[Nephrogenic systemic fibrosis]. / Fibrosi nefrogenica sistemica.

Nephrogenic systemic fibrosis (NSF) is a new, rare, and severe disease occurring in patients with renal failure who have been exposed to gadolinium. The pathogenesis of NSF is not completely known. In fact, the first warning about a significant relationship between NSF and gadolinium (a contrast medium used in magnetic resonance imaging) was only issued in 2006. No cases of NSF have been reported in Italy to date. A nationwide investigation should therefore be carried out to assess the real prevalence of NSF within the Italian uremic population. Furthermore, we need guidelines to reduce the risk of NSF in renal patients undergoing MRI with contrast medium.

The role of surveillance in mature arteriovenous fistula management.

The existing guidelines recommend arteriovenous fistulae (AVF) surveillance by access blood flow (Qa) measurement and the correction of hemodynamically significant stenoses to prolong access survival. Unfortunately, many studies supporting these recommendations are inadequate methodologically; therefore, both the optimal criteria for surveillance and the value of preventive stenosis repair in AVF remain controversial. Recent literature confirms that Qa measurement allows an accurate identification of both stenosis (area under the curve (AUC) ranging from 0.80-0.93) and access at risk of failure (AUC ranging from 0.82-0.98) in AVFs and suggests a Qa <700-1000 ml/min and/or a reduction in Qa >25% as optimal predictors for stenosis and a Qa <400 ml/min for incipient thrombosis. Recent prospective studies evaluated whether Qa surveillance could improve AVF patency rates compared to monitoring based on clinical and dialysis-related criteria alone. The majority of studies have historical, rather than concurrent, control groups and provide conflicting results, some showing a reduction and some showing no change in thrombosis rates by Qa monitoring. On the other hand, the few randomized controlled studies available show that Qa surveillance, when coupled with preemptive intervention, reduces the already low thrombosis rate in AVF and suggest that the functional access life can be prolonged. However, there is still the need for additional methodologically adequate studies to understand fully the role of surveillance in AVF management.

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.

Ambulatory blood pressure measurement in assessing the antihypertensive effect of benazepril plus hydrochlorothiazide in a fixed combination.

Ambulatory 24-hour blood pressure monitoring was used to assess the antihypertensive efficacy of the angiotensin-converting enzyme (ACE) inhibitor benazepril in combination with the diuretic hydrochlorothiazide (HCTZ) in 17 mildly to moderately hypertensive patients. Compared with placebo, benazepril 10 mg + HCTZ 12.5 mg induced a statistically and clinically significant reduction in the mean, systolic, and diastolic blood pressures. Cumulative percentages of diastolic blood pressure readings < 90 mmHg were also greater with the combination treatment than with placebo. No patient discontinued the treatment because of adverse effects.

Systemic hemodynamic pattern in primary hyperparathyroidism and its changes after parathyroidectomy.

Twelve patients (7 men and 5 women) with an average age of 53 years (range 37-69) were hospitalized for renal stones and found to have primary hyperparathyroidism. Five were hypertensive and 7 normotensive. The systemic hemodynamics, plasma renin activity and glomerular filtration rate were evaluated before and at least 6 months after removal of a parathyroid adenoma. After surgery the mean intra-arterial blood pressure fell in almost all patients, due to some reduction in the peripheral vascular resistance index with no change in the cardiac index. However, the hemodynamic variations were not uniform in all patients. No change was seen in plasma renin activity and glomerular filtration rate. A positive correlation between the percent change in mean arterial pressure and percent decrease in total serum calcium was found. The results obtained indicate that it is likely that hypercalcemia plays some role both in patients with high and those with normal blood pressure. The systemic hemodynamic changes after parathyroidectomy indicate that the fall in peripheral vascular resistance could have a certain influence.

Effects of ketanserin administration on lipid metabolism and platelet aggregation in hypertensive patients.

Lowering blood pressure is not totally effective in preventing the atherosclerotic complications of systemic hypertension. In hypertensive patients both platelet hyperaggregation and dyslipidemia have been suggested as important risk factors. The effect of 8 weeks' treatment with ketanserin on blood pressure, serum lipid parameters (cholesterol, triglycerides, LDL, HDL-C, apolipoprotein A1 and B) and platelet aggregation, induced by collagen, ADP, arachidonic acid, was evaluated in 10 patients with essential hypertension. Ketanserin was effective in lowering blood pressure in all patients, 6 of whom became normotensive. Both CHOL and TG levels and APO B were significantly reduced, whereas HDL-C and APO A1 were significantly increased after treatment. These results might be attributed to the antagonistic activity of ketanserin on alpha-1 adrenoceptors with a consequent inhibition of phosphodiesterase. Platelet aggregation, after stimulation with collagen and arachidonic acid, was significantly reduced secondary to the inhibition of intraplatelet serotonin synthesis and release. These results suggest that keranserin is effective in reducing blood pressure and in achieving normal serum lipid pattern and platelet aggregation. Therefore, this drug might be helpful in controlling the main risk factors for cardiovascular damage.

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.

Effects of ACE inhibition in normotensive patients with chronic glomerular disease and normal renal function.

A double-blind, placebo-controlled study was carried out to assess the effects of a three-month treatment with a new ACE inhibitor, Benazepril (BNZ), on systemic and renal hemodynamics, and urine protein excretion, in 20 patients with chronic glomerulonephritis, normal blood pressure (130/83 +/- 16/10 mm Hg), and normal renal function (creatine clearance 106 +/- 25 ml/min). Treatments with placebo or BNZ were assigned randomly. A wide range of proteinuria lowering effect was observed in overall population (from 1 to 84%, average 34%). Following the arbitrary level of a 30% reduction, two well-matched subgroups (10 patients for each one) were obtained: "good responders" (average decrease 51%), and "poor responders" (average decrease 17%). The main distinctive feature between the two groups was a higher plasma renin activity level in good than in poor responders. A positive correlation between the fall in proteinuria and blood pressure was found. Although the decrease in blood pressure seems to represent the major factor in determining the reduction in proteinuria, a multiple correlation analysis showed that the most prominent role (71%) was attributable to the combined decrease in blood pressure and filtration fraction, and then also to the efferent arteriole dilatation. Our conclusion is that ACE inhibitors are capable of also reducing proteinuria in patients with renal disease with normal blood pressure, the effect being more pronounced in those exhibiting humoral, systemic and renal hemodynamic patterns, indicating a greater activity of circulating and renal renin angiotensin system.

Renal functional reserve in patients with essential hypertension: effect of inhibition of the renin--angiotensin system.

1. Urinary albumin excretion and the effect of an acute oral protein load (a meat meal) on glomerular filtration rate ('renal functional reserve') were evaluated in 15 essential hypertensive patients with preserved renal function and compared with 12 normal subjects. 2. Seven patients had microalbuminuria (greater than 30 mg/day) that was not correlated with blood pressure values. 3. After an oral protein load, an average increase of 20% in glomerular filtration rate (from 91 +/- 19 to 110 +/- 27 ml min-1 1.73 m-2 was found in the hypertensive patients. This change was not statistically different from that observed in normal controls (from 102 +/- 7 to 124 +/- 9 ml min-1 1.73 m-2). The glomerular response in hypertensive patients was independent of age, duration of hypertension, blood pressure, plasma renin activity, urinary albumin excretion and retinal vascular alterations. 4. All patients were re-evaluated after 6 weeks treatment with a new orally active angiotensin-converting enzyme inhibitor, benazepril. Systolic, diastolic and mean blood pressures were lowered in all the patients, but the drug did not affect the glomerular response to acute protein ingestion or the magnitude of urinary albumin excretion. 5. The findings of a normal 'renal functional reserve' and a lack of change in both urinary albumin excretion and the glomerular response after angiotensin-converting enzyme inhibition cast doubt on the existence of increased intraglomerular pressure in hypertensive patients.

Antihypertensive therapy with ketanserin: effects on central and renal hemodynamics, and microalbuminuria.

Ten patients with essential hypertension and normal renal function were treated with ketanserin (20-40 mg twice a day), administered for 8 weeks. In all patients, the changes in systemic and renal hemodynamics, and in urine albumin excretion, were assessed. Ketanserin monotherapy effectively lowered blood pressure in all patients. No change in cardiac output, pulse rate and stroke volume was observed; peripheral vascular resistance was significantly decreased. Plasma volume was unaltered. Renal plasma flow, glomerular filtration rate and filtration fraction were stable, with a slight but not significant reduction in renal vascular resistance. Urine albumin excretion remained unchanged. No relevant side effects were observed during the treatment period. In conclusion, our results confirm that ketanserin alone is an effective antihypertensive agent in patients with uncomplicated essential hypertension. The blood pressure lowering effect is mainly due to the systemic vasodilatation; renal hemodynamics and function are well preserved.

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.

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.

Systemic and renal hemodynamic changes after two-month treatment with enalapril in patients with essential hypertension.

Twelve essential hypertensive patients with normal renal function were treated once daily with a new angiotensin converting enzyme inhibitor, enalapril maleate, for about two months. In all patients, the drug-induced changes in blood pressure (BP), systemic and renal hemodynamics, plasma renin activity (PRA), and urine aldosterone (UA) were evaluated. Mean arterial pressure was significantly lowered. No significant changes in cardiac index, heart rate, and stroke index were observed, while peripheral vascular resistance index was significantly decreased. Plasma and blood volumes were not significantly altered. The effects on renal hemodynamics consisted of a significant increase in renal plasma flow (RPF), a decrease in renal vascular resistance, and no change in glomerular filtration rate (GFR). UA excretion was significantly reduced during enalapril therapy. The drug was well tolerated, and no side effects were observed. In summary, enalapril is able to reduce blood pressure through a vasodilatatory effect without change in cardiac output. It increases renal blood flow with no change in glomerular filtration rate.

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.

Hypertension in primary immunoglobulin A nephropathy (Berger's disease): hemodynamic alterations and mechanisms.

Twenty-two patients with primary IgA nephropathy (Berger's disease), 12 with normal and 10 with high blood pressure, were studied. The mean intra-arterial pressure was 88 +/- 6 mm Hg in the normotensive group and 113 +/- 10mm Hg in hypertensive patients; plasma renin activity was high in normotensives and normal in hypertensives. The glomerular filtration rate was 83 +/- 23 and 73 +/- 26 ml/m in 1.73 m2 in normotensive and hypertensive patients, respectively (p = n.s.). Blood volume was high in IgA nephropathy patients: 82 +/- 12 ml/kg body weight in normotensives and 96 +/- 7 ml/kg body weight in hypertensives. Mean arterial pressure was significantly correlated with blood volume (r = 0.541, p less than 0.01), but not with plasma renin activity and glomerular filtration rate. The cardiac index was high in both groups: 4.20 +/- 0.88 liters/min/m2 in normotensive and 3.95 +/- 0.87 liters/min/m2 in hypertensive patients. The total peripheral resistance index was significantly lower than normal in normotensives (1,659 +/- 387 dyn/s/cm-5/m2) and significantly higher (2,419 +/- 562 dyn/s/cm-5 m2) in hypertensives. The cardiac index did not correlate with blood volume and mean arterial pressure; a positive correlation was found between mean arterial pressure and peripheral vascular resistance (r = 0.630, p less than 0.01). No correlation was observed between blood volume and plasma renin activity. Our study indicates that hypertension in IgA nephropathy is primarily volume dependent, and that this increase in blood volume is not related to the deterioration of renal function. The role of the renin-angiotensin system in the maintenance of the hypertension is not well-defined.(ABSTRACT TRUNCATED AT 250 WORDS)