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Background. The true incidence of lead (Pb) overload as a cause of chronic renal failure (CRF) is unknown. Also, it is unclear if CRF per se could generate an increment in the body Pb burden. Most studies of chronic Pb intoxication have been performed on cohorts or patients with a past history of occupational exposure. Therefore we studied the body Pb burden in CRF of known aetiology versus those patients with CRF with gout and hypertension of unclear aetiology without a past history of Pb exposure. In addition we studied patients diagnosed with essential hypertension. Methods. We studied 296 patients lacking a past history of Pb exposure, who were subdivided into four groups : group I (n=30), normal control subjects ; group II (n=104), patients with 'essential' hypertension and normal renal function ; group III (n=132), patients with CRF of uncertain aetiology in association with hypertension and/or gout, and group IV (n=30), patients with CRF of known aetiology. The blood and urine Pb levels were assessed before and after an EDTA test. Results. No abnormal test results were obtained for patients in groups I and IV. The EDTA test was abnormal in 16 patients (15.4%) in group II and in 74 patients (56.1%) in group III. A positive correlation was observed between plasma creatinine levels and post-EDTA urinary Pb in group III, but not in group I. No correlation regarding plasma creatinine and the duration of hypertension or gout were demonstrated. The bone Pb levels, measured in 12 patients with pathological EDTA test results, were positively correlated to the plasma creatinine levels. Conclusions. A high percentage of patients with gout, hypertension, and CRF have an excessive Pb burden, and about 15% of the patients diagnosed as 'essential' hypertensives also show high Pb burdens. It is remarkable that a history of overt Pb exposure was lacking in the whole study population.

Hematocrit increase with recombinant erythropoietin (rEPO) has been associated with increased progression of renal insufficiency in experimental models of renal mass reduction. The aim of the present study was to assess the effects of therapy with rEPO and various antihypertensives on the progression of chronic renal insufficiency and on arterial hypertension in an experimental model of renal mass reduction. Rats subjected to a two-thirds nephrectomy were randomly assigned to an untreated control group or to therapy with rEPO (subcutaneously, at an initial dose of 40 U/kg thrice weekly), rEPO plus verapamil (subcutaneously, 0.5 mg/kg/day), or rEPO plus enalapril (orally, 50 mg/l in the drinking water). Combining enalapril and rEPO therapy controlled systemic blood pressure (BP) and the increase in proteinuria. Glomerular injury, as assessed 16 weeks after renal ablation, was more marked in the animals treated with rEPO with or without either antihypertensive. The morphometric analyses showed greater glomerular tuft areas in the three groups receiving rEPO than in the controls. The glomerular tuft area was directly correlated with the rate of glomerulosclerosis. In about 11 % of the rEPO-treated hypertensive rats, the lesions showed severe hypertensive vasculopathy; in the animals treated with rEPO plus enalapril, the lesions were less severe. We conclude that therapy with rEPO was associated to renal damage which could not be attenuated by enalapril despite controlling BP and proteinuria, and may have a nonhemodynamic cause. Therapy with rEPO might trigger lesions usually associated with severe arterial hypertension; concomitant therapy with enalapril attenuates hypertensive vasculopathy.

Renal endothelin-1 (ET-1) production is diminished in spontaneously hypertensive rats. An increase has been reported of renal ET-1 production associated with progression of renal disease in rats with reduced renal mass. The purpose of the present study was to investigate the evolution over time of the urinary ET-1 excretion in an experimental model of renal mass reduction not caused by renal infarction. Rats were subjected to 23 nephrectomy (right nephrectomy and resection of the lower left renal pole) and thereafter randomly assigned to a notreatment control group or to treatment with recombinant erythropoietin, recombinant erythropoietin plus verapamil, or recombinant erythropoietin plus enalapril. The urinary ET-1 excretion was decreased by week 16 after nephrectomy as compared with healthy animals and with the levels 6 weeks after nephrectomy. The temporal evolution of urinary ET-1 excretion in the various groups of rats showed a trend toward decrease in all groups except the one receiving enalapril. The urinary ET-1 excretion correlated directly with creatinine clearance and inversely with tubulointerstitial damage. We observed an inverse correlation between urinary ET-1 excretion and arterial blood pressure 16 weeks after nephrectomy. These results indicate that renal ET-1 production decreases with the progression of renal disease and in relation with the severity of tubulointerstitial damage. The decrease in renal ET-1 production might contribute to the development and perpetuation of renal disease-associated arterial hypertension; this situation may be favorably modified by the use of enalapril.

We report a case of congenital magnesium-losing kidney with associated hypercalciuria and ocular derangements consisting of myopia, bilateral macular colobomata and bilateral papillary dysversion and hypoplasia. Our patient provides further evidence of the existence of an oculorenal syndrome associating abnormalities in the renal handling of magnesium and calcium, and myopia and chorioretinal disease.

Hypomagnesemic hypocalcemia in chronic renal disease is a rare finding. Controversy remains regarding the role of decreased magnesium in producing impaired parathyroid hormone (PTH) secretion versus target organ unresponsiveness to PTH. We describe six patients with severe chronic renal disease in whom hypocalcemia and hypomagnesemia were detected. Five patients had chronic interstitial nephropathy; all of them showed renal magnesium wasting. One patient had chronic glomerulonephritis and a malabsorption syndrome and showed a low rate of urinary excretion of magnesium. The administration of magnesium increased calcium levels in all patients. We have found elevated PTH levels in absolute terms, which, however, were inappropriate to correct hypocalcemia; the PTH levels increased in three patients and not in the other three after magnesium replacement. We conclude that in patients with tubulointerstitial nephropathies, chronic renal losses of magnesium can produce hypomagnesemic hypocalcemia.

A 65-year-old woman with previously known rheumatoid arthritis and chronic renal failure of possible glomerular origin was admitted to the hospital because of hemoptysis and respiratory insufficiency. Antineutrophil cytoplasmic antibodies (ANCAs) with antimyeloperoxidase activity were detected in her serum. The lung biopsy specimen evidenced alveolar hemorrhage. Under immunosuppressive therapy with steroids and cyclophosphamide, the patient's condition improved both clinically and radiologically, and the ANCA became negative after 6 months' therapy.

Treatment with recombinant human erythropoietin (rHuEPO) has solved the problem of anemia in patients on dialysis. However, its application to predialysis patients has raised some doubts about its effects on the progression of renal disease and on blood pressure (BP) and hemodynamic regulation. We have prospectively studied over at least 6 months a group of 11 predialysis patients receiving rHuEPO treatment (initial dose, 1,000 U subcutaneously three times a week). Clinical assessment and biochemical and hematologic measurements were made once every 2 weeks. Twenty-four-hour ambulatory BP monitoring, echocardiography, and determination of neurohumoral mediators of hemodynamics were performed once every 3 months. An adequate hematologic response was found (hemoglobin, 11.7 ± 0.4 g/dL v 9 ± 0.3 g/dL) without changes in the progression of renal disease. A decrease in cardiac output and an increase in total peripheral resistance was seen as anemia improved. A trend toward decreased left ventricular (LV) thickness and a significant decrease in LV mass index (from 178.2 ± 20.6 g/m 2 to 147.3 ± 20.6 g/m 2 ) were observed. Blood pressure control did not improve; moreover, in some patients an increase in systolic values was detected by ambulatory BP. Casual BP remained seemingly stable. Sequential determinations of neurohumoral mediators of hemodynamic substances (endothelin, renin, norepinephrine, epinephrine, dopamine) failed to explain these results. Ambulatory BP reveals a worse control in some patients who were previously hypertensive and confirms the utility of this technique in the assessment of patients under erythropoietin treatment. The trend toward LV hypertrophy regression without improved BP control confirms the role of anemia among the multiple factors leading to LV hypertrophy in end-stage renal disease (ESRD), and opens therapeutic possibilities. Better control of BP may avoid a potential offsetting of beneficial effects that correcting anemia would have on the cardiovascular system.

Hemodialysis with acetate, DL-lactate and bicarbonate: A hemodynamic and gasometric study. Using invasive techniques we have studied various hemodynamic and gasometric parameters in the course of hemodialysis (HD) with different buffers in an animal model. HD sessions of 180 minutes at zero ultrafiltration were carried out on three groups of eight uremic dogs each, under anesthesia and constant mechanical ventilation. The three groups differed only in the buffer used: acetate (Group AC), equal proportions of DL-lactate and acetate (Group AC+LA), and bicarbonate (Group BC). No hemodynamic changes were seen in Group BC. In the AC and AC+LA groups we observed on minute 1 a decrease of the mean blood pressure (MBP) and of the systemic vascular resistances (SVR). These parameters returned to baseline values within the first 30 minutes in Group AC+LA. In Group AC the SVR also returned to baseline values after the minute 30, but the MBP remained below baseline throughout the study period, together with cardiac index and left ventricular stroke work index decreases. Only in Group AC did we see a flattening of the ventricular function curves. Only in this Group was there a decrease of the arterial oxygen pressure (PaO 2 ) with an associated increase of the alveolo-arterial and arterio-venous O 2 differences. The O 2 consumption was not modified in any of the groups. Acetate as a single buffer induces hemodynamic instability through peripheral vasodilation and reduction of myocardial contractility. The myocardial depression induced by acetate, in its turn, causes a reduction in PaO 2 . The mixed acetate+lactate buffer is hemodynamically better tolerated than acetate as single buffer, as it induces only vasodilation.