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Updated: Jan 8, 2026

Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
Published on: May 2, 2025
Fasting urine osmolality and risk of kidney disease progression in patients with type 2 diabetes
Jian-Jun Liu1, Sylvia Liu1, Joe de Keizer2
1Clinical Research Unit, Khoo Teck Puat Hospital, Singapore, Singapore.
Background And Hypothesis:
Urinary concentrating capacity largely depends on the structural and functional integrity of distal tubule and peritubular compartment whilst fasting urine osmolality represents the closest estimation of the maximal urinary concentrating ability. We hypothesize that a low fasting urine osmolality is associated with high risk for kidney disease progression beyond estimated glomerular filtration rate (eGFR) reduction and albuminuria in patients with type 2 diabetes.
Methods:
In this prospective study, fasting urine osmolality was measured in 1711 participants from the SMART2D (Singapore Study of Macro-angiopathy and Micro-Vascular Reactivity in Type 2 Diabetes) cohort in Singapore and 1097 participants from SURDIAGENE (SURvie, DIAbete de type 2 et GENEtique) cohort in France. The primary outcome was a composite of end-stage kidney disease or doubling of serum creatinine concentration. The secondary outcome was rapid kidney function decline (RKFD) defined as eGFR decline ≥5 mL/min/1.73 m2 per year.
Results:
A total of 239 and 82 kidney events were identified during a mean (standard deviation) of 6.6 (1.6) and 7.4 (3.7) years of follow-up in the SMART2D and SURDIAGENE cohorts, respectively. Compared with the upper tertile, participants with fasting urine osmolality in the lowest tertile had an increased risk of the composite kidney events after adjustment for known clinical risk factors [adjusted harzard ratio 2.94 (1.12-7.69) and 1.74 (0.85-3.58)]. They also had higher odds of experiencing RKFD [adjusted odds ratio 1.47 (0.95-2.28) and 1.84 (1.06-3.19), respectively]. Exploratory analysis revealed that low fasting urine osmolality was associated with high risk of the primary kidney outcome independent of plasma copeptin concentration or urinary kidney injury molecule-1, an established biomarker of proximal tubule injury.
Conclusions:
A low level of fasting urine osmolality is associated with increased risk of kidney disease progression independent of conventional risk factors. This readily accessible biomarker may potentially improve risk stratification for patients with type 2 diabetes.
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