Use of the urine-to-plasma urea ratio to predict ADPKD progression

Heida, J.E.; Gansevoort, R.T.; Messchendorp, A.L.; Meijer, E.; Casteleijn, N.F.; Boertien, W.E.; Zittema, D.; DIPAK Consortium

doi:doi:10.2215/CJN.10470620

Background and objectives Predictingdiseaseprogression in patientswith autosomaldominantpolycystic kidney disease (ADPKD) poses a challenge, especially in early- stage disease when kidney function is not yet affected. Ongoing growth of cysts causes maximal urine-concentrating capacity to decrease from early on. We therefore hypothesized that the urine-to-plasmaurea ratio, as a reflection of the urine-concentrating capacity, can be used as a marker to predict ADPKD progression. Design The urine- to-plasma urea ratio was calculated by dividing concentrations of early morning fasting spot urine urea by plasma urea. First, this ratio was validated as surrogate marker in 30 patients with ADPKD who underwent a prolongedwater deprivation test. Thereafter, associationwith kidney outcomewas evaluated in 583 patients with ADPKDwith a broad range of kidney function. Multivariable mixed-model regressionwas used to assess association with eGFR slope, and logarithmic regression to identify...Show moreBackground and objectives Predictingdiseaseprogression in patientswith autosomaldominantpolycystic kidney disease (ADPKD) poses a challenge, especially in early- stage disease when kidney function is not yet affected. Ongoing growth of cysts causes maximal urine-concentrating capacity to decrease from early on. We therefore hypothesized that the urine-to-plasmaurea ratio, as a reflection of the urine-concentrating capacity, can be used as a marker to predict ADPKD progression. Design The urine- to-plasma urea ratio was calculated by dividing concentrations of early morning fasting spot urine urea by plasma urea. First, this ratio was validated as surrogate marker in 30 patients with ADPKD who underwent a prolongedwater deprivation test. Thereafter, associationwith kidney outcomewas evaluated in 583 patients with ADPKDwith a broad range of kidney function. Multivariable mixed-model regressionwas used to assess association with eGFR slope, and logarithmic regression to identify patients with rapidly progressive disease, using a cutoff of 23.0 ml/min per 1.73 m2 per year. The urine-to-plasma urea ratio was compared with established predictors, namely, sex, age, baseline eGFR, Mayo Clinic height-adjusted total kidney volume class, and PKD gene mutation. Results The maximal urine-concentrating capacity and urine-to-plasma urea ratio correlated strongly (R50.90; P,0.001). Next, the urine-to-plasma urea ratio was significantly associated with rate of eGFR decline during a median follow-up of 4.0 (interquartile range, 2.6-5.0) years, both crude and after correction for established predictors (b50.58; P50.02). The odds ratio of rapidly progressive diseasewas 1.35 (95% confidence interval, 1.19 to 1.52; P,0.001) for every 10 units decrease in urine-to-plasma urea ratio, with adjustment for predictors. A combined risk score of the urine-to-plasma urea ratio, MayoClinic height-adjusted total kidney volume class, and PKD mutation predicted rapidly progressive disease better than each of the predictors separately. Conclusions The urine-to-plasma urea ratio, which is calculated fromroutine laboratory measurements, predicts disease progression in ADPKD in addition to other risk markers.Show less

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Use of the urine-to-plasma urea ratio to predict ADPKD progression