Racial differences in the relationship between high-normal 25-hydroxy vitamin d and parathyroid hormone levels in early stage chronic kidney disease / Diferenças raciais na relação entre níveis normais-elevados de 25-hidroxivitamina d e hormônio da paratireóide na doença renal crônica em estágio inicial

ABSTRACT Aim: Current guidelines do not address between-person variability in markers of bone and mineral metabolism across subgroups of patients, nor delineate treatment strategies based upon such factors. Methods: A cross sectional study was carried out to analyze data from 20,494 United States Veterans and verify the variability of Vitamin D (25(OH)D) and parathyroid hormone (PTH) levels across race and stage of chronic kidney disease. Results: PTH levels were higher in Black Americans (BA) than White Americans (WA) at all levels of 25(OH)D and across eGFR strata. There was a progressive decline in PTH levels from the lowest (25(OH)D < 20) to highest quartile (25(OH)D >=40) in both BA (134.4 v 90 pg/mL, respectively) and WA (112.5 v 71.62 pg/mL) (p<0.001 for all comparisons). Conclusion: In this analysis, higher than normal 25(OH)D levels were well tolerated and associated with lower parathyroid hormone values in both blacks and whites. Black Americans had higher PTH values at every level of eGFR and 25(OH)D levels suggesting a single PTH target is not appropriate.

RESUMO Objetivo: as diretrizes atuais não abordam a variabilidade entre as pessoas nos marcadores do metabolismo ósseo e mineral em subgrupos de pacientes, nem traçam estratégias de tratamento com base em tais fatores. Métodos: realizamos um estudo transversal para analisar dados de 20.494 veteranos de guerra dos Estados Unidos e verificar a variabilidade nos níveis de vitamina D (25 (OH) D) e hormônio da paratireóide (PTH) entre a raça e o estágio da doença renal crônica. Resultados: os níveis de PTH foram maiores em americanos negros (AN) do que em americanos brancos (AB) em todos os níveis de 25 (OH) D e em todos os estratos de TFGe. Houve um declínio progressivo nos níveis de PTH do quartil mais baixo (25 (OH) D <20) para o quartil mais alto (25 (OH) D> = 40) em AN (134,4 v 90 pg/mL, respectivamente) e AB (112,5 v 71,62 pg/mL) (p <0,001 para todas as comparações). Conclusão: Nesta análise, níveis de 25 (OH) D acima do normal foram bem tolerados e associados a valores mais baixos do hormônio da paratireóide em negros e brancos. Os americanos negros tinham valores de PTH mais altos em todos os níveis de TFGe e 25 (OH) D, sugerindo que uma única meta de PTH não é apropriado.

Racial differences in the relationship between high-normal 25-hydroxy vitamin d and parathyroid hormone levels in early stage chronic kidney disease.

AIM: Current guidelines do not address between-person variability in markers of bone and mineral metabolism across subgroups of patients, nor delineate treatment strategies based upon such factors. METHODS: A cross sectional study was carried out to analyze data from 20,494 United States Veterans and verify the variability of Vitamin D (25(OH)D) and parathyroid hormone (PTH) levels across race and stage of chronic kidney disease. RESULTS: PTH levels were higher in Black Americans (BA) than White Americans (WA) at all levels of 25(OH)D and across eGFR strata. There was a progressive decline in PTH levels from the lowest (25(OH)D < 20) to highest quartile (25(OH)D >=40) in both BA (134.4 v 90 pg/mL, respectively) and WA (112.5 v 71.62 pg/mL) (p<0.001 for all comparisons). CONCLUSION: In this analysis, higher than normal 25(OH)D levels were well tolerated and associated with lower parathyroid hormone values in both blacks and whites. Black Americans had higher PTH values at every level of eGFR and 25(OH)D levels suggesting a single PTH target is not appropriate.

Prevalence of abnormalities in electrocardiogram conduction in dialysis patients: a comparative study / Prevalência de anormalidades de condução no eletrocardiograma de pacientes em diálise: um estudo comparativo

ABSTRACT Background: The electrocardiogram (ECG) can aid in identification of chronic kidney disease (CKD) patients at high risk for cardiovascular diseases. Cohort studies describe ECG abnormalities in patients on hemodialysis (HD), but we did not find data comparing ECG abnormalities among patients with normal kidney function or peritoneal dialysis (PD) to those on hemodialysis. We hypothesized that ECG conduction abnormalities would be more common, and cardiac conduction interval times longer, among patients on hemodialysis vs. those on peritoneal dialysis and CKD 1 or 2. Methods: Retrospective review of adult inpatients' charts, comparing those with billing codes for "Hemodialysis" vs. inpatients without those charges, and an outpatient peritoneal dialysis cohort. Patients with CKD 3 or 4 were excluded. Results: One hundred and sixty-seven charts were reviewed. ECG conduction intervals were consistently and statistically longer among hemodialysis patients (n=88) vs. peritoneal dialysis (n=22) and CKD stage 1 and 2 (n=57): PR (175±35 vs 160±44 vs 157±22 msec) (p=0.009), QRS (115±32 vs. 111±31 vs 91±18 msec) (p=0.001), QT (411±71 vs. 403±46 vs 374±55 msec) (p=0.006), QTc (487±49 vs. 464±38 vs 452±52 msec) (p=0.0001). The only significantly different conduction abnormality was prevalence of left bundle branch block: 13.6% among HD patients, 5% in PD, and 2% in CKD 1 and 2 (p=0.03). Conclusion: To our knowledge, this is the first study to report that ECG conduction intervals are significantly longer as one progresses from CKD Stage 1 and 2, to PD, to HD. These and other data support the need for future research to utilize ECG conduction times to identify dialysis patients who could potentially benefit from proactive cardiac evaluations and risk reduction.

RESUMO Introdução: O eletrocardiograma (ECG) pode auxiliar na identificação de pacientes com doença renal crônica (DRC) e alto risco para doenças cardiovasculares. Estudos de coorte descrevem anormalidades no ECG de pacientes em hemodiálise (HD), mas não encontramos dados comparando anormalidades no ECG entre pacientes com função renal normal ou aqueles em diálise peritoneal (DP), com aqueles em hemodiálise. Nossa hipótese foi de que as anormalidades de condução no ECG seriam mais comuns, e o intervalo de condução cardíaca seria mais longo entre os pacientes em hemodiálise comparados àqueles em diálise peritoneal e DRC 1 ou 2. Métodos: revisão retrospectiva dos prontuários de pacientes adultos internados, comparando aqueles com códigos de cobrança para "Hemodiálise" versus pacientes internados sem esses encargos, e uma coorte de pacientes em diálise peritoneal ambulatorial. Pacientes com DRC 3 ou 4 foram excluídos. Resultados: Cento e sessenta e sete prontuários foram revisados. Os intervalos de condução no ECG foram consistente- e estatisticamente mais longos entre os pacientes em hemodiálise (n = 88) vs. em diálise peritoneal (n = 22) e DRC estágios 1 e 2 (n = 57): PR (175 ± 35 vs 160 ± 44 vs 157 ± 22 msec) (p = 0,009); QRS (115 ± 32 vs. 111 ± 31 vs 91 ± 18 ms) (p = 0,001); QT (411 ± 71 vs. 403 ± 46 vs 374 ± 55 ms) (p = 0,006 ), QTc (487 ± 49 vs. 464 ± 38 vs 452 ± 52 ms) (p = 0,0001). A única anormalidade de condução significativamente diferente foi a prevalência de bloqueio do ramo esquerdo: 13,6% nos pacientes em HD, 5% em DP e 2% na DRC 1 e 2 (p = 0,03). Conclusão: Pelo que sabemos, este é o primeiro estudo a relatar que os intervalos de condução no ECG são significativamente maiores à medida que se progride das DRC Estágios 1 e 2, para DP, e para HD. Esses e outros dados corroboram a necessidade de estudos futuros para utilizar os tempos de condução no ECG para identificar pacientes em diálise que poderiam se beneficiar de avaliações cardíacas proativas e assim redução de risco.

Prevalence of abnormalities in electrocardiogram conduction in dialysis patients: a comparative study.

BACKGROUND: The electrocardiogram (ECG) can aid in identification of chronic kidney disease (CKD) patients at high risk for cardiovascular diseases. Cohort studies describe ECG abnormalities in patients on hemodialysis (HD), but we did not find data comparing ECG abnormalities among patients with normal kidney function or peritoneal dialysis (PD) to those on hemodialysis. We hypothesized that ECG conduction abnormalities would be more common, and cardiac conduction interval times longer, among patients on hemodialysis vs. those on peritoneal dialysis and CKD 1 or 2. METHODS: Retrospective review of adult inpatients' charts, comparing those with billing codes for "Hemodialysis" vs. inpatients without those charges, and an outpatient peritoneal dialysis cohort. Patients with CKD 3 or 4 were excluded. RESULTS: One hundred and sixty-seven charts were reviewed. ECG conduction intervals were consistently and statistically longer among hemodialysis patients (n=88) vs. peritoneal dialysis (n=22) and CKD stage 1 and 2 (n=57): PR (175±35 vs 160±44 vs 157±22 msec) (p=0.009), QRS (115±32 vs. 111±31 vs 91±18 msec) (p=0.001), QT (411±71 vs. 403±46 vs 374±55 msec) (p=0.006), QTc (487±49 vs. 464±38 vs 452±52 msec) (p=0.0001). The only significantly different conduction abnormality was prevalence of left bundle branch block: 13.6% among HD patients, 5% in PD, and 2% in CKD 1 and 2 (p=0.03). CONCLUSION: To our knowledge, this is the first study to report that ECG conduction intervals are significantly longer as one progresses from CKD Stage 1 and 2, to PD, to HD. These and other data support the need for future research to utilize ECG conduction times to identify dialysis patients who could potentially benefit from proactive cardiac evaluations and risk reduction.

ANCA associated vasculitis: experience of a tertiary care referral center / Vasculite associada a ANCA: experiência de um centro de referência de atendimento terciário

ABSTRACT Background and objectives: Anti-neutrophil cytoplasmic autoantibodies (ANCA) associated vasculitis is a small vessel vasculitis with insufficient epidemiologic estimates in the United States. We aimed to determine demographic and clinical features of ANCA associated vasculitis patients presenting to a large tertiary care referral center in Upstate New York. Design, setting, participants, and measurements: A retrospective analysis of cases with pauci-immune GN on renal biopsy and clinical diagnosis of ANCA vasculitis presenting over 11 years was conducted. Outcomes of interest were: demographics, ANCA antibody positivity, patient and renal survival, and regional trends. Results: 986 biopsies were reviewed, 41 cases met the criteria for inclusion: 18 GPA, 19 MPA, and 4 double positive (anti-GBM disease plus ANCA vasculitis). Mean age at presentation was 52.4 years (SD 23.7), 23 (56%) were male and median creatinine was 2.6 mg/dL. The median patient follow up was 77 weeks (IQR 10 - 263 weeks), with a 3-month mortality rate of 5.7% and a 1-year estimated mortality rate of 12%. Thirteen patients required hemodialysis at the time of diagnosis; 7 patients came off dialysis, with median time to renal recovery of 4.86 weeks (IQR 1.57 - 23.85 weeks). C-ANCA positivity (p < 0.001) and C-ANCA plus PR3 antibody pairing (p = 0.005) was statistically significant in GPA versus MPA. P-ANCA positivity was observed in MPA versus GPA (p = 0.02) and double positive versus GPA (p = 0.002), with P-ANCA and MPO antibody pairing in MPA versus GPA (p = 0.044). Thirty-seven of the 41 cases were referred locally, 16 cases were from within a 15-mile radius of Albany, Schenectady, and Saratoga counties. Conclusions: ANCA vasculitis is associated with end stage renal disease and increased mortality. Our study suggests the possibility of higher regional incidence of pauci-immune GN in Upstate New York. Further studies should investigate the causes of clustering of cases to specific regions.

RESUMO Introdução e objetivos: A vasculite associada a anticorpos anticitoplasma de neutrófilo (ANCA) é uma vasculite de pequenos vasos com estimativas epidemiológicas insuficientes nos Estados Unidos. Nosso objetivo foi determinar características demográficas e clínicas de pacientes com vasculite associada à ANCA, apresentando-se a um grande centro de referência de atendimento terciário em Upstate New York. Formato, cenário, participantes e medidas: Foi realizada uma análise retrospectiva dos casos de GN pauci-imune em biópsias renais e diagnóstico clínico de vasculite ANCA por mais de 11 anos. Os resultados de interesse foram: dados demográficos, positividade de anticorpos ANCA, sobrevidas renal e de pacientes e tendências regionais. Resultados: 986 biópsias foram revisadas, 41 casos preencheram os critérios de inclusão: 18 GPA, 19 PAM, e 4 duplo-positivos (doença anti-MBG com vasculite ANCA). A média de idade na apresentação foi de 52,4 anos (DP 23,7), 23 (56%) eram do sexo masculino e mediana de creatinina de 2,6 mg/dL. O acompanhamento mediano dos pacientes foi de 77 semanas (IQR 10 - 263 semanas), com uma taxa de mortalidade de 3 meses de 5,7% e uma taxa de mortalidade estimada em 1 ano de 12%. Treze pacientes necessitaram de hemodiálise no momento do diagnóstico; 7 pacientes saíram da diálise, com tempo médio para recuperação renal de 4,86 semanas (IQR 1,57 - 23,85 semanas). A positividade para C-ANCA (p < 0,001) e o pareamento de anticorpos C-ANCA mais PR3 (p = 0,005) foram estatisticamente significantes em GPA versus PAM. A positividade de P-ANCA foi observada em PAM versus GPA (p = 0,02) e duplo positivo versus GPA (p = 0,002), com pareamento de anticorpos P-ANCA e MPO em PAM versus GPA (p = 0,044). Trinta e sete dos 41 casos foram encaminhados localmente, 16 casos foram de dentro de um raio de 15 milhas dos condados de Albany, Schenectady e Saratoga. Conclusões: A vasculite por ANCA está associada à doença renal terminal e aumento da mortalidade. Nosso estudo sugere a possibilidade de maior incidência regional de GN pauci-imune no norte do estado de Nova York. Novos estudos devem investigar as causas do acúmulo de casos em regiões específicas.

TpTe and TpTe/QT: novel markers to predict sudden cardiac death in ESRD? / TpTe e TpTe/QT: novos marcadores para prever morte súbita cardíaca na DRT?

ABSTRACT Introduction: Reliable markers to predict sudden cardiac death (SCD) in patients with end stage renal disease (ESRD) remain elusive, but echocardiogram (ECG) parameters may help stratify patients. Given their roles as markers for myocardial dispersion especially in high risk populations such as those with Brugada syndrome, we hypothesized that the Tpeak to Tend (TpTe) interval and TpTe/QT are independent risk factors for SCD in ESRD. Methods: Retrospective chart review was conducted on a cohort of patients with ESRD starting hemodialysis. Patients were US veterans who utilized the Veterans Affairs medical centers for health care. Average age of all participants was 66 years and the majority were males, consistent with a US veteran population. ECGs that were performed within 18 months of dialysis initiation were manually evaluated for TpTe and TpTe/QT. The primary outcomes were SCD and all-cause mortality, and these were assessed up to 5 years following dialysis initiation. Results: After exclusion criteria, 205 patients were identified, of whom 94 had a prolonged TpTe, and 61 had a prolonged TpTe/QT interval (not mutually exclusive). Overall mortality was 70.2% at 5 years and SCD was 15.2%. No significant difference was observed in the primary outcomes when examining TpTe (SCD: prolonged 16.0% vs. normal 14.4%, p=0.73; all-cause mortality: prolonged 55.3% vs. normal 47.7%, p=0.43). Likewise, no significant difference was found for TpTe/QT (SCD: prolonged 15.4% vs. normal 15.0%, p=0.51; all-cause mortality: prolonged 80.7% vs. normal 66.7%, p=0.39). Conclusions: In ESRD patients on hemodialysis, prolonged TpTe or TpTe/QT was not associated with a significant increase in SCD or all-cause mortality.

RESUMO Introdução: Marcadores confiáveis para predizer morte súbita cardíaca (MSC) em pacientes com doença renal terminal (DRT) permanecem elusivos, mas os parâmetros do ecocardiograma (ECG) podem ajudar a estratificar os pacientes. Devido a seus papéis como marcadores para a dispersão miocárdica, especialmente em populações de alto risco, como aquelas com síndrome de Brugada, nós hipotetizamos que o intervalo pico da onda T ao final da onda T (TpTe) e TpTe/QT são fatores de risco independentes para MSC na DRT. Métodos: Revisão retrospectiva do prontuário foi realizada em uma coorte de pacientes com DRT iniciando a hemodiálise. Os pacientes eram veteranos de guerra americanos que utilizavam os centros médicos do Veterans Affairs para atendimento médico. A idade média de todos os participantes foi de 66 anos e a maioria era do sexo masculino, consistente com uma população veterana dos EUA. ECGs que foram realizados dentro de 18 meses após o início da diálise, e foram avaliados manualmente para TpTe e TpTe/QT. Os desfechos primários foram MSC e mortalidade por todas as causas, e estes foram avaliados até 5 anos após o início da diálise. Resultados: Após o critério de exclusão, foram identificados 205 pacientes, dos quais 94 com TpTe prolongado e 61 com intervalo TpTe/QT prolongado (não mutuamente exclusivo). A mortalidade geral foi de 70,2% em 5 anos e a MSC foi de 15,2%. Nenhuma diferença significativa foi observada nos desfechos primários ao se avaliar o TpTe (MSC: prolongado 16,0% versus normal 14,4%, p = 0,73; mortalidade por todas as causas: prolongado 55,3% vs. normal 47,7%, p = 0,43). Da mesma forma, nenhuma diferença significativa foi encontrada para TpTe/QT (MSC: prolongado 15,4% vs. normal 15,0%, p = 0,51; mortalidade por todas as causas: prolongado 80,7% vs. normal 66,7%, p = 0,39). Conclusões: Em pacientes com insuficiência renal terminal em hemodiálise, TpTe ou TpTe/QT prolongados não foram associados a um aumento significativo da morte súbita ou mortalidade por todas as causas.

ANCA associated vasculitis: experience of a tertiary care referral center.

BACKGROUND AND OBJECTIVES: Anti-neutrophil cytoplasmic autoantibodies (ANCA) associated vasculitis is a small vessel vasculitis with insufficient epidemiologic estimates in the United States. We aimed to determine demographic and clinical features of ANCA associated vasculitis patients presenting to a large tertiary care referral center in Upstate New York. Design, setting, participants, and measurements: A retrospective analysis of cases with pauci-immune GN on renal biopsy and clinical diagnosis of ANCA vasculitis presenting over 11 years was conducted. Outcomes of interest were: demographics, ANCA antibody positivity, patient and renal survival, and regional trends. RESULTS: 986 biopsies were reviewed, 41 cases met the criteria for inclusion: 18 GPA, 19 MPA, and 4 double positive (anti-GBM disease plus ANCA vasculitis). Mean age at presentation was 52.4 years (SD 23.7), 23 (56%) were male and median creatinine was 2.6 mg/dL. The median patient follow up was 77 weeks (IQR 10 - 263 weeks), with a 3-month mortality rate of 5.7% and a 1-year estimated mortality rate of 12%. Thirteen patients required hemodialysis at the time of diagnosis; 7 patients came off dialysis, with median time to renal recovery of 4.86 weeks (IQR 1.57 - 23.85 weeks). C-ANCA positivity (p < 0.001) and C-ANCA plus PR3 antibody pairing (p = 0.005) was statistically significant in GPA versus MPA. P-ANCA positivity was observed in MPA versus GPA (p = 0.02) and double positive versus GPA (p = 0.002), with P-ANCA and MPO antibody pairing in MPA versus GPA (p = 0.044). Thirty-seven of the 41 cases were referred locally, 16 cases were from within a 15-mile radius of Albany, Schenectady, and Saratoga counties. CONCLUSIONS: ANCA vasculitis is associated with end stage renal disease and increased mortality. Our study suggests the possibility of higher regional incidence of pauci-immune GN in Upstate New York. Further studies should investigate the causes of clustering of cases to specific regions.

TpTe and TpTe/QT: novel markers to predict sudden cardiac death in ESRD?

INTRODUCTION: Reliable markers to predict sudden cardiac death (SCD) in patients with end stage renal disease (ESRD) remain elusive, but electrocardiogram (ECG) parameters may help stratify patients. Given their roles as markers for myocardial dispersion especially in high risk populations such as those with Brugada syndrome, we hypothesized that the Tpeak to Tend (TpTe) interval and TpTe/QT are independent risk factors for SCD in ESRD. METHODS: Retrospective chart review was conducted on a cohort of patients with ESRD starting hemodialysis. Patients were US veterans who utilized the Veterans Affairs medical centers for health care. Average age of all participants was 66 years and the majority were males, consistent with a US veteran population. ECGs that were performed within 18 months of dialysis initiation were manually evaluated for TpTe and TpTe/QT. The primary outcomes were SCD and all-cause mortality, and these were assessed up to 5 years following dialysis initiation. RESULTS: After exclusion criteria, 205 patients were identified, of whom 94 had a prolonged TpTe, and 61 had a prolonged TpTe/QT interval (not mutually exclusive). Overall mortality was 70.2% at 5 years and SCD was 15.2%. No significant difference was observed in the primary outcomes when examining TpTe (SCD: prolonged 16.0% vs. normal 14.4%, p=0.73; all-cause mortality: prolonged 55.3% vs. normal 47.7%, p=0.43). Likewise, no significant difference was found for TpTe/QT (SCD: prolonged 15.4% vs. normal 15.0%, p=0.51; all-cause mortality: prolonged 80.7% vs. normal 66.7%, p=0.39). CONCLUSIONS: In ESRD patients on hemodialysis, prolonged TpTe or TpTe/QT was not associated with a significant increase in SCD or all-cause mortality.

Hydralazine-associated adverse events: a report of two cases of hydralazine-induced ANCA vasculitis / Eventos adversos associados à hidralazina: um relatório de dois casos de vasculite associada ao ANCA induzida por hidralazina

Abstract Hydralazine is a direct-acting vasodilator, which has been used in treatment for hypertension (HTN) since the 1950s. While it is well known to cause drug-induced lupus (DIL), recent reports are indicating the emergence of the drug-induced anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (DIV). Herein, we describe two patients (aged 57 and 87 years) who presented with severe acute kidney injury (AKI), proteinuria, and hematuria. Both were receiving hydralazine for the treatment of hypertension. ANCA serology was positive in both patients along with anti-histone antibodies (commonly seen in drug-induced vasculitis). Renal biopsy revealed classic crescentic (pauci-immune) glomerulonephritis in these patients and hydralazine was discontinued. During the hospital course, the 57-year-old patient required dialysis therapy and was treated with steroids and rituximab for the ANCA disease. Renal function improved and the patient was discharged (off dialysis) with a serum creatinine of 3.6 mg/dL (baseline = 0.9 mg/dL). At a follow-up of 2 years, the patient remained off dialysis with advanced chronic kidney disease (CKD) (stage IIIb). The 87-year-old patient had severe AKI with serum creatinine at 10.41 mg/dL (baseline = 2.27 mg/dL). The patient required hemodialysis and was treated with steroids, rituximab, and plasmapheresis. Unfortunately, the patient developed catheter-induced bacteremia and subsequently died of sepsis. Hydralazine can cause severe AKI resulting in CKD or death. Given this extremely unfavorable adverse-event profile and the widespread availability of alternative anti-hypertensive agents, the use of hydralazine should be carefully considered.

Resumo A hidralazina é um vasodilatador de ação direta, que vem sendo utilizado no tratamento da hipertensão arterial (HA) desde a década de 1950. Embora seja bem conhecido por causar lúpus induzido por drogas (LID), relatórios recentes estão indicando o surgimento da vasculite associada ao anticorpo citoplasmático anti-neutrófilo (ANCA), induzida por drogas (VID). Aqui, descrevemos dois pacientes (com idade entre 57 e 87 anos) que apresentaram lesão renal aguda grave (LRA), proteinúria e hematúria. Ambos estavam usando hidralazina para o tratamento da hipertensão. A sorologia para ANCA foi positiva em ambos os pacientes, juntamente com anticorpos anti-histona (comumente vistos na vasculite induzida por drogas). A biópsia renal revelou glomerulonefrite rapidamente progressiva clássica (pauci-imune) nestes pacientes e a hidralazina foi interrompida. Durante a internação hospitalar, o paciente de 57 anos necessitou de diálise e foi tratado com esteroides e rituximab para a doença do ANCA. A função renal melhorou e o paciente recebeu alta (fora da diálise) com creatinina sérica de 3,6 mg/dL (basal = 0,9 mg/dL). Em um seguimento de 2 anos, o paciente permaneceu fora da diálise com doença renal crônica avançada (DRC) (estágio IIIb). O paciente de 87 anos apresentava IRA grave com creatinina sérica em 10,41 mg/dL (valor basal de = 2,27 mg/dL). O paciente necessitou de hemodiálise e foi tratado com esteroides, rituximabe e plasmaferese. Infelizmente, o paciente desenvolveu bacteremia induzida por cateter e, posteriormente, evoluiu a óbito por sepse. A hidralazina pode causar IRA grave, resultando em DRC ou óbito. Dado este perfil de eventos adversos extremamente desfavorável e a disponibilidade generalizada de agentes anti-hipertensivos alternativos, o uso de hidralazina deve ser considerado com muita parcimônia.

Complement activation in atypical hemolytic uremic syndrome and scleroderma renal crisis: a critical analysis of pathophysiology.

Scleroderma is an autoimmune disease that affects multiple systems. While pathophysiologic mechanisms governing the development of scleroderma are relatively poorly understood, advances in our understanding of the complement system are clarifying the role of complement pathways in the development of atypical hemolytic uremic syndrome and scleroderma renal crisis. The abundant similarities in their presentation as well as the clinical course are raising the possibility of a common underlying pathogenesis. Recent reports are emphasizing that complement pathways appear to be the unifying link. This article reviews the role of complement system in the development of atypical hemolytic uremic syndrome and scleroderma renal crisis, and calls for heightened awareness to the development of thrombotic angiopathy in patients with scleroderma.

Hydralazine-associated adverse events: a report of two cases of hydralazine-induced ANCA vasculitis.

Hydralazine is a direct-acting vasodilator, which has been used in treatment for hypertension (HTN) since the 1950s. While it is well known to cause drug-induced lupus (DIL), recent reports are indicating the emergence of the drug-induced anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (DIV). Herein, we describe two patients (aged 57 and 87 years) who presented with severe acute kidney injury (AKI), proteinuria, and hematuria. Both were receiving hydralazine for the treatment of hypertension. ANCA serology was positive in both patients along with anti-histone antibodies (commonly seen in drug-induced vasculitis). Renal biopsy revealed classic crescentic (pauci-immune) glomerulonephritis in these patients and hydralazine was discontinued. During the hospital course, the 57-year-old patient required dialysis therapy and was treated with steroids and rituximab for the ANCA disease. Renal function improved and the patient was discharged (off dialysis) with a serum creatinine of 3.6 mg/dL (baseline = 0.9 mg/dL). At a follow-up of 2 years, the patient remained off dialysis with advanced chronic kidney disease (CKD) (stage IIIb). The 87-year-old patient had severe AKI with serum creatinine at 10.41 mg/dL (baseline = 2.27 mg/dL). The patient required hemodialysis and was treated with steroids, rituximab, and plasmapheresis. Unfortunately, the patient developed catheter-induced bacteremia and subsequently died of sepsis. Hydralazine can cause severe AKI resulting in CKD or death. Given this extremely unfavorable adverse-event profile and the widespread availability of alternative anti-hypertensive agents, the use of hydralazine should be carefully considered.

Complement activation in atypical hemolytic uremic syndrome and scleroderma renal crisis: a critical analysis of pathophysiology / Ativação de complemento em síndrome urêmica hemolítica atípica e crise renal por esclerodermia: uma análise crítica da fisiopatologia

ABSTRACT Scleroderma is an autoimmune disease that affects multiple systems. While pathophysiologic mechanisms governing the development of scleroderma are relatively poorly understood, advances in our understanding of the complement system are clarifying the role of complement pathways in the development of atypical hemolytic uremic syndrome and scleroderma renal crisis. The abundant similarities in their presentation as well as the clinical course are raising the possibility of a common underlying pathogenesis. Recent reports are emphasizing that complement pathways appear to be the unifying link. This article reviews the role of complement system in the development of atypical hemolytic uremic syndrome and scleroderma renal crisis, and calls for heightened awareness to the development of thrombotic angiopathy in patients with scleroderma.

RESUMO A esclerodermia é uma doença autoimune que afeta múltiplos sistemas. Embora os mecanismos fisiopatológicos que regem o desenvolvimento da esclerodermia sejam relativamente pouco compreendidos, os avanços em nossa compreensão do sistema do complemento estão esclarecendo o papel das vias do complemento no desenvolvimento da síndrome urêmica hemolítica atípica e da crise renal da esclerodermia. As abundantes semelhanças em sua apresentação, bem como o curso clínico, estão aumentando a possibilidade de uma patogênese subjacente comum. Relatórios recentes estão enfatizando que as vias de complemento parecem ser o link unificador. Este artigo analisa o papel do sistema do complemento no desenvolvimento da síndrome urêmica hemolítica atípica e da crise renal na esclerodermia, e exige maior conscientização para com o desenvolvimento da angiopatia trombótica em pacientes com esclerodermia.