Effect of small vs large muscle mass endurance training on maximal oxygen uptake in organ transplanted recipients.

Maximal oxygen consumption (V̇O2max) is impaired in heart (HTx), kidney (KTx), and liver (LTx) transplanted recipients and the contribution of the cardiovascular, central, and peripheral (muscular) factors in affecting V̇O2max improvement after endurance training (ET) has never been quantified in these patients. ET protocols involving single leg cycling (SL) elicit larger improvements of the peripheral factors affecting O2 diffusion and utilization than the double leg (DL) cycling ET. Therefore, this study aimed to compare the effects of SL-ET vs DL-ET on V̇O2max. We determined the DL-V̇O2max and maximal cardiac output before and after 24 SL-ET vs DL-ET sessions on 33 patients (HTx = 13, KTx = 11 and LTx = 9). The DL-V̇O2max increased by 13.8% ± 8.7 (p < 0.001) following the SL-ET, due to a larger maximal O2 systemic extraction; meanwhile, V̇O2max in DL-ET increased by 18.6% ± 12.7 (p < 0.001) because of concomitant central and peripheral adaptations. We speculate that in transplanted recipients, SL-ET is as effective as DL-ET to improve V̇O2max and that the impaired peripheral O2 extraction and/or utilization play an important role in limiting V̇O2max in these types of patients. Novelty: SL-ET increases V̇O2max in transplanted recipients because of improved peripheral O2 extraction and/or utilization. SL-ET is as successful as DL-ET to improve the cardiorespiratory fitness in transplanted recipients. The model of V̇O2max limitation indicates the peripheral factors as a remarkable limitation to the V̇O2max in these patients.

Analysis of the Clinical and Epidemiological Meaning of Screening Test for SARS-CoV-2: Considerations in the Chronic Kidney Disease Patients during the COVID-19 Pandemic.

The COronaVIrus Disease 19 (COVID-19) pandemic is an emerging reality in nephrology. In a continuously changing scenario, we need to assess our patients' additional risk in terms of attending hemodialysis treatments, follow-up peritoneal dialysis, and kidney transplant visits. The prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-20 infection in the general population plays a pivotal role in estimating the additional COVID-19 risk in chronic kidney disease (CKD) patients. Unfortunately, local prevalence is often obscure, and when we have an estimation, we neglect the number of asymptomatic subjects in the same area and, consequently, the risk of infection in CKD patients. Furthermore, we still have the problem of managing COVID-19 diagnosis and the test's accuracy. Currently, the gold standard for SARS-CoV-2 detection is a real-time reverse transcription-polymerase chain reaction (rRT-PCR) on respiratory tract samples. rRT-PCR presents some vulnerability related to pre-analytic and analytic problems and could impact strongly on its diagnostic accuracy. Specifically, the operative proceedings to obtain the samples and the different types of diagnostic assay could affect the results of the test. In this scenario, knowing the local prevalence and the local screening test accuracy helps the clinician to perform preventive measures to limit the diffusion of COVID-19 in the CKD population.

Pilot health technology assessment study: organizational and economic impact of remote monitoring system for home automated peritoneal dialysis.

PURPOSE: Follow-up of automated peritoneal dialysis (APD) has been improved by data transmission by cellular modem and internet cloud. With the new remote patient monitoring (RPM) technology, clinical control and prescription of dialysis are performed by software (Baxter Claria-Sharesource), which allows the center to access home operational data. The objective of this pilot study was to determine the impact of RPM compared to traditional technology, in clinical, organizational, social, and economic terms in a single center. METHODS: We studied 21 prevalent APD patients aged 69 ± 13 years, on dialysis for a median of 9 months, for a period of 6 months with the traditional technology and 6 months with the new technology. A relevant portion of patients lived in mountainous or hilly areas. RESULTS: Our study shows more proactive calls from the center to patients after the consultation of RPM software, reduction of calls from patients and caregivers, early detection of clinical problems, a significant reduction of unscheduled visits, and a not significant reduction of hospitalizations. The analysis also highlighted how the RPM system lead to relevant economic savings, which for the health system have been calculated € 335 (mean per patient-month). With the social costs represented by the waste of time of the patient and the caregiver, we calculated € 685 (mean per patient-month). CONCLUSION: In our pilot report, the RPM system allowed the accurate assessment of daily APD sessions to suggest significative organizational and economic advantages, and both patients and healthcare providers reported good subjective experiences in terms of safety and quality of follow-up.

Gadolinium-Based Contrast Media Nephrotoxicity in Kidney Impairment: The Physio-Pathological Conditions for the Perfect Murder.

Gadolinium-based contrast media (GBCM) toxicity in patients with kidney disease is a concern for the possible development of systemic nephrogenic fibrosis and possible renal complications. This review focuses on the pathological mechanisms underlying the potential kidney toxicity of gadolinium. Gadolinium, as a free compound (Gd3+), is highly toxic in humans because it competes with divalent calcium (Ca2+) and magnesium (Mg2+) ions, interfering in some relevant biologic processes. Its toxicity is blunted by the complexing of Gd3+ with a carrier, allowing its use in magnetic resonance imaging. The binding reaction between gadolinium and a carrier is thermodynamically reversible. Consequently, under some conditions, gadolinium can be released in the interstitial space as a free Gd3+ compound with the possibility of toxicity. Other metals such as iron, copper, and calcium can interfere with the binding between gadolinium and its carrier because they compete for the same binding site. This process is known as transmetallation. In patients with kidney impairment, conditions such as low clearance of the Gd-carrier complex, acid-base derangements, and high serum phosphorous can increase the presence of free Gd3+, leading to a higher risk for toxicity.

Gadolinium-based contrast media exposure and the possible risk of subclinical kidney damage: a pilot study.

PURPOSE: We performed a pilot study to evaluate the feasibility of future research about the presence of subclinical kidney damage after Gadolinium-based contrast media exposure. The future study aims to understand which are the behaviors of two markers of kidney damage, such as urinary NephroCheck (NC) and/or neutrophil gelatinase-associated lipocalin (NGAL). Specifically, after GBCM exposure, NC urinary detection should identify proximal tubule damage while NGAL urinary detection should be related to distal tubule damage. METHODS: We performed a pilot study in patients who had Gadolinium exposure. The feasibility of future study is reached when at least 90% of candidates completed the pilot study. In each patient, we tested urinary NC and NGAL levels 24 h before magnetic resonance imaging (MRI) and 12-24 h after the exposure. Furthermore, we evaluated the administration of other nephrotoxic agents, the presence of comorbidity, and kidney function by S-creatinine and urine protein before the MRI. RESULTS: We enrolled 35 candidates of whom 33 patients completed all study procedures. Our population had a mean age of 60.7 ± 14.8 years with normal kidney function with a median S-creatinine equal to 0.7 mg/dl (Interquartile range [IQR] 0.6-0.91). Urinary NC levels increased from 0.21 ng2/ml2 (IQR 0.11-0.4) before MRI to 0.34 ng2/ml2 (IQR 0.16-0.86) (p = 0.005). Conversely, we did not appreciate any significant modification in urinary NGAL (p = 0.53). CONCLUSION: Our pilot study seems adequate in terms of feasibility and encourages us to focus our future research on renal proximal tubule, as the principal site of subclinical kidney damage after Gadolinium exposure.

Home dialysis and home assistance: from institutional aids to a sustainable model / [Dialisi domiciliare e assistenza a domicilio: dalle provvidenze istituzionali verso un modello sostenibile].

Home dialysis, and mainly peritoneal dialysis, is indicated as the optimal choice as far as the comfort and lifestyle of uremic patients is concerned. Despite this, home treatments show a lack of growth. The reasons are mainly linked to the patients' cognitive, psychosocial, familiar and physical barriers due to aging and morbidity. To overcome these barriers, we analyzed all the available institutional aids: civil disability, not-self-sufficiency funds, home, social and nursing assistance, expenses refunds. The assessment of the patients' needs is performed through validated instruments such as multidimensional evaluation (VMD) and equivalent economic index (ISEE). Overall, economic relief is limited to low income patients, and those in serious distress. Some Italian regions have issued specific measures dedicated to home dialysis. Our review shows a great heterogeneity of measures, centered in some cases on economic aids and on home assistance in others. Moreover, some Italian dialysis centers directly provide caregivers for home dialysis. The international literature describes many experiences relating to home dialysis assistance. Their common message is that, in developed countries, economic help is generally sustainable despite the heterogeneity of health care systems. Home support and economic aids for dialysis, in fact, are made possible by the overall savings enabled by home treatments and by the careful redistributions of the funds.

[The advantages of remote patient monitoring in automated peritoneal dialysis].

The follow-up automated peritoneal dialysis (APD) patients has been recently improved as data can be transmitted remotely to an internet cloud. The introduction of remote patient monitoring (RPM) technologies also allows a better clinical control and tailoring of dialysis treatment through a web-based software (Claria-Sharesource Baxter). The aim of the present study is to determine the impact of RPM in a single center, both in clinical and organizational terms, compared to traditional technologies. We studied 26 prevalent APD patients aged 69±13 years, observing them for a period of six months while using the traditional technology and then further six months using the new technology. The patients had been on dialysis for 9 months before the start of the study and a relevant portion of them lived in mountainous or hilly areas. Our study shows an increase in the number of proactive calls from the center to the patients, a reduction of anxiety in patients and caregivers, an earlier detection of clinical problems, a reduction of unscheduled (urgent) visits and finally a reduction of hospitalizations after the adoption of RPM software. In our experience, the RPM system showed a good performance and a simple interface, allowing for the precise assessment of daily APD. Furthermore, RPM system improved the interaction between patients and healthcare providers, with a significant benefit in terms of safety and of care quality.

Are E-test and Vitek2 good choices for tigecycline susceptibility testing when comparing broth microdilution for MDR and XDR Acinetobacter baumannii?

This study reports the results of antimicrobial susceptibility testing of 10 MDR and 74 XDR Acinetobacter bauman- nii clinical isolates from our hospital routine. We used three different methods: two automated systems (Sensititre and VITEK 2) and one standardized manual method (E-test). Since many published papers refer to in vitro tests performed by E-test, the aim of this study was to test if this method is reliable for testing tigecycline. The results obtained show that E-test significantly overestimates the MIC of the broth microdilution (reference test), thus ob- taining a significant number of major errors (resistant instead of sensitive). VITEK 2 also shows the same problem, but it is less critical. We therefore conclude that these methods do not seem to be very reliable in the performance of susceptibility testing of MDR and XDR Acinetobacter baumannii against tigecycline.

[Trend in PD in non-pediatric public centers in Italy: results of the 2010 GSDP-SIN census and comparison with the 2008 and 2005 censuses]. / Andamento della DP in Italia nei centri pubblici non pediatrici: Risultati del censimento GSDP-SIN 2010 e confronto con i censimenti 2008 e 2005.

The 2010 Italian Society of Nephrology Peritoneal Dialysis Study Group (GSPD-SIN) census (Cs-10) involved the 224 Centers performing PD in Italy. PD was used as 1st treatment in 23.3% (1429/4695) of pts (Cs-08:22.8%; Cs-05:24.2%), with 53.4% of them using CAPD. The use of incremental CAPD increased in Cs-10 (Cs-10:35.3%; Cs-08:25.7%; Cs-05:13.6%; p<0.0001). The number of prevalent pts was 4,222 (Cs-10:16.6%; Cs-08:16.6%; Cs-05:16.8%; p=NS), 45.7% of whom were on CAPD; 24.4% (Cs-08:21.8%; p<0.05) required assistance (family member:80.6%; caregiver:12.6%; nurse: 3.0%; RSA:3.4%). In Cs-10 the PD out rate (1,354 pts, of whom ep/100pt-yrs for drop-out: 12.4; death: 12.9; Tx: 7.5) was not different to previous years. The peritonitis rate was 0.30 ep/yr/pt, 18.5% of which with negative culture. There were 44 episodes of EPS in the period 2009-10 (0.53 ep/100yrs); while in the previous 5-year period there were 146 (0.70 ep/100pt-yrs). PET is performed by 98% of the centers, mostly using 2.27% (70.5%). Home visits are carried out by 59.1% of the centers. If regular (8.9% of the centers), they are associated with fewer ep/mth of peritonitis (61.2 vs 38.8) and lower drop-out (8.6 vs 12.8 ep/100 pt/yr - p<0.05) Cs-10 confirms the good results PD is having in the Centers that use it. Incremental CAPD and assisted PD are increasing. EPS remains a rare event. Standard PET is the most frequently-used evaluation of the peritoneal membrane. Though home visits are associated with lower peritonitis and drop-out rates, they are carried out regularly by a minority of the Centers.

The peritoneal dialysis catheter.

The results obtained from the positioning and management of the catheter for peritoneal dialysis depend on the techniques used, but also and above all, on the experience of the practitioners. A comparison between practitioners may help to change their convictions, as well as to further improve results, in the interests of patient welfare. This is the aim of these Best Practice Guidelines..

Peritoneal ultrafiltration in patients with advanced decompensated heart failure.

The aim of the Best Practice guidelines on peritoneal ultrafiltration (UF) in patients with treatment-resistant advanced decompensated heart failure (TR-AHDF) is to achieve a common approach to the management of decompensated heart failure in those situations in which all conventional treatment options have been unsuccessful, and to stimulate a closer cooperation between nephrologists and cardiologists. The standardization of the case series of different centers would allow a better definition of the results published in the literature, without which they are nothing more than anecdotes. TR-AHDF is characterized by the persistence of severe symptoms even when all possible pharmacological and surgical options have been exhausted. These patients are often treated with methods that allow extracorporeal UF - slow continuous ultrafiltration (SCUF) and continuous renal replacement therapy (CRRT) - which have to be performed in hospital facilities. Peritoneal ultrafiltration (PUF) can be considered a treatment option in patients with TR-AHDF when, despite the fact that all treatment options have been used, patients meet the following criteria: • stage D decompensated heart failure (ACC/AHA classification); • INTERMACS level 4 decompensated heart failure; • INTERMACS frequent flyer profile; • chronic renal failure (estimated glomerular filtration rate <50 ml/min per 1.73 m2: KDOQI classification stage 3 chronic kidney disease); • no obvious contraindications to peritoneal UF. PUF treatment modes are derived from the treatment regimens proposed by various authors to obtain systemic UF in patients with severe decompensated heart failure, using manual and automated incremental peritoneal dialysis involving various glucose concentrations in addition to the single icodextrin exchange. These guidelines also identify a minimum set of tests and procedures for the follow-up phase, to be supplemented, according to the center's resources and policy, with other tests that are less routine or more complex also from a logistic/organizational standpoint, emphasizing the need for the patient's clinical and treatment program to involve both the nephrologist and the cardiologist. The pathophysiological aspects of a deterioration in kidney function in patients with decompensated heart failure are also considered, and the results of PUF in patients with decompensated heart failure reported in the various case series are reviewed.

Neutrophil gelatinase-associated lipocalin in peritoneal effluent: evaluation in peritoneal dialysis patients in basal condition.

PURPOSE: In the present study, we assessed expression of neutrophil gelatinase-associated lipocalin (NGAL) in peritoneal effluent (pNGAL) from peritoneal dialysis (PD) patients, and we evaluated factors that might affect its level in basal conditions. METHODS: Our cross-sectional study included all 69 patients on PD at our institution. We evaluated patient history, hydration status, residual renal function, indices of dialysis adequacy, peritoneal transport type, serum C-reactive protein, ferritin, serum NGAL (sNGAL) and pNGAL. Univariate and multivariate linear regression models were used to evaluate predictors of pNGAL. RESULTS: Of the study patients, 39 (56.5%) were men, and 54 (78.3%) were on continuous ambulatory PD. Median age in the group was 61 years [interquartile range (IQR): 46.5 - 71 years]. Median sNGAL was 487 ng/mL (IQR: 407 - 586 ng/mL), and median pNGAL was 35 ng/mL (IQR: 21 - 46 ng/mL). dNGAL correlated directly with weekly dialytic clearance of creatinine (ρ = 0.291, p = 0.02) and with sNGAL (ρ = 0.269, p = 0.031). The same variables were also independent predictors of pNGAL (ß = 0.30 and 0.29 respectively, both p < 0.05) in multivariate analysis. CONCLUSIONS: In our analysis, basal levels of pNGAL were influenced by sNGAL and by dialytic clearance of creatinine.

Soluble transferrin receptors and reticulocyte hemoglobin concentration in the assessment of iron deficiency in hemodialysis patients.

BACKGROUND: Diagnosing iron deficiency in hemodialysis (HD) patients is crucial for correct anemia management. Hypochromic erythrocytes appear to be the best available marker, but they are often unavailable. Transferrin saturation (TSAT) and ferritin are also indicated as reference markers by guidelines. We evaluated the usefulness of soluble transferrin receptor (s-TfR) and reticulocyte hemoglobin concentration (CHr), which have been recently proposed as more sensitive functional iron deficiency indicators. METHODS: A single-center unselected cohort of 39 chronic HD patients underwent a cross-sectional determination of hemoglobin (Hb), hematocrit (Hct), CHr, transferrin, iron, TSAT, ferritin, folate, vitamin B12 and s-TfR. Twenty-nine patients (74.4%) were treated with subcutaneous erythropoietin (EPO) at a dose of 122 +/- 98 U/kg/week and 24 patients (61.5%) were treated with intravenous (i.v.) iron gluconate, 62.5 mg/week. RESULTS: Hb was 11.1 +/- 1.2 g/dL, Hct 34.4 +/- 3.7%, CHr 32.7 +/- 3.8 pg, transferrin 170 +/- 31 mg/dL, iron 60.2 +/- 25.9 mg/dL, TSAT 30 +/- 18%; ferritin 204 +/- 219 ng/mL, folate 4.2 +/- 1.0 mcg/L, vitamin B12 0.58 +/- 0.15 mcg/L, and s-TfR 1.94 +/- 0.83 mg/L. Both TSAT and s-TfR significantly correlated with CHr, but no relationship could be found between s-TfR and TSAT or between s-TfR and ferritin. Dividing the population into two groups based on iron repletion (ferritin >100 ng/mL and TSAT >20%) we found no differences for CHr levels and significantly lower levels of s-TfR in the replete group (s-TfR 1.71 +/- 0.70 vs. 2.29 +/- 0.90 mg/L; p=0.033). Analysis of 2x2 tables demonstrated that 44% of patients with TSAT >20% had elevated (>1.5 mg/L) s-TfR, indicating a possible functional iron deficiency, but covariance analysis showed that TSAT had a better correlation to CHr. CONCLUSIONS: No clear-cut advantages in the use of CHr content and s-TfR levels as single diagnostic tests could be demonstrated by this cross-sectional study. However, our results suggest that the combined use of TSAT <20% and s-TfR >1.5 mg/L (therefore, including all patients with low TSAT, but also patients with high s-TfR despite normal TSAT) could improve functional iron deficiency detection in dialysis patients suspected of having inflammatory conditions.

Determination of high and low molecular weight molecules of icodextrin in plasma and dialysate, using gel filtration chromatography, in peritoneal dialysis patients.

OBJECTIVE: The aim of this study was to apply high performance liquid chromatography (HPLC) with modern gel filtration media to determine high molecular weight (HMW) icodextrin fractions and low molecular weight (LMW) icodextrin metabolites in dialysate and plasma in peritoneal dialysis (PD) patients on treatment with icodextrin, and to explore the potential relationships between these compounds, alpha-amylase activity, and glomerular filtration rate. DESIGN: Retrospective study of dialysate and plasma samples from PD patients. SETTING: Samples were collected at one PD center. PATIENTS: Blood and dialysate samples were obtained from PD patients who were subdivided into three groups: patients using only glucose-based peritoneal dialysis fluid (GPDF; GLU group, n = 23), patients studied after the first long dwell with icodextrin-based peritoneal dialysis fluid (IPDF; 1st ICO group, n = 24), and patients who were regular users of IPDF for the long dwells (ICO group, n = 9). METHODS: LMW icodextrin metabolites [i.e., maltose (G2), maltotriose (G3), maltotetraose (G4), maltopentaose (G5), maltohexaose (G6), and maltoheptaose (G7)] and HMW fractions were determined in plasma and dialysate using two different gel filtration HPLC methods. Enzymatic hydrolysis with amyloglucosidase to glucose yielded the total carbohydrate content and this was used to validate the HPLC results. alpha-Amylase activity was determined using a routine method. RESULTS: The results obtained by gel filtration HPLC yielded values of LMW metabolites and HMW fractions in plasma and dialysate in agreement with results obtained with enzymatic hydrolysis. HMW fractions were not detectable in plasma. Absorption of icodextrin from the peritoneal cavity during the long dwell (10 - 16 hours) was, on average, 39% of the amount instilled. During the long dwell, there was a relative decrease in the dialysate concentration of the largest HMW fractions (>21.4 kDa). Plasma concentration of the LMW icodextrin metabolites G2-G7 was highest in the ICO group (2.65+/-0.54 mg/mL) but also higher in the 1st ICO group (1.97+/-0.57 mg/mL) compared with the GLU group (0.52+/-0.23 mg/mL). Plasma alpha-amylase activity was significantly lower in the 1st ICO group and in the ICO group compared with the GLU group. CONCLUSIONS: Accurate analysis of HMW icodextrin fractions in dialysate and LMW icodextrin metabolites in plasma and dialysate in PD patients can be achieved by gel filtration HPLC with two different columns. This method can be used to study the complex pattern of changes in icodextrin and its metabolites in plasma and dialysate. The finding that HMW icodextrin fractions were not detected in plasma was unexpected, and differs from results of previous studies by other researchers.

Middle molecule and small protein removal in children on peritoneal dialysis.

BACKGROUND: Dialysis efficiency has a great influence on the outcome of patients. Few data are available on the removal of solutes with molecular weights higher than urea and creatinine. The aim of our study was to assess the transport and the removal of substances with molecular weights up to 15 kD and to evaluate the contribution of residual renal function in peritoneal dialysis (PD) children. METHODS: Seventeen patients of 12 +/- 4 years undergoing automated PD were studied. Ten patients had 563 +/- 355 mL/day of urine output, and 7 were anuric. During a standardized nightly intermittent PD (NIPD) session, a single-injection inulin clearance was performed. Urea, creatinine, inulin (measured by HPLC), cystatin C and beta2-microglobulin (beta2m) were measured in blood, urine and dialysate. Clearances (L/week/1.73 m2) and weekly solute removal index (SRI) were calculated for all the solutes; weekly Kt/V was calculated for urea. RESULTS: In non-anuric versus anuric patients the total clearances were: urea 82.6 +/- 18.3 versus 71.3 +/- 26.4; creatinine 82.7 +/- 28.6 versus 47.8 +/- 18.8; inulin 42.8 +/- 11.3 versus 32.8 +/- 20.4; beta2m 14.2 +/- 13.8 versus 9.2 +/- 8.3; cystatin C 20.2 +/- 9.4 versus 9.7 +/- 4.8. In the patients with residual diuresis, the urea was removed mainly by PD (69.2%), while inulin, beta2m and cystatin C were removed by renal clearance (64.0%, 79.5% and 62.8%, respectively). Total, peritoneal and renal weekly Kt/V values in the subjects with residual renal function, were 2.86 +/- 0.70, 1.99 +/- 0.40 and 0.87 +/- 0.43, respectively. Peritoneal weekly Kt/V in the anuric patients was 2.36 +/- 0.85; total weekly Kt/V in the total group was 2.65 +/- 0.78. Weekly SRIs in non-anuric versus anuric patients were: urea 2.56 +/- 0.58 versus 2.09 +/- 0.74; creatinine 2.66 +/- 0.73 versus 1.46 +/- 0.56; inulin 2.36 +/- 0.92 versus 1.64 +/- 1.60; beta2m 1.26 +/- 1.10 versus 1.20 +/- 1.90; cystatin C 1.72 +/- 0.83 versus 1.58 +/- 1.62. CONCLUSIONS: Solutes removed during PD tend to decrease following an increase in molecular weight of the substance. Since anuric patients are at higher risk of middle molecule and small protein accumulation, more attention should be paid to the removal of middle molecules. Further studies should be undertaken to evaluate whether removing them has a clinical impact and to determine their threshold levels.