hronic kidney disease (CKD) as a progressive disease is defined as the decreased kidney function—glomerular filtration rate (GFR) < 60 ml/min/1.73 m
2 for 3 months or more (Levey
et al., 2005). It is a public health problem that is rapidly increasing, particularly in developing countries (Khajehdehi
et al., 2014, Levey
et al., 2007). Hypertension and diabetes are main reasons for developing kidney disease in adults (Chobanian
et al., 2003, Stevens
et al., 2008). Prevalence, mortality rate, and cost of care for patients on dialysis, kidney transplant, and end stage renal disease (ESRD) have increased during the last two decades (Hamer and El Nahas, 2006, USRDS, 1999). The prevalence of CKD varies in different nations based on the age of study population and among men and women (Zhang and Rothenbacher, 2008). A study in the United Stated of America (USA) reported that CKD prevalence was 1.5% in adult population (mean age 43.9 years) in 2005 (Kramer
et al., 2005). In another study the prevalence was reported 43.3% among people aged over 45 years (McClellan
et al., 2006). In a systematic review of 26 studies, the median prevalence of CKD in persons over 30 years of age was 7.2% (Zhang and Rothenbacher, 2008). A number of studies have investigated the prevalence of CKD in Iran. A study reported the prevalence of 18.9% among people aged over 20 years (Hosseinpanah
et al., 2009). Another study reported 19.5% for the prevalence for CKD among Iranian adults (Najafi
et al., 2012). In a study conducted by Safarnejad et al. the prevalence of chronic renal insufficiency (defined as GFR of 15-59 ml/min per 1.73 m2) was 8.1% among Iranian adult population (Safarinejad, 2009). The prevalence of this disease in our country is higher than countries such as USA, Australia, and Norway based on the previous studies (Hamer and El Nahas, 2006, Kopple, 2001b). The possible reason can be that the risk factors of CKD including diabetes and dyslipidemia in Iranian population are more than other countries (Najafi
et al., 2012, Safarinejad, 2009). Furthermore, the elderly population in Iran is growing and it might be contributed to the increasing prevalence of patients with CKD (Cibulka and Racek, 2007).
CKD has a major impact on health; it not only leads to kidney failure but also is associated
with increased levels of inflammatory markers
and plasma homocysteine (Shlipak
et al., 2003), anemia (Hsu, 2002), increased vascular calcification (Raggi
et al., 2002), abnormal levels of apo lipoproteins (Shlipak
et al., 2003), endothelial dysfunction and arterial stiffness (London
et al., 2003), as well as premature mortality. In 2003, American heart association (AHA) declared that patients with CKD are considered as people at high risk for cardiovascular diseases (Sarnak
et al., 2003).
Metabolic conditions and several other factors affect nutritional status of patients with CKD. Factors such as poor appetite, inadequate nutrient intake, insulin resistance, infection, and oxidative stress are associated with nutritional depletion (Chung
et al., 2012). Furthermore, protein-energy wasting (PEW) usually observed in these patients, especially in the end stages of the disease (Ikizler
et al., 2013). Because malnutrition is associated with increased morbidity and mortality and also according to the increasing incidence of this disease in Iran, it is important to recognize nutrition status to manage and improve the quality of life in these patients. Hence, in this narrative review we aimed to assess nutritional status in Iranian CKD patients for the first time.
Materials and Methods
This narrative review manuscript was extracted by searching the creditable databases, including PubMed, Scopus, Embase, Science Direct, Google scholar, Magiran, and scientific information database (SID) using keywords such as chronic kidney disease, malnutrition, renal disease, end stage renal disease, nutritional deficiency, malnutrition, quality of life, vitamin deficiency, wasting, and Iran from the published literature (English and Persian language). In this regard, a variety of studies including prospective cohort, retrospective, case-control, clinical guidelines, and review articles were studied up to 2016.
Results
Protein-energy wasting (PEW) in patients with CKD: In spite of the advancements in medical science, mortality rates are still high in CKD patients (Kalantar-Zadeh
et al., 2006). These patients especially the ESRD ones suffer from catabolic conditions. Weight loss, reduced fat and muscle mass (Su
et al., 2013), increased inflammatory markers (den Hoedt
et al., 2014), decreased levels of serum albumin (that is affected by both inflammatory and nutritional conditions) (Kim
et al., 2013), metabolic acidosis (Kalantar‐Zadeh
et al., 2004), altered intracellular insulin like growth factor 1(IGF-1) and insulin signaling (Bonanni
et al., 2011), as well as endocrine disorders (Ros and Carrero, 2013) are common in these patients. On the other hand, Anorexia resulting from uremia (Carrero
et al., 2007), restrictive diet that limits potassium, phosphorus, or sodium intake, loss of nutrients in the dialysis, and other factors affect food intake and thus disrupt the energy balance (Ikizler
et al., 1994). One of the main mechanisms that lead to muscle atrophy in patients with CKD is associated with increased catabolism of Ubiquitin-proteasome system (UPS) mediated protein (that reduces muscle proteins) and activation musculoskeletal myostatin (which inhibits cellular proliferation and muscle synthesis) in uremic situation (Mitch and Goldberg, 1996). In addition, the extensive tissue damage will increase the level of circulating actin that consumes gelsolin (the protein that assembles and disassembles actin) (Zhang
et al., 2011). Increased level of actin and reduced level of gelsolin are associated with increased risk of mortality (Gracia-Iguacel
et al., 2014). Another mechanism is related to insulin resistance. Insulin-like growth factor 1 can lead to an upregulation of myostatin and a declined proliferation of satellite muscle cell by activating the phosphoinositide 3-kinase pathway (Zhang
et al., 2010). This situation leads to loss of protein and energy in patients with CKD. In fact, PEW is a pathological condition associated with sustained reduction in protein and energy reserves due to inadequate intake and increased catabolism as a result of reasons already mentioned (Fouque
et al., 2008, Mak
et al.). The prevalence of PEW in CKD patients have been reported 18-75% in various studies (Leinig
et al., 2011). This variety is due to different assessment methods and cut-off points (Gracia-Iguacel
et al., 2014). However, according to our review, only one study has been conducted on prevalence of PEW in Iran by Tabibi et al. They reported that the prevalence rates of mild-to-moderate and severe PEW were 60.5% and 1% in hemodialysis patients, respectively (Tabibi
et al., 2012). It seems that this prevalence is high in Iran. Protein-energy wasting in kidney disease patients can lead to events that affect different systems and organs (Kovesdy and Kalantar-Zadeh, 2009). In these patients, muscle catabolism increased due to inflammation, reduction of nutrients, metabolic acidosis, and other factors. Reduction of muscle mass can affect the arteries and heart function, it also might cause ventricular hypertrophy together with other factors such as water and sodium retention (Gracia-Iguacel
et al., 2014). Moreover, in PEW patients nutritional deficiency is associated with chronic immunodeficiency state (Vanholder and Ringoir, 1993), increased oxidative stress, delay in wound healing (Vanholder
et al., 1993), and susceptibility to infections (Dong
et al., 2011, Gracia-Iguacel
et al., 2013). These reasons are leading to an increase in overall mortality (Gracia-Iguacel
et al., 2014).
As previously mentioned, the most important reason for PEW in patients with CKD is inadequate dietary protein and energy intake and also additional nutrient loss during dialysis (Combarnous
et al., 2002, Kloppenburg
et al., 1999, Wang
et al., 2003). A study in Tehran showed that protein and energy intakes were less than the recommended rates in 86.1 and 94.1% of hemodialysis patients, respectively (Taghdir
et al., 2011). In another study conducted by Pasdar et al., lack of energy and protein intakes in hemodialysis patients were 66 and 30%, respectively (Pasdar Khoshknab and Keshavarz, 1996). These prevalence rates were reported as 88 and 84.5%, respectively in a study conducted by Ashabi study et al. (As habi
et al., 2011). These results were consistent with findings of a study conducted by Pourghaderi et al. (Pourghaderi
et al., 2015). Average rates of energy and protein intake were reported as 17.5 kcal/kg and 0.8 g/ kg of bodyweight per day in dialysis patients, that are lower than the recommended daily intakes (Mardani
et al., 2016). Several approaches can be used to avoid inadequate nutrition intake. Energy and protein intake in patients with stage 3-5 CKD who are clinically stable and not on dialysis, should be 30–35 kcal/ kg and 0.6–0.8 g/kg of ideal body weight per day, respectively to prevent loss of muscle protein (Cano
et al., 2009, Kopple, 2001a). It is therefore worth noting that in patients who have hyper catabolic conditions such as infection, these values should be adjusted. In patients with end-stage renal disease who are on dialysis, the minimum rate of protein and energy requirements should be 1.2 g/kg and 30–35 kcal/kg of ideal body weight per day, respectively according to the physical activity level (for both hemo- and peritoneal dialysis). Notably, at least 50% of protein should be of high biological value (Ikizler
et al., 2013).
Consumption of high-protein meals or supplements during dialysis is a strategy to meet the recommendation, especially in at-risk patients (Kalantar-Zadeh and Ikizler, 2013). The important issue in these patients is control of phosphorus intake. Studies have shown that increased protein intake and low serum phosphorous can get the best result in hemodialysis patients (Shinaberger
et al., 2008). So, when a protein is recommended, its phosphorus content should also be noted. Patients who received this recommendation are not able to prevent weight loss and muscle building, so, nutritional supplementation is the next step. Furthermore, in cases of patients who are unable to tolerate oral supplements (such as severe anorexia or dysphagia) tube feeding is used (Cano
et al., 2009).
Vitamins and minerals status in patients with CKD: Vitamin deficiency is common in CKD patients who do not take supplements (Piper, 1985). The reasons for this deficiency can be due to the low dietary intake caused by anorexia, loss through dialysis, kidney functional limitations, and limited foods because of their high potassium or phosphorus contents. Moreover, some drugs interfere with nutrients that can lead to deficiency (Piper, 1985, Steiber and Kopple, 2011). According to our review, a limited number of studies have been conducted on the micronutrient intake in Iranian CKD patients. In a study carried out by Ashoupour et al., 96.8 and 97.9% of hemodialysis patients had low intakes of vitamin A and E, respectively. In addition, this study showed that in 50-100% of patients, thiamine, riboflavin, niacin, pyridoxine, cobalamin, folate, and vitamin C intakes were lower than the recommended levels. In addition, in 36-99% of patients calcium, iron, magnesium, and zinc intake rates were lower than the recommendation (Ashourpour
et al., 2012). Mardani et al. carried out an investigation in Khorramabad and showed that the intake of calcium, magnesium, zinc, sodium, and potassium in more than 90% of the patients was lower than the recommended level. Furthermore, this study found that 5-50% of the patients were not taking the recommended amounts of riboflavin, pyridoxine, B12, folate, and vitamin C. However, 98% and 60% of these patients had deficient amounts of fat soluble vitamins E and A, respectively (Mardani
et al., 2016). The results of these studies in Iran are consistent with findings of most other studies (Cho
et al., 2008, Kalantar-Zadeh
et al., 2002, Raimundo
et al., 2006, Wang
et al., 2007).
Some studies expressed that vitamin C deficiency in dialysis patients is due to restrictions in the consumption of fruit and vegetables in order to reduce hyperkalemia. Dietary vegetables restriction might also lead to folic acid deficiency. In addition, cooking vegetables to reduce their potassium content causes inactivation of vitamin C (Chazot and Kopple, 1997, Wang
et al., 2001). While meat, beans, and dairy products are rich in vitamin B groups, they have a high phosphorus content; so, consumption of these foods are limited by patients (Sprenger
et al., 1983). In addition, consumption of protein-rich foods (meats and sea foods) is limited because of anorexia in these patients, which can lead to zinc and iron deficiency (Pollock
et al., 1997).
Lack of nutrients in patients with CKD has devastating effects on the endothelial dysfunction, antioxidant capacity, and increases vascular calcification and mortality (Wen
et al., 2008). Some studies suggested that patients need dietary supplements for water soluble vitamins and minerals (Mardani
et al., 2016). More studies are therefore needed for better illustration.
Quality of life in patients with CKD: One of the important aspects of patients with CKD, which is usually neglected, is the quality of life (QoL). Studies have indicated that kidney disease is associated with reduced QoL and increased mortality (Feroze
et al., 2011). In addition, poor values in QoL are associated with worse situation in malnutrition markers (such as Low levels of albumin, creatinine, and decreased muscle mass) (Mazairac
et al., 2011). Moreover, poor QoL in mental aspect is common in dialysis patients (Allen
et al., 2002). These patients are facing with problems such as hospitalization, dietary restrictions, loss of appetite due to uremia, complications such as cardiovascular disease, depression, fear of failure, and memory loss and all these factors can affect daily activities of their life (Gracia-Iguacel
et al., 2014, Pakpour
et al., 2010). A study conducted by Pakpour and et al., on Iranian patients showed that the QoL scores in all scales in patients undergoing hemodialysis were significantly lower than those of the general population (Pakpour
et al., 2010), which is consistent with most of other studies (Ahari
et al., 2007, Vos
et al., 2006). Further studies are required to determine and control factors affecting the quality of life in these patients.
According to the authors' knowledge, this is the
first review article over nutritional status of CKD patients in Iran. Although the data presented in this review are not conclusive, it seems that nutritional status in these patients is not desirable. This manuscript can encourage researchers to develop new strategies to improve these patients' life conditions. Finally, through this study, we hope to shed some light on this issue.
Conclusions
Paying attention to the nutritional status of CKD patients is very important. According to the previous studies most Iranian CKD patients suffer from lack of protein, energy, and some micronutrients. Nutrition education programs are suggested for patients, their families, and health professionals. Furthermore, using nutritional supplementation in these patients appears to be useful in order to decreased morbidity and mortality. In addition, more widespread research should be performed on the causes of malnutrition to find appropriate strategies for the patients.
Authors’ contributions
Abdollahi SH wrote the manuscript. Razmpoosh E and Toupchian O provided critical revision of the manuscript. Salehi-Abargouei A edited the manuscript. All of the authors approved the content of the manuscript and agreed on all aspects of the work.