Kidney and Blood Pressure Research最新文献

{"title":"Co-Deposition of IgM and C3 May Indicate Unfavorable Renal Outcomes in Adult Patients with Primary Focal Segmental Glomerulosclerosis","authors":"Ş. Mirioğlu, Y. Caliskan, Y. Ozluk, A. Dirim, Zulal Istemihan, A. Akyildiz, H. Yazıcı, A. Turkmen, I. Kílícaslan, M. Sever","doi":"10.1159/000501827","DOIUrl":"https://doi.org/10.1159/000501827","url":null,"abstract":"Background/Aims: We aimed to investigate the effects of glomerular IgM and C3 deposition on outcomes of adult patients with primary focal segmental glomerulosclerosis (FSGS). Methods: In this retrospective analysis, 86 consecutive adult patients with biopsy-proven primary FSGS were stratified into 3 groups according to their histopathological features: IgM– C3–, IgM+ C3–, and IgM+ C3+. Primary outcome was defined as at least a 50% reduction in baseline estimated glomerular filtration rate (eGFR) or development of kidney failure, while complete or partial remission rates were secondary outcomes. Results: Glomerular IgM deposits were found in 44 (51.1%) patients, 22 (25.5%) of which presented with accompanying C3 deposition. Patients in IgM+ C3+ group had higher level of proteinuria (5.6 g/24 h [3.77–8.5], p = 0.073), higher percentage of segmental glomerulosclerosis (20% [12.3–27.2], p = 0.001), and lower levels of eGFR (69 ± 37.2 mL/min/1.73 m2, p = 0.029) and serum albumin (2.71 ± 0.85 g/dL, p = 0.045) at the time of diagnosis. Despite 86.3% of patients in IgM+ C3+ group (19/22) received immunosuppressive treatment, the primary outcome was more common in patients in the IgM+ C3+ group compared with patients in IgM+ C3– and IgM– C3– groups (11 [50%] vs. 2 [9%] and 11 [26.1%] respectively [p = 0.010]). Complete or partial remission rates were lower in patients in the IgM+ C3+ group (5/22, 22.7%), as well (p = 0.043). Multivariate Cox regression analysis revealed that IgM and C3 co-deposition was an independent risk factor associated with primary outcome (hazard ratio 3.355, 95% CI 1.349–8.344, p = 0.009). Conclusions: Glomerular IgM and C3 co-deposition is a predictor of unfavorable renal outcomes in adult patients with primary FSGS.","PeriodicalId":17810,"journal":{"name":"Kidney and Blood Pressure Research","volume":"94 1","pages":"961 - 972"},"PeriodicalIF":0.0,"publicationDate":"2019-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73238902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diuretic Resistance in Cardio-Nephrology: Role of Pharmacokinetics, Hypochloremia, and Kidney Remodeling","authors":"C. Masella, D. Viggiano, I. Molfino, M. Zacchia, G. Capolongo, P. Anastasio, M. Simeoni","doi":"10.1159/000502648","DOIUrl":"https://doi.org/10.1159/000502648","url":null,"abstract":"Background: Diuretic resistance is among the most challenging problems that the cardio-nephrologist must address in daily clinical practice, with a considerable burden on hospital admissions and health care costs. Indeed, loop diuretics are the first-line therapy to overcome fluid overload in heart failure patients. The pathophysiological mechanisms of fluid and sodium retention are complex and depend on several neuro-hormonal signals mainly acting on sodium reabsorption along the renal tubule. Consequently, doses and administration modalities of diuretics must be carefully tailored to patients in order to overcome under- or overtreatment. The frequent and tricky development of diuretic resistance depends in part on post-diuretic sodium retention, reduced tubular secretion of the drug, and reduced sodium/chloride sensing. Sodium and chloride depletions have been recently shown to be major factors mediating these processes. Aquaretics and high-saline infusions have been recently suggested in cases of hyponatremic conditions. This review discusses the limitations and strengths of these approaches. Summary: Long-term diuretic use may lead to diuretic resistance in cardio-renal syndromes. To overcome this complication intravenous administration of loop diuretics and a combination of different diuretic classes have been proposed. In the presence of hyponatremia, high-saline solutions in addition to loop diuretics might be beneficial, whereas aquaretics require caution to avoid overcorrection. Key Messages: Diuretic resistance is a central theme for cardio-renal syndromes. Hyponatremia and hypochloremia may be part of the mechanisms for diuretic resistance. Aquaretics and high-saline solutions have been proposed as possible new therapeutic solutions.","PeriodicalId":17810,"journal":{"name":"Kidney and Blood Pressure Research","volume":"31 1","pages":"915 - 927"},"PeriodicalIF":0.0,"publicationDate":"2019-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90109062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sodium-Glucose Cotransporter 2 (SGLT2) Inhibition in Kidney Transplant Recipients with Diabetes Mellitus","authors":"M. Mahling, Anja Schork, S. Nadalin, A. Fritsche, N. Heyne, M. Guthoff","doi":"10.1159/000501854","DOIUrl":"https://doi.org/10.1159/000501854","url":null,"abstract":"Background: Sodium-glucose cotransporter 2 (SGLT2) inhibition has been shown to reduce cardiovascular mortality and preserve kidney function in patients with type 2 diabetes. Kidney transplant recipients with diabetes demonstrate increased risk and accelerated progression of micro- and macrovascular complications and may specifically benefit from SGLT2 inhibition. However, potential concerns of SGLT2 inhibition include volume depletion and urinary tract infections. Objectives: We report data on the use of SGLT2 inhibitors in a case series of ten patients with diabetes after kidney transplantation in order to analyze efficacy, safety, and the effect on renal function. Methods: Patients with a stable allograft function and no history of recurrent urinary tract infections were eligible. The SGLT2 inhibitor empagliflozin was given as add-on to preexisting antidiabetic treatment with initial dose reduction of the latter. Results: Median estimated glomerular filtration rate at baseline was 57 mL/min/1.73 m2 and remained stable throughout the follow-up of 12.0 (5.3–12.0) months. Median HbA1c decreased from 7.3 to 7.1%. The rate of urinary tract infections and other side effects was low. Conclusions: SGLT2 inhibition is feasible and well tolerated in selected kidney transplant recipients with diabetes. Whether SGLT2 inhibition is able to reduce cardiovascular mortality and improve allograft survival in these patients has to be addressed in further studies.","PeriodicalId":17810,"journal":{"name":"Kidney and Blood Pressure Research","volume":"68 1","pages":"984 - 992"},"PeriodicalIF":0.0,"publicationDate":"2019-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78824155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Abdominal Aortic Calcification on Central Haemodynamics and Decline of Glomerular Filtration Rate in Patients with Chronic Kidney Disease Stages 3 and 4","authors":"Hanna Jansson, A. Saeed, M. Svensson, Kristina Finnved, M. Hellström, G. Guron","doi":"10.1159/000501687","DOIUrl":"https://doi.org/10.1159/000501687","url":null,"abstract":"Background/Aim: Calcifications of large arteries are frequent in chronic kidney disease (CKD) and may contribute to the high cardiovascular risk in this population. The aim of this study was to examine whether abdominal aortic calcification volume (AACV) was a predictor of the rate of decline in glomerular filtration rate (GFR) in a cohort of patients with CKD stages 3 and 4. Methods: Eighty-four patients with CKD stages 3 and 4 were enrolled in this prospective observational study. At study entry, and annually, GFR was measured by plasma 51Cr-EDTA clearance. At baseline, haemodynamics was assessed and AACV was determined by computer tomography. Results: The mean follow-up time was 3.4 years and mean decline in GFR was –2.69 mL/min/1.73 m2 per year. At baseline, abdominal aortic calcification (AAC) was detected in 66 patients (79%). A binary logistic regression analysis revealed that age was the only statistically significant independent predictor of AAC. In patients with AAC, male gender (B = 0.413, p = 0.030), aortic diastolic blood pressure (B = –0.025, p = 0.001) and ankle-brachial index (B = –1.666, p = 0.002) were independently associated with AACV using a multiple linear regression analysis. Neither the presence nor the extent of AAC was significantly associated with the rate of change in GFR during follow-up. Conclusion: In this cohort of patients with CKD stages 3 and 4, only age was an independent predictor of the presence of AAC. AACV was not associated with the rate of decline in GFR.","PeriodicalId":17810,"journal":{"name":"Kidney and Blood Pressure Research","volume":"24 1","pages":"950 - 960"},"PeriodicalIF":0.0,"publicationDate":"2019-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84965931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MicroRNA-145 Involves in the Pathogenesis of Renal Vascular Lesions and May Become a Potential Therapeutic Target in Patients with Juvenile Lupus Nephritis","authors":"Z. Cai, W. Xiang, Xia-Biao Peng, Yan Ding, W. Liao, Xiaojie He","doi":"10.1159/000500923","DOIUrl":"https://doi.org/10.1159/000500923","url":null,"abstract":"Aims: The current study was conducted with the central objective of investigating the expression of microRNA-145 (miR-145) in renal vascular lesions (RVLs) in juvenile lupus nephritis (JLN) and its possible mechanism. Methods: The clinical data of 49 JLN patients confirmed by renal biopsy were collected and followed by grouping according to the RVLs score after hematoxylin-eosin staining: mild, moderate, and severe groups. In situ hybridization was used to detect the expression of miR-145 in renal vessels which was then being compared among different RVLs groups. Up-LV-miR-145 and LV-miR-NC lentiviral vectors were constructed and transfected into human vascular smooth muscle cells (HVSMCs), respectively. After HVSMCs were treated with 10.0 µg/L platelet-derived growth factor (PDGF)-BB for 24 h, the proliferation, migration, and apoptosis of endothelial cells were detected by MTT, Transwell assay, and flow cytometry, respectively. Western blot was used to detect expression of alpha-smooth muscle actin (α-SM-actin) and osteopontin (OPN). Results: The expression of miR-145 in renal vascular cells was statistically significant. The higher the inner membrane ratio, the lesser the miR-145 expression. After treatment with PDGF-BB, expression of miR-145 in HVSMCs decreased, proliferation and migration ability enhanced, apoptosis decreased, α-SM-actin decreased, and OPN increased. The proliferation and migration ability of HVSMCs in the LV-miR-145 group suppressed, apoptosis enhanced, α-SM-actin increased, and OPN decreased. Conclusions: Our study revealed that miR-145 expression decreased with the increase of vascular damage. miR-145 can inhibit proliferation, migration, and differentiation phenotypic transformation of HVSMCs induced by PDGF-BB. miR-145 may be involved in the pathogenesis of RVLs and may be a new target for treatment of RVLs in lupus nephritis.","PeriodicalId":17810,"journal":{"name":"Kidney and Blood Pressure Research","volume":"9 1","pages":"643 - 655"},"PeriodicalIF":0.0,"publicationDate":"2019-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91385976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Clinicopathological Characteristics of Henoch-Schönlein Purpura Nephritis with Presentation of Nephrotic Syndrome","authors":"Jiaxing Tan, Yi Tang, Yicong Xu, S. Yan, Yuanyuan Xu, L. Tan, Z. Zhong, Padamata Tarun, W. Qin","doi":"10.1159/000501459","DOIUrl":"https://doi.org/10.1159/000501459","url":null,"abstract":"Background: Henoch-Schönlein purpura nephritis (HSPN) is a common vasculitis involving the kidneys, with a lower incidence in adults. Meanwhile, nephrotic syndrome (NS) can appear in HSPN. However, the clinicopathological features and renal outcome of adult-onset HSPN presenting with NS (NS-HSPN) have not been well clarified. Methods: A total of 191 HSPN patients were prospectively analyzed and comparisons were made between NS-HSPN and non-NS-HSPN. Multivariate Cox regression analysis was carried out to find the unfavorable factors of renal outcome of NS-HSPN. Results: Among the 191 patients, 44 (23.0%) had NS-HSPN. Apart from edema and abdominal pain, patients with NS-HSPN tended to have lower levels of erythrocytes and hemoglobulin in blood as well as a greater number of erythrocytes in urine (p < 0.05). Mesangial proliferation was the most common pathological lesion in HSPN and the rates of crescent formation were significantly different, with 54.5% in NS-HSPN and 33.3% in non-NS-HSPN (p < 0.05). Notably, 18.2 and 4.8% of patients reached the composite endpoints in the NS-HSPN and non-NS-HSPN groups, respectively (p < 0.05), demonstrating that NS-HSPN patients were more likely to progress to end-stage renal disease and had a worse outcome. We also found that hypertension, estimated glomerular filtration rate (eGFR), cystatin, and tubular atrophy/interstitial fibrosis (HR > 1, p < 0.05) at onset were correlated with adverse outcome in NS-HSPN. Conclusion: NS-HSPN had more severe clinicopathological manifestations and poorer prognosis. The adverse predictors of NS-HSPN principally depend on clinicopathological presentation rather than on different therapies, and hypertension, eGFR, cystatin, and tubular atrophy/interstitial fibrosis can serve as independent risk factors in NS-HSPN.","PeriodicalId":17810,"journal":{"name":"Kidney and Blood Pressure Research","volume":"50 1","pages":"754 - 764"},"PeriodicalIF":0.0,"publicationDate":"2019-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85807372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mutation Hot Spot Region in the HOGA1 Gene Associated with Primary Hyperoxaluria Type 3 in the Chinese Population","authors":"Wenying Wang, Yi Liu, Lulu Kang, R. He, Jin-qing Song, Yanhan Li, Jun Li, Yanling Yang","doi":"10.1159/000501458","DOIUrl":"https://doi.org/10.1159/000501458","url":null,"abstract":"Background: Primary hyperoxaluria type 3 (PH3) is a rare autosomal recessive disorder that affects glyoxylate metabolism. PH3 is caused by defects in 4-hydroxy-2-oxoglutarate aldolase, which is encoded by the HOGA1 gene. However, only 3 cases of PH3 have been described in Asians until today. This study aimed to determine the clinical and mutation spectra of patients from mainland China with PH3. Methods: We applied targeted next-generation sequencing to four non-consanguineous, unrelated Chinese families with PH3 to identify the genes hosting disease-causing mutations. This approach was confirmed by Sanger sequencing. Results: Five patients (2 boys and 3 girls) from four unrelated Chinese families were admitted because of kidney stones. Five HOGA1 gene sequence mutations were detected, including two novel mutations, c.811C>T (p.R271C) and c.812G>A (p.R271H). These compound heterozygous mutations were detected in a female PH3 patient (patient 4). Other patients included 2 boys who had heterozygous c.834_834+1GG>TT and c.834G>A (p.A278A) mutations (patients 1 and 2), a girl with homozygous c.834G>A (p.A278A) mutation (patient 3), and a girl with heterozygous c.834_834+1GG>TT and c.346C>T (p.Q116X) mutations (patient 5). The mutations in the c.834_834+1 region, including c.834G>A, c.834+1G>T, and c.834_834+1GG>TT, account for 5/8 of alleles in our study and 3/4 of alleles reported among Chinese patients. All patients in this study received hyperhydration and urine alkalinization treatment. Conclusion: Five PH3 cases were reported. Potential mutation hot spot region (c.834_834+1) in the Chinese population and two novel mutations were found.","PeriodicalId":17810,"journal":{"name":"Kidney and Blood Pressure Research","volume":"12 1","pages":"743 - 753"},"PeriodicalIF":0.0,"publicationDate":"2019-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87399421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low-Grade Albuminuria Is Associated with Left Ventricular Hypertrophy and Diastolic Dysfunction in Patients with Hypertension","authors":"Tingjun Wang, Hongbin Zhong, Guili Lian, Xiaoqi Cai, Jin Gong, Chaoyi Ye, Liang-di Xie","doi":"10.1159/000500782","DOIUrl":"https://doi.org/10.1159/000500782","url":null,"abstract":"Introduction: Microalbuminuria is a risk factor for cardiovascular morbidity and mortality in hypertensive patients. However, the relationship between low-grade albuminuria, a higher level of albuminuria below microalbuminuria threshold, and hypertension-related organ damage is unclear. Left ventricular (LV) hypertrophy (LVH) is well recognized to be a subclinical organ damage of hypertension, and LV diastolic dysfunction is also reported to be an early functional cardiac change of hypertension that predicts heart failure. The present study aimed to investigate the association of low-grade albuminuria with LVH and LV diastolic dysfunction in hypertensive patients. Methods: This cross-sectional observational clinical study was retrospectively performed in 870 hypertensive patients admitted to our hospital. Urinary albumin to creatinine ratio (UACR) was calculated to assess the levels of albuminuria: macroalbuminuria (≥300 mg/g), microalbuminuria (≥30 mg/g, but <300 mg/g), and normal albuminuria (<30 mg/g). Low-grade albuminuria was defined as sex-specific highest tertile within normal albuminuria (8.1–29.6 mg/g in males and 11.8–28.9 mg/g in females). LVH and LV diastolic dysfunction were identified as recommended by American Society of Echocardiography. Results: Of the 870 patients, 765 (87.9%) had normal albuminuria, 77 (8.9%) had microalbuminuria, and 28 (3.2%) had macroalbuminuria. Percentage of LVH and LV diastolic dysfunction was increased with ascending UACR. UACR was independently associated with LVH and LV diastolic dysfunction, even in patients with normal albuminuria. Multivariable logistic regression showed that the patients with the highest tertile within normal albuminuria had nearly 80% increase in LVH and nearly 60% increase in LV diastolic dysfunction (adjusted OR for LVH 1.788, 95% CI 1.181–2.708, p = 0.006; adjusted OR for LV diastolic dysfunction 1.567, 95% CI 1.036–2.397, p = 0.034). After further stratification analyses in patients with normal albuminuria, it was shown that this independent association persisted in female patients, those who were younger than 70 years old, and those with duration of hypertension <15 years. Conclusion: Low-grade albuminuria was associated with LVH and LV diastolic dysfunction in hypertensive patients, especially in patients younger than 70 years old, and those with duration of hypertension <15 years.","PeriodicalId":17810,"journal":{"name":"Kidney and Blood Pressure Research","volume":"19 1","pages":"590 - 603"},"PeriodicalIF":0.0,"publicationDate":"2019-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82526669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Visit-to-Visit Variability in Total Cholesterol Correlates with the Progression of Renal Function Decline in a Chinese Community-Based Hypertensive Population","authors":"Yu-Qin Yan, Yu-qing Huang, Dan Zhou, Song-tao Tang, Ying-qing Feng","doi":"10.1159/000501367","DOIUrl":"https://doi.org/10.1159/000501367","url":null,"abstract":"Background: Studies have demonstrated that cholesterol variability is an independent predictor of cerebrovascular and cardiovascular events. Objective: This study aimed to investigate the association of visit-to-visit variability in total cholesterol (TC) with kidney decline in a Chinese community-based population. Methods: We assessed intraindividual variability in TC among 6,465 hypertensive participants and correlated the results with endpoints. TC variability was measured using standard deviation (SD), average successive variability (ASV), coefficient of variation (CV), and variability independent of the mean (VIM). The endpoint of this study was progression of renal function decline defined as a decrease in estimated glomerular filtration rate (eGFR) ≥30% and to a level <60 mL/min/1.73 m2 during follow-up if the baseline eGFR was ≥60 mL/min/1.73 m2, or a decrease in eGFR ≥50% during follow up if the baseline eGFR was <60 mL/min/1.73 m2. Results: After a median follow-up of 27 months, 13.5% (n = 877) of the participants experienced progression of renal function decline. In the multivariable-adjusted Cox model, each 1-SD increase in TC variability (by SD) increased the risk of renal function decline by 11% (HR = 1.11; 95% CI 1.034–1.197; p = 0.004); this was independent of the baseline eGFR, mean follow-up TC levels, and the lipid-lowering therapy. Similar results were found for the 3 other measures of variability, i.e., ASV, CV, and VIM. Conclusion: In subjects with hypertension, visit-to-visit variability in TC is an independent predictor of renal function decline.","PeriodicalId":17810,"journal":{"name":"Kidney and Blood Pressure Research","volume":"8 1","pages":"727 - 742"},"PeriodicalIF":0.0,"publicationDate":"2019-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84166039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Organ Handling of Soluble Klotho in Humans","authors":"D. Picciotto, A. Murugavel, Francesca Ansaldo, G. M. Rosa, A. Sofia, Samantha Milanesi, F. Viazzi, Michela Saio, M. Balbi, G. Garibotto, D. Verzola","doi":"10.1159/000501316","DOIUrl":"https://doi.org/10.1159/000501316","url":null,"abstract":"Background: Chronic kidney disease (CKD) reduces both Klotho expression and its shedding into circulation, an effect that accelerates progression and cardiovascular complications. However, the mechanisms that regulate Klotho release by the human kidney are still unknown. Methods: We measured plasma Klotho across the kidney, splanchnic organs and lung in 22 patients (71 ± 2 years, estimated glomerular filtration rate [eGFR] 60 ± 5.4 mL/min 1.73 m2) during elective diagnostic cardiac catheterizations. Results: Although the Klotho average renal vein concentrations were remarkably higher (by ∼9%) than arterial values, the kidney removed Klotho (or was at zero balance) in 7 subjects, indicating that the kidney contribution to systemic Klotho is not constant. Klotho fractional enrichment across the kidney was inversely related to plasma sodium (r = 0.43, p = 0.045) and acid uric acid levels (r = 0.38, p = 0.084) and directly, to renal oxygen extraction (r = 0.56, p = 0.006). In multivariate analysis, renal oxygen extraction was the only predictor of the enrichment of Klotho across the kidney, suggesting the dependence of renal Klotho release on tubular hypoxia or oxidative metabolism. Klotho balance was neutral across the lung. In patients with eGFR <60 mL/min, Klotho was also removed by splanchnic organs (single pass fractional extraction ∼11%). Conclusions: The present study identifies kidney oxygen uptake as a predictor of Klotho release, and splanchnic organs as a site for Klotho removal. This study provides new understanding of kidney Klotho release and suggests that modulating kidney oxygen metabolism could increase Klotho delivery, as an option to slow disease progression and blunt organ damage.","PeriodicalId":17810,"journal":{"name":"Kidney and Blood Pressure Research","volume":"79 1","pages":"715 - 726"},"PeriodicalIF":0.0,"publicationDate":"2019-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82132700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}