Early referral to nephrological care improves long-term survival and hospitalization after dialysis initiation, independent of optimal dialysis start - a call for harmonization of reimbursement policies.

Early treatment of kidney disease can slow disease progression and reduce the increased risk of mortality associated with end-stage kidney disease. However, uncertainty exists whether early referral (ER) to nephrological care per se or an optimal dialysis start impacts patient outcome after dialysis initiation. We determined the effect of ER and suboptimal dialysis start on the 3-year mortality and hospitalizations after dialysis initiation. Between January 2015 and July 2018, 349 patients with ≥1 month of follow-up started dialysis at nine Romanian dialysis clinics. After excluding patients with COVID-19 during follow-up, 254 patients (97 ER and 157 late referral) were included in this retrospective study. The observational period was truncated at 3 years, death, or loss to follow-up. Clinical and laboratory data were retrieved from the quality database of the nephrological care providers. Patients were followed for a median (25-75%) of 36 (16-36) months. At dialysis start, ER patients had higher hemoglobin, phosphate, and albumin levels and started dialysis less often via a central dialysis catheter (p < 0.001 for each). Logistic regression analysis demonstrated an independent lower risk for frequent hospitalizations for ER patients (odds ratio 0.22 (95% confidence interval 0.1-0.485), p < 0.001), and Cox regression analysis revealed an improved survival (hazard ratio 0.540 (95% confidence interval 0.325-0.899), p = 0.02), both independent of optimal dialysis start. In conclusion, early referral to nephrological care was associated with improved survival and lower hospitalization rates during the three years after dialysis initiation, independent of optimal dialysis start. These results strongly support the reimbursement of nephrological care before dialysis initiation.

Twenty years of real-world data to estimate chronic kidney disease prevalence and staging in an unselected population.

Chronic kidney disease (CKD) represents a global public health burden, but its true prevalence is not fully characterized in the majority of countries. We studied the CKD prevalence in adult users of the primary, secondary and tertiary healthcare units of an integrated health region in northern Portugal (n = 136 993; representing ∼90% of the region's adult population). Of these, 45 983 (33.6%) had at least two estimated glomerular filtration rate (eGFR) assessments and 30 534 (22.2%) had at least two urinary albumin:creatinine ratio (UACR) assessments separated by at least 3 months. CKD was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines as a persistent decrease in eGFR (<60 ml/min/1.73 m2) and/or an increase in UACR (≥30 mg/g). The estimated overall prevalence of CKD was 9.8% and was higher in females (5.5%) than males (4.2%). From these, it was possible to stratify 4.7% according to KDIGO guidelines. The prevalence of CKD was higher in older patients (especially in patients >70 years old) and in patients with comorbidities. This is the first real-world-based study to characterize CKD prevalence in a large, unselected Portuguese population. It probably provides the nearest estimate of the true CKD prevalence and may help healthcare providers to guide CKD-related policies and strategies focused on prevention and on the improvement of cardiovascular disease and other outcomes.

20 Years of Real-World Data to Estimate the Prevalence of Heart Failure and Its Subtypes in an Unselected Population of Integrated Care Units.

Introduction: Heart failure (HF) is a clinical syndrome caused by structural and functional cardiac abnormalities resulting in the impairment of cardiac function, entailing significant mortality. The prevalence of HF has reached epidemic proportions in the last few decades, mainly in the elderly, but recent evidence suggests that its epidemiology may be changing. Objective: Our objective was to estimate the prevalence of HF and its subtypes, and to characterize HF in a population of integrated care users. Material and Methods: A non-interventional cross-sectional study was performed in a healthcare center that provides primary, secondary and tertiary health cares. Echocardiographic parameters (left ventricle ejection fraction (LVEF) and evidence of structural heart disease) and elevated levels of natriuretic peptides were used to define two HF phenotypes: (i) HF with a reduced ejection fraction (HFrEF, LVEF ≤ 40% and either NT-proBNP ≥ 400 pg/mL (≥600 pg/mL if atrial fibrillation (AF)/flutter) or BNP ≥ 100 pg/mL (≥125 pg/mL if AF/flutter)) and (ii) HF with a non-reduced ejection fraction (HFnrEF), which encompasses both HFpEF (LVEF ≥ 50% and either NT-proBNP ≥ 200 pg/mL (≥600 pg/mL if AF/flutter) or BNP ≥ 100 pg/mL (≥125 pg/mL if AF/flutter) in the presence of at least one structural cardiac abnormality) and HF with a mildly reduced fraction (HFmrEF, LVEF within 40−50% and either NT-proBNP ≥ 200 pg/mL (≥600 pg/mL if AF/flutter) or BNP ≥ 100 pg/mL (≥125 pg/mL if AF/flutter) in the presence of at least one structural cardiac abnormality). The significance threshold was set at p ≤ 0.001. Results: We analyzed 126,636 patients with a mean age of 52.2 (SD = 18.3) years, with 57% (n = 72,290) being female. The prevalence of HF was 2.1% (n = 2700). The HF patients' mean age was 74.0 (SD = 12.1) years, and 51.6% (n = 1394) were female. Regarding HF subtypes, HFpEF accounted for 65.4% (n = 1765); 16.1% (n = 434) had HFmrEF and 16.3% (n = 439) had HFrEF. The patients with HFrEF were younger (p < 0.001) and had a history of myocardial infarction more frequently (p < 0.001) compared to HFnrEF, with no other significant differences between the HF groups. The HFrEF patients were more frequently prescribed CV medications than HFnrEF patients. Type 2 Diabetes Mellitus (T2D) was present in 44.7% (n = 1207) of the HF patients. CKD was more frequently present in T2D vs. non-T2D HF patients at every stage (p < 0.001), as well as stroke, peripheral artery disease, and microvascular disease (p < 0.001). Conclusions: In this cohort, considering a contemporary definition, the prevalence of HF was 2.1%. HFrEF accounted for 16.3% of the cases, with a similar clinical−epidemiological profile having been previously reported in the literature. Our study revealed a high prevalence of patients with HFpEF (65.4%), raising awareness for the increasing prevalence of this entity in cardiology practice. These results may guide local and national health policies and strategies for HF diagnosis and management.

Premature Mortality in Type 2 Diabetes Mellitus Associated with Heart Failure and Chronic Kidney Disease: 20 Years of Real-World Data.

INTRODUCTION: Type 2 diabetes mellitus (T2D) increases the risk of heart failure (HF) and chronic kidney disease (CKD). Nonetheless, evidence of cardiovascular (CV) prognosis is relatively scarce in young T2D patients. PURPOSE: To estimate the risk of all-cause death, CV death, and non-fatal major CV events (MACEs) in T2D patients younger than 65 years old. METHODS: We designed a retrospective cohort study using incident cases of either T2D, HF, or CKD in the population aged 40-65 years, from 1st January 2000 to 31st December 2019. Each individual was followed for up to one year. The primary analysis consisted of survival analysis with Cox proportional hazards to compare one-year risk of all-cause death, CV death, and MACEs between T2D without HF or CKD (T2D), T2D with HF (T2D-HF), and T2D with CKD (T2D-CKD) groups. RESULTS: A total of 14,986 incident adult diabetic patients from the last two decades in our institution were included with an average age at cohort inclusion of 55-58 years old. Glycemic control was similar among groups. The adjusted hazard ratio (HR) of one-year all-cause death was 2.77 (95% CI: 2.26-3.40) for T2D-HF and 3.09 (2.77-3.45) for T2D-CKD compared with the baseline T2D risk. The highest event rate (T2D-CKD) was 0.15 per person-year. The adjusted HR of one-year CV death was 2.75 (95% CI: 2.19-3.46) for T2D-CKD and 2.59 (1.72-3.91) for T2D-HF. The non-fatal MACE risk was significantly increased in T2D-HF or T2D-CKD compared with T2D (2.82 (CI95%: 2.34-3.41) for T2D-CKD vs. 1.90 (CI95%: 1.66-2.17) for T2D-CKD) with a 32% event rate in non-fatal MACEs. CONCLUSIONS: Coexistence of HF or CKD is associated with increased premature mortality as well as non-fatal CV events in T2D patients under 65 years old.

Improved immunologic response to COVID-19 vaccine with prolonged dosing interval in haemodialysis patients.

Vaccination against 2019 coronavirus disease (COVID-19) can reduce disease incidence and severity. Dialysis patients demonstrate a delayed immunologic response to vaccines. We determined factors affecting the immunologic response to COVID-19 vaccines in haemodialysis patients. All patients within a Swedish haemodialysis network, vaccinated with two doses of COVID-19 vaccine 2-8 weeks before inclusion, were eligible for this cross-sectional study. Severe adult respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein antibody levels were determined by EliA SARS-CoV-2-Sp1 IgG test (Thermo Fisher Scientific, Phadia AB) and related to clinical and demographic parameters. Eighty-nine patients were included. Patients were vaccinated with two doses of Comirnaty (BNT162b2, 73%) or Spikevax (mRNA-1273, 23,6%). Three patients received combinations of different vaccines. Response rate (antibody titres >7 U/mL) was 89.9%, while 39.3% developed high antibody titres (>204 U/mL), 47 (43-50) days after the second dose. A previous COVID-19 infection associated with higher antibody titres (median (25th-75th percentile) 1558.5 (814.5-3,763.8) U/mL vs 87 (26-268) U/mL, P = .002), while time between vaccine doses did not differ between groups (P = .7). Increasing SARS-CoV-2 antibody titres were independently associated with increasing time between vaccine doses (B 0.241, P = .02), decreasing serum calcium levels (B -0.233, P = .007) and previous COVID-19 (B 1.078, P < .001). In conclusion, a longer interval between COVID-19 mRNA vaccine doses, lower calcium and a previous COVID-19 infection were independently associated with a stronger immunologic vaccination response in haemodialysis patients. While the response rate was good, only a minority developed high antibody titres, 47 (43-50) days after the second vaccine dose.

Humoral immunogenicity and tolerability of heterologous ChAd/BNT compared with homologous BNT/BNT and ChAd/ChAd SARS-CoV-2 vaccination in hemodialysis patients : A multicenter prospective observational study.

BACKGROUND: After the reports of severe adverse reactions to the AstraZeneca ChAdOx1-S-nCoV-19 vaccine, patients who had received one dose of ChAdOx1-S-nCoV-19 vaccine were recommended a second dose of Pfizer's BNT162b2 vaccine. In hemodialysis patients, we compared the humoral immunogenicity and tolerability of homologous vaccination with ChAdOx1-nCoV-19/ChAdOx1-nCoV-19 (ChAd/ChAd) and BNT162b2/BNT162b2 (BNT/BNT) with heterologous vaccination of first dose of ChAdOx1-nCoV-19 and a second dose with BNT162b2 (ChAd/BNT). METHODS: In a multicenter prospective observational study, SARS-CoV-2 spike-IgG antibody levels, Nucleocapsid-protein-IgG-antibodies, and vaccine tolerability were assessed 6 weeks after second SARS-CoV-2 vaccination in 137 hemodialysis patients and 24 immunocompetent medical personnel. RESULTS: In COVID-19-naïve hemodialysis patients, significantly higher median SARS-CoV-2-spike IgG levels were found after ChAd/BNT (N = 16) compared to BNT/BNT (N = 100) or ChAd/ChAd (N = 10) (1744 [25th-75th percentile 276-2840] BAU/mL versus 361 [25th-75th percentile 120-936] BAU/mL; p = 0.009; 1744 [25th-75th percentile 276-2840] BAU/mL versus 100 [25th-75th percentile 41-346] BAU/mL; p = 0.017, respectively). Vaccinated, COVID-19-naïve medical personnel had median SARS-CoV-2 spike-IgG levels of 650 (25th-75th percentile 217-1402) BAU/mL and vaccinated hemodialysis patients with prior COVID-19 7047 (25th-75th percentile 685-10,794) BAU/mL (N = 11). In multivariable regression analysis, heterologous vaccination (ChAd/BNT) of COVID-19-naïve hemodialysis patients was independently associated with SARS-CoV-2 spike-IgG levels. The first dose of ChAd and the second dose of BNT after the first vaccination with ChAd (heterologous vaccination, ChAd/BNT) were associated with more frequent but manageable side effects compared with homologous BNT. CONCLUSIONS: Within the limitations of this study, heterologous vaccination with ChAd/BNT appears to induce stronger humoral immunity and more frequent but manageable side effects than homologous vaccination with BNT/BNT or with ChAd/ChAd in COVID-19-naïve hemodialysis patients.

Time-dependent evolution of IgG antibody levels after first and second dose of mRNA-based SARS-CoV-2 vaccination in haemodialysis patients: a multicentre study.

BACKGROUND: Vaccination programs are essential for the containment of the coronavirus disease 2019 pandemic, which has hit haemodialysis populations especially hard. Early reports suggest a reduced immunologic response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in dialysis patients, in spite of a high degree of seroconversion. We aimed to identify risk factors for a reduced efficacy of an mRNA vaccine in a cohort of haemodialysis patients. METHOD: In a multicentre study, including 294 Portuguese haemodialysis patients who had received two doses of BNT162b2 with a 3-week interval, immunoglobulin G-class antibodies against the SARS-CoV-2 spike protein were determined 3 weeks after the first dose (M1) and 6 weeks after the second dose (M2). The threshold for seroconversion was 10 UR/mL. Demographic and clinical data were retrieved from a quality registry. Adverse events were registered using a questionnaire. RESULTS: At M2, seroconversion was 93.1% with a median antibody level of 197.5 U/mL (1.2-3237.0) and a median increase of 180.0 U/mL (-82.9 to 2244.6) from M1. Age [beta -8.9; 95% confidence interval (95% CI) -12.88 to -4.91; P < 0.0001], ferritin >600 ng/mL (beta 183.93; 95% CI 74.75-293.10; P = 0.001) and physical activity (beta 265.79; 95% CI 30.7-500.88; P = 0.03) were independent predictors of SARS-CoV-2 antibody levels after two vaccine doses. Plasma albumin >3.5 g/dL independently predicted the increase of antibody levels between both doses (odds ratio 14.72; 95% CI 1.38 to 157.45; P = 0.03). Only mild adverse reactions were observed in 10.9% of patients. CONCLUSIONS: The SARS-CoV-2 vaccine BNT162b2 is safe and effective in haemodialysis patients. Besides age, iron status and nutrition are possible modifiable modulators of the immunologic response to SARS-CoV-2 mRNA vaccines. These data suggest the need for an early identification of populations at higher risk for diminished antibody production and the potential advantage of the implementation of oriented strategies to maximize the immune response to vaccination in these patients.

Immunogenicity and tolerability of COVID-19 vaccination in peritoneal dialysis patients-A prospective observational cohort study.

BACKGROUND: In peritoneal dialysis (PD) patients, information on the immunogenicity and tolerability of SARS-CoV-2 vaccination is still scarce. We compared the immunogenicity and tolerability of SARS-CoV-2 vaccination of PD patients with that of medical personnel. METHODS: In a prospective observational cohort study, PD patients and immunocompetent medical personnel were evaluated for SARS-CoV-2 spike-IgG- and Nucleocapsid-IgG-antibody-levels before, 2 weeks after the first, and 6 weeks after the second SARS-CoV-2 vaccination and vaccine tolerability after the first and second vaccination. RESULTS: In COVID-19-naïve PD patients (N = 19), lower SARS-CoV-2-spike-IgG-levels were found compared with COVID-19-naïve medical personnel (N = 24) 6 weeks after second vaccination (median 1438 AU/ml [25th-75th percentile 775-5261] versus 4577 [1529-9871]; p = 0.045). This finding resulted in a lower rate of strong vaccine response (spike-IgG ≥ 1000 AU/ml) of COVID-19-naïve PD patients compared with medical personnel (58% versus 92%; p = 0.013), but not for seroconversion rate (spike-IgG ≥ 50 AU/ml: 100% vs. 100%; p > 0.99). After first vaccination, COVID-naïve PD patients presented with significantly fewer side effects than medical personnel (number of any side effect: 1 [1-2] vs. 4 [1-7]; p = 0.015). A similar pattern with slightly decreased frequencies of side effects was observed for tolerability of second SARS-CoV-2 vaccination in PD patients and medical personnel (number of any side effects: 1 [1-1] vs. 2 [1-5]; p = 0.006). CONCLUSIONS: SARS-CoV-2 vaccination in COVID-19-naïve PD patients appeared to induce a very high rate of seroconversion but a substantially lower rate of patients with a strong response compared with medical personnel. Vaccination appeared to be safe in the PD patients studied.

Oral Colonization of Staphylococcus Species in a Peritoneal Dialysis Population: A Possible Reservoir for PD-Related Infections?

Peritoneal dialysis-related infections are important morbidity/mortality causes, being staphylococci the most prevalent agents. Since Staphylococcus aureus nasopharynx carriage is a known risk factor for PD infections and the oral cavity is a starting point for systemic diseases development, we aimed at comparing the oral staphylococci colonization between PD patients and controls and studying the association with PD-related infections. Saliva samples were plated in Mannitol salt, and isolates were identified by DnaJ gene sequencing. Staphylococci PD-related infections were recorded throughout the 4-year period following sample collection. Staphylococcus colonization was present in >90% of the samples from both groups (a total of nine species identified). PD patients presented less diversity and less prevalence of multispecies Staphylococcus colonization. Although all patients presenting Staphylococcus epidermidis PD-related infections were also colonized in the oral cavity by the same agent, only 1 out of 7 patients with ESI caused by S. aureus presented S. aureus oral colonization. Staphylococci are highly prevalent in the oral cavity of both groups, although PD patients presented less species diversity. The association between oral Staphylococcus carriage and PD-related infections was present for S. epidermidis but was almost inexistent for S. aureus, so, further studies are still necessary to evaluate the infectious potential of oral Staphylococcus carriage in PD.

Phase Angle Predicts Arterial Stiffness and Vascular Calcification in Peritoneal Dialysis Patients.

OBJECTIVES: Fluid overload (FO) is frequently present in peritoneal dialysis (PD) patients and is associated with markers of malnutrition, inflammation, and atherosclerosis/calcification (MIAC) syndrome. We examined the relationships in stable PD patients between phase angle (PhA) and the spectrum of uremic vasculopathy including vascular calcification and arterial stiffness and between PhA and changes in serum fetuin-A levels. METHODS: Sixty-one stable adult PD patients were evaluated in a cross-sectional study (ST1). Phase angle was measured by multifrequency bioimpedance analysis (InbodyS10, Biospace, Korea) at 50 kHz. Augmentation index (AI), a surrogate marker of arterial stiffness, was assessed by digital pulse amplitude tonometry (Endo PAT, Itamar Medical, Caesarea, Israel). Vascular calcification was assessed by simplified calcification score (SCS). Serum fetuin-A levels were measured by ELISA (Thermo scientific; Waltham, MA, USA). Serum albumin was used as a nutritional marker, and serum C-reactive protein (CRP) was used as an inflammatory marker. The same assessments were carried out longitudinally (ST2) in the first 33 patients who completed 1 year of evaluation in ST1. RESULTS: In ST1, patients with PhA < 6° had higher CRP levels, AI, and SCS and lower serum albumin and fetuin-A levels, in comparison with patients with PhA ≥ 6°. In addition, PhA was a predictor of both AI (ß = -0.351, p = 0.023) and SCS ≥ 3 (EXP (B) = 0.243, p = 0.005). In ST2, the increase of PhA over time was associated with decreases in both AI (r = -0.378, p = 0.042) and CRP levels (r = -0.426, p = 0.021), as well as with the increase in serum fetuin-A levels (r = 0.411, p = 0.030). CONCLUSIONS: Phase angle predicts both arterial stiffness and vascular calcification in stable PD patients.

Oral Yeast Colonization and Fungal Infections in Peritoneal Dialysis Patients: A Pilot Study.

Peritonitis and exit-site infections are important complications in peritoneal dialysis (PD) patients that are occasionally caused by opportunistic fungi inhabiting distant body sites. In this study, the oral yeast colonization of PD patients and the antifungal susceptibility profile of the isolated yeasts were accessed and correlated with fungal infection episodes in the following 4 years. Saliva yeast colonization was accessed in 21 PD patients and 27 healthy controls by growth in CHROMagar-Candida® and 18S rRNA/ITS sequencing. PD patients presented a lower oral yeast prevalence when compared to controls, namely, Candida albicans. Other species were also isolated, Candida glabrata and Candida carpophila. The antifungal susceptibility profiles of these isolates revealed resistance to itraconazole, variable susceptibility to caspofungin, and higher MIC values of posaconazole compared to previous reports. The 4-year longitudinal evaluation of these patients revealed Candida parapsilosis and Candida zeylanoides as PD-related exit-site infectious agents, but no correlation was found with oral yeast colonization. This pilot study suggests that oral yeast colonization may represent a limited risk for fungal infection development in PD patients. Oral yeast isolates presented a variable antifungal susceptibility profile, which may suggest resistance to some second-line drugs, highlighting the importance of antifungal susceptibility assessment in the clinical practice.

Asymptomatic Effluent Protozoa Colonization in Peritoneal Dialysis Patients.

Currently, chronic kidney disease (CKD) is a global health problem. Considering the impaired immunity of CKD patients, the relevance of infection in peritoneal dialysis (PD), and the increased prevalence of parasites in CKD patients, protozoa colonization was evaluated in PD effluent from CKD patients undergoing PD. Overnight PD effluent was obtained from 49 asymptomatic stable PD patients. Protozoa analysis was performed microscopically by searching cysts and trophozoites in direct wet mount of PD effluent and after staining smears. Protozoa were found in PD effluent of 10.2% of evaluated PD patients, namely Blastocystis hominis, in 2 patients, and Entamoeba sp., Giardia sp., and Endolimax nana in the other 3 patients, respectively. None of these patients presented clinical signs or symptoms of peritonitis at the time of protozoa screening. Our results demonstrate that PD effluent may be susceptible to asymptomatic protozoa colonization. The clinical impact of this finding should be further investigated.

Low prevalence of oral protozoa colonization in Portuguese healthy and end-stage renal disease patients undergoing peritoneal dialysis / Baja prevalencia de la colonización oral de protozoos en Portugueses saludables y o pacientes renales del último estadio de enfermedad y que necesitan de diálisis del peritoneo

Infections are a major complication in end-stage renal disease (ESRD) patients undergoing peritoneal dialysis (PD). Because the oral cavity may act as a source of systemic pathogens, some authors advocated specific measures when these patients are submitted to oral interventions, such as the administration of prophylactic antibiotics. Oral protozoa colonization may vary significantly with geographic distribution and to our knowledge no studies were performed in Portugal. The aim of the present study was to evaluate protozoa colonization in the saliva of ESRD patients undergoing PD and of their family members, living in the north of Portugal. Saliva was collected from 39 PD patients with a mean time on PD therapy of 12.7 - 15.9 months, and from 18 healthy volunteers (ESRD family members) for microscopic evaluation of protozoa by Lugols’ direct smear and specific staining techniques (Giemsa, Trichrome and Kinyoun). After the analysis of 456 smears obtained from 57 participants, only one PD patient (2.6%) presented an amoeba trophozoite in saliva. In conclusion, very low oral protozoa colonization was found, both on PD patients and family controls, suggesting that the oral protozoa colonization of Portuguese population is low and not significantly modified by the presence of end-stage chronic kidney disease. Further studies are required to address this issue.

Las infecciones son la principal complicación en pacientes renales del último estadio (ESRD) y que necesitan de diálisis del peritoneo (PD). Como la cavidad oral puede funcionar como una fuente de patógenos sistémicos, algunos autores indican medidas específicas cuando esos pacientes son sometidos a intervenciones orales, como la administración de antibióticos profilácticos. La colonización oral puede variar significativamente con la distribución geográfica. Según nuestros conocimientos, no han sido realizados estudios similares en Portugal. El principal objetivo fue evaluar la colonización de protozoos en saliva de pacientes ESRD del Norte de Portugal que hacían PD y, también, de sus familiares. Muestras de saliva fueron recogidas de 39 pacientes PD, con tiempo medio de terapia de PD de 12,7-15,9 meses y, también de 18 voluntarios saludables (familiares de ESRD). Las mismas utilizadas para evaluación microscópica de protozoos en laminas con lugol y tinciones especificas (Giemsa, Trichrome and Kinyoun). Después del análisis de 456 laminas, obtenidas de los 57 participantes, solamente en un paciente PD (2.6%) se observó un trofozoíto del ameba. En conclusión, se encontró una baja prevalencia de colonización oral de protozoos en el grupo estudiado. Así, la colonización oral de la población Portuguesa por protozoos es baja y no se cambia con la evolución de la enfermedad. Para mejor analizar esta situación, futuros estudios son necesarios.

Fibroblast growth factor 23 is associated with left ventricular hypertrophy, not with uremic vasculopathy in peritoneal dialysis patients.

AIMS: Cardiovascular (CV) events are the leading cause of morbidity and mortality in patients with chronic kidney disease (CKD), including those patients on peritoneal dialysis (PD). Fibroblast growth factor 23 (FGF23) has been associated with left ventricular hypertrophy (LVH) and mortality in patients with CKD. However, the role of FGF23 in uremic vasculopathy remains unclear. In this study, we aimed to assess the relationship between FGF23 and LVH, endothelial dysfunction, vascular calcification, and arterial stiffness in 48 stable PD patients. METHODS: Left ventricular mass index (LVMI) was assessed using 2-D echocardiography. Intact FGF23 blood levels were evaluated using an ELISA kit (Immutopics, Inc., San Clemente, CA, USA). Reactive hyperemia index (RHI) is a surrogate marker of endothelial dysfunction and the augmentation index (AI) is a surrogate marker of arterial stiffness. Both were assessed using peripheral arterial tonometry (EndoPAT 2000). Vascular calcification (VC) was assessed using the Adragão score. RESULTS: In unadjusted analysis; FGF23 was positively correlated with serum Pi (r = 0.487, p < 0.001), serum urea (r = 0.351, p = 0.015), serum creatinine (r = 0.535, p < 0.001), dialysis vintage (r = 0.309, p = 0.033), and LVMI (r = 0.369, p = 0.027) and was negatively correlated with age (r = -0.343, p = 0.017), residual renal function (r = -0.359, p < 0.012), and AI (r = -0.304, p = 0.038). In multivariate adjusted analysis, FGF23 was associated with LVMI (ß = 0.298, p = 0.041), serum Pi (ß = 0.345, p = 0.018), and age (ß = -0.372, p = 0.007) independent of dialysis vintage, gender, residual renal function (RRF), albumin, C-reactive protein and systolic blood pressure. There were no associations found between FGF23 and RHI, AI, or VC in multivariable- adjusted models. CONCLUSIONS: Our results show that FGF23 is associated with LVH but not with endothelial dysfunction, arterial stiffness, or vascular calcification in PD patients.

Clinical value of natriuretic peptides in chronic kidney disease.

According to several lines of evidence, natriuretic peptides (NP) are the main components of a cardiac-renal axis that operate in clinical conditions of decreased cardiac hemodynamic tolerance to regulate sodium homeostasis, blood pressure and vascular function. Even though it is reasonable to assume that NP may exert a relevant role in the adaptive response to renal mass ablation, evidence gathered so far suggest that this contribution is probably complex and dependent on the type and degree of the functional mass loss. In the last years NP have been increasingly used to diagnose, monitor treatment and define the prognosis of several cardiovascular (CV) diseases. However, in many clinical settings, like chronic kidney disease (CKD), the predictive value of these biomarkers has been questioned. In fact, it is now well established that renal function significantly affects the plasmatic levels of NP and that renal failure is the clinical condition associated with the highest plasmatic levels of these peptides. The complexity of the relation between NP plasmatic levels and CV and renal functions has obvious consequences, as it may limit the predictive value of NP in CV assessment of CKD patients and be a demanding exercise for clinicians involved in the daily management of these patients. This review describes the role of NP in the regulatory response to renal function loss and addresses the main factors involved in the clinical valorization of the peptides in the context of significant renal failure.

Effects of starting hemodialysis with an arteriovenous fistula or central venous catheter compared with peritoneal dialysis: a retrospective cohort study.

BACKGROUND: Although several studies have demonstrated early survival advantages with peritoneal dialysis (PD) over hemodialysis (HD), the reason for the excess mortality observed among incident HD patients remains to be established, to our knowledge. This study explores the relationship between mortality and dialysis modality, focusing on the role of HD vascular access type at the time of dialysis initiation. METHODS: A retrospective cohort study was performed among local adult chronic kidney disease patients who consecutively initiated PD and HD with a tunneled cuffed venous catheter (HD-TCC) or a functional arteriovenous fistula (HD-AVF) in our institution in the year 2008. A total of 152 patients were included in the final analysis (HD-AVF, n = 59; HD-TCC, n = 51; PD, n = 42). All cause and dialysis access-related morbidity/mortality were evaluated at one year. Univariate and multivariate analysis were used to compare the survival of PD patients with those who initiated HD with an AVF or with a TCC. RESULTS: Compared with PD patients, both HD-AVF and HD-TCC patients were more likely to be older (p<0.001) and to have a higher frequency of diabetes mellitus (p = 0.017) and cardiovascular disease (p = 0.020). Overall, HD-TCC patients were more likely to have clinical visits (p = 0.069), emergency room visits (p<0.001) and hospital admissions (p<0.001). At the end of follow-up, HD-TCC patients had a higher rate of dialysis access-related complications (1.53 vs. 0.93 vs. 0.64, per patient-year; p<0.001) and hospitalizations (0.47 vs. 0.07 vs. 0.14, per patient-year; p = 0.034) than HD-AVF and PD patients, respectively. The survival rates at one year were 96.6%, 74.5% and 97.6% for HD-AVF, HD-TCC and PD groups, respectively (p<0.001). In multivariate analysis, HD-TCC use at the time of dialysis initiation was the important factor associated with death (HR 16.128, 95%CI [1.431-181.778], p = 0.024). CONCLUSION: Our results suggest that HD vascular access type at the time of renal replacement therapy initiation is an important modifier of the relationship between dialysis modality and survival among incident dialysis patients.

Hypertension and angiogenesis in the aging kidney: a review.

With advanced aging, main components of the kidney are altered, including blood vessels, glomeruli and tubulointerstitium. Disruption in these 3 elements is interconnected and associated with several modifications, such as loss of kidney mass and systemic, metabolic and immunologic diseases. In this review we focus on renal blood vessels, the key role of hypertension and angiogenesis in the elderly kidney, the hemodynamic and molecular mechanisms underlying this aging process and the main factors involved. So far, the present data suggests a strong association between renal disease and hypertension and the impairment of regulatory mechanisms, such as angiogenesis in the aging kidney. The endothelium is a key player in vascular control and appears to be also disrupted in many compensatory functions (i.e., vasodilation). Perspectives for the management of the dysfunctional aging kidney are also addressed.

Local modulation of the natriuretic peptide system in the rat remnant kidney.

BACKGROUND: The natriuretic peptide (NP) system plays a central role in the renal adaptations to acute volume expansion. However, the modulation of the NP system in chronic renal insufficiency (CRI) remains to be elucidated. In the present study, we evaluated cardiac haemodynamics, plasma type-B natriuretic peptide (BNP) levels and the expression of natriuretic peptide receptor A (NPR-A) and NPR-C in the renal cortex (RC) and medulla (RM) of Sham and (3/4) nephrectomized ((3/4)nx) rats, up to 26 weeks after surgery. METHODS: Male Wistar-Han rats (190-220 g; n = 49) were randomly assigned to (3/4)nx or Sham surgery. Two, 10 and 26 weeks after surgery, non-invasive blood pressure (BP) and left ventricular (LV) haemodynamics were performed, and urine and blood were collected for metabolic studies and plasma BNP determination. In addition, tissue samples from RC and RM were obtained for NPR-A and NPR-C quantification (RT-PCR and western blotting) as well as NPR-A immunodetection. RESULTS: In (3/4)nx rats, the progressive interstitial fibrosis and tubular atrophy were accompanied by a time-dependent increase of BP and impaired natriuretic response to volume expansion (VE). This was accompanied in (3/4)nx rats by an early and time-dependent elevation of BNP circulating levels that was not associated with cardiac dysfunction or increased myocardial BNP gene expression. In (3/4)nx rats, NPR-A expression in the remnant RM was consistently reduced at 2, 10 and 26 weeks, and this was accompanied by an increase in NPR-C expression in the remnant RC from (3/4)nx rats. CONCLUSIONS: BP elevation and compromised natriuretic response to VE in (3/4)nx rats is associated with increased circulating BNP levels in the absence of cardiac dysfunction. This is accompanied in (3/4)nx rats by both impaired NPR-A expression in the RM and upregulation of NPR-C in the RC suggesting a novel mechanism for NP resistance in CRI.

[Lupus nephritis treatment]. / Tratamento da nefrite lúpica.

Systemic lupus erithematosus (SLE) is a multiorganic inflammatory disease characterized by a significant morbidity and mortality related not just to disease evolution but also to therapeutic side effects. Sixty percent of SLE patients develop renal disease related to lupus. Moreover, several studies report that lupus nephritis is an important predictor of both renal impairment and global mortality in these patients. In lupus nephritis, the renal biopsy still represents a cornerstone for both histological grading and therapeutical management. Several classification schemes for lupus nephritis based mainly on morphological parameters have been proposed so far. In the WHO grading system the most severe form of lupus nephritis is the diffuse proliferative lupus nephritis or lupus nephritis class IV. In fact, several authors have documented an invariable course to end stage renal failure in these patients, in the absence of specific therapy. Despite the considerable improvement observed since the introduction of corticosteroid and cyclophosphamide treatment, a significant number of patients still present an incomplete response to therapy. Moreover, even in the cases of good response to therapy adverse events related to the treatment such as infertility, hemorrhagic cystitis or increased susceptibility to infection frequently supervenes.