SOMATOSTATIN IS NOT ASSOCIATED WITH DISEASE SEVERITY OR RATE OF DISEASE PROGRESSION IN PATIENTS WITH AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE

Introduction and Aims: Somatostatin (SST) is a key regulator hormone and is produced by a variety of cells. In the kidney, SST leads to inhibition of intracellular production of cyclic adenosinemonophosfate (cAMP). In autosomal dominant polycystic kidney disease (ADPKD), high levels of cAMP in renal tubular cells result in cyst formation and cyst growth and consequently renal function loss. SST analogues are suggested to be beneficial in slowing the rate of disease progression in ADPKD. We therefore investigated whether physiological concentrations of SST are associated with parameters of disease severity and disease progression in patients with ADPKD.

Methods: At baseline, fasting concentrations of SST were measured in plasma with an enzyme immunoassay. Kidney function was measured (mGFR), by (125)I-iothalamate and height adjusted total kidney volume (htTKV) by MRI. Disease progression was expressed as annual change in mGFR and htTKV. Multivariable linear regression was used to investigate the association of SST with disease parameters.

Results: We included 133 patients with ADPKD, without metabolic disorders such as diabetes, age 41±11yrs, 44% female, mGFR 75±32 ml/min/1.73m2, htTKV 863 (527-1305) mL/m, SST concentration 48.5 (34.3-77.8) pg/mL. At baseline the well-known associations of SST with age (st. β=0.18, p=0.05) and sex (men 56.7 (38.7-77.7) vs. women 38.8 (27.8-63.8) pg/mL, p=0.01) were confirmed. However, SST was neither associated with mGFR nor htTKV, after adjustment for age and sex (st. β=0.14, p=0.06 and st. β=0.13, p=0.2 resp.). During follow-up for 3.8±1.2 yrs, annual changes in mGFR and htTKV were -3.0±3.0 mL/min/1.73m2 and 6.2±5.9% resp. Baseline SST was neither associated with annual change in mGFR nor with annual change in htTKV (st. β= -0.02, p=0.9 and st. β=-0.07, p=0.5 resp.).

Conclusions: In this cohort of patients with ADPKD, fasting plasma concentrations of SST are neither associated with disease severity at baseline, nor with rate of disease progression during follow-up, indicating that SST cannot be used as a biomarker. SST analogues characterized by high affinity for the SST receptors have been suggested to be beneficial to slow the rate of disease progression in these patients. Given our data, we hypothesize that the physiological plasma SST concentrations may be too low to result in pathophysiological effects in ADPKD.