The Relationship of Osmolality and Kidney Outcomes in Patients with Autosomal Dominant Polycystic Kidney Disease

Background Current treatment of autosomal dominant polycystic kidney disease (ADPKD) is mainly focused on inhibiting cystogenesis through arginine vasopressin suppression and there have been interests in achieving similar vasopressin suppression by reduction of osmolality with increased water intake. However, the causal relationship between serum osmolality and kidney outcome remained unclear in ADPKD patients. We aim to evaluate the relationship of serum osmolality and its effect on kidney outcome in ADPKD patients. Methods Three hundred and eleven tolvaptan treatment-naïve ADPKD patients were recruited prospectively from the CysticHK cohort, a territory-wide ADPKD registry across twelve tertiary hospitals in Hong Kong. Beside clinical data, serial measurement of serum and urinary osmolality were obtained every six months over five years. All participants were treated according to the standard of clinical care. The primary outcome was the 40% decline from baseline eGFR. Results Patients with a high serum osmolality have a worse kidney outcome, as shown by the Kaplan-Meier plots (log-rank p=<0.001) and the Cox regression model that showed a 5.91 times higher risk of reaching 40% eGFR decline compared to the top with bottom quartiles of osmolality (p=0.018). In contrast, there is an inverse relationship for urine osmolality. A ROC analysis to assess the predictive efficacy of osmolality for identifying those at high risk of kidney decline also showed a good performance for serum osmolality (AUC 0.81, 95%CI, 0.73-0.89; p<0.001). The urinary osmolality did not show a clinical meaningful predictive efficacy (AUC 0.35, 95%CI 0.28-0.43; p=0.003). Conclusions Serum osmolality may be a possible surrogate marker for the clinical monitoring of ADPKD patients, especially when access to copeptin level is limited; and high serum osmolality conveys possible detrimental effect on the kidney outcomes.