Francesco Pizzarelli

Magnitude of Underascertainment of Impaired Kidney Function in Older Adults with Normal Serum Creatinine

OBJECTIVES: To estimate in a community‐dwelling elderly population the magnitude of renal function misclassification, occurring when persons with normal serum creatinine have reduced glomerular filtration rate (GFR), and to describe the participant characteristics related to misclassification.

Application of 2011 American College of Cardiology Foundation/American Society of Echocardiography Appropriateness Use Criteria in Hospitalized Patients Referred for Transthoracic Echocardiography in a Community Setting

BACKGROUND A recent American College of Cardiology Foundation and American Society of Echocardiography document updated previous appropriate use criteria (AUC) for echocardiography. The aim of this study was to explore the application of the new AUC, and the resulting appropriateness rate, in hospitalized patients referred for transthoracic echocardiography (TTE) in a community setting. METHODS A total of 931 consecutive inpatients referred for TTE were prospectively recruited in five community hospitals. Patients were categorized as having appropriate, uncertain, or inappropriate indications for TTE according to the AUC. An additional group of 259 inpatients, discharged without having been referred for TTE, was also considered. RESULTS In the group referred for TTE, the large majority of indications (98.8%) were classifiable according to the AUC with good interobserver reproducibility. Indications were appropriate in 739 patients (80.3%), of uncertain appropriateness in 46 (5.0%), and inappropriate in 135 (14.7%). Compared with patients with appropriate or uncertain indications, those with inappropriate indications were younger and more often referred by noncardiologists. Most common causes of inappropriate indications were related to the lack of changes in clinical status or to the absence of cardiovascular symptoms and signs. Examinations with appropriate or uncertain indications had an impact on clinical decision making more often than those with inappropriate indications (86.7% vs 14.1%, P < .0001). In the group discharged without having been referred for TTE, TTE might have been appropriate in 16.2% of cases. CONCLUSIONS Clinical application of the new AUC was highly feasible in a community setting. Although inpatient referral for TTE was appropriate in most patients, strategies aimed at implementing these criteria in clinical practice are desirable.

Predictivity of survival according to different equations for estimating renal function in community-dwelling elderly subjects

BACKGROUND Detection of subjects with early chronic kidney disease (CKD) is important because some will progress up to stage 5 CKD, and most are at high risk of cardiovascular morbidity and mortality. While validity and precision of estimated glomerular filtration rate (eGFR) equations in tracking true GFR have been repeatedly investigated, their prognostic performance for mortality has not been hitherto compared. This is especially relevant in an elderly population in whom the risk of death is far more common than progression. METHODS We analysed data of participants in the InCHIANTI study, a community-based cohort study of older adults. Twenty-four-hour creatinine clearance (Ccr), Cockcroft-Gault (C-G) and Modification of Diet in Renal Disease (MDRD)-derived equations (six and four input variables) were calculated at enrolment (1998-2000), and all-cause mortality and cardiovascular mortality were prospectively ascertained by Cox regression over a 6-year follow-up. RESULTS Of the 1270 participants, 942 (mean age 75 years) had complete data for this study. The mean renal function ranged from 77 ml/min/1.73 m(2) by Ccr to 64 ml/min/1.73 m(2) by C-G. Comparisons among equations using K/DOQI staging highlight relevant mismatches, with a prevalence of CKD ranging from 22% (MDRD-4) to 40% (C-G). Reduced renal function was a strong independent predictor of death. In a Cox model--adjusted for demographics, physical activity, comorbidities, proteinuria and inflammatory parameters-participants with Ccr 60-90 ml/min/1.73 m(2) and Ccr <60 ml/min/1.73 m(2) were, respectively, 1.70 (95% CI: 1.02-2.83) and 1.91 (95% CI: 1.11-3.29) times more likely to die over the follow-up compared to those with Ccr >90 ml/min/1.73 m(2). For the C-G, the group with values <60 ml/min/1.73 m(2) had a significant higher all-cause mortality compared to those with values >90 ml/min/1.73 m(2) (HR 2.59, 95% CI: 1.13-5.91). The classification based on the MDRD formulae did not provide any significant prognostic information. The adjusted risk of all-cause mortality followed a similar pattern when Ccr and estimating equations were introduced as continuous variables or dichotomized as higher or lower than 60 ml/min. C-G was the best prognostic indicator of cardiovascular mortality. Possibly, Ccr and C-G are better prognostic indicators than MDRD-derived equations because they incorporate a stronger effect of age. CONCLUSIONS In a South-European elderly population, the prevalence of CKD is high and varies widely according to the method adopted to estimate GFR. Researchers and clinicians who want to capture the prognostic information on mortality related to kidney function should use the Ccr or C-G formula and not MDRD equations. These results highlight the importance of strategies for early detection and clinical management of CKD in elderly subjects.

Thermal balance and dialysis hypotension.

Many Studies Have Confirmed Our Original Observation That Dialysate T Set At About 35° C Affords A Better Hemodynamic Protection Than The Standard Dialysate T Of 37-38° C. In This Review We Present Some New Data On The Hemodynamic Mechanism Of The Protective Effect Of Cold Dialysis On Blood Pressure. The Study Was Based On Serial Assessment Of The Percent Changes Occurring During Dialysis Treatment In Estimated Stroke Volume (Aortic Blood Flow Determined By Doppler Echocardiography), Blood Volume (Hemoglobinometry), Arterial Pressure (Dynamap), And Heart Rate (Ecg), From Which Cardiac Output (Co) Indexes And Total Peripheral Vascular Resistances (Tpvr) Were Derived. Of The 14 Pts Studied, 7 Showed A Drop In Mean Arterial Pressure (Map) Of 25° Or Greater During Standard Dialysis (Unstable Patients). Compared With The 7 Patients Having More Stable Intradialysis Map, Unstable Pts Showed Greater Reduction In Co Which Was Disproportionately Greater Than The Reduction In Blood Volume, And A Paradoxical Decrease In Tpvr, The Difference Being Highly Significant (P ≤ 0.01 For Both Changes). When Crossed-Over To Cold Dialysis, Along With A Significantly Lower Reduction In Map (P ≤ 0.01) The Unstable Pts Showed A Lower Decrease In Co Which Paralleled The Reduction In Blood Volume, And An Increase In Tpvr. These Changes Were Highly Significant (P ≤ 0.01). Data Suggest That Dialysis Hypotension Is Characterized By An Impaired Venous Return, Probably Due To The Peripheral Blood Pooling (Increased Ratio Between The ‘Unstressed’ And ‘Stressed’ Blood Volume) Associated With The Decrease In Tpvr. Exposure Of Extracorporeal Blood To Cold Dialysate Favours The Venous Return To The Heart By Increasing Tpvr And The ‘Stressed’ Blood Volume.

High-volume online haemodiafiltration improves erythropoiesis-stimulating agent (ESA) resistance in comparison with low-flux bicarbonate dialysis: results of the REDERT study

BACKGROUND In haemodialysis (HD) patients, anaemia is associated with reduced survival. Despite treatment with erythropoiesis-stimulating agents (ESAs), a large number of patients with chronic kidney disease show resistance to this therapy and require much higher than usual doses of ESAs in order to maintain the recommended haemoglobin (Hb) target, and recent studies suggest that hepcidin (HEP) may mediate the ESA resistance index (ERI). High-volume online haemodiafiltration (HV-OL-HDF) has been shown to improve anaemia and to reduce the need for ESAs in HD patients; this effect is associated with a reduced inflammatory state in these patients. The aim of the REDERT study (role of haemodiafiltration on ERI) was to investigate the effect of different dialysis techniques on ERI and HEP levels in chronic dialysis patients. METHODS A single cross-over, randomized, multicentre study (A-B or B-A) was designed. Forty stable HD patients from seven different dialysis units (male 65%, mean age 67.6 ± 14.7 years and mean dialytic age 48 ± 10 months) were enrolled. Patients were randomized to the standard bicarbonate dialysis (BHD) with low-flux polysulfone (PS) membrane group or to the HV-OL-HDF group with high-flux PS membranes and exchange volume of >20 L/session. After 6 months, patients were shifted to the other dialytic group for a further 6 months. Clinical data, Hb, ESA doses and iron metabolism were recorded every month. HEP, beta2-microglobulin (b2MG) and C-reactive protein (CRP) were determined every 3 months, and ERI was calculated monthly as the weekly ESA dose per kilogram of body weight divided by Hb level. Data were analysed using paired-samples t-test, Wilcoxon signed-rank test and Spearmans correlation coefficient. RESULTS Dialysis efficiency for small molecules assessed as Kt/V was significantly increased in HV-OL-HDF from 1.47 ± 0.24 to 1.49 ± 0.16; P < 0.01. A significant reduction of b2MG was obtained in HV-OL-HDF from month 3 whereas CRP values were not significantly changed during the study period either in BHD or HV-OL-HDF.ERI was significantly reduced in HV-OL-HDF at month 3 and 6 (from 9.1 ± 6.4 UI/weekly/Kg/Hb to 6.7 ± 5.3 UI/weekly/Kg/Hb; P < 0.05) due to a higher ESA consumption in BHD in spite of similar Hb levels. HEP levels were reduced in HV-OL-HDF with respect to BHD after 3 and 6 months. Iron consumption was not significantly different during BHD or HV-OL-HDF treatment as well as transferrin, ferritin and TSAT levels. A significant positive linear correlation between HEP and ERI (r(2) = 0.258, P < 0.001) was observed. CONCLUSIONS In a uraemic patient population with low-grade inflammation treated with HV-OL-HDF, we observed a significant reduction of ERI values as well as HEP levels. The positive correlation between these two parameters supports a role for HEP in the development of ERI in the dialytic population. Moreover, the lower b2MG and the higher Kt/V achieved in HV-OL-HDF confirms the better depurative effect of this technique in comparison with BHD with respect to middle molecules and small-molecular-weight molecules.

Relationship Between Renal Function and Functional Decline: Role of the Estimating Equation

BACKGROUND Several formulas are available to estimate glomerular filtration rate (GFR) at the bedside. A decrease in GFR has been associated with poorer performance. We hypothesized that it is related to worsening disability as well. The aim of this study was to evaluate whether the Modification of Diet in Renal Disease formulas can predict worsening disability better than the classic Cockcroft-Gault formula or the measured creatinine clearance. METHODS We studied 666 participants in the InCHIANTI study with 6 years of follow-up data. We evaluated whether directly measured creatinine clearance and GFR estimated using the Modification of Diet in Renal Disease and Cockcroft-Gault formulas predict new disability defined as the loss of ≥ 1 ADL over the 6-year follow-up. RESULTS The mean age was 73.1 years (SD: 6.1), 57.7% were women. Fewer than 5% of participants were disabled at baseline. Eighty-one (12.2%) participants experienced a decline in activities of daily life score at follow-up. Declining GFR was associated with increasing risk of worsening disability (Mantel-Haenszel P < .001), with an increased steepness in the curve at GFR below 60 mL/min. The relative risks for worsening disability in people with GFR less than 60 mL/min/m were 3.19 (95% CI: 2.12-4.79) and 4.40 (95% CI: 2.80-6.94) using the Modification of Diet in Renal Disease and the Cockcroft-Gault equations, respectively. The corresponding figures obtained with measured creatinine clearance was 3.95 (95% CI: 2.60-6.01). After adjustment for potential confounders, however, these estimates were substantially reduced. CONCLUSION Estimation of renal function with the Cockcroft-Gault or Modification of Diet in Renal Disease formulas can help to identify elderly at risk of worsening disability. The mechanism by which reduced kidney function predicts disability should be further investigated.

Double-Chamber On-Line Hemodiafiltration: A Novel Technique with Intra-Treatment Monitoring of Dialysate Ultrafilter Integrity

On-line hemodiafiltration is a technique that relies on the re-injection of pyrogen-free substitution fluid obtained by cold filtration of dialysate. Therefore, safety of this treatment modality depends on the quality of dialysate and, mainly, on the integrity of the ultrafilter(s) employed. Double-chamber on-line hemodiafiltration is a new technique where re-infusion takes place inside the dialyser by means of dialysate backfiltration. The peculiar geometry of the dialyser allows intra-treatment assessment of its fibre integrity. In this paper, we tested feasibility and safety of this new modality of on-line treatment. The extracorporeal blood and infusate pressure values resulted well inside the safety range. Blood urea clearances and β2 removal were consistent with the figures usually found in standard hemodiafiltration. Whole blood production of cytokines was similar when blood was exposed to saline or infusate, both values being comparable to the spontaneous whole blood cytokine release. The on-line dialyser fibre integrity check showed a great sensitivity even for minimal dialyser damage. We conclude that double-chamber on-line hemodiafiltration is a feasible and safe procedure. Our preliminary results encourage the undertaking of multicentre, prospective, randomised studies.

Natural history of older adults with impaired kidney function: the InCHIANTI study

The aim of this study was to assess the kidney function of an older community-dwelling population at baseline and appraise its evolution after 3 years of follow-up in terms of chronic kidney disease (CKD) stage progression, magnitude of glomerular filtration rate (GFR) changes, and value of serum creatinine. This was a prospective population-based study of 676 Italian participants, aged 65 years and older. GFR was estimated using the Cockcroft-Gault equation and the Modification of Diet in Renal Disease Study equation. Using the Cockcroft-Gault equation. A total of 33% of participants had criteria of CKD (GFR < 60 mL/min) at baseline; among them, the majority remained stable, 10% improved, and 7% progressed to more severe CKD stages at follow-up. Loss of GFR in participants with GFR < 60 mL/min was significantly lower (1.4 mL/min per year) than in participants with GFR ≥ 60 mL/min (3.3 mL/min per year) at baseline. Most participants classified with CKD stage 2 (GFR 60-89 mL/min) or stage 3 (GFR 30-59 mL/min) at baseline did not change stage, whereas 55% of people with CKD stage 1 (GFR > 90 mL/min) at baseline worsened to stage 2 and 10% worsened to stage 3. An abnormal high level of serum creatinine at baseline did not help to predict who might worsen at follow-up. Older people with CKD displayed a low progression of renal disease and therefore are at higher risk for co-morbidities related to CKD than for progression to end-stage renal disease.

Non-invasive monitoring of hemodynamic parameters during hemodialysis.

We studied in 13 hemodialysis patients intradialytic variations of blood volume (BV) and cardiac output, by means of non-invasive methods. We found a weak correlation, r 0.2 or less, between BV variations and intradialysis blood pressure variations. The sensitivity of the former in describing the variations of the latter was only 32%. During the 30 min preceeding the hypotensive crisis the percent BV variations did not show any predictive trend. On the contrary, refilling increased as blood pressure dropped and a weak inverse relation (r -0.35) was found between these two parameters. Unstable patients had predialytic blood volume values significantly lower than stable ones and comparable to healthy subjects. On the contrary, the correlation between percent variations of cardiac output index and MAP was 0.68 with a sensitivity and specificity of 90% and 59%, respectively. Unfortunately these promising results were obtained only with an estimate of cardiac output obtained by echocardiography and not by transthoracic impedance cardiography, which is much more feasible than the former as on-line monitoring of cardiac output. On-line monitoring of hemodynamic parameters is an appealing but still unsolved task.

Effectiveness of Bortezomib in Cardiac AL Amyloidosis: A Report of Two Cases

Cardiac involvement is a major prognostic determinant in patients with primary AL amyloidosis. The clinical results of standard therapeutic approaches are suboptimal. It has been recently shown that bortezomib, an inhibitor of the proteasome, can induce rapid favourable responses in AL amyloidosis improving cardiac function and survival. Herein we report on two patients with cardiac amyloidosis treated by bortezomib who experienced partial or total remission of hematologic disease and of cardiac involvement. However, death of one patient, suffering from chronic kidney disease stage 5, due to fulminant respiratory syndrome suggests the need for caution in bortezomib use if patients have this comorbid condition.