Impaired glucose oxidation and glucose-induced thermogenesis in renal transplant recipients.

BACKGROUND: Renal transplant recipients often show various metabolic abnormalities including reduced glucose tolerance, impaired insulin sensitivity and altered lipid metabolism. However, the acute effects of carbohydrate ingestion on substrate utilization and energy expenditure have not been fully elucidated. METHODS: We evaluated: (i) basal energy expenditure (EE) and substrate utilization, (ii) metabolic fate of an oral glucose load, and (iii) substrate-induced thermogenesis in: (a) 15 non-diabetic renal transplant recipients (Tx) (BMI 25+/-1) on triple immunosuppressive therapy, (b) 11 patients with primary glomerulonephritis (BMI 25+/-1) (Cort) receiving prednisone treatment, and (c) 12 healthy subjects (BMI 26+/-1) (N). Continuous indirect calorimetry was performed in the basal post-absorptive state for 60 min and continued for an additional 180 min following an oral glucose load (75 g). RESULTS: In the basal state, EE was similar in the three study groups. It averaged 14.6+/-0.7, 15.7+/-1.3, and 14.1+/-0.8 cal/kg/min in Tx, Cort, and N respectively. Glucose oxidation was higher in N (1.3+/- 0.2 mg/kg/min) than in Tx (0.7+/-0.2) and Cort (1.0+/-0.2) (P<0.05 in N vs. Tx and vs. Cort), whereas lipid oxidation was lower in N (0.6+/-0.1 mg/kg/min) than in Tx (0.9+/-0.1) and Cort (0.9+/-0.05) (P<0.03 in N vs. Tx and vs. Cort). After glucose ingestion, total carbohydrate oxidation averaged 21.2+/-2, 31.0+/-3, and 29.6+/-3 g, which represented 28+/-3, 41+/-3 and 39+/-2% of the total glucose load in Tx, Cort and N respectively (P<0.01 Tx vs Cort and N). The cumulative increase of EE (180 min) was 9.7+/-2, 13.2+/-3 and 13+/-3 kcal in Tx, Cort, and N respectively. CONCLUSIONS: The present data show that in non-diabetic renal transplant recipients basal EE is normal. However, basal lipid oxidation is higher and glucose oxidation is lower than in healthy subjects. In addition, the oxidative disposal of a glucose load and substrate-induced thermogenesis are impaired.

Correlation between glomerular morphology and renal haemodynamic response to amino-acid administration in patients with IgA nephropathy.

RATIONALE: To establish relationship, if any, between renal morphology and renal haemodynamic response to amino acids. DESIGN AND METHODS: We investigated the correlation between renal haemodynamic regulation and morphology in a group of 15 patients with primary IgA nephropathy (IgAN) (age 26 +/- 2 years, BMI 24.4 +/- 1, GFR 64 +/- 5 ml/min, RPF 377 +/- 34 ml/min, FF 0.17 +/- 0.02). Twelve normal subjects (age 30 +/- 3 years, BMI 24 +/- 1, GFR 82 +/- 6 ml/min, RPF 421 +/- 42 ml/min, FF 0.19 +/- 0.02) were studied as controls. IgA patients were divided into two groups according to the histological staging of glomerular lesions: group I (n = 7) stage II, and group II (n = 8) stage III-IV. RESULTS: In the basal state GFR was similar in the two groups and averaged 64 +/- 9 and 64 +/- 6 ml/min respectively. In contrast, FF was significantly lower in group II (0.14 +/- 0.01) (P < 0.05) in comparison to group I (0.21 +/- 0.03) and controls (0.19 +/- 0.02). In order to evaluate the renal functional reserve, all study groups underwent to an intravenous amino-acid infusion designed to increase plasma amino acid levels twofold (total from 2096 +/- 145 to 4301 +/- 221 mumol/l in IgA nephropathy patients and from 2272 +/- 83 to 3844 +/- 238 mumol/l in controls). In response to amino-acid infusion, GFR rose significantly in group I (GFR 20 +/- 2% and RPF 37 +/- 4% versus basal) and controls (GFR 20 +/- 2% and RPF 20 +/- 3% versus basal) (both P < 0.01 vs basal). In contrast, in patients with more severe glomerular lesions (group II) neither GFR nor RPF rose significantly (GFR -1 +/- 4% and RPF -8 +/- 6% versus basal) (P NS versus basal, P < 0.01 versus group I and controls). CONCLUSIONS: The data show that in IgA nephropathy: severe forms of glomerular lesions are associated with a complex alteration of glomerular haemodynamic regulation, characterized by lower basal FF and loss of haemodynamic response to hyperaminoacidaemia.

Renal hemodynamics in renal transplant recipients. The role of reduced kidney mass and cyclosporine administration.

It has been hypothesized that both the cyclosporine (CsA) treatment and the reduction of renal mass may affect the renal hemodynamic regulation in kidney transplant recipients. To address this question, we evaluated the renal hemodynamic response to hyperaminoacidemia (i.v. mixed amino acid infusion 3.3 mg/kg/minute for 150 minutes) in four study groups: (1) 16 renal transplant recipients (Tx), (2) 6 uninephrectomized (Nx) subjects, (3) 7 subjects treated with CsA for chronic uveitis (CsA), and (4) 9 normal controls (NC). In response to amino acid administration (AA), glomerular filtration rate (GFR) rose significantly in NC subjects (80 +/- 6 vs. 91 +/- 6 ml/minute; P<0.01) and Nx patients (57 +/- 3 vs. 68 +/- 7 ml/minute; P<0.01) and failed to increase in Tx recipients (39 +/- 3 vs. 37 +/- 3 ml/minute) and CsA-treated patients (58 +/- 3 vs. 53 +/- 4 ml/minute). Renal plasma flow (RPF) did not change in Tx recipients (243 +/- 27 vs. 235 +/- 25 ml/minute) but rose significantly in all other groups (257 +/- 17 vs. 344 +/- 33 in NX, 364 +/- 6l vs. 441 +/- 55 in CsA, 412 +/- 49 vs. 472 +/- 72 ml/min in NC subjects; P<0.05 vs. basal). Basal renal vascular resistances were significantly higher in Tx (0.29 +/- 0.04 mmHg/mlxmin; P<0.01 vs. all other groups) than in Nx (0.21 +/- 0.01 mmHg/mlxmin), CsA (0.23 +/- 0.04 mmHg/mlxmin) (both P<0.01 vs. NC subjects), and NC subjects (0.13 +/- 0.02 mmHg/mlxmin). Renal vascular resistance failed to decline in Tx (0.31 +/- 0.04 mmHg/mlxmin) during AA infusion but declined significantly in all other groups. In Tx, basal GFR was positively correlated to renal allograft volume (r=0.547, P<0.03); however, no relationship was found between the latter and basal RPF or the AA induced changes in GFR. In summary, the present study demonstrates that in kidney transplant recipients and in CsA-treated subjects, the renal functional reserve to hyperaminoacidemia is impaired. This is at variance to what is observed in normal controls and uninephrectomized subjects. In renal transplant recipients, basal but not amino acid stimulated GFR correlates with renal allograft volume. We conclude that basal GFR is related to renal volume in Tx and that the response to hyperaminoacidemia seems to be affected by chronic CsA administration.

Hepatitis C virus-related acute and chronic hepatitis in hemodialysis patients.

The incidence of HCV antibodies has been evaluated in 123 chronic hemodialysis (HD) patients (Group A; 55 M and 68 F) and in 37 consecutive HD patients (group B) admitted to our hospitals for acute hepatitis. In group A, HCV antibodies were present in 27% of the patients. 20 of 36 (55%) had previously received blood transfusions. 21 patients (58%) were also positive for HBV Ab. In 8 patients, ALT were significantly increased. In group B, the diagnosis of HCV-related acute hepatitis was made in 11 patients. 8 of them had previously received blood transfusions. Seroconversion occurred 2-3 months after onset of the disease.

Elevated dietary protein intake impairs the renal hemodynamic response to hyperaminoacidemia in patients with primary glomerular diseases.

We have evaluated the renal hemodynamic response to a mixed amino acid infusion in 7 control subjects and in 8 patients with primary glomerulonephritis (GN). In order to evaluate the role of dietary protein intake in this response, GN patients were maintained for 3 weeks on two separate dietary regimens providing 130 +/- 5 g of protein/day (study 1) and 60 +/- 3 g of protein/day (study 2), respectively. Normal subjects were studied while consuming a free diet. In GN patients, following the reduction in dietary protein intake basal RPF and GFR decreased from 589 +/- 109 to 422 +/- 81 ml/1.73 m2/min (p less than 0.01, vs. study 1) and from 75 +/- 7 to 70 +/- 8 ml/1.73 m2/min (p = NS). Filtration fraction rose from 0.14 +/- 0.02 to 0.19 +/- 0.03 (p less than 0.05). In study 1, during amino acid infusion GFR and RPF did not change significantly from baseline (75 +/- 7 vs. 66 +/- 8 ml/1.73 m2/min at 180 min and 589 +/- 109 vs. 567 +/- 102 ml/1.73 m2/min, respectively). These results are at variance with data obtained in normal controls in whom both GFR and RPF rose significantly following hyperaminoacidemia. In contrast, when dietary protein intake was reduced, a normal renal hemodynamic response to amino acid infusion was restored (GFR went from 70 +/- 8 to 90 +/- 18 ml/1.73 m2/min and RPF from 422 +/- 81 to 517 +/- 90 ml/1.73 m2/min, both p less than 0.05 vs. basal), both absolute and percentage increases were similar to what was observed in controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Toxicity in uremia. 1. Correlation between PTH levels and depressed cell proliferation.

Cell proliferation is significantly depressed in uremia; to assess the influence of PTH on it, normal lymphocytes were cultured in presence of uremic patients' serum with low or high plasma PTH levels (Group A; PTH less than 2.5 ng/ml; Group B: PTH greater than 12 ng/ml), and serum of normal subjects (Group C). Cell proliferation was lowered by serum from both groups (p A vs C less than 0.004; p B vs C less than 0.001). However, the depressing effect was more evident when group B serum was employed (p A vs B less than 0.002).

Toxicity in uremia. 2. Correlation between PTH levels and impaired aspecific immunity.

The role of PTH in depressing polynuclear leucocyte (PMN) phagocytosis in uremia was investigated. The hydrophobicity and phagocytic activity of normal PMN was tested in presence of uremic patients' serum with low (Group A) or high (Group B) levels of plasma PTH. The PMN phagocytic index was lowered by serum of both groups, but more in presence of Group B serum (p A vs B less than 0.002). Similarly, the contact angle of cells was affected more in presence of serum of patients with high PTH levels (p B vs A less than 0.003; p B vs C less than 0.002).

Screening haemodialysis patients for infection with human immune deficiency virus (HIV).

A group of 484 patients having regular haemodialysis was tested for the presence of antibodies to the human immunodeficiency virus (HIV). With a commercial enzyme-linked immunoassay kit, the serum of 17 appeared positive. When these 17 samples were retested by a different method, however, none was found to contain antibodies to the virus. Furthermore, evaluation of the clinical state of these 17 patients for the presence of any prodromal symptoms associated with the acquired immune deficiency syndrome was negative. It is therefore suggested that patients having regular haemodialysis are presently at low risk of contracting infection by HIV. By contrast, 81% of these patients had antibodies to cytomegalovirus.

Hemoperfusion in diabetic coma.

Hemoperfusion on ionic exchange resins in the therapy of diabetic keto-acidosis (DKA) coma is proposed. Resins used are strong anionic resins in mixed form able to release bicarbonates and to trap ketoanions and organic anions in a stoichiometric manner. A series of trials in open circuit are performed in order to search for a suitable mixture of resins and to establish the amounts of HCO3- and ketoanions respectively released or entrapped. Therefore, ten simulated hemoperfusions in closed circuit systems were performed, utilizing cartridges containing 1,700 g of mixed resin (9% HCO3- form and 91% Cl- form). The results indicate that all side effects of bicarbonate i.v. therapy of DKA coma are avoided because of the smooth HCO3- administration to the patient. Furthermore, a good removal of ketoanions and organic acids is obtained without changing the blood osmolality.

L-glutaminase and L-asparaginase by extracorporeal route in acute lymphoblastic leukemia therapy.

Use of L-asparaginase by the extracorporeal route in the therapy of acute lymphoblastic leukemia (ALL) has been proposed. Results, however, are not so satisfactory as i.v. administration of this enzyme, because the levels of L-asparagine do not fall for a sufficient length of time due to the antagonistic action of the L-asparagine-synthetase. To avoid the L-asparagine rebound we have utilized, by extracorporeal route, L-glutaminase together with L-asparaginase, in order to reduce L-asparagine and L-glutamine levels. We have therefore performed a series of experiments in vitro and in vivo either using L-asparaginase alone or together with L-glutaminase. Results show that, contrary to what happens when L-asparaginase is used alone, L-asparagine levels decrease and remain low even after 24 hours from the treatment, when L-glutaminase is added to the system. Thus a lowering of L-glutamine levels, which seems to play an important role in the therapy of ALL, is obtained.

Modulated nitrogen intake for patients on low-protein diets.

In order to overcome malnutrition and poor palatability associated with long lasting low-protein intakes, a diet was devised based on modulated nitrogen intake and energy supply of at least 155 KJ/kg a day. Each patient underwent three different regimens (A, B, C) of protein intake. In period A, the protein intake was 0.33 g/kg a day. In period B, the patients were given 0.33 g/kg a day during day 1, 2, 3, 5, 6 and 1.00 g/kg a day during day 4 and day 7 of the week. In period C the daily protein intake was the mean of the weekly value from day 1 to 7 of period B. Data obtained show that in period A the urea appearance rate was equal to that in period B and lower than that in period C.

Cold carbon haemofiltration apparatus.

Four uraemic patients underwent haemofiltration (HF) for two months, three times a week, with an infusion of about 20L of electrolyte solution. For another two months, HF was performed with diafiltrate reinfusion after regeneration on cold carbon and ionic exchange resins. Carbon (26.8g) and resins (10g/kg b.w) were needed. The data obtained in HF and in closed-circuit HF periods were similar, but during the closed-circuit HF treatment there was better control of acid-base balance.

Protein requirement of patients on CAPD: a study on nitrogen balance.

Nitrogen balance studies were performed in 8 patients undergoing CAPD. Patients were studied in a metabolic ward for 14 days while eating a diet providing 1.2 g/kg B.W. of proteins and supplying 166-188 KG/Kg. From these studies it is concluded that 1.2 g/Kg are a safe intake for patients on CAPD. Nevertheless it is strongly suggested that patients on CAPD should undergo a nitrogen balance study in order to ascertain whether such a diet is safe or should be modified for energy and/or protein supply.