Immunoglobulin A nephropathy complicating pulmonary tuberculosis.

A 31-year-old man who presented with smear- and culture-negative pulmonary tuberculosis had associated macroscopic hematuria, elevation of serum creatinine and immunoglobulin A (IgA) levels, overt proteinuria, and peripheral edema. Renal biopsy revealed focal mesangial proliferation with IgA deposits, and a diagnosis of IgA nephropathy was made. The patient received treatment with isoniazide and rifampin. After 4 months, pulmonary lesions were almost completely healed, and a significant improvement of creatinine clearance with normalization of serum creatinine and IgA levels and disappearance of proteinuria were observed. Treatment with isoniazide and rifampin was discontinued after 6 months, without reappearance of either pulmonary or renal symptoms. Two years after the diagnosis of IgA nephropathy, the patient is in good general condition. Serum creatinine and IgA levels are normal, proteinuria is absent, and there is neither macrohematuria nor microhematuria. These findings suggest that IgA nephropathy may be a consequence of tuberculosis, possibly due to an abnormal IgA-mediated immune response against Mycobacterium tuberculosis with formation of nephrotoxic immune complexes.

Clustering of endothelial markers of vascular damage in human salt-sensitive hypertension: influence of dietary sodium load and depletion.

The contributing role of vascular endothelium in the development of hypertension-related vascular damage is well accepted. Salt-sensitive hypertension is characterized by a cluster of renal, hormonal, and metabolic derangements that might favor the development of cardiovascular and renal damage. To evaluate endothelial involvement in salt-sensitive essential hypertension, plasma levels of several markers of endothelial damage such as endothelin-1 (ET-1), von Willebrand factor (vWf), and soluble (S-) adhesion molecules E-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and 24-hour urinary albumin excretion (UAE) were measured in 39 nondiabetic, nonobese, never-treated essential hypertensive patients after intermediate (120 mmol/d), high (220 mmol/d), and low (20 mmol/d) NaCl diets. Patients were classified as salt sensitive (n=18) or salt resistant (n=21) according to their blood pressure responses to changes in dietary NaCl intake. Salt-sensitive hypertensives showed higher plasma ET-1 (P<0.05), vWf (P<0.005), and S-E-selectin levels (P<0.04) and increased UAE (P<0.05) than salt-resistant hypertensives. By contrast, circulating S-ICAM-1 and S-VCAM-1 concentrations were not significantly higher in salt-sensitive (596. 56+/-177.05 ng/mL and 541.06+/-157.84 ng/mL, respectively) than salt-resistant patients (516.86+/-147.99 ng/mL and 449.48+/-158.91 ng/mL, respectively). During the intermediate NaCl diet, plasma ET-1 responses to oral glucose load were greater in salt-sensitive (P<0. 05) than in salt-resistant patients. A marked (P<0.05) hyperinsulinemic response to oral glucose load was evident in salt-sensitive but not salt-resistant patients after each diet. This study shows increased plasma levels of the endothelium-derived substances E-selectin, vWf, and ET-1 in salt-sensitive hypertensives. Our findings support the hypothesis that salt sensitivity is correlated with an increased risk for developing hypertension-related cardiovascular damage.

Elevated plasma and urinary endothelin-I levels in human salt-sensitive hypertension.

1. The behaviour of the potent vasoconstrictive endothelium-derived peptide endothelin-1 was evaluated in salt-sensitive hypertension. 2. Circulating and urinary endothelin-1 levels were evaluated in 30 men (mean age 44.6 +/- 3.1 years) with uncomplicated essential hypertension after three consecutive 2-week periods on an intermediate (120 mmol), low (20 mmol) and high (240 mmol) NaCl diet. On the same occasions, blood pressure was measured to identify salt-sensitive patients (n = 16), i.e. those patients showing a mean blood pressure increase > 10 mmHg when switching from a low to a high NaCl diet, and salt-resistant patients (n = 14), i.e. those who did not show such mean blood-pressure variations. 3. Plasma endothelin-1 levels were higher (P < 0.005) in salt-sensitive than in salt-resistant hypertensive patients after intermediate-, low- and high-NaCl diets. Urinary endothelin-1 excretion was similar in both groups after an intermediate-NaCl diet, whereas it was significantly higher in salt-sensitive than in salt-resistant hypertensive subjects after low (P < 0.002) and high (P < 0.007) NaCl diets. High NaCl intake induced a significant increase in plasma endothelin-1 levels (P < 0.002) as compared with intermediate and low NaCl diet levels in salt-sensitive patients, but did not in salt-resistant subjects. No significant NaCl intake-related variations of urinary endothelin-1 excretion were observed in either group. 4. Salt-sensitive hypertensives are characterized by increased levels of endothelin-1 in both plasma and urine. This fact suggests that blood-pressure sensitivity to NaCl intake could be associated with an increased risk of developing both renal and cardiovascular damage.

Elevated plasma endothelin-1 levels as an additional risk factor in non-obese essential hypertensive patients with metabolic abnormalities.

Circulating endothelin-1 concentration was evaluated in 93 lean patients with essential hypertension, of whom 16 had impaired glucose tolerance and hyperlipidaemia, 25 had impaired glucose tolerance, 28 had hyperlipidaemia and 24 had no metabolic abnormalities; we also studied 22 control subjects. All groups were age- and sex-matched. Plasma endothelin-1 levels were higher (p < 0.05) in hypertensive patients with impaired glucose tolerance and hyperlipidaemia than in the remaining groups and were directly correlated with fasting insulin levels (r = 0.506, p = 0.045). Therefore, circulating endothelin-1 concentrations are elevated in hypertensive patients with a high-risk profile due to the presence of metabolic abnormalities, and might favour the development of vascular damage.

Circulating endothelin-1 concentrations in patients with chronic hypoxia.

AIMS: To evaluate the behavior of plasma endothelin-1 in patients with chronic hypoxia. METHODS: Fifteen male patients (mean age 52.1 +/- 3.1 years) with mild chronic obstructive pulmonary disease (COPD) were studied. Twelve healthy men (mean age 48.3 +/- 5.4 years) served as controls. Both patients and controls underwent standard pulmonary function tests, echocardiographic evaluation, and arterial blood gas evaluation. Blood samples for endothelin-1 assay were taken from a previously incannulated antecubital vein after 60 minutes of rest in the supine position. Endothelin-1 was measured by radioimmunoassay after extraction from plasma. RESULTS: Patients with chronic hypoxia had lower PaO2 values (66.1 +/- 6.2 mmHg) than controls (83.8 +/- 2.7 mmHg) but PaCO2 values were similar (38.1 +/- 2.5 v 36.7 +/- 3.1 mmHg, respectively). Arterial pulmonary pressure, therefore, was higher in patients (18.1 +/- 3.7 mmHg) than in controls (10.4 +/- 2.7 mmHg) as were circulating endothelin-1 concentrations (1.22 +/- 0.36 v 0.57 +/- 0.1 pg/ml). Furthermore, plasma endothelin-1 concentrations were negatively correlated with PaO2 and directly correlated with pulmonary pressure levels. No significant correlations were found in controls. CONCLUSIONS: These results show a clear relation between chronic hypoxia and circulating endothelin-1 concentrations. Therefore, chronic hypoxia may be regarded as an important stimulus for endothelin-1 release and as one of the main contributors to increased vasoconstriction in the vascular pulmonary bed which often accompanies lung disease.

Effects of atrial natriuretic factor infusion on plasma prorenin levels in hypertensive males.

To evaluate the influence of atrial natriuretic factor (ANF) infusion on circulating prorenin, 20 essential hypertensive males, aged between 40 and 60 years, were studied. After 2 weeks under normal sodium intake (120 mmol NaCl per day), patients were randomly assigned to receive either ANF (0.01 fmol/Kg/min) (n.12 patients) or its vehicle (50 mL of isotonic saline) (n.8 patients) over a period of 60 minutes. Blood samples for plasma renin activity (PRA), prorenin and aldosterone (PAC) were taken at time -60, 0, 20, 40, 60, 120, 180, 240 minutes (infusion time: from 0 to 60 minutes). PRA and PAC decreased during the ANF infusion (PRA: from 0.33 +/- 0.05 ng/L/s at time 0 to 0.10 +/- 0.06 ng/L/s at 60 minutes, p < 0.0001; PAC: from 389.2 +/- 99.8 pmol/L at time 0 to 148.7 +/- 44.3 pmol/L at 60 minutes, p < 0.0001), while returned immediately to baseline levels after the infusion was stopped (PRA: 0.37 +/- 0.11 ng/L/s at 180 minutes, PAC: 251.6 +/- 72.1 pmol/L at time 180 minutes). On the contrary, plasma prorenin increased during ANF infusion (from 1.66 +/- 0.58 ng/L/s at time 0 to 2.44 +/- 0.72 ng/L/s at 60 minutes, p < 0.05), and returned to baseline levels after the end of the infusion (1.86 +/- 0.83 ng/L/s at 180 minutes). These data indicate that ANF infusion may alter only the circulating levels of active renin, without affecting plasma prorenin secretion.

Unilateral adrenal hypersecretion of both aldosterone and cortisol in two first cousins with a syndrome of mineralocorticoid excess but without signs of hypercortisolism.

A 38 year old woman and her first cousin, a 41 year old man, presented both with hypertension, hypokalemia, hyperaldosteronism, and low plasma renin activity in our Hospital. In both patients, plasma and urine aldosterone were constantly above the normal range, even on a high NaCl diet (250 mEq/day), while the plasma aldosterone response to postural changes was normal. In the female patient abdominal ultrasonic scan, CT scan, MRI, and adrenal gland phlebography were normal, but blood from the left adrenal vein contained 1002 pg/ml of aldosterone, versus 91 pg/ml in the contralateral one. Interestingly, the secretion of cortisol was also lateralized (plasma cortisol levels being of 28.8 mcg% in the left, 2.3 mcg% in the right adrenal gland), although neither clinical nor laboratory signs of hypercortisolism were present. Spironolactone treatment (100 mg/daily) completely reversed the syndrome of mineralocorticoid excess. After 2 years, patient has normal blood pressure and serum K+ levels.

[Sodium-modulating hormones and the pressor response to sodium chloride in essential arterial hypertension]. / Ormoni sodiomodulanti e risposta pressoria al cloruro di sodio nell'ipertensione arteriosa essenziale.

Some predictive markers for NaCl sensitivity, related to the red blood cell membrane or to circulating proteins, have already been described in human essential hypertension. The present study was planned to investigate whether or not some hormones produced by the kidney or acting at the kidney level could be used as new markers for NaCl sensitivity. The study was conducted in 28 not previously treated outpatients affected by uncomplicated mild to moderate essential hypertension. After 15 days on a normal NaCl diet, plasma renin activity (PRA), plasma atrial natriuretic peptide (ANP), and the urinary excretion of active kallikrein were evaluated. The sensitivity of blood pressure to changes in NaCl intake was then assessed in all patients, according to a randomized double blind cross-over design. Each patient was assigned to a high (240 mmol of NaCl/day for 15 days) or low (40 mmol of NaCl/day for 15 days) NaCl intake. During the assessment of NaCl sensitivity, the double blindness was achieved by the use of capsules containing either NaCl or placebo. Fifteen patients (11 males and 4 females) resulted as NaCl-sensitive, while 13 patients (8 males and 5 females) were classified as NaCl-resistant. Our results indicate that PRA levels were significantly lower in the NaCl-sensitive group than in the NaCl-resistant one (0.108 +/- 0.05 ng/L/s vs 0.247 +/- 0.16 ng/L/s, p < 0.007), in the presence of raised levels of plasma ANP in NaCl-sensitive hypertensives (18.08 +/- 4.61 fmol/mL vs 12.45 +/- 3.77 fmol/mL, p < 0.006).(ABSTRACT TRUNCATED AT 250 WORDS)

Renal sodium excretory function during acute oxygen administration.

To evaluate the effect of O2 administration and O2 removal on renal Na+ excretion, 12 hypoxemic eucapnic patients affected by chronic obstructive pulmonary disease (COPD) and 9 normal subjects were studied. After 1 h in the supine position, O2 was administered for 3 h by a tight-fitting face-mask. Urine and blood samples for renal Na+ excretion evaluation were taken at times 0, 60 and 180 min. After O2 removal both the blood and the urine samples were taken again for a further 3 h. In normal subjects, urinary Na+ excretion did not vary after both O2 administration and removal. On the contrary, in patients affected by COPD renal Na+ excretion significantly increased during O2 administration (from basal values of 0.08 +/- 0.01 to 0.17 +/- 0.02 mEq/min at 180 min, p < 0.05), and returned to baseline levels (0.13 +/- 0.03 mEq/min) after 3 h from O2 removal. The basal fractional excretion of filtered Na+ was significant lower in hypoxemic patients than in normal subjects (0.72 +/- 0.3% in patients with COPD vs. 0.95 +/- 0.7% in normal subjects, p < 0.05), while, at the end of O2 administration, it became higher in patients with COPD than in controls (1.62 +/- 0.4% in patients with COPD vs. 0.89 +/- 0.5 in control subjects, p < 0.001). In conclusion, our findings showed an oxygen-related increase of both the urinary Na+ excretion and the fractional excretion of filtered sodium in patients affected by COPD.

Effects of short-time insulin suppression on renal sodium excretion in type II diabetic hypertensives.

The effects of a short-time insulin suppression on Na+ excretion were evaluated in 9 type II diabetic hypertensive males. All patients had a body mass index < 26 and normal plasma lipid levels. After 2 weeks under constant NaCl intake (120 mEq of NaCl daily) either octreotide, a somatostatin analogue, or its vehicle were infused in a forearm vein during acute volume expansion (0.20 ml/kg/min isotonic saline given intravenously over a period of 30 min). A double blind randomized cross-over design was followed, and each patient was given both infusions at one week interval. Blood and urine samples for the evaluation of plasma insulin and serum and urine Na+ were taken at time-30, 0, 30, 60, 90, 120, and 240 min. Our data showed that octreotide completely suppressed insulin levels (from time 0 to 60 min). During acute volume expansion+octreotide, Na+ excretion was 0.20 +/- 0.15 mEq/min at time 0, 0.23 +/- 0.21 mEq/min at time 30, 0.64 +/- 0.24 mEq/min at 60 (p < 0.05 vs time 0), 0.71 +/- 0.35 mEq/min at 90 (p < 0.05 vs time 0), 0.78 +/- 0.10 mEq/min at 120 (p < 0.01 vs time 0) and 0.71 +/- 0.12 mEq/min at 240 min (p < 0.05 vs time 0). As compared to acute volume expansion alone, octreotide induced a significant increase of Na+ excretion at 60 and 90 min (p < 0.05). In conclusion, a short-time insulin suppression, as obtained by the somatostatin analogue octreotide, enhances the natriuretic response to intravenous saline load in lean type II diabetic hypertensives.