Irritable Bowel Syndrome in Renal Transplant Patients: Prevalence, Link with Quality of Life, Anxiety, and Depression

Abstract

Background: Gastrointestinal complications are common in renal transplant recipients and may arise from any part of the gastrointestinal tract. Irritable bowel syndrome (IBS) is highly common in the general population, but the status is not known in renal transplant patients. In this study, we evaluated the prevalence of IBS and its association with health-related quality of life (HRQOL), anxiety, and depression in renal transplant patients. Methods: One hundred and ninety-eight patients were enrolled in this study. Sociodemographic and laboratory variables were recorded. Severity of depressive and anxiety symptoms and HRQOL were assessed by the Beck Depression Inventory, State-Trait Anxiety Inventory, and Short Form 36 (SF-36), respectively. Diagnosis of IBS was based on Rome III criteria. Results: The mean age was 38 ± 10 years and 61% were male. The mean transplant duration was 62 ± 54 months. Among 198 patients, 55 (27%) had IBS. Patients with IBS had lower SF-36 scores and had higher depressive and anxiety symptoms than patients without IBS. Conclusions: IBS is highly prevalent in renal transplant patients. The presence of IBS is closely related with HRQOL anxiety and depression.

• irritable bowel syndrome
• anxiety
• depression
• renal transplantation
• Roma III criteria

INTRODUCTION

Upper and lower gastrointestinal system symptoms are common in renal transplant patients. Patients often complain of nausea, vomiting, diarrhea, bloating, and constipation. Most of these symptoms are related to infections or medications. If these gastrointestinal disorders cannot be diagnosed and treated appropriately, quality of life (QOL) of the patients may be disturbed.

Irritable bowel syndrome (IBS) is a disease characterized by cramps, abdominal pain, bloating, and a variable cycle of constipation and diarrhea. It is associated with great distress and discomfort.¹ Despite it being so common, pathophysiology is still not fully elucidated. Physical examination and laboratory findings are most often normal. Even though there exist various criteria for diagnosis, Roma III criteria are the most common and the latest one that is being used.²

The association between psychiatric disorders and IBS has been known for a long time. IBS patients have higher rates of major depressive and anxiety disorders.³ Although epidemiological data show that IBS and depression are interrelated, the nature of this association could have not been elucidated.

The impaired health-related quality of life (HRQOL) in hemodialysis (HD) patients compared with normal population is restored after successful renal transplantation. However, data from the literature show that it is impaired again at the long term.⁴ Because IBS is closely related with HRQOL and depression in the general population, HD and peritoneal dialysis patients,^3,5 we hypothesized that similar relationship may exist in renal transplant patients. Thus, we investigated the prevalence and its effect on HRQOL, depression, and anxiety in renal transplant patients.

METHODS

One hundred and ninety-eight adult renal transplant patients who were being followed at the organ transplantation unit of Ege University, Izmir, Turkey, and who were willing to be involved in this cross-sectional study with an inform consent were enrolled. Patients with a history of renal transplant at least 6 months prior to the study, who had history of any major physiatric disorders, had serum creatinine higher than 5 mg/dL, had a history of active liver disease during the study period, and patients with alarm symptoms (unexpected weight loss not explained by routine investigation, blood mixed with stools, and family history of colon cancer), with previous history of antibiotic use in the last 1 month, Crohn’s disease, ulcerative colitis, and with celiac disease were excluded. Sociodemographic, clinical, and laboratory data were recorded from patients’ charts. Major parameters of interest were dialysis duration prior to transplantation, date of transplantation and current graft functions, serum albumin, and hemoglobin levels.

After conducting a baseline general physical examination, patients were divided into two groups (IBS present or absent) according to the Rome III criteria. Endoscopy or colonoscopy was not specifically performed in any of the patients.

Depression and Anxiety Scoring

The Turkish version of the Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory (STAI) were used to determine depression and anxiety symptoms. BDI is a 21-item self-reported inventory that measures characteristic attitudes and symptoms of depression. Each item is formulated as a 4-point Likert item, ranging from 0 to 3, with higher scores indicating more severe depressive symptoms.⁶ The maximal total score for the scales is 63. BDI is referred as a valid index of depression and it has been shown that BDI scores correlate well with the diagnostic criteria for depression. STAI is a 20-item, self-report measure designed to assess anxiety. It is scored from 1 to 4 and the maximum score is 80. In this test, patients indicate how they feel generally and currently, where they rate the frequency and intensity of their feelings of anxiety on a 4-point scale ranging from 1 (almost never or nothing) to 4 (almost always or a lot).⁷

QOL Assessment

In order to evaluate the HRQOL of the patients, a short form of medical outcomes study (SF-36) was used, which was adapted to and validated for the Turkish population.⁸ The test consists of 36 items assigned to eight subscales. Each subscale is scored with a range of 0–100; higher score implicating a better HRQOL. These eight subscales can be summarized in a Physical Component Summary Score and Mental Component Summary Score. SF-36 has been commonly used and validated in patients with renal transplantation.⁹ SF-36 is also a well-standardized questionnaire for assessing the HRQOL of IBS.⁵

Statistical Analysis

All parameters were expressed as mean ± SD. A p-value of less than 0.05 was considered as statistically significant. Comparisons between two groups were assessed by independent t-test analysis. Binary logistic regression analysis adjusted for the dependent variables obtained from univariate analysis was performed to predict factors associated with IBS. All statistical analyses were performed by using SPSS version 15 (SPSS Inc., Chicago, IL, USA).

RESULTS

The mean age of the patients was 38 ± 10 years and 61% were male. The mean HD duration prior to renal transplantation was 34 ± 47 months and the mean HD duration of post-transplant follow-up was 62 ± 54 months. History of diabetes was present in 14% of the cases. Four of the 198 cases were under thyroid hormone replacement therapy with normal thyroid function tests. One hundred and forty-four patients received an immunosuppressive regime consisting of a steroid, a mycophenolate derivative, and a calcineurin inhibitor (CNI); 24 received a steroid, an azathioprine, and a CNI; 28 received a steroid, mycophenolate derivative, and a mammalian target of rapamycin inhibitor (mTORi); and finally 2 patients received a steroid, an azathioprine, and an mTORi. Sociodemographic, laboratory data and depression, anxiety, and SF-36 results are shown in Table 1. In the whole group, BDI score was positively correlated with STAI (r = 0.716, p < 0.001) and negatively correlated with physical functions (r = −0.466, p < 0.001), physical role (r = −0.485, p < 0.001), pain (r = −0.372, p < 0.001), general health (r = −0.533, p < 0.001), vitality (r = −0.605, p < 0.001), mental health (r = −0.666, p < 0.001), social functions (r = −0.541, p < 0.001), and emotional role (r = −0.534, p < 0.001). On the other hand, STAI was positively correlated with BDI (r = 0.716, p < 0.001) and negatively correlated with physical functions (r = −0.488, p < 0.001), physical role (r = −0.480, p < 0.001), pain (r = −0.400, p < 0.001), general health (r = −0.518, p < 0.001), vitality (r = −0.602, p < 0.001), mental health (r = −0.765, p < 0.001), social functions (r = −0.485, p < 0.001), and emotional role (r = −0.448, p < 0.001).

Table 1.  Characteristics of the whole study population (n = 198).

Variables	Mean ± SD	Range
Age (years)	38 ± 10	18–63
Sex (male, %)	55
Dialysis vintage (months)	34 ± 47	0–244
Transplantation time (months)	62 ± 54	6–271
Urea (mg/dL)	51 ± 27	17–191
Creatinine (mg/dL)	1.4 ± 0.7	0.5–4.8
Hemoglobin (g/dL)	13.1 ± 1.7	7.6–16.9
Albumin (g/dL)	4.6± 0.3	3.1–5.5
BDI	8.9 ± 7.2	0–37
STAI	41.1± 9.3	20–67
Physical function	75.1 ± 18.2
Physical role	65.2 ± 36.4
Pain	75.3 ± 22.1
General health	57.4 ± 20.3
Vitality	69.2 ± 19.5
Mental health	70.2 ± 17.6
Social function	75.9 ± 52.4
Emotional role	63.1 ± 36.3

Note: BDI, Beck Depression Inventory; STAI, State-Trait Anxiety Inventory.

Among 198 patients, 55 (27%) were diagnosed as having IBS. The comparative sociodemographic characteristics and laboratory parameters of patients with and without IBS are given in Table 2. Table 2 demonstrates the comparative BDI, STAI, and SF-36 scores of patients with and without IBS. In both groups, depression and anxiety scores were significantly correlated with SF-36 scores.

Table 2.  Comparison of patients with and without IBS.

	IBSpositive(n = 55)	IBSnegative(n = 143)	p-Value
Age (years)	37 ± 8	38 ± 10	NS
Dialysis vintage (months)	36 ± 45	34 ± 48	NS
Transplantation time (months)	65 ± 52	61 ± 55	NS
Creatinine (mg/dL)	1.5 ± 0.7	1.4 ± 0.6	NS
Hemoglobin (gr/dL)	12.7 ± 1.8	13.2 ± 1.7	NS
Albumin (gr/dL)	4.6 ± 0.3	4.6 ± 0.3	NS
BDI	12.7 ± 7.9	7.4 ± 6.4	<0.001
STAI	45.1 ± 8.6	39.4 ± 9.1	<0.001
Physical function	71.5 ± 19.3	77.1 ± 18.3	NS
Physical role	50.4 ± 39.1	71.1 ± 34.2	<0.001
Pain	64.2 ± 23.5	80.2 ± 20.0	<0.001
General health	47.5 ± 20.7	61.3 ± 18.8	<0.001
Vitality	63.5 ± 19.9	71.4 ± 18.4	0.01
Mental health	65.1 ± 17.4	72.1 ± 16.8	0.01
Social function	69.0 ± 25.4	80.4 ± 23.0	0.003
Emotional role	56.4 ± 36.36	66.6 ± 35.8	NS

Note: BDI, Beck Depression Inventory; STAI, State-Trait Anxiety Inventory; IBS, irritable bowel syndrome; NS, nonsignificant.

As can be seen in Table 2, patients with IBS had significantly higher anxiety and depression scores and lower SF-36 results. In multivariate binary logistic regression analysis, depression [Relative risk (RR) = 1.09, 95% confidence interval (CI): 1.03–1.15, p = 0.002] and pain score in SF-36 (RR = 0.98, 95% CI 0.96–0.99, p = 0.02) were independent variables associated with IBS (model χ²: 26.3, p < 0.001).

Patients who were on mycophenolate mofetil had higher IBS rates compared with patients on mycophenolic acid (p = 0.02). There were no differences between CNIs and mTORi.

DISCUSSION

Previous studies in dialysis patients have shown higher IBS rates compared with the normal population along with negative effects on and depression.⁵ In renal transplant patients, gastrointestinal symptoms were linked to impaired HRQOL by Gastrointestinal Symptom Rating Scale (GSRS).¹⁰ Our study further shows that renal transplant patients with IBS, diagnosed according to the Roma III criteria, have higher depression and anxiety and worse HRQOL.

Recent advances over the last decades in transplantation procedures and immunosuppressive treatments have led to increased 1-year kidney graft survival rates to over 90%.¹¹ Consequently, research has focused on better HRQOL for renal transplant patients.¹² Studies have shown improved, if not totally cured, life expectancy and QOL in renal transplantation patients compared with the maintenance dialysis patients.¹³ HRQOL and physical health do not get normalized even in individuals with perfectly functioning kidney grafts and furthermore, seem to remain constant in post-transplant period.¹⁴ Psychopathologic symptoms such as anxiety and depression, adaptive demands, new stress factors such as immunosuppressive drugs and their potential medication side effects, and fear of rejection disturb the well-being of the patients and urge the physician and the patient for psychosocial support.¹⁴

IBS is a common, neglected, and often disabling gastrointestinal disorder which cannot be fully attributed to structural or biochemical abnormalities in the human body. For a long time, it was proposed that IBS was only a form of somatization disorders. However, recent data suggest that alterations in the neuro-enteric axis may be responsible. Several diagnostic criteria have been proposed in the literature, but Roma III criteria are the latest valid criteria used. Previously, it was shown that patients with IBS had worse HRQOL when compared with patients who did not have IBS.¹⁵ Despite not being a mortal disorder, chronic nature of IBS can lead to a disturbed HRQOL, affecting daily routine of the patients. In addition, IBS does not only affect the colon but other parts of the gastrointestinal tract and sensory system, causing problems there, too.¹⁶ The majority of the IBS patients complain of functional disorders of indefinable origin, such as headache, lower back pain, dysuria, depression, sleeping disorders, anxiety, and attention fatigue.¹⁷ Low-grade mucosal inflammation and consequent cytokine release are important in the pathophysiological association between IBS and depression. All these factors may play a role in the association between HRQOL and IBS.

The prevalence of IBS in the general population is 9–20%.^18,19 In these patients, major depressive disorder frequency was up to two-thirds of the patient. This was further counter-confirmed in another study where IBS has been reported in 30% of the non-renal patients with depression. In a recent study, the prevalence of IBS in patients with chronic renal failure on HD or peritoneal dialysis has been shown to be higher than the subjects with normal renal function, with no difference in relation to dialysis type.²⁰ In another study, a prevalence of 29.2% was reported in 236 HD patients and a positive association between IBS and depression was suggested.⁵

Our study shows the high burden of IBS on HRQOL, anxiety, and depression in renal transplant patients. Gastrointestinal system symptoms are common in renal transplant patients.²¹ These symptoms may be caused by increased stress, infections, and/or recurrence of a preexisting gastrointestinal pathology. In addition, immunosuppressive drugs may cause gastrointestinal side effects either directly or by favoring the development of bacterial and/or viral infection. Recently, Kleinman et al.²² investigated the presence and severity of gastrointestinal symptoms and their impact on QOL in renal transplant recipients by using GSRS and the Gastrointestinal Quality of Life Index. They reported worse HRQOL in patients with higher scores. Similarly, Ekberg et al.,²³ by using the same index reported a high prevalence of gastrointestinal symptoms in Scandinavian renal transplant recipients and its association with impaired QOL in an observational survey based on postal questionnaires. This finding was confirmed by various other studies. Of importance none of these studies used the Roma III criteria, which is the most common and validated criteria. In addition, the effect on anxiety was never investigated.

In our study, there were no differences between patients with and without IBS with regard to HD duration prior to dialysis, post-transplant follow-up, serum creatinine, albumin, and hemoglobin levels confirming that biochemical and clinical parameters are not helpful in the diagnosis.

Drug-induced gastrointestinal symptoms may be observed in renal transplant patients. This is especially seen in patients on mycophenolate mofetil. In our unit, we first decrease the dose and if no response is seen change mycophenolate mofetil to mycophenolate sodium if our evaluations show that it is associated with drugs. In our study, patients on mycophenolate mofetil had more IBS according to the survey, despite no clinical symptoms. Furthermore, the significant difference between patients with IBS and not regarding depression, anxiety, and QOL suggests that they may be non-related to drugs.

Our study has limitations. First of all, because our study had a cross-sectional design, our findings do not prove a cause–effect relationship. Second is the fact that we did not perform sophisticated tests such as endoscopy or colonoscopy. This may be regarded as a major limitation at first glance. However, majority of the studies in the literature have validated the use of only Roma II or III criteria.

As a conclusion, renal transplant patients have increased prevalence of IBS. IBS is associated with worsening of HRQOL and higher frequency of depression and anxiety.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.