Disease In Chronic Kidney Disease Patients Research Articles

P1134HIGH PREVALENCE OF SLEEP-DISODERED BREATHING AND ITS ASSOCIATION WITH RENAL FUNCTION AMONG CHRONIC KIDNEY DISEASE PATIENTS (CKD1-5,HD AND PD) : A CROSS-SECTIONAL STUDY

Abstract Background and Aims Sleep-disordered breathing (SDB) is known as a novel risk factor for cardiovascular disease, and one of five adults suffer from SDB in general population. In non-dialysis chronic kidney disease (CKD) and hemodialysis (HD) patients, a high prevalence of SDB has been reported due to the excess accumulation of extracellular fluid. However, precise prevalence and associated factors of SDB in patients with peritoneal dialysis (PD) has not been known. This cross-sectional study aimed to investigate the prevalence and determinant factors associated with SDB in patients with CKD. Method This was a single-center retrospective cohort study recruited 334 patients with CKD stages 1-3a, 3b-5, HD, and PD enrolled from 2018 to 2020. All patients were hospitalized and received our CKD educational program, and did not have sleep complaints. The diagnosis and assessment of the severity of SDB were evaluated using PULSOX-Me300 and SAS2100 systems. The 3% oxygen desaturation index and SpO2 were measured during sleep. SDB was defined as 3% oxygen desaturation index (ODI)>15.0 and SpO2<92% in this study. Results Proportion of the patients with CKD1-3a, CKD3b-5, HD, and PD were 28%, 53%, 11%, and 8%, respectively. Thirty-one% of the patients were diagnosed with SBD in all CKD patients. In a generalized linear model, 3% ODI>15.0 and SpO2<92% were significantly correlated with apnea hypopnea index (p<0.05, r=0.87 and p<0.05, r=-0.45, respectively). Further, it became clear that the proportion of 3%ODI>15 and SpO2<92% was significantly higher in PD patients (50%) than in other CKD patients. Furthermore, 3% ODI was significantly correlated with BMI and HDL cholesterol levels in PD patients (p<0.05, r=0.67 and p<0.05, r=-0.54, respectively). Conclusion We reported for the first time that the prevalence of SDB was very high and that the severity of SDB was significantly associated with BMI in patients with PD. These findings suggest that the extracellular fluid overload and excess glucose exposure due to PD fluid might accelerate SDB in patients with PD. Further clinical studies are needed to determine whether PD-associated SDB might influence the development of cardiovascular disease in CKD patients.

Vascular Calcification in Chronic Kidney Disease: The Role of Vitamin K- Dependent Matrix Gla Protein.

Arterial calcification is highly prevalent in chronic kidney disease (CKD) patients and is associated with cardiovascular (CV) morbidity and mortality. Patients at early CKD stages are more likely to suffer a fatal CV event than to develop end-stage renal disease and require hemodialysis treatment. The heavy CV burden of these patients cannot be solely explained by traditional calcification risk factors. Moreover, the pathophysiologic mechanisms underlying this association are complex and yet not fully understood. Although vascular calcification was regarded as a passive degenerative process for over a century, this theory changed by recent evidence that pointed toward an active process, where calcification promoters and inhibitors were involved. Matrix Gla Protein (MGP) has been established as a strong inhibitor of calcification both in vitro and in vivo. Not only it prevents mineralization of the arterial wall, but it is the only factor that can actually reverse it. To become fully active, MGP must undergo carboxylation of specific protein bound glutamate residues, a process fully dependent on the availability of vitamin K. Low vitamin K status leads to inactive, uncarboxylated forms of MGP and has been repeatedly associated with accelerated vascular calcification. Aim of this review is to present the pathophysiologic mechanisms underlying the activation and function of MGP and review the existing, accumulating data regarding the association between vitamin K, MGP and vascular calcification/CV disease in CKD patients.

Relationship Between Epicardial Adipose Tissue and Body Composition as Determined by Multi-Frequency Bioelectrical Impedance Analysis in Patients with Stage 5 Chronic Kidney Disease.

BackgroundThe main cause of mortality among chronic kidney disease (CKD) patients is cardiovascular disease (CVD). Epicardial adipose tissue (EAT) is considered to be novel cardiovascular risk factor. We assessed EAT in non-dialyzed stage 5 CKD patients and explored the association of EAT with body composition as determined by multi-frequency BIA.Material/MethodsThe present included 70 stage 5 CKD patients who had not undergone dialysis and 40 healthy control subjects. EAT thickness was assessed by echocardiography. Hydration status and body composition were evaluated by multi-frequency bioelectrical impedance analysis.ResultsStage 5 CKD patients had significantly higher EAT thickness than healthy subjects (6.56±1.18 vs. 4.05±1.45, p<0.001). Fat tissue mass, systolic blood pressure (SBP), age, fat tissue index, and body mass index were positively correlated with EAT thickness in the CKD patient group (p<0.05). Lean tissue mass, lean tissue index (LTI), and high-density lipoprotein (HDL) were negatively correlated with EAT thickness in the CKD patient group (p<0.05). Stepwise multiple regression analysis showed that age, SBP, and LTI were independently associated with EAT thickness in CKD patients.ConclusionsWe found significantly higher EAT thickness in stage 5 CKD patients who were not on dialysis compared to healthy controls. EAT was significantly associated with age, SBP, and LTI in CKD patients. Interventions to reduce the risk factors associated with EAT thickness might protect against CVD disease in CKD patients.

Metastatic Pulmonary Calcification With Coexisting Nonspecific Interstitial Pneumonia: A Case Report

Abstract Patients with underlying chronic kidney disease (CKD) often have elevated serum calcium and parathyroid hormones due to compromised kidney function. We present a case of a 63-year-old female nonsmoker with surgical history of three renal transplants (at age 47, 51, and 58) along with thyroidectomy and parathyroidectomy who came to the emergency department with complaint of persistent dry cough and shortness of breath for the last 2 months. The patient had been on immunosuppressive drugs, tacrolimus, prednisolone, and mycophenolic acid since her first renal transplant as well as on cinacalcet after parathyroidectomy (at age 54). Initial computed tomography (CT) scan demonstrated ground-glass opacities in bilateral upper lobes while bronchoscopy revealed few inflammatory cells without any fungi or bacteria. Repeat CT scan performed 5 days later due to rapid progression of her clinical symptoms showed worsening of ground-glass opacities in bilateral upper lobes and new nodules in right middle and lower lung lobes. The wedge lung biopsy revealed metastatic pulmonary calcification (MPC) in the right upper lobe while nonspecific interstitial pneumonia (NISP) in the right lower lobe confirmed the coexistence of two different pathological processes most likely complicating the patient’s clinical symptoms. Despite comprehensive medical therapy, patient’s symptoms have been progressively worsening and she is currently undergoing evaluation for both renal and lung transplants. Our case report not only presents a rare case of MPC coexisting with NSIP but also sheds light on the associated morbidity due to pulmonary diseases in CKD patients.

SUN-193 GDF-15, Hepcidin, and Iron deficiency Anaemia as Predictors of Disease Progression and Mortality in CKD Patients

Anaemia is one of the common complications of Chronic Kidney Disease (CKD) that has been strongly associated with adverse clinical outcomes. An interplay between emerging biomarkers of inflammation and anaemia has been shown to play a vital role in the increased risk of cardiovascular disease in CKD patients. This association may partly be responsible for the persistent increased risk of mortality despite correction of anaemia in CKD patients.

Novel aspects of PCSK9 and lipoprotein receptors in renal disease-related dyslipidemia

Chronic kidney disease (CKD) is a global health problem with a profound impact on quality of life. Cardiovascular disease is established as a major cause of morbidity and mortality in patients with CKD. Dyslipidemia is frequently observed in CKD patients, suggesting a causal relation between dyslipidemia and cardiovascular disease in CKD patients. Currently, lipid-lowering drugs such as statins, are the primary choice for lipid lowering therapy in high-risk populations. Despite many studies showing CVD risk reduction with statins, CVD still remains the leading cause of the death in CKD. This underscores the need for new therapeutic approaches to reduce cardiovascular risk in CKD patients. Reduced lipoprotein lipase activity, increased very low-density lipoprotein production, increased proprotein convertase subtilisin kexin type 9 (PCSK9) expression and loss of hepatic heparan sulfate proteoglycans (HSPG) syndecan-1 have been associated with CKD-related dyslipidemia. Low-density lipoprotein receptor (LDLR), low-density lipoprotein receptor-related protein 1 (LRP-1) and syndecan-1, are the most important hepatic receptors for lipoprotein clearance. However, their contributions to the pathogenesis of dyslipidemia and cardiovascular disease in CKD remain unclear. Interestingly, in CKD, increased plasma lipid levels are associated with elevated levels of PCSK9. This promotes the proteolysis of LDLR, suggesting a role for PCSK9 in CKD-associated dyslipidemia. Fully humanized monoclonal antibodies targeting PCSK9 have been approved by the US Food and Drug Administration and the European Medicines Agency as lipid lowering treatment for patients with hypercholesterolemia. In CKD sub-group analysis, ODYSSEY COMBO I and ODYSSEY COMBO II studies demonstrated strong reduction in LDL-C by alirocumab compared to placebo and ezetimibe and when added to statins. However, their efficacy in reducing plasma TG is controversial. Therefore, further research work is need for a detailed analysis on efficacy and safety of PCSK9 antibodies in CKD groups. Interestingly, novel findings on PCSK9 interaction with HSPG might shed new insight on altered lipid metabolism in CKD. In this review, we discuss various aspects of lipoprotein metabolism and hepatic lipoprotein receptor signaling pathways along with the concept of renal disease-related dyslipidemia. Furthermore, this review highlights the drawbacks of current lipid-lowering therapies and proposes novel approaches for lipid management in CKD.

Chronic kidney disease and urological disorders: systematic use of uroflowmetry in nephropathic patients.

BackgroundChronic kidney disease (CKD) is a highly prevalent condition. Urologic disorders are known causes of CKD, but often remain undiagnosed and underestimated also for their insidious onset and slow progression. We aimed to evaluate the prevalence of urological unrecognized diseases in CKD patients by uroflowmetry.MethodsWe enrolled consecutive stable CKD outpatients. The patients carried out two questionnaires, the International Prostate Symptom Score and Incontinence Questionnaire-Short Form, and they also underwent uroflowmetry, evaluating max flow rate (Qmax), voiding time and voided volume values.ResultsA total of 83 patients (43 males, mean age of 59.8 ± 13.3 years) were enrolled. Our study showed 28 males and 10 females with a significant reduction of Qmax (P < 0.001) while 21 females reported a significant increase of Qmax (P < 0.001) with a prevalence of 49.5% of functional urological disease. Moreover, we showed a significant association between Qmax and creatinine (P = 0.013), estimated glomerular filtration rate (P = 0.029) and voiding volume (P = 0.05). We have not shown significant associations with age (P = 0.215), body mass index (P = 0.793), systolic blood pressure (P = 0.642) or diastolic blood pressure (P = 0.305). Moreover, Pearson’s chi-squared test showed a significant association between Qmax altered with CKD (χ2 = 1.885, P = 0.170) and recurrent infection (χ2 = 8.886, P = 0.012), while we have not shown an association with proteinuria (χ2 = 0.484, P = 0.785), diabetes (χ2 = 0.334, P = 0.563) or hypertension (χ2 = 1.885, P = 0.170).ConclusionsWe showed an elevated prevalence of urological diseases in nephropathic patients; therefore, we suggest to include uroflowmetry in CKD patient assessment, considering the non-invasiveness, repeatability and low cost of examination. Uroflowmetry could be used to identify previously unrecognized urological diseases, which may prevent the onset of CKD or progression to end-stage renal disease and reduce the costs of management.

Management of Blood Pressure and Heart Rate in Chronic Kidney Disease.

Hypertension is considered a major health problem in patients with chronic kidney disease (CKD) as approximately 80-85% of CKD patients' suffer from hypertension in the United States. Hypertension is the second leading cause of CKD after diabetes and is strongly related to morbidity and mortality. It has been found that there is a relation among hypertension, glomerular filtration rate (GFR) and creatinine levels. Since there is a strong relation between hypertension and CKD, and hypertension seems to lead to cardiovascular diseases, which have epidemic proportions in CKD, this review article discusses the etiology of hypertension and the existing optimal therapies that contribute to the hypertension and heart rate management. There are many approaches that contribute to the management of hypertension and heart rate in CKD patients. Lifestyle modifications in combination with drug therapy lead to the better control of hypertension in CKD patients. Hypertension is strongly related to cardiovascular diseases in CKD patients. Since this relation exists and hypertension leads to cardiovascular diseases, the management of hypertension and increased heart rate should be a main therapeutic target in these patients.

Elevated Phosphate Levels Trigger Autophagy-Mediated Cellular Apoptosis in H9c2 Cardiomyoblasts

Background/Aim: In chronic kidney disease (CKD), kidneys fail to maintain phosphorus homeostasis in serum. Elevated phosphorus levels in serum have been associated with cardiovascular diseases in CKD patients and in normal individuals. In this study, we evaluated the level of autophagy- and apoptosis-related markers under different concentrations of hyperphosphate in myocardial cells. Methods: Modulation inflicted on the levels of various survival-, autophagy-, and apoptosis-related markers were determined by Western blotting analysis using total protein extract. FITC-annexin V staining was performed to quantify the apoptotic cells in all groups. Results: Hyperphosphate treatments showed to induce autophagy-related proteins beclin-1, ATG7, and LC3 II through the pAMPK-ULK1 pathway in Western blotting analysis. Further, apoptosis-associated proteins such as Bax, Bid, cytochrome c, and c-caspase-9 were also upregulated with hyperphosphate treatment. 3-Methyladenine, an autophagy inhibitor, inhibited apoptosis significantly in FITC-annexin V staining, and the inhibition of Bax, cytochrome c, and c-caspase-3 was shown by Western blotting. Conclusion: The results suggest that hyperphosphate in H9c2 cardiomyoblasts would lead to cellular apoptosis via autophagy, which is mediated by the pAMPK signaling pathway. Our findings revealed the possible mechanism responsible for the heart damage under hyperphosphatemia.

OP.1A.02] INNATE IMMUNITY AND CARDIO-RENAL RISK IN STAGE 2-5 CKD PATIENTS

Objective: The soluble form of urokinase-type plasminogen activator (suPAR) is a powerful marker for immune activation that accurately predict clinical outcomes in patients with sepsis or infectious diseases. Alterations in innate immunity and Inflammation are major risk factors for the high risk for cardiovascular disease in patients with chronic kidney disease (CKD) but whether suPAR predicts cardiovascular and renal complications independently of established risk factors in CKD is still unknown. Design and method: We measured plasma suPAR levels (ELISA) and a series of traditional and CKD-specific risk factors in 753 stage G2-5 CKD patients. We estimated the risk for GFR loss (>30%) or kidney failure, time to death and first cardiovascular event by multivariate Cox regression analysis adjusting for traditional risk factors and a large series of CKD-specific risk factors. Results: suPAR was gender-dependent and associated with lower GFR and higher proteinuria, older age, diabetes, higher systolic BP, C Reactive Protein (CRP), phosphate, PTH, FGF23, ADMA and lower Hb, 25OH vitD and 1,25OH2 vitD (all P < 0.001). Over a 31 +/− 10 months follow-up 42 patients died and 95 had a renal event. suPAR was a strong predictor of the combined end-point death and cardiovascular events [HR (500pg/ml): 1.09, 95%CI: 1.04–1.14] in a Cox's regression analysis adjusting for a large series of potential confounders including background cardiovascular disease, the GFR, proteinuria, age, gender, smoking, diabetes, systolic BP and anti-hypertensive treatment, phosphate, Hb, serum albumin, BMI, CRP, ADMA and FGF23. Separate analyses of time to death and time to first CV event were both highly significant (P < 0.01) in crude and adjusted analyses. Conclusions: Elevated suPAR levels robustly predict incident cardiovascular events and death in CKD patients. These findings go along with biological knowledge documenting a strong role of suPAR in atherosclerosis and support the contention that suPAR is causally implicated in cardiovascular disease in CKD patients.

Comment on Indoxyl Sulfate—Review of Toxicity and Therapeutic Strategies. Toxins 2016, 8, 358

Recently, the clinical and experimental evidences that support the toxic effects of indoxyl sulfate, a protein-bound uremic toxin in chronic kidney disease (CKD) patients, has been discussed. In this panorama, the authors described several in vitro and in vivo studies, suggesting that indoxyl sulfate may play a part in the pathogenesis of low turnover bone disease. However, the discussion claims the need for relevant clinical studies in CKD patients whose bone turnover biomarkers and bone histomorphometry were assessed in order to demonstrate the association between serum levels of indoxyl sulfate and bone turnover. We would like to underline the availability of this clinical data to support the concept that indoxyl sulfate may play a part in the pathogenesis of low turnover bone disease in CKD patients.

Biopsy vs. peripheral computed tomography to assess bone disease in CKD patients on dialysis: differences and similarities

Chronic kidney disease (CKD) patients are at high risk of bone disease. Although bone biopsy is considered the best method to evaluate bone disease, it is expensive and not always available. Here we have compared, for the first time, data obtained from bone biopsy and HR-pQCT in a sample of CKD patients on dialysis. HR-pQCT and dual-energy X-ray absorptiometry (DXA) were performed in 31 CKD patients (30 on dialysis). Biopsies were analyzed by quantitative histomorphometry, and classified according to TMV. We have found an inverse correlation between radius cortical density measured by HR-pQCT, with serum, as well as histomorphometric bone remodeling markers. Trabecular density and BV/TV measured through HR-pQCT in the distal radius correlated with trabecular and mineralized trabecular bone volume. Trabecular number, separation, and thickness obtained from HR-pQCT and from bone biopsy correlated with each other. Patients with cortical porosity on bone histomorphometry presented lower cortical density at the distal radius. Cortical density at radius was higher while bone alkaline phosphatase was lower in patients with low turnover. Combined, these parameters could identify the turnover status better than individually. There was an agreement between HR-pQCT and bone biopsy parameters, particularly in cortical compartment, which may point to a new perspective on the fracture risk assessment for CKD patients. Besides classical bone resorption markers, HR-pQCT provided some clues on the turnover status by measurements of cortical density at radius, although the significance of this finding warrants further studies.

Prevalence of anemia and cardiovascular diseases in chronic kidney disease patients: a single tertiary care centre study

Background: Chronic kidney disease (CKD) is recognized as a global health issue having high mortality and morbidity rates putting a substantial burden on global resources. CKD has become a recognised independent risk factor for several adverse health outcomes including cardiovascular disease (CVD). Anaemia is an anticipated consequence as renal function declines, and can develop at any stage of CKD. There is a strong association between anemia and cardiovascular complications in CKD patients and many studies have proven that anemia plays a key role in worsening CVD in CKD patients. The objective of this study was to study the prevalence of anemia and cardiovascular diseases in CKD patients and establish an association between them.Methods: This study was conducted between January 2008 and June 2008 for a period of six months at a Government tertiary referral institution in south India. During this period, all newly diagnosed cases of chronic kidney disease based on the National Kidney foundation definition were included in this study. All the patients were evaluated based on detailed history taking, clinical examination and laboratory investigations after an informed consent was obtained from them. Staging of CKD was done based on the national kidney foundation (NKF/KDIGO) staging system. GFR was estimated using the abbreviated MDRD (Modification of Diet in Renal Disease) formula.Results: Of the 333 newly diagnosed CKD patients, a large majority (264, 79.28%) of the patients in the study presented in stage 5 CKD. The mean Hb in the study was 8.42±2.20 g/dl. Anemia was present in 90.39% while 25.53% had an Hb of &lt;7g/dl. The prevalence of anemia increased from stage 3 (66.6%) to stage 5 (94.7%) and this correlation was statistically significant (p&lt;0.0005). 167 (50.15% ) were found to have some form of cardiovascular disease, of which 120 (71.86%) were males and 47 (28.14%) were females. 83.93% had left ventricular hypertrophy, 16.17% had ischemic heart disease and 7.78% had congestive heart failure. 56.3% of patients in the age group 41-60 years had cardiovascular disease. The correlation between cardiovascular disease and age was statistically significant (p = 0.04139). And it was found that cardiovascular disease was more common when the cause of CKD was Diabetic nephropathy (65.8%) and hypertensive nephrosclerosis (84.6%). The correlation between the cardiovascular disease and etiological diagnosis of CKD was statistically significant. (p&lt;0.0005).Cardiovascular disease was present in 61.2 % of the study population with diabetes mellitus and in 56.4% of the study population with hypertension. The correlations between CVD and diabetes and hypertension were statistically significant. Cardiovascular disease was present in 61.2% of the study population with Hemoglobin &lt;7 gm/dl, 41.7% with Hb between 7-11 gm/dl and the correlation between cardiovascular disease and the level of Hb was highly significant in CKD patients.Conclusions: Thus there is a strong association between the clinical trial of anemia, CKD and CVD and prompt identification and management of common risk factors and adequate correction of anemia is necessary to slow progression of CKD and prevent cardiovascular events.

Could physical exercise help modulate the gut microbiota in chronic kidney disease?

Chronic kidney disease (CKD) patients have several metabolic disorders caused by chronic oxidative stress and inflammation. The imbalance of gut microbiota has been identified as a factor that may contribute to the development of these disorders, which can promote cardiovascular disease in CKD patients. Among several strategies to modulate gut microbiota, physical exercise could represent a new nonpharmacological approach. Although exercise can reduce cardiovascular risk in CKD patients through its beneficial effects on oxidative stress and inflammation, there are no available data regarding the relationship between exercise and modulation of gut microbiota in CKD patients. This review is intended to provide a brief overview of the hypothesis regarding gut microbiota modulation through physical exercise, with a particular emphasis on CKD.

Cognitive Changes in Chronic Kidney Disease and After Transplantation.

Cognitive impairment is very common in chronic kidney disease (CKD) and is strongly associated with increased mortality. This review article will discuss the pathophysiology of cognitive impairment in CKD, as well as the effect of dialysis and transplantation on cognitive function. In CKD, uremic toxins, hyperparathyroidism and Klotho deficiency lead to chronic inflammation, endothelial dysfunction and vascular calcifications. This results in an increased burden of cerebrovascular disease in CKD patients, who consistently have more white matter hyperintensities, microbleeds, microinfarctions and cerebral atrophy on magnetic resonance imaging scans. Hemodialysis, although beneficial in terms of uremic toxin clearance, also contributes to cognitive decline by causing rapid fluid and osmotic shifts. Decreasing the dialysate temperature and increasing total dialysis time limits these shifts and helps maintain cognitive function in hemodialysis patients. For many patients, kidney transplantation is the preferred treatment modality, because it reverses the underlying mechanisms causing cognitive impairment in CKD. These positive effects have to be balanced against the possible neurotoxicity of infections and immunosuppressive medications, especially glucocorticosteroids and calcineurin inhibitors. A limited number of studies have addressed the overall effect of transplantation on cognitive function. These have mostly found an improvement after transplantation, but have a limited applicability to daily practice because they have only included relatively young patients.

P-Cresyl sulfate suppresses lipopolysaccharide-induced anti-bacterial immune responses in murine macrophages in vitro.

p-Cresyl sulfate (pCS) is a known uremic toxin that is metabolized from p-cresol produced by intestinal bacteria. Abnormal accumulation of pCS in the blood is a characteristic of chronic kidney disease (CKD). pCS is suggested to cause immune dysfunction and increase the risk of infectious diseases in CKD patients. In this study, we focused on the effects of pCS on macrophage functions related to host defense. We evaluated the effects of pCS on cytokine production, nitric oxide (NO) production, arginase activity, expression of cell-surface molecules, and phagocytosis in the macrophage-like cell line, RAW264.7. pCS significantly decreased interleukin (IL)-12 p40 production and increased IL-10 production. pCS also decreased NO production, but did not influence arginase activity. pCS suppressed lipopolysaccharide-induced CD40 expression on the cell surface, but did not influence phagocytosis. We further assessed whether the effects of pCS observed in the macrophage-like cell line were consistent in primary macrophages. Similar to RAW264.7 cells, pCS decreased IL-12 p40 and p70 production and increased IL-10 production in primary peritoneal macrophages. These data indicate that pCS suppresses certain macrophage functions that contribute to host defense, and may play a role in CKD-related immune dysfunction.

The Prevalence of Fabry Disease in Patients with Chronic Kidney Disease in Turkey: The TURKFAB Study

Background/Aims: Fabry disease is a treatable cause of chronic kidney disease (CKD) characterized by a genetic deficiency of α-galactosidase A. European Renal Best Practice (ERBP) recommends screening for Fabry disease in CKD patients. However, this is based on expert opinion and there are no reports of the prevalence of Fabry disease in stage 1-5 CKD. Hence, we investigated the prevalence of Fabry disease in CKD patients not receiving renal replacement therapy. Methods: This prospective study assessed α-galactosidase activity in dried blood spots in 313 stage 1-5 CKD patients, 167 males, between ages of 18-70 years whose etiology of CKD was unknown and were not receiving renal replacement therapy. The diagnosis was confirmed by GLA gene mutation analysis. Results: Three (all males) of 313 CKD patients (0.95%) were diagnosed of Fabry disease, for a prevalence in males of 1.80%. Family screening identified 8 aditional Fabry patients with CKD. Of a total of 11 Fabry patients, 7 were male and started enzyme replacement therapy and 4 were female. The most frequent manifestations in male patients were fatigue (100%), tinnitus, vertigo, acroparesthesia, hypohidrosis, cornea verticillata and angiokeratoma (all 85%), heat intolerance (71%), and abdominal pain (57%). The most frequent manifestations in female patients were fatigue and cornea verticillata (50%), and tinnitus, vertigo and angiokeratoma (25%). Three patients had severe episodic abdominal pain attacks and proteinuria, and were misdiagnosed as familial Mediterranean fever. Conclusions: The prevalence of Fabry disease in selected CKD patients is in the range found among renal replacement therapy patients, but the disease is diagnosed at an earlier, treatable stage. These data support the ERBP recommendation to screen for Fabry disease in patients with CKD of unknown origin.

The Role of the Gut Microbiome on Chronic Kidney Disease.

Chronic kidney disease (CKD) is estimated to affect nearly 500 million people worldwide and cardiovascular (CV) disease is a major cause of death in this population. However, therapeutic interventions targeting traditional CV risks are not effective at lowering the incidence of CV events or at delaying the progression of the disease in CKD patients. In recent years, disturbances of normal gut microbiome were recognized in the pathogenesis of diverse chronic diseases. Gut dysbiosis is being unraveled in CKD and pointed as a nontraditional risk factor for CV risk and CKD progression. The most often reported changes in gut microbiome in CKD are related to the lower levels of Bifidobacteriaceae and Lactobacillaceae and to higher levels of Enterobacteriaceae. Although metagenomics brought us an amplified vision on the microbial world that inhabits the human host, it still lacks the sensitivity to characterize the microbiome up to species level, not revealing alterations that occur within specific genus. Here, we review the current state-of-the-art concerning gut dysbiosis in CKD and its role in pathophysiological mechanisms in CKD, particularly in relation with CV risk. Also, the strategies towards prevention and treatment of gut dysbiosis in CKD progression will be discussed.

Neurological complications in chronic kidney disease patients.

Chronic kidney disease (CKD) is associated with a high prevalence of cerebrovascular disorders such as stroke, white matter diseases, intracerebral microbleeds and cognitive impairment. This situation has been observed not only in end-stage renal disease patients but also in patients with mild or moderate CKD. The occurrence of cerebrovascular disorders may be linked to the presence of traditional and non-traditional cardiovascular risk factors in CKD. Here, we review current knowledge on the epidemiological aspects of CKD-associated neurological and cognitive disorders and discuss putative causes and potential treatment. CKD is associated with traditional (hypertension, hypercholesterolaemia, diabetes etc.) and non-traditional cardiovascular risk factors such as elevated levels of oxidative stress, chronic inflammation, endothelial dysfunction, vascular calcification, anaemia and uraemic toxins. Clinical and animal studies indicate that these factors may modify the incidence and/or outcomes of stroke and are associated with white matter diseases and cognitive impairment. However, direct evidence in CKD patients is still lacking. A better understanding of the factors responsible for the elevated prevalence of cerebrovascular diseases in CKD patients may facilitate the development of novel treatments. Very few clinical trials have actually been performed in CKD patients, and the impact of certain treatments is subject to debate. Treatments that lower LDL cholesterol or blood pressure may reduce the incidence of cerebrovascular diseases in CKD patients, whereas treatment with erythropoiesis-stimulating agents may be associated with an increased risk of stroke but a decreased risk of cognitive disorders. The impact of therapeutic approaches that reduce levels of uraemic toxins has yet to be evaluated.

Vascular and Valvular Calcifications in Chronic Kidney Disease: An Update

In chronic kidney disease (CKD) and end-stage renal disease patients cardiovascular disease is the main cause of morbidity and mortality, with incidence of cardiac related mortality increasing as renal function declines. Even after controlling for traditional cardiovascular risk factors such as smoking, age, gender, dyslipidaemia, and arterial hypertension, patients with CKD have a higher incidence of major cardiovascular events. CKD is characterised by the presence of many other non-traditional cardiovascular risk factors, such as chronic inflammation and accelerated atherosclerosis, oxidative stress, and especially, secondary hyperparathyroidism. This review will summarise the current evidence on vascular calcifications and valvular heart disease in CKD patients, from pathophysiology to therapeutic strategies.