Introduction

The incidence of end-stage renal disease (ESRD) is increasing in industrialized countries. In the United States, the incidence has risen from 200 to 350 per million population (pmp)/incident dialysis patients-year (1)

The main risk factors for ESRD in industrialized countries are the aging of the population, diabetes mellitus, and hypertension.

The incidence of renal replacement therapy (RRT) in Europe, according to 2012 European Renal Association–European Dialysis and Transplant Association estimates, is 133 pmp (2). Moreover, according to data collected by the Italian Dialysis and Transplantation Registry for the year 2009, a total of 8,461 patients were receiving RRT: 88% of patients were receiving haemodialysis (HD) and 12% of patients were receiving peritoneal dialysis (PD). (3) Of the 45,892 dialysis patients (764.6 pmp), 10% were receiving PD (4,028 patients).

Due to recent evidence demonstrating the clinical advantages offered by PD (ie, less hospitalizations, improved survival rates, and maintenance of residual renal function) and because of the need to limit social and healthcare costs, it has become increasingly important to assess the relative advantages and disadvantages of current RRT methods.(4)

The aim of this epidemiological study was to observe the clinical and therapeutic management of patients undergoing PD in Italy, thereby providing a comprehensive picture of clinical practice that may lead to improvements in the therapeutic management of these patients.

Objectives

• Primary objective:

The primary objective of this study was to describe changes in clinical parameters compared with reference values according to Kidney Disease Outcomes Quality Initiative (K-DOQI) guidelines (GLs) in patients undergoing PD for the following aspects: anemia, hypertension, and mineral bone disorders (MBDs).

• Secondary objectives:

The secondary objectives of this study were to describe comorbiditiesy and hospitalizations related to infectious disease, cardiovascular disease (CVD), and MBD.

Methods and data collection

ATENA was a longitudinal (12-month retrospective period, plus a 6-month prospective period), non-interventional, epidemiological investigation performed between 27 February  2013 and 28 March 2014.

During outpatient clinic visits, data was collected on demographics and lifestyle parameters. Anthropometric variables, data relating to dialysis treatment, dialysis method, and renal status, in addition to CKD, MBDs, and lipid parameters were also collected. Furthermore, information on medical history and clinical events (duration of dialysis treatment, concomitant diseases, ongoing pharmacological treatments, hospitalizations related to dialysis, switch to HD, or renal transplant and death) were collected. Each participating subject was also asked to complete the Kidney Disease Quality of Life-Short Form questionnaire (KDQOL-SF 1.3). Final data review and approval were completed by the primary investigator at each study site.

Main Inclusion Criteria

• Male or female patients undergoing PD who have been treated for ≥12 months
• Patients >18 years
• Patients who have signed an informed consent form

Main Exclusion Criteria

• Patients enrolled in clinical trials or who have already taken part in the survey
• Patients who switched from HD to PD
• Organ transplantation patients•Patients presenting with diseases that reduce life expectancy to <1 year

Conduct of the study

• Male and female adult patients in an outpatient setting presenting with ESRD and receiving PD treatment for ≥12 months were selected by nephrologists across 15 clinical sites in Italy. 
• Patients were followed per current clinical practice; no additional diagnostic or monitoring procedures were applied unless permitted by the Italian GLs for non-interventional studies
• The choice of medical treatment, if any, was made independently by the physician during routine practice and was not influenced by the study protocol.

Statistical Analysis

The sample size was calculated, taking into consideration a PD prevalence of approximately 9% out of the overall population of dialysis patients (approximately 4,000 patients). It was estimated that a sample size of 375 patients would allow for a 95% confidence interval (CI) equal to ±4.9% for the most undefined response (50%). All data are presented as mean ± standard deviation (SD), median, or percentage. Comparisons between 2 groups  with non-parametric continuous variables were calculated using the Mann-Whitney test, whereas an unpaired t test was used to compare 2 groups of normally distributed variables.

Results

A total of 378 patients were included in the ATENA study and 42 patients (11.1%) withdrew before the end of the study.

The mean age of patients at baseline was 64.7±14.3 years and 58.9% (n=223) were males; 97.1% of patients were white and the mean duration of PD (before the baseline visit) was 2.6 years.

The most frequent comorbidities recorded at baseline were hypertension (87.8%; n=332), ≥1 CVD (39.7%; n=150), 1 CVD (23.3%; n=88), 2 CVDs (9.8%; n=37); 3 CVDs (3.9%; n=15), >3 CVDs (2.6%; n=10), dyslipidemia (24.1%; n=91), type 1 diabetes (4.2%; n=16), type 2 diabetes (20.1%; n=76), neoplasia (8.2%; n=31), and recurrent peritonitis (7.9%; n=30) (Figure 1).

The most frequent concomitant medications included anti-anemia agents (80.1%; n=303), acid-related agents (75.4%; n=285), diuretics (74%; n=282), and lipid lowering agents (59.8%; n=226).

Mean hemoglobin (Hb) levels were significantly reduced over the 4 visits (11.6 g/dL 12 months before the baseline visit, 11.4 g/dL  6 months before the baseline visit, 11.4 g/dL at the baseline visit, and 11.3 g/dL after 6 months of treatment; P=0.006). In approximately 30% of patients, Hb levels were below the lower limit of normal range (≤11 g/dL) over  the 4 visits (Figure 2).

Levels of systolic and diastolic blood pressure did not change over the 4 visits (P=0.1 and P=0.16, respectively). The change in proportion of patients with high systolic (>140 mmHg) and diastolic blood pressure (>90 mmHg) over the 4 visits is shown in Figure 3.

Approximately 50% of patients (46.5%–52.2%) presented with high systolic blood pressure (>140 mmHg), whereas approximately 20% of patients (18.7%–23.3%) had high diastolic blood pressure (>80 mmHg) during all observations.

Median levels of serum intact parathyroid hormone (iPTH), calcium (Ca), and phosphorus (P) did not significantly change in patients over the 4 visits.

Approximately 34% of patients (32.4%–38%) had normal iPTH levels according to KDOQI GL ranges (150–300 pg/mL; Figure 4).  Approximately 67% of patients reported mean iPTH values within the normal range according to K-DIGO guidelines (maximum 69% at the assessment 6 months prior to the baseline visit).

Over the study period, 237  of 378 patients (62.7%) were hospitalized for various reasons. The mean (±SD) length of hospital stay was 11.71±17.04 days. The incidence of the most frequent causes of hospitalization are summarized in figure 5.

The main reasons for hospitalization were peritonitis (15.3 cases/100 person-years; 95% CI, 5.0–14.2; 1 episode every 80 months), cardiovascular disease (11.2 cases/100 person-years; 95% CI, 8.6–11.4), and other infections excluding peritonitis (5.2 cases/100 person-years; 95% CI, 3.5–7.4;  Table 2). The exit site infection (ESI) amounts to 1 infection every 230 months.

Conclusions

• Hypertension and CVD were the most frequent comorbidities in patients undergoing dialysis.
• Peritonitis was the leading cause of hospitalization.
• Secondary Hyperparathyroidism and anemia were frequent, mean Hb levels were reduced over the 4 visits, and approximately 34% of patients (as per K-DOQI GLs) had normal iPTH levels. At the end of the study, 55% of patients had P values above the upper limit and approximately 17% of patients reported Ca values below the lower limit. These data suggest that it is necessary to closely monitor Hb, iPTH, Ca, and P in patients undergoing dialysis.

References

1.US Renal Data System: USRDS 2009 Annual Data Report: Atlas of Chronic Kidney Disease and End-Stage Renal Disease in the United States National Institute of Health. Volume 1. Bethesda, MD: National Institute of Health, National Institute of Diabetes and Digestive and Kidney Disease; 2009.

2. Pippias M, Stel VS, Abad Diez JM, et al. Renal replacement therapy in Europe: a summary of the 2012 ERA-EDTA Registry Annual Report.
Clin Kidney J. 2015;8(3):248-61.

3. Registro Italiano di Dialisi e Trapianto. Società Italiana di Nefrologia . RIDT -SIN 2011. Available at:  www.sinridt.org/web/eventi/RIDT/index.cfm Accessed Sept 9th, 2015

4. Lukowsky LR, Mehrotra R, Kheifets L, Arah OA, Nissenson AR, Kalantar-Zadeh K. Comparing mortality of peritoneal and hemodialysis patients in the first 2 years of dialysis therapy: a marginal structural model analysis. Clin J Am Soc Nephrol. 2013;8(4):619-28.

Acknowledgment and disclosures

AbbVie funded the study. AbbVie was responsible for the study design, research, analysis, data collection, interpretation of data, writing, reviewing and approving of the publication.

Crepaldi, Galli, Dell’Aquila and Caputo have no conflict of interest. Russo is consultant for Baxter, Roche and Abbvie.

Umberto di Luzio Paparatti, Alessandro Possidoni, Sara Di Fino, and Anna Maria Costanzo are employees of AbbVie and may own AbbVie stock options.