Key words : Early complications, Immunosuppression, Iraq, Renal transplant

Introduction
Kidney transplant is the best available therapy for end-stage renal disease (ESRD). A successful transplant offers a better quality of life and better chance of survival. The number of kidneys available for transplant is limited; therefore, it is vital to optimize graft survival. Graft longevity requires that patients follow their medication regimen in terms of dosing and timing of intake.¹

Adherence is the extent to which people follow the instructions they are given for prescribed treatments.² Medication nonadherence (MNA) is a deviation from the prescribed medication regimen sufficient to influence the regimen’s intended effect adversely.³

A report from the World Health Organization in 2003 indicated that MNA is a growing problem, reaching an average of 50% in developed countries, and is reported to be much higher in developing countries.⁴ Although MNA is ubiquitous in adolescents, adult transplant recipients may also not have good adherence to their medications.⁵

Kidney transplant recipients have substantially higher rates of MNA than other recipients of solid organs. A review of 38 papers estimated that the nonadherence rate is between 28% and 52%.^6,7

Medication nonadherence leads to increased risk of acute and chronic rejection with graft loss.8 A meta-analysis indicated that nonadherent patients were 7 times more at risk of graft failure than adherent patients.⁹ Life expectancy is 4 times lower in nonadherent patients than in adherent patients.⁶

Medication nonadherence may result from an intentional decision (missing or altering doses without consulting health care professionals) or from an unintentional interruption to the patient’s routine (forgetting to take medications).⁷ Nonadherence before transplant is an independent predictor of nonadherence after transplant.^10,11

Barriers to medication adherence are related to socioeconomic, cultural, educational, and condition-related factors, to health beliefs, and to patient- and medication-related circumstances.¹²

In Iraq, ambulatory follow-up and transplant medications are funded by the public health system. There are about 5000 renal transplant recipients in Iraq with a transplant rate of 16.6 per million population.¹³ In some countries, more than 50% of the annual transplant budget is related to immunosuppressant drugs.¹⁴

Different tools can measure MNA. The simplest one is discussing medication adherence as an intrinsic vital part during patient contact. The gold standard approach is the electronic monitoring of MNA.¹² Validated, structured immunosuppressive drug adherence questionnaires are also helpful tools. The Basel Assessment of Adherence to Immunosuppressive Medications (BAASIS) scale or the Transplant Effects Questionnaire systematically gauges any deviations in taking or timing adherence and/or dose reductions and have advantages compared with unstructured interviews.¹⁵

In this study, we sought to measure the adherence of Iraqi adult renal transplant recipients to immunosuppressive medications using the BAASIS scale and to describe demographic and transplant factors with regard to immunosuppressive medications.

Materials and Methods
Setting and study design
This cross-sectional study was conducted in the outpatient clinic pharmacy of the Nephrology and Renal Transplantation Center, The Medical City of Baghdad, from January to November 2020. The study employed the convenience sampling method.

Patients
For this study, 75 adult renal transplant recipients who had received their first grafts within 3 to 12 months were recruited. All patients received blood group-compatible kidneys from living donors. Transplant recipients received triple therapy with calcineurin inhibitors, mycophenolate mofetil, and steroids. Stable allograft function and stable calcineurin inhibitor trough levels were requirements to be included in the study. Trough levels were 4 to 8 ng/mL for tacrolimus and 150 to 250 ng/mL for cyclosporine.

Exclusion criteria
Patients under 18 years, those who were more than 1 year posttransplant, and those with allograft dysfunction were not eligible. In addition, patients with reported literacy impairment or poor cognition were not included.

Ethical approval
In accordance with the 2018 Iraqi research ethics code, all participants provided consent before participation. The scientific committee approved our study.

Protocol
All patients had an interview with a pharmacist in the outpatient pharmacy unit. Patient demographic and transplant follow-up data were retrieved from patient medical records in the outpatient department.

Sociodemographic, clinical, and transplant data included age, sex, marital status, education level and occupation, primary cause of ESRD, time since transplant, any complications after renal transplant (infection and acute rejection), and type and number of immunosuppressive medications. In addition, patient participants declared whether or not they needed assistance from a family member to take their medications.

Evaluation of adherence
We used an Arabic version of the BAASIS scale. The scale had been previously validated as an easily administered tool to assess adherence to drug therapies in terms of the number of dosages and times prescribed by transplant physicians compared with actual times adopted by the recipient.¹⁶

The Arabic version of the scale was developed and reviewed in collaboration with a linguistic professional to make it understandable to the study participants. Before distribution, the questionnaire was pretested on 15 individuals to look for any ambiguity in the questions and to allow comments from responders.

The survey consisted of 4 questions: (1) Did you forget to take immunosuppressive medications in the previous 4 weeks? (2) Did you take several doses of immunosuppressive medications within the previous 4 weeks? (3) Did you take the immunosuppressive agents with more than 2 hours difference compared with prescribed time in the previous 4 weeks? (4) Did you take a dose of immunosuppressive medications that is lower than the one prescribed by the physician?

Responses to each questions were either “No” or “Yes.” Nonadherence was considered whenever there was a positive response (Yes) to any question. For each “Yes” response, 5 to 6 additional questions were asked to assess the frequency of nonadherence. Responses to all questions were collected, and the total score was weighted out of 12.

Outcome
Outcome was the rate of adherence to immunosuppressive medications in renal transplant recipients using the BAASIS scale.

Statistical analyses
All statistical analyses were conducted with the statistical package for the Social Science Software version 24.0 (IBM Corp). For all statistical tests, a 5% level of significance was adopted. Chi-square tests were used to analyze associations between categorical variables. A binary logistic regression was used to predict the odds of the values of the independent variables (predictors). Odds were defined as the probability that a particular outcome was a case divided by the probability of no instance. P < .05 was considered significant.

Results
Of the 75 renal transplant patients who participated in this study, 68% were men and 32% were women, with a mean age of 39.44 ± 12.06 years. All patients denied smoking or alcohol consumption. Table 1 shows the demographic data of the study group.

In 57% of the study group, the primary cause of ESRD was unknown. Study patients had a mean time of 8.11 ± 3.12 months after their first transplant. The need for a caregiver was reported in 28% of the participants. Table 2 shows the baseline transplant data of the study group.

According to the BAASIS scale, during the previous 4 weeks, 82.6% of the participants did not forget to take their medications, 93.3% did not take additional immunosuppressive doses, 72% never took the immunosuppressive more than 2 hours from the time prescribed, and 90.7% did not take a lower dose than the prescribed one. Total adherence to immunosuppressive medications was reported in 65.3% of the patients, whereas 34.6% did not adhere to one (25.3%) or more (9.3%) of their immunosuppressive medications (Figure 1).

Table 3 shows the relationship between sociodemographic factors and the rate of adherence among the study participants. Interestingly, 4 patients had a biopsy-proven acute rejection, with all 4 being noncompliant with medications. There was a significant association between the adherence rate and the occurrence of complications posttransplant (P = .015).

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