[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.

[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.

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.

[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.

Calcitriol pulse therapy for severe hyperparathyroidism or calcium salts as phosphate binders in renal dialysis patients?

The concurrent use of calcitriol (CAL) pulse therapy to reduce parathyroid hormone (PTH) secretion and of calcium (Ca) salts as the most appropriate phosphate binders was evaluated for over 1 year in a group of 14 patients with good divalent ion control on CaCO3 therapy but with increasing levels of serum intact PTH. CAL pulse therapy was effective and safe in only 2 patients; in the remaining subjects it resulted in hypercalcemia and/or hyperphosphatemia, not reversed by adjusting the dialysate Ca concentration and or CaCO3 dose, and had to be stopped. Therefore, CAL pulse therapy does not seem to be compatible with Ca salts which, in our opinion, deserve priority in the therapy of renal dialysis patients.

[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.

[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.

New reinfusate composition in high UF haemodiafiltration: electrolyte solution combined with bicarbonate.

When high-permeability membranes are employed, high UF should be used in order to obtain optimal uraemic toxin removal and to avoid backfiltration. A high UF requires the infusion of an electrolyte solution including Ca2+ and Mg2+ which cannot be associated with bicarbonate in prepackaged solutions because of the risk of precipitation; therefore acetate or lactate are used as buffers. This study evaluated whether bicarbonate can be infused together with an electrolyte solution in high UF HDF, and if so, the clinical advantages that could be obtained by substituting acetate with bicarbonate in the reinfusate. In 12 patients on postdilutional high UF (121 +/- 10 ml/min) HDF (Qb 400, Qd 500 ml/min, dialysate containing Na, 141 +/- 2; K, 2.5; Ca, 3.5; Mg, 0.7; Cl, 111 +/- 2; acetate, 3; bicarbonate, 34 mEq/l; TMP 400 mmHg), an acid bag (Na, 128; K, 4; Ca, 7; Mg, 2; Cl, 141; acetate, 8 mEq/l), and a basic bag (Na, 150; HCO3, 80; Cl, 70 mEq/l), each containing 2 litres, were simultaneously infused through a Y connection. The final composition of reinfusate at the drip-chamber, combined with the above dialysate, allowed a negative intradialytic mass balance for Na, K, Mg and a positive one for Ca, acetate, to maintain prepostdialytic plasma values of these ions as well as bicarbonate close to normal limits. Furthermore, in five high-risk patients, clinical data were evaluated on high UF HDF, infusing a solution containing either acetate or bicarbonate, and an improvement of vascular stability was observed with the bicarbonate reinfusate.(ABSTRACT TRUNCATED AT 250 WORDS)

[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.

[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.

Improvement of anemia in patients on chronic dialysis treated by hemodiafiltration.

A group of patients with severe anemia on standard hemodialysis were transferred to polyacrylnitrile hemodiafiltration (HDF), which was arranged in order to obtain an ultrafiltration rate (UF) higher than 100 ml/min. During HDF, despite a significant reduction of the dialysis time, all patients had a significant decrease of predialytic BUN and serum creatinine, and a significant improvement of anemia. Furthermore, a close direct correlation was detected between the percent increase of hemoglobin and the length of time on HDF. Therefore, high-UF HDF represents a valid dialytic strategy to improve anemic states, permitting a significant reduction of the dialysis time and, thus, offering a better life quality for the patients.

Improved bone morphology by normalizing serum magnesium in chronically hemodialyzed patients.

The dialysate magnesium concentration (dMg) was reduced from 1 to 0.5 mEq/l in a group of patients on chronic hemodialysis (RDT). Serum parameters and bone biopsy findings were evaluated before and after a 1-year period on the lower dMg. All patients were receiving only calcium carbonate before and during the study period. Serum magnesium (sMg) decreased significantly and fell in the normal range with low dMg, whereas the other serum parameters did not change significantly except serum phosphorous which increased, still remaining within the normal limits. Furthermore, a significant reduction of the osteomalacia pattern (evaluated by osteoid volume, osteoid surface and osteoid thickness index) was observed in all patients after 1 year on dMg of 0.5 mEq/l, whereas there was no significant variation in bone resorption patterns (resorption surface and osteoclasts). Therefore, normal sMg is recommended in RDT patients, by arranging their dMg according to individual need, in the hypothesis that high bone Mg content, attributed to hypermagnesemia, could interfere with the mineralization process.