Monitoring anti-PLA2R antibody titres to predict the likelihood of spontaneous remission of membranous nephropathy.

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.

Systemic sclerosis and microscopic polyangiitis after systemic exposure to silicone.

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.

Association between urinary biomarkers and disease progression in adults with autosomal dominant polycystic kidney disease.

BACKGROUND: Height-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. METHODS: This 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. RESULTS: The 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, ß2-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 ß2-microglobulin, MCP-1 and VEGF improved the capacity to predict the decline of eGFR in ADPKD patients compared with htTKV alone. CONCLUSIONS: The urinary levels of molecules associated with either renal ischaemia (VEGF and MCP-1) or tubular damage (ß2-microglobulin) are associated with renal function deterioration in ADPKD patients, and are, therefore, candidates as biomarkers of ADPKD progression.

Prevalence and Risk Factors for Major Infections in Patients with Antineutrophil Cytoplasmic Antibody-associated Vasculitis: Influence on the Disease Outcome.

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.

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.

Long-term effectiveness of cinacalcet in non-dialysis patients with chronic kidney disease and secondary 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.

Valor de los niveles urinarios de interleucina 6, factor de crecimiento epidérmico, proteína quimioatractante de monocitos de tipo 1 y factor de crecimiento transformante Beta1 para la predicción de la extensión de las lesiones de fibrosis en biopsias de enfermos con nefropatía IgA / Value of urinary levels of interleukin-6, epidermal growth factor, monocyte chemoattractant protein type1 and transforming growth factor Beta1 in predicting the extent of fibrosis lesions in kidney biopsies of patients with IgA nephropathy

Objetivo: Analizar las asociaciones entre el nivel urinario de IL-6, EGF, MCP-1 y TGFβ1 y las características clínicas, bioquímicas y anatomopatológicas en enfermos con nefropatía IgA primaria y determinar su capacidad para realizar una estimación de la extensión de las lesiones de esclerosis glomerular e intersticial. Pacientes y métodos: Se estudió a 58 enfermos con nefropatía IgA. Se determinaron los niveles urinarios de IL-6, EGF, MCP-1 y TGFβ1 en el momento del diagnóstico. Tras realizar un análisis de la extensión de las lesiones renales mediante morfometría cuantitativa y mediante los criterios de Oxford, se analizó la capacidad de dichas moléculas para estimar la extensión 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 extensión de la fibrosis intersticial, pero no a la presencia de proliferación mesangial, intracapilar o extracapilar. EGF presentó una asociación negativa con la fibrosis intersticial. Al categorizar a los enfermos según la clasificación 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 regresión múltiple como mediante regresión logística, los niveles de MCP-1, IL-6 y EGF fueron predictores independientes de la superficie de fibrosis, tras ajustar por edad y FGe. Conclusión: La determinación de la concentración urinaria de IL-6, EGF y MCP-1 proporciona una información adicional que mejora de forma significativa la estimación de la superficie de fibrosis intersticial (AU)

Objective: To analyse the associations between urinary levels of IL-6 EGF, MCP-1 and TGFβ1 and clinical, biochemical and histopathological characteristics in patients with primary IgA nephropathy and their ability to predict the extent of lesions of glomerular and/or interstitial sclerosis. Patients and methods: A total of 58 patients with IgA nephropathy were studied. We determined the urine levels of IL-6, EGF, MCP-1, and TGFβ1 at the time of diagnosis. The extent of glomerular and interstitial fibrosis was analyzed by quantitative morphometry and kidney biopsies were classified according to the Oxford criteria. We analysed the ability of these molecules to predict the extent of glomerular and interstitial fibrosis lesions. Results: IL-6, TGFβ1 and MCP-1 were associated with focal glomerulosclerosis and interstitial fibrosis extension but not with the presence of mesangial, extracapillary or endocapillary proliferation. EGF showed a negative association with interstitial fibrosis. By categorising patients according to the Oxford classification, patients with T1 and T2 scores had significantly higher levels of IL-6, MCP-1, TGF-β1 and significantly lower levels of EGF than patients with T0 scores. By multiple regression and logistic regression analyses, the levels of MCP-1, IL-6 and EGF were independent predictors of the fibrosis surface, after adjusting for age and eGFR. Conclusion: The urinary concentration of IL-6, EGF and MCP-1 provides additional information that significantly improves the estimation of the surface of interstitial fibrosis in patients with IgA nephropathy (AU)

Value of urinary levels of interleukin-6, epidermal growth factor, monocyte chemoattractant protein type1 and transforming growth factor ß1 in predicting the extent of fibrosis lesions in kidney biopsies of patients with IgA nephropathy. / Valor de los niveles urinarios de interleucina 6, factor de crecimiento epidérmico, proteína quimioatractante de monocitos de tipo 1 y factor de crecimiento transformante ß1 para la predicción de la extensión de las lesiones de fibrosis en biopsias de enfermos con nefropatía IgA.

OBJECTIVE: To analyse the associations between urinary levels of IL-6 EGF, MCP-1 and TGFß1 and clinical, biochemical and histopathological characteristics in patients with primary IgA nephropathy and their ability to predict the extent of lesions of glomerular and/or interstitial sclerosis. PATIENTS AND METHODS: A total of 58 patients with IgA nephropathy were studied. We determined the urine levels of IL-6, EGF, MCP-1, and TGFß1 at the time of diagnosis. The extent of glomerular and interstitial fibrosis was analyzed by quantitative morphometry and kidney biopsies were classified according to the Oxford criteria. We analysed the ability of these molecules to predict the extent of glomerular and interstitial fibrosis lesions. RESULTS: IL-6, TGFß1 and MCP-1 were associated with focal glomerulosclerosis and interstitial fibrosis extension but not with the presence of mesangial, extracapillary or endocapillary proliferation. EGF showed a negative association with interstitial fibrosis. By categorising patients according to the Oxford classification, patients with T1 and T2 scores had significantly higher levels of IL-6, MCP-1, TGF-ß1 and significantly lower levels of EGF than patients with T0 scores. By multiple regression and logistic regression analyses, the levels of MCP-1, IL-6 and EGF were independent predictors of the fibrosis surface, after adjusting for age and eGFR. CONCLUSION: The urinary concentration of IL-6, EGF and MCP-1 provides additional information that significantly improves the estimation of the surface of interstitial fibrosis in patients with IgA nephropathy.

Estudio de las variables asociadas a la activación local del complemento en la nefropatía IgA idiopática / Study of the variables associated with local complement activation in IgA nephropathy

Objetivos: 1) Identificar las variables que se asocian con los niveles urinarios de MBL, C4d y C5b-9 en enfermos con nefropatía IgA idiopática. 2) Analizar si los niveles urinarios de MBL o C4d son útiles para identificar la presencia de depósitos mesangiales de C4d/MBL. Pacientes y método: Se estudió a 96 enfermos con nefropatía IgA primaria. Se registraron las variables demográficas, clínicas y bioquímicas en el momento del diagnóstico. Las lesiones renales se cuantificaron mediante la clasificación de Oxford. En las biopsias, se realizaron tinciones inmunohistoquímicas para MBL, properdina, C4d, y C5b-9. En orina, se determinó el nivel de properdina, MBL, C4d y C5b-9. Resultados: Los predictores independientes de los niveles de C4d y MBL en orina fueron el depósito 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 excreción urinaria de C4d tuvo una sensibilidad del 90% (IC 95%: 58,7-99) y una especificidad del 73% (IC 95%: 54-87) para la detección de depósitos 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 depósitos mesangiales de MBL. Conclusión: El principal predictor de la concentración urinaria de C4d y MBL es la presencia de depósitos mesangiales de ellas. La MBL podría contribuir a la activación del complemento en la luz tubular a través de la vía de las lectinas. Los niveles urinarios de MBL y C4d podrían ser biomarcadores sensibles y específicos para la identificación de los enfermos que presentan depósitos mesangiales de MBL o C4d (AU)

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 to 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 (AU)

Study of the variables associated with local complement activation in IgA nephropathy. / Estudio de las variables asociadas a la activación local del complemento en la nefropatía IgA idiopática.

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 to 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.

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.

Insuficiencia renal aguda relacionada con medicamentos en pacientes hospitalizados / Drug-related acute renal failure in hospitalised patients

Antecedentes: La información sobre la incidencia de insuficiencia renal aguda (IRA) intrahospitalaria relacionada con medicamentos y las características de los pacientes es escasa. Objetivo: Estimar 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. Métodos: Cohorte 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. Resultados: Un 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. Conclusiones: La 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 (AU)

Introduction: The information available on the incidence and the characteristics of patients with acute renal failure (ARF) related to drugs is scarce. Objectives: To 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 methods: We 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. Results: A 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. Conclusions: Half 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 (AU)

Drug-related acute renal failure in hospitalised patients.

INTRODUCTION: The information available on the incidence and the characteristics of patients with acute renal failure (ARF) related to drugs is scarce. OBJECTIVES: To 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 METHODS: We 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. RESULTS: A 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, ß-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. CONCLUSIONS: Half 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.

Características clínicas, evolución y pronóstico de la nefropatía membranosa idiopática en función de la presencia de anticuerpos contra el receptor tipo M de la fosfolipasa A2 / Clinical features, course and prognosis of idiopathic membranous nephropathy depending on the presence of antibodies against M-type phospholipase A2 receptor

En la nefropatía membranosa (NM), la presencia de anticuerpos antirreceptor tipo M de fosfolipasa A2 se considera altamente específica para las formas idiopáticas, pero no se ha demostrado que la presencia de dichos anticuerpos se asocie a un determinado perfil clínico. Objetivo: Analizar si existe alguna diferencia en cuanto al perfil clínico inicial, evolución y pronóstico entre pacientes con NM idiopática en función de la presencia de anticuerpos anti-PLA2R. Métodos: Se estudió a 85 enfermos conNMidiopática, 55 eran anti-PLA2R positivos y 30 negativos. Se registraron las variables clínicas, bioquímicas y anatomopatológicas al momento del diagnóstico, la frecuencia de remisión espontánea, la incidencia de respuesta al tratamiento de primera línea, la frecuencia y número de recidivas, la supervivencia de la función renal libre de tratamiento sustitutivo renal, la supervivencia de la función renal libre de insuficiencia renal crónica y la frecuencia de aparición de enfermedades neoplásicas, infecciosas o autoinmunes durante el seguimiento. Resultados: Al momento del diagnóstico, los enfermos anti-PLA2R negativos presentaron significativamente mayor edad y frecuencia de remisión espontánea. No se apreciaron diferencias en la respuesta al tratamiento de primera línea, frecuencia ni número de recidivas, supervivencia de la función renal libre de tratamiento sustitutivo renal ni supervivencia de función renal libre de insuficiencia renal crónica. Conclusiones: Los enfermos conNMidiopática anti-PLA2R negativos presentaronmayor edad, menor filtrado glomerular inicial y mayor frecuencia de remisión espontánea que los enfermos anti-PLA2R positivos. Sin embargo, entre ambos grupos de enfermos, no se observaron diferencias en cuanto a la respuesta y al tratamiento, aparición de recidivas ni pronóstico final (AU)

In membranous nephropathy, the presence of antibodies against M-type phospholipase A2 receptor is considered highly specific for idiopathic forms. However, no specific association to a particular clinical profile has been found for such antibodies. Objective: To assess potential differences in initial clinical profile, course and prognosis of idiopathic membranous nephropathy depending on the presence of anti-PLA2R antibodies. Methods: Eighty-five patients with idiopathic membranous nephropathy were included (55 anti-PLA2R-positive and 30 anti-PLA2R-negative). Clinical, biochemical and pathological variables were recorded at the time of diagnosis. Frequency of spontaneous remission, incidence of response to first-line therapy, frequency and number of recurrences, survival of renal function free from renal replacement therapy, survival of renal function free from chronic renal insufficiency and frequency of occurrence of malignant, infectious or autoimmune diseases during follow-up were recorded. Results: At the time of diagnosis, anti-PLA2R-negative patients were significantly older and had a higher frequency of spontaneous remission. No differences were noted in the response to first-line treatment, frequency and number of recurrences, survival of renal function free from renal replacement therapy, or survival of renal function free from chronic renal insufficiency. Conclusions: Anti-PLA2R-negative patients with idiopathic membranous nephropathy were older and experienced spontaneous remission more often than anti-PLA2R-positive patients. No differences in terms of treatment response, recurrences, and final prognosis were observed between both groups of patients (AU)

Clinical features, course and prognosis of idiopathic membranous nephropathy depending on the presence of antibodies against M-type phospholipase A2 receptor.

UNLABELLED: In membranous nephropathy, the presence of antibodies against M-type phospholipase A2 receptor is considered highly specific for idiopathic forms. However, no specific association to a particular clinical profile has been found for such antibodies. OBJECTIVE: To assess potential differences in initial clinical profile, course and prognosis of idiopathic membranous nephropathy depending on the presence of anti-PLA2R antibodies. METHODS: Eighty-five patients with idiopathic membranous nephropathy were included (55 anti-PLA2R-positive and 30 anti-PLA2R-negative). Clinical, biochemical and pathological variables were recorded at the time of diagnosis. Frequency of spontaneous remission, incidence of response to first-line therapy, frequency and number of recurrences, survival of renal function free from renal replacement therapy, survival of renal function free from chronic renal insufficiency and frequency of occurrence of malignant, infectious or autoimmune diseases during follow-up were recorded. RESULTS: At the time of diagnosis, anti-PLA2R-negative patients were significantly older and had a higher frequency of spontaneous remission. No differences were noted in the response to first-line treatment, frequency and number of recurrences, survival of renal function free from renal replacement therapy, or survival of renal function free from chronic renal insufficiency. CONCLUSIONS: Anti-PLA2R-negative patients with idiopathic membranous nephropathy were older and experienced spontaneous remission more often than anti-PLA2R-positive patients. No differences in terms of treatment response, recurrences, and final prognosis were observed between both groups of patients.

Evolución del título de anticuerpos contra el receptor tipo M de la fosfolipasa A2 y respuesta clínica en pacientes con nefropatía membranosa idiopática tratados con tacrolimus / Evolution of antibody titre against the M-type phospholipase A2 receptor and clinical response in idiopathic membranous nephropathy patients treated with tacrolimus

Introducción y objetivos: Se ha descrito que el nivel de anticuerpos circulantes contra el receptor tipo M de la fosfolipasa A2 tiene correlación significativa con la actividad clínica de la enfermedad en la nefropatía membranosa idiopática (NMI). Sin embargo, la utilidad de la monitorización del título de anticuerpos como predictor de respuesta clínica tras el inicio del tratamiento no ha sido formalmente analizada. En el siguiente estudio se analiza el valor predictivo de la evolución del título de anticuerpos anti-PLA2R sobre la respuesta clínica en enfermos con NMI tratados con tacrolimus. Pacientes y métodos: 36 enfermos con síndrome nefrótico secundario a NMI, con criterios de indicación de tratamiento inmunosupresor, fueron tratados con tacrolimus en monoterapia. Se determinó el nivel de anticuerpos anti-PLA2R antes del tratamiento y a los 3, 6, 9 y 12 meses tras su inicio. Se analizó el valor predictivo de la pendiente de reducción en el título de anticuerpos y de la reducción absoluta y relativa en el título de anticuerpos a los 3 y 6 meses sobre el tiempo hasta la remisión y sobre la probabilidad de remisión a los 6, 9 y 12 meses. Resultados: La reducción relativa en el título de anticuerpos anti-PLA2R fue significativamente mayor en los enfermos que presentaron remisión y precedió a la respuesta clínica. No se apreció asociación entre el título de anticuerpos previo al tratamiento con el tiempo medio de respuesta o la respuesta a los 12 meses. La pendiente de reducción en el título de anticuerpos se asoció significativamente con el tiempo hasta la evidencia de remisión. La reducción relativa en el título de anticuerpos anti-PLA2R a los 3 meses tuvo una elevada sensibilidad y especificidad para predecir la respuesta a los 6 y 9 meses, pero no a los 12 meses, mientras que la reducción relativa en el título de anticuerpos a los 6 meses tuvo una elevada sensibilidad y especificidad para predecir la respuesta a los 12 meses. Conclusión: En enfermos con NMI asociada a anticuerpos anti-PLA2R, la monitorización del título de anticuerpos tras el inicio del tratamiento es útil para estimar el período de tiempo hasta la remisión y para predecir la probabilidad de remisión a los 12 meses (AU)

Introduction and objectives: The level of circulating antibodies against M-type phospolipase A2 receptor has been reported as having a significant correlation with clinical activity in idiopathic membranous nephropathy. However, the usefulness of monitoring antibody titre as a predictor of clinical response following the onset of treatment has not been formally analysed. The predictive value of the evolution of anti-PLA2R antibody titre on the clinical response of idiopathic membranous nephropathy patients treated with tacrolimus is analysed in the following study. Patients and method: 36 patients with nephrotic syndrome secondary to idiopathic membranous nephropathy with immunosuppressive treatment indication criteria were treated with tacrolimus in monotherapy. The level of anti-PLA2R antibodies was determined before treatment and at 3, 6, 9 and 12 months after the onset of treatment. The study analysed the predictive value of the reduction in antibody titre and the relative and absolute reduction in antibody titre at 3 and 6 months over the period until remission and on the probability of remission at 6, 9 and 12 months. Results: The relative reduction in the anti-PLA2R antibody titre was significantly greater in those patients with remission and it preceded the clinical response. No association was observed between the antibody titre prior to treatment and the mean response time or the response at 12 months. Reduction in antibody titre is significantly associated with the time until signs of remission. Relative reduction in anti-PLA2R antibody titre at 3 months had a high sensitivity and specificity to predict the response at 6 and 9 months, but not at 12 months; however the relative reduction in the antibody titre at 6 months had a high sensitivity and specificity for predicting the response at 12 months. Conclusion: In patients with IMN associated with anti-PLA2R antibodies, the monitoring of antibody titre following the onset of treatment is useful for estimating the time period until remission and predicting the probability of remission at 12 months (AU)

Evolution of antibody titre against the M-type phospholipase A2 receptor and clinical response in idiopathic membranous nephropathy patients treated with tacrolimus.

INTRODUCTION AND OBJECTIVES: The level of circulating antibodies against M-type phospolipase A2 receptor has been reported as having a significant correlation with clinical activity in idiopathic membranous nephropathy. However, the usefulness of monitoring antibody titre as a predictor of clinical response following the onset of treatment has not been formally analysed. The predictive value of the evolution of anti-PLA2R antibody titre on the clinical response of idiopathic membranous nephropathy patients treated with tacrolimus is analysed in the following study. PATIENTS AND METHOD: 36 patients with nephrotic syndrome secondary to idiopathic membranous nephropathy with immunosuppressive treatment indication criteria were treated with tacrolimus in monotherapy. The level of anti-PLA2R antibodies was determined before treatment and at 3, 6, 9 and 12 months after the onset of treatment. The study analysed the predictive value of the reduction in antibody titre and the relative and absolute reduction in antibody titre at 3 and 6 months over the period until remission and on the probability of remission at 6, 9 and 12 months. RESULTS: The relative reduction in the anti-PLA2R antibody titre was significantly greater in those patients with remission and it preceded the clinical response. No association was observed between the antibody titre prior to treatment and the mean response time or the response at 12 months. Reduction in antibody titre is significantly associated with the time until signs of remission. Relative reduction in anti-PLA2R antibody titre at 3 months had a high sensitivity and specificity to predict the response at 6 and 9 months, but not at 12 months; however the relative reduction in the antibody titre at 6 months had a high sensitivity and specificity for predicting the response at 12 months. CONCLUSION: In patients with IMN associated with anti-PLA2R antibodies, the monitoring of antibody titre following the onset of treatment is useful for estimating the time period until remission and predicting the probability of remission at 12 months.

[Clinical features and prognosis of patients with scleroderma renal crisis]. / Características clínicas y pronóstico de los pacientes con crisis renal esclerodérmica.

BACKGROUND AND OBJECTIVE: Scleroderma renal crisis is a severe complication of systemic sclerosis, which causes arterial hypertension and acute renal failure. Early treatment of these patients with ACE inhibitors may improve prognosis. We aimed to analyze the frequency, clinical and epidemiological characteristics, morbidity and mortality and prognosis of scleroderma renal crisis. PATIENTS AND METHODS: Retrospective study of a cohort of 328 patients with SSc, of whom 194 had the limited form, 64 the diffuse form, 49 the sine scleroderma and 21 preescleroderma. We considered different subtypes of disease: limited (188), diffuse (63), scleroderma sine scleroderma (46) and preescleroderma (21). The data were obtained from a review of medical records. The differences in the prevalence of variables were analyzed by the Fisher's test. RESULTS: A renal crisis was observed in 14 patients (4.26%), 3 men and 11 women, 64% had the diffuse form of the disease, 28% had the limited form, and 7.69% had the scleroderma sine scleroderma. The average time was 48 months. All received ACE inhibitors. The mortality was 85% (18 months) and 85% required dialysis. CONCLUSIONS: Renal crisis is a rare manifestation of scleroderma which mainly affects patients with diffuse involvement of the disease in the early stages. These patients have a poor prognosis despite treatment with ACE inhibitors.