Renal excretion of kallikrein and eicosanoids in patients with type 1 (insulin-dependent) diabetes mellitus. Relationship to glomerular and tubular function.
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 alpha, 2,3 dinor 6-keto prostaglandin F1 alpha, 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.
Harvey
J N
JN
Academic Unit of Medicine, General Infirmary, Leeds, UK.
Edmundson
A W
AW
Jaffa
A A
AA
Martin
L L
LL
Mayfield
R K
RK
D000328:Adult; D000704:Analysis of Variance; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology* / Q000652:urine; D015777:Eicosanoids / Q000652:urine*; D005919:Glomerular Filtration Rate / Q000502:physiology*; D006801:Humans; D007610:Kallikreins / Q000652:urine*; D007684:Kidney Tubules / Q000503:physiopathology*; D011453:Prostaglandins / Q000652:urine; D012079:Renal Circulation / Q000502:physiology; D013931:Thromboxanes / Q000652:urine
D015777:Eicosanoids; D011453:Prostaglandins; D013931:Thromboxanes; D007610:Kallikreins