Consequences of morbid obesity on the kidney. Where are we going?

Obesity and morbid obesity are modifiable risk factors for the development and progression of kidney disease. Obesity has reached epidemic proportions and is currently an important health problem in Europe, so it is necessary to develop therapeutic and preventive strategies. The obesity-related glomerulopathy has been defined as a secondary form of focal segmental glomerulosclerosis, and its most characteristic feature is glomerulomegaly. The renal evolution of patients with obesity-related glomerulopathy (ORG) who have not been treated is unfavourable. However, morbidly obese patients with ORG that underwent bariatric surgery and drastic weight loss had a better outcome. Many inflammatory factors have been implicated in the pathogenic mechanism of renal disease in obesity. Hypoadiponectinaemia, hyperleptinaemia and hyperaldosteronism have been associated with glomerular injury in obese patients. The application of modern techniques has provided important insights that increase the current understanding of ORG. However, further investigation is needed

Long-Term Normal Renal Function after Drastic Weight Reduction in Patients with Obesity-Related Glomerulopathy

No long-term studies of renal function evolution in morbidly obese (MO) patients after weight loss are available. The aim of our work was to ascertain the long-term influence of drastic weight reduction on renal function in MO patients with obesity-related glomerular lesions. 92 MO patients with normal renal function and biopsy evidence of mild obesity-related glomerulopathy underwent bariatric surgery (BS) and subsequent drastic weight loss. A long-term prospective follow-up (mean duration: 76 ± 42 months) was carried out. Basal renal biopsies and basal and long-term metabolic and renal function studies were performed in all cases. Linear mixed models were applied. Blood pressure dropped early after BS and remained stable thereafter. Creatinine clearance and BMI fell in the first 2 years, rose slightly after 5 years and then remained stable. Serum creatinine and albuminuria decreased throughout the follow-up period. Renal function and albuminuria evolution showed non-significant differences in relation to the number of glomerular lesions. Drastic weight loss in BS-treated MO patients with pre-surgical normal renal function and mild obesity-related glomerular lesions is associated with short- and long-term maintenance of normal renal function and improvement in both arterial hypertension and albuminuria

Measured GFR in murine animal models: review on methods, techniques, and procedures

Animal models; Glomerular filtration rate; Kidney damageModels animals; Taxa de filtració glomerular; Dany renalModelos animales; Tasa de filtración glomerular; Daño renalChronic kidney disease (CKD) is one of the most common chronic diseases worldwide, with increasing rates of morbidity and mortality. Thus, early detection is essential to prevent severe adverse events and the progression of kidney disease to an end stage. Glomerular filtration rate (GFR) is the most appropriate index to evaluate renal function in both clinical practice and basic medical research. Several animal models have been developed to understand renal disease induction and progression. Specifically, murine models are useful to study the pathogenesis of renal damage, so a reliable determination of GFR is essential to evaluate the progression of CKD. However, as in clinical practise, the estimation of GFR in murine by levels of serum/urine creatinine or cystatin-C could not be accurate and needed other more reliable methods. As an alternative, the measurement of GFR by the clearance of exogenous markers like inulin, sinistrin, 51Cr-EDTA, 99mTc-DTPA, 125I-iothalamate, or iohexol could be performed. Nevertheless, both approaches—estimation or measurement of GFR—have their limitations and a standard method for the GFR determination has not been defined. Altogether, in this review, we aim to give an overview of the current methods for GFR assessment in murine models, describing each methodology and focusing on their advantages and limitations.Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This work is supported by funding from the Instituto de Salud Carlos III with the following grants: AERR is a recipient of a contract from the Sara Borrell programme (C21/00142) and STT of PFIS FI20/00147

Immunological Pattern in IgA Nephropathy

The current gold-standard diagnostic technique for IgA nephropathy (IgAN), the leading form of primary glomerulonephritis, is renal biopsy. CD89 (the main IgA receptor) is expressed on the surface of monocytes and plays a role in disease pathogenesis. Immunocomplexes formed by sCD89 (soluble form) and Gd-IgA1 are related to disease prognosis. We hypothesize that reduced CD89 surface expression on monocytes may be a marker of disease severity. We aimed to analyze leukocyte subpopulations in peripheral blood and CD89 surface expression on monocytes in a prospective study of 22 patients and 12 healthy subjects (HS). Leukocyte subpopulations and CD89 expression were analyzed by flow cytometry. IgAN patients had a higher percentage of activated and effector memory CD4 + and CD8 + T lymphocytes, a lower percentage of transitional B lymphocytes and plasmablasts, and a higher percentage of CD56 dim CD16 + NK cells and myeloid dendritic cells compared with HS. Correlations between reduced CD89 expression levels on nonclassical monocytes, histological findings of a poor prognosis on renal biopsy and baseline renal function were observed. IgAN patients show a characteristic immunological pattern in peripheral blood. A reduced expression level of CD89 on nonclassical monocytes identifies patients with a worse renal prognosis

Long-Term Normal Renal Function after Drastic Weight Reduction in Patients with Obesity-Related Glomerulopathy

Aims: No long-term studies of renal function evolution in morbidly obese (MO) patients after weight loss are available. The aim of our work was to ascertain the long-term influence of drastic weight reduction on renal function in MO patients with obesity-related glomerular lesions. Methods: 92 MO patients with normal renal function and biopsy evidence of mild obesity-related glomerulopathy underwent bariatric surgery (BS) and subsequent drastic weight loss. A long-term prospective follow-up (mean duration: 76 ± 42 months) was carried out. Basal renal biopsies and basal and long-term metabolic and renal function studies were performed in all cases. Linear mixed models were applied. Results: Blood pressure dropped early after BS and remained stable thereafter. Creatinine clearance and BMI fell in the first 2 years, rose slightly after 5 years and then remained stable. Serum creatinine and albuminuria decreased throughout the follow-up period. Renal function and albuminuria evolution showed non-significant differences in relation to the number of glomerular lesions. Conclusions: Drastic weight loss in BS-treated MO patients with pre-surgical normal renal function and mild obesity-related glomerular lesions is associated with short- and long-term maintenance of normal renal function and improvement in both arterial hypertension and albuminuria

Integrated miRNA–mRNA Analysis Reveals Critical miRNAs and Targets in Diet-Induced Obesity-Related Glomerulopathy

This study aimed to investigate obesity-related glomerulopathy (ORG) at cellular, structural, and transcriptomic levels. Thirty Wistar rats were randomized into two groups: 15 rats were fed with a standard diet (SD-rats), and 15 rats were fed with a high-fat diet (HFD-rats). After 10 weeks, the weight, kidney function, histological features, and transcriptomic changes were assessed. HFD-rats gained significantly more weight (55.8% vs. 29.2%; p < 0.001) and albuminuria (10,384.04 ng/mL vs. 5845.45 ng/mL; p < 0.001) compared to SD-rats. HFD-rats exhibited early stages of ORG, with predominant mesangial matrix increase and podocyte hypertrophy (PH). These lesions correlated with differentially expressed (DE) genes and miRNAs. Functional analysis showed that miR-205, which was DE in both the kidneys and urine of HFD-rats, negatively regulated the PTEN gene, promoting lipid endocytosis in podocytes. The downregulation of PTEN was proved through a higher PTEN/nephrin ratio in the SD-rats and the presence of lipid vacuoles in HFD-podocytes. This study has found a specific targetome of miRNAs and gene expression in early stages of ORG. Also, it emphasizes the potential value of miR-205 as a urinary biomarker for detecting podocyte injury in ORG, offering a tool for early diagnosis, and opening new avenues for future therapeutic research of obesity-related glomerulopathy

The Role of Vascular Lesions in Diabetes Across a Spectrum of Clinical Kidney Disease

Introduction: The clinical-histologic correlation in diabetic nephropathy is not completely known. Methods: We analyzed nephrectomy specimens from 90 patients with diabetes and diverse degrees of proteinuria and glomerular filtration rate (GFR). Results: Thirty-six (40%) subjects had normoalbuminuria, 33 (37%) microalbuminuria, and 21 (23%) non-nephrotic proteinuria. Mean estimated GFR (eGFR) was 65±23 (40% 10% to 20% of the sample. Moderate hyalinosis and arteriolar sclerosis were observed in 80% to 100% of cases with normoalbuminuria, microalbuminuria, proteinuria, as well as in class I, II, or III. Conclusions: Weak correspondence between analytical parameters and kidney histology was found. Thus, disease may progress undetected from the early clinical stages of the disease. Finally, vascular damage was a very common finding, which highlights the role of ischemic intrarenal disease in diabetes

Risk factors for non-diabetic renal disease in diabetic patients

Background. Diabetic patients with kidney disease have a high prevalence of non-diabetic renal disease (NDRD). Renal and patient survival regarding the diagnosis of diabetic nephropathy (DN) or NDRD have not been widely studied. The aim of our study is to evaluate the prevalence of NDRD in patients with diabetes and to determine the capacity of clinical and analytical data in the prediction of NDRD. In addition, we will study renal and patient prognosis according to the renal biopsy findings in patients with diabetes. Methods. Retrospective multicentre observational study of renal biopsies performed in patients with diabetes from 2002 to 2014. Results. In total, 832 patients were included: 621 men (74.6%), mean age of 61.7 6 12.8 years, creatinine was 2.8 6 2.2 mg/dL and proteinuria 2.7 (interquartile range: 1.2–5.4) g/24 h. About 39.5% (n ¼ 329) of patients had DN, 49.6% (n ¼ 413) NDRD and 10.8% (n ¼ 90) mixed forms. The most frequent NDRD was nephroangiosclerosis (NAS) (n ¼ 87, 9.3%). In the multivariate logistic regression analysis, older age [odds ratio (OR) ¼ 1.03, 95% CI: 1.02–1.05, P < 0.001], microhaematuria (OR ¼ 1.51, 95% CI: 1.03–2.21, P ¼ 0.033) and absence of diabetic retinopathy (DR) (OR ¼ 0.28, 95% CI: 0.19–0.42, P < 0.001) were independently associated with NDRD. Kaplan–Meier analysis showed that patients with DN or mixed forms presented worse renal prognosis than NDRD (P < 0.001) and higher mortality (P ¼ 0.029). In multivariate Cox analyses, older age (P < 0.001), higher serum creatinine (P < 0.001), higher proteinuria (P < 0.001), DR (P ¼ 0.007) and DN (P < 0.001) were independent risk factors for renal replacement therapy. In addition, older age (P < 0.001), peripheral vascular disease (P ¼ 0.002), higher creatinine (P ¼ 0.01) and DN (P ¼ 0.015) were independent risk factors for mortality. Conclusions. The most frequent cause of NDRD is NAS. Elderly patients with microhaematuria and the absence of DR are the ones at risk for NDRD. Patients with DN presented worse renal prognosis and higher mortality than those with NDRD. These results suggest that in some patients with diabetes, kidney biopsy may be useful for an accurate renal diagnosis and subsequently treatment and prognosis

1er. Coloquio de educación para el diseño en la sociedad 5.0

Las memorias del 1er. Coloquio de Educación para el Diseño en la Sociedad 5.0 debenser entendidas como un esfuerzo colectivo de la comunidad de académicos de la División de Ciencias y Artes para el Diseño, que pone de manifiesto los retos y oportunidades que enfrenta la educación en diseño en un contexto de cambio acelerado y rompimiento de paradigmas.El evento se realizó el pasado mes de mayo de 2018 y se recibieron más de 50 ponencias por parte de las profesoras y profesores de la División.Las experiencias y/o propuestas innovadoras en cuanto a procesos de enseñanza y aprendizaje que presentan los autores en cada uno de sus textos son una invitación a reflexionar sobre nuestra situación actual en la materia, y emprender acciones en la División para continuar brindando una educación de calidad en diseño a nuestras alumnas, alumnos y la sociedad.Adicionalmente, se organizaron tres conferencias magistrales sobre la situación actual de la educación en Diseño y de las Instituciones de Educación Superior, impartidas por el Mtro. Luis Sarale, profesor de la Universidad Nacional de Cuyo en Mendoza (Argentina), y Presidente en su momento, de la Red de Carreras de Diseño en Universidades Públicas Latinoamericanas (DISUR), el Dr. Romualdo López Zárate, Rector de la Unidad Azcapotzalco, así como del Mtro. Luis Antonio Rivera Díaz, Jefe de Departamento de Teoría y Procesos del Diseño de la División de la Ciencias de la Comunicación y Diseño, en la Unidad Cuajimalpa de nuestra institución.La publicación de estas memorias son un esfuerzo divisional, organizado desde la Coordinación de Docencia Divisional y la Coordinación de Tecnologías del Aprendizaje, del Conocimiento y la Comunicación, para contribuir a los objetivos planteados en el documento ACCIONES:Agenda CyAD2021, en particular al eje de Innovación Educativa. Es necesario impulsar a todos los niveles de la División espacios de discusión orientados a reflexionar sobre el presente y futuro en la educación del diseñador, que contribuya a mejorar la calidad de la docencia y favorezca al fortalecimiento de los procesos de enseñanza y aprendizaje.Finalmente, extiendo un amplio reconocimiento a todos los miembros de la División que hicieron posible este evento, así como a todos los ponentes y participantes por compartir su conocimiento para que la División sea cada día mejor

Consequences of morbid obesity on the kidney. Where are we going?

Obesity and morbid obesity are modifiable risk factors for the development and progression of kidney disease. Obesity has reached epidemic proportions and is currently an important health problem in Europe, so it is necessary to develop therapeutic and preventive strategies. The obesity-related glomerulopathy has been defined as a secondary form of focal segmental glomerulosclerosis, and its most characteristic feature is glomerulomegaly. The renal evolution of patients with obesity-related glomerulopathy (ORG) who have not been treated is unfavourable. However, morbidly obese patients with ORG that underwent bariatric surgery and drastic weight loss had a better outcome. Many inflammatory factors have been implicated in the pathogenic mechanism of renal disease in obesity. Hypoadiponectinaemia, hyperleptinaemia and hyperaldosteronism have been associated with glomerular injury in obese patients. The application of modern techniques has provided important insights that increase the current understanding of ORG. However, further investigation is needed