Dietary protein intake is a pivotal issue in the progression and treatment of the chronic kidney disease (CKD) patients. The early primary care on moderate-to-advanced CKD stages of well-known causative factors such as reduction of accumulation of nitrogenous wastes, metabolic derangements and protein-energy wasting (PEW), have showed a central role to slow onset of dialysis1,2 and mortality rates3 in CKD population.

Guidelines on CKD4,5 and Nutrition,6,7 recommend two tentative nutritional approaches for managing dietary protein intake in CKD stages 4,5. A low-protein diet (LPD), consists of 0.6–0.8g/kg BW/day or a very low-protein diet (VLPD), providing a protein intake between 0.3 and 0.4g/kg BW/day supplemented with essential aminoacids (EAA) and ketoanalogues (KA). Both therapeutic strategies preserve renal function in well-nourished patients8–10 whereas, the ideal recommendation of dietary protein restriction on the progression of CKD, and its potential consequences on nutritional status and body composition still unclear.

PEW is frequently associated with higher risk of morbidity and mortality.3 Lack of appetite and uremic anorexia interferes on nutritional status and body composition measures in CKD patients. Bioelectrical impedance (BIA), is a non-invasive method for the assessment of body composition and conditions associated with expanded extracellular water (ECW).11 Previous studies12,13 reported that BIA-derived measures may be important in glomerular filtration rate (GFR) prediction and several studies14,15 demonstrated that the inclusion of muscle mass improved GFR estimations. Dumler et al.,16 showed that CKD patients with stable renal function following a daily dietary protein intake (0.6–0.8g/kg normalized body weight/day), had no loss of body cell mass (BCM) or fat-free mass (FFM) over a 9-month period measured by BIA. Thus, assessment and follow-up by nutritional indicators and body composition measures could be useful to early diagnosis of being wasted. These results push up to study whether the body composition in CKD patients stages 3–5 according to their daily dietary protein intake might predispose to muscle wasting because of dietary restrictions and the catabolic effects of uremia. There is little evidence with regard to the dietary protein intake restriction on body composition in moderate-advanced CKD. This study aimed to analyze usual dietary protein intake and its potential contribution on body composition in CKD patients on stages 3–5.

The results of this study revealed that low dietary protein intake in CKD patients on stages 3, 4–5, was associated with loss of muscle mass even in patients receiving dietary counseling and nutritional follow-up at the advanced-CKD unit. In this study, older ages and lower e-GFR in CKD patients showed lower protein intake and loss of muscle mass, especially in women.

nPna an indirect measure of protein intake was showed as a strong and independent predictor of morbidity and mortality in CKD patients25 and dialysis patients.26 Clinical practice guideline for CKD patients,4–7 defined as those with e-GFR<30mL/min/1.73m2, have recommended reducing dietary protein intake to 0.8g/kg/day in adults both with and without diabetes to slow disease progression, and achieve/maintain adequate s-albumin concentration and nutritional status. In the current study, overall nPna values were slightly increased, but only 57% of the eligible CKD patients correctly achieved the low protein intake reduction. Patients with CKD on stage 3, had mean nPna values closed to current protein intake recommendation, whilst advanced CKD on stages 4–5, showed higher daily protein intake. In this study, diet adherence of usual nutritional recommendation was low, being observed a 67.9% of CKD patients with nPna≥0.8g/kg BW/day. However, a dietary protein intake <0.8g/kg BW/day (G1), showed significantly depletion of MAMC, BCM%, FFM% and PA in a similar way compared with one another nPna categories. These findings are of importance because the loss of muscle mass and wasting has been demonstrated to be associated with poor outcomes in CKD patients.27,28

PEW is common in CKD patients and is associated with a subsequent increased risk of mortality.3 Dietary protein and energy intake may be masked in patients with advanced CKD due to uremic anorexia, inter-current illness, systemic inflammation, fluid overload and/or excessive dietary protein restriction. S-albumin concentration and BMI are the most often used indicators of nutritional assessment in daily clinical practice29,30 However, both are influenced by several non-nutritional factors, including proteinuria, fluid overload and inflammation statuses.31,32 In the current study, PEW was assessed by MIS, as a nutritional screening tool previously validated in CKD and dialysis patients together with commonly used nutritional-inflammatory markers. Overall, only 15% of CKD patients were wasted. In accordance with previous studies,33,34 the prevalence of PEW in the study was low compared with others.35,36 Furthermore, despite of low e-GFR (mean 19.4±8.7mL/min/1.73m2), a common used marker of protein turnover such as s-albumin was ≥4g/dL in all nPna groups. Therefore, a routine nutritional screening (i.e. MIS) could decreased the contribution of each indicator by combining s-albumin and BMI. In fact, this study found significantly positive correlation between nPna with e-GFR, BCM%, MM% and s-albumin, but not Ln s-CRP and BMI. These findings suggest that a multifactorial approach in CKD patients is mandatory.

Additional methods such as BIA and anthropometric measures may be also clinically useful to assess nutritional status. Body composition analysis in patients with CKD are characterized by high content of ECW associated with sodium retention and a decreased of BCM, both related with well-known causes as inflammation, fluid overload and wasting.22,31,32 In this study, exchange Na/K and ECW% were significantly higher as protein intake was <0.8g of protein/kg BW/day. Additionally, BIA-derived parameters such as FFM% and MM% were also diminished. Linear regression analysis showed that BIA-measures as resistance, MM% and s-albumin were independent predictors of nPna in the study population, but an inverse relation was found with BCM%. These findings suggest that a high protein intake could worsen renal function and, consequently the homeostasis of internal environment. Nevertheless, parameters such as exchange Na/K, FFM% and FM% were not found significant predictors of nPna in the linear regression analysis. Thus, in addition to common used nutritional markers, data suggest that body composition parameters should be taken into account in the nutritional monitoring, in patients with CKD. In this clinical setting, a “tailored diet prescription” considering gender-aged and body composition differences is required.

Prescription of a KA/EAA supplemented VLPD may be considered in well-nourished not-inflamed CKD patients aimed to preserve the renal function and metabolic disturbances related to uremic milieu. However, in wasted patients with alterations of fluid status and body composition parameters may be further considered dietary protein intake definition. There are potential limitations to be taking into account in this study. The sample size of this study due to its nature as a single-center cross-sectional study may reduce the generalizability of the findings. First, there are fluctuations in nPna from day to day caused by changes in daily protein intake or endogenous protein catabolism related with e-GFR value in CKD patients. Monitoring sequentially the body composition measures (i.e. muscle mass), could provide early nutritional interventions. Second, for nPna to accurately estimate protein intake, the patient's protein metabolism should be at equilibrium or nearly so at the time of measurement. This condition is not always met, particularly in CKD patients with many comorbidities, inflammation or acute disease states. In this study, eligible CKD patients were stabilized for at least 3 months before enrolment. Third, nPna could be masked usual dietary protein intake in wasted-inflamed patients. Assessment of nutritional-inflammatory status by validated nutritional tools, could early diagnose inadequate food intake and nutritional related-problems (i.e. PEW) in CKD patients.

In conclusion, controlled protein intake is one of the mainstays of CKD patients. A low protein intake in patients with CKD stages 3, 4–5, was associated with muscle wasting, even in patients receiving dietary advice and nutritional follow-up in the advanced-CKD unit. The loss of muscle mass appears as an early indicator of being wasting. Factors such as advanced age and loss of eGFR, showed lower protein intake and were associated with muscle loss, especially in women. In addition, of standard medical care, assessment of nutritional status and body composition should be included to prevent, diagnose and/or treat PEW.

Further longitudinal studies are required for evaluating the contribution of different protein intake in uremic symptoms, nutritional status, body composition and CKD progression.

GB designed the study, collected the data, analyzed and interpreted the results, and drafted the manuscript. AN collected the data and drafted the manuscript. MR, analyzed, interpreted the results, and drafted the manuscript. YC analyzed and interpreted the statistical results. JST analyzed, interpreted the results, and drafted the manuscript. All of the authors read and approved the final version of manuscript.

None.

The authors declare that they have no conflict of interests.