The impact of type III sodium‐dependent phosphate transporters (Pit 1 and Pit 2) on podocyte and kidney function

2021 ◽  
Author(s):  
Tomasz Kulesza ◽  
Agnieszka Piwkowska
Keyword(s):  
Kidney Function ◽  
Phosphate Transporters ◽  
Type Iii ◽  
Sodium Dependent ◽  
The Impact

The type III transporters (PiT-1 and PiT-2) are the major sodium-dependent phosphate transporters in the mice and human brains

2016 ◽  
Vol 1637 ◽  
pp. 128-136 ◽  
Author(s):  
Masatoshi Inden ◽  
Masaki Iriyama ◽  
Miho Zennami ◽  
Shin-ichiro Sekine ◽  
Akira Hara ◽  
...  
Keyword(s):  
Phosphate Transporters ◽  
Type Iii ◽  
Sodium Dependent ◽  
Human Brains

scholarly journals POS1121 DEMOGRAPHICS, COMORBIDITIES, AND RENAL FUNCTION OF UNCONTROLLED GOUT PATIENTS WHO RECEIVED PEGLOTICASE: FINDING FROM A LARGE US CLAIMS DATABASE

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 839.2-840
Author(s):  
C. Vesel ◽  
A. Morton ◽  
M. Francis-Sedlak ◽  
B. Lamoreaux
Keyword(s):  
Kidney Function ◽  
Real World ◽  
Randomized Clinical Trials ◽  
Small Subset ◽  
Phase 3 ◽  
Claims Database ◽  
Medical Diagnoses ◽  
Ckd Stage ◽  
Before And After ◽  
The Impact

Background:NHANES data indicate that approximately 9.2 million Americans have gout,1 with a small subset having uncontrolled disease.2 Pegloticase is a PEGylated recombinant uricase enzyme indicated for treating uncontrolled gout that markedly reduces serum uric acid levels (sUA)3 and resolves tophi in treatment responders.4 Despite pegloticase availability in the US for many years, real world demographics of pegloticase users in the treatment of uncontrolled gout have not been previously reported in a population-based cohort.Objectives:This study utilized a large US claims database to examine demographics and co-morbidities of uncontrolled gout patients treated with pegloticase. Kidney function before and after pegloticase treatment and concomitant therapy with immunomodulators were also examined.Methods:The TriNetX Diamond database includes de-identified data from 4.3 million US patients with gout (as of September 2019), including demographics, medical diagnoses, laboratory values, procedures (e.g. infusions, surgeries), and pharmacy data. Patients who had received ≥1 pegloticase infusion were included in these analyses. The number of infusions was evaluated for a subgroup of patients who were in the database ≥3 months before and ≥2 years after the first pegloticase infusion (i.e. first infusion prior to September 2017) to ensure only complete courses of therapy were captured. In this subpopulation, kidney function before and after pegloticase therapy was examined, along with the presence of immunomodulation prescriptions (methotrexate, mycophenolate mofetil, azathioprine, leflunomide) within 60 days prior to and 14 days after the first pegloticase infusion.Results:1494 patients treated with pegloticase were identified. Patients were 63.1 ± 14.0 years of age (range: 23–91), mostly male (82%), and white (76%). Mean sUA prior to pegloticase was 8.7 ± 2.4 mg/dL (n=50), indicating uncontrolled gout in the identified population. The most commonly reported comorbidities were chronic kidney disease (CKD, 48%), essential hypertension (71%), type 2 diabetes (39%), and cardiovascular disease (38%), similar to pegloticase pivotal Phase 3 trial populations. In patients with pre-therapy kidney function measures (n=134), pre-treatment eGFR averaged 61.2 ± 25.7 ml/min/1.73 m2, with 44% having Stage 3-5 CKD. In patients with complete therapy course capture and pre- and post-therapy eGFR measures (n=48), kidney function remained stable (change in eGFR: -2.9 ± 18.2 ml/min/1.73 m2) and CKD stage remained the same or improved in 81% of patients. In 791 patients with complete treatment course capture, patients had received 8.7 ± 13.8 infusions (median: 3, IQR: 2-10). Of these, 189 (24%) patients received only 1 pegloticase infusion and 173 (22%) received ≥12 infusions. As the data cut-off for this analysis pre-dated emerging data on the use of immunomodulation as co-therapy, only 19 of 791 (2%) patients received immunomodulation co-therapy with pegloticase.Conclusion:This relatively large group of patients with uncontrolled gout treated with pegloticase had similar patient characteristics of those studied in the phase 3 randomized clinical trials. Patients with uncontrolled gout are significantly burdened with systemic co-morbid diseases. The majority of patients had stable or improved kidney function following pegloticase treatment. As these results reflect patients initiating treatment prior to 2018, before co-treatment with immunomodulation was introduced, this cohort only included a small percentage of patients who were co-treated with an immunomodulator. Future studies using more current datasets are needed to evaluate real world outcomes in patients treated with pegloticase/immunomodulator co-therapy and to evaluate the impact of systemic co-morbid diseases.References:[1]Chen-Xu M, et al. Arthritis Rheumatol 2019 71:991-999.[2]Fels E, Sundy JS. Curr Opin Rheumatol 2008;20:198-202.[3]Sundy J, et al. JAMA 2011;306:711-720.[4]Mandell BF, et al. Arthritis Res Ther 2018;20:286.Disclosure of Interests:Claudia Vesel Shareholder of: Horizon Therapeutics plc, Employee of: Horizon Therapeutics plc, Allan Morton Speakers bureau: Sanofi, Amgen, and Horizon, Megan Francis-Sedlak Shareholder of: Horizon Therapeutics plc, Employee of: Horizon Therapeutics plc, Brian LaMoreaux Shareholder of: Horizon Therapeutics plc, Employee of: Horizon Therapeutics plc.

scholarly journals The Impact of Allogeneic Hematopoietic Stem Cell Transplantation on Kidney Function in Children—A Single Center Experience

2021 ◽  
Vol 10 (5) ◽  
pp. 1113
Author(s):  
Kinga Musiał ◽  
Krzysztof Kałwak ◽  
Danuta Zwolińska
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Serum Creatinine ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Kidney Function ◽  
Hematopoietic Stem ◽  
Oncological Patients ◽  
The Impact

Background: Knowledge about the impact of allogeneic hematopoietic stem cell transplantation (alloHSCT) on renal function in children is still limited. Objectives: The aim of the study was to evaluate kidney function in children undergoing alloHSCT, with special focus on differences between patients transplanted due to oncological and non-oncological indications. Materials and Methods: The data of 135 children undergoing alloHSCT were analyzed retrospectively. The serum creatinine and estimated glomerular filtration rate (eGFR) values were estimated before transplantation at 24 h; 1, 2, 3, 4 and 8 weeks; and 3 and 6 months after alloHSCT. Then, acute kidney injury (AKI) incidence was assessed. Results: Oncological children presented with higher eGFR values and more frequent hyperfiltration rates than non-oncological children before alloHSCT and until the 4th week after transplantation. The eGFR levels rose significantly after alloHSCT, returned to pre-transplant records after 2–3 weeks, and decreased gradually until the 6th month. AKI incidence was comparable in oncological and non-oncological patients. Conclusions: Children undergoing alloHSCT due to oncological and non-oncological reasons demonstrate the same risk of AKI, but oncological patients may be more prone to sustained renal injury. Serum creatinine and eGFR seem to be insufficient tools to assess kidney function in the early post-alloHSCT period, when hyperfiltration prevails, yet they reveal significant differences in long-term observation.

Effects of Sex and Physical Activity Level on Serum Biomarker-Based Physiological Dysregulation: The Impact to Predict Frailty and Mortality in the Quebec NuAge Cohort

Gerontology ◽  
2021 ◽  
pp. 1-14
Author(s):  
Ahmed Ghachem ◽  
Frédérik Dufour ◽  
Tamas Fülöp ◽  
Pierrette Gaudreau ◽  
Alan A. Cohen
Keyword(s):  
Physical Activity ◽  
Older Adults ◽  
Kidney Function ◽  
Oxygen Transport ◽  
Physical Activity Level ◽  
Rate Of Change ◽  
Activity Level ◽  
Men And Women ◽  
Physiological Dysregulation ◽  
The Impact

<b><i>Background:</i></b> Age-related changes in biological processes such as physiological dysregulation (the progressive loss of homeostatic capacity) vary considerably among older adults and may influence health profiles in late life. These differences could be related, at least in part, to the impact of intrinsic and extrinsic factors such as sex and physical activity level (PAL). <b><i>Objectives:</i></b> The objectives of this study were (1) to assess the magnitude and rate of changes in physiologi­cal dysregulation in men and women according to PAL and (2) to determine whether/how sex and PAL mediate the apparent influence of physiological dysregulation on health outcomes (frailty and mortality). <b><i>Methods:</i></b> We used data on 1,754 community-dwelling older adults (age = 74.4 ± 4.2 years; women = 52.4%) of the Quebec NuAge cohort study. Physiological dysregulation was calculated based on Mahalanobis distance of 31 biomarkers regrouped into 5 systems: oxygen transport, liver/kidney function, leukopoiesis, micronutrients, and lipids. <b><i>Results:</i></b> As expected, mean physiological dysregulation significantly increased with age while PAL decreased. For the same age and PAL, men showed higher levels of physiological dysregulation globally in 3 systems: oxygen transport, liver/kidney function, and leukopoiesis. Men also showed faster global physiological dysregulation in the liver/kidney and leukopoiesis systems. Overall, high PAL was associated with lower level and slower rate of change of physiological dysregulation. Finally, while mortality and frailty risk significantly increased with physiological dysregulation, there was no evidence for differences in these effects between sexes and PAL. <b><i>Conclusion:</i></b> Our results showed that both sex and PAL have a significant effect on physiological dysregulation levels and rates of change. Also, although a higher PAL was associated with lower level and slower rate of change of physiological dysregulation, there was no evidence that PAL attenuates the effect of physiological dysregulation on subsequent declines in health at the end of life. Substantial work remains to understand how modifiable behaviors impact the relationship between physiological dysregulation, frailty, and mortality in men and women.

scholarly journals Sodium-Dependent Phosphate Transporters in Osteoclast Differentiation and Function

PLoS ONE ◽  
2015 ◽  
Vol 10 (4) ◽  
pp. e0125104 ◽  
Author(s):  
Giuseppe Albano ◽  
Matthias Moor ◽  
Silvia Dolder ◽  
Mark Siegrist ◽  
Carsten A. Wagner ◽  
...  
Keyword(s):  
Osteoclast Differentiation ◽  
Phosphate Transporters ◽  
Sodium Dependent ◽  
And Function

scholarly journals Impact of Inorganic Carbon Availability on Microcystin Production by Microcystis aeruginosa PCC 7806

2007 ◽  
Vol 73 (21) ◽  
pp. 6994-7002 ◽  
Author(s):  
Sabine J�hnichen ◽  
Tilo Ihle ◽  
Thomas Petzoldt ◽  
J�rgen Benndorf
Keyword(s):  
Microcystis Aeruginosa ◽  
Type Strain ◽  
Inorganic Carbon ◽  
Wild Type Strain ◽  
Light Cycle ◽  
Variable Fluorescence ◽  
Wild Type ◽  
Dark Light ◽  
Sodium Dependent ◽  
The Impact

ABSTRACT Batch culture experiments with the cyanobacterium Microcystis aeruginosa PCC 7806 were performed in order to test the hypothesis that microcystins (MCYSTs) are produced in response to a relative deficiency of intracellular inorganic carbon (Ci,i). In the first experiment, MCYST production was studied under increased Ci,i deficiency conditions, achieved by restricting sodium-dependent bicarbonate uptake through replacement of sodium bicarbonate in the medium with its potassium analog. The same experimental approach was used in a second experiment to compare the response of the wild-type strain M. aeruginosa PCC 7806 with its mcyB mutant, which lacks the ability to produce MCYSTs. In a third experiment, the impact of varying the Ci,i status on MCYST production was examined without suppressing the sodium-dependent bicarbonate transporter; instead, a detailed investigation of a dark-light cycle was performed. In all experiments, a relative Ci,i deficiency was indicated by an elevated variable fluorescence signal and led to enhanced phycocyanin cell quotas. Higher MCYST cell quotas (in the first and third experiments) and increased total (intracellular plus extracellular) MCYST production (in the first experiment) were detected with increased Ci,i deficiency. Furthermore, the MCYST-producing wild-type strain and its mcyB mutant showed basically the same response to restrained inorganic carbon uptake, with elevated variable fluorescence and phycocyanin cell quotas with increased Ci,i deficiency. The response of the wild type, however, was distinctly stronger and also included elevated chlorophyll a cell quotas. These differences indicate the limited ability of the mutant to adapt to low-Ci,i conditions. We concluded that MCYSTs may be involved in enhancing the efficiency of the adaptation of the photosynthetic apparatus to fluctuating inorganic carbon conditions in cyanobacterial cells.

scholarly journals The impact of kidney function on outcomes following high risk myocardial infarction: findings from 27 610 patients

2013 ◽  
Vol 16 (3) ◽  
pp. 289-299 ◽  
Author(s):  
George V. Moukarbel ◽  
Zi-Fan Yu ◽  
Kenneth Dickstein ◽  
Yingxin Rachel Hou ◽  
Janet T. Wittes ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
High Risk ◽  
Kidney Function ◽  
The Impact
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