- Sham surgery
- Bilateral adrenalectomy
- Bilateral adrenalectomy + angiotensin 2
- Bilateral adrenalectomy + aldosterone
Angioedema: Two cases of angioedema with respiratory symptoms were reported with Tekturna use in the clinical studies. Two other cases of periorbital edema without respiratory symptoms were reported as possible angioedema and resulted in discontinuation. The rate of these angioedema cases in the completed studies was 0.06%. In addition, 26 other cases of edema involving the face, hands, or whole body were reported with Tekturna use including 4 leading to discontinuation. In the placebo controlled studies, however, the incidence of edema involving the face, hands or whole body was 0.4% with Tekturna compared with 0.5% with placebo. In a long term active control study with Tekturna and HCTZ arms, the incidence of edema involving the face, hand or whole body was 0.4% in both treatment arms [see Warnings and Precautions (5.2)].
Hypertensive emergencies are characterized by severe elevations in BP (>180/120 mmHg) complicated by evidence of impending or progressive target organ dysfunction… Examples include hypertensive encephalopathy, intracerebral hemorrhage, acute MI, acute left ventricular failure with pulmonary edema, unstable angina pectoris, dissecting aortic aneurysm, or eclampsia.
Strange that acute renal failure is not mentioned as a complication. The recommendation is to reduce the blood pressure by no more than 25% in the first minutes to an hour and subsequently shoot for 160/100 for the next 2-6 hours. The authors point to 2 exceptions: aortic dissection where the SBP should be less than 100 and in acute stroke where the data is less clear. (a moment of clairvoyance for the JNCVII crew as they correctly predicted the lack of benefit from aggressive blood pressure control in the midst of an acute stroke. This was confirmed with 2011’s SCAST study)
|Meta-analysis showing the lack of benefit from blood pressure treatment in acute stroke|
|IV blood pressure agents helpful in hypertensive emergency from JNCVII|
The first article we looked at was Bert Jan van den Born’s retrospective review. These authors looked at patients with malignant hypertension. Cases were identified by looking at every hospital admission with the diagnosis of hypertension and then screening the charts for an ophthmology exam showing:
- bilateral flame-shaped retinal hemorrhages
- bilateral linear “splinter” retinal hemorrhages
- or “cotton-wool” exudates.
|Wonderful pic of cotton-wool exudates and splinter hemorrhages. Thanks ACP|
|Flame hemorrhages. Without permission from AAO|
If I had to wait for an ophtho consult to make a diagnosis, half my patients would be ready for discharge with the diagnosis still pending.
After patients were deemed to have hypertensive urgency, they were categorized as having MAHA. This was defined as a low platelet count with either an elevated LDH or schistocytes. Additionally the LDH/schistocytes and the platelets had to recover following recovery from the hypertensive crisis.
The endpoints were creatinine and proteinuria at admission and follow-up creatinine.
The study found 110 patients that met the criteria, and 97 were ultimately available for analysis.
- 4 were excluded because the retinal changes were due to intracranial masses rather than hypertension.
- 5 were excluded because of a lack of platelet count
- 4 were excluded because they had an alternative explanation for thrombocytopenia
- black (73 vs 35%)
- hypertensive (242/150 vs 225/145
- uremic (Cr 7.8 vs 1.4)
- proteinuric (88% vs 41%)
|To convert creatinine from micromol to mg/dl, divide by 88|
Improvement of renal function, defined as a reduction of serum creatinine >50% compared with baseline, was noted in 17 patients during follow-up. Cox regression analysis showed that MAHA and systolic blood pressure at admission were the most powerful indicators of renal improvement with an HR of 0.24 (95% CI, 0.08 to 0.75) and 1.02 per mm Hg increase in systolic blood pressure (95% CI, 1.01 to 1.05; Table 4). Improvement of kidney function over time in patients with and without MAHA is shown in Figure 4.
- pre-existing CKD
- higher creatinine on presentation
- more proteinuria
- more microscopic hematuria.
The third article was a case report and lit review by Shavit et al. The article defines malignant nephrosclerosis as renal failure due to malignant hypertension. They describe three cases with varying outcomes:
- 55 year old admitted with a blood pressure of 220/130, Cr 11, normal platelet count, LDH 1,100. A renal biopsy showed concentric intimal hyperplasia, fibrinoid necrosis of arteriolar wall, shrinkage of the glomerular tufts. The patient remained dialysis dependent 2 years after presentation.
- 55 year old admitted with 240/125, Cr 13, LDH 1,430, normal platelet count. Kidney biopsy revealed intimal thickening, luminal narrowing, fibrinoid necrosis. His creatinine improved over 2 months and he remained dialysis free with significant CKD 2 years after presentation.
- 28 year old admitted with a blood pressure of 210/135, Cr 4.5, K 2.9, normal platelet count. Kidney biopsy showed severe intimal thickening, and fibrinoid necrosis. Creatinine improved over 2 weeks to 1.8 and remains stable at 3 years of follow-up.
They mention research finding low levels of ADAMTS13 in malignant hypertension. ADAMTS13 level fall as LDH levels rise and platelet count fall. A follow-up study of 21 patients failed to confirm these findings.
The next article we pulled was by Akimoto et al, Clinical Features of Malignant Hypertension with Thrombotic Microangiopathy. This was retrospective review of 16 cases of malignant hypertension. MH was defined as an elevated blood pressure with retinal changes. MAHA was defined by an increase in LDH, low hemoglobin and low haptoglobin. Additionally to meet the definition of MAHA patients needed to normalize these indices after correction of the blood pressure. Of note 7 patients had biopsies. Five of those biopsies showed evidence of malignant nephrosclerosis (fibrinoid necrosis) but only 3 of them met the authors’ clinical definition of MAHA. Interesting that those reasonable clues could be missing 40% of cases.
They found higher aldosterone levels in patients with MAHA than in patients without. They found a tight correlation between aldosterone levels and LDH, R2 of 0.4 (p=0.0096).
Four of the seven patients with MAHA required dialysis, however 2 were able to come off. Three of the nine patients without MAHA required dialysis and none recovered renal function.