SummaryBackground and objectives A multidisciplinary team (MDT) approach to chronic kidney disease (CKD) may help optimize care of CKD and comorbidities. We implemented an MDT quality improvement project for persons with stage 3 CKD and comorbid diabetes and/or hypertension. Our objective was to decrease the rate of decline of GFR.Design, setting, participants, & measurements We used a 4-year historical cohort to compare 1769 persons referred for usual nephrology care versus 233 referred for MDT care within an integrated, not-for-profit Health Maintenance Organization (HMO). Usual care consisted of referral to an outside nephrologist. The MDT consisted of an HMO-based nephrologist, pharmacy specialist, diabetes educator, dietitian, social worker, and nephrology nurse. Both groups received usual primary care. The primary outcome was rate of decline of GFR. Secondary outcomes were LDL, hemoglobin A1c, and BP.Results In multivariate repeated-measures analyses, MDT care was associated with a mean annual decline in GFR of 1.2 versus 2.5 ml/min per 1.73 m 2 for usual care. In stratified analyses, the significant difference in GFR decline persisted only in those who completed their referrals. There were no differences in the secondary outcomes between groups. ConclusionsIn this integrated care setting, MDT care resulted in a slower decline in GFR than usual care. This occurred despite a lack of significant differences for secondary disease-specific measures, suggesting that other differences in the MDT population or care process accounted for the slower decline in GFR in the MDT group.

Recent evidence suggests that the potent constrictor peptide, endothelin (ET) has a mediating role in cyclosporine A (CsA)-related renal vasoconstriction. However, the nature of the CsA-ET interaction and effect on the renal vasculature is uncertain. The purpose of the present study was twofold: (a) to determine if CsA exposure caused direct local release of ET from the endothelium of the renal microvasculature and (b) to determine if locally generated ET has paracrine effects on the underlying vascular smooth muscle to induce vasoconstriction. Experiments were performed in isolated rat renal arterioles. First it was determined that both afferent arteriole (AA) and efferent arteriole (EA) exhibited concentration-dependent decreases in lumen diameter to increasing molar concentrations of CsA. The AA was more sensitive to the vasoconstrictive effects of CsA than the EA. Next, the blocking effect of a recently synthesized putative ETA receptor antagonist was verified in both the AA and EA, where it was found that the cyclic peptide cyclo D-Asp-L-Pro-D-Val-L-Leu-D-Trp totally inhibited the vasoconstriction observed with ET addition. Finally, the role of locally stimulated ET in CsA-induced vasoconstriction was tested by determining the effect of the ETA receptor antagonist on CsA-induced AA and EA constriction. In the AA the vasoconstrictor effect of 1011 M CsA was completely blocked by the ETA receptor antagonist. However, in contrast to AA, 10 1 M CsA in EA in the presence of the ETA receptor antagonist decreased EA lumen diameter by a mean of 41% from baseline (4.80±0.75 ,um vs 7.80±0.84 ,tm, P < 0.05). This change in lumen diameter was similar to that induced by CsA alone. These data suggest that CsA directly constricts renal microvessels. This effect is mediated by ET in the AA but not the EA. (J.

The effects of atriopeptin III (AP III) on in vitro prepared afferent (AA) and efferent arterioles (EA) from rat kidneys were tested in a system in which lumen diameter could be measured. AP III (10(-13)-10(-7) M) had no effect on lumen diameter of AA that were not preconstricted. When AA were preconstricted with either angiotensin II (ANG II) or norepinephrine (NE), however, AP III increased lumen diameter in a concentration-dependent manner to the preconstriction baseline value. Maximal vasodilation occurred at 10(-10) M AP III. Unlike AA, EA constricted by 50% to 10(-10) M AP III further constricted EA that were pretreated with ANG II or NE. Dilation in ANG II-preconstricted AA to AP III was not inhibited by indomethacin. Constriction of EA to AP III was not altered by [Sar1-Ala8] ANG II, enalapril, OKY 046, or phentolamine. Results indicate that in isolated renal arterioles AP III dilates preconstricted AA but constricts EA that have either not been pretreated or have been preconstricted with other agonists. The effect of AP III on preconstricted AA does not require vasodilator prostaglandin mediation. The constrictor effect of AP III on EA is not dependent on angiotensin, thromboxane, or alpha-adrenergic mediation.

No abstract

The specific intrarenal sites and mechanism of endothelin (ET) vascular action are controversial. In this study afferent (AA) and efferent arterioles (EA) were isolated from the kidneys of normal Sprague-Dawley rats. Their respective concentration-dependent changes in lumen diameter in response to ET-1 were compared with those of angiotensin II (ANG II) and norepinephrine (NE). In a second series of experiments, the duration of vasoconstriction to comparable transient submaximal ET-1, ANG II, and NE concentrations in AA and EA was examined. The role of angiotensin II in mediating endothelin vasoconstriction also was examined with the converting-enzyme inhibitor captopril (CAP) and the competitive inhibitor [Sar1,Ala8]ANG II (SAR). The half-maximal constriction concentration (EC50) of ET-1 was less in EA than AA (P < 0.01). EC50 of ET-1 in AA was similar to that of ANG II, but was less than that of NE (P < 0.001). In EA the EC50 of ET-1 was also similar to that of ANG II, but much less than that of NE (P < 0.001). In both AA and EA the duration of ET-1 constriction was at least twice that of ANG II and more than fivefold that of NE. Neither CAP (10(-6) M) nor SAR (10(-7) M) changed the vasoconstrictor response to submaximal concentrations of ET-1 in AA or EA. It is concluded that ET-1 is a potent and prolonged constrictor agonist with a small, but significantly greater, concentration-dependent effect in EA than AA. The constrictor effect of ET-1 does not require ANG II activity.