EFFECT OF A SOMATOSTATIN ANALOG, OCTREOTIDE, ON RENAL HEMODYNAMICS AND ALBUMINURIA IN ACROMEGALIC PATIENTS

Although insulin-like growth factor I increases renal function, the renal haemodynamic abnormality underlying the glomerular hyperfiltration in acromegaly is unknown. In normal subjects, amino acids and low doses of dopamine increase the glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), presumably by a predominant vasodilation of the afferent and efferent glomerular arterioles, respectively. We studied baseline GFR and ERPF (determined with I-125-iothalamate and I-131-hippuran, respectively), the renal stimulatory effects of amino acid and dopamine infusion, and albuminuria before and after 3 months octreotide treatment in seven acromegalic patients with metabolically active disease. Octreotide reduced growth hormone concentrations from 14.7 +/- 3.0 to 5.5 +/- 1.0-mu-g l-1 (mean+/-SEM, n = 7; P < 0.001) and insulin-like growth factor I levels from 4.12 +/- 1.31 to 2.44 +/- 0-68 kU l-1 (P < 0.02). Glucagon concentrations did not change. Baseline GFR and ERPF declined from 132 +/- 5 to 117 +/- 6 and from 547 +/- 32 to 478 +/- 31 ml min-1 1.73 m-2, respectively (P < 0.05 for both). Initially the response to amino acids was impaired (increment in GFR: 4.8 +/- 6.0%, NS; ERPF: -1.5 +/- 6.8%, NS), whereas the response to dopamine was normal (GFR: 10.6 +/- 1.1%, P < 0.05: ERPF: 33.2 +/- 3.1%, P < 0.01). After octreotide, amino acid infusion increased GFR by 15.0 + 6.8% (P < 0.02) and ERPF by 11.3 +/- 5.6% (P < 0.02), while the dopamine response was unchanged. Initially, six patients were normo-albuminuric and one had intermittent micro-albuminuria. Octreotide reduced albuminuria by 22% overnight (median; P < 0.05), and by 65% during the clearance studies (P < 0.05). In conclusion, afferent glomerular vasodilation appears to be an important characteristic of the glomerular hyperfiltration in acromegaly. Octreotide reverses this abnormality and reduces albuminuria.