Different kidney function trajectory patterns before dialysis in elderly patients: clinical implications and outcomes.

Background. Identifying trajectories of kidney disease progression in chronic kidney disease (CKD) patients may help to deliver better care. We aimed to identify and characterize trajectories of renal function decline in CKD patients and to investigate their association with mortality after dialysis.Methods. This retrospective cohort study included 378 CKD patients who initiated dialysis (aged 65 years and over) between 2009 and 2016. Were considered mixed models using linear quadratic and cubic models to define the trajectories, and we used probabilistic clustering procedures. Patient characteristics and care practices at and before dialysis were examined by multivariable multinomial logistic regression. The association of these trajectories with mortality after dialysis was examined using Cox models.Results. Four distinct groups of eGFR trajectories decline before dialysis were identified: slower decline (18.3%), gradual decline (18.3%), early rapid decline (41.2%), and rapid decline (22.2%). Patients with rapid eGFR decline were more likely to have diabetes, more cognitive impairment, to have been hospitalized before dialysis, and were less likely to have received pre-dialysis care compared to the patients with a slower decline. They had a higher risk of death within the first and fourth year after dialysis initiation, and after being more than 4 years in dialysis.Conclusions. There are different patterns of eGFR trajectories before dialysis initiation in the elderly, that may help to identify those who are more likely to experience an accelerated decline in kidney function, with impact on pre ESKD care and in the mortality risk after dialysis.

Association between severe chronic kidney disease defined by cystatin-c and creatinine and clinical outcomes in an elderly population - an observational study / Associação entre doença renal crônica grave definida por cistatina-c e creatinina e desfechos clínicos em uma população idosa - um estudo observacional

ABSTRACT Introduction: Estimated glomerular filtration rate (eGFR) based on serum cystatin-C (sCys) seems as accurate as when based on serum creatinine (sCr), but sCys seems a better predictor of adverse outcomes. We aimed to study whether sCys could be a reliable tool for the prediction of adverse outcomes in elderly patients with severe chronic kidney disease (CKD). Methods: A group of 348 elderly patients with non-end-stage CKD (stages 1-4, according to eGFR-EPI sCr and/or sCys), referred to our consultation unit during 2016, was retrospectively studied and divided into four exclusive categories: CKD_stage4_neither (eGFR-sCr≥30mL/min; eGFR-sCys≥30mL/min), CKD_stage4_sCr_only (eGFR-sCr<30mL/min), CKD_stage4_sCys_only (eGFR-sCys<30mL/min) and CKD_stage4_combined (eGFRsCr<30mL/min; eGFR-sCys<30mL/min). Baseline characteristics, predictors of death, and clinical events (cardiovascular events and admissions for cardiovascular, acute kidney injury or infectious events) were explored until December 2018. Results: A 77±7.4 year-old cohort, with a modified Charlson Comorbidty Index (mCCI) of 3 (IQR:1-4), was followed-up during 29 (IQR: 26-33) months. There were no significant differences between the characteristics of the stage 4 groups. Survival analysis was stratified by follow-up at 12 months, and in the first year, survival curves of CKD_stage4_sCys_only and CKD_stage4_combined groups were significantly lower than the other groups (p=0.028). Adjusting for age, sex, and mCCI, CKD_stage4_sCys_only, conversely to CKD_stage4_sCr_only, had higher rates of clinical events (p<0.05) than CKD_stage4_neither group. Conclusion: In elderly patients with discordant CKD staging, sCys-based eGFR seems to be a better predictor of adverse outcomes than sCr-based eGFR. Patients with stage 4 CKD defined by sCr alone seem to behave similar to those with less severe CKD.

RESUMO Introdução: A taxa estimada de filtração glomerular (TFGe) com base na cistatina-C sérica (Cis-C) parece ser tão precisa quanto aquela baseada na creatinina sérica (Cr), mas cis-C parece ser um melhor preditor de resultados adversos. Nosso objetivo foi avaliar se a cis-C poderia ser uma ferramenta confiável para a previsão de desfechos adversos em pacientes idosos com doença renal crônica grave (DRC). Métodos: Um grupo de 348 pacientes idosos com DRC em estágio não terminal (estágios 1-4, de acordo com TFGe-EPI Cr e/ou Cis-C), encaminhados para nossa unidade de consulta durante 2016, foi estudado retrospectivamente e dividido em quatro categorias exclusivas: DRC_estágio 4 nenhum (TFGe-Cr≥30mL/min; TFGe -Cis-C≥30mL/min), DRC_estágio 4_Cr apenas (TFGe-Cr <30mL/min), DRC_estágio 4 _Cis-C_apenas (TFGe-Cis-C <30 mL/min), DRC_estágio4_combinado (TFGe-Cis-C <30mL/min. TFGe-Cr <30mL/min). Características basais, preditores de óbito e eventos clínicos (eventos cardiovasculares e internações por doenças cardiovasculares, lesão renal aguda ou eventos infecciosos) foram explorados até dezembro de 2018. Resultados: Uma coorte de 77 ± 7,4 anos, com índice de comorbidade de Charlson modificado (mCCI) de 3 (IQR: 1-4), foi acompanhada durante 29 (IQR: 26-33) meses. Não houve diferenças significativas entre as características dos grupos no estágio 4. A análise de sobrevida foi estratificada pelo acompanhamento aos 12 meses, sendo que no primeiro ano, as curvas de sobrevida dos grupos DRC_estágio4_Cis-C_apenas e DRC_estágio4_ combinado foram significativamente inferiores quando comparadas com os restantes grupos (p = 0,028). Ajustando para idade, sexo e mCCI, DRC_estágio4_Cis-C_apenas, ao contrário do grupo DRC_estágio4_Cr_apenas, teve maiores taxas de eventos clínicos (p <0,05) do que o grupo DRC_estágio4_nenhum. Conclusão: Em pacientes idosos com estadiamento discordante da DRC, a TFGe baseada na Cis-C parece ser um melhor preditor de resultados adversos do que a TFGe baseada na Cr. Pacientes com DRC em estágio 4, definida apenas por Cr, parecem se comportar de forma semelhante àqueles com DRC menos grave.

Granulomatosis with Polyangiitis: Recurrence or Treatment Consequences?

Granulomatosis with polyangiitis (GPA) is the most common antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). We describe the case of a 38-year-old woman with relapsing GPA who presented with intracranial hypertension, followed by the appearance of cavitated lung nodules despite treatment with azathioprine. Clinical improvement and ANCA titre reduction were observed after rituximab treatment. We report a rare form of GPA relapse and highlight the challenge of following-up patients with GPA, in whom can be hard to distinguish relapse from the consequences of long-term immunosuppression. LEARNING POINTS: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a rare inflammatory disease with pauci-immune focal necrotising lesions that affect small and medium vessels. It has a wide clinical presentation, affecting mainly the upper and lower respiratory tract and kidneys.Granulomatosis with polyangiitis (GPA) is frequently associated with PR3-ANCA and is risk factor for relapse.Follow-up of ANCA titres, which may rise before the development of symptoms, is crucial for recurrence diagnosis. Titres can also be used to distinguish recurrence from the consequences of long-term immunosuppression.

Association between severe chronic kidney disease defined by cystatin-c and creatinine and clinical outcomes in an elderly population - an observational study.

INTRODUCTION: Estimated glomerular filtration rate (eGFR) based on serum cystatin-C (sCys) seems as accurate as when based on serum creatinine (sCr), but sCys seems a better predictor of adverse outcomes. We aimed to study whether sCys could be a reliable tool for the prediction of adverse outcomes in elderly patients with severe chronic kidney disease (CKD). METHODS: A group of 348 elderly patients with non-end-stage CKD (stages 1-4, according to eGFR-EPI sCr and/or sCys), referred to our consultation unit during 2016, was retrospectively studied and divided into four exclusive categories: CKD_stage4_neither (eGFR-sCr≥30mL/min; eGFR-sCys≥30mL/min), CKD_stage4_sCr_only (eGFR-sCr<30mL/min), CKD_stage4_sCys_only (eGFR-sCys<30mL/min) and CKD_stage4_combined (eGFRsCr<30mL/min; eGFR-sCys<30mL/min). Baseline characteristics, predictors of death, and clinical events (cardiovascular events and admissions for cardiovascular, acute kidney injury or infectious events) were explored until December 2018. RESULTS: A 77±7.4 year-old cohort, with a modified Charlson Comorbidty Index (mCCI) of 3 (IQR:1-4), was followed-up during 29 (IQR: 26-33) months. There were no significant differences between the characteristics of the stage 4 groups. Survival analysis was stratified by follow-up at 12 months, and in the first year, survival curves of CKD_stage4_sCys_only and CKD_stage4_combined groups were significantly lower than the other groups (p=0.028). Adjusting for age, sex, and mCCI, CKD_stage4_sCys_only, conversely to CKD_stage4_sCr_only, had higher rates of clinical events (p<0.05) than CKD_stage4_neither group. CONCLUSION: In elderly patients with discordant CKD staging, sCys-based eGFR seems to be a better predictor of adverse outcomes than sCr-based eGFR. Patients with stage 4 CKD defined by sCr alone seem to behave similar to those with less severe CKD.

Predicting 6-Month Mortality in Incident Elderly Dialysis Patients: A Simple Prognostic Score.

AIM: Mortality in end-stage renal disease (ESRD) remains high, particularly among elderly, who represents the most rapidly growing segment of the ESRD population in wealthier countries. We developed and validated a risk score in elderly patients to predict 6-month mortality after dialysis initiation. METHODS: We used data from a cohort of 421 patients, aged 65 years and over who started dialysis between 2009 and 2016, in our Nephrology department. The predictive score was developed using a multivariable logistic regression analysis. A bootstrapping technique was used for internal validation. RESULTS: The overall mortality within 6 months was 14.0%. Five independent predictors were identified, and a points system was constructed: age 75 years or older (2 points), coronary artery disease (2), cerebrovascular disease with hemiplegia (2), time of nephrology care before dialysis (<3.0 months [2]; ≥3 to <12 months [1]), and serum albumin levels (3.0-3.49 g/dL [1]; <3.0 g/dL [2]). A score of 6 identified patients with a 70% risk of 6-month mortality. Model performance was good in both discrimination (area under the curve of 0.793; [95% CI 0.73-0.86]) and validation (concordance statistics of 0.791 [95% CI 0.73-0.85]). CONCLUSIONS: We developed a simple prediction score based on readily available clinical and laboratory data that can be a practical and useful tool to assess short-term prognosis in elderly patients starting dialysis. It may help to inform patients and their families about ESRD treatment options and provide a more patient-centered overall approach to care.

End-stage renal disease versus death in a Portuguese cohort of elderly patients: an approach using competing event analysis.

Chronic kidney disease (CKD) is higher in elderly, but mortality outweighs the risk of end-stage renal disease (ESRD). Our aim was to identify prognostic markers for ESRD or death in elderly CKD, within a competing-risk analysis. This is a longitudinal study of consecutive newly referred patients with CKD ages 65 years, followed until the time of the first event (ESRD or death), using a competing-risk analysis. A modified Charlson Comorbidity Index (mCCI) was subdivided into subgroups (0-2, 3-4, ≥5). Patients were followed for hospitalizations that occurred prior to the outcomes. Among 416 patients, age 76±8 years, 52% male, median estimated glomerular filtration rate of 32 mL/min per 1.73 m2, 50% had diabetes, and 67% cardiovascular disease. Over a median follow-up of 3.6 years, 36 patients progressed to ESRD (8.7%) and 103 died (24.8%). Older age (subdistribution HR (sHR)=1. 06; p<0.001), creatinine≥1.6 mg/dL (sHR=2.03, p=0.004), hemoglobin <11 g/dL (sHR=1.91, p=0.003), mCCI score≥5 (sHR=3.01, p<0.001) and having one or more hospitalizations (sHR=1.73, p<0.001) were associated with death before ESRD. The independent predictors for ESRD with competing risk of death were: lower age (sHR=0.94; p=0.009), creatinine≥1.6 mg/dL (sHR=3.26, p=0.006), hemoglobin <11 g/dL (sHR=2.15, p=0.027), peripheral vascular disease (sHR=3.45, p=0.001) and having one or more hospitalizations (sHR=1.56, p=0.031). Elderly referred patients with CKD are near threefold more likely to die than progress to ESRD. A competing-risk framework based on available clinical and laboratory data may discriminate between those outcomes and could be used as a decision-making tool.

Unrecognized Fibrinogen A α-Chain Amyloidosis: Results From Targeted Genetic Testing.

BACKGROUND: Fibrinogen A α-chain (AFib) amyloidosis results from autosomal-dominant mutations in the gene encoding AFib (FGA). Patients with this disorder typically present with proteinuria. Isolated cases of AFib amyloidosis, carrying the FGA p.Glu545Val variant, were identified in the district of Braga, in northwest Portugal. This observation led us to hypothesize that this disorder might be an unrecognized cause of kidney disease in that region and prompted us to carry out targeted genetic testing for the p.Glu545Val variant in the local hemodialysis population and family members of identified cases. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: 3 groups of participants: (1) kidney biopsy registry, n=4; (2) hemodialysis facility, n=122 of 267 patients; and (3) genetically at-risk individuals; n=69 of 167 family members. OUTCOMES: Kidney disease, kidney disease progression, and survival. RESULTS: The p.Glu545Val variant was identified in all 4 patients of the biopsy registry, 12 of 122 (9.8%) hemodialysis patients tested, and 34 of 69 (49%) relatives tested. These 50 cases belonged to 13 unrelated families with kidney disease or amyloidosis identified in 61% of probands. 35 individuals presented with hypertension at a mean of 51.0±10.4 years. Of these, 30 developed kidney disease at a mean of 56.7±12.0 years, and 21 initiated dialysis therapy at a mean of 61.4±11.3 years. Heart, liver, spleen, colon, and ileum were involved along the progression of the disease. Kidney disease was formerly attributed to hypertension in 25% of patients with AFib amyloidosis undergoing hemodialysis. LIMITATIONS: Retrospective data collection for patients with amyloidosis previously diagnosed. CONCLUSIONS: AFib amyloidosis appears to be an under-recognized disorder in Braga, Portugal, where we found a high frequency of the FGA p.Glu545Val variant. Due to the nonspecific nature of its major clinical features, the diagnosis of AFib amyloidosis should have a high index of suspicion, particularly in populations in which hypertension is prevalent.

Monoclonal gammopathy of renal significance: Diagnostic workup.

The clinical spectrum of diseases associated with monoclonal gammopathies is wide and they are most commonly the consequence of renal deposition of monoclonal immunoglobulin or its components. The differential diagnosis is difficult and renal biopsy is essential. To distinguish many of these pathologies is necessary to use techniques that are not always available, even in tertiary central hospitals. This review will discuss the clinical presentation, pathologic features, treatment, prognosis and common diagnostic difficulties of these entities.

Incorporating Scoring Risk Models for Care Planning of the Elderly with Chronic Kidney Disease.

Mortality in chronic kidney disease remains high, particularly among the elderly, who represent the most rapidly growing segment of the end-stage renal disease population in wealthier countries. The management of older adults with chronic kidney disease has become a clinical challenge, and care for those patients expected to progress to end-stage renal disease should focus on evaluating the overall benefit of offering renal replacement therapy to them. Predictive mortality models may help to inform shared decision-making in the trajectory of the elderly with chronic kidney disease. This review discusses current literature on the available predictive models for predicting survival in elderly chronic kidney disease patients and reflects the author's own interpretation and experience.

ANCA-positive vasculitis: Clinical implications of ANCA types and titers / Vasculite ANCA positiva: implicações clínicas dos tipos e dos títulos de ANCA

SUMMARY Introduction: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is an autoimmune disease that can affect multiple organs, the kidney being one of the most affected. Apart from the diagnostics value of ANCA, they have also been advocated as biomarkers of the disease activity. Recently, the genetic changes found in polyangiitis associated with serine-protease proteinase 3 (PR3)-ANCA or myeloperoxidase (MPO)-ANCA raised the possibility of immune-pathogenic and therapeutic differences. Objective: To identify differences in the number of relapses, inflammatory markers, outcomes and renal histology related to the types of ANCA. To analyze the implications of ANCA titers in prognosis. Method: A retrospective observational study in a Portuguese tertiary hospital. Results: There were no differences in the progression of renal function, histological pattern and initial treatment with regard to ANCA subtypes. As for the evaluated parameters, there were no significant differences according to the types of ANCA, except for mean CRP values within the normal range, which was 6.3±1.3 mg/L for MPO-ANCA and 12.4±10.14 mg/L for PR3-ANCA (p=0.04). We found that 66.7% of the MPO-ANCA-positive showed no relapses versus 40% in the case of PR3-ANCA-positive. There was no correlation between the ANCA titers at presentation, during remission, and in the last evaluation, and the number of relapses. Conclusion: PR3-ANCA patients have a mean CRP value within the normal range significantly higher than that of MPO-ANCA patients (p=0.04), which seems to reveal greater inflammatory activity in the first.

RESUMO Introdução: a vasculite associada aos anticorpos anticitoplasma de neutrófilos (ANCA) é uma doença autoimune que pode acometer vários órgãos, sendo o rim um dos mais afetados. Além dos ANCA serem marcadores de diagnóstico, foram também defendidos como marcadores de atividade. Recentemente as alterações genéticas encontradas entre as poliangeítes serina-protease 3 da proteinase (PR3)-ANCA ou mieloperoxidase (MPO)-ANCA levantam a possibilidade de diferenças imunopatogênicas e terapêuticas. Objetivos: identificar diferenças quanto a número de recidivas, marcadores inflamatórios, desfechos e histologia renal relativamente aos tipos de ANCA. Analisar implicações dos títulos de ANCA no prognóstico. Método: estudo retrospectivo observacional em hospital terciário português. Resultados: não se verificaram diferenças quanto à evolução da função renal, ao padrão histológico e ao tratamento inicial relativamente aos subtipos de ANCA. Nos parâmetros analíticos avaliados, não se verificaram diferenças significativas relativas aos tipos de ANCA, à exceção do valor médio de PCR no intervalo que foi de 6,3±1,3 mg/L nos MPO-ANCA e 12,4±10,14 mg/L nos PR3-ANCA (p=0,04). Verificamos que 66,7% dos MPO-ANCA positivos não apresentaram recidivas versus 40% dos PR3-ANCA positivos. Não se verificou nenhuma correlação entre os títulos de ANCA à apresentação, durante a remissão e na última avaliação com o número de recidivas. Conclusão: os indivíduos PR3-ANCA apresentaram um valor médio de PCR nos intervalos superior aos indivíduos MPO-ANCA (p=0,04), o que parece evidenciar uma maior atividade inflamatória nos primeiros.

ANCA-positive vasculitis: Clinical implications of ANCA types and titers.

INTRODUCTION: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is an autoimmune disease that can affect multiple organs, the kidney being one of the most affected. Apart from the diagnostics value of ANCA, they have also been advocated as biomarkers of the disease activity. Recently, the genetic changes found in polyangiitis associated with serine-protease proteinase 3 (PR3)-ANCA or myeloperoxidase (MPO)-ANCA raised the possibility of immune-pathogenic and therapeutic differences. OBJECTIVE: To identify differences in the number of relapses, inflammatory markers, outcomes and renal histology related to the types of ANCA. To analyze the implications of ANCA titers in prognosis. METHOD: A retrospective observational study in a Portuguese tertiary hospital. RESULTS: There were no differences in the progression of renal function, histological pattern and initial treatment with regard to ANCA subtypes. As for the evaluated parameters, there were no significant differences according to the types of ANCA, except for mean CRP values within the normal range, which was 6.3±1.3 mg/L for MPO-ANCA and 12.4±10.14 mg/L for PR3-ANCA (p=0.04). We found that 66.7% of the MPO-ANCA-positive showed no relapses versus 40% in the case of PR3-ANCA-positive. There was no correlation between the ANCA titers at presentation, during remission, and in the last evaluation, and the number of relapses. CONCLUSION: PR3-ANCA patients have a mean CRP value within the normal range significantly higher than that of MPO-ANCA patients (p=0.04), which seems to reveal greater inflammatory activity in the first.