Deficiency In Chronic Kidney Disease Patients Research Articles

Dysbiosis in Patients with Chronic Kidney Disease: Let Us Talk About Vitamin K.

This narrative review aimed to summarize the current evidence on the connection between dysbiosis and vitamin K deficiency in patients with chronic kidney disease (CKD). The presence of dysbiosis (perturbations in the composition of the microbiota) has been described in several non-communicable diseases, including chronic kidney disease, and it has been hypothesized that dysbiosis may cause vitamin K deficiency. Patients with CKD present both vitamin K deficiency and gut dysbiosis; however, the relationship between gut dysbiosis and vitamin K deficiency remains to be addressed. Recently, few studies in animals have demonstrated that a dysbiotic environment is associated with low production of vitamin K by the gut microbiota. Vitamin K plays a vital role in blood coagulation as well as in the cardiovascular and bone systems. It serves as a cofactor for γ-glutamyl carboxylases and thus is essential for the post-translational modification and activation of vitamin K-dependent calcification regulators, such as osteocalcin, matrix Gla protein, Gla-rich protein, and proteins C and S. Additionally, vitamin K executes essential antioxidant and anti-inflammatory functions. Dietary intake is the main source of vitamin K; however, it also can be produced by gut microbiota. This review discusses the effects of uremia on the imbalance in gut microbiota, vitamin K-producing bacteria, and vitamin K deficiency in CKD patients, leading to a better understanding and raising hypothesis for future clinical studies.

Biological Role of Vitamin K-With Particular Emphasis on Cardiovascular and Renal Aspects.

Vitamin K (VK) plays many important functions in the body. The most important of them include the contribution in calcium homeostasis and anticoagulation. Vascular calcification (VC) is one of the most important mechanisms of renal pathology. The most potent inhibitor of this process—matrix Gla protein (MGP) is VK-dependent. Chronic kidney disease (CKD) patients, both non-dialysed and hemodialysed, often have VK deficiency. Elevated uncarboxylated matrix Gla protein (ucMGP) levels indirectly reflected VK deficiency and are associated with a higher risk of cardiovascular events in these patients. It has been suggested that VK intake may reduce the VC and related cardiovascular risk. Vitamin K intake has been suggested to reduce VC and the associated cardiovascular risk. The role and possibility of VK supplementation as well as the impact of anticoagulation therapy on VK deficiency in CKD patients is discussed.

Evaluation of Iron Status by Reticulocyte Haemoglobin Content (Chr) in Chronic Kidney Disease Patients on Haemodialysis and Erythropoietin.

Diagnosing iron deficiency with currently available tests is difficult in patients with chronic kidney disease (CKD) due to the inflammatory state associated with uraemia. The aim of this study was to evaluate the importance of reticulocyte haemoglobin (CHr) as a diagnostic tool of iron deficiency and a predictor to intravenous iron therapy in a cohort of CKD patients on haemodialysis in Sri Lanka. This was a descriptive cross sectional study involving hundred (100) patients with CKD on regular haemodialysis and erythropoietin. Patients were categorised into groups depending on serum ferritin, transferrin saturation and reticulocyte haemoglobin (CHr). All patients with CHr < 29pg were treated with a single dose of intravenous(IV) iron 500mg. The CHr was measured 72h after the IV iron treatment to assess the response. Within the population mean haemoglobin was 9.27g/dL, mean serum ferritin was 243.5ng/mL, mean transferrin saturation was 18.6% and mean CHr was 29.2pg. Thirty three of the 100 patients (33%) were subjected to IV iron therapy and there was a significant increase of CHr 72h after IV iron treatment (p < 0.001). As a diagnostic tool in iron deficiency in CKD patients on haemodialysis, CHr showed a sensitivity of 56%, specificity of 73% and positive predictive value of 84%. Reticulocyte haemoglobin (CHr) can be used as an early predictor of response to IV iron therapy. However, further evaluation is necessary to consider CHr as a diagnostic tool to detect iron deficiency in CKD patients on haemodialysis.

Evaluation of the relationship between neutrophil-to-lymphocyte ratio and 25-hydroxy vitamin D levels in hemodialysis patients, Isfahan, Iran

Introduction: Chronic low-grade inflammation is a comorbid factor in Chronic kidney disease (CKD), and especially in chronic dialysis patients. Recently, neutrophil-to-lymphocyte ratio (NLR), which is very available and affordable, has emerged as an inflammatory index in many disorders such as CKD. Several studies also have shown the anti-inflammatory effects of vitamin D, and scientists believe that we must prevent vitamin D deficiency in CKD patients. Vitamin D supplementation may decrease mortality and morbidity in end-stage renal disease (ESRD) patients. Objectives: There are few studies on the association between serum 25-hydroxy vitamin D levels and NLR in ESRD patients. Therefore, we tried to evaluate this correlation, hoping to be a key for more researches. Patients and Methods: We enrolled 140 ESRD hemodialysis patients in a cross-sectional study and evaluated the correlation of NLR with serum 25-hydroxy vitamin D levels and some demographic factors in these patients. Results: Our results showed a statistically significant negative correlation between NLR and serum 25-hydroxy vitamin D levels (P=0.010, r= -0.216). However, other variables such as disease duration and age had no correlation with NLR (P=0.649, r= - 0.039 and P=0.781, r= - 0.024, respectively). We also used a linear regression test to check any confounder associated with NLR, and the regression was only significant for serum 25-hydroxy vitamin D levels (P=0.011, B=-0.009). Conclusion: Based on the results, serum 25-hydroxy vitamin D levels can be considered a predictor for NLR in hemodialysis patients.

Serum Neutrophil Gelatinase-Associated Lipocalin and Iron Status in Predialysis Chronic Kidney Disease at Zagazig University

Background: The burden of chronic kidney disease (CKD) is substantial. Anemia is a common feature of CKD. Objective: The aim was to predict about iron status by serum neutrophil gelatinase-associated lipocalin (NGAL) levels and role of serum NGAL as biomarker of iron deficiency in CKD patients. Patients and Methods: A prospective, case-control comparative study that was conducted at Nephrology Outpatient Clinic and Internal Medicine Department, Zagazig University Hospitals. Seventy two participants were divided into two groups: Group I included 36 participants with no chronic kidney disease and group II that included 36 chronic kidney disease patients. Laboratory investigations included iron parameters and serum NGAL levels were measured Results: S. Iron, TIBC, S. Ferritin and calculated T. sat” were statistically analyzed and showed that there was a statistical significant difference between the two studied groups. NGAL level was higher in CKD group than in the non-CKD group. A significant positive correlation between serum NGAL and T sat & serum ferritin and there was a significant negative correlation between NGAL and eGFR, HB and serum iron. Conclusion: Patients had significantly higher NGAL levels when compared to controls and this means that it had an important role in iron metabolism in those patients. There was statistically significant direct correlation between serum NGAL levels and serum ferritin levels and T. sat and inverse correlation with iron. Serum NGAL could be a good biomarker for iron status in CKD patients but not better than the ordinary used methods “serum ferritin and T. sat”.

Complications métaboliques en insuffisance rénale chronique : hyperphosphatémie, hyperkaliémie et anémie

Metabolic complications of chronic kidney disease (CKD) are frequent; the aims of this review are to present a 2018 update for hyperkalemia, hyperphosphatemia and anemia.Hyperkalemia is defined by a plasma level above 5.0 mmol/L, after ruling out pre-analytical problems such as hemolysis. It is frequent in CKD, most often due to drugs and notably renin/ angiotensin blockers. Chronic hyperkalemia is deleterious, with an increased risk of mortality. Therapeutic strategies to decrease the incidence and severity of hyperkalemia are therefore crucial in nephrology: experts recommend to maintain the renin/angiotensin blockers as long as possible, whilst associating diuretics and potassium binders.There are apparent discrepancies between optimal protein intake and decreased phosphate intake in CKD; this is even more important in dialysis since protein decrease is associated with denutrition and subsequent increased risk of mortality. Nutritional phosphate intake from vegetables are less absorbed; in contrast, phosphate additives are almost completely absorbed in the gastro-intestinal tract. These “hidden” intake may increase the total daily phosphate intake by 1 000 mg. As such in addition to optimized dialysis, phosphate binders should be used but compliance may be challenging on the long-term. Educational programs focused on phosphate are also mandatory in CKD patients.“Absolute” iron deficiency is less frequent than “functional” iron deficiency in CKD patients: both require the use of iron supplementation, and the latter may benefit from additional erythropoietin stimulating agents (ESA) when hemoglobin is below 10 g/dL. Intravenous iron is more efficient to correct iron deficiency both in pre-dialysis and dialysis especially in patients with chronic deficiency. Last generation intravenous preparations have largely demonstrated their safety. One indication of iron supplementation one should not forget in nephrology is the patient with moderate CKD and heart failure since the expected benefits are multiple, notably in terms of quality of life, renal function and functional capacity.Cet article fait partie du numéro supplément Innovations en Néphrologie réalisé avec le soutien institutionnel de Vifor Fresenius Medical Care Renal Pharma.

Budget Impact Analysis of Oral Fisiogen Ferro Forte® versus Intravenous Iron for the Management of Iron Deficiency in Chronic Kidney Disease in Spain.

Iron deficiency is a frequent complication of chronic kidney disease (CKD) that is associated with a decrease in the quality of life of patients and an increase in the risk of other clinical complications. Iron therapy represents one of the fundamentals of patients with CKD. Sucrosomial® oral iron allows Fisiogen Ferro Forte® to be used in all patients who are intolerant to treatment by the oral route of administration, or who present with malabsorption of conventional oral iron preparations. The main objective of this study was to assess the economic impact of the oral iron Fisiogen Ferro Forte® for the management of iron deficiency in CKD patients in Spain. A 4-year budget impact model was developed for the period 2017-2020 for CKD patients with iron deficiency who were candidates for intravenous iron due to a lack of response to oral iron, from the perspective of the Spanish healthcare system. Three subgroups of CKD patients were included in the analysis: predialysis, peritoneal dialysis, and post-transplant. The intravenous iron formulations Ferinject®, Venofer®, and Feriv® were considered appropriate comparators to be used in the model. National data on the prevalence of CKD for the three subgroups of patients were obtained from the literature, and input data on drug utilization and outpatient hospitalizations associated with iron administration were obtained by consulting nephrologists. Nephrology experts were also asked about resources used during medical visits and monitoring tests. Based on the unit costs for each iron therapy and the resources used, the total treatment cost per patient associated with each product was obtained to estimate the global budget impact of increasing the use of Fisiogen Ferro Forte®. The average annual budget savings due to an increase in Fisiogen Ferro Forte® and a decrease in intravenous iron have been estimated at €398,685, €180,937, and €195,842 over 4years for the predialysis, peritoneal dialysis, and post-transplant groups, respectively. The increase in the use of Fisiogen Ferro Forte® leads to overall budget savings of €775,464 for the Spanish National Health Service over 4years.

An Underestimation of 25-OH Vitamin D in Patients with Renal Disease by the Abbott Architect Immunoassay.

To the Editor: Patients with advanced chronic kidney disease (CKD)1 typically have reduced serum 1,25-hydroxyvitamin D (1,25-OHD) concentrations due to the inability to convert inactive 25-hydroxyvitamin D (25-OHD) to active 1,25-OHD. However, decreased 1,25-OHD can also be a result of 25-OHD deficiency due to coexisting conditions, such as liver disease, intestinal malabsorption, or urinary wasting of the vitamin-bound 25-OHD binding protein. The National Kidney Foundation Kidney Disease: Improving Global Outcomes has detailed guidelines for the prevention and treatment of vitamin D insufficiency and deficiency in CKD patients. According to the guidelines, patients in CKD stages 2–4 should have …

Impact of Vitamin D Supplementation on Arterial Vasomotion, Stiffness and Endothelial Biomarkers in Chronic Kidney Disease Patients

BackgroundCardiovascular events are frequent and vascular endothelial function is abnormal in patients with chronic kidney disease (CKD). We demonstrated endothelial dysfunction with vitamin D deficiency in CKD patients; however the impact of cholecalciferol supplementation on vascular stiffness and vasomotor function, endothelial and bone biomarkers in CKD patients with low 25-hydroxy vitamin D [25(OH)D] is unknown, which this study investigated.MethodsWe assessed non-diabetic patients with CKD stage 3/4, age 17–80 years and serum 25(OH)D <75 nmol/L. Brachial artery Flow Mediated Dilation (FMD), Pulse Wave Velocity (PWV), Augmentation Index (AI) and circulating blood biomarkers were evaluated at baseline and at 16 weeks. Oral 300,000 units cholecalciferol was administered at baseline and 8-weeks.ResultsClinical characteristics of 26 patients were: age 50±14 (mean±1SD) years, eGFR 41±11 ml/min/1.73 m2, males 73%, dyslipidaemia 36%, smokers 23% and hypertensives 87%.At 16-week serum 25(OH)D and calcium increased (43±16 to 84±29 nmol/L, p<0.001 and 2.37±0.09 to 2.42±0.09 mmol/L; p = 0.004, respectively) and parathyroid hormone decreased (10.8±8.6 to 7.4±4.4; p = 0.001). FMD improved from 3.1±3.3% to 6.1±3.7%, p = 0.001.Endothelial biomarker concentrations decreased: E-Selectin from 5666±2123 to 5256±2058 pg/mL; p = 0.032, ICAM-1, 3.45±0.01 to 3.10±1.04 ng/mL; p = 0.038 and VCAM-1, 54±33 to 42±33 ng/mL; p = 0.006. eGFR, BP, PWV, AI, hsCRP, von Willebrand factor and Fibroblast Growth Factor-23, remained unchanged.ConclusionThis study demonstrates for the first time improvement of endothelial vasomotor and secretory functions with vitamin D in CKD patients without significant adverse effects on arterial stiffness, serum calcium or FGF-23.Trial RegistrationClinicalTrials.gov NCT02005718

Peripheral Treg count and it’s determinants in unsensitized and sensitized chronic kidney disease patients

Sensitization to HLA antigens resulting in anti-HLA antibodies (panel reactive antibodies; PRA) is a major problem in chronic kidney disease (CKD) patients awaiting transplantation. Induction of anti-HLA antibodies normally occurs through blood transfusion, pregnancy and prior transplantation. However, some patients develop these antibodies for unknown immunological reasons. It is hypothesized that deviations in immune regulation may account for PRA positivity in these patients. We, therefore, investigated whether a quantitative deficiency in peripheral natural regulatory T cells (CD4(+)CD25(high)Foxp3(+); nTreg) plays a role in this phenomenon. Peripheral blood mononuclear cells from 14 patients with positive (Class I and Class II; 10-100 %) and 25 patients with negative PRA, who had not previously been sensitized by blood transfusion, pregnancy and prior transplantation and who had not received any immunomodulatory treatment within the last year, were analyzed for absolute lymphocyte and nTreg numbers through flow cytometry. Samples from 10 healthy people were also used as control. Mean absolute nTreg numbers were determined to be severely reduced in CKD patients (12 ± 9; n = 39) compared with healthy individuals (53 ± 17; n = 10) (p = 0.008). However, absolute nTreg numbers were similar between PRA- (12 ± 11) and PRA+ (11 ± 8) groups. Interestingly, there was a moderate correlation between the nTreg numbers and HLADR2 genotype (n = 9, r = 0.508, p < 0.05). This is the first study to demonstrate that the quantitative peripheral nTreg deficiency in CKD patients does not show a causal relationship with the presence of anti-HLA antibodies.

The effect of Helicobacter pylori on vitamin B12blood levels in chronic renal failure patients: A single blind control trial

Helicobacter pylori (HP) is a common infection worldwide and has been associated with severe morbidity. The level of vitamin B 12 in HP-infected chronic kidney disease (CKD) patients is reported to be lower than in the general population. The present study has been designed to evaluate the vitamin B 12 level in HP-infected CKD patients. We assessed the serum levels of vitamin B 12 in 50 CKD patients with positive HP serology, one and three months after the eradication of HP infection. There were significant differences between the serum levels of vitamin B 12 in the study patients before (806.98 ± 466.82) and after (760.36 ± 433.93) eradication treatment (P <0.001). We conclude that our study suggests the correlation between vitamin B 12 deficiency in CKD patients and the HP infection status.

Clinical and demographic predictors for vitamin D deficiency in multiethnic Asian patients with chronic kidney disease.

BackgroundVitamin D deficiency is common in patients with chronic kidney disease (CKD) and can cause skeletal and extraskeletal complications. The purpose of this study is to determine the clinical and demographic risk factors for vitamin D deficiency in multiethnic CKD patients in Singapore, a sun-rich country, so that patients at risk can be identified and treated early.MethodsPre-dialysis CKD patients from the National University Hospital (NUH), Singapore, Outpatient Renal Clinic who had their serum 25-hydroxyvitamin D [25(OH)D] levels measured between January 2008 and October 2010 were included. Their clinical and demographic parameters were collected from hospital databases and medical charts. Logistic regression was used to identify potential predictors for vitamin D deficiency in these patients. Two models, Mt30 and Mt16, were built using threshold serum 25(OH)D levels of ≤30 and <16 ng/mL, respectively.ResultsOf the 219 patients included, 82.7 and 25.6% had serum 25(OH)D levels ≤30 and <16 ng/mL, respectively. Predictors identified for vitamin D deficiency include absence of vitamin D supplementation, type 2 diabetes mellitus (DM), non-cancer diagnosis, younger age, Malay race, treatment with calcitriol and higher serum bicarbonate (CO2) levels. Common predictors for the two models were lack of vitamin D supplementation and DM. The areas under the receiver-operating characteristic (ROC) curve for the validation sets were 0.697 and 0.687 for the Mt30 and Mt16 models, respectively.ConclusionsVitamin D deficiency is common among multiethnic CKD patients in Singapore. Risk factors identified in this study include absence of vitamin D supplementation, DM, non-cancer diagnosis, young age, Malay race, calcitriol treatment and higher serum CO2. The knowledge of these risk factors is useful for predicting vitamin D deficiency in CKD patients in Singapore.

CYP24A1 and kidney disease

Patients with chronic renal disease have elevated serum phosphate levels, elevated fibroblast-like growth factor 23 (FGF-23), and declining vitamin D status. These changes are related and may be responsible for elevated 25-hydroxyvitamin D-24-hydroxylase (CYP24A1) and dysfunctional vitamin D metabolism. This review focuses on the biochemistry and pathophysiology of CYP24A1 and the utility of blocking this enzyme with CYP24A1 inhibitors in chronic kidney disease (CKD) patients. CYP24A1 is the cytochrome P450 enzyme that catalyzes the conversion of 25-hydroxyvitamin D3 (25-OHD3) and its hormonal form, 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], into 24-hydroxylated products targeted for excretion. The CYP24A1-null phenotype is consistent with the catabolic role of CYP24A1. A number of polymorphisms of CYP24A1 have recently been identified. New data from the uremic rat and humans suggest that dysfunctional vitamin D metabolism is due to changes in CYP24A1 expression caused by phosphate and FGF-23 elevations. Changes in serum phosphate and FGF-23 levels in the CKD patient increase CYP24A1 expression resulting in decreased vitamin D status. Vitamin D deficiency may exacerbate defective calcium and phosphate homeostasis causing renal osteodystrophy and contribute to the other complications of renal disease. These findings argue for increased focus on correcting vitamin D deficiency in CKD patients by blocking CYP24A1 activity.

Incident isolated 1,25(OH)2D3 deficiency is more common than 25(OH)D deficiency in CKD

Vitamin D deficiencies are well described in general populations and in those with chronic kidney disease (CKD). Although serum 25(OH)D may be a good indicator of vitamin D status in healthy individuals, the hydroxylated product, 1,25(OH)(2)D, essential for important biological functions such as mineral metabolism, bone turnover, regulation of protein synthesis, cell differentiation and proliferation may be a more suitable indicator for individuals with CKD. We report an observational prospective cohort study of the incidence after 12 months of new isolated 1,25(OH)(2)D and new 25(OH)D deficiency in CKD patients (estimated glomerular filtration rate [eGFR] <60 ml/min), who were vitamin D replete at baseline. All analyses were run in a central laboratory. Of 1,256 patients who completed the study at 12 months, 631 were replete in both 25(OH)D and 1,25(OH)(2)D at baseline; at 12 months, 65% remained replete, 25% developed an isolated 1,25(OH)(2)D deficiency, whereas only 6% developed an isolated 25(OH)D deficiency. Based on the multinomial logistic regression model, factors that were associated with 12-month changes in vitamin D status were diabetes, baseline values of eGFR, albumin and both 25(OH)D and 1,25(OH)(2)D (all p values <0.03). Patients with diabetes, lower albumin, lower eGFR, lower levels of 25(OH)D and 1,25(OH)(2)D at baseline were at increased risk of developing isolated 1,25(OH)(2)D deficiency. The high incidence of new isolated 1,25(OH)(2)D deficiency as compared with new 25(OH)D deficiency, in the presence of 25(OH)D sufficiency, brings into question the value of measuring 25(OH)D levels in CKD. The significance of these findings and implications for replacement strategies require further study.

Intravenous Iron Versus Erythropoiesis-Stimulating Agents: Friends or Foes in Treating Chronic Kidney Disease Anemia?

Patients with chronic kidney disease (CKD), especially those requiring maintenance hemodialysis treatments, may lose up to 3 g of iron each year because of frequent blood losses. Higher doses of erythropoiesis-stimulating agents (ESAs) may worsen iron depletion and lead to an increased platelet count (thrombocytosis), ESA hyporesponsiveness, and hemoglobin variability. Hence, ESA therapy requires concurrent iron supplementation. Traditional iron markers such as serum ferritin and transferrin saturation ratio (TSAT) (ie, serum iron divided by total iron-binding capacity [TIBC]), may be confounded by non-iron-related conditions. Whereas serum ferritin <200 ng/mL suggests iron deficiency in CKD patients, ferritin levels between 200 and 1,200 ng/mL may be related to inflammation, latent infections, malignancies, or liver disease. Protein-energy wasting may lower TIBC, leading to a TSAT within the normal range, even when iron deficiency is present. Iron and anemia indices have different mortality predictabilities, in that high serum ferritin but low iron, TIBC, and TSAT levels are associated with increased mortality, whereas hemoglobin exhibits a U-shaped risk for death. The increased mortality associated with targeting hemoglobin above 13 g/dL may result from iron depletion-associated thrombocytosis. Intravenous (IV) iron administration may not only decrease hemoglobin variability and ESA hyporesponsiveness, it may also reduce the greater mortality associated with the much higher ESA doses that have been used in some patients when targeting higher hemoglobin levels.

Consequences of low plasma histidine in chronic kidney disease patients: associations with inflammation, oxidative stress, and mortality

BackgroundHistidine is considered as an antiinflammatory and antioxidant factor. Histidine deficiency may contribute to an impaired nutritional state in patients with chronic kidney disease (CKD). ObjectiveWe aimed to investigate the consequences of plasma histidine deficiency in CKD patients. DesignCKD patients (n = 325; 203 M) with a median age of 54 y (range: 19–70 y) were evaluated shortly before the beginning of renal replacement therapy. The median glomerular filtration rate was 6.4 mL/min (range: 0.8–14.5 mL/min). Nutritional status was assessed by subjective global assessment. Survival was followed for up to 60 mo; 101 patients died. ResultsPlasma histidine concentrations were significantly lower in CKD patients with history of cardiovascular disease, presence of plaques, protein-energy wasting, and inflammation. Plasma histidine was negatively associated with age, C-reactive protein, interleukin-6, leukocytes, thrombocytes, fibrinogen, hepatocyte growth factor, adhesion molecules, insulin-like growth factor-1, and 8-hydroxy-2′-deoxyguanosine and was positively associated with handgrip strength, hemoglobin, S-albumin and fetuin-A. A multivariate regression analysis showed that histidine concentrations were independently associated with hepatocyte growth factor, hemoglobin, and fetuin-A. In unadjusted analysis, a low histidine concentration was associated with all-cause mortality (log rank chi-square test = 8.9; P = 0.002). After adjustment for age, sex, cardiovascular disease, inflammation, diabetes mellitus, serum S-albumin, and amino acid supplementation, the association between low histidine and mortality remained significant (hazard ratio: 1.55; 95% CI: 1.02, 2.40; P < 0.05). ConclusionLow plasma concentrations of histidine are associated with protein-energy wasting, inflammation, oxidative stress, and greater mortality in CKD patients.