Ester Morelli

Plasma Parameters of the Prothrombotic State in Chronic Uremia

We measured plasma parameters of the prothrombotic state, namely thrombin-antithrombin III complex (TAT), fibrinopeptide A (FPA). D-dimer (DD), von Willebrand factor (vWF), tissue-type plasminogen activator (tPA), beta-thromboglobulin (beta TG), platelet factor 4 (PF4) and serotonin (5HT) in a series of 51 adult patients with chronic uremia: 22 were on maintenance hemodialysis (MHD) and 29 on conservative dietary treatment. Serum tumor necrosis factor alpha (TNF) was determined as well. Uremics presented significantly higher levels of TAT, FPA, DD, vWF, TNF, beta TG and 5HT than normal controls. Patients on conservative treatment showed lower levels of TAT, DD, TNF and beta TG than patients on MHD. Our results provide evidence that a prothrombotic state exists in chronic uremia and that MHD patients have a higher degree of hypercoagulation. Both hemodialysis procedure and uremia-related factors are likely to contribute to the hemostatic derangement.

Potassium Removal Increases the QTc Interval Dispersion during Hemodialysis

This study was planned to clarify the mechanism(s) by which hemodialysis increases the QTc dispersion, a marker of risk of ventricular arrhythmias. To this aim, 10 uremic patients, without any relevant heart diseases, underwent two different types of hemodialysis schedules. In the first, 1 h of isolated high rate ultrafiltration preceded the standard diffusive procedure. In the second, during the first hour of standard bicarbonate hemodialysis, the decrease of plasma potassium concentration was prevented by increasing K+ concentration in the dialysate, according to its pre dialysis plasma levels. During the high rate ultrafiltration period, together with ECG signs of increased sympathetic nervous system activity and catecholamines secretion, the QTc dispersion did not change significantly. Instead, an evident increment was observed 1 h after the start of the diffusive hemodialysis, then slowly progressing until the end of the dialysis and finally returning to the pre dialysis values within 2 h after the end of the session. To the contrary, the increase of the QTc dispersion was totally blunted during a standard hemodialysis procedure in absence of plasma K+ decrease, but appeared again when the K+ dialysate fluid concentration was restored to 2 mmol/l. This study provides evidence that the increase of QTc dispersion occurring on hemodialysis is mainly related to the diffusive process, more precisely to the K+ removal. This is one more reason to focus attention on K+ removal rate especially when hemodialysis treatment is given in uremics affected by cardiac diseases with high risk of arrhythmias.

A Low-Nitrogen Low-Phosphorus Vegan Diet for Patients with Chronic Renal Failure

The nutritional treatment of chronic renal failure with a low-protein low-phosphorus diet (conventional low-protein diet, CLPD) is effective in reducing uremic intoxication, slowing the progression of renal failure and preventing secondary hyperparathyroidism. Unfortunately, in some patients, the poor palatability and the high cost of the protein-free substitutes, together with difficulties in following the diet away from home, can make good compliance difficult, possibly causing low energy intake and malnutrition. Here the results are reported of an attempt we made to overcome these drawbacks, using a diet supplying only natural foods of plant origin in definite proportions to give an essential amino acid supply satisfying the recommended dietary allowance. This is possible thanks to an appropriate cereal-legume mixture, supplying proteins complementary for essential amino acids. Additional positive features of this special vegan diet (SVD) are the high ratio of unsaturated to saturated fatty acids, the absence of cholesterol, and the lower net acid production in comparison with a mixed diet. This study indicates that the results obtained with the SVD are similar to those obtained with the CLPD. Therefore the SVD can be a substitute for the CLPD in the management of patients with mild chronic renal failure. The SVD is the diet of choice when products made of starch are not available or poorly tolerated.

Effect of Hemodialysis on the Dispersion of the QTc Interval

The QTc dispersion reflects the underlying regional heterogeneity of the recovery of the ventricular excitability, thereby it is considered as a novel marker of risk of ventricular arrhythmias. Because a higher incidence of ventricular arrhythmias is described during and after hemodialysis, the aim of this study has been to evaluate the QTc dispersion before and after uncomplicated hemodialysis session. Twenty chronic uremics without heart failure, ischemic heart disease or dialysis hypotension were selected. The QTc dispersion was determined as the difference between the longer and the shorter QTc interval measured on a 12-lead electrocardiogram. Following the hemodialysis session, the QTc dispersion increased from 30 ± 9 to 54 ± 17 ms (p < 0.001) associated with the expected reduction of potassium and magnesium and with the increase of extracellular calcium concentration. However, no correlation has been observed between the QTc dispersion increase and the degree of the intradialytic changes of plasma electrolytes, blood pressure or body weight. In summary, the hemodialysis treatment per se does induce an increase of the QTc dispersion, likely due to the rapid changes of electrolyte plasma concentrations. This can potentially contribute to the arrhythmogenic effect of the hemodialysis procedure, reflecting an enhanced regional heterogeneity of ventricular repolarization. The clinical importance of the increase of QTc dispersion as risk factor of ventricular arrhythmias, particularly in hemodialyzed patients suffering from ischemic or hypertrophic heart diseases, should be the matter of further investigations.

Low Urine Citrate Excretion as Main Risk Factor for Recurrent Calcium Oxalate Nephrolithiasis in Males

To better define the relative role of metabolic factors in the recurrence of stone formation, we studied the 24-hour urinary excretion of calcium (uCa), citrate (uCit), oxalic acid (uOx) and uric acid (uUa) in 73 male patients with primary calcium oxalate urolithiasis. According to the episodes of stone formation per year, we identified 51 recurrent stone formers (RSF) and 22 single stone formers (SSF). 20 normal adult males constituted the control group (C). uCa and uOx were higher in RSF than in C, but quite similar in SSF and RSF. The only difference between RSF and SSF was uCit, significantly lower (2.06 +/- 1.04 mmol/24 h) in RSF than in SSF (3.22 +/- 1.18 mmol/24 h, p less than 0.001) and in C (3.42 +/- 1.33 mmol/24 h, p less than 0.001). Hypocitraturia (uCit less than 1.5 mmol/24 h) was found in 16 of 51 RSF (31.4%) and in 1 of 22 SSF (4.5%). These data confirm that high levels of uCa and uOx represent a risk factor for lithogenesis, but also strongly indicate the low uCit excretion as the most important urinary abnormality accounting for the recurrence of calcium oxalate stones.

Reversal of Hyperparathyroidism in Severe Uremics Following Very Low-Protein and Low-Phosphorus Diet

Serum iPTH levels decreased markedly in 16 severe chronic uremic patients who changed from a standard low-protein diet to a very low-nitrogen and very low-phosphorus diet supplemented with essential a

Responses of the skin microcirculation to acetylcholine in patients with essential hypertension and in normotensive patients with chronic renal failure.

Aims: To assess the endothelial function of the skin microcirculation in chronic renal failure (CRF) independent of hypertension, we investigated the changes of the cutaneous blood flow induced by iontophoretic delivery of acetylcholine (ACh) and of sodium nitroprusside (SNP) in CRF patients free from arterial hypertension and in patients with essential hypertension. Methods: The study included 20 patients affected by CRF (mean creatinine clearance 12 ± 2 ml/min) without arterial hypertension (mean blood pressure 96 ± 1 mm Hg), 15 patients affected by essential hypertension (mean blood pressure 124 ± 1 mm Hg), and 20 normal controls. The changes of skin blood flow following iontophoretic delivery of ACh and of SNP were measured by laser Doppler flowmetry. Results: Following maximal ACh or SNP delivery, the change of blood flow from the baseline was similar both in normals (683 ± 92 vs. 684 ± 87%) and in CRF patients (778 ± 108 vs. 803 ± 124%), whereas in the hypertensives the response to ACh was lower than to SNP (434 ± 48 vs. 702 ± 98%, p < 0.01). Since the third ACh delivery dose, the skin blood flow increments were significantly lower in the hypertensive than in the CRF or in the normal control groups, whereas no difference was observed between uremics and controls. Conclusions: The endothelium-dependent hyperemia following ACh iontophoretic delivery is impaired in the skin microcirculation of essential hypertensive patients, but this is not the case in CRF patients with no history of arterial hypertension. This suggests that CRF per se, independent of arterial hypertension, is not associated with endothelial dysfunction of skin microcirculation.

A Special, Supplemented ‘Vegan’ Diet for Nephrotic Patients

High dietary protein intake, in the past recommended for nephrotic syndrome, does not improve hypoproteinemia and may accelerate progressive renal damage. In contrast, low-protein diets reduce proteinuria and preserve renal function in experimental renal models of nephrotic syndrome. In this study, 20 steroid-resistant, nephrotic patients were treated with a pure vegetarian, low-protein diet, supplemented with essential amino acids and ketoanalogues (supplemented vegan diet, SVD) for 4.6 +/- 3.1 months. Before the study, these patients followed an unrestricted protein, low-sodium diet (LSD). Proteinuria, daily urea nitrogen excretion and creatinine clearance decreased significantly on SVD. A similar lowering effect of SVD was observed on serum total cholesterol. Seven of the 20 patients changed from LSD to SVD and vice-versa on 3 occasions, and in all cases, we found an increase of proteinuria during the LSD period. Serum albumin, HDL cholesterol, triglycerides and anthropometric measurements did not change on SVD. Our data suggest that SVD exerts a favorable effect on proteinuria and hypercholesterolemia in nephrotic patients, without inducing clinical or laboratory signs of malnutrition.

Changes in Heart Rate Variability in Chronic Uremic Patients during Ultrafiltration and Hemodialysis

Background: The analysis of heart rate variability (HRV) is a useful tool to evaluate cardiac autonomic modulation, which is frequently impaired in chronic uremia. Aims: The aim of this study was to evaluate HRV in chronic uremics and to separately investigate the acute changes induced by volume depletion and solute removal during a hemodialysis session. Methods: Fourteen uremic patients (8 males and 6 females, aged 50 ± 15 years) on maintenance hemodialysis and 14 sex- and age-matched healthy controls were studied. Both groups underwent ambulatory electrocardiogram monitoring to evaluate the HRV time and frequency domain indices. The hemodialysis session was performed by 1 h of high-rate isolated ultrafiltration followed by 3 h of bicarbonate diffusive procedure. Results: In uremic patients, the overall variability in the frequency [low-frequency power (LF): 505 ± 473, vs. 1,446 ± 654; high-frequency power (HF): 133 ± 162 vs. 512 ± 417; p < 0.001] and time domain indices (standard deviation of normal R-R intervals: 101.9 ± 33.3 vs. 181.7 ± 44.1 ms; p < 0.001) was markedly reduced compared to controls, whereas mean heart rate (83 ± 12.4 vs. 60.9 ± 8.8 bpm; p < 0.001) and LF/HF ratio (5.8 ± 3.5 vs. 2.2 ± 0.8; p < 0.001) were increased. Isolated ultrafiltration produced a marked further decrease in HRV indices, but the subsequent diffusive hemodialysis procedure, with a low ultrafiltration rate, made HRV increase again. Conclusions: Chronic uremics showed abnormal autonomic modulation with sympathetic-vagal imbalance. The unbalanced hypersympathetic response to body fluid depletion is related to the ultrafiltration rate. Low interdialytic weight gain and a low ultrafiltration rate, associated with adequate hemodialysis, should be the preferable strategy for uremic patients with autonomic dysfunction.

Secondary Hyperparathyroidism in Severe Chronic Renal Failure Is Corrected by Very-Low Dietary Phosphate Intake and Calcium Carbonate Supplementation

The main purpose of our study was to verify the effect of a very-low-protein, low-phosphorus diet, supplemented with essential amino acids and keto analogues and with calcium carbonate, on circulating levels of intact parathyroid hormone (i-PTH) in severe chronic renal failure patients with secondary hyperparathyroidism, not treated with any vitamin D preparation. To this aim, we shifted 21 chronic uremics (12 males, 9 females; age 56 ± 13 years) with serum creatinine >6.5 mg/dl and i-PTH >150 pg/ml, from a standard low-protein diet (0.6 g/kg/day approximately) to a very-low-protein (0.3 g/kg/day), very-low-phosphorus (5 mg/kg/day) diet supplemented with a mixture of essential amino acids and calcium keto analogues (Ketodiet), calcium carbonate (2–4 g/day), iron, and vitamin B12 preparations. The energy supply of both diets was 30–35 kcal/kg/day. Exclusion criteria were a poor compliance with dietary or supplement prescriptions or signs of autonomic hyperparathyroidism. After 4 ± 2 months of Ketodiet, the i-PTH serum levels decreased by 49% as a mean (from 441 ± 233 to 225 ± 161 pg/ml, p < 0.001); serum phosphorus and alkaline phosphatase decreased, whereas serum calcium increased. The great reduction of serum and urinary urea demonstrated a good compliance with Ketodiet, and no sign of protein malnutrition was observed. These findings confirm that even in severe chronic uremic patients dietary phosphorus restriction and calcium carbonate supplementation lower i-PTH serum levels. This is one of the goals of the dietary treatment that can be safely achieved, provided good compliance both with the dietary prescriptions and with adequate energy and supplement intakes.