Systemic sclerosis and microscopic polyangiitis after systemic exposure to silicone

Glomerulonefritis creixent; Implants mamaris de silici; Esclerosi sistèmicaCrescentic glomerulonephritis; Silicon breast implants; Systemic sclerosisGlomerulonefritis creciente; Implantes mamarios de silicio; Esclerosis sistémicaThe 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. Pifarr

Minimal Change Disease Is Associated With Endothelial Glycocalyx Degradation and Endothelial Activation

Endothelial glycocalyx; Glomerular endothelial cell; Minimal change diseaseGlicocàlix endotelial; Cèl·lula endotelial glomerular; Malaltia de canvis mínimsGlicocálix endotelial; Célula endotelial glomerular; Enfermedad de cambios mínimosIntroduction 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

Activation of the acute inflammatory phase response in idiopathic nephrotic syndrome: association with clinicopathological phenotypes and with response to corticosteroids

Glomeruloesclerosis; Inflamación; Síndrome nefróticoGlomerulosclerosis; Inflammation; Nephrotic syndromeGlomeruloesclerosi; Inflamació; Síndrome nefròticaBackground 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

Long-term effectiveness of cinacalcet in non-dialysis patients with chronic kidney disease and seconday hyperparathyroidism

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

Effectiveness of Cinacalcet in Patients with Chronic Kidney Disease and Secondary Hyperparathyroidism Not Receiving Dialysis.

Background Secondary hyperparathyroidism (SHPT) is a common complication in chronic kidney disease (CKD) patients. Cinacalcet could be a therapeutic option although its use is controversial in patients not receiving dialysis. Thus, the aim of this study is to assess the effectiveness and safety of cinacalcet in patients with CKD and SHPT without renal replacement treatment (RRT) and without renal transplantation (RT). Methods A retrospective observational study was conducted. Patients were included if they had collected cinacalcet, under off-label use, during 2010 and 2011. Patients selected were followed from the beginning of cinacalcet therapy for one year of treatment. Results A total of 37 patients were included with CKD stage 3 (38%), 4 (51%) and 5 (11%). Baseline mean PTH value was 400.86 ± 168.60 mg/dl. At 12 months, a 67% of patients achieved at least a 30% reduction in their PTH value (p<0.001; CI 49.7-83.6), and the overall mean reduction of PTH values was 38% (p< 0.001; IC -49.1, -27.5). A 28% of the patients achieved KDOQI PTH goals (p = 0.003, CI 12%-50%). At 12 months, mean serum calcium values decreased by 6% and mean serum phosphorus values increased by 13%. A 19% of patients experienced hypocalcemia episodes while an increase of 24% in hyperphosphatemia episodes was observed. A 25% of patients finished cinacalcet before a year of treatment. Main withdrawal reasons were: gastrointestinal and other discomfort (8%), hypocalcaemia (8%), non-compliance (3%), interactions (3%) and excess of efficacy (3%). Conclusions Cinacalcet was effective in patients with CKD and SHPT not receiving dialysis. Electrolytic imbalances could be managed with administration of vitamin D and analogues or phosphate binders

Development and Validation of a Model to Predict Severe Hospital-Acquired Acute Kidney Injury in Non-Critically Ill Patients

Lesión renal aguda; Registros electrónicos de datos de salud; Adquirido en el hospitalLesió renal aguda; Registres electrònics de dades de salut; Adquirit a l'HospitalAcute kidney injury; Electronic health data records; Hospital-acquiredBackground. 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 European Renal Association - European Dialysis and Transplant Association (ERA-EDTA) Registry Annual Report 2016 : a summary

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.Peer reviewe

Efficacy and Safety of PCSK9 Inhibitors in Hypercholesterolemia Associated With Refractory Nephrotic Syndrome

Inhibidors de PCSK9; Hipercolesterolèmia; Síndrome nefròticaInhibidores de PCSK9; Hipercolesterolemia; Síndrome nefróticoPSCK9 inhibitors; Hypercholesterolemia; Nephrotic syndromeIntroduction 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

Effectiveness of Cinacalcet in Patients with Chronic Kidney Disease and Secondary Hyperparathyroidism Not Receiving Dialysis.

BACKGROUND:Secondary hyperparathyroidism (SHPT) is a common complication in chronic kidney disease (CKD) patients. Cinacalcet could be a therapeutic option although its use is controversial in patients not receiving dialysis. Thus, the aim of this study is to assess the effectiveness and safety of cinacalcet in patients with CKD and SHPT without renal replacement treatment (RRT) and without renal transplantation (RT). METHODS:A retrospective observational study was conducted. Patients were included if they had collected cinacalcet, under off-label use, during 2010 and 2011. Patients selected were followed from the beginning of cinacalcet therapy for one year of treatment. RESULTS:A total of 37 patients were included with CKD stage 3 (38%), 4 (51%) and 5 (11%). Baseline mean PTH value was 400.86 ± 168.60 mg/dl. At 12 months, a 67% of patients achieved at least a 30% reduction in their PTH value (p<0.001; CI 49.7-83.6), and the overall mean reduction of PTH values was 38% (p< 0.001; IC -49.1, -27.5). A 28% of the patients achieved KDOQI PTH goals (p = 0.003, CI 12%-50%). At 12 months, mean serum calcium values decreased by 6% and mean serum phosphorus values increased by 13%. A 19% of patients experienced hypocalcemia episodes while an increase of 24% in hyperphosphatemia episodes was observed. A 25% of patients finished cinacalcet before a year of treatment. Main withdrawal reasons were: gastrointestinal and other discomfort (8%), hypocalcaemia (8%), non-compliance (3%), interactions (3%) and excess of efficacy (3%). CONCLUSIONS:Cinacalcet was effective in patients with CKD and SHPT not receiving dialysis. Electrolytic imbalances could be managed with administration of vitamin D and analogues or phosphate binders

Study of the variables associated with local complement activation in IgA nephropathy

Objectives: 1. To identify the variables that are associated with urinary levels of properdin, MBL, C4d, and C5b-9 in patients with idiopathic IgA nephropathy. 2. To analyse whether urinary levels of MBL and/or C4d are useful for identifying the presence of mesangial deposits of C4d/MBL. Patients and method: A total of 96 patients with IgA nephropathy were studied. Demographic, clinical and biochemical variables were recorded at the time of diagnosis. Renal lesions were quantified using the Oxford classification. Immunohistochemical staining for MBL, MASP-2, properdin, C4d, and C5b-9 was performed in kidney biopsies, and in urine, the levels of properdin, MBL, C4d and C5b-9 were determined. Results: In multivariate analysis, the independent predictors of C4d and MBL levels in urine were the mesangial deposits of each protein and, to a lesser extent, the urinary protein excretion. The independent predictors of urinary levels of C5b-9 were MBL properdin and proteinuria. Urinary excretion of C4d had a sensitivity of 90% (95% CI: 58.7–99) and a specificity of 73% (95% CI: 54–87) for detecting mesangial C4d deposits, and the level of MBL had a sensitivity of 83.9% (95% CI: 62–95) and a specificity of 81.6% (95% CI: 65–92) for identifying mesangial deposits of MBL. Conclusion: The main predictor of urinary concentration of C4d and MBL was the presence of their respective mesangial deposits. Urine MBL may contribute to complement activation in the tubular luz through the lectin pathway. Urinary levels of MBL and C4d could be sensitive and specific biomarkers for the identification of patients with mesangial deposits of MBL and C4d