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Simeone Andrulli

Publications and source records attributed to Simeone Andrulli.

18 recordsLinked to original sources

Dialysis adequacy and response to erythropoiesis-stimulating agents: what is the evidence base?

Despite an increase in the use and average dose of erythropoiesis-stimulating agents (ESA) over the past 15 years, a substantial percentage of patients still do not achieve hemoglobin targets recommended by international guidelines. A clear relationship among hemoglobin or hematocrit levels, ESA dose, and increase in dialysis dose has been pointed out by a number of prospective or retrospective studies. This is particularly true in patients receiving inadequate dialysis. Increasing attention also has been paid to the relationship between dialysis, increased inflammatory stimulus, and ESA response because dialysate contamination and low-compatible treatments may increase cytokine production and consequently inhibit erythropoiesis. The biocompatibility of dialysis membranes and flux are other important factors. However, in highly selected, adequately dialyzed patients without iron or vitamin depletion, the effect of these treatment modalities on anemia seems to be smaller than expected. The role of on-line treatments still is controversial given that it is still difficult to discriminate between the effect of on-line hemodiafiltration per se from that of an increased dialysis dose. Very preliminary results obtained with short or long nocturnal daily hemodialysis on anemia correction are encouraging.

Anemia↗

Predictors of outcome in Henoch-Schönlein nephritis in children and adults.

BACKGROUND: Factors predictive of renal outcome were investigated in 219 cases of biopsy-proven Henoch-Schönlein purpura nephritis (HSPN); 83 children and 136 adults enrolled in a national study were followed up for up to 27 years (median, 4.5 years). METHODS: The criterion for defining disease progression was time elapsed until doubling of baseline creatinine level and until dialysis therapy. Age, sex, data at onset (renal function, proteinuria, hematuria, hypertension, and crescents), and data during follow-up (proteinuria and therapy) were tested as covariates. RESULTS: Multivariate Cox regression analysis indicated the following parameters as independent prognostic predictors: age (adults versus children, relative risk, 3.57; 95% confidence interval, 1.18 to 10.79; P = 0.024 for creatinine level doubling; relative risk, 14.89; 95% confidence interval, 1.72 to 129.07; P = 0.014 for dialysis therapy), sex (females versus males, relative risk, 5.71; 95% confidence interval, 1.67 to 19.55; P = 0.006 for creatinine level doubling; relative risk, 26.03; 95% confidence interval, 2.64 to 256.73; P = 0.005 for dialysis therapy), and mean proteinuria during follow-up (for each 1 g/d of protein increase, relative risk, 1.77; 95% confidence interval, 1.35 to 2.32; P < 0.001 for creatinine level doubling; relative risk, 1.73; 95% confidence interval, 1.18 to 2.52; P = 0.005 for dialysis therapy). Information for mean proteinuria levels during follow-up increased the sensitivity at logistic regression to 62.5%, with dialysis therapy as the end point. No data detected at diagnosis, including renal function impairment, proteinuria, hypertension, and crescentic nephritis (involving > 50% of glomeruli in only 2.6%), were significantly related to functional decline at multivariate Cox. CONCLUSION: This analysis indicates that, even more than when decreased renal function, severe proteinuria, hypertension, or crescents are present at onset, the risk for progression of HSPN (greater in adults and females) was associated with increasing mean proteinuria levels during follow-up.

Adolescent↗

Nutritional-inflammation status and resistance to erythropoietin therapy in haemodialysis patients.

BACKGROUND: Chronic kidney disease patients who are resistant to erythropoietin (EPO) treatment may suffer from malnutrition and/or inflammation. METHODS: In a cross-sectional study of haemodialysis patients, we investigated the relationship between the natural logarithm of the weekly EPO dose normalized for post-dialysis body weight and outcome measures of nutrition and/or inflammation [BMI, albumin and C reactive protein (CRP)] by means of multiple linear regression analysis. On the basis of the decile distribution of weekly EPO doses, we also evaluated four groups of patients: untreated, hyper-responders, normo-responders and hypo-responders. RESULTS: Six hundred and seventy-seven adult haemodialysis patients were recruited from five Italian centres. BMI and albumin were lower in the hypo-responders than in the other groups (21.3+/-3.8 vs 24.4+/-4.7 kg/m(2), P<0.001; and 3.8+/-0.6 vs 4.1+/-0.4 g/dl, P<0.001), whereas the median CRP level was higher (1.9 vs 0.8 mg/dl, P = 0.004). The median weekly EPO dose ranged from 30 IU/kg/week in the hyper-responsive group to 263 IU/kg/week in the hypo-responsive group. Transferrin saturation linearly decreased from the hyper- to hypo-responsive group (37+/-15 to 25+/-10%, P = 0.003), without any differences in transferrin levels. Ferritin levels were lower in the hypo-responsive than in the other patients (median 318 vs 445 ng/ml, P = 0.01). At multiple linear regression analysis, haemoglobin, BMI, albumin, CRP and serum iron levels were independently associated with the natural logarithm of the weekly EPO dose (R(2) = 0.22). CONCLUSIONS: Our findings support a clear association between EPO responsiveness and nutritional and inflammation variables in haemodialysis patients; iron deficiency is still a major cause of hypo-responsiveness.

Aged↗

Inflammation and resistance to treatment with recombinant human erythropoietin.

Despite an increase in the use and average dose of recombinant human EPO (rh-EPO) over the last 15 years, a substantial percentage of patients still do not achieve hemoglobin targets recommended by international guidelines. The definition of rh-EPO resistance has been introduced to identify those patients in whom the target hemoglobin level is not attained despite a greater-than-usual dose of erythropoietin-stimulating agent (ESA). In recent years, increasing attention has been paid to the relationship between dialysis, increased inflammatory stimulus, malnutrition, and ESA response. About 35% to 65% of hemodialysis patients show signs of inflammation that could be a cause of anemia through the suppression of bone marrow erythropoiesis by a number of cytokines. A large proportion of chronic kidney disease patients also have protein-energy malnutrition and wasting; low serum albumin levels, together with other more specific nutritional markers, are predictors of rh-EPO response. A diminished nutritional state could then be a feature of patients who are resistant to ESA treatment, with malnutrition probably being a consequence of a chronic inflammatory state. Starting from the hypothesis that anemia, partially attributable to a reduced response to ESA, could be the link among malnutrition, inflammation, and the poor outcome of chronic kidney disease patients, we designed a multicenter observational study, the Malnutrition-Inflammation-Resistance-Treatment Outcome Study (MIRTOS), aimed at evaluating the impact and possible causes of resistance to ESA in a large sample of hemodialysis patients. We hope the results of MIRTOS will represent a step forward toward a better understanding of the factors influencing the response to ESA in hemodialysis patients.

Anemia↗

Mini-peritoneal equilibration test: A simple and fast method to assess free water and small solute transport across the peritoneal membrane.

BACKGROUND: Loss of ultrafiltration (UF) of peritoneal membrane is one of the most important causes of peritoneal dialysis failure. UF is determined by osmotic forces acting mainly across small pores (UFSP) and ultrasmall pores or free water transport. At present, only semiquantitative estimates or complicated computer simulations are available to assess free water transport. The aim of this study was to assess free water transport during a 3.86% peritoneal equilibration test lasting 1 hour. In this condition, sodium transport is mainly due to convection, allowing the estimate of ultrafiltration of small pores and then of free water transport (total UF - UFSP). METHODS: In 52 peritoneal dialysis patients we performed a 3.86% peritoneal equilibration test (4 hours) and a 3.86% mini-peritoneal equilibration test (1 hour) and compared UF and small solute transports obtained with the two methods. RESULTS: During the 3.86% mini-peritoneal equilibration test, UFSP and free water transport were 279 +/- 142 mL and 215 +/- 86 mL, respectively; free water transport well correlated to total UF during the 3.86% peritoneal equilibration test (r= 0.67). The groups of peritoneal transporters, categorized according to glucose dialysate ratio (D/D(0)) and to creatinine/plasma ratio (D/P(Creat)), were in good agreement for the two peritoneal equilibration tests (weighted kappa 0.62 and 0.61, respectively). CONCLUSION: The 3.86% mini-peritoneal equilibration test is a simple and fast method to assess free water transport. It also gives information about total UF and small solute transports and it is in good agreement with the 3.86% peritoneal equilibration test.

Adult↗

Relationship between urea clearance and ionic dialysance determined using a single-step conductivity profile.

BACKGROUND: On-line determination of ionic dialysance (ID) has been used to measure the clearance of small solutes like urea. However, attempts to determine the in vivo relationship between ID and urea clearance have led to discordant findings. The aim of this study was to determine the relationship between the mean values of repeated instantaneous determinations of ID throughout a dialysis session ((m)ID), obtained using a single-step inlet dialysate conductivity profile, and the mean values of urea clearance corrected for access recirculation (K(eu1)), total recirculation (access plus cardiopulmonary recirculation, K(eu2)), and the entire postdialysis urea rebound (K(wb)). METHODS: Eighty-two anuric patients on chronic thrice-weekly hemodialysis were studied using an Integra machine equipped with the Diascan module for the automatic determination of ID. The mean values of repeated ID measurements made at 30-minute intervals were compared with K(eu1) (available for only 31 patients), K(eu2), and K(wb). RESULTS: The results in all 82 patients were: (m)ID = 176 +/- 23 mL/min; K(eu2) = 181 +/- 25 mL/min; K(wb) = 159 +/- 22 mL/min. The mean (m)ID/K(wb) and (m)ID/K(eu2) ratios were, respectively, 1.11 +/- 0.06 and 0.98 +/- 0.06. The results in the 31 patients for whom K(eu1) values were available were: (m)ID = 179 +/- 24 mL/min and K(eu1) = 200 +/- 27 mL/min; the mean (m)ID/K(eu1) ratio was 0.90 +/- 0.05. CONCLUSION: The mean value of repeated ID determinations obtained using a single-step conductivity profile underestimates urea clearance corrected for access recirculation, and may be considered an adequate estimate of urea clearance corrected for total recirculation.

Anuria↗

Is it the agent or the blood pressure level that matters for renal and vascular protection in chronic nephropathies?

Over the recent years, it has been clearly documented that hypertension and proteinuria are the major factors responsible for progression of chronic kidney disease (CKD). Therefore, a target BP of at least 130/80 mm Hg has been suggested in order to reduce the rate of progression and cardiovascular mortality. Some antihypertensive agents, such as ACE inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), and perhaps calcium channel blockers (CCBs), may also be capable of reducing CKD progression because they halt some of the pathogenetic mechanisms involved in renal damage, some of which is unrelated to reduction of proteinuria, per se. Although this specific effect seemed to be partially independent of blood pressure reduction, it remains controversial whether these drugs are really superior to other antihypertensive agents when blood pressure values recommended by guidelines are achieved. This issue is still a matter of debate because in published trials, target and achieved blood pressure values were constantly higher than those recommended today. Nevertheless, available findings seem to indicate that the renoprotective effect of these agents is at least partially independent of a better BP control. The only way to definitely solve this issue would be a new randomized trial. However, the clinical relevance of this trial is debatable, considering that we need all the drugs available to reach these recommended BP values.

Animals↗

Sodium removal and sodium concentration during peritoneal dialysis: effects of three methods of sodium measurement.

BACKGROUND: Sodium removal (NaR) may have a major impact on the survival of peritoneal dialysis patients. The dialysate/plasma sodium concentration ratio (D/P(Na)) is an indirect index of transcellular water transport by aquaporin channels, and thus of ultrafiltration. Sodium concentration can be assessed by means of flame photometry (F), and direct (D-ISE) or indirect ion-selective electrodes (I-ISE), but these methods have different properties. I-ISE is being used increasingly in clinical laboratories. The aim of this study was to evaluate NaR and D/P(Na) using the three different measurement methods. METHODS: We performed peritoneal equilibration tests (PETs) in 44 peritoneal dialysis patients and calculated the NaR. We also calculated D/P(Na) during the test; plasma and dialysate sodium concentrations were measured by F, D-ISE and I-ISE. RESULTS: NaR was lower (P<0.001) with D-ISE (69+/-29 mmol) than with F (81+/-29 mmol) or I-ISE (79+/-28 mmol). D/P(Na) was also lower at baseline (0.92+/-0.02 vs 0.95+/-0.02 and 0.95+/-0.02; P<0.001), after 60 min (0.87+/-0.03 vs 0.90+/-0.03 and 0.90+/-0.03; P<0.001) and at the end of PET (0.88+/-0.04 vs 0.92+/-0.04 and 0.92+/-0.04; P<0.001) when measured by D-ISE in comparison with F and I-ISE, respectively. CONCLUSIONS: NaR and D/P(Na) were lower when measured by the D-ISE method compared with the F and I-ISE methods. NaR and D/P(Na) were similar when measured by F or I-ISE. I-ISE can be used reliably in the evaluation of NaR and D/P(Na) in everyday clinical practice of peritoneal dialysis.

Clinical Chemistry Tests↗

Corticosteroid effectiveness in IgA nephropathy: long-term results of a randomized, controlled trial.

Proteinuria plays a causal role in the progression of IgA nephropathy (IgAN). A previous controlled trial showed that steroids are effective in reducing proteinuria and preserving renal function in patients with IgAN. The objective of this study was to evaluate the long-term effectiveness of steroids in IgAN, examine the trend of proteinuria during follow-up (starting from the hypothesis that the degree of reduction in proteinuria may influence IgAN outcome), and evaluate how histologic scores can influence steroid response. A secondary analysis of a multicenter, randomized, controlled trial of 86 adult IgAN patients who were receiving supportive therapy or intravenous methylprednisolone plus oral prednisone for 6 mo was conducted. Ten-year renal survival was significantly better in the steroid than in the control group (97% versus 53%; log rank test P = 0.0003). In the 72 patients who did not reach the end point (doubling in baseline serum creatinine), median proteinuria significantly decreased (1.9 g/24 h at baseline, 1.1 g/24 h after 6 mo, and 0.6 g/24 h after a median of 7 yr). In the 14 progressive patients, proteinuria increased from a median of 1.7 g/24 h at baseline to 2.0 g/24 h after 6 mo and 3.3 g/24 h after a median of 5 yr. Steroids were effective in every histologic class. Cox multivariate regression analyses showed that, in addition to steroids, a low baseline histologic score, a reduction in proteinuria after 6 mo, and no increase in proteinuria during follow-up all were independent predictors of a beneficial outcome. Steroids significantly reduce proteinuria and protect against renal function deterioration in IgAN. The histologic picture and proteinuria during early and late follow-up improve the prediction of outcome, but considerable variability remains outside the model.

Adrenal Cortex Hormones↗

Ionic dialysance allows an adequate estimate of urea distribution volume in hemodialysis patients.

BACKGROUND: An adequate estimation of urea distribution volume (V) in hemodialysis patients is useful to monitor protein nutrition. Direct dialysis quantification (DDQ) is the gold standard for determining V, but it is impractical for routine use because it requires equilibrated postdialysis plasma water urea concentration. The single pool variable volume urea kinetic model (SPVV-UKM), recommended as a standard by Kidney Disease Outcomes Quality Initiative (K/DOQI), does not need a delayed postdialysis blood sample but it requires a correct estimate of dialyser urea clearance. METHODS: Ionic dialysance (ID) may accurately estimate dialyzer urea clearance corrected for total recirculation. Using ID as input to SPVV-UKM, correct V values are expected when end-dialysis plasma water urea concentrations are determined in the end-of-session blood sample taken with the blood pump speed reduced to 50 mL/min for two minutes (U(pwt2')). The aim of this study was to determine whether the V values determined by means of SPVV-UKM, ID, and U(pwt2') (V(ID)) are similar to those determined by the "gold standard" DDQ method (V(DDQ)). Eighty-two anuric hemodialysis patients were studied. RESULTS: V(DDQ) was 26.3 +/- 5.2 L; V(ID) was 26.5 +/- 4.8 L. The (V(ID)-V(DDQ)) difference was 0.2 +/- 1.6 L, which is not statistically significant (P= 0.242). Anthropometric volume (V(A)) calculated using Watson equations was 33.6 +/- 6.0 L. The (V(A)-V(DDQ)) difference was 7.3 +/- 3.3 L, which is statistically significant (P < 0.001). CONCLUSION: Anthropometric-based V values overestimate urea distribution volume calculated by DDQ and SPVV-UKM. ID allows adequate V values to be determined, and circumvents the problem of delayed postdialysis blood samples.

Hemodialysis Solutions↗

The quality of dialysis water.

INTRODUCTION: Every week, haemodialysis patients are exposed to approximately 400 l of water used for the production of dialysis fluids which, albeit with the interposition of a semi-permeable artificial membrane, come into direct contact with the bloodstream. It is therefore clearly important to know and monitor the chemical and microbiological purity of dialysis water. METHODS: In this review, we analyse the sources of chemical and microbiological water contamination, and the problems involved in water purification systems and modalities. We also analyse the compliance of dialysis units with the microbiological standards established by the most widely accepted guidelines relating to the quality of dialysis fluids. RESULTS: The risk of chemical contamination is due mainly to the primary pollution of municipal water, whereas the most important microbiological problem is the control of bacterial growth in the water treatment and distribution system. Dialysis water treatment implies various levels of pre-treatment, a final purification module (which, in many cases, is reverse osmosis: RO) and a hydraulic circuit for the distribution of the purified water. RO-based treatment systems produce water of optimal chemical and microbial quality, and so dialysis units need to concentrate on maintaining this quality level in the long term by means of effective maintenance and disinfection strategies. The most widely accepted standards for water purity are those recommended by the Association for the Advancement of Medical Instrumentation and the European Pharmacopea, which respectively allow bacterial growth of <200 and <100 c.f.u./ml, and an endotoxin concentration of <2 and <0.25 IU/ml. However, a number of multicentre studies have reported that 7-35% of water samples have bacterial growth of >200 c.f.u./ml, and up to 44% have endotoxin levels of >5 IU/ml. CONCLUSIONS: The results of multicentre studies indicate that the microbial quality of dialysis fluids is still a too often neglected problem, particularly as there is evidence of a possible relationship between dialysis fluid contamination and long-term morbidity. The time has now come to take advantage of innovations in water treatment processes and improvements in dialysis machines in order to modify clinical practices and start improvement processes aimed at decreasing the risk of microbial contamination to the minimum, as it has already been successfully done in the case of chemical contamination.

Dialysis Solutions↗

Sodium removal during pre-dilution haemofiltration.

BACKGROUND: Cardiovascular instability still affects a large percentage of uraemic patients undergoing extracorporeal substitutive treatments. Post-dilution haemofiltration has been reported to be a method for improving cardiovascular stability; however, the limited removal of small molecular weight solutes together with the need for high blood flow from the fistula greatly restrict the use of this treatment. To increase the solute clearances and to partially resolve the necessity for high blood flow, the replacement solution, in a quantity about double that used in post-dilution mode, can be administered in pre-dilution mode. A high vascular stability has also been observed for pre-dilution haemofiltration. Since the lower morbidity may be due to less sodium removal when compared with haemodialysis, it would be important to characterize the sodium transport in this kind of treatment. METHODS: Nine patients underwent nine pre-dilution haemofiltration treatments (one for each patient) with on-line prepared substitution fluid. RESULTS: As mean values, total (NaF(pw)) and ionized (NaE(pw)) plasma water sodium concentrations increased from 149.4 +/- 2.8 mEq/l to 151.1 +/- 2.4 mEq/l, and from 143.1 +/- 2.8 to 144.5 +/- 1.2 mEq/l, respectively, during the treatment, suggesting a hypotonic concentration of net ultrafiltrate. Plotting the difference between final and initial ionized plasma water concentrations (fNaE(pw) - iNaE(pw)) against the difference between initial plasma water values and ionized sodium concentration in the reinfusate (iNaE(pw) - NaE(R)), a significant negative correlation was found, with the regression line that intercepts the abscissa at the (iNaE(pw) - NaE(R)) value of 8.8 mEq/l; this means that to avoid changes in NaE(pw) in our patients, the NaE(R) should be lower than the iNaE(pw) by this amount. This is quite different from the theoretical value of approximately 4 mEq/l necessary to avoid changes in NaE(pw) during haemodialysis. The ratio between the total sodium concentration in the ultrafiltrate (NaF(uf)) and NaF(pw) (alpha) at the post-reinfusion site was 0.96 and decreased to 0.94 when NaF(pw) values at the pre-reinfusion site were considered. This last value is quite close to the theoretical alpha value of post-dilution haemofiltration. CONCLUSION: As for post-dilution haemofiltration, less sodium removal, compared with haemodialysis, can partly explain the improved cardiovascular stability during pre-dilution haemofiltration.

Hemofiltration↗

Convection versus diffusion in dialysis: an Italian prospective multicentre study.

The concept of dialysis adequacy has to be widened to include medium size and large molecule removal in addition to urea kinetics. The HEMO study found a non-significant trend toward a beneficial effect on mortality of high-flux dialysis compared with low-flux dialysis. In that study, the beneficial effect of convection could have been attenuated by the fact that 'internal filtration' in high-flux haemodialysis (HD) is lower than that expected by convection in haemofiltration (HF) or haemodiafiltration (HDF). To explore the putative beneficial effect of convection, this Italian multicentre study was planned, comparing on-line convective treatments (HF and HDF) with standard, low-flux HD. The enrolled patients will be evaluated prospectively on their usual treatment for 2 months (baseline period) and subsequently randomized to continue either with low-flux HD (50%) or to start on-line convective treatment (50%), HF or HDF according to a 1:1 ratio. The primary end point of the study will be cardiovascular stability and blood pressure control. As secondary aims of the study, the impact on symptoms, morbidity and mortality will be assessed. Feasibility and patient compliance during HF and HDF treatments will also be evaluated. The experimental phase of the study, of at least 2 years, is divided into a 3-month adaptation period and a subsequent evaluation period. A recruitment period of 1 year is planned. The study design has adequate power to detect an absolute reduction of 3% hypotensive episodes with the experimental convective treatments compared with standard low-flux HD.

Convection↗

Role of combination therapy with ACE inhibitors and calcium channel blockers in renal protection.

Over recent years, a target blood pressure of 125/75 mm Hg has been sought in order to reduce the rate of chronic renal disease (CKD) progression and cardiovascular mortality. Some antihypertensive agents, such as angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists and calcium channel blockers also may be capable of reducing CKD progression because they halt some of the pathogenetic mechanisms involved in renal damage. The possibility that combination treatments with ACE inhibitors and calcium-channel blockers may confer additive or even synergistic renoprotective effects other than blood pressure control is not only fascinating, but also particularly important because multidrug antihypertensive regimens are required to obtain adequate blood pressure in the majority of patients with CKD. This combination may provide better blood pressure control, appears to be better tolerated with fewer side effects than either drug alone, and may exert a greater renoprotective effect in patients at risk for renal failure than either an ACE inhibitors or a calcium channel blocker. However, the current available data are too few to confirm this hypothesis. Cardiovascular disease accounts for more than 50% of the deaths of hemodialysis patients. Thus, care must be taken to prevent and treat the cardiovascular risk factors optimally from the early phase of CKD, and for this reason effective antihypertensive therapy is the most important treatment, not only in order to delay CKD progression, but also to reduce the burden of cardiovascular disease. In this perspective combination therapy with ACE inhibitors and calcium channel blockers can give further advantages.

Angiotensin-Converting Enzyme Inhibitors↗

The role of blood volume reduction in the genesis of intradialytic hypotension.

BACKGROUND: The aim of this multicenter prospective study was to investigate the role of relative blood volume (RBV) reduction on intradialytic hypotension. METHODS: One hundred twenty-three patients on chronic hemodialysis therapy were considered a priori normotensive (reference group A), intradialytic hypotension prone (group B), and hypertensive (group C). RBV was continuously monitored, and diastolic and systolic blood pressure (SBP) and heart rate (HR) were measured at 20-minute intervals during three dialysis sessions. RESULTS: Intradialytic RBV reduction was -13.8% +/- 7.0% and similar in the three groups (P = 0.841). SBP and RBV decreased during dialysis, with a sharp initial decrease (in the first 20 minutes for SBP and the first 40 minutes for RBV), followed by a slower decrease. The lying bradycardic response before dialysis was less in group B than group A (a decrease of 3 +/- 7 versus 9 +/- 9 beats/min; P < 0.001). When symptomatic hypotension occurred, RBV reduction was not significantly different from that recorded at the same time during hypotension-free sessions (-13.9% +/- 6.4% versus -12.7% +/- 5.2%; P = 0.149). Group, baseline plasma-dialysate sodium gradient, RBV line irregularity, and early RBV and HR reduction during dialysis influenced the relative risk for symptomatic hypotension with a sensitivity of 80% versus 30% for RBV alone. CONCLUSION: We found no difference in reduction in RBV in the three groups and no critical RBV level for the appearance of symptomatic hypotension. With variables easily available within 40 minutes of dialysis, RBV monitoring increases the prediction of symptomatic hypotension.

Aged↗

Is it the agent or the blood pressure level that matters for renal protection in chronic nephropathies?

Some antihypertensive agents may be capable of reducing chronic renal insufficiency (CRI) progression because they halt some of the pathogenic mechanisms involved in renal damage. Although this effect seems to be partially independent of BP reduction, it is still unclear whether these drugs are really superior to other antihypertensive agents when the BP values recommended by the present guidelines are actually achieved. This is particularly true when considering that, in published trials, target and achieved BP values were constantly higher than those nowadays recommended. Furthermore, in the majority of these studies, patients treated with ACE-inhibitors (ACE-I) or Angiotensin II receptor antagonists (ATIIRA) achieved lower BP values than those in control groups and BP values during 24 h were not recorded. Anyway, taking into account the role of baseline and follow-up BP values, the treatment effect remained significant in almost all of the multivariate models. These findings suggest that the renoprotective effect of these agents (ACE-I, ATIIRA) is partially independent of better BP control. However, caution should be paid in attributing true biologic renoprotective properties to drugs just on the basis of statistical adjustments of BP values, although robustly performed, without being aware of what those BP values actually reflect.

Angiotensin Receptor Antagonists↗

ACE inhibitors and angiotensin II receptor blockers in IgA nephropathy with mild proteinuria: the ACEARB study.

Few studies have investigated IgA nephropathy patients presenting with 'favorable' clinical features at onset, such as normal renal function, proteinuria<1 g/24 hours and the absence of hypertension, and no controlled clinical trials have tested the effects of treatment in such patients who may nevertheless develop end-stage renal disease. It is therefore important to find a well-tolerated and economic therapy capable of decreasing their risk of high proteinuria and blood pressure levels. The aim of this multicenter open-label randomized clinical trial is to test whether blocking the renin-angiotensin system (RAS) decreases the risk of progression in patients aged 3-60 years with biopsy-proven benign IgA glomerulonephritis, proteinuria levels of 0.3-0.9 g/24 hours, and normal renal function and blood pressure. The RAS is blocked by first using a single drug class (angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker), and then combining the 2 classes as soon as the 1-drug blockade has become ineffective. We plan to enroll 378 patients over the next 3 years and randomize them to receive ramipril 5 mg/day (3 mg/m2 in children) (group A), irbesartan 300 mg/day (175 mg/m 2 in children) (group B) or supportive therapy (group C); if an increase in proteinuria of at least 50% from baseline is detected after 6 months of treatment, the other RAS inhibitor will be added. The observation period will be at least 5 years (except in the case of the development of the primary end point).

Adolescent↗