Effects of oral administration of heparan sulphate in the rat remnant kidney model.

Heparins are useful for the protection of residual renal function in several nephropathies, but the anticoagulant action and the need of parenteral administration are two main drawbacks limiting their use in chronic renal failure patients. Heparan sulphate (HS) is a heparin-like mucopolysaccharide devoid of anticoagulant action and active orally. In this study, the effects of HS oral administration have been evaluated in 18 subtotally nephrectomized rats;18 untreated remnant kidney rats served as control. No mortality was observed in the HS-treated rats, whereas in the control rats the survival rate was 72.2% at 18 weeks. At the end of the study, HS-treated rats showed lower urinary protein excretion (44 +/- 22 vs. 80 +/- 54 mg/24 h, p < 0.01), lower urea plasma levels (75 +/- 34 vs. 134 +/- 105 mg/dl, p < 0.01) and higher creatinine clearance (66 +/- 15 vs. 47 +/- 21 ml/min. 10(2), p < 0.05) than control rats. Remnant kidney weight (2.3 +/- 1.1 vs. 1.3 +/- 0.2 g, p < 0.01) and heart weight (1.3 +/- 0.2 vs. 1.1 +/- 0.1 g, p < 0.05) were greater in the control than in the HS-treated rats, as well as the systemic blood pressure values (167 +/- 19 vs. 115 +/- 32 mm Hg, respectively, p < 0.001). The remnant kidney histological examination in the HS-treated rats showed a lower prevalence of glomerular sclerosis, mesangial proliferation, and a much less evident tubulointerstitial damage than in controls. The antiproliferative and anti-inflammatory actions of HS together with its protective action on the endothelium are the putative mechanisms that could account for our findings. In conclusion, the present study supports evidence of an antiproteinuric and a renoprotective effect of orally administered HS in subtotally nephrectomized rats. This is in keeping with the well-known effects exerted also by other heparins, but the effectiveness of an orally available heparin-like product in this animal model could suggest the possibility of a clinical use also in progressing chronic renal failure patients.

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.

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.

[The resistance of activated partial thromboplastin time to heparin infusion during hemodialysis]. / Resistenza del tempo parziale di tromboplastina attivata alla infusione di eparina durante emodialisi.

Activated partial thromboplastin time (aPTT) during heparin infusion in 10 patients on regular dialytic treatment was evaluated. At end-dialysis (3 hours) plasma heparinization ranged between 2000-4000 IU and from the clinical point of view dialytic performance was good. At end-dialysis aPTT was 53 +/- 14 seconds: this value is under the prescribed aPTT prolongation (1.5-2 times baseline values) to achieve a therapeutic heparin plasma level. Physiopathological implications of this aPTT "resistance" to heparin infusion are studied.

Oral activated charcoal in patients with uremic pruritus.

Twenty-three chronic uremic patients on maintenance hemodialysis and suffering from severe pruritus were treated with activated powdered charcoal (6 g daily p.o.). In 10 patients pruritus disappeared completely, and in 10 other patients a partial effect was observed. The favorable results persisted for several weeks after discontinuation of the treatment. Only 3 cases were totally unresponsive. No relevant undesirable side effects were observed with the exception of 1 case who showed treatment intolerance. It is concluded that activated charcoal per os is a safe, effective, and low-cost therapy for patients with uremic pruritus, but its mechanism of action is unknown.

Free-hand ultrasound-guided renal biopsy: report of 650 consecutive cases.

In the past 4 years we have carried out 650 percutaneous renal biopsies (PRB), 54 on transplanted and 596 on native kidneys. PRB was performed with a 14-gauge one-piece disposable needle that was introduced free-handedly into the lumbar wall without any form of fixed guidance or support. Ultrasound was used to locate the kidney pole and to follow the progression of the needle tip in the renal parenchyma. The time needed for the whole procedure was about 5 min. The tissue specimen was adequate for histological evaluation in 98.8% of the cases. The prevalence of post-biopsy complications (haematuria, pain, anaemia) was 2.5%. Haematuria was not a common complication (1.6%) in our series, whereas clinically silent perirenal haematoma was common. Mild perirenal bleeding (volume < 5 ml) was found in 40 of a series of 150 patients (26.6%) who underwent ultrasound scan 24 h after the PRB. Haematoma exceeding 100 ml was revealed with US in only 0.6% of the patients. We conclude that free-hand ultrasound-guided PRB makes this technique easier, highly successful, time-saving and almost free of severe side effects.

Dipsogenic factors operating in chronic uremics on maintenance hemodialysis.

Thirst and hyperdipsia of anuric chronic uremics on maintenance hemodialysis and the possible dipsogenic factors were studied. Exaggerated thirst was present in 213 (86%) of the 247 studied patients. It usually started 4-6 h after the end of the dialysis session, persisted during the whole interdialytic period and often disappeared during the subsequent dialysis. Hyperdipsia, as indicated by the high body weight gain (> 4%) in the interdialytic periods, was present in 33.6% of patients. The highest rate of increase of body weight occurred in the first hours following the end of dialysis sessions. Hypernatremia, potassium depletion, increasing plasma urea levels and elevated plasma angiotensin II levels were considered as the possible dipsogenic factors of a nonpsychic nature. Sodium is certainly of paramount importance for its obliged extracellular position, and when sodium intake is elevated, hypernatremia is very likely the cause of exaggerated thirst and weight gain in patients on hemodialysis. Potassium depletion may cause thirst in animals, but this condition is extremely rare in patients on maintenance hemodialysis, who often accumulate it. In these patients it is, therefore, unlikely that potassium depletion is a dipsogenic factor. Increasing serum urea levels exert an evident dipsogenic effect in anephric rats and urea, when infused into normal volunteers, stimulates thirst. The extracellular urea levels in the interdialytic period are certainly higher than the intracellular ones, as a consequence of its continuous accumulation, and this creates an osmotic gradient with a dipsogenic effect. When this gradient is reversed, following hemodialysis (which removes first the extracellular urea), the dipsogenic effect disappears.(ABSTRACT TRUNCATED AT 250 WORDS)

Dipsogenic effect of urea in rats.

Anephric rats injected subcutaneously with urea in isotonic saline drank much more than anephric control animals receiving isotonic saline alone. The pattern of water intake and urine output of normal rats, repeatedly injected with urea solution, was similar to that of rats injected with dipsogenic hypertonic NaCl and quite different from that of rats receiving furosemide. A well-evident dipsogenic effect (unrelated to the urine output) was observed in normal rats repeatedly injected with urea solution and having a rapid rise of serum urea concentrations. On the contrary, in rats receiving a single load of urea and showing first a very rapid increase, then followed by a slow decrease of serum urea concentrations, the dipsogenic effect was present only initially. These results demonstrate that urea exerts a direct dipsogenic action which may be interpreted as a consequence of an osmotic gradient between the extra- and the intracellular fluid. When this is positive, as in the case of a rapid rise of serum urea levels, cell dehydration ensues and thirst is stimulated. On the contrary, when serum urea levels are decreasing and, presumably, when the intra- and the extracellular concentrations of urea are in equilibrium, no cellular dehydration occurs and thirst does not appear.

In defense of creatinine clearance.

The ratios creatinine clearance (Crcl)/inulin clearance (INcl) obtained in 523 measurements and reported in 14 papers have been analyzed and the values of CRcl corresponding to those of INcl have been evaluated. The day-to-day coefficient of variation of CRcl has also been measured in 123 persons, including patients with stable chronic renal failure and patients with normal renal function. The data obtained indicate that CRcl is not less sensitive than INcl, and that its changes are not blunted, if compared with similar changes of INcl. The day-to-day coefficient of variation has been found not to be greater than that of INcl. In conclusion, CRcl is not a misleading method to obtain approximate information on renal function, if it is correctly executed and interpreted.

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.

Vegan supplemented diet in nephrotic syndrome.

Thirteen patients (7 males, 6 females, aged 17-68 years) affected by primary, steroid-resistant, nephrotic syndrome and normal renal function were treated with a vegan, low-protein (0.7 g/kg per day) diet supplemented with essential amino acids and Ketoanalogues (VSD) for 3.9 +/- 2.9 months. These patients were studied at the beginning (following an unrestricted protein diet (UPD) supplying about 1 g/kg per day of mixed proteins) and at the end of VSD period. Urinary protein excretion decreased from 8.7 +/- 2.6 to 5.6 +/- 2.4 g/day (P less than 0.01), serum total cholesterol from 334.6 +/- 97.1 to 275.6 +/- 49.4 mg/dl (P less than 0.05). Serum albumin, HDL-cholesterol, triglycerides, and anthropometric measurements (triceps skinfold thickness and middle arm muscle circumference) did not change. Urinary urea nitrogen decreased from 7.5 +/- 1.8 to 3.8 +/- 1.2 g/day (P less than 0.005), according to dietary prescriptions. Creatinine clearance changed from 104.4 +/- 28.7 to 89.3 +/- 16.7 ml/min (n.s.) and no correlation was found with the changes in urinary protein excretion. This data suggest that VSD reduces proteinuria and exerts favourable effects on hypercholesterolaemia. Protein malnutrition was absent in these patients, probably because of the essential amino acids and ketoanalogues supplementation.

Nutritional treatment of renal failure in type 1 diabetic nephropathy.

This study reports the effects of a low-protein, low-phosphorus, supplemented diet in 8 type 1 diabetics with renal failure. The rate of decline of creatinine clearance, the changes of the urinary protein loss, of total serum protein, of the daily insulin requirement, of the nutritional status and of some hormonal derangements were examined. The rate of decline of creatinine clearance decreased from 1.38 +/- 0.27 ml/min/month during a previous 15.9-month period of unrestricted protein diet, to 0.03 +/- 0.37 ml/min/month during the 17.4 months on supplemented diet. Urinary protein loss significantly decreased, and total serum protein increased. The daily insulin requirement decreased and no deterioration of the nutritional status occurred. Secondary hyperparathyroidism was partially reversed and the mild hypothyroidism corrected. A restricted protein and phosphorus diet supplemented with essential amino acids and ketoanalogs seems to exert several beneficial and no unwanted side effects in type 1 diabetics with renal failure.