Superior mesenteric artery blood flow in systemic sclerosis patients.

OBJECTIVE: Intestinal involvement is frequently observed in systemic sclerosis (SSc) and is associated with malnutrition and a decreased survival rate. Vascular lesions are claimed to underlie and precede these changes. The aim of this study was to establish whether a reduced mesenteric blood flow was present in SSc patients with no signs or symptoms of small bowel involvement. METHODS: Superior mesenteric artery (SMA) blood flow in the fasting state was measured by colour Doppler ultrasonography in 27 SSc patients and in 25 controls. The effect of a balanced liquid meal on mesenteric blood flow was measured in six matched patients and controls. RESULTS: In fasting SSc patients, there were reductions in mean SMA diameter (P<0.001), blood flow (213+/-92 vs 398+/-125 ml/min in controls, P<0.0001) and pulsatility index (3.49+/-1.0 vs 4.13+/-0.97 in controls, P<0.07). In both groups, the meal increased basal flow values and the differences between controls and patients in the fasting state were not significant. CONCLUSIONS: In the absence of symptoms of small bowel involvement, reversible SMA vasoconstriction is demonstrable in the fasting state in SSc patients.

Effect of increased arterial resistance index on long-term outcome of well-functioning kidney grafts.

An abnormal vascular status is present in the transplanted kidney. To define whether vascular factors might influence kidney function of the graft, the renal volume, blood flow and vascular resistance of a group of healthy subjects were compared with those of a group of well functioning renal transplants by color Doppler ultrasonography. Sixty healthy subjects and 75 well functioning cadaver renal transplant recipients were compared by color Doppler ultrasonography. Subsequently, 15 couples of donors and recipients of a living related renal graft were compared to observe the differences between the two organs of the same subject in a different environment. The variables studied were: the diameters and the volume of the kidney, renal blood flow and renal resistance index (RI). The group of cadaver renal transplant patients showed higher mean blood pressure (P = 0.009), higher serum creatinine levels (P = 0.0001) and lower endogenous creatinine clearance (P < 0.0001) than healthy controls. The length (P < 0.00001) and volume (P < 0.001) of the kidneys of cadaver transplanted patients were significantly greater than those of healthy subjects, while the length and volume of the living donors kidneys were identical to those of the recipients. RI, measured on renal vessels, showed lower values in healthy subjects and in kidney donors than in transplanted patients (P < 0.00001). Well functioning transplanted kidneys showed increased renal arterial RI. This non-immunologic factor did not appear to be detrimental with renal function in time, at least until 50 months after successful grafting.

Effect of iloprost infusion on the resistance index of renal vessels of patients with systemic sclerosis.

OBJECTIVE: To investigate the effect of iloprost, a stable prostacycline analog, on kidney blood flow in patients with systemic sclerosis (SSc), using color flow Doppler sonography. METHODS: The acute effect of the drug was studied in 10 patients with SSc with elevated resistance index (RI) levels (all RI values reported are multiplied by 100). Iloprost was administered intravenously (2 ng/kg/min for a period of 8 h). To study the effects of chronic drug administration, 16 patients with SSc were randomly assigned to 2 groups of 8 cases each. The first group was treated with 9 infusions of iloprost in 6 mo. The second group was treated with slow release nifedipine (40 mg/day) for 6 mo. RESULTS: Interlobar artery RI (median 67 vs 61; p = 0.02) and cortical vessel RI (median 65 vs 54; p = 0.001) were reduced after acute treatment. In chronic drug administration, RI values were not modified by nifedipine, while iloprost reduced the RI of the interlobar (median 69 vs 61; p < 0.03) and cortical arteries (median 66 vs 58: p < 0.01). CONCLUSION: Our findings suggest iloprost might be useful for treatment of scleroderma renal vasospasm.

The transplanted nephronic mass influences renal vascular resistance and blood flow of the kidney graft.

In order to assess whether the transplanted nephronic mass plays a role in the progression of chronic graft dysfunction, 83 well-functioning renal transplants were investigated. Plasma creatinine, creatinine clearance, renal volume, blood flow and renal vascular resistance were measured. The weight of the donor was considered as an index of the transplanted renal parenchyma and the weight of the recipient as an index of the required nephronic mass. To evaluate the adequacy of the transplanted nephronic mass, the ratio between the donor and the recipient's weight was calculated. This ratio showed a mean of 1.06 +/- 0.18 and a range between 0.63 and 1.6, indicating that a parenchymal mass between 30 and 80% of the physiologic one was transplanted in these subjects. Patients were divided into two groups: group A patients with a ratio > 1, group B patients with a ratio < 1. In group A, a regression analysis did not show any relationship between transplant age and creatinine clearance, renal volume, blood flow and renal vascular resistance as assessed by echo-color-Doppler ultrasonography. In patients with reduced nephronic mass, group B, there was a negative relationship between renal blood flow and transplant duration (p = 0.03) and a positive relationship between transplant age and renal vascular resistance (p = 0.01) and renal volume (p = 0.01). These data support the hypothesis that the difference in weight between donor and recipient may influence the outcome of the graft.

Renal vascular damage in systemic sclerosis patients without clinical evidence of nephropathy.

OBJECTIVE: To evaluate the use of color-flow Doppler ultrasonography, a direct, noninvasive technique, for measurement of kidney blood flow in patients with systemic sclerosis (SSc). METHODS: Twenty-five normal volunteers and 25 SSc patients (median disease duration 8 years, range 2-21 years) were studied. All were free of clinical symptoms of renal damage. The resistance index (RI) was determined on main, interlobar, and cortical vessels. RESULTS: In SSc patients, the RI was significantly increased at every sampling site examined (P < 0.001). RI values were strongly correlated with disease duration (main artery r = 0.56, P < 0.04; interlobar artery r = 0.63, P < 0.02; cortical artery r = 0.75, P < 0.002). Regression analysis showed no relationship between RI and creatinine clearance values. CONCLUSION: Color-flow Doppler ultrasonography is a sensitive and noninvasive technique for evaluating vascular damage of the kidney in patients with SSc.

Randomized study with cyclosporine in kidney transplantation: 10-year follow-up.

This study presents the 10-yr follow-up results of a multicenter controlled trial on 108 recipients of cadaveric renal transplantation, randomized to receive cyclosporine (N = 55) or azathioprine (N = 53), both in combination with steroids. The 10-yr patient survival rate was 89% in the cyclosporine group and 83% in the azathioprine group (P = not significant [NS]); the 10-yr graft survival was 56% and 35%, respectively (log-rank test, P = 0.009). The half-life of grafts functioning after 1 yr was 15.4 +/- 3.9 versus 10.6 +/- 3.6, P = NS). The rate of early rejection in the cyclosporine group was significantly lower than that in the azathioprine group (0.30 versus 1.4, P < 0.01). Although the mean creatinine clearance rate was always higher in the azathioprine group, the decline in graft function from the first to the tenth yr was not significantly different between the two groups (-13.0 +/- 16.4 versus -12.3 +/- 19 mL/min, P = NS). In cadaveric renal transplantation, cyclosporine allows better graft survival than azathioprine, not only in the short term but also in the long term, with similar attrition of graft function for up to 10 yr.

Relevance of resistive index ultrasonographic measurement in renal transplantation.

The usefulness of the ultrasonographic measurement of resistive index (RI) is not yet fully understood. To obtain a better definition of its relevance in renal disease we studied this parameter in a group of 212 renal transplant patients, aged between 15 and 55 years: 81 first grafts with an excellent renal function, 44 hypertensive patients, 30 type II diabetics, 29 cases of chronic graft dysfunction, 28 cases during an episode of acute rejection. RI was measured in three different renal vascular areas: prerenal, interlobar and cortical. A two-way analysis of variance showed a statistical significance for the site of RI sampling and the type of pathology. There was no interaction between the two variables studied (p = 0.30). Plasma creatinine levels, analyzed as covariate, showed a high statistical correlation with RI values (p = 0.0001). The mean RI of the 80 transplanted patients with normal creatinine plasma levels showed a remarkable homogeneity and a statistically significant progressive reduction of the values from the main renal artery to the interlobar and cortical vessels (p = 0.00001). In the other groups a greater dispersion of data was present. RI values significantly increased in hypertensive and diabetic patients (p = 0.05) but more in acute rejection (p = 0.0001) or chronic graft dysfunction (p = 0.01). In acute rejection and in chronic graft dysfunction the curve of RI values tended to become flat, while in hypertensive and diabetic patients the aspect of the curve became steeper. In conclusion, RI is a hemodynamic index that reflects the vascular status of the explored area and is not only the simple expression of reduction of the kidney functional units. The differences observed in the various kidney areas stress the importance of measuring this parameter at more than one vascular site. The increase in RI values on the kidney cortex vessels is likely to be an index of glomerular hyperfiltration. If this hypothesis is true the measure of RI might be a reliable method for diagnosing in the kidney vascular damage, glomerular hypertension and hypertrophy.

The well-functioning renal graft evaluated by color Doppler flowmetry.

The value of color Doppler ultrasound in the renal transplant follow-up has been evaluated. To do so we used a standardized protocol of analysis on a group of 86 outpatients with different transplant ages and a good and stable graft function defined as a plasma creatinine level < 105 microM/l. Renal volume increased after transplantation and averaged 198 +/- 54 cm3. The graft volume was positively related to the transplant age (p = 0.04). Mean renal blood flow/1.73 m2 body surface area was 301 +/- 98 ml/min, a value at the lower limit of normality. A statistical inverse relationship between renal blood flow and transplant age was found (p = 0.04). Renal vascular resistances increased along with the transplant age (p = 0.003). Renal function evaluated by creatinine plasma levels and creatinine clearance values did not show any statistical correlation with color Doppler findings in normal grafts. In conclusion, ultrasound measures allow us to obtain more sensitive information about the graft status and might be used for a better evaluation of the transplant follow-up.

Cyclosporine renal cortical vasoconstriction measured by colour Doppler imaging in kidney transplantation.

Important side-effects limit the use of cyclosporine A (CSA), the most insidious of which is nephrotoxicity, which manifests as a preglomerular arteriolar vasoconstriction causing a reduction in glomerular filtration rate (GFR) and renal plasma flow (RPF). This condition is initially purely functional, but with time can become anatomic and irreversible. In clinical practice we lack suitable methods for evaluating CSA vasoconstriction. Our present knowledge is based on indirect information obtained from repeated measurerments of plasma creatinine levels and from blood concentrations of the drug. Sometimes more complex and non-routine tests, such as the evaluation of GFR and RPF, or invasive methods, such as renal biopsy, are also employed. In this study we used the colour-Doppler technique to measure directly the vascular effects of CSA in patients with transplanted kidneys, evaluating changes in blood flow at the hilus and on the cortex of the kidney when the drug was at trough or peak levels.

Mechanisms of cyclosporine-induced hypertension.

The mechanisms of cyclosporine A (Cs A) nephrotoxicity are not clear, but may be associated with high blood pressure and high serum uric acid levels even when kidney function is still normal. To evaluate proximal tubular resorption and its relationship with erythrocyte cation transport systems that are known to be abnormal in essential hypertension, we measured fractional excretion of endogenous uric acid (FE Ur%) and exogenous lithium (FE Li%), erythrocyte sodium concentration, Na-K pump, Na-K cotransport and Li-Na countertransport in two groups of kidney transplant recipients with normal kidney function (creatinine less than 1.6 mg/dL), one treated with Cs A and steroid (Cs A group) and the other with azathioprine and steroid (Aza group). Patients were matched for sex, body mass index, and age. Antihypertensive treatment was measured using arbitrary scores. Erythrocyte sodium transport systems were similar in the two groups. Despite normal kidney function, the Cs A group had higher blood pressure (mean blood pressure 108.6 +/- 3.1 mmHg vs 98.3 +/- 2.4, p less than 0.01), although taking more antihypertensive treatment, and increased proximal tubular resorption (FE Li%: 12.8 +/- 1.5 vs 20.5 +/- 1.7, p less than 0.001) and global proximal tubular resorption (FE Ur%: 5.2 +/- 0.48 vs 7.09 +/- 0.41, p less than 0.05). These findings may explain the greater prevalence of hypertension in the Cs A group. Increased urate resorption may be involved in interstitial abnormalities, which are the earliest signs of Cs A toxicity. Cs A did not modify erythrocyte ion transport systems.

High plasma ionized calcium with normal PTH and total calcium levels in normal-function kidney transplant recipients.

Hypercalcemia is a postrenal transplant complication. We found a high frequency of elevated plasma ionized calcium values (65.8%) in 41 normal-function renal graft recipients. In 8 patients increased free calcium was associated with high PTH levels, whereas in 19 PTH was not increased but free calcium was high. In the other 14 patients both free calcium and PTH were in the normal range. The mean transplant duration was different in the three groups: shorter in high PTH patients, longer in normal free calcium patients, intermediate in normal PTH and high free calcium patients. Our findings confirm that a condition of hyperparathyroidism persists in the first post-transplant period, and suggest that this complication evolves towards normalization of the blood chemistry values, passing through a condition of inappropriate PTH secretion with elevated plasma free calcium which in this period is the only marker of parathyroid hyperfunction.