RESUMO
INTRODUCTION: Sub-optimal weight loss following Roux-en-Y gastric bypass (RYGB) represents an important clinical challenge in a significant number of patients. Early identification of such patients would be advantageous, as it could aid in the selective implementation of targeted adjunct interventions during the first post-operative year. METHODS: Clinical audit data from 1137 patients undergoing RYGB between 2013 and 2016 at the Instituto Sallet in Brazil were prospectively registered in an online database (BOLD) and analyzed. RESULTS: Forty-eight percent of patients achieving less than 5% total weight loss after the first post-operative month achieved a 20% total weight loss at 1 year (n = 626; OR = 0.6 CI = 95%). Eighty-three percent of patients losing between 5 and 10% at 1 month and 95% of patients losing greater than 10% at 1 month had lost at least 20% of total body weight after the first post-operative year. Forty-four percent of patients achieving less than 10% total weight loss after the third post-operative month achieved 20% total weight loss at 1 year (n = 494; OR = 0.3 CI = 95%). CONCLUSION: Total bodyweight reduction after RYGB of < 5% at 1 month and < 10% at 3 months is associated with suboptimal weight loss at 1 year. These results reinforce findings from other studies reporting that patients tend to follow a common weight loss trajectory. Identifying the patients with weight trajectory requiring adjunct therapies early on is crucial so appropriate adjustments can be made to post-operative care.
Assuntos
Derivação Gástrica , Obesidade Mórbida , Índice de Massa Corporal , Brasil , Seguimentos , Humanos , Obesidade Mórbida/cirurgia , Estudos Retrospectivos , Redução de PesoRESUMO
Importance: Early-stage chronic kidney disease (CKD) characterized by microalbuminuria is associated with future cardiovascular events, progression toward end-stage renal disease, and early mortality in patients with type 2 diabetes. Objective: To compare the albuminuria-lowering effects of Roux-en-Y gastric bypass (RYGB) surgery vs best medical treatment in patients with early-stage CKD, type 2 diabetes, and obesity. Design, Setting, and Participants: For this randomized clinical trial, patients with established type 2 diabetes and microalbuminuria were recruited from a single center from April 1, 2013, through March 31, 2016, with a 5-year follow-up, including prespecified intermediate analysis at 24-month follow-up. Intervention: A total of 100 patients with type 2 diabetes, obesity (body mass indexes of 30 to 35 [calculated as weight in kilograms divided by height in meters squared]), and stage G1 to G3 and A2 to A3 CKD (urinary albumin-creatinine ratio [uACR] >30 mg/g and estimated glomerular filtration rate >30 mL/min) were randomized 1:1 to receive best medical treatment (n = 49) or RYGB (n = 51). Main Outcomes and Measures: The primary outcome was remission of albuminuria (uACR <30 mg/g). Secondary outcomes were CKD remission rate, absolute change in uACR, metabolic control, other microvascular complications, quality of life, and safety. Results: A total of 100 patients (mean [SD] age, 51.4 [7.6] years; 55 [55%] male) were randomized: 51 to RYGB and 49 to best medical care. Remission of albuminuria occurred in 55% of patients (95% CI, 39%-70%) after best medical treatment and 82% of patients (95% CI, 72%-93%) after RYGB (P = .006), resulting in CKD remission rates of 48% (95% CI, 32%-64%) after best medical treatment and 82% (95% CI, 72%-92%) after RYGB (P = .002). The geometric mean uACRs were 55% lower after RYGB (10.7 mg/g of creatinine) than after best medical treatment (23.6 mg/g of creatinine) (P < .001). No difference in the rate of serious adverse events was observed. Conclusions and Relevance: After 24 months, RYGB was more effective than best medical treatment for achieving remission of albuminuria and stage G1 to G3 and A2 to A3 CKD in patients with type 2 diabetes and obesity. Trial Registration: ClinicalTrials.gov Identifier: NCT01821508.
Assuntos
Complicações do Diabetes/complicações , Diabetes Mellitus Tipo 2/complicações , Derivação Gástrica , Obesidade/complicações , Obesidade/cirurgia , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
BACKGROUND: Mechanical stress is a key pathogenic driver of apoptosis in the tubular epithelium in obstructive nephropathy. Heat shock protein 70 (Hsp70) and Wilms' tumor (WT-1) have been proposed to represent linked downstream effectors of the cytoprotective properties of NO. In the present study, we sought to evaluate whether the cytoprotective effects of L-arginine in neonatal obstructive nephropathy may be associated with NO-dependent increases in WT-1 and Hsp70 expression. METHODS: Neonatal Wistar-Kyoto rats were submitted to complete unilateral ureteral obstruction (UUO) and treated thereafter with vehicle, L-NAME or L-arginine by daily gavage for 14 days to block or augment NO levels, respectively. Normal rat kidney epithelial cells by NRK-52E were exposed to mechanical stress in vitro in the presence or absence of L-NAME, L-arginine, sodium nitroprusside (SNP), L-arginine + SNP or L-arginine/L-NAME. Induction of apoptosis and the mRNA expression of WT-1 and Hsp70 genes were assessed. RESULTS: WT-1 and Hsp70 genes expression decreased in the presence of L-NAME and following UUO coincident with increased tubular apoptosis. L-arginine treatment increased NO levels, reduced apoptosis and restored expression levels of WT-1 and Hsp70 to control levels. L-arginine treatment in vitro reduced basal apoptotic rates and prevented apoptosis in response to mechanical strain, an effect enhanced by SNP co-incubation. L-NAME increased apoptosis and prevented the anti-apoptotic action of L-arginine. CONCLUSIONS: L-arginine treatment in experimental neonatal UUO reduces apoptosis coincident with restoration of WT-1 and Hsp70 expression levels and directly inhibits mechanical strain-induced apoptosis in an NO-dependent manner in vitro. This potentially implicates an NO-Hsp70-WT-1 axis in the cytoprotective effects of L-arginine.
Assuntos
Arginina/farmacologia , Proteínas de Choque Térmico HSP70/metabolismo , Nefropatias/tratamento farmacológico , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico/metabolismo , Obstrução Ureteral/tratamento farmacológico , Proteínas WT1/metabolismo , Animais , Apoptose/efeitos dos fármacos , Células Cultivadas , Citoproteção , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/fisiologia , Fibrose , Expressão Gênica/efeitos dos fármacos , Proteínas de Choque Térmico HSP70/genética , Córtex Renal/patologia , Nefropatias/etiologia , Nefropatias/patologia , Nefropatias/fisiopatologia , Túbulos Renais/patologia , Masculino , Nitroprussiato/farmacologia , Ratos , Ratos Endogâmicos WKY , Estresse Mecânico , Obstrução Ureteral/complicações , Obstrução Ureteral/fisiopatologia , Proteínas WT1/genéticaRESUMO
Urinary heat shock protein 70 (Hsp70) is rapidly increased in patients with clinical acute kidney injury, indicating that it constitutes a component of the endogenous stress response to renal injury. Moreover, experimental models have demonstrated that Hsp70 activation is associated with the cytoprotective actions of several drugs following obstruction, including nitric oxide (NO) donors, geranylgeranylacetone, vitamin D, and rosuvastatin. Discrete and synergistic effects of the biological activities of Hsp70 may explain its cytoprotective role in obstructive nephropathy. Basic studies point to a combination of effects including inhibition of apoptosis and inflammation, repair of damaged proteins, prevention of unfolded protein aggregation, targeting of damaged protein for degradation, and cytoskeletal stabilization as primary effectors of Hsp70 action. This review summarizes our understanding of how the biological actions of Hsp70 may affect renal cytoprotection in the context of obstructive injury. The potential of Hsp70 to be of central importance to the mechanism of action of various drugs that modify the genesis of experimental obstructive nephropathy is considered.
Assuntos
Proteínas de Choque Térmico HSP70/metabolismo , Nefropatias/metabolismo , Animais , Apoptose/fisiologia , Proteínas de Choque Térmico HSP70/genética , Humanos , Inflamação/metabolismo , Nefropatias/genética , Óxido Nítrico/metabolismo , Obstrução Ureteral/metabolismoRESUMO
BACKGROUND/AIMS: Unilateral ureteric obstruction (UUO) in neonatal rodents can be used as a paradigm for in utero obstruction in humans and a platform for studying the potential of novel therapies for congenital obstructive nephropathy. The present study examined the effect of rosuvastatin (Ros) on key morphometric measures of renal injury and corresponding gene expression correlates following neonatal UUO in the rat. METHODS: Neonatal rats subjected to UUO and controls were treated daily with vehicle or Ros for 14 days. Quantification of tubular dilatation, glomerular size and number and tubulointerstitial fibrotic area was performed and changes validated by reference to appropriate renal gene expression correlates. RESULTS: UUO increased tubular diameter and interstitial fibrosis by 2.7- and 7-fold, respectively, in parallel with increases in renal transforming growth factor-ß(1) (TGF-ß(1)) and tumor necrosis factor-α (TNF-α) mRNA levels. Glomerular number and size were reduced by 52 and 33%, respectively. Reductions in WT-1 mRNA and protein expression were noted following obstruction occurring in tandem with reduced mRNA levels for BMP-7 and E-cadherin. Ros attenuated tubular dilatation (33%) and interstitial fibrosis (72%) in association with the normalization of renal TGF-ß(1) and TNF-α mRNA levels. Ros improved glomerular number and size (30 and 50%), and preserved mRNA and protein expression levels of WT-1 and normalized mRNA levels for BMP-7 and E-cadherin. CONCLUSIONS: Ros treatment attenuated all changes, most notably the increase in interstitial fibrosis. Notably, Ros treatment was unable to completely salvage glomerular development. Together these data highlight the therapeutic potential and limitations of Ros in neonatal obstruction.