University of Groningen Adjustment to kidney transplantation Schulz, Torben

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Adjustment to kidney transplantation Schulz, Torben

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Schulz, T. (2018). Adjustment to kidney transplantation: Predictors of perceived health and psychological distress. Rijksuniversiteit Groningen.

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Adjustment to kidney transplantation:

predictors of perceived health and psychological distress

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The studies described in this thesis were financially supported by the Ubbo Emmius programme of the University of Groningen and conducted within the Graduate School for Health Research SHARE. Printing of this thesis was financially supported by the Graduate School for Health Research SHARE, the University Medical Center Groningen, and the University of Groningen.

Cover: age fotostock©BSIP/ESTIOT Printed by: Zalsman Groningen

ISBN: 978-94-034-1000-5 (printed book) ISBN: 978-94-034-0999-3 (pdf)

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Adjustment to kidney

transplantation

Predictors of perceived health and psychological distress

Proefschrift

ter verkrijging van de graad van doctor aan de Rijksuniversiteit Groningen

op gezag van de

rector magnificus prof. dr. E. Sterken

en volgens besluit van het College voor Promoties. De openbare verdediging zal plaatsvinden op

maandag 22 oktober 2018 om 14.30 uur

door

Torben Schulz

geboren op 30 september 1975

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Promotores

Prof. dr. A.V. Ranchor Prof. dr. R.J. Ploeg

Prof. dr. J.J. Homan van der Heide

Copromotor

Dr. J. Niesing

Beoordelingscommissie

Prof. dr. U. Bültmann Prof. dr. A.W.M. Evers Prof. dr. F.J. Bemelman

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CONTENTS

Chapter 1 Introduction 9

Chapter 2 Perceived health after kidney transplantation: A cross-sectional

comparison of long-term and short-term cohorts

Torben Schulz, Jan Niesing, Jaap J. Homan van der Heide, Ralf Westerhuis, Rutger J. Ploeg, Adelita V. Ranchor

Transplantation Proceedings (2013), 45, 2184-2190.

29

Chapter 3 The role of personal characteristics in the relationship between health

and psychological distress among kidney transplant recipients

Torben Schulz, Jan Niesing, Roy E. Stewart, Ralf Westerhuis, Mariet Hagedoorn, Rutger J. Ploeg, Jaap J. Homan van der Heide, Adelita V. Ranchor

Social Science & Medicine (2012), 75, 1547-1555.

47

Chapter 4 Great expectations? Pre-transplant quality of life expectations and

distress after kidney transplantation: a prospective study

British Journal of Health Psychology (2014), 19, 823-838.

73

Chapter 5 Changes of perceived control after kidney transplantation: a

prospective study

Journal of Advanced Nursing (2017), 73(7), 1712– 1721.

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changes in distress

Alicia M. de Vries, Torben Schulz, Ralf Westerhuis, Gerjan J. Navis, Jan Niesing, Adelita V. Ranchor, Maya J. Schroevers

British Journal of Health Psychology (2017), 22, 524-541.

Chapter 7 Trajectories of perceived health status in kidney and liver

transplantation

Torben Schulz, Coby Annema, Roy E. Stewart, Karin M. Vermeulen, Mariet Hagedoorn, Jaap J. Homan van der Heide, Ralf Westerhuis, Robert J. Porte, Herold J. Metselaar, Bart van Hoek, Rutger J. Ploeg, Jan Niesing, Adelita V. Ranchor

Submitted.

141

Chapter 8 General discussion

165 Summary 191 Samenvatting 197 Acknowledgements 203

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Chapter 1

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End-stage renal disease (ESRD) is a life-threatening condition with wide-ranging implications for patients’ lives. Among the available treatments, kidney transplantation is regarded as the best option in terms of patient survival and cost-effectiveness. More recently, evidence has accumulated which suggests that recipients of kidney transplants also experience better health-related quality of life. However, despite advances in our knowledge about the impact of different treatment options for ESRD on patients’ health-related quality of life, the process of adjustment to kidney transplantation remains poorly understood. Some of the issues requiring further investigation are the underlying mechanisms of improvement, explanations for individual differences in outcomes, and long-term impact of kidney transplantation. Accordingly, this research was undertaken to fill a few of these gaps and identify determinants of adjustment to kidney transplantation, with particular focus on individual characteristics of patients. Findings are expected to increase our understanding of the adjustment process after kidney transplantation, and in doing so will hopefully open new avenues to further improve the health-related quality of life of patients living with a kidney transplant.

This opening chapter begins with an introduction to end-stage renal disease and its epidemiology, followed by a brief description of available treatment options. Next, the patient experience and the role individual characteristics may play in the adjustment process is discussed. Subsequently, setting, design, and aims of the two studies conducted for this research project are outlined. The chapter concludes with a brief preview of the individual scientific articles at the heart of this thesis.

End Stage Renal Disease

Definition

The kidneys fulfil a range of vital functions, including excretion of metabolic waste products, regulation of water and electrolyte metabolism, maintenance of acid-base homeostasis and endocrine functions, such as haemoglobin synthesis, vitamin D metabolism, and modulation of blood pressure. (Rinschen, Völker, & Brinkkötter, 2014). In advanced stages of chronic kidney disease (CKD), most of these functions are disrupted. CKD is defined as “abnormalities of kidney structure or function, present for > 3 months, with implications for health” (Stevens, Levin, & Kidney Disease: Improving Global Outcomes Chronic Kidney Disease Guideline Development Work Group Members, 2013). According to clinical practice

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11 guidelines, six stages of CKD are differentiated based on glomerular filtration rate [GFR: a measure of kidney function based on serum creatinine concentration adjusted for age, gender, and ethnicity] and albuminuria [presence of protein in the urine] (Stevens et al., 2013). Stages range from an asymptomatic condition [GFR > 60 mL/min/1.73 m² and urinary albumin < 30 mg/g] to kidney failure [GFR < 15 mL/min/1.73 m² and urinary albumin > 300 mg/g] (Parrish, 2016). The terms kidney failure and ESRD are often used interchangeably, but technically the term ESRD is reserved for situations where renal replacement therapy (RRT) has been initiated (National Kidney Foundation, 2002). However, given that kidney failure is ultimately fatal without adequate treatment in the form of RRT, in the developed world ESRD and kidney failure usually coincide.

Epidemiology

Every year approximately 441,000 people globally initiate RRT, corresponding to an incidence of 73 per million population [pmp] (Anand, Bitton, & Gaziano, 2013). In 2010, 2.6 million people worldwide received RRT, a prevalence of 379 pmp (Liyanage et al., 2015). Forecasts predict that the number of people treated with RRT will more than double by 2030, mainly due to ageing populations and the growing prevalence of diabetes and hypertension (Liyanage et al., 2015).

With a 14 % increase between 2001 and 2014, the incidence of ESRD in the Netherlands is considered relatively stable (United States Renal Data System, 2016). In 2015, 1996 patients (118 pmp) started RRT (Nefrodata, 2016a). However, the prevalence of ESRD in the Netherlands has increased significantly, as indicated by a 49 % rise between 2000 and 2013 (United States Renal Data System, 2016). In 2016 16,727 patients (985 pmp) were registered as treated with RRT (Nefrodata, 2016a).

It is foreseeable that the growing number of patients with ESRD will place enormous demands on health-care budgets. Dialysis and kidney transplantation are amongst the most expensive treatments covered by basic health insurance in the Netherlands. The annual expense for dialysis amounts to approximately € 80,000 to € 120,000 per patient. Kidney transplantation and care for the recipient cost about € 80,000 per patient during the first year, but is considerably less expensive than dialysis in subsequent years (Nierstichting, 2016). In 2011, ESRD ranked 17th among the most expensive conditions in terms of health expenditure in the Netherlands with a total of € 800,000,000 spent on its treatment

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(Volksgezondheidenzorg.info, 2011). These numbers imply that 0.9 % of the entire Dutch health care budget was allocated for the treatment of 0.09 % of the population. Given the growing prevalence of ESRD and the immense costs associated with its treatment, progress in the prevention and management of ESRD becomes increasingly important.

Treatment

Dialysis

Kidney transplantation aside, dialysis is the only renal replacement therapy for ESRD. Dialysis removes metabolic waste products and corrects imbalances of salt, water, and acid-base homeostasis to some extent [5 – 15 % of kidney function (Nierstichting, 2016)], but is unable to substitute endocrine functions of the kidney (Levy, Brown, & Daley, 2009a). Two types of dialysis are distinguished: peritoneal dialysis (PD) and haemodialysis (HD).

In PD the blood is purified inside the body using the peritoneum as a semi-permeable membrane. Dialysate (i.e. cleansing fluid) is introduced into the peritoneal cavity through a catheter and draws excess fluid and metabolic waste products out of the blood. By means of diffusion, the dialysate becomes progressively saturated after which it is drained from the body and replaced, a process referred to as an exchange (Findlay & Isles, 2015; National Kidney Foundation, 2015a; Nierstichting, n.d.). There are two subtypes of PD, continuous ambulatory PD (CAPD) and automated PD (APD). In CAPD, patients themselves carry out four to five exchanges daily during waking hours, each exchange taking 20 –30 minutes. In APD, exchanges are managed automatically by a machine called cycler, with each cycle taking 1 to 1.5 hours. APD usually takes place at home during the night while the patient sleeps (Findlay & Isles, 2015; National Kidney Foundation, n.d.).

In HD, the blood is processed inside an external artificial kidney, also called dialyzer, as part of a dialysis circuit (Levy, Brown, & Daley, 2009a; National Kidney Foundation, 2015b). By means of a vascular access patients’ circulation is connected to the dialyzer, through which blood is pumped and purified in the process. Inside the dialyzer a thin semi-permeable membrane separates the blood from the dialysate, which draws excess fluid and metabolic waste products out of the blood (Levy, Brown, & Daley, 2009a; National Kidney Foundation, 2015b). HD treatment is carried out at hospitals, dialysis centres, or at home. In its most common form, in-centre HD, treatment takes place at a dialysis unit or hospital every other day three times a week with each session taking about four hours (National

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13 Kidney Foundation, 2015a). Some dialysis centres also offer the possibility of night-time HD. Another option is HD at home allowing more frequent dialysis treatment, six or seven times per week with fewer hours per session or with longer sessions during the night (Levy, Brown, & Daley, 2009a; National Kidney Foundation, 2015b).

In 2016, 6,452 patients in the Netherlands were treated with dialysis; 5592 (87 %) with haemodialysis and 860 with peritoneal dialysis, a 34 % increase from 2001 (Nefrodata, 2016a). Dialysis treatment is associated with high mortality. In 2014, 1154 (18 %) of 6466 patients on dialysis in the Netherlands died (ERA-EDTA Registry, 2016).

Kidney transplantation

Kidney transplantation is the preferred treatment option for ESRD because it is associated with lower mortality, more cost-effective, and affords patients better health-related quality of life than dialysis (Klarenbach, Tonelli, Chui, & Manns, 2014; Kontodimopoulos & Niakas, 2008; Liem, Bosch, Arends, Heijenbrok-Kal, & Hunink, 2007; Wyld, Morton, Hayen, Howard, & Webster, 2012). To receive a transplant, patients have to be placed on the waiting list for kidneys from deceased donors, which is only accessible for patients who have started dialysis, or find a living donor willing to donate one of their kidneys. In either case, patients are initially assessed by a consulting nephrologist to ensure their suitability for transplantation. Kidneys of deceased donors are allocated according to a complex system, taking multiple variables, such as histocompatibility, waiting time, urgency, and age into account. Organs from deceased donors are scarce, a fact that is reflected in the average waiting time of over three years observed in the Netherlands (Nederlandse Transplantatie Stichting, 2015). As a consequence, the number of transplantations with living donor kidneys has rapidly increased during the last decade.

The transplant surgery itself takes two to four hours and the native kidneys are only removed if they cause severe problems such as frequent kidney infections (Levy, Brown, & Daley, 2009b; University of California San Francisco, 2016). During surgery the kidney is placed in the anterior part of the lower abdomen in the pelvis in the iliac fossa (Gunabushanam, Matas, & Humar, 2015). After artery and vein of the kidney are joined to iliac artery and vein blood flow to the kidney is restored. The ureter is then joined to the bladder to complete the operation (Gunabushanam et al., 2015; Kidney Research UK, 2013). Recovery in the hospital takes usually three to seven days. After the operation, patient and

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kidney are monitored carefully and depending on the success of the procedure and subsequent performance of the transplanted organ, kidney function is partially restored.

Since 2001, there are more patients in the Netherlands who live with a kidney transplant than patients on dialysis (Nefrodata, 2016b). Moreover, the number of patients living with a functioning kidney graft has more than doubled from 4918 in 2001 to 10,275 in 2016 (Nefrodata, 2016b). Since 2008 the majority of transplantations in the Netherlands are performed with kidneys from living donors (Nefrodata, 2016c); of 983 kidney transplantations in 2015, 513 (52 %) involved a living donor kidney (Nederlandse Transplantatie Stichting, 2015). On average, kidneys from living donors survive longer. According to figures for the cohort 2005 - 2009, 94.2 % of kidneys from living donors are still functioning after five years compared to 87.9 % of kidneys from deceased donors (ERA-EDTA Registry, 2016).

The patient experience

Perceived health and psychological distress

ESRD and dialysis treatment put considerable strain on patients. Besides the time-consuming dialysis sessions, patients treated with dialysis are also required to adhere to restrictions of diet and fluid intake, as dialysis only partially substitutes the functions of the kidney. In addition, patients face distressing symptoms such as fatigue and itching (Danquah, Meininger, Zimmerman, Bergstrom, & Diamond, 2010; Murtagh, Addington-Hall, & Higginson, 2007; Scherer, Combs, & Brennan, 2017). Overall, this implies major disruptions of patients’ lives and contributes to the intrusiveness of the illness and its treatment (Griva, Jayasena, Davenport, Harrison, & Newman, 2009; Polaschek, 2003; Urquhart-Secord et al., 2016). Accordingly, a number of studies have suggested that perceived health is lower and psychological distress higher among patients treated with dialysis than among kidney transplant recipients and the general population (Alvares, Cesar, Acurcio, Gurgel Andrade, & Cherchiglia, 2012; Czyzewski, Sanko-Resmer, Wyzgal, & Kurowski, 2014; Landreneau, Lee, & Landreneau, 2010; Liem et al., 2007; Ozcan et al., 2015; Tonelli et al., 2011).

Kidney transplantation liberates patients from the restrictions imposed by dialysis. However, despite the advantages kidney transplantation has over dialysis treatment in terms of mortality, perceived health and possibly psychological distress, it is not without

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15 drawbacks. While the longevity of kidney transplants has significantly improved, the threat of rejection remains. Besides being a perpetual concern for some patients, this also means that kidney transplantation is in many cases only a temporary solution and a number of patients will outlive their kidney and require a second or even third transplant. Another drawback is that, although individual outcomes might differ substantially, kidney function is rarely restored to the level of healthy individuals. This implies that in many cases some symptoms associated with advanced stages of chronic kidney disease, such as fatigue, will persist, albeit to a lesser degree (Goedendorp, Hoitsma, Bloot, Bleijenberg, & Knoop, 2013). In addition, patients have to take immunosuppressive medication to counter the immune response; genetically unfamiliar tissue is normally attacked by the immune system of the host and causes the kidney to cease functioning (i.e. rejection). While much progress has been made over the last decades, immunosuppressive medication continues to have unpleasant and sometimes severe adverse effects, suspected to accumulate over time (Afshar, Rebollo-Mesa, Murphy, Murtagh, & Mamode, 2012; Kugler et al., 2009; Teng et al., 2015). Furthermore, prolonged exposure to immunosuppressants has been linked to the development of chronic conditions such as cardiovascular diseases, diabetes, and malignancies (AlBugami & Kiberd, 2014; McCaughan & Courtney, 2015; Sharif & Cohney, 2016; Stoumpos, Jardine, & Mark, 2015). These drawbacks of kidney transplantation might explain why perceived health has often been found to remain lower when compared to the general population (Dew et al., 1997; Dobbels, De Bleser, De Geest, & Fine, 2007; Landreneau et al., 2010; von der Lippe et al., 2014; Wei et al., 2013).

Despite the growing number of kidney transplant recipients living for many years with a transplanted kidney, the long-term perspective on patient-reported outcomes has received little research attention. One of the few studies conducted among long-term kidney transplant recipients corroborated that their general health perceptions were lower than those of the general population (Neipp et al., 2006). Whether differences exist in perceived health between short-term and long-term kidney transplant recipients remains presently unknown and is therefore, one of the subjects addressed in this thesis.

According to earlier research, the course of important patient-reported outcomes such as health-related quality of life displays similarities across different types of organ transplants and it has been suggested that sub-groups with a different course can be identified (Goetzmann et al., 2008; Villeneuve et al., 2016). So far, however, no attempts

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have been made to discern sub-groups of patients who differ with regards to the course of perceived health and to identify correlates thereof. Results could facilitate early recognition of at-risk patients and thus will be amongst the topics investigated in this thesis.

Individual characteristics

Although research has repeatedly found that kidney transplant recipients experience better perceived health and less psychological distress, outcomes vary considerably between patients. Attempts to explain these differences have so far mainly focused on socio-demographic and medical determinants. Most notably, a greater burden in terms of symptoms and comorbidities has repeatedly been linked to reduced perceived health and increased psychological distress (Bohlke et al., 2009; Gentile et al., 2013; Prihodova et al., 2010; Rosenberger et al., 2006). However, given that perceived health and psychological distress are inherently subjective, individual characteristics of patients are likely to have added importance when explaining differences in post-transplant outcomes. Preliminary support for this claim comes from a few studies linking individual characteristics, such as control beliefs and neuroticism to better physical and mental quality of life of kidney transplant recipients (Goetzmann et al., 2008; Griva et al., 2009; Prihodova et al., 2010). Yet, previous research in other patient populations has suggested some additional factors that might play a crucial role in the adjustment process.

Cognitive adaptation theory (Taylor, Kemeny, Reed, Bower, & Gruenewald, 2000; Taylor, 1983) proposes that aside from perceived control, optimism and self-esteem are of particular significance. Firstly, perceived control refers to an individual’s belief that important outcomes in one’s life are under one’s control. Higher levels of perceived control were shown to be associated with better perceived health and less psychological distress in the general population, as well as across a range of illnesses, including ESRD (Birmele, Le Gall, Sautenet, Aguerre, & Camus, 2012; Gadalla, 2009; Griva et al., 2009; Helgeson, Reynolds, Siminerio, Becker, & Escobar, 2014; Stewart & Yuen, 2011; Theofilou, 2012). Secondly, optimism, defined as a generalized expectation of positive outcomes (Scheier & Carver, 1985), is reported to have beneficial effects on adjustment and psychological distress in different patient populations (Avvenuti, Baiardini, & Giardini, 2016; Nes & Segerstrom, 2006; Rasmussen, Scheier, & Greenhouse, 2009; Stewart & Yuen, 2011). Finally, self-esteem refers to global feelings of self-worth (Rosenberg, 1965) and the process of

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17 regaining self-esteem is hypothesized to be another fundamental task in the adjustment process (Taylor, 1983). Accordingly, a number of studies suggest that self-esteem makes a positive contribution to adjustment (Christianson, Weis, & Fouad, 2013; Peter, Mueller, Cieza, & Geyh, 2012; Stewart & Yuen, 2011). In this thesis, these three characteristics will be examined as potential mediators in the relationship between objective health and psychological distress.

An additional variable to be examined is the expectations of patients. Previous research indicates that patients overestimate the quality of life they will achieve after transplantation (Cleemput, Kesteloot, De Geest, Dobbels, & Vanrenterghem, 2003; Smith et al., 2008; Trivedi, Rosaasen, & Mansell, 2016). Yet, it remains unknown whether this overestimation might result in increased psychological distress. This thesis aims to answer this question and clarify the role of optimism in this process.

While previous research suggests that levels of perceived control are higher among kidney transplant recipients than among dialysis patients (Griva et al., 2009; Griva, Davenport, Harrison, & Newman, 2012) it is unclear whether these differences reflect actual changes of perceived control instigated by transplantation. In addition to addressing this subject this thesis will investigate whether potential changes in perceived control affect the course of psychological distress.

A number of studies suggest that psychological functioning improves after kidney transplantation (Landreneau et al., 2010; Liem et al., 2007; Ozcan et al., 2015), yet the underlying process remains unclear. Self-regulation theory might offer a useful framework to understand this phenomenon. According to this perspective, individuals have an inherent tendency to pursue personal goals (Heckhausen, Wrosch, & Schulz, 2010). Moreover, research indicates that medical conditions can impede important goals, with negative consequences for well-being (Janse, Sprangers, Ranchor, & Fleer, 2016; Stefanic, Caputi, & Iverson, 2014). Kidney transplantation is likely to remove many impediments and could in this way improve well-being. Therefore, this thesis will examine changes in goal disturbance after kidney transplantation and their relationship with changes in psychological distress and explore whether this association is mediated by perceived control.

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Outline of research

Setting and design

The current research project included two independent studies conducted among patients of the University Medical Center Groningen (UMCG). Located in the North, the UMCG is one of the largest hospitals in the Netherlands with more than 10,000 employees and room for more than 1300 patients, providing medical care for more than three million people living in the provinces Groningen, Friesland, and Drenthe and beyond. The UMCG is also the largest transplant centre in the Netherlands and since 2007 among the few hospitals in the world to perform all forms of organ [kidney, heart, lung, liver, pancreas, and small intestine] and tissue transplants in adults and children. Transplantation has been a cornerstone of the UMCG ever since the first kidney transplant in Groningen was performed in 1968 (University Medical Center Groningen, 2009). In 2015, a total of 176 kidney transplantations were performed in the UMCG, not including combined transplantations of more than one organ (Nederlandse Transplantatie Stichting, 2015).

The first study employed a cross-sectional design and was conducted among patients who had received a kidney transplant at the UMCG between 1993 and 2008 and were still living with a functioning kidney graft at the time of data collection. The second study used a prospective design and followed patients between 2008 and 2013 from the waiting list for kidney transplantation in the UMCG until one year after transplantation. At the time this study was initiated, patients on the waiting list in the UMCG emanated from dialysis centres located in Almelo, Apeldoorn, Deventer, Emmen, Enschede, Groningen, Leeuwarden and Zwolle. Patients were assessed once a year until they were transplanted. After successful transplantation, patients were assessed again at three, six and twelve months post-transplant. At each assessment, data were collected on socio-demographic variables, symptoms, comorbidity, perceived health, psychological distress, perceived control, optimism, self-esteem, and quality of life.

Aims

The main objective of the studies included in this thesis was to clarify how individual characteristics might influence perceived health and psychological distress. Chapter 2 deals with the evaluation of the long-term impact of kidney transplantation on perceived health and identifies differences between short- and long-term kidney transplant recipients.

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19 Chapter 3 investigates the interrelation of objective health and psychological distress and how it is affected by perceived control, optimism, and self-esteem. Chapter 4 examines how patients’ quality of life expectations prior to transplantation affect post-transplant psychological distress and clarifies the role of optimism in this process. Chapter 5 describes three patterns of change in perceived control from pre- to post-transplant and explores whether these patterns are differentially related to the course of psychological distress. Chapter 6 explores the association of pre- to post-transplant changes in goal disturbance and importance with changes in psychological distress and whether this association is mediated by perceived control. Chapter 7 identifies trajectories of perceived health and predictors thereof, among kidney and liver transplant recipients, in an attempt to develop a model for early recognition of patients at risk of poor post-transplant outcomes. Finally, Chapter 8 discusses the conclusions drawn from previous chapters and the potential implications of findings for future research and clinical practice.

It is anticipated that the improved understanding of the role of individual characteristics for the adjustment process of kidney transplant recipients could help to facilitate the identification of patients at-risk of suboptimal outcomes after kidney transplantation. Conversely, results of this thesis could highlight key components for interventions aiming to improve patients’ perceived health and psychological distress. Expectations are that this might eventually contribute to a further increase in the number of patients able to enjoy the maximum benefits life after kidney transplantation can potentially offer.

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REFERENCES

Afshar, M., Rebollo-Mesa, I., Murphy, E., Murtagh, F. E. M., & Mamode, N. (2012). Symptom burden and associated factors in renal transplant patients in the U.K. Journal of Pain and Symptom Management, 44(2), 229-238. doi:10.1016/j.jpainsymman.2011.08.005 AlBugami, M., & Kiberd, B. (2014). Malignancies: Pre and post transplantation strategies.

Transplantation Reviews, 28(2), 76-83. doi:10.1016/j.trre.2013.12.002

Alvares, J., Cesar, C. C., Acurcio, F. d. A., Gurgel Andrade, E. I., & Cherchiglia, M. L. (2012). Quality of life of patients in renal replacement therapy in Brazil: Comparison of treatment modalities. Quality of Life Research, 21(6), 983-991. doi:10.1007/s11136-011-0013-6

Anand, S., Bitton, A., & Gaziano, T. (2013). The gap between estimated incidence of end-stage renal disease and use of therapy. Plos One, 8(8), e72860.

doi:10.1371/journal.pone.0072860

Avvenuti, G., Baiardini, I., & Giardini, A. (2016). Optimism's explicative role for chronic diseases. Frontiers in Psychology, 7, 295. doi:10.3389/fpsyg.2016.00295

Birmele, B., Le Gall, A., Sautenet, B., Aguerre, C., & Camus, V. (2012). Clinical,

sociodemographic, and psychological correlates of health-related quality of life in chronic hemodialysis patients. Psychosomatics, 53(1), 30-37.

Bohlke, M., Marini, S. S., Rocha, M., Terhorst, L., Gomes, R. H., Barcellos, F. C., . . . Sesso, R. (2009). Factors associated with health-related quality of life after successful kidney transplantation: A population-based study. Quality of Life Research, 18(9), 1185-1193. doi:10.1007/s11136-009-9536-5

Christianson, H. F., Weis, J. M., & Fouad, N. A. (2013). Cognitive adaptation theory and quality of life in late-stage cancer patients. Journal of Psychosocial Oncology, 31(3), 266-281. doi:10.1080/07347332.2013.778936

Cleemput, I., Kesteloot, K., De Geest, S., Dobbels, F., & Vanrenterghem, Y. (2003). Health professionals' perceptions of health status after renal transplantation: A comparison with transplantation candidates' expectations. Transplantation, 76(1), 176-182. doi:10.1097/01.TP.0000072807.46212.FA

Czyzewski, L., Sanko-Resmer, J., Wyzgal, J., & Kurowski, A. (2014). Assessment of health-related quality of life of patients after kidney transplantation in comparison with hemodialysis and peritoneal dialysis. Annals of Transplantation, 19, 576-585.

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21 Danquah, F. V. N., Meininger, J., Zimmerman, L., Bergstrom, N., & Diamond, P. M. (2010).

Frequency, severity, and distress of dialysis-related symptoms reported by patients on hemodialysis. Nephrology Nursing Journal, 37(6), 627-639.

Dew, M. A., Switzer, G. E., Goycoolea, J. M., Allen, A. S., DiMartini, A., Kormos, R. L., & Griffith, B. P. (1997). Does transplantation produce quality of life benefits? A quantitative analysis of the literature. Transplantation, 64(9), 1261-1273.

Dobbels, F., De Bleser, L., De Geest, S., & Fine, R. N. (2007). Quality of life after kidney transplantation: The bright side of life? Advances in Chronic Kidney Disease, 14(4), 370-378. doi:10.1053/j.ackd.2007.07.005

ERA-EDTA Registry. (2016). ERA-EDTA registry annual report 2014. (). Amsterdam, the Netherlands: Academic Medical Center, Department of Medical Informatics. Findlay, M., & Isles, C. (2015). Peritoneal dialysis. In M. Findlay, & C. Isles (Eds.), Clinical

companion in Nephrology (pp. 199-203). Cham: Springer.

Gadalla, T. M. (2009). Determinants, correlates and mediators of psychological distress: A longitudinal study. Social Science & Medicine, 68(12), 2199-2205.

doi:10.1016/j.socscimed.2009.03.040

Gentile, S., Beauger, D., Speyer, E., Jouve, E., Dussol, B., Jacquelinet, C., & Briancon, S. (2013). Factors associated with health-related quality of life in renal transplant

recipients: Results of a national survey in France. Health and Quality of Life Outcomes, 11, 88. doi:10.1186/1477-7525-11-88

Goedendorp, M. M., Hoitsma, A. J., Bloot, L., Bleijenberg, G., & Knoop, H. (2013). Severe fatigue after kidney transplantation: A highly prevalent, disabling and multifactorial symptom. Transplant International, 26(10), 1007-1015. doi:10.1111/tri.12166 Goetzmann, L., Ruegg, L., Stamm, M., Ambuhl, P., Boehler, A., Halter, J., . . . Klaghofer, R.

(2008). Psychosocial profiles after transplantation: A 24-month follow-up of heart, lung, liver, kidney and allogeneic bone-marrow patients. Transplantation, 86(5), 662-668. doi:10.1097/TP.0b013e3181817dd7

Griva, K., Davenport, A., Harrison, M., & Newman, S. P. (2012). The impact of treatment transitions between dialysis and transplantation on illness cognitions and quality of life - A prospective study. British Journal of Health Psychology, 17, 812-827.

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22

Griva, K., Jayasena, D., Davenport, A., Harrison, M., & Newman, S. P. (2009). Illness and treatment cognitions and health related quality of life in end stage renal disease. British Journal of Health Psychology, 14, 17-34. doi:10.1348/135910708X292355

Gunabushanam, V., Matas, A., & Humar, A. (2015). Kidney transplantation. In A. Humar, & M. L. Sturdevant (Eds.), Atlas of organ transplantation (2nd ed., pp. 109-154). London: Springer.

Heckhausen, J., Wrosch, C., & Schulz, R. (2010). A motivational theory of life-span development. Psychological Review, 117(1), 32-60. doi:10.1037/a0017668 Helgeson, V. S., Reynolds, K. A., Siminerio, L. M., Becker, D. J., & Escobar, O. (2014).

Cognitive adaptation theory as a predictor of adjustment to emerging adulthood for youth with and without type 1 diabetes. Journal of Psychosomatic Research, 77(6), 484-491. doi:10.1016/j.jpsychores.2014.09.013

Janse, M., Sprangers, M. A. G., Ranchor, A. V., & Fleer, J. (2016). Long-term effects of goal disturbance and adjustment on well-being in cancer patients. Quality of Life Research, 25(4), 1017-1027. doi:10.1007/s11136-015-1139-8

Kidney Research UK. (2013). Kidney transplantation. Retrieved from

https://www.kidneyresearchuk.org/health-information/kidney-transplantation Klarenbach, S. W., Tonelli, M., Chui, B., & Manns, B. J. (2014). Economic evaluation of

dialysis therapies. Nature Reviews Nephrology, 10(11), 644-652. doi:10.1038/nrneph.2014.145

Kontodimopoulos, N., & Niakas, D. (2008). An estimate of lifelong costs and QALYs in renal replacement therapy based on patients' life expectancy. Health Policy, 86(1), 85-96. doi:10.1016/j.healthpol.2007.10.002

Kugler, C., Geyer, S., Gottlieb, J., Simon, A., Haverich, A., & Dracup, K. (2009). Symptom experience after solid organ transplantation. Journal of Psychosomatic Research, 66(2), 101-110. doi:10.1016/j.jpsychores.2008.07.017

Landreneau, K., Lee, K., & Landreneau, M. D. (2010). Quality of life in patients undergoing hemodialysis and renal transplantation - a meta-analytic review. Nephrology Nursing Journal, 37(1), 37-44.

Levy, J., Brown, E., & Daley, C. (2009a). Haemodialysis. Oxford handbook of dialysis (3rd ed., pp. 70-156). Oxford: Oxford University Press.

(24)

23 Levy, J., Brown, E., & Daley, C. (2009b). Transplantation for dialysis patients. Oxford

handbook of dialysis (3rd ed., pp. 433-440). Oxford: Oxford University Press.

Liem, Y. S., Bosch, J. L., Arends, L. R., Heijenbrok-Kal, M. H., & Hunink, M. G. (2007). Quality of life assessed with the medical outcomes study short form 36-item health survey of patients on renal replacement therapy: A systematic review and meta-analysis. Value in Health, 10(5), 390-397. doi:10.1111/j.1524-4733.2007.00193.x

Liyanage, T., Ninomiya, T., Jha, V., Neal, B., Patrice, H. M., Okpechi, I., . . . Perkovic, V. (2015). Worldwide access to treatment for end-stage kidney disease: A systematic review. Lancet, 385(9981), 1975-1982. doi:10.1016/S0140-6736(14)61601-9

McCaughan, J. A., & Courtney, A. E. (2015). The clinical course of kidney transplant

recipients after 20 years of graft function. American Journal of Transplantation, 15(3), 734-740. doi:10.1111/ajt.13041

Murtagh, F. E., Addington-Hall, J., & Higginson, I. J. (2007). The prevalence of symptoms in end-stage renal disease: A systematic review. Advances in Chronic Kidney Disease, 14(1), 82-99. doi:10.1053/j.ackd.2006.10.001

National Kidney Foundation. (2002). K/DOQI clinical practice guidelines for chronic kidney disease: Evaluation, classification, and stratification. American Journal of Kidney Diseases, 39(2 Suppl 1), S1-266.

National Kidney Foundation. (2015a). Dialysis. Retrieved from https://www.kidney.org/atoz/content/dialysisinfo

National Kidney Foundation. (2015b). Hemodialysis. Retrieved from https://www.kidney.org/atoz/content/hemodialysis

National Kidney Foundation. (n.d.). Peritoneal dialysis. Retrieved from https://www.kidney.org/atoz/content/peritoneal

Nederlandse Transplantatie Stichting. (2015). Jaarverslag 2015 Nederlandse Transplantatie Stichting. Leiden: Nederlandse Transplantatie Stichting.

Nefrodata. (2016a). Category/Report: 1. Volume/ 1.1. Aantal patiënten met nierfunctievervangende therapie op 1 januari in Nederland. Retrieved from https://ivisualz.nl/ivisualz/chartFlash/charts

Nefrodata. (2016b). Category/Report: 1. Volume/ 1.2. Aantal patiënten dialyse en transplantatie. Retrieved from https://ivisualz.nl/ivisualz/chartFlash/charts

(25)

24

Nefrodata. (2016c). Category/Report: 3. Transplantatie/ 3.1. Aantal transplantaties. Retrieved from https://ivisualz.nl/ivisualz/chartFlash/charts

Neipp, M., Karavul, B., Jackobs, S., Meyer zu Vilsendorf, A., Richter, N., Becker, T., . . . Klempnauer, J. (2006). Quality of life in adult transplant recipients more than 15 years after kidney transplantation. Transplantation, 81(12), 1640-1644.

doi:10.1097/01.tp.0000226070.74443.fb

Nes, L. S., & Segerstrom, S. C. (2006). Dispositional optimism and coping: A meta-analytic review. Personality and Social Psychology Review, 10(3), 235-251.

doi:10.1207/s15327957pspr1003_3

Nierstichting. (2016). Feiten en cijfers over behandeling nierfalen. Retrieved from https://www.nierstichting.nl/leven-met-een-nierziekte/feiten-en-cijfers/

Nierstichting. (n.d.). Dialyse. Retrieved from https://www.nierstichting.nl/leven-met-een-nierziekte/dialyse/#peritoneaaldialyse

Ozcan, H., Yucel, A., Avsar, U. Z., Cankaya, E., Yucel, N., Gozubuyuk, H., . . . Aydinli, B. (2015). Kidney transplantation is superior to hemodialysis and peritoneal dialysis in terms of cognitive function, anxiety, and depression symptoms in chronic kidney disease. Transplantation Proceedings, 47(5), 1348-1351.

doi:10.1016/j.transproceed.2015.04.032

Parrish, A. R. (2016). Advances in chronic kidney disease. International Journal of Molecular Sciences, 17(8), 1-4. doi:10.3390/ijms17081314

Peter, C., Mueller, R., Cieza, A., & Geyh, S. (2012). Psychological resources in spinal cord injury: A systematic literature review. Spinal Cord, 50(3), 188-201.

doi:10.1038/sc.2011.125

Polaschek, N. (2003). Living on dialysis: Concerns of clients in a renal setting. Journal of Advanced Nursing, 41(1), 44-52. doi:10.1046/j.1365-2648.2003.02504.x

Prihodova, L., Nagyova, I., Rosenberger, J., Roland, R., van Dijk, J. P., & Groothoff, J. W. (2010). Impact of personality and psychological distress on health-related quality of life in kidney transplant recipients. Transplant International, 23(5), 484-492.

doi:10.1111/j.1432-2277.2009.01003.x

Rasmussen, H. N., Scheier, M. F., & Greenhouse, J. B. (2009). Optimism and physical health: A meta-analytic review. Annals of Behavioral Medicine, 37(3), 239-256.

(26)

25 Rinschen, M. M., Völker, L. A., & Brinkkötter, P. T. (2014). Kidney: Overview. In E. Lammert,

& M. Zeeb (Eds.), Metabolism of human diseases: Organ physiology and pathophysiology (pp. 331-337). Wien: Springer.

Rosenberg, M. (1965). Society and the adolescent self-image. Princeton, N.J.: Princeton University Press.

Rosenberger, J., van Dijk, J. P., Nagyova, I., Zezula, I., Geckova, A. M., Roland, R., . . . Groothoff, J. W. (2006). Predictors of perceived health status in patients after kidney transplantation. Transplantation, 81(9), 1306-1310.

doi:10.1097/01.tp.0000209596.01164.c9

Scheier, M. F., & Carver, C. S. (1985). Optimism, coping, and health: Assessment and implications of generalized outcome expectancies. Health Psychology, 4(3), 219-247. Scherer, J. S., Combs, S. A., & Brennan, F. (2017). Sleep disorders, restless legs syndrome,

and uremic pruritus: Diagnosis and treatment of common symptoms in dialysis patients. American Journal of Kidney Diseases, 69(1), 117-128.

doi:10.1053/j.ajkd.2016.07.031

Sharif, A., & Cohney, S. (2016). Post-transplantation diabetes - state of the art. Lancet Diabetes & Endocrinology, 4(4), 337-349. doi:10.1016/S2213-8587(15)00387-3 Smith, D., Loewenstein, G., Jepson, C., Jankovich, A., Feldman, H., & Ubel, P. (2008).

Mispredicting and misremembering: Patients with renal failure overestimate

improvements in quality of life after a kidney transplant. Health Psychology, 27(5), 653-658. doi:10.1037/a0012647

Stefanic, N., Caputi, P., & Iverson, D. C. (2014). Investigating physical symptom burden and personal goal interference in early-stage breast cancer patients. Supportive Care in Cancer, 22(3), 713-720. doi:10.1007/s00520-013-2026-x

Stevens, P. E., Levin, A., & Kidney Disease: Improving Global Outcomes Chronic Kidney Disease Guideline Development Work Group Members. (2013). Evaluation and management of chronic kidney disease: Synopsis of the kidney disease: Improving global outcomes 2012 clinical practice guideline. Annals of Internal Medicine, 158(11), 825-830. doi:10.7326/0003-4819-158-11-201306040-00007

Stewart, D. E., & Yuen, T. (2011). A systematic review of resilience in the physically ill. Psychosomatics, 52(3), 199-209.

(27)

26

Stoumpos, S., Jardine, A. G., & Mark, P. B. (2015). Cardiovascular morbidity and mortality after kidney transplantation. Transplant International, 28(1), 10-21.

doi:10.1111/tri.12413

Taylor, S., Kemeny, M., Reed, G., Bower, J., & Gruenewald, T. (2000). Psychological resources, positive illusions, and health. American Psychologist, 55(1), 99-109. doi:10.1037//0003-066X.55.1.99

Taylor, S. E. (1983). Adjustment to threatening events: A theory of cognitive adaptation. American Psychologist, 38(11), 1161-1173. doi:10.1037/0003-066X.38.11.1161 Teng, S., Zhang, S., Zhang, W., Lin, X., Shang, Y., Peng, X., & Liu, H. (2015). Symptom

experience associated with immunosuppressive medications in chinese kidney transplant recipients. Journal of Nursing Scholarship, 47(5), 425-434.

doi:10.1111/jnu.12157

Theofilou, P. (2012). Quality of life and mental health in hemodialysis and peritoneal dialysis patients: The role of health beliefs. International Urology and Nephrology, 44(1), 245-253. doi:10.1007/s11255-011-9975-0

Tonelli, M., Wiebe, N., Knoll, G., Bello, A., Browne, S., Jadhav, D., . . . Gill, J. (2011).

Systematic review: Kidney transplantation compared with dialysis in clinically relevant outcomes. American Journal of Transplantation, 11(10), 2093-2109.

doi:10.1111/j.1600-6143.2011.03686.x

Trivedi, P., Rosaasen, N., & Mansell, H. (2016). The health-care provider's perspective of education before kidney transplantation. Progress in Transplantation, 26(4), 322-327. doi:10.1177/1526924816664081

United States Renal Data System. (2016). 2016 USRDS Annual data report: Epidemiology of kidney disease in the United States - Chapter 13: International comparisons. Bethesda, MD: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases.

University Medical Center Groningen. (2009). UMCG_CorporateBrochure. Retrieved from http://www.umcg.nl/SiteCollectionDocuments/English/UMCG_CorporateBrochure.pdf University of California San Francisco. (2016). Kidney transplant. Retrieved from

http://transplant.surgery.ucsf.edu/conditions--procedures/kidney-transplant.aspx Urquhart-Secord, R., Craig, J. C., Hemmelgarn, B., Tam-Tham, H., Manns, B., Howell, M., . . .

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27 international nominal group technique study. American Journal of Kidney Diseases, 68(3), 444-454. doi:10.1053/j.ajkd.2016.02.037

Villeneuve, C., Laroche, M., Essig, M., Merville, P., Kamar, N., Coubret, A., . . . EPIGREN Study Grp. (2016). Evolution and determinants of health-related quality-of-life in kidney transplant patients over the first 3 years after transplantation. Transplantation, 100(3), 640-647. doi:10.1097/TP.0000000000000846

Volksgezondheidenzorg.info. (2011). Ranglijst ziekten op basis van zorgkosten. Retrieved from https://www.volksgezondheidenzorg.info/ranglijst/ranglijst-ziekten-op-basis-van-zorgkosten

von der Lippe, N., Waldum, B., Brekke, F. B., Amro, A. A. G., Reisaeter, A. V., & Os, I. (2014). From dialysis to transplantation: A 5-year longitudinal study on self-reported quality of life. BMC Nephrology, 15, 191. doi:10.1186/1471-2369-15-191

Wei, T., Chiang, Y., Hsieh, C., Weng, L., Lin, S., & Lin, M. (2013). Health related quality of life of long-term kidney transplantation recipients. Biomedical Journal, 36(5), 243-251. doi:10.4103/2319-4170.113186

Wyld, M., Morton, R. L., Hayen, A., Howard, K., & Webster, A. C. (2012). A systematic review and meta-analysis of utility-based quality of life in chronic kidney disease treatments. Plos Medicine, 9(9), e1001307. doi:10.1371/journal.pmed.1001307

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Chapter 2

Perceived health after kidney transplantation: A

cross-sectional comparison of long-term and

short-term cohorts

Torben Schulz

Jan Niesing

Jaap J. Homan van der Heide

Ralf Westerhuis

Rutger J. Ploeg

Adelita V. Ranchor

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ABSTRACT

Although increased longevity of grafts has led to a growing number of long-term kidney transplant recipients, knowledge about the perceived health of these patients remains limited. A cross-sectional sample of 609 patients (60% response) was stratified into a short-term (<1 year), midshort-term (>1 and <8 years), and long-short-term cohort (>8 and <15 years post-transplantation). Cohorts were compared for perceived health (Visual Analogue Scale of the EQ-5D), number of symptoms, and number of comorbidities by analysis of variance/covariance and multivariate regression analyses. Long-term patients reported more symptoms, (F[2, 606] = 3.09, P = .046) and more comorbidities, (F[2, 588] = 4.75, P = .009) but similar levels of perceived health, (F[2, 550] = 2.37, P > .05). Furthermore, symptoms were less influential for perceived health among long versus shortterm (z = -2.08, P = .038) or midterm cohorts (z = -2.60, P = .009). Previously identified predictors of perceived health accounted for less variance in the long-term as opposed to short-term (z = 4.30, P < .001) and midterm cohort (z = 2.07, P = .039). Despite more symptoms and comorbidities, the perceived health of long-term kidney transplant recipients was comparable to the short- and midterm, possibly due to selective survival or patient adjustment. Because kidney function and symptoms were predominantly associated with short-term perceived health, there is an urgent need to identify variables associated with long-term perceived health.

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INTRODUCTION

Kidney transplantation is the preferred treatment for end stage renal disease (ESRD) in terms of patient survival and perceived health, i.e. self-rated health or general health perception (Tonelli et al., 2011). Pre- to post-transplant improvements of perceived health are well-documetned during the first years after transplantation (Dobbels, De Bleser, De Geest, & Fine, 2007; Landreneau, Lee, & Landreneau, 2010; Liem, Bosch, Arends, Heijenbrok-Kal, & Hunink, 2007). However, because the majority of studies involve patients with relatively short post-transplantation intervals (Dobbels et al., 2007), it remains unclear whether perceived health several years after transplantation still matches the short-term outcomes. At the same time, the number of long-term kidney transplant recipients grows due to increased longevity of kidney grafts (Hariharan et al., 2000; A. Ojo et al., 2000). Consequently, long-term outcomes become increasingly relevant.

Few studies have investigated long-term perceived health and the evidence provided is inconclusive. In patient samples averaging five to eight years post-transplantation, positive as well as negative associations between time since transplantation and perceived health have been reported (Chisholm, Spivey, & Nus, 2007; Rebollo et al., 2000). A recent prospective study reassessed patients after a period of six years and found no significant association between time since transplantation and perceived health, but suggested that physical aspects of health-related quality of life deteriorate over time (Griva et al., 2011).

Previous research has identified several socio-demographic and medical variables influencing perceived health, including age, gender, educational level, diabetes, duration of dialysis, and kidney function (Bohlke et al., 2009; Griva et al., 2002; Prihodova et al., 2010; Rosenberger et al., 2006). Adverse effects of immunosuppression and comorbidity are particularly associated with perceived health (Prihodova et al., 2010; Rosenberger et al., 2006). However, it is unclear whether long-term kidney transplant recipients experience more symptoms, as most studies aggregate results involving a variety of different organ transplants. One of these studies among patients averaging five years post-transplantation, reported an increase of the number of symptoms with time since transplantation (Hathaway, Winsett, Prendergast, & Subaiya, 2003), whereas in a similar sample the number of gastrointestinal symptoms decreased over time (Winsett, Stratta, Alloway, Wicks, & Hathaway, 2001). According to a recent review, most studies investigating symptom

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experience after organ transplantation find that patients report more symptoms as time since transplantation increases (Kugler et al., 2009).

Although the prevalence of comorbidity among kidney transplant recipients is higher than in the general population (Al-Aradi et al., 2009), it has not been investigated whether long-term kidney transplant recipients experience more comorbidities than those with shorter post-transplant intervals. However, expectations are that the number of comorbidities will increase over time, because prolonged immunosuppression is associated with the development of medical conditions, such as cardiovascular disease, diabetes, infections, and malignancies (Allamani, Sennesael, & Vendemeulenbroucke, 2010; Chow & Li, 2008; Fishman, 2007; Kauffman, Cherikh, McBride, Cheng, & Hanto, 2006; A. O. Ojo, 2006).

Therefore, this study aims to enhance knowledge of the perceived health of long-term kidney transplant recipients that could, in turn, inform patient education and provide targets for interventions to improve long-term perceived health. This aim translates to the following hypotheses: long-term kidney transplant recipients experience lower perceived health, more symptoms and more comorbidities than those with shorter post-transplantation intervals; and long-term and short-term perceived health are equally influenced by the same factors.

METHODS

Procedure

Of 1036 patients who had received a single-organ, kidney-only transplantation between January 1, 1993, and April 28, 2008; were living with a functioning kidney graft; and were at least 18 years of age, 22 patients were excluded due to unknown address (N = 13), inability to comprehend Dutch (N = 7), and visual impairment (N = 2), resulting in an eligible group of 1014 patients.

Patients received an information letter inviting them to participate in the study and asking their permission to use data from their medical records. Non-responders received a reminder after three and seven weeks. The study protocol was approved by the Medical Ethical Committee of the University Medical Center Groningen.

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33 Measures

Age, gender, time since transplantation, donor type, one-year 24-hour creatinine clearance, last 24-hour creatinine clearance, and primary kidney disease were collated from medical records. Educational level, duration of dialysis and dialysis modality were established by patient self-report.

Perceived health was assessed with the Visual Analogue Scale of the EQ-5D (EQ-VAS; The EuroQol Group, 1990). The EQ-VAS measures respondents’ perceived health on a vertical scale running from 0-100, with endpoints labeled ‘best imaginable health state’ and ‘worst imaginable health state’. Studies in the general population and different patient populations show that the EQ-5D with VAS has acceptable reliability and validity (Brazier, Roberts, Tsuchiya, & Busschbach, 2004; Cleemput et al., 2004; Hoeymans, van Lindert, & Westert, 2005).

A symptom checklist was constructed to assess adverse effects of immunosuppression by selecting and compiling items from other questionnaires (Derogatis, Rickels, & Rock, 1976; Derogatis, 1986; Dobbels et al., 2008; Franke et al., 1999). The resultant 45-item symptom checklist had good face validity and was approved by a consulting nephrologist. It included the following symptoms: muscle pain, chest pain, joint pain, bone pain, headaches, stomach pain, muscle cramps, dizziness, exhaustion, shortness of breath, nausea, poor appetite, thirst, swollen legs or feet, numbness in hands or feet, itching, skin problems, bruises, diarrhea, constipation, memory problems, concentration problems, forgetfulness, hearing loss, decreased visual acuity, changed sense of taste, increased appetite, bleeding gums, increased growth of gums, alterations of gums, increased hair growth, excessive body hair, alterations of the face, swollen face, swollen face in the morning, sleeplessness, trouble falling asleep, awakening in the early morning, sleep that is restless or disturbed, nightmares, tiredness, reduced sexual interest, reduced sexual activity, less pleasure derived from sex, and impaired sexual functioning. Patients indicated which of these symptoms they currently experienced (yes/no). The total number of symptoms was calculated by adding up symptoms for each patient. Divergent validity was confirmed by a significant negative correlation with perceived health (r = -0.49, p < 0.001; Franke et al., 1999). Also, women reported more symptoms than men (t(536) = -3.03, p = 0.003), indicating adequate discriminant validity (Dobbels et al., 2008; Kugler et al., 2009).

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The number of comorbidities was assessed by a checklist of twenty common medical conditions adapted from the Central Office for Statistics in the Netherlands (Arnold et al., 2004; Kempen, Ormel, Brilman, & Relyveld, 1997). It included the follwing medical conditions: asthma, chronic bronchitis, chronic obstructive pulmonary disease; airway infection; serious hart condition or heart attack; high blood pressure; (consequences of) stroke; stomach ulcer; serious bowel disorder; gallstones or infection of gall bladder; liver infection or cirrhosis; chronic bladder infection; diabetes mellitus; thyroid gland disorder; back problems for at least 3 months or slipped disc; rheumatoid arthritis or other joint complaints; epilepsy; migraine or chronic headache; serious dermatological disorders such as psoriasis and eczema; cancer; permanent injury as result of an accident; and psychological problems, e.g. anxiety, depression, and burnout. Patients indicated whether they had a medical condition (yes/no) and if they had received treatment for this condition in the last twelve months (yes/no). For each patient, the total number of comorbidities was calculated by adding up those medical conditions for which treatment had been received. Previous research suggests that self-reports of comorbidity tend to be accurate representations of actual comorbidity (Kriegsman, Penninx, van Eijk, Boeke, & Deeg, 1996; van den Bos, 1995).

Statistical analysis

The sample was stratified into three cohorts based on time since transplantation. As the first year post-transplantation is a transitional phase, it was used as cut-off point for the first cohort. The interval from one to fifteen years post-transplantation was then split along the median of eight years. Thus, stratification resulted in a short-term (≤ 1 year after transplantation), mid-term (> 1 and ≤ 8 years after transplantation) and long-term cohort (> 8 and ≤ 15 years after transplantation). Pearson Chi-square and analysis of variance were used to identify differences in socio-demographic and medical variables between the cohorts. Variables that differed and were significantly associated with perceived health, number of symptoms or number of comorbidities, respectively were considered confounders and adjusted for in subsequent analyses. Analysis of variance and covariance were used to compare perceived health, number of symptoms and number of comorbidities across cohorts. Perceived health was regressed separately for each cohort by simultaneously entering the same set of predictors identified by literature review (age,

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35 gender, educational level, kidney function, duration of dialysis, diabetes as opposed to other primary kidney diseases, number of symptoms and number of comorbidities). Unstandardized regression coefficients of predictors that were significant for all cohorts were compared following procedures described elsewhere (Clogg, Petkova, & Haritou, 1995). Multiple correlation coefficients were compared by transforming R to r’with Fisher’s z transformation and calculating z-scores for the difference between each pair of cohorts (Cohen, Cohen, West, & Aiken, 2003). Statistical analyses were conducted with SPSS 19 IBM.

RESULTS

A total of 609 questionnaires (60% response rate) were returned. Response rates were 67% for the short-term, 58% for the mid-term and 62% for the long-term cohort and did not differ significantly between cohorts.

Participants were significantly older than non-participants at the time of data collection and at the time of their transplantation (both p < 0.001). Participants and non-participants did not differ on gender, donor type, one-year 24-hour creatinine clearance or last 24-hour creatinine clearance. Except for differences in age and age at transplantation the sample was representative of the target population.

Medical and socio-demographic characteristics of the whole sample and the cohorts are presented in Table 1. Comparison of the cohorts revealed differences in age at transplantation, pretransplantation dialysis modality, and donor type.

Older age at transplantation was significantly associated with lower perceived health (r = -0.14, p = .001) and more comorbidities (r = 0.15, p < .001). Patients with a kidney from a deceased donor had significantly more comorbidities than patients with a kidney from a living donor (t(591) = 2.21, p = .028). No differences were found between patients who had and those who had not dialysed (all t < 1.31, all p > .19). Consequently, age at transplantation and donor type were considered confounders and used as covariates in further analyses.

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36 Tab le 1. De m o grap h ic a n d me d ical ch ar act eris ti cs o f t o ta l p at ie n t samp le a n d co h o rts b as ed o n t im e si n ce t ra n sp lan ta tio n . To ta l (N = 609) Sh o rt -ter m co h o rt ≤ 1 ye ar (N = 77 ) Mid -ter m co h o rt > 1 an d ≤ 8 ye ar s (N = 34 9) Lo n g-ter m co h o rt > 8 an d ≤ 15 y ear s (N = 18 3) Varia b le % o r m ean ± SD (ran ge ) F(df) , Χ² (d f) o r t(d f) p Age a t tra n sp lan ta tio n (y ear s) 47.9 ± 12. 7 (16 -74) 52.4 ± 12. 5 (21 -70) a 48.9 ± 12. 8 (16 -74) b 44.1 ± 11. 8 (16 -70) ab 14.49 (2,6 06) <0.00 1 Age (y ear s) 53.7 ± 12. 3 (20 -82) 52.8 ± 12. 4 (21 -71) 53.0 ± 12. 6 (20 -80) 55.4 ± 11. 7 (26 -82) 2.58 (2,60 6) ns G en d er (% mal e) 55.5% 49.4% 56.7% 55.7% 1.40 (2) ns Ed u cat ion al le ve l 2.82 (4) ns Ele m en ta ry 50 .2% 43 .2% 49 .6% 54 .2% Se con d ary 28 .4% 31 .1% 29 .3% 25 .7% U n iv e rs ity 21.4% 25.7% 21.2% 20.1% Prim ar y k id n ey d is eas e 2.38 (6) ns G lom eru lon ep h ritis 38.5% 41.0% 36.8% 40.9% Con ge n ita l a n d h ere d ita ry k id n ey d is eas es 26.2% 27.9% 26.0% 26.0% Re n al va scu lar d is ea se s a n d d iab etes m elli tu s 12.8% 11.5% 14.4% 10.5% Ot h er o r u n kn o w n ca u se s 22.4% 19.7% 22.8% 22.7% Pre -tra n sp lan t d ialy sis mod ali ty 13.53 (6 ) 0.035 He m od ialys is 42 .4% 41 .8% 40 .8% 45 .8% Pe riton eal d ialys is 40 .4% 37 .3% 41 .1% 40 .4% Bot h 6.8% 4.5% 5.7% 9.6% N o n e 10.4% 16.4% c 12.4% d 4.2% cd Pre -tra n sp lan t d ialy sis d u ra tio n (y ear s) 3.3 ± 2.7 (0 -2 0) 2.8 ± 2.7 (0 -1 5) 3.3 ± 2.5 (0 -1 5) 3.5 ± 2.9 (0 -2 0) 2.08 (2,57 2) ns Don o r ty p e (% d ece as ed d o n o r) 68.0% 42.9% ef 65.9 % eg 82.5 % fg 40.78 (2 ) <0.00 1 1 -y ear 24 -h o u r cre at in in e cl ea ra n ce (mL/ m in ) 57.4 ± 18. 3 (15 -116) N /A 57.1 ± 18. 4 (15 -116) 59.0 ± 18. 1 (21 -114) -1.12 ( 479) ns La st 24 -h o u r cre at in in e cle ar an ce (mL/ m in ) 57.3 ± 20. 1 (13 -117) 52.6 ± 16. 9 (21 -86) 58.8 ± 20. 3 (13 -112) 55.9 ± 20. 2 (16 -117) 2.80 (2,55 3) ns Tim e si n ce t ra n sp lan ta tio n (y ear s) 5.8 ± 4.2 (0 -1 5) 0.5 ± 0.3 (0 -1) hi 4.1 ± 1.9 (1 -8) hj 11.3 ± 2.0 (8 -1 5) ij 1319 .44 (2,606 ) <0.00 1 N o te: n s = n o n -s ignifi can t; ab h ij p < 0.001; cd e fg p < 0. 05

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37 The comparison of cohorts is presented in Table 2. Patients in the long-term cohort reported more symptoms than patients in the short-term cohort and more comorbidities than patients in the short-term and mid-term cohort. Cohorts did not differ with regards to perceived health.

Table 2. Unadjusted means and standarddeviations (adjusted means and standard error) of perceived health, symptoms and comorbidities of total patient sample and cohorts based on time since transplantation.

Total (N=609) Short-term cohort ≤ 1 year (N=77) Mid-term cohort > 1 and ≤ 8 years (N=349) Long-term cohort > 8 and ≤ 15 years (N=183) F(df) p Perceived health 74.1 ± 14.1 74.5 ± 12.3 (75.3 ± 1.7*) 74.7 ± 14.8 (74.9 ± 0.8*) 72.8 ± 13.6 (72.1 ± 1.1*) 2.37 (2, 550) ns Symptoms 14.6 ± 8.6 12.8 ± 7.6a 14.4 ± 8.4 15.6 ± 9.2a 3.09 (2, 606) 0.046 Comorbidities 1.8 ± 1.6 1.6 ± 1.3 (1.5 ± 0.2†)b 1.7 ± 1.6 (1.7 ± 0.1†)c 2.0 ± 1.7 (2.1 ± 0.1†)bc 4.75 (2, 588) 0.009 Note: ns = non-significant; * adjusted for age at transplantation; † adjusted for age at transplantation and donor type.

abc

p < 0.05

Results of regression analyses of perceived health for each cohort are presented in Tables 3 through 5. Being the largest group, elementary education was used as reference in the analyses. Secondary as opposed to elementary education, higher 24-hour creatinine clearance and fewer symptoms were associated with better perceived health in the short-term cohort. Secondary as opposed to elementary education, fewer symptoms and fewer comorbidities were associated with better perceived health in the mid-term cohort. Fewer symptoms and fewer comorbidities were associated with better perceived health in the long-term cohort.

Further analyses revealed that the unstandardized regression coefficient of the number of symptoms was smaller in the long-term (B = -0.391, SE = 0.117) than in the short-term (B = -0.923, SE = 0.228, with z = -2.08, p = .038) and mid-short-term cohort (B = -0.775, SE = 0.090, with z = 2.60, p = .009).

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38

Table 3. Multiple linear regression of perceived health ≤ 1 year post-transplant (N=77); explained variance and standardized regression coefficients.

Predictor Adjusted R² (Multiple

correlation)

β 0.721 (0.897)

Age 0.073

Gender 0.030

Education elementary vs. secondary 0.292*

Education elementary vs. university 0.235

Diabetes mellitus vs. other kidney disease -0.102

Duration of dialysis -0.059

Last 24-hour creatinine clearance 0.451**

Symptoms -0.559**

Comorbidities -0.134

* p < 0.05; ** p < 0.01

Table 4. Multiple linear regression of perceived health > 1 and ≤ 8 years post-transplant (N=349); explained variance and standardized regression coefficients.

correlation)

β 0.408 (0.655)

Age -0.101

Gender -0.012

Education elementary vs. secondary 0.115*

Duration of dialysis -0.040

Last 24-hour creatinine clearance 0.070

Symptoms -0.470***

Comorbidities -0.242***

* p < 0.05; *** p < 0.001

Table 5. Multiple linear regression of perceived health > 8 and ≤ 15 years post-transplant (N=183); explained variance and standardized regression coefficients.

correlation)

β 0.220 (0.516)

Age -0.133

Gender -0.075

Education elementary vs. secondary -0.051

Duration of dialysis 0.027

Last 24-hour creatinine clearance 0.118

Symptoms -0.273**

Comorbidities -0.220**