardized both in patients with chronic kidney disease than in healthy subjects. In recent years, vitamin D has set a right or wrong in all fields, to almost become a fashion .. are urgently needed guidelines

Thank you every one for answers, I highly appreciated your valuable opinion.

Despite what some poorly designed, biased studies suggest, there is a profound difference between D2 and D3, D3 hands down being the more bioavailable of the two. But again, if our interest is really to get the patient well we will address the addressable handful of underlying causes that bring almost all chronic disease: nutrition deficiencies (micronutrients particularly that which have dissappeared from the modern GMO and processed food supply), chronic dehydration (usually due to too much of a diuretic called caffeine and by not drinking enough water), heavy metal accumulations (lead is rising in the population and in the food supply), lack of restorative sleep (not remedied with a medicatiion), lack of adequate exercise (does not help that public schools elimiated PE), food and environmental toxicities (Aspertame and the other artificial sweeteners and food dyes are poison yet they still dominate the US food supply), HFCS, subclinical infections (usually from the teeth and jaw--rampant in those who do not floss daily), and unhealed injuries (usually of the spine, bringing various levels of stenosis and neuropathy). Bring in the sunshine, a daily wallk--combined with the foregoing--and watch the Mitochondria do the rest of the work. The way to wellness is wellness.

I confirm again that Vit D3 and Paricalclcitol in uremic people are considered and used for contrasting PTH bad effects ; a long term prescription can stimulate hypercalcemia and hyperphosphoremia and then induce arterial calcifications ; in other condition they can induce a great decrease of PTH concetration and then the adinamic bone disease ( PTH level has to be maintained between 3 - 4 fold normal values )

If the question is vitamin D deficiency (not hyper PTH) I would like say again: give parent compound (inactive 25 OH Vit D3) not active form (namely calcitriol). Some months later look at PTH

Marco and Ennio, thank you for re-emphasizing that--I thought somewhere in the comments so far that someone or someones had brought that out but in a cursory review during a busy day could not find them. I hope, too, that those charged with untangling the unfortunate health status of these kids will go deeper into causal factors and address those, as well. It is not just a matter of a quick drug fix or surgical procedure, but the searching and undoing of years of egregious health exposures and habits that got them where they are. We blame genetics, but in our opinion genetics only kick in after the real underlying factors are allowed to do their dirty work. Restoring health is always the noble and correct place to start--indeed, Hippocrates had it right, though he spent 20 years imprisoned for saying it and other self-evident truisms: Let food be thy medicine. Thanks again.

The European Best Practice Guidelines are stessing that:

- In patients with and elevated or rising PTH, calcitriol, or vitamin D analogs, or calcimimetics, or a combination of calcimimetics and calcitriol or vitamin D analogs should be used to lower iPTH.

The use of calcitriol or vitamin D analogs is effective in decreasing serum PTH levels and ALP levels (but may increase calcium and Phosphorus levels). The use of cinacalcet lowers serum PTH, calcium, phosphorus, the calcium phosphorus product, and b-ALP.

Of course, the best way to get vitamin D would be exposure to sunlight, which is not so easy in the CE climate!

ERBPG 4.2.4. In patients with CKD stage 5D and increased or

increasing PTH levels, calcitriol, vitamin D analogues, calcimimetics, or a combination of calcimimetics and calcitriol or vitamin D analogues should be used to decrease PTH levels.

The suggestions offered by newer therapeutic lines, do not yet seem to be based on clinical evidence of high grade and lack reliable data on the effectiveness of the correction of the "anomalies" laboratoristiche their CKD-MBD.L 'hyperphosphatemia is a powerful stimulus on the parathyroid yet this takes little account in the dietary prescriptions for dialysis. We know what the intake of phosphorus of our dialysis?

Vitamin D( Nutritional) deficiency is almost universal in my CKD patients.There is no good evidence that correction of this deficiency leads to improvement in any outcomes in CKD patients.However in patients with low vitamin D levels and high PTH ,i give them vitamin D3supplementation 60000 units orally per week for 6 to 8 weeks and then once a month for 6 months and recheck vit D3 and PTH levels to decide further course of action.

It is recommended to maintain levels of 25OH above 20-30 ug/mL. in a recent study, Fernández Juárez et al (PRONEDI study, CJASN November 2013) have shown a faster progression to ESRD in diabetic patiens with 25 OH levels < 15 when compared with patients with levels above 15.

To Vijay Kher: I think that vitaminD (nutritional i.e. inactive parent compound) deficit must be corrected in every case namely even if PTH is low. Are you agree ?

The use/abuse of Vitamin D compounds in dialyisis patients presents a long history and I think nephrologysts have some "skeleton in their closet" about this. In the past I remember that e.v Calcitriol was used to control hyperparathyroidism and that nephrologists tried to bring up serum calcium levels to better inhibit PTH release; in the past much less importance was given to systemic calcifications!!

Today a lot of dialysis patients are treated with Vit D compounds to control PTH release; moreover someone suggests the use of combining different Vit D (inactive and calcitriol or paricalcitol) to control hyperparathiroidism and systemic deficency.

My opinion is that there is a great risk of hypercalcemia and hyperphosphoremia in dialysis patients in ESRD patients. Where are the proofs of a beneficial effect of Vit D status correction in ESRD patients? Someone showed a greater survival treating 25 OH deficency in ESRD patients? I think that it is better to avoid other "skeleton in our closet" and to be extremely cautious with Vit D use in dialysis patients other than hypeparathiroidism treatment.

to Lucio Manenti. I have some "skeleton in my closet" too, and I don't want other ones. However Inactive 25 (OH) vit D is the same of sun light and of salmon. Are all dangerous? My opinion is that inactive 25(OH) cannot led to hypercalcemia or hyperphosphoremia. 1 alfa hydroxylase is tightly regulated and it is the rate-limiting step. I give it only the capability to work

Vitamin D is always made better by sunlight than from a pill--if a patient deficient in Vitamin D needs to be handed a prescription that says, "30 minute walk in the sun daily" so be it. We keep forgetting nature does it better than man.

The various activated vitamin D products are used as a means to

treat SHPT and are often limited by adverse effects such as

hypercalcemia and hyperphosphatemia. Observational studies

show a survival benefit from treatment with activated vitamin

D in dialysis patients that is independent of PTH, calcium, or

phosphorus level, suggesting that all patients with CKD could

benefit from some form of vitamin D replacement therapy. No

RCT are available to prove this hypothesis.

Teresa is correct, from theory to practice this is all very complex for translational purposes. I have often felt we are putting the cart before the horse when looking for a one-size-fits-all solution. Nature has already taken care of that through diet, exercise, hydration, and abstinance from all that we know is detrimental to one's health--including medications that cause more problems than they solve. Treatment programs that leave out the basics are always doomed to fail in the end.

Since there is much more than vitamin D alone involved in CKD patients, I like the European pediatric guidilenes approach better, where the basic parameter is Ca*P product, and Ca- and non-Ca phosphate binders and Calcitriol are given according to those results. Sounds more "physiologic" to me, that isolated parameters. Guidelines downloadable on ESPN website.

Check out p 87 in the attached file

At pag 88 I also read:"and in the CKD population with vitamin D deficiency, simple vitamin D replenishment is all that is indicated until new evidence becomes available"

Dear Colleagues,

The latest observations you have made are a further demonstration that we have no clear ideas that are needed clinical evidence and several longitudinal studies before we can write the guidelines.

Good point, Teresa. I think guidelines should start with that which is optimal. Getting exercise, sunlight, adequate quality sleep, reduction of all unnecessary medications, rectifying of any nutrient and micronutrient deficiencies, hydration, refrain from caffeine and other drugs, adopting a basically organic diet, no microwaving of food, and I believe that is the best place to start in any treatment program. Anything else would be suboptmal and rsks endangering the health of the patient.

I read with interest all of our contributions to discussion: I think that 25 (OH) can be administered without risk to dialysis patients;in my experience there aren't problems related to hypercalcemia. In Italy, Dr Luigi Morrone started an interesting work trying to answer this point of discussion (Nutrivita Study); another question which is your conduct in kidney transplant patients with low 25(OH) D....?

I hope in our discussions on the kidneys that we acknowledge how damaging most prescription drugs are to them. We have seen so many dialysis cases on 10-12 meds and wonder how their healthcare providers expect their kidneys to survive. Polypharmacy can drive stage 1 to stage 5 in a matter of months. It is far better to attack underlying causes (diet, lifestyle, toxicities, medications, hydration, caffeine, subclinical infections, injuries--yes, they add up!)...anything less is wasting precious resources.

And Max, what about the fact that polypharmacy often means that not only kidneys are diseased, but also other ogansystems in the body? I agree with you that attacking underlying causes should be highly addressed in current medical daily practice, however sometimes other comorbidities make changes rather impossible. Therefore I'd suggest we start looking at a patient with a broader view, combining expertise from different (disease) domains, instead of focusing on single organ systems alone.

So far, most of the information about vitamin D deficiency and effects on human body are associations, leaving us the question whether vitamin D deficiency is cause or consequence in diseased individuals. Let the waiting for the longitudinal studies begin...

Absolutely agree, Laura. Actually, that was my point. That is why my research has centered upon underlying causes of all chronic disease--addressing symptoms, (which are uncountable) and ignoring underlying factors (which are essentially few) is in my thinking the biggest reason renal disease is such a clinical minefield. Of course, those underlying issues (some of them named above) are what brought on the chronic conditions in the renal problem, in the first place. And I think your implication is correct that many cases of Vit D3 deficiencies are consequential to those contributors that cause disease. Longitudinal and broader are keywords, for sure. Thank you!

Hi,

I agree on the point that the patient should be examined in a comprehensive manner and that you can not focus only on organ damage, but who has the clinical skills to do this? internist or specialist? until we realize that today is more than ever necessary to exercise the medical art in a multidisciplinary way we'll be here to ask the significance of the low levels of vitamin D in patients with polypathology and pluriterapie. Thanks for your attention

In renal transplant recipients with low levels of Vitamin D I Agree to analyze the situation mainly bone, usually altered by the previous condition of the dialysate, especially if the duration of the substitution therapy dialysis was long, analyze the levels of parathyroid hormone, the dose of steroids taken, renal function, proteinuria, diet, underlying disease, the age and the age of the graft according to me ... These are all necessary assessments before deciding whether or not to administer vitamin D. ..

Multidisciplinary is key, I feel, Theresa. Usually no one individual has the wherewithal or time or training to do a comprehensive review we are talking about here. But for the patient's sake it is often necessary.

This is indeed a very tricky subject, like putting the patient between Scylla and Caribda... nevertheless a meta analysis of studies on vit D level in CKD and dialysis has shown that the mortality correlates with lower level of vit D. Regards, Michaela

Michaela, thanks for the attachement (I have just dowloaded it). Sincerely marco