Serum levels of miR-126 and miR-223 and outcomes in chronic kidney disease patients

AbstractDysfunction of the circadian clock has been implicated in the pathogenesis of cardiovascular disease. The CLOCK protein is a core molecular component of the circadian oscillator, so that mice with a mutated Clock gene (Clk/Clk) exhibit abnormal rhythms in numerous physiological processes. However, here we report that chronic kidney disease (CKD)-induced cardiac inflammation and fibrosis are attenuated in Clk/Clk mice even though they have high blood pressure and increased serum angiotensin II levels. A search for the underlying cause of the attenuation of heart disorder in Clk/Clk mice with 5/6 nephrectomy (5/6Nx) led to identification of the monocytic expression of G protein-coupled receptor 68 (GPR68) as a risk factor of CKD-induced inflammation and fibrosis of heart. 5/6Nx induces the expression of GPR68 in circulating monocytes via altered CLOCK activation by increasing serum levels of retinol and its binding protein (RBP4). The high-GPR68-expressing monocytes have increased potential for producing inflammatory cytokines, and their cardiac infiltration under CKD conditions exacerbates inflammation and fibrosis of heart. Serum retinol and RBP4 levels in CKD patients are also sufficient to induce the expression of GPR68 in human monocytes. Our present study reveals an uncovered role of monocytic clock genes in CKD-induced heart failure.

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SP400VERY LOW PROTEIN DIET REDUCES SERUM LEVELS OF INDOXYL SULFATE AND P-CRESYL SULFATE IN CHRONIC KIDNEY DISEASE

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfx148.sp400 ◽

2017 ◽

Vol 32 (suppl_3) ◽

pp. iii253-iii253 ◽

Cited By ~ 1

Author(s):

Maria Teresa Rocchetti ◽

Carmela Cosola ◽

Ighli di Bari ◽

Lucia Di Micco ◽

Emanuele De Simone ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Serum Levels ◽

Indoxyl Sulfate ◽

Protein Diet ◽

Low Protein Diet ◽

Low Protein

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P0754FGF23 AND URINARY PHOSPHATE EXCRETION FOR ESTIMATION OF NEPHRON NUMBER: DIFFERENCES BETWEEN CHRONIC KIDNEY FAILURE AND KIDNEY TRANSPLANTATION

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0754 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Marzia Pasquali ◽

Natalia De Martini ◽

Lida Tartaglione ◽

Silverio Rotondi ◽

Marta Catalfamo ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Transplantation ◽

Kidney Disease ◽

Mineral Metabolism ◽

Chronic Kidney Failure ◽

Serum Levels ◽

Nephron Number ◽

Phosphate Excretion ◽

Single Nephron ◽

The Difference

Abstract Background and Aims Assuming that FGF23 levels correlate with phosphate excretion per nephron, nephron number can be estimated by measuring FGF23 levels and urinary phosphate excretion (FEP). Kuro-O proposed that the ratio of FEP to serum FGF23 levels should correlate with nephron number and is defined as the Nephron Index (NI). The aim of the study is calculating NI as nephron number estimation in patients affected by various degree of chronic kidney disease, both transplanted and not. Method In 147 CRF patients kidney function, mineral metabolism biomarkers and NI were evaluated. Nephron Index was calculated following Kuro-o’s equation (kuro-o 2019): NI=FEP·Ps·eGFRFGF23 Observed patients were divided into two groups: patients with CKD (noTX) and transplanted ones (TX). Results noTX group was made up of 67 patients (40 males and 27 females) affected by CKD stages from G1 to G5. TX group was composed by 80 patient (49 males and 31 females) with various degree of CKD (G1T-G4T) showing mean graft age of 83,2 ± 54,8 months (range: 10,3-268,0). The two groups differed for age (mean age 59 ± 15,6 years in CKD, 55± 10,3years in TX). Mean eGFR did not differ between TX and noTX but NI was higher in TX since FEP was higher despite lower FGF23 levels in TX. The difference in FGF23 levels does not appear to depend on Klotho and PTH whose serum levels were no different between Tx and noTx. (Table1). As far as correlations are concerned, NI correlated with eGFR, FGF23, PTH and 1,25D in both group, while NI correlated with FEP only in the TX group. It's interesting that no correlation existed between FGF23 and sP, FEP, eGFR and sKlotho in TX differently from noTX (Table2). Discussion. NI could not be properly defined as nephron number estimation in TX pts. However it may represent higher function of residual nephrons, since higher FEP did not correlate to FGF23 and could be determined by compensatory hyperfiltration (increased single nephron GFR) in transplanted patients. Conclusion After kidney transplantation, high NI value could have a functional meaning rather than represent residual number of nephrons.

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Serum levels and activity of indoleamine2,3-dioxygenase and tryptophanyl-tRNA synthetase and their association with disease severity in patients with chronic kidney disease

Biomarkers ◽

10.3109/1354750x.2013.790074 ◽

2013 ◽

Vol 18 (5) ◽

pp. 379-385 ◽

Cited By ~ 10

Author(s):

Yu-Shi Bao ◽

Ying Ji ◽

Shi-Lei Zhao ◽

Lin-Lin Ma ◽

Ru-Juan Xie ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Disease Severity ◽

Serum Levels ◽

Trna Synthetase

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Solubleα-Klotho Serum Levels in Chronic Kidney Disease

International Journal of Endocrinology ◽

10.1155/2015/872193 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8 ◽

Cited By ~ 39

Author(s):

Silverio Rotondi ◽

Marzia Pasquali ◽

Lida Tartaglione ◽

Maria Luisa Muci ◽

Giusy Mandanici ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Renal Disease ◽

Clinical Significance ◽

Serum Levels ◽

Serum Phosphate ◽

Renal Tubules ◽

Ckd Stage ◽

Tubular Transport ◽

Negative Effect

Transmembraneα-Klotho (TM-Klotho), expressed in renal tubules, is a cofactor for FGF23-receptor. Circulating soluble-α-Klotho (s-Klotho) results from TM-Klotho shedding and acts on Phosphate (P) and Calcium (Ca) tubular transport. Decreased TM-Klotho, described in experimental chronic kidney disease (CKD), prevents actions of FGF23 and lessens circulating s-Klotho. Thus, levels of s-Klotho could represent a marker of CKD-MBD. To evaluate the clinical significance of s-Klotho in CKD we assayed serum s-Klotho and serum FGF23 in 68 patients (age58±15; eGFR45±21 mL/min). s-Klotho was lower than normal (519±183versus845±330 pg/mL,P<.0001) in renal patients and its reduction was detectable since CKD stage 2 (P<.01). s-Klotho correlated positively with eGFR and serum calcium (Cas) and negatively with serum phosphate (Ps), PTH and FGF23. FGF23 was higher than normal (73±51versus36±11,P<.0002) with significantly increased levels since CKD stage 2 (P<.001). Our data indicate a negative effect of renal disease on circulating s-Klotho starting very early in CKD. Assuming that s-Klotho mirrors TM-Klotho synthesis, low circulating s-Klotho seems to reflect the ensuing of tubular resistance to FGF23, which, accordingly, is increased. We endorse s-Klotho as an early marker of CKD-MBD.

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Influence of Metabolic Syndrome on Factors Associated with Chronic Kidney Disease: A Cross-Sectional Study

Current Nutrition & Food Science ◽

10.2174/1573401317666210702103247 ◽

2021 ◽

Vol 17 ◽

Author(s):

Camila Santos Marreiros ◽

Thaís Rodrigues Nogueira ◽

Paulo Pedro do Nascimento ◽

Diana Stefany Cardoso de Araújo ◽

Nayara Vieira do Nascimento Monteiro ◽

...

Keyword(s):

Metabolic Syndrome ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Serum Levels ◽

Cross Sectional Study ◽

Serum Glucose ◽

Cross Sectional ◽

Significance Level ◽

Glucose Levels ◽

Progression Of Kidney Disease

Background: Metabolic Syndrome (MetS) is defined by the presence of three or more of the following components: inadequate fasting serum glucose levels and elevated waist circumference, hypertension and dyslipidemia, which represent a potential risk for the development and/or worsening of Chronic Kidney Disease. Objective: This research aimed to investigate the presence of MetS and its influence on associated factors in patients with Chronic Kidney Disease undergoing hemodialysis. Methods: This is an evaluation of a cross-sectional multicenter research project, carried out with 95 patients with Chronic Kidney Disease, seen at outpatient clinics in the state capital Piaui. Anthropometric, biochemical and hemodynamic parameters were determined. The data were analyzed using the Stata® v.12 software (Statacorp, College Station, Texas, USA), adopting a significance level of p < 0,05. The survey received ethical approval (nº 2.527.329). Results: It was observed that individuals with elevated BMI, WC, NC, SBP, DBP were more likely to develop MetS, with significant differences (p <0.001). In addition, it was found that serum levels of glucose, insulin, HOMA-IR, TC, LDL, TG and blood pressure were higher in the group with MetS. Conclusion: It was concluded that changes in the parameters analyzed in patients with CKD reinforce MetS as a predictive condition for worsening nutritional status and a factor for the progression of kidney disease.

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MO566THE BONE EXPRESSION OF WNT INHIBITORS IN THE EXPERIMENTAL MODEL OF EARLY CHRONIC KIDNEY DISEASE

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab086.004 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Evdokia Bogdanova ◽

Natalia Semenova ◽

Olga Galkina ◽

Irina Zubina ◽

Olga Beresneva ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Experimental Model ◽

Inorganic Phosphate ◽

Molecular Mechanisms ◽

Fibroblast Growth Factor 23 ◽

Bone Matrix ◽

Serum Levels ◽

Chow Diet ◽

Dickkopf 1

Abstract Background and Aims Molecular mechanisms implicated in the initial stages of inorganic phosphate (Pi) imbalance in chronic kidney disease (CKD) remain poorly understood.The aim of the study was to evaluate whether canonical Wnt pathway inhibitors (iWnt) involved in early response to Pi retention in CKD. Methods Mild CKD was induced by 3/4 nephrectomy (NE) in spontaneously hypertensive rats (SHR) fed rat chow diet containing 0.6 % phosphate. Controls were sham operated SHR (SO). Duration of experimental exposure (NE or SO) was 2 and 6 months. Serum levels of creatinine (Cr), inorganic phosphate (Pi), fractional Pi excretion (FEPi), intact parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), alfa-Klotho (KL), sclerostin (SOST) and Dickkopf-1 (DKK1) were measured. The following morphological characteristics by light microscopy of bone metaphysis and kidney tissues: the area of renal interstitial fibrosis (RF) (Masson's trichrome), bone matrix volume (MV), the active osteoblasts to trabecular cells number ratio (aOB/cells), eroded surface to bone surface ratio (ES/BS) (hematoxylin & eosin), and bone SOST and DKK1 proteins expression (by IHC) were analyzed and calculated quantitatively. Statistical comparisons among groups were performed using Mann–Whitney U-test and Kruskal-Wallis H-test. Results Serum Cr, RF and indices of Pi exchange in the experimental model corresponded to early CKD (Table). Pi elevated in NE6 suggestive for its renal retention. KL level decreased (Table) in all experimental groups vs control. No differences were observed in serum levels FGF23 (p=0.62) and PTH (p=0.63). Serum SOST and DKK1 levels were significantly higher in NE6 group compared to SO6 (Table). The bone SOST and DKK1 expression increased in NE6 compared to SO6 (Figure). aOB/cells were lower in NE2, SO6 and NE6 vs SO2 (all p-values<=0.041). ES/BS increased in NE2 (vs SO2) while being lowest in NE6 and SO6 animals (Table). SOST and DKK1 metaphyseal expression increased in NE6 compared to SO2, SO6, NE2 (Figure). Osteocyte SOST expression increased in SO6 compared to SO2 and NE2 without differences in later groups. Osteoblast SOST expression was also higher in SO6 vs SO2 (Figure). Conclusion Increased serum levels of sclerostin and Dickkopf-1 and their bone expression are apparent in early stages of experimental CKD associating with hyperphosphatemia. Alterations of bone resorption and osteoblast depopulation occurred before the increase of serum Pi likely reflecting incipient stages of renal Pi retention. These molecular and cellular events seem to be independent of systemic FGF23 and PTH response.

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Association between Protein-Bound Uremic Toxins and Asymptomatic Cardiac Dysfunction in Patients with Chronic Kidney Disease

Toxins ◽

10.3390/toxins10120520 ◽

2018 ◽

Vol 10 (12) ◽

pp. 520 ◽

Cited By ~ 6

Author(s):

Shanmugakumar Chinnappa ◽

Yu-Kang Tu ◽

Yi Chun Yeh ◽

Griet Glorieux ◽

Raymond Vanholder ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Cardiac Dysfunction ◽

Serum Levels ◽

Significant Negative Correlation ◽

Cross Sectional Study ◽

Left Ventricular ◽

Uremic Toxins ◽

Cross Sectional ◽

The Individual

Although the relationship between protein-bound uremic toxins (PBUTs) and cardiac structure and cardiac mortality in chronic kidney disease (CKD) has been studied in the past, the association between cardiac dysfunction and PBUTs has not yet been studied. We therefore evaluated the association between impaired peak cardiac performance and the serum free and total concentrations of potentially cardiotoxic PBUTs. In a cross-sectional study of 56 male CKD patients (stages 2–5 (pre-dialysis)) who were asymptomatic with no known cardiac diseases or diabetes we measured peak cardiac power (CPOmax), aerobic exercise capacity (VO2max), and echocardiographic parameters of cardiac morphology and evaluated their association with PBUTs. The serum total and free concentrations of indoxyl sulfate (IXS), p-cresyl sulfate (PCS), p-cresyl glucuronide, indole acetic acid, and hippuric acid showed significant negative correlation with CPOmax and VO2max. IXS and PCS were independently associated with CPOmax and VO2max even after controlling for eGFR. No correlation between left ventricular mass index (LVMI) and PBUTs was seen. The present study for the first time has demonstrated the association between subclinical cardiac dysfunction in CKD and serum levels of a panel of PBUTs. Further studies are required to evaluate the mechanism of cardiotoxicity of the individual uremic toxins.

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A Pilot Randomized Crossover Trial Assessing the Safety and Short-Term Effects of Walnut Consumption by Patients with Chronic Kidney Disease

Nutrients ◽

10.3390/nu12010063 ◽

2019 ◽

Vol 12 (1) ◽

pp. 63 ◽

Cited By ~ 1

Author(s):

Pilar Sanchis ◽

Marilisa Molina ◽

Francisco Berga ◽

Elena Muñoz ◽

Regina Fortuny ◽

...

Keyword(s):

Risk Factors ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Inositol Phosphates ◽

Control Diet ◽

Fibroblast Growth Factor 23 ◽

Serum Levels ◽

Short Term ◽

Daily Consumption ◽

Randomized Crossover Trial

The aim of this study of patients with chronic kidney disease (CKD) is to assess the safety of daily consumption of walnuts on the physiological levels of phosphorous, potassium, parathyroid hormone (PTH), and fibroblast growth factor 23 (FGF23), and to assess the short-term benefits of this intervention on risk factors associated with cardiovascular events. This led us to perform a prospective, randomized, crossover, pilot clinical trial examined 13 patients with CKD. Subjects were randomly assigned to a diet of 30 g of walnuts per day or the control diet. After 30 days, each group was given a 30-day washout period, and then switched to the alternate diet for 30 days. Urinary and serum levels of phosphorous and potassium, multiple vascular risk factors, and urinary inositol phosphates (InsPs) were measured at baseline and at the end of the intervention period. Our results showed that the walnut dietary supplement led to reduced blood pressure, LDL cholesterol, and albumin excretion, but had no effect on the physiological levels of phosphorous, potassium, PTH, and FGF23. This is the first report to show that daily consumption of walnuts by patients with CKD does not alter their physiological levels of phosphorous, potassium, PTH, and FGF23 when included in a sodium-, protein-, phosphate-, and potassium-controlled diet, and it could be an effective strategy for reducing cardiovascular risk in patients with CKD.

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Triiodothyronine attenuates the progression of renal injury in a rat model of chronic kidney disease

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2017-0252 ◽

2018 ◽

Vol 96 (6) ◽

pp. 603-610 ◽

Cited By ~ 1

Author(s):

Sahar M. El Agaty

Keyword(s):

Nitric Oxide ◽

Chronic Kidney Disease ◽

Nitric Oxide Synthase ◽

Kidney Disease ◽

Renal Injury ◽

Serum Levels ◽

Female Rats ◽

Renal Tubules ◽

Oxide Synthase ◽

Remnant Kidney

This study was designed to investigate whether and how triiodothyronine (T3) affects renal function in an experimental model of chronic kidney disease. Twenty-four female rats were divided into the following groups: sham-operated control group (n = 8), 5/6 nephrectomized group (Nx, n = 8), and 5/6 nephrectomized group treated with T3 for 2 weeks (T3-Nx, n = 8). T3 administration significantly decreased serum levels of urea, creatinine, tumour necrosis factorα, and interleukin-6 compared with serum levels in the Nx group. The levels of malondialdehyde, transforming growth factor β, fibronectin, and collagen IV, as well as the expression of inducible nitric oxide synthase, nuclear factor κB, poly(ADP-ribose) polymerase, caspase-3, and Bax were all significantly decreased, though not normalized, in the remnant kidney of rats in the T3-Nx group compared with Nx rats. Glutathione, heme oxygenase-1 levels, as well as endothelial nitric oxide synthase expression were increased in the remnant kidney of the T3-Nx group. Histological studies revealed focal necrosis of renal tubules associated with inflammatory cell infiltration and fibrosis in the Nx group. These changes were alleviated in T3-Nx rats. This study showed that T3 administration attenuated the clinical and histological signs of renal injury in 5/6 nephrectomized rats by mitigating renal oxidative stress, inflammation, apoptosis, and fibrosis.

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