scholarly journals Intestinal phosphate absorption: The paracellular pathway predominates?

2019 ◽  
Vol 244 (8) ◽  
pp. 646-654 ◽  
Author(s):  
Matthew Saurette ◽  
R Todd Alexander
Keyword(s):  
Kidney Disease ◽  
Animal Studies ◽  
Western Diet ◽  
Phosphate Absorption ◽  
Sodium Hydrogen ◽  
Sodium Hydrogen Exchanger ◽  
Gradient Based ◽  
Intestinal Phosphate Absorption ◽  
Stage Renal Disease ◽  
End Stage

Hyperphosphatemia is nearly universal in patients with advanced chronic kidney disease and end stage renal disease. Given the considerable negative sequelae associated with hyperphosphatemia, i.e. increased cardiovascular disease, hastening of renal failure and death, reducing serum phosphate is a goal of therapy. In the absence of sufficient renal function, intestinal phosphate absorption is the remaining target to reduce plasma phosphate levels. Much work has been done with respect to understanding transcellular phosphate absorption. Both animal studies using inducible or intestinal NaPi-2b knockout mice and specific NaPi-2b inhibitors revealed this transporter as the primary mechanism mediating transcellular phosphate absorption in the intestine. However, this has not translated into effective phosphate lowering therapies in patients with kidney disease. More recently, it was observed that inhibition of the epithelial sodium hydrogen exchanger, sodium–hydrogen exchanger isoform 3 (NHE3), or its genetic deletion, decreases intestinal phosphate absorption. The mechanism mediating this effect is through increased transepithelial resistance and reduced paracellular phosphate permeability. Thus, NHE3 inhibition reduces paracellular phosphate permeability in the intestine. The transepithelial potential difference across intestinal epithelium is lumen negative and phosphate commonly exists as a divalent anion. Further, consumption of the typical Western diet provides a large lumen to blood phosphate concentration gradient. Based on these observations we argue herein that the paracellular phosphate absorption route is the predominant pathway mediating intestinal phosphate absorption in humans. Impact statement This review summarizes the work on transcellular intestinal phosphate absorption, arguing why this pathway is not the predominant pathway in humans consuming a “Western” diet. We then highlight the recent evidence which is strongly consistent with paracellular intestinal phosphate absorption mediating the bulk of intestinal phosphate absorption in humans.

scholarly journals Small Intestinal Phosphate Absorption: Novel Therapeutic Implications

2021 ◽  
pp. 1-9
Author(s):  
Jerry Yee ◽  
David Rosenbaum ◽  
Jeffrey W. Jacobs ◽  
Stuart M. Sprague
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Paracellular Pathway ◽  
Phosphate Binders ◽  
Phosphate Absorption ◽  
Therapeutic Implications ◽  
Sodium Hydrogen ◽  
Sodium Hydrogen Exchanger ◽  
Dietary Phosphate ◽  
Intestinal Phosphate Absorption

<b><i>Background:</i></b> Chronic kidney disease (CKD) affects approximately 15% of adults in the USA. As CKD progresses, urinary phosphate excretion decreases and results in phosphate retention and, eventually, hyperphosphatemia. As hyperphosphatemia is associated with numerous adverse outcomes, including increased cardiovascular mortality, reduction in phosphorus concentrations is a guideline-recommended, established clinical practice. Dietary phosphate restriction, dialysis, and phosphate binders are currently the only options for phosphate management. However, many patients with hyperphosphatemia have phosphorus concentrations &#x3e;5.5 mg/dL, despite treatment. <b><i>Summary:</i></b> This review pre­sents recent advances in the understanding of intestinal phosphate absorption and therapeutic implications. Dietary phosphate is absorbed in the intestine through two distinct pathways, paracellular absorption and transcellular transport. Recent evidence indicates that the paracellular route accounts for 65–80% of total phosphate absorbed. Thus, the paracellular pathway is the dominant mechanism of phosphate absorption. Tenapanor is a first-in-class, non-phosphate binder that inhibits the sodium-hydrogen exchanger 3 or solute carrier family 9 member 3 (SLC9A3) encoded by the SLC9A3 gene, and blocks paracellular phosphate absorption. <b><i>Key Messages:</i></b> Targeted inhibition of sodium-hydrogen exchanger 3 effectively reduces paracellular permeability of phosphate. Novel therapies that target the paracellular pathway may improve phosphate control in chronic kidney disease.

scholarly journals Investigation of the Impact of Endodontic Therapy on Survival among Dialysis Patients in Taiwan: A Nationwide Population-Based Cohort Study

2021 ◽  
Vol 18 (1) ◽  
pp. 326
Author(s):  
Chih-Chien Chiu ◽  
Ya-Chieh Chang ◽  
Ren-Yeong Huang ◽  
Jenq-Shyong Chan ◽  
Chi-Hsiang Chung ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Renal Disease ◽  
End Stage Renal Disease ◽  
Root Canal ◽  
Dialysis Patients ◽  
Root Canal Therapy ◽  
Risk Of Death ◽  
Stage Renal Disease ◽  
End Stage

Objectives Dental problems occur widely in patients with chronic kidney disease (CKD) and may increase comorbidities. Root canal therapy (RCT) is a common procedure for advanced decayed caries with pulp inflammation and root canals. However, end-stage renal disease (ESRD) patients are considered to have a higher risk of potentially life-threatening infections after treatment and might fail to receive satisfactory dental care such as RCT. We investigated whether appropriate intervention for dental problems had a potential impact among dialysis patients. Design Men and women who began maintenance dialysis (hemodialysis or peritoneal dialysis) between January 1, 2000, and December 31, 2015, in Taiwan (total 12,454 patients) were enrolled in this study. Participants were followed up from the first reported dialysis date to the date of death or end of dialysis by December 31, 2015. Setting Data collection was conducted in Taiwan. Results A total of 2633 and 9821 patients were classified into the RCT and non-RCT groups, respectively. From the data of Taiwan’s National Health Insurance, a total of 5,092,734 teeth received RCT from 2000 to 2015. Then, a total of 12,454 patients were followed within the 16 years, and 4030 patients passed away. The results showed that members of the non-RCT group (34.93%) had a higher mortality rate than those of the RCT group (22.79%; p = 0.001). The multivariate-adjusted hazard ratio for the risk of death was 0.69 (RCT vs. non-RCT; p = 0.001). Conclusions This study suggested that patients who had received RCT had a relatively lower risk of death among dialysis patients. Infectious diseases had a significant role in mortality among dialysis patients with non-RCT. Appropriate interventions for dental problems may increase survival among dialysis patients. Abbreviations: CKD = chronic kidney disease, ESRD = end-stage renal disease, RCT = root canal therapy.

scholarly journals The Severity of Diabetic Retinopathy Is an Independent Factor for the Progression of Diabetic Nephropathy

2020 ◽  
Vol 10 (1) ◽  
pp. 3
Author(s):  
Shi-Chue Hsing ◽  
Chia-Cheng Lee ◽  
Chin Lin ◽  
Jiann-Torng Chen ◽  
Yi-Hao Chen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Retinopathy ◽  
Kidney Disease ◽  
Renal Disease ◽  
Disease Progression ◽  
Renal Disease Progression ◽  
Hazard Ratios ◽  
Stage Renal Disease ◽  
End Stage

(1) Background: It has rarely been studied whether the severity of diabetic retinopathy (DR) could influence renal disease progression in end-stage renal disease (ESRD) and chronic kidney disease (CKD) in patients with type 2 diabetes. The aim of this study was to evaluate renal disease progression in ESRD and CKD according to DR severity in patients with type 2 diabetes. (2) Methods: We included 1329 patients and divided the cohort into two end-points. The first was to trace the incidence of ESRD in all enrolled participants and the other was to follow their progression to CKD. (3) Results: Significantly higher crude hazard ratios (HRs) of ESRD incidence in all enrolled participants were noted, and this ratio increased in a stepwise fashion. However, after adjustment, DR severity was not associated with ESRD events. Therefore, a subgroup of 841 patients without CKD was enrolled to track their progression to CKD. Compared with no diabetic retinopathy, the progression of CKD increased in a stepwise fashion, from mild nonproliferative diabetic retinopathy (NPDR) to moderate NPDR, to severe NPDR and to proliferative diabetic retinopathy (PDR), both in the crude and adjusted models. (4) Conclusions: The severity of retinopathy appeared to be associated with renal lesions and the development of CKD. Our findings suggest that the severity of DR is a risk factor for progression to CKD. Therefore, diabetic retinopathy is useful for prognosticating the clinical course of diabetic kidney disease.

scholarly journals Therapeutic Strategies for Diabetic Kidney Disease

Diabetology ◽  
2021 ◽  
Vol 2 (1) ◽  
pp. 31-35
Author(s):  
Keiichiro Matoba
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Intensive Therapy ◽  
Therapeutic Strategies ◽  
Therapeutic Interventions ◽  
Hemodynamic Changes ◽  
Diabetic Kidney ◽  
Global Epidemic ◽  
Stage Renal Disease ◽  
End Stage

Diabetic kidney disease (DKD) is a global epidemic leading to end-stage renal disease (ESRD) and susceptibility to cardiovascular disease, with few therapeutic interventions. A hallmark of DKD is the activation of the renin-angiotensin-aldosterone system and hemodynamic changes in glomerulus. Although intensive therapy with agents that targets those abnormalities lowers the risk of DKD progression, it does not completely abolish the risk of ESRD and cardiovascular events. Recent studies have illustrated the importance of renal inflammation, oxidative stress, and activated Rho-associated protein kinase (ROCK) signaling as essential pathogenesis for the development of DKD. In this commentary, these topics will be discussed.

scholarly journals Molecular Pathophysiology of Autosomal Recessive Polycystic Kidney Disease

2021 ◽  
Vol 22 (12) ◽  
pp. 6523
Author(s):  
Adrian Cordido ◽  
Marta Vizoso-Gonzalez ◽  
Miguel A. Garcia-Gonzalez
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Molecular Basis ◽  
Autosomal Recessive ◽  
Polycystic Kidney ◽  
Phenotypic Spectrum ◽  
New Gene ◽  
Stage Renal Disease ◽  
End Stage ◽  
Molecular Pathophysiology

Autosomal recessive polycystic kidney disease (ARPKD) is a rare disorder and one of the most severe forms of polycystic kidney disease, leading to end-stage renal disease (ESRD) in childhood. PKHD1 is the gene that is responsible for the vast majority of ARPKD. However, some cases have been related to a new gene that was recently identified (DZIP1L gene), as well as several ciliary genes that can mimic a ARPKD-like phenotypic spectrum. In addition, a number of molecular pathways involved in the ARPKD pathogenesis and progression were elucidated using cellular and animal models. However, the function of the ARPKD proteins and the molecular mechanism of the disease currently remain incompletely understood. Here, we review the clinics, treatment, genetics, and molecular basis of ARPKD, highlighting the most recent findings in the field.

Serum Sodium Levels and Patient Outcomes in an Ambulatory Clinic-Based Chronic Kidney Disease Cohort

2015 ◽  
Vol 41 (3) ◽  
pp. 200-209 ◽  
Author(s):  
Sang-Woong Han ◽  
Anca Tilea ◽  
Brenda W. Gillespie ◽  
Fredric O. Finkelstein ◽  
Margaret A. Kiser ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Patient Outcomes ◽  
Serum Sodium ◽  
Risk Of Mortality ◽  
Ambulatory Patients ◽  
Lower Egfr ◽  
Stage Renal Disease ◽  
End Stage ◽  
Improve Patient

Background: Chronic kidney disease (CKD) patients are prone to both hypo- and hypernatremia. Little has been published on the epidemiology of hypo- and hypernatremia in ambulatory patients with non-dialysis CKD. Methods: Data collected in two contemporaneous CKD cohort studies, the Renal Research Institute (RRI)-CKD study (n = 834) and the Study of Treatment of Renal Insufficiency: Data and Evaluation (STRIDE) (n = 1,348) were combined and analyzed to study the association between serum sodium (Na+) and clinical outcomes. Results: Baseline estimated glomerular filtration rate (eGFR) and Na+ were 26 ± 11 ml/min/1.73 m2 and 140.2 ± 3.4 mEq/l, respectively. The prevalence of Na+ ≤135 mEq/l and ≥144 mEq/l was 6 and 16%, respectively. Higher baseline Na+ was significantly associated with male sex, older age, systolic blood pressure, BMI, serum albumin, presence of heart failure, and lower eGFR. The risk of end-stage renal disease (ESRD) was marginally significantly higher among patients with Na+ ≤135 mEq/l, compared with 140< Na+ <144 mEq/l (referent), in time-dependent models (adjusted hazard ratio, HR = 1.52, p = 0.06). Mortality risk was significantly greater at 135< Na+ ≤140 mEq/l (adjusted HR = 1.68, p = 0.02) and Na+ ≥144 mEq/l (adjusted HR = 2.01, p = 0.01). Conclusion: CKD patients with Na+ ≤135 mEq/l were at a higher risk for progression to ESRD, whereas both lower and higher Na+ levels were associated with a higher risk of mortality. While caring for CKD patients, greater attention to serum sodium levels by clinicians is warranted and could potentially help improve patient outcomes.

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