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Kidney transplant (KT) is the best technique for renal replacement treatment in terms of survival, costs, and quality of life. Several factors have been related to health-related quality of life (HRQOL) at different times after KT. The objectives of the study were to quantify the HRQOL in a prevalent cohort of KT patients and to describe the variables that influenced HRQOL.In this cross-sectional study of a cohort of 64 KT patients, we measured HRQOL using the 36-item Short Form Health Survey. Variables measured included the following: physical functioning, role physical (RP), bodily pain (BP), general perception of health, vitality, social functioning (SF), role emotional (RE), and mental health. Demographic and analytical variables were collected. We describe the variables that influenced HRQOL.A large dispersion was observed in the RP, BP, SF, and RE categories. There were no differences in values between men and women who underwent KT. Diabetes, previous dialysis, deceased donor, age, kidney function, anemia, and malnutrition were associated with worse scores.This study suggests that HRQOL in KT patients is very heterogeneous and highly polarized. The factors that influence HRQOL are multiple and need to be addressed globally. Further studies are needed to understand the factors that influence HRQOL in the long term.

Kidney international 103(2), 391-402 (2022). doi:10.1016/j.kint.2022.09.017, Published by Elsevier, New York, NY

Background Models developed to predict hospital-acquired acute kidney injury (HA-AKI) in non-critically ill patients have a low sensitivity, do not include dynamic changes of risk factors and do not allow the establishment of a time relationship between exposure to risk factors and AKI. We developed and externally validated a predictive model of HA-AKI integrating electronic health databases and recording the exposure to risk factors prior to the detection of AKI. Methods The study set was 36 852 non-critically ill hospitalized patients admitted from January to December 2017. Using stepwise logistic analyses, including demography, chronic comorbidities and exposure to risk factors prior to AKI detection, we developed a multivariate model to predict HA-AKI. This model was then externally validated in 21 545 non-critical patients admitted to the validation centre in the period from June 2017 to December 2018. Results The incidence of AKI in the study set was 3.9%. Among chronic comorbidities, the highest odds ratios (ORs) were conferred by chronic kidney disease, urologic disease and liver disease. Among acute complications, the highest ORs were associated with acute respiratory failure, anaemia, systemic inflammatory response syndrome, circulatory shock and major surgery. The model showed an area under the curve (AUC) of 0.907 [95% confidence interval (CI) 0.902–0.908), a sensitivity of 82.7 (95% CI 80.7–84.6) and a specificity of 84.2 (95% CI 83.9–84.6) to predict HA-AKI, with an adequate goodness-of-fit for all risk categories (χ2 = 6.02, P = 0.64). In the validation set, the prevalence of AKI was 3.2%. The model showed an AUC of 0.905 (95% CI 0.904–0.910), a sensitivity of 81.2 (95% CI 79.2–83.1) and a specificity of 82.5 (95% CI 82.2–83) to predict HA-AKI and had an adequate goodness-of-fit for all risk categories (χ2 = 4.2, P = 0.83). An online tool (predaki.amalfianalytics.com) is available to calculate the risk of AKI in other hospital environments. Conclusions By using electronic health data records, our study provides a model that can be used in clinical practice to obtain an accurate dynamic and updated assessment of the individual risk of HA-AKI during the hospital admission period in non-critically ill patients.

Introduction Treatment of hypercholesterolemia in refractory nephrotic syndrome remains a therapeutic challenge. There is not enough evidence supporting the efficacy of statins, and these drugs can be associated with an increased incidence of adverse effects. Herein we summarize our clinical experience with 12 patients suffering from refractory nephrotic syndrome with associated vascular disease and uncontrolled hypercholesterolemia despite treatment with statins who were treated with proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors. Methods Twelve adult patients with primary nephrotic syndrome refractory to multiple lines of immunosuppressive treatment who suffered from clinical atheromatous vascular disease were treated with PCSK9 inhibitors according to the prescription guidelines for secondary prevention of cardiovascular events. Eight patients with refractory nephrotic syndrome without vascular disease treated with atorvastatin comprised the control group. Results Four weeks after treatment with PCSK9 inhibitors, a statistically significant decrease in total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels was observed without significant changes in serum albumin levels or proteinuria. The mean LDL-C decrease was 36.8% ± 4.9% mmol/L at 4 weeks and remained unchanged throughout the follow-up period. In the control group, there were no significant changes in the levels of total cholesterol or LDL-C during the follow-up period. At the diagnosis of nephrotic syndrome, plasma PCSK9 levels were 334 ± 40 ng/mL and correlated significantly with serum LDL-C levels (r = 0.49, P = 0.023). Six months after starting treatment with PCSK9 inhibitors, plasma PCSK9 levels were significantly reduced to values of 190 ± 36 ng/mL (P = 0.001) with a mean relative reduction of 42.3% ± 12.6%. No local adverse effects were seen at the injection site and no significant changes were seen in the levels of transaminase, creatine phosphokinase, or aldolase. Conclusion PCSK9 inhibitors may be an effective and safe alternative for the treatment of hypercholesterolemia associated with refractory nephrotic syndrome., Graphical abstract

Endothelial glycocalyx; Glomerular endothelial cell; Minimal change disease Glicocàlix endotelial; Cèl·lula endotelial glomerular; Malaltia de canvis mínims Glicocálix endotelial; Célula endotelial glomerular; Enfermedad de cambios mínimos Introduction Minimal change disease (MCD) is considered a podocyte disorder triggered by unknown circulating factors. Here, we hypothesized that the endothelial cell (EC) is also involved in MCD. Methods We studied 45 children with idiopathic nephrotic syndrome (44 had steroid sensitive nephrotic syndrome [SSNS], and 12 had biopsy-proven MCD), 21 adults with MCD, and 38 healthy controls (30 children, 8 adults). In circulation, we measured products of endothelial glycocalyx (EG) degradation (syndecan-1, heparan sulfate [HS] fragments), HS proteoglycan cleaving enzymes (matrix metalloprotease-2 [MMP-2], heparanase activity), and markers of endothelial activation (von Willebrand factor [vWF], thrombomodulin) by enzyme-linked immunosorbent assay (ELISA) and mass spectrometry. In human kidney tissue, we assessed glomerular EC (GEnC) activation by immunofluorescence of caveolin-1 (n = 11 MCD, n = 5 controls). In vitro, we cultured immortalized human GEnC with sera from control subjects and patients with MCD/SSNS sera in relapse (n = 5 per group) and performed Western blotting of thrombomodulin of cell lysates as surrogate marker of endothelial activation. Results In circulation, median concentrations of all endothelial markers were higher in patients with active disease compared with controls and remained high in some patients during remission. In the MCD glomerulus, caveolin-1 expression was higher, in an endothelial-specific pattern, compared with controls. In cultured human GEnC, sera from children with MCD/SSNS in relapse increased thrombomodulin expression compared with control sera. Conclusion Our data show that alterations involving the systemic and glomerular endothelium are nearly universal in patients with MCD and SSNS, and that GEnC can be directly activated by circulating factors present in the MCD/SSNS sera during relapse.

Background The reason why mesangial C4d deposits are detected in only certain biopsies of immunoglobulin A nephropathy (IGAN) remains unclear. We analyse the association between IgA glycosylation patterns, mesangial C4 deposition and clinical phenotypes in IgAN. Methods This cross-sectional study included 145 patients with idiopathic IgAN. We measured the serum levels of three different IgA1 lectin-binding specificities using enzyme-linked immunosorbent assays with and without treatment with neuraminidase and we analysed the relationship between these glycoforms, C4d mesangial deposits and clinical phenotypes. Results C4d-positive versus Cd4-negative patients had higher proteinuria [median 3.1 g/g (0.9–4.2) versus 1.8 (1–2.2); P = 0.000], haematuria [223 cells/µL (32–278) versus 99 (25–186); P = 0.000] and higher levels of IgA binding to neuraminidase untreated Helix aspersa (HA IgA1 neu−; 150.6 ± 52 U versus 96.2 ± 64.1; P = 0.000), neuraminidase untreated Helix pomatia (HPA IgA1 neu−; 0.34 ± 0.15 U versus 0.27 ± 0.13; P = 0.04), Triticum vulgaris (TV IgA1; 85.1 ± 31.7 U versus 42.2 ± 26.9; P = 0.000) and Canavalia ensiformis (ConA IgA1; 32.5 ± 18 U versus 16.7 ± 9.38; P = 0.000). The levels of HA IgA1 neu−, HPA IgA1 neu−, TV IgA1 and ConA IgA1 were all associated with the mesangial deposition of C4d, extracapillary proliferation and acute kidney injury. In receiver operating characteristics curves, HA IgA1 neu−, HPA IgA1 neu−, TV IgA1 and ConA IgA1 significantly discriminated between C4d-positive ad C4d-negative biopsies. In logistics models, TV IgA1 and ConA IgA1 were the only independent predictors of mesangial C4d deposits. Conclusions In IgAN, the severity of the disease is associated with the level of IgA exposing N-acetyl-d-galactosamine, N-acetyl-d-glucosamine or mannose, whereas C4d deposits are only associated with elevated levels of IgA1 glycoforms exhibiting glycan residues with specificity for mannose and N-acetyl-d-glucosamine binding lectins.

Objectives Idiopathic focal segmental glomerulosclerosis (FSGS) has been linked to immunological and inflammatory response dysregulations. The aim of this study was to find endotypes of FSGS patients using a cluster (CL) analysis based on inflammatory and immunological variables, and to analyse whether a certain endotype is associated with response to treatment with corticosteroids. Methods This prospective observational study included patients with idiopathic FSGS diagnosed by kidney biopsy. Serum levels of soluble interleukin (IL)-1 receptor, tumoural necrosis factor alpha, Interferon gamma (IFNγ), IL-6, IL-17, IL-12, IL-23, IL-13, IL-4, IL-5, IL-6, haemopexin (Hx), haptoglobin (Hgl), soluble urokinase-type plasminogen activator receptor (suPAR) and urinary CD80 (uCD80) were measured with enzyme-linked immunosorbent assay or nephelometry. T-helper lymphocyte populations and T-regulatory lymphocytes were analysed by flow cytometry. A factorial analysis followed by a k-means CL analysis was performed. Results A total of 79 FSGS patients were included. Three CLs were identified. CL1 (27.8%) included IL-12, IL-17, IL-23 and a T helper 17 (Th17) pattern. CL2 (20.2%) included IL-4, IL-5, IL-13, immunoglobulin E and Th2 pattern. CL3 (51.8%) included IL-6, Hx, Hgl, suPAR and uCD80. There were no differences in age, gender, kidney function, albumin or proteinuria among CLs. About 42/79 patients (53.1%) showed cortico-resistance. The prevalence of cortico-resistance was significantly lower in CL2 (4/16, 25%) than in CL1 (16/26, 72.7%) and CL3 (22/41, 53.7%) (P = 0.018), with no significant differences between CLs 1 and 3 (P = 0.14). Conclusions Patients with FSGS and indistinguishable clinical presentation at diagnosis were classified in three distinct CLs according to predominant Th17, Th2 and acute inflammatory responses that display differences in clinical response to treatment with corticosteroids., Graphical Abstract

Summary Long-term observation of patients with ANCA-associated vasculitis (AAV) allows the identification of different longitudinal patterns of ANCA levels during follow-up. This study aimed to characterize these patterns and to determine their prognostic significance. All ANCA determinations performed in two university hospitals during a 2-year period were retrospectively reviewed. Patients were included in the analysis if they had high titers of anti-myeloperoxidase (anti-MPO) or anti-proteinase 3 (anti-PR3) antibodies at least once, ≥ 5 serial ANCA determinations and AAV diagnosed by biopsy or American College of Rheumatology (ACR) classification criteria. Patients’ time–course ANCA patterns were classified as monophasic, remitting, recurrent or persistent. Associations between ANCA patterns and prognostic variables (relapse rate and renal outcome) were analysed by univariate and multivariate statistics. A total of 99 patients [55 with microscopic polyangiitis (MPA), 36 with granulomatosis with polyangiitis (GPA) and eight with eosinophilic granulomatosis with polyangiitis (EGPA)] were included. Median follow-up was 9 years. Among patients diagnosed with MPA or GPA, recurrent or persistent ANCA patterns were associated with a higher risk of clinical relapse [hazard ratio (HR) = 3·7, 95% confidence interval (CI) = 1·5–9·1 and HR = 2·9, 95% CI = 1·1–8·0, respectively], independently of clinical diagnosis or ANCA specificity. In patients with anti-MPO antibodies, the recurrent ANCA pattern was associated with worsening renal function [odds ratio (OR) = 5·7, 95% CI = 1·2–26·0]. Recurrent or persistent ANCA patterns are associated with a higher risk of clinical relapse. A recurrent ANCA pattern was associated with worsening renal function in anti-MPO-associated vasculitis.

Resumen: Antecedentes y objetivos: La biopsia renal transyugular (BTY) es una alternativa a la biopsia renal ecoguiada percutánea en caso de que existan contraindicaciones para su realización. En la actualidad, pocos centros realizan este procedimiento y la literatura acerca de las indicaciones, complicaciones y rentabilidad diagnóstica es limitada. El objetivo de este estudio es analizar las indicaciones, rendimiento diagnóstico, seguridad y complicaciones de la biopsia renal transyugular percutánea en los últimos 15 años en nuestro centro. Material y métodos: Estudio descriptivo retrospectivo que revisa las biopsias renales transyugulares (BTY) realizadas en el Hospital Vall d’Hebrón de 2003 a 2018 para lo cual se ha llevado a cabo una revisión exhaustiva de las historias clínicas de los pacientes sometidos a este procedimiento durante el periodo de estudio. Resultados: Durante el periodo de estudio se realizaron 56 BTY. Los pacientes fueron 31 hombres (55,4%) y 25 mujeres (44,6%), con una mediana de edad de 62 años (rango intercuartil (IQ) 25-75 [52,5-69,5]). La mediana de creatinina fue 2,69 mg/dL (IQ 25-75 [1,7-4,3]) y la de proteinuria (en 24 horas) de 2.000 mg (IQ 25-75[0,41-4,77]. Más de la mitad presentaban hematuria en el momento de la biopsia. La presión arterial media sistólica fue de 140 +/- 26 mmHg y diastólica 75 +/- 15 mmHg. La biopsia se realizó por insuficiencia renal aguda en 19 pacientes, enfermedad renal crónica en 12 y síndrome nefrótico en 10 casos; en 15 pacientes se realizó por otros motivos. Se decidió realización del procedimiento por vía transyugular por imposibilidad técnica ecoguiada en 16 de 56 casos (incluyendo riñones infracostales, obesidad y enfermedad pulmonar obstructiva crónica), alteraciones en hemostasia (n = 6), trombocitopenia (n = 5) y riñón único (n = 7). El 12,5% de las biopsias fueron hepato-renales. Se obtuvo diagnóstico histológico en dos tercios de las biopsias renales. La media de cilindros obtenidos fue de de 2,5 ± 1,3, y la media de glomérulos 6,6 ± 6,2. Los diagnósticos histológicos más frecuentes fueron nefropatía IgA, glomerulonefritis membranoproliferativa y microangiopatía trombótica. Se observaron tres complicaciones mayores: rotura de fórnix y dos requerimientos transfusionales por sangrado y hematoma subcapsular. Conclusiones: En nuestro centro, la realización de BTY permitió el diagnóstico histológico en dos tercios de los pacientes que presentaban contraindicación para la realización de biopsia renal ecoguiada, permitiendo el diagnóstico y posterior tratamiento dirigido en dichos pacientes. Abstract: Background and objectives: Transjugular renal biopsies (TRB) are an alternative when percutaneous ultrasound renal biopsy is contraindicated. Few sites are currently carrying out this procedure, with limited literature existing on the indications, complications and diagnostic yield thereof. The aim of the study is to analyse the indications, diagnostic yield, safety and complications of percutaneous transjugular renal biopsies in our site over the last 15 years. Material and methods: Retrospective descriptive study of all transjugular renal biopsies performed in our site, the Hospital Vall d’Hebron, between 2003 and 2018. For this, an exhaustive review of the clinical records of patients subjected to this procedure during the study period was conducted. Results: 56 TRBs were performed during the study period. Out of the patients, 31 were men (55.4%) and 25 were women (44.6%), with a median age of 62 years (IQ range 25-75 [52.5-69.5]). More than half presented with haematuria at the time of biopsy, with a median creatinine of 2.69 mg/dL (IQ 25-75 [1.7-4.3]) and median proteinuria at 24 hours of 2000 mg (IQ 25-75 [0.41-4.77]).The mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) were 140 +/- 26 mmHg and 75 +/- 15 mmHg, respectively. The biopsy was carried out owing to acute kidney failure in 19 patients, chronic kidney disease in 12 patients and nephrotic syndrome in 10 patients; in 15 patients it was carried out for other reasons. The most frequent TRB indication was technical impossibility in 16 of 56 cases (including infracostal kidneys, obesity and COPD), alterations in haemostasis (n = 6), thrombocytopenia (n = 5) and solitary kidney (n = 7). 12.5% of the biopsies were hepato-renal. Histological diagnoses were obtained in two thirds of the renal biopsies. The average number of cylinders obtained was 2.5 ± 1.3, with the average number of glomeruli being 6.6 ± 6.2. The most frequent histological diagnoses were IgA nephropathy, membranoproliferative glomerulonephritis and thrombotic microangiopathy. Three major complications were observed: fornix rupture and two transfusion requirements due to bleeding and subcapsular hematoma. Conclusions: In our site, TRB allowed for a histological diagnosis in 2/3 of patients for whom percutaneous ultrasound renal biopsy is contraindicated. This allowed us to diagnose and subsequently treat said patients.

Background Kidney biopsies of patients with diabetic nephropathy (DN) and normal kidney function may exhibit interstitial fibrosis (IF) without reduction of glomerular filtration rate (GFR) because of hyperfiltration. The aim of our study was to analyse the performance of a set of biomarkers of tubular injury to estimate the extent of IF in patients with DN and normal kidney function. Methods This cross-sectional study included 118 adults with DN diagnosed by kidney biopsy and GFR ≥90 mL/min/1.73 m2 and a control group of healthy subjects. We measured the urinary excretion of monocyte chemoattractant protein-1 (MCP-1) neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver-type fatty acid-binding protein (L-FABP), β2-microglobulin and dickkopf-3 protein (DKK-3) at the time of kidney biopsy. GFR was measured by chromium-51 labeled ethylenediamine tetraacetic acid (Cr-EDTA) (measured GFR). IF was quantified using a quantitative morphometric procedure. Predictive multivariate models were developed to estimate the IF surface. Results Patients with DN showed significantly higher levels of DKK-3, MCP-1 and L-FABP and significantly lower levels of epidermal growth factor (EGF) than healthy controls. There were no significant between-group differences in the levels of β2-microglobulin, KIM-1 or NGAL. IF was negatively associated with EGF and positively with age, proteinuria, MCP-1, DKK-3 and L-FABP, but not with β2-microglobulin, KIM-1, NGAL or GFR. The best model to predict IF surface accounted for 59% of its variability and included age, proteinuria, EGF, DKK-3 and MCP-1. Conclusions Our study provides a model to estimate the IF in DN that can be useful to assess the progression of IF in patients with normal kidney function.

Background Activation of parietal–epithelial cells (PECs) with neo-expression of CD44 has been found to play a relevant role in the development of focal and segmental glomerulosclerosis (FSGS). The aim of this study was to analyse whether the expression of CD44 by PECs in biopsies of minimal change disease (MCD) is associated with the response to corticosteroids, with kidney outcomes and/or can be considered an early sign of FSGS. Methods This multicentric, retrospective study included paediatric and adult patients with MCD. Demographic, clinical and biochemical data were recorded, and biopsies were stained with anti-CD44 antibodies. The association between PECs, CD44 expression and the response to corticosteroids, and kidney outcomes were analysed using logistic, Kaplan–Meier and Cox regression analyses. Results A total of 54 patients were included: 35 (65%) Conclusions In patients with a light microscopy pattern of MCD, CD44-positive staining of PECs is associated with a higher prevalence of steroid resistance and worse kidney outcomes, and can be considered an early sign of FSGS.

Glomerulonefritis creixent; Implants mamaris de silici; Esclerosi sistèmica Crescentic glomerulonephritis; Silicon breast implants; Systemic sclerosis Glomerulonefritis creciente; Implantes mamarios de silicio; Esclerosis sistémica The relationship between silicon breast implants (SBIs) and autoimmune/inflammatory syndrome induced by adjuvants (ASIA) has been extensively analysed, with discordant results. We present a 45-year-old woman with confirmed systemic exposure to SBI who developed systemic sclerosis (SSc) followed by anti-neutrophil cytoplasmic antibody anti-myeloperoxidase vasculitis with renopulmonary syndrome. The novelty of our case is, first, confirmation of systemic exposure to SBI and, second, chronologic development of not one, but two severe autoimmune diseases. Controversy may still remain regarding SBIs and ASIA because it is unclear that previous studies confirmed systemic exposure to silicon in their cohort of patients. Grant number: PI18/00356 - Instituto de Salud Carlos III - FEDER "Una manera de hacer Europa" - CERCA Programme/Generalitat de Catalunya - IRBLleida - Fundació Dr. Pifarré

Lesión renal aguda; Registros electrónicos de datos de salud; Adquirido en el hospital Lesió renal aguda; Registres electrònics de dades de salut; Adquirit a l'Hospital Acute kidney injury; Electronic health data records; Hospital-acquired Background. The current models developed to predict hospital-acquired AKI (HA-AKI) in non-critically ill fail to identify the patients at risk of severe HA-AKI stage 3. Objective. To develop and externally validate a model to predict the individual probability of developing HA-AKI stage 3 through the integration of electronic health databases. Methods. Study set: 165,893 non-critically ill hospitalized patients. Using stepwise logistic regression analyses, including demography, chronic comorbidities, and exposure to risk factors prior to AKI detection, we developed a multivariate model to predict HA-AKI stage 3. This model was then externally validated in 43,569 non-critical patients admitted to the validation center. Results. The incidence of HA-AKI stage 3 in the study set was 0.6%. Among chronic comorbidities, the highest odds ratios were conferred by ischemic heart disease, ischemic cerebrovascular disease, chronic congestive heart failure, chronic obstructive pulmonary disease, chronic kidney disease and liver disease. Among acute complications, the highest odd ratios were associated with acute respiratory failure, major surgery and exposure to nephrotoxic drugs. The model showed an AUC of 0.906 (95% CI 0.904 to 0.908), a sensitivity of 89.1 (95% CI 87.0–91.0) and a specificity of 80.5 (95% CI 80.2–80.7) to predict HA-AKI stage 3, but tended to overestimate the risk at low-risk categories with an adequate goodness-of-fit for all risk categories (Chi2: 16.4, p: 0.034). In the validation set, incidence of HA-AKI stage 3 was 0.62%. The model showed an AUC of 0.861 (95% CI 0.859–0.863), a sensitivity of 83.0 (95% CI 80.5–85.3) and a specificity of 76.5 (95% CI 76.2–76.8) to predict HA-AKI stage 3 with an adequate goodness of fit for all risk categories (Chi2: 15.42, p: 0.052). Conclusions. Our study provides a model that can be used in clinical practice to obtain an accurate dynamic assessment of the individual risk of HA-AKI stage 3 along the hospital stay period in non-critically ill patients. This research received no external funding.

The number of kidney transplant (KT) recipients has increased in recent years, saturating kidney transplant visits at transplant centers (TCs). Furthermore, some patients live far from TCs, which adds displacement costs to their expenses. To solve these problems, joint follow-up of KT recipients has been initiated at TCs and referral hospitals.We performed a cross-sectional study in a cohort of 64 KT recipients during joint follow-up in TCs and the Hospital Arnau de Villanova (HAV) using a survey that evaluated the displacement costs as well as the advantages and disadvantages of each.Distance (320 km [IQR, 300-340 km] vs 15 km [IQR, 4-60 km]; P.001), time (240 minutes [IQR, 210-240 minutes] vs 40 minutes [IQR, 30-68 minutes]; P.001), total economic cost per visit (€60 [IQR, €50-90] vs €10 [IQR, €2-15]; P.001), and annual COThis study suggests that joint follow-up between TCs and referral hospitals is an economic and ecological solution for follow-up in KT recipients living far away and visiting their referral hospital, which is the preferred choice for most patients.

Background : Secondary hyperparathyroidism (SHPT) is a common complication of chronic kidney disease (CKD). Cinacalcet use is controversial in non-dialysis patients. Methods : This retrospective observational study recruited patients receiving cinacalcet (off-label use) in 2010 and 2011. Patients were followed for three years from the beginning of treatment using an intention-to-treat approach. Results : Forty-one patients were studied: 14 CKD stage 3 (34.1%), 21 CKD stage 4 (51.2%), and 6 CKD stage 5 (14.6%). Median baseline parathyroid hormone (PTH) was 396 (101-1,300) pg/mL. Upon cinacalcet treatment (22 ± 12 months), PTH levels decreased by ≥ 30% in 73.2% of patients (P < 0.001; 95% confidence interval [CI], 59-87%), with a mean time for response of 18.7 months (95% CI, 15.4-22.1). Sixteen patients were followed for 36 months and treated for 32 ± 9 months. Mean reduction in their PTH levels was 50.1% (P < 0.001; 95% CI, 33.8-66.4%) at 36 months, with 62.5% of patients (P < 0.001; 95% CI, 35.9-89.1%) presenting reductions of ≥ 30%. Serum calcium levels decreased from 9.95 ± 0.62 mg/dL to 9.21 ± 0.83 and 9.12 ± 0.78 mg/dL at 12 and 36 months, respectively (P < 0.001). Serum phosphorus levels increased from 3.59 ± 0.43 to 3.82 ± 0.84 at 12 months (P = 0.180), remaining so at 36 months (P = 0.324). At 12 and 36 months, 2 (12.5%) patients experienced hypocalcemia. Meanwhile, 1 (6.3%) and 4 (25.0%) patients reported hyperphosphatemia at 12 and 36 months, respectively. Conclusion : Cinacalcet remained effective for at least 36 months in non-dialysis patients with SHPT. Electrolytic disturbances were managed with concurrent use of vitamin D and its analogs or phosphate binders.

Background Data on the activation of the acute inflammatory response and its clinicopathological associations in idiopathic nephrotic syndrome (INS) are scarce and discordant. Objective To analyse the associations between the activation of the inflammatory response, the clinicopathological characteristics of disease and the response to treatment with steroids in patients with INS. Methods A total of 101 patients with INS due to minimal change disease (MCD; n = 44), focal segmental glomerulosclerosis (FSGS; n = 33) and membranous nephropathy (MN; n = 24) and 50 healthy controls were included. At diagnosis, we measured the levels of haemopexin (Hx), haptoglobin (Hgl), interleukin-6 (IL-6), soluble urokinase-type plasminogen activator receptor (suPAR), tumour necrosis factor-α (TNF-α), soluble IL-1 receptor, interferon-γ and C-reactive protein. We analysed their clinicopathological associations. In MCD and FSGS patients, we determined the association between the levels of these variables and steroid resistance. Results The levels of Hx, Hgl, TNF-α, suPAR and IL-6 were higher in patients with INS than in healthy controls, and were not associated with proteinuria, estimated glomerular filtration rate or serum albumin. In MCD and FSGS patients, Hx, Hgl, IL-6 and TNF-α levels were similar and significantly higher than in MN patients. In patients with MCD and FSGS, multivariate analyses identified FSGS and the levels of Hx, Hgl or IL-6 as independent predictors of steroid resistance. Conclusions The activation of the inflammatory response in patients with INS is heterogeneous and more prevalent in MCD or FSGS patients than in those with MN. In MCD and FSGS, elevated levels of Hx, Hgl or IL-6 are independently associated with steroid resistance.

Background The Madrid Acute Kidney Injury Prediction Score (MAKIPS) is a recently described tool capable of performing automatic calculations of the risk of hospital-acquired acute kidney injury (HA-AKI) using data from from electronic clinical records that could be easily implemented in clinical practice. However, to date, it has not been externally validated. The aim of our study was to perform an external validation of the MAKIPS in a hospital with different characteristics and variable case mix. Methods This external validation cohort study of the MAKIPS was conducted in patients admitted to a single tertiary hospital between April 2018 and September 2019. Performance was assessed by discrimination using the area under the receiver operating characteristics curve and calibration plots. Results A total of 5.3% of the external validation cohort had HA-AKI. When compared with the MAKIPS cohort, the validation cohort showed a higher percentage of men as well as a higher prevalence of diabetes, hypertension, cardiovascular disease, cerebrovascular disease, anaemia, congestive heart failure, chronic pulmonary disease, connective tissue diseases and renal disease, whereas the prevalence of peptic ulcer disease, liver disease, malignancy, metastatic solid tumours and acquired immune deficiency syndrome was significantly lower. In the validation cohort, the MAKIPS showed an area under the curve of 0.798 (95% confidence interval 0.788–0.809). Calibration plots showed that there was a tendency for the MAKIPS to overestimate the risk of HA-AKI at probability rates ˂0.19 and to underestimate at probability rates between 0.22 and 0.67. Conclusions The MAKIPS can be a useful tool, using data that are easily obtainable from electronic records, to predict the risk of HA-AKI in hospitals with different case mix characteristics.

Background In anti-phospholipase A2 receptor (PLA2R) membranous nephropathy (MN) there is controversy whether spontaneous remission (SR) can be predicted using a single titre or by assessing the dynamic changes in anti-PLA2R antibody (ab) titres. The study objective was to identify the optimal dynamics of anti-PLA2Rab titres to predict SR in MN. Methods A total of 127 nephrotic patients with anti-PLA2R-MN were prospectively followed up for 6 months under conservative treatment. Anti-PLA2Rabs and proteinuria were assessed at diagnosis and monthly thereafter. The primary endpoint (PEP) was a reduction of proteinuria ≥50% at 6 months. Logistic models with baseline and evolutive anti-PLA2Rab titres were developed to predict the PEP. Results A total of 28 patients (22%) reached the PEP. These patients were more frequently female and had significantly lower baseline proteinuria and anti-PLA2Rab titres. An anti-PLA2R titre ≤97.5 RU/mL at diagnosis had a sensitivity of 71% and a specificity of 81% to predict the PEP. The model including baseline anti-PLA2Rabs and a reduction ≥15% at 3 months predicted the PEP with a sensitivity of 93% and a specificity of 80%, with an area under the curve that was significantly greater than that obtained with relative changes of proteinuria in the same period of time {odds ratio [OR] 0.95 [95% confidence interval (CI) 0.91–0.98 versus OR 0.79 [95% CI 0.70–0.88], respectively; P = 0.0013}. Conclusions Combining the baseline anti-PLA2Rab titres with their relative changes at 3 months after diagnosis gives the earliest prediction for achieving a reduction of urinary protein excretion ≥50% at 6 months in MN, thereby shortening the observation period currently recommended to make individualized decisions to start immunosuppressive therapy., Graphical Abstract Graphical Abstract

Background Serum levels of soluble urokinase-type plasminogen activator receptor (suPAR) are high in some patients with idiopathic nephrotic syndrome (INS). Given that suPAR constitutes a predictor of vascular disease and has been associated with endothelial dysfunction, we hypothesized that suPAR levels are related to endothelial activation or dysfunction in INS patients. The aims of this study were to evaluate the relationship between serum concentrations of endothelial biomarkers and suPAR in patients with different histological patterns of INS and healthy controls, and to determine the demographic, clinical and biochemical characteristics of INS patients that influence suPAR serum levels. Methods This observational, cross-sectional study included patients with INS, diagnosed with minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS) or membranous nephropathy (MN) by renal biopsy. Patient demographic, clinical and biochemical characteristics were recorded and blood samples were obtained at the time of diagnosis. Measurements of suPAR and endothelial molecules via serum levels were performed using Enzyme-Linked ImmunoSorbent Assay kits. Results Patients with nephrotic syndrome (n = 152) caused by FSGS, MCD or MN had increased circulating levels of endothelial markers. suPAR levels positively correlated with age and the serum levels of almost all endothelial markers. Generally, endothelial cell molecules positively correlated with each other. suPAR levels were not associated with the histopathological pattern of INS. Conclusions In patients with INS secondary to FSGS, MCD and NM, circulating levels of suPAR are independent of the primary renal disease, and significantly associated with age, glomerular filtration rate and the levels of various endothelial markers.

Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER); Red de Investigación Renal (RedInRen); European Renal Association-European Dialysis and Transplant Association (ERA-EDTA); Fundación Renal Iñigo Álvarez de Toledo (FRIAT); Fundación para la Investigación Biomédica Hospital 12 de Octubre (i+12); Centre National de la Recherche Scientifique; Fondation Maladies Rares (LAM-RD_20170304); National Research Agency (ANR, grants MNaims ANR-17-CE17-0012-01); "Investments for the Future" Laboratory of Excellence SIGNALIFE, a network for innovation on signal transduction pathways in life sciences (ANR-11-LABX-0028-01); Initiative of Excellence (IDEX; UCAJedi ANR-15-IDEX-01); Fondation pour la Recherche Médicale (FRM, ING20140129210, DEQ20180339193, FDT201805005509). A cyclical corticosteroid-cyclophosphamide regimen is recommended for patients with primary membranous nephropathy at high risk of progression. We hypothesized that sequential therapy with tacrolimus and rituximab is superior to cyclical alternating treatment with corticosteroids and cyclophosphamide in inducing persistent remission in these patients. This was tested in a randomized, open-label controlled trial of 86 patients with primary membranous nephropathy and persistent nephrotic syndrome after six-months observation and assigned 43 each to receive six-month cyclical treatment with corticosteroid and cyclophosphamide or sequential treatment with tacrolimus (full-dose for six months and tapering for another three months) and rituximab (one gram at month six). The primary outcome was complete or partial remission of nephrotic syndrome at 24 months. This composite outcome occurred in 36 patients (83.7%) in the corticosteroid-cyclophosphamide group and in 25 patients (58.1%) in the tacrolimus-rituximab group (relative risk 1.44; 95% confidence interval 1.08 to 1.92). Complete remission at 24 months occurred in 26 patients (60%) in the corticosteroid-cyclophosphamide group and in 11 patients (26%) in the tacrolimus-rituximab group (2.36; 1.34 to 4.16). Anti-PLA2R titers showed a significant decrease in both groups but the proportion of anti-PLA2R-positive patients who achieved immunological response (depletion of anti-PLA2R antibodies) was significantly higher at three and six months in the corticosteroid-cyclophosphamide group (77% and 92%, respectively), as compared to the tacrolimus-rituximab group (45% and 70%, respectively). Relapses occurred in one patient in the corticosteroid-cyclophosphamide group, and three patients in the tacrolimus-rituximab group. Serious adverse events were similar in both groups. Thus, treatment with corticosteroid-cyclophosphamide induced remission in a significantly greater number of patients with primary membranous nephropathy than tacrolimus-rituximab.

Resumen Objetivo Analizar las asociaciones entre el nivel urinario de IL-6, EGF, MCP-1 y TGFβ1 y las caracteristicas clinicas, bioquimicas y anatomopatologicas en enfermos con nefropatia IgA primaria y determinar su capacidad para realizar una estimacion de la extension de las lesiones de esclerosis glomerular e intersticial. Pacientes y metodos Se estudio a 58 enfermos con nefropatia IgA. Se determinaron los niveles urinarios de IL-6, EGF, MCP-1 y TGFβ1 en el momento del diagnostico. Tras realizar un analisis de la extension de las lesiones renales mediante morfometria cuantitativa y mediante los criterios de Oxford, se analizo la capacidad de dichas moleculas para estimar la extension de las lesiones glomerulares e intersticiales de fibrosis. Resultados La IL-6, MCP-1 y TGF-β1 se asociaron a glomeruloesclerosis focal y a la extension de la fibrosis intersticial, pero no a la presencia de proliferacion mesangial, intracapilar o extracapilar. EGF presento una asociacion negativa con la fibrosis intersticial. Al categorizar a los enfermos segun la clasificacion de Oxford, los enfermos con scores T1 y T2 presentaron niveles significativamente superiores de IL-6, MCP-1 y TGFβ1, y niveles de EGF significativamente inferiores que los enfermos con T0. Tanto mediante regresion multiple como mediante regresion logistica, los niveles de MCP-1, IL-6 y EGF fueron predictores independientes de la superficie de fibrosis, tras ajustar por edad y FGe. Conclusion La determinacion de la concentracion urinaria de IL-6, EGF y MCP-1 proporciona una informacion adicional que mejora de forma significativa la estimacion de la superficie de fibrosis intersticial.

BACKGROUND. Urinary CD80 has emerged as potential biomarker in idiopathic nephrotic syndrome (INS). However, its cellular source remains controversial. The aim of the study was to assess whether CD80 is truly expressed by glomerular cells in INS patients during relapse and in the LPS mouse model of podocyte injury. METHODS. The presence of CD80 in glomeruli was evaluated by combining immunohistochemistry, immunogold labeling and in situ hybridization techniques. RESULTS. CD80 was present along the surface of glomerular endothelial cells (GEC) and rarely in podocytes in six of nine minimal change disease (MCD) patients in relapse, two of eleven patients with focal segmental glomerulosclerosis in relapse and absent in controls. In mice, CD80 was upregulated at mRNA and protein level in GEC and podocytes, in a similar pattern to that seen in MCD patients. CONCLUSION. Glomerular endothelial cells and podocytes can express CD80 in patients with MCD during relapse. A better understanding of the role of CD80 in glomerular cells may provide further insights into the mechanisms of proteinuria in INS.

Objective.To analyze the role that infections play on the antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) outcome.Methods.A retrospective study of adult patients with AAV diagnosed in a tertiary center. Clinical features, laboratory findings, treatment, relapses, major infections, and outcome were evaluated.Results.Included were 132 patients [51 microscopic polyangiitis (MPA), 52 granulomatosis with polyangiitis (GPA), 29 eosinophilic GPA (EGPA)] with a mean followup of 140 (96–228) months. ANCA were positive in 85% of cases. A total of 300 major infections, mainly bacterial (85%), occurred in 60% patients during the followup. Lower respiratory tract (64%) and urinary tract infections (11%) were the most frequent, followed by bacteremia (10%). A total of 7.3% opportunistic infections were observed, most due to systemic mycosis. Up to 46% of all opportunistic infections took place in the first year of diagnosis, and 55% of them under cyclophosphamide (CYC) treatment. Bacterial infections were associated with Birmingham Vasculitis Activity Score (version 3) > 15 at the disease onset, a total cumulative CYC dose > 8.65 g, dialysis, and development of leukopenia during the followup. Leukopenia was the only factor independently related to opportunistic infections. Forty-four patients died, half from infection. Patients who had major infections had an increased mortality from any cause.Conclusion.Our results confirm that major infections are the main cause of death in patients with AAV.

Publisher's version (útgefin grein), Background: This article summarizes the ERA-EDTA Registry's 2016 Annual Report, by describing the epidemiology of renal replacement therapy (RRT) for end-stage renal disease (ESRD) in 2016 within 36 countries. Methods: In 2017 and 2018, the ERA-EDTA Registry received data on patients undergoing RRT for ESRD in 2016 from 52 national or regional renal registries. In all, 32 registries provided individual patient data and 20 provided aggregated data. The incidence and prevalence of RRT and the survival probabilities of these patients were determined. Results: In 2016, the incidence of RRT for ESRD was 121 per million population (pmp), ranging from 29 pmp in Ukraine to 251 pmp in Greece. Almost two-thirds of patients were men, over half were aged ≥65 years and almost a quarter had diabetes mellitus as their primary renal diagnosis. Treatment modality at the start of RRT was haemodialysis for 84% of patients. On 31 December 2016, the prevalence of RRT was 823 pmp, ranging from 188 pmp in Ukraine to 1906 pmp in Portugal. In 2016, the transplant rate was 32 pmp, varying from 3 pmp in Ukraine to 94 pmp in the Spanish region of Catalonia. For patients commencing RRT during 2007-11, the 5-year unadjusted patient survival probability on all RRT modalities combined was 50.5%. For 2016, the incidence and prevalence of RRT were higher among men (187 and 1381 pmp) than women (101 and 827 pmp), and men had a higher rate of kidney transplantation (59 pmp) compared with women (33 pmp). For patients starting dialysis and for patients receiving a kidney transplant during 2007-11, the adjusted patient survival probabilities appeared to be higher for women than for men., The ERA-EDTA Registry is funded by the European Renal Association – European Dialysis and Transplant Association (ERA-EDTA). This article was written by Anneke Kramer et al. on behalf of the ERA-EDTA Registry, which is an official body of the ERA-EDTA. In addition, Dr. Caskey reports funding from the National Health Service during the conduct of the study. Dr. Finne reports personal fees from Baxter, outside the submitted work and Dr. Slon Roblero reports personal fees from NxStage, outside the submitted work.

BackgroundHeight-adjusted total kidney volume (htTKV) is considered as the best predictor of kidney function in patients with autosomal dominant polycystic kidney disease (ADPKD), but its limited predictive capacity stresses the need to find new biomarkers of ADPKD progression. The aim of this study was to investigate urinary biomarkers of ADPKD progression.MethodsThis observational study included ADPKD patients, and two comparator groups of ischaemic and non-ischaemic kidney injury: benign nephroangiosclerosis patients and non-ischaemic chronic kidney disease (CKD) patients. Proteinuria, htTKV and urinary levels of molecules are associated with ischaemia and/or tubular injury. The slope of estimated glomerular filtration rate (eGFR) was used as a dependent variable in univariate and multivariate models of kidney function decline.ResultsThe study included 130 patients with ADPKD, 55 with nephroangiosclerosis and 40 with non-ischaemic CKD. All patients had increased urinary concentrations of biomarkers associated with tubular lesions (liver fatty acid-binding protein, kidney injury molecule-1, β2-microglobulin) and molecules overexpressed under ischaemic conditions [hypoxia-inducible factor-1α, vascular endothelial growth factor (VEGF) and monocyte chemoattractant protein-1 (MCP-1)]. These biomarkers correlated positively with htTKV and negatively with the eGFR slope. htTKV was the single best predictor of the eGFR slope variability in univariate analyses. However, a multivariate model including urinary levels of β2-microglobulin, MCP-1 and VEGF improved the capacity to predict the decline of eGFR in ADPKD patients compared with htTKV alone.ConclusionsThe urinary levels of molecules associated with either renal ischaemia (VEGF and MCP-1) or tubular damage (β2-microglobulin) are associated with renal function deterioration in ADPKD patients, and are, therefore, candidates as biomarkers of ADPKD progression.

ResumenAntecedentesLa información sobre la incidencia de insuficiencia renal aguda (IRA) intrahospitalaria relacionada con medicamentos y las características de los pacientes es escasa.ObjetivoEstimar la incidencia de IRA relacionada con medicamentos en pacientes hospitalizados y comparar sus características con las de los pacientes con IRA relacionada con otras causas.MétodosCohorte prospectiva de pacientes con IRA intrahospitalaria (julio de 2010-julio de 2011). Se recogió información sobre características y antecedentes de los pacientes, factores de riesgo y gravedad de la IRA según la clasificación RIFLE, y medicación durante la hospitalización. El análisis de la imputabilidad de los fármacos y la evaluación de la relación causal se realizó siguiendo los métodos y el algoritmo del Sistema Español de Farmacovigilancia.ResultadosUn total de 194 casos presentaron un episodio de IRA intrahospitalaria. La edad mediana de los pacientes fue de 72 años (RI 20); el 60% eran hombres. La incidencia de IRA intrahospitalaria fue de 9,6 por cada 1.000 ingresos. Un 77,8% de los casos presentaron riesgo o daño renal según la clasificación RIFLE. En 105 (54,1%) casos, la IRA se relacionó con medicamentos; principalmente diuréticos, medicamentos que actúan sobre el sistema renina-angiotensina, inmunosupresores, bloqueadores β-adrenérgicos, bloqueantes de los canales de calcio, medios de contraste y antiinflamatorios no esteroideos. La morbilidad cardiovascular fue mayor y la frecuencia de factores de riesgo de IRA y la mortalidad menores en los pacientes con IRA relacionada con medicamentos.ConclusionesLa mitad de los episodios de IRA intrahospitalaria se relacionaron con medicamentos. Los pacientes con IRA relacionada con medicamentos presentaron más antecedentes patológicos cardiovasculares, pero menos factores de riesgo de IRA y una menor mortalidad.AbstractIntroductionThe information available on the incidence and the characteristics of patients with acute renal failure (ARF) related to drugs is scarce.ObjectivesTo estimate the incidence of drug-related ARF in hospitalised patients and to compare their characteristics with those of patients with ARF due to other causes.Material and methodsWe selected a prospective cohort of patients with ARF during hospital admission (July 2010-July 2011). Information on patients’ demographics, medical antecedents, ARF risk factors, ARF severity according to the RIFLE classification and hospital drug administration was collected. We analysed the relationship of drugs with the ARF episodes using Spanish Pharmacovigilance System methods and algorithm.ResultsA total of 194 cases had an episode of hospital-acquired ARF. The median age of patients was 72 years [IQR 20]; 60% were men. The ARF incidence during hospitalization was 9.6 per 1,000 admissions. According to the RIFLE classification, a risk of kidney damage or kidney injury was present in 77.8% of cases. In 105 (54.1%) cases, ARF was drug-related; the drugs most frequently involved were diuretics, agents acting on the renin-angiotensin system, immunosuppressants, β-blocking agents, calcium channel blockers, contrast media and non-steroid anti-inflammatory drugs. Patients with drug-related ARF had more multi-morbidity, fewer ARF risk factors and lower mortality.ConclusionsHalf of ARF episodes during hospitalisation were drug related. Patients with drug-related ARF had higher cardiovascular morbidity than those with ARF related to other causes, but they had a lower frequency of ARF risk factors and mortality.

IgA nephropathy (IgAN), a frequent cause of chronic kidney disease worldwide, is characterized by mesangial deposition of galactose-deficient IgA1-containing immune complexes. Complement involvement in IgAN pathogenesis is suggested by the glomerular deposition of complement components and the strong protection from IgAN development conferred by the deletion of the CFHR3 and CFHR1 genes ( Δ CFHR3-CFHR1 ). Here we searched for correlations between clinical progression and levels of factor H (FH) and FH-related protein 1 (FHR-1) using well-characterized patient cohorts consisting of 112 patients with IgAN, 46 with non-complement-related autosomal dominant polycystic kidney disease (ADPKD), and 76 control individuals. Patients with either IgAN or ADPKD presented normal FH but abnormally elevated FHR-1 levels and FHR-1/FH ratios compared to control individuals. Highest FHR-1 levels and FHR-1/FH ratios are found in patients with IgAN with disease progression and in patients with ADPKD who have reached chronic kidney disease, suggesting that renal function impairment elevates the FHR-1/FH ratio, which may increase FHR-1/FH competition for activated C3 fragments. Interestingly, Δ CFHR3-CFHR1 homozygotes are protected from IgAN, but not from ADPKD, and we found five IgAN patients with low FH carrying CFH or CFI pathogenic variants. These data support a decreased FH activity in IgAN due to increased FHR-1/FH competition or pathogenic CFH variants. They also suggest that alternative pathway complement activation in patients with IgAN, initially triggered by galactose-deficient IgA1-containing immune complexes, may exacerbate in a vicious circle as renal function deterioration increase FHR-1 levels. Thus, a role of FHR-1 in IgAN pathogenesis is to compete with complement regulation by FH.

Background and objectives The prognostic value of mesangial C4d deposits in IgA nephropathy has been analyzed in patients with reduced GFR but has not been analyzed in those with normal kidney function. The main objective of the study was to analyze the prognostic value of C4d deposits and association with response to treatment in patients with IgA nephropathy and normal GFR. Design, setting, participants, & measurements This retrospective cohort study included 190 patients with idiopathic IgA nephropathy diagnosed by kidney biopsy between 1988 and 2005. The patients had GFR≥80 ml/min per 1.73 m 2 at the time of diagnosis, and they had a paraffin-embedded kidney biopsy with eight glomeruli available. Results In total, 170 (89%) and 20 (11%) patients were >18 and P =0.04). During follow-up, C4d-positive patients showed a higher number of nephritic flares (median [range]: 1.4 [0–5] versus 0.9 [0–2]; P =0.04), had a higher protein-to-creatinine ratio (median [interquartile range]: 1.32 g/g [0.7–1.7] versus 0.89 g/g [0.1–1.3]; P P 2 per year; P =0.04). Furthermore, the presence of mesangial C4d deposits was an independent predictor of long-term kidney survival. Conclusions C4d deposits may be one of the earliest poor prognostic variables available for patients with idiopathic IgA nephropathy and normal kidney function at the time of diagnosis. However, Cd4 deposits alone are not associated with the response to angiotensin blockers or corticosteroid treatment.

Resumen Objetivos 1) Identificar las variables que se asocian con los niveles urinarios de MBL, C4d y C5b-9 en enfermos con nefropatia IgA idiopatica. 2) Analizar si los niveles urinarios de MBL o C4d son utiles para identificar la presencia de depositos mesangiales de C4d/MBL. Pacientes y metodo Se estudio a 96 enfermos con nefropatia IgA primaria. Se registraron las variables demograficas, clinicas y bioquimicas en el momento del diagnostico. Las lesiones renales se cuantificaron mediante la clasificacion de Oxford. En las biopsias, se realizaron tinciones inmunohistoquimicas para MBL, properdina, C4d, y C5b-9. En orina, se determino el nivel de properdina, MBL, C4d y C5b-9. Resultados Los predictores independientes de los niveles de C4d y MBL en orina fueron el deposito mesangial de cada una de ellas y, en menor grado, la proteinuria. Los predictores independientes de los niveles urinarios de C5b-9 fueron los niveles de MBL y properdina, y la proteinuria. La excrecion urinaria de C4d tuvo una sensibilidad del 90% (IC 95%: 58,7-99) y una especificidad del 73% (IC 95%: 54-87) para la deteccion de depositos mesangiales de C4d y el nivel de MBL tuvo una sensibilidad del 83,9% (IC 95%: 62-95) y una especificidad del 81,6% (IC 95%: 65-92) para identificar depositos mesangiales de MBL. Conclusion El principal predictor de la concentracion urinaria de C4d y MBL es la presencia de depositos mesangiales de ellas. La MBL podria contribuir a la activacion del complemento en la luz tubular a traves de la via de las lectinas. Los niveles urinarios de MBL y C4d podrian ser biomarcadores sensibles y especificos para la identificacion de los enfermos que presentan depositos mesangiales de MBL o C4d.

Background: Mycophenolate (MF) is effective as induction and maintenance treatment in patients with lupus nephritis (LN). This study evaluates the efficacy and safety of MF in patients with refractory and relapsing LN. Methods: Data were retrospectively obtained for 85 patients (35 refractory and 50 relapsing) from 11 nephrology departments in Spain. The primary endpoints were the incidence and cumulative number of renal responses and relapses and their relationship with baseline clinical and analytical data. The secondary endpoint was the appearance of side effects. Results: The main clinical and analytical variables were similar both in refractory and relapsing LN. Most of the patients had received cyclophosphamide, and all of them switched to MF. 74 patients (87%) achieved a response (69% partial, 31% complete). Age at starting MF, gender, pathological classification, body mass index, blood pressure, baseline renal function, and proteinuria were not associated with achieving response. After stopping MF, 3 of 19 patients (15.7%) relapsed, all at 6 months of follow-up. No differences were found between clinical and analytical variables and number of relapses. Side effects were unremarkable, except for 1 patient, who died of thrombocytopenia and ovarian hemorrhage. Conclusions: Switching to MF from other immunosuppressive treatments is effective and safe in refractory and relapsing LN.