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.

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.

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.

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)

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.