Real-life experience with inotersen at CEPARM, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro.

BACKGROUND: Hereditary transthyretin amyloidosis (ATTRv) is an inherited, progressive, and fatal disease still largely underdiagnosed. Mutations in the transthyretin (TTR) gene cause the TTR protein to destabilize, misfold, aggregate, and deposit in body tissues, which makes ATTRv a disease with heterogeneous clinical phenotype. OBJECTIVE: To describe the long-term efficacy and safety of inotersen therapy in patients with ATTRv peripheral neuropathy (ATTRv-PN). METHODS: Patients who completed the NEURO-TTR pivotal study and the NEURO-TTR OLE open-label extension study migrated to the present study and were followed-up for at least 18 more months to an average of 67 months and up to 76 months since day 1 of the inotersen therapy (D1-first dose of inotersen). Disease progression was evaluated by standard measures. RESULTS: Ten ATTRv-PN patients with Val30Met mutation were included. The mean disease duration on D1 was of 3 years, and the mean age of the patients was of 46.8 years. During an additional 18-month follow up, neurological function, based on the Neuropathy Impairment Score and the Polyneuropathy Disability Score, functionality aspects (Karnofsky Performance Status), and nutritional and cardiac aspects were maintained. No new safety signs have been noted. CONCLUSION: The treatment with inotersen was effective and well tolerated for the average of 67 months and up to 76 months. Our results are consistent with those of larger phase-III trials.

ANTECEDENTES: Amiloidose hereditária por transtirretina (ATTRv) é uma doença hereditária, progressiva e fatal ainda largamente subdiagnosticada. Mutações no gene transtirretina (TTR) promovem desestabilização, desdobramento, agregação e depósito da proteína TTR em tecidos do corpo, o que faz da ATTRv uma doença de fenótipo clínico heterogêneo. OBJETIVO: Descrever a eficácia e segurança da terapia com inotersena no longo prazo em pacientes com neuropatia periférica ATTRv (ATTRv-PN). MéTODOS: Pacientes que completaram o estudo pivotal NEURO-TTR e o estudo de extensão aberta NEURO-TTR OLE migraram para este estudo e foram acompanhados por no mínimo 18 meses adicionais, em média por 67 meses, e por até 76 meses, desde o dia 1 da terapia com inotersena (D1­primeira dose de inotersena). A progressão da doença foi avaliada por medidas padronizadas. RESULTADOS: Dez pacientes com ATTRv-PN com mutação Val30Met foram incluídos. A duração média da doença no D1 era de 3 anos, e a média de idade dos pacientes era de 46,8 anos. Durante o período de acompanhamento adicional de 18 meses, a função neurológica, baseada no Neuropathy Impairment Score e no Polyneuropathy Disability Score, os aspectos de funcionalidade (Karnofsky Performance Status), nutricional e cardíacos estavam mantidos. Não se observou nenhum novo sinal de segurança. CONCLUSãO: O tratamento com inotersena foi eficaz e bem tolerado por 67 meses em média, e por até 76 meses. Nossos resultados são consistentes com os de estudos maiores de fase III.

Patellar and quadriceps tendon rupture are associated with hip fracture in hemodialysis patients with severe hyperparathyroidism.

Spontaneous rupture of the patellar (PTR) and quadriceps (QTR) tendon is infrequent. Systemic diseases such as diabetes mellitus, CKD, and secondary hyperparathyroidism (SHPT) are risk factors. The present cohort study aimed to evaluate risk factors associated with tendon rupture in hemodialysis (HD) patients with SHPT, as well as outcomes including surgical complications, re-ruptures, and fracture. Baseline clinical, laboratorial data, and radiographs were analyzed. Patients were followed up from March 2012 to March 2020. One-hundred thirty-one patients (≥18 yr of age, on HD ≥ 6 mo, with SHPT) were included. Incidence rates of PTR and QTR were 2.3 and 1.7/10000 HD patients/yr, respectively. The mean age of patients with tendon rupture was 44.0 ± 11.2 yr. These patients exhibited higher serum levels of phosphorus (6.3 ± 1.5 mg/dL vs 5.6 ± 1.1 mg/dL; P = .005), PTH (2025.7 ± 667.6 pg/mL vs 1728.4 ± 684.8 pg/mL; P = .035), and C-reactive-protein (35.4 ± 32.9 mg/dL vs 17 ± 24.5 mg/dL; P = .002) compared to the group without tendon rupture. The mean follow-up was 56.7 ± 27.1 mo. No patient required a new surgical approach or experienced re-rupture. Of all patients, 31% experienced hip fracture: 50% in the group with rupture (29.5 ± 17.4 mo after the tendon rupture) vs 26% without tendon rupture (P = .015). After adjustment, the hazard ratio for hip fracture was 2.87 (95% CI, 1.27-6.49; P = .012). Patients with SHPT and high levels of phosphorus, PTH, and inflammatory markers were at greater risk for tendon rupture. Surgical complication rates were low. However, results suggest that tendon rupture of knee extensor mechanism in HD patient with SHPT should be regarded as a "red flag" for future hip fracture.

Chronic hypoparathyroidism is associated with increased cortical bone density evaluated using high-resolution peripheral quantitative computed tomography.

PURPOSE: This cross-sectional study aimed to assess bone mineral density (BMD), bone microarchitecture and fracture prevalence in women with chronic postsurgical hypoparathyroidism (hypoPT). METHODS: Twenty-seven women with postsurgical hypoPT and 44 age-matched healthy women were included. Dual-energy X-ray absorptiometry was used to evaluate areal BMD and vertebral fracture assessment. High-resolution peripheral quantitative computed tomography assessed microarchitecture and volumetric BMD at the distal radius and tibia. Biochemical parameters, including fibroblast growth factor 23, C-terminal cross-linking telopeptide of type I collagen (ICTP), and procollagen type I N-terminal propeptide (P1NP), were also measured. Previous low-impact fractures were assessed and the 10-year fracture risk was estimated using the FRAX tool for the Brazilian population. RESULTS: No participant had prevalent clinical fractures, and both groups showed low risk for major and hip based on FRAX tool, but two hypoPT patients had moderate to severe morphometric vertebral fractures. Women with hypoPT had increased aBMD in the lumbar spine, femoral neck and total hip (p < 0.05) and higher cortical vBMD in the radius (p = 0.020) and tibia (p < 0.001). Trabecular bone was not affected. Both P1NP and ICTP suggested low bone turnover rates, but no significant correlation was observed between bone density or microstructure and any of the biochemical parameters. CONCLUSIONS: The prevalence of fragility fractures was low in HypoPT women and compatible with low fracture risk estimated by the FRAX tool. Patients had a higher aBMD and cortical vBMD than those of healthy control women, but the association with decreased bone turnover remains unclear.

Assessment of trabecular and cortical parameters using high-resolution peripheral quantitative computed tomography, histomorphometry and microCT of iliac crest bone core in hemodialysis patients.

Patients with end-stage renal disease develop changes in bone quality and quantity, which can be assessed using different methods. This study aimed to compare and to correlate bone parameters obtained in vivo using high-resolution peripheral quantitative computed tomography (HR-pQCT) with those obtained by bone biopsy using histomorphometry and microcomputed tomography (microCT) analysis of the iliac crest core, and to evaluate if HR-pQCT is helpful in aiding with categorization of those with high turnover. Twenty hemodialysis patients, 13 females (7 postmenopausal), underwent bone biopsy from 2018 to 2020. The mean age was 48.5 ± 10.6 years, and the mean hemodialysis vintage was 15 years. Histomorphometry identified mineralization defects, low turnover, and high turnover in 65%, 45%, and 35% of the patients, respectively. The highest values of trabecular bone volume (BV/TV) were obtained by histomorphometry, while the highest values of cortical thickness (Ct.Th) were obtained by HR-pQCT at the distal tibia. Moderate correlations were found between BV/TV values obtained by microCT of the bone core and HR-pQCT at the distal radius (r = 0.531, p = 0.016) and at the distal tibia (r = 0.536, p = 0.015). BV/TV values obtained from the bone core by histomorphometry and microCT were also significantly correlated (r = 0.475, p = 0.04). Regarding Ct.Th, there was a strong correlation between the radius and tibia HR-pQCT (r = 0.800, p < 0.001), between bone core microCT and the distal radius HR-pQCT (r = 0.610, p < 0.01), as between histomorphometry and microCT (r = 0.899, p < 0.01). In groups classified by bone turnover, patients with high turnover presented lower BV/TV, Tb.N, Tb.Th, and Ct.Th than those with low turnover in peripheral sites using HR-pQCT. By this method, it was possible to identify low turnover from tibia BV/TV > 12,4% plus Tb.Sp ≤ 0.667 mm (AUC 0.810, 95% CI 0.575 to 0.948) and high turnover from total bone mineral density (BMD) ≤ 154.2 mg HA/cm3 (AUC 0.860, 95% CI 0.633 to 0.982, p < 0.001) and cortical BMD ≤ 691.6 mg HA/cm3 (AUC 0.840, 95% CI 0.609 to 0.963, p < 0.001). In conclusion, HR-pQCT had significant correlation with iliac crest bone in BV/TV and Ct.Th, which are known to provide bone strength. This method is quick and non-invasive and may be helpful in categorizing those with high versus low turnover in hemodialysis patients.

High ankle-brachial index predicts cardiovascular events and mortality in hemodialysis patients with severe secondary hyperparathyroidism / Índice tornozelo-braquial elevado prediz eventos e mortalidade cardiovasculares nos pacientes em hemodiálise com hiperparatireoidismo secundário grave

Abstract Introduction: Vascular calcification related to severe secondary hyperparathyroidism (SHPT) is an important cause of cardiovascular and bone complications, leading to high morbidity and mortality in patients with chronic kidney disease (CKD) undergoing hemodialysis (HD). The present study aimed to analyze whether ankle-brachial index (ABI), a non-invasive diagnostic tool, is able to predict cardiovascular outcomes in this population. Methods: We selected 88 adult patients on HD for at least 6 months, with serum iPTH>1,000pg/mL. We collected clinical data, biochemical and hormonal parameters, and ABI (sonar-Doppler). Calcification was assessed by lateral radiography of the abdomen and by simple vascular calcification score (SVCS). This cohort was monitored prospectively between 2012 and 2019 for cardiovascular outcomes (death, myocardial infarction (MI), stroke, and calciphylaxis) to estimate the accuracy of ABI in this setting. Results: The baseline values were: iPTH: 1770±689pg/mL, P: 5.8±1.2 mg/dL, corrected Ca: 9.7±0.8mg/dL, 25(OH)vit D: 25.1±10.9ng/mL. Sixty-five percent of patients had ABI>1.3 (ranging from 0.6 to 3.2); 66% had SVCS≥3, and 45% aortic calcification (Kauppila≥8). The prospective evaluation (51.6±24.0 months), provided the following cardiovascular outcomes: 11% of deaths, 17% of nonfatal MI, one stroke, and 3% of calciphylaxis. After adjustments, patients with ABI≥1.6 had 8.9-fold higher risk of cardiovascular events (p=0.035), and ABI≥1.8 had 12.2-fold higher risk of cardiovascular mortality (p=0.019). Conclusion: The presence of vascular calcifications and arterial stiffness was highly prevalent in our population. We suggest that ABI, a simple and cost-effective diagnostic tool, could be used at an outpatient basis to predict cardiovascular events in patients with severe SHPT undergoing HD.

Resumo Introdução: A calcificação vascular relacionada ao hiperparatireoidismo secundário (HPTS) grave é uma causa importante de complicações cardiovasculares e ósseas, levando a alta morbidade e mortalidade em pacientes com doença renal crônica (DRC) em hemodiálise (HD). O presente estudo objetivou analisar se o índice tornozelo-braquial (ITB), uma ferramenta diagnóstica não invasiva, pode predizer desfechos cardiovasculares nesta população. Métodos: Selecionamos 88 adultos em HD há pelo menos 6 meses, com PTHi sérico>1.000pg/mL. Coletamos dados clínicos, parâmetros bioquímicos e hormonais, e ITB (sonar-Doppler). A calcificação foi avaliada por radiografia lateral do abdome e por escore de calcificação vascular simples (ECVS). Esta coorte foi monitorada prospectivamente entre 2012 e 2019 para desfechos cardiovasculares (óbito, infarto do miocárdio (IM), acidente vascular cerebral e calcifilaxia) para estimar a precisão do ITB neste cenário. Resultados: Os valores basais foram: PTHi: 1770±689pg/mL, P: 5,8±1,2 mg/dL, Ca corrigido: 9,7±0,8mg/dL, 25(OH)vit D: 25,1±10,9ng/Ml; 65% dos pacientes apresentaram ITB>1,3 (variando de 0,6 a 3,2); 66% tiveram ECVS≥3, e 45% calcificação da aorta (Kauppila≥8). A avaliação prospectiva (51,6±24,0 meses) forneceu os seguintes desfechos cardiovasculares: 11% de óbitos, 17% de IM não fatal, um AVC, 3% de calcifilaxia. Após ajustes, pacientes com ITB≥1,6 tiveram risco 8,9 vezes maior de eventos cardiovasculares (p=0,035), e ITB≥1,8 apresentaram risco 12,2 vezes maior de mortalidade cardiovascular (p=0,019). Conclusão: A presença de calcificações vasculares e rigidez arterial foi altamente prevalente em nossa população. Sugerimos o ITB, uma ferramenta diagnóstica simples e econômica, para ser usada em ambulatório para prever eventos cardiovasculares em pacientes com HPTS grave em HD.

High ankle-brachial index predicts cardiovascular events and mortality in hemodialysis patients with severe secondary hyperparathyroidism.

INTRODUCTION: Vascular calcification related to severe secondary hyperparathyroidism (SHPT) is an important cause of cardiovascular and bone complications, leading to high morbidity and mortality in patients with chronic kidney disease (CKD) undergoing hemodialysis (HD). The present study aimed to analyze whether ankle-brachial index (ABI), a non-invasive diagnostic tool, is able to predict cardiovascular outcomes in this population. METHODS: We selected 88 adult patients on HD for at least 6 months, with serum iPTH>1,000pg/mL. We collected clinical data, biochemical and hormonal parameters, and ABI (sonar-Doppler). Calcification was assessed by lateral radiography of the abdomen and by simple vascular calcification score (SVCS). This cohort was monitored prospectively between 2012 and 2019 for cardiovascular outcomes (death, myocardial infarction (MI), stroke, and calciphylaxis) to estimate the accuracy of ABI in this setting. RESULTS: The baseline values were: iPTH: 1770±689pg/mL, P: 5.8±1.2 mg/dL, corrected Ca: 9.7±0.8mg/dL, 25(OH)vit D: 25.1±10.9ng/mL. Sixty-five percent of patients had ABI>1.3 (ranging from 0.6 to 3.2); 66% had SVCS≥3, and 45% aortic calcification (Kauppila≥8). The prospective evaluation (51.6±24.0 months), provided the following cardiovascular outcomes: 11% of deaths, 17% of nonfatal MI, one stroke, and 3% of calciphylaxis. After adjustments, patients with ABI≥1.6 had 8.9-fold higher risk of cardiovascular events (p=0.035), and ABI≥1.8 had 12.2-fold higher risk of cardiovascular mortality (p=0.019). CONCLUSION: The presence of vascular calcifications and arterial stiffness was highly prevalent in our population. We suggest that ABI, a simple and cost-effective diagnostic tool, could be used at an outpatient basis to predict cardiovascular events in patients with severe SHPT undergoing HD.

Beneficial effects of intradialytic cardiopulmonary rehabilitation.

INTRODUCTION: Patients on hemodialysis (HD) present high mortality from cardiovascular complications and high morbidity, including decreasing functional capacity and quality of life. OBJECTIVE: To analyze clinical and laboratory responses of patients in HD to intradialytic cardiopulmonary rehabilitation on an outpatient basis. METHODS: We evaluated 14 patients in a prospective study for 8 months using cardiopulmonary rehabilitation protocol (CRehab) consisted of intradialytic aerobic exercise with a cycle ergometer. We analyzed heart rate (HR), systolic (SBP) and diastolic blood pressure (DBP), peripheral oxygen saturation (SpO2) and modified Borg scale. We evaluated cardiac function by echocardiogram, functional capacity by six minutes walk test (6MWT), and quality of life by SF-36 survey, before and after CRehab. Biochemical data and KT/Vsp were collected form medical records. RESULTS: During CRehab, the results of HR, SBP, DBP, SpO2 and Borg scale showed no significant changes. 6MWT test showed progressive increase in the distance covered (p < 0.001) as well as a reduction in the scale of Borg post-6MWT (p = 0.009). There was no significant change in any biochemical data or in KT/Vsp. There was increase in left ventricular ejection from 65.7 ± 10.2% to 73.6 ± 10.1% (p = 0.028) and in left ventricular diastolic diameter (p = 0.027). According to SF-36 survey, patients showed improvement in three areas: physical role functioning (p = 0.012), bodily pain (p = 0.007) and vitality (p = 0.009). CONCLUSION: The intradialytic CRehab applied in this population was safe and allowed objective improvement of functional capacity and exercise tolerance, subjective improvement in the perception of effort, significant increase in cardiac function and better quality of life in different domains.

Beneficial effects of intradialytic cardiopulmonary rehabilitation / Efeitos benéficos da reabilitação cardiopulmonar intradialítica

Abstract Introduction: Patients on hemodialysis (HD) present high mortality from cardiovascular complications and high morbidity, including decreasing functional capacity and quality of life. Objective: To analyze clinical and laboratory responses of patients in HD to intradialytic cardiopulmonary rehabilitation on an outpatient basis. Methods: We evaluated 14 patients in a prospective study for 8 months using cardiopulmonary rehabilitation protocol (CRehab) consisted of intradialytic aerobic exercise with a cycle ergometer. We analyzed heart rate (HR), systolic (SBP) and diastolic blood pressure (DBP), peripheral oxygen saturation (SpO2) and modified Borg scale. We evaluated cardiac function by echocardiogram, functional capacity by six minutes walk test (6MWT), and quality of life by SF-36 survey, before and after CRehab. Biochemical data and KT/Vsp were collected form medical records. Results: During CRehab, the results of HR, SBP, DBP, SpO2 and Borg scale showed no significant changes. 6MWT test showed progressive increase in the distance covered (p < 0.001) as well as a reduction in the scale of Borg post-6MWT (p = 0.009). There was no significant change in any biochemical data or in KT/Vsp. There was increase in left ventricular ejection from 65.7 ± 10.2% to 73.6 ± 10.1% (p = 0.028) and in left ventricular diastolic diameter (p = 0.027). According to SF-36 survey, patients showed improvement in three areas: physical role functioning (p = 0.012), bodily pain (p = 0.007) and vitality (p = 0.009). Conclusion: The intradialytic CRehab applied in this population was safe and allowed objective improvement of functional capacity and exercise tolerance, subjective improvement in the perception of effort, significant increase in cardiac function and better quality of life in different domains.

Resumo Introdução: Pacientes em hemodiálise (HD) têm alta mortalidade e morbidade por complicações cardiovasculares, inclusive por redução da capacidade funcional e qualidade de vida. Objetivo: Analisar a evolução clínica e laboratorial de pacientes em HD ambulatorial submetidos à reabilitação cardiopulmonar (RCP) intradialítica. Métodos: Avaliamos 14 pacientes em um estudo prospectivo por 8 meses, utilizando protocolo de RCP com exercícios aeróbicos intradialíticos. Analisamos frequência cardíaca (FC), pressão arterial sistólica (PAS) e diastólica (PAD), saturação periférica de oxigênio (SpO2) e escala de Borg modificada em todas as sessões de HD. Avaliamos função cardíaca por ecocardiograma, capacidade funcional (CF) pelo teste de caminhada de seis minutos (TC6M), e qualidade de vida pelo Questionário SF-36, antes e depois da RCP. Dados bioquímicos e de Kt/Vsp foram coletados dos prontuários. Resultados: Durante a RCP, os resultados de FC, PAS, PAD, SpO2 e escala de Borg não mostraram alterações significativas. No TC6M observamos aumento progressivo da distância percorrida (p < 0,001) e redução na escala de Borg pós-TC6M entre D0-D180 (p = 0,009). Não houve alteração significativa nos testes bioquímicos e no KT/Vsp. Houve aumento na fração de ejeção de 65,7 ± 10,2 para 73,6 ± 10,1% (p = 0,028) e no diâmetro diastólico do ventrículo esquerdo (p = 0,027). No questionário SF-36, houve melhora significativa nos domínios: limitação física (p = 0,012), dor (p = 0,007) e vitalidade (p = 0,009). Conclusão: A RCP intradialítica nesta população foi segura e permitiu melhora objetiva da CF e tolerância ao exercício, melhora subjetiva na percepção do esforço, aumento significativo da função cardíaca, bem como melhoria na qualidade de vida em diferentes domínios.

Bone Density Is Directly Associated With Glomerular Filtration and Metabolic Acidosis but Do Not Predict Fragility Fractures in Men With Moderate Chronic Kidney Disease.

Hyperparathyroidism, vitamin D deficiency, increased fibroblast growth factor-23 (FGF-23), and metabolic acidosis promote bone fragility in chronic kidney disease (CKD). Although useful in predicting fracture risk in the general population, the role of dual-energy X-ray absorptiometry (DXA) in CKD remains uncertain. This cross-sectional study included 51 men aged 50-75 yr with moderate CKD. The stage 4 CKD patients had higher levels of parathyroid hormone (p<0.001), FGF-23 (p=0.029), and lowest 25-hydroxyvitamin D (p=0.016), bicarbonate (p<0.001), total femur (p=0.003), and femoral neck (p=0.011) T-scores compared with stage 3 CKD patients. Total femur and femoral neck T-scores were directly correlated with serum bicarbonate (p=0.003, r=0.447 and p=0.005, r=0.427, respectively) and estimated glomerular filtration rate (p=0.024, r=0.325 and p=0.003, r=0.313, respectively) but were not significantly associated with parathyroid hormone, 25-hydroxyvitamin D, or FGF-23. Only 3.9% of the participants had osteoporosis on DXA scan, whereas 31.4% reported a low-impact fracture. Our data point to a pivotal role of metabolic acidosis for bone impairment and to the inadequacy of DXA to evaluate bone fragility in CKD patients.

Osteoporosis management in patient with renal function impairment.

Aging is associated with decreases in bone quality and in glomerular filtration. Consequently, osteoporosis and chronic kidney disease (CKD) are common comorbid conditions in the elderly, and often coexist. Biochemical abnormalities in the homeostasis of calcium and phosphorus begin early in CKD, leading to an increase in fracture risk and cardiovascular complications since early stages of the disease. The ability of DXA (dual energy X-ray absorptiometry) to diagnose osteoporosis and to predict fractures in this population remains unclear. The management of the disease is also controversial: calcium and vitamin D, although recommended, must be prescribed with caution, considering vascular calcification risk and the development of adynamic bone disease. Furthermore, safety and effectiveness of osteoporosis drugs are not established in patients with CKD. Thus, risks and benefits of antiosteoporosis treatment must be considered individually.

Osteoporosis management in patient with renal function impairment / Manejo da osteoporose no paciente com função renal comprometida

Aging is associated with decreases in bone quality and in glomerular filtration. Consequently, osteoporosis and chronic kidney disease (CKD) are common comorbid conditions in the elderly, and often coexist. Biochemical abnormalities in the homeostasis of calcium and phosphorus begin early in CKD, leading to an increase in fracture risk and cardiovascular complications since early stages of the disease. The ability of DXA (dual energy X-ray absorptiometry) to diagnose osteoporosis and to predict fractures in this population remains unclear. The management of the disease is also controversial: calcium and vitamin D, although recommended, must be prescribed with caution, considering vascular calcification risk and the development of adynamic bone disease. Furthermore, safety and effectiveness of osteoporosis drugs are not established in patients with CKD. Thus, risks and benefits of antiosteoporosis treatment must be considered individually.

O envelhecimento associa-se tanto ao declínio da qualidade óssea quanto da filtração glomerular. Consequentemente, osteoporose e doença renal crônica (DRC) são comorbidades frequentes em idosos, e muitas vezes coexistem. Anormalidades bioquímicas na homeostase do cálcio e do fósforo surgem precocemente na DRC, causando aumento do risco de fraturas e de complicações cardiovasculares desde fases precoces da doença. A capacidade da densitometria (DXA) em diagnosticar osteoporose e predizer fraturas nessa população é questionável. O manejo da doença é também controverso; cálcio e vitamina D são recomendados com cautela, devido ao risco de calcificações vasculares e de doença óssea adinâmica. Além disso, a segurança e a eficácia dos medicamentos para osteoporose ainda não estão estabelecidas em pacientes com DRC. Assim, riscos e benefícios do tratamento para osteoporose devem ser considerados individualmente nesses pacientes.

Renal tubular dysfunction in patients with primary Sjögren syndrome.

Primary Sjögren's syndrome (pSS) is an important cause of renal tubular dysfunction in adults, mainly due to acquired type 1 distal renal tubular acidosis (RTA 1) and concentration defects (CD). This cross-sectional study evaluated renal tubular function of patients with pSS, by detecting proximal tubular injury (through measurements of urinary ß2 microglobulin and albumin), RTA 1 (through an acidification protocol using furosemide and fludrocortisone), and CD (through water deprivation test, WDT). A total of 25 patients with pSS were evaluated and despite a preserved renal function (eGFR 92.5 ± 26.3 mL/min/1.73 m(2)), 24% were diagnosed as RTA 1. On the other hand, CD was diagnosed in 28% of the patients who presented worse renal function (eGFR 68.6 ± 27.7 mL/min/1.73 m(2)). Increased ß2 microglobulin was found in 16% of the patients, and all of them had impaired renal function (eGFR 39.5 ± 11.9 mL/min/1.73 m(2)). These data showed a high prevalence of tubular dysfunction, mainly RTA 1 and CD, in patients with pSS, and suggest that patients with this disorder should be evaluated by the acidification protocol used in this study and WDT for proper diagnosis. Proximal tubular injury was less common, and probably associated with worsening of renal function.

Educação à distância em nefrologia na Amazônia: processos e resultados / Distance education in nephrology in the Amazon region: processes and results

A carência de docentes qualificados na Região Amazônica levou à adoção de tecnologias de Educação à Distância para organizar a disciplina de Nefrologia do quarto ano do curso de graduação em Medicina da Faculdade São Lucas (FSL), localizada em Porto Velho (RO). Neste trabalho, descrevemos a construção do curso na plataforma Moodle, usando uma estrutura de módulos para discutir os principais tópicos de Nefrologia em fóruns de discussão assíncronos online com base em problemas clínicos ilustrativos, e mostramos os resultados do curso, que já foi realizado com três turmas de alunos, bem como as avaliações da metodologia, realizadas pelos alunos e pela instituição.

The relative lack of qualified teachers in the Amazon Region led to the adoption of Distance Education technologies in order to implement Nephrology classes in the fourth year of the medical course in São Lucas College (Faculdade de São Lucas), located in Porto Velho, Rondonia. In this paper, we describe the construction of the course on the Moodle platform, using a modular structure to discuss the main topics of Nephrology in online asynchronous forums based on illustrative clinical problems, and we also show the results of the classes, which has already been completed with 3 groups of medical students, and the evaluation of the methodology by the students and by the institution.

Bone disease in patients with chronic kidney disease under conservative management.

CONTEXT AND OBJECTIVE: Few studies have focused on bone disease in patients with chronic kidney disease under conservative treatment. The objective was to evaluate bone disease in patients with chronic kidney disease. DESIGN AND SETTING: Case series, at the Nephrology Division, Hospital Universitário Pedro Ernesto. METHODS: 131 patients with creatinine clearance from 10 to 60 ml/min/1.73 m(2) were followed up for at least one year. Serum creatinine, albumin, calcium, phosphorus, alkaline phosphatase, total CO2 (tCO2), intact parathyroid hormone (iPTH), and alkaline phosphatase were measured. Creatinine clearance was calculated from 24-hour urine creatinine measurements and protein ingestion estimates from urea assays. RESULTS: Patients presenting creatinine clearance < 30 ml/min/1.73 m(2) had higher iPTH values, but normal serum levels for calcium, phosphorus, alkaline phosphatase and tCO2. Patients presenting iPTH values of twice the normal upper limit (144 pg/ml) showed lower tCO2 values. Bone alkaline phosphatase was evaluated in 37 patients with creatinine clearance < 30 ml/min/1.73 m(2), showing correlation with alkaline phosphatase but not with parathyroid hormone. Bone biopsy on nine patients with creatinine clearance < 30 ml/min/1.73 m(2) and iPTH > 144 pg/ml showed osteitis fibrosa (4), mild lesion (4) and high turnover (1). CONCLUSION: The present data suggest the importance of early control for iPTH and metabolic acidosis, among patients under conservative management for chronic kidney disease, in order to prevent complications related to bone disease.

Bone disease in patients with chronic kidney disease under conservative management

CONTEXTO E OBJETIVO: A doença óssea em pacientes com doença renal crônica sob tratamento conservador tem sido pouco estudada. O objetivo do estudo foi avaliar a doença óssea em pacientes com doença renal crônica. TIPO DE ESTUDO E LOCAL: Estudo de casos, na Disciplina de Nefrologia, Hospital Universitário Pedro Ernesto. MÉTODOS: Foram avaliados por pelo menos um ano 131 pacientes com clearance de creatinina variando de 10 a 60 ml/min/1,73 m2. No plasma, foram medidos creatinina, albumina, cálcio, fósforo, fosfatase alcalina, CO2 total (tCO2), hormônio paratiroidiano intacto (iPTH) e fosfatase alcalina. Da urina de 24 horas, foram avaliadas o clearance de creatinina e a ingestão protéica. RESULTADOS: Pacientes com clearance de creatinina < 30 ml/min/1,73 m² apresentaram maior nível de iPTH, apesar de valores normais para.cálcio, fósforo, fosfatase alcalina e tCO2. Pacientes com valores de iPTH duas vezes acima do valor superior da normalidade (144 pg/ml) apresentaram menor valor de tCO2. Fosfatase alcalina óssea foi avaliada em 37 pacientes com clearance de creatinina < 30 ml/min/1,73m², mostrando correlação com a fosfatase alcalina, mas não com o iPTH. Biópsia óssea em nove pacientes com clearance de creatinina < 30 ml/min/1,73m² e iPTH > 144 pg/ml mostrou osteíte fibrosa (4), lesão mínima (4) e alto remodelamento (1). CONCLUSAO: Os resultados apontam para a importância de um controle precoce do iPTH e da acidose metabólica em pacientes sob tratamento conservador para doença renal crônica, no intuito de prevenir as complicações relacionadas com a doença óssea.