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.

Cutaneous plasmacytoma in a hemodialysis patient.

BACKGROUND: Extramedullary plasma cell dyscrasias are rare. CASE REPORT: We report a case of a 56-year-old male Caucasian hemodialysis patient with cutaneous plasmacytoma. The diagnosis was made a few months after surgical removal of his renal graft due to chronic rejection. Investigations for the presence of an associated myeloma were negative. He underwent local radiotherapy with complete resolution of the skin lesion. CONCLUSIONS: Nephrologists should be aware that the frequency of post-transplant lymphoproliferative disorders is increasing in the dialysis population, especially in those previously or currently treated with immunosuppressive drugs.

[Diabetes and atherosclerotic coronary damage in uremia]. / Diabete e danno coronarico negli uremici.

BACKGROUND: Cardiovascular risk factors are common findings in uraemics, but the impact of each single factor on the development of atherosclerosis is still a matter of debate. PATIENTS AND METHODS: In order to evaluate the relationship between diabetes and ischaemic heart disease (IHD) in uraemia, we carried out a retrospective study comparing the results of 33 coronary angiographies performed in non-diabetic patients with those of 13 diabetics (2 had type 1 diabetes, 8 were treated with insulin, 2 with sulfonylureas and 3 received no therapy). Coronary angiography was performed in 29 patients awaiting kidney transplantation and in 17 subjects with IHD. RESULTS: Age, sex, length of time on renal replacement therapy, smoking history, clinical diagnosis of cerebrovascular and peripheral vascular disease, systolic blood pressure (BP), cholesterol, triglycerides, calcium, phosphate, albumin and degree of anaemia were comparable in the two groups. On the contrary, frequency of IHD (77 vs. 30%, p<0.01) and atrial fibrillation (23 vs. 3%, p<0.05) were higher, while diastolic BP (79 +/- 7 vs. 85 +/- 8 mmHg, p<0.05) and calcium phosphate product (47 +/- 10 vs. 57 +/- 15 mg2/dL2, p<0.05) were lower in diabetics than in non-diabetics. Stenotic lesions of the three major coronary arteries were more prevalent in diabetics than in non-diabetics (left anterior descending artery (LAD) 100 vs. 48%, p<0.01; right coronary artery (RCA) 77 vs. 39%, p<0.05; left circumflex artery (LCA) 69 vs. 24%, p<0.01) and in the same way diabetics showed higher narrowing percentage (LAD 74 +/- 30 vs. 30 +/- 36%, p<0.01; RCA 71 +/- 41 vs. 26 +/- 38, p<0.01; LCA 41 +/- 38 vs. 15 +/- 29, p<0.05). CONCLUSIONS: Our study demonstrates that although the uraemic milieu is a risk factor for IHD, diabetes increases the degree of atherosclerotic vascular damage independently of the other cardiovascular risk factors.

Relationship between diabetes mellitus and degree of coronary artery disease in uraemic patients investigated with coronary angiography.

Prevalence of cardiovascular disease is high in diabetic patients on renal replacement therapy (RRT); therefore we examined the role of diabetes mellitus on determining the degree of coronary artery stenosis. Twenty-five patients underwent coronary angiography, 12 were awaiting kidney transplantation and the examination was performed regardless of cardiac symptoms, 13 were affected by ischaemic heart disease (IHD). Diabetic and nondiabetic status together with the other risk factors for cardiovascular disease such as age, sex, length of time on RRT, smoking and elevated phosphorus levels history, clinical diagnosis of IHD, cerebrovascular and peripheral vascular disease, mean blood pressure, cholesterol, triglycerides, calcium, phosphate, albumin, haemoglobin, haematocrit and weekly dose of erythropoietin were derived from clinical records. All investigated parameters were matched in diabetic (group 1, n=10) and nondiabetic patients (group 2, n=15) and showed no differences. Clinical evidence of IHD was detected in 80% of patients in group 1 and 46% in group 2 and the percentage of patients on the renal transplant waiting list was not statistically different in the two groups (30 vs 60%). In 60% of patients in group 1 there were 3 or more stenotic lesions equal or greater than 75% of normal reference segment in the major coronary arteries, whilst in 53% in group 2 there were no haemodynamically significant narrowings. Narrowing percentage of the coronaries in group 1 and 2 were: right coronary artery 83 +/- 30 vs 32 +/- 41 (p<0.05), left anterior descending artery 80 +/- 25 vs 44 +/- 34 (p<0.05), left circumflex artery 46 +/- 37 vs 18 +/- 29 (p=0.05) respectively. Our study confirms that IHD is a clinical feature of uraemic diabetic patients and that diabetes is the main cardiovascular risk factor for determining the degree of coronary stenosis.

[Mesenteric ischemia in hemodialysis patients: case report and review of the literature]. / L'ischemia mesenterica negli emodializzati: descrizione di un caso e revisione della letteratura.

Mesenteric infarction is increasingly observed in uremic elderly patients with widespread atherosclerosis. A 77-year-old man on renal replacement therapy since June 1997 was admitted because of abdominal pain. The surgical diagnosis was massive intestinal infarction and the patient died a few hours later. A colonoscopy had been performed a few weeks before and a well-limited necrosis of the caecum mucosa had been detected. Hypotensive episodes were frequent during his hemodialysis sessions. In this work we discuss age, symptoms, laboratory investigations, risk factors and the evolution of case reports published during the last few years. Nephrologists should take into account the possibility of mesenteric ischemia in uremic patients with manifest arterio-occlusive disease, abdominal pain and leukocytosis, especially if hypotension is the major complication of the hemodialysis sessions.

[Coronary angiography in uraemic patients awaiting kidney transplantation]. / L'indagine coronarografica negli uremici in lista di attesa per trapianto renale.

BACKGROUND: Cardiovascular disease is the leading cause of morbidity and mortality in uraemia. Coronary angiography (CA) in patients awaiting kidney transplantation (PAKT) is still a matter of debate. In order to evaluate atherosclerotic coronary damage in PAKT, CAs of 12 PAKT were matched with those of 13 dialysis patients (P) affected by ischaemic heart disease IHD. METHODS: Age sex, length of time on renal replacement therapy, diabetes, smoking and hyperphosphataemia history, clinical diagnosis of IHD, cerebrovascular (CV) and peripheral vascular (PV) disease, mean blood pressure (BP), cholesterol, triglycerides, calcium, phosphate, albumin, haemoglobin, haematocrit and weekly dose of erythropoietin (EPO-dose) were derived from clinical records. RESULTS: PAKT were younger (48 9 vs 63 9 years, p < 0.01) and had higher diastolic BP values (86+/-10 vs 79+/-4 mmHg, p < 0.05) than IHD P. On the contrary all the other parameters investigated were not different in the two groups of P. Prevalence of IHD in PAKT was 16% while frequency of CV and VP disease were not different in the two groups. In 9 of IHD P stenotic lesions >/=75% of normal reference segment were diagnosed in 3 or more vessels whilst in PAKT there were atherosclerotic lesions in right coronary artery, left anterior descending artery and left circumflex artery in 41, 66 and 33% respectively. Narrowing percentage of the coronaries in PAKT and IHD P were: right coronary artery 27+/-42 vs 75+/-35, p < 0.05, left anterior descending artery 29+/-25 vs 86+/-15, p < 0.001, left circumflex artery 11 16 vs 47+/-38, p < 0.05 respectively. CONCLUSIONS: Our study shows that atherosclerotic coronary damage is present in PAKT and, although not hemodynamically significant, it could be an important risk factor for clinical expression of IHD. We conclude that CA should be performed in PAKT especially in those over 45 years.

Potassium-based dilutional method to measure hemodialysis access recirculation.

BACKGROUND: Assessment of access recirculation (AR) is crucial to dialysis efficiency and there is thus a need for a method yielding a highly accurate, fast, easy and economical measurement that can be applied in any busy dialysis clinic. Non-urea based dilutional methods are more accurate than urea based methods and avoid problems with cardiopulmonary recirculation, but they require expensive specialized devices, which limit their applicability. METHODS: We developed a simple dilutional method of AR which does not require any specific device, based on the determination of serum potassium [K+] in two samples. Briefly, a basal sample is drawn at the time of needle insertion (basal [K+]); needles are connected to blood lines and blood flow rate is quickly increased to 300 ml/mm; a second sample (arterial [K+]) is drawn from the arterial line port within 5 to 10 seconds, to avoid errors due to cardiopulmonary recirculation of the normal saline entering the blood stream. At this time, if recirculation is present, part of the normal saline will enter the arterial line and dilute the serum [K+]. The AR formula is: AR (%) = 100 x [1 - arterial K+/basal K+]. We compared our method with the two-needle urea and ultrasound velocity dilution methods. RESULTS: AR values by the ultrasound method > 10% were hypothesized as gold standard for AR, against which values obtained with the potassium method were compared. The potassium based method showed: sensitivity (100%,); specificity (95%); predictive value, positive (91%); predictive value, negative (100%). In addition, the potassium based method appears to be more reliable than the two-needle urea based method. CONCLUSION: Our method, similar to other dilutional methods, is not influenced by cardiopulmonary recirculation or veno-venous disequilibrium and is fast and accurate. Moreover it is very simple, economical, and can easily be performed in any dialysis unit.

Proteinuria as a modifiable risk factor for the progression of non-diabetic renal disease.

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors reduce urine protein excretion and slow the progression of renal disease. The beneficial effect in slowing the progression of renal disease is greater in patients with higher urine protein excretion at the onset of treatment. We hypothesized that the greater beneficial effect of ACE inhibitors on the progression of renal disease in patients with higher baseline levels of proteinuria is due to their greater antiproteinuric effect in these patients. METHODS: Data were analyzed from 1860 patients enrolled in 11 randomized controlled trials comparing the effect of antihypertensive regimens, including ACE inhibitors to regimens not including ACE inhibitors on the progression of non-diabetic renal disease. Multivariable linear regression analysis was used to assess the relationship between the level of proteinuria at baseline and changes in urine protein excretion during follow-up. The Cox proportional hazards analysis was used to assess the relationship between changes in urine protein excretion during follow-up and the effect of ACE inhibitors on the time to doubling of baseline serum creatinine values or onset of end-stage renal disease. RESULTS: Mean (median) baseline urine protein excretion was 1.8 (0.94) g/day. Patients with higher baseline urine protein excretion values had a greater reduction in proteinuria during the follow-up in association with treatment with ACE inhibitors and in association with lowering systolic and diastolic blood pressures (interaction P < 0.001 for all). A higher level of urine protein excretion during follow-up (baseline minus change) was associated with a greater risk of progression [relative risk 5.56 (3.87 to 7.98) for each 1.0 g/day higher protein excretion]. After controlling for the current level of urine protein excretion, the beneficial effect of ACE inhibitors remained significant [relative risk for ACE inhibitors vs. control was 0.66 (0.52 to 0.83)], but there was no significant interaction between the beneficial effect of ACE inhibitors and the baseline level of urine protein excretion. CONCLUSIONS: The antiproteinuric effects of ACE inhibitors and lowering blood pressure are greater in patients with a higher baseline urine protein excretion. The greater beneficial effect of ACE inhibitors on renal disease progression in patients with higher baseline proteinuria can be explained by their greater antiproteinuric effects in these patients. The current level of urine protein excretion is a modifiable risk factor for the progression of non-diabetic renal disease. ACE inhibitors provide greater beneficial effect at all levels of current urine protein excretion.

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.

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.

Angiotensin-converting enzyme inhibitors and progression of nondiabetic renal disease. A meta-analysis of patient-level data.

PURPOSE: To examine the efficacy of ACE inhibitors for treatment of nondiabetic renal disease. DATA SOURCES: 11 randomized, controlled trials comparing the efficacy of antihypertensive regimens including ACE inhibitors to the efficacy of regimens without ACE inhibitors in predominantly nondiabetic renal disease. STUDY SELECTION: Studies were identified by searching the MEDLINE database for English-language studies evaluating the effects of ACE inhibitors on renal disease in humans between May 1977 (when ACE inhibitors were approved for trials in humans) and September 1997. DATA EXTRACTION: Data on 1860 nondiabetic patients were analyzed. DATA SYNTHESIS: Mean duration of follow-up was 2.2 years. Patients in the ACE inhibitor group had a greater mean decrease in systolic and diastolic blood pressure (4.5 mm Hg [95% CI, 3.0 to 6.1 mm Hg]) and 2.3 mm Hg [CI, 1.4 to 3.2 mm Hg], respectively) and urinary protein excretion (0.46 g/d [CI, 0.33 to 0.59 g/d]). After adjustment for patient and study characteristics at baseline and changes in systolic blood pressure and urinary protein excretion during follow-up, relative risks in the ACE inhibitor group were 0.69 (CI, 0.51 to 0.94) for end-stage renal disease and 0.70 (CI, 0.55 to 0.88) for the combined outcome of doubling of the baseline serum creatinine concentration or end-stage renal disease. Patients with greater urinary protein excretion at baseline benefited more from ACE inhibitor therapy (P = 0.03 and P = 0.001, respectively), but the data were inconclusive as to whether the benefit extended to patients with baseline urinary protein excretion less than 0.5 g/d. CONCLUSION: Antihypertensive regimens that include ACE inhibitors are more effective than regimens without ACE inhibitors in slowing the progression of nondiabetic renal disease. The beneficial effect of ACE inhibitors is mediated by factors in addition to decreasing blood pressure and urinary protein excretion and is greater in patients with proteinuria. Angiotensin-converting inhibitors are indicated for treatment of nondiabetic patients with chronic renal disease and proteinuria and, possibly, those without proteinuria.

The role of iron status markers in predicting response to intravenous iron in haemodialysis patients on maintenance erythropoietin.

BACKGROUND: Iron deficiency (ID) is the main cause of hyporesponsiveness to erythropoietin in haemodialysis patients and its detection is of value since it is easily corrected by intravenous iron. Markers of iron supply to the erythron, including erythrocyte zinc protoporphyrin (Er-ZPP), percentage of hypochromic erythrocytes (Hypo), reticulocyte haemoglobin content (CHr) and soluble transferrin receptor (sTfR), may be more accurate predictors of ID than ferritin (Fer) and transferrin saturation (TSat), but relative diagnostic power and best threshold values are not yet established. METHODS: In 125 haemodialysis patients on maintenance erythropoietin, the diagnostic power of the above parameters was evaluated by ROC curve, multivariate regression, and stepwise discriminant analyses. Diagnosis of ID was based on haemoglobin response to intravenous iron (992 mg as sodium ferric gluconate complex over an 8-week period). RESULTS: Fifty-one patients were considered iron deficient (haemoglobin increase by 1.9+/-0.5 g/dl) and 74 as iron replete (haemoglobin increase by 0.4+/-0.3 g/dl). ROC curve analysis showed that all tests had discriminative ability with the following hierarchy: Hypo (area under curve W=0.930, efficiency 89.6% at cut-off >6%), CHr (W=0.798, efficiency 78.4% at cut-off < or =29 pg), sTfR (W=0.783, efficiency 72.4% at cut-off >1.5 mg/l), Er-ZPP (W=0.773, efficiency 73.0% at cut-off >52 micromol/mol haem), TSat (W=0.758, efficiency 70.4% at cut-off <19%) and ferritin (W=0.633, efficiency 64.0% at cut-off <50 ng/ml). Stepwise discriminant analysis identified Hypo as the only variable with independent diagnostic value, able to classify 87.2% of patients correctly. Additional tests did not substantially improve diagnostic efficiency of Hypo >6% alone. CONCLUSIONS: In haemodialysis patients on maintenance erythropoietin, Hypo >6% is the best currently available marker to identify those who will improve their response after intravenous iron. Cost-effectiveness suggests that this parameter should be a first-line tool to monitor iron requirements in clinical practice.

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.

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.