Effect of renin-angiotensin-aldosterone system inhibition, dietary sodium restriction, and/or diuretics on urinary kidney injury molecule 1 excretion in nondiabetic …
F Waanders, VS Vaidya, H van Goor… - American journal of …, 2009 - Elsevier
American journal of kidney diseases, 2009•Elsevier
BACKGROUND: Tubulointerstitial damage has an important role in chronic kidney diseases
(CKDs) with proteinuria. Urinary kidney injury molecule 1 (KIM-1) reflects tubular KIM-1 and
is considered a sensitive biomarker for early tubular damage. We hypothesized that a
decrease in proteinuria by using therapeutic interventions is associated with decreased
urinary KIM-1 levels. STUDY DESIGN: Post hoc analysis of a randomized, double-blind,
placebo-controlled, crossover trial. SETTING & PARTICIPANTS: 34 patients without diabetes …
(CKDs) with proteinuria. Urinary kidney injury molecule 1 (KIM-1) reflects tubular KIM-1 and
is considered a sensitive biomarker for early tubular damage. We hypothesized that a
decrease in proteinuria by using therapeutic interventions is associated with decreased
urinary KIM-1 levels. STUDY DESIGN: Post hoc analysis of a randomized, double-blind,
placebo-controlled, crossover trial. SETTING & PARTICIPANTS: 34 patients without diabetes …
BACKGROUND
Tubulointerstitial damage has an important role in chronic kidney diseases (CKDs) with proteinuria. Urinary kidney injury molecule 1 (KIM-1) reflects tubular KIM-1 and is considered a sensitive biomarker for early tubular damage. We hypothesized that a decrease in proteinuria by using therapeutic interventions is associated with decreased urinary KIM-1 levels.
STUDY DESIGN
Post hoc analysis of a randomized, double-blind, placebo-controlled, crossover trial.
SETTING & PARTICIPANTS
34 patients without diabetes with proteinuria from our outpatient renal clinic.
INTERVENTION
Stepwise 6-week interventions of losartan, sodium restriction (low-sodium [LS] diet), their combination, losartan plus hydrochlorothiazide (HCT), and the latter plus an LS diet.
OUTCOMES & MEASUREMENTS
Urinary excretion of KIM-1, total protein, and N-acetyl-β-d-glucosaminidase (NAG) as a positive control for tubular injury.
RESULTS
Mean baseline urine protein level was 3.8 ± 0.4 (SE) g/d, and KIM-1 level was 1,706 ± 498 ng/d (increased compared with healthy controls; 74 ng/d). KIM-1 level was decreased by using placebo/LS (1,201 ± 388 ng/d; P < 0.05), losartan/high sodium (1,184 ± 296 ng/d; P = 0.09), losartan/LS (921 ± 176 ng/d; P < 0.05), losartan/high sodium plus HCT (862 ± 151 ng/d; P < 0.05) and losartan/LS plus HCT (743 ± 170 ng/d; P < 0.05). The decrease in urinary KIM-1 levels paralleled the decrease in proteinuria (R = 0.523; P < 0.001), but not blood pressure or creatinine clearance. 16 patients reached target proteinuria with protein less than 1 g/d, whereas KIM-1 levels normalized in only 2 patients. Urinary NAG level was increased at baseline and significantly decreased during the treatment periods of combined losartan plus HCT only. The decrease in urinary NAG levels was not closely related to proteinuria.
LIMITATIONS
Post hoc analysis.
CONCLUSIONS
Urinary KIM-1 level was increased in patients with nondiabetic CKD with proteinuria and decreased in parallel with proteinuria by using losartan, sodium restriction, their combination, losartan plus HCT, and the latter plus sodium restriction. These results are consistent with the hypothesis of amelioration of proteinuria-induced tubular damage. Long term studies are warranted to evaluate whether targeting treatment on KIM-1 can improve outcomes in patients with CKD with proteinuria.
Elsevier