The Role of the L-Arginine-Nitric Oxide Molecular Pathway in Autosomal Dominant Polycystic Kidney Disease.

Recently, arginine has been proven to play an important role in ADPKD physiopathology. Arginine auxotrophy in ADPKD induces cell hyperproliferation, blocking the normal differentiation of renal tube cells and causing cyst formation. We explored the L-arginine (Arg)-nitric oxide (NO) molecular pathway in ADPKD, a multisystemic arginine auxotrophe disease. We developed a prospective case-control study that included a group of 62 ADPKD subjects with an estimated filtration rate over 60 mL/min/1.73 mp, 26 subjects with chronic kidney disease with an eGFR > 60 mL/min/1.73 mp, and a group of 37 healthy subjects. The laboratory determinations were the serum level of arginine, the enzymatic activity of arginase 2 and inducible nitric oxide synthase, the serum levels of the stable metabolites of nitric oxide (nitrate, direct nitrite, and total nitrite), and the endogenous inhibitors of nitric oxide synthesis (asymmetric dimethylarginine and symmetric dimethylarginine). In the ADPKD group, the levels of the arginine and nitric oxide metabolites were low, while the levels of the metabolization enzymes were higher compared to the control group. Statistical analysis of the correlations showed a positive association between the serum levels of Arg and the eGFR and a negative association between Arg and albuminuria. ADPKD is a metabolic kidney disease that is auxotrophic for arginine. Exploring arginine reprogramming and L-Arg-NO pathways could be an important element in the understanding of the pathogenesis and progression of ADPKD.

Prognostic role of glomerular electron microscopy lesions in IgA nephropathy: "the devil is in the details".

INTRODUCTION: Transmission electron microscopy enables examination of ultrastructural glomerular changes; while this tool has already been applied in IgA nephropathy (IgAN), limited information exists on the prognostic value in this disease. We aimed to systematically investigate ultrastructural lesions and assess their role in predicting the evolution of IgA nephropathy to end-stage kidney disease. METHODS: A single-center retrospective study was performed on 107 consecutive IgAN patients (median age 42 years, 67% male, estimated glomerular filtration rate 46 mL/min, proteinuria 1.0 g/g) between 2010 and 2015, who were followed-up until end-stage kidney disease, death, or end of study (January 2021). A pathologist evaluated the Mesangial hypercellularity (M), Endocapillary hypercellularity (E), Segmental glomerulosclerosis (S), and Tubular atrophy/interstitial fibrosis-Crescents (C) (MEST-C) score and transmission electron microscopy lesions according to a comprehensive protocol that encompassed all glomerular structures. RESULTS: Patients were followed up for a median of 7.1 years; 32 (43%) reached end-stage kidney disease. Patients who reached kidney failure had higher comorbidity score, more frequent arterial hypertension, lower estimated glomerular filtration rate, and higher MEST-C score. In terms of transmission electron microscopy lesions, patients who progressed to end-stage kidney disease had more frequent podocyte activation, effacement, and presence of microvilli; more frequent signs of endothelial cell activation and fenestration; higher mesangial cell proliferation. In the univariate Cox proportional hazard regression, higher MEST-C score and lesions detected by transmission electron microscopy in podocytes, endothelial cells, and mesangial cell proliferation were associated with shorter kidney survival time. In the multivariate Cox proportional hazard regression, only higher MEST-C score, presence of podocytes with microvilli, and mesangial cell proliferation were associated with end-stage kidney disease. CONCLUSION: This study shows that, besides the MEST-C score, the presence of podocytes with microvilli and mesangial cell proliferation are associated with poor kidney survival in IgAN patients, highlighting the prognostic value of lesions detected by transmission electron microscopy.

Bone marrow macrophage iron content and sideroblast count in iron- and ESA-naïve patients with CKD-related anemia.

BACKGROUND: Since in chronic kidney disease (CKD) iron deficiency anemia (IDA) can coexist with inflammation-induced immobilization of iron in macrophages (anemia of chronic disorders - ACD), we assessed the utility of ferritin, transferrin saturation (TSAT), and hepcidin for differentiation of mixed IDA-ACD from ACD, using bone marrow (BM) examination as reference. METHODS: This cross-sectional, single-center study analyzed 162 non-dialysis iron and epoietin-naïve CKD patients (52% males, median age 67 years, eGFR 14.2 mL/min 1.73 m2, hemoglobin 9.4 g/dL). BM aspiration, serum hepcidin (ELISA), ferritin, TSAT, and C-Reactive protein (CRP) were the main studied parameters. RESULTS: ACD was seen in 51%, IDA-ACD in 40%, while "pure" IDA in only 9%. In univariate and binomial analyses, IDA-ACD differed from ACD by lower ferritin and TSAT, but not by hepcidin or CRP. Correspondingly, in receiver operating curve analysis, ferritin and TSAT differentiated IDA-ACD from ACD, at cutoffs of 165 ng/mL and 14%, but with moderate precision (sensitivity and specificity of 72%, and 61%, respectively). CONCLUSION: The mixed pattern IDA-ACD could be more prevalent than estimated in non-dialysis CKD. Ferritin and, to a lesser degree, TSAT are useful in the diagnosis of IDA superimposed on ACD, while hepcidin, although reflecting BM macrophages iron, seems to have limited utility.

How useful is kidney biopsy for the management of glomerulopathies in the elderly?

BACKGROUND: The use of kidney biopsy in elderly individuals is still matter of discussion. The purpose of this study is to assess the utility of kidney biopsy for the management of glomerulopathies in an Eastern European cohort, targeting patients older than 65 years. METHODS: This retrospective study included 875 adults (147 older than 65 years), with biopsy-proven glomerulopathies, followed up for 71.1 (95% CI 68.2-73.9) months. The primary endpoint was chronic renal replacement therapy initiation. Statistical evaluation was performed with IBM SPSS software version 20, Analyse-it, and SAS Studio. The Kaplan-Meier method was used to estimate the time to death and the log-rank test was used for comparisons. The multivariate Cox proportional hazard analysis was used to evaluate the risk of death. RESULTS: Secondary glomerulopathies were more frequent in patients aged > 65 years (52.4% vs. 41.9%, p = 0.004). Membranous nephropathy and amyloidosis were the most frequent primary and secondary glomerulopathies in this age group. Kidney biopsy complications were low (< 4%) in both age groups. In 42% of the elderly, the result of biopsy guided the immunosuppressive therapy. While the all-cause mortality rate was higher (OR 4.2; 95% CI 2.7-6.7; p < 0.0001) in elderly individuals, the rate of renal replacement therapy initiation was similar (31.3 vs 26%; p = 0.1) in both age groups. In the competitive risk analysis, kidney survival was similar irrespective of age [CIF 0.4 (95% CI 0.26-0.53) vs. 0.34 (95% CI 0.28-0.39), p = 0.08]. However, after adjusting for the confounding factors, younger age was associated with an increased risk of renal replacement therapy (HR = 1.57, p = 0.01), along with secondary glomerulopathies. CONCLUSION: The diagnosis of an underlying glomerulopathy guided the therapy in almost one-half of the elderly patients who underwent a kidney biopsy, provided important prognostic information and had a low complications rate; kidney biopsy may therefore be considered a safe, reliable procedure in the management of glomerulopathies, even in patients over 65 years of age.

Immunosuppressive therapy versus supportive care in IgA nephropathy patients with stage 3 and 4 chronic kidney disease.

The use of immunosuppressive therapy for immunoglobulin A nephropathy (IgAN) patients with stage 3 or 4 chronic kidney disease (CKD) is controversial. We performed a monocentric retrospective study on 83 consecutive IgAN patients with stage 3 or 4 CKD and proteinuria ≥0.75 g/d (age 41 [33-56] years, 72% male, estimated glomerular filtration rate 36.1 [25.4-47.5] mL/min/1.73 m2) who received uncontrolled supportive care (Supp) (n = 36), corticosteroids/corticotherapy (CS) (n = 14), or CS combined with monthly pulses of cyclophosphamide (CS + CFM) (n = 33) between 2010 and 2017. Patients were followed until composite endpoint (doubling of serum creatinine, end-stage kidney disease (dialysis or kidney transplant) or death, whichever came first) or end of study (January 2020). Patients were followed for a median of 29 (95% confidence interval = 25.2-32.7) months, and 12 (15%) patients experienced the composite endpoint. Within the limitation of a retrospective study, our results suggest no benefit from immunosuppressive therapy in patients with IgAN with stage 3 and 4 CKD as compared with supportive care. There were no differences between the 3 studied groups regarding age, estimated glomerular filtration rate, proteinuria, Oxford classification score, arterial hypertension, and therapy with renin-angiotensin system inhibitors. Mean kidney survival time for the entire cohort was 81.0 (95% confidence interval = 73.1-89.0) months, without significant differences between the 3 groups. In univariate and multivariate Cox regression analysis adjusted for IgAN progression factors, immunosuppressive therapy was not associated with better kidney survival when compared with supportive therapy.

Intravenous Iron-Carbohydrate Nanoparticles and Their Similars. What Do We Choose?

Anemia is highly prevalent worldwide and iron deficiency is the first cause. Iron deficiency has not only hematologic effects but also non-hematologic effects - immune, metabolic, cognitive dysfunctions and poor cardiovascular and renal outcomes - which generally precede anemia. Iron therapy not only significantly improves the hematological parameters but also has non-hematologic benefits. Given that its efficacy and safety has been revealed over the years, intravenous (IV) iron therapy is frequently used. Intravenous iron products are nanoparticles largely consisting in an iron core surrounded by a carbohydrate shell. They are classified as non-biological complex molecules, being different from small commonly used molecules, with properties and biological behavior impossible to be completely characterized only by physicochemical analysis. To date, there is no appropriate regulatory evaluation system for these medicines and several follow-on versions of the IV iron originators (e.g., iron sucrose) were approved using the same regulatory pathway as for generics. Because of this vulnerability in an adequate pathway for approval, both non-clinical and clinical studies suggested no therapeutic equivalence (thus no interchangeability) between iron sucrose originator (Venofer®), and iron sucrose similars. In this review we aimed to underline the importance of intravenous iron therapy as well as raise awareness regarding the differences between nanomedicines and their intended similar but not identical copies. The potential implications of these differences impact patients (safety, efficacy) but also the medical system (higher costs).

Inflammation-based modified Glasgow prognostic score and renal outcome in chronic kidney disease patients: is there a relationship?

BACKGROUND: Chronic kidney disease (CKD) progression is presumably related to inflammatory response. The modified Glasgow prognostic score (mGPS), based on a combination of albumin and C-reactive protein, has been derived from oncology and validated in multiple diseases. AIMS: To evaluate the relationship between the mGPS and CKD progression. METHODS: The present retrospective unicentric cohort study included 547 CKD patients (age 60.2 years; 53% male; estimated glomerular filtration (eGFR) 42.0 mL/min; mean change -2 mL/min/year) admitted between 1 January 2007 and 31 December 2012. Patients' records were reviewed from the CKD diagnosis to one of the four outcomes: end-stage kidney disease (ESKD), death, loss to follow up or until 31 July 2017. RESULTS: The mGPS score was 0 for 420 (78%), 1 for 110 (19%) and 2 for 17 (3%) patients. More patients with rapid CKD progression were found in the group with the highest mGPS (P = 0.05). mGPS was negatively correlated with baseline eGFR and positively with albuminuria. In the multivariate analysis, mGPS was associated with the eGFR slope. During the study period, 130 (24%) patients died and 109 (20%) reached ESKD. The mean kidney survival time was 8.1 (95% confidence interval 7.9-8.4) years. Patients with zero mGPS had better kidney survival than those with the score of 1 and 2 (Kaplan-Meier, P = 0.02). However, the kidney survival differences were not present after adjusting for CKD progression risk factors. CONCLUSION: The inflammation-based mGPS score was associated with eGFR decline in CKD patients. Therefore, could prove useful in improving risk stratification of CKD patients.

Long-Term Intravenous Iron Therapy and Morbidity in Hemodialysis Patients.

Objective: The aim of this study was to describe long-term intravenous iron therapy-associated morbidity in hemodialysis patients from a single Hemodialysis Center. Material and methods: We conducted an observational retrospective cohort study from 01 January to 31 December 2015. Two hundred and twenty prevalent patients on maintenance hemodialysis therapy for at least 12 months (mean age 53±13 years, 56% males, median hemodialysis vintage 5 (1-26) years) were included. Diabetic nephropathy as primary kidney disease, pregnancy and incomplete data records regarding study aims were exclusion criteria. We compared the frequency, duration and causes of hospitalizations in iron sucrose-treated versus gender and age-matched iron non-treated patients. Differences between groups were assessed using Chi-square and Kruskal-Wallis H tests. A p value µ0.05 was considered statistically significant. Results: From the entire cohort, 68% were iron-treated. One in five patients were treated with higher doses (400 mg monthly), and lower doses were used (100-200 mg monthly) in 80% of patients. There were no differences regarding the rates of admission between the two groups (56/100 patient-years in the iron sucrose-treated vs. 50/100 patient-years in the iron-untreated group, p=0.1). Still, the hospitalization rate significantly increased with the administered iron dose (0.4 vs. 0.7 vs. 0.8/100 patient-years for 100 mg vs. 200 mg vs. 400 mg monthly, respectively, p=0.006). Hospitalization rates due to infectious and cardiovascular diseases were similar for both groups (12/100 patient-years vs. 5.7/100 patient-years, p=0.3 and 11.3/100 patient-years vs. 4.3/100 patient-years, p=0.2, respectively). Conclusion: Higher doses of intravenous iron sucrose appear to be associated with an elevated risk of hospitalization. Nonetheless, long-term intravenous iron therapy seems to have a limited influence in terms of specific cause of morbidity in non-diabetic hemodialysis patients.

Coding practice in national and regional kidney biopsy registries.

BACKGROUND: Kidney biopsy registries all over the world benefit research, teaching and health policy. Comparison, aggregation and exchange of data is however greatly dependent on how registration and coding of kidney biopsy diagnoses are performed. This paper gives an overview over kidney biopsy registries, explores how these registries code kidney disease and identifies needs for improvement of coding practice. METHODS: A literature search was undertaken to identify biopsy registries for medical kidney diseases. These data were supplemented with information from personal contacts and from registry websites. A questionnaire was sent to all identified registries, investigating age of registries, scope, method of coding, possible mapping to international terminologies as well as self-reported problems and suggestions for improvement. RESULTS: Sixteen regional or national kidney biopsy registries were identified, of which 11 were older than 10 years. Most registries were located either in Europe (10/16) or in Asia (4/16). Registries most often use a proprietary coding system (12/16). Only a few of these coding systems were mapped to SNOMED CT (1), older SNOMED versions (2) or ERA-EDTA PRD (3). Lack of maintenance and updates of the coding system was the most commonly reported problem. CONCLUSIONS: There were large gaps in the global coverage of kidney biopsy registries. Limited use of international coding systems among existing registries hampers interoperability and exchange of data. The study underlines that the use of a common and uniform coding system is necessary to fully realize the potential of kidney biopsy registries.

Clinical features and outcome of maintenance hemodialysis patients with COVID-19 from a tertiary nephrology care center in Romania.

BACKGROUND: There is limited information about the clinical characteristics, treatment and outcome of maintenance hemodialysis patients with COVID-19. Moreover, regional differences are also conceivable since the extend and severity of outbreaks varied among countries. METHODS: In this retrospective, observational, single-center study, we analyzed the clinical course and outcomes of 37 maintenance hemodialysis patients (median age 64 years, 51% men) hospitalized with COVID-19 from 24 March to 22 May 2020 as confirmed by real-time PCR. RESULTS: The most common symptoms at admission were fatigue (51%), fever (43%), dyspnea (38%) and cough (35%). There were 59% mild/moderate patients and 41% severe/critical patients. Patients in the severe/critical group had a significantly higher atherosclerotic burden since diabetic kidney disease and vascular nephropathies were the most common primary kidney diseases and eighty percent of them had coronary heart disease. Also, Charlson comorbidity score was higher in this group. At admission chest X-ray, 46% had ground-glass abnormalities. Overall, 60% patients received hydroxychloroquine, 22% lopinavir-ritonavir, 11% tocilizumab, 24% systemic glucocorticoids, and 54% received prophylactic anticoagulation. Seven (19%) patients died during hospitalization and 30 were discharged. The main causes of death were cardiovascular (5 patients) and respiratory distress syndrome (2 patients). In Cox regression analysis, lower oxygen saturation, anemia and hypoalbuminemia at admission were associated with increased mortality. CONCLUSIONS: In conclusion, we observed a high mortality rate among maintenance hemodialysis patients hospitalized for COVID-19. Anemia, lower serum albumin and lower basal oxygen saturation at admission were factors associated with poor prognosis.

Non-diabetic glomerular lesions in diabetic kidney disease: clinical predictors and outcome in an Eastern European cohort.

PURPOSE: Since patients' prognosis depends on the lesions identified by kidney biopsy (KB), we aimed to evaluate predictors of non-diabetic kidney disease (NDKD) in diabetic subjects and to assess their kidney outcome as compared to diabetic nephropathy (DN). METHODS: 180 adults diagnosed by KB with DN (n = 120) or NDKD (n = 60), over a 10 year time-span, were retrospectively included and followed for a mean of 48.1 (95% CI 43.1-53.1) months. Patients with superimposed specific lesions over DN and with steroid-induced diabetes were excluded. The primary endpoint was renal replacement therapy (RRT) initiation. Only subjects who were alive at the end of follow-up (73 with DN and 38 with NDKD) entered the kidney survival analysis. RESULTS: Membranous nephropathy (9%) was the most common NDKD. Predictors for NDKD were shorter duration of diabetes (OR 0.88; 95% CI 0.81-0.96, p = 0.004), absence of diabetic retinopathy (OR 0.08; 95% CI 0.01-0.44, p = 0.003), and nephrotic syndrome at presentation (OR 3.55; 95% CI 1.39-9.04, p = 0.008). Subjects with NDKD needed RRT later as those with DN [82 (95% CI 67-97.1) vs. 45 (95% CI 34-56.5) months, p = 0.001]. In an adjusted Cox model, biopsy diagnosed DN independently predicted RRT (OR 4.43; 95% CI 1.54-12.7, p = 0.006). Other predictors were lower eGFR, higher proteinuria, and absence of renin-angiotensin inhibitor therapy. CONCLUSION: As one-third of the investigated subjects had NDKD, and NDKD was associated with a better kidney survival, independently predicted by the type of glomerular lesion, KB appears the most reliable tool to guide therapy and to assess outcome in patients with diabetic kidney disease.

Acute Effects of Iron Sucrose and Iron Carboxymaltose on Endothelial Function in Nondialysis Chronic Kidney Disease Patients.

BACKGROUND: Intravenous iron is commonly prescribed in chronic kidney disease (CKD) patients. Iron sucrose (IS) and ferric carboxymaltose (FCM) are 2 frequently used formulations. Experimental data showed that this 2 intravenous iron preparations have different potential to induce oxidative stress and by that endothelial dysfunction. Still, direct comparisons in clinical settings are rather scarce. STUDY QUESTION: Are there any acute changes in endothelial function after single intravenous iron infusions of IS and FCM in nondialysis CKD patients? STUDY DESIGN: This was a prospective, crossover study in which 31 patients with CKD stages 3-5 (80% stages 3 and 4, 81% female, 55% older than 60 years, 23% diabetes mellitus, and 94% arterial hypertension) who required intravenous iron as part of their routine medical care were enrolled. MEASURES AND OUTCOMES: The effect of flow-mediated vasodilatation infusions containing 250-mL 10% glucose, 500-mg FCM, and 200-mg IS, both in 250-mL 0.9% saline solution, was compared. The infusions were administered over 30 minutes, 72 hours apart, in the mentioned order. Ultrasound measurement of the brachial artery flow-mediated vasodilation (FMD) performed 15 minutes before and after each infusion was used to assess endothelial function. The outcome was the post/preinfusion difference (Δ) in FMD. RESULTS: The baseline FMD was similar before each study intervention. The arterial reactivity significantly decreased only after IS infusion [ΔFMD -2.3 (-5.65 to -0.33) vs. 1.0 (-1.49 to 1.80) after glucose, P = 0.01], but not after FCM [ΔFMD -0.8 (-2.50 to 0.65), P = 0.27 vs. glucose]. Moreover, the arterial reactivity was higher after IS as compared to FCM. CONCLUSIONS: Endothelial dysfunction seems to be acutely induced by a single dose of intravenous IS, but not by FCM, in nondialysis CKD patients.

Renal anemia and hydration status in non-dialysis chronic kidney disease: Is there a link?

Rationale: Anemia, a common feature in chronic kidney disease (CKD), has multiple contributors to its pathogenesis. Besides the well recognized erythropoietin and iron deficiencies, hydration status might be involved. Objective: To assess the prevalence and correlations of anemia, iron deficiency and overhydration in patients with stage 2 to 5 CKD. Methods and Results: This cross-sectional study enrolled 125 erythropoietin and iron therapy naïve non-dialysis CKD patients, without a identifiable cause of anemia. Parameters of hematological, iron, inflammatory and nutritional status were measured. The overhydration parameter (OH) assessed by bioimpedance spectroscopy was used to characterize hydration status. The prevalence of decreased hemoglobin (Hb) <110g/L increased along CKD stages from 0% to 40% (p=0.008). Fluid overload (OH >1L) and lower serum albumin (<40g/L) were more common in stage 5 versus stage 3 CKD (53% vs. 10%, p<0.001, and 27% vs. 3%, p=0.02, respectively), suggesting a potential dilutional reduction in serum proteins. Conversely, decreased iron stores (ferritin <100mcg/L) and iron availability (transferrin saturation, TSAT<0.20) were similarly prevalent irrespective of kidney function decline. Hemoglobin was positively correlated with estimated glomerular filtration rate (eGFR), serum albumin, and transferrin saturation, but inversely with OH. However, in a model of multiple linear regression which explained 32% of hemoglobin variation, only eGFR and overhydration remained the independent predictors of anemia. Discussion: As fluid overload is a common denominator for hemoglobin and TSAT levels, and is closely related to the declining kidney function, it should be considered in the management of renal anemia, at least in advanced CKD.

Metabolic Acidosis of Chronic Kidney Disease and Cardiovascular Disorders.

The burden of chronic diseases, which include both cardiovascular diseases (CVD) and chronic kidney disease (CKD), is constantly growing worldwide. Moreover, bidirectional links between kidney and heart disorders are commonly recognized and the pathogenesis of these interactions is a matter of current interest in medicine. One remarkable aspect, extensively showed by epidemiological studies, is the very high prevalence of CVD in patients with CKD, up to thirty times higher than in the general population. Since the traditional cardiovascular risk factors cannot solely account for this difference, numerous abnormalities due to the decline in glomerular filtration rate were hypothesized to be involved as non-traditional risk factors for CVD. Among them, the metabolic acidosis frequently seen in advanced CKD was studied, but conflicting results were reported. Therefore, we intend to briefly summarize the current knowledge and points of controversy regarding the possible influence of CKD-related chronic metabolic acidosis on cardiovascular diseases.

Metabolic acidosis of chronic kidney disease and subclinical cardiovascular disease markers: Friend or foe?

The effect of chronic metabolic acidosis (MA) on cardiovascular disease (CVD) in the setting of chronic kidney disease (CKD) is largely unknown. Therefore, we aimed to study this relationship in nondialysis CKD patients.This cross-sectional, single-center study prospectively enrolled 95 clinically stable CKD patients (median age 61 (58, 65) years, 60% male, median eGFR 27 (22, 32) mL/min). Data on CKD etiology, CVD history, CVD traditional, and nontraditional risk factors were obtained. Also, markers of subclinical CVD were assessed: intima-media thickness (IMT), abdominal aortic calcifications (Kauppila score-AACs), cardio-ankle vascular index (CAVI), ankle-brachial index (ABI), ejection fraction, and interventricular septum thickness. Using the serum bicarbonate cutoff value of 22 mEq/L, comparisons between MA (<22 mEq/L; 43 patients) and non-MA (≥22 mEq/L; 52 patients) groups were performed.Vascular (40%), tubulointerstitial (24%), and glomerular (22%) nephropathies were the main causes of CKD. Twenty-three percent of patients had diabetes mellitus, but only 5% were considered to have diabetic nephropathy. Patients with chronic MA had lower eGFR (P < .01), higher iPTH (P = .01), higher serum phosphate (P < .01), and increased serum cholesterol (P = .04) and triglycerides (P = .01).Higher ABI (P = .04), lower IMT (P = .03), CAVI (P = .05), and AACs (P = .03) were found in patients with chronic MA.Separate binomial logistic regression models were performed using ABI (cutoff 0.9), CAVI (cutoff 9), IMT (cutoff 0.1 cm), and AACs (cutoff 1) as dependent variables. MA was used as independent variable and adjustments were made for iPTH, serum phosphate, eGFR, proteinuria, cholesterol, triglycerides, CVD score. The absence of MA was retained as an independent predictor only for the presence of AACs.In conclusion, the present study shows a potential advantageous effect of MA on vascular calcifications in predialysis CKD patients. Thus, a guideline relaxation of the serum bicarbonate target might prove to be beneficial in CKD patients at high risk of vascular calcifications. However, one should always consider the negative effects of MA. Therefore, additional research is warranted before any clear clinical recommendation.

Subclinical cardiovascular disease markers and vitamin D deficiency in non-dialysis chronic kidney disease patients.

INTRODUCTION: Since 25-hydroxyvitamin D (25(OH)D) deficiency has been linked to an increased risk for cardiovascular disease (CVD) in the hemodialysis population, we aimed to determine the relationship between serum 25(OH)D level and markers of subclinical CVD in non-dialysis chronic kidney disease (CKD) patients. MATERIAL AND METHODS: This cross-sectional, single-center study prospectively enrolled 87 clinically stable CKD patients (median age: 61 (57-66) years, 51% male, median estimated glomerular filtration rate (eGFR): 32 (27-37) ml/min). Five markers of subclinical CVD were assessed: intima-media thickness, abdominal aortic calcifications (AAC) using the Kauppila score, cardio-ankle vascular index, ankle-brachial index (ABI) and interventricular septum thickness. RESULTS: Vascular (37%), glomerular (23%) and interstitial (18%) nephropathies were the main causes of CKD. 25(OH)D had a median value of 14 (12.5-17.1) ng/ml, and its levels decreased with eGFR (rs = 0.19; p = 0.04). Patients with 25(OH)D deficiency (54%) were older, had a higher serum alkaline phosphatase level, lower ABI and higher AAC score. There were no differences between the two groups regarding other traditional or non-traditional risk factors for atherosclerosis. The association between subclinical CVD markers and 25(OH)D was further evaluated in multivariable binomial logistic regression models adjusted for CV risk factors. Lower 25(OH)D level was retained as an independent predictor only for pathological ABI. CONCLUSIONS: This is the first study to evaluate the relationship between a large set of subclinical CVD markers and 25(OH)D deficiency in non-dialysis CKD patients. We found that hypovitaminosis D is associated with subclinical peripheral arterial disease, independently of other cardiovascular risk factors.

Prevalence of chronic kidney disease and its association with cardio-metabolic risk factors in the adult Romanian population: the PREDATORR study.

PURPOSE: PREDATORR is the first national study analyzing the prevalence of chronic kidney disease and its prognosis and association with socio-demographic, cardio-metabolic and lifestyle risk factors in the adult Romanian population. METHODS: Chronic kidney disease was defined according to the KDIGO 2012 criteria as an estimated glomerular filtration rate <60 mL/min/1.73 m(2) and/or urinary albumin-to-creatinine ratio ≥30 mg/g. The socio-demographic, lifestyle and anamnestic data were collected through interviewer-administered questionnaires. Physical examination and biochemical assays were also performed. RESULTS: This cross-sectional study conducted between December 2012 and February 2014 in Romania included 2717 adults. The overall age- and sex-adjusted prevalence of chronic kidney disease was 6.74 % (95 %CI 5.60-7.88 %), of which 3.31 % (2.50-4.13 %) had only reduced kidney function (estimated glomerular filtration rate <60 mL/min/1.73 m(2)), 2.98 % (2.21-3.76 %) had only albuminuria, and 0.45 % (0.14-0.74 %) had both. The prevalence of chronic kidney disease increased with age and was similar in women and in men. Age, hyperuricemia, impaired glucose regulation (diabetes/prediabetes), hypertriglyceridemia and a family history of renal disease were independent risk factors for the presence of chronic kidney disease. CONCLUSIONS: The PREDATORR study showed a high prevalence of chronic kidney disease in the adult Romanian population providing data on its prognosis and association with several cardio-metabolic risk factors.

Bone marrow iron distribution, hepcidin, and ferroportin expression in renal anemia.

OBJECTIVES: The hepcidin-ferroportin system is involved in both conditions associated with iron-restricted erythropoiesis in renal anemia: iron deficiency and anemia of chronic disorders. As serum hepcidin could aid diagnosis, we investigated its relationships with bone marrow iron distribution, hepcidin-ferroportin expression in bone marrow cells, and peripheral iron indices in non-dialysis chronic kidney disease (CKD) patients. METHODS: Fifty-four epoetin and iron naive CKD patients entered this prospective, observational study. According to bone marrow iron distribution (iliac crest biopsy, Perls' stain), 26 had iron deficiency anemia, 21 anemia of chronic disorders and 7 had normal iron stores. Medullar hepcidin and ferroportin expression (immunofluorescence (IF), semiquantitative scales) and serum hepcidin (Hep25 - ELISA) were the main studied parameters. RESULTS: Low hepcidin and high ferroportin expression by erythroblast and macrophage were seen in iron deficiency anemia, while the opposites were true in anemia of chronic disorders. In regression analysis, higher Hep25 and ferritin predicted hepcidin expression (R(2)=0.48; P < 0.0001), while lower ferritin and Hep25 - predicted ferroportin expression (R(2) = 0.29; P = 0.003) by erythroblast; inflammation had no contribution. In ROC analysis, serum hepcidin and ferritin had similar moderate utility in differentiating iron deficiency anemia from anemia of chronic disorders (AUC 0.63 95% CI 0.47-0.79 and 0.76 95% CI 0.61-0.90, respectively). CONCLUSIONS: Thus, in anemic epoetin naive non-dialysis CKD patients, hepcidin and ferroportin expression by erythroblast and macrophage are closely related to bone marrow iron distribution. Although the hepcidin-ferroportin system seems regulated by ferritin-driven Hep25, serum hepcidin and peripheral iron indices are of little help in describing bone marrow iron status.

Abdominal aortic calcification and renal resistive index in patients with chronic kidney disease: is there a connection?

BACKGROUND: We aimed to evaluate the relationship between abdominal aortic calcification (AAC) and renal resistive index (RRI), parameters associated with cardiovascular outcome, in non-dialysis chronic kidney disease (CKD) patients. METHODS: Seventy-seven stable patients mainly in CKD stages 3B and 4 (44 and 28%), median age 69 years, with a positive history of systemic atherosclerosis were prospectively enrolled. RRI, carotid intima-media thickness (IMT), Kauppila score for AAC (AACs), cardio-ankle vascular index (CAVI) and ankle-brachial index (ABI) were assessed. Traditional and non-traditional atherosclerosis risk factors were also evaluated. RESULTS: Vascular (50%), diabetic (26%) and primary glomerular nephropathies (8 %) were the main causes of CKD. AAC was highly prevalent (77%). In the whole cohort, RRI was directly related to AACs (rs = 0.35, p < 0.001). AACs correctly identified patients with RRI >0.7 in 69% (56-81%) of cases, a cut-off of 5 resulting the best combination of sensitivity (65%) and specificity (68%). Compared to those with AACs <5, patients with AACs >5 were older, had higher serum cholesterol, C-reactive protein and IMT, lower ABI, but similar CAVI, estimated glomerular filtration rate, serum calcium and phosphate. In the whole cohort, AACs was negatively correlated with ABI (rs = -0.51, p < 0.001) and positively with IMT (rs = 0.27, p = 0.01), supporting a role for Kauppila score in integrating information on both intra- and extrarenal atherosclerosis. CONCLUSIONS: As Kauppila score correlates with RRI in non-dialysis CKD patients, it could be a fast, convenient and relatively inexpensive tool for estimating RRI, and consequently the intrarenal vascular status, but further research is warranted.

Catheter-related infections in chronic hemodialysis: a clinical and economic perspective.

PURPOSE: Central venous catheters emerged as a major risk factor for infectious complications in hemodialysis (HD) patients. We aimed to assess the incidence of bacteremia in catheter-dependent HD patients and to characterize its clinical and economic impact. METHODS: We retrospectively collected clinical data and healthcare costs from 15 months for 75 admitted catheter-dependent HD patients, to document the type of bacteremia (complicated or not), pathogen and inflammation. RESULTS: Bacteremia (97 % with Staphylococcus aureus, 33 % methicillin-resistant) was present in 51 % patients, with an overall infections incidence of 5.79 per 1,000 catheter-days. Metastatic complications occurred in 21 % of bacteremic patients and were associated with higher mortality (38 vs. 4 %; p = 0.001). Although, in patients starting dialysis on catheter (41 %) as compared to those using catheter as bridge angioaccess, inflammation (higher C-reactive protein; p = 0.006) and anemia (lower Hb; p = 0.008) were more pronounced, bacteremia occurred in a lower proportion (32 vs. 64 %, p = 0.007). The total medical costs were 47 % higher in patients with complicated bacteremia than in those without bacteremia (p = 0.008) and 45 % higher in patients starting HD on catheter than in those using catheter as bridge angioaccess (p = 0.002). CONCLUSIONS: Despite the limitations resulting from retrospective cross-sectional single-center design, our study suggests that patients already on HD who required catheters as bridge angioaccess were more prone to bacteremia. This highlights the importance of close angioaccess monitoring to avoid unnecessary catheter usage. A similar increase in costs when initiating dialysis on catheter as in case of complicated bacteremia strongly supports the initial placement of a native arteriovenous fistula.