LIM/16 - Laboratório de Fisiopatologia Renal
URI Permanente desta comunidade
O Laboratório de Fisiopatologia Renal é ligado ao Departamento de Clínica Médica da Faculdade de Medicina da Universidade de São Paulo (FMUSP).
Linhas de pesquisa: hipertensão experimental: cloreto de sódio; nefropatias progressivas e doença óssea metabólica (osteodistrofia renal, osteoporose).
Site oficial: http://limhc.fm.usp.br/portal/lim16-laboratorio-de-fisiopatologia-renal/
Linhas de pesquisa: hipertensão experimental: cloreto de sódio; nefropatias progressivas e doença óssea metabólica (osteodistrofia renal, osteoporose).
Site oficial: http://limhc.fm.usp.br/portal/lim16-laboratorio-de-fisiopatologia-renal/
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- LIM/16 - Laboratório de Fisiopatologia Renal
- LIM/16 - Laboratório de Fisiopatologia Renal
- LIM/16 - Laboratório de Fisiopatologia Renal
Submissões Recentes
Mixed uremic osteodystrophy: an ill-described common bone pathology in patients with chronic kidney disease
(2023) ELKHOULI, Ekbal; NAGY, Eman; SANTOS, Cassia Gomes S.; BARRETO, Fellype Carvalho; CHAER, Juliana; JORGETTI, Vanda; EL-HUSSEINI, Amr
Renal osteodystrophy (ROD) starts early and progresses with further loss of kidney function in patients with chronic kidney disease (CKD). There are four distinct types of ROD based on undecalcified bone biopsy results. Adynamic bone disease and osteomalacia are the predominant forms of low bone turnover, while hyperparathyroid bone disease and mixed uremic osteodystrophy (MUO) are typically associated with high bone turnover. MUO is a prevalent but poorly described pathology that demonstrates evidence of osteomalacia on top of the high bone formation/resorption. The prevalence of MUO ranges from 5 to 63% among different studies. The pathogenesis of MUO is multi-factorial. Altered phosphate homeostasis, hypocalcemia, vitamin D deficiency, increased FGF-23, interleukins 1 and 6, TNF-& alpha;, amyloid, and heavy metal accumulation are the main inducers of MUO. The clinical findings of MUO are usually non-specific. The use of non-invasive testing such as bone turnover markers and imaging techniques might help to suspect MUO. However, it is usually impossible to precisely diagnose this condition without performing bone biopsy. The principal management of MUO is to control the maladaptive hyperparathyroidism along with correcting any nutritional mineral deficiencies that may induce mineralization defect. MUO is a common but still poorly understood bone pathology category; it demonstrates the complexity and difficulty in understanding ROD. A large prospective bone biopsy-based studies are needed for better identification as proper diagnosis and management would improve the outcome of patients with MUO.
Evaluation of glomerular sirtuin-1 and claudin-1 in the pathophysiology of nondiabetic focal segmental glomerulosclerosis
(2023) LOPES-GONCALVES, Guilherme; COSTA-PESSOA, Juliana Martins; PIMENTA, Ruan; TOSTES, Ana Flavia; SILVA, Eloisa Martins da; LEDESMA, Felipe Lourenco; MALHEIROS, Denise Maria Avancini Costa; ZATZ, Roberto; THIEME, Karina; CAMARA, Niels Olsen Saraiva; OLIVEIRA-SOUZA, Maria
Focal segmental glomerulosclerosis (FSGS) is the leading cause of nephrotic syndrome, which is characterized by podocyte injury. Given that the pathophysiology of nondiabetic glomerulosclerosis is poorly understood and targeted therapies to prevent glomerular disease are lacking, we decided to investigate the tight junction protein claudin-1 and the histone deacetylase sirtuin-1 (SIRT1), which are known to be involved in podocyte injury. For this purpose, we first examined SIRT1, claudin-1 and podocin expression in kidney biopsies from patients diagnosed with nondiabetic FSGS and found that upregulation of glomerular claudin-1 accompanies a significant reduction in glomerular SIRT1 and podocin levels. From this, we investigated whether a small molecule activator of SIRT1, SRT1720, could delay the onset of FSGS in an animal model of adriamycin (ADR)-induced nephropathy; 14 days of treatment with SRT1720 attenuated glomerulosclerosis progression and albuminuria, prevented transcription factor Wilms tumor 1 (WT1) downregulation and increased glomerular claudin-1 in the ADR + SRT1720 group. Thus, we evaluated the effect of ADR and/or SRT1720 in cultured mouse podocytes. The results showed that ADR [1 mu M] triggered an increase in claudin-1 expression after 30 min, and this effect was attenuated by pretreatment of podocytes with SRT1720 [5 mu M]. ADR [1 mu M] also led to changes in the localization of SIRT1 and claudin-1 in these cells, which could be associated with podocyte injury. Although the use of specific agonists such as SRT1720 presents some benefits in glomerular function, their underlying mechanisms still need to be further explored for therapeutic use. Taken together, our data indicate that SIRT1 and claudin-1 are relevant for the pathophysiology of nondiabetic FSGS.
Remote vs. face-to-face activities in the teaching of renal pathophysiology in the context of social isolation during the early phase of the COVID-19 pandemic
(2023) HAYDAR, Ahmed; SANTOS, Itamar Souza; ARCON, Luis Carlos; MARTINS, Milton de Arruda; TEMPSKI, Patricia Zen; ZATZ, Roberto
The advent of the COVID-19 pandemic forced medical schools around the world to adopt emergency remote learning as a resort to avoid interruption of courses. However, the effectiveness of online classes as an educational strategy has been questioned by medical educators and students. In a prospective observational study design, students enrolled in a renal physiology and pathophysiology course were exposed to either face-to-face or remote synchronous classes. Students taught online obtained significantly higher mean scores than the group who had in-person classes, both groups assessed with identical exams. Appropriate screening tests suggested that fraud is unlikely to have significantly influenced these results and that the observed differences in performance reflected increased learning by the remote group. These observations suggest that online classes can help to maintain the continuity of physiology and pathophysiology courses during periods of social isolation and may contribute to improving learning under normal conditions.
Effects of nutritional supplementation stabilizing muscle mass loss in older patients on hemodiafiltration
(2023) SILVA, Luana Cristina A. de; CORREIA, Marilia A. de; GOUVEIA, Renata Daniel; SOUZA, Mayara S.; JR, Carlos P. Isaac; PARRILLO, Fernando; MOYSES, Rosa M. A.; DALBONI, Maria Aparecida; ELIAS, Rosilene M.
Background & aims: Malnutrition is common in older individuals with end-stage renal disease on maintenance dialysis. Whether nutritional supplementation may improve skeletal muscle mass (SMM) and survival rate in this population is uncertain. We aimed to analyze the effect of a year of nutritional supplementation on muscle mass and survival rate in older patients on hemodiafiltration.Methods: In this observational study, older patient (>= 65 years old) on maintenance hemodiafiltration were selected to receive nutritional counselling + nutritional supplementation (N = 85, Supp+) or nutritional counselling alone (N = 47, Supp-) and followed for 1 year. The outcomes were a change in SMM and sarcopenia diagnosis. The secondary outcome was 1-year mortality rate. Nutritional parameters included calf circumference, body mass index, anthropometric measurements, subjective global assessment, and handgrip strength (HGS). Data were evaluated using GLM for repeated measures with adjustment for covariates (age and diabetes).Results: Malnutrition was found in 50.8% of patients. At baseline, patients from the Supp+ group were older and had worse nutritional parameters including hand grip strength, calf circumference, anthro-pometric findings and sarcopenia (all p values < 0.05). During the follow-up, there was no significant change in sarcopenia (from 50.8% to 58.3%, p = 0.108), and there was a more pronounced decrease in the SMM index in the Supp-group (p = 0.049), with a significant intervention interaction (p = 0.030). Twenty deaths occurred, 7 (35%) in the Supp-and 13 (65%) in the Supp+ group (p = 0.540). SMM index (relative risk 0.90, p = 0.030) and age (relative risk 1.07, p = 0.046) were independently associated with higher mortality rates. Conclusion: Nutritional supplementation in older and malnourished individuals undergoing hemodia-filtration mitigates the loss of the SMM index and benefits survival rate.(c) 2023 European Society for Clinical Nutrition and Metabolism.
Older patients are less prone to fast decline of renal function: a propensity-matched study
(2023) PINA, Paula M. R.; ARCON, Luis Carlos; ZATZ, Roberto; MOYSES, Rosa M. A.; ELIAS, Rosilene M.
PurposeDespite CKD is common among older patients, and although factors associated with CKD progression have been explored over decades, little is known about the decline of renal function specifically in older individuals.MethodsWe included adult patients with CKD on conservative management in a propensity-score matched study 1:1 older (> 65 year) and young (<= 65 yr). Factors associated with the slope of the decline of eGFR such as proteinuria, initial eGFR, diabetes, sex, and use of angiotensin-converting enzyme inhibitor/angiotensin receptor block (ACEI/ARB) were analyzed. Inclusion criteria were at least two consultations in the service and an initial eGFR lower than 45 ml/min/m(2), in the period between January 2012 and December 2017.ResultsCrude analysis of eGFR decline shows a slower progression of older patients when compared to younger patients in both absolute change [- 2.0 (- 4.5, - 1.0) vs. -3.0 (- 7.0, - 1.0) ml/min/1.73m(2), p < 0.001] and slope of eGFR reduction [- 2.2 (- 4.4, - 1.0) vs. 3.1 (- 6.7, - 1.2)) ml/min/1.73m(2), p < 0.001]. Patients considered fast progressors (> 5 ml/min/1.73 m(2)/year decline in eGFR) were less likely to be older (35.2% young vs. 22.0% older, p < 0.001). Adjusted logistic multivariate regression confirmed that older patients had less odds ratio of eGFR decline, independently of the presence of proteinuria, diabetes, ACEI/ARB use, sex, baseline eGFR, baseline phosphate and baseline 25(OH) vitamin D.ConclusionOlder patients present slower CKD progression even after multiple adjustments. This information should be taken into consideration while treating these patients on conservative management and should be kept in mind while planning dialysis start.
Hepatocyte Nuclear Factor 4 alpha is a novel osteoblast transcription factor that regulates osteogenesis and plays a role in ROD pathogenesis
(2023) MARTINEZ-CALLE, Marta; COURBON, Guillaume; HUNT-TOBEY, Bridget; FRANCIS, Connor; SPINDLER, Jadeah; WANG, Xueyan; REIS, Luciene M. dos; MARTINS, Carolina S. W.; MOYSES, Rosa M. A.; MARTIN, Aline; DAVID, Valentin
Increased Expression of DKK-1 in an Adynamic Bone Disease Model: Role of Phosphate
(2023) TRUYTS, Tania; FERREIRA, Juliana; NEVES, Katia; OLIVEIRA, Ivone; DOMINGUEZ, Wagner; JORGETTI, Vanda; MOYSES, Rosa; REIS, Luciene dos
Chronic Kidney Disease-Associated Frailty is characterized by changes in Muscular Expression of RANKL and FNDC5, which are partially reverted after Parathyroidectomy
(2023) DUQUE, Eduardo J.; CRISPILHO, Shirley; OLIVEIRA, Ivone B.; REIS, Luciene M. dos; FURUKAWA, Luzia; TAKAYAMA, Liliam; PEREIRA, Rosa M.; SHINJO, Samuel K.; AVESANI, Carla; JORGETTI, Vanda; ELIAS, Rosilene M.; MOYSES, Rosa M.
Effect of aluminum accumulation on bone and cardiovascular risk in the current era
(2023) CARBONARA, Cinthia E. M.; ROZA, Noemi A. V.; QUADROS, Kelcia R. S.; FRANCA, Renata A.; ESTEVES, Andre B. A.; PAVAN, Celia R.; BARRETO, Joaquim; REIS, Luciane M. dos; JORGETTI, Vanda; SPOSITO, Andrei C.; OLIVEIRA, Rodrigo Bueno
BackgroundThe prevalence of aluminum (Al) intoxication has declined over the past 3 decades. However, different groups still report on the diagnosis of Al in bone. Prolonged and low-intensity exposures to Al may not be captured by serum Al measurements, preventing its proper diagnosis. We hypothesize that bone Al accumulation may be related to bone and cardiovascular events in the current Era. AimsTo detect the diagnosis of bone Al accumulation; to explore bone and cardiovascular consequences of Al accumulation. MethodsThis is a sub-analysis of The Brazilian Registry of Bone Biopsy, a prospective, multicentre cohort, with a mean follow-up of 3.4 years, including patients with CKD undergoing bone biopsy; bone fracture and major cardiovascular events (MACE) were adjudicated; Al accumulation was identified by solochrome-azurine staining; history of previous Al accumulation was registered based on information provided by the nephrologist who performed the bone biopsy; bone histomorphometry parameters, clinical data, and general biochemistry were registered. Results275 individuals were considered; 96 (35%) patients have diagnosed with bone Al accumulation and were younger [50 (41-56) vs. 55 (43-61) years; p = 0.026], had lower body mass index [23.5 (21.6-25.5) vs. 24.3 (22.1-27.8) kg/m(2); p = 0.017], higher dialysis vintage [108 (48-183) vs. 71 (28-132) months; p = 0.002], presented pruritus [23 (24%) vs. 20 (11%); p = 0.005], tendon rupture [7 (7%) vs. 3 (2%); p = 0.03) and bone pain [2 (0-3) vs. 0 (0-3) units; p = 0.02]. Logistic regression reveals that prior bone Al accumulation [OR: 4.517 (CI: 1.176-17.353); p = 0.03] and dialysis vintage [OR: 1.003 (CI: 1.000-1.007); p = 0.046] as independent determinants of bone Al accumulation; minor perturbations in dynamic bone parameters and no differences in bone fractures rate were noted; MACE was more prevalent in patients with bone Al accumulation [21 (34%) vs. 23 (18%) events; p = 0.016]. Cox regression shows the actual/prior diagnosis of bone Al accumulation and diabetes mellitus as independent predictors for MACE: [HR = 3.129 (CI: 1.439-6.804; p = 0.004) and HR = 2.785 (CI: 1.120-6.928; p = 0.028]. ConclusionsAn elevated proportion of patients have bone Al accumulation, associated with a greater prevalence of bone pain, tendon rupture, and pruritus; bone Al accumulation was associated with minor perturbations in renal osteodystrophy; actual/prior diagnosis of bone Al accumulation and diabetes mellitus were independent predictors for MACE.
Overview of renal osteodystrophy in Brazil: a cross-sectional study
(2023) CARBONARA, Cinthia E. M.; ROZA, Noemi A. V.; REIS, Luciene M. dos; CARVALHO, Aluizio B.; JORGETTI, Vanda; OLIVEIRA, Rodrigo Bueno de
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.