Abstract
We examined the course of glomerular injury in 12 Pima Indians with long-standing (>8 years) type 2 diabetes mellitus, normal serum creatinine, and microalbuminuria. They were compared with a group of 10 Pima Indians in Arizona with new-onset (<5 years) type 2 diabetes, normal renal function, and normoalbuminuria (<30 mg albumin/g creatinine on random urine specimens). A combination of physiological and morphological techniques was used to evaluate glomerular function and structure serially on two occasions separated by a 48-month interval. Clearances of iothalamate and p-aminohippuric acid were used to determine glomerular filtration rate (GFR) and renal plasma flow, respectively. Afferent oncotic pressure was determined by membrane osmometry. The single nephron ultrafiltration coefficient (Kf) was determined by morphometric analysis of glomeruli and mathematical modeling. The urinary albumin-to-creatinine ratio (median + range) increased from 84 (28 to 415) to 260 (31 to 2232) mg/g between the two examinations (P = 0.01), and 6 of 12 patients advanced from incipient (ratio = 30 to 299 mg/g) to overt nephropathy (>/=300 mg/g). A 17% decline in GFR between the two examinations from 186 +/- 41 to 155 +/- 50 mL/min (mean +/- SD; P = 0.06) was accompanied by a 17% decline in renal plasma flow (P = 0.003) and a 6% increase in plasma oncotic pressure (P = 0.02). Computed glomerular hydraulic permeability was depressed by 13% below control values at both examinations, a result of a widened basement membrane and a reduction in frequency of epithelial filtration slits. The filtration surface area declined significantly, however, from 6.96 +/- 2.53 to 5.51 +/- 1.62 x 105 mm2 (P = 0.01), a change that was accompanied by a significant decline in the number of mesangial cells (P = 0.001), endothelial cells (P = 0.038), and podocytes (P = 0.0005). These changes lowered single nephron Kf by 20% from 16.5 +/- 6.0 to 13.2 +/- 3.6 nL/(minutes + mm Hg) between the two examinations (P = 0.02). Multiple linear regression analysis revealed that among the determinants of GFR, only the change in single nephron Kf was related to the corresponding change in GFR. We conclude that a reduction in Kf is the major determinant of a decline in GFR from an elevated toward a normal range as nephropathy in type 2 diabetes advances from an incipient to an overt stage.
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
