Using datasets to ascertain the generalizability of clinical cohorts: the example of the European QUALity study on the treatment of advanced chronic kidney disease.

BACKGROUND: Cohort studies are among the most robust of observational studies but have issues with external validity. This study assesses threats to external validity (generalizability) in the European QUALity (EQUAL) study, a cohort study of people >65 years of age with Stage 4/5 chronic kidney disease. METHODS: Patients meeting the EQUAL inclusion criteria were identified in The Health Improvement Network database and stratified into those attending renal units, a secondary care cohort (SCC) and a not primary care cohort (PCC). Survival, progression to renal replacement therapy (RRT) and hospitalization were compared. RESULTS: The analysis included 250, 633 and 2464 patients in EQUAL, PCC and SCC. EQUAL had a higher proportion of men compared with PCC and SCC (60.0% versus 34.8% versus 51.4%). Increasing age ≥85 years {odds ratio [OR] 0.25 [95% confidence interval (CI) 0.15-0.40]} and comorbidity [Charlson Comorbidity Index ≥4, OR 0.69 (95% CI 0.52-0.91)] were associated with non-participation in EQUAL. EQUAL had a higher proportion of patients starting RRT at 1 year compared with SCC (8.1% versus 2.1%; P < 0.001). Patients in the PCC and SCC had increased risk of hospitalization [incidence rate ratio 1.76 (95% CI 1.27-2.47) and 2.13 (95% CI 1.59-2.86)] and mortality at 1 year [hazard ratio 3.48 (95% CI 2.1-5.7) and 1.7 (95% CI 1.1-2.7)] compared with EQUAL. CONCLUSIONS: This study provides evidence of how participants in a cohort study can differ from the broader population of patients, which is essential when considering external validity and application to local practice.

Kidney function and symptom development over time in elderly patients with advanced chronic kidney disease: results of the EQUAL cohort study.

BACKGROUND: Initiation of renal replacement therapy often results from a combination of kidney function deterioration and symptoms related to chronic kidney disease (CKD) progression. We investigated the association between kidney function decline and symptom development in patients with advanced CKD. METHODS: In the European Quality study on treatment in advanced CKD (EQUAL study), a European prospective cohort study, patients with advanced CKD aged ≥65 years and a kidney function that dropped <20 mL/min/1.73 m2 were followed for 1 year. Linear mixed-effects models were used to assess the association between kidney function decline and symptom development. The sum score for symptom number ranged from 0 to 33 and for overall symptom severity from 0 to 165, using the Dialysis Symptom Index. RESULTS: At least one kidney function estimate with symptom number or overall symptom severity was available for 1109 and 1019 patients, respectively. The mean (95% confidence interval) annual kidney function decline was 1.70 (1.32; 2.08) mL/min/1.73 m2. The mean overall increase in symptom number and severity was 0.73 (0.28; 1.19) and 2.93 (1.34; 4.52) per year, respectively. A cross-sectional association between the level of kidney function and symptoms was lacking. Furthermore, kidney function at cohort entry was not associated with symptom development. However, each mL/min/1.73 m2 of annual kidney function decline was associated with an extra annual increase of 0.23 (0.07; 0.39) in the number of symptoms and 0.87 (0.35; 1.40) in overall symptom severity. CONCLUSIONS: A faster kidney function decline was associated with a steeper increase in both symptom number and severity. Considering the modest association, our results seem to suggest that repeated thorough assessment of symptom development during outpatient clinic visits, in addition to the monitoring of kidney function decline, is important for clinical decision-making.

Renal function decline in older men and women with advanced chronic kidney disease-results from the EQUAL study.

INTRODUCTION: Understanding the mechanisms underlying the differences in renal decline between men and women may improve sex-specific clinical monitoring and management. To this end, we aimed to compare the slope of renal function decline in older men and women in chronic kidney disease (CKD) Stages 4 and 5, taking into account informative censoring related to the sex-specific risks of mortality and dialysis initiation. METHODS: The European QUALity Study on treatment in advanced CKD (EQUAL) study is an observational prospective cohort study in Stages 4 and 5 CKD patients ≥65 years not on dialysis. Data on clinical and demographic patient characteristics were collected between April 2012 and December 2018. Estimated glomerular filtration rate (eGFR) was calculated using the CKD Epidemiology Collaboration equation. eGFR trajectory by sex was modelled using linear mixed models, and joint models were applied to deal with informative censoring. RESULTS: We included 7801 eGFR measurements in 1682 patients over a total of 2911 years of follow-up. Renal function declined by 14.0% [95% confidence interval (CI) 12.9-15.1%] on average each year. Renal function declined faster in men (16.2%/year, 95% CI 15.9-17.1%) compared with women (9.6%/year, 95% CI 6.3-12.1%), which remained largely unchanged after accounting for various mediators and for informative censoring due to mortality and dialysis initiation. Diabetes was identified as an important determinant of renal decline specifically in women. CONCLUSION: In conclusion, renal function declines faster in men compared with women, which remained similar after adjustment for mediators and despite a higher risk of informative censoring in men. We demonstrate a disproportional negative impact of diabetes specifically in women.

International prescribing patterns and polypharmacy in older people with advanced chronic kidney disease: results from the European Quality study.

BACKGROUND: People with chronic kidney disease (CKD) are at high risk of polypharmacy. However, no previous study has investigated international prescribing patterns in this group. This article aims to examine prescribing and polypharmacy patterns among older people with advanced CKD across the countries involved in the European Quality (EQUAL) study. METHODS: The EQUAL study is an international prospective cohort study of patients ≥65 years of age with advanced CKD. Baseline demographic, clinical and medication data were analysed and reported descriptively. Polypharmacy was defined as ≥5 medications and hyperpolypharmacy as ≥10. Univariable and multivariable linear regressions were used to determine associations between country and the number of prescribed medications. Univariable and multivariable logistic regression were used to determine associations between country and hyperpolypharmacy. RESULTS: Of the 1317 participants from five European countries, 91% were experiencing polypharmacy and 43% were experiencing hyperpolypharmacy. Cardiovascular medications were the most prescribed medications (mean 3.5 per person). There were international differences in prescribing, with significantly greater hyperpolypharmacy in Germany {odds ratio (OR) 2.75 [95% confidence interval (CI) 1.73-4.37]; P < 0.001, reference group UK}, the Netherlands [OR 1.91 (95% CI 1.32-2.76); P = 0.001] and Italy [OR 1.57 (95% CI 1.15-2.15); P = 0.004]. People in Poland experienced the least hyperpolypharmacy [OR 0.39 (95% CI 0.17-0.87); P = 0.021]. CONCLUSIONS: Hyperpolypharmacy is common among older people with advanced CKD, with significant international differences in the number of medications prescribed. Practice variation may represent a lack of consensus regarding appropriate prescribing for this high-risk group for whom pharmacological treatment has great potential for harm as well as benefit.

The dominant prognostic value of physical functioning among quality of life domains in end-stage kidney disease.

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.

Uraemic symptom burden and clinical condition in women and men of ≥65 years of age with advanced chronic kidney disease: results from the EQUAL study.

BACKGROUND: The epidemiology and prognosis of chronic kidney disease (CKD) differ by sex. We aimed to compare symptom prevalence and the clinical state in women and men of ≥65 years of age with advanced CKD receiving routine nephrology care. METHODS: The European QUALity study on treatment in advanced chronic kidney disease (EQUAL) study follows patients from six European countries of ≥65 years of age years whose estimated glomerular filtration rate (eGFR) dropped to ≤20 mL/min/1.73 m2 for the first time during the last 6 months. The Dialysis Symptom Index was used to assess the prevalence and severity of 33 uraemic symptoms. Data on the clinical state at baseline were collected from medical records. Prevalence was standardized using the age distribution of women as the reference. RESULTS: The results in women (n = 512) and men (n = 967) did not differ with age (77.0 versus 75.7 years) or eGFR (19.0 versus 18.5). The median number of symptoms was 14 [interquartile range (IQR) 9-19] in women, and 11 (IQR 7-16) in men. Women most frequently reported fatigue {39% [95% confidence interval (CI) 34-45]} and bone/joint pain [37% (95% CI 32-42)] as severe symptoms, whereas more men reported difficulty in becoming sexually aroused [32% (95% CI 28-35)] and a decreased interest in sex [31% (95% CI 28-35)]. Anaemia [73% (95% CI 69-77) versus 85% (95% CI 82-87)] was less common in women than in men, as were smoking history and cardiovascular comorbidity. However, a diagnosis of liver disease other than cirrhosis, psychiatric disease and mild malnutrition were more common among women. CONCLUSIONS: Women in secondary care with an incident eGFR ≤20 mL/min/1.73 m2 reported a higher symptom burden, while their clinical state was considered similar or even more favourable as compared with men.

The impact of symptoms on health-related quality of life in elderly pre-dialysis patients: effect and importance in the EQUAL study.

BACKGROUND: Quality of life (QoL) is an important outcome in chronic kidney disease (CKD). Patients feel that symptoms are an important determinant of QoL. However, this relation is unknown. The aims of this study were to investigate the impact of the number and severity of symptoms on QoL in elderly pre-dialysis patients, assessed by both the effect of symptoms and their importance relative to kidney function, and other clinical variables on QoL. METHODS: The European Quality study (EQUAL study) is an ongoing European prospective follow-up study in late Stage 4/5 CKD patients aged ≥65 years. We used patients included between March 2012 and December 2015. Patients scored their symptoms with the Dialysis Symptom Index, and QoL with the research and development-36 (RAND-36) item Health Survey (RAND-36). The RAND-36 results in a physical component summary (PCS) and a mental component summary (MCS). We used linear regression to estimate the relation between symptoms and QoL at baseline and after 6 months, and to calculate the variance in QoL explained by symptoms. RESULTS: The baseline questionnaire was filled in by 1079 (73%) patients (median age 75 years, 66% male, 98% Caucasian), and the follow up questionnaire by 627 (42%) patients. At baseline, every additional symptom changed MCS with -0.81 [95% confidence interval (CI): -0.91 to -0.71] and PCS with -0.50 (95% CI: -0.62 to -0.39). In univariable analyses, number of symptoms explained 22% of MCS variance and 11% of PCS variance, whereas estimated glomerular filtration rate only explained 1%. CONCLUSIONS: In elderly CKD Stage 4/5 patients, symptoms have a substantial impact on QoL. This indicates symptoms should have a more prominent role in clinical decision-making.

Neuropeptide Y and chronic kidney disease progression: a cohort study.

Background: Neuropeptide Y (NPY) is a sympathetic neurotransmitter that has been implicated in various disorders including obesity, gastrointestinal and cardiovascular diseases. Methods: We investigated the relationship between circulating NPY and the progression of the glomerular filtration rate (GFR) and proteinuria and the risk for a combined renal endpoint (>30% GFR loss, dialysis/transplantation) in two European chronic kidney disease (CKD) cohorts including follow-up of 753 and 576 patients for 36 and 57 months, respectively. Results: Average plasma NPY was 104 ± 32 pmol/L in the first CKD cohort and 119 ± 41 pmol/L in the second one. In separate analyses of the two cohorts, NPY associated with the progression of the estimated GFR (eGFR) and proteinuria over time in both unadjusted and adjusted {eGFR: -3.60 mL/min/1.73 m2 [95% confidence interval (CI): -4.46 to - 2.74] P < 0.001 and -0.83 mL/min/1.73 m2 (-1.41 to - 0.25, P = 0.005); proteinuria: 0.18 g/24 h (0.11-0.25) P < 0.001 and 0.07 g/24 h (0.005-0.14) P = 0.033} analyses by the mixed linear model. Accordingly, in a combined analysis of the two cohorts accounting for the competitive risk of death (Fine and Gray model), NPY predicted (P = 0.005) the renal endpoint [sub-distribution hazard ratio (SHR): 1.09; 95% CI: 1.03-1.16; P = 0.005] and the SHR in the first cohort (1.14, 95% CI: 1.04-1.25) did not differ (P = 0.25) from that in the second cohort (1.06, 95% CI: 0.98-1.15). Conclusions: NPY associates with proteinuria and faster CKD progression as well as with a higher risk of kidney failure. These findings suggest that the sympathetic system and/or properties intrinsic to the NPY molecule may play a role in CKD progression.

Systematic DNA Study for Fabry Disease in the End Stage Renal Disease Patients from a Southern Italy Area.

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.

Mutations in the GLA Gene and LysoGb3: Is It Really Anderson-Fabry Disease?

Anderson-Fabry disease (FD) is a rare, progressive, multisystem storage disorder caused by the partial or total deficit of the lysosomal enzyme α-galactosidase A (α-Gal A). It is an X-linked, lysosomal enzymopathy due to mutations in the galactosidase alpha gene (GLA), encoding the α-Gal A. To date, more than 900 mutations in this gene have been described. In our laboratories, the study of genetic and enzymatic alterations related to FD was performed in about 17,000 subjects with a symptomatology referable to this disorder. The accumulation of globotriaosylsphingosine (LysoGb3) was determined in blood of positives. Exonic mutations in the GLA gene were detected in 471 patients (207 Probands and 264 relatives): 71.6% of mutations were associated with the classic phenotype, 19.8% were associated with the late-onset phenotype, and 8.6% of genetic variants were of unknown significance (GVUS). The accumulation of LysoGb3 was found in all male patients with a mutation responsible for classic or late-onset FD. LysoGb3 levels were consistent with the type of mutations and the symptomatology of patients. α-Gal A activity in these patients is absent or dramatically reduced. In recent years, confusion about the pathogenicity of some mutations led to an association between non-causative mutations and FD. Our study shows that the identification of FD patients is possible by associating clinical history, GLA gene analysis, α-Gal A assay, and blood accumulation of LysoGB3. In our experience, LysoGB3 can be considered a reliable marker, which is very useful to confirm the diagnosis of Fabry disease.

Body mass index trend in haemodialysis patients: the shift of nutritional disorders in two Italian regions.

BACKGROUND: In the USA, the increase in the prevalence of obesity in the general population has been accompanied by a marked increase in the prevalence and incidence of obesity in the dialysis population. However, secular trends of body mass index (BMI) have not been investigated in European renal registries. METHODS: We investigated the secular trend of BMI across 18 years (1994-2011) in two haemodialysis (HD) registries (Calabria in southern Italy and Emilia in northern Italy) on a total of 16 201 prevalent HD patients and in a series of 3559 incident HD patients. We compared trends in BMI for HD patients with those in the background general population of the same regions. RESULTS: The average BMI rose from 23.5 kg/m(2) in 1994 to 25.5 (+8.5%) in 2011 in the Calabria registry and from 23.7 in 1998 to 25.4 (+7.1%) in 2011 in the Emilia registry (P < 0.001). The proportion of obese patients (i.e. with BMI >30 kg/m(2)) rose from 6 to 14% in Calabria and from 6 to 16% in Emilia (P < 0.001). These patterns were fully confirmed in incident patients and were mirrored by a substantial decline in the prevalence of underweight-normal and underweight (P < 0.001) patients. Of note, the steepness of the increase in BMI in haemodialysis patients was 3.7 times more pronounced than that in the coeval, age- and sex-matched general population of Calabria and Emilia. CONCLUSIONS: In two regional haemodialysis registries in Italy a steady increase in overweight and obese patients is observed. These patterns are more pronounced than those found in the general population. If further confirmed in other European haemodialysis cohorts, these findings may have relevant public health implications.

Competitive interaction between fibroblast growth factor 23 and asymmetric dimethylarginine in patients with CKD.

Both fibroblast growth factor 23 (FGF-23) and asymmetric dimethylarginine (ADMA) are associated with progression of CKD. We tested the hypothesis that ADMA and FGF23 are interactive factors for CKD progression in a cohort of 758 patients with CKD in Southern Europe (mean eGFR±SD, 36±13 ml/min per 1.73 m(2)) and in a central European cohort of 173 patients with CKD (MMKD study, mean eGFR, 64±39 ml/min per 1.73 m(2)). In the first cohort, 214 patients had renal events (decrease in eGFR of >30%, dialysis, or kidney transplantation) during a 3-year follow-up. Both intact FGF-23 and ADMA predicted the incidence rate of renal events in unadjusted and adjusted analyses (P<0.001). There was a strong competitive interaction between FGF-23 and ADMA in the risk of renal events (P<0.01 in adjusted analyses); the risk associated with raised ADMA levels was highest in patients with low FGF-23 levels. These results were confirmed in the MMKD cohort, in which FGF-23 level was again an effect modifier of the relationship between plasma ADMA level and renal events (doubling of baseline serum creatinine, dialysis, or kidney transplantation) in the adjusted analyses (P<0.01). Furthermore, in the MMKD cohort there was a parallel, independent competitive interaction between symmetric dimethylarginine level and c-terminal FGF-23 level for the risk for renal events (P=0.001). These findings indicate that the association of ADMA level with the risk of CKD progression is modified by FGF-23 level and provide further evidence that dysregulation of the nitric oxide system is involved in CKD progression.

Children of a lesser god or miracles? An emotional and behavioural profile of children born to mothers on dialysis in Italy: a multicentre nationwide study 2000-12.

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.

Mortality from infections and malignancies in patients treated with renal replacement therapy: data from the ERA-EDTA registry.

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.

Analysis of data from the ERA-EDTA Registry indicates that conventional treatments for chronic kidney disease do not reduce the need for renal replacement therapy in autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is a major cause of end-stage kidney failure, but is often identified early and therefore amenable to timely treatment. Interventions known to postpone the need for renal replacement therapy (RRT) in non-ADPKD patients have also been tested in ADPKD patients, but with inconclusive results. To help resolve this we determined changes in RRT incidence rates as an indicator for increasing effective renoprotection over time in ADPKD. We analyzed data from the European Renal Association-European Dialyses and Transplant Association Registry on 315,444 patients starting RRT in 12 European countries between 1991 and 2010, grouped into four 5-year periods. Of them, 20,596 were due to ADPKD. Between the first and last period the mean age at onset of RRT increased from 56.6 to 58.0 years. The age- and gender-adjusted incidence rate of RRT for ADPKD increased slightly over the four periods from 7.6 to 8.3 per million population. No change over time was found in the incidence of RRT for ADPKD up to age 50, whereas in recent time periods the incidence in patients above the age of 70 clearly increased. Among countries there was a significant positive association between RRT take-on rates for non-ADPKD kidney disease and ADPKD. Thus, the increased age at onset of RRT is most likely due to an increased access for elderly ADPKD patients or lower competing risk prior to the start of RRT rather than the consequence of effective emerging renoprotective treatments for ADPKD.

Snoring amplifies the risk of heart failure and mortality in dialysis patients.

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.

The children of dialysis: live-born babies from on-dialysis mothers in Italy--an epidemiological perspective comparing dialysis, kidney transplantation and the overall population.

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.

Renal replacement therapy for autosomal dominant polycystic kidney disease (ADPKD) in Europe: prevalence and survival--an analysis of data from the ERA-EDTA Registry.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the fourth most common renal disease requiring renal replacement therapy (RRT). Still, there are few epidemiological data on the prevalence of, and survival on RRT for ADPKD. METHODS: This study used data from the ERA-EDTA Registry on RRT prevalence and survival on RRT in 12 European countries with 208 million inhabitants. We studied four 5-year periods (1991-2010). Survival analysis was performed by the Kaplan-Meier method and by Cox proportional hazards regression. RESULTS: From the first to the last study period, the prevalence of RRT for ADPKD increased from 56.8 to 91.1 per million population (pmp). The percentage of prevalent RRT patients with ADPKD remained fairly stable at 9.8%. Two-year survival of ADPKD patients on RRT (adjusted for age, sex and country) increased significantly from 89.0 to 92.8%, and was higher than for non-ADPKD subjects. Improved survival was noted for all RRT modalities: haemodialysis [adjusted hazard ratio for mortality during the last versus first time period 0.75 (95% confidence interval 0.61-0.91), peritoneal dialysis 0.55 (0.38-0.80) and transplantation 0.52 (0.32-0.74)]. Cardiovascular mortality as a proportion of total mortality on RRT decreased more in ADPKD patients (from 53 to 29%), than in non-ADPKD patients (from 44 to 35%). Of note, the incidence rate of RRT for ADPKD remained relatively stable at 7.6 versus 8.3 pmp from the first to the last study period, which will be discussed in detail in a separate study. CONCLUSIONS: In ADPKD patients on RRT, survival has improved markedly, especially due to a decrease in cardiovascular mortality. This has led to a considerable increase in the number of ADPKD patients being treated with RRT.

Dexamethasone intravitreal implant for treatment of patients with persistent diabetic macular edema.

PURPOSE: To report the 6-month anatomical and best-corrected visual acuity (BCVA) response after primary intravitreal dexamethasone implantation (Ozurdex®) in patients with refractory diabetic macular edema (DME). METHODS: Retrospective review of the medical records of 58 patients with decreased visual acuity, due to refractory DME, who underwent a single injection of Ozurdex between November 2010 and January 2012, at the Instituto de Microcirurgia Ocular, Barcelona, Spain. RESULTS: At baseline, the mean foveal thickness (FT) was 543.24 ± 156.51 µm. Mean (±SD) values of FT did decrease to 346.82 ± 123.74 µm at month 1 and 341.12 ± 129.64 µm at month 3. Data on the 6-month follow-up showed a mild increase to 420.16 ± 152.15 µm. All of the FT reduction outcomes were statistically significant, with respect to baseline data (p = 0.0001). The baseline BCVA data was 0.66 ± 0.36 logarithm of the minimum angle of resolution (logMAR). The mean BCVA improved to 0.52 ± 0.32 logMAR (p = 0.0001) and 0.44 ± 0.27 logMAR (p = 0.0001) after 1 and 3 months, respectively. At the last visit (6-month follow-up), the mean BCVA increased to 0.51 ± 0.31 logMAR (p = 0.0001). CONCLUSIONS: In this study, intravitreal treatment with a dexamethasone implant safely reduced DME and improved visual acuity in a difficult-to-treat patient population with long-standing refractory DME.

Pulmonary congestion predicts cardiac events and mortality in ESRD.

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.