LIM/16 - Laboratório de Fisiopatologia Renal

URI Permanente desta comunidade

https://observatorio.fm.usp.br/handle/OPI/3658
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/

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article 0 Citação(ões) na Scopus
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.
article 1 Citação(ões) na Scopus
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.
article 0 Citação(ões) na Scopus
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.
article 0 Citação(ões) na Scopus
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.
article 1 Citação(ões) na Scopus
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.
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