Renal excretion of kallikrein and eicosanoids in patients with Type 1 (insulin-dependent) diabetes mellitus. Relationship to glomerular and tubular function

Summary Glomerular filtration rate, renal plasma flow, renal tubular sodium reabsorption (derived from lithium clearance) and renal excretion rates of kallikrein, prostaglandin E₂ and systemic and renally-derived metabolites of prostacyclin and thromboxane A₂ were measured in patients with Type 1 (insulin-dependent) diabetes mellitus and in normal subjects. Diabetic patients with glomerular hyperfiltration had greater active kallikrein and prostaglandin E₂ excretion than patients with normal glomerular filtration rate or than normal control subjects. Both active kallikrein and prostaglandin E₂ excretion correlated directly with glomerular filtration rate. Active kallikrein excretion correlated directly with the reabsorption of sodium in the distal tubule. The excretion rates of 6-keto prostaglandin F₁, 2,3 dinor 6-keto prostaglandin F₁, thromboxane B₂, 2,3 dinor thromboxane B₂ and 11-dehydro thromboxane B₂ excretion were not different between the groups. This study confirms in man our previous finding of increased renal kallikrein production in the hyperfiltering streptozotocin-diabetic rat model. Given that kinins generated by kallikrein are extremely potent vasodilators and stimulate the renal production of eicosanoids that also regulate glomerular function, our findings suggest that increased kallikrein activity and prostaglandin E₂ production may contribute to renal vasodilatation and hyperfiltration in human diabetes. The localization of kallikrein in the distal connecting tubule makes it plausible that altered sodium transport in the distal tubule may be a signal to increase generation of kallikrein.