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Biomedical subjects

G Verzetti

Publications and source records attributed to G Verzetti.

At least 19 recordsLinked to original sources

Urea as a marker of adequacy in hemodialysis: lesson from in vivo urea dynamics monitoring.

BACKGROUND: "Dialysis dose," a concept developed by Sargent and Gotch based on urea kinetic modeling, is a useful and recognized tool that is used to quantitate and optimize a dialysis-efficacy program. However, it has been shown that oversimplification of the "dialysis adequacy" concept to the Kt/V index might lead to dramatic underdialysis and subsequent deleterious consequences on morbidity and mortality of dialysis patients. With this perspective, the determination of Kt/V must be very cautious and rely on accurate measurement of postdialysis urea concentration and its use integrated as a tool in a quality-assurance process. METHODS: In this study, we analyzed urea dynamics by means of a blood side (ultrafiltrate) continuous online urea monitoring system interfaced with a two-pool model hosted in a microcomputer. The study was designed to provide instantaneous dialysis performances (body and dialyzer clearances, dialyzer mass transfer coefficient) and to determine the in vivo functional permeability characteristics of the patient [intercompartment urea mass transfer coefficient (Kc)]. Thirteen end-stage renal disease patients (age 54 +/- 16 years; 12 male and 1 female) were studied during nine consecutive dialysis sessions (3 weeks). RESULTS: Urea kinetics obtained from the urea monitoring system fitted closely the urea kinetic modeling prediction, confirming the validity of the double-pool model structure. Effective in vivo urea mass transfer coefficient averaged 912 +/- 235 mL/min/1.73 m2, a value close to those reported with more invasive methods. Large variations ranging from 363 to 1249 mL/min were observed among patients, confirming very large interindividual patient permeability differences. Interestingly, the urea mass transfer coefficient was inversely correlated with the postdialysis rebound values. Intraindividual variations were also noted as a function of time denoting functional changes in urea mass transfer coefficient values. The urea distribution volume was 38.1 +/- 7, 8 L (53 +/- 8% body weight). V1 referring to the extracellular volume and V2 to the intracellular volume were 9 +/- 2 L (13 +/- 2% body weight) and 29.2 +/- 6.6 L (41 +/- 1.3% body wt), respectively. The extracellular/intracellular volume ratio was 0.31 (approximately one third) and was not as usually defined by the paradigm 1/2 ratio. CONCLUSION: Online double-pool urea kinetic modeling gave a new insight in urea kinetic modeling approach. Urea dynamics fit perfectly a double-compartment model structure. Accessible extracellular volume to hemodialysis is smaller than expected. The in vivo urea mass transfer coefficient must be considered as an individual and variable characteristic of ESRD patients that should be taken into consideration when prescribing the hemodialysis schedule.

Adult↗

[Pharmacoeconomics in hemodialysis. Role of iron in the treatment with erythropoietin].

BACKGROUND: Although its efficacy is well known, the high economic cost of erythropoietin (EPO) raises the question of pharmacoeconomics in HD. An optimal Hb level with the lowest dosage of EPO seams to be correlated to the way of administration and an adequate iron supplementation. METHODS: The study evaluates the influence of iron supplementation on the control of EPO-related expenses. RESULTS: A serum ferritin level higher than 50 pg/ml in hemodialysis patients on chronic EPO therapy turned out to be adequate to keep an optimal Hb level. Our data show that this value, as far as pharmacoeconomic is concerned, is highly underestimated. CONCLUSIONS: A higher i.v. iron supplementation correlates with a significant raise of serum ferritin level and saves on EPO-related expenses up to 1 million/per patient/per year.

Economics, Pharmaceutical↗

Production of platelet-activating factor in patients with sepsis-associated acute renal failure.

BACKGROUND: Studies in experimental animals have suggested that platelet-activating factor (PAF) is a mediator of sepsis-associated acute renal failure (ARF). In the present study we have evaluated whether an increased concentration of PAF within circulation or urine of septic patients correlated with the worsening of renal function. METHODS: The concentration of PAF and selected cytokines (TNF, IL-1, IL-6, IL-8) was evaluated in blood and urine of 12 patients with septic shock and ARF for 4 consecutive days. RESULTS: The data obtained indicate that blood and urinary concentrations of PAF and of IL-1, IL-6 and IL-8 were significantly higher in septic patients than in controls subjects and in patients with chronic renal failure. The concentration of TNF was significantly increased only in urine. A significantly positive correlation was found among blood concentration of PAF and heart rate (r = 0.4193, P < 0.017), serum creatinine (r = 0.3671, P < 0.038), serum IL-6 (r = 0.5475, P < 0.005) and urine excretion of IL-8 (r = 0.3984, P < 0.044), whereas a negative correlation was present with the number of circulating platelets (r = -0.4285, P < 0.018). Moreover, a positive correlation among the concentration of PAF in urine and the serum concentration of IL-6 (r = 0.5654, P < 0.006) and urine excretion of IL-6 (r = 0.6589, P < 0.0008) and IL-8 (r = 0.6371, P < 0.0004) were found. CONCLUSIONS: These results demonstrate in humans during ARF associated with septic shock the production of PAF, a mediator that has been previously implicated in the pathogenesis of experimental endotoxin-induced shock and renal injury. The observation that blood and urinary concentrations of PAF correlated with some of the clinical and laboratory parameters related to the severity of ARF and sepsis suggests that PAF may contribute to the development of renal injury in septic patients.

Acute Kidney Injury↗

Haemolipodialysis.

Haemodialysis is associated with increased oxidant stress. This appears to be due to (1) an increased production of free radicals during haemodialysis, (2) a net reduction of many antioxidants and (3) factors intrinsic to the uremic state. These alterations can lead to cardiovascular disease and many of the pathologies associated with chronic renal failure. Haemolipodialysis (HLD) is a new haemodialytic technique aimed at reducing oxidant stress and removing hydrophobic or protein bound toxins. The technique uses dialysate containing ascorbic acid (vitamin C) and polyunsaturated unilamellar liposomes containing alpha-tocopherol (vitamin E). The liposomes interact with blood components at the haemodialysis membrane without passage through the membrane. Vitamin C and vitamin E are added to the system to protect the cell and plasma components from reactive oxygen species produced from activated inflammatory cells. This technique may provide a new approach in preventing free radical-associated pathologies in chronic haemodialysis patients.

Ascorbic Acid↗

[24 Hour arterial pressure in insulin-dependent diabetics and non-insulin-dependent diabetics with preserved renal function].

BACKGROUND: The aim of the study was to value the behaviour of systolic (S) and diastolic (D) arterial pressure (AP)/24 hrs in a group of diabetic patients insulin-dependent (IDDM) and non insulin-dependent (NIDDM) with preserved renal function. METHODS: We examined 65 diabetic patients (aged 39.1 +/- 23.3), 33 IDDM (aged 18.2 +/- 7.5; years of diabetes: 5.8 +/- 4.9) and 32 NIDDM (aged 60.7 +/- 11.4; years of diabetes: 7.2 +/- 7.5). In all of them we computed BMI and determined creatinine clearance, glycosylated haemoglobin A, total and HDL-associated cholesterol, triglyceridemia, middle glycemia and microalbuminuria. AP measurement was performed by 24 hrs monitoring (periodicity 15') using a Takeda 2420 measurer. Chronobiological characteristics of AP were analysed by statistical method of cosinor according to Halberg, examining if there was or not a blood pressure circadian rhythm (PCR) (p < 0.05) and its characteristics represented by the mesor, the amplitude and the acrophase. Moreover the patients were subjected to a diet with fixed contents of sodium (130 mEq/day) and afterwards we drew (every 4 hours) renin (R), aldosterone (A1) and atrial natriuretic factor (ANF) which were analysed with cosinor's method. The purpose was not to compare the two populations, not homogeneous between them and not different only for the years of diabetes, but to study their blood pressure behaviour, the rhythm, the order of the indicated hormones for possible pathogenetic connections. RESULTS: NIDDM presented higher blood pressure values (PAS 134.2 +/- 3.5 and PAD 80.9 +/- 2 mmHg) than IDDM (PAS 116.6 +/- 1 and PAD 66.4 +/- 1.7 mmHg), still in limits of substantial normality. The acrophase was in the midday for NIDDM (PAS 11:25', PAD 12:06') and in the early afternoon for IDDM (PAS 14:15', PAD 14:06'). Analysing the trend of the AP in the single cases, PCR was present in 70% and absent in 30% of IDDM while it was persistent in 56% and disappeared in 44% of NIDDM. IDDM without PCR differed from those with it in years of diabetes (p < 0.001), body weight (p < 0.02), BMI (p < 0.01), triglyceridemia (p < 0.05), all more elevated, as well as in higher PAS and PAD (p < 0.001) and in higher concentration of ANF (p < 0.05). The same comparison was done in NIDDM. Patients without PCR were older (p < 0.025), had higher PAS (p < 0.025) and PAD (p < 0.001) and also a more activated ANF (p < 0.001). CONCLUSIONS: This hormonal anomaly may be ascribed to a lower excretion of sodium with consequent expansion of extracellular volume due to antinatriuretic action of insulin often found at high plasmatic levels particularly in NIDDM.

Adolescent↗

Acetate-free biofiltration versus bicarbonate haemodialysis in the treatment of patients with diabetic nephropathy: a cross-over multicentric study.

BACKGROUND: Morbidity and mortality rates in diabetic patients on regular dialysis treatment (RDT) are higher than in non-diabetic-subjects on RDT. Moreover, diabetic patients experience an intradialitic morbidity unacceptably higher than in patients with other causes of terminal renal failure. The aim of the present investigation was to compare standard bicarbonate haemodialysis (BHD) with acetate-free biofiltration (AFB) in a group of 41 diabetic patients stable on dialysis treatment for 25 +/- 22 months. METHODS: Twenty-four type II and 17 type I diabetic patients, all requiring insulin therapy, were included and were followed for 1 year in a 6-month cross-over randomized study for both methods. The analysis was carried out on dialysis symptoms, interdialysis symptoms, and nutritional status, and the multivariate analysis of variance for repeated measures on the same subjects in the two techniques was used. RESULTS: AFB significantly reduced dialytic and extradialytic symptoms (P=0.003 and 0.001 respectively). Cardiovascular collapses decreased by 43%, and other dialysis symptoms showed a similar trend (-35%). The interdialysis symptoms decreased by 28% and were accompanied by an increase in subjective wellbeing (39%) when patients were switched from traditional haemodialysis to AFB. Acid base control was better with AFB (P=0.01), both at the beginning and during the session. Slightly significant differences were also obtained for Kt/V (AFB 1.48 +/- 0.29 vs BHD 1.38 +/- 0.30), while no significant difference was noted with respect to sodium mass balance, nutritional status, calorie-protein intake, nPCR, blood glucose profile, and insulin requirements. The number of hospital admissions and the mortality rate, which were much lower during the AFB than the BHD period, were not analysed statistically. CONCLUSIONS: AFB allows better control of some metabolic aspects, reduces intra- and extradialysis symptoms, and improves patient quality of life. Whether the long-term prognosis can be improved by AFB remains to be established with further studies.

Acetates↗

Regulation of nitric oxide synthesis in uraemia.

Nitric oxide (NO) is a cell-to-cell mediator involved in the regulation of vascular tone and in the mechanisms of host defence. Since uraemic syndrome is characterized by abnormalities in blood pressure and flow and by impairment of white cell function, we studied the regulation of nitric oxide synthase (NOS) activity by uraemic plasma. We used three different cellular types having different levels of NOS activity: tEnd.1 murine endothelial cell line transformed by mT oncogene of polyomavirus had a high NOS activity and expressed endothelial-NOS (eNOS) and inducible-NOS (iNOS) isoforms; human endothelial cells from cord umbilical vein (HUVEC) had low enzymatic activity and expressed only eNOS; finally, J774 murine macrophage line was characterised by iNOS induced after treatment with cytokines. We demonstrated that most (79%) of end-stage uraemic plasma studied inhibited NOS activity in tEnd.1 and in cytokine induced -J774, whereas they were ineffective on HUVEC. Twenty percent of plasma samples (14 of 67) activated NOS activity in tEnd.1 and in J774 cells, but not in HUVEC, suggesting the presence of molecule(s) which influence iNOS. The effect of plasma was not dependent on the type of haemodialysis treatment. A great number of plasmas from patients with moderate renal failure also inhibited NOS activity in tEnd.1, suggesting that the accumulation of molecules affecting NOS was caused by the renal failure rather than the haemodialytic treatment. However, the haemodialysis modified the effect of plasmas on NOS activity. Plasma taken after haemodialysis session showed a reduced inhibitory activity in tEnd.1 and in some cases it enhanced NOS activity. Simultaneously, molecules reducing NOS activity accumulated in the ultrafiltrate. The plasma concentration of NG-NG dimethyl-L-arginine (asymmetrical dimethylarginine, ADMA), an inhibitor of NOS, increased in end-stage uraemic patients and was reduced by haemodialysis. However, the concentrations reached in uraemic plasmas were lower than the ADMA IC50 on tEnd.1 NOS, indicating that this compound contributes with other molecules to the inhibitory effect of uraemic plasma. Haemodialysis reduced also the enhanced effect exerted by some plasmas on NOS in J774. Therefore, the effect of end-stage uraemic plasma on NOS activity derive from the balance between inhibitors and activators.

Analysis of Variance↗

Benign monoclonal gammopathy presenting with severe renal failure.

A patient with monoclonal gammopathy and renal failure due to kappa light chain deposition in the glomerular basement membrane is reported. After 8 months, he developed a progressive and severe renal failure requiring haemodialysis. 30 months later, the monoclonal gammopathy was unchanged. Clinical features, as well as kinetic and immunological studies, were consistent with a diagnosis of benign monoclonal gammopathy (BMG). This case suggests that the renal failure complicating a monoclonal gammopathy is not related to its malignancy.

Adult↗

[Changes in plasma concentrations of adrenal androgens in patients with chronic renal insufficiency].

The present study points out that the CHRONIC RENAL FAILURE (CRF) represents a situation of decreased adrenal function: at least for delta 5 Steroids which are markedly reduced when compared with normal subjects. Peripheral plasma levels of Pregnenolone (delta 5 P) ranged in CRF between 190 and 860 pg/ml; Dehydroepiandrosterone-sulphate (DHA-S) 0.1-2.2 ng/ml and Dehydroepiandrosterone (DHA) 200-3100 pg/ml. Cortisol was in the normal range or slightly elevated (70-175 ng/ml). A significant correlation between basal concentration and the time of dialysis was observed. It is interesting to notice how the phase levels of delta 5 P, DHA-S and DHA are reduced ad from the beginning of the haemodialysis treatment and that during such a treatment a further progressive decrease occurs reaching concentrations with are similar to those found in pre-puberty. This phenomenon appears to be the evidence of a progressive metabolic involution of the adrenal gland due to the exhaustion of enzymatic activities and of receptorial structures. Furthermore, these results suggest speculation on interrelationship between adrenal and gonadal activity in these patients.

Adrenal Glands↗

[Circulating opioid peptides in chronic renal failure: acute effect of dialysis treatment].

In 14 patients affected by chronic renal failure (7 males and 7 females) it has been evaluated the secretion of beta LPH, beta EP, ACTH and Cortisol in basal conditions and immediately after a dialytic treatment. For beta LPH and beta EP measurements on each thawed plasma a silic acid extraction and a successive peptides separation by a Sephadex G-75 column chromatography preceeded the two specific RIAs. Basal beta LPH plasma levels resulted significantly higher than in normal controls, while that of beta EP, ACTH and Cortisol were in the normal range. The dialytic treatment was able to increase ACTH and Cortisol plasma levels, without to modified beta LPH and beta EP plasma levels.

Adrenocorticotropic Hormone↗

[Immunological determination of various blood proteins in clinical nephrology].

The serum levels of certain proteins were determined in 130 nephropathics collected into 8 different diagnostic groups, and in 20 normal subjects considered as a control group. The purpose was mainly to assess the clinico-diagnostic interest of such a measurement in nephrological practice. The results point to its clinical usefulness, particularly in differential diagnosis. It is possible to formulate interesting physiopathological interpretations notwithstanding the limitations of the eminently clinical features of the research.

Acute Disease↗