scholarly journals Serum bicarbonate is associated with kidney outcomes in autosomal dominant polycystic kidney disease

2020 ◽  
Author(s):  
Charles J Blijdorp ◽  
David Severs ◽  
Usha M Musterd-Bhaggoe ◽  
Ronald T Gansevoort ◽  
Robert Zietse ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Kidney Function ◽  
Autosomal Dominant ◽  
Hazard Ratio ◽  
Ammonium Excretion ◽  
Serum Bicarbonate ◽  
Polycystic Kidney ◽  
Baseline Serum ◽  
Autosomal Dominant Polycystic Kidney

Abstract Graphical Abstract Background Metabolic acidosis accelerates progression of chronic kidney disease, but whether this is also true for autosomal dominant polycystic kidney disease (ADPKD) is unknown. Methods Patients with ADPKD from the DIPAK (Developing Interventions to halt Progression of ADPKD) trial were included [n = 296, estimated glomerular filtration rate (eGFR) 50 ± 11 mL/min/1.73 m2, 2.5 years follow-up]. Outcomes were worsening kidney function (30% decrease in eGFR or kidney failure), annual eGFR change and height-adjusted total kidney and liver volumes (htTKV and htTLV). Cox and linear regressions were adjusted for prognostic markers for ADPKD [Mayo image class and predicting renal outcomes in ADPKD (PROPKD) scores] and acid–base parameters (urinary ammonium excretion). Results Patients in the lowest tertile of baseline serum bicarbonate (23.1 ± 1.6 mmol/L) had a significantly greater risk of worsening kidney function [hazard ratio = 2.95, 95% confidence interval (CI) 1.21–7.19] compared with patients in the highest tertile (serum bicarbonate 29.0 ± 1.3 mmol/L). Each mmol/L decrease in serum bicarbonate increased the risk of worsening kidney function by 21% in the fully adjusted model (hazard ratio = 1.21, 95% CI 1.06–1.37). Each mmol/L decrease of serum bicarbonate was also associated with further eGFR decline (−0.12 mL/min/1.73 m2/year, 95% CI −0.20 to −0.03). Serum bicarbonate was not associated with changes in htTKV or htTLV growth. Conclusions In patients with ADPKD, a lower serum bicarbonate within the normal range predicts worse kidney outcomes independent of established prognostic factors for ADPKD and independent of urine ammonium excretion. Serum bicarbonate may add to prognostic models and should be explored as a treatment target in ADPKD.

scholarly journals Risk of Hospital Encounters With Kidney Stones in Autosomal Dominant Polycystic Kidney Disease: A Cohort Study

2021 ◽  
Vol 8 ◽  
pp. 205435812110002
Author(s):  
Vinusha Kalatharan ◽  
Blayne Welk ◽  
Danielle M. Nash ◽  
Stephanie N. Dixon ◽  
Justin Slater ◽  
...  
Keyword(s):  
Cohort Study ◽  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Kidney Stones ◽  
Autosomal Dominant ◽  
Significant Risk ◽  
Hazard Ratio ◽  
Cox Proportional Hazards Model ◽  
Polycystic Kidney ◽  
Autosomal Dominant Polycystic Kidney

Background: There is a perception that patients with autosomal dominant polycystic kidney disease (ADPKD) are more likely to develop kidney stones than the general population. Objective: To compare the rate of hospital encounter with kidney stones and the rate of stone interventions between patients with and without ADPKD. Design: Retrospective cohort study. Setting: Ontario, Canada. Patients: Patients with and without ADPKD who had a prior hospital encounter between 2002 and 2016. Measurements: Rate of hospital encounter with kidney stones and rate of stone intervention. Methods: We used inverse probability exposure weighting based on propensity scores to balance baseline indicators of health between patients with and without ADPKD. We followed each patient until death, emigration, outcomes, or March 31, 2017. We used a Cox proportional hazards model to compare event rates between the two groups. Results: Patients with ADPKD were at higher risk of hospital encounter with stones compared with patients without ADPKD (81 patients of 2094 with ADPKD [3.8%] vs 60 patients of 1902 without ADPKD [3.2%]; 8.9 vs 5.1 events per 1000 person-years; hazard ratio 1.6 [95% CI, 1.3-2.1]). ADPKD was not associated with a higher risk of stone intervention (49 of 2094 [2.3%] vs 47 of 1902 [2.4%]; 5.3 vs 3.9 events per 1000 person-years; hazard ratio 1.2 [95% CI = 0.9-1.3]). Limitations: We did not have information on kidney stone events outside of the hospital. There is a possibility of residual confounding. Conclusion: ADPKD was a significant risk factor for hospital encounters with kidney stones.

scholarly journals A study of sirolimus and mTOR kinase inhibitor in a hypomorphic Pkd1 mouse model of autosomal dominant polycystic kidney disease

2019 ◽  
Vol 317 (1) ◽  
pp. F187-F196 ◽  
Author(s):  
Sara J. Holditch ◽  
Carolyn N. Brown ◽  
Daniel J. Atwood ◽  
Andrew M. Lombardi ◽  
Khoa N. Nguyen ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Mouse Model ◽  
Polycystic Kidney Disease ◽  
Kidney Function ◽  
Autosomal Dominant ◽  
Kinase Inhibitor ◽  
Polycystic Kidney ◽  
Mtor Kinase ◽  
Autosomal Dominant Polycystic Kidney ◽  
Cyst Growth

Autosomal dominant polycystic kidney disease (PKD) is characterized by cyst formation and growth, which are partially driven by abnormal proliferation of tubular cells. Proproliferative mechanistic target of rapamycin (mTOR) complexes 1 and 2 (mTORC1 and mTORC2) are activated in the kidneys of mice with PKD. Sirolimus indirectly inhibits mTORC1. Novel mTOR kinase inhibitors directly inhibit mTOR kinase, resulting in the inhibition of mTORC1 and mTORC2. The aim of the present study was to determine the effects of sirolimus versus the mTOR kinase inhibitor torin2 on cyst growth and kidney function in the Pkd1 p.R3277C ( Pkd1RC/RC) mouse model, a hypomorphic Pkd1 model orthologous to the human condition, and to determine the effects of sirolimus versus torin2 on mTORC1 and mTORC2 signaling in PKD1−/− cells and in the kidneys of Pkd1RC/RC mice. In vitro, both inhibitors reduced mTORC1 and mTORC2 phosphorylated substrates and negatively impacted cellular metabolic activity, as measured by MTT assay. Pkd1RC/RC mice were treated with sirolimus or torin2 from 50 to 120 days of age. Torin2 was as effective as sirolimus in decreasing cyst growth and improving loss of kidney function. Both sirolimus and torin2 decreased phosphorylated S6 protein, phosphorylated eukaryotic translation initiation factor 4E-binding protein 1, phosphorylated Akt, and proliferation in Pkd1RC/RC kidneys. In conclusion, torin2 and sirolimus were equally effective in decreasing cyst burden and improving kidney function and mediated comparable effects on mTORC1 and mTORC2 signaling and proliferation in the Pkd1RC/RC kidney.

scholarly journals Long-term trajectory of kidney function in autosomal-dominant polycystic kidney disease

2019 ◽  
Vol 95 (5) ◽  
pp. 1253-1261 ◽  
Author(s):  
Alan S.L. Yu ◽  
Chengli Shen ◽  
Douglas P. Landsittel ◽  
Jared J. Grantham ◽  
Larry T. Cook ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Kidney Function ◽  
Autosomal Dominant ◽  
Polycystic Kidney ◽  
Autosomal Dominant Polycystic Kidney

scholarly journals Urinary metabolites associate with the rate of kidney function decline in patients with autosomal dominant polycystic kidney disease

PLoS ONE ◽  
2020 ◽  
Vol 15 (5) ◽  
pp. e0233213 ◽  
Author(s):  
Shosha E. I. Dekker ◽  
Aswin Verhoeven ◽  
Darius Soonawala ◽  
Dorien J. M. Peters ◽  
Johan W. de Fijter ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Kidney Function ◽  
Autosomal Dominant ◽  
Urinary Metabolites ◽  
Polycystic Kidney ◽  
Autosomal Dominant Polycystic Kidney ◽  
Kidney Function Decline

scholarly journals Kidney Function and Plasma Copeptin Levels in Healthy Kidney Donors and Autosomal Dominant Polycystic Kidney Disease Patients

2014 ◽  
Vol 9 (9) ◽  
pp. 1553-1562 ◽  
Author(s):  
Debbie Zittema ◽  
Else van den Berg ◽  
Esther Meijer ◽  
Wendy E. Boertien ◽  
Anneke C. Muller Kobold ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Kidney Function ◽  
Autosomal Dominant ◽  
Polycystic Kidney ◽  
Kidney Donors ◽  
Autosomal Dominant Polycystic Kidney

scholarly journals Effect of Lanreotide on Kidney Function in Patients With Autosomal Dominant Polycystic Kidney Disease

JAMA ◽  
2018 ◽  
Vol 320 (19) ◽  
pp. 2010 ◽  
Author(s):  
Esther Meijer ◽  
Folkert W. Visser ◽  
Rene M. M. van Aerts ◽  
Charles J. Blijdorp ◽  
Niek F. Casteleijn ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Kidney Function ◽  
Autosomal Dominant ◽  
Polycystic Kidney ◽  
Autosomal Dominant Polycystic Kidney

scholarly journals Association between urinary biomarkers and disease progression in adults with autosomal dominant polycystic kidney disease

2019 ◽  
Vol 13 (4) ◽  
pp. 607-612
Author(s):  
Alfons Segarra-Medrano ◽  
Marisa Martin ◽  
Irene Agraz ◽  
Mercè Vilaprinyó ◽  
Betty Chamoun ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Kidney Function ◽  
Autosomal Dominant ◽  
Kidney Injury ◽  
Polycystic Kidney ◽  
Β2 Microglobulin ◽  
Urinary Levels ◽  
Autosomal Dominant Polycystic Kidney ◽  
Egfr Slope

Abstract Background Height-adjusted total kidney volume (htTKV) is considered as the best predictor of kidney function in patients with autosomal dominant polycystic kidney disease (ADPKD), but its limited predictive capacity stresses the need to find new biomarkers of ADPKD progression. The aim of this study was to investigate urinary biomarkers of ADPKD progression. Methods This observational study included ADPKD patients, and two comparator groups of ischaemic and non-ischaemic kidney injury: benign nephroangiosclerosis patients and non-ischaemic chronic kidney disease (CKD) patients. Proteinuria, htTKV and urinary levels of molecules are associated with ischaemia and/or tubular injury. The slope of estimated glomerular filtration rate (eGFR) was used as a dependent variable in univariate and multivariate models of kidney function decline. Results The study included 130 patients with ADPKD, 55 with nephroangiosclerosis and 40 with non-ischaemic CKD. All patients had increased urinary concentrations of biomarkers associated with tubular lesions (liver fatty acid-binding protein, kidney injury molecule-1, β2-microglobulin) and molecules overexpressed under ischaemic conditions [hypoxia-inducible factor-1α, vascular endothelial growth factor (VEGF) and monocyte chemoattractant protein-1 (MCP-1)]. These biomarkers correlated positively with htTKV and negatively with the eGFR slope. htTKV was the single best predictor of the eGFR slope variability in univariate analyses. However, a multivariate model including urinary levels of β2-microglobulin, MCP-1 and VEGF improved the capacity to predict the decline of eGFR in ADPKD patients compared with htTKV alone. Conclusions The urinary levels of molecules associated with either renal ischaemia (VEGF and MCP-1) or tubular damage (β2-microglobulin) are associated with renal function deterioration in ADPKD patients, and are, therefore, candidates as biomarkers of ADPKD progression.

Sign in / Sign up

Export Citation Format

Share Document