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Background and Objectives: End stage renal disease (ESRD) patients are exposed to the risk of ionizing radiation during repeated imaging studies. The variability in diagnostic imaging policies and the accompanying radiation doses across various renal units is still unknown. We studied this variability at the centre level and quantified the associated radiation doses at the patient level., Methods: Fourteen Italian nephrology departments enrolled 739 patients on haemodialysis and 486 kidney transplant patients. The details of the radiological procedures performed over one year were recorded. The effective doses and organ doses of radiation were estimated for each patient using standardized methods to convert exposure parameters into effective and organ doses RESULTS: Computed tomography (CT) was the major contributor (> 77%) to ionizing radiation exposure. Among the haemodialysis and kidney transplant patients, 15% and 6% were in the high (≥ 20 mSv per year) radiation dose groups, respectively. In haemodialysis patients, the most exposed organs were the liver (16 mSv), the kidney (15 mSv) and the stomach (14 mSv), while the uterus (6.2 mSv), the lung (5.7 mSv) and the liver (5.5 mSv) were the most exposed in kidney transplant patients. The average cumulative effective dose (CED) of ionizing radiation among centres in this study was highly variable both in haemodialysis (from 6.4 to 18.8 mSv per patient-year; p = 0.018) and even more so in kidney transplant (from 0.6 to 13.7 mSv per patient-year; p = 0.002) patients., Conclusions: Radiation exposure attributable to medical imaging is high in distinct subgroups of haemodialysis and transplant patients. Furthermore, there is high inter-centre variability in radiation exposure, suggesting that nephrology units have substantially different clinical policies for the application of diagnostic imaging studies.

Incidence of kidney replacement therapy (KRT) stabilizes or declines both in Europe and in the US; however, it is predictable that global prevalence of KRT will double by 2030. In this paper, we focus on the patterns of incidence, mortality, and prevalence of KRT in Italy, and we compare, when possible, the findings with other countries. The Italian Dialysis and Transplantation Registry (IDTR) currently collects aggregate data from regional registries. In Italy, KRT yearly incidence is around 160 patients per million population (pmp). This incidence showed an increasing trend up until 2011 with an average annual percentage change (AAPC) of 1.8%, after which it stabilized. Older age is an important determinant for KRT incidence, and it is strongly associated with the variability between Italian regions. Incidence is very stable within patients less than 50 years old; however, it greatly differs between regions for patients over 75 years old, ranging from 400 to 900 pmp. Moreover, the incidence for patients over 50 years old declined from 366 pmp in 2011 to 285 in 2017. An age-period-cohort (APC) model showed a very strong cohort effect, which shows the decline in incidence seems mainly due to the better health conditions of people born after 1940. Mortality rate in KRT patients was 109 per 1000 patient-year (py) between 2011 and 2017 with great differences among treatment modalities: 162 per 1000 py in haemodialysis, 117 per 1000 py in peritoneal dialysis, and 16 per 1000 py in kidney transplantation. Premature death is better detected by the standard expected years of life lost (YLL). The distribution of YLL rate per age shows a sharp increase between 40 and 70 years old both in haemodialysis and peritoneal dialysis patients with an AAPC of 5.2% and 4.1% respectively. Transplanted patients experience a very low YLL rate at any age. KRT prevalence was 1118 pmp in 2017 and it should be close to 1175 pmp by 2025 with a projected increase of transplanted patients' prevalence to 500 pmp, and a decrease of dialysis patients from 714 to 680 pmp. The proportion of patients treated with one of the three modalities strictly depends on age, with a sharp increase of haemodialysis after the age of 50. All data suggests the necessity to improve the care of middle and older age patients who experience the higher incidence of disease and mortality.

Background: The prognostic relevance of health-related quality of life (HRQoL) has been scarcely studied in the dialysis population and the prognostic power for mortality of the HRQoL domains is unknown., Methods: We tested the prognostic value for mortality of the HRQoL domains included in the 36-item Short Form Health Survey (SF-36) by Cox's regression analysis and by state-of-the-art prognostic techniques {explained variation in mortality [R2], calibration, discrimination [Harrell's C], risk reclassification [Net Reclassification Index (NRI)], Integrated Discrimination Index [IDI]} in a cohort of 951 patients on chronic haemodialysis., Results: In multivariable Cox models, all but two domains (role limitation due to physical health and due to emotional problems) were independently related with mortality. Physical functioning was the domain adding the highest explanatory power (R2+5.3%) to a basic model including established risk factors for mortality in the dialysis population. The same domain improved risk calibration and showed the highest Harrell's C (+1.7%) and the highest reclassification power (categorical NRI + 8.7%, continuous NRI +46%, P ≤ 0.006) and the highest IDI (+3.4%, P < 0.001). These results were fully confirmed in analyses testing the additional prognostic power of SF-36 domains when combined to a well-validated risk score in dialysis patients., Conclusions: Physical functioning holds the highest prognostic power for mortality among the domains of SF-36. The gain in prognostic ability by this domain is relevant for clinical practice. Physical functioning has the potential for refining the prognosis and for informing exercise programmes in the dialysis population., (© The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background/aims: Fabry disease (FD) is a lysosomal storage disorder characterized by pervasive renal involvement. However, this disease is underdiagnosed in patient with chronic kidney disease (CKD), including those with end stage renal disease (ESRD), so their investigation represents an unexploited opportunity for early diagnosis of the disease and for its identification in relatives of affected patients., Methods: We investigated Fabry disease in a clinical and biological database including ESRD patients of unknown cause in a geographical area with 2 million residents. The study was based on state of art GLA gene sequencing and was extended to relatives of affected ESRD patients., Results: Among ESRD patients qualified for enrollment into this study, a previously undiagnosed young man harboring the mutation p.I91T was identified. The study of the proband's family led to the identification of 8 additional cases. In another ESRD male patient, we identified the functional polymorphism p.D313Y. Furthermore, in 55 ESRD patients (24.2%) we found intronic polymorphisms of uncertain functional relevance in the non-coding regions of the GLA gene., Conclusion: A comprehensive survey of ESRD patients in a geographical area of 2 million residents identified one undiagnosed case of Fabry disease and led to the identification of 8 additional cases among his relatives. Screening protocols starting from the dialysis population and upstream extended to families of affected individuals may be an effective strategy to maximize the early identification of subjects with Fabry disease., (© 2018 The Author(s). Published by S. Karger AG, Basel.)

The rate of senescence can be inferred from the acceleration by which mortality rates increase over age. Such a senescence rate is generally estimated from parameters of a mathematical model fitted to these mortality rates. However, such models have limitations and underlying assumptions. Notably, they do not fit mortality rates at young and old ages. Therefore, we developed a method to calculate senescence rates from the acceleration of mortality directly without modeling the mortality rates. We applied the different methods to age group-specific mortality data from the European Renal Association-European Dialysis and Transplant Association Registry, including patients with end-stage renal disease on dialysis, who are known to suffer from increased senescence rates (n = 302,455), and patients with a functioning kidney transplant (n = 74,490). From age 20 to 70, senescence rates were comparable when calculated with or without a model. However, when using non-modeled mortality rates, senescence rates were yielded at young and old ages that remained concealed when using modeled mortality rates. At young ages senescence rates were negative, while senescence rates declined at old ages. In conclusion, the rate of senescence can be calculated directly from non-modeled mortality rates, overcoming the disadvantages of an indirect estimation based on modeled mortality rates., (© The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Alkaline phosphatase (Alk-Phos) is a powerful predictor of death in patients with end-stage kidney disease (ESKD) and oxidative stress is a strong inducer of Alk-Phos in various tissues. We tested the hypothesis that oxidative stress, as estimated by a robust marker of systemic oxidative stress like γ-Glutamyl-Transpeptidase (GGT) levels, may interact with Alk-Phos in the high risk of death in a cohort of 993 ESKD patients maintained on chronic dialysis. In fully adjusted analyses the HR for mortality associated with Alk-Phos (50 IU/L increase) was progressively higher across GGT quintiles, being minimal in patients in the first quintile (HR: 0.89, 95% CI: 0.77-1.03) and highest in the GGT fifth quintile (HR: 1.13, 95% CI: 1.03-1.2) (P for the effect modification = 0.02). These findings were fully confirmed in sensitivity analyses excluding patients with preexisting liver disease, excessive alcohol intake, or altered liver disease biomarkers. GGT amplifies the risk of death associated with high Alk-Phos levels in ESKD patients. This observation is compatible with the hypothesis that oxidative stress is a strong modifier of the adverse biological effects of high Alk-Phos in this population.

Background: Pregnancy on dialysis is increasingly being reported. This study evaluates the behavioural profile of the children of mothers on dialysis and the parental stress their mothers undergo when compared with a group of mothers affected by a different chronic disease (microcythaemia) and a group of healthy control mothers., Methods: Between 2000 and 2012, 23 on-dialysis mothers gave birth to 24 live-born children in Italy (23 pregnancies, 1 twin pregnancy, one of the twins deceased soon after delivery); of these, 16 mothers and 1 father (whose wife died before the inquiry) were included in the study (1 mother had died and the father was unavailable; 2 were not asked to participate because their children had died and 3 were unavailable; children: median age: 8.5, min-max: 2-13 years). Twenty-three mothers affected by transfusion-dependent microcythaemia or drepanocitosis (31 pregnancies, 32 children) and 35 healthy mothers (35 pregnancies, 35 children; median age of the children: 7, min-max: 1-13 years) were recruited as controls. All filled in the validated questionnaires: 'Child Behaviour Checklist' (CBCL) and the 'Parental Stress Index-Short Form' (PSI-SF)., Results: The results of the CBCL questionnaire were similar for mothers on dialysis and healthy controls except for pervasive developmental problems, which were significantly higher in the dialysis group, while microcythaemia mothers reported higher emotional and behavioural problems in their children in 8 CBCL sub-scales. Two/16 children in the dialysis and 3/32 in the microcythaemia group had pathological profiles, as assessed by T-scores (p: ns). PSI-SF indicated a normal degree of parental stress in microcythaemia subjects and healthy controls, while mothers on dialysis declared significantly lower stress, suggesting a defensive response in order to minimize problems, stress or negativity in their relationship with their child., Conclusions: According to the present analysis, the emotional and behavioural outcome is normal in most of the children from on-dialysis mothers. A 'positive defence' in the dialysis mothers should be kept in mind when tailoring psychological support for this medical miracle., (© The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: Infections and malignancies are the most common non-cardiovascular causes of death in patients on chronic renal replacement therapy (RRT). Here, we aimed to quantify the mortality risk attributed to infections and malignancies in dialysis patients and kidney transplant recipients when compared with the general population by age group and sex., Methods: We followed 168 156 patients included in the ERA-EDTA registry who started RRT in 1993-2007 until 1 January 2012. Age- and cause-specific mortality rates per 1000 person-years (py) and mortality rate ratios (MRRs) compared with the European general population (WHO) were calculated. To identify risk factors, we used Cox regression., Results: Infection-related mortality was increased 82-fold in dialysis patients and 32-fold in transplant recipients compared with the general population. Female sex, diabetes, cancer and multisystem disease were associated with an increased risk of infection-related mortality. The sex difference was most pronounced for dialysis patients aged 0-39 years, with women having a 32% (adjusted HR 1.32 95% CI 1.09-1.60) higher risk of infection-related mortality than men. Mortality from malignancies was 2.9 times higher in dialysis patients and 1.7 times higher in transplant recipients than in the general population. Cancer and multisystem disease as primary causes of end-stage renal disease were associated with higher mortality from malignancies., Conclusion: Infection-related mortality is highly increased in dialysis and kidney transplant patients, while the risk of malignancy-related death is moderately increased. Young women on dialysis may deserve special attention because of their high excess risk of infection-related mortality. Further research into the mechanisms, prevention and optimal treatment of infections in this vulnerable population is required., (© The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: A successful pregnancy is an exceptional event on dialysis. Few data are available comparing pregnancy rates on dialysis, transplantation and the overall population. The aim of the study was to assess the incidence of live births from mothers on chronic dialysis compared with the overall population and with kidney transplant patients., Methods: The setting of the study is in Italy between 2000-12. Data on dialysis was aquired by phone inquiries that were carried out between June and September, 2013, involving all the public dialysis centres in Italy; the result was a 100% response rate. The date included was end-stage renal disease, type of dialysis, residual glomerular filtration rate, changes in dialysis and therapy, hospitalization; week of birth, birth weight, centile; and outcome of mother and child. Information on transplantation was acquired by inquiry by the kidney and pregnancy study group who were contacted by phone or e-mail; the result was a 60% response rate. Data concerning prevalence of women in childbearing age (20-45) were obtained from the Italian Dialysis and Transplant Registries (2010-11 update). Official site of the Italian Ministry of Health., Results: During the study period, 23 women on dialysis (three on peritoneal dialysis) delivered live-born babies and one woman delivered twins (24 babies). Three babies died in the first weeks-months of life (including one twin); 19 of 21 singletons with available data were pre-term (33.3% <34 weeks); the prevalence of children <10th gestational age-adjusted centile was 33.3%. Birth weight and gestational age were lower in children from on-dialysis mothers as compared with 110 pregnancies following kidney graft, (weight: 1200 versus 2500 g; gestational age: 30 versus 36 weeks; P < 0.001). Incidence of live-born babies was inferred as 0.7-1.1 per 1000 female dialysis patients aged 20-45 and 5.5-8.3 per 1000 grafted patients in the same age range (Italian live-birth rates: 72.5 per 1000 women aged 20-45 years)., Conclusions: Having a baby while on dialysis is rare but not impossible, though early mortality remains high. There is a 'scale of probability' estimating that women on dialysis have a 10-fold lower probability of delivering a live-born baby than those who have undergone renal transplantation, who in turn have a 10-fold lower probability of delivering a live-born baby as compared with the overall population., (© The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: Snoring, an indicator of sleep-disordered breathing (SDB), associates with all-cause and cardiovascular (CV) mortality in high-risk conditions such as chronic heart failure (HF). Because SDB and HF are exceedingly frequent in end-stage kidney disease (ESKD), we hypothesized that SDB as detected by snoring may impact upon the relationship between chronic HF and all-cause and CV mortality in these patients., Methods: We tested this hypothesis in a cohort of 827 ESKD patients, followed up for 2.3 years., Results: In this population, snoring was a strong modifier of the risk of chronic HF for all-cause and CV death. In fully adjusted Cox models, the hazard ratio (HR) associated to chronic HF for the study outcomes was highest in heavy snorers [all-cause death: HR 2.6 (95% CI 1.6-4.3, p < 0.001); CV death: HR 4.0 (95% CI 2.1-7.6, p < 0.001)], intermediate in moderate snorers [all-cause death: HR 1.6 (95% CI 1.1-2.2, p = 0.01); CV death: HR 1.8 (95% CI 1.2-2.8, p = 0.01)], and lowest and not significant in non-snorers [all-cause death: HR 0.9 (95% CI 0.6-1.6, p = NS); CV death: HR 0.8 (95% CI 0.4-1.6, p = NS)]., Conclusions: Snoring is a strong and independent effect modifier of the relationship between chronic HF and all-cause and CV mortality in ESKD. Since SDB and snoring are in part attributable to reversible pharyngeal oedema, intensified surveillance and treatment of chronic HF snorers on dialysis may translate into better clinical outcomes in this very high-risk population, an issue which remains to be tested in specifically designed clinical trials.

Pulmonary congestion is highly prevalent and often asymptomatic among patients with ESRD treated with hemodialysis, but whether its presence predicts clinical outcomes is unknown. Here, we tested the prognostic value of extravascular lung water measured by a simple, well validated ultrasound B-lines score (BL-US) in a multicenter study that enrolled 392 hemodialysis patients. We detected moderate-to-severe lung congestion in 45% and very severe congestion in 14% of the patients. Among those patients with moderate-to-severe lung congestion, 71% were asymptomatic or presented slight symptoms of heart failure. Compared with those patients having mild or no congestion, patients with very severe congestion had a 4.2-fold risk of death (HR=4.20, 95% CI=2.45-7.23) and a 3.2-fold risk of cardiac events (HR=3.20, 95% CI=1.75-5.88) adjusted for NYHA class and other risk factors. Including the degree of pulmonary congestion in the model significantly improved the risk reclassification for cardiac events by 10% (P<0.015). In summary, lung ultrasound can detect asymptomatic pulmonary congestion in hemodialysis patients, and the resulting BL-US score is a strong, independent predictor of death and cardiac events in this population.

Background and Objectives: Patients with the hereditary disease Alport syndrome commonly require renal replacement therapy (RRT) in the second or third decade of life. This study compared age at onset of RRT, renal allograft, and patient survival in men with Alport syndrome receiving various forms of RRT (peritoneal dialysis, hemodialysis, or transplantation) with those of men with other renal diseases., Design, Setting, Participants, & Measurements: Patients with Alport syndrome receiving RRT identified from 14 registries in Europe were matched to patients with other renal diseases. A linear spline model was used to detect changes in the age at start of RRT over time. Kaplan-Meier method and Cox regression analysis were used to examine patient and graft survival., Results: Age at start of RRT among patients with Alport syndrome remained stable during the 1990s but increased by 6 years between 2000-2004 and 2005-2009. Survival of patients with Alport syndrome requiring dialysis or transplantation did not change between 1990 and 2009. However, patients with Alport syndrome had better renal graft and patient survival than matched controls. Numbers of living-donor transplantations were lower in patients with Alport syndrome than in matched controls., Conclusions: These data suggest that kidney failure in patients with Alport syndrome is now being delayed compared with previous decades. These patients appear to have superior patient survival while undergoing dialysis and superior patient and graft survival after deceased-donor kidney transplantation compared with patients receiving RRT because of other causes of kidney failure.

To define whether age modifies the prognosis of patients with chronic kidney disease (CKD) on nephrology care, we prospectively followed patients with CKD who have been receiving nephrology care in a clinic for 1 year or more. The incidence of end-stage renal disease (ESRD), defined by the occurrence of dialysis or transplant, or death without ESRD was estimated by a competing-risk approach, and interactions between age and risk factors tested in Cox models over a median follow-up period of 62.4 months. Of 1248 patients with stage III–V CKD, 481 were younger than 65, 410 were between 65 and 75, and 357 were over 75 years old. Within each age class, the mean estimated glomerular filtration rate(eGFR) was 31, 32, and 29 ml/min per 1.73 m2, respectively. There were 394 ESRD events and 353 deaths. The risk of ESRD was higher than the risk of death without ESRD for ages <60 years, and independent of eGFR. The ESRD risk diminished with aging but still prevailed for eGFRs of 25–35 in patients between 65 and 75 years and with an eGFR below 15 in those up to 85 years old. Proteinuria significantly increased the risk of ESRD with advancing age. Surprisingly, the unfavorable effects of cardiovascular disease on ESRD and of diabetes on survival significantly decreased with increasing age. Male gender, higher phosphate, lower body mass index, and hemoglobin were age-independent predictors for ESRD, while cardiovascular disease, lower hemoglobin, higher proteinuria and uric acid, and ESRD also predicted death. Thus, in older patients on nephrology care, the risk of ESRD prevailed overmortality even when eGFR was not severely impaired. Proteinuria increases ESRD risk, while the predictive role of other modifiable risk factors was unchanged compared with younger patients.

Background: Relative survival, a methodology previously used in epidemiologic studies of cancer, compares the observed survival of a patient cohort with expected survival derived from general population life tables. We examined relative survival in patients treated by long-term dialysis in the Italian Dialysis and Transplantation Registry in order to determine the prognosis of dialysis patients., Study Design: Cohort study drawn from a registry., Setting & Participants: Patients enrolled in the Italian Dialysis and Transplantation Registry., Factors: Sex, age, primary kidney disease, renal replacement therapy modality, and main comorbid conditions., Outcomes: Death from any cause., Measurements: Relative survival ratio (the ratio of observed survival in the population of interest to the survival expected given the age- and period-specific mortality of the general population) and excess mortality rate (difference between observed and expected mortality rates)., Results: In January 2000 to December 2008, a total of 27,642 patients were included. The 5-year relative survival estimate was 55.6% (95% CI, 54.7%-56.5%). The excess mortality rate showed a peak at 3 months (21 deaths/100 patient-years), then decreased, becoming constant from the end of year 1 to year 8, with leveling off at about 10 deaths/100 patient-years. Older age, systemic diseases, and diabetes showed the strongest association with excess mortality. Peritoneal dialysis was associated with a lower relative excess risk in only the first year of treatment., Limitations: The patient cohort comprises about half the Italian patients beginning dialysis therapy in the period., Conclusions: This study highlights the applicability of relative survival methods in dialysis patients. This measure allows estimation of disease prognosis and severity comparisons among chronic diseases. The excess mortality rate appears to be a more sensitive and informative measure than the simple proportion of survivors., (Copyright © 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

This paper reports on a first analysis of data of the second survey promoted by the Italian Society of Nephrology (SIN), with particular regard to data referring to the nephrologist's workload. The survey was carried out through a Web-based questionnaire that participants could fill in online between March and December 2010. The data were validated against those of the Italian Dialysis and Transplant Registry (RIDT) and therefore refer to 31 December 2008, the date of the last RIDT report. Accurate completion of the questionnaires and reminders were monitored by the presidents of the regional sections of the SIN and the regional registries' chairpersons under the coordination of four area managers and a census committee. The response to the survey represented 42% of all nephrology centers, treating about 50% of all dialysis patients in Italy. The response percentage varied widely among regions (from 5% to 100% of the centers). After exclusion of the three regions with responses below 10%, it reached 68%, which was sufficient to give an idea of the state of nephrology in Italy. However, due to this wide variability, it was not possible to make an overall comparison of the regional situations, hence data for complex and simple structures were assessed separately. Despite the limits due to the incomplete participation in the survey, this article provides a clear description of the state of nephrology in Italy. The results confirm the hypothesis presented in the work of Bocconi Cergas, namely that the nephrology market is broader than nephrologists are able to control. The work of the nephrologist, which still seems to be focused mainly on dialysis in its various forms, should be directed more towards the development of methods for early detection of kidney disease and close follow-up. The ultimate aim is the early diagnosis of kidney disease and hence prevention of its complications, so that the focus no longer needs to be on ESKD treatment systems.

Hypertriglyceridemia is the most prevalent lipid alteration in end-stage renal disease, and we studied the relationship between serum triglycerides and all-cause and cardiovascular death in these patients. Since abdominal fat modifies the effect of lipids on atherosclerosis, we analyzed the interaction between serum lipids and waist circumference (WC) as a metric of abdominal obesity. In a cohort of 537 hemodialysis patients, 182 died, 113 from cardiovascular causes, over an average follow-up of 29 months. In Cox models that included traditional and nontraditional risk factors, there were significant strong interactions between triglycerides and WC to both all-cause and cardiovascular death. A fixed (50 mg/dl) excess in triglycerides was associated with a progressive lower risk of all-cause and cardiovascular mortality in patients with threshold WC <95 cm but with a progressive increased risk in those above this threshold. A significant interaction between cholesterol and WC with all-cause and cardiovascular death emerged only in models excluding the triglycerides-WC interaction. Neither high-density lipoprotein (HDL) nor non-HDL cholesterol or their interaction terms with WC were associated with study outcomes. Thus, the predictive value of triglycerides and cholesterol for survival and atherosclerotic complications in hemodialysis patients is critically dependent on WC. Hence, intervention studies in end-stage renal disease should specifically target patients with abdominal obesity and hyperlipidemia.

Background: the relationships between the adipose tissue cytokines leptin and adiponectin (ADPN) and clinical outcomes have not been well studied in haemodialysis (HD) patients and remain highly controversial. As central obesity is an important modifier of the effect of various risk factors for clinical outcomes, we tested the hypothesis that waist circumference (WC) modifies the link between these cytokines and both overall and cardiovascular death in HD patients., Methods: a total of 537 HD patients participated in a prospective cohort study., Results: leptin and ADPN were inversely related to each other and robustly associated with WC (P < 0.001). During follow-up (average 29 months, range 1-47 months) 182 patients died, including 115 from cardiovascular causes. In analyses adjusting for potential confounders, there were strong interactions between leptin and WC in relationship to both all-cause (P < 0.001) and cardiovascular death (P = 0.002). Accordingly, a fixed excess of leptin signalled a gradually increasing risk for all-cause and cardiovascular mortality in patients with a large WC but an opposite effect in those with a relatively small WC. An interaction between ADPN and WC for all-cause (P = 0.01) and cardiovascular mortality (P = 0.01) emerged only in models excluding the leptin-WC interaction, suggesting that these adipokines share a common pathway leading to adverse clinical events in HD patients., Conclusions: the predictive value of leptin and ADPN for all-cause and cardiovascular death in HD patients appears to be critically dependent on WC. These findings support the hypothesis that disturbances in adipokine levels are involved in adverse clinical outcomes in HD patients with abdominal obesity.

Background: Recent studies have indicated a stabilization in the incidence rates of renal replacement therapy (RRT) for end-stage renal disease (ESRD) in a number of European countries. The aim of this study was to provide an update on the incidence, prevalence and outcomes of RRT in Europe over the past decade., Methods: Nineteen European national or regional renal registries with registry data from 1997 to 2006 participated in the study. Incidence and prevalence trends were analysed with Poisson and Joinpoint regression. Cox regression methods were used to examine patient survival., Results: The total adjusted incidence rate of RRT for ESRD increased from 109.9 per million population (pmp) in 1997 to 119.7 pmp in 2000, i.e. an average annual percentage change (AAPC) of 2.9% (95% CI 2.1-3.8%). Thereafter, the incidence increased at a much lower rate to 125.4 pmp in 2006 [AAPC 0.6% (95% CI 0.3-0.8%)]. This change in the trend of the incidence of RRT was largely due to a stabilization in the incidence rates of RRT for females aged 65-74 years, males aged 75-84 years and patients receiving RRT for ESRD due to hypertension/renal vascular disease. The overall adjusted prevalence in Europe continued to increase linearly at 2.7% per year. Between the periods 1997-2001 and 2002-2006, the risk of death decreased for all treatment modalities, with the most substantial improvement in patients starting peritoneal dialysis [19% (95% CI 15-22%)] and in patients receiving a kidney transplant [17% (95% CI 11-23%)]., Conclusion: This European study shows that the annual rise of the overall incidence rate of RRT for ESRD has diminished and that in several age groups the incidence rates have now stabilized. The survival of dialysis patients and kidney transplant recipients has continued to improve.

Background: Chronic kidney disease (CKD) is an emerging worldwide problem. The lack of attention paid to kidney disease is well known and has been described in previous publications. However, little is known about the magnitude of the problem in highly specialized hospitals where serum creatinine values are used to estimate GFR values., Methods: We performed a cross-sectional evaluation of hospitalized adult patients who were admitted to the medical or surgical department of Santa Maria della Misericordia Hospital in 2007. Information regarding admissions was derived from a database. Our goal was to assess the prevalence of CKD (defined as an estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m2) and detection of CKD using diagnostic codes (Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM]). To reduce the impact of acute renal failure on the study, the last eGFR obtained during hospitalization was the value used for analysis, and intensive care and nephrology unit admissions were excluded. We also excluded patients who had ICD-9-CM codes for renal replacement therapy, acute renal failure, and contrast administration listed as discharge diagnoses., Results: Of the 18,412 patients included in the study, 4,748 (25.8%) had reduced eGFRs, falling into the category of Kidney Disease Outcomes Quality Initiative (KDOQI) stage 3 (or higher) CKD. However, the diagnosis of CKD was only reported in 19% of these patients (904/4,748). It is therefore evident that there was a "gray area" corresponding to stage 3 CKD (eGFR 30-59 ml/min), in which most CKD diagnoses are missed. The ICD-9 code sensitivity for detecting CKD was significantly higher in patients with diabetes, hypertension, and cardiovascular disease (26.8%, 22.2%, and 23.7%, respectively) than in subjects without diabetes, hypertension, or cardiovascular disease (p < 0.001), but these values are low when the widely described relationship between such comorbidities and CKD is considered., Conclusion: Although CKD was common in this patient population at a large inpatient regional hospital, the low rates of CKD detection emphasize the primary role nephrologists must play in continued medical education, and the need for ongoing efforts to train physicians (particularly primary care providers) regarding eGFR interpretation and systematic screening for CKD in high-risk patients (i.e., the elderly, diabetics, hypertensives, and patients with CV disease).

Objective: The aim of this study was to investigate the predictive value for all-cause and cardiovascular (CV) death of anthropometric measurements of abdominal obesity in patients with end-stage renal disease (ESRD)., Background: Surrogate measures of abdominal obesity and segmental fat distribution (waist circumference and waist/hip ratio [WHR]) are stronger predictors of all-cause and CV death than body mass index (BMI) in the general population, but the issue has never been investigated in patients with ESRD., Methods: We performed a prospective cohort study in 537 patients with ESRD (age 63 +/- 15 years)., Results: In BMI-adjusted Cox models, waist circumference was a direct predictor of all-cause and CV mortality (p < 0.001), whereas BMI showed an inverse relationship (p < 0.001) with these outcomes. The incidence rates of overall and CV death were maximal in patients with relatively lower BMI scores (below the median) and higher waist circumferences (at least the median) and minimal in patients with higher BMI scores (at least the median) and small waist circumferences (below the median). The prognostic power of waist circumference for all-cause (hazard ratio [HR] [10-cm increase]: 1.23; 95% confidence interval [CI]: 1.02 to 1.47; p = 0.03) and CV mortality (HR: 1.37; 95% CI: 1.09 to 1.73; p = 0.006) remained significant after adjustment for CV comorbidities and traditional and emerging risk factors. WHR was found to be related to all-cause (p = 0.009) and CV mortality (p = 0.07)., Conclusions: Abdominal obesity underlies a high risk of all-cause and CV mortality in patients with ESRD. Redefinition of nutritional status by combining the metrics of abdominal obesity and BMI may refine prognosis in the ESRD population.

The enzyme gamma-glutamyltransferase (GGT) is an established marker of liver function and alcohol consumption and represents the major factor responsible for the extra-cellular catabolism of the main antioxidant in mammalian cells, Glutathione. ESRD is a condition characterized by a high risk of death and cardiovascular (CV) complications and with a high prevalence of liver disease but the link between GGT and clinical outcomes has never been studied in this population. We tested the predictive power of GGT for overall and cardiovascular mortality in a cohort study in 584 ESRD patients. Over a 4 years follow up 194 patients died. GGT was higher in non-survivors (median 25 UI/l, interquartile range 16-45 UI/l) than in survivors (22, 15-33 UI/l) (P=0.006). On univariate Cox regression analysis plasma GGT predicted both all-cause [HR (10 UI/l increase): 1.04, 95% CI: 1.01-1.06, P=0.006] and cardiovascular mortality [HR: 1.03, 95% CI: 1.00-1.05, P=0.04]. These relationships held true in multivariate Cox regression analyses [HR: 1.06, 95% CI: 1.03-1.10 (P<0.001) and 1.05, 95% CI: 1.01-1.10, P=0.01] adjusting for liver disease as well as Framingham risk factors and non traditional risk factors including C reactive Protein (CRP). High GGT in ESRD patients is a strong, independent risk marker for all cause and cardiovascular death. The predictive power of GGT for these outcomes likely reflects the involvement of this enzyme in oxidative stress mechanisms.

Background: The New York Heart Association (NYHA) classification is a strong predictor of mortality and an established instrument for risk stratification in patients with heart disease but data on the validity of this classification in end-stage renal disease (ESRD) are sparse., Methods: In this study, we tested the predictive value of the NYHA in patients with ESRD and compared it with that of two established indexes of disease severity, i.e. the Khan index and the renal disease severity score (RDSS). The study cohort was composed of 1322 incident patients in a dialysis registry (772 male and 550 female, age 61+/-16 years)., Results: During the follow-up period (41+/-27 months) 551 patients died. A multivariate COX model including the NYHA classification explained 39% of the variation in mortality, a figure almost identical to that of a model based on the RDSS (37%) and superior (P<0.001) to that provided by the Khan index-based model (32%). The area under the receiver operating characteristic curve of NYHA classification, as related to all-cause mortality, was 0.74 (95% CI: 0.71-0.77, P<0.001). Again, RDSS had a predictive value for mortality (0.74, 95% CI: 0.72-0.77) identical to that of NYHA and higher than that of the Khan index (0.70, 95% CI: 0.67-0.72)., Conclusion: The NYHA is a powerful predictor of mortality in ESRD and provides prognostic information equal or superior to that given by other established indexes of disease severity. Given the pervasive nature of cardiovascular disease in ESRD, this classification may be recommended for risk stratification in this population.

The Italian Registry of Dialysis and Transplantation (RIDT) was born in 1996 under the aegis of the Italian Society of Nephrology, and it is organized as a federation of regional registries. This study aimed to completely revise the epidemiological data collected during the first 5 yrs (1996-2001) of RIDT activity to evaluate the trends of the main epidemiological features. During this period, regional registries were not always able to assure complete and exhaustive information according to RIDT requirements, owing to different levels of organization and functioning. To avoid any possible error in data analysis, information inadequately assessed was refused. The incidence of end-stage renal disease (ESRD) patients on renal replacement therapy (RRT) in Italy has increased from 114 pmp in 1996 to 139 pmp in 2001, that means an increase of 3.5%/yr, corresponding to 5718 patients during 1996 and 8000 patients during 2001. Primary renal diseases (according to the EDTA) in incident ESRD patients are vascular and diabetic nephropathy. Main dialysis modality in incident patients was hemodialysis (HD) (85%), while peritoneal dialysis (PD) was only 15%; pre-emptive transplantation was a very unusual modality. The prevalence of ESRD patients at 31 December was 693 pmp in 1996 and 827 pmp in 2001; among dialysis patients, the corresponding rates were 575 pmp and 657 pmp, respectively. Consequently, the number of dialyzed patients increased, respectively, from 28892 to 37919. The prevalent dialysis modality was bicarbonate dialysis in 74% of cases, followed by hemodiafiltration (HDF) in 15%, continuous ambulatory peritoneal dialysis (CAPD) in 7% and APD in 3%. The gross mortality rate in dialyzed patients was stable during this period, at approximately 14%, the main causes of death being cardiovascular diseases and cachexia.

Background: A reduction in salivary and lacrimal secretion has been described in several diseases. However, such alterations have not been investigated fully in patients with chronic renal failure. The aim of the present study is to estimate the frequency of alterations in salivary and lacrimal secretion in long-term hemodialysis patients., Methods: Sixty-three hemodialysis patients and 23 healthy control subjects were studied. In all of them, we tested salivary secretion (Saxon's test), lacrimal secretion (Shirmer's test), and the presence of xerostomia and xerophthalmia symptoms. In a subgroup of patients, we performed other tests to evaluate evidence of ocular lesions and tissue damage to salivary glands. We also tested the relationship between salivary and lacrimal secretion and autonomic nervous system function., Results: On average, salivary and lacrimal secretion were markedly reduced in uremic patients compared with healthy controls, and alterations in salivary gland function were related strongly to salivary gland fibrosis and atrophy. Xerophthalmia often was asymptomatic, but frequently was associated with corneal lesions. Xerostomia and xerophthalmia were unrelated to autonomic dysfunction and hepatitis C virus infection., Conclusion: A reduction in lacrimal and salivary secretion is frequent in long-term dialysis patients. Such alterations often are asymptomatic and could be the expression of acceleration of an age-dependent decline in glandular function and attendant fibrosis and atrophy.

Plasma ANF concentration in uraemic patients is very sensitive to changes in extracellular volume. It is unknown, however, if the release of this vasoactive hormone has a compensatory role in the haemodynamic response to extracellular volume expansion in these patients. We investigated the effect of isolated ultrafiltration followed by isovolumic re-expansion by saline in seven haemodialysis patients. The experiment was repeated on two occasions and the UF rate as well as the rate of volume re-expansion in the two studies were accurately matched. During the phase of volume re-expansion, we infused either ANF (0.83 microgram/min) or a placebo, in random order and cross-over. Central venous pressure, arterial pressure, haematocrit, and plasma ANF concentration were measured in baseline conditions, after ultrafiltration, and 0, 15, and 30 min after isovolumic re-expansion. In the control experiment (placebo), isolated ultrafiltration caused a marked reduction in central venous pressure and in arterial pressure and a pronounced haematocrit increase. These changes were reversed by volume re-expansion. In the active experiment, during the phase of volume re-expansion ANF infusion doubled plasma ANF concentration as compared to control experiment but it did not affect the ongoing haemodynamic response nor the haematocrit changes. Doubling of plasma ANF concentration has no influence on the haemodynamic and microcirculatory adaptations to acute volume expansion in haemodialysis patients. The data indicate that it is unlikely that raised plasma ANF concentration has a major role in the cardiovascular response to acute extracellular volume expansion in these patients.

A number of reports on dialysis and transplantation for diabetic patients in the UK and USA are available. The aim of the present survey was to assess the prevalence, main characteristics and complications of diabetic patients treated by dialysis and transplantation in Italy. On 31 December 1987 in Italy, 1605 diabetic patients were being treated by dialysis or transplantation. The prevalence was 28 per million compared with the UK and the USA where the corresponding figures were 17 and 78 per million respectively. The annual incidence in 1987 was 9 per million (UK: 4 per million; USA: 33 per million). The mean age of the Italian diabetic patients was 59 years whereas that for British diabetic patients similarly evaluated was 48 years. Of the Italian diabetic patients 67% had NIDDM (UK: 22%; USA: 50%). Haemodialysis was used in 81% of the Italian patients, peritoneal dialysis in 14%, and only 5% were transplanted. This is in contrast to the UK where only 18% of the patients were treated by haemodialysis and 39% were transplanted. Amongst Italian patients who started RRT in 1987, 9% died within the year, and of the remainder 38% had severe bilateral visual impairment (UK 35%), 3% had had amputations (UK 6%), 7% had suffered from disabling strokes (UK 6%) and 7% had had a myocardial infarction (UK 17%). Before 31 December 1987 another 2.2% developed severe bilateral visual impairment, 0.6% underwent amputations, 1.0% had a disabling stroke and 0.6% suffered from a myocardial infarction. The proportion of diabetic patients treated by RRT in Italy is twice that of the UK but only half that of the USA.(ABSTRACT TRUNCATED AT 250 WORDS)

The application of a new statistical method ('breakpoint' test) to the study of the progression of chronic renal failure is described. This test establishes whether the best fit of a series of GFR measurements is linear or broken. Such an approach avoids the analytical constraint of the time of intervention assumed by other methods. Re-analysis by this test of previous studies of low-protein diet suggests that in some cases the effect of the dietary regimen has been overemphasized.

The authors carried out a retrospective survey assessing the total proportion of diabetic patients and relative proportion of patients with Type I and Type II diabetes among patients receiving renal replacement therapy and those evaluated for chronic renal failure in a southern Italian renal unit during the period 1972-1986. The proportion of diabetics among patients accepted for renal replacement therapy was 10% (34/336); of the 34 diabetic patients, only one was clearly affected by Type I diabetes, 26 had Type II diabetes, and the classification was uncertain in four patients. Similar relative proportions of Types I and II diabetes were observed among patients referred during the same period for evaluation of chronic renal failure.