Original InvestigationPathogenesis and Treatment of Kidney DiseaseEffect of Renin-Angiotensin-Aldosterone System Inhibition, Dietary Sodium Restriction, and/or Diuretics on Urinary Kidney Injury Molecule 1 Excretion in Nondiabetic Proteinuric Kidney Disease: A Post Hoc Analysis of a Randomized Controlled Trial
Section snippets
Patients and Protocol
This study is a post hoc analysis of a randomized, double-blind, placebo-controlled, crossover trial. The protocol was described in detail elsewhere.13 In brief, all included patients were aged 18 to 70 years and did not have diabetes. Patients had stable proteinuria with protein greater than 2 g and less than 10 g/d and stable kidney function (ie, creatinine clearance >30 mL/min and <6 mL/min/y decrease in the year preceding the study; creatinine clearance in mL/min may be converted to mL/s by
Patient Characteristics and Dietary Adherence
Thirty-four patients (25 men, 9 women; all white; mean age, 50 years; range, 23 to 68 years) were included. Baseline characteristics are listed in Table 1. Diagnoses were membranous glomerulopathy (7 patients), focal segmental glomerular sclerosis (8 patients), membranoproliferative glomerulonephritis (2 patients), minimal change disease with secondary glomerulosclerosis (2 patients), hypertensive nephropathy (5 patients), immunoglobulin A nephropathy (5 patients), Alport syndrome (1 patient),
Discussion
In proteinuric patients without diabetes with well-preserved and stable kidney function, urinary KIM-1 and NAG excretion were markedly increased, indicating tubular damage. Antiproteinuric treatment decreased urinary KIM-1 excretion in these patients, which was quantitatively related to the efficacy of proteinuria reduction, but not to blood pressure. Because the decrease in urinary KIM-1 excretion also occurred during the placebo/LS period, it appears to be caused by the lower proteinuria as
Acknowledgements
We thank Corrie Nieuwenhout, BSc, for skillful assistance at the outpatient clinic; Nynke Halbesma, MSc, for assistance with statistical analyses; Jacco Zwaagstra, BSc, for technical assistance; and Mieneke Rook, MD, for critically reviewing the manuscript.
Support: This study was supported by Merck Sharp & Dohme (grant MSGP NETH-15-01). The work in Dr Bonventre's laboratory was supported by National Institutes of Health grants DK39773, DK072381, and DK074099. Dr Vaidya was supported by a
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2020, Kidney MedicineCitation Excerpt :Urinary NGAL and KIM-1 levels are both well-established biomarkers for AKI, known to increase rapidly after AKI and to signify cellular injury within the kidney tubular structures.27 However, more recent data have indicated both NGAL and KIM-1 levels to be increased in patients with CKD compared with healthy adults,28-30 and there is evidence to suggest that tubular injury, detected by elevated urinary NGAL and KIM-1 levels, confers a higher risk for CKD progression in the absence of AKI.18 Furthermore, urinary NGAL and KIM-1 levels are both increased in association with hyperuricemia even in the absence of significant kidney disease.31
Originally published online as doi:10.1053/j.ajkd.2008.07.021 on September 29, 2008