Cardiorenal Syndrome in End-Stage Kidney Disease

Background: Cardiorenal syndrome (CRS) in patients with end-stage kidney disease (ESKD) represents mainly cardiovascular disease (CVD) due to various complications associated with renal dysfunction—defined as type 4 CRS by Ronco et al.—because the effect of cardiac dysfunction on the kidneys does not need to be taken into consideration, unlike in non-dialysis dependent chronic kidney disease (CKD). Summary: Patients with ESKD are often in a state of chronic inflammation due to the upregulation of proinflammatory cytokines. Chronic inflammation leads to malnutrition and consequently to vascular endothelial dysfunction and vascular calcification, which is referred to as malnutrition-inflammation-atherosclerosis (MIA) syndrome and acts as a major risk factor for CVD. Anemia also plays a crucial role in CVD, and individuals with erythropoietin-resistant anemia have a particularly high risk of CVD. However, caution is emphasized because not only anemia itself, but also the overtreatment of anemia with erythropoiesis-stimulating agents aimed at elevating hemoglobin to ≥13 g/dl can also increase the risk of CVD. In CKD-mineral and bone disorder (CKD-MBD), phosphate load triggers the interactions between various factors such as calcium, parathyroid hormone, vitamin D, and fibroblast growth factor 23, promoting vascular calcification and thus becoming a risk factor for CVD. Key Messages: In addition to traditional atherosclerosis risk factors such as hypertension, diabetes, and dyslipidemia, the involvement of MIA syndrome, anemia, and CKD-MBD accompanying CKD have also become a focus for investigation as major players in CRS in patients with ESKD.

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SP572WHAT ARE THE DETERMINING FACTORS OF VASCULAR CALCIFICATION AND IS THERE ANY RELATIONSHIP BETWEEN VASCULAR CALCIFICATION, ARTERIAL STIFFNESS, FIBROBLAST GROWTH FACTOR-23 AND FETUIN-A IN END-STAGE KIDNEY DISEASE PATIENTS ON REGULAR HEMODIALYSIS?

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfx152.sp572 ◽

2017 ◽

Vol 32 (suppl_3) ◽

pp. iii327-iii327

Author(s):

Yelda Ozturk ◽

Siyar Erdogmus ◽

Neval Duman

Keyword(s):

Growth Factor ◽

Kidney Disease ◽

Arterial Stiffness ◽

Vascular Calcification ◽

Fibroblast Growth Factor 23 ◽

Fibroblast Growth ◽

End Stage Kidney Disease ◽

Determining Factors ◽

End Stage ◽

Regular Hemodialysis

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FGF23 and Phosphate–Cardiovascular Toxins in CKD

Toxins ◽

10.3390/toxins11110647 ◽

2019 ◽

Vol 11 (11) ◽

pp. 647 ◽

Cited By ~ 7

Author(s):

Vogt ◽

Leifheit-Nestler

Keyword(s):

Kidney Disease ◽

Vascular Calcification ◽

Ventricular Hypertrophy ◽

Fibroblast Growth Factor 23 ◽

Left Ventricular ◽

Serum Phosphate ◽

Cardiovascular Outcome ◽

Therapeutic Interventions ◽

Direct Targeting ◽

End Stage

Elevated levels of fibroblast growth factor 23 (FGF23) and phosphate are highly associated with increased cardiovascular disease and mortality in patients suffering from chronic kidney disease (CKD). As the kidney function declines, serum phosphate levels rise and subsequently induce the secretion of the phosphaturic hormone FGF23. In early stages of CKD, FGF23 prevents the increase of serum phosphate levels and thereby attenuates phosphate-induced vascular calcification, whereas in end-stage kidney disease, FGF23 fails to maintain phosphate homeostasis. Both hyperphosphatemia and elevated FGF23 levels promote the development of hypertension, vascular calcification, and left ventricular hypertrophy by distinct mechanisms. Therefore, FGF23 and phosphate are considered promising therapeutic targets to improve the cardiovascular outcome in CKD patients. Previous therapeutic strategies are based on dietary and pharmacological reduction of serum phosphate, and consequently FGF23 levels. However, clinical trials proving the effects on the cardiovascular outcome are lacking. Recent publications provide evidence for new promising therapeutic interventions, such as magnesium supplementation and direct targeting of phosphate and FGF receptors to prevent toxicity of FGF23 and hyperphosphatemia in CKD patients.

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Relaxin Is an Independent Risk Factor Predicting Death in Male Patients With End-Stage Kidney Disease

Circulation ◽

10.1161/01.cir.0000128598.72920.b5 ◽

2004 ◽

Vol 109 (19) ◽

pp. 2266-2268 ◽

Cited By ~ 16

Author(s):

Berthold Hocher ◽

Reinhard Ziebig ◽

Rolfdieter Krause ◽

Gernot Asmus ◽

Hans -H Neumayer ◽

...

Keyword(s):

Risk Factor ◽

Kidney Disease ◽

Independent Risk Factor ◽

End Stage Kidney Disease ◽

Male Patients ◽

End Stage

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Hypobilirubinemia Might be a Possible Risk Factor of End-Stage Kidney Disease Independently of Estimated Glomerular Filtration Rate

Kidney & Blood Pressure Research ◽

10.1159/000339027 ◽

2012 ◽

Vol 36 (1) ◽

pp. 47-54 ◽

Cited By ~ 13

Author(s):

Eiji Oda ◽

Ryuzi Aoyagi ◽

Yoshifusa Aizawa

Keyword(s):

Risk Factor ◽

Glomerular Filtration Rate ◽

Kidney Disease ◽

Glomerular Filtration ◽

Filtration Rate ◽

Estimated Glomerular Filtration Rate ◽

End Stage Kidney Disease ◽

End Stage

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Microscopic hematuria is a risk factor for end-stage kidney disease in patients with biopsy-proven diabetic nephropathy

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2020-001863 ◽

2020 ◽

Vol 8 (2) ◽

pp. e001863

Author(s):

Sadanori Okada ◽

Ken-ichi Samejima ◽

Masaru Matsui ◽

Katsuhiko Morimoto ◽

Riri Furuyama ◽

...

Keyword(s):

Blood Pressure ◽

Risk Factor ◽

Diabetic Nephropathy ◽

Kidney Disease ◽

Renal Biopsy ◽

Renal Pathology ◽

Microscopic Hematuria ◽

Vascular Lesions ◽

End Stage Kidney Disease ◽

End Stage

IntroductionThere are fewer reports about whether the presence of hematuria affects the progression of chronic kidney disease in patients with diabetic nephropathy. We analyzed whether microscopic hematuria in diabetic nephropathy is a risk factor for end-stage kidney disease (ESKD).Research design and methodsThe present study was a retrospective cohort study of patients with biopsy-proven diabetic nephropathy. We recruited 397 patients with diabetic nephropathy, which was confirmed by renal biopsy between June 1981 and December 2014 and followed them until October 2018 or death. Patients with microscopic hematuria before renal biopsy were defined as the hematuria group (n=91), and the remainder as the no-hematuria group (n=306). The main outcome was the occurrence of ESKD, which was defined by the requirement of permanent renal replacement therapies.ResultsThe systolic and diastolic blood pressure, serum creatinine and proteinuria were significantly higher, and the estimated glomerular filtration rate was significantly lower in the hematuria group compared with the no-hematuria group. Pathological evaluations revealed that glomerular, tubulointerstitial and vascular lesions in the hematuria group were significantly more severe. During a median of 10.1 years, 44 and 52 patients developed ESKD in the hematuria group and the no-hematuria group, respectively. Survival analyses showed that the incidence of ESKD was significantly higher in the hematuria group compared with the no-hematuria group (log-rank, p<0.0001). The multivariable Cox proportional hazards models revealed a significant association between hematuria and the incidence of ESKD after adjusting for clinically relevant factors, including proteinuria and renal pathology (adjusted HR 1.64, 95% CI 1.03 to 2.60). The subgroups of men, proteinuria ≥0.5 g/day, and systolic blood pressure ≥132 mm Hg showed a stronger association between hematuria and ESKD than their opposing subgroups.ConclusionsMicroscopic hematuria is a risk factor for ESKD in diabetic nephropathy, independent of proteinuria and renal pathology.

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Clinical Inference of Serum and Bone Sclerostin Levels in Patients with End-Stage Kidney Disease

Journal of Clinical Medicine ◽

10.3390/jcm8122027 ◽

2019 ◽

Vol 8 (12) ◽

pp. 2027 ◽

Cited By ~ 1

Author(s):

Annelies De Maré ◽

Anja Verhulst ◽

Etienne Cavalier ◽

Pierre Delanaye ◽

Geert J. Behets ◽

...

Keyword(s):

Kidney Disease ◽

Bone Formation ◽

Bone Metabolism ◽

Bone Histomorphometry ◽

Serum Markers ◽

End Stage Kidney Disease ◽

Serum Samples ◽

Mineral And Bone Disorder ◽

Bone Biopsies ◽

End Stage

Mounting evidence indicates that sclerostin, a well-known inhibitor of bone formation, may qualify as a clinically relevant biomarker of chronic kidney disease-related mineral and bone disorder (CKD-MBD), including abnormal mineral and bone metabolism and extraskeletal calcification. For this purpose, in this study we investigate the extent to which circulating sclerostin, skeletal sclerostin expression, bone histomorphometric parameters, and serum markers of bone metabolism associate with each other. Bone biopsies and serum samples were collected in a cohort of 68 end-stage kidney disease (ESKD) patients. Serum sclerostin levels were measured using 4 different commercially available assays. Skeletal sclerostin expression was evaluated on immunohistochemically stained bone sections. Quantitative bone histomorphometry was performed on Goldner stained tissue sections. Different serum markers of bone metabolism were analyzed using in-house techniques or commercially available assays. Despite large inter-assay differences for circulating sclerostin, results obtained with the 4 assays under study closely correlated with each other, whilst moderate significant correlations with skeletal sclerostin expression were also found. Both skeletal and circulating sclerostin negatively correlated with histomorphometric bone and serum parameters reflecting bone formation and turnover. In this study, the unique combined evaluation of bone sclerostin expression, bone histomorphometry, bone biomarkers, and serum sclerostin levels, as assessed by 4 different assays, demonstrated that sclerostin may qualify as a clinically relevant marker of disturbed bone metabolism in ESKD patients.

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