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 ◽  
...  

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.

2008 ◽  
Vol 149 (15) ◽  
pp. 691-696
Author(s):  
Dániel Bereczki

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.


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 ◽  
...  

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.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Xiaoguang Xu ◽  
James Eales ◽  
Xiao Jiang ◽  
Eleanor Sanderson ◽  
David Scannali ◽  
...  

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.


2020 ◽  
Vol 5 (1) ◽  
pp. e10-e10
Author(s):  
Zebunnesa Zeba ◽  
Kaniz Fatema ◽  
Ahmed Faisal Sumit ◽  
Rahelee Zinnat ◽  
Liaquat Ali

Introduction: Early identification of chronic kidney disease (CKD) provides valuable opportunities for effective interventions that reduce the risk of outcomes, particularly renal failure. Objectives: This study aimed to screen the Bangladeshi asymptomatic adult population for CKD to identify potential risk factors for its development. Patients and Methods: The screening program was carried out among the 400 subjects in the Thakurgaon district of Bangladesh to identify people with the risk of CKD. All the subjects were asymptomatic and previously been never diagnosed with kidney diseases. Demographic data were collected by a structured questionnaire. Urinary protein was tested by dipstick method, and serum creatinine was measured by an auto-analyzer. Estimated glomerular filtration rate (eGFR) was calculated by using standard formula. CKD was diagnosed and classified according to the National Kidney Foundation (NKF) Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines. Results: A total of 18.2% respondents were found to have likely CKD to whom 82% were in stage 1 and 18% were in stage 2. The majority of the likely CKD respondents (30.1%) were in age >60 years. The prevalence of proteinuria was significantly (P=0.0001) higher among previously documented CKD patients compared to the control group. Logistic analysis revealed that after adjustments, CKD showed a significant association with diabetes mellitus (ORs: 7.46, P=0.00), smoking (ORs: 2.36, P=0.02), obesity (ORs: 3.98, P=0.00) and hypertension (ORs: 1.16, P=0.66) compared to control. Conclusion: A substantial number of adults were found to be unaware of the existence of CKD hence, large-scale prevention programs should be undertaken to reduce the classical risk factors of these disorders.


2021 ◽  
Vol 11 (3) ◽  
pp. 97-102
Author(s):  
Kamel El-Reshaid

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.


2018 ◽  
Vol 49 (3) ◽  
pp. 998-1009 ◽  
Author(s):  
Niki Prakoura ◽  
Panagiotis Kavvadas ◽  
Christos E.  Chadjichristos

Chronic kidney disease is an incurable to date pathology with a continuously growing incidence that contributes to the increase of the number of deaths worldwide. With currently no efficient prognostic or therapeutic options being available, the only possibility for treatment of end-stage renal disease is renal replacement therapy through dialysis or transplantation. Understanding the molecular mechanisms participating in the progression of renal diseases and uncovering the pathways implicated will permit the identification of novel and more efficient targets of therapy. Connexin43 was recently identified as a novel player in the development of chronic kidney disease. It was found de novo expressed and/or differentially localized in various renal cell populations during progression of renal disease, indicating an abnormal connexin signaling, both in patients and animal models. Subsequent in vivo studies demonstrated that connexin43 is involved in mediating inflammatory and fibrotic processes contributing to renal damage. Genetic, pharmaco-genetic or peptide-based inhibition of connexin43 in animal models and cell culture systems was successful in preventing the progression of the pathology and preserving the cell phenotypes. This review will summarize the recent advances on connexin43 in the field of kidney diseases and discuss the potential of future connexin43-based therapies against chronic kidney disease.


2017 ◽  
Vol 7 (1) ◽  
pp. 26-32
Author(s):  
Ranjit Ranjan Roy ◽  
Abdullah Al Mamun ◽  
M Abdul Matin ◽  
Md Rafiqul Islam

Background: Bangladesh is a small country of south Asia with a population of 153 million, among them 66 million are under age of 18years. The exact prevalence of chronic kidney disease (CKD) in children is not well known due to lack of a national registry. But in Bangabandhu sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh, the incidence is 7.9% in 2013 and there are approximately thirty five hundred thousand around the country. There are 4.4% of children with renal disease prevalent in the country. But unfortunately, there is diagnostic problem and the treatment facility is very limited. Only few centers provide the renal replacement therapy in this country and only two centers do pediatric renal transplantation. So, to tackle this large burden with very limited resource, it is important to try and reduce the incidence of chronic kidney disease, especially end stage renal disease. We can handle the present situation with our existing resource with some modification of health care delivery system with contribution from government, non government organizations (NGO'S) and affluent people. This article highlights chronic kidney disease in children, present treatment modality and some fiiture directive to handle such a crucial problem, thus may help thousands of children from such a devastating situation.J Shaheed Suhrawardy Med Coll, 2015; 7(1):26-32


Author(s):  
Anqun Chen ◽  
Jin Xu ◽  
Han Lai ◽  
Vivette D D’Agati ◽  
Tian-Jun Guan ◽  
...  

Abstract Background Chronic kidney disease (CKD) is a common cause of morbidity and mortality in human immunodeficiency virus (HIV)-positive individuals. Among the HIV-related kidney diseases, HIV-associated nephropathy (HIVAN) is a rapidly progressive renal disease characterized by collapsing focal glomerulosclerosis (GS), microcystic tubular dilation, interstitial inflammation and fibrosis. Although the incidence of end-stage renal disease due to HIVAN has dramatically decreased with the widespread use of antiretroviral therapy, the prevalence of CKD continues to increase in HIV-positive individuals. Recent studies have highlighted the role of apoptosis signal-regulating kinase 1 (ASK1) in driving kidney disease progression through the activation of p38 mitogen-activated protein kinase and c-Jun N-terminal kinase and selective ASK-1 inhibitor GS-444217 was recently shown to reduce kidney injury and disease progression in various experimental models. Therefore we examined the efficacy of ASK1 antagonism by GS-444217 in the attenuation of HIVAN in Tg26 mice. Methods GS-444217-supplemented rodent chow was administered in Tg26 mice at 4 weeks of age when mild GS and proteinuria were already established. After 6 weeks of treatment, the kidney function assessment and histological analyses were performed and compared between age- and gender-matched control Tg26 and GS-444217-treated Tg26 mice. Results GS-444217 attenuated the development of GS, podocyte loss, tubular injury, interstitial inflammation and renal fibrosis in Tg26 mice. These improvements were accompanied by a marked reduction in albuminuria and improved renal function. Taken together, GS-4442217 attenuated the full spectrum of HIVAN pathology in Tg26 mice. Conclusions ASK1 signaling cascade is central to the development of HIVAN in Tg26 mice. Our results suggest that the select inhibition of ASK1 could be a potential adjunctive therapy for the treatment of HIVAN.


2021 ◽  
Vol 28 (1) ◽  
Author(s):  
Dalia Abdel Moneim Mahmoud ◽  
Ahmed Saad ◽  
Yasmine Hassan Abdelhamid ◽  
Yomna El Hawary

Abstract Background More attention has recently targeted families of children with chronic kidney diseases displaying depressive symptoms and major psychosocial burden due to the long-standing nature of the illness and its alarming complications. A cross sectional comparative study was conducted to assess the rate of occurrence of both depression severity and psychological burden, personal and role strain in a sample of Egyptian caregivers of children with chronic kidney disease. Results Thirty caregivers of children with CKD were enrolled compared to 30 matched controls during a 6-month period. A short pre-designed sheet including socio-demographic data, and general medical, psychiatric and family history was used, and Beck Depression Inventory, Zarit Burden Interview, Holmes and Rahe Socioeconomic Stress Scale, and Occupational Stress Questionnaire were answered. More than half of the caregivers of children with chronic kidney disease reported moderate depression (53.3%), while 30% and 16.7% reported mild and severe depression respectively. The majority of cases 80% had moderate psychological burden. And 70% of cases reported minimal socioeconomic stress compared to 40% in the control. Logistic regression analysis showed that ZBI and SRRS scores were significantly linked to depression and burden found in caregivers of children with CKD (P = 0.001 and 0.031) respectively. Conclusion The rate of occurrence of depression and psychological burden is significantly high in caregivers of children with chronic kidney disease; therefore, this population must be assessed and provided with liaison psychological rehabilitation.


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