Plasma glycocalyx pattern: a mirror of endothelial damage in chronic kidney disease.

Background: Endothelial damage and cardiovascular disease complicate chronic kidney disease (CKD). The increased atherogenicity observed in patients with CKD can be linked to microinflammation and endothelial damage. Circulating endothelial glycocalyx degradation products, such as perlecan and decorin, tend to be elevated in CKD. We aimed to explore the association between the plasma perlecan and decorin levels and this pro-inflammatory and atherogenic state by studying monocyte subpopulations and intracellular adhesion molecule (ICAM)-1 expression in patients with CKD. Methods: We studied 17 healthy controls, 23 patients with advanced CKD, 25 patients on haemodialysis, 23 patients on peritoneal dialysis and 20 patients who underwent kidney transplantation. Perlecan and decorin levels were evaluated using enzyme-linked immunosorbent assays, and the monocyte phenotype was analysed using direct immunofluorescence and flow cytometry. Results: The plasma perlecan levels were higher in patients with CKD than in the healthy controls. These levels were associated with a higher prevalence of ICAM-1+ monocytes. Conversely, patients with advanced CKD (pre-dialysis) had higher plasma decorin levels, which were associated with a reduced ICAM-1 expression per monocyte. Conclusions: Elevated perlecan levels in CKD may be associated with a higher prevalence of ICAM-1+ monocytes and a pro-inflammatory phenotype. Elevated decorin levels may act as a negative regulator of ICAM-1 expression in monocytes. Therefore, perlecan and decorin may be related to inflammation and monocyte activation in CKD and may act as potential markers of endothelial damage.

Hemodialysis-Associated Immune Dysregulation in SARS-CoV-2-Infected End-Stage Renal Disease Patients.

Patients on hemodialysis show dysregulated immunity, basal hyperinflammation and a marked vulnerability to COVID-19. We evaluated the immune profile in COVID-19 hemodialysis patients and the changes associated with clinical deterioration after the hemodialysis session. Recruited patients included eight hemodialysis subjects with active, PCR-confirmed SARS-CoV-2 infection, five uninfected hemodialysis patients and five healthy controls. In SARS-CoV-2-infected hemodialysis patients TNF-α, IL-6 and IL-8 were particularly increased. Lymphopenia was mostly due to reduction in CD4+ T, B and central memory CD8+ T cells. There was a predominance of classical and intermediate monocytes with reduced HLA-DR expression and enhanced production of pro-inflammatory molecules. Immune parameters were analysed pre- and post-hemodialysis in three patients with COVID-19 symptoms worsening after the hemodialysis session. There was a higher than 2.5-fold increase in GM-CSF, IFN-γ, IL-1ß, IL-2, IL-6, IL-17A and IL-21 in serum, and augmentation of monocytes-derived TNF-α, IL-1ß and IL-8 and CXCL10 (p < 0.05). In conclusion, COVID-19 in hemodialysis patients associates with alteration of lymphocyte subsets, increasing of pro-inflammatory cytokines and monocyte activation. The observed worsening during the hemodialysis session in some patients was accompanied by augmentation of particular inflammatory cytokines, which might suggest biomarkers and therapeutic targets to prevent or mitigate the hemodialysis-related deterioration during SARS-CoV-2 infection.

Effect of Kidney Transplantation on Accelerated Immunosenescence and Vascular Changes Induced by Chronic Kidney Disease.

Kidney transplantation is the best option for patients with end-stage renal disease. Despite the improvement in cardiovascular burden (leading cause of mortality among patients with chronic kidney disease), cardiovascular adverse outcomes related to the inflammatory process remain a problem. Thus, the aim of the present study was to characterize the immune profile and microvesicles of patients who underwent transplantation. We investigated the lymphocyte phenotype (CD3, CD4, CD8, CD19, and CD56) and monocyte phenotype (CD14, CD16, CD86, and CD54) in peripheral blood, and endothelium-derived microvesicles (annexin V+CD31+CD41-) in plasma of patients with advanced chronic kidney disease (n = 40), patients with transplantation (n = 40), and healthy subjects (n = 18) recruited from the University Hospital "12 de Octubre" (Madrid, Spain). Patients with kidney transplantation had B-cell lymphopenia, an impairment in co-stimulatory (CD86) and adhesion (CD54) molecules in monocytes, and a reduction in endothelium-derived microvesicles in plasma. The correlations between those parameters explained the modifications in the expression of co-stimulatory and adhesion molecules in monocytes caused by changes in lymphocyte populations, as well as the increase in the levels of endothelial-derived microvesicles in plasma caused by changes in lymphocyte and monocytes populations. Immunosuppressive treatment could directly or indirectly induce those changes. Nevertheless, the particular characteristics of these cells may partly explain the persistence of cardiovascular and renal alterations in patients who underwent transplantation, along with the decrease in arteriosclerotic events compared with advanced chronic kidney disease. In conclusion, the expression of adhesion molecules by monocytes and endothelial-derived microvesicles is related to lymphocyte alterations in patients with kidney transplantation.

¿Es adecuada la diálisis peritoneal para pacientes mayores de 65 años? Estudio multicéntrico prospectivo / Is peritoneal dialysis suitable technique CKD patients over 65 years? A prospective multicenter study

Escenario: La prevalencia de enfermedad renal crónica (ERC) aumenta en población mayor de 65años y asocia morbilidad, dependencia y fragilidad. La diálisis peritoneal (DP) se ha considerado una técnica de paciente joven y vida activa. Hipótesis: La DP puede ser adecuada en pacientes de edad avanzada. Buscamos resultados desfavorables que contravengan esta hipótesis. Objetivo: Describir el tratamiento con DP en mayores de 65años, evaluar su evolución clínica comparada con los menores de 65 e identificar áreas de mejora asistencial. Estudio: Prospectivo, observacional y multicéntrico en incidentes en DP, seguimiento hasta evento o fin del estudio (ene-2003 a ene-2018).Resultados: Se incluyen 2.435 pacientes; el 31,9% (777) eran mayores de 65 años. El tiempo medio de seguimiento fue de 2,1años para ambos grupos. El grupo de edad avanzada era 25años mayor, con más comorbilidad: diabetes (29,5% vs. 17,2%; p<0,001), evento CV previo (34,5% vs. 14,0%; p<0,001) e índice de Charlson sin edad (3,8 vs. 3,0; p<0,001). No encontramos diferencias en cumplimiento de objetivos intermedios de eficacia de DP, control de anemia o hipertensión durante el seguimiento. La tasa de peritonitis fue mayor en la cohorte mayor de 65años (0,65 vs. 0,45 episodios/paciente-año; p<0,001), aunque la distribución gérmenes, tasa de ingreso y evolución final fue similar en ambos grupos. Lógicamente, registramos mayor mortalidad en el grupo mayor de 65años (28,4% vs. 9,4%), aunque el tiempo de permanencia en DP fue similar (2,1años). La principal causa de salida fue el trasplante renal en jóvenes (48,3%), mientras que en los pacientes de mayor edad fue el paso a hemodiálisis, principalmente por cansancio de cuidador/autocuidado (20,2%) y no por fallo de la técnica (7,3%). (AU)

Background: Chronic kidney disease (CKD) is increasing in patients older than 65years and is related to morbidity, frailty, and dependence. Peritoneal dialysis (PD) has classically been associated with young patients with an active life. Hypothesis: PD should be offered to patients over 65years. We search for any unfavorable results that may advice not to recommend PD therapy for this group. Objective: To describe PD treatment and outcomes in patients >65years, to compare their results with patients <65years and to identify areas with room for improvement in a real-life study. Study: Prospective, observational, and multicenter study performed in incident PD patients, from January 2003 until January 2018. Results: We included 2,435 PD patients, 31.9% were older than 65years; there was a difference of 25years between both groups. Median follow up was 2.1years. Older than 65years group had more comorbidity: Diabetes (29.5% vs 17.2%; p<0.001), previous CV events 34.5% vs 14.0%; p<0.001), Charlson index (3.8 vs 3.0; p<0.001). We did not find differences in efficacy and PD adequacy objectives fulfillment, anaemia management or blood pressure during follow-up. Peritonitis rate was higher in older 65years group (0.65 vs 0.45 episodes/patient/year; p<0.001), but there was not differences in germs, admission rate and follow up. Mortality was higher in older 65years group (28.4% vs 9.4%) as expected. PD permanence probability was similar (2.1years). The main cause of PD withdrawal was transplant in group <65years (48.3%) and transfer to HD in group >65years. The main reason was caregiver or patient fatigue (20.2%), and not technique failure (7.3%). (AU)

Oxidative Stress in Patients with Advanced CKD and Renal Replacement Therapy: The Key Role of Peripheral Blood Leukocytes.

Oxidative stress plays a key role in the pathophysiology of chronic kidney disease (CKD). Most studies have investigated peripheral redox state focus on plasma, but not in different immune cells. Our study analyzed several redox state markers in plasma and isolated peripheral polymorphonuclear (PMNs) and mononuclear (MNs) leukocytes from advanced-CKD patients, also evaluating differences of hemodialysis (HD) and peritoneal dialysis (PD) procedures. Antioxidant (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH)) and oxidant parameters (xanthine oxidase (XO), oxidized glutathione (GSSG), malondialdehyde (MDA)) were assessed in plasma, PMNs and MNs from non-dialysis-dependent-CKD (NDD-CKD), HD and PD patients and healthy controls. Increased oxidative stress and damage were observed in plasma, PMNs and MNs from NDD-CKD, HD and PD patients (increased XO, GSSG and MDA; decreased SOD, CAT, GPX and GSH; altered GSSG/GSH balance). Several oxidative alterations were more exacerbated in PMNs, whereas others were only observed in MNs. Dialysis procedures had a positive effect on preserving the GSSG/GSH balance in PMNs. Interestingly, PD patients showed greater oxidative stress than HD patients, especially in MNs. The assessment of redox state parameters in PMNs and MNs could have potential use as biomarkers of the CKD progression.

Is peritoneal dialysis suitable technique CKD patients over 65 years? A prospective multicenter study.

BACKGROUND: Chronic kidney disease (CKD) is increasing in patients older than 65 years and is related to morbidity, frailty, and dependence. Peritoneal dialysis (PD) has classically been associated with young patients with an active life. HYPOTHESIS: PD should be offered to patients over 65 years. We search for any unfavorable results that may advice not to recommend PD therapy for this group. OBJECTIVE: To describe PD treatment and outcomes in patients > 65 years, to compare their results with patients < 65 years and to identify areas with room for improvement in a real-life study. STUDY: Prospective, observational, and multicenter study performed in incident PD patients, from January 2003 until January 2018. RESULTS: We included 2,435 PD patients, 31.9% were older than 65 years; there was a difference of 25 years between both groups. Median follow up was 2.1 years. Older than 65 years group had more comorbidity: Diabetes (29.5% vs 17.2%; p < 0.001), previous CV events 34.5% vs 14.0%; p < 0.001), Charlson index (3.8 vs 3.0; p < 0.001). We did not find differences in efficacy and PD adequacy objectives fulfillment, anaemia management or blood pressure during follow-up. Peritonitis rate was higher in older 65 years group (0.65 vs 0.45 episodes/patient/year; p < 0.001), but there was not differences in germs, admission rate and follow up. Mortality was higher in older 65 years group (28.4% vs 9.4%) as expected. PD permanence probability was similar (2.1 years). The main cause of PD withdrawal was transplant in group < 65 years (48.3%) and transfer to HD in group > 65 years. The main reason was caregiver or patient fatigue (20.2%), and not technique failure (7.3%). Multivariate Cox regression analysis showed a relation (HR [95%CI]) between mortality and age > 65 years 2.4 [1.9-3.0]; DM 1.6 [1.3-2.1]; CV events 2.1 [1.7-2.7]. Multivariate Cox regression analysis identify a relation between technique failure and age > 65 years 1.5 [1.3-1.9]; DM 1.6 [1.3-1.9] and previous transplant 1.5 [1.2-2.0]. CONCLUSION: Patients older than 65 years fulfilled PD adequacy criteria during the follow up. We believe PD is a valid option for patients older 65 years. It is necessary to try to prevent infections and patient/caregiver fatigue, to avoid HD transfer for reasons not related to technique failure.

Nrf2 Plays a Protective Role Against Intravascular Hemolysis-Mediated Acute Kidney Injury.

Massive intravascular hemolysis is associated with acute kidney injury (AKI). Nuclear factor erythroid-2-related factor 2 (Nrf2) plays a central role in the defense against oxidative stress by activating the expression of antioxidant proteins. We investigated the role of Nrf2 in intravascular hemolysis and whether Nrf2 activation protected against hemoglobin (Hb)/heme-mediated renal damage in vivo and in vitro. We observed renal Nrf2 activation in human hemolysis and in an experimental model of intravascular hemolysis promoted by phenylhydrazine intraperitoneal injection. In wild-type mice, Hb/heme released from intravascular hemolysis promoted AKI, resulting in decreased renal function, enhanced expression of tubular injury markers (KIM-1 and NGAL), oxidative and endoplasmic reticulum stress (ER), and cell death. These features were more severe in Nrf2-deficient mice, which showed decreased expression of Nrf2-related antioxidant enzymes, including heme oxygenase 1 (HO-1) and ferritin. Nrf2 activation with sulforaphane protected against Hb toxicity in mice and cultured tubular epithelial cells, ameliorating renal function and kidney injury and reducing cell stress and death. Nrf2 genotype or sulforaphane treatment did not influence the severity of hemolysis. In conclusion, our study identifies Nrf2 as a key molecule involved in protection against renal damage associated with hemolysis and opens novel therapeutic approaches to prevent renal damage in patients with severe hemolytic crisis. These findings provide new insights into novel aspects of Hb-mediated renal toxicity and may have important therapeutic implications for intravascular hemolysis-related diseases.

Glomerular Hematuria: Cause or Consequence of Renal Inflammation?

Glomerular hematuria is a cardinal symptom of renal disease. Glomerular hematuria may be classified as microhematuria or macrohematuria according to the number of red blood cells in urine. Recent evidence suggests a pathological role of persistent glomerular microhematuria in the progression of renal disease. Moreover, gross hematuria, or macrohematuria, promotes acute kidney injury (AKI), with subsequent impairment of renal function in a high proportion of patients. In this pathological context, hemoglobin, heme, or iron released from red blood cells in the urinary space may cause direct tubular cell injury, oxidative stress, pro-inflammatory cytokine production, and further monocyte/macrophage recruitment. The aim of this manuscript is to review the role of glomerular hematuria in kidney injury, the role of inflammation as cause and consequence of glomerular hematuria, and to discuss novel therapies to combat hematuria.

Nefropatía IgA: qué pacientes están en riesgo de progresar a enfermedad renal terminal y cómo deberían ser tratados? / IgA nephropathy: What patients are at risk of progression to end-stage renal disease and how should they be treated?

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Síndrome de Heyde: resolución de anemia tras reemplazo valvular aórtico en paciente en hemodiálisis / Heyde syndrome: Correction of anemia after aortic valve replacement in a hemodialysis patient

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Efectos adversos de la acumulación renal de hemoproteínas. Nuevas herramientas terapéuticas / Adverse effects of the renal accumulation of haem proteins. Novel therapeutic approaches

La hemoglobina y la mioglobina son hemoproteínas que juegan un papel fundamental en el organismo ya que participan en el transporte de oxígeno. Sin embargo, debido a su estructura química, estas moléculas pueden ejercer efectos deletéreos cuando se liberan al torrente sanguíneo de forma masiva, como sucede en determinadas condiciones patológicas asociadas a rabdomiólisis o hemólisis intravascular. Una vez en el plasma, estas hemoproteínas se pueden filtrar y acumular en el riñón, donde resultan citotóxicas, principalmente para el epitelio tubular, e inducen fracaso renal agudo y enfermedad renal crónica. En la presente revisión analizaremos los distintos contextos patológicos que provocan la acumulación renal de estas hemoproteínas, su relación con la pérdida de función renal a corto y largo plazo, los mecanismos fisiopatólogicos responsables de sus efectos adversos y los sistemas de defensa que contrarrestan tales acciones. Por último, describiremos los distintos tratamientos utilizados actualmente y mostraremos nuevas opciones terapéuticas basadas en la identificación de nuevas dianas celulares y moleculares, prestando especial atención a los diversos ensayos clínicos que se encuentran en marcha en la actualidad (AU)

Haemoglobin and myoglobin are haem proteins that play a key role as they help transport oxygen around the body. However, because of their chemical structure, these molecules can exert harmful effects when they are released massively into the bloodstream, as reported in certain pathological conditions associated with rhabdomyolysis or intravascular haemolysis. Once in the plasma, these haem proteins can be filtered and can accumulate in the kidney, where they become cytotoxic, particularly for the tubular epithelium, inducing acute kidney failure and chronic kidney disease. In this review, we will analyse the different pathological contexts that lead to the renal accumulation of these haem proteins, their relation to both acute and chronic loss of renal function, the pathophysiological mechanisms that cause adverse effects and the defence systems that counteract such actions. Finally, we will describe the different treatments currently used and present new therapeutic options based on the identification of new cellular and molecular targets, with particular emphasis on the numerous clinical trials that are currently ongoing (AU)

Podocytes are new cellular targets of haemoglobin-mediated renal damage.

Recurrent and massive intravascular haemolysis induces proteinuria, glomerulosclerosis, and progressive impairment of renal function, suggesting podocyte injury. However, the effects of haemoglobin (Hb) on podocytes remain unexplored. Our results show that cultured human podocytes or podocytes isolated from murine glomeruli bound and endocytosed Hb through the megalin-cubilin receptor system, thus resulting in increased intracellular Hb catabolism, oxidative stress, activation of the intrinsic apoptosis pathway, and altered podocyte morphology, with decreased expression of the slit diaphragm proteins nephrin and synaptopodin. Hb uptake activated nuclear factor erythroid-2-related factor 2 (Nrf2) and induced expression of the Nrf2-related antioxidant proteins haem oxygenase-1 (HO-1) and ferritin. Nrf2 activation and Hb staining was observed in podocytes of mice with intravascular haemolysis. These mice developed proteinuria and showed podocyte injury, characterized by foot process effacement, decreased synaptopodin and nephrin expression, and podocyte apoptosis. These pathological effects were enhanced in Nrf2-deficient mice, whereas Nrf2 activation with sulphoraphane protected podocytes against Hb toxicity both in vivo and in vitro. Supporting the translational significance of our findings, we observed podocyte damage and podocytes stained for Hb, HO-1, ferritin and phosphorylated Nrf2 in renal sections and urinary sediments of patients with massive intravascular haemolysis, such as atypical haemolytic uraemic syndrome and paroxysmal nocturnal haemoglobinuria. In conclusion, podocytes take up Hb both in vitro and during intravascular haemolysis, promoting oxidative stress, podocyte dysfunction, and apoptosis. Nrf2 may be a potential therapeutic target to prevent loss of renal function in patients with intravascular haemolysis. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Adverse effects of the renal accumulation of haem proteins. Novel therapeutic approaches. / Efectos adversos de la acumulación renal de hemoproteínas. Nuevas herramientas terapéuticas.

Haemoglobin and myoglobin are haem proteins that play a key role as they help transport oxygen around the body. However, because of their chemical structure, these molecules can exert harmful effects when they are released massively into the bloodstream, as reported in certain pathological conditions associated with rhabdomyolysis or intravascular haemolysis. Once in the plasma, these haem proteins can be filtered and can accumulate in the kidney, where they become cytotoxic, particularly for the tubular epithelium, inducing acute kidney failure and chronic kidney disease. In this review, we will analyse the different pathological contexts that lead to the renal accumulation of these haem proteins, their relation to both acute and chronic loss of renal function, the pathophysiological mechanisms that cause adverse effects and the defence systems that counteract such actions. Finally, we will describe the different treatments currently used and present new therapeutic options based on the identification of new cellular and molecular targets, with particular emphasis on the numerous clinical trials that are currently ongoing.

Changes in the clinical presentation of immunoglobulin A nephropathy: data from the Spanish Registry of Glomerulonephritis.

Background: Immunoglobulin A nephropathy (IgAN) is the most common glomerulonephritis in the world, but there is little epidemiological data about possible changes in its presentation over the years. Available information about the influence of age on the form of clinical presentation is also scarce. Methods: The aim of the study was to analyse all renal biopsies performed between 1994 and 2013 and recorded in the Spanish Registry of Glomerulonephritis with a histological diagnosis of IgAN. The study was divided into five 4-year periods (1994-97, 1998-2001, 2002-05, 2006-09 and 2010-13) and patients were divided into four age groups: ≤16, 17-44, 45-64 and ≥65 years. Results: From 20.974 renal biopsies recorded, 2961 (14.1%) corresponded to IgAN. The prevalence of IgAN remained stable, but a significant increase in age [from 37.6 (SD 17.7) in 1994-97 to 44.9 (SD 16.8) years in 2010-13; P = 0.001] and worse renal function at presentation [from serum creatinine (SCr) 1.9 (SD 1.9) in 1994-97 to 2.3 (SD 2.1) mg/dL in 2010-13; P = 0.001] were observed over the years. Nephrotic-range proteinuria and acute kidney injury (AKI) as forms of presentation were significantly more common among patients ≥65 years (17.7% and 43.2%, respectively) as compared with the other age groups [≤16 (11.4% and 13.1%, respectively), 17-44 (13.1% and 13%, respectively) and 45-64 (12.1% and 21.3%, respectively)]. Blood pressure, SCr and proteinuria were also significantly higher at presentation among elderly patients. Conclusions: Although the prevalence of IgAN in Spain has remained stable over the years, patients are significantly older and present with significantly worse renal function in the last years. The incidence of nephrotic-range proteinuria (17.7%) and AKI (43.2%) as forms of presentation is remarkable among patients ≥65 years of age.

Gastrointestinal complications induced by sevelamer crystals.

BACKGROUND: Sevelamer is a phosphate binder widely used in chronic kidney disease (CKD) patients. Sevelamer, as well as other resin-based binders, can crystallize leading to the formation of concretions. Sevelamer crystals (SC) have been associated with gastrointestinal (GI) mucosal injury. We describe three new cases of GI lesions associated with SC and review previously reported cases. METHODS: We describe three new cases of GI lesions associated with SC and review previously reported cases. RESULTS: We found 16 previously reported cases of SC-induced GI lesions. The mean patient age was 61 years (interquartile range 51.5-71.75), 62.5% were females and 10 patients were diabetic. In 13 cases, SC was found inside the GI mucosa. Six patients had history of major abdominal surgery. GI bleeding was the most common clinical symptom (n = 7), with three patients presenting with acute abdomen requiring surgical intervention. Although, SC-induced lesions were observed in all GI segments, intestine was involved in 81% of the cases. Endoscopic examination revealed mainly erosions and ulcerations (n = 7) and pseudoinflammatory polyps (n = 5). No association between sevelamer doses and the severity of GI lesions was found. However, diabetics patients seemed to develop GI lesions with smaller doses of sevelamer as compared with non-diabetic patients, in spite of their fewer GI comorbidities. CONCLUSIONS: SC-induced GI lesions should be considered in CKD patients treated with sevelamer who present GI symptoms, especially lower GI bleeding, once other causes have been ruled out. Diabetics seem more prone to develop SC- associated GI lesions. Sevelamer therapy should be avoided if possible in patients with a history of major abdominal surgery or chronic constipation, because of the high risk of serious GI complications.

Is High-Volume Online Hemodiafiltration Associated With Malnutrition?

Chronic malnutrition is a common problem in patients with end-stage renal disease on hemodialysis. Some studies have reported albumin loss into dialysis fluid during postdilution online hemodiafiltration (OL-HDF). The aim of the study was to assess the nutritional status of patients on high-volume OL-HDF and to demonstrate that higher convective clearances are not associated with malnutrition due to possible loss of nutrients with ultrafiltration. Demographic and clinical data, corporal composition with bioimpedance spectroscopy, dialysis features, albumin loss into dialysis fluid and laboratory parameters were collected in twenty-eight patients with ESRD undergoing postdilution OL-HDF with stable convective volumes over 28 L/session. Convective volume (CV) in the last six months was 32.51 ± 3.52 L per session. Cross-sectional analysis of dialysis features showed 32.7 ± 3.34 L of CV and high reduction rates of beta-2-microglobulin (84.2 ± 3.8%) and cystatin-C (81.6 ± 3.47%). Beta-2-microglobulin reduction showed a positive correlation with prealbumin levels (P = 0.048). CV was only correlated with cystatin-C reduction (P = 0.025). Estimated albumin loss into dialysis fluid (1.82 ± 1.05 g/session) was not related to laboratory or bioimpedance nutritional parameters, or to CV. Among patients with higher CV, serum albumin levels maintained more stability during the observational period. High volume OL-HDF results in better convective clearances and is not associated with malnutrition. Albumin and nutrients loss into dialysis fluid should not be a limiting factor of the substitution volume.

Remission of Hematuria Improves Renal Survival in IgA Nephropathy.

Hematuria is a cardinal symptom in IgA nephropathy, but its influence on the risk of disease progression has been scarcely investigated. We followed a cohort of 112 patients with IgA nephropathy for a mean±SEM period of 14±10.2 years, during which clinical and analytic risk factors (including urine sediment examination) were regularly recorded. According to the magnitude of time-averaged hematuria, we classified patients as those with persistent hematuria and those with negative or minimal hematuria. We also classified patients according to the magnitude of time-averaged proteinuria (>0.75 or ≤0.75 g/d). The proportion of patients reaching ESRD or a 50% reduction of renal function was significantly greater among patients with persistent hematuria than patients with minimal or negative hematuria (30.4% and 37.0% versus 10.6% and 15.2%, respectively; P=0.01). Multivariable analysis revealed time-averaged hematuria, time-averaged proteinuria, renal function at baseline, and the presence of tubulointerstitial fibrosis on renal biopsy as independent predictors of ESRD. After hematuria disappearance, which occurred in 46% of the patients, the rate of renal function decline changed from -6.45±14.66 to -0.18±2.56 ml/min per 1.73 m2 per year (P=0.001). Patients with time-averaged proteinuria >0.75 g/d had significantly poorer renal survival than those with time-averaged proteinuria ≤0.75 g/d. However, on further classification by time-averaged hematuria, only those patients with time-averaged proteinuria >0.75 g/d and persistent hematuria had significantly worse renal survival than those in the other three groups. In conclusion, remission of hematuria may have a significant favorable effect on IgA nephropathy outcomes.