Renin measurement

Vaughan ED, Buhler FR, Laragh JH. Renovascular hypertension Renin measurements to indicate hypersecretion and contralateral suppression, estimate renal plasma flow, and score for surgical curability. Am J Med 1973 55 402-14. 

Latta, J. Improved measurement of plasma renin activity... 

Table 5.4 Hypothetical experiment measuring the IC50 values of a competitive inhibitor for HIV aspartyl protease and for human renin, at a fixed substrate concentration of 50 iM...

For a series of renin inhibitors a good correlation between the measured membrane permeability and log D was found (r2 = 0.8). The model has been validated against a human perfusion model [10], as well as being extended by including molecular weight as a third parameter [27]. A further development of the model is to chronically cannulate the animals so that they can be allowed to recover [28]. This model should avoid any effects from the anesthetic on the absorption process. 

Once vasodilatation was considered to be a good strategy, as it improves HF symptoms. However later studies showed that the disease itself was not influenced. The accent of HF treatment has moved to progression prevention with rigorous suppression of the renin angiotensin aldosterone system. Therapy with /3-blockers was also proven to be effective for the reduction of mortality. These treatments should be started early and the evaluation of their effectiveness in individual patients is difficult. As brain natriuretic peptide (BNP) is produced by the heart and more BNP is released in heart failure, the measurement of BNP in the blood has become popular as surrogate marker for the severity of heart failure and for the response of treatment for heart failure. 

Prednisolone can cause an abrupt rise in proteinuria in patients with nephrotic syndrome. A placebo-controlled study in 26 patients aged 18-68 years with nephrotic syndrome has clarified the mechanisms responsible for this (163). Systemic and renal hemodynamics and urinary protein excretion were measured after prednisolone (125 mg or 150 mg when body weight exceeded 75 kg) and after placebo. Prednisolone increased proteinuria by changing the size-selective barrier of the glomerular capillaries. Neither the renin-angiotensin axis nor prostaglandins were involved in these effects of prednisolone on proteinuria. 

It is important to realize how difficult it is to define the in vivo inhibition of ACE. The enzyme may be explored for its N-terminal active sites by measurement of a constant and maximally increased level of N-acetyl SDKP in plasma and urine (211), but the residual activity of the C-ter-minal sites is probably not being measured. The methods for in vitro measurement of plasma ACE, except perhaps that described by Nuss-berger et al. (256), do not appropriately quantify global ACE inhibition. Moreover, the consequences of enzyme blockade are modified by secondary activation of the RAS (233). Residual amounts of angiotensin II secondary to a reactive rise in renin and angiotensin I may explain why the administration of an angiotensin II antagonist still has an additive effect on blood pressure and possibly on the heart, the vessels, and the kidney when added to certain doses of ACE inhibitors (228, 229, 257). 

The activities of renin in plasma and serum are measured in the diagnosis of hypertension. The natural substrate for renin is angiotensin. Several synthetic peptides have been used in renin assays. Recently, Nakamura-lmajo et al. (1992) used N-(2-pyridyl)glycine (pg) as a fluorescent tag on a nonapeptide. 

FIGURE 6.4 Kinetic analysis of urea ( ) and inulin H (A) plasma concentrations (upper panel) and renal excretion rates (middle panel) before, during, and after dialysis of a dog with intact kidneys. Inulin was not dia-lyzable but urea concentrations entering and leaving the dialyzer are both shown. The bottom panel shows CLg estimates for urea (—) and inulin (—), and measured plasma renin activity ( ). (Reproduced with permission from Bowsher DJ, Krejcie TC, Avram Mf, Chow MJ, del Greco F, Atkinson AJ Jr. J Lab Clin Med 1985 105 489-97.)... 

Concentrations of adrenal mineralocorticoids (e.g., aldosterone and DOC) and factors of the renin-angiotensin system (e.g., renin) are routinely measured in body fluids by various immunoassay and instrument-based methods. Aldosterone, like cortisol, is secreted episodically, with the highest circulating concentrations at about the time of awakening and the lowest concentrations shortly after sleep onset aldosterone concentrations, however, are only modestly stimulated by ACTH secretion.In healthy subjects, a low-sodium diet, maintaining an upright posture, and use of diuretics ail increase plasma aldosterone concentrations,... 

Another simple and convenient stimulation test consists of sodium restriction and upright posture. A low-salt diet containing less than 20mmol/da7 of sodium is administered for 3 to 5 daysj urine is collected for creatinine and sodium measurements until equilibrium with the new diet is established. At that point, a plasma renin activity is obtained after 2 hours of standing. A normal response is a twofold to threefold increase in plasma renin output. 

The determination of plasma renin responsiveness, however, is not sufficient to diagnose primary aldosteronism because suppressed PRA also occurs in about 25% of patients with essential hypertension. Primary aldosteronism can be differentiated from other hypermineralocorticoid states on the basis of inappropriate secretion of aldosterone. The demonstration of an elevated concentration of aldosterone in blood or urine in a patient with an unequivocally suppressed PRA concentration (a plasma aldosterone/ plasma PRA ratio >50) is presumptive evidence of primary aldosteronism. Because hypokalemia has a suppressive effect on aldosterone secretion, the potassium deficit should be replaced before aldosterone measurements are done. To establish aldosterone autonomy, the clinician may attempt to suppress aldosterone production with rapid volume expansion (see Box 51-10), with a potent mineralocorticoid (see Box 51-11), or as mentioned with captopril. Failure... 

Used as a screening test, an elevated plasma renin activity after furosemide stimulation or when correlated with urinary sodium excretion can suggest renal artery stenosis as the cause of the hypertension (Figure 51-18). If there is arteriographic evidence for renal artery stenosis, measurement of plasma renin in specimens obtained from selective... 

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