Cardiovascular risk factors in childhood obesity.

Childhood obesity is the "disease of the century". This article reviews the early cardiovascular risk factors and the recommendations to prevent them in the overweight and obese children. A comprehensive search of published literature was carried out to identify all articles published on this topic in English and Italian from 1999 to 2020.

CHILDHOOD IDIOPATHIC NEPHROTIC SYNDROME AND ATOPIC DISEASES: IS THERE A RELATIONSHIP?

Nephrotic syndrome is a condition of massive proteinuria that leads to hypoalbuminaemia and oedema. In the pediatric age, the most common form of nephrotic syndrome is childhood idiopathic nephrotic syndrome (CINS). Although the etiological mechanisms underlying CINS are still unclear, the disease is considered to be immune-mediated. Several studies have previously reported a possible association between CINS and atopy, with the latter defined as abnormal immunoglobulin-E response on the background of a T-helper 2 (Th2)-driven immune system. In fact, both experimental and clinical studies have suggested that idiopathic nephrotic syndrome can be associated and/or triggered by a wide array of atopic diseases, though this remains a highly controversial topic. Exposure to inhalant-allergens (and/or introduction of food-allergens) has been previously correlated with the onset and/or the relapse of CINS in some children and a significant worse response to steroid therapy has been also described in reports of CINS associated to concomitant atopic diseases. In this review, we analyzed previous studies with the aim to clarify, basing on the existent literature, the association between atopy and idiopathic nephrotic syndrome. Additionally, we also speculated on the underlying immunological pathways that could potentially make some children prone to both CINS and atopic diseases.

HIGH-MOBILITY GROUP BOX 1 IN ALLERGIC AND NON ALLERGIC UPPER AIRWAY INFLAMMATION.

High mobility group box 1, an evolutionary ancient protein conserved in the eukaryotic kingdom, exerts intra- and extra- cellular functions, orchestrating a homeostatic defensive response in challenged tissues. Its action associated with various inflammatory cells is essential for the occurrence, progression, and persistence of asthma, rhinitis, and nasal polyposis. The recent discovery of High mobility group box 1, as a critical mediator of inflammation, stimulated an increasing interest in the field of inflammation research, suggesting new therapies for atopic and non-atopic inflammatory processes.

Genetic associations of fatigue and other symptom domains of the acute sickness response to infection.

The acute sickness response to infection is a conserved set of changes in physiology and behaviour, featuring fever, fatigue, musculo-skeletal pain, disturbed mood, and cognitive difficulties. The manifestations differ somewhat between individuals, including those infected with pathogens which do not have genetic variability--suggesting host determinants. Principal components analysis (PCA) was applied to acute phase, self-report symptom data from subjects in the Dubbo Infection Outcomes Study (n=296) to empirically derive indices of fatigue, pain, neurocognitive difficulties, and mood disturbance, as well as overall illness severity. Associations were sought with functional single nucleotide polymorphisms (SNPs) in the cytokine genes, interleukin (IL)-6, tumour necrosis factor (TNF)-α, interferon (IFN)-γ, and IL-10. The summed individual symptom indices correlated with overall severity and also with functional status. The relative contribution of individual symptom domains to the overall illness was stable over time within subjects, but varied between subjects with the same infection. The T allele of the IFN-γ +874 T/A SNP was associated with increased fatigue (p=0.0003; OR: 3.3). The C allele of the IL-10 -592 C/A SNP exerted a protective effect on neurocognitive difficulties (p=0.017; OR: 0.52); while the A allele for the IL-10 -592 SNP was associated with increased mood disturbance (p=0.044; OR: 1.83), as was the G allele of the IL-6 -174 G/C SNP (p=0.051; OR: 1.83). The acute sickness response has discrete symptom domains including fatigue, which have unique genetic associations. These data provide novel insights into the pathophysiology of fatigue states.

The economic value of screening haemodialysis patients for methicillin-resistant Staphylococcus aureus in the USA.

Methicillin-resistant Staphylococcus aureus (MRSA) can cause severe infections in patients undergoing haemodialysis. Routine periodic testing of haemodialysis patients and attempting to decolonize those who test positive may be a strategy to prevent MRSA infections. The economic value of such a strategy has not yet been estimated. We constructed a Markov computer simulation model to evaluate the economic value of employing routine testing (agar-based or PCR) at different MRSA prevalence, spontaneous clearance, costs of decolonization and decolonization success rates, performed every 3, 6 or 12 months. The model showed periodic MRSA surveillance with either test to be cost-effective (incremental cost-effectiveness ratio ≤$50 000/quality-adjusted life-year) for all conditions tested. Agar surveillance was dominant (i.e. less costly and more effective) at an MRSA prevalence ≥10% and a decolonization success rate ≥25% for all decolonization treatment costs tested with no spontaneous clearance. PCR surveillance was dominant when the MRSA prevalence was ≥20% and decolonization success rate was ≥75% with no spontaneous clearance. Routine periodic testing and decolonization of haemodialysis patients for MRSA may be a cost-effective strategy over a wide range of MRSA prevalences, decolonization success rates, and testing intervals.

Prevention of infectious complications in peritoneal dialysis: best demonstrated practices.

Peritoneal dialysis (PD) related infections continue to be a serious complication for PD patients. Peritonitis can be associated with pain, hospitalization and catheter loss as well as a risk of death. Peritonitis risk is not evenly spread across the PD population or programs. Very low rates of peritonitis in a program are possible if close attention is paid to the causes of peritonitis and protocols implemented to reduce the risk of infection. Protocols to decrease infection risk in PD patients include proper catheter placement, exit-site care that includes Staphylococcus aureus prophylaxis, careful training of patients with periodic retraining, treatment of contamination, and prevention of procedure-related and fungal peritonitis. Extensive data have been published on the use of antibiotic prophylaxis to prevent exit site infections. There are fewer data on training methods of patients to prevent infection risk. Quality improvement programs with continuous monitoring of infections, both of the catheter exit site and peritonitis, are important to decrease the PD related infections in PD programs. Continuous review of every episode of infection to determine the root cause of the event should be routine in PD programs. Further research is needed examining approaches to decrease infection risk.

Preventing peritoneal dialysis related infections.

Peritonitis is still a serious problem in peritoneal dialysis (PD) patients and is associated with mortality. To improve outcomes in PD patients, attention must be focused on preventing peritonitis. This involves attention to training, connection methodologies, PD catheter insertion protocols. To prevent catheter-related peritonitis, the use of gentamicin cream at the exit site for daily routine care is recommended. Other causes of peritonitis include bowel sources, fungal overgrowth often related to prolonged antibiotic care, and peritonitis secondary to procedures. Relapsing peritonitis and refractory exit site infections should be managed by replacing the catheter. Every PD program needs to closely examine every episode to determine the cause, and then undertake an approach to prevent further episodes.

The outcome of peritonitis in patients on automated peritoneal dialysis.

We reviewed all peritonitis over the last decade to compare patient outcomes on automated peritoneal dialysis (APD) and continuous ambulatory peritoneal dialysis (CAPD). There were 327 episodes of peritonitis in 198 patients during this period. The rates were 0.57 per patient-year and 0.55 per patient-year on APD and CAPD respectively. For 52% of the episodes, the patients were admitted and managed with a mixture of CAPD and APD, so that no further analysis of outcomes was performed. For 48% (158) of the episodes, the patients were treated as outpatients and remained on their existing modality: 49 on APD and 100 on CAPD (9 catheter-related peritonitis excluded). In the APD group, 5 catheters were eventually removed for recurrent or refractory peritonitis. One other patient died in conjunction with peritonitis. Therefore, the adverse outcome was 12% on APD (6/49 episodes). In the CAPD group, 5 catheters were removed for refractory or relapsing peritonitis (including 1 for peritonitis with a leak). One other patient with fungal peritonitis died. Therefore, the adverse outcome on CAPD was 6% (6/100 episodes), which is not statistically different from the 12% on APD (p = 0.21). In summary, the incidence of peritonitis was similar on APD and CAPD, with one half the patients in each group requiring admission. In peritonitis treated on an outpatient basis, failure was twice as high with continuation of APD as compared with continuation of CAPD, but the difference was nonsignificant. Further studies on managing peritonitis in patients on APD are needed.

Peritoneal dialysis clearance can replace residual renal function.

OBJECTIVE: There is controversy whether increasing peritoneal clearance effectively substitutes for declining residual renal function. We studied the impact of renal and peritoneal clearances on outcome, controlling for comorbidity. DESIGN: Registry database. SETTINGS: Four dialysis centers. PATIENTS: Incident peritoneal dialysis patients. METHODS: Data were collected prospectively on 90 incident patients between 1991 and 1999. At the end of their first year on peritoneal dialysis, patients were divided into groups based on the first year's clearance results: group 1 (n = 62) had weekly Kt/W greater than or equal to 2.0 and creatinine clearance (CCr/1.73 m2) greater than or equal to 60 L throughout the first year; group 2 (n = 28) fell below these targets due to loss of residual renal function and then reached targets due to prescription change. MAIN OUTCOME MEASURES: Patient and technique survival. RESULTS: Both groups were similar in baseline characteristics except age (57 years vs 49 years, p = 0.02) and initial albumin (34.4 g/L vs 37.5 g/L, p = 0.001). One-year patient survival after grouping was similar in both groups (86.3% vs 80.9%, p = 0.72). Cox proportional hazard model, controlling for comorbidity, did not show "group" to be a significant predictor of outcome (p = 0.96). One-year technique survival after grouping was similar in both groups (77.3% vs 83.2%, log rank p = 0.89). For technique failure, Cox proportional hazard model showed peritonitis (p = 0.004) to be the only significant predictor of worse outcome. CONCLUSIONS: Peritoneal dialysis patients with improved clearances due to prescription changes had survival comparable to patients who never fell below target. This suggests that loss of residual renal function may be replaced by increasing peritoneal dialysis clearance. A large multicenter trial to study this important question further is needed.

The influence of demographic factors and modality on loss of residual renal function in incident peritoneal dialysis patients.

OBJECTIVE: To determine whether gender, race, diabetes, peritoneal dialysis (PD) modality, and comorbid conditions influence loss of residual renal function (RRF). DESIGN: Retrospective study of incident PD patients, using database of prospectively collected demographic, laboratory, and clearance data. SETTING: Peritoneal Dialysis Registry of the University of Pittsburgh Medical Center. PATIENTS: The study included 184 continuous ambulatory PD and automated PD patients who had at least two 24-hour urine collections for glomerular filtration rate (GRF) between April 1991 and March 2000. 836 urine collections were analyzed. OUTCOME MEASURES: Loss of RRF was defined as the slope of the decline in GFR as measured by the average of creatinine and urea clearances in 24-hour urine collections. Stepwise forward regression was used to identify demographic and laboratory factors associated with loss of GFR. Spearman correlations were used to assess the significance of associations. RESULTS: The median rate of decline of renal function was -0.17 mL/minute/month. Gender, race, diabetes, automated PD, peritoneal equilibration test, protein equivalent of nonprotein nitrogen appearance normalized to body surface area, and serum albumin did not predict loss of RRF. Cardiac disease was the only variable affecting decline of RRF (p = 0.045). CONCLUSION: Modality of PD and patient demographic factors do not contribute to the rate at which RRF is lost in incident PD patients. Additional study of the factors contributing to the decline and maintenance of RRF is needed.

Charlson comorbidity index as a predictor of outcomes in incident peritoneal dialysis patients.

A previous study at our center used the Charlson Comorbidity Index (CCI) (an index of comorbidity that includes age) to predict outcomes in a mixed group of incident and prevalent dialysis patients. The purpose of this study was to examine the usefulness of the CCI as a predictor in incident peritoneal dialysis (PD) patients and to examine whether it was a better predictor than simply the number of comorbid conditions or other known predictors, such as age, albumin level, diabetes, and cardiovascular disease. Since 1990, we have collected prospectively comorbidity data at the start of PD. All patients with known comorbidity and serum albumin and who did not have a prior history of hemodialysis or transplant were included (n = 268). Time at risk began at day 1 of PD training. Cox proportional hazards best subset selection was used to screen models to predict patient survival. Candidate models were analyzed further for proportionality and other model assumptions. Univariate analysis showed that significant predictors of mortality were CCI (chi-square = 43.3, P < 0.0001), age (chi-square = 23.7, P < 0.0001), cardiac disease (chi-square = 19.9, P <0.0001), number of comorbid conditions (chi-square = 15.6, P < 0.0001), serum albumin at the start of dialysis (chi-square = 15.3, P = 0.0001), and diabetes (chi-square = 4, P < 0.05). In multivariate analysis, CCI alone was the best predictor. The addition of serum albumin did not improve the model significantly (chi-square = 51.86 versus 49.34). For every increase of 1 in the CCI score, the relative risk of death was 1.54 (95% confidence interval, 1.36 to 1.74). CCI alone scored at the start of PD is a strong predictor of patient survival in incident end-stage renal disease patients on PD. This simple-to-calculate index would be useful to adjust for confounding in future studies and in the adjustment of case mix if Medicare moves to a capitated payment system.

Staphylococcus aureus infections in dialysis patients: focus on prevention.

Staphylococcus aureus infections are a major cause of morbidity and hospitalization in dialysis patients. The risk of infection relates to the type of access. Patients with acute hemodialysis (HD) catheters are at the greatest risk of S. aureus bacteremia, followed by tunneled HD catheters, and grafts. Patients with a fistula have a rate similar to that of peritoneal (PD) patients. In PD patients, however, S. aureus is the second most common cause of peritonitis, is often associated with a catheter infection, and frequently requires catheter removal for resolution. S. aureus infections in dialysis patients are much more common in nasal carriers. S. aureus moves from the nasal reservoir to the hands and skin, and from there to infect the access. Therefore, prevention of infection can be aimed at treating the carriage or in applying antibiotics at the catheter exit site, thus preventing colonization and subsequent infection of the catheter. For HD patients with a permanent access (either fistula or graft), intranasal mupirocin, twice a day for 5 days followed by a once weekly application, is effective in reducing the risk of S. aureus bacteremia. Cost analysis indicates that treating all patients would result in more cost savings than treating just carriers. For patients with acute HD catheters, exit site mupirocin applied as part of routine care during each HD treatment, reduces the risk of S. aureus exit site infection and bacteremia. For PD patients, S. aureus infections can be diminished by using mupirocin at the exit site as part of daily exit site care. Prophylaxis against S. aureus is under utilized in dialysis patients and, if implemented, could lower the rate of these serious infections.

Peritoneal infections.

Peritoneal dialysis related infections include infection of the catheter exit site, subcutaneous pathway, or effluent. Exit-site infections, predominately owing to Staphylococcus aureus, are defined as purulent drainage at the exit site, although erythema may be a less serious type of exit-site infection. Tunnel infections are underdiagnosed clinically, and sonography of the tunnel is useful to delineate the extent of the infection and to evaluate response to antibiotic therapy. S aureus infections occur more frequently in S aureus carriers and immunosuppressed patients and can be reduced by mupirocin prophylaxis either intranasally or at the exit site. Patients with peritonitis present with cloudy effluent and usually pain, although 6% of patients may initially have pain without cloudy effluent. A white blood cell count of 100 or greater per microL, 50% of which are polymorphonuclear cells, has long been the hallmark of peritonitis. Empiric therapy is controversial, with some recommending cefazolin and others vancomycin (with cefatazidime for Gram-negative coverage). The choice should depend on the center's antibiotic sensitivity profile; those centers with a high rate of Enterococcus- or methicillin resistant organisms should use vancomcycin. Peritonitis episodes occurring in association with a tunnel infection with the same organism seldom resolve with antibiotics and require catheter removal. Other indications for catheter removal are refractory peritonitis, relapsing peritonitis, tunnel infection with inner-cuff involvement that does not respond to antibiotic therapy (based on ultrasound criteria), fungal peritonitis, and enteric peritonitis owing to intra abdominal pathology. Centers can reduce dialysis related infections to very low levels by proper catheter selection and insertion, careful selection and training of patients, avoidance of spiking techniques, and use of antibiotic prophylaxis against S. aureus. Further research is required to identify methods to reduce the risk of enteric peritonitis.

Pattern of noncompliance with dialysis exchanges in peritoneal dialysis patients.

The purpose of the study is to evaluate the pattern of noncompliance in peritoneal dialysis (PD) patients using home visit supply inventories. Ninety-two patients were enrolled at the start of dialysis. Noncompliance, defined as performance of less than 90% of prescribed exchanges, was found in 30% of patients during the first 6 months of PD. Patients who were noncompliant with prescribed exchanges at the start of PD had greater rates of death (P = 0.03), transfer to hemodialysis secondary to uremia (P < 0.05), hospitalization (P < 0.001), and days hospitalized (P < 0.001) compared with compliant patients. Delivered Kt/V was 18% less in noncompliant compared with compliant patients (2.1 versus 2.57; P = 0.007). Serial evaluations of compliance in 53 patients showed that 72% were consistently compliant, 2% were consistently noncompliant, 15% were noncompliant at the beginning of PD but became compliant at follow-up, and 11% were intermittently noncompliant. The likelihood of future compliance in a patient compliant at the first home visit was 88%. Patients who were independent with their dialysis exchanges were more likely to be noncompliant (27%) than patients dependent on someone else to perform their dialysis (8%; P = 0.05). Serial 24 hour creatinine excretion was not a useful method to determine compliance. We recommend a home visit during the first 6 months of PD to determine compliance. Those found compliant probably do not need repeated evaluations, whereas noncompliant patients should be reevaluated in a few months. Involving another person in the dialysis might relieve some of the burden on patients who may be initially unable to cope with home dialysis. Identification of noncompliant patients and awareness of risk factors should reduce noncompliance and improve patient outcomes.

Normalization of clearances in peritoneal dialysis using a formula for body water derived from an end-stage renal disease population.

OBJECTIVE: To compare body water (V) estimates from the Chertow formula (Vc), which was derived in an end-stage renal disease population, to V estimates from the Watson formulas (Vw) in continuous ambulatory peritoneal dialysis (CAPD) patients. To identify CAPD patients in whom Vc is preferred to Vw for clearance studies. DESIGN: Retrospective analysis of clearance studies. SETTING: Dialysis units of four academic medical centers. PARTICIPANTS: 302 subjects on CAPD. INTERVENTION: 613 clearance studies by standard methods. MAIN OUTCOME MEASURES: Comparisons between Vc and Vw, and between urea clearance normalized by Vc [(KtVc)ur] and Vw [(Kt/Vw)ur]. RESULTS: Vc exceeded Vw by 3.5 +/- 1.6 L (p < 0.001), or 9.6% on average. This degree of overestimation of Vw is in the range of body water estimates found in CAPD subjects with severe volume overload (> 5% of body weight) in previous studies. Total (Kt/Nw)ur exceeded total (Kt/Vc)ur by 8.6%. By linear regression, Vc = -0.589 + (1.112 x Vw), r = 0.983. Vw exceeded Vc in only 12 studies. Young age, short height, low body weight, and low prevalence of diabetes characterized the studies with Vw > Vc. Total (Kt/Vw)ur was adequate (> or = 2.0 weekly) in 276 studies. Among these, 74 studies had inadequate total (Kt/Vc)ur (< 2.0 weekly). By logistic regression, the predictors of inadequate (Kt/Vc)ur, when (Kt/Vw)ur was adequate, included the presence of diabetes, great height, and long duration of CAPD. CONCLUSIONS: Vc provides estimates of body water exceeding those provided by Vw in a great majority of CAPD patients. Consequently, approximately 25% of the clearance studies that are adequate when Vw is used as the normalizing parameter may be inadequate when Vc is used. Vc may provide a more appropriate estimate of body water than Vw in CAPD patients with volume overload.