Prevalence and Modifiable Factors for Holistic Non-Adherence in Renal Transplant Patients: A Cross-Sectional Study

Figures & data

Table 1 Definitions of Adherence, Non-Adherence, and Subtypes

Name	Definition
Adherence	It is the behavioral pattern that is indicative of the patient’s motivation and empowerment in relation to their treatment, oriented to the compliance of the therapeutic regimen. It differs from simple therapeutic compliance because the patient assumes an active and responsible role in relation to the post-transplant instructions and recommendations, as part of a positive patient-physician alliance.
Non-adherence	It is the modification or non-compliance with the therapeutic regimen that endangers the graft’s survival or functionality, made by the patient consciously or unconsciously, openly or secretly, intentionally or unintentionally. Operationally, a non-adherent patient fails to attend monthly check-ups, omits or modifies the doses of his medications, or persistently disobeys medical orders regarding taking biopsies, hospitalization, laboratory tests, and/or careful behavior (smoking, diet).
Non-adherence subtypes
Incidental non-adherence	This is accidental non-adherence, resulting from the patient’s ignorance of the high importance of perfect discipline in the schedule and calendar of their medication intake, medical controls, laboratory tests, and other procedures ordered by their physician. It is more frequent in the first post-transplantation weeks. It seems to be more frequent in people with low educational backgrounds and/or coming from rural areas, who find it difficult to understand and adapt to medical technology.
Apathetic non- adherence	It is non-adherence resulting from the patient’s psychological compromise. These are patients with clinically significant psychological pathology (depressed, distressed or psychotic) who are not interested in their treatment commitments as a result of this pathology.
Invulnerable non- adherence	It is the irresponsible behavior that characterizes many adolescents, dedicated workers, and in general, patients who evolve so successfully post-transplant that they dedicate themselves to their “normal” life and forget about the importance of the treatment. They miss one or several doses, delay the schedule for taking immunosuppressors, come back on time (or definitely late) and act as if nothing is going to happen because of these “small” oversights.
Disguised non- adherence	It is the non-adherent behavior of non-competent patients (children, intellectual disability, and patients with cognitive deficits). In this case, non-adherence is an irresponsible behavior (involuntary or deliberate) of the person empowered to administer their treatment, such as their caregiver.
Opposition non- adherence	It is the deliberate behavior of purposely oppose to the treatment. This is the case of a patient who refuses the therapeutic measures his transplant imposes on him—for example, a patient who is trying to avoid the appearance of a certain side effect that is unwilling to tolerate.
Non-specific non- adherence	When the interviewer considers that they cannot classify the patient in any of the five previous groups, a good example is the case of non-adherence (or suspected non-adherence) due to administrative reasons from the insurer.
Other definitions
Immunosuppression non-adherence	Any failure in immunosuppression compliance. Understand by having missed one or more doses of immunosuppressive medication in the previous four weeks.
Suboptimal immunosuppressor levels	Immunosuppressor levels are requested for dose adjustment and regarding the patient’s clinical condition. The main reasons are renal function worsening, acute rejection, clinical or paraclinical findings of toxicity, recurrent infection, secondary or adverse events, and pharmaceutical modifications that affect immunosuppressor metabolism. The suboptimal levels are defined as: Tacrolimus <5 ng/mL. Sirolimus <4 ng/mL. Everolimus <4 ng/mL. Cyclosporine <100 ng/mL.

Note: The required levels of immunosuppression can change depending clinical status of the patients.

Table 2 Characterization of Adherent and Non-Adherent Patients. Definitions for Each Variable are in Appendix 2

Variables	Total (N=1030)	Non-Adherent (n=317)	Adherent (n=713)	P-value	Non-Adjusted OR for Non-Adherence (CI 95%)
Age in years, median [IQR]	47 [36–58]	44 [34–56]	48 [37–59]	0.002*^a	0.98 (0.97–0.99)
Sex, n(%)				0.174 ^b
Feminine	427 (41.5)	121 (38.2)	306 (42.9)		reference
Masculine	603 (58.5)	196 (61.8)	407 (57.1)		1.21 (0.92–1.59)
Marital status, n(%)				0.001*^b
Single	319 (31)	117 (36.9)	202 (28.3)		reference
Stable marital union	581 (56.4)	152 (47.9)	429 (60.2)		0.61 (0.45–0.82)
Dissolved marital union	58 (5.6)	17 (5.4)	41 (5.8)		0.71 (0.38–1.29)
Underage	17 (1.7)	9 (2.8)	8 (1.1)		1.94 (0.72–5.30)
Other	55 (5.3)	22 (6.9)	33 (4.6)		1.15 (0.63–2.05)
Transplant care, n(%)				<0.001*^b
Single center transplant care by our group	701 (68.1)	173 (54.6)	528 (74.1)		reference
Divided transplant care	329 (31.9)	144 (45.4)	185 (25.9)		2.37 (1.80–3.13)
Time after transplant, n(%)				<0.001*^b
Between 0 and 12 months	134 (13.0)	22 (6.9)	112 (15.7)		reference
Between 13 and 60 months	419 (40.7)	112 (35.3)	307 (43.1)		1.83 (1.12–3.10)
61 months or more	477 (46.3)	183 (57.7)	294 (41.2)		3.14 (1.95–5.25)
Number of transplants, n(%)				0.379^b
First	1002 (97.3)	311 (98.1)	691 (96.9)		reference
Second or more	28 (2.7)	6 (1.9)	22 (3.1)		0.60 (0.22–1.42)
Donor type, n(%)				0.170 ^b
Cadaveric	712 (69.1)	229 (72.2)	483 (67.7)		reference
Living	318 (30.9)	88 (27.8)	230 (32.3)		0.80 (0.60–1.07)
Anxiogenic events^†, n(%)				0.555 ^b
No	594 (57.7)	178 (56.2)	416 (58.3)		reference
Yes	436 (42.3)	139 (43.8)	297 (41.7)		1.09 (0.83–1.42)
Social support^†, n(%)				0.010*^b
Functional	889 (86.3)	259 (81.7)	630 (88.4)		reference
Poor	103 (10.0)	40 (12.6)	63 (8.8)		1.54 (1.00–2.34)
Inadequate	38 (3.7)	18 (5.7)	20 (2.8)		2.18 (1.12–4.21)
Education reinforcement^†, n(%)				<0.001*^b
Nursing	559 (54.3)	220 (69.4)	339 (47.5)		reference
Nursing and psychology	471 (45.7)	97 (30.6)	374 (52.5)		0.40 (0.30–0.53)
Psychopathology, n(%)				<0.001*^b
No	652 (63.3)	123 (38.8)	529 (74.2)		reference
Yes	378 (36.7)	194 (61.2)	184 (25.8)		4.53 (3.42–6.02)
Psychopathological diagnosis, n(%)				<0.001*^b
Affective Disorder	115 (11.2)	54 (17.0)	61 (8.6)		3.80 (2.51–5.77)
Personality disorder	70 (6.8)	50 (15.8)	20 (2.8)		10.75 (6.26–19.09)
Adaptive disorder	43 (4.2)	8 (2.5)	35 (4.9)		0.98 (0.41–2.06)
Intellectual disability and other developmental disorders	32 (3.1)	20 (6.3)	12 (1.7)		7.16 (3.45–15.47)
Dementia and organic disorders	15 (1.5)	13 (4.1)	2 (0.3)		27.95 (7.59–180.27)
Other	103 (10.0)	49 (15.5)	54 (7.6)		3.90 (2.52–6.02)
No psychopathological diagnosis	652 (63.3)	123 (38.8)	529 (74.2)		reference

Notes: ^aComparison by Mann-Whitney U-test. ^bComparison by chi-square test. *Statistically significant result p<0.05. ^†First 3 months post-transplant follow-up.

Figure 1 Graphic representation of non-adherence subtypes by sex. (A) Non-adherence subtypes in total population. (B) Non-adherence subtypes in women. (C) Non-adherence subtypes in men.

Table 3 The Multivariate Model with the Results of the Factors Associated with Non-Adherence. *Statistically Significant p < 0.05 **Very Statistically Significant p < 0.005 ^†First 3 months post-transplant follow-up.

Variables	Adjusted OR for Non-Adherence Full Model		Adjusted OR for Non-Adherence Reduced Model
	OR (CI 95%)	p-value	OR (CI 95%)	p-value
Age (years)	0.97 (0.96–0.98)	<0.001**	0.97 (0.96–0.98)	<0.001**
Sex (Reference feminine)
Masculine	1.39 (1.00–1.94)	0.046*	–	–
Transplant care
(Reference Single center transplant care by our group)
Divided transplant care	1.41 (0.95–2.10)	0.088	–	–
Education reinforcement^†
(Reference only nursing)
Nursing and psychology	0.42 (0.27–0.64)	<0.001**	0.36 (0.25–0.51)	<0.001**
Anxiogenic events^†
(Reference no)
Yes	1.04 (0.75–1.43)	0.798	–	–
Social support^†
(Reference functional)
Poor	2.03 (1.22–3.36)	0.005*	2.09 (1.26–3.46)	0.003*
Inadequate	2.31 (1.06–4.99)	0.032*	2.31 (1.07–4.99)	0.031*
Psychopathological diagnosis
(Reference no psychopathological diagnosis)
Affective Disorder	4.18 (2.63–6.66)	<0.001**	3.71 (2.39–5.77)	<0.001**
Personality disorder	11.26 (6.26–20.97)	<0.001**	11.56 (6.45–21.45)	<0.001**
Adaptive disorder	1.26 (0.50–2.84)	0.585	1.07 (0.43–2.37)	0.866
Intellectual disability and other developmental disorders	5.24 (2.38–11.95)	<0.001**	5.50 (2.52–12.44)	<0.001**
Dementia and organic disorders	44.46 (11.10–300.66)	<0.001**	49.53 (12.52–332.7)	<0.001**
Other	3.54 (2.22–5.63)	<0.001**	3.64 (2.29–5.78)	<0.001**
Time after transplant
(Reference between 0 and 12 months)
Between 13 and 60 months	1.50 (0.85–2.73)	0.163	1.51 (0.87–2.72)	0.152
61 months or more	2.21 (1.23–4.11)	0.009*	2.38 (1.35–4.36)	0.003*

Figure 2 Relative frequencies of adherence and non-adherence in (A) patients transplanted and followed by a single center (Colombiana de trasplantes) and (B) patients transplanted by another group and followed by our center.