EXPERIMENTAL AND CLINICAL TRANSPLANTATION

Objectives: Kidney transplant offers an improved quality of life and prolonged survival for patients with end-stage renal disease. This study aimed to compare balance and fall risk between kidney transplant recipients and healthy adults and to determine the relationship between biochemical parameters and fall risk and balance in kidney transplant recipients. As far as we know, this is the first study in the literature that evaluated whether balance changes occur in kidney transplant recipients using the Tetrax Interactive Balance System (Sunlight Medical Ltd., Ramat Gan, Israel).

Materials and Methods: Our study included 131 kidney transplant recipients (80 male/53 female; mean age of 39 ± 12 y) and 158 healthy volunteers (86 male/69 female; mean age of 40 ± 15 y). Groups were statistically matched in age, male/female patients, and body mass index. Fall index percentages were calculated using the Tetrax posturography device. Risk of falling was compared between kidney transplant recipients and healthy participants. Kidney transplant recipients were divided into 3 groups based on risk of falling. Demographic and clinical characteristics of kidney transplant recipients were recorded, and statistical analyses were performed to analyze these parameters versus balance measurements.

Results: Risk of falling was not significantly different between groups according to Tetrax measurements (32.4 ± 23.4 vs 31.6 ± 21.7; P = .08). Serum creatinine levels were significantly higher in kidney transplant recipients with a higher risk of falling (1.17 ± 0.37 vs 1.63 ± 1.18 mg/dL; P = .01). The use of oral antidiabetic drugs was shown to increase the risk of falling (P = .02).

Conclusions: Although patients with end-stage renal disease are thought to have balance impairments, kidney transplant recipients in our study had balance control similar to that shown in the healthy population. Graft function in kidney transplant recipients is important for the balance system.

Key words : End-stage renal disease, Postural balance, Renal transplantation, Tetrax posturography device, Transplant recipients

Balance is defined as the ability to maintain a position within the limits of stability or base of support. It is classified as an activity by the International Classification of Functioning, Disability, and Health.¹ Balance is essential for the performance of many activities in daily life. Many systems, such as the central nervous system, somatosensory system, vestibular system, visual system, muscular strength, and cognitive functions, are related to balance control. Pathologies of these systems may result in balance impairment and increased risk of falling, fracture, and/or musculoskeletal injury.² Morbidity and mortality rates related to falling are high. Significant financial cost may ensue, especially due to hip fractures. If the impact of kidney transplant (KT) on balance and fall risk can be quantitatively determined, countermeasures can be produced as mitigation.

Kidney transplant is the most ideal method among renal replacement treatments. Kidney transplant offers an improved quality of life and prolonged survival for patients with end-stage renal disease (ESRD). The positive improvements in quality of life after KT also lead to increased physical activity among KT recipients (KTRs), although at more sedentary rates than shown in healthy populations.³ However, some aspects of KT can also be negative. Neurotoxicity is a significant clinical adverse effect of immunosuppressive treatment in KTRs. Calcineurin inhibitors (CNI) are especially associated with neurotoxicity.⁴ Muscle atrophy, central neurologic disorders, tremor, peripheral neuropathy, altered cognition, visual disturbances, seizures, headache, tremor, and fatigue may be observed as side effects of immunosuppressive therapy.^3-5 Therefore, intense pharmacologic treatment may increase the risk of falling in KTRs.

This study aimed to compare balance and fall risk between KTRs and healthy adults and aimed to determine the relationship between biochemical parameters and fall risk and balance assessments in KTRs. As far as we know, this is the first study that evaluated whether there are balance changes in KTRs using the Tetrax Interactive Balance System (Sunlight Medical Ltd., Ramat Gan, Israel).

Materials and Methods

Study group selection
This prospective cross-sectional study investigated the risk of falling in KTRs compared with healthy volunteers. This study was approved by the Baskent University Institutional Review Board and Ethics Committee (Project no: KA17/352) and supported by the Baskent University Research Fund. Informed consents were obtained from all participants. All procedures that involved human participants were in accordance with the ethical standards of the institutional research committee and in accordance with the 1975 Helsinki Declaration and its later amendments or comparable ethical standards.

Our power analysis during biostatistical preliminary assessment indicated a study population of 272 patients (136 patients for each group) with 95% confidence level and 80% power.³

Inclusion criteria
Study participants were between 18 and 65 years old. Participants were divided into 2 groups. The first group included KTRs who underwent renal transplant between 2010 and 2017 at the Department of Transplantation at Baskent University Adana Dr Turgut Noyan Research and Training Center. Kidney transplant recipients at least 3 months posttransplant were considered eligible for the KTR study group. Healthy volunteers with absence of chronic diseases were enrolled in the control group. Participants in the control group were selected from hospital employees and relatives of patients.

Exclusion criteria
Participants were excluded for the following: (1) any neurologic or musculoskeletal disorder (eg, Parkinson disease, stroke, epilepsy); (2) uncorrected vision impairments; (3) orthopedic surgery to the lower limbs; and (4) inability to walk without support.

Study data
We included 131 KTRs (80 male/54 female patients; mean age of 39 ± 12 y) and 158 healthy volunteers (86 male/69 female volunteers; mean age of 40 ± 15 years). Groups were statistically matched in age, number of men and women, and body mass index. A medical history survey was administered by a physician to potential healthy volunteers to assess their eligibility.

Procedures
Age, sex, weight, and height of all participants were recorded. Weight and height were measured using a scale and stadiometer, respectively. Body mass index (body weight [kg]/height² [m²]) was calculated. Diabetes mellitus, hypertension, and atherosclerotic heart disease were determined through medical history survey. Dialysis duration, transplant duration, and the number of drugs used were also investigated and recorded. Dialysis duration was defined as time in months elapsed from the first day of dialysis to transplant. Transplant duration was defined as time in months elapsed from the day of transplant to the day of balance assessment. The use of prednisolone, tacrolimus, mammalian target of rapamycin inhibitors, cyclosporine, mycophenolate mofetil/sodium, azathioprine, antihypertensive drugs, insulin, oral antidiabetics, and antihyperlipidemic drugs was recorded for the KTR group. Blood pressures were also recorded on day of balance assessment.

The following laboratory parameters were recorded: hemoglobin, serum levels of fasting glucose, creatinine, alanine aminotransferase, sodium, and potassium. Hemoglobin levels were determined using the Cell Dyn 3700 hematology analyzer (Abbott Laboratories, Abbott Park, IL, USA). Other biochemical parameters were assessed via standard laboratory methods using the Roche Hitachi 902 chemistry analyzer (Roche Diagnostics Corporation, Indianapolis, IN, USA). The last 2 serum levels of immunosuppressive drugs were recorded and averaged.

Balance measurements
Balance measurement outcomes were assessed by the same assistant health staff using the same method. This involved the Tetrax Interactive Balance System to measure static posturography. Fall index percentages were calculated for all patients and healthy volunteers using the Tetrax posturography device (Sunlight Medical Ltd.). This interactive balance assessment device can monitor postural oscillations and evaluate an individual’s balance. The system uses the Tetrax 4-point balance platforms, which can record the vertical pressure fluctuations from the heels and the tiptoes of the subject. During measurement, the individual tries to stand on the platform for a period of time (approximately 5 min), and the postural stability of the individual is measured electronically. Results defined the individual’s general stability, weight distribution, Fourier transformations (postural sway), and synchronizations between foot parts. These parameters were analyzed to determine the individual’s fall index. This index is shown to be related to the risk of falls, and this risk of falling was compared between KTRs versus healthy volunteers. Fall index scores (from 0% to 100%) were divided into 3 categories of fall risk. Fall index scores from 0 to 36 were considered to be low risk, those from 37 to 58 were considered to be medium risk, and those from 59 to 100 were considered to be high risk.6,7 Kidney transplant recipients were divided into these 3 categories based on their risk of falling.

Demographic and clinical characteristics of KTRs were recorded, and statistical analysis was performed between these parameters and balance measurements. We also asked KTRs whether they had experienced an increased number of falls posttransplant and the frequency of falls over 6 months posttransplant.

Statistical analyses
Statistical analysis was performed using the statistical package SPSS software (version 17.0; SPSS Inc., Chicago, IL, USA). For continuous variables, normality was checked by Kolmogorov-Smirnov and Shapiro-Wilk tests and by histograms. All numerical data are expressed as median values (minimum-maximum) or as proportions. Categorical variables were compared between groups with chi-square test or Fisher exact test. Comparisons between groups were made with t tests or one-way analyses of variance for normally distributed data and with Mann-Whitney U test or Kruscall-Wallis test for data not normally distributed. P < .05 was considered statistically significant.

Of 140 adult patients who underwent KT in our center between February 2010 and December 2017, 131 KTRs were included in this study. Nine were excluded because 1 had visual impairment, 6 had neurologic defects, and 2 had history of orthopedic surgery.

Fall index scores were similar in KTRs versus healthy volunteers (32.4 ± 23.4 vs 31.6 ± 21.7; P = .08). Demographic results and fall index score of both groups are summarized in Table 1.

Serum creatinine levels were significantly higher in KTRs with a higher risk of falling (1.17 ± 0.37 vs 1.63 ± 1.18 mg/dL; P = .01). There were no statistically significant differences between other laboratory parameters and the risk of falling. Characteristics of KTRs according to fall risk categories are shown in Table 2.

The use of oral antidiabetic drugs was shown to increase the risk of falling (P = .02). However, there was no statistically significant difference between other drugs and the risk of falling. Effect of drugs on risk of falling in KTRs is shown in Table 3. All KTRs were using prednisolone at 5 mg/day.

Balance control in KTRs was not related to serum levels of immunosuppressive drugs. The effects of mean blood levels of immunosuppressive drugs on risk of falling in KTRs are shown in Table 4. The number of falls after KT or in the last 6 months before the day of assessment was not increased in KTRs.

We found that balance in KTRs was similar to that shown in our healthy population. There are several studies evaluating balance systems in patients with ESRD in the literature.^2,5,8-10 Previous studies have shown that risk of falling was increased in patients with ESRD undergoing hemodialysis compared with that shown in healthy adults.^5,8-10 Increased risk of falling was also shown in patients with ESRD who were on peritoneal dialysis.² Many factors such as mineral bone disorder, electrolyte imbalance, anemia, metabolic acidosis, hypotension, arrhythmia, malnutrition, muscle atrophy, polypharmacy, and peripheral and autonomic neuropathy can contribute to increased risk of falling in patients with ESRD.⁹ Complications are more commonly seen in KTRs who are treated with long-term maintenance dialysis before KT. These complications are often cardiovascular, cerebrovascular, bone, and muscle disorders.^2,9 These irreversible disorders may cause a further deterioration in balance. As a result, the risk of falling is expected to increase in KTRs compared with healthy people.

To the best of our knowledge, there was only 1 study on balance of KTRs in the literature. In this study, Zanotto and associates used balance tests to show greater impaired balance in KTRs than in healthy adults.³ The number of KTRs included in that study was noticeably lower than in our study (19 vs 133 patients). The method used by Zanotto and colleagues to measure the risk of falling was also different from ours (ARGO stabilimetric platform vs Tetrax 4-point balance platform). Our study was the first to measure quantitative data using the Tetrax Interactive Balance System in KTRs; thus our study is the first to investigate falling risk in KTRs using an electronic balance system. This posturographic device also offers a method with proven reliability.⁹

Kidney transplant can have many positive effects on patients with ESRD, including improved cognitive function and increased physical activity.¹¹ However, KT also introduces intense immunosuppressive therapies that can cause neurotoxicity and consequently musculoskeletal disorders. Therefore, we suggest that risk of falling is increased in KTRs compared with that shown in the healthy population. Nevertheless, our study showed that KT in general had a positive impact on balance and risk of falling among patients with ESRD.

The Tetrax device that we used for balance measurements gives a fall index score that can be classified as low, medium, and high risk for falling.^6,7 When patients were examined according to these categories, we found that serum creatinine levels were higher in patients in the high-risk group. We also found that the risk of falling was higher in KTRs with worse graft function. Kidneys are known to have important roles in many systems in our body. This study showed that kidneys also have an important role for the body’s balance control.

When we compared serum hemoglobin, glucose, alanine aminotransferase, sodium, and potassium levels of our patients versus their fall index measurements, we observed no associations. Anemia in older age patients correlates with reduced muscle strength, poor physical performance, and disability.¹² Although not statistically significant, we found hemoglobin levels to be higher in the KTR group with low risk of falling.

Presence of diabetes or insulin use was not associated with risk of falling in our study; however, the use of oral antidiabetic drugs was shown to increase the risk of falling. Because of the small number of patients using oral antidiabetic drugs, we could not reach a definitive conclusion about the effects of oral antidiabetic drugs on balance.

Neuropathy is a common complication of CNI use. Regimens free of CNIs can perhaps benefit patients neurologically.4 We expected that the risk of falling would be increased in patients who were on CNI-based therapy. However, we found no statistically significant difference between patients on CNI-based therapy and those who were not. Although we suspected that blood pressure may be related to the risk of falling, no relationship between blood pressure and risk of falling was shown in our study. Although not statistically significant, the presence of comorbid conditions like diabetes mellitus, hypertension, and atherosclerotic heart disease seemed to be related to risk of falling in KTRs. In addition, risk of falling was lower in KTRs with shorter dialysis duration before KT, although not significantly.

In our study, balance was not impaired in KTRs compared with healthy volunteers, although graft dysfunction was related to balance control and use of oral antidiabetic medication was associated with increased risk of falling. The important limitations of our study include the absence of balance measurements of patients before KT. Another limitation was that exclusion criteria (visual impairment, neurologic defects, and orthopedic surgery) were determined only through medical history survey.

Although patients with ESRD are thought to have balance impairment, KTRs in our study demonstrated balance controls similar to that shown in the healthy population. Graft function in KTRs is important for the balance system. Further studies could help strengthen our findings.

Volume: 18 Issue: 1 January 2020 - Supplement - 1

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