Proteinuria, but Not eGFR, Predicts Stroke Risk in Chronic Kidney Disease: Chronic Renal Insufficiency Cohort Study.

BACKGROUND AND PURPOSE: Chronic kidney disease is associated with an increased risk of cardiovascular events. However, the impact of chronic kidney disease on cerebrovascular disease is less well understood. We hypothesized that renal function severity would be predictive of stroke risk, independent of other vascular risk factors. METHODS: The study population included 3939 subjects enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study, a prospective observational cohort. Stroke events were reported by participants and adjudicated by 2 vascular neurologists. Cox proportional hazard models were used to compare measures of baseline renal function with stroke events. Multivariable analysis was performed to adjust for key covariates. RESULTS: In 3939 subjects, 143 new stroke events (0.62 events per 100 person-years) occurred over a mean follow-up of 6.4 years. Stroke risk was increased in subjects who had worse baseline measurements of renal function (estimated glomerular filtration rate and total proteinuria or albuminuria). When adjusted for variables known to influence stroke risk, total proteinuria or albuminuria, but not estimated glomerular filtration rate, were associated with an increased risk of stroke. Treatment with blockers of the renin-angiotensin system did not decrease stroke risk in individuals with albuminuria. CONCLUSIONS: Proteinuria and albuminuria are better predictors of stroke risk in patients with chronic kidney disease than estimated glomerular filtration rate. The impact of therapies targeting proteinuria/albuminuria in individuals with chronic kidney disease on stroke prevention warrants further investigation.

Early inhibition of the renin-angiotensin system improves the long-term graft survival of single pediatric donor kidneys transplanted in adult recipients.

Transplanting single pediatric donor kidneys into adult recipients has an increased risk of hyperfiltration injury and graft loss. It is unknown if renin-angiotensin system (RAS) blockers are beneficial in this setting. We retrospectively analyzed 94 adults who received single kidneys from donors <10 years old during 1996-2009. The recipients were divided into group 1 with RAS blockers (n = 40) and group 2 without RAS blockers (n = 54) in the first year of transplant. There was no significant difference in any donor/recipient demographic between the two groups. Graft function, incidence of delayed graft function, acute rejection, and persistent proteinuria were not statistically different either. Kaplan-Meier estimated death-censored graft survivals were significantly better in group 1 than in group 2: 95 vs. 81.2%, 82.4 vs. 61.2%, 72.6 vs. 58.5%, and 68.5 vs. 47.2% at 1, 3, 5, and 7 years, respectively (log rank P = 0.043). Multivariable analysis found persistent proteinuria was a risk factor for graft loss (OR 2.70, 95% CI 1.33-5.49, P = 0.006), while RAS blockers reduced the risk of graft loss (OR 0.38, 95% CI 0.18-0.79, P = 0.009). Early RAS blockade therapy in the first year of transplant is associated with superior long-term graft survival among adults transplanted with single pediatric donor kidneys.

Urine angiotensinogen and salt-sensitivity and potassium-sensitivity of blood pressure.

OBJECTIVE: Urinary excretion of angiotensinogen [urine angiotensinogen (UAGT)] has been proposed as a biomarker of intrarenal renin-angiotensin system activity. We investigated the association between UAGT and salt-sensitivity and potassium-sensitivity of blood pressure (BP) among Genetic Epidemiology Network of Salt Sensitivity study participants. METHODS: The intervention consisted of a 7-day low-sodium diet (51.3  mmol sodium/day), 7-day high-sodium diet (307.8  mmol sodium/day), and 7-day high-sodium diet with potassium supplementation (307.8  mmol sodium/day and 60  mmol potassium/day). Twenty-four-hour UAGT was estimated at baseline and at the end of each intervention for 100 randomly selected participants. RESULTS: Median UAGT (µg/24  h) and UAGT-to-creatinine ratio (UAGT/Cr, µg/g) were significantly reduced during the low-sodium and potassium-supplementation interventions and increased during the high-sodium intervention (both P = 0.01). Baseline log-transformed UAGT and UAGT/Cr ratio were significantly positively associated with BP at baseline and at the end of each intervention. For example, one standard deviation higher log-UAGT/Cr ratio (1.2  µg/g) was associated with a 5.0-mmHg (95% confidence interval 2.3-7.8) higher SBP at the end of the high-sodium intervention, after adjusting for multiple covariates (P = 0.003). In addition, one standard deviation higher log-UAGT/Cr ratio was associated with a 1.6-mmHg increase in age-adjusted and sex-adjusted SBP from the low-sodium intervention to the high-sodium intervention (95% confidence interval 0.1-3.1, P = 0.04). This association was no longer statistically significant after multivariable adjustment. CONCLUSION: These data indicate that elevated UAGT are associated with BP sodium sensitivity. Augmentation of intrarenal renin-angiotensin system activity may play an important role in developing salt-sensitive hypertension.