Vitamin Deficiency and Supplementation in CKD: An Interview
Patients with chronic kidney disease (CKD), including those receiving dialysis, may be at increased risk of developing vitamin deficiencies due to anorexia, poor dietary intake, protein energy wasting, restricted diet, dialysis loss, or inadequate sun exposure for vitamin D. In a Review recently published in AJKD, Angela Yee-Moon Wang and colleagues emphasize the need for individualized assessment of the use of vitamin supplementation in the CKD population rather than a “one size fits all” approach that had been adopted in the past.
AJKDBlog Interviews Editor Timothy Yau (@Maximal_Change) caught up with Dr. Wang (@aymwanghkuhk) to discuss why patients with kidney disease are at higher risk for vitamin deficiency, the specific manifestations, and how/when to supplement.
Professor Angela Yee-Moon Wang is an academic nephrologist and Clinician Scientist at the Department of Renal Medicine, Singapore General Hospital, Duke-National University of Singapore Medical School. She is passionate about research in cardiovascular-kidney-metabolic complications and renal nutrition in kidney disease. She is presenting this interview on behalf of the author group of their recently published Review: Rengin Elsurer Afsar, Elizabeth J. Sussman-Dabach, Jennifer A. White, Helen MacLaughlin, and Talat Alp Ikizler.
AJKDBlog: Let’s start with a general question about this issue. What are some of the reasons patients with kidney disease are at higher risk for vitamin deficiencies, and how does this manifest?
Dr. Wang: With advanced CKD, patients may have poor appetite, anorexia, inflammation, protein-energy wasting (PEW) or altered taste, all of which may reduce dietary intake or variety. Additionally, patients may be asked to limit intake of foods such as fruits, vegetables, whole grains, dairy products, beans and fermented foods for potassium and phosphorus concerns but these foods constitute a healthy dietary pattern. A specific issue for patients receiving peritoneal dialysis includes abdominal fullness from PD dwells, which may limit food intake. Water-soluble vitamins are also lost during dialysis treatment. All these factors may account for the higher risk of vitamin deficiencies. The manifestations of vitamins deficiency may be summarized in Table 1 of the article. Table 2 provides the key food sources of the various vitamins for our patients and healthcare providers.
Clinical Manifestations of Vitamin Deficiencies. Table 1 from Wang et al, © National Kidney Foundation.
Natural Food Sources of Vitamins. Table 2 from Wang et al, © National Kidney Foundation.
AJKDBlog: You reference the 2020 KDOQI nutrition guidelines in CKD – where do they stand
on the issue of vitamin supplementation in kidney disease, and does your review paper offer any additional insight beyond their conclusions?
Dr. Wang: The overall clinical trial evidence in this area remains quite weak since the publication of 2020 KDOQI nutrition guidelines in CKD. There are no randomized trials to support benefits on kidney, cardiovascular or patient-centered outcomes with any vitamin supplementation. The general principle we suggest is to ensure adequate intake of various vitamins of our patients through natural food sources and watch out for patients who may be at higher risk of vitamin deficiencies due to poor appetite, PEW, or loss during dialysis.
Nutritional vitamin D deficiency should be corrected but the supplementation dose and formulation need to be personalized, taking into consideration the degree of 25-hydroxyvitamin D deficiency, parathyroid hormone levels, CKD stage and local formulation. Routine supplementation of vitamins A and E is not supported due to potential toxicity. The additional insight our review provides is the importance to personalize the decision whether to provide vitamins supplementation on an individual basis. While more trial data are required to elucidate the roles of vitamin supplementation, all patients with CKD should undergo periodic assessment of dietary intake and aim to receive various vitamins through natural food sources and a healthy eating pattern that includes vitamin-dense foods.
AJKDBlog: I want to start backwards and ask a question before we jump into the specific vitamins A-E. When I was in training (2009), nearly all of my dialysis patients were on Nephrocap multivitamins. I remember reading one of the first posts on Renal Fellow Network on this topic. Has this practice of providing water soluble vitamins to ESKD patients fallen out of practice, and if so, why?
Dr. Wang: Clinical practice guidelines now offer more nuanced recommendations regarding vitamin supplementation, focusing on specific deficiencies rather than routine supplementation for all patients. There has been a shift towards nutritional supplementation based on individual patient needs rather than a one-size-fits-all approach. Importantly, there are no large-scale, definitive studies that have tested the long-term outcomes of routine water-soluble vitamin supplementation in ESKD patients, leaving the practice based largely on observational data and expert opinion. Increased emphasis on dietary management and the involvement of dietitians in the care of ESKD patients have improved nutritional status through tailored diets that meet the specific needs of each patient. This approach can reduce the need for additional supplementation by ensuring a varied diet is encouraged.
AJKDBlog: Nephrologists think about Vitamin D and its derivatives more than any of the others, so I want to focus on some of those that are lesser discussed. For example, vitamin A supplementation is rarely given to patients, and is relatively contraindicated in patients with kidney disease. Can you explain why?
Dr. Wang: Normally, the kidneys help regulate vitamin A levels in the body, but in kidney disease, this regulation is disrupted. We know that vitamin A is stored in the liver, and with CKD both retinol and retinol binding protein are elevated in the blood, likely due to increased hepatic synthesis rather than due to reduced GFR. This can lead to the accumulation of vitamin A and its metabolites, so supplementation with vitamin A carries a high risk of hypervitaminosis A and toxicity. Symptoms of vitamin A toxicity include dry skin, hair loss, liver damage, bone pain, and an increased risk of fractures. So the relative contraindication of vitamin A supplementation in ESKD patients is due to the altered metabolism of vitamin A in kidney disease, the high risk of toxicity, and the lack of evidence for its benefit.
AJKDBlog: Many of the Vitamin B subgroups can actually be measured and supplemented if needed. What are some of the big takeaways concerning Vit B supplementation in kidney disease that may differ from the general population?
Dr. Wang: Patients with CKD are at higher risk for water-soluble B vitamins deficiency compared to the general population, primarily due to inadequate dietary intake and intradialytic losses in patients on maintenance dialysis. Special consideration must be given to folic acid supplementation in dialysis patients of childbearing age or in pregnant patients, who are at moderate risk for low folate state and neural tube defects. One must bear in mind that folic acid supplementation may mask vitamin B12 deficiency, requiring additional screening for B12 levels. It should be noted that high replacement doses of vitamin B12 may induce cyanide toxicity in patients with CKD, albeit the risk is small.
AJKDBlog: Vitamin C is interesting because many CKD patients are low in these levels, but high dose repletion has been associated with oxalate nephropathy. How should we approach Vit C supplementation as clinicians, since it is not something that is routinely measured?
Dr. Wang: That is correct, vitamin C is not routinely measured as part of treatment or care for CKD patients at any stage. As a clinician, it’s important to look for clinical signs and symptoms of vitamin C deficiency, including bleeding gums, perifollicular hemorrhages, poor wound healing, joint pain and swelling, and bruising easily, among others. Many of these symptoms are not exclusive to vitamin C deficiency however knowing what they are could lead a clinician to check vitamin C levels if their patient is experiencing these symptoms and make a diagnosis and treatment plan if appropriate.
AJKDBlog: I was surprised to see so much discussion about Vitamin K and its reduced function in patients with kidney disease. Can you discuss the effects of Vitamin K deficiency on patients and the data related to repletion?
Dr. Wang: Vitamin K is an interesting one right now and there are ongoing studies to watch out for. Vitamin K works in many pathways involved in clotting, bone metabolism and helps to inhibit vascular calcification. Several medications commonly used in CKD, such as anticoagulants, phosphate binders, calcimimetics and proton-pump inhibitors can interfere with vitamin K and its actions, and dietary intake of vitamin K can be poor, so deficiency is relatively common.
Vitamin K deficiency can have significant effects, including higher risk of vascular calcification and cardiovascular disease and bone disease – things we commonly see in people with kidney failure. So far, the trials show that supplementation with vitamin K can improve vitamin K status, but most haven’t shown a direct benefit on vascular outcomes. These studies are mostly small and the optimal dose of vitamin K hasn’t yet been determined. There are more studies underway right now, but at this stage all we can say is that supplementation reduces deficiency, but whether that is beneficial for longer-term outcomes, we still don’t know.
Many people with CKD can obtain sufficient vitamin K from food sources like green leafy vegetables (vitamin K1) and fermented foods, meat, and cheese (vitamin K2). However, keeping vitamin K intake consistent is key. A renal dietitian can help tailor a diet plan that includes vitamin K containing foods, while considering the patient’s overall nutritional needs and restrictions. Consistent intake of vitamin K is important to avoid fluctuations that could affect medication efficacy. Patients should discuss any dietary changes or supplementation with their healthcare provider to manage potential interactions.
AJKDBlog: Last question, and I want it to be something that the readers can take with them to clinical practice since vitamin deficiencies are often not on the forefront of their minds. If you have a patient with advanced CKD or on dialysis, how and when should you assess their dietary vitamin intake and/or assess their levels with lab analysis?
Dr. Wang: Optimal screening for vitamin deficiencies is not well established in patients with moderate to advanced kidney disease apart from several select vitamins such as B12 and folic acid in patients on maintenance dialysis. For practical purposes, patients at higher risk for deficiencies are e.g., the ones with progressive weight loss, acute illnesses, and poor dietary intake or those following a highly restricted diet. Since most vitamin deficiencies are mild and moderate, and result in clinically subtle findings, more stringent adherence to daily requirements with appropriate levels of supplementation would be more effective than screening individual vitamin deficiencies. CKD and dialysis patients should have regular monitoring by kidney dietitians to prevent nutritional deficiencies.
To view Wang et al [FREE], please visit AJKD.org.
Title: Vitamin Supplement Use in Patients With CKD: Worth the Pill Burden?
Authors: Angela Yee-Moon Wang, Rengin Elsurer Afsar, Elizabeth J. Sussman-Dabach, Jennifer A. White, Helen MacLaughlin, T. Alp Ikizler
DOI: 10.1053/j.ajkd.2023.09.005
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