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Biomedical subjects

V Panichi

Publications and source records attributed to V Panichi.

51 records · Page 3Linked to original sources

Effect of increasing doses of lisinopril on proteinuria of normotensive patients with IgA nephropathy and normal renal function.

The antiproteinuric effect of angiotensin converting enzyme (ACE) inhibition in patients with renal disease is well known, but the results of clinical studies appear to vary considerably from a partial decrease to a fall of 100% in urinary protein excretion. This may have been due to the use of different doses of ACE inhibitor, different renal pathology and non-standardized sodium intake. In 16 proteinuric patients with biopsy-proven IgA nephropathy, with normal renal function and blood pressure, maintained at controlled sodium intake < or = 80 mEqII, the efficacy of increasing doses of the ACE inhibitor lisinopril was studied. The lisinopril doses were 5, 10, 15 and 20 mg, administered for 4 weeks. Between each dose increment a placebo period of 3 weeks was interposed. Proteinuria stepwise decreased from the control period by 39%, 44%, 61% and 67% with lisinopril at 5, 10, 15 and 20 mg, respectively. The blood pressure decreased by 22% with lisinopril 5 mg; a similar fall was observed with the dose increment. Although the glomerular filtration rate remained unchanged, the renal plasma flow increased by 21%, 26%, 24% and 28% and the filtration fraction increased by 28% mean. The ACE plasma levels decreased by 33%, 64%, 76% and 83%. A close correlation was found between an increase in lisinopril dosage and the fall in urinary protein excretion (r = 0.88, p < 0.001). The antiproteinuric effect of lisinopril is dose-related and may be attributable to some extent to the fall in systemic (and intraglomerular) blood pressure, but it is best attributed to the modification of glomerular sieving function.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Intravenous immunoglobulin therapy of membranous nephropathy: efficacy and safety.

Preliminary results of the efficacy of high-dose intravenous human IgG in patients with biopsy-confirmed idiopathic membranous nephropathy (IMGN) were reported. Five patients with normal renal function (creatinine clearance 125.2 +/- 16 ml/min/1.73 m2 BSA) (Group A) and 4 patients with moderate renal insufficiency (creatinine clearance 65.5 +/- 8.3 ml/min/1.73 m2 BSA) (Group B) received pulse doses of IgG (0.4 g/kg BW) for 3 consecutive days; these 3-day boli were repeated 3 times at 21-day intervals; since then for a 10-month period one bolus once every 3 weeks has been administered. Five responder patients at the end of the trial received a new renal biopsy. In 4 Group A patients complete remission of proteinuria (daily proteinuria less than 0.2 g) was observed, whereas 1 patient showed partial remission (proteinuria 2 g/day). In Group B patients, 1 showed complete remission and 2 partial remission; in 1 patient no variation of proteinuria was noted. In responder patients clinical and biological findings of the nephrotic syndrome disappeared and a statistically significant increase of creatinine clearance was observed. In control biopsies at the end of the trial the immunofluorescence staining failed to find immunodeposits and recovery of glomerular lesions at light microscopy. In conclusion, IgG therapy seems to be of benefit to patients with IMGN but a randomized clinical trial to confirm this preliminary report is needed.

Adult↗

Fractional shortening/end-systolic stress correlation in the evaluation of left ventricular contractility in patients treated by acetate dialysis and lactate haemofiltration.

Fractional shortening/end-systolic stress (FS/ESS) correlation by echocardiography is a reliable index of left ventricular function. Acetate infusion or preload reduction due to water compartment re-equilibrium may induce ventricular derangements during dialytic treatment. In 13 patients on lactate haemofiltration (LHF) (mean age 56.8 +/- 11.9 years on regular dialytic treatment (RDT) for 75.3 +/- 56.5 months) and in seven patients on acetate haemodialysis (AHD) (mean age 48 +/- 10.7 years; on RDT for 43.9 +/- 49.2 months) fractional shortening/end-systolic stress was evaluated before and after single dialytic session. The following biochemical parameters were also studied: haematocrit (Htc), plasmatic osmolarity, ionised Ca, Na, K, and blood gases. In both groups the mean fractional shortening/end-systolic stress correlation maintained the same correlation coefficient before and after treatment (r = -0.68, P less than 0.001). Lactate haemofiltration and acetate haemodialysis by reducing the volume expansion and preload (mean interdialytic body-weight increase 2.5 +/- 0.8 kg in our patients), may decrease left ventricular contractility (Starling's law). Furthermore, acetate was postulated as a myocardial depressant. Dialysis-induced myocardial contractility variations plotted against fractional shortening/end-systolic stress correlation allowed the division of our patients into four different groups: (1) patients with increased fractional shortening and reduced end-systolic stress; (2) patients with unchanged fractional shortening and reduced end-systolic stress; (3) patients with reduced fractional shortening and increased end-systolic stress; and (4) patients with reduced fractional shortening and unchanged or reduced end-systolic stress. These groups include patients treated with either lactate haemofiltration or acetate haemodialysis. Our data cannot confirm the postulated acetate myocardial depressant activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates↗

Lack of nocturnal serum thyrotropin (TSH) surge in patients with chronic renal failure undergoing regular maintenance hemofiltration: a case of central hypothyroidism.

Thyrotropin (TSH) secretion was evaluated in a group of patients with chronic renal failure (CRF) undergoing regular maintenance hemofiltration and in normal controls. The study group included 68 patients (39 males and 29 females, age range 39-73 years, mean: 53 years). In all patients blood was drawn at 08:30-09:00 h; in 20 patients the nocturnal (24:00-02:00 h) serum TSH peak was also evaluated; 12 patients underwent stimulation test with synthetic TSH-releasing hormone (TRH). TSH was measured by an ultrasensitive immunoradiometric assay. CRF patients showed a significant decrease in serum total and free thyroxine and triiodothyronine concentrations, which in a substantial proportion of subjects were below the lower normal limit. Serum reverse triiodothyronine and thyroxine-binding globulin values did not differ in the two groups. Despite this trend of thyroid hormones to decrease, no patient had supranormal TSH values as in primary hypothyroidism. While the mean morning TSH concentrations of CRF patients did not differ from those of controls, the mean nocturnal values were significantly reduced in CRF (1.0 +/- 0.2 vs 3.2 +/- 0.4 mU/l, p less than 0.0005) and the nocturnal serum TSH surge was not observed in 18 of the 20 patients (90%) in whom it was evaluated. The mean serum TSH peak value after TSH-releasing hormone (TRH) administration was also reduced in CRF patients, and the TSH response to TRH was blunted in 3 out of 12 patients (25%). The results of this study demonstrate a major impairment of TSH secretion in CRF, which baseline TSH measurements in the morning and the evaluation of the TSH response to TRH may not reveal.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Renal effects of enalapril in hypertensive patients with glomerulonephritis.

Renal effects of enalapril maleate in ten hypertensive patients with glomerulonephritis were evaluated after 1 and 16 weeks of therapy. Systemic blood pressure decreased, glomerular filtration rate was not significantly changed, and sodium fractional excretion and renal plasma flow increased, whereas renal vascular resistances and filtration fraction decreased acutely at the end of the study. Proteinuria diminished, but no variations in qualitative pattern were observed. ACE inhibitors, promoting efferent rather than afferent arteriolar vasodilatation and reduction of glomerular permeability coefficient, may reduce glomerular capillary hypertension and the development of proteinuria.

Blood Pressure↗

Ultrafiltration: a rational treatment for heart failure.

Patients with late-stage congestive heart failure with significant fluid overload respond well to ultrafiltration. The response is relatively long-standing and includes enhanced responsiveness to diuretics. Ultrafiltration is simple and highly cost effective. Furthermore, it possesses many advantages over massive or drastic pharmacological therapy. In the following paper, we report our own experience and review the world literature.

Blood Volume↗

C reactive protein in patients with chronic renal diseases.

Base-line serum levels of plasma C-reactive protein (CRP) are predictive of future myocardial infarction and sudden cardiac death in apparently healthy subjects, suggesting the hypothesis that chronic inflammation might be important in the pathogenesis of atherothrombosis. CRP production is mediated by several inflammatory mediators: interleukin 6 (IL-6) is currently felt to be the major cytokine influencing the acute phase response. CRP and other acute phase proteins are elevated in dialysis patients and cardiovascular diseases represent the single largest cause of mortality in chronic renal failure patients. Little information is available, however regarding CRP and IL-6 plasma levels in pre-dialysis renal failure. Plasma CRP was determined by a modification of the laser nephelometry technique; IL-6 by immunoassay (RD System); and fibrinogen, serum albumin, cholesterol, triglycerides, hematocrit, white blood cell count, erythrocytic sedimentation rate (ESR) and urinary protein levels by standard laboratory techniques. Results were obtained in 102 chronic pre-dialysis patients whose mean age was 53+/-5.8 years with a mean creatinine clearance (C(Cr)) of 52+/-37 mL/min). CRP was greater than 5 mg/L in 25% of the global population. CRP and IL-6 were 4.0+/-4.6 mg/L and 5.8+/-5.6 pg/mL, respectively and were not significantly correlated (r=0.11, p=n.s.). CRP and IL-6 were however related with renal function (CRP versus C(Cr) r=-0.40 p <0.001; IL- 6 versus C(Cr) r=-0.45; p <0.001). When patients were divided in two groups according to renal function, CRP resulted 7.4+/-6.3 mg/L in the group of patients with a C(Cr) lower than 20 mL/min (n=32) and 2.76+/-4.35 in the group of patients with a C(Cr) higher than 20 mL/min (n = 70) (p <0.0001). CRP and IL-6 were positively related with ESR (r=0.32 and 0.46 respectively). Serum albumin levels were not significantly different in the two groups of patients (3.2+/-0.4 versus 3.0+/-0.5 g/dL). CRP and serum albumin were not significantly related (r=0.17). CRP and IL-6 correlated positively with ESR (r=0.32 and 0.46 respectively). In pre-dialysis patients we have demonstrated an increase in both CRP and IL-6 that occurs as renal function decreases. These data provided evidence of the activation - even in the predialysis phase of renal failure - of mechanisms known to contribute to the enhanced cardiovascular morbidity and mortality of the uremic syndrome.

C-Reactive Protein↗

Plasma C-reactive protein is linked to backfiltration associated interleukin-6 production.

Bacterial contamination of dialysate may enhance cytokine production in hemodialysis. The authors tested the hypothesis that C-reactive protein and interleukin-6 (IL-6) may be linked in a large group of patients exposed to backfiltration of dialysate over a long period of observation. Plasmas stored in a recently published multicenter study were reevaluated. Plasma C-reactive protein and IL-6 concentrations in patients with chronic uremia undergoing hemodiafiltration, which is known to be associated with backfiltration (Group II, 12 patients), were compared with those found in patients treated with a modified hemodiafiltration modality without backfiltration (Group I, 16 patients), and in patients shifted from one modality to the other (Group III, 27 patients), and in 10 patients on hemodialysis (Group IV) in a 1 year multicenter study. Plasma C-reactive and IL-6 both increased significantly (p < 0.002), but slowly (after 8 months) in Group II compared with I, and during the 4 month period in hemodiafiltration with backfiltration in Group III. Backfiltration of dialysate with a moderate to low degree of contamination may enhance synthesis of cytokine and C-reactive protein in the long term. Thus, the relevance for dialytic strategies aiming at improving dialysate quality or at reducing backfiltration is highlighted.

C-Reactive Protein↗

Treatment with 1,25-dihydroxyvitamin D3 preserves glomerular slit diaphragm-associated protein expression in experimental glomerulonephritis.

In this study, we investigated the effect of 1,25(OH)2D3 on proteinuria and on the alteration of slit diaphragm-associated proteins induced by anti-Thy 1.1 in Wistar rats. Four groups of animals were studied: group I, anti-Thy 1.1 treated rats; group II, anti-Thy1.1 treated group that at day 2, after the onset of overt proteinuria, started the treatment with 1,25(OH)2D3; group III, normal control rats injected with vehicle alone; group IV, rats that received only 1,25(OH)2D3. At day 2, in group I and II, before the administration of 1,25(OH)2D3, protein excretion was significantly increased when compared to controls. Overt proteinuria was maintained until day 14 in group I whereas in group II protein excretion was significantly reduced from day 3 to day 14. Moreover, treatment with 1,25(OH)2D3 abrogated podocytes injury, detected as desmin expression and loss of nephrin and zonula occludens-1 (ZO-1), two slit diaphragm-associated proteins, and glomerular polyanion staining, that were observed in group I. In conclusion, these results suggest that 1,25(OH)2D3 administrated with a therapeutic regiment may revert proteinuria, counteracting glomerular podocyte injury.

Animals↗

Alterations of the cytokine network in hemodialysis.

This study focuses on the mechanisms responsible for monocyte activation and enhanced cytokine production in hemodialysis. Particular emphasis is given to recent recognition of a link between cytokine production and chronic inflammation following long-term complications in today's hemodialysis population, namely cardiovascular disease and malnutrition.

Chronic Disease↗

[Anti-cytokine therapy: present status and future perspectives in nephrology].

The increasing understanding of the role of cytokines in chronic inflammatory disease, autoimmunity and neoplastic disease has led to a new generation of therapeutic agents, the anti-cytokine blocking agents. In this article, we review current knowledge of two different available approaches: the use of Thalidomide and the anti-cytokine antibody immune therapy. Thalidomide is an immunodulatory and antiangiogenic drug; the most pronounced effect of this drug is the inhibition of tumor necrosis factor-alpha (TNF-alpha ) production. A few years after its withdrawal from the European and Canadian markets due to severe teratogenic effects, the unexpected activity of Thalidomide in reactive lepromatous leprosy stimulated further study. After some confirmatory placebo-controlled trials, multiple researches are now in progress to evaluate the optimal dose of Thalidomide in several autoimmune and neoplastic diseases. Both passive and active immunization can safely, transiently and effectively be used, as documented by animal experimentation and confirmed by clinical trials. Novel anti-cytokine therapeutic compounds, based on passive antibody immunization, are now available to treat rheumatoid arthritis and have been shown to help in Crohn's disease and in several other autoimmune diseases, and to control neoangiogenesis in cancer patients. The durability of the benefit, safety and pharmacoeconomic issues will determine whether this early success will prove to be a major breakthrough in the treatment of these painful and incurable diseases and eventually of other chronic inflammatory conditions in uremic patients.

Cytokines↗