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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Breakfast Chia Apple Oatmeal
By Majd Isreb, MD, FACP, FASN, IFMCP
This is one of my favorite breakfast recipes. It is a healthy plant-based breakfast with 7 g protein and 10 g of fiber to start you day right.
Ingredients
Direction
- Boil 1 cup of water then add oats, chia seeds and chopped apple.
- Cook for 5 minutes, stirring over medium heat.
- Sprinkle cinnamon and nutmeg.
- Add raw stevia to taste
- Add 4 oz of almond milk if desired.
- Garnish with chopped apples and blueberries (optional)
Enjoy
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Root Causes of Itching in Kidney Disease
Uremic toxin-induced neurologic changes
Several studies showed that patients with CKD have an imbalance of opioid receptors in the central and peripheral nervous system. Interestingly, itching in CKD correlates better with the level of uremic toxins than with glomerular filtration rate (GFR, a measurement of how well the kidneys are working). These toxins play an important role in these neurologic changes that are common in CKD. Most of these toxins are generated by the gut microbiome and are excreted by the renal tubules and not by glomerular filtration (or GFR). Measuring these toxins can be helpful. This can be done by a metabolomic test such as Genova’s Metabolomix+.
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Inflammation
CKD is an inflammatory disorder. Elevated inflammatory markers have been found to be associated with itching in kidney disease. Measuring inflammatory markers such as hsCRP, Th-1 cells, and IL-6 can be helpful in the assessment of the root cause of itching in CKD.
Dehydration
Dehydration can also lead to dry skin and worsens itching in CKD patients. Correcting the dehydration can be important in the management of itching.
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Drug-induced itching
Many medications that are used in CKD have been associated with itching. These include calcium channel blockers, hydrochlorothiazide, and ACE inhibitors. In addition, other medications such as opioids, anticoagulants, and antibiotics can cause itching.
The itch-scratch-itch cycle
One of the major problems with itching is that it leads to scratching, and this can cause skin damage. The latter can cause further itching and the cycle continues.
Natural Treatments for itching in kidney disease
There are many steps you can take to get rid of itching in kidney disease and a kidney disease rash. The first step is to visit a healthcare provider to help you determine the root cause. You can download this two-page handout to guide you in the natural treatment of itching. There is hope that you’ll relieve this frustrating problem and have comfortable skin once again.
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3 years of lifestyle interventions improved exercise capacity and decreased the losses in neuromuscular and cardiorespiratory fitness in CKD patients
In this study, researchers randomized 161 patients with stage 3-4 CKD to either get usual care or usual care plus lifestyle “intervention” for 3 years.
The lifestyle intervention comprised of care from a multidisciplinary team, including a nephrologist, nurse practitioner, exercise physiologist, dietitian, diabetes educator, psychologist, and social worker.
The patients were coached for 8 weeks and then followed for 34 months with a home-based program.
The study did not look at the progression of CKD but it found that a 3-year lifestyle intervention doubled the percentage of CKD patients meeting physical activity guidelines, improved exercise capacity, and decreased the losses in neuromuscular and cardiorespiratory fitness.
It appears that the study mainly focused on exercise. So imagine the benefit of a comprehensive lifestyle modification plan that includes nutrition, exercise, stress management, sleep improvement, and attention to toxin exposure and gut-kidney connection. That’s what we focus on.
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Curcumin powder did not improve markers of vascular dysfunction in PKD
This is essentially a negative study.
It demonstrated that Curcumin powder did not improve markers of vascular dysfunction in children and young adults with PKD. The study was conducted for only one year using a dose of 25 mg/kg per day of curcumin.
This is a classic supplement or nutrient study that is usually underpowered or conducted for short periods of time for a disease that takes years or even decades to evolve. Nevertheless, the study proved that short-term use of curcumin is not beneficial for vascular health for young patients with polycystic kidney disease.
Low serum zinc levels were associated with infections in CKD patients
This did not really need research but it is now studied and it is official: Low zinc levels in patients with CKD lead to infection (..well among other things).
This retrospective study analyzed data from 299 CKD patients who had serum zinc levels checked to evaluate anemia. They used the level of 50 mcg/dl as the cutoff between low or “high” zinc values.
Low serum zinc values remained an independent risk factor for infection-related hospitalization. This was especially true for patients taking proton pump inhibitors (PPIs) medications.
Read about the effect of Zinc on kidney health in this blog.
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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.
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Altered vitamin K biodistribution may decrease the benefit of vitamin K2 supplementation in advance CKD
In this study, investigators sought to determine if there are other causes for vitamin K deficiency in advanced CKD beyond decreased dietary intake. They compared vitamin K uptake and distribution into circulating lipoproteins after a single administration of vitamin K1 plus K2 (MK-4 and MK-7) between patients on dialysis and healthy individuals.
They found that patients with uremia and advanced kidney disease don’t incorporate MK-7 well into HDL and LDL particles compared to healthy individuals. In addition, the combination of a statin and PPI was associated with signs of functional vitamin K2 deficiency in these patients.
In essence, patients with advanced kidney disease may not benefit as well from vitamin K2 supplementation. This highlights the importance of optimizing vitamin K2 status at earlier stages in CKD.
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Higher levels of deoxycholic acid were associated with a higher risk of progression in CKD
Deoxycholic acid is one of the secondary bile acids, which are metabolic byproducts of intestinal bacteria. Intestinal bacteria metabolize the primary bile acid, cholic acid, into deoxycholic acid (DCA).
Researchers studied 3,147 CRIC study participants who had fasting DCA levels. DCA levels above the median were independently associated with higher risks of ESKD and all-cause mortality.
This study highlights the importance of the microbiome and dysbiosis in the progression of kidney disease as we discussed in our blog.
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The higher number of medications a kidney patient takes the faster her kidney disease progresses
In a study performed in Japan of 1117 CKD patients under nephrological care, the use of a higher number of medications was associated with an increased risk of kidney failure, cardiovascular events, and all-cause mortality in patients with CKD. This is one of the major reasons we advocate for lifestyle modifications and coaching as the first and major step in the management of kidney disease.
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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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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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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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