Fasting urine osmolality and risk of kidney disease progression in patients with type 2 diabetes

Background and Hypothesis Urinary concentrating capacity largely depends on 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 eGFR reduction and albuminuria in patients with type 2 diabetes. Methods In this prospective study, fasting urine osmolality was measured in 1711 participants from SMART2D cohort in Singapore and 1097 participants from SURDIAGENE 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/1.73m2 per year or greater. Results 239 and 82 kidney events were identified during a mean (SD) of 6.6 (1.6) and 7.4 (3.7) years of follow-up in SMART2D and SURDIAGENE cohorts, respectively. Compared to 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 HR 2.94 [1.12–7.69] and 1.74 [0.85–3.58]). They also had higher odds of experiencing RKFD (adjusted OR 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 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.