GFR decline and prior dysuria among Nicaraguan sugarcane workers

Abstract Background Inhibiting enteropeptidase, a gut serine protease regulating protein digestion, suppresses food intake and ameliorates obesity and diabetes in mice. However, the effects of enteropeptidase inhibition on the kidney parameters are largely unknown. Here, we evaluated the chronic effects of an enteropeptidase inhibitor, SCO-792, on kidney function, albuminuria, and kidney pathology in spontaneously hypercholesterolaemic (SHC) rats, a rat chronic kidney disease (CKD) model. Methods SCO-792, an orally available enteropeptidase inhibitor, was administered (0.03% and 0.06% (w/w) in the diet) for five weeks to 20-week-old SHC rats showing albuminuria and progressive decline in glomerular filtration rate (GFR). The effects of SCO-792 and the contribution of amino acids to these effects were evaluated. Results SCO-792 increased the faecal protein content, indicating that SCO-792 inhibited enteropeptidase in SHC rats. Chronic treatment with SCO-792 prevented GFR decline and suppressed albuminuria. Moreover, SCO-792 improved glomerulosclerosis and kidney fibrosis. Pair feeding with SCO-792 (0.06%) was less effective in preventing GFR decline, albuminuria, and renal histological damage than SCO-792 treatment, indicating the enteropeptidase-inhibition-dependent therapeutic effects of SCO-792. SCO-792 did not affect the renal plasma flow, suggesting that its effect on GFR was mediated by an improvement in filtration fraction. Moreover, SCO-792 increased hydrogen sulphide production capacity, which has a role in tissue protection. Finally, methionine and cysteine supplementation to the diet abrogated SCO-792-induced therapeutic effects on albuminuria. Conclusions SCO-792-mediated inhibition of enteropeptidase potently prevented GFR decline, albuminuria, and kidney fibrosis; hence, it may have therapeutic potential against CKD.

Download Full-text

Diabetic nephropathy in a sibling and albuminuria predict early GFR decline: a prospective cohort study

BMC Nephrology ◽

10.1186/1471-2369-14-124 ◽

2013 ◽

Vol 14 (1) ◽

Cited By ~ 7

Author(s):

Douglas Gunzler ◽

Anthony J Bleyer ◽

Robert L Thomas ◽

Alicia O’Brien ◽

Gregory B Russell ◽

...

Keyword(s):

Cohort Study ◽

Diabetic Nephropathy ◽

Prospective Cohort Study ◽

Prospective Cohort ◽

Gfr Decline

Download Full-text

GFR Decline as an End Point for Clinical Trials in CKD: A View From Europe

American Journal of Kidney Diseases ◽

10.1053/j.ajkd.2014.10.001 ◽

2014 ◽

Vol 64 (6) ◽

pp. 838-840 ◽

Cited By ~ 6

Author(s):

Peter G.M. Mol ◽

Romaldas Maciulaitis ◽

Thorsten Vetter

Keyword(s):

Clinical Trials ◽

End Point ◽

Gfr Decline

Download Full-text

Albuminuria during treatment with angiotensin type II receptor blocker is a predictor for GFR decline among non-diabetic hypertensive CKD patients

PLoS ONE ◽

10.1371/journal.pone.0202676 ◽

2018 ◽

Vol 13 (8) ◽

pp. e0202676

Author(s):

Mi-Yeon Yu ◽

Dong Ki Kim ◽

Jung Hwan Park ◽

Sung Joon Shin ◽

Sang Ho Lee ◽

...

Keyword(s):

Receptor Blocker ◽

Type Ii ◽

Gfr Decline ◽

Angiotensin Type

Download Full-text

Urine Proteomics Revealed a Significant Correlation Between Urine-Fibronectin Abundance and Estimated-GFR Decline in Patients with Bardet-Biedl Syndrome

Kidney & Blood Pressure Research ◽

10.1159/000488096 ◽

2018 ◽

Vol 43 (2) ◽

pp. 389-405 ◽

Cited By ~ 11

Author(s):

Marianna Caterino ◽

Miriam Zacchia ◽

Michele Costanzo ◽

Giuliana Bruno ◽

Davide Arcaniolo ◽

...

Keyword(s):

Estimated Gfr ◽

Bardet Biedl Syndrome ◽

Urine Proteomics ◽

Gfr Decline

Download Full-text

Glomerular resistances predict long-term GFR decline in type 2 diabetic patients without overt nephropathy: a longitudinal subgroup analysis of the DEMAND trial

Acta Diabetologica ◽

10.1007/s00592-021-01804-9 ◽

2021 ◽

Author(s):

Fabiola Carrara ◽

Piero Ruggenenti ◽

Annalisa Perna ◽

Ilian Petrov Iliev ◽

Flavio Gaspari ◽

...

Keyword(s):

Subgroup Analysis ◽

Diabetic Patients ◽

Overt Nephropathy ◽

Type 2 Diabetic Patients ◽

Gfr Decline ◽

Type 2 Diabetic

Download Full-text

Short- and Long-Term Evaluation of Renal Function after Radical Cystectomy and Cutaneous Ureterostomy in High-Risk Patients

Journal of Clinical Medicine ◽

10.3390/jcm9072191 ◽

2020 ◽

Vol 9 (7) ◽

pp. 2191

Author(s):

Massimiliano Creta ◽

Ferdinando Fusco ◽

Roberto La Rocca ◽

Marco Capece ◽

Giuseppe Celentano ◽

...

Keyword(s):

Renal Function ◽

Radical Cystectomy ◽

Urinary Diversion ◽

Kidney Injury ◽

Risk Patients ◽

Term Evaluation ◽

Gfr Decline ◽

American Society ◽

American Society Of Anesthesiologists ◽

Cutaneous Ureterostomy

Deterioration of renal function has been reported after radical cystectomy (RC) with urinary diversion. We investigated renal function changes in elderly bladder cancer (BCa) patients who underwent RC with cutaneous ureterostomy (CU) urinary diversion. We performed a retrospective, observational study. BCa patients aged ≥75 with an American Society of Anesthesiologists (ASA) class greater than II were included. Glomerular filtration rate (GFR) was the main outcome measure. GFR values were recorded preoperatively, at discharge, at 6-month follow-up, and yearly up to 60 months. A total of 70 patients with a median age of 78.0 years were identified. Median preoperative GFR was 74.3 mL/min/1.73 m2 and declined significantly to 54.6 mL/min/1.73 m2 after 6 months (p < 0.001). A gradual GFR decline was observed thereafter, reaching a median value of 46.2 after 60 months. Preoperative GFR and acute kidney injury were significant predictors of fast deterioration of GFR and of 25% deterioration of GFR after 12 months. Elderly BCa patients with high comorbidity rates undergoing RC with CU should be carefully informed about the risk of GFR deterioration and the need for adequate monitoring.

Download Full-text

Urinary excretion of epidermal growth factor and rapid loss of kidney function

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa208 ◽

2020 ◽

Author(s):

Jon Viljar Norvik ◽

Laura R Harskamp ◽

Viji Nair ◽

Kerby Shedden ◽

Marit D Solbu ◽

...

Keyword(s):

Growth Factor ◽

Epidermal Growth Factor ◽

General Population ◽

Urinary Excretion ◽

Assessment System ◽

Sensitivity Analyses ◽

Increased Risk ◽

Gfr Decline ◽

Epidermal Growth ◽

End Stage

Abstract Background Lower urinary excretion of the kidney tubule–specific biomarker epidermal growth factor (uEGF) is associated with increased risk of renal function [glomerular filtration rate (GFR)] loss in diabetes and in patients with established chronic kidney disease (CKD). We investigated whether uEGF is associated with rapid GFR decline or incident CKD in the general population. Methods Subjects without CKD or diabetes were recruited from the general population in Tromso, Norway [Renal Iohexol Clearance Survey (RENIS); N = 1249] and Groningen, the Netherlands [Prevention of REnal and Vascular END-stage disease (PREVEND); N = 4534], with a median follow-up of 5.6 and 7.4 years, respectively. GFR was measured by iohexol clearance in the RENIS and estimated using the CKD Epidemiology Collaboration creatinine–cystatin C equation in the PREVEND study. Rapid GFR decline was defined as an annual GFR loss >3.0 mL/min/1.73 m2 and in sensitivity analyses as subjects with the 10% steepest GFR slope within each cohort. Results Lower baseline uEGF excretion was associated with rapid GFR loss in both cohorts {RENIS, odds ratio [OR] per 1 μg/mmol lower uEGF 1.42 [95% confidence interval (CI) 1.06–1.91], P = 0.02; PREVEND, OR 1.29 [95% CI 1.10–1.53], P < 0.01}, adjusted for baseline GFR, albumin:creatinine ratio and conventional CKD risk factors. Similar results were obtained using the outcome of the 10% steepest GFR slope in each cohort. Lower uEGF levels were associated with incident CKD in the combined analysis of both cohorts. Conclusions Lower uEGF levels are associated with increased risk of rapid GFR loss and incident CKD in the general population. This finding, together with previous findings in CKD and high-risk populations, supports that uEGF may serve as a broadly applicable biomarker representing the tubular component of the current glomerulus-centric clinical risk assessment system.

Download Full-text