Plasma prorenin activity and complications in children with insulin-dependent diabetes mellitus.

Background: Renin, secreted into the blood by the juxtaglomerular cells of the kidneys, is derived from a larger precursor, prorenin. Plasma prorenin activity is increased in patients with insulin-dependent (Type I) diabetes mellitus who have microvascular complications of their disease. We undertook this study to determine prospectively whether rising prorenin activity can predict the development of complications in young patients with Type I diabetes.

Prorenin and vascular complications of diabetes.

A high plasma prorenin is a marker of microvascular complications of diabetes. We have followed 56 adults and 120 children with uncomplicated insulin-dependent (type 1) diabetes. When plasma prorenin rises above the normal range in an adolescent or adult with type 1 diabetes, signs of nephropathy, retinopathy, or neuropathy follow within one to two years.

Plasma prorenin and renin in childhood and adolescence.

We studied 108 subjects (age range, 4 to 76 years) to determine the effect of age on prorenin (inactive renin), active renin, and plasma renin activity in normal children, adolescents, and adults. Children and adolescents had lower prorenin concentrations and higher plasma renin activity and active renin concentrations than did adults. Prorenin concentrations were positively correlated with age over the range of 4 to 76 years, while plasma renin activity and active renin concentration were negatively correlated with age.

Microalbuminuria and increased plasma prorenin. Prevalence in diabetics followed up for four years.

When urinary albumin excretion was measured by radioimmunoassay, most diabetics excreted more albumin than nondiabetic subjects. Microalbuminuria was defined as an albumin excretion greater than 30 mg/g of urinary creatinine, more than twice the upper limit of normal. Intermittent microalbuminuria was found in 20% of patients with insulin-dependent diabetes mellitus (IDDM) or non-insulin-dependent diabetes mellitus (NIDDM).

The long-term course of cyclosporine-associated chronic nephropathy.

We evaluated a chronic renal injury in 37 cardiac transplant recipients treated for 12 to 24 months with cyclosporine (CsA). Twenty-four cardiac transplant recipients treated with azathioprine for more than 24 months served as controls. Despite equivalent cardiac performance, GFR in those treated with CsA was depressed, 47 +/- 3 versus 94 +/- 4 ml/min/1.

Plasma renin and prorenin (inactive renin) in diabetes mellitus: effects of intravenous furosemide.

PRA, active renin, and prorenin were measured in 32 normotensive diabetic patients and 14 normal subjects of similar ages before and after iv injection of 40 mg furosemide. The majority of the diabetic patients had normal PRA and active renin levels before and after furosemide, but in 4 normal subjects and 5 diabetic patients PRA did not rise after furosemide treatment to at least 0.25 ng angiotensin I/(L.

Increased plasma inactive renin in diabetes mellitus. A marker of microvascular complications.

Plasma renin exists in an active form or as an inactive zymogen that resembles a prorenin present in homogenates of human kidneys. We examined the relation of diabetes and its microvascular complications with the level of plasma inactive renin activated by dialysis to pH 3.3.

Cyclosporine-associated chronic nephropathy.

We evaluated glomerular filtration in 17 recipients of heart transplants who were treated for 12 months or longer with cyclosporine (cyclosporin A). The control group consisted of 15 heart-transplant recipients who were treated with azathioprine and who had also survived for at least 12 months. Despite an equivalent cardiac output, the glomerular filtration rate was depressed (51 +/- 4 vs.

Hypertension caused by an aldosterone-secreting adenoma. Occurrence in a 7-year-old child.

A 7-year-old girl had hyperaldosteronism due to an adrenal cortical adenoma, a rare, surgically remediable cause of hypertension. Although the plasma potassium concentration was only slightly below normal, and the plasma aldosterone concentration was in a high normal range, the consistently suppressed plasma renin activity suggested primary aldosteronism. This diagnosis was confirmed by the failure of saline infusion to lower the plasma aldosterone concentration.

Increased inactive renin in diabetes mellitus without evidence of nephropathy.

PRA, active renin, and inactive renin (IR; activated by dialysis to pH 3.3 and 7.4) were measured in the plasma of 53 patients with diabetes mellitus and 32 normal volunteers (group 1).

Changes in active and inactive renin throughout pregnancy.

In the first trimester of pregnancy, inactive renin in plasma rapidly increases (to 5 times the average concentration in plasma of nonpregnant controls), then declines slowly until midpregnancy, and falls quickly to the normal range after delivery. Inactive renin has the same large apparent molecular weight in pregnancy as in control plasma. Amniotic fluid contains very high levels of inactive renin; its mobility on Sephadex G-100 is the same as that of inactive plasma renin, but a lower molecular weight is indicated by the delayed elution of inactive renin of amniotic fluid from Sephacryl S-200.

Human kidney cathepsins B and H activate and lower the molecular weight of human inactive renin.

Cathepsins B, H, and D, extracted from human kidneys, activate human inactive renin. Inactive renin, obtained from human kidneys, contains two components of Mr 53,000 and 50,000. Upon incubation with 0.

Primary aldosteronism: effects of inhibition of ACTH and potassium administration on plasma aldosterone concentration.

The relative roles of ACTH, angiotensin and potassium in influencing aldosterone secretion in primary aldosteronism were assessed by direct or indirect means. In untreated patients with primary aldosteronism caused either by adrenal adenoma or hyperplasia plasma aldosterone and cortisol concentrations fluctuated in unison and dexamethasone reduced both hormones markedly. Only when renin-angiotensin system was greatly activated and plasma potassium normalized by medical treatment was dexamethasone less successful in lowering plasma aldosterone concentration.

Effects of angiotensin III and ACTH on aldosterone secretion.

ACTH and des-Asp1-angiotensin II (AIII) can raise plasma aldosterone. To assess the threshold for ACTH and AIII stimulated adrenal steroidogenesis we infused ACTH (from 0.03 to 10 ng ACTH/min) and AIII (from 0.

Inactive renin of high molecular weight (big renin) in normal human plasma. Activation by pepsin, trypsin, or dialysis to pH 3.3 and 7.5.

Normal plasma contains inactive renin, which becomes active when plasma is dialyzed to pH 3.3 and to pH 7.5, or treated with pepsin or trypsin.

Primary aldosteronism due to unilateral adrenal hyperplasia.

A 45-yr-old man with hypertension, hypokalemia, low plasma renin, and hyperaldosteronism was studied. Plasma and urine aldosterone were consistently above normal, remaining abnormally high even on a 300-meq sodium intake. Plasma aldosterone had a marked circadian rhythm, which was correlated with plasma cortisol.

Adrenocorticotropin-stimulated secretion of aldosterone and cortisol, computed from plasma and red blood cell measurements.

The dynamic response of the adrenal cortex to ACTH infusion is analyzed by simulating the distribution, binding, and metabolism of cortisol and aldosterone in a multicompartmental model. The model includes the effects of temperature and cortisol concentration on aldosterone binding in plasma and the distribution between plasma and red blood cells, as verified by new observations. The secretion rates of cortisol and aldosterone were computed from serial measurements of plasma concentrations of endogenous steroids and infused tracers.

A comparison of cold and acid activation of big renin and of inactive renin in normal plasma.

Normal human plasma contains "inactive renin," whose ability to generate angiotensin I increases after exposure to pH 3.3. Big renin is a partially inactive enzyme of larger molecular weight, which is also activated at pH 3.

Big renin in plasma of healthy subjects on high sodium intake.

Normal human plasma contains not only active renin but also an inactive form of renin which, after exposure to low pH, can generate angiotensin I from renin substrate. When healthy volunteers were given first a diet containing 400 mmol sodium and then a diet containing 10 mmol sodium for 4 days the changes in salt intake stimulated large changes in active plasma-renin and smaller changes in inactive renin. Inactive renin comprises a larger fraction of total renin in plasma of salt-loaded healthy subjects than salt depleted subjects.

Effect of bedrest on circadian rhythms of plasma renin, aldosterone, and cortisol.

Previous studies of normal men after 5 d of bedrest showed that circulatory instability on head-up tilt or standing is preceded by increased plasma renin activity (PRA) at bedrest. In the present study, the circadian rhythms of PRA, aldosterone, and cortisol have been observed in five normal men on a constant diet. In ambulatory controls, PRA and aldosterone increased normally after standing.

Transient fall and subsequent return of high aldosterone secretion by adrenal adenoma during continued dexamethasone administration.

Plasma aldosterone concentration was consistently decreased by 50% or more in 6 patients with aldosterone-producing adenoma on the first day of dexamethasone administration, only to rise subsequently with continued use of dexamethasone while plasma cortisol concentration remained suppressed. The secondary rise in plasma aldosterone was not related to measured changes in known stimuli of aldosterone secretion. It is probable that the observations result from intrinsic alteration of aldosterone synthesis in the adenoma during prolonged ACTH suppression.

The effects of temperature and plasma cortisol on distribution of aldosterone between plasma and red blood cells: influence on metabolic clearance rate and on hepatic and renal extraction of aldosterone.

Aldosterone enters red blood cells (RBC) to a greater extent at 37 C than at lower temperatures. The ratio of 3H-aldosterone concentration in RBC to that in plasma increases from 0.2 at 4 C to 0.