P. Palazzi

Effect of Cyclosporin A on Renal Cortical Resistances Measured by Color Doppler Flowmetry on Renal Grafts

Doppler spectra were recorded at different cyclosporin A (CSA) levels (trough and peak) in 30 stable renal-transplanted outpatients: 15 with unimpaired renal function (plasma creatinine < 150 mumol/l) and 15 with renal impairment (plasma creatinine 150-350 mumol/l). Pulsatility (PI) and resistive indexes (RI) have been measured in the renal artery at the hilum and in the renal cortex. RI and PI were markedly increased (p < 0.0001) in the cortex at peak time while in the renal artery no significant changes were observed. These variations were statistically related with CSA blood levels (PI = p < 0.02; r = 0.54, RI = p < 0.05; r = 0.45). These effects were also found in the presence of renal damage. CSA dose-dependently reduces cortical blood flow, causing a persistent arteriolar vasoconstriction and a reduction in diastolic flow. This effect can be measured in man in a noninvasive and repeatable way using color Doppler sonograms.

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.

Fibrillary Glomerulonephritis in Castleman's Disease

Castlemans disease is an uncommon lymph node disorder which can be associated with renal disease. In this report we describe a patient with fever, weight loss, anorexia, increase in inflammatory proteins, anemia and nephrotic syndrome. Castlemans disease, plasma cell type, was diagnosed by histologic analysis after surgical excision of a pelvic lymph node. The disease was considered localized, since further investigations did not show any other pathologic mass. After resection of the pelvic lymphoid mass, clinical remission of systemic symptoms and laboratory abnormalities was observed, with the exception of the nephrotic syndrome. Renal biopsy was performed and showed a pattern compatible with fibrillary glomerulonephritis. Progressive decline in renal function was observed, despite immunosuppressive therapy.

Nonacidotic kidney proximal tubulopathy with absorptive hypercalciuria

We studied three patients with proximal tubulopathy characterized by defective reabsorption of phosphate, glucose, amino acids, urate, and low molecular weight proteins. This tubulopathy differs from Fanconi syndrome in that the patients had normal plasma bicarbonate and absorptive hypercalciuria associated with increased 1,25-dihydroxyvitamin D levels. The youngest patient was rachitic and may be classified with previously described patients, whereas the other two patients presented with nonrachitic osteopenic bone disease and their tubulopathy started during adult life. Kidney defects appeared sequentially in one of the nonrachitic patients. The two brothers of the youngest patient had similar kidney and bone disturbances. One of the other two patients had a brother with similar kidney reabsorption defects; an additional brother was probably affected and a sister presented with glycosuria, but no other reabsorption defects. The findings in these two families suggest a genetic transmission of proximal tubulopathy. The third case was sporadic. Renal histology of the three patients showed a great number of giant cells in the tubular lumen. We conclude that, at least in our adult patients, tubulopathy may represent a new entity among the proximal tubular dysfunction cases described to date. The features of this proximal defect suggest that it may be caused by a selective alteration of luminal cell membrane transport of phosphate, glucose, amino acids, urate, and proteins in the presence of a normal sodium gradient across the tubular cell membrane.

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.