RESUMO
Sporadic cases of apolipoprotein A-IV medullary amyloidosis have been reported. Here we describe five families found to have autosomal dominant medullary amyloidosis due to two different pathogenic APOA4 variants. A large family with autosomal dominant chronic kidney disease (CKD) and bland urinary sediment underwent whole genome sequencing with identification of a chr11:116692578 G>C (hg19) variant encoding the missense mutation p.L66V of the ApoA4 protein. We identified two other distantly related families from our registry with the same variant and two other distantly related families with a chr11:116693454 C>T (hg19) variant encoding the missense mutation p.D33N. Both mutations are unique to affected families, evolutionarily conserved and predicted to expand the amyloidogenic hotspot in the ApoA4 structure. Clinically affected individuals suffered from CKD with a bland urinary sediment and a mean age for kidney failure of 64.5 years. Genotyping identified 48 genetically affected individuals; 44 individuals had an estimated glomerular filtration rate (eGFR) under 60 ml/min/1.73 m2, including all 25 individuals with kidney failure. Significantly, 11 of 14 genetically unaffected individuals had an eGFR over 60 ml/min/1.73 m2. Fifteen genetically affected individuals presented with higher plasma ApoA4 concentrations. Kidney pathologic specimens from four individuals revealed amyloid deposits limited to the medulla, with the mutated ApoA4 identified by mass-spectrometry as the predominant amyloid constituent in all three available biopsies. Thus, ApoA4 mutations can cause autosomal dominant medullary amyloidosis, with marked amyloid deposition limited to the kidney medulla and presenting with autosomal dominant CKD with a bland urinary sediment. Diagnosis relies on a careful family history, APOA4 sequencing and pathologic studies.
Assuntos
Amiloidose , Apolipoproteínas A , Nefrite Intersticial , Insuficiência Renal Crônica , Humanos , Pessoa de Meia-Idade , Nefrite Intersticial/diagnóstico , Nefrite Intersticial/genética , Nefrite Intersticial/complicações , Mutação , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/genética , Insuficiência Renal Crônica/complicaçõesRESUMO
BACKGROUND: Frailty is a condition characterized by a decline in physical function and functional capacity. Common symptoms of frailty, such as weakness and exhaustion, are prevalent in patients with chronic kidney disease (CKD). The increased vulnerability of frail patients with coexisting CKD may place them at a heightened risk of encountering additional health complications. The purpose of this systematic review was to explore the link between frailty, CKD and clinical outcomes. METHODS: We searched for cross sectional and prospective studies in the general population and in the CKD population indexed in EMBASE, Pubmed, Web of Science, CINAHL, Cochrane and Ageline examining the association between frailty and CKD and those relating frailty in patients with CKD to clinical outcomes. RESULTS: We screened 5,066 abstracts and retrieved 108 studies for full text review. We identified 7 studies associating frailty or physical function to CKD. From the 7 studies, we identified only two studies that related frailty in patients with CKD to a clinical outcome. CKD was consistently associated with increasing frailty or reduced physical function [odds ratios (OR) 1.30 to 3.12]. In patients with CKD, frailty was associated with a greater than two-fold higher risk of dialysis and/or death [OR from 2.0 to 5.88]. CONCLUSIONS: CKD is associated with a higher risk of frailty or diminished physical function. Furthermore, the presence of frailty in patients with CKD may lead to a higher risk of mortality. Further research must be conducted to understand the mechanisms of frailty in CKD and to confirm its association with clinical outcomes.
Assuntos
Idoso Fragilizado/estatística & dados numéricos , Debilidade Muscular/mortalidade , Aptidão Física , Diálise Renal/estatística & dados numéricos , Insuficiência Renal Crônica/mortalidade , Insuficiência Renal Crônica/reabilitação , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Taxa de SobrevidaRESUMO
BACKGROUND: Individuals with chronic kidney disease (CKD) have low levels of physical activity and physical function. Although guidelines endorse exercise counseling for individuals with CKD, it is not yet part of routine care. OBJECTIVE: We investigated the effect of attending a real-life exercise counseling clinic (ECC) on physical function in individuals with CKD. DESIGN: Retrospective analysis of prospectively collected observational data with quasi-experimental design. SETTING AND PARTICIPANTS: Patients with all stages of CKD registered in a large provincial renal program were eligible. The exposed cohort who attended the ECC between January 1, 2011, and March 15, 2014, included 214 individuals. The control cohort included 292 individuals enrolled in an observational study investigating longitudinal change in frailty during the same time period. PREDICTOR/FACTOR: Attendance at an ECC. OUTCOMES AND MEASUREMENTS: Change in physical function as measured by Short Physical Performance Battery (SPPB) score, physical activity level (Human Activity Profile [HAP]/Physical Activity Scale for the Elderly [PASE]), and health-related quality of life (HRQOL; EQ5D/VAS) over 1 year. RESULTS: Eighty-seven individuals in the ECC cohort and 125 participants in the control cohort completed 1-year follow-up. Baseline median SPPB score was 10 (interquartile range [IQR]: 9-12) and 9 (IQR: 7-11) in the ECC and control cohorts, respectively (P < .01). At 1 year, SPPB scores were 10 (IQR: 8-12) and 9 (IQR: 6-11) in the ECC and control cohorts, respectively (P = .04). Mean change in SPPB over 1 year was not significantly different between groups: -0.33 (95% confidence interval [CI]: -0.81 to 0.15) in ECC and -0.22 (95% CI: -0.61 to 0.17) in control (P = .72). There was no significant difference in the proportion of individuals in each cohort with an increase/decrease in SPPB score over time. There was no significant change in physical activity or HRQOL over time between groups. LIMITATIONS: Quasi-experimental design, low rate of follow-up attendance. CONCLUSIONS: In this pragmatic study, exercise counseling had no significant effect on change in SPPB score, suggesting that a single exercise counseling session alone is inadequate to improve physical function in CKD.
CONTEXTE: Les personnes atteintes d'insuffisance rénale chronique (IRC) ont des capacités physiques réduites et sont généralement peu actives physiquement. Bien que les recommandations aillent dans le sens d'encourager ces patients à adopter un programme d'exercices, on observe que cela ne fait toujours pas partie de la routine de soins. OBJECTIF DE L'ÉTUDE: Mesurer l'effet de la fréquentation d'une clinique de consultation en entraînement (CCE) sur la condition physique des individus atteints d'IRC. TYPE D'ÉTUDE: Il s'agit d'un modèle d'étude quasi expérimental sous forme d'une analyse rétrospective de données observationnelles colligées prospectivement. CADRE DE L'ÉTUDE ET PARTICIPANTS: Étaient admissibles tous les patients atteints d'IRC, peu importe le stade, inscrits à un vaste programme de santé rénale provincial. La cohorte exposée, soit les patients ayant fréquenté une CCE entre le 1er janvier 2011 et le 15 mars 2014, était composée de 214 sujets. La cohorte contrôle était constituée de 292 individus participant à une étude observationnelle qui évaluait les changements longitudinaux de fragilité physique pendant la même période. FACTEUR PRÉDICTIF: La fréquentation d'une CCE. MESURES: Pendant un an, on a mesuré le niveau d'activité physique, la qualité de vie relative à l'état de santé et les changements dans les capacités physiques des participants (test SPPB - Short Physical Performance Battery Score). RÉSULTATS: Seuls 87 patients de la cohorte exposée et 125 de la cohorte contrôle ont complété le suivi. Les médianes initiales au test SPPB étaient de 10 (EI: 9-12) et de 9 (EI: 7-11) respectivement (p < 0,01). Après un an, les scores au test SPPB étaient pratiquement inchangés: médiane de 10 (EI: 8-12) pour la cohorte exposée et de 9 pour la cohorte contrôle (EI: 6-11) (p = 0,04). Pendant l'année du suivi, la variation moyenne du score au test SPPB a été semblable dans les deux groupes: −0,33 (IC 95 % −0,81 à 0,15) dans la cohorte exposée et −0,22 (IC 95 % −0,61 à 0,17) dans le groupe contrôle (p = 0,72). Au fil du temps, la proportion d'individus ayant présenté une diminution ou une augmentation du score au test SPPB était similaire dans les deux groupes; et aucun changement significatif dans le niveau d'activité physique ou la qualité de vie relative à l'état de santé n'avait été observé entre les groupes. LIMITES DE L'ÉTUDE: Les résultats sont limités par le modèle quasi expérimental de l'étude et la faible participation au suivi sur un an. CONCLUSION: Cette étude pragmatique démontre que le fait de consulter pour un programme d'entraînement n'a que peu d'effet sur le score obtenu au test SPPB. Cette observation suggère qu'une seule séance de consultation en vue d'adopter un programme d'entraînement n'est pas suffisante pour améliorer la condition physique des patients atteints d'IRC.
RESUMO
BACKGROUND: Frailty, a manifestation of unsuccessful aging, is highly prevalent in people with chronic kidney disease (CKD) and is associated with comorbid conditions in cross-sectional studies. Longitudinal studies investigating the progression of frailty in those with advanced non-dialysis CKD are lacking. OBJECTIVES: Canadian Frailty Observation and Interventions Trial (CanFIT). To determine the natural history, prevalence of perceived and measured frailty and its association with dialysis treatment choices and adverse outcomes in patients with advanced CKD. DESIGN: Longitudinal observational study, designed to collect data from 600 participants over 2 years. SETTING: Interprofessional non-dialysis CKD clinics at four tertiary health care centres in central Canada. PATIENTS: People with CKD stage 4 and 5 (eGFR <30 ml/min/1.73 m(2)) who are not on dialysis at enrollment. MEASUREMENTS: Multiple Frailty Definitions: Short Physical Performance Battery (SPPB), Fried Frailty Criteria, Frailty Index. Dialysis start: In-Centre Hemodialysis, Home Hemodialysis or Peritoneal Dialysis Outcomes: Death, Opt-out or Lost to follow up. METHODS: We will perform physical and cognitive assessments annually. We plan to analyze the relationships between frailty, treatment choices and patient centered outcomes. RESULTS: We have recruited 217 participants in 2 centres; of these, 56 % had reduced physical function at baseline, as defined by the SPPB. Risk of reduced physical function was 8 fold higher in those with diabetes after adjusting for age, gender, eGFR and comorbidities. LIMITATIONS: Referred population, use of SPPB as a measure of frailty, inter-operator variability in measurement of hand grip and gait speed, cross-sectional analysis of baseline data in the subset recruited to date. CONCLUSIONS: People with advanced CKD have a high burden of reduced physical function, especially those with diabetes. We will continue enrollment into the CanFIT study to further understand the clinical history of CKD and frailty in this population.
CONTEXTE: La fragilité, une manifestation du vieillissement malheureux, est très répandue chez les personnes atteintes d'insuffisance rénale chronique (IRC) et est associée à des conditions de comorbidité dans les études transversales. Rares sont les études longitudinales destinées à étudier la progression de la fragilité chez les personnes atteintes d'IRC avancée qui ne reçoivent pas de dialyse. OBJECTIFS: Canadian Frailty Observation and Interventions Trial (CanFIT). Déterminer l'évolution naturelle, la prévalence de la fragilité perçue et mesurée, de même que son association avec les options de traitement à la dialyse et les effets indésirables sur les patients atteints d'IRC avancée. TYPE D'ÉTUDE: Étude longitudinale d'observation visant à recueillir les données de 600 patients sur deux ans. CONTEXTE: Des unités interprofessionnelles d'IRC qui ne pratiquent pas la dialyse dans quatre centres de soins tertiaires du centre du Canada. PARTICIPANTS: Des personnes atteintes d'IRC de stade 4 et 5 (R-EGF <30 ml/min/1,73 m2) qui ne recevaient pas de dialyse au moment de l'inscription. MESURES: Diverses définitions de la fragilité : le Short Physical Performance Battery (SPPB), les critères de fragilité de Fried et l'indice de fragilité. Le lieu de l'amorce de la dialyse : la dialyse en centre, la dialyse à domicile; ou les résultats de la dialyse péritonéale : le décès, le refus ou la perte de suivi. MÉTHODES: Nous effectuerons des examens physiques et cognitifs sur une base annuelle. Nous planifions analyser la relation entre la fragilité, le choix du traitement et les résultats axés sur le patient. RÉSULTATS: Nous avons recruté 217 participants dans 2 centres; parmi ceux-ci, 56 % présentaient d'entrée de jeu une réduction des fonctions physiques, telles que définies par le SPPB. Les risques de subir une réduction des fonctions physiques étaient 8 fois supérieurs chez les patients souffrant de diabète, après ajustement selon l'âge, le sexe, le R-EGF et les comorbidités. LIMITES DE L'ÉTUDE: La population désignée, le recours au SPPB pour mesurer la fragilité, la variabilité des intervenants dans la mesure de la vitesse de préhension et de marche, l'analyse transversale des données de référence du sous-ensemble recruté jusqu'à maintenant. CONCLUSIONS: Les personnes atteintes d'IRC avancée sont accablées d'une forte réduction de la fonction physique, et particulièrement celles qui sont atteintes de diabète. Nous poursuivrons l'inscription à l'étude de CanFIT afin d'approfondir les connaissances au sujet de l'évolution clinique de l'IRC et la fragilité des personnes atteintes.
RESUMO
BACKGROUND: It is unknown whether favorable long-term data on the safety of living kidney donation can be extrapolated to populations at higher risk of chronic kidney disease. Indigenous people (i.e., Aboriginals) have a high prevalence of risk factors for chronic kidney disease and Aboriginal living donor outcomes need to be defined. METHODS: We performed a retrospective cohort study of all 38 Aboriginal donors donating at our center since 1970 and 76 randomly selected white donor controls to determine the long-term rates of hypertension, diabetes, and renal function postdonation. RESULTS: Follow-up was obtained for 91% of both Aboriginal and white donors (mean follow-up approximately 14 years). Hypertension has been diagnosed more frequently among Aboriginal donors (Ab 42% vs. white 19%, P=0.02). Notably, all 11 Aboriginal donors more than 20 years postdonation have developed hypertension. Diabetes has also been diagnosed more frequently among Aboriginal donors (Ab 19% vs. white 2%, P=0.005), including 5 of 11 (45%) more than 20 years postdonation. Follow-up estimated glomerular filtration rate was higher in Aboriginal donors (Ab 77+/-17 vs. white 67+/-13 mL/min/1.73 m, P=0.002) but not significantly different in adjusted analyses. One Aboriginal donor developed end-stage renal disease 14 years postdonation. CONCLUSIONS: Aboriginal living kidney donors at our center have high rates of hypertension and diabetes on long-term follow-up, although renal function is preserved to date. This profile is similar to that of the general unselected Aboriginal population despite detailed medical evaluation before donation. These findings have important implications for donor counseling and may have implications for other high-risk donor populations.
Assuntos
Indígenas Norte-Americanos , Transplante de Rim/fisiologia , Doadores Vivos , Peso Corporal , Creatinina/sangue , Feminino , Seguimentos , Humanos , Masculino , Manitoba , Pessoa de Meia-Idade , Ontário , Pais , Proteinúria/epidemiologia , Irmãos , Resultado do TratamentoRESUMO
We report two cases of severe lactic acidosis due to massive metformin ingestion. The first case was a 37-year-old man who was discovered several hours after ingesting 45 g of metformin. He had severe lactic acidosis (blood pH 6.81, bicarbonate 4 mEq/L, lactate 25.7 mEq/L). Despite intravenous bicarbonate therapy, he decompensated and was placed on a combination of hemodialysis and charcoal hemoperfusion for a continuous time of 25 hours. His hospital course was complicated by acute renal failure requiring a period of intermittent hemodialysis. He has since made a complete recovery. The second case was a 53-year-old man who ingested 50 g of metformin. He also presented with severe lactic acidosis (blood pH 6.85, bicarbonate 3 mEq/L and lactate 28.4 mEq/L) and deteriorated despite intravenous bicarbonate therapy. He was placed on hemodialysis as a continuous therapy for 21 hours. His hospital course was complicated by acute renal failure requiring a period of intermittent hemodialysis. He has subsequently made a complete recovery. Metformin-associated lactic acidosis carries a high mortality rate. Prolonged hemodialysis should be considered as an early treatment option in these cases.