FC 062OBESITY AS A CAUSE OF KIDNEY DISEASE - INSIGHTS FROM MENDELIAN RANDOMISATION STUDIES

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Xiaoguang Xu ◽  
James Eales ◽  
Xiao Jiang ◽  
Eleanor Sanderson ◽  
David Scannali ◽  
...  
Keyword(s):  
Waist Circumference ◽  
Kidney Disease ◽  
Renal Disease ◽  
Kidney Diseases ◽  
Causal Effects ◽  
Mendelian Randomisation ◽  
Uk Biobank ◽  
Anthropometric Indices ◽  
Health And Disease ◽  
Kidney Health

Abstract Background and Aims Obesity and kidney diseases are common complex disorders with an increasing clinical and economic impact on healthcare around the globe. We aim to examine if modifiable anthropometric indices of obesity exert putatively causal effects on different measures of kidney health and disease. Method We performed conventional observational and Mendelian randomisation (MR) study to examine if modifiable anthropometric indices of obesity exert putatively causal effects on different kidney health and disease-related phenotypes. These analyses were conducted using approximately 300,000 participants of white-British ancestry from UK Biobank and up to 480,000 participants of predominantly European ancestry from genome-wide association studies. Results The Mendelian randomisation analysis indicated that increasing values of genetically predicted BMI and waist circumference were causally linked to changes in renal function indices including reduced estimated glomerular filtration (PeGFRcystatineC=5.96 × 10-59 for BMI and PeGFRcystatineC=1.72 × 10-69 for waist circumference) and increased blood urea nitrogen (PBUN=2.01 × 10-10 for BMI and PBUN=4.54 × 10-12 for waist circumference) in UK Biobank individuals. These associations were replicated using data from CKDGen Consortium individuals (PeGFRcystatineC=1.47 × 10-5 for BMI and PeGFRcystatineC=7.63 × 10-5 for waist circumference; PBUN=1.96 × 10-4 for BMI and PBUN=3.10 × 10-3 for waist circumference). One standard deviation increase in genetically-predicted BMI and waist circumference decreased the relative odds of kidney health index by 14% and 18% (OR=0.86; 95%CI: 0.82-0.92; P=9.18 × 10-6 for BMI and OR=0.82; 95%CI: 0.75-0.90; P=2.12 × 10-5 for waist circumference). Approximately 13-16% of the causal effect of obesity indices on kidney health was mediated by blood pressure. Obesity increased the risk of both acute and chronic kidney disease of several aetiologies including hypertensive renal disease (OR=1.79; 95%CI: 1.14-2.82; P=1.15 × 10-2 for BMI and OR=2.41; 95%CI: 1.30-4.45; P=5.03 × 10-3 for waist circumference), renal failure (OR=1.51; 95%CI: 1.25-1.83; P=2.60 × 10-5 for BMI and OR=1.86; 95%CI: 1.43-2.42; P=4.16 × 10-6 for waist circumference) and CKD (OR=1.50; 95%CI: 1.16-1.96; P=2.44 × 10-3 for BMI and OR=1.83; 95%CI: 1.28-2.63; P=9.49 × 10-4 for waist circumference) and diabetic nephropathy (OR=1.92; 95%CI: 1.44-2.54; P=6.86 × 10-6 for BMI). Conclusion These findings indicate that obesity is causally linked to indices of renal health and the risk of different kidney diseases. This evidence substantiates the value of weight loss as a strategy of preventing and/or counteracting a decline in kidney health as well as decreasing the risk of renal disease.

scholarly journals Obesity as a cause of kidney disease - insights from Mendelian randomisation studies

2020 ◽  
Author(s):  
Xiaoguang Xu ◽  
James M. Eales ◽  
Xiao Jiang ◽  
Eleanor Sanderson ◽  
David Scannali ◽  
...  
Keyword(s):  
Waist Circumference ◽  
Kidney Disease ◽  
Renal Disease ◽  
Association Studies ◽  
Mendelian Randomisation ◽  
Genome Wide Association Studies ◽  
Uk Biobank ◽  
Health Index ◽  
Genome Wide ◽  
Kidney Health

Objective: To examine if modifiable anthropometric indices of obesity exert putatively causal effects on different measures of kidney health and disease. Design: Conventional observational and Mendelian randomisation study. Setting: UK Biobank and international genome-wide association studies. Participants: Approximately 300,000 participants of white-British ancestry from UK Biobank and up to 480,000 participants of predominantly European ancestry from genome-wide association studies. Main outcome measures: Estimated glomerular filtration, blood urea nitrogen, kidney health index, chronic kidney disease, hypertensive renal disease, renal failure, acute renal failure, other disorders of kidney and ureters, IgA nephropathy and diabetic nephropathy. Results: The Mendelian randomisation analysis indicated that increasing values of genetically predicted body mass index (BMI) and waist circumference were causally linked to changes in renal function indices including reduced estimated glomerular filtration and increased blood urea nitrogen in UK Biobank individuals. These associations were replicated using data from CKDGen Consortium individuals. One standard deviation increase in genetically-predicted BMI and waist circumference decreased the relative odds of kidney health index by 14% and 18% (OR=0·86 ; 95%CI: 0·82-0·92 ; P=9·18×10-6 for BMI and OR=0·82 ; 95%CI: 0·75-0·90 ; P=2·12×10-5 for waist circumference, respectively). Approximately 13-16% of the causal effect of obesity indices on kidney health was mediated by blood pressure. Obesity increased the risk of both acute and chronic kidney disease of several aetiologies including hypertensive renal disease and diabetic nephropathy. Conclusions: These findings indicate that obesity is causally linked to indices of renal health and the risk of different kidney diseases. This evidence substantiates the value of weight loss as a strategy of preventing and/or counteracting a decline in kidney health as well as decreasing the risk of renal disease.

Stroke in chronic renal failure

2008 ◽  
Vol 149 (15) ◽  
pp. 691-696
Author(s):  
Dániel Bereczki
Keyword(s):  
Risk Factors ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Renal Disease ◽  
Chronic Renal Disease ◽  
Kidney Diseases ◽  
Cerebrovascular Diseases ◽  
Lipid Lowering ◽  
Increased Risk ◽  
Intracerebral Hemorrhages

Chronic kidney diseases and cardiovascular diseases have several common risk factors like hypertension and diabetes. In chronic renal disease stroke risk is several times higher than in the average population. The combination of classical risk factors and those characteristic of chronic kidney disease might explain this increased risk. Among acute cerebrovascular diseases intracerebral hemorrhages are more frequent than in those with normal kidney function. The outcome of stroke is worse in chronic kidney disease. The treatment of stroke (thrombolysis, antiplatelet and anticoagulant treatment, statins, etc.) is an area of clinical research in this patient group. There are no reliable data on the application of thrombolysis in acute stroke in patients with chronic renal disease. Aspirin might be administered. Carefulness, individual considerations and lower doses might be appropriate when using other treatments. The condition of the kidney as well as other associated diseases should be considered during administration of antihypertensive and lipid lowering medications.

MO046NGS PANEL PERFORMANCE IN THE DIAGNOSIS OF HEREDITARY RENAL DISEASE IN SOUTHERN SPAIN

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
María del Mar Del Águila García ◽  
Antonio M Poyatos Andújar ◽  
Ana Isabel Morales García ◽  
Margarita Martínez Atienza ◽  
Susana García Linares ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Renal Disease ◽  
Polycystic Kidney Disease ◽  
Genetic Study ◽  
Alport Syndrome ◽  
Autosomal Dominant ◽  
Kidney Diseases ◽  
Polycystic Kidney ◽  
Autosomal Dominant Polycystic Kidney ◽  
Hereditary Renal Disease

Abstract Background and Aims Hereditary renal disease (HRD) is still underdiagnosed: although we know aspects related to autosomal dominant polycystic kidney disease (ADPKD), we know little about the incidence and prevalence of other entities such as Alport syndrome. Altogether, HRD can represent 15% of individuals undergoing renal replacement therapy (RRT) or could even be higher. The advancement of genetics at the healthcare level let to achieve accurate and early renal diagnoses, as well as the incorporation of genetic counseling to families, all of which will result in better management of the disease in its initial stages and the possibility of offering reproductive options that avoid transmission to offspring. Our objective is to know the performance offered by the implementation of the ERH panel through Next Generation Sequencing (NGS) in our healthcare area. Method Observational-descriptive study of 259 probands (141 men / 118 women), mean age of 46 years (30 pediatric / 123 over 50 years), with chronic kidney disease and suspected hereditary cause attended in the specialized consultation of our centers from October 2018 to October 2020. The DNA extracted from leukocytes obtained by venipuncture was processed with Nephropathies Solution version 3 panel (SOPHiA Genetics) according to the manufacturer's protocol. This panel covers the coding regions and splicing junctions of 44 HRD-related genes such as nephrotic syndromes, polycystic kidney diseases, Bartter syndromes, Alport syndrome, CAKUT or tubulopathies (table 1). The sequencing of the libraries was done in a MiSeq (Illumina Inc), the bioinformatic analysis of the data and annotation of variants was performed using the SOPHiA DDM 5.8.0.3 software, and the revision of variants by consulting the main databases (ClinVar, Exac, HGMD, NCBI, PKD Foundation, LOVD). Results The panel was informative (pathogenic or probably pathogenic) in 80/259 patients (31%) and 56/259 cases (21.66%) of variants of uncertain significance (VSI) were detected. Autosomal dominant polycystic kidney disease accounted for 76.2% of the variants identified (56.2% PKD1, 20% PKD2), following Alport syndrome with 15% and the alterations in the PKHD1 gene associated with renal polycystic disease in its recessive form with about 4% (Figure 1). We have also identified a case of autosomal dominant tubulointerstitial kidney disease associated with the UMOD gene that was not suspected until the genetic study was performed. We highlight that 45% (36/80) of the variants identified as responsible for the renal disease are not yet described. Overall, the most prevalent type of mutation is that which produces displacement in the reading frame or frameshift (Figure 2). Individually, frameshift is the most frequent alteration in PKD1, PKD2 and COL4A5, while for PKHD1, COL4A3 and COL4A4 it is missense. Conclusion Our NGS HRD panel a) offers an adequate diagnostic performance at the healthcare level, with definitive results in 1 out of 3 cases and has also allowed the performance of many carrier studies among family members b) is able of diagnosing the most frequent disease, ADPKD and Alport syndrome, as well as unresolved or poorly characterized cases, and c) opens the horizon for new diagnoses, all without increasing costs by outsourcing services. All this makes the genetic study of renal pathology a useful and efficient strategy. These results encourage us to enhance the resources in this area that we consider to be of strategic value.

scholarly journals Human podocyte depletion in association with older age and hypertension

2016 ◽  
Vol 310 (7) ◽  
pp. F656-F668 ◽  
Author(s):  
Victor G. Puelles ◽  
Luise A. Cullen-McEwen ◽  
Georgina E. Taylor ◽  
Jinhua Li ◽  
Michael D. Hughson ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Renal Disease ◽  
Kidney Diseases ◽  
Demographic Data ◽  
Older Age ◽  
Glomerular Hypertrophy ◽  
Caucasian American ◽  
White American ◽  
Podocyte Loss ◽  
Inner Cortex

Podocyte depletion plays a major role in the development and progression of glomerulosclerosis. Many kidney diseases are more common in older age and often coexist with hypertension. We hypothesized that podocyte depletion develops in association with older age and is exacerbated by hypertension. Kidneys from 19 adult Caucasian American males without overt renal disease were collected at autopsy in Mississippi. Demographic data were obtained from medical and autopsy records. Subjects were categorized by age and hypertension as potential independent and additive contributors to podocyte depletion. Design-based stereology was used to estimate individual glomerular volume and total podocyte number per glomerulus, which allowed the calculation of podocyte density (number per volume). Podocyte depletion was defined as a reduction in podocyte number (absolute depletion) or podocyte density (relative depletion). The cortical location of glomeruli (outer or inner cortex) and presence of parietal podocytes were also recorded. Older age was an independent contributor to both absolute and relative podocyte depletion, featuring glomerular hypertrophy, podocyte loss, and thus reduced podocyte density. Hypertension was an independent contributor to relative podocyte depletion by exacerbating glomerular hypertrophy, mostly in glomeruli from the inner cortex. However, hypertension was not associated with podocyte loss. Absolute and relative podocyte depletion were exacerbated by the combination of older age and hypertension. The proportion of glomeruli with parietal podocytes increased with age but not with hypertension alone. These findings demonstrate that older age and hypertension are independent and additive contributors to podocyte depletion in white American men without kidney disease.

scholarly journals Polynomial Mendelian Randomization reveals widespread non-linear causal effects in the UK Biobank

2021 ◽  
Author(s):  
Jonathan Sulc ◽  
Jenny Sjaarda ◽  
Zoltan Kutalik
Keyword(s):  
Causal Inference ◽  
Large Scale ◽  
Causal Effect ◽  
Causal Effects ◽  
Mendelian Randomisation ◽  
Uk Biobank ◽  
Individual Level ◽  
Glucose Levels ◽  
Causal Function ◽  
The Uk

Causal inference is a critical step in improving our understanding of biological processes and Mendelian randomisation (MR) has emerged as one of the foremost methods to efficiently interrogate diverse hypotheses using large-scale, observational data from biobanks. Although many extensions have been developed to address the three core assumptions of MR-based causal inference (relevance, exclusion restriction, and exchangeability), most approaches implicitly assume that any putative causal effect is linear. Here we propose PolyMR, an MR-based method which provides a polynomial approximation of an (arbitrary) causal function between an exposure and an outcome. We show that this method provides accurate inference of the shape and magnitude of causal functions with greater accuracy than existing methods. We applied this method to data from the UK Biobank, testing for effects between anthropometric traits and continuous health-related phenotypes and found most of these (84%) to have causal effects which deviate significantly from linear. These deviations ranged from slight attenuation at the extremes of the exposure distribution, to large changes in the magnitude of the effect across the range of the exposure (e.g. a 1 kg/m2 change in BMI having stronger effects on glucose levels if the initial BMI was higher), to non-monotonic causal relationships (e.g. the effects of BMI on cholesterol forming an inverted U shape). Finally, we show that the linearity assumption of the causal effect may lead to the misinterpretation of health risks at the individual level or heterogeneous effect estimates when using cohorts with differing average exposure levels.

scholarly journals World Kidney Day 2021 with the theme of living well with kidney disease; a review of current concepts

2021 ◽  
Vol 6 (1) ◽  
pp. e08-e08
Author(s):  
Mohammad Bahadoram ◽  
Saeede Labaykee ◽  
Bhaskar VKS Lakkakula ◽  
Bijan Keikhaei ◽  
Mitra Nekouei Shahraki ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Kidney Diseases ◽  
Steering Committee ◽  
International Federation ◽  
One Dimension ◽  
Global Awareness ◽  
Awareness Campaign ◽  
Living Well ◽  
Care Partners ◽  
Kidney Health

Since 2006, by considering one dimension of kidney disease, each year, the International Society of Nephrology (ISN) and the International Federation of Kidney Foundations (IFKF) have consistently and unanimously declared a World Kidney Day (WKD) around a specific kidney disease to increase the global awareness about kidney diseases. WKD, which is celebrated in more than 150 countries worldwide, is an international kidney health awareness campaign emphasizing the importance of the kidneys to reduce the global prevalence of kidney diseases and their related health problems by promoting patients and providing education. The present review aims to summarize the themes of previous WKD campaigns and the advocacy of the 2021 WKD campaign theme "Living well with kidney disease". The 2021 WKD Steering Committee advocates for the empowerment of CKD patients, their family members, and care partners, along with both drug and non-drug therapeutic programs to achieve better health outcomes.

scholarly journals B-mode gray-scale ultrasound abnormalities in adult patients: A useful tool in diagnosis of kidney diseases

2021 ◽  
Vol 11 (3) ◽  
pp. 97-102
Author(s):  
Kamel El-Reshaid
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Renal Disease ◽  
Kidney Diseases ◽  
Obstructive Uropathy ◽  
Reflux Nephropathy ◽  
Review Article ◽  
Renal Infarction ◽  
Ultrasound Scanning ◽  
Disease Prognosis

Ultrasound scanning of the urogenital tract has a pivotal role in revealing most etiologies of renal disease.  Moreover, it is also of value in assessment of disease prognosis and its progression.  In this review article, details of the examination technique, ultrasonic kidney norms and the clinicoradiological correlation regarding acute and chronic kidney disease are presented.  Specific characteristics of diseases viz. acute and chronic glomerulopathy, diabetes, amyloidosis, chronic reflux nephropathy, Nephroangiosclerosis, vasculitis, nephrocalcinosis, cystic diseases of the kidney, renal infarction and obstructive uropathy are presented. Keywords: acute, chronic, diagnosis, diseases, ultrasound, kidney.

What We Do and Do Not Know about Women and Kidney Diseases; Questions Unanswered and Answers Unquestioned: Reflection on World Kidney Day and International Woman’s Day

2018 ◽  
Vol 45 (4) ◽  
pp. 364-375 ◽  
Author(s):  
Giorgina B. Piccoli ◽  
Mona Alrukhaimi ◽  
Zhi-Hong Liu ◽  
Elena Zakharova ◽  
Adeera Levin ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Causes Of Death ◽  
Kidney Diseases ◽  
Adult Population ◽  
Future Generations ◽  
Access To Education ◽  
Chronic Kidney Diseases ◽  
Child Bearing ◽  
Education Medical ◽  
Kidney Health

Chronic kidney disease affects approximately 10% of the world’s adult population: it is within the top 20 causes of death worldwide, and its impact on patients and their families can be devastating. World Kidney Day and International Women’s Day in 2018 coincide, thus offering an opportunity to reflect on the importance of women’s health and specifically their kidney health, on the community and the next generations, as well as to strive to be more curious about the unique aspects of kidney disease in women so that we may apply those learnings more broadly. Girls and women, who make up approximately 50% of the world’s population, are important contributors to society and their families. Gender differences continue to exist around the world in access to education, medical care, and participation in clinical studies. Pregnancy is a unique state for women, offering an opportunity for diagnosis of kidney disease, but also a state where acute and chronic kidney diseases may manifest, and which may impact future generations with respect to kidney health. There are various autoimmune and other conditions that are more likely to have an impact on women, with profound consequences for child bearing, and on the fetus. Women have different complications on dialysis than men, and are more likely to be donors than recipients of kidney transplants. In this editorial, we focus on what we do and do not know about women, kidney health, and kidney disease, and what we might learn in the future to improve outcomes worldwide.

scholarly journals An examination of multivariable Mendelian randomization in the single sample and two-sample summary data settings

2018 ◽  
Author(s):  
Eleanor Sanderson ◽  
George Davey Smith ◽  
Frank Windmeijer ◽  
Jack Bowden
Keyword(s):  
Mendelian Randomization ◽  
Causal Effect ◽  
Causal Effects ◽  
Single Sample ◽  
Mendelian Randomisation ◽  
Uk Biobank ◽  
Level Data ◽  
Wide Range ◽  
Using Data ◽  
Summary Data

AbstractBackgroundMendelian Randomisation (MR) is a powerful tool in epidemiology which can be used to estimate the causal effect of an exposure on an outcome in the presence of unobserved confounding, by utilising genetic variants that are instrumental variables (IVs) for the exposure. This has been extended to Multivariable MR (MVMR) to estimate the effect of two or more exposures on an outcome.Methods/ResultsWe use simulations and theory to clarify the interpretation of estimated effects in a MVMR analysis under a range of underlying scenarios, where a secondary exposure acts variously as a confounder, a mediator, a pleiotropic pathway and a collider. We then describe how instrument strength and validity can be assessed for an MVMR analysis in the single sample setting, and develop tests to assess these assumptions in the popular two-sample summary data setting. We illustrate our methods using data from UK biobank to estimate the effect of education and cognitive ability on body mass index.ConclusionMVMR analysis consistently estimates the effect of an exposure, or exposures, of interest and provides a powerful tool for determining causal effects in a wide range of scenarios with either individual or summary level data.

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