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B Cianciaruso

Publications and source records attributed to B Cianciaruso.

At least 55 records · Page 3Linked to original sources

Net release or uptake of histidine and carnosine in kidney of dogs.

Previous studies are equivocal as to whether the dog kidney produces histidine. Because one possible source of renal histidine is carnosine (beta-alanyl-L-histidine), we investigated net renal production (release) or utilization (uptake) (Qmet) of histidine and carnosine in 19 female dogs after they were fed histidine-free (9 dogs) or histidine-containing diets (10 dogs). Diets were fed in short-(2-11 days) or long-term (52-57 days) studies. Dogs were infused with half-normal saline for 120 min followed by an infusion of half-normal saline containing carnosine, 50 mumol/min. Renal Qmet histidine, calculated from either plasma or whole blood values, was positive during infusion of half-normal saline. During carnosine infusion, Qmet histidine increased markedly, and there was net renal uptake of carnosine. The Qmet histidine and carnosine were not different in the dogs fed histidine-free vs. histidine-containing diets. Thus there is net renal release of histidine in female dogs that increases when carnosine is administered. Qmet histidine or carnosine do not change adaptively when dogs are fed histidine-free diets.

Animals↗

Effects of angiotensin II on plasma ADH, prostaglandin synthesis, and water excretion in normal humans.

To verify whether angiotensin II (ANG II) stimulates ADH release in humans and to evaluate whether endogenous prostaglandins influence the resulting renal effect of ADH, nonpressor and low pressor doses of ANG II were infused in nine normal volunteers under normal conditions (control study) and after prostaglandin synthesis inhibition with aspirin (ASA study). During ANG II infusion plasma ADH increased in both conditions. Plasma PGE2, urinary PGE2, and urinary 6-keto-PGF1 alpha increased only in the control study, whereas they were undetectable in the plasma and significantly reduced in the urine in the ASA study. ANG II caused a significant fall of glomerular filtration rate, renal plasma flow (with an increase in filtration fraction), fractional sodium excretion, and urine output in both studies. Despite the reduced urine output, urine osmolality decreased significantly in the control study, whereas it increased after aspirin administration. These results suggest that intravenous ANG II stimulates ADH release in humans but that the renal effects of the resulting increase in plasma ADH are different depending on the presence or absence of endogenous prostaglandins.

6-Ketoprostaglandin F1 alpha↗

Mechanism of action of indomethacin in tubular defects.

Indomethacin, a potent prostaglandin synthesis inhibitor, has been proven to be effective in a number of tubular defects characterized by enhanced prostaglandin (namely, prostaglandin E2 (PGE2) production, but its mechanism of action is poorly understood. To elucidate further the mechanism(s) by which indomethacin reverses the abnormal tubular functions, five children with different tubular defects (nephrogenic diabetes insipidus, three cases; Fanconi syndrome, one case; and pseudohypoaldosteronism, one case) were treated with indomethacin. Indomethacin, 1 mg/kg every eight hours, was given for 1 week to all children and then was given chronically to four of the children who responded to the drug. Its use was suspended in a 10 year-old-boy with nephrogenic diabetes insipidus because it proved ineffective. To assess the site along the nephron where indomethacin affects the solute and water excretion, an acute water load study was performed in three responsive children before and during the treatment. Indomethacin did not significantly alter the glomerular filtration rate but was effective in reducing diuresis and levels of urinary sodium and potassium excretion. In the child with Fanconi syndrome, indomethacin was also effective in controlling the urinary loss of phosphate, urate, glucose, and bicarbonate. Results of the water load studies show that indomethacin decreases the delivery of solute from the proximal tubule, reduces the fractional free water clearance, and increases the urine-plasma osmolar ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Role of plasma vasopressin in the impairment of water excretion in nephrotic syndrome.

To verify whether or not an increased secretion of ADH may cause the water retention commonly observed in nephrotic syndrome, 16 nephrotic patients and 13 normal control subjects were studied in basal conditions and following a water load or an iso-osmotic blood volume expansion by 20% albumin infusion. In the basal condition there were no differences in plasma ADH, urine output, urinary osmolality (UOsm), and plasma renin activity between nephrotic patients and control subjects; POsm, PNa+, UNaV, and blood volume (BV) instead, were significantly lower in nephrotic patients than in control subjects. Following the water load control subjects reached a minimal UOsm of 82 +/- 12 mOsm/kg at 60 min and excreted completely the ingested water in 150 min; nephrotic patients reached a minimal UOsm of 160 +/- 111 mOsm/kg at 120 min, and the water was eliminated completely in 240 min. Plasma ADH decreased significantly in the first hour following water load only in control subjects. A significant direct correlation was observed between plasma ADH and POsm in control subjects (ADH = -85 + 0.30 POsm, P less than 0.001) but not in nephrotic patients. Plasma ADH was inversely correlated with BV in nephrotic patients (ADH = 15.47 -0.17 BV, P less than 0.001) but not in normal control subjects. In nephrotic patients with reduced BV the expansion of BV with 20% albumin was effective in reducing the plasma levels of ADH and promoting a water diuresis. Our results demonstrate a sustained volume mediated secretion of ADH in the nephrotic syndrome, which is responsible for the impairment in water excretion.

Adolescent↗

Water excretion in nephrotic syndrome. Relationship between blood volume and plasma vasopressin.

In order to verify whether or not an increased secretion of ADH may cause the water retention commonly observed in nephrotic syndrome, 12 nephrotic patients and 11 normal subjects were studied in basal conditions and following a water load or iso-osmotic blood volume expansion. A significant direct correlation was observed between plasma ADH and Posm in controls but not in nephrotics. Plasma ADH was inversely correlated with BV in nephrotics but not in controls. Blood volume expansion in nephrotic patients was effective in reducing plasma ADH and promoting a water diuresis. These results demonstrate a sustained volume mediated secretion of ADH in nephrotic syndrome, which is responsible for the impairment in water excretion.

Blood Volume↗

Histidine, an essential amino acid for adult dogs.

Twenty-seven adult female mongrel dogs were studied to evaluate whether histidine is an essential amino acid. Dogs were tube-fed isocaloric, isonitrogenous amino acid diets which provided either no histidine or 67 mg histidine/kg body weight/day. The histidine-free diet was fed to 10 dogs for 5.6 +/- 3.6 (SD) days and to six dogs for 59.2 +/- 6.0 days. In the short-term studies, there were no differences between the responses of the dogs fed the histidine-free and histidine-replete diets. In the long-term studies, dogs fed the histidine-free diet developed a significant decrease in plasma and muscle histidine, muscle carnosine, body weight, hematocrit and serum albumin. The dogs fed the histidine-free diet tried to avoid the feedings, and after several weeks, they often manifested reduced activity and listlessness. One dog died on the 72nd day. None of these manifestations occurred in the dogs fed the histidine-replete diet in the long-term studies. Plasma zinc and copper were not different in the two groups of dogs. However, at the end of the long-term studies, the dogs fed the histidine-free diet had significantly lower final whole blood zinc and copper concentrations as compared to the histidine-replete dogs. These findings indicate that histidine is an essential amino acid in adult female dogs. The syndrome associated with histidine-deficiency tends to develop slowly over many days to several weeks.

Amino Acids↗

[Treatment of arterial hypertension with minoxidil in renal insufficiency].

Minoxidil was administered to 13 patients with arterial hypertension resistant to ordinary antihypertensive drugs and with various degrees of renal failure. Four patients were followed in this way for 50 weeks. Blood pressure values fell from 208 +/- 9.8/124 +/- 4.8 to 153.1 +/- 7.8/86.9 +/- 2.6 at the end of the treatment period. Propanolol and furosemide were used to offset sodium retention and reflex tachycardia. There was no decrease in renal function. In patients examined for the longest period, the minoxidyl dose, after an intermediate reduction stage, reached the 8th week value. Hypertrichosis was the most disturbing side-effect, especially for the female patients. The question of pericarditis is discussed.

Adult↗

Relationship between serum albumin concentration and tubular reabsorption of glucose in renal disease.

Micropuncture studies in rats and dogs have provided evidence for a cause-and-effect relationship between peritubular protein concentration and proximal tubular reabsorption (PTR). If this effect is obtained in man, hypoalbuminemia in nephrotic syndrome should lead to a fall in PTR. Sodium excretion, however, is very low in nephrotic patients; but this sodium retention may be due to distal over-reabsorption. Glucose may be used as a marker of PTR. Because of the linkage between glucose and sodium, glucose reabsorption is expected to be suppressed when PTR of sodium is suppressed. Glucose titration studies were performed in 21 patients with chronic glomerulonephritis without renal failure divided in three groups: I (six patients) with serum albumin greater than 3 g/100 ml; II (five patients) with serum albumin of 2 to 3 g/100 ml; and III (10 patients with edema and nephrotic syndrome) with serum albumin less than 2 g/100 ml. The minimum threshold for glucose decreased in nephrotic patients (group III), and its fall was related directly to hypoalbuminemia. The splay of titration curve was markedly increased in group III when compared to the titration curves of patients without nephrotic syndrome (groups I and II). The splay point was 0.78 in group I, 0.52 in group II, and 0.37 in group III. These data provide evidence that glucose reabsorption is decreased in nephrotic syndrome and are consistent with a fall in PTR in nephrotic syndrome.

Adult↗

[Predictive and diagnostic factors of malnutrition in hemodialysis patients].

The relationship between malnutrition and inflammation is by now well established. IL-6 and, probably, other proinflammatory cytokines (mainly IL-1 and TNF) may represent the link between these two entities since these interleukins may promote loss of appetite, muscle protein breakdown and reduced hepatic synthesis of "negative" acute phase proteins like albumin, prealbumin and transferrin. IL-6 also stimulates up to 1000 fold the hepatic synthesis of "positive" acute phase proteins, mainly C-reactive Protein (CRP) and Serum Amyloid A. The association between CRP and cardiovascular mortality in the general population, as well as in haemodialysed uraemic patients, is well established. These crucial interrelationships have modified the interpretation of serum albumin concentration in the diagnosis of malnutrition; a reduced serum albumin concentration, in fact, in the presence of high CRP values should point towards a diagnosis of inflammation, though the inflammation may often induce weight loss or a condition of malnutrition. After switching most patients to a more biocompatible dialysis membrane and improvement of the quality of the dialysis fluid (by adopting hydrophobic filters at the water entry of dialysis devices and bicarbonate powder cartridges) nephrologists have focused their attention on other sources of inflammation (e.g. artificial vascular protheses, presence of infected thrombi, Clamidiae, Helicobacter Pilori, dental granulomas etc.). Starting from these assumptions the diagnosis of malnutrition, once focused mainly on serum albumin reduction, must be based on other parameters (clinical history of body mass wasting, dietary and anthropometric assessment, subjective global assessment, bioimpedance analysis etc.). All these investigations, however, must be examined together to obtain suitable information on the risk of malnutrition in dialysis patients. A comprehensive approach to malnutrition-inflammation in dialysis patients is the object of the present nephrology conference.

Acute-Phase Proteins↗

[Anderson-Fabry's disease: diagnostic problems, therapeutic relevance, and clinical experience in the treatment of the disease with enzyme replacement therapy in nephropathic patients].

Aim of this study was to confirm the initial results of a clinical trial on the treatment of Fabry's disease carried out in 13 Italian Nephrology Units. Fabry's disease is a rare, X-linked inherited disease, characterized by a-galactosidase (a-GAL) deficiency, a lysosomial enzymatic activity that results in the accumulation of neutral glycosphingolipids in the endothelial cells of the whole body, and causes painful crises, acroparesthesiae, angiokeratomas, corneal and lens dystrophy, and progressive damage to kidneys, heart and central nervous system, as well as potentially leading to death. The present availability of the recombinant form of a-GAL allows us to prevent or stop the long-term complications of this disease. A clinical trial, generously supported by Genzyme, was started on February 2001. In this trial 20 patients affected by Fabry's disease were periodically treated with agalsidase-beta, the commercial form of the enzyme. The initial results of the trial have indicated that the drug is capable of reducing both the number and intensity of painful crises, improving the patient's sensation of well-being, thus suggesting that this therapeutic approach might theoretically increase life expectancy in these patients.

Chromosomes, Human, X↗

[Conservative therapy Guidelines for chronic renal failure].

In recent years, many national and international organizations have developed clinical practice guidelines for the most important areas of nephrology. In 1999, the Italian Society of Nephrology (SIN) was one of the first scientific societies to publish (in Giornale Italiano di Nefrologia) the Guidelines for the Treatment of Chronic Renal Failure. Since then, new evidence has accumulated on several aspects of the conservative treatment of chronic kidney disease (CKD). These new data have been included in the present version of the guidelines. The first section of the new guidelines underline the importance of the early detection of CKD and early referral to a nephrologist. The second and third sections are dedicated to the dietetic treatment of chronic renal failure, even when associated with nephrotic syndrome. The fourth section analyzes the anti-hypertensive treatment of renal failure, focusing on the choice of anti-hypertensive drugs to retard the progression of renal failure and reduce cardiovascular mortality. This section highlights the reno-protective role of ACE inhibitors and of AII receptor antagonists in diabetic and nondiabetic nephropathies. The Appendix describes methods for the evaluation of the patient's nutritional status and for protein intake in chronic renal failure.

Humans↗

Management of hypertension in chronic kidney disease: the Italian multicentric study.

BACKGROUND: Guidelines have indicated the achievement of blood pressure target (BP <130/80 mmHg) as a priority in the conservative treatment of chronic kidney disease (CKD), but the current implementation of these recommendations in clinical practice is unknown. METHODS: We assessed control rates, treatment and clinical correlates of hypertension in 1201 adult non-dialyzed CKD patients followed up by a nephrologist for at least 6 months. RESULTS: Estimated glomerular filtration rate (GFR) was 32 (SD 15) mL/min/1.73 m2. BP target was not achieved in 88% of patients (95% confidence interval (95% CI): 86-90%). In 84% of patients, BP levels were also above the target at the first visit to the nephrology unit 4.5 yrs previously. The risk of not achieving BP target during the nephro-logy follow-up was associated with older age (odds ratio (OR): 1.24, 95% CI 1.06-1.45, p=0.008), diabetes (OR: 2.25, 95% CI 1.20-4.20, p=0.011), and the duration of hypertension (OR: 1.13, 95% CI 1.02-1.24, p=0.016). Among patients with uncontrolled BP, about 70% received multidrug antihypertensive therapy including renin-angiotensin system (RAS) inhibitors; conversely, diuretic treatment was prescribed in a minority of patients (37%), and at insufficient doses in half the cases, despite the insufficient implementation of a low salt diet (18%). CONCLUSIONS: BP target was not reached in most CKD patients routinely seen in the renal clinics. The main barrier to guideline implementation is possibly the inadequate treatment of extracellular volume expansion despite the large prevalence of factors, such as older age and diabetes, which further enhance the intrinsic BP salt sensitivity of CKD.

Aged↗

[Fabry nephropathy in a female with superposed IgA glomerulonephritis].

BACKGROUND: In Anderson-Fabry disease (AFd), the kidney is affected in all hemizygous males and in some heterozygous females. Female carriers can present subtle renal abnormalities due to glycosphingolipid (GSL) accumulation within renal cells. Renal biopsy is rarely performed in female Fabry patients because clinical renal manifestations are usually lacking. However, female carriers can accumulate GSL in their renal cells despite the absence of clinically evident kidney disease. CASE REPORT: We performed a kidney biopsy in a 52-year-old female patient, a Fabry disease carrier. The patient showed normal glomerular filtration rate, persistent microhematuria and proteinuria (about 1.7 g/24 hr), cornea "verticillata", and evident left ventricular hypertrophy. The molecular study documented a missense mutation R227Q in exon 5 of the alpha-galactosidase A gene. Optical microscopy showed electron-dense mesangial deposits due IgA glomerulonephritis, as confirmed by immunofluorescence. We decided to start therapy with angiotensin-converting enzyme inhibitors (ACE-I). After 8 months of treatment, the patient demonstrated proteinuria of 0.9 g/24 hr. To decide when to start treatment using enzyme replacement therapy (ERT) with human recombinant GAL A (Fabrazyme), we decided to perform an electron microscopy study of the renal biopsy. The renal ultrastructural findings were typical GSL inclusions in all kinds of glomerular cells, in tubular epithelial cells and in endothelial cells of interstitial capillaries, confirming the hypothesis of Fabry nephropathy. Consequently, Fabrazyme was given at a standard dose of 1 mg/kg every 2 weeks. After 24 months of combined treatment (ACE-I-Fabrazyme), proteinuria decreased to 0.2 g/24 hr. CONCLUSIONS: The importance of performing the ultrastructural examination of the kidney biopsy is stressed, especially in heterozygous Fabry patients to evaluate the need to treat them with ERT and to evaluate the degree of renal involvement.

Angiotensin-Converting Enzyme Inhibitors↗