The assessment of human health impact caused by industrial and civil activities in the Pace Valley of Messina.

The impact of industrial and civil activities on an agricultural and residential area is presented in a detailed and global analysis. The examined area is the Pace river valley situated in the northern zone of Messina (Italy). The sources of pollution present in the area are: a Municipal Solid Waste Incinerator operating since 1979, a disused urban solid waste landfill which was used for 30 years, an urban solid waste treatment facility with heavy vehicles traffic, and two open pits for the production of bitumen. Large quantities of toxic, carcinogenic substances and criteria pollutants are released into the environment and represent potential hazards to human health. The analysis is performed using the EHHRA-GIS tool which employs an integrated, multimedia, multi-exposure pathways and multi-receptor risk assessment model that is able to manage all the steps which constitute the human health risk analysis in a georeferenced structure. The transport of pollutants in different environmental media is assessed applying models (AERMOD, GMS, CALINE) that take into account the particular three-dimensional morphology of the terrain. The results obtained, combined with a probabilistic risk assessment and a sensitivity analysis of calculation parameters, are a comprehensive assessment of the total human health risk in the area. Finally human health risks caused by toxic and carcinogenic substances are compared with acceptable legal limits in order to support environmental managers' decisions.

Recurrence of autonomous hyperparathyroidism in calcium nephrolithiasis.

In a woman with bilateral recurrent calcium nephrolithiasis and hypercalciuria, hypercalcemia developed and she underwent parathyroid surgery, which led to excision of a histologically-confirmed adenoma. The patient became normocalcemic but remained hypercalciuric despite reduction of dietary calcium intake. Several calculi recurred in both kidneys. Four to six years after parathyroidectomy, hypercalcemia recurred and the patient underwent a new surgical exploration; a parathyroid gland with diffuse adenomatous aspects and another gland with pure hyperplasia were excised. Once again, after surgery the patient became normocalcemic but remained hypercalciuric. Evidence for a "renal calcium leak" hypercalciuria was obtained, and thiazide administration led to normalization of urinary calcium excretion. In calcium nephrolithiasis, persistent hypercalciuria may lead to recurrence of autonomous hyperparathyroidism.

Serum lipids in patients with chronic renal failure on long-term, protein-restricted diets.

Disordered lipid metabolism is believed to play an important role in accelerating the progression of chronic renal disease toward uremia. We examine this hypothetic role of lipids in a large population of patients on long-term dietary protein restriction. In our experience, there is no conclusive evidence that lipids may accelerate the progression of functional deterioration in patients with reduced renal function. Hyperlipidemia seems to be only one among the many factors affecting the prognosis of primary renal disease. Dietary protein restriction is effective in maintaining normal or only slightly elevated serum lipid levels in patients with early renal failure. Moreover, patients with renal failure maintained on this diet, which provides an elevated ratio of polyunsaturated to saturated fatty acids, have a more favorable lipid composition of erythrocyte membrane (low percentage of saturated fatty acids and high percentage of polyunsaturated fatty acids) when compared with patients on an unrestricted diet.

Captopril in patients with type II diabetes and renal insufficiency: systemic and renal hemodynamic alterations.

PURPOSE: To our knowledge, clinical studies on the long-term use of angiotensin converting enzyme inhibitors in patients with type II diabetes mellitus and nephropathy with incipient renal failure are nonexistent. We therefore assessed the effects of long-term treatment with captopril on systemic and renal hemodynamics and urinary protein excretion in patients with type II diabetes mellitus and the clinical syndrome of diabetic nephropathy. PATIENTS AND METHODS: Twelve patients, 10 men and two women, with an average age of 52 years (range, 40 to 66), participated in the study. After the basal hemodynamic evaluation, the patients received captopril in two daily doses. The dosage was adjusted at weekly intervals in order to obtain normalization of blood pressure without exceeding the maximum allowable dosage. Four patients also received furosemide (20 to 40 mg/day). RESULTS: After six months of treatment, the intra-arterial blood pressure fell (from 162 +/- 17/103 +/- 5 to 139 +/- 26/89 +/- 10 mm Hg) due to the reduction in total peripheral vascular resistance index (from 3,720 +/- 658 to 3,190 +/- 762 dynes/second/cm-5/m2), with no change in cardiac index (2.78 +/- 0.36 to 2.79 +/- 0.47 liters/minute/m2). No significant change was seen in renal vascular resistance (from 30,175 +/- 5,371 to 30,173 +/- 5,372 dynes/second/cm-5/1.73 m2) and in filtration fraction (from 26 +/- 8 to 27 +/- 10 percent). A slight, not significant, decrease in renal plasma flow (from 243 +/- 97 to 217 +/- 108 ml/minute/1.73 m2), in glomerular filtration rate (from 57 +/- 17 to 51 +/- 19 ml/minute/1.73 m2), and in proteinuria (from 4.50 +/- 3.10 to 3.40 +/- 2.31 g/day) was also observed. CONCLUSION: Our findings suggest that captopril is an effective antihypertensive agent in patients with diabetic nephropathy, but the renal beneficial effects seem to be limited when this syndrome is complicated by renal insufficiency.

Prevention of calcium nephrolithiasis with low-dose thiazide, amiloride and allopurinol.

We report 5 years' experience with low-dose hydrochlorothiazide, 50 mg/day and amiloride, 5 mg/day, in 519 patients with recurrent calcium nephrolithiasis. Additional treatment with allopurinol, 100 mg/day was prescribed for approximately 50 percent of the patients. All patients had active stone formation, having 3,464 stones in 3,126 patient-years (6.67 stones per patient, 1.10 stones per year). Hypercalciuria was present in 65 percent of the patients and hyperuricosuria in 24 percent. The administration of low-dose hydrochlorothiazide was effective in reducing urinary calcium excretion in most patients. It is possible that the hypocalciuric effect of hydrochlorothiazide were enhanced by amiloride, an agent which has been shown to cause hypocalciuria when given alone. Significant side effects requiring discontinuation of the drug were observed in only 5 percent of the patients. During 872.8 patient-years of treatment, only 53 new stones were formed (0.10 stones per patient, 0.06 stones per year) in contrast with the 916 predicted ones. The difference (chi-square) is statistically significant (p less than 0.001). These results show that the administration of low-dose hydrochlorothiazide and amiloride, either alone or in association with allopurinol, is clinically effective in reducing the rate of recurrence of calcium nephrolithiasis.

Systemic haemodynamics in renovascular hypertension: changes after revascularization with percutaneous transluminal angioplasty.

The systemic haemodynamic pattern and its changes after at least 6 months of successful percutaneous transluminal angioplasty (PTRA) was evaluated in a group of patients with renovascular hypertension (RVH). Fourteen patients, nine males and five females, aged 21 to 58 years, were studied; 12 had fibrodysplastic and two had atherosclerotic stenosing renal vascular lesions. Seven were cured and seven improved. Hypertension was characterized by increased plasma volume (PV) and total peripheral vascular resistance (TPR). Mean peripheral plasma renin activity (PRA) and 24-h urine aldosterone (UA) were elevated. However, the vasoconstriction did not appear to be related to the increased activity of the renin-angiotensin system. After at least 6 months of a successful PTRA, the fall in blood pressure (BP) was associated with a decrease in TPR; PV appeared normal, and PRA and UA became normal.

Systemic and renal effects of a new angiotensin converting enzyme inhibitor, benazepril, in essential hypertension.

Seventeen essential hypertensive patients with normal renal function were treated with a new non-sulphydryl orally active angiotensin converting enzyme (ACE) inhibitor, benazepril, 10 mg given once or twice daily, according to diastolic blood pressure levels, for 6 weeks. In all patients, changes in blood pressure, systemic and renal hemodynamics, plasma renin activity and urinary aldosterone and albumin excretions were assessed at the end of a 2-week placebo run-in period and at the end of the study. Benazepril monotherapy controlled blood pressure well. No changes in cardiac output, heart rate or stroke volume were observed, while peripheral vascular resistance was significantly decreased (-11%, P less than 0.05). Plasma volume was unaltered. The glomerular filtration rate was stable, but effective renal plasma flow was increased because of the marked reduction in renal vascular resistance (-35%) and, therefore, the filtration fraction was decreased. Urinary albumin excretion remained unchanged. A significant increase in plasma renin activity (P less than 0.001) and a decrease in urinary aldosterone excretion were seen. No side effects were observed during the treatment period. In conclusion, our results suggest that benazepril alone is an effective antihypertensive agent in patients with essential hypertension. The blood pressure lowering effect is due mainly to systemic vasodilation and is observed up to 24 h after administration of the drug. The vasodilation appears to be more consistent in the renal than in the systemic circulation.

Renal reserve in patients with solitary kidneys.

The first part of this article focuses on the risk of functional deterioration in subjects with solitary kidneys; the long-term clinical outcome of various subgroups of patients is reviewed. Thereafter, the pathophysiology of the renal functional reserve in subjects with a 50% reduction in renal parenchyma and the results coming from studies eliciting the renal reserve in these subjects are summarized. Finally, the clinical significance of the renal functional reserve and its usefulness in clinical practice are critically discussed.

Diuretics in hypertension.

Despite the consistent reduction in the incidence of stroke and coronary events demonstrated in numerous clinical trials in young and elderly hypertensive subjects, the use of diuretics has declined as a first-line therapy in hypertension. The metabolic dose-dependent side effects and the increasing availability of new drugs appear the two main reasons for the decline. Although the neutral metabolic effects and the perception of a more physiological approach to hypertension has been advocated with the newer agents, no definite proof has been reported on the long-term effects on cardiovascular end-points. Many of adverse effects of diuretics can be limited by the use of low doses. For this reason, as well as their efficacy, safety, and cost-effectiveness, diuretics should remain a first-line therapy for hypertensive patients.

Effect of dietary manipulation on the lipid abnormalities in patients with chronic renal failure.

Disorders of lipid metabolism could play an important role in mediating the progression of chronic renal disease toward uremia. The hypothesis of the nephrotoxicity of lipids has been considered in a large population of patients on long-term dietary protein restriction. In our experience, there is no evidence that lipid disorders may accelerate the progression of renal disease. Hypercholesterolemia and/or hypertriglyceridemia are probably only some of the many factors affecting the prognosis of renal disease. Dietary protein restriction seems to be effective in maintaining normal or only slightly elevated serum lipids in patients with early renal failure, even after years of dietary treatment, despite the natural progression of renal functional deterioration. Moreover, this dietary regimen has a favorable effect on lipid composition of erythrocyte membrane when compared with those of patients on a free diet.

The role of systemic hypertension in the progression of nondiabetic renal disease.

BACKGROUND: A role for hypertension in the progression of renal disease has been convincingly shown in experimental animals only. In human studies, the relation between hypertension and progression is difficult to demonstrate due to several confounding factors: age, gender, race; the difficult choice of blood pressure (BP) parameters that correlate with progression; the abnormal circadian BP pattern; and the many non-hemodynamic factors of progression. An important role for hypertension in progressive nondiabetic renal disease has been suggested by observational studies and clinical trials originally intended to evaluate the effect of dietary protein restriction on progression. In addition, several studies, summarized by a recent meta-analysis, have shown that pharmacological agents which lower both BP and proteinuria, mainly the angiotensin-converting enzyme inhibitors (ACEI), significantly slow the rate of progression in these diseases. METHODS: In this article we review the effect of lowering BP on the progression of nondiabetic chronic renal disease, the patient characteristics that are associated with a greater or lesser benefit of blood pressure reduction, and the choice of antihypertensive regimens associated with better outcomes in patients with renal disease. RESULTS: Lower levels of achieved BP are associated with a slower decline in renal function, both in patients with and without proteinuria. ACEI are effective BP lowering agents and are associated with better preservation of renal function as opposed to antihypertensive regimens without ACEI. This protective effect of ACEI is in addition to their BP and urine protein lowering effects. The protective effect of ACEI on renal function is more pronounced in patients with proteinuria. CONCLUSION: In patients with nondiabetic renal disease and proteinuria, the risk of progression can be minimized by lowering both BP and proteinuria. ACEI have an additional beneficial effect.

Long-term progression of chronic renal insufficiency in the AIPRI Extension Study. The Angiotensin-Converting-Enzyme Inhibition in Progressive Renal Insufficiency Study Group.

The Angiotensin-converting-enzyme Inhibition on Progressive Renal Insufficiency (AIPRI) Study showed that the ACE inhibitor benazepril provides protection against loss of renal function in patients with chronic renal insufficiency (CRI) caused by various renal diseases. As a result of unexpectedly low mortality in the placebo group, there was a substantial imbalance in mortality during the course of this study (8 patients on benazepril vs. 1 on placebo). The aim of the extension study was to follow-up the patients from the AIPRI core study until autumn 1996, focusing on CRI progression and mortality. Data collection was post hoc. Patients were treated according to investigators' usual practices, without knowledge of the core study trial medication or (initially) the core trial results. A new primary efficacy parameter was defined as the time from the start of core study treatment to the occurrence of the first event in the combined composite end-point of dialysis, renal transplantation or death related to renal disease. Serial serum creatinine levels and all-cause mortality were also recorded. The median total follow-up for core + extension periods was 6.6 years. Many patients from both treatment groups (64% on benazepril and 61% on placebo) received ACE inhibitors during follow-up. In the intention-to-treat analysis of the core + extension data, only 79 of 300 patients from the benazepril group, compared to 102 of the 283 patients from the placebo group needed dialysis or renal transplantation, or died related to renal disease (P < 0.013, log-rank test). The mortality imbalance seen in the core trial was not evident with the longer follow-up (25 deaths in the benazepril and 23 in the placebo group, before dialysis). These data clearly demonstrate a long-term beneficial effect in patients randomized to take benazepril during the core study, but because treatment during the extension period was not randomized, the results of this intention-to-treat analysis need to be interpreted with care.

Early dietary protein and phosphorus restriction is effective in delaying progression of chronic renal failure.

A diet containing about 40 kcal/kg, 0.6 g/kg of protein, 700 mg of phosphorus, and 1,000 to 1,500 mg of calcium (orally supplemented) was prescribed to three groups of patients with chronic renal failure for 6 to 76 months. The mean serum creatinine values were 2.18 mg/dl in group 1 (25 patients), 4.24 mg/dl in group 2 (20 patients), and 6.10 mg/dl in group 3 (8 patients). An additional group of 30 patients (group 4) who had followed no specific dietary treatment for 3 to 72 months was taken as control. The plots of reciprocal serum creatinine against time gave slopes of -0.0008, -0.0010, and -0.0041 in the three groups of patients on the protein-restricted diet, and a slope of -0.020 in the patients on the free diet. The differences between the slopes in patients in groups 1, 2, and 3 versus that in patients in group 4 are statistically significant (analysis of variance and F ratio: P less than 0.01). During the follow-up period a decline in reciprocal serum creatinine greater than the mean values in the whole group was observed in 37.5% of patients in group 3, in 20% of those in group 2, and in only 12% of those in group 1. Thus, the degree of functional renal deterioration is critical in modulating the effects of dietary protein and phosphorus restriction. Several nonimmunologic factors, including hypertension, infection, electrolyte abnormalities, and low-calorie intake, appeared to play an important role in influencing the rate of progression of renal failure in patients on dietary protein restriction.

Dietary therapy in chronic renal failure. (A comedy of errors).

Controversies still exist about the use and the effects of low protein diets in chronic renal failure. The contrasting - sometimes opposite - results published over the last 30 years in several studies can be read and explained by a series of errors included in those studies. The new Comedy of Errors starts from the misinterpretation of experimental studies, the lack of appropriacy of clinical trials' design; it continues with neglecting the role of patients' compliance as well as of other clinical findings, here included the role of blood pressure. Finally pitfalls in the intrepretation of the results of clinical trials and meta-analyses were identified.

Hypertension and progression of renal disease.

That systemic hypertension is involved in the progression of human renal disease is mostly suggested by the way anti-hypertensive treatment affects the course of the disease. Clinical evidence has been obtained from observational studies as well as from studies of dietary protein restriction. In addition, several trials have compared the effects of different antihypertensive agents. The angiotensin-converting-enzyme inhibitors have the best renoprotective effect when compared to conventional agents and calcium channel blockers. In most studies, ACE-inhibitors approximately halved the risk of progressive renal functional deterioration in patients with non-diabetic nephropathies; this protection was associated with a significant reduction in systemic blood pressure and proteinuria. Statistical analysis, however, also suggests a direct effect of ACE-inhibitors on the kidney.

Resolution of renal disease: mission impossible?

Several studies have extensively shown that both dietary and pharmacological intervention can prevent the progression of renal damage. The best results may be obtained by optimizing blood pressure control, reducing proteinuria levels in non diabetic nephropathies, and further achieving a good glycemic control in diabetic nephropathies. The earlier the treatment is started, the better the results. Since slowing progression of renal disease has been established, the challenge of the future seems to be the resolution of an established renal damage. Few studies have suggested that this process of regression is possible. Experimental animal studies, based on repeated renal morphological investigations, showed resolution of glomerular lesions in 40% of animals treated with either ACEI or AIIRA. Resolution of renal lesions (62%) has been claimed in a single study and in a small number of patients with diabetic nephropathy after 10-year pancreas transplantation. Confirmation studies are awaited.

Severe preeclampsia in antithrombin III deficiency with no history of venous thromboembolism.

Complications of pregnancy, such as preeclampsia, placental abruption, fetal growth retardation, still-birth and fetal death are associated with an increased frequency of pro-thrombotic abnormalities. We describe a case of severe preeclampsia and multiple placental infarctions in a 28-year-old woman at 31 weeks' gestation. Despite a negative personal history for venous thromboembolism, coagulation screening for thrombophilia detected an isolated antithrombin III deficiency. In view of the high prevalence of pro-thrombotic complications, laboratory screening for thrombophilia would be advantageous in women with complicated pregnancies, to ensure adequate management in high-risk situations, as suggested by larger-scale clinical investigations.

Effects of acetate on glucose metabolism and cellular ATP content during hemodialysis.

In view of multiple interactions of acetate with intermediary metabolism, we studied the effects of the exogenous acetate load during dialysis on glucose and energy metabolism. IV glucose tolerance test (glucose 0.33 g/kg BW) and platelet ATP content were evaluated in 16 patients before and after a single hemodialysis session with acetate 38 mEq/l in the dialysate. IV glucose tolerance was greatly impaired in all patients after hemodialysis (K: 1.08 +/- 0.30 vs predialysis value of 2.05 +/- 0.85, p less than 0.001). Platelet ATP content was unchanged by dialysis (3.74 +/- 1.02 mumol/10(11) PLTs before and 3.55 +/- 0.69 mumol/10(11) PLTs after), however, individual variations in platelet ATP content ranged from +32 to -31% of the initial values. Postdialysis plasma acetate levels ranged from 1.5 to 9.2 mmol/l and were inversely correlated with postdialysis glucose tolerance test (r: -0.61, p less than 0.01) and platelet ATP content variations (r: -0.51, p less than 0.05). Our study demonstrates that glucose utilization is acutely impaired by acetate dialysis and suggests that the reduced glycolytic activity may be due to a negative feed-back mechanism in the presence of exogenous fuel. It also demonstrates a great variability in platelet ATP content following hemodialysis, which probably depends on the different patients' ability to oxidize acetate.

Modification of serum and membrane lipid composition induced by diet in patients with chronic renal failure.

Disorders of lipid metabolism during chronic renal failure (CRF) play a crucial role in the pathogenesis of early cardiovascular complication of this syndrome. In addition, some experimental evidence suggests that hyperlipidemia may accelerate progression of renal disease. We have studied 65 patients with CRF (S-creatinine 1.5-9.0 mg/dl), 52.3% of whom were hypertensive. Patients were divided in 2 groups matched for age, sex and degree of renal failure: group 1 was kept for 36 +/- 8 months on a free diet; group 2 was kept for 39 +/- 6 months on a low-protein diet with an elevated polyunsaturated/saturated fatty acid (PUFA/SFA) ratio. We found significantly higher levels of triglycerides (TG) and lower levels of esterified cholesterol in high density lipoprotein (HDL-C) in group 1 than in group 2. Patients on the diet had a lower percentage of membrane SFA and a higher percentage of PUFA than patients on free diet. Only in group 1 a direct correlation between cholesterol/phospholipid (Chol/P) ratio and age was observed; in group 2, a negative correlation between levels of PUFA and TG and between linoleic/oleic (Lin/Ol) ratio and serum Chol was shown. S-creatinine levels were directly correlated with Chol/P ratio in group 1 and indirectly with Lin/Ol ratio and PUFA in group 2. These data show that a low-protein diet, containing an elevated PUFA/SFA ratio, is able to counteract lipid abnormalities in patients with CRF and the normalization of this pattern is associated with significant improvement of membrane lipid composition and, presumably, of "functional" activity of cell membranes with a better control of supposed "renal lipoprotein toxicity".

Effect of protein-restricted diet on serum lipids and atherosclerosis risk factors in patients with chronic renal failure.

Early changes in lipid metabolism and appearance of atherosclerosis risk factors play a key role in the development of cardiovascular disease of chronic renal failure (CRF). In the effort to evaluate the effects of protein restricted diet on dyslipidemia, we studied 122 patients with CRF (S-creatinine 1.3-9 mg/dl); 58.2% of whom were on antihypertensive drugs treatment. Patients had been separated into 6 groups: group 1 was kept on a free diet; groups 2, 3, 4, 5, 6 were kept on a protein-restricted diet from 12, 24, 36, 48, 60 months, respectively. We found hypertriglyceridemia, pathologic levels of esterified cholesterol in high density lipoprotein (HDL-C) and pathologic apolipoprotein A1/B ratio in group 1; the comparison with other groups--whose values were normal range after 12, 24 months of treatment--showed significant differences. The lipidic parameters were independent of the duration of CRF and of patients' age. Serum creatinine showed a significant correlation with tryglicerides and HDL-C values only in group 1. Total cholesterol and apolipoprotein B were significantly greater in hypertensives than in normotensives. In our opinion, a moderate restriction in protein intake could be effective in preventing and in halting the early alterations of lipid metabolism in CRF.