Adipokines as a link between obesity and chronic kidney disease

Adipocytes secrete a number of bioactive adipokines that activate a variety of cell signaling pathways in central and peripheral tissues. Obesity is associated with the altered production of many adipokines and is linked to a number of pathologies. As an increase in body weight is directly associated with an increased risk for developing chronic kidney disease (CKD), there is significant interest in the link between obesity and renal dysfunction. Altered levels of the adipokines leptin, adiponectin, resistin, and visfatin can decrease the glomerular filtration rate and increase albuminuria, which are pathophysiological changes typical of CKD. Specifically, exposure of the glomerulus to altered adipokine levels can increase its permeability, fuse the podocytes, and cause mesangial cell hypertrophy, all of which alter the glomerular filtration rate. In addition, the adipokines leptin and adiponectin can act on tubular networks. Thus, adipokines can act on multiple cell types in the development of renal pathophysiology. Importantly, most studies have been performed using in vitro models, with future studies in vivo required to further elucidate the specific roles that adipokines play in the development and progression of CKD.

Download Full-text

Soluble Fas affects erythropoiesis in vitro and acts as a potential predictor of erythropoiesis-stimulating agent therapy in patients with chronic kidney disease

AJP Renal Physiology ◽

10.1152/ajprenal.00433.2019 ◽

2020 ◽

Vol 318 (4) ◽

pp. F861-F869

Author(s):

Daniela Mendes Chiloff ◽

Danilo Candido de Almeida ◽

Maria A. Dalboni ◽

Maria Eugênia Canziani ◽

Sunil K. George ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Glomerular Filtration Rate ◽

Kidney Disease ◽

Glomerular Filtration ◽

Filtration Rate ◽

Dependent Manner ◽

Potential Predictor ◽

Soluble Fas ◽

Esa Therapy

Serum soluble Fas (sFas) levels are associated with erythropoietin (Epo) hyporesponsiveness in patients with chronic kidney disease (CKD). Whether sFas could predict the need for erythropoiesis-stimulating agent (ESA) usage and its influence in erythropoiesis remain unclear. We evaluated the relation between sFas and ESA therapy in patients with CKD with anemia and its effect on erythropoiesis in vitro. First, we performed a retrospective cohort study with 77 anemic patients with nondialysis CKD. We performed in vitro experiments to investigate whether sFas could interfere with the behavior of hematopoietic stem cells (HSCs). HSCs were isolated from umbilical cord blood and incubated with recombinant sFas protein in a dose-dependent manner. Serum sFas positively correlated with Epo levels ( r = 0.30, P = 0.001) but negatively with hemoglobin ( r = −0.55, P < 0.001) and glomerular filtration rate ( r = −0.58, P < 0.001) in patients with CKD at baseline. Elevated sFas serum levels (4,316 ± 897 vs. 2,776 ± 749, P < 0.001) with lower estimated glomerular filtration rate (26.2 ± 10.1 vs. 33.5 ± 14.3, P = 0.01) and reduced hemoglobin concentration (11.1 ± 0.9 vs. 12.5 ± 1.2, P < 0.001) were identified in patients who required ESA therapy compared with patients with non-ESA. Afterward, we detected that the sFas level was slight correlated with a necessity of ESA therapy in patients with nondialysis CKD and anemia. In vitro assays demonstrated that the erythroid progenitor cell frequency negatively correlated with sFas concentration ( r = −0.72, P < 0.001). There was decreased erythroid colony formation in vitro when CD34+ HSCs were incubated with a higher concentration of sFas protein (1.56 ± 0.29, 4.33 ± 0.53, P < 0.001). Our findings suggest that sFas is a potential predictor for ESA therapy in patients with nondialysis CKD and that elevated sFas could affect erythropoiesis in vitro.

Download Full-text

Providing Care for Transgender Persons With Kidney Disease: A Narrative Review

Canadian Journal of Kidney Health and Disease ◽

10.1177/2054358120985379 ◽

2021 ◽

Vol 8 ◽

pp. 205435812098537

Author(s):

David Collister ◽

Nathalie Saad ◽

Emily Christie ◽

Sofia Ahmed

Keyword(s):

Cardiovascular Disease ◽

Chronic Kidney Disease ◽

Glomerular Filtration Rate ◽

Kidney Disease ◽

Hormone Therapy ◽

Glomerular Filtration ◽

Filtration Rate ◽

Transgender Persons ◽

Increased Risk ◽

The Impact

Purpose of review: Nephrologists are increasingly providing care to transgender individuals with chronic kidney disease (CKD). However, they may lack familiarity with this patient population that faces unique challenges. The purpose of this review is to discuss the care of transgender persons and what nephrologists should be aware of when providing care to their transgender patients. Sources of information: Original research articles were identified from MEDLINE and Google Scholar using the search terms “transgender,” “gender,” “sex,” “chronic kidney disease,” “end stage kidney disease,” “dialysis,” “transplant,” and “nephrology.” Methods: A focused review and critical appraisal of existing literature regarding the provision of care to transgender men and women with CKD including dialysis and transplant to identify specific issues related to gender-affirming therapy and chronic disease management in transgender persons. Key findings: Transgender persons are at an increased risk of adverse outcomes compared with the cisgender population including mental health, cardiovascular disease, malignancy, sexually transmitted infections, and mortality. Individuals with CKD have a degree of hypogonadotropic hypogonadism and decreased levels of endogenous sex hormones; therefore, transgender persons with CKD may require reduced exogenous sex hormone dosing. Exogenous estradiol therapy increases the risk of venous thromboembolism and cardiovascular disease which may be further increased in CKD. Exogenous testosterone therapy increases the risk of polycythemia which should be closely monitored. The impact of gender-affirming hormone therapy on glomerular filtration rate (GFR) trajectory in CKD is unclear. Gender-affirming hormone therapy with testosterone, estradiol, and anti-androgen therapies changes body composition and lean body mass which influences creatinine generation and the performance for estimated glomerular filtration rate (eGFR) equations in transgender persons. Confirmation of eGFR with measured GFR is reasonable if an accurate knowledge of GFR is needed for clinical decision-making. Limitations: There are limited studies regarding the intersection of transgender persons and kidney disease and those that exist are mostly case reports. Randomized controlled trials and observational studies in nephrology do not routinely differentiate between cisgender and transgender participants. Implications: This review highlights important considerations for providing care to transgender persons with kidney disease. Additional research is needed to evaluate the performance of eGFR equations in transgender persons, the effects of gender-affirming hormone therapy, and the impact of being transgender on outcomes in persons with kidney disease.

Download Full-text

Beyond the tubule: pathological variants of LRP2, encoding the megalin receptor, result in glomerular loss and early progressive chronic kidney disease

AJP Renal Physiology ◽

10.1152/ajprenal.00295.2020 ◽

2020 ◽

Vol 319 (6) ◽

pp. F988-F999

Author(s):

Jennifer R. Charlton ◽

Weizhen Tan ◽

Ghaleb Daouk ◽

Lisa Teot ◽

Seymour Rosen ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Glomerular Filtration Rate ◽

Kidney Disease ◽

Glomerular Filtration ◽

Filtration Rate ◽

Kidney Injury ◽

Glomerular Proteinuria ◽

Increased Risk ◽

Kidney Injury Molecule 1 ◽

Deficient Mice

Pathogenic variants in the LRP2 gene, encoding the multiligand receptor megalin, cause a rare autosomal recessive syndrome: Donnai-Barrow/Facio-Oculo-Acoustico-Renal (DB/FOAR) syndrome. Because of the rarity of the syndrome, the long-term consequences of the tubulopathy on human renal health have been difficult to ascertain, and the human clinical condition has hitherto been characterized as a benign tubular condition with asymptomatic low-molecular-weight proteinuria. We investigated renal function and morphology in a murine model of DB/FOAR syndrome and in patients with DB/FOAR. We analyzed glomerular filtration rate in mice by FITC-inulin clearance and clinically characterized six families, including nine patients with DB/FOAR and nine family members. Urine samples from patients were analyzed by Western blot analysis and biopsy materials were analyzed by histology. In the mouse model, we used histological methods to assess nephrogenesis and postnatal renal structure and contrast-enhanced magnetic resonance imaging to assess glomerular number. In megalin-deficient mice, we found a lower glomerular filtration rate and an increase in the abundance of injury markers, such as kidney injury molecule-1 and N-acetyl-β-d-glucosaminidase. Renal injury was validated in patients, who presented with increased urinary kidney injury molecule-1, classical markers of chronic kidney disease, and glomerular proteinuria early in life. Megalin-deficient mice had normal nephrogenesis, but they had 19% fewer nephrons in early adulthood and an increased fraction of nephrons with disconnected glomerulotubular junction. In conclusion, megalin dysfunction, as present in DB/FOAR syndrome, confers an increased risk of progression into chronic kidney disease.

Download Full-text

Correlation Between Cognitive Function Impairment and Chronic Kidney Disease With a Low Glomerular Filtration Rate at Sanglah Hospital Denpasar

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2020.4691 ◽

2020 ◽

Vol 8 (B) ◽

pp. 752-756

Author(s):

Anak Agung Ayu Putri Laksmidewi ◽

Cok Istri Gangga Dewi Dewi ◽

Yennny Kandarini

Keyword(s):

Chronic Kidney Disease ◽

Glomerular Filtration Rate ◽

Cognitive Impairment ◽

Cognitive Function ◽

Kidney Disease ◽

Glomerular Filtration ◽

Filtration Rate ◽

Control Group ◽

Case Group ◽

Increased Risk

BACKGROUND: Chronic kidney disease is a condition of chronic kidney damage with abnormal structure and function of the kidneys that lasts more than 3 months, accompanied or not by a decrease in glomerular filtration rate. Organic kidney disease leaves accumulated organic waste that cannot be removed by the kidneys. Furthermore, several biochemical and metabolic mechanisms such as chronic inflammation and oxidative stress can cause executive disorders. AIM: The aim of the study was to find out an increased risk of impaired cognitive function in patients with chronic kidney disease with a low glomerular filtration rate in Sanglah Hospital. METHOD: This study uses a retrospective case–control analytic observational study design. We included all patients with chronic kidney disease in Sanglah Hospital in December 2017–January 2018. This study involved 46 subjects with chronic kidney disease who met eligibility criteria, classified as a case group with cognitive impairment and a control group without cognitive impairment. RESULTS: Each decrease in glomerular filtration rate < 30 ml/min/173 m2 in patients with chronic renal failure correlates with an increased incidence of cognitive impairment of around 15–25%. The risk of chronic kidney disease patients with glomerular filtration rate < 30 ml/min/1.73 m2 decreased cognitive function 13 times compared to subjects with glomerular filtration rate > 30 ml/min/ 1.73 m2. CONCLUSION: Low glomerular filtration rate correlate with increased risk of cognitive impairment.

Download Full-text