Colchicine for CKD!
In a multi-center, nested, case-control study in three Korean hospitals, patients with CKD stage 3 and 4 who are using drugs including colchicine, allopurinol, and febuxostat for high uric acid or chronic gout were studied over a period of 10 years. The progression of CKD was compared between 3085 compared to 11715 control patients.
Colchicine use was associated with a lower risk of adverse kidney outcomes in CKD patients with hyperuricemia, or chronic gout.
Unlike a study published two years ago in NEJM which excluded patients with advanced CKD, this study included patients with kidney function as low as 15 ml/min. Colchicine is known to anti-inflammatory. It also protects against kidney fibrosis.
There are concerns about myopathy and neuropathy with the intake of colchicine. It is, therefore, important to adjust the dose with advanced kidney disease and to be cautious when using it with patients who are on other myopathy-inducing drugs such as statin drugs.
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Long sleep duration is associated with decline in kidney function
This study is retrospective, longitudinal cohort study included 82,001 participants who visited a primary care center in Japan. Patients were categorized into CKD risk groups and sleep duration categories according to their self-reported average nightly sleep duration. The relationship between average nightly sleep duration and the incidence of composite renal outcome was studied.
Researchers found that an average sleep durations ≥8 h/night were associated with an increased risk of kidney function decline over time.
There are many reasons that connect sleep problems with poor kidney function. We summarized these in this blog.
Risk of environmental heavy metal toxicity is higher in CKD
In a study of 5,638 NHANES participants, lead and cadmium levels were higher in patients with CKD than those without it. This was also associated with decreased urinary lead excretion. Each decrease in estimated GFR by 10 ml/min/1.73m2 was associated with 0.05 mcg/dL increase in lead levels and 0.02 mcg/dL of cadmium levels. This association was even stronger among black participants.
The study concluded that CKD increases the susceptibility to heavy metal environmental exposure by reducing its elimination.
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This routine should take no longer than an hour. Your kidneys and health deserve an hour from you every morning. I understand many of us have hectic lives, but if you are busy, try to go to bed early and wake up one hour earlier the next morning. Trust me, it is worth it. An hour morning routine beats dialysis any time. This could be the first step in how to heal your kidneys naturally.
Start with water
At night the body loses a lot of water due to sweat and breathing. In fact, in a small study presented at an Associated Professional Sleep Societies meeting in 2009, healthy young men were found to lose ¼ lbs. per hour while asleep. That is about 2 lbs. in eight hours of sleep.
This is why you should start your day with water. The rest of the routine can be done according to your judgment and comfort. Start with drinking two glasses of filtered water if you are not on any water restrictions. This is even more important for patients with polycystic kidney disease and kidney stones. If you are wondering how much water to drink in PKD, check out our calculator here.
Exercise
Exercise for about 20 minutes. The type and duration of exercise depend on an individual’s level of functioning, endurance, and preference. Studies on exercise in chronic kidney disease (CKD) have included resistance training and aerobic activities that use large muscle groups continuously such as walking, cycling, and jogging.
High-intensity interval training (HIIT) was shown to offer superior benefits in individuals with metabolic disease. In the few studies of HIIT in CKD, it was found to be a safe and feasible option for individuals with CKD.
If you are new to exercising, start slow and try to gradually get to 20 minutes of strenuous exercise five to six days a week. It is best to alternate between aerobic exercise and resistance training. If you absolutely can’t fit exercise into your morning routine, you can move it to whatever time that works for you. The benefits are all the same. Consistency is the key here.
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Meditation
Meditate for at least 10 minutes. Meditation is a great way to start your day, manage stress, and stimulate your vagus nerve, which connects the brain with many vital organs including the kidneys. There are many ways to meditate and many types of meditations. Mindfulness meditation is the most tested in kidney patients. It has been shown to improve the quality of life, reduce anxiety and depression, reduce sympathetic overactivity, improve sleep, and improve blood pressure.
To practice mindfulness meditation such as Benson’s relaxation technique, sit in a comfortable position or on a meditation cushion, close your eyes, relax your shoulders and muscles, and focus on your breathing. Say a word with every exhalation. Pick a positive word like “gratitude.” As your mind starts racing to distract you from your breath, try to return to the word you chose. Practicing this every day will make you better at it, and you will be able to reap all the benefits with consistency.
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Journaling
Journaling is a great way to write your thoughts and plan your day. It has similar benefits to meditation. In fact, journaling was found to reduce stress and depression, boost the immune system, and improve memory among many other benefits. You can write whatever comes to mind. Think of it as a thought download. This should also not take more than 10 minutes.
Meditation and journaling can also be moved to a different time of the day for busy individuals with similar benefits. If you are very busy, consider meditation in the morning and journaling in the evening.
Cold shower
Taking a cold shower has many benefits for kidney patients. It increases endorphins and fights off depression, and it improves metabolism and circulation. Most importantly, it stimulates the vagus nerve and improves renal circulation. It may also soothe itchy skin, which is common in CKD patients. Cold showers help with post-workout muscle soreness. The benefits of a cold shower begin when the water temperature dips to 60 degrees Fahrenheit. This is 40 degrees lower than the typical steamy shower.
Now, I know it will be hard to turn that shower knob from hot to cold in the morning. The way to do it is to start with your hot shower. Then gradually lower the temperature at the end of the shower every day by turning the knob to cold. Give your body time to adjust. You can start with 30 seconds under the cold and gradually increase it to a maximum of three minutes. A quick shower for kidney health takes 10 minutes.
Plant-based breakfast
A good plant-based breakfast can be a super healthy way to start your day. A plant-based or plant-dominant diet has been linked to better kidney health and to slow the progression of kidney disease. There are many options that you can prepare in less than 10 minutes or plan the day before. You can find a few recipes in this e-book.
The bottom line
Your kidneys and health deserve an hour from you every morning. This morning routine can improve kidney health and help slow the progression of early kidney disease. If you’re wondering how to heal kidneys, this routine could serve as the first step, or it could be all you need for heathier kidneys. You can modify it to fit your schedule so that you’re at least doing some of the suggested morning actions every day. If you’ve been wondering how to improve kidney function, this morning routine is an important step in the right direction.
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Causes of magnesium deficiency
Poor dietary choices
There has been a steady decline in magnesium content in cultivated fruits and vegetables over the past 100 years. This is caused by the depletion of magnesium in soil over time. In addition, utilizing phosphate-based fertilizers leads to the formation of magnesium phosphate salts that are not soluble. This means the soil is deprived of both components: magnesium and phosphorus.
On top of that, the rise of ultra-processed food and drinks have also contributed to the depletion of magnesium in the modern standard American diet. Grain bleaching and vegetable cooking and adding preservatives can lead to a significant loss of magnesium content. Preservatives such as various forms of phosphate and oxalate can bind with magnesium and prevent its absorption. Phosphoric acid in soft drinks has similar effects.
The addition of fluoride to drinking water also prevents magnesium absorption by binding to it and forming insoluble complexes. Finally, drinking caffeine and alcohol can also lead to an increase in the excretion of magnesium by the kidneys, causing magnesium deficiency.
Drug-induced magnesium deficiency
Many medications can interfere with magnesium absorption or increase its excretion, leading to deficiency. Most of the medications leading to magnesium deficiency are summarized in the following table:
| Medication class | Example | Mechanism |
| Anti-diabetic medications | Insulin, insulin mimetics | Interferes with Na/Mg exchange leading to renal loss |
| Antimicrobial | Gentamicin, pentamidine, foscarnet, amphotericin B | Increased renal loss |
| Beta agonists | Salbutamol | Renal loss and cellular shifts |
| Bisphosphonate | Pamidronate | Renal loss |
| Cardiac glycoside | Digoxin | Increased renal loss |
| Chemotherapy agents | Cisplatin | Renal loss |
| Diuretics | Thiazide diuretics | Renal loss |
| Proton-pump inhibitors | Omeprazole | Decreased GI absorption |
Measuring magnesium status
Simply put, there is no ideal test for assessing magnesium status in the body. Mg blood levels are tightly controlled and represent only 0.8% of total body stores (0.5% in red blood cells and 0.3% in the serum). Red blood cell Mg levels have been used as an alternative method, but this too does not represent total body stores and is not well validated. Measuring urine Mg requires measuring a 24-hour urine specimen. This too has been found to be imperfect due to large variations from day to day.
The Mg retention test has been proposed as a more accurate way to assess Mg status. Here, the patient receives an intravenous Mg load (0.25 mmol magnesium/kg body weight at a rate of 2.5 mmol/hour), and a 24-hour urine specimen is collected before and after the load. The percentage of administered magnesium that is retained by the body (not excreted in urine) determines magnesium status. This test is not standardized yet, but retention of 25%-50% may indicate a moderate deficiency, and retention of more than that may indicate severe deficiency.
Ideally, measuring muscle or bone magnesium may be more reflective of accurate magnesium stores but this is obviously not practical. Combining a serum Mg test, a 24-hour urinary Mg, and assessing dietary Mg intake is the most comprehensive and practical evaluation of a patient’s magnesium status.
Combining a serum Mg test, a 24-hour urinary Mg, and assessing dietary Mg intake is the most comprehensive and practical evaluation of a patient’s magnesium status
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Patients at high risk for magnesium deficiency include:
- Diabetics
- Heart disease patients
- Osteoporosis patients
- People who eat a diet high in processed food and soda
- People who suffer from leg cramps
- People with metabolic syndrome
- People who take certain medications
Those patients at risk of magnesium deficiency should be targeted for additional testing and supplementation.
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What type of magnesium should I take?
The type of magnesium supplement used depends on the exact indication. Magnesium supplements are available as oxide, hydroxide, gluconate, chloride, citrate, lactate, malate, taurate, L-threonate, sulfate, glycinate, orotate, and carbonate salts. In addition to magnesium citrate’s direct effects on kidney stones, magnesium benefits the person with kidney disease through its effects on blood pressure, insulin sensitivity, vascular health, and bone. The following indications are listed with the recommended types of magnesium supplements and doses. These doses are for prevention only. Patients who are deficient may need higher doses. Magnesium supplements should be discontinued or decreased in kidney patients if the serum magnesium level is higher than 2.6.
| Indication | Mg type | Dose |
| Prevention of kidney stones | Magnesium citrate | 400 mg daily |
| Bone health | Magnesium citrate or chloride | 400 mg daily |
| Improving blood pressure | Magnesium taurate | 400 mg once or twice daily |
| Improving insulin sensitivity | Magnesium taurate | 400 mg once or twice daily |
| Improving vascular health | Magnesium glycinate or orotate | 200-400 mg daily |
| Phosphate binder | Magnesium carbonate | 250 mg with meals |
We recommend using high-quality supplements. This article can be a useful guide.
The bottom line
Magnesium is essential to many biological functions, as I described in part one, “Magnesium and Kidneys.” It has many health benefits for kidney, bone, and vascular health. Assessing magnesium status is difficult but magnesium deficiency is very common and underrecognized. Supplementing magnesium may be important for patients with kidney disease. The type of supplement used depends on the indication. As always, it is recommended that you check with a Functional or Integrative Medicine provider and nephrologist before taking any new supplement.
The post Magnesium Deficiency: Assessment and Management for Better Kidney Health appeared first on Integrative Kidney.]]>Low magnesium levels have been associated with a number of adverse events, such as high risk for heart disease. However, little is understood about magnesium and kidney health. Here, we will discuss the potential benefits of magnesium on the kidneys. This is one of two articles on magnesium and kidneys. For more on how to test and treat kidney patients with magnesium deficiency, see part two, “Magnesium Deficiency: Assessment and Management for Better Kidney Health.”
Dietary sources of magnesium
A daily intake of 3.6 mg/kg is necessary to maintain magnesium balance in humans under normal conditions. This is estimated to be between 320 to 420 mg/day (13–17 mmol/day) for adults. Sadly, there has been a steady decline in magnesium content in cultivated fruits and vegetables over the past 100 years. This is due to depletion of magnesium in soil over time. This, along with the rise of ultra-processed food, sodas, and taking medications such as proton pump inhibitors and diuretics that deplete magnesium levels (polypharmacy), has led to rising prevalence of magnesium deficiency.
Traditionally, the highest food sources of magnesium are:
- Leafy greens (78 mg/serving on average)
- Nuts (80 mg/serving on average)
- Pumpkin seeds have the highest level of magnesium per serving (156 mg).
- Whole grains (46 mg/serving on average)
A complete list of foods high in magnesium can be found here.
Can Magnesium Help Kidney Function?
There are many potential benefits of magnesium for kidney health including improving blood pressure control, insulin sensitivity, bone health, vascular health, and preventing kidney stones. Let’s explore the data.
Magnesium and blood pressure control
Magnesium supplementation may help reduce blood pressure (BP) by increasing the production of nitric oxide. Nitric oxide acts as a signaling molecule that helps relax blood vessels, which lowers BP. In fact, a review of 34 studies showed that supplementing magnesium with an average dose of 368 mg per day for 3 months can decrease systolic BP by 2.00 mmHg and diastolic BP by 1.78 mmHg. This supplementation was accompanied by 0.05 mmol/L increase in serum magnesium levels.
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Magnesium and insulin sensitivity
Diabetes is one of the major risk factors for kidney disease worldwide. Higher dietary intake of magnesium has been correlated with lower diabetes incidence. A review of 18 studies in people with diabetes showed that magnesium supplements reduced fasting plasma glucose levels. In people who are at high risk for diabetes, magnesium supplementation significantly improved plasma glucose levels after a 2-hour oral glucose tolerance test. These effects are thought to be due to the effects of magnesium on insulin receptors and signaling that allows for improvement in glucose transport and utilization.
Magnesium and vascular health
Magnesium levels have been associated with a lower incidence of cardiovascular disease. In fact, supplementing with magnesium was associated with improvement in vascular flow and endothelial function. Endothelial function refers to the lining of the blood vessels, which is involved in regulating blood vessel health and blood clotting.
Studies in patients receiving dialysis have shown that having a lower serum magnesium level is a significant risk for cardiovascular mortality. Laboratory data show that magnesium inhibits high phosphate-induced calcification of vascular smooth muscle cells. Calcification of arteries is a strong predictor of heart disease and heart-disease-related death.
Magnesium and vitamin D
Magnesium is essential to vitamin D metabolism. Vitamin D that we eat or make in our skin from sun exposure circulates in the blood and is bound to vitamin D binding protein (VDBP). VDBP binding activity depends on adequate magnesium levels. In addition, magnesium is an essential cofactor for the enzymes that activate vitamin D. Studies have demonstrated that magnesium deficiency is associated with impaired vitamin D metabolism.
On the other hand, taking large doses of vitamin D can induce severe depletion of magnesium. This is thought to be due to the overutilization of magnesium. Therefore, adequate magnesium supplementation should be an important part of vitamin D therapy.
Adequate magnesium supplementation should be an important part of vitamin D therapy.
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Magnesium and bone health
Besides magnesium’s effects on vitamin D metabolism, it is an essential component of hydroxyapatite, an essential component of bone and teeth. In fact, 60% of total Mg is stored in the bone. Low magnesium intake was found to be associated with lower bone mineral density in postmenopausal women. Magnesium deficiency contributes to osteoporosis directly by acting on crystal formation and on bone cells and indirectly by impacting the secretion and the activity of parathyroid hormone (PTH) and by promoting oxidative stress and inflammation.
In addition, a review of 8 studies looked at magnesium and chronic kidney disease (CKD). The study investigated magnesium supplementation on parameters of CKD-related mineral bone disease (CKD-MBD). Mg supplementation improved PTH levels and carotid intima-media thickness (CIMT). Low serum Mg levels were also found to impact PTH and worsen osteoporosis in CKD patients, particularly with diabetes.
Magnesium and kidney stones
Mg acts as an inhibitor of calcium oxalate crystallization and stone formation in the urine. It also decreases the absorption of dietary oxalate in the gut. Mg supplementation in patients with kidney stones was found to decrease the incidence of stone formation even in patients without signs of Mg deficiency.
Magnesium as a phosphate binder
Hyperphosphatemia (high phosphate level) is common in advanced kidney disease. Many kidney patients with stage 4 and above use binders that bind phosphate (or “phosphorus,” as it is commonly known) in the food and prevent it from getting absorbed. High phosphate levels have been associated with poor bone and vascular health in kidney patients. In fact, higher dietary phosphate load can be seen in earlier stages of CKD, and it can do harm even before it is detected.
Magnesium carbonate has been successfully used as a phosphate binder. Magnesium based phosphate binders were also found to reduce vascular calcifications in rats with kidney disease. Iron-magnesium hydroxycarbonate was also studied and found to be well tolerated and can effectively lower phosphate levels in dialysis patients. It is essential to know that most of the magnesium used as a phosphorus binder will not be absorbed.
The bottom line on magnesium and kidneys
Magnesium is essential to many biological functions. It has many health benefits for kidney, bone, and vascular health. Optimizing magnesium status is, therefore, an important step in the integrative approach to kidney health. In part two of this blog, “Magnesium Deficiency: Assessment and Management for Better Kidney Health,” we will discuss practical steps for figuring out a person’s actual magnesium status, the best form of magnesium to take, and the dose I recommend for each condition.
The post Magnesium and kidneys appeared first on Integrative Kidney.]]>We combed through multiple medical journals looking for the latest research on the Integrative approach to kidney health. We know your time is valuable so we curated and summarized these studies for you. Welcome to the November edition of InKidney Research and News.
Is phosphorus toxic to the kidneys?
In this detailed study, researchers found that excessive intake of phosphate (phosphorus) increases a substance called FGF-23. One of FGF-23 main tasks is to maintain phosphorus balance in the blood. It does that by increasing the excretion of phosphorus in the urine. This study found that the presence of high phosphorus in the kidney tubules causes them to bind with calcium forming tiny crystals that are very toxic to the tubular cells and leads to fibrosis. Investigators found that a level of FGF-23 above 53 pg/mL is associated with progression of kidney disease in humans.
Coffee and caffeine consumption and the risk of kidney stones
Investigators used Mendelian randomization to study the link between coffee consumption and the risk of kidney stones. They looked into the UK and Finland genetic databases and tried to find the association between coffee drinking genotype and kidney stone phenotype.
The study found that genetically predicted coffee and caffeine consumption was associated with a lower risk of kidney stones. This supports other observational studies that indicated the same.
But of course, the study means that consumption of black coffee is associated with decreased risk for kidney stones. It does not addresses latté or triple caramel Frappuccino. So, as always drink coffee in moderation.
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One in every 5 CKD patients receives a nephrotoxic medication
This study published ahead of print looked into the use of nephrotoxic medications in the US and Sweden. They studied a total of 74,135 patients with stage 3-5 CKD. In one year, one in every 5 patients with CKD, received a nephrotoxic medication.
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By Majd Isreb, MD, FACP, FASN, IFMCP
What is vitamin A?
Vitamin A is an essential fat-soluble nutrient known for its role in good vision. It is also needed for cellular growth and differentiation. Since skin and gut cells are some of the fastest-growing cells in the human body, they are most sensitive to vitamin A deficiency. Vitamin A is also important for cells of the immune system. Vitamin A plays an important role in these processes:
- Growth and differentiation of all cells
- Embryonic development
- Organ formation in utero
- Normal immune function
- Eye development and vision
- Red blood cell production
Chemically, vitamin A is a group of organic compounds that share a beta-ionone ring with an isoprenoid chain. These compounds are often referred to as “retinoids.” The name of the retinoid depends on the number of the rings, the size of the isoprenoid chain, and the end group. These include -carotene, -carotene, retinal, retinol (which is vitamin A per se), all-trans-retinoic acid, all-trans-retinyl ester, 9-cis-retinoic acid, and 11-cis-retinal. Now, forget about all these different compounds, and let’s simplify things by calling them all vitamin A.
Diet and vitamin A
Vitamin A is consumed in the diet either as preformed vitamin A or as a precursor provitamin A carotenoid. Provitamin A carotenoids are converted to vitamin A in human intestinal cells. Sources of preformed vitamin A include eggs, liver, butter, milk, and fortified cereals. Provitamin A carotenoids are mainly found in vegetables such as carrots, spinach, collards, pumpkins, and squash. The most common type is beta-carotene. On average, the standard American diet provides approximately 700-800 micrograms of “retinol activity equivalents (RAE)” per day. Most of that comes as preformed vitamin A. The recommended dietary allowance of RAE for men and women is 900 and 700 micrograms/day, respectively. This makes deficiency of vitamin A rare. I will not discuss the complex absorption of vitamin A in the gut and storage in the liver and cellular mechanisms of action in detail here. These are described in detail elsewhere. However, it is important to remember that the presence of fat in the diet greatly enhances vitamin A absorption since it is fat-soluble. It is also worth noting that excessive intake of preformed vitamin A can cause elevated vitamin A levels. But elevated vitamin A does not usually occur after increased intake of provitamin A carotenoids. This is because the conversion of carotenoids to vitamin A is regulated by a negative feedback loop. When adequate levels of vitamin A are present, the body downregulates the production of vitamin A from carotenoids.
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Effects of vitamin A on the bone
Before we discuss the effects of vitamin A on bone in detail, we should review the processes of bone formation and maintenance.
Bone formation and maintenance
Our bones contain a small number of cells surrounded by a mesh of collagen fibers that provide a scaffolding for salt crystals. These salt crystals are made of calcium, phosphate, and carbonate which combine to create, the so-called, hydroxyapatite. The latter incorporates other salts like magnesium hydroxide, fluoride, and sulfate as it hardens, or calcifies, on the collagen scaffolding. Hydroxyapatite crystals give bones their hardness and strength, while collagen fibers give them flexibility. There are four types of cells that are found within the bone: osteoblasts, osteocytes, osteogenic cells, and osteoclasts. In adults, two processes are responsible for changes in the skeleton: modeling and remodeling. Bone modeling describes the process of new bone formation or bone resorption on a given bone surface. This process is important for bone growth and shaping during childhood and adolescence. Bone remodeling, on the other hand, is the process that is used to maintain and renew healthy bones during adulthood. In other words, in bone modeling either bone formation or bone resorption occurs, while in bone remodeling both bone resorption and bone formation occur together. For remodeling to occur the bone must be “dissolved,” and then a new bone is formed. In this process, osteoclasts dissolve old bone tissue at specific sites. This process is called resorption. Subsequently, new bone tissue is formed by the osteoblasts. Even though it may seem counterintuitive, bone resorption (breaking down old bone) is necessary for building new, healthy bone. So, in essence, modeling leads to the formation of new bone tissue where needed, while remodeling helps maintain and strengthen existing bone tissue.
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The role of vitamin A
Vitamin A has two different effects on bone depending on the dose. While adequate vitamin A intake was shown to maintain healthy bones, high levels of vitamin A have been shown to cause the opposite. Let me explain.
Good effects
Studies have shown that vitamin A is important for bone resorption. This is essential for maintaining healthy bone by remodeling as we discussed. In fact, adequate intake of vitamin A has been found to improve bone mineral density and decrease the risk of fractures.
Not-so-good effects
In the early 1900s, researchers found more osteoclasts in the bones of animals with high vitamin A levels. Later animal studies showed that excess vitamin A led to the formation of bones with a “moth-eaten appearance.” It was also demonstrated that vitamin A stimulated bone resorption. Recently, it was noted that vitamin A can stimulate mineral release and bone degradation in mouse bones. These effects were blocked by osteoclast inhibitors such as bisphosphonate and calcitonin. In essence, vitamin A can increase osteoclast formation and differentiation causing increased bone resorption. This is good for the maintenance of healthy bones but becomes harmful when there is excessive resorption at high levels of vitamin A. The evidence that supports this comes from studies that showed an increased risk of hip fractures in the lowest and highest vitamin A blood levels. There are other studies that also showed that a high daily intake of vitamin A was associated with decreased bone mineral density. In the NHANES study in the US, for example, daily vitamin A intake of more than 3,000 micrograms was associated with an increased risk of hip fracture. However, there was no increased risk of fractures with high beta-carotene intake. This low-dose versus high-dose phenomenon has been seen with other nutrients and is described as a U-shaped hormetic response. At low doses, there are symptoms of nutritional deficiency but at high doses, there are symptoms of toxicity.
The interaction between vitamin A & vitamin D3
As we noted before, nutrients don’t work solo. Optimal bone health requires optimization of vitamin D, vitamin K2, calcium, phosphorus, and magnesium. There have been reports of vitamins D and A opposing each other. Some studies showed that vitamin D protects against vitamin A toxicity. On the other side, excess vitamin A was also shown to reduce the effects of vitamin D toxicity. In humans, high vitamin A intake was found to decrease the ability of vitamin D to enhance calcium absorption in the gut. Studies have shown that the negative effects of excess vitamin A on bone mineral density and fracture risk are amplified when accompanied by vitamin D deficiency.
Vitamin A and kidney health
Several studies have shown that vitamin A levels increase with worsening kidney function and advanced CKD. This, along with the prevalence of vitamin D deficiency in this population, adds another layer of complexity to bone problems in kidney disease. This common complication of kidney disease is called chronic kidney disease-associated mineral bone disease (CKD-MBD). In CKD-MBD, there is abnormal bone turnover and increased vascular and soft tissue calcifications. Increasing intake of preformed vitamin A at the advanced stage of CKD can lead to worsening bone abnormality and elevated calcium levels in the blood. This, in turn, can increase the risk of vascular calcifications. Therefore, supplementing vitamin A in patients with advanced CKD is not generally recommended on a regular basis. Natural vitamin A intake through a diet high in carotenoids should be sufficient.
Assessing vitamin A status
Unfortunately, it is difficult to assess vitamin A status in an individual. This is because most vitamin A is stored in the liver and is released as needed to the blood. The two common ways to measure vitamin A status are measuring serum retinol and retinyl ester concentrations. There are also labs that measure beta-carotene levels. Serum retinol levels are only helpful if they are very low or very high. Levels < 1.05 micromol/L indicate vitamin A insufficiency. It has been suggested to use the ratio of serum retinyl esters to total serum vitamin A (retinol plus retinyl esters) as a marker for excess vitamin A. Serum retinyl ester levels exceeding 10% of total serum vitamin A may reflect excess vitamin A stores and potential toxicity.
How much vitamin A should I take?
Considering the above, we recommend our patients get most of their vitamin A from the diet (either as preformed vitamin A or provitamin A carotenoids). CKD patients can eat eggs, liver, butter, milk, carrots, spinach, collards, squash, and pumpkin with guidance from their dietitian/nutritionist and nephrologist. The following recommendations for CKD patients are based on anecdotal practice since the literature doesn’t support specific recommendations. Patients with stage I-IIIa CKD may take up to 2500-3000 IU of supplemental vitamin A (or RAE 900 microgram/day for men and 700 microgram/day for women.) Patients with stage IIIb-IV CKD should decrease their intake of vitamin A supplements by 50%. Supplementation with vitamin A is not recommended for patients with an estimated GFR of less than 20 ml/min. If supplementation is desired during periods of sickness (for example, a respiratory illness) to boost the immune system, we recommend using beta-carotene supplements instead of preformed vitamin A supplements.
The Bottom Line
Vitamin A has a great impact on bone health. It is essential for bone resorption and remodeling. However, excess vitamin A intake can lead to bone weakness and fractures. In patients with advanced CKD, vitamin A tends to accumulate, and supplementation is not recommended. If supplementation is desired to boost the mucosal immune system during periods of sickness and high demand, look for supplements that provide much of their vitamin A in the form of beta-carotene. The individualized integrative approach to CKD-MBD necessitates careful nutritional assessment and evaluation of vitamin A levels in addition to vitamins D, K, magnesium, calcium, and phosphorus. This can help develop a tailored lifestyle and nutrition plan that can be incorporated into the medical management of CKD.
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Lifestyle modifications do indeed prevent CKD and delay its progression
This study is coming from Japan. Researchers found that two years of healthy lifestyle choices prevent against the development of kidney disease and protein in the urine. Lifestyle modifications also slowed the decline in kidney function.
They studied 451,534 people (277,494 men and 174,040 women) aged 20–79 years. Healthy lifestyle choices in this study were defined as: 1. No smoking 2. Healthy eating habits, and 3. Low BMI
Now, we all know that there is more to lifestyle modifications than this but this is definitely a start.
Is Urea by itself toxic?
The authors in this study published in NDT definitely think so. They noted that the accumulation of uremic toxins is a risk factor for mortality and accelerated atherogenesis in patients with CKD. The researchers found that a post-translational protein modification called carbamylation is a predictor of CKD progression. They also noted that urea by itself promotes the carbamylation of proteins.
So urea is not just a benign marker and should be classified as a uremic toxin. The level of protein carbamylation may be used as a marker for risk stratification of CKD outcomes.
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Magnesium, bones, and kidneys… What?!
This study is coming from the dialysis world. It’s a meta-analysis that examined the effects of magnesium supplementation on chronic kidney disease mineral bone disease (CKD-MBD). As the researchers mentioned, magnesium supplementation in dialysis patients is controversial. However, this study showed that it helps by regulating calcium and parathyroid hormone and it decreases carotid intima-media thickness.
This is in the dialysis population. So paying attention to magnesium balance and supplementation may have a much better role in bone and vascular health in earlier stages of CKD. Optimizing vitamin D, vitamin K2, vitamin A, calcium, phosphorus , and magnesium is very important to improve bone and vascular health in CKD patients.
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The Role of Dietary Fiber Supplementation in Regulating Uremic Toxins in Patients With Chronic Kidney Disease: A Meta-Analysis of Randomized Controlled Trials
Gut-derived uremic toxins, including indoxyl sulfate (IS) and p-cresyl sulfate (PCS), are waste products that accumulate in the body due to decreased clearance by the failing kidneys. These accumulated uremic toxins are a risk factor associated with cardiovascular disease, progression of kidney dysfunction, mineral bone disorders, and increased mortality in patients with CKD. This meta-analysis showed that dietary fiber supplementation could decrease IS and PCS levels in patients with CKD.
https://www.jrnjournal.org/article/S1051-2276(20)30291-0/fulltext
Causal effects of physical activity or sedentary behaviors on kidney function: an integrated population-scale observational analysis and Mendelian randomization study
The health benefits of exercise and regular physical activity are vast. Using Mendelian randomization (MR) to assess causality, this study found that “the genetic predisposition to a higher degree of physical activity was associated with a lower risk of CKD and a higher eGFR, while the genetically predicted television watching duration was associated with a higher risk of CKD and a lower eGFR.”
https://academic.oup.com/ndt/advance-article/doi/10.1093/ndt/gfab153/6214515?login=true
Prevalence of Inflammatory Bowel Disease and Celiac Disease in Patients with IgA Nephropathy over Time
Poor gut health and a lack of intestinal wall integrity is linked to many diseases, including IgA nephropathy (IgAN). The results of this Finnish study showed an increase in the prevalence of inflammatory bowel disease (IBD) in patients with newly diagnosed IgAN over a 36-year period.
https://www.karger.com/Article/Abstract/511555
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Genetic testing for patients with kidney disease can have a remarkable impact on their care. The availability of “broad-panel genetic testing” for kidney patients ushers in a new era of nephrology and patient care. Tests that used to cost thousands of dollars and took months for results can now be done for a fraction of the cost in just a few weeks. New commercially available genetic tests utilize next-generation sequencing to identify multiple gene variants simultaneously. These tests can help in the management of kidney disease in multiple ways. In this blog, we will focus on the clinical utility of genetic testing for kidney transplant evaluation.
Genetic Testing for Kidney Transplant Evaluation
During the evaluation of a patient for a kidney transplant (the recipient), the assessment usually focuses on answering these questions:
- Can the recipient survive elective transplant surgery?
- Can the recipient tolerate immunosuppression after the transplant?
- Can the recipient have a good outcome?
In addition, evaluation of living donors try to answer questions about their suitability for donation and their risk of developing kidney failure in the future.
Living Donor Evaluation
One of the most pressing questions when evaluating a living donor is: Will this donor develop kidney disease in the future if s/he donates a kidney now? Several studies have shown an increased risk of the donor developing kidney disease after donation. This risk is higher if the donor and the recipient are related. This may indicate that genetic factors play a role in this risk.
In 2017, the Kidney Disease Improving Global Outcomes (KDIGO) Guidelines suggested that “transplant programs should have a strategy for evaluating for inherited kidney disease in donor candidates when there is a family history of kidney failure and the recipient’s cause of kidney failure is uncertain.”
These guidelines suggested genetic testing of living related donors with specific diseases such as focal segmental glomerulosclerosis (FSGS), atypical hemolytic uremic syndrome, Alport disease, sickle cell trait, and autosomal dominant tubulointerstitial kidney disease.
Genetic testing of a living relative donor can be especially important if the recipient has polycystic kidney disease. If this mutation is identified in the recipient, the donor can then be tested and excluded if s/he has the mutation. This can give greater assurance to both the donor and recipient.
Other genetic variants are associated with increased risk of chronic kidney disease (CKD) such as APOL1 gene variants that are associated with increased risk for nephropathy in patients of African ancestry. Incorporating testing for these genetic risk variants in the evaluation of the donor may help replace race for calculation of the so-called Kidney Donor Risk Index that is used to predict the longevity of the transplant graft.
While it is still too early to incorporate the genetic risk variants for diabetic kidney disease and IgA nephropathy in transplant evaluation, getting more clarity on the utility of the risk variants can have a tremendous impact on the care of current patients.
Recipient Evaluation
Kidney disease is silent in its progression and symptoms do not develop until the advanced stages of CKD. One in 10 patients with advanced kidney diseases presents with end-stage kidney disease (ESKD). In many of these cases, the laboratory workup is inconclusive, and their kidneys are often too atrophic to biopsy. Unlike kidney biopsies, genetic data can be informative even after ESKD has developed.
Genetic evaluation of the recipient is, therefore, helpful in identifying the causative mutation that could have led to the disease. Using targeted gene testing, researchers were able to identify pathogenic mutations in 19% of waitlisted transplant patients under the age of 40. Broad panel genetic testing can likely have an even higher yield. Indeed, broad panel genetic testing has been shown to identify the cause of CKD in up to one-third of the patients with an unknown cause.
Genetic testing of the recipient can also help in providing individualized post-transplant care. Finding a specific mutation that leads to a localized disease in the kidneys can decrease concerns about the recurrence of the disease after transplantation.
Also, a genetic diagnosis can often point to the likelihood of disease in another organ and can prompt referral and evaluation.
Currently, researchers are collecting phenotypic and genetic information on patients receiving transplants in the iGeneTRAiN consortium. Analyzing this data in the future may have a significant impact on our understanding of transplant graft outcome.
Pharmacogenomics
Wouldn’t it be a relief to be able to predict in advance how someone might respond to a medication? This would save time, eliminate guesswork, and improve patient outcomes. Thanks to advances in a field of genetics called pharmacogenomics (PGx), clinicians have begun to use genetic information to personalize drug therapy.
Accurate pharmacogenomics data are now available on two transplant medications: tacrolimus and azathioprine. Although the latter is not commonly used, the former is used often. Tacrolimus is metabolized by the enzyme encoded in the gene CYP3A5. Variants in this gene can classify the patient into one of three phenotypes: extensive metabolizer, intermediate metabolizer, and poor metabolizer. Indeed, pharmacogenomic data can now be used to optimize the initial dose of tacrolimus.
Many other medications commonly used by patients have pharmacogenomic data which can also be used to optimize their dosing. Medications such as clopidogrel, voriconazole, and allopurinol are a few of these. We discussed these medications in-depth in our previous blog about pharmacogenomics.
The Bottom Line
Genetic testing is gradually becoming a significant part of the transplant evaluation of the donor and the recipient. It is particularly useful in the evaluation of living donors with a family history of kidney disease. This data has the potential to transform the care of kidney transplant patients and improve their outcomes.
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As mentioned in a previous blog, the integrative approach to many kidney diseases should be personalized, yet comprehensive. It starts with understanding an individual’s genetic predisposition, current and previous lifestyle choices and exposures, triggers of the current disease process, and unique nutritional status. In addition, it’s important to identify an individual’s spiritual, mental and emotional state. This type of approach can help the provider develop a personalized plan that includes attainable lifestyle modifications for the patient.
The ability of the patient to make these changes is the cornerstone of this tailored management plan. Although implementing and adhering to lifestyle modifications can be challenging, it’s not a reason to quit. In order to understand how to overcome these challenges, we talked about the brain and implementing changes in this blog. Understanding synaptic pruning and neuroplasticity can help us in this process.
Implementing Lifestyle Modifications
Now let’s utilize what we discussed above to help patients implement the lifestyle modifications we recommend for those with kidney disease. Of course, willpower varies from person to person. So, what we are suggesting here might not be for everyone, but we think the information is helpful.
Think about it
Now that we know that the brain is hardwired to follow habits, we can approach lifestyle habits without judging or beating ourselves up. The first step in implementing lifestyle modifications is to think about these changes. It will help to write down or talk to someone about the thoughts associated with these changes. Think about lifestyle habits that are currently working and any that are not in order to help identify patterns. Identifying these patterns can be a good starting point to help the brain perceive the need for change. Remember, the brain wants to be efficient and it will always default to the “pre-wired” unhealthy habits if we let it. So, spending extra energy and utilizing that pre-frontal cortex to teach the brain new things is required in the beginning.
Pick one thing
Once patterns have been identified, it’s best to implement one change at a time to avoid overwhelming the brain. It can be helpful to work with a provider or coach to devise a plan of action. Oftentimes, it is beneficial to start with easier changes, as successful implementation of the new habits can help build momentum. For example, an individual may decide an easy change would be to not snack or drink sugary beverages/alcohol after dinner. It is important to note that what is easy for one person may not be as easy for another, so personalization of an action plan is critical.
Plan it
Having a plan can make or break a person’s ability to stick with the new habits. It’s easy for the brain to default to old habits when there isn’t a plan in place. For example, using the weekend to plan out and/or prepare meals for the upcoming week can help ensure healthy eating habits during the week for someone who orders take-out when they get home tired after work. Taking the guess work out of things can set someone up for success.
Learn from mistakes
Let’s face it, mistakes can happen. They don’t indicate failure or give reason to quit. There may have been some variables that were not accounted for. It’s important to learn from mistakes and improve the planning process for the future.
Repeat, repeat, repeat
The most important step in making these modifications permanent is repetition. Repetition creates new patterns and neural pathways via synaptic pruning so that the brain will default to them instead of the previous unhealthy habits. The amount of time this takes depends on the individual’s willpower and commitment. This is not going to be easy but, as they say practice makes perfect.
The Bottom Line
Implementing lifestyle modifications is crucial in the fight against the chronic kidney disease epidemic and foundational to the integrative approach to kidney health. It can be a challenging process but understanding the brain’s efficacy and patterns can help individuals make the changes needed to lead a healthier lifestyle.
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