A high intake of ultra-processed food is associated with a 24% increased risk of developing kidney disease
In this study published ahead of print, researchers studied 14,679 middle-aged adults without CKD at baseline in the Atherosclerosis Risk in Communities (ARIC) study. They divided them according to their ultra-processed food consumption into 4 quartiles.
During a median follow-up of 24 years, there were 4,859 cases of incident CKD. After adjusting for a range of confounders including lifestyle factors, demographic characteristics, and health behaviors, participants in the highest quartile of UPF consumption had a 24% higher of developing CKD compared to those in the lowest quartile.
Substituting one serving of ultra-processed foods with minimally processed foods decreased the risk of CKD by 6%.
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Coffee consumption is associated with a decreased risk of acute kidney injury
The same cohort of the ARIC study above was evaluated for the risk of developing acute kidney injury (AKI) according to their coffee consumption (cups/day).
1694 cases of incident AKI were noted during the 24 years of follow-up. Drinking more than 2 cups of coffee a day was associated with a 17% less risk of developing AKI. This association remained significant after adjusting for all other variables.
45% of CKD patients are on potentially inappropriate medication
In a study of 375 patients published in Clinical Nephrology, patients with chronic kidney disease (CKD) were checked for potentially inappropriate medications (PIM). PIMs were checked based on kidney function (PIM-K) and age (PIM-E).
PIM-K were defined by prescription instructions of product labeling, while PIM-E were defined by BEERS, PRISCUS, and FORTA criteria. If you are not familiar with these criteria, you can learn about them here.
44.5% of all CKD patients had PIM-K. The risk for PIM-K was increased by 3.8 with 10 or more prescriptions and by 8.7 with an eGFR below 30 mL/min/1.73m2.
This study emphasizes the importance of caution and paying special attention to medication prescribing in CKD and elderly patients.
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The post June Research And News appeared first on Integrative Kidney.]]>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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The root cause of IgA nephropathy
IgA nephropathy is a kidney disease that is defined by the pathologic appearance of glomerular deposition of IgA immune complexes. However, this definition does not address the root cause of the disease.
It has been increasingly recognized that IgA immune complex that deposit in the kidneys predominantly contain polymeric IgA1 lacking galactose within its O-glycosylated hinge region.
In this study, researchers found that patients with IgA nephropathy have elevated levels of certain B cells that are enriched for λ light chains. These cells are predestined for homing to upper respiratory and digestive tract mucosal tissues. In the mucosal tissues, these B cells mature and excrete abnormal IgA in the setting of upper respiratory or digestive infection. You can read more IgA nephropathy by reading our blog here.
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Metformin: Some people love it and some people hate it… But it sure is getting a lot of attention lately
This study was done in rats with “non-diabetic kidney disease.” CKD was established in these rats by feeding them high adenine diet. Then they were randomized to receive either metformin or canagliflozin (an SGLT-2 inhibitor).
Metformin, but not canagliflozin, halted the decline in kidney function. Additionally, kidneys of metformin-treated animals showed less interstitial area and inflammation as compared to the vehicle group.
Metformin is increasingly being studied in humans for various kidney diseases. If used judiciously it may be a cheap alternative to preserving kidney function.
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Tremor + gum disease + nephrotic Syndrome = ?
In this study, investigators in Beijing looked into the manifestation of mercury poisoning in 172 patients. 26.74% of these patients had kidney injury (3/4 were women) and most of them had nephrotic syndrome. The most common finding on the biopsy was membranous nephropathy.
Other findings of chronic mercury poisoning were neurotoxicity and gingivitis. Chelation with DMPS alone was as effective as chelation and prednisone in reversing kidney injury.
The most common source of exposure without kidney disease was industrial exposure. Interestingly, the most common source of exposure leading to kidney disease was cosmetics containing ionic mercury (mercury concentration in one of the patients cosmetic was 4600 mg/kg – national standards are < 1 mg/kg).
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Air pollution is linked to kidney disease
PM 2.5 refers to particulate matters that are up to 2.5 microns in size. Because of their small size, they are considered to be the worst of all air pollutants. They reach the alveoli and enter the blood stream. This study looked at the link between PM 2.5 and chronic kidney disease (CKD) in the Twin-cities area of Minnesota. Researchers found that the risk of CKD increases with higher levels of PM 2.5. This remained true after adjusting to all other variable.
It is, therefore, important to think of air pollution as a mediator of CKD and minimize exposure to it.
Block "fundamentals" not found
A Study reaffirms the role of the gut kidney connection in diabetic kidney disease
You know we discussed the role of the gut-kidney connection in the progression of CKD. You can find many of our blogs discussing this here. Dysbiosis can be a predisposing factor or a mediator when it comes to kidney disease. This study looked at the contribution of impairment in the intestinal barrier (leaky gut) to kidney injury in diabetic kidney disease (DKD). In diabetic mice with impaired intestinal integrity intestine-derived Klebsiella oxytoca and elevated IL-17 were detected in the circulation. This was associated with epithelial renal tubular injury and faster progression to kidney failure as compared to control.
So, always think about the gut when it comes to kidney disease. A personalized comprehensive gut restoration protocol is a must to heal the gut.
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A gut-derived uremic toxin is associated with inflammation
Speaking of the gut, we discussed monocyte to HDL ration (MHR) in a previous email. If you missed it, you can read about it on our Instagram page. This study looked at the connection between Indole-3-acetic acid which is a gut-derived uremic toxin and MHR in patients with kidney disease. The study was conducted on 67 patients with CKD. Researchers found that Indole-3-acetic acid levels are directly related to MHR levels. The latter was associated with higher levels of fibrinogen, arterial hypertension, CRP.
So, as they say, when in doubt think about the gut.
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It turns out they are not that “reno-protective” after all
According to this study performed on mice and humans, medications that are used to inhibit the renin-angiotensin system (ACEi or ARBs) can lead to hypertrophy (overgrowth) in the small arteries inside the kidneys.
In essence, with time the renin-producing cells transform from endocrine cells to matrix-producing cells. They end up surrounding the vessel walls and inducing the accumulation of adjacent smooth muscle cells and extracellular matrix, resulting in blood flow obstruction, focal ischemia, and fibrosis.
So do these medications protect the kidneys?
Vitamin C deficiency causes epigenetic changes in the renal tubules
In this study performed on mice who are dependent on dietary vitamin C, researchers used the sophisticated single-cell RNA sequencing to map out the DNA/RNA methylation in the renal cells.
They found that vitamin C deficiency can cause acute tubular injury (ATN) by causing epigenetic modifications of DNA/RNA in these cells.
The oxidation-resistant vitamin C derivative, ascorbyl phosphate magnesium, promoted DNA demethylation and prevented the progression of cisplatin-induced ATN.
The effects of SGLT-2 inhibitors on electrolytes
This is a meta-analysis that aimed to look at the comparative effects of various SGLT-2 inhibitors on electrolyte balances in diabetes.
The study found that all SGLT-2 inhibitors can lead to a mild increase in magnesium and phosphate levels. Dapagliflozin was associated with the highest increase in magnesium.
Interestingly, the study did not find any effects on other electrolytes. Other studies have demonstrated that SGLT-2 inhibitors can:
1. Increase magnesium level
2. Increase potassium level
3. Lower sodium level
4. Increase phosphate level
5. Lower uric acid level
We still don’t know their effects on other micronutrients such as zinc and others.
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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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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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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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Knowledge Does Not Correspond to Adherence to Renal Diet Restrictions in Patients With Chronic Kidney Disease
Education or knowledge alone is not sufficient to make meaningful lifestyle changes. It is not enough for a patient to meet with a doctor, dietitian, or nutritionist once and be expected to be educated about diet and other modifications.
The researchers in this study proved and concluded that “instruction efforts should go beyond providing nutrient-based diet information, and instead emphasize healthy food patterns and incorporate counseling to promote behavior change.”
In another word, patients need to be educated and coached to achieve better lifestyles and outcomes.
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Apixaban, compared with warfarin, was associated with a lower risk of CKD stage progression
In this study, researchers studied 12,816 patients who received either apixaban or warfarin for non-valvular atrial fibrillation. Apixaban was associated with slower progression of CKD than warfarin. We think that this underlines the role of vitamin K in vascular and kidney health.
Periodontal disease was associated with incident kidney disease
Researchers studied data from the Hispanic community health study to see if there is any association between periodontal disease and the development of kidney disease.
They found that the presence of ≥30% of sites with probing depth ≥4 mm and absence of functional dentition (<21 permanent teeth present) were each associated with increased risk for incident low eGFR.
Does treating periodontal disease prevent the development and progression of CKD? Research does not have the answer yet but we think so.
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