Renal excretion and cyst accumulation of β2microglobulin in polycystic kidney disease

Renal excretion and cyst accumulation of β2microglobulin in polycystic kidney disease. To determine the extent to which proximal tubule function is altered β2microglobulin (β2m), creatinine and Na were measured in serum, urine and cyst fluid of patients with autosomal dominant polycystic kidney disease and various degrees of renal insufficiency. Fractional excretion (FEβ2m) was 0.11 ± 0.03% in six normal subjects and 0.13 ± 0.05% in nine patients with serum creatinine levels less than 1.6 mg/dl. In five patients with serum creatinine levels above 3.0 mg/dl, FEβ2m was elevated (range 3.5 to 196%) and serum levels were higher than normal (30,600 ± 6,910 µg/liter vs. 1,268 ± 111). In seven patients β2m levels in 33 proximal cysts (cyst/serum Na > 0.8) equalled those in serum (cyst/serum β2m 0.98 ± 0.20), whereas in 21 distal cysts (cyst/serum Na < 0.4) β2m was less than in serum (cyst/serum β2m 0.17 ± 0.07). Analysis of fluid in two patients with polycystic kidney nephrectomy several weeks post-transplant indicated that proximal cyst epithelium is permeable to β2m, but less so than to creatinine or urea. These studies show that proximal cysts cannot develop or maintain gradients for β2m, whereas distal cysts maintain low levels of the protein despite end–stage renal failure. The normal FEβ2m values in nonazotemic autosomal dominant polycystic kidney disease patients and the low distal cyst levels of β2m in end-stage kidneys indicate that the cystic proximal nephrons do not contribute appreciably to the final urine. These findings are consistent with the view that a relatively small number of cystic tubules ultimately compromise the function of non-cystic nephrons