Objectives: Muscle wasting occurs in renal recipients due to decreased physical performance, and decreased respiratory muscle strength may occur due to changes in structure and function. Data are scarce regarding the roles of sarcopenia and nutritional status on respiratory muscle function in these patients. Here, we evaluated interactions among peripheral muscle strength, sarcopenia, nutritional parameters, and respiratory muscle function in renal transplant recipients.
Materials and Methods: Ninety-nine patients were prospectively enrolled between September and April 2016 at Baskent University. Forced vital capacity values (via pulmonary function tests), respiratory muscle strength (via maximal static inspiratory and expiratory pressures), and peripheral muscle strength (via hand grip strength test) were recorded. Nutritional parameters, fat weight, arm circumference, waist circumference, and C-reactive protein levels were also recorded.
Results: Of 99 patients, 68 were renal transplant recipients (43 men, mean age: 39.09 ± 10.70 y) and 31 were healthy participants (14 men, mean age: 34.94 ± 10.95 y). Forced vital capacity (P < .001, r = 0.65), maximal inspiratory (P = .002, r = 0.39) and expiratory (P < .001, r = 0.4) pressure, and hand grip strength showed significant relations in transplant recipients. Positive correlations were found between serum albumin levels and both hand grip strength (P = .16, r = 0.347) and forced vital capacity (P = .03, r = 0.436). Forced vital capacity was statistically different between renal recipients and healthy participants (P = .013), whereas maximal inspiratory and expiratory pressures were not (P ˃ .05). No statistically significant relation was observed between biochemical parameters and maximal inspiratory and expiratory pressures (P ˃ .05).
Conclusions: Respiratory function and peripheral muscle strength were significantly related in renal transplant recipients, with significantly lower peripheral muscle strength suggesting the presence of inadequate respiratory function. Peripheral and respiratory muscle training and nutritional replacement strategies could help to improve postoperative respiratory function.
Key words : Muscle weakness, Renal transplantation, Respiratory system
Peripheral muscle weakness is a common problem in chronic renal failure (CRF) patients. Several factors, including comorbid conditions, prolonged hospitalization episodes, malnutrition, systemic inflammation, uremic myopathy, secondary hyperparathyroidism, anemia, and steroid myopathy are responsible for peripheral muscle weakness and physical performance in CRF patients. A few studies have shown that respiratory muscle weakness is associated with peripheral muscle weakness and sarcopenia in CRF patients.1-3
Limited data exist about the prevalence and risk factors of sarcopenia and muscle weakness in renal transplant recipients (RTRs) in the literature.4,5 The effects of factors related to renal transplant on respiratory muscles are also not fully understood. Our study was performed to determine factors affecting peripheral and respiratory muscle functions in RTRs.
Materials and Methods
This study was conducted at Baskent University Hospital and was approved by the Ethics Committee of Baskent University School of Medicine. Each patient provided written informed consent to use their clinical data for study purposes.
In this study, we prospectively collected data from all eligible participants (68 RTRs and 31 healthy individuals) between September 1 and April 30, 2016, at Baskent University.
Patients were selected according to the following exclusion criteria: (1) irregular drug use or patient noncompliance; (2) lack of regular follow-up data; (3) previous bone marrow transplant or other solid-organ transplant before or at the time of renal transplant; (4) malignant disease, rheumatologic or chronic inflammatory disease of unknown origin, or systemic vasculitis history; (5) acute rejection during the 1st year posttransplant; (6) graft failure (glomerular filtration rate < 30 mL/min); (7) presence of active infection; (8) receiving antiaggregant or anticoagulant therapy; and (9) unstabilized metabolic condition. With the exclusion criteria applied, our study enrolled 68 RTRs (37.72 ± 10.90 years old at 6.07 ± 4.86 years posttransplant, 25 female) who showed no serious complications and maintained graft function.
Clinical and biochemical measurements
The clinical and biochemical parameters of the patients in the 1st year after transplant were prospectively recorded. Body compositions of all patients were analyzed with the use of the Tanita BC-420MA Body Composition Analyzer (Tanita, Tokyo, Japan). Nutritional parameters (serum vitamin B12, vitamin D, albumin, phosphorus, magnesium), fat weight, muscle mass, bone mass, triceps skinfold thickness, upper arm circumference, waist circumference, hand grip strength (HGS) test, and C-reactive protein levels were collected and recorded. Immunosuppressive drugs administered were also recorded. Forced vital capacity (FVC) values were collected from the pulmonary function tests. The respiratory muscle strength was measured by maximal inspiratory pressure (MIP) and maximal expiratory pressures (MEP). Measurements for FVC, MIP, and MEP were performed using a Carefusion Jaeger Masterscreen PFT Pro Germany System, (Yorba Linda, CA, USA) according to European Respiratory Guidelines for MIP and MEP measurements.6-8 Peripheral muscle strength was measured by HGS test using a hand dynamometer (Takei Scientific Instruments Co., Japan).
Data analyses were performed with SPSS software (SPSS: An IBM Company, version 20.0, IBM Corporation, Armonk, NY, USA). Continuous variables are expressed as means ± standard deviation. Frequencies are expressed as both numeric (n) and percentage (%). Chi-square tests were used to compare parameters between patients and healthy participants (controls). The level of significance was set at P < .05.
We enrolled 99 patients (57 males/42 females) in this study. The patients’ demographics are shown in Table 1. Sixty-eight RTRs (43 males/25 females, mean age: 39.09 ± 10.7 y) and 31 health participants (14 males/25 females, mean age: 34.94 ± 10.95 y) were included. Most patients (77.9%) were nonsmokers with a history of renal transplant from a living donor (79.8%). Major causes (75%) of renal disease in transplant recipients included glomerulonephritis (16 patients), hypertension (13 patients), urologic factors (9 patients), and unknown (13 patients). Mean time since transplant was 6.07 ± 4.86 years. Various combinations of immunosuppressive drugs were administered during the posttransplant period, with the most common agent being prednisolone; however, mycophenolate mofetil, sirolimus, tacrolimus, and cyclosporine were also administered in all RTRs.
The blood chemistry and hemogram data are shown in Table 2. The mean values for all parameters were similar and within normal ranges for both RTRs and healthy participants. Anthropometric measurements and respiratory function tests of RTRs and healthy participants are shown in Table 3. Anthropometric measurement results and respiratory muscle force were not significantly different between RTRs and healthy participants (P > .05).
There was a statistically significant relationship between FVC (P < .001, r = 0.65), MIP (P = .002, r = 0.39), MEP (P < .001, r = 0.4), and HGS in RTRs. Positive correlations were found between serum albumin levels and both HGS (P = .16, r = 0.347) and FVC (P = .03, r = 0.436). In our study, FVC was statistically different between RTRs and healthy participants (P = .013), whereas MIP and MEP were not (P > .05). No statistically significant relation was observed between biochemical parameters and MIP and MEP (P > .05) (Table 4).
Sarcopenia is an age-related problem presenting as progressive declines in both muscle mass and its function. It is associated with frailty, disability, and increased risk of mortality. Although sarcopenia is originally known as a condition related to aging, various international societies presently recognize the important role of catabolic diseases, such as chronic kidney disease, in its cause.9-12 The prevalence of sarcopenia varies widely in the elderly population due to the lack of a consensus about its definition and its diagnostic criteria.13 Although the prevalence of muscle weakness and sarcopenia is 5% to 13% in patients between 60 and 70 years of age, it ranges from 11% to 50% in patients older than 80 years old.14 Despite several studies showing the prevalence of sarcopenia due to aging, a recent study showed that chronic kidney disease contributes to peripheral muscle weakness and sarcopenia and sarcopenia may develop at an earlier age in RTRs.13 In our study, no significant difference was found between male and female patients in our RTR population, which is similar to the literature. Our findings indicated that sarcopenia may occur in RTRs at a younger age compared with the general population. We believe that many other factors, including social isolation, a restricted and sedentary lifestyle, and adverse effects of immunosuppressive drugs, could also play important roles in muscle weakness and sarcopenia in younger RTRs.
A muscle examination has a critical role in the evaluation of patients who present with weakness. Together with the history and general physical examination, demonstrating the presence of muscle weakness is the first step in the diagnosis of respiratory muscle weakness.15 Respiratory muscle strength can be assessed by measuring MIP and MEP. Maximal inspiratory pressure reflects the strength of the diaphragm and other inspiratory muscles, whereas MEP reflects the strength of the abdominal and other expiratory muscles.6 Weakness of the respiratory muscles can dominate the respiratory clinical manifestations in the later stages of some systemic diseases, including diabetes, chronic kidney disease, and neurologic and neuromuscular disorders.16 No data exist in the literature comparing the prevalence of sarcopenia and the relation between both peripheral and respiratory muscle functions in RTRs.
In our study, although respiratory muscle functions were correlated with peripheral muscle strength, they were not associated with patients’ serum nutritional parameters. This result could be explained by the normal biochemical, hormonal, and vitamin levels in our population. We suggest that further studies are needed to establish the effects of altered levels of nutritional parameters on respiratory muscle functions in RTRs.
Many drugs used for therapeutic interventions can be toxic to muscle tissue, often leading to considerable morbidity.17 The use of systemic glucocorticoids causes muscle weakness.18 Although animal models and clinical experience confirm the detrimental effects of steroids on muscle structure and function, studies in patients with Cushing syndrome do not uniformly show muscle atrophy.19 The most commonly received immunosuppressive drug was prednisolone, but mycophenolate mofetil, sirolimus, tacrolimus, and cyclosporine were also used in our patients. Therefore, we suggest that immunosuppressive treatment could be a factor for the muscle weakness and sarcopenia in these patients.
There is evidence that physical training improves muscle mass and strength in glucocorticoid-treated patients with peripheral muscle wasting.20 A study performed by Pomidori and associates showed the positive effects of a 6-month moderate-intensity exercise program on respiratory muscle strength in patients with chronic kidney disease.21 Therefore, we believe that relevant peripheral muscle exercise programs during the posttransplant period could be useful to improve muscle weakness and sarcopenia in RTRs.
Karacan and associates researched pulmonary function and respiratory muscle force in RTRs, patients who are on continuous ambulatory peritoneal dialysis, and CRF patients.5 They found decreased MIP and MIP values in 24 RTRs. Peripheral muscle functions and the relation between nutritional parameters and pulmonary muscle function were not mentioned in their study. They maintained that the only responsible factor affecting respiratory muscles was corticosteroid use. In the present study, we enrolled a larger group of RTRs and compared their results with healthy participants. We also investigated the relation between nutritional factors and muscle force in both the transplant and healthy groups and could not find any responsible factors, unlike shown by Karacan and associates.
Our study has some limitations. First, our RTRs all had normal nutritional parameters. Therefore, we could not investigate the effects of malnutrition and loss of muscle mass on respiratory muscle function. Second, we did not show the effects of exercise programs on both peripheral and respiratory muscle force. Third, we could not compare peripheral and respiratory muscle functions between the pre- and postoperative periods because our study design did not cover the preoperative period of the RTRs. We believe that further studies are needed to support this information.
Our results demonstrated that respiratory function was related to peripheral muscle strength in RTRs. Peripheral muscle strength can indicate respiratory muscle strength in these patients. We suggest that peripheral and respiratory muscle training and nutritional replacement strategies after renal transplant could help to improve muscle function.
Volume : 15
Issue : 1
Pages : 249 - 253
DOI : 10.6002/ect.mesot2016.P120
From the 1Department of Pulmonary Diseases, 2Department of Nephrology, and the 3Department of General Surgery, Baskent University, Ankara, Turkey
Acknowledgements: The authors declare that they have no sources of funding for this study, and they have no conflicts of interest to declare.
Corresponding author: Gaye Ulubay, Baskent University, Department of Pulmonary Diseases, Fevzi Çakmak Cd. 10. Sk. No: 45, Bahçelievler, Ankara, Turkey
Phone: +90 312 212 6868
Table 1. Participant Demographics
Table 2. Laboratory Test Results of Renal Transplant Recipients and Healthy Participants
Table 3. Anthropometric Measurements and Respiratory Function Tests of Renal Transplant Recipients and Healthy Participants
Table 4. Correlations Between Maximal Inspiratory Pressure, Maximal Expiratory Pressure, and Other Variables (All Patients)