Renal osteodystrophy and clinical outcomes: a prospective cohort study / Osteodistrofia renal e desfechos clínicos: um estudo de coorte prospectivo

Abstract Introduction: Renal osteodystrophy (ROD) refers to a group of bone morphological patterns that derive from distinct pathophysiological mechanisms. Whether the ROD subtypes influence long-term outcomes is unknown. Our objective was to explore the relationship between ROD and clinical outcomes. Methods: This study is a subanalysis of the Brazilian Registry of Bone Biopsies (REBRABO). Samples from individual patients were classified as having osteitis fibrosa (OF), mixed uremic osteodystrophy (MUO), adynamic bone disease (ABD), osteomalacia (OM), normal/minor alterations, and according to turnover/mineralization/volume (TMV) system. Patients were followed for 3.4 yrs. Clinical outcomes were: bone fractures, hospitalization, major adverse cardiovascular events (MACE), and death. Results: We enrolled 275 participants, of which 248 (90%) were on dialysis. At follow-up, 28 bone fractures, 97 hospitalizations, 44 MACE, and 70 deaths were recorded. ROD subtypes were not related to outcomes. Conclusion: The incidence of clinical outcomes did not differ between the types of ROD.

Resumo Introdução: Osteodistrofia renal (OR) refere-se a um grupo de padrões morfológicos ósseos que decorrem de mecanismos fisiopatológicos distintos. É desconhecido se os subtipos de OR influenciam desfechos em longo prazo. Nosso objetivo foi explorar as relações entre OR e desfechos. Métodos: Este estudo é uma subanálise do Registro Brasileiro de Biópsias Ósseas (REBRABO). As amostras de cada paciente foram classificadas em osteíte fibrosa (OF), osteodistrofia urêmica mista (MUO), doença óssea adinâmica (ABD), osteomalácia (OM), alterações normais/menores, e pelo sistema Remodelação / Mineralização / Volume (RMV). Os pacientes foram acompanhados por 3,4 anos. Os eventos clínicos foram: fraturas ósseas, hospitalizações, eventos cardiovasculares adversos maiores (MACE), e óbito. Resultados: Analisamos 275 indivíduos, 248 (90%) deles estavam em diálise. No acompanhamento, 28 fraturas ósseas, 97 hospitalizações, 44 MACE e 70 óbitos foram registrados. Os subtipos de OR não foram relacionados aos desfechos clínicos. Conclusão: A incidência de desfechos clínicos não diferiu entre os tipos de OR.

Renal osteodystrophy and clinical outcomes: a prospective cohort study.

INTRODUCTION: Renal osteodystrophy (ROD) refers to a group of bone morphological patterns that derive from distinct pathophysiological mechanisms. Whether the ROD subtypes influence long-term outcomes is unknown. Our objective was to explore the relationship between ROD and clinical outcomes. METHODS: This study is a subanalysis of the Brazilian Registry of Bone Biopsies (REBRABO). Samples from individual patients were classified as having osteitis fibrosa (OF), mixed uremic osteodystrophy (MUO), adynamic bone disease (ABD), osteomalacia (OM), normal/minor alterations, and according to turnover/mineralization/volume (TMV) system. Patients were followed for 3.4 yrs. Clinical outcomes were: bone fractures, hospitalization, major adverse cardiovascular events (MACE), and death. RESULTS: We enrolled 275 participants, of which 248 (90%) were on dialysis. At follow-up, 28 bone fractures, 97 hospitalizations, 44 MACE, and 70 deaths were recorded. ROD subtypes were not related to outcomes. CONCLUSION: The incidence of clinical outcomes did not differ between the types of ROD.

Overview of renal osteodystrophy in Brazil: a cross-sectional study / Visão geral da osteodistrofia renal no Brasil: um estudo transversal

Abstract Introduction: The epidemiologic profile of renal osteodystrophy (ROD) is changing over time and cross-sectional studies provide essential information to improve care and health policies. The Brazilian Registry of Bone Biopsy (REBRABO) is a prospective, nationalmulticenter cohort that includes patients with chronic kidney disease (CKD) undergoing bone biopsy. REBRABO aims to provide clinical information on ROD. The main objective of this subanalysis was to describe the profile of ROD, including clinically relevant associations. Methods: From Aug/2015 to Dec/2021, 511 patients with CKD who performed bone biopsy were included in the REBRABO platform. Patients with no bone biopsy report (N = 40), GFR > 90 mL/min (N = 28), without asigned consent (N = 24), bone fragments inadequate for diagnosis (N = 23), bone biopsy indicated by a specialty other than nephrology (N = 6), and < 18 years old (N = 4) were excluded. Clinical-demographic data (e.g., age, sex, ethnicity, CKD etiology, dialysis vintage, comorbidities, symptoms, and complications related to ROD), laboratory (e.g., serum levels of total calcium, phosphate, parathormone, alkaline phosphatase, 25-hydroxyvitamin D, and hemoglobin), and ROD (e.g., histological diagnosis) were analyzed. Results: Data from 386 individuals were considered in this subanalysis of REBRABO. Mean age was 52 (42-60) years; 198 (51%) were male; 315 (82%) were on hemodialysis. Osteitis fibrosa (OF) [163 (42%)], adynamic bone disease (ABD) [96 (25%)] and mixed uremic osteodystrophy (MUO) [83 (21%)] were the most frequent diagnosis of ROD in our sample; 203 (54%) had the diagnosis of osteoporosis, 82 (56%) vascular calcification; 138 (36%) bone aluminum accumulation, and 137 (36%) iron intoxication; patients with high turnover were prone to present a higher frequency of symptoms. Conclusions: A high proportion of patients were diagnosed with OF and ABD, as well as osteoporosis, vascular calcification and clinical symptoms.

Resumo Introdução: O perfil epidemiológico da osteodistrofia renal (OR) está mudando com o tempo e estudos transversais fornecem informações essenciais para melhorar cuidados e políticas de saúde. O Registro Brasileiro de Biópsia Óssea (REBRABO) é uma coorte nacional multicêntrica prospectiva que inclui pacientes com doença renal crônica (DRC) submetidos à biópsia óssea. O REBRABO visa fornecer informações clínicas sobre OR. O principal objetivo desta subanálise foi descrever o perfil da OR, incluindo associações clinicamente relevantes. Métodos: De Ago/2015 a Dez/2021, 511 pacientes com DRC que realizaram biópsia óssea foram incluídos na plataforma REBRABO. Excluíram-se os pacientes sem laudo de biópsia óssea (N = 40), TFG > 90 mL/min (N = 28), sem consentimento assinado (N = 24), fragmentos ósseos inadequados para diagnóstico (N = 23), biópsia óssea indicada por especialidade que não a nefrologia (N = 6), e < 18 anos de idade (N = 4). Foram analisados dados clínico-demográficos (por exemplo, idade, sexo, etnia, etiologia da DRC, tempo da diálise, comorbidades, sintomas e complicações relacionadas à OR), laboratoriais (níveis séricos de cálcio total, fosfato, paratormônio, fosfatase alcalina, 25-hidroxivitamina D e hemoglobina), e OR (diagnóstico histológico). Resultados: Dados de 386 indivíduos foram considerados nesta subanálise do REBRABO. A idade média foi 52 (42-60) anos; 198 (51%) eram homens; 315 (82%) estavam em hemodiálise. Osteíte fibrosa (OF) [163 (42%)], doença óssea adinâmica (DOA) [96 (25%)] e osteodistrofia urêmica mista (OUM) [83 (21%)] foram os diagnósticos mais frequentes de OR na amostra; 203 (54%) apresentaram diagnóstico de osteoporose, 82 (56%) calcificação vascular; 138 (36%) acúmulo ósseo de alumínio, e 137 (36%) intoxicação por ferro; pacientes com remodelação óssea aumentada eram propensos a apresentar maior frequencia de sintomas. Conclusões: Uma alta proporção de pacientes foi diagnosticada com OF e DOA, assim como osteoporose, calcificação vascular e sintomas clínicos.

Overview of renal osteodystrophy in Brazil: a cross-sectional study.

INTRODUCTION: The epidemiologic profile of renal osteodystrophy (ROD) is changing over time and cross-sectional studies provide essential information to improve care and health policies. The Brazilian Registry of Bone Biopsy (REBRABO) is a prospective, nationalmulticenter cohort that includes patients with chronic kidney disease (CKD) undergoing bone biopsy. REBRABO aims to provide clinical information on ROD. The main objective of this subanalysis was to describe the profile of ROD, including clinically relevant associations. METHODS: From Aug/2015 to Dec/2021, 511 patients with CKD who performed bone biopsy were included in the REBRABO platform. Patients with no bone biopsy report (N = 40), GFR > 90 mL/min (N = 28), without asigned consent (N = 24), bone fragments inadequate for diagnosis (N = 23), bone biopsy indicated by a specialty other than nephrology (N = 6), and < 18 years old (N = 4) were excluded. Clinical-demographic data (e.g., age, sex, ethnicity, CKD etiology, dialysis vintage, comorbidities, symptoms, and complications related to ROD), laboratory (e.g., serum levels of total calcium, phosphate, parathormone, alkaline phosphatase, 25-hydroxyvitamin D, and hemoglobin), and ROD (e.g., histological diagnosis) were analyzed. RESULTS: Data from 386 individuals were considered in this subanalysis of REBRABO. Mean age was 52 (42-60) years; 198 (51%) were male; 315 (82%) were on hemodialysis. Osteitis fibrosa (OF) [163 (42%)], adynamic bone disease (ABD) [96 (25%)] and mixed uremic osteodystrophy (MUO) [83 (21%)] were the most frequent diagnosis of ROD in our sample; 203 (54%) had the diagnosis of osteoporosis, 82 (56%) vascular calcification; 138 (36%) bone aluminum accumulation, and 137 (36%) iron intoxication; patients with high turnover were prone to present a higher frequency of symptoms. CONCLUSIONS: A high proportion of patients were diagnosed with OF and ABD, as well as osteoporosis, vascular calcification and clinical symptoms.

AGEs accumulation is related to muscle degeneration and vascular calcification in peritoneal dialysis patients.

BACKGROUND: Patients with chronic kidney disease (CKD) are affected by dynapenia, sarcopenia, and vascular calcification. Advanced glycation end products (AGEs) may accumulate in peritoneal dialysis (PD) patients and favor sarcopenia via changes in collagen cross-linking, muscle protein breakdown, and the calcification of arterial smooth muscle cells via p38-MAPK activation. The aim of this study is to explore the relationships between AGEs, muscle degeneration, and coronary artery calcification. METHODS: This was a clinical observational study in patients with CKD undergoing PD, in which serum and skin AGEs (AGEs-sAF), cumulative glucose load, muscle strength and functional tests, muscle ultrasounds with elastography, coronary artery calcium (CAC) quantification, and muscle density by multislice computed tomography were measured. RESULTS: 27 patients aged 48±16 years, dialysis vintage of 27±17 months, had AGEs-sAF levels of 3.09±0.65 AU (elevated in 13 [87%] patients), grip strength levels of 26.2±9.2 kg (11 [42%] patients with dynapenia), gait speed of 1.04±0.3 m/s (abnormal in 14 [58%] patients) and "timed-up-and-go test" (TUG) of 10.5±2.2s (abnormal in 7 [26%] patients). Correlations between AGEs-sAF levels and femoral rectus elastography (R=-0.74; p=0.02), anterior-tibialis elastography (R= -0.68; p=0.04) and CAC (R=0.64; p=0.04) were detected. Cumulative glucose load correlated with femoral rectal elastography (R=-0.6; p=0.02), and serum glycated hemoglobin concentrations correlated with psoas muscle density (R= -0.58; p=0.04) and CAC correlated with psoas muscle density (R=0.57; p=0.01) and lumbar square muscle density (R=-0.63; p=0.005). CONCLUSIONS: The study revealed associations between AGEs accumulation and lower muscle stiffness/density. Associations that linked muscle degeneration parameters with vascular calcification were observed.

Renal osteodystrophy and clinical outcomes: data from the Brazilian Registry of Bone Biopsies - REBRABO.

INTRODUCTION: Mineral and bone disorders (MBD) are major complications of chronic kidney disease (CKD)-related adverse outcomes. The Brazilian Registry of Bone Biopsy (REBRABO) is an electronic database that includes renal osteodystrophy (RO) data. We aimed to describe the epidemiological profile of RO in a sample of CKD-MBD Brazilian patients and understand its relationship with outcomes. METHODS: Between August 2015 and March 2018, 260 CKD-MBD stage 3-5D patients who underwent bone biopsy were followed for 12 to 30 months. Clinical-demographic, laboratory, and histological data were analyzed. Bone fractures, hospitalizations, and death were considered the primary outcomes. RESULTS: Osteitis fibrosa, mixed uremic osteodystrophy, adynamic bone disease, osteomalacia, osteoporosis, and aluminum (Al) accumulation were detected in 85, 43, 27, 10, 77, and 65 patients, respectively. The logistic regression showed that dialysis vintage was an independent predictor of osteoporosis (OR: 1.005; CI: 1.001-1.010; p = 0.01). The multivariate logistic regression revealed that hemodialysis treatment (OR: 11.24; CI: 1.227-100; p = 0.03), previous parathyroidectomy (OR: 4.97; CI: 1.422-17.241; p = 0.01), and female gender (OR: 2.88; CI: 1.080-7.679; p = 0.03) were independent predictors of Al accumulation; 115 patients were followed for 21 ± 5 months. There were 56 hospitalizations, 14 deaths, and 7 fractures during follow-up. The COX regression revealed that none of the variable related to the RO/turnover, mineralization and volume (TMV) classification was an independent predictor of the outcomes. CONCLUSION: Hospitalization or death was not influenced by the type of RO, Al accumulation, or TMV classification. An elevated prevalence of osteoporosis and Al accumulation was detected.

Clinical and microbiological effects of dialyzers reuse in hemodialysis patients / Efeitos clínicos e microbiológicos do reúso de dialisadores em pacientes em hemodiálise

Abstract Introduction: Chronic kidney disease (CKD) has a high prevalence and is a worldwide public health problem. Reuse of dialyzers is a cost reduction strategy used in many countries. There is controversy over its effects on clinical parameters and microbiological safety. Methods: In this clinical crossover study, 10 patients performed consecutive hemodialysis (HD) sessions divided in two phases: "single use" sessions (N = 10 HD sessions) followed by "dialyzer reuse" sessions (N = 30 HD sessions). Clinical, laboratory, and microbiological parameters were collected in the following time points: "single use", 1st, 6th, and 12th sessions with reuse of dialyzers, including bacterial cultures, endotoxins quantification in serum and dialyzer blood chamber, and detection of hemoglobin and protein residues in dialyzers. Results: Mean age of the sample was 37 ± 16 years, 6 (60%) were men, and 5 (50%) were white. CKD and HD vintage were 169 ± 108 and 47 (23-111) months, respectively. Serum C-reactive protein (CRP) [4.9 (2.1) mg/mL], ferritin (454 ± 223 ng/mL), and endotoxin levels [0.76 (0.61-0.91) EU/mL] were high at baseline. Comparison of pre- and post-HD variations of serum levels of CRP and endotoxins in the "single use" versus "reuse" phases did not result in differences (p = 0.8 and 0.4, respectively). Samples of liquid in the dialyzer inner chamber were negative for the growth of bacteria or endotoxins. There was no significant clinical manifestation within and between the phases. Conclusion: Dialyzers reuse was safe from a clinical, microbiological, and inflammatory point of view. The dialyzer performance remained adequate until the 12th reuse.

Resumo Introdução: A doença renal crônica (DRC) é um problema de saúde pública mundial de alta prevalência. O reúso de dialisadores é uma estratégia de redução de custos empregada em muitos países. Seus efeitos sobre parâmetros clínicos e de segurança microbiológica são alvo de controvérsia. Métodos: No presente estudo clínico cruzado, 10 pacientes realizaram sessões consecutivas de hemodiálise (HD) divididas em duas fases: a primeira com sessões de "uso único" (N = 10 sessões de HD) e a segunda com sessões com "reúso de dialisadores" (N = 30 sessões de HD). Parâmetros clínicos, laboratoriais e microbiológicos foram registrados nos seguintes momentos: "uso único", 1a, 6a e 12a sessões com reúso de dialisadores, incluindo culturas bacterianas, quantificação de endotoxinas no soro e na câmara interna do dialisador e detecção de hemoglobina e resíduos de proteína nos dialisadores. Resultados: A idade média da amostra foi de 37 ± 16 anos seis (60%) eram homens e cinco (50%) eram brancos. Os tempos com DRC e em HD foram de 169 ± 108 e 47 (23-111) meses, respectivamente. Os níveis séricos de proteína C-reativa (PCR) [4,9 (2,1) mg/mL], ferritina (454 ± 223 ng/mL) e endotoxinas [0,76 (0,61-0,91) UE/mL] estavam elevados no início do estudo. A diferença dos níveis séricos de PCR e endotoxinas pré e pós-HD nas fases de "uso único" e "reúso" não foi significativa (p = 0,8 e 0,4, respectivamente). As amostras de líquido retiradas da câmara interna do dialisador foram negativas para crescimento de bactérias e endotoxinas. Não houve registro de manifestações clínicas significativas nas fases do estudo. Conclusão: O reúso de dialisadores foi seguro dos pontos de vista clínico, microbiológico e inflamatório. O desempenho do dialisador permaneceu adequado até o 12º reuso.

Endothelial Microparticles in Uremia: Biomarkers and Potential Therapeutic Targets.

Endothelial microparticles (EMPs) are vesicles derived from cell membranes, which contain outsourced phosphatidylserine and express adhesion molecules, such as cadherin, intercellular cell adhesion molecule-1 (ICAM-1), E-selectin, and integrins. EMPs are expressed under physiological conditions and continue circulating in the plasma. However, in pathologic conditions their levels increase, and they assume a pro-inflammatory and pro-coagulant role via interactions with monocytes; these effects are related to the development of atherosclerosis. Chronic kidney dysfunction (CKD) characterizes this dysfunctional scenario through the accumulation of uremic solutes in the circulating plasma, whose toxicity is related to the development of cardiovascular diseases. Therefore, this review aims to discuss the formation of EMPs and their biological effects in the uremic environment. Data from previous research demonstrate that uremic toxins are closely associated with the activation of inflammatory biomarkers, cardiovascular dysfunction processes, and the release of EMPs. The impact of a decrease in circulating EMPs in clinical studies has not yet been evaluated. Thus, whether MPs are biochemical markers and/or therapeutic targets has yet to be established.

Clinical and microbiological effects of dialyzers reuse in hemodialysis patients.

INTRODUCTION: Chronic kidney disease (CKD) has a high prevalence and is a worldwide public health problem. Reuse of dialyzers is a cost reduction strategy used in many countries. There is controversy over its effects on clinical parameters and microbiological safety. METHODS: In this clinical crossover study, 10 patients performed consecutive hemodialysis (HD) sessions divided in two phases: "single use" sessions (N = 10 HD sessions) followed by "dialyzer reuse" sessions (N = 30 HD sessions). Clinical, laboratory, and microbiological parameters were collected in the following time points: "single use", 1st, 6th, and 12th sessions with reuse of dialyzers, including bacterial cultures, endotoxins quantification in serum and dialyzer blood chamber, and detection of hemoglobin and protein residues in dialyzers. RESULTS: Mean age of the sample was 37 ± 16 years, 6 (60%) were men, and 5 (50%) were white. CKD and HD vintage were 169 ± 108 and 47 (23-111) months, respectively. Serum C-reactive protein (CRP) [4.9 (2.1) mg/mL], ferritin (454 ± 223 ng/mL), and endotoxin levels [0.76 (0.61-0.91) EU/mL] were high at baseline. Comparison of pre- and post-HD variations of serum levels of CRP and endotoxins in the "single use" versus "reuse" phases did not result in differences (p = 0.8 and 0.4, respectively). Samples of liquid in the dialyzer inner chamber were negative for the growth of bacteria or endotoxins. There was no significant clinical manifestation within and between the phases. CONCLUSION: Dialyzers reuse was safe from a clinical, microbiological, and inflammatory point of view. The dialyzer performance remained adequate until the 12th reuse.

The enigma of aluminum deposition in bone tissue from a patient with chronic kidney disease: a case report.

About four decades ago, the relationship between dialysis-dementia and aluminum (Al) began to be established. The restriction of drugs containing Al and improvements on water quality used for dialysis resulted in the clinical disappearance of Al intoxication. However, high prevalence of Al deposition in bone tissue from Brazilian dialysis patients is still being detected. Through the case report of a patient on hemodialysis (HD) for one year, presenting significant Al deposition in bone tissue, we speculated if this problem is not being underestimated. We used extensive investigation to identify potential sources of Al exposure with a careful review of medication history and water quality controls. Al concentration was measured by different methods, including mass spectrometry, in poly-electrolyte concentrate solutions and solution for peritoneal dialysis, in an attempt to elucidate the possible sources of contamination. The objective of this case report is to alert the medical community about a potential high prevalence of Al deposition in bone tissue and to discuss the possible sources of contamination in patients with chronic kidney disease (CKD).

The enigma of aluminum deposition in bone tissue from a patient with chronic kidney disease: a case report / O enigma da deposição de alumínio no tecido ósseo de um paciente com doença renal crônica: relato de caso

ABSTRACT About four decades ago, the relationship between dialysis-dementia and aluminum (Al) began to be established. The restriction of drugs containing Al and improvements on water quality used for dialysis resulted in the clinical disappearance of Al intoxication. However, high prevalence of Al deposition in bone tissue from Brazilian dialysis patients is still being detected. Through the case report of a patient on hemodialysis (HD) for one year, presenting significant Al deposition in bone tissue, we speculated if this problem is not being underestimated. We used extensive investigation to identify potential sources of Al exposure with a careful review of medication history and water quality controls. Al concentration was measured by different methods, including mass spectrometry, in poly-electrolyte concentrate solutions and solution for peritoneal dialysis, in an attempt to elucidate the possible sources of contamination. The objective of this case report is to alert the medical community about a potential high prevalence of Al deposition in bone tissue and to discuss the possible sources of contamination in patients with chronic kidney disease (CKD).

RESUMO Cerca de quatro décadas atrás, a relação entre demência relacionada à diálise e alumínio (Al) começou a ser estabelecida. A restrição de medicamentos contendo Al e melhorias na qualidade da água utilizada na diálise resultaram no desaparecimento clínico da intoxicação por Al. Contudo, no Brasil continua a ser identificada uma elevada prevalência de deposição de Al no tecido ósseo de pacientes em diálise. O presente relato de caso de um paciente em hemodiálise (HD) há um ano com deposição significativa de Al no tecido ósseo nos leva a especular se esse problema não tem sido subestimado. Realizamos uma ampla investigação para identificar possíveis fontes de exposição ao Al, com uma revisão cuidadosa do histórico de medicação e dos controles de qualidade da água. A concentração de Al foi medida por diferentes métodos, incluindo espectrometria de massa, nos concentrados polieletrolíticos para hemodiálise e soluções de diálise peritoneal, na tentativa de elucidar as possíveis fontes de contaminação. O objetivo do presente relato de caso é alertar a comunidade médica sobre uma possível elevada prevalência de deposição de Al no tecido ósseo e discutir as possíveis fontes de contaminação nos pacientes com doença renal crônica (DRC).

Hypercalcemia in children: three cases report with unusual clinical presentations.

Hypercalcemia is a rare condition in childhood; the most common causes are primary hyperparathyroidism, malignancy, prolonged immobilisation, thyrotoxicosis, thiazide diuretic, supplements containing calcium, milk-alkali syndrome, vitamin D intoxication, infections and idiopathic. We present three cases of severe hypercalcemia of unusual causes in children. The first patient had high fever, poor general condition, weight loss and myalgia. Extensive preliminary investigation did not define the etiology, but a review of medical history revealed prolonged contact with pet bird and a positive serology for Chlamydia confirmed the diagnosis of psittacosis. The second patient had generalized lymphadenopathy and hepatosplenomegaly with fever a month ago. Paracoccidioides brasiliensis was identified in myelogram; the patient showed partial improvement with the use of co-trimoxazole, with subsequent emergence of multiple osteolytic lesions. A smear of gastric lavage was positive for Mycobacterium tuberculosis and the patient was treated with rifampicin, isoniazid, ethambutol and pyrazinamide, with improvement of clinical condition. The third patient was treated by hypercalciuria and idiopathic hypomagnesiuria with daily use of cholecalciferol; the patient had a two quilograms of weight loss in the past two months. No cause of hypercalcemia could be detected in laboratory workout. The capsules of cholecalciferol were analyzed and presented an amount of 832,000 IU of vitamin D per capsule. Acute hypercalcemia in childhood may be due to exogenous vitamin D intoxication, as well as infectious causes. The possible causal relationship between psittacosis and occurrence of hypercalcemia alert to the need for detailed investigation of the epidemiological antecedents.

Advanced glycation end-products (AGEs) accumulation in skin: relations with chronic kidney disease-mineral and bone disorder.

INTRODUCTION: Chronic kidney disease (CKD) is associated with high morbidity and mortality rates, main causes related with cardiovascular disease (CVD) and bone mineral disorder (CKD-BMD). Uremic toxins, as advanced glycation end products (AGEs), are non-traditional cardiovascular risk factor and play a role on development of CKD-BMD in CKD. The measurement of skin autofluorescence (sAF) is a noninvasive method to assess the level of AGEs in tissue, validated in CKD patients. OBJECTIVE: The aim of this study is analyze AGEs measured by sAF levels (AGEs-sAF) and its relations with CVD and BMD parameters in HD patients. METHODS: Twenty prevalent HD patients (HD group) and healthy subjects (Control group, n = 24), performed biochemical tests and measurements of anthropometric parameters and AGEs-sAF. In addition, HD group performed measurement of intact parathormone (iPTH), transthoracic echocardiogram and radiographies of pelvis and hands for vascular calcification score. RESULTS: AGEs-sAF levels are elevated both in HD and control subjects ranged according to the age, although higher at HD than control group. Single high-flux HD session does not affect AGEs-sAF levels. AGEs-sAF levels were not related to ventricular mass, interventricular septum or vascular calcification in HD group. AGEs-sAF levels were negatively associated with serum iPTH levels. CONCLUSION: Our study detected a negative correlation of AGEs-sAF with serum iPTH, suggesting a role of AGEs on the pathophysiology of bone disease in HD prevalent patients. The nature of this relation and the clinical application of this non-invasive methodology for evaluation AGEs deposition must be confirmed and clarified in future studies.

Advanced glycation end-products (AGEs) accumulation in skin: relations with chronic kidney disease-mineral and bone disorder / Acúmulo dos produtos finais da glicação avançada (AGEs) na pele: relações com o distúrbio mineral e ósseo na doença renal crônica

Abstract Introduction: Chronic kidney disease (CKD) is associated with high morbidity and mortality rates, main causes related with cardiovascular disease (CVD) and bone mineral disorder (CKD-BMD). Uremic toxins, as advanced glycation end products (AGEs), are non-traditional cardiovascular risk factor and play a role on development of CKD-BMD in CKD. The measurement of skin autofluorescence (sAF) is a noninvasive method to assess the level of AGEs in tissue, validated in CKD patients. Objective: The aim of this study is analyze AGEs measured by sAF levels (AGEs-sAF) and its relations with CVD and BMD parameters in HD patients. Methods: Twenty prevalent HD patients (HD group) and healthy subjects (Control group, n = 24), performed biochemical tests and measurements of anthropometric parameters and AGEs-sAF. In addition, HD group performed measurement of intact parathormone (iPTH), transthoracic echocardiogram and radiographies of pelvis and hands for vascular calcification score. Results: AGEs-sAF levels are elevated both in HD and control subjects ranged according to the age, although higher at HD than control group. Single high-flux HD session does not affect AGEs-sAF levels. AGEs-sAF levels were not related to ventricular mass, interventricular septum or vascular calcification in HD group. AGEs-sAF levels were negatively associated with serum iPTH levels. Conclusion: Our study detected a negative correlation of AGEs-sAF with serum iPTH, suggesting a role of AGEs on the pathophysiology of bone disease in HD prevalent patients. The nature of this relation and the clinical application of this non-invasive methodology for evaluation AGEs deposition must be confirmed and clarified in future studies.

Resumo Introdução: A doença renal crônica (DRC) apresenta elevadas taxas de morbidade e mortalidade, sendo a doença cardiovascular (DCV) e o distúrbio mineral e ósseo da DRC (DMO-DRC) complicações frequentes. As toxinas urêmicas, dentre elas os produtos finais da glicação avançada (AGEs), são fatores de risco cardiovascular não tradicionais e se encontram envolvidas no desenvolvimento do DMO-DRC na DRC. A medida da autofluorescência da pele (sAF) é método não invasivo para quantificação do acúmulo tecidual de AGEs validado em pacientes portadores de DRC. Objetivos: O objetivo deste estudo é avaliar as relações entre os AGEs medidos por sAF (AGEs-AF) e parâmetros de DCV e DMO-DRC em pacientes em hemodiálise (HD). Métodos: 20 pacientes em HD (grupo HD) e 24 indivíduos hígidos (grupo controle) foram submetidos à análise bioquímica sérica, medidas antropométricas e de sAF. O grupo HD realizou medida de hormônio intacto da paratireoide (PTHi), ecocardiograma transtorácico e radiografias de pelve e mãos para pesquisa de calcificação vascular. Resultados: Os níveis de AGEs-sAF foram elevados para a idade nos grupos HD e controle, porém mais elevados no grupo HD. Sessão única de HD de alto-fluxo não afetou os níveis de AGEs-sAF. Os níveis teciduais de AGEs não se correlacionaram com massa ventricular, espessura de septo interventricular ou calcificação vascular no grupo HD. Os níveis de AGEs-sAF se correlacionaram negativamente com os níveis séricos de PTHi. Conclusão: Nosso estudo detectou correlação negativa entre os níveis de AGEs-sAF e os níveis séricos de PTHi, sugerindo que os AGEs estejam envolvidos na fiosiopatologia da doença óssea em pacientes em HD. A natureza desta relação e a aplicação clínica deste método não invasivo de avaliação do acúmulo tecidual de AGEs deve ser confirmada e elucidada por estudos futuros.

Hypercalcemia in children: three cases report with unusual clinical presentations / Hipercalcemia em crianças: relato de três casos com apresentações clínicas incomuns

Abstract Hypercalcemia is a rare condition in childhood; the most common causes are primary hyperparathyroidism, malignancy, prolonged immobilisation, thyrotoxicosis, thiazide diuretic, supplements containing calcium, milk-alkali syndrome, vitamin D intoxication, infections and idiopathic. We present three cases of severe hypercalcemia of unusual causes in children. The first patient had high fever, poor general condition, weight loss and myalgia. Extensive preliminary investigation did not define the etiology, but a review of medical history revealed prolonged contact with pet bird and a positive serology for Chlamydia confirmed the diagnosis of psittacosis. The second patient had generalized lymphadenopathy and hepatosplenomegaly with fever a month ago. Paracoccidioides brasiliensis was identified in myelogram; the patient showed partial improvement with the use of co-trimoxazole, with subsequent emergence of multiple osteolytic lesions. A smear of gastric lavage was positive for Mycobacterium tuberculosis and the patient was treated with rifampicin, isoniazid, ethambutol and pyrazinamide, with improvement of clinical condition. The third patient was treated by hypercalciuria and idiopathic hypomagnesiuria with daily use of cholecalciferol; the patient had a two quilograms of weight loss in the past two months. No cause of hypercalcemia could be detected in laboratory workout. The capsules of cholecalciferol were analyzed and presented an amount of 832,000 IU of vitamin D per capsule. Acute hypercalcemia in childhood may be due to exogenous vitamin D intoxication, as well as infectious causes. The possible causal relationship between psittacosis and occurrence of hypercalcemia alert to the need for detailed investigation of the epidemiological antecedents.

Resumo A hipercalcemia é uma condição pouco comum na infância; dentre as causas mais comuns destacam-se hiperparatireoidismo primário, neoplasia, imobilização prolongada, tireotoxicose, diurético tiazídico, suplementos contendo cálcio, síndrome leite-álcali, intoxicação por vitamina D, infecções e causa idiopática. Apresentamos três casos de hipercalcemia grave por causas incomuns em crianças. O primeiro paciente tinha história de febre alta acompanhada de queda do estado geral, emagrecimento e mialgia. Extensa investigação preliminar não definiu a etiologia, porém uma revisão da história clínica revelou contato prolongado com ave de estimação e uma sorologia positiva para clamídia confirmou o diagnóstico de psitacose. O segundo paciente apresentava adenomegalia generalizada e hepatoesplenomegalia acompanhadas de febre por um mês, tendo sido identificado Paracoccidioides brasiliensis no mielograma; o paciente apresentou melhora parcial com uso de sulfametoxazol+trimetoprima, com posterior surgimento de múltiplas lesões osteolíticas. Uma baciloscopia do lavado gástrico foi positiva para Mycobacterium tuberculosis, tratado com rifampicina, isoniazida, pirazinamida e etambutol, com boa evolução. O terceiro paciente já era acompanhado por hipercalciúria e hipomagnesiúria idiopáticas e fazia uso diário de colecalciferol; perdeu dois quilogramas nos últimos dois meses. Nenhuma causa de hipercalcemia pôde ser detectada nos exames laboratoriais. As cápsulas de colecalciferol foram analisadas e encontrou-se uma quantidade de 832.000 UI de vitamina D. A hipercalcemia aguda na infância pode ser decorrente de intoxicação exógena por vitamina D, bem como de causas infecciosas. A possível relação causal entre psitacose e ocorrência da hipercalcemia alerta para a necessidade de investigação detalhada dos antecedentes epidemiológicos.

Patient in chronic hemodialysis with right atrial mass: thrombus, fungal endocarditis or atrial myxoma?

We present the case report of a 19-year-old patient with chronic kidney disease due to chronic glomerulonephritis, in hemodialysis (HD) by central catheter, with the incidental finding of a mass of 28x16 mm in right atrium (RA). The diagnosis of thrombus, infective endocarditis or myxoma were considered. Given the context of immunosuppression and difficult access vascular therapeutic practice has proved complex. Although Doppler echocardiography suggested thrombus in RA, nuclear magnetic resonance imaging (MRI) indicated for the diagnosis of myxoma in RA. In both conditions, the proposed surgical approach was limited by intense immunosuppression history and the risk of infectious complications. Throughout the treatment, the general state of K.M.F. remained satisfactory and revealed no signs or symptoms related to atrial dysfunction. The absence of fever and negative blood cultures excluded infective endocarditis. Prior echocardiogram report without masses in the RA decreased the chance of cardiac myxoma. The therapeutic response to anticoagulation confirmed the diagnosis of thrombosis. After 180 days of anticoagulation, there was significant reduction in mass. The patient developed asymptomatic. The diagnosis of mass in RA can be a challenge and only the evolution of the case was able to guide the appropriate conduit. While MRI has high sensitivity and specificity for the diagnosis of cardiac myxoma, the interpretation of images can be subjective. Controversial point is the removal of the catheter in such cases, which is subject discussed throughout the report.