Malnutrition and inflammatory parameters in patients with chronic kidney disease stages 3–5 from northern India

Malnutrition is highly prevalent in chronic kidney disease (CKD). This study is conducted to find out the prevalence of malnutrition and its association with inflammation in patients with CKD stages 3–5. This is a hospital-based cross-sectional study conducted at the Sri Ram Murti Smarak Institute of Medical Science, Uttar Pradesh, India. CKD stages 3–5 patients were included. The nutritional status was assessed by subjective global assessment (SGA). Anthropometric and biochemical measurements were also checked at the time of enrollment. A total of 213/354 (60.2%) of patients were malnourished. The triceps skinfold thickness (TSFT) was 8.2 ± 1.2 mm and 10.9 ± 1.2 mm in the malnourished and well-nourished groups, respectively; p < 0.001. TSFT was ≤ 10 mm in 91.1% of patients with malnutrition. Mid-arm muscle circumference (MAMC) was 21.3 ± 2.2 cm and 24 ± 2.9 cm, and the body mass index (BMI) was 19.8 ± 1.5 and 22.5 ± 1.4 kg/m2 in the malnourished and well-nourished group, respectively; p < 0.001. A significant direct correlation between BMI, TSFT, MAMC, and eGFR was noted. Median eGFR was 11.9 ml/min/1.73 m2 in the malnourished compared to 24.2 ml/min/1.73 m2 in the well-nourished group; p < 0.001. Serum ferritin level was 246.77 ± 18.24 mg/L in the malnourished group, higher than the well-nourished group at 237.23 ± 16.13 mg/L; p < 0.001. CRP was elevated (> 0.6 mg/dl) in 53.5% patients with malnutrition; p 0.003. Malnutrition is highly prevalent in the CKD population. The incidence increases as the eGFR decrease. TSFT ≤ 10 mm compares favorably with SGA in detecting malnutrition (sensitivity > 90%), and BMI > 20 kg/m2 compares favorably with SGA in ruling out malnutrition (specificity 97%). Malnutrition and inflammation often coexist. Early detection and appropriate management are crucial.


Introduction
Malnutrition is frequent in patients with chronic kidney disease, with prevalence varying from 28 to 65% [1][2][3][4][5]. It affects the quality of life and is associated with increased mortality and morbidity [6][7][8][9]. Causes of malnutrition in chronic kidney disease (CKD) patients include reduced food intake due to the effect of uremia, reduced absorption of nutrients from the oedematous gut, metabolic acidosis, increased protein loss during dialysis especially peritoneal dialysis, inflammation, oxidative stress, carbonyl stress, and hormonal disorders [10][11][12][13]. There is no single ideal or well-established laboratory method for the diagnosis of malnutrition in patients with CKD. In 1987, Detzky AS et al. [14] described a special methodology, named subjective global assessment (SGA) for

Open Access
The Egyptian Journal of Internal Medicine the assessment of nutritional status. It is an easy and simple method of assessing nutritional status and does not require any additional laboratory testing [15,16]. It has been found to strongly correlate with other subjective and objective measures of nutrition in patients with pre-dialysis CKD [17] and patients on hemodialysis [18] or peritoneal dialysis [19]. Malnutrition was found in 46% of CKD patients studied using the SGA criteria by Oladele CO et al. [20] A higher prevalence of 54.8% was observed in a similar study by Liman et al. [21], using the SGA. There is a paucity of data on the nutritional status of chronic kidney disease stages 3-5 in patients from northern India, necessitating this study.

Material and methods
This is a hospital-based cross-sectional study conducted in the Department of Nephrology, Sri Ram Murti Smarak Institute of Medical Science, Uttar Pradesh, India, from 1st October 2018 to 30th May 2020. Patients with chronic kidney disease stages 3-5 were included. Patients on dialysis, patients with nephrotic range proteinuria, and patients on steroids were excluded. CKD was defined as an estimated glomerular filtration rate < 60 ml/min/ m 2 for more than 3 months. The estimated glomerular filtration rate (eGFR) was calculated using creatininebased CKD-EPI (chronic kidney disease epidemiology collaboration formula) 2009. The nutrition status was assessed by subjective global assessment (SGA). SGA was performed by one observer for all the patients, and this was based on medical history and clinical examination. Medical history included an assessment of weight and weight change, dietary intake, gastrointestinal symptoms, and the patient's functional capacity related to nutritional status. Physical examination focussed on loss of subcutaneous fat and muscle wasting, the presence of edema, and ascites. Patients were classified into class A (well-nourished), B (mildly to moderately malnourished), and C (severely malnourished) depending on the results of medical history and physical examination. Anthropometric and biochemical measurements were also taken at the time of enrollment. These anthropometric variables can be measured by different methods including dual-energy X-ray absorptiometry or bioelectrical impedance analysis; however, conventional anthropometric measures in the form of body mass index (BMI), triceps skinfold thickness (TSFT), and mid-arm muscle circumference (MAMC) were used owing to financial constraints and nonavailability of these modalities at the study center. TSFT was measured in the midline of the posterior aspect of the arm, over the triceps muscle at the level, 1 cm proximal to the halfway between the acromion process and the olecranon process with the elbow flexed at 90°. A vertical fold of skin and subcutaneous tissue were picked gently with the left thumb, and the tips of Harpenden caliper were applied perpendicular to the skinfold at the marked level. MAMC was measured using a measuring tape, midway between the olecranon process and the acromion. The left upper limb was used for the calculation of TSFT and MAMC in all the patients. Height was measured using a stadiometer, and weight was measured using a standard weighing scale to the nearest 0.1 kg. The study was approved by the hospital ethics committee.

Statistical analysis
Continuous variables are presented as mean ± SD. Nonparametric data are expressed as median and range.

Discussion
Malnutrition in CKD is not entirely explained by reduced nutritional intake. A delicate interplay of multiple factors, including hormonal imbalances, decreased appetite and food intake, inflammation, increased catabolism, nutrient losses in dialysate, and metabolic derangements, predispose chronic kidney disease patients to malnutrition. There is a paucity of data regarding the prevalence of malnutrition in patients with chronic kidney disease in India. This study highlights the prevalence of malnutrition in CKD stages 3-5 patients from a single center in North India. In our study, out of 354 patients, 213 (60.2%) were malnourished as per SGA criteria. Out of 213 malnourished patients, 118 (55.4%) were mild to moderately malnourished (class B), and 95 (44.6%) were severely malnourished (class C). This is similar to the previously reported prevalence of 28 to 65% [1][2][3][4][5]. A prevalence of   [7] also showed male predominance with 61% of patients with CKD and malnutrition being men. This could be because men are more likely to seek medical attention than women. However, the role of hormonal factors could not be ruled out. In our study, there was no statistical difference in age between the patients with malnutrition compared to those who were wellnourished. These findings were similar to the study done by Jai Prakash et al. [5] Diabetes mellitus was the most common cause of chronic kidney disease in our study followed by hypertension, chronic nondiabetic glomerulonephritis, and chronic tubulointerstitial nephritis.     [24]. This reveals that the incidence of malnourishment increases with deteriorating renal function. Serum albumin in the malnourished and well-nourished groups was 3.03 ± 0.64 mg/ dl and 3.50 ± 0.56 mg/dl, respectively; p-value < 0. 001. Similar findings were reported by Emmanuel I. Agaba et al. [25] and by Jai Prakash et al. [5]. Pre-dialysis hypoalbuminemia has also been found to be a strong predictor of mortality in CKD patients undergoing maintenance dialysis [8,[26][27][28]. The low level of serum albumin is also reported as a marker of malnutrition [25,29,30]. Hemoglobin in the malnourished group was significantly low compared to the well-nourished group (7.74 ± 0.95 mg/ dl and 8.84 ± 0.95mg/dl, respectively; p-value < 0.001). Similar trends were observed by the studies of Emmanuel I. Agaba et al. [25] and Lowrie E. G. et al. [26]. In our study, serum triglyceride (TG) was the only significant parameter found to be increased in malnourished CKD patients as compared to the well-nourished group (149.59 ± 15.28 vs 138. ± 17.23 mg/dl, p < 0.001). Similar observations were made by Emmanuel I. et al. [25] and Jai Prakash et al. [5]. The presence of increased serum TG levels further heightens the already increased cardiovascular risk in malnourished CKD patients. In our study, serum cholesterol was not statistically different between the malnourished and the well-nourished group.
In the subgroup analysis of patients with eGFR ≤ 30 ml/ min/1.73 m 2 and > 30 ml/min/1.73m 2 , the anthropometric indices in the form of TST, MAMC, and BMI and the laboratory indices in the form of hemoglobin, total protein, and albumin were significantly lower in the malnourished group in comparison with the well-nourished group.
Renal failure contributes to inflammation as a result of the accumulation of pro-inflammatory compounds and a decrease in the activity of superoxide dismutase, and glutathione peroxidase leading to increased oxidative stress and decreased antioxidative activity [31]. High sensitivity CRP was elevated (> 0.6 mg/dl) in 114/213 (53.5%) patients with malnutrition and 53/141 (37.6%) of wellnourished patients; p-value 0.003. Similar observations were made in the study by Jai Prakash et al. [5] in which 83/131 (63%) malnourished patients had elevated CRP compared to 24/72 (33%) in the well-nourished group. Serum ferritin level was 246.77 ± 18.24 mg/L and 237.23 ± 16.13 mg/L, respectively, in the malnourished and well-nourished group, p-value < 0.001. Similar observations were made by Jai Prakash et al. [5]. Serum ferritin and CRP are the markers of inflammation and are significantly elevated in malnourished CKD patients. Serum albumin is also considered a negative phase reactant, and low serum albumin in CKD is thought to be a marker of inflammation than malnutrition. In patients with eGFR > 30 ml/min/1.73 m 2 , the difference in serum ferritin between the malnourished and the well-nourished group did not reach the statistical difference. This suggests that ferritin as an inflammatory marker becomes more important with eGFR ≤ 30 ml/min/1.73 m 2 . However, this needs to be reproduced in a bigger study.
This study has certain limitations. It is a single-center hospital-based study and does not reflect the true prevalence of malnutrition in CKD patients in the community. The majority of patients belonged to CKD stage 5 which might be the reason for the very high prevalence of malnutrition in our study group. The high sensitivity of TSFT ≤ 10 mm and high specificity of BMI ≥ 20 kg/m 2 need to be reproduced in a bigger study.

Conclusions
Malnutrition is highly prevalent in the pre-dialysis CKD population. The incidence increases with the decrease in eGFR. TSFT ≤ 10 mm compares favorably with SGA in detecting malnutrition (sensitivity > 90%), and BMI > 20 kg/m 2 compares favorably with SGA in ruling out malnutrition (specificity 97%). Malnutrition and inflammation often coexist. Early detection and appropriate management are needed.