Metabolic acidosis often accompanies low glomerular filtration rate and induces secretion of endothelin, which in turn might mediate kidney injury. Here we tested whether treatment of metabolic acidosis in patients with low glomerular filtration rate reduced the progression of kidney disease. Fifty-nine patients with hypertensive nephropathy and metabolic acidosis had their blood pressure reduced with regimens that included angiotensin-converting enzyme inhibition. Thirty patients were then prescribed sodium citrate, and the remaining 29, unable or unwilling to take sodium citrate, served as controls. All were followed for 24 months with maintenance of their blood pressure reduction. Urine endothelin-1 excretion, a surrogate of kidney endothelin production, and N-acetyl-beta-D-glucosaminidase, a marker of kidney tubulointerstitial injury, were each significantly lower, while the rate of estimated glomerular filtration rate decline was significantly slower. The estimated glomerular filtration rate was statistically higher after 24 months of sodium citrate treatment compared to the control group. Hence it appears that sodium citrate is an effective kidney-protective adjunct to blood pressure reduction and angiotensin-converting enzyme inhibition.

Dietary casein promotes a progressive decline in the glomerular filtration rate (GFR) of remnant kidneys associated with metabolic acidosis and an endothelin-mediated increase in renal acidification. We tested whether diets that affect the acid-base status contributes to the decline of GFR through endothelin receptors in rats with a remnant kidney. Rats on a casein diet had metabolic acidosis at baseline and developed a progressive decline in GFR after renal mass reduction. Dietary sodium bicarbonate but not sodium chloride ameliorated metabolic acidosis and prevented the decrease in GFR but only after the sodium bicarbonate-induced increase in blood pressure was treated. Dietary soy protein did not induce baseline metabolic acidosis and rats with remnant kidney on a soy diet had no decrease in their GFR. By contrast, rats with a remnant kidney on soy protein given dietary acid developed metabolic acidosis and a decreased GFR. This decline in GFR was prevented in either case by endothelin A but not endothelin A/B receptor antagonism. Our study suggests that the casein-induced decline in GFR of the remnant kidney is mediated by metabolic acidosis through endothelin A receptors.

Reduction in blood pressure can be achieved by inducing immunity against targets in the RAAS. The target antigen and selection of adjuvant are crucial factors determining effectiveness and safety of the vaccine. CYT006-AngQb (angiotensin II vaccine) reduced blood pressure in humans but the results were not reproducible with more frequent dosing. Vaccines for hypertension are still in the early phase. We hope for an effective vaccine for hypertension in the years to come.

Acute massive pulmonary embolism (PE) is a frequently fatal event that causes significant compromise of hemodynamic stability. Unfortunately, mortality rates for PE have remained relatively constant despite advances in prophylactic and treatment measures. In addition to embolus size, symptom recognition for diagnosis and emergent treatment are two distinct factors that dictate survival. Treatment generally includes thrombolytic agents; however, not all patients are candidates for aggressive thrombolytic management. Development of catheter thrombectomy devices provides an alternative treatment modality for severe cases when thrombolytics are contraindicated. Catheter thrombectomy devices have undergone major advances over the last decade, but literature support of their success is limited.

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A 74-year-old hypertensive woman presented with abdominal discomfort and a pulsatile abdominal mass. Anterior abdominal angiography during cardiac blood pool, and renal scintigraphic imaging demonstrated a large abdominal aortic aneurysm. 1, 2 Before endovascular repair with an aortoiliac endograft, the abdominal aneurysm measured 7.5 x 7.0 cm on abdominal computed tomography. This study demonstrates that a suspected abdominal aortic aneurysm can be confirmed using the addition of anterior abdominal imaging with normal posterior imaging at the time of renal scintigraphy.

PurposeRenal endothelin 1 (ET-1) production is increased in the 5/6 nephrectomy experimental model of chronic kidney disease (CKD) and in rats with normal GFR ingesting mineral acid or acid-producing dietary protein. Unpublished data from our laboratory support that amelioration of the acid retention in experimental CKD with dietary alkali decreases renal ET-1 production as measured by urine excretion of endothelin 1 (UET-1V). We hypothesized that the same is true in human CKD.MethodsWe recruited 18 healthy controls, 21 subjects with primary hypertension without CKD, and 19 subjects with CKD (plasma creatinine 1.5-6.0 mg/dL) and primary hypertension without diabetes, evidence of glomerulonephritis, or history of renal replacement therapy. We reduced systolic blood pressure (SBP) in the latter 2 groups toward 130 mm Hg over 6 months. We then prescribed oral Na+ citrate to CKD subjects with TCO2 < 22 mM (n = 12) but not to those with TCO2 $ 22 mM (n = 7) and followed each for an additional 6 months. We measured UET-1V (ng/g creatinine or ng/g Cr) in a spot am specimen and venous blood TCO2 at 0, 6, and 12 months.SummaryUET-1V was higher than healthy controls (3.1 6 0.4 ng/g Cr) in hypertensives without CKD (5.9 6 1.1 ng/g Cr, p < .03 vs controls) and in hypertensives with CKD (5.1 6 0.7 ng/g Cr, p < .02 vs controls). After SBP reduction, UET-1V in hypertensives without CKD (3.5 6 0.4 ng/g Cr) was not different from healthy controls (p = .23) but that for hypertensives with CKD (5.3 6 0.5 ng/g Cr) remained higher than control (p < .001) and was now higher than hypertensives without CKD (p < .007). TCO2 increased in CKD subjects prescribe Na+ citrate (20.1 6 0.4 to 23.9 6 0.4 mM, p < .001 paired t) but decreased in those not prescribed Na+ citrate (23.6 6 0.5 to 23.0 6 0.5 mM, p < .03 paired t). Although UET-1V was not different between CKD subjects before Na+ citrate (p = .85), UET-1V decreased in those prescribed Na+ citrate (5.4 6 0.6 to 4.1 6 0.4 ng/g Cr, p < .02, paired t) but did not change in those not prescribed Na+ citrate (5.2 6 1.0 to 6.1 6 1.0 ng/g Cr, p = .10, paired t). Follow-up UET-1V was lower in CKD subjects prescribed compared to those not prescribed Na+ citrate (p < .04).ConclusionsThe data show that primary hypertensives with compared to those without CKD have higher UET-1V despite improved BP control that is decreased by oral Na+ citrate. These studies support the contention that subjects with CKD have increased renal ET-1 production that is mediated by the associated positive acid balance.