Abstract | BACKGROUND: Markers currently used to predict the likelihood of rapid disease progression in patients with autosomal dominant polycystic kidney disease ( ADPKD) are expensive and time consuming to assess and often have limited sensitivity. New, easy-to-measure markers are therefore needed that alone or in combination with conventional risk markers can predict the rate of disease progression. In the present study, we investigated the ability of tubular damage and inflammation markers to predict kidney function decline. METHODS: RESULTS: Included were 302 patients of whom 53.3% were female, with an average age of 48 ± 7 years, eGFR of 52 ± 12 mL/min/1.73 m2, and a height-adjusted total kidney volume (htTKV) of 1,082 (736-1,669) mL/m. At baseline, all urinary damage and inflammation markers were associated with baseline eGFR, also after adjustment for age, sex and baseline htTKV. For longitudinal analyses only patients randomized to standard care were considered (n = 152). A stepwise backward analysis revealed that β2MG and MCP-1 showed the strongest association with rapidly progressive disease. A urinary biomarker score was created by summing the ranking of tertiles of β2MG and MCP-1 excretion. The predictive value of this urinary biomarker score was higher compared to that of the Mayo htTKV classification (area under the curve [AUC] 0.73 [0.64-0.82] vs. 0.61 [0.51-0.71], p = 0.04) and comparable to that of the predicting renal outcomes in - ADPKD score (AUC 0.73 [0.64-0.82] vs. 0.65 [0.55-0.75], p = 0.18). In a second independent cohort with better kidney function, similar results were found for the urinary biomarker score. CONCLUSION: Measurement of urinary β2MG and MCP-1 excretion allows selection of ADPKD patients with rapidly progressive disease, with a predictive value comparable to or even higher than that of TKV or PKD mutation. Easy and inexpensive to measure urinary markers therefore hold promise to help predict prognosis in ADPKD.
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Authors | A Lianne Messchendorp, Esther Meijer, Folkert W Visser, Gerwin E Engels, Peter Kappert, Monique Losekoot, Dorien J M Peters, Ron T Gansevoort, on behalf of the DIPAK-1 study investigators |
Journal | American journal of nephrology
(Am J Nephrol)
Vol. 50
Issue 5
Pg. 375-385
( 2019)
ISSN: 1421-9670 [Electronic] Switzerland |
PMID | 31600749
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2019 The Author(s) Published by S. Karger AG, Basel. |
Chemical References |
- B2M protein, human
- Biomarkers
- CCL2 protein, human
- Chemokine CCL2
- Peptides, Cyclic
- beta 2-Microglobulin
- lanreotide
- Somatostatin
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Topics |
- Adult
- Biomarkers
(urine)
- Chemokine CCL2
(urine)
- Disease Progression
- Female
- Follow-Up Studies
- Glomerular Filtration Rate
- Humans
- Kidney Failure, Chronic
(diagnosis, epidemiology, etiology, prevention & control)
- Kidney Tubules
(immunology, pathology)
- Longitudinal Studies
- Male
- Middle Aged
- Peptides, Cyclic
(therapeutic use)
- Polycystic Kidney, Autosomal Dominant
(complications, drug therapy, pathology, urine)
- Predictive Value of Tests
- Prognosis
- Prospective Studies
- Somatostatin
(analogs & derivatives, therapeutic use)
- Time Factors
- beta 2-Microglobulin
(urine)
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