Effect of pravastatin on kidney function and urinary protein excretion in autosomal dominant polycystic kidney disease

2009 ◽  
Vol 44 (1) ◽  
pp. 56-61 ◽  
Author(s):  
Robert G. Fassett ◽  
Jeff S. Coombes ◽  
David Packham ◽  
Kenneth F. Fairley ◽  
Priscilla Kincaid-Smith
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Kidney Function ◽  
Autosomal Dominant ◽  
Urinary Protein Excretion ◽  
Urinary Protein ◽  
Polycystic Kidney ◽  
Protein Excretion ◽  
Autosomal Dominant Polycystic Kidney

Overt proteinuria and microalbuminuria in autosomal dominant polycystic kidney disease.

1994 ◽  
Vol 5 (6) ◽  
pp. 1349-1354
Author(s):  
A B Chapman ◽  
A M Johnson ◽  
P A Gabow ◽  
R W Schrier
Keyword(s):  
Mean Arterial Pressure ◽  
Kidney Disease ◽  
Arterial Pressure ◽  
Polycystic Kidney Disease ◽  
Autosomal Dominant ◽  
Urinary Protein Excretion ◽  
Urinary Protein ◽  
Polycystic Kidney ◽  
Protein Excretion ◽  
Autosomal Dominant Polycystic Kidney

The amount of proteinuria is a prognostic indicator in a variety of glomerular disorders. To examine the importance of urinary protein excretion in autosomal dominant polycystic kidney disease, this study determined the clinical characteristics of autosomal dominant polycystic kidney disease patients with established proteinuria and the frequency of microalbuminuria in hypertensive autosomal dominant polycystic kidney disease patients without proteinuria. In 270 autosomal dominant polycystic kidney disease patients, mean 24-h urinary protein excretion was 259 +/- 22 mg/day. Forty-eight of 270 autosomal dominant poly-cystic kidney disease patients had over proteinuria (> 300 mg/day). The patients with established proteinuria had higher mean arterial pressures, larger renal volumes, and lower creatinine clearances than did their nonproteinuric counterparts (all P < 0.0001), a greater pack year smoking history (P < 0.05), and the projection of a more aggressive course of renal disease (P < 0.05). All autosomal dominant polycystic kidney disease patients with established proteinuria were hypertensive, as compared with 67% without established proteinuria (P < 0.001). Forty-nine patients with hypertension and left ventricular hypertrophy without established proteinuria were examined for microalbuminuria; 41% demonstrated microalbuminuria. Those with microalbuminuria had higher mean arterial pressure, larger renal volumes and increased filtration fraction. Therefore, established proteinuria and microalbuminuria in autosomal dominant polycystic kidney disease patients are associated with increased mean arterial pressure and more severe renal cystic involvement.

scholarly journals Factors relating to urinary protein excretion in children with autosomal dominant polycystic kidney disease.

1998 ◽  
Vol 9 (10) ◽  
pp. 1908-1914 ◽  
Author(s):  
C Sharp ◽  
A Johnson ◽  
P Gabow
Keyword(s):  
Kidney Disease ◽  
Renal Disease ◽  
Polycystic Kidney Disease ◽  
Autosomal Dominant ◽  
Urinary Protein Excretion ◽  
Polycystic Kidney ◽  
Protein Excretion ◽  
Autosomal Dominant Polycystic Kidney ◽  
Overt Proteinuria ◽  
Excretion Rates

Adults with autosomal dominant polycystic kidney disease (ADPKD) who have overt proteinuria (>300 mg/d) have higher mean arterial pressures, lower creatinine clearances, larger renal volumes, and a more aggressive course of renal disease than ADPKD patients without proteinuria. This study examines the relationship between proteinuria and microalbuminuria and similar factors in ADPKD children. A total of 189 children from 81 ADPKD families was included in the analysis. The ADPKD children (n = 103) had significantly greater urine protein excretion rates than the non-ADPKD children (n = 86) (3.9+/-0.3 versus 2.8+/-0.2 mg/m2 per h, P < 0.001). Children with severe renal cystic disease (> 10 cysts; n = 54) had greater protein excretion than those with moderate disease (< or = 10 cysts; n = 49) (4.4+/-0.5 versus 3.3+/-0.2 mg/m2 per h, P < 0.05). The ADPKD children had significantly greater albumin excretion rates than the non-ADPKD children (32+/-6 versus 10+/-2 mg/m2 per 24 h, P < 0.001), and a higher percentage of ADPKD children had significant microalbuminuria (>15 mg/m2 per 24 h in boys and >23 mg/m2 per 24 h in girls) than their unaffected siblings (30% versus 10%, P < 0.05). Thirty percent of ADPKD children had albuminuria and 23% had overt proteinuria. For all ADPKD children, there was no correlation between proteinuria and hypertension. However, there was a significant correlation between urinary protein excretion and diastolic BP among children diagnosed after the first year of life (r = 0.23, P < 0.05). Therefore, proteinuria and albuminuria occur early in the course of ADPKD and may be markers of more severe renal disease.

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.

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