|Year : 2021 | Volume
| Issue : 1 | Page : 12-15
Micronutrients in hemodialysis patients: A single-center study
Anil Kumar Bhalla, Vaibhav Tiwari, Anurag Gupta, Vinant Bhargawa, Manish Malik, Ashwani Gupta, Devinder Singh Rana
Department of Nephrology, Sir Ganga Ram Hospital, New Delhi, India
|Date of Submission||26-Jul-2021|
|Date of Acceptance||27-Jul-2021|
|Date of Web Publication||21-Oct-2021|
Dr. Anil Kumar Bhalla
Director, Department of Nephrology, Sir Ganga Ram Hospital, New Delhi
Source of Support: None, Conflict of Interest: None
Introduction: In end-stage chronic kidney disease, nephrologists must consider the homeostasis of the multiple water-soluble ions and vitamins that are influenced by renal replacement therapy. While certain ions such as potassium and calcium are closely monitored, little is known about the handling of trace elements and vitamins in the dialysis population. Material and Methods: This was a single-centered, observational, retrospective, cross-sectional study to analyze the serum levels of clinically relevant vitamins (Vitamin D, Vitamin B12, folate) and microelements (iron, zinc) among maintenance hemodialysis (MHD) patients during June 2020–June 2021. Results: Two hundred and twenty-five patients on MHD were included in the study. The mean age was 54 years. Diabetic kidney disease (32%) was the most common basic kidney disease. The majority of patients (76%) were undergoing twice-weekly MHD. Iron was the most deficient microelement among MHD patients (64%). Vitamin D was deficient in 85% of the population. Mean zinc levels were 90 ± 18 with 19% of the patients having low zinc levels. Vitamin B12 and folate were deficient in 3% and 5% of patients, respectively. However, 40% and 32% of the patients had levels of Vitamin B12 and folate above the measurable limit. There was no association of deficient micronutrients and age, sex, and dialysis frequency. Conclusion: Iron and zinc are mostly deficient among MHD patients. Vitamin supplements should be carefully prescribed as the majority of patients had an excess of Vitamin B12 and folate rather than deficiency.
Keywords: Chronic kidney disease, hemodialysis, micronutrients
|How to cite this article:|
Bhalla AK, Tiwari V, Gupta A, Bhargawa V, Malik M, Gupta A, Rana DS. Micronutrients in hemodialysis patients: A single-center study. J Renal Nutr Metab 2021;7:12-5
|How to cite this URL:|
Bhalla AK, Tiwari V, Gupta A, Bhargawa V, Malik M, Gupta A, Rana DS. Micronutrients in hemodialysis patients: A single-center study. J Renal Nutr Metab [serial online] 2021 [cited 2022 May 26];7:12-5. Available from: http://www.jrnm.in/text.asp?2021/7/1/12/328955
| Introduction|| |
The kidney is an important organ to main salt-water homeostasis. Apart from the usual sodium, potassium, calcium, etc., the kidney is also an important organ to maintain the homeostasis of trace elements [Table 1] and water-soluble vitamins. A considerable focus has been put on macronutrients (protein and carbohydrate) in the form of protein-energy wasting among hemodialysis (HD) patients. However, studies evaluating the role of micronutrients in poor outcomes are largely lacking. Micronutrients such as coenzyme Q10, L-carnitine, and taurine are essential aids in maintaining physiological energy homeostasis. The role of micronutrient deficiency has been implicated in heart failure, cognitive disturbance, and advance renal failure., Hemodialysis is a special situation where blood is constantly exposed to an artificial membrane and nonphysiological solution called dialysate., Since it is impossible to enact the physiology of renal tubules, various elements leech in and out of the blood. It has been observed that water-soluble vitamins are dialyzed and blood concentration tends to be low without supplementation, whereas fat-soluble vitamins are usually normal or elevated as they are not dialyzed. Few studies have been done to study the effect of HD on trace elements such as zinc, selenium, and lead.,,,,,, Most of the studies have concluded that the concentration of these trace elements has been significantly altered due to HD. Since outcomes of HD have been poor in general, various factors have been implicated. Disturbance in the microenvironment has been implicated as one of the causes. This study has been conducted to study the prevalence of deficiency of micronutrients, namely iron, zinc, Vitamin D, folate, and Vitamin B12 among maintenance HD (MHD) patients.
| Materials and Methods|| |
Study population and data source
This is a retrospective cross-sectional single-centered study. The study population includes all the adults (>18 years) undergoing maintenance HD (>3 months) in this center. Patients were excluded from this study if their total treatment lasted <90 days or if they did not have at least one serum Vitamin B12 (B12), 25 OH Vitamin D (Vitamin D), iron, folate, and zinc measurement during the study period of 3 months.
Laboratory parameters collected from the Electronic Medical Record include complete blood count, creatinine, albumin, parathyroid hormone (PTH), Vitamin D, calcium, and phosphorous.
All blood samples were collected predialysis. Most laboratory values were measured monthly, including hemoglobin, creatinine, calcium, phosphorus, albumin, and ferritin. All repeated measures during the 90 days of study treatment were averaged and their summary estimates were used in all analyses.
Reference values for Vitamin D
Based on clinical definitions and for purposes of interpretability, Vitamin D levels ≥30 ng/dL were considered replete, whereas Vitamin D deficiency was defined as level <30.
Patients' baseline demographics, clinical characteristics, and laboratory measurements across serum B12 and folate categories were summarized as means ± standard deviation, or median (interquartile range) where appropriate, and were compared using Chi-square tests where appropriate.
| Results|| |
From September 2020 to December 2020, 225 MHD patients were included in the study. The mean age of the patients was 54 years. The majority of the patients were male (56%). Diabetic kidney disease was the most common basic kidney disease (32%) [Table 2]. Around 2% of the patient had undergone transplantation previously. The majority of the patients were getting twice-weekly HD (72%).
|Table 2: Characteristics of population, dialysis, and laboratory parameters|
Click here to view
The biochemical profile of the patients showed that the majority of the patient had anemia (28%), hypoalbuminemia (40%), and elevated PTH levels (93%) [Table 2].
Iron was the most deficient micronutrient among MHD patients (64%) [Table 3]. Mean Zinc levels were 90 ± 18 with 19% of the patients having low zinc levels. Vitamin D was deficient (<30 ng/mL) in 85% of the patients. Vitamin B12 and folate were deficient in 3% and 5% of patients, respectively. However, 40% and 32% of the patients had levels of Vitamin B12 and folate above the measurable limit. There was no association between dialysis frequency and microelements and vitamins levels. Similarly, there was no association of age, sex, and albumin levels with the micronutrient [Table 4].
|Table 3: Distribution of iron, zinc, folate, Vitamin D, and Vitamin B12 among hemodialysis population|
Click here to view
|Table 4: Association of iron, zinc, folate, Vitamin D, and Vitamin B12 with various factors|
Click here to view
| Discussion|| |
Trace elements levels among the HD population have a different layout from the general population due to restricted diet, poor renal clearance, medications, and exposure to dialysate, etc., This study was conducted to assess the levels of clinically relevant minerals and vitamins among the HD population.
Zinc is one of the minerals which are deficient in the majority of the HD population in various studies.,,> Zinc is an important element that has a role in almost every aspect of gene transcription and protein synthesis. It is a cofactor for more than 70 enzymes. Its deficiency may range from growth retardation, impotence, dermatitis to immune dysfunction. In contrast to the study by Gómez de Oña et al., where authors reported a 59% deficiency among the HD population, we had only 19% of patients with levels lower than the reference range. A probable cause of this lower prevalence of zinc deficiency may be because, during COVID 19 pandemic in India, zinc supplementation was widely promoted as an immune booster and the majority of the population including ESRD patients were taking it as a supplement.,
Iron deficiency among HD patients is multifactorial that includes malnutrition, gastrointestinal blood loss, and dialysis treatment. On average, HD patients lose 1–2 g of iron annually. Hence, it was not surprising to find the majority of the HD population (64%) deficient in iron.
Vitamin D deficiency is universal among HD patients. Our results of 85% deficient HD patients are similar to other reports where authors have reported a prevalence of 70%–90%.,,
Most of the HD patients have mild-to-moderate deficiency of folate.,,, This may be due to multiple factors including malnutrition, restricted diet, and medication. Since folate is water soluble, a significant amount is lost during HD. Folate plays a key role in the metabolism of nucleotides and amino acids including that of homocysteine. In addition, insufficient folate intake is linked to neural tube defects, megaloblastic anemia, coronary heart disease, and colon and breast cancers. In contrast, Vitamin B12 levels among HD patients more or less correlate well with the general population.,,> B12 is a coenzyme involved in the catabolism of methylmalonic acid and homocysteine and B12 deficiency is also associated with megaloblastic anemia as well as neurologic and cognitive sequelae. Vitamin B12, owing to its large molecular weight, poorly diffuses during the HD as compared to folate. In this study, we find only a small fraction of the population having B12 and folate below the reference range. Interestingly, a significant number of individuals had their levels beyond the upper limit. This may be due to the overenthusiastic supplementation of these vitamins. Maintaining levels beyond the upper limit as any additional benefit is a subject of further evaluation. However, many studies have correlated increased mortality with increasing levels of B12. In the study by Soohoo et al., authors found that higher B12 concentrations are associated with higher all-cause mortality in HD patients independent of sociodemographic and laboratory variables, whereas lower folate concentrations were associated with higher all-cause mortality. In patients with chronic inflammation, like the HD population, decreased production of transcobalamin II may lead to reduced uptake of circulating B12 by peripheral tissues, and heightened synthesis of transcobalamins I and III further augments accumulation of B12 in serum.,, This may be a protective phenomenon to conserve Vitamin B12 from utilization by pathogens causing inflammation and infection. Thus, in chronic inflammatory conditions such as HD, higher serum B12 may indicate functional B12 deficiency in the peripheral tissues that may eventually lead to hyperhomocysteinemia, cardiovascular sequelae, and death. Whether Vitamin B12 and folate supplementation doing more harm than good, we need more studies to further studies conclusively answer this question.
This study is limited by its cross-sectional observational nature. However, this is the first study from India evaluating zinc, Vitamin B12, and folate levels among the HD population.
| Conclusion|| |
Iron, zinc, and Vitamin D are mostly deficient among MHD patients. Vitamin supplements should be carefully prescribed as the majority of patients had an excess of Vitamin B12 and folate rather than deficiency. The frequency of MHD was not associated with any micronutrient deficiency.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Qian Q. Salt, water and nephron: Mechanisms of action and link to hypertension and chronic kidney disease. Nephrology (Carlton) 2018;23 Suppl 4:44-9.
Kasama RK. Trace minerals in patients with end-stage renal disease. Semin Dial 2010;23:561-70.
Gómez-Pinilla F. Brain foods: The effects of nutrients on brain function. Nat Rev Neurosci 2008;9:568-78.
Soukoulis V, Dihu JB, Sole M, Anker SD, Cleland J, Fonarow GC, et al
. Micronutrient deficiencies an unmet need in heart failure. J Am Coll Cardiol 2009;54:1660-73.
Covic A, Gusbeth-Tatomir P. Trace elements in end-stage renal disease--unfamiliar territory to be revealed. BMC Nephrol 2009;10:12.
Kiziltas H, Ekin S, Erkoc R. Trace element status of chronic renal patients undergoing hemodialysis. Biol Trace Elem Res 2008;124:103-9.
Zima T, Tesař V, Mestek O, Němeček K. Trace elements in end-stage renal disease. Blood Purif 1999;17:182-6.
Tonelli M, Wiebe N, Bello A, Field CJ, Gill JS, Hemmelgarn BR, et al.
Concentrations of trace elements in hemodialysis patients: A prospective cohort study. Am J Kidney Dis 2017;70:696-704.
Tonelli M, Wiebe N, Hemmelgarn B, Klarenbach S, Field C, Manns B, et al.
Trace elements in hemodialysis patients: A systematic review and meta-analysis. BMC Med 2009;7:25.
Tonelli M, Wiebe N, Bello A, Field CJ, Gill JS, Hemmelgarn BR, et al.
Concentrations of trace elements and clinical outcomes in hemodialysis patients: A prospective cohort study. Clin J Am Soc Nephrol 2018;13:907-15.
Rucker D, Thadhani R, Tonelli M. Trace element status in hemodialysis patients. Semin Dial 2010;23:389-95.
Forman JP, Giovannucci E, Holmes MD, Bischoff-Ferrari HA, Tworoger SS, Willett WC, et al.
Plasma 25-hydroxyvitamin D levels and risk of incident hypertension. Hypertension 2007;49:1063-9.
Navarro-Alarcon M, Reyes-Pérez A, Lopez-Garcia H, Palomares-Bayo M, Olalla-Herrera M, Lopez-Martinez MC. Longitudinal study of serum zinc and copper levels in hemodialysis patients and their relation to biochemical markers. Biol Trace Elem Res 2006;113:209-22.
Hsieh YY, Shen WS, Lee LY, Wu TL, Ning HC, Sun CF. Long-term changes in trace elements in patients undergoing chronic hemodialysis. Biol Trace Elem Res 2006;109:115-21.
Gómez de Oña C, Martínez-Morillo E, Gago González E, Vidau Argüelles P, Fernández Merayo C, Álvarez Menéndez FV. Variation of trace element concentrations in patients undergoing hemodialysis in the north of Spain. Scand J Clin Lab Invest 2016;76:492-9.
Wessels I, Rolles B, Rink L. The potential impact of zinc supplementation on COVID-19 pathogenesis. Front Immunol 2020;11:1712.
Chinni V, El-Khoury J, Perera M, Bellomo R, Jones D, Bolton D, et al.
Zinc supplementation as an adjunct therapy for COVID-19: Challenges and opportunities. Br J Clin Pharmacol. 2021 Mar 19;10.1111/bcp.14826. doi: 10.1111/bcp.14826.
Eschbach JW, Cook JD, Scribner BH, Finch CA. Iron balance in hemodialysis patients. Ann Intern Med 1977;87:710-3.
Bansal B, Bansal S, Mithal A, Kher V, Marwaha R. Vitamin D deficiency in hemodialysis patients. Indian J Endocrinol Metab 2012;16:270-3.
Jabbar Z, Aggarwal PK, Chandel N, Kohli HS, Gupta KL, Sakhuja V, et al.
High prevalence of Vitamin D deficiency in north Indian adults is exacerbated in those with chronic kidney disease. Nephrology (Carlton) 2009;14:345-9.
Nazzal ZA, Hamdan Z, Natour N, Barbar M, Rimawi R, Salaymeh E. Prevalence of Vitamin D deficiency among hemodialysis patients in Palestine: A cross-sectional study. Experimental Biology, 2006:20;2417-9. DOI: 10.1096/fj.06-6374fje PMID: 17023519.
Chiu YW, Chang JM, Hwang SJ, Tsai JC, Chen HC. Pharmacological dose of vitamin B12 is as effective as low-dose folinic acid in correcting hyperhomocysteinemia of hemodialysis patients. Ren Fail 2009;31:278-83.
Bayés B, Pastor MC, Bonal J, Juncà J, Hernandez JM, Riutort N, et al.
Homocysteine, C-reactive protein, lipid peroxidation and mortality in haemodialysis patients. Nephrol Dial Transplant 2003;18:106-12.
Dierkes J, Domrose U, Westphal S, Ambrosch A, Bosselmann HP, Neumann KH, et al.
Cardiac troponin T predicts mortality in patients with end-stage renal disease. Circulation 2000;102:1964-9.
Clase CM, Ki V, Holden RM. Water-soluble vitamins in people with low glomerular filtration rate or on dialysis: A review. Semin Dial 2013;26:546-67.
Leblanc M, Pichette V, Geadah D, Ouimet D. Folic acid and pyridoxal-5'-phosphate losses during high-efficiency hemodialysis in patients without hydrosoluble vitamin supplementation. J Ren Nutr 2000;10:196-201.
Fairfield KM, Fletcher RH. Vitamins for chronic disease prevention in adults: Scientific review. JAMA 2002;287:3116-26.
de Arteaga J, Ledesma F, Garay G, Chiurchiu C, de la Fuente J, Douthat W, et al.
High-dose steroid treatment increases free water transport in peritoneal dialysis patients. Nephrol Dial Transplant 2011;26:4142-5.
Mallamaci F, Zoccali C, Tripepi G, Fermo I, Benedetto FA, Cataliotti A, et al.
Hyperhomocysteinemia predicts cardiovascular outcomes in hemodialysis patients. Kidney Int 2002;61:609-14.
Fletcher RH, Fairfield KM. Vitamins for chronic disease prevention in adults: Clinical applications. JAMA 2002;287:3127-9.
Soohoo M, Ahmadi SF, Qader H, Streja E, Obi Y, Moradi H, et al.
Association of serum Vitamin B12 and folate with mortality in incident hemodialysis patients. Nephrol Dial Transplant 2017;32:1024-32.
Salles N, Herrmann F, Sakbani K, Rapin CH, Sieber C. High Vitamin B12 level: A strong predictor of mortality in elderly inpatients. J Am Geriatr Soc 2005;53:917-8.
Seetharam B, Li N. Transcobalamin II and its cell surface receptor. Vitam Horm 2000;59:337-66.
Sviri S, Khalaila R, Daher S, Bayya A, Linton DM, Stav I, et al.
Increased Vitamin B12 levels are associated with mortality in critically ill medical patients. Clin Nutr 2012;31:53-9.
[Table 1], [Table 2], [Table 3], [Table 4]