Long-term effects of moderate protein diet on renal function and low-grade inflammation in older adults with type 2 diabetes and chronic kidney disease

doi:10.1016/j.nut.2014.03.007

Nutrition

Volume 30, Issue 9, September 2014, Pages 1045-1049

https://doi.org/10.1016/j.nut.2014.03.007 Get rights and content

Abstract

Objectives

The aim of this study was to determine the long-term effects of a moderate protein diet (MPD) on renal function, low-grade inflammation, and oxidative stress in older adults with type 2 diabetes, which to date are unclear.

Methods

Seventy-four older adults with type 2 diabetes and chronic kidney disease (stage G3b–G4) were enrolled in the study. During the 4-wk baseline period (T0), all patients were asked to follow a normal protein diet regimen, providing 1.1 g/kg daily. Successively, all patients were asked to follow an MPD, for 36 mo, providing 0.7 g/kg daily, for only 6 d/wk. Patients who refused to follow an MPD treatment were included in the control (NPD [normal protein diet] group). During the 36 mo of the study, creatinine clearance, blood urea nitrogen, proteinuria, blood pressure, glycated hemoglobin (Hb)A_1c, fat-free mass, low-grade inflammation (interleukin-6 and C-reactive protein) were evaluated monthly and oxidative stress (urinary 8-epiprostaglandin [Epi-PG]F2α) was evaluated every 3 mo.

Results

During T0, mean creatinine clearance, proteinuria, blood urea nitrogen, blood pressure, HbA_1c, fat free mass, low-grade inflammation, and oxidative stress were similar in both groups. After 36 mo, a significant reduction in decline of renal function was observed in the MPD group but not in controls (2.4 ± 0.2 versus 5.7 ± 0.5 mL·min·y, respectively; P < 0.05 versus control). Similarly, a significant reduction in proteinuria, serum interleukin-6, serum C-reactive protein, and urinary 8-Epi-PGF2α excretion, was observed in the MPD group (P < 0.05 versus NPD).

Conclusion

In older adults with type 2 diabetes, long-term effects of an MPD regimen are associated with a significant decline of renal function, proteinuria, low-grade inflammation, and oxidative stress without a change in fat-free mass.

Introduction

Experimental animal models have demonstrated the beneficial effects of dietary protein restriction in delaying the progression of renal disease [1]. In fact, dietary protein restriction may retard the decline of renal function and alleviates uremic symptoms caused by the accumulation of phosphorus, sulphates, organic acids, and urea [2], [3]. It has been suggested that dietary protein restriction also may delay the need for dialysis therapy [4], and favors the correction of secondary hyperparathyroidism and metabolic acidosis [5]. However, data on dietary protein restriction are unclear. In a recent study with 112 patients with type 2 diabetes mellitus (T2DM) and overt nephropathy, it was reported that protein restriction was neither feasible nor efficacious. The authors reported that the prescribed protein intake in the low-protein diet group was not statistically different from the protein intake in the normal protein diet group. Thus, non-adherence to the prescribed dietary protein restriction may result in an underestimation of its beneficial effects, in this study [6]. In fact, adherence to dietary protein restriction also could affect depressive symptoms. We previously demonstrated that the reduction of a dietary protein restriction regimen, from 7 to 6 d/wk was associated with an improvement in depressive symptoms and health-related quality of life in older patients with T2DM [7]. Furthermore, it has been reported that a reduced protein intake has an antioxidant effect in chronic kidney disease (CKD) in animals and humans [8], [9]. In an animal study, dietary protein restriction appeared to ameliorate inflammation, suppress oxidative stress, and reduce proteinuria [10]. Additionally it has been reported that unsaturated lipids also might be linked to anti-inflammatory status [11]. In this regard, little data are available on the long-term effects of a moderate protein diet (MPD) restriction regimen in older adults. Thus, in this study, we evaluated the effects of an MPD regimen, after 36 mo, on the decline of renal function, low-grade inflammation, oxidative stress, proteinuria, and body composition in older patients with T2DM and CKD.

Section snippets

Patient population

In the study protocol, 74 older patients with T2DM participated. All patients were clinically assessed with a medical history, physical examination, and routine laboratory tests. Eligibility criteria for all patients included age >65 y; CKD (stage G3b–G4 defined according to the Kidney Disease: Improving Global Outcomes classification) [12] and T2DM (defined according to American Diabetes Association) [13] for at least 15 y and treated by diet plus insulin injection. All participants had

Results

At baseline (T0), BMI, fat-free mass (FFM,) systolic blood pressure (SBP), diastolic blood pressure (DBP), glycated hemoglobin (Hb)A_1c, serum creatinine, blood urea nitrogen (BUN), and urinary protein excretion were similar in both study groups and are reported in Table 1.

Discussion

In this study, we reported that, an MPD regimen (6 d/wk) in older patients with T2DM significantly reduced renal failure by 42% (5.7 versus 2.4 mL/min annually; P < 0.001). This beneficial effect is also associated with an improvement in low-grade inflammation, oxidative stress, and proteinuria. Additionally, the MPD did not affect either glycemic control or nutritional status, demonstrating its sustainability long-term.

The role of an MPD regimen in older adults is not clear. Dietary protein

Conclusions

The present findings suggest that, in older individuals with T2DM, an MPD restriction (providing about 0.7 g/kg per day, 6 d/wk) may be useful in the management of diabetic nephropathy. In fact, the MPD induced a significant reduction in decline of renal function, proteinuria, low-grade inflammation, and oxidative stress. Additionally, these results were not associated with changes in FFM or glycemic control. A limitation of the present study is represented by the sample size and larger, future

Acknowledgments

This work was supported by the Italian Regional Founds (prot. 5725 06/03/2009).

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Personalized Low-Protein Diet Prescription in CKD Population: Merging Evidence From Randomized Trials With Observational Data
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Nutritional therapy is a cornerstone of the clinical management of chronic kidney disease (CKD). Nevertheless, randomized controlled trials often have failed to show a relevant benefit of low-protein diets in nonselected CKD populations in terms of slowing the progression of kidney disease and need for dialysis. The more the target population is selected, the less the results can be generalizable to implement in clinical practice. On the contrary, observational studies, especially if performed with patient-centered, flexible approaches, point toward an extensive implementation of dietary protein restriction in different and unselected CKD populations. The observational evidence cannot be disregarded anymore. The most recent guidelines advise implementing low-protein diets or even very-low-protein diets in all CKD patients as early as stage 3. However, the lack of data from large randomized controlled trials on unselected CKD populations as well as on specific subpopulations, such as diabetic or obese patients, which nowadays comprise the majority of CKD subjects, reduces the generalizability of the recommendations. For some patient populations, such as those encompassing very old, nephrotic, or pregnant patients, the literature is even more limited because of the lower prevalence of these conditions and diffused prejudices against reducing protein intake. This pragmatic review discusses the need for integrating information derived from randomized trials with evidence derived from observational studies to guide feasible strategies for more successful implementation of low-protein diets in the treatment of all segments of the CKD population.
Impact of low-protein diet on cardiovascular risk factors and kidney function in diabetic nephropathy: A systematic review and meta-analysis of randomized-controlled trials
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Of those, thirty studies were discarded for these different reasons. Finally, eighteen [10,24–40] studies with twenty treatment arm met the eligibility criteria and were included in the quantitative meta-analysis. Characteristics of the pooled studies are presented in Table 1.
To assess the efficacy of low-protein diets (LPD) on cardiovascular risk factors and kidney function in diabetic nephropathy (DN) based on randomized controlled trials (RCTs).
A comprehensive systematic search was undertaken in PubMed/MEDLINE, Web of Science, SCOPUS and Embase databases from inception until January 2022 without using time or language restrictions. RCTs which reported the effects of LPD on cardiovascular risk factors and kidney function in DN were considered.
The results of the present study showed that a LPD significantly reduces urinary urea (WMD: −244.49 g/day, 95 % CI: −418.83, −70.16, P = 0.006) and HbA1c (WMD: −0.20, 95 % CI: −0.39, −0.01, P = 0.036) levels. However, the results did not show neither significant nor beneficial effect on other renal function and cardiovascular risk factors. Furthermore, the results of subgroup analysis showed LPD caused a further decrease in HbA1c during the follow-up period of ≤ 24 weeks, protein intake less than 0.8 g/kg/d and in individuals younger than 50 years. Albuminuria also showed a greater reduction in people under the age of 50 with type 1 diabetes (DMT1) following a LPD.
The results of the present study showed that LPD significantly reduces urinary urea and HbA1c.
Admission kidney function is a strong predictor for the response to nutritional support in patients at nutritional risk
2021, Clinical Nutrition
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In most patients, however, the etiology of CKD was not proven by kidney biopsy but relied on clinical parameters including past history of diabetes or hypertension – the most common risk factors for CKD [29,37–39]. Based on the ESPEN Guidelines, particularly for patients with diabetic nephropathy, a restriction of dietary protein is advised [3,40–43], as previous research found an improvement in kidney function through low-protein diet in this patient population [41,43]. However, other studies could not replicate these findings of a low-protein diet [17,18].
Patients with chronic kidney disease (CKD) are at substantial risk of malnutrition, which negatively affects clinical outcomes. We investigated the association of kidney function assessed at hospital admission and effectiveness of nutritional support in hospitalized medical patients at risk of malnutrition.
This is a secondary analysis of an investigator-initiated, randomized-controlled, Swiss multicenter trial (EFFORT) that compared individualised nutritional support with usual hospital food on clinical outcomes. We compared effects of nutritional support on mortality in subgroups of patients stratified according to kidney function at the time of hospital admission (estimated glomerular filtration rates [eGFR] <15, 15–29, 30–59, 60–89 and ≥ 90 ml/min/1.73 m²).
We included 1943 of 2028 patients (96%) from the original trial with known admission creatinine levels. Admission eGFR was a strong predictor for the beneficial effects of nutritional support in regard to lowering of 30-day mortality. Patients with an eGFR <15, 15–29 and 30–59 had the strongest mortality benefit (odds ratios [95%CI] of 0.24 [0.05 to 1.25], 0.37 [0.14 to 0.95] and 0.39 [0.21 to 0.75], respectively), while patients with less severe impairment in kidney function had a less pronounced mortality benefits (p for interaction 0.001). A similar stepwise association of kidney function and response to nutritional support was found also for other secondary outcomes.
In medical inpatients at nutritional risk, admission kidney function was a strong predictor for the response to nutritional therapy. Initial kidney function may help to individualize nutritional support in the future by identification of patients with most clinical benefit.
Registered under ClinicalTrials.gov Identifier no. NCT02517476.
Effect of different dietary approaches compared with a regular diet on systolic and diastolic blood pressure in patients with type 2 diabetes: A systematic review and meta-analysis
2020, Diabetes Research and Clinical Practice
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Age range of the participants was 29.4 to 72 years old. Three studies were conducted in Iran [16–18], 1 in Japan [19], 7 in USA [20–26], 3 in United Kingdom [27–29], 2 in Italy [30,31], 2 in Korea [32,33] and 1 in each of the countries of Netherland [34], Mexico [35], Malaysia [36], Sweden [37], Israel [38] and Greece [39]. Twenty two studies were parallel in design, and two studies were crossover.
We aimed to investigate the effect of different dietary approaches on systolic and diastolic blood pressure (SBP and DBP) in Type II diabetes (T2D).
A systematic search was performed in Web of Science, PubMed, Scopus and Cochrane library without any language and time restriction up to December 2018, to retrieve the randomized controlled trials (RCTs) which examined the effects of different dietary approaches on SBP and DBP in T2D patients. Meta-analyses were carried out using a random effects model. I2 index was used to evaluate the heterogeneity.
Twenty four RCTs with 1130 patients were eligible. The dietary modifications were more effective in reducing both SBP and DBP vs. control diet. The Low-sodium, High-fiber, DASH, Low-fat, Low-protein and Vegan dietary approach were significantly more effective in reducing SBP compared to a control diet. The High-fiber, Low-fat, Low-protein and Vegan diet were significantly more effective in reducing DBP. The Low-sodium and High fiber diets had the greatest lowering effect on SBP and DBP in T2D patients.
Adopting healthful dietary modifications were more effective in reducing both SBP and DBP vs. control. The High-fiber and Low-sodium diets had the greatest lowering effect on SBP and DBP in T2D.
Effects of Low Protein Diet on Nuclear Factor Erythroid 2–Related Factor 2 Gene Expression in Nondialysis Chronic Kidney Disease Patients
2020, Journal of Renal Nutrition
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Inflammation and oxidative stress are usually present in CKD patients, leading to higher cardiovascular risk, and they are also key mediators of the advance of renal injury, atherosclerosis, a catabolic state, and malnutrition.42 Giordano et al. (2014)43 studied the effects of a long-term moderate protein diet (0.7 g/kg) in CKD patients with type II diabetes and observed a reduction in the renal function decline, proteinuria levels, IL-6 levels, C-reactive protein levels, and oxidative stress. The NF-κB transcription factor has an essential role in inflammation and is highly expressed in CKD patients.44
Low protein diets (LPD; 0.6 g/kg/day), prescribed for nondialysis chronic kidney disease (CKD) patients, have demonstrated numerous benefits. LPDs may modulate inflammation and oxidative stress through the nuclear factor erythroid 2-related factor 2 (Nrf2), which encodes antioxidant and phase II detoxifying enzymes. LPDs also inhibit or antagonize nuclear factor kB (NF-kB) activity, which orchestrates inflammatory and oxidative stress responses. The objective of this study was to evaluate the effects of LPD on Nfr2 and NF-κB messenger RNA (mRNA) expression in nondialysis CKD patients.
In this longitudinal study, a LPD was prescribed for 30 nondialysis CKD patients for 6 months. Peripheral blood mononuclear cells were isolated, and quantitative real-time polymerase chain reaction analysis was performed to evaluate Nrf2, NF-κB, and NADPH quinine oxidoreductase-1 mRNA expression. Thiobarbituric acid–reactive substance (TBARS) levels, a marker of lipid peroxidation, were also evaluated.
(Age 55.5 ± 14.0 years; body mass index 29.1 ± 5.9 kg/m²; glomerular filtration rate 35.6 ± 12.2 mL/minute). After 6 months of nutritional intervention, Nrf2 mRNA expression increased from 0.85 (0.47-1.56) to 1.28 (0.63-2.63) nmol/mL (P = .03), and TBARS levels were significantly decreased from 1.78 (1.31-2.38) to 1.30 (1.07-2.22) nmol/mL (P = .04). NF-κB mRNA expression showed no significant difference after 6 months, but the Nrf2/NF-κB ratio was increased.
In this study, a LPD appeared to modulate Nrf2 expression and decrease the levels of TBARS in nondialysis CKD patients. However, more studies are needed to confirm the effectiveness of LPD on the modulation of transcription factors involved with oxidative stress and inflammation in nondialysis CKD patients.
Low-protein diet supplemented with ketoacids delays the progression of diabetic nephropathy by inhibiting oxidative stress in the KKAy mice model
2018, British Journal of Nutrition

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Applied nutritional investigationLong-term effects of moderate protein diet on renal function and low-grade inflammation in older adults with type 2 diabetes and chronic kidney disease

Abstract

Objectives

Methods

Results

Conclusion

Introduction

Section snippets

Patient population

Results

Discussion

Conclusions

Acknowledgments

Kidney Int

J Ren Nutr

Nutrition

Am J Kidney Dis

Kidney Int

Kidney Int

Kidney Int

J Nutr Biochem

Am J Clin Nutr

Endocr Pract

Low-Protein Diet Study Group. Long-term effect of modification of dietary protein intake on the progression of diabetic nephropathy: a randomised controlled trial

Diabetologia

Long term effects of low protein diet on depressive symptoms and quality of life in elderly type II diabetic patients

Clin Nephrol

High-calorie diet with moderate protein restriction prevents cachexia and ameliorates oxidative stress, inflammation and proteinuria in experimental chronic kidney disease

Clin Exp Nephrol

KDIGO Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease

Kidney Int

Standards of Medical Care in Diabetes 2011

Diabetes Care

Applied nutritional investigation
Long-term effects of moderate protein diet on renal function and low-grade inflammation in older adults with type 2 diabetes and chronic kidney disease