Respiratory syncytial virus vs. Influenza virus infection: mortality and morbidity comparison over 7 epidemic seasons in an elderly population.

BACKGROUND: Respiratory syncytial virus (RSV) infection is gaining interest due to the recent development of vaccines, but it is still misdiagnosed in the elderly. The primary objective was to compare all-cause mortality at day 30. Secondary objectives were to compare clinical presentation, and rates of consolidative pneumonia, hospitalization, and intensive care unit (ICU) admission. METHODS: Single-centre retrospective study conducted in a French university hospital during 7 epidemic seasons. All patients aged ≥75 years were included. RESULTS: 558 patients were included: 125 with RSV and 433 with Influenza. Median age was 84.8 years. RSV patients had more respiratory symptoms (wheezing, dyspnea), whereas Influenza patients had more general symptoms (fever, asthenia, myalgia). Consolidative pneumonia (28.8% vs. 17.2%; p = 0.004), hospitalization rates (83.2% vs. 70%; p = 0.003), ICU admissions (7.2% vs. 3.0%; p = 0.034) and length of stay (9 days [2-16] vs. 5 days [0-12]; p = 0.002), were higher in the RSV group. Mortality rates at day 30 were comparable (RSV 9.6%, Influenza 9.7%; p = 0.973). CONCLUSIONS: This study included the largest cohort of RSV-infected patients aged over 75, documented in-depth thus far. RSV shares a comparable mortality rate with Influenza but is associated with higher rates of consolidative pneumonia, hospitalization, ICU admissions, and extended hospital stays.

Hyper/hypoglycemia and acute kidney injury in critically ill patients.

BACKGROUND & AIMS: Abnormalities of blood glucose (BG) concentration (hyper- and hypoglycemia), now referred to with the cumulative term of dysglycemia, are frequently observed in critically ill patients, and significantly affect their clinical outcome. Acute kidney injury (AKI) may further complicate glycemic control in the same clinical setting. This narrative review was aimed at describing the pathogenesis of hyper- and hypoglycemia in the intensive care unit (ICU), with special regard to patients with AKI. Moreover, the complex relationship between AKI, glycemic control, hypoglycemic risk, and outcomes was analyzed. METHODS: An extensive literature search was performed, in order to identify the relevant studies describing the epidemiology, pathogenesis, treatment and outcome of hypo- and hyperglycemia in critically ill patients with AKI. RESULTS AND CONCLUSION: Patients with AKI are at increased risk of both hyper-and hypoglycemia. The available evidence does not support a protective effect on the kidney by glycemic control protocols employing Intensive Insulin Treatment (IIT), i.e. those aimed at maintaining normal BG concentrations (80-110 mg/dl). Recent guidelines taking into account the high risk for hypoglycemia associated with IIT protocols in critically ill patients, now suggest higher BG concentration targets (<180 mg/dl or 140-180 mg/dl) than those previously recommended (80-110 mg/dl). Notwithstanding the limited evidence available, it seems reasonable to extend these indications also to ICU patients with AKI.

[Disglycemia in patients with acute kidney injury in the ICU]. / Alterazioni glicemiche nel danno renale acuto in terapia intensiva.

Derangements of glucose metabolism are common among critically ill patients. Critical illness- associated hyperglycemia (CIAH) is characterized by raised blood glucose levels in association with an acute event that is reversible after resolution of the underlying disease. CIAH has many causes, such as changes in counter-regulatory hormone status, release of sepsis mediators, insulin resistance, drugs and nutritional factors. It is associated with increased mortality risk. This association appears to be strongly influenced by diabetes mellitus as a comorbidity, suggesting the need for an accurate individualization of glycemic targets according to baseline glycemic status. Hypoglycemia is also very common in this clinical context and it has a negative prognostic impact. Many studies based on intensive insulin treatment protocols targeting normal blood glucose values have in fact documented both an increased incidence of hypoglycemia and an increased mortality risk. Finally, glycemic control in the ICU is made even more complex in the presence of acute kidney injury. On one hand, there is in fact a reduction of both the renal clearance of insulin and of gluconeogenesis by the kidney. On the other hand, the frequent need for renal replacement therapy (dialysis / hemofiltration) may result in an energy intake excess, under the form of citrate, lactate and glucose in the dialysate/reinfusion fluids. With regard to the possible renal protective effects afforded by intensive glycemic control protocols, the presently available evidence does not support a reduction in the incidence of AKI and/or the need for RRT with this approach, when compared with standard glucose control. Thus, the most recent guidelines now suggest higher blood glucose targets (<180 mg/dl or 140-180 mg/dl) than in the past (80-110 mg/dl). Albeit with limited evidence, it seems reasonable to extend these indications also to patients with AKI in the intensive care unit. Further studies are needed in order to better ascertain the effects of dysglycemia on the outcome of patients with AKI.

Echographic renal dimensions can predict glomerular filtration rate of potential living kidney donors.

In potential living kidney donors, glomerular filtration rate (GFR) is often evaluated from the creatinine clearance (Ccr) or is predicted using formulas based on serum creatinine (SCr) or cystatin C (SCys) concentration. Ultrasonography is used to evaluate renal structure and dimensions. The objective of the present study was to evaluate the possibility of estimation of GFR from echographic renal dimensions in 66 potential live kidney donors (46 women and 20 men; age range, 25-73 years). The GFR was measured as the renal clearance of technetium 99m diethylenetriamine pentaacetic acid. The GFR was also estimated from the SCr concentration using the Cockcroft-Gault (CG-Ccr) and Modification of Diet in Renal Disease (MDRD-GFR) formulas and from SCys (Cys-GFR). Renal diameters were measured using conventional gray-scale renal ultrasound to estimate total and parenchymal renal volume using ellipsoid formulas. The GFR was predicted from renal dimensions on the basis of their relationship to measured GFR. Estimates of GFR obtained using renal volume more close correlated with measured GFR than did CG-Ccr, MDRD-GFR, or Cys-GFR. The mean difference from measured GFR was null. The GFR estimated from renal volume demonstrated better agreement with measured GFR and a lower prediction error vs values from the other prediction formulas (18.3 vs 22-34 mL/min). The GFR values predicted from renal volume were quite accurate as indicators of GFR less than 80 mL/min. In potential living kidney donors, sonographic renal volume provided more accurate estimates of GFR, with lower prediction error, compared with formulas based on SCr or SCys.

[Role of beta-glucan in the treatment of recurrent candidiasis and HPV-correlated lesions and reparative process of epidermis]. / Beta-glucano e terapia delle candidosi recidivanti e delle disepitelizzazioni cutanee iatrogene.

AIM: The aim of the study was to examine the effects of beta-glucan treatment in women with recurrent vulvar candidiasis or previously treated with diathermocoagulation (DTC) for vulvar lesions caused by human papillomavirus (HPV) infection. METHODS: From January to March 2008, 23 women with a history of recurrent candidiasis and 209 women who underwent to DTC for HPV-correlated vulvar lesions were recruited at the Department of Obstetrics and Gynaeco-logy of San Camillo-Forlanini Hospital of Rome. The two groups were treated with two cycles of a daily topical application of beta-glucan for 15 consecutive days with a suspension of 20 days. The effects of beta-glucan were analyzed at the 1st and the 3rd month from the start of the therapy. RESULTS: A total of 209 women, 21 with recurrent candidiasis and 188 who underwent to DTC for HPV-correlated lesions, completed the study. After the first month of treatment we not found any evidence of disease in both groups; otherwise we observed, a month after the term of the therapy, 5% and 3% of recurrence of candidiasis or lesions secondary to HPV infection, respectively, even if with low grade. CONCLUSIONS: Our results demonstrate the efficacy of beta-glucan treatment for recurrent candidiasis, HPV-correlated lesions and in the reparative process of epidermis.

Recurrent syncope in elderly patients and tilt test table outcome: the role of comorbidities.

Syncope is a common disorder that can lead to serious consequences in the elderly. Tilt-test is a safe, useful specific tool to investigate recurrent syncope also in the elderly. Comorbidities and medication use, widely present in elderly patients, affecting the hemodynamic response, can influence the tilt-test outcome. The aim of this study was to evaluate the influence of these confounding factors on tilt-test results in elderly patients with recurrent syncope. We included in this study a consecutive group of 87 patients>75 years (82.1+/-4.3 years) with unexplained syncope. They underwent passive upright tilt-test. Heart rate an blood pressure were recorded using non-invasive devices. The patients were classified according to the modified Vasovagal Syncope International Study (VASIS). Comorbidities were measured with the geriatric index of comorbidities (GIC), which is a composite score taking into account both the number of diseases and their severity as measured by Greenfield's IDS. The tilt-test was positive in 22 patients. There were no significant differences in clinical characteristics, and medication use between the tilt-test negative and positive patients, except for the GIC score (1.12+/-0.5 vs. 2.42+/-0.48; p=0.001) and for a reduced number of medications in the former group (5.7+/-3.1 vs. 8.2+/-2.4; p=0.001). This study suggests that comorbidities and the number of medications could influence tilt test outcome.

Living kidney transplantation: evaluation of renal function and morphology of potential donors.

The evaluation of potential living kidney donors requires an accurate study of renal function and morphology. The gold standard to assess renal function is the measurement of glomerular filtration rate (GFR). However, GFR is often estimated from serum creatinine (SCr), cystatin C (SCys), or creatinine clearance (CCr). Otherwise, GFR is predicted using formulas based on SCr or SCys. Ultrasound scanning evaluates morphology and dimensions, while scintigraphy provides information on morphofunctional symmetry of kidneys. The aim of this study in 79 potential donors was to assess the accuracy of the tests employed to estimate GFR and the utility of renal ultrasound and scintigraphy for morphofunctional evaluation of potential donors. GFR (clearance of (99m)Tc-DTPA) was compared with estimates obtained with Cockcroft and Gault (CG-CCr) and Modification of Diet in Renal Disease (MDRD-GFR) formulas, and from SCys (Cys-GFR). The correlation with GFR was statistically significant for SCys and for all estimates, but not for SCr. CCr showed a poor agreement with GFR, with a large range of agreement and a marked and significant overestimation of GFR (33.8 mL/min). The accuracy of CG-CCr and MDRD-GFR as indicators of a GFR < 80 mL/min was better than that of Cys-GFR and CCr. However, their mean prediction errors versus GFR were relevant. Renal dimensions, particularly renal volume, showed a good correlation with GFR. The correlation was higher than that of all prediction equations. The direct measurement of GFR remains the reference method to assess renal function in potential kidney donors. The measurement of renal dimensions can provide useful information also on renal function.

Single- and multi-frequency bioelectrical impedance analyses to analyse body composition in maintenance haemodialysis patients: comparison with dual-energy x-ray absorptiometry.

The aim of this study was to evaluate the adequacy of single-frequency (sf-BIA) and multi-frequency bioelectrical impedance analyses (mf-BIA), in comparison with dual-energy x-ray absorptiometry (DXA), to evaluate body composition in maintenance haemodialysis (MHD) patients. Body composition of 27 adult MHD patients (9 f, 18 m), BMI 17.5-34.4 kg m(-2), was examined with DXA and BIA, with two different sf-BIA and 1 mf-BIA analysers. Biochemical markers of nutritional status and adequacy of dialytic treatment were also determined. Fat mass (FM) estimated by the different BIA analysers was found to be slightly but significantly higher than FM measured by DXA. In contrast, fat-free mass (FFM) obtained with BIA was found to be slightly but significantly lower than FFM DXA. No significant differences were found between LBM-DXA (that is FFM-DXA minus bone mass) and the different FFM BIA. The lowest mean prediction error versus DXA values was found with sf1BIA. In any case, a close correlation was found between all BIA values and DXA values, particularly for FFM. Furthermore, FFM and LBM results were significantly correlated with serum creatinine, which in MHD patients is an indicator of muscle mass. These results indicate that BIA can be used to evaluate body composition in MHD patients.

Kidney dimensions at sonography are correlated with glomerular filtration rate in renal transplant recipients and in kidney donors.

The gold standard to assess renal function is the measurement of glomerular filtration rate (GFR). For practical reasons, renal function is often evaluated from serum creatinine (S Cr) or cystatin C (S Cys), and GFR is predicted from SCr. Ultrasound scanning of the kidneys is used only to evaluate renal morphology. The aim of this study was to evaluate the relationship between sonographic renal dimensions and GFR in renal transplant recipients and in kidney donors. GFR (urinary clearance of (99m)Tc-DTPA), S Cr, and S Cys were measured in 33 donors (28 females [F], 5 males [M]; SCr, 0.81-1.90 mg/dL) and 30 recipients (8 F, 22 M; SCr, 0.96-2.42 mg/dL). GFR was also predicted using the Cockcroft and Gault (CG) formula and with the simplified Modification of Diet in Renal Disease (MDRD) formula. Length, width, and depth of kidneys and renal sinus were measured using renal sonography. Among sonographic measurements, kidney length showed the best correlation with GFR. A closer correlation with GFR was found in donors (r = 0.639; P < .00007) than in recipients (r = 0.511; P < .005). In either case, the correlation of kidney length with GFR was greater than that of S Cr or S Cys, and similar to that of CG or MDRD GFR. Accuracy of kidney length as an indicator of GFR impairment was not statistically different from laboratory tests. Only in donors did CG show better accuracy. In conclusion, renal dimensions at sonography closely correlated with GFR. Thus, renal sonography can give information also on the function of the renal graft and of the remaining kidney of living donors.

Parathyroid hormone and large related C-terminal fragments increase at different rates with worsening of renal function in chronic kidney disease patients. A possible indicator of bone turnover status?

BACKGROUND: The intact parathyroid hormone (PTH) serum value has been the non-invasive biomarker of choice for the early diagnosis of renal bone disease in the chronic kidney disease (CKD) patient population. It has now been known that the intact PTH assay value is the sum of 1-84 PTH (true hypercalcemic PTH) and large C-terminal PTH fragments, mainly 7-84 PTH, a fragment with hypocalcemic hormone actions. AIM: The aim of this study was to investigate the differences among the different functional stages of CKD in the following PTH parameters: intact PTH, 1-84 PTH, 7-84 PTH, and the ratio 1-84 PTH/7-84 PTH. GFR (clearance of 99mTc-DTPA) was measured in 164 (85 males and 79 females) adult CKD patients with different degrees of renal function impairment (serum creatinine 0.50 12.1 mg/dl, mean 2.00). PATIENTS AND METHODS: Plasma concentrations of calcium, phosphate, 1-84 PTH and intact PTH were also measured. The value of 7-84 PTH was calculated as the difference between intact PTH and 1-84 PTH. The reduction of, GFR was accompanied by an increase of intact PTH, with a prevalent increase of 7-84 PTH over 1-84 PTH, resulting in a decrease of the ratio 1-84 PTH/7-84 PTH. RESULTS: The values of 7-84 PTH showed a discrimination between Stages 1 and 2 (GFR > 60 ml/min ) and Stage 3 (GFR 30 60 ml/ min) CKD patient populations. In fact, 7-84 PTH was already significantly increased in patients at CKD Stage 3. The analysis of individual patients indicated that a low value (< 1.4) of the ratio 1-84 PTH/7-84 PTH, suggestive for low bone turnover, was already found in more than 20% of CKD Stage 3 patients. CONCLUSION: The results of the present study demonstrate that the reduction in GFR is accompanied by a higher increase in 7-84 PTH with respect to 1-84 PTH, which suggests the possibility that bone metabolism and calcemic status are already reduced in patients with moderate renal failure (CKD Stage 3).

Cognitive function by brain event-related potentials (ERP) in elderly with borderline isolated systolic hypertension (BISH).

Several studies have shown a relationship between BISH and cerebrovascular events, but no studies have investigated a relationship with cognitive function. The aim was to assess the cognitive function in the elderly with recent BISH. According to WHO Guidelines (1999), we selected 10 elderly normotensives, 10 elderly with recently diagnosed (<2 years) BISH, and 10 elderly with recently diagnosed (<2 years) isolated systolic hypertension (ISH). They were submitted to 24-hr ambulatory blood pressure (BP) monitoring (ABPM) and to cognitive assessment by mini mental state examination (MMSE) and the recording of brain ERP, of type N2 and P300. The elderly with BISH, compared to normotensives, showed N2 wave latency values significantly higher, but similar P300 potential latency values and MMSE scores. The elderly with ISH showed N2 and P300 latency significantly higher than the normotensives. The gradual increase of the ERP latency values of the BISH and ISH elderly, in comparison to the normotensives, seems to indicate a gradual alteration of the cognitive processes related to the increase of BP.

Global approach to cardiovascular risk in chronic kidney disease: reality and opportunities for intervention.

The current implementation into nephrology clinical practice of guidelines on treatment of cardiovascular (CV) risk factors in chronic kidney disease (CKD) is unknown. We designed a cross-sectional analysis to evaluate the prevalence and treatment of eight modifiable CV risk factors in 1058 predialysis CKD patients (stage 3: n=486; stage 4: n=430, stage 5: n=142) followed for at least 1 year in 26 Italian renal clinics. The median nephrology follow-up was 37 months (range: 12-391 months). From stages 3 to 5, hypertension was the main complication (89, 87, and 87%), whereas smoking, high calcium-phosphate product and malnutrition were uncommon. The prevalence of proteinuria (25, 38, and 58%), anemia (16, 32, and 51%) and left ventricular hypertrophy (51, 55, and 64%) significantly increased, while hypercholesterolemia was less frequent in stage 5 (49%) than in stages 4 and 3 (59%). The vast majority of patients received multidrug antihypertensive therapy including inhibitors of renin-angiotensin system; conversely, diuretic treatment was consistently inadequate for both frequency and dose despite scarce implementation of low salt diet (19%). Statins were not prescribed in most hypercholesterolemics (78%), and epoietin treatment was largely overlooked in anemics (78%). The adjusted risk for having a higher number of uncontrolled risk factors rose in the presence of diabetes (odds ratio 1.29, 95% confidence interval 1.00-1.66), history of CV disease (odds ratio 1.48, 95% confidence interval 1.15-1.90) and CKD stages 4 and 5 (odds ratio 1.75, 95% confidence interval 1.37-2.22 and odds ratio 2.85, 95% confidence interval 2.01-4.04, respectively). In the tertiary care of CKD, treatment of hypertension is largely inadequate, whereas therapy of anemia and dyslipidemia is frequently omitted. The risk of not achieving therapeutic targets is higher in patients with diabetes, CV disease and more advanced CKD.

Renal effects of cardiac angiography with different low-osmolar contrast media.

The aim of this study was to evaluate the renal effects of cardiac angiography performed with three low-osmolar contrast media (CM): iopromide (IPR), ioversol (IVR) and ioxaglate (IOX). IPR and IVR are non-ionic CM, IOX is an ionic CM. Different parameters of renal function were determined before and 6, 24, 48, 72 hrs after angiography in 45 patients: 15 patients were examined with IPR, 15 with IVR and 15 with IOX. Glomerular effects--Plasma creatinine increased slightly at the 24th hour after IVR and IOX and at 48 hours after IOP. A significant increase in plasma beta2-microglobulin was observed, at the same time, only after IOX. A significant decrease in creatinine clearance was found at 6 hours after IOX. No significant variations in glomerular filtration rate (GFR) and in effective renal plasma flow were found at 48 hours after cardiac angiography; while filtration fraction was significantly reduced after IOP and IOX. Tubular effects--A marked decrease in sodium clearance and a relevant increase of urinary activities of different tubular enzymes were found after cardiac angiography with all CM, but were more evident after the ionic CM IOX, than after the two non-ionic agents. These tubular effects reached the maximum between 6 and 24 hours and returned to baseline within 72 hrs after cardiac angiography. In conclusion, slight glomerular effects were observed mainly after IOX. A reversible tubular malfunction was found with the three low-osmolar CM and was more evident after ionic CM IOX. thus suggesting that other mechanisms, besides osmolarity, play a role in tubular toxicity due to CM. In no patient did the glomerular and tubular effects of CM have a clinical relevance.

Reappraisal of serum beta2-microglobulin as marker of GFR.

INTRODUCTION: Beta 2 microglobulin (beta2M) is filtered by the glomeruli and reabsorbed by the proximal tubular cells where it is metabolized. Its plasma concentration increases with decreasing renal function. AIM: To compare serum creatinine (Cr) and serum beta2M as markers of GFR. PATIENTS AND METHODS: In 160 adult patients, with various kidney diseases and different GFR, serum Cr (autoanalyzer), serum beta2M (RIA) and GFR (bladder cumulative method using 99mTc-DTPA as glomerular tracer) were measured in the same day. RESULTS: A linear relationship was observed between In GFR and both In serum Cr (lnCr=3.112-0.716 lnGFR; r=0.92) and ln serum beta2M (lnbeta2M= 4.274-0.814 lnGFR; r = 0.90). With decreasing GFR the increase in serum beta2M was higher than that of serum Cr (see regression coefficients that are significantly different). The normal upper limit of serum Cr corresponds to a GFR 48.1 mL/min while that of serum beta2M to a GFR 65.0. With decreasing GFR the increase of serum beta2M occurs before than that of serum Cr. CONCLUSIONS: With declining renal function, serum beta2M increases more and before than serum Cr. Serum beta2M is a good endogenous marker of GFR, better than serum Cr.

Relationship between renal function and blood level of chromogranin A.

Chromogranin A (CGA) is a low MW (49,000) acidic hydrophilic protein. It is synthesized in the chromaffm granules of the neuroendocrine cells, and has been found circulating in the blood of healthy subjects. The aim of this study was to assess the relationship between serum levels of CGA and renal function. One hundred two renal patients (45 M and 57 F; age 14-76 years, mean 52) participated in the study. Glomerular filtration rate (GFR) was measured by the bladder cumulative method, using 99mTc-DTPA as a tracer. Blood CGA was determined by RIA. Plasma creatinine, beta2microglobulin (beta2m) and tumor associated trypsin inhibitor (TATI) were also determined. The reduction in renal function was associated with an increase in all of the above studied parameters. In patients with advanced renal failure (GFR <20 mL/min) CGA levels increased by 22-fold as compared to the patients with normal renal function (GFR> 100 mL/min). The other studied parameters were also increased but to a lesser degree, e.g., TATI 14-, beta2m 8- and creatinine 5-fold. The results of this study demonstrate that renal handling of the CGA is similar to other low MW proteins, and it accumulates in the blood in renal failure.