Verapamil versus amlodipine in proteinuric non-diabetic nephropathies treated with trandolapril (VVANNTT study): design of a prospective randomized multicenter trial.

Angiotensin converting enzyme inhibitors (ACEI) are the most effective antiproteinuric agents and should be used as first-line drugs in both diabetic and non-diabetic proteinuric nephropathies. The role of calcium channel blockers (CCB) is much more controversial. In diabetic patients verapamil and diltiazem seem more effective than dihydropyridines in reducing urinary protein excretion, and have additive effects with ACEI, but little is available on chronic treatment of non-diabetic nephropathies for non-dihydropyridine CCBs. To test whether the combination of verapamil 180 mg or amlodipine 5 mg with trandolapril 2 mg reduces urinary protein excretion more than trandolapril 2 mg alone, we planned a prospective, randomized, double-blind, multicenter trial. The secondary aims are to evaluate the effects of both treatments on the selectivity of proteinuria and check their safety. Consecutive patients aged between 18 and 70 years with non-diabetic proteinuria > or =2 g/24 h and plasma creatinine < 3 mg/dl or creatinine clearance > or = 20 ml/min are asked to participate. After a four-week run-in during which previous antihypertensive therapy is withdrawn, a single dose of trandolapril 2 mg is given once a day in open conditions for four weeks. At the end of this period patients are randomly assigned to receive once a day, in a double blind fashion, either trandolapril 2 mg and verapamil 180 mg [plus a placebo], or trandolapril 2 mg plus amlodipine 5 mg. They are monitored after one, two, five and eight months.

Effects of high CaCO3 supplements on serum calcium and phosphorus in patients on regular hemodialysis treatment.

The effect of high doses of CaCO3 on serum phosphorus and calcium (sPi,sCa) and the changes in serum aluminum (sAl) induced by Al(OH)3 interruption were investigated in patients on regular hemodialysis treatment. Some patients were administered Al(OH)3 and CaCO3, others only the former or the latter and others nothing. Al(OH)3 was stopped in all but one in whom it was only reduced, and CaCO3 was started or increased in all patients. A better control of sPi and serum Ca-Pi product was observed during high Ca supplementation, despite Al(OH)3 discontinuation, and was associated with a significant decrease of sAl. As expected, taking into account the dialysate Ca level of 4 mEq/l, a significant hypercalcemia occurred in some patients, especially in those who had a normal predialytic sPi without Al(OH)3 supplementation. Therefore, lowering the dialysate Ca concentration according to individual need and increasing interdialytic oral Ca supplements can be recommended with the dual purpose of keeping a positive Ca balance and correcting hyperphosphatemia.

Amyloid bone disease and highly permeable synthetic membranes.

The effect of different highly permeable membranes on amyloid bone disease (ABD) was retrospectively evaluated in patients on renal replacement therapy (RRT) in our Unit with a dialytic age of more than 4 years. A group of 36 patients (age 60 +/- 12 years) after a variable period (28 +/- 29 months) on hemodialysis with cuprophane membrane (CU-HD), were moved to HDF with a reinfusate volume of 22 +/- 1 1/session, for a period of 65 +/- 26 months using the following membranes: AN69 1.6 m2, PAN 1.8, PMMA 2.1, PS 1.3, polyamide (PA) 1.3 and 1.6. Bone x-rays of wrists, hips and shoulders were taken annually and the presence of ABD was evaluated according to generally accepted criteria. ABD occurred in 4 patients after a period of 73 +/- 30 months on CU-HD only; it developed in 4/7 patients an AN69, in 4/6 on PAN, in 3/5 on PMMA, in 3/5 on PS; no patient of the 13 on PA developed ABD. Comparing patients on PA with those on other synthetic membranes, no significant difference was found in dialysis time (73 +/- 19 vs 83 +/- 28 months) as well as in age (59 +/- 13 vs 61 +/- 11 years) at ABD on set, when present. These data strongly encourage prospective studies enrolling more patients for a longer period of observation in order to evaluate possible differences on ABD development among various synthetic membranes.

The optimal use of PAN membrane in RDT.

In order to compare the efficiency of PAN (Biospal 3000S) for small molecules, Cr, BUN, UA and Pi clearances were determined during hemodiafiltration with both pre and postdilution fluid (PreHDF, PostHDF) and during biofiltration in 3 regular dialysis treatment patients. The highest clearances were obtained during PostHDF. Therefore, since the small molecules are still considered the most important toxins in chronic renal failure, these findings indicate that optimal use of PAN is with PostHDF, in which high diffusion and convection are combined, in order to obtain best dialytic efficiency.

Serum phosphate concentration with relation to the hematocrit value in uremic patients on chronic hemodialysis.

The acute effects of hemodialysis on the serum inorganic phosphorus levels (sPi) with relation to the predialysis plasma volume (PV) and the hematocrit (Ht) values were studied in a group of chronic uremic patients on regular hemodialysis. The results obtained confirmed the close direct correlation between predialysis sPi and fall in sPi induced by hemodialysis. Furthermore, the present fall in sPi induced by hemodialysis was found to be directly correlated to the PV values, and inversely to the HT values. An equation was derived from these data to predict in the individual patients the postdialysis sPi levels, utilizing both the predialysis sPi and the Ht values; this equation showed a better predictive capability than similar expression based on the use of the predialysis sPi value alone.

[Plasma levels of homocysteine in patients on hemodiafiltration]. / Livelli plasmatici di omocisteina in pazienti in emodiafiltrazione.

BACKGROUND: Hyperhomocysteinemia is an independent risk factor for cardiovascular diseases, and is a common finding in patients on regular dialysis treatment. Hemodialysis lowers homocysteine plasma levels in variable amounts, and it was also suggested that folic acid and vitamin B12 supplements can reduce such levels. The purpose of the present study was to evaluate homocysteine plasma levels in patients on hemodiafiltration who received vit. B12 and folate supplements such as to keep their plasma levels in the normal range. METHODS: A retrospective study was carried out in a group of 36 patients on hemodiafiltration, who received routinely folate and vit. B12 supplements i.v. Pre-dialysis plasma levels of folate and vit. B12 and pre-postdialysis homocysteine concentration were evaluated. The latter was correlated with other parameters. RESULTS: The present study confirmed high homocysteine levels in patients on RDT and their reduction due to dialysis, demonstrated a weak negative correlation of pre-dialysis homocysteine with vit. B12 plasma level, but no correlation with folic acid. CONCLUSIONS: This study showed a good efficiency of hemodiafiltration using high permeability membranes on homocysteine removal, whereas the negative correlation between folate and homocysteine plasma level was not confirmed.

[Arterial pressure in idiopathic calcium nephrolithiasis]. / Pressione arteriosa nella nefrolitiasi calcica idiopatica.

Hypertension and calcium nephrolithiasis show some common features, such as the high prevalence of hypercalciuria and of elevated urinary sodium excretion. 28 patients with idiopathic calcium stone disease and 17 normals were studied: all the subjects were evaluated for the mean arterial pressure, and for the metabolic risk factors for calcium stone disease. The mean arterial pressure proved to be higher in patients with calcium nephrolithiasis than in normals. In normals the mean arterial pressure showed a direct relationship with the urinary calcium, while in the group of stone patients it had a direct relationship with the urinary sodium excretion. The lack of relationship between the mean arterial pressure and calcium excretion, in patients with calcium stones, suggests an impaired tubular calcium handling in such patients.

[Magnesium hydroxide in idiopathic calcium nephrolithiasis]. / Idrossido di magnesio nella nefrolitiasi calcica idiopatica.

BACKGROUND: While in vitro the protective effect of magnesium on calcium oxalate crystallization is well known, its clinical relevance in calcium nephrolithiasis is still debated. Therefore, the clinical and metabolic effects of magnesium hydroxide therapy were evaluated in calcium stone formers. METHODS: Nine patients (7 M, 2 F), selected for a low urinary magnesium excretion (uMg 56 +/- 12 mg/day), were given Mg hydroxide (500 mg/day), with clinical and metabolic controls at 3, 12 and 18 months. RESULTS: Urinary Mg/uCreat increased throughout the study; uOx/uCreat decreased significantly; uCa/uCreat increased but not significantly. The stone recurrence rate decreased from 0.75 to 0.11 stones/year/patient, throughout the study period. The decrease of uOx is considered a more important risk factor in calcium stone patients than a similar uCa change; it may be due to a reduced intestinal Ox absorption, for the formation of insoluble and not absorbed Mg oxalate. CONCLUSION: In conclusion, Mg hydroxide therapy was encouraging in patients with calcium nephrolithiasis and low uMg; nevertheless a longer period of treatment is needed to confirm these data.

[Hemodiafiltration with high-level ultrafiltration versus hemodialysis. Longitudinal study]. / Emodiafiltrazione ad alta ultrafiltrazione vs emodialisi. Studio longitudinale.

A group of well nourished young patients was examined during 2 longterm consecutive high efficiency dialytic schedules to detect possible clinical and biochemical differences. The patients were first studied during hemodialysis with a 1.2 m2 cuprophan membrane and blood flow of 400 ml/min and, then, during hemodiafiltration with an ultrafiltration rate greater than 100 ml/min by using high permeability membranes with a surface greater than or equal to 1.4 m2. As expected by the higher clearances obtained on hemodiafiltration, this technique resulted in a significant reduction of dialysis time and of BUN and serum creatinine, associated with a significant increase of hemoglobin, possibly related to a better deintoxication. Furthermore, the dry body weight decreased significantly during hemodialysis, whereas it increased significantly during hemodiafiltration, despite unchanged dietary habits, indicating possible differences in the nutrients utilization during the 2 dialytic schedules. Therefore, in chronically dialyzed patients, highly permeable synthetic membranes should be preferred to cuprophan because of a supposed better biocompatibility and should be used with the highest ultrafiltration rate in order to obtain a better dialytic efficiency and to avoid the risk of backfiltration.

[Optimization of extracorporeal dialytic treatment: on-line hemodiafiltration]. / Ottimizzazione del trattamento dialitico extracorporeo: l'emodiafiltrazione on-line.

The study evaluates the potential of high ultrafiltration on-line hemodialfiltration (HDF) as a means of achieving the goals of extracorporeal RDT: the removal of small and medium-sized molecules, vascular stability and biocompatibility. The removal of small molecules was correlated with the UF rate and therefore with reinfusate volume. Medium-sized molecules were only removed from high permeability synthetic membranes in HD, but to a greater extent in HDF because of higher absorption. Vascular stability during the dialytic session is improved by convective processes, as is confirmed by a low prevalence of arterial hypertension in HDF patients. This suggests that HDF facilitates the achievement of dry body weight and therefore an improved correction of hydrosaline retention which is the main cause of hypertension in RDT patients. The biocompatibility of the dialytic system depends on the membrane and the dialysate. Synthetic membranes were shown to be much less toxic than cellulosic membranes and ultrapure dialysate was a useful aid to reduce the risk of inflammatory stimuli. On-line HDF associated the value of low-cost sterile dialysate-reinfu sate with a highly efficient and well tolerated technique.

[Can malnutrition be prevented in patients on chronic extracorporeal dialysis?]. / Può essere prevenuta la malnutrizione nei pazienti in dialisi extracorporea cronica?

In the attempt to prevent malnutrition, a seven year longitudinal evaluation was carried out in 24 RDT patients in order to assess the efficacy of the following strategy: 1) Counseling for an adequate physical activity and a high caloric intake limiting dietary restrictions to fluids, salt and fruit. 2) Improvement of anemia by increasing dialysis dose and/or by administering EPO. 3) The use of high UF HDF in order to employ more biocompatible membranes and to improve small and middle molecules removal. Nutritional status was assessed by a biochemical screening and by evaluating the variations of dry body weight (BW), which had to be also confirmed by a normal cardiac volume. Moreover in all patients a 4 consecutive days dietary record was obtained one year before the end of the observation period. During this period the mean dry BW increased significantly except in the two last years, when it remained stable. The increase of BW was associated with a reduced incidence of hypertension, a significant increase of Hb and reduction of BUN and sCr. The remaining biochemical parameters were constantly in the normal range. The dietary record showed a mean caloric-proteic intake similar to that recommended for the general population. These data point out that the above strategy can prevent malnutrition in patients on RDT. It must be confirmed whether the use of more biocompatible membranes and the removal of the middle molecules can play an important role in this setting.

[Electrolyte balance and acid-base equilibrium in high ultrafiltration hemodiafiltration]. / Bilancio elettrolitico ed equilibrio acido-base in emodiafiltrazione ad alta ultrafiltrazione.

Electrolyte and acid-base balance was evaluated in 14 high UF (124 +/- 7 ml/min) hemodiafiltration sessions. The dialysate contained (in mEq/l): Na 138-140, K 2-3, Ca 3.5, Mg 0.5-0.7, Cl 106-110, acetate 38 or acetate 3 and bicarbonate 35-38. The fluid, infused in postdilutional mode, was 23.5 +/- 21 per session (session length 203 +/- 22 minuti), 80% containing Na 138, K 2, Ca 3.5, Mg 1, Cl 109.5, acetate 35 and 20% Na 145, HCO3 100, Cl 45. The balance was: negative for Na (-255 +/- 220 mEq), for K (-74 +/- 22 mEq) and for Mg (-166 +/- 141 mg), positive for Ca (215 +/- 147 mg) and for acetate (590 +/- 15 and 966 +/- 412 mmol); the electrolytes and bicarbonate plasma values were within of close to normal limits during the session. An unphysiological feature was the positive balance of acetate which, though, was metabolized during the interdialytic period as to return to normal predialytic values. Therefore, in high UF HDF, the above combination of dialysate and reinfusate allows a reasonable electrolyte and acid-base balance; however, bicarbonate should be the only buffer in order to avoid unphysiological levels of other buffers in the biological fluids.

Magnesium status in chronically haemodialyzed patients: the role of dialysate magnesium concentration.

Serum magnesium concentration (sMg) increases in advanced renal failure, and in patients on regular dialysis treatment Mg status mainly depends upon the dialysate Mg concentration (dMg). In fact in uraemia, whereas the intracellular (muscle and blood cell) Mg content seems similar to that of normals and not to be influenced by dMg, the extracellular fluid Mg level as well as Mg content in some organs (skin, bone, etc) parallel the dMg. In the present paper, Mg status and its clinical implications in patients on regular dialysis treatment were therefore reviewed in an attempt to define an optimal dMg. Up to now, dialysis patients have been kept hypermagnesaemic on the assumption that a high sMg suppresses parathyroid hormone secretion (PTH), although this hypothesis has not been confirmed in later papers. On the other hand, more recent clinical studies suggest the possibility of noxious effects of Mg overload on various organs. Therefore, future trends should be towards reducing dMg to such values as will allow sMg to fluctuate across the normal range both in the interdialytic and intradialytic period. The more widespread use of Mg-containing phosphate binders implies the need of a further reduction of dMg which, however, carries the risk of symptomatic postdialytic hypomagnesaemia. Thus, since Mg is retained in uraemia and should be removed by dialysis, it is difficult to associate the use of Mg-containing drugs with an optimal dMg while avoiding severe hypermagnesaemia and hypomagnesaemia.

Serum magnesium and nerve conduction velocity in uraemic patients on chronic haemodialysis.

In 18 patients on regular haemodialysis treatment, the dialysate magnesium concentration (dMg) was lowered (from 0.5 to 0.25 mmol/litre) and the correlation between serum Mg level (sMg) and nerve conduction velocity was investigated before and one year after dMg variation, in order to ascertain whether hypermagnesaemia plays a role in the pathogenesis of peripheral neuropathy in patients on regular dialysis. The normalization of sMg (from 1.27 +/- SD 0.16 to 0.98 +/- 0.09 mmol/litre) did not result in any improvement in nerve conduction velocity, though such improvement has previously been reported; however, this discrepancy could be explained by the fact that sMg was not excessively high at the beginning of the study.

[The diagnosis and treatment of dysphagia]. / Diagnosi e trattamento della disfagia.

The structures in the head and neck are important in respiration, deglutition and communication. The post surgical head and neck cancer patient will probably exhibit a variety of disorders in both speech and swallowing. This study examined swallowing problems in three groups of patients following ablative surgery for pharyngolaryngeal carcinoma: supraglottic laryngectomies, hemilaryngectomies and subtotal laryngectomies. A total of 28 patients were studied. Videofluoroscopic studies with liquid and thick paste were completed one week post initiation of oral feeding following surgery and during the rehabilitation treatment.

[Vocal function after cordectomy (traditional surgical treatment vs CO2 laser): a comparative objective-instrumental evaluation]. / Valutazione obiettivo-strumentale della funzionalità glottica residua dopo cordectomia tradizionale e cordectomia CO2 laser.

Concerning the wider use of the CO2 laser in the treatment of laryngeal diseases, the Authors, in a comparative study based on an objective-instrumental evaluation, evaluated residual vocal function after traditional surgical treatment (chordectomy) vs. CO2 laser treatment. Forty-one patients treated for T1a glottic carcinoma (U.I.C.C. 1987) in last 8 years were examined Vocal function following CO2 laser surgery was evaluated in 17 patients (16 males and 1 female, aged between 38 and 78, with an average age of 53) and compared to vocal function of 24 patients treated with traditional chordectomy (23 males and 1 female, aged between 51 and 73, with an average age of 58). All patients showed a minimum follow-up of 30 months and none, at the time of evaluation, had undergone phonatory re-education. Glottic functionality evaluation was performed as follows: Evaluation of anatomical and functional results by means of a rigid fiberoptic laryngoscopy and subsequent photographic documentation for successive comparative evaluation. Evaluation of residual voice quality by phoniatricians otorhinolaryngologists and the patients themselves. Recording and electroacoustic analysis of some vocal samples. Laryngeal objectivity of surgical results were constantly related to subjective and instrumental voice evaluation. Phonatory results in patients treated with CO2 laser were better than those found in patients treated with traditional chordectomy.

[Wallenberg's syndrome: an assessment of the dysphagic and postural symptomatology]. / La sindrome di Wallenberg: valutazione della sintomatologia disfagica e posturale.

Dysphagia and postural disorders are the most important symptoms of the Wallenberg [correction of Wallemberg] syndrome, which takes in a considerable number of neurological symptoms including an alternate sensitive syndrome, the Claude Bernard Horner syndrome, paralysis of the half palate, of the half pharynx and of the vocal fold on the side of the injury, a vestibular syndrome and, finally, a cerebellar hemisyndrome. In the course of this study, four patients with the Wallenberg [correction of Wallemberg] syndrome were examined and underwent further periodical checks after injury. All the patients were fed employing a naso-gastric tube and in one case an emergency tracheostomy was performed because acute dyspnea. The diagnostic protocol following included the collection of a series of anamnestic data, an objective study of U.A.D.T. with fiberoptic endoscopy, swallowing simulation, dynamic radiologic examination (videofluoroscopy) and computerized static posturography. This routine was repeated upon every successive check. During the first observation a substantial uniformity of physiopathological characteristics was found in all the patients. Following logopedic and rehabilitation treatment, a high degree of diversity in the results obtained was observed in three patients (one of the patients was absent from successive checks). The most interesting phenomenon was the difference in time necessary to rehabilitate the swallowing reflex only after which it was possible to reassume oral alimentation. After two months of physiokinesitherapy, computerized static posturography, which initially revealed a sharp increase in the number of oscillations, showed a partial improvement of the postural disease with a reduction in oscillation amplitude. Even though the number of case followed was limited, our experience encourages us to underline importance of immediate rehabilitation therapy and of the collaboration of patients and their family members.

[C-reactive protein and homocysteinemia in patients undergoing on-line hemodiafiltration]. / Proteina C-reattiva e omocisteinemia in emodiafiltrazione on-line.

PURPOSE: In renal disease therapy (RDT) patients, high plasma homocysteine (tHcy) is common and high C-reactive protein(CRP) levels can be observed, attributed to the inflammatory process caused by the dialysis itself. Hyperhomocysteinemia and bioincompatibility are considered independent vascular risk factors. This study evaluated the behavior of these parameters in patients undergoing on-line hemodiafiltration (OL-HDF). METHODS: In 56 patients, HDF was performed using high permeability polyamide membranes, exchanging in the post-dilution mode 16-18 L/session of a reinfusate obtained by the on-line system (triple filtration AK200, Gambro). CRP was measured by an immunological method at the start and the end of the session in patients without comorbidities (group 1, n=30)and with inflammatory diseases (group 2, n=26). In 23 of the 56 patients, tHCY was measured (by high performance liquid chromatography (HPLC)) before and after the mid-week session on different schedule of folinic acid, vitamin B12 and vitamin B6. RESULTS: Pre-dialytic CRP was in the normal range in group 1 patients, whereas it was higher in group 2 patients; dialysis did not induce a significant change in either group. The intradialytic percentage tHcy decrease was approximately 50% regardless of the pre-dialytic value, which was significantly different according to the vitamin supplements administered. CONCLUSIONS: HDF, as performed in this study, demonstrated biocompatibility and efficient Hcy removal; therefore, it can prevent cardiovascular disease (CVD) in patients on regular extracorporeal dialysis.