scholarly journals Albuminuria in kidney transplant recipients is associated with increased urinary serine proteases and activation of the epithelial sodium channel

2018 ◽  
Vol 315 (1) ◽  
pp. F151-F160 ◽  
Author(s):  
Gitte R. Hinrichs ◽  
Jannie S. Michelsen ◽  
Rikke Zachar ◽  
Ulla G. Friis ◽  
Per Svenningsen ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Sodium Channel ◽  
Kidney Transplant ◽  
Serine Proteases ◽  
Collecting Duct ◽  
Extracellular Volume ◽  
Epithelial Sodium Channel ◽  
Renal Outcome ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients

Albuminuria predicts adverse renal outcome in kidney transplant recipients. The present study addressed the hypothesis that albuminuria is associated with increased urine serine proteases with the ability to activate the epithelial sodium channel (ENaC) and with greater extracellular volume and higher blood pressure. In a cross-sectional design, kidney transplant recipients with ( n = 18) and without ( n = 19) albuminuria were included for office blood pressure measurements, estimation of volume status by bioimpedance, and collection of spot urine and plasma samples. Urine was analyzed for serine proteases and for the ability to activate ENaC current in vitro. Urine exosome protein was immunoblotted for prostasin and γ-ENaC protein. In the present study, it was found that, compared with nonalbuminuria (8.8 mg/g creatinine), albuminuric (1,722 mg/g creatinine) kidney transplant recipients had a higher systolic and diastolic blood pressure, despite receiving significantly more antihypertensives, and a greater urinary total plasminogen, active plasmin, active urokinase-type plasminogen activator, and prostasin protein abundance, which correlated significantly with u-albumin. Fluid overload correlated with systolic blood pressure, urinary albumin/creatinine, and plasminogen/creatinine. Urine from albuminuric kidney transplant recipients evoked a greater amiloride- and aprotinin-sensitive inward current in single collecting duct cells (murine cell line M1). γENaC subunits at 50 and 75 kDa showed increased abundance in urine exosomes from albuminuric kidney transplant recipients when compared with controls. These findings show that albuminuria in kidney transplant recipients is associated with hypertension, ability of urine to proteolytically activate ENaC current, and increased abundance of γENaC. ENaC activity could contribute to hypertension and adverse outcome in posttransplant proteinuria.

scholarly journals Conditional Transgenic Mice for Studying the Role of the Glucocorticoid Receptor in the Renal Collecting Duct

Endocrinology ◽  
2008 ◽  
Vol 150 (5) ◽  
pp. 2202-2210 ◽  
Author(s):  
Aurélie Nguyen Dinh Cat ◽  
Antoine Ouvrard-Pascaud ◽  
François Tronche ◽  
Maud Clemessy ◽  
Daniel Gonzalez-Nunez ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Glucocorticoid Receptor ◽  
Sodium Channel ◽  
Leucine Zipper ◽  
Collecting Duct ◽  
Extracellular Volume ◽  
Epithelial Sodium Channel ◽  
Sodium Reabsorption ◽  
Renal Collecting Duct

The mineralocorticoid receptor (MR) is a major regulator of renal sodium reabsorption and body fluid homeostasis. However, little is known about glucocorticoid receptor (GR)-dependent renal effects. Glucocorticoids may activate both receptors, so it is difficult to distinguish between MR- and GR-mediated effects in vivo. To overcome this complexity, we used a transgenic mouse model allowing conditional GR overexpression (doxycycline inducible TetON system, Hoxb7 promoter) in the renal collecting duct (CD) to identify GR-regulated genes involved in sodium transport in the CD. In microdissected cortical CD, induction of GR expression led (after 2 d of doxycycline) to increased α-epithelial sodium channel and glucocorticoid-induced leucine zipper and decreased abundance of with-no-lysine kinase 4 transcripts, without modification of Na,K-ATPase, serum- and glucocorticoid-kinase-1, or MR expression. No changes occurred in the upstream distal and connecting tubules [distal convoluted tubule (DCT), connecting tubule (CNT)]. Sodium excretion was unaltered, but the urinary aldosterone concentration was reduced, suggesting compensation of transitory extracellular volume expansion that subsequently disappeared. At steady state, i.e. after 15 d of doxycycline administration, transcript abundance remained altered in the CD, whereas mirror changes appeared in the DCT and CNT. Plasma aldosterone or glucocorticoids and blood pressure were all unaffected. These experiments show that: 1) GR, in addition to MR, controls epithelial sodium channel- and glucocorticoid-induced leucine zipper expression in vivo in the CD; 2) with-no-lysine kinase 4 is negatively controlled by GR; and 3) the DCT and CNT compensate for these alterations to maintain normal sodium reabsorption and blood pressure. These results suggest that enhanced GR expression may contribute to enhanced sodium retention in some pathological situations.

Sex differences in ambulatory blood pressure levels, control, and phenotypes of hypertension in kidney transplant recipients

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Maria Korogiannou ◽  
Pantelis Sarafidis ◽  
Marieta P. Theodorakopoulou ◽  
Maria Eleni Alexandrou ◽  
Efstathios Xagas ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Sex Differences ◽  
Kidney Transplant ◽  
Ambulatory Blood Pressure ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients

scholarly journals Correlation between Serotonin Concentration and Blood Pressure in Kidney Transplant Recipients Treated with Cyclosporine

Nephron ◽  
1996 ◽  
Vol 72 (2) ◽  
pp. 336-337 ◽  
Author(s):  
A. Azzadin ◽  
J. Malyszko ◽  
J.S. Malyszko ◽  
W. Buczko ◽  
M. Mysliwiec
Keyword(s):  
Blood Pressure ◽  
Kidney Transplant ◽  
Transplant Recipients ◽  
Serotonin Concentration ◽  
Kidney Transplant Recipients

scholarly journals Osmoregulation Performance and Kidney Transplant Outcome

2019 ◽  
Vol 30 (7) ◽  
pp. 1282-1293 ◽  
Author(s):  
Manal Mazloum ◽  
Jordan Jouffroy ◽  
François Brazier ◽  
Christophe Legendre ◽  
Antoine Neuraz ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Renal Outcome ◽  
Plasma Sodium ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Loading Test ◽  
Water Loading ◽  
All Cause Mortality ◽  
Allograft Loss ◽  
Transplantation Outcomes

BackgroundKidney transplant recipients have an impaired ability to dilute urine but seldom develop baseline hyponatremia before ESRD. Although hyponatremia is a risk factor for adverse events in CKD and in kidney transplant recipients, it remains unclear whether subtler alterations in osmoregulation performance are associated with outcome.MethodsWe studied a single-center prospective cohort of 1258 kidney transplant recipients who underwent a water-loading test 3 months after transplant to determine osmoregulation performance. Measured GFR (mGFR) was performed at the same visit. A group of 164 healthy candidates for kidney donation served as controls. We further evaluated the association of osmoregulation performance with transplantation outcomes and subsequent kidney function.ResultsUnlike controls, most kidney transplant recipients failed to maintain plasma sodium during water loading (plasma sodium slope of −0.6±0.4 mmol/L per hour in transplant recipients versus −0.12±0.3 mmol/L per hour in controls; P<0.001). Steeper plasma sodium reduction during the test independently associated with the composite outcome of all-cause mortality and allograft loss (hazard ratio [HR], 1.73 per 1 mmol/L per hour decrease in plasma sodium; 95% confidence interval [95% CI], 1.23 to 2.45; P=0.002) and allograft loss alone (HR, 2.04 per 1 mmol/L per hour decrease in plasma sodium; 95% CI, 1.19 to 3.51; P=0.01). The association remained significant in a prespecified sensitivity analysis excluding patients with hyperglycemia. In addition, a steeper plasma sodium slope 3 months after transplantation independently correlated with lower mGFR at 12 months (β=1.93; 95% CI, 0.46 to 3.41; P=0.01).ConclusionsReduced osmoregulation performance occurs frequently in kidney transplant recipients and is an independent predictor of renal outcome.

scholarly journals BLOOD PRESSURE LEVELS DEPENDING ON THE DIFFERENCES IN THE LEVELS OF SALT INTAKE IN KIDNEY TRANSPLANT RECIPIENTS

2020 ◽  
Vol 104 (S3) ◽  
pp. S440-S440
Author(s):  
Hajime Hirano ◽  
Ryoici Maenosono ◽  
Yuya Fujiwara ◽  
Syunri Taniguchi ◽  
Hirofumi Uehara ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Kidney Transplant ◽  
Salt Intake ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients

FC 127SODIUM-GLUCOSE COTRANSPORTER 2 INHIBITORS (SGLT2I) SHORT-TERM OUTCOME IN DIABETIC KIDNEY TRANSPLANT RECIPIENTS

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Jude Yagan ◽  
Tarek S H Mahmoud ◽  
Osama Geith
Keyword(s):  
Diabetes Mellitus ◽  
Blood Pressure ◽  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Kidney Transplant ◽  
Standard Of Care ◽  
Diabetic Patients ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Short Term

Abstract Background and Aims The emergence of positive data on the use of sodium glucose co-transporter inhibitors (SGLT2i) in the last several years, begged the question of whether their positive outcomes can be seen in kidney transplant recipients, as they have the same and even more pronounced cardiovascular risk factors than the general population and in addition, we got better in improving graft and patients survival in the short term , but we lack the tools to improve long term patients and graft survival where so many patients die from cardiovascular disease with a functioning graft or lose their graft from chronic changes and chronic antibody mediated rejection with difficult to control blood pressure and proteinuria For these reasons we need more powerful tools , like the SGLT2i bearing in mind the unique side effects that might be amplified in kidney transplant recipients receiving immunosuppression like urinary tract infection, and the dip in serum creatinine. Method We collected data retrospectively from transplant records of patients with type II diabetes mellitus (T2D) or post-transplant diabetes mellitus (PTDM) (n=79) who were receiving SGLT2i agents plus standard of care [SOC] management and compared them to (n=56) similar diabetic patients who were only on SOC management. Results The two groups were comparable regarding age, sex, type of donor, type of diabetes (T2D PTDM), post-transplant period, induction immunosuppression and use of CNI. Though improvement of HbA1c was not significantly different between the two groups, patients on SGLT2i showed better drop in HbA1c compared to the SOC group (0.7% versus 0.5% respectively). Reduction of BMI was equal between the two groups (-1.1%) and there was no significant difference in the number of blood pressure medications (average 2 drugs per patient). Kidney function was assessed by the eGFR using CKD-EPI equation and by urine albumin/creatinine ratio (ACR). The eGFR was calculated at start then at 1,3,6 and 12 months. In SGLT2i group, eGFR showed a dip at 3 months (from 66 to 63.35 ml/min) then started to improve gradually toward the end of the year and maintained at a level close to baseline (65.44 ml/min). The SOC group showed gradual drop in eGFR over the year from 65.76 to 63.19 ml/min. Urine ACR reduced in the SGLT2i group from 48.79 to 23.79 mg/mmol creatinine and increased from 42.84 to 63.16 mg/mmol creatinine in the SOC group. The incidences of graft rejection, urinary tract infection, genital infection, myocardial infarction, heart failure or cerebrovascular stroke were not different between the groups. Conclusion Use of SGLT2i in managing diabetic patients post kidney transplantation is safe and has better short-term outcomes on renal function with comparable safety compared to standard of care therapy.

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