High protein intake stimulates glomerular prostaglandin formation in remnant kidneys

1987 ◽  
Vol 252 (6) ◽  
pp. F1088-F1094 ◽  
Author(s):  
R. A. Stahl ◽  
S. Kudelka ◽  
U. Helmchen

Reduction of renal mass in the rat results in an increased glomerular prostaglandin (PG) and thromboxane (TX) formation that modulates renal hemodynamics. To evaluate whether dietary protein intake could exert effects on renal PG and TX formation after reduction of approximately 70% of renal mass, rats with remnant kidneys were placed on either a high-protein (HP) or a low-protein (LP) diet. After 2 wk on the diet, proteinuria, glomerular filtration rate (GFR), urinary PGE2 excretion, and glomerular PGE2, 6-keto PGF1 alpha, and TxB2 biosynthesis were significantly greater in the rats on HP diets. Two-wk administration of the thromboxane synthesis inhibitor UK 38485 reduced renal TxB2 formation by approximately 70%. In addition, chronic UK 38485 treatment significantly inhibited papillary PGE2 production. Neither chronic nor bolus administration of UK 38485 had an effect on proteinuria or GFR in rats on HP diets. Chronic UK 38485 treatment, however, reduced GFR and proteinuria in rats on LP diets. The bolus administration of UK 38485 did not alter GFR in animals receiving a LP diet. The cyclooxygenase inhibitor indomethacin reduced GFR only in rats on HP diets. The data demonstrate that HP intake stimulates renal prostanoid formation. The increased prostaglandin formation on HP intake modulates GFR in these rats.

Critical Care ◽  
2022 ◽  
Vol 26 (1) ◽  
Author(s):  
Wolfgang H. Hartl ◽  
Philipp Kopper ◽  
Andreas Bender ◽  
Fabian Scheipl ◽  
Andrew G. Day ◽  
...  

Abstract Background Proteins are an essential part of medical nutrition therapy in critically ill patients. Guidelines almost universally recommend a high protein intake without robust evidence supporting its use. Methods Using a large international database, we modelled associations between the hazard rate of in-hospital death and live hospital discharge (competing risks) and three categories of protein intake (low: < 0.8 g/kg per day, standard: 0.8–1.2 g/kg per day, high: > 1.2 g/kg per day) during the first 11 days after ICU admission (acute phase). Time-varying cause-specific hazard ratios (HR) were calculated from piece-wise exponential additive mixed models. We used the estimated model to compare five different hypothetical protein diets (an exclusively low protein diet, a standard protein diet administered early (day 1 to 4) or late (day 5 to 11) after ICU admission, and an early or late high protein diet). Results Of 21,100 critically ill patients in the database, 16,489 fulfilled inclusion criteria for the analysis. By day 60, 11,360 (68.9%) patients had been discharged from hospital, 4,192 patients (25.4%) had died in hospital, and 937 patients (5.7%) were still hospitalized. Median daily low protein intake was 0.49 g/kg [IQR 0.27–0.66], standard intake 0.99 g/kg [IQR 0.89– 1.09], and high intake 1.41 g/kg [IQR 1.29–1.60]. In comparison with an exclusively low protein diet, a late standard protein diet was associated with a lower hazard of in-hospital death: minimum 0.75 (95% CI 0.64, 0.87), and a higher hazard of live hospital discharge: maximum HR 1.98 (95% CI 1.72, 2.28). Results on hospital discharge, however, were qualitatively changed by a sensitivity analysis. There was no evidence that an early standard or a high protein intake during the acute phase was associated with a further improvement of outcome. Conclusions Provision of a standard protein intake during the late acute phase may improve outcome compared to an exclusively low protein diet. In unselected critically ill patients, clinical outcome may not be improved by a high protein intake during the acute phase. Study registration ID number ISRCTN17829198


2019 ◽  
Vol 109 (3) ◽  
pp. 517-525 ◽  
Author(s):  
Casey M Rebholz ◽  
Zihe Zheng ◽  
Morgan E Grams ◽  
Lawrence J Appel ◽  
Mark J Sarnak ◽  
...  

ABSTRACT Background Accurate assessment of dietary intake is essential, but self-report of dietary intake is prone to measurement error and bias. Discovering metabolic consequences of diets with lower compared with higher protein intake could elucidate new, objective biomarkers of protein intake. Objectives The goal of this study was to identify serum metabolites associated with dietary protein intake. Methods Metabolites were measured with the use of untargeted, reverse-phase ultra-performance liquid chromatography–tandem mass spectrometry quantification in serum specimens collected at the 12-mo follow-up visit in the Modification of Diet in Renal Disease (MDRD) Study from 482 participants in study A (glomerular filtration rate: 25–55 mL · min−1 · 1.73 m−2) and 192 participants in study B (glomerular filtration rate: 13–24 mL · min−1 · 1.73 m−2). We used multivariable linear regression to test for differences in log-transformed metabolites (outcome) according to randomly assigned dietary protein intervention groups (exposure). Statistical significance was assessed at the Bonferroni-corrected threshold: 0.05/1193 = 4.2 × 10−5. Results In study A, 130 metabolites (83 known from 28 distinct pathways, including 7 amino acid pathways; 47 unknown) were significantly different between participants randomly assigned to the low-protein diet compared with the moderate-protein diet. In study B, 32 metabolites (22 known from 8 distinct pathways, including 4 amino acid pathways; 10 unknown) were significantly different between participants randomly assigned to the very-low-protein diet compared with the low-protein diet. A total of 11 known metabolites were significantly associated with protein intake in the same direction in both studies A and B: 3-methylhistidine, N-acetyl-3-methylhistidine, xanthurenate, isovalerylcarnitine, creatine, kynurenate, 1-(1-enyl-palmitoyl)-2-arachidonoyl-GPE (P-16:0/20:4), 1-(1-enyl-stearoyl)-2-arachidonoyl-GPE (P-18:0/20:4), 1-(1-enyl-palmitoyl)-2-arachidonoyl-GPC (P-16:0/20:4), sulfate, and γ-glutamylalanine. Conclusions Among patients with chronic kidney disease, an untargeted serum metabolomics platform identified multiple pathways and metabolites associated with dietary protein intake. Further research is necessary to characterize unknown compounds and to examine these metabolites in association with dietary protein intake among individuals without kidney disease. This trial was registered at clinicaltrials.gov as NCT03202914.


2014 ◽  
Vol 111 (7) ◽  
pp. 1253-1262 ◽  
Author(s):  
Stine-Mathilde Dalskov ◽  
Martha Müller ◽  
Christian Ritz ◽  
Camilla T. Damsgaard ◽  
Angeliki Papadaki ◽  
...  

For decades, it has been debated whether high protein intake compromises bone mineralisation, but no long-term randomised trial has investigated this in children. In the family-based, randomised controlled trial DiOGenes (Diet, Obesity and Genes), we examined the effects of dietary protein and glycaemic index (GI) on biomarkers of bone turnover and height in children aged 5–18 years. In two study centres, families with overweight parents were randomly assigned to one of five ad libitum-energy, low-fat (25–30 % energy (E%)) diets for 6 months: low protein/low GI; low protein/high GI; high protein/low GI; high protein/high GI; control. They received dietary instructions and were provided all foods for free. Children, who were eligible and willing to participate, were included in the study. In the present analyses, we included children with data on plasma osteocalcin or urinary N-terminal telopeptide of collagen type I (U-NTx) from baseline and at least one later visit (month 1 or month 6) (n 191 in total, n 67 with data on osteocalcin and n 180 with data on U-NTx). The level of osteocalcin was lower (29·1 ng/ml) in the high-protein/high-GI dietary group than in the low-protein/high-GI dietary group after 6 months of intervention (95 % CI 2·2, 56·1 ng/ml, P= 0·034). The dietary intervention did not affect U-NTx (P= 0·96) or height (P= 0·80). Baseline levels of U-NTx and osteocalcin correlated with changes in height at month 6 across the dietary groups (P< 0·001 and P= 0·001, respectively). The present study does not show any effect of increased protein intake on height or bone resorption in children. However, the difference in the change in the level of osteocalcin between the high-protein/high-GI group and the low-protein/high-GI group warrants further investigation and should be confirmed in other studies.


Nutrients ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 1330 ◽  
Author(s):  
Hélio Coelho-Júnior ◽  
Luiz Milano-Teixeira ◽  
Bruno Rodrigues ◽  
Reury Bacurau ◽  
Emanuele Marzetti ◽  
...  

(1) Background: The present work aims to conduct a systematic review and meta-analysis of observational studies, in order to investigate the association of relative protein intake and physical function in older adults; (2) Methods: Observational studies, that investigated the association between protein intake and physical function in older adults, were retrieved from MEDLINE, SCOPUS, CINAHL, AgeLine, EMBASE, and Cochrane-CENTRAL. Two independent researchers conducted study selection and data extraction; (3) Results: Very high protein intake (≥1.2 g/kg/day) and high protein intake (≥1.0 g/kg/day) groups showed better lower limb physical functioning and walking speed (WS) performance, respectively, in comparison to individuals who present relative low protein (<0.80 g/kg/day) intake. On the other hand, relative high protein intake does not seem to propitiate a better performance on isometric handgrip (IHG) and chair rise in comparison to relative low protein intake. In addition, there were no significant differences in the physical functioning of high and middle protein intake groups; (4) Conclusions: In conclusion, findings of the present study indicate that a very high (≥1.2 g/kg/day) and high protein intake (≥1.0 g/kg/day) are associated with better lower-limb physical performance, when compared to low protein (<0.80 g/kg/day) intake, in community-dwelling older adults. These findings act as additional evidence regarding the potential need to increase protein guidelines to above the current recommendations. However, large randomized clinical trials are needed to confirm the addictive effects of high-protein diets (≥1.0 g/kg/day) in comparison to the current recommendations on physical functioning. All data are available in the Open ScienceFramework.


1992 ◽  
Vol 67 (2) ◽  
pp. 223-233 ◽  
Author(s):  
J. G. H. Sterck ◽  
J. Ritskes-Hoitinga ◽  
A. C. Beynen

Increased intakes of protein have been shown to reduce kidney calcification (nephrocalcinosis) in female rats. Two questions were addressed in the present study. First, can protein-induced inhibition of nephrocalcinosis be demonstrated when the diets used are balanced for calcium, magnesium and phosphorus in the added protein? Second, can the protein effect be explained by the frequently observed magnesiuria after giving high-protein diets? Nephrocalcinosis was induced in female rats by giving purified diets containing 151 g casein/kg and either an increased concentration of P (6 v. 2 g/kg) or a decreased concentration of Mg (0·1 v. 0·4 g/kg). To these diets 151 g ovalbumin/kg was added at the expense of glucose, and the diets were balanced for Ca, Mg and P in ovalbumin. The diets were given for 29 d. In rats fed on the diet containing 151 g protein/kg, an increased intake of P or a decreased intake of Mg caused nephrocalcinosis as measured chemically by analysis of kidney Ca as well as histologically by scoring kidney sections stained according to Von Kossa's method. The addition of ovalbumin to the diet prevented the induction of nephrocalcinosis. High P intake and low Mg intake with the low-protein diets induced enhanced loss of albumin in urine, suggesting that nephrocalcinosis caused kidney damage. Increased protein intake with a non-calcinogenic diet also caused increased albumin excretion in urine. Irrespective of the composition of the background diet, increased protein intake caused increased urinary excretion of Mg. When all dietary groups were considered, differences in nephrocalcinosis and urinary Mg output were not proportionally related.Nephrocalcinosis: Phosphorus: Magnesium: Protein: Rat


2020 ◽  
pp. 1-13
Author(s):  
Teuni H Rooijackers ◽  
Marga C Ocké ◽  
Linda M Hengeveld ◽  
Marjolein Visser ◽  
Jolanda MA Boer

Abstract Objective: Investigate protein intake patterns over the day and their association with total protein intake in older adults. Design: Cross-sectional study utilising the dietary data collected through two non-consecutive, dietary record-assisted 24-h recalls. Days with low protein intake (n 290) were defined using the RDA (<0·8 g protein/kg adjusted BW/d). For each day, the amount and proportion of protein ingested at every hour of the day and during morning, mid-day and evening hours was calculated. Amounts and proportions were compared between low and high protein intake days and related to total protein intake and risk of low protein intake. Setting: Community. Participants: 739 Dutch community-dwelling adults ≥70 years. Results: The mean protein intake was 76·3 (sd 0·7) g/d. At each hour of the day, the amount of protein ingested was higher on days with a high protein intake than on days with a low protein intake and associated with a higher total protein intake. The proportion of protein ingested during morning hours was higher (22 v. 17 %, P < 0·0001) on days with a low protein intake, and a higher proportion of protein ingested during morning hours was associated with a lower total protein intake (P < 0·0001) and a higher odds of low protein intake (OR 1·04, 95 % CI 1·03, 1·06). For the proportion of protein intake during mid-day or evening hours, opposite but weaker associations were found. Conclusions: In this sample, timing of protein intake was associated with total protein intake. Additional studies need to clarify the importance of these findings to optimise protein intake.


2020 ◽  
Vol 31 (8) ◽  
pp. 1667-1679 ◽  
Author(s):  
Gang-Jee Ko ◽  
Connie M. Rhee ◽  
Kamyar Kalantar-Zadeh ◽  
Shivam Joshi

Although high-protein diets continue to be popular for weight loss and type 2 diabetes, evidence suggests that worsening renal function may occur in individuals with—and perhaps without—impaired kidney function. High dietary protein intake can cause intraglomerular hypertension, which may result in kidney hyperfiltration, glomerular injury, and proteinuria. It is possible that long-term high protein intake may lead to de novo CKD. The quality of dietary protein may also play a role in kidney health. Compared with protein from plant sources, animal protein has been associated with an increased risk of ESKD in several observational studies, including the Singapore Chinese Health Study. Potential mediators of kidney damage from animal protein include dietary acid load, phosphate content, gut microbiome dysbiosis, and resultant inflammation. In light of such findings, adopting current dietary approaches that include a high proportion of protein for weight reduction or glycemic control should be considered with care in those at high risk for kidney disease. Given the possibility of residual confounding within some observational studies and the conflicting evidence from previous trials, long-term studies including those with large sample sizes are warranted to better ascertain the effects of high protein intake on kidney health.


2020 ◽  
Author(s):  
Henny Puspitasari ◽  
Partini Trihono ◽  
Pustika Wahidiyat

Abstract Background: Very preterm birth rate was 10.8% of all preterm in Asia. Early aggressive nutritional strategies in very preterm neonates is important for catching up growth; however, preterm kidneys have fewer, immature functional nephrons. Studies have showed that high protein intake induces nephron hypertrophy, proteinuria, and glomerular sclerosis through single nephron glomerular hyperfiltration (SNGHF), which leads to glomerulotubular injury. Aim: to analyse the correlation between protein intake and glomerulotubular injury in very preterm neonates. Method: A prospective cohort study was conducted in neonatal units of two hospitals in Jakarta. Urine samples were taken three times at post-natal ages 0-48 hours (T1), 72 hours (T2), and 21 days (T3) for determining the urinary neutrophil gelatinase-associated lipocalin to creatinine (uNGAL/Cr) ratio. Protein intake were given in accordance with local guideline while considering the clinical condition of participants. Protein levels from formula milk were recorded daily from 14-21 days of age, while breastmilk protein was measured twice by using a human milk analyser. Urinary NGAL (uNGAL) was tested with an ELISA. Glomerulotubular injury was defined as a uNGAL/Cr ratio ≥1 SD (22.74 ng/mg) at post-natal age 21 days. High protein intake was defined as average protein intake ≥ 3 g/kg/day.Results: Fifty-nine very preterm neonates were recruited, of which 39 completed the study. Glomerulotubular injury was found in 9 of 39 participants (23%). The proportion of glomerulotubular injury in very preterm neonates who had received high protein intake vs low protein intake was 5 of 29 vs 4 of 10 participants, respectively. The median of uNGAL/Cr ratio was not significantly different in the high vs low protein intake group (3.54 (range: 0.69-89.16) ng/mg vs (6.88 (range: 0.32-66.64)) ng/mg, respectively. The uNGAL/C ratio was not correlated with protein intake. However, it was inversely correlated with gestational age and birth weight.Conclusions: The proportion of glomerulotubular injury in very preterm neonates given high protein diet was 5 of 29. The uNGAL/Cr ratio was increased at the post-natal age of 72 hours and decreased in 21 days in both high and low protein intake groups. High protein intake was not correlated with glomerulotubular injury.


1987 ◽  
Vol 252 (1) ◽  
pp. F83-F90 ◽  
Author(s):  
F. D. Seney ◽  
E. G. Persson ◽  
F. S. Wright

Compared with the effects of a 6% protein diet, feeding rats a 40% protein diet for 10 days increases glomerular filtration rate and decreases the activity of the tubuloglomerular (TG) feedback control system. The decrease in TG feedback activity results from an increase in the threshold at which the loop of Henle flow rate initiates feedback responses. To determine whether this protein-dependent shift in the TG feedback response curve is caused by changes in either the signal or the sensing mechanism in the feedback pathway, we used micropuncture and microperfusion techniques to study the TG feedback system of rats fed high- or low-protein (40 or 6% casein) diets for approximately 7-10 days. Compared with the rats fed the low-protein diet, in the high-protein group distally measured single nephron glomerular filtration rate was 17% higher, and Na and Cl concentrations in early distal tubule fluid were 30-50% lower. Early distal osmolality was not different in the two groups. TG feedback responses assessed by changes in stop-flow pressure during perfusion of the distal nephron with NaCl solutions did not differ between diet groups. We conclude that the sensing mechanism in the TG feedback system is not altered by this manipulation of dietary protein, whereas the signal eliciting the TG feedback response is affected. Because rats fed a high-protein diet have higher rates of Na and Cl absorption between the late proximal and early distal tubules than do rats fed a low-protein diet, early distal Na and Cl concentrations are reduced, and the signal for TG feedback is diminished in rats fed the high-protein diet.


2021 ◽  
Author(s):  
Henny Adriani Puspitasari ◽  
Partini Pudjiastuti Trihono ◽  
Pustika Amalia Wahidiyat

Abstract Background: Very preterm birth rate was 10.8% of all preterm in Asia. Early aggressive nutritional strategies in very preterm neonates is important for catching up growth; however, preterm kidneys have fewer, immature functional nephrons. Studies have showed that high protein intake induces nephron hypertrophy, proteinuria, and glomerular sclerosis through single nephron glomerular hyperfiltration (SNGHF), which leads to glomerulotubular injury. Aim: to analyse the correlation between protein intake and glomerulotubular injury in very preterm neonates. Method: A prospective cohort study was conducted in neonatal units of two hospitals in Jakarta. Urine samples were taken three times at post-natal ages 0-48 hours (T1), 72 hours (T2), and 21 days (T3) for determining the urinary neutrophil gelatinase-associated lipocalin to creatinine (uNGAL/Cr) ratio. Protein intake were given in accordance with local guideline while considering the clinical condition of participants. Protein levels from formula milk were recorded daily from 14-21 days of age, while breastmilk protein was measured twice by using a human milk analyser. Urinary NGAL (uNGAL) was tested with an ELISA. Glomerulotubular injury was defined as a uNGAL/Cr ratio ≥1 SD (22.74 ng/mg) at post-natal age 21 days. High protein intake was defined as average protein intake ≥ 3 g/kg/day. Results: Fifty-nine very preterm neonates were recruited, of which 39 completed the study. Glomerulotubular injury was found in 9 of 39 participants (23%). The proportion of glomerulotubular injury in very preterm neonates who had received high protein intake vs low protein intake was 5 of 29 vs 4 of 10 participants, respectively. The median of uNGAL/Cr ratio was not significantly different in the high vs low protein intake group (3.54 (range: 0.69-89.16) ng/mg vs (6.88 (range: 0.32-66.64)) ng/mg, respectively. The uNGAL/C ratio was not correlated with protein intake. However, it was inversely correlated with gestational age and birth weight. Conclusions: The proportion of glomerulotubular injury in very preterm neonates given high protein diet was 5 of 29. The uNGAL/Cr ratio was increased at the post-natal age of 72 hours and decreased in 21 days in both high and low protein intake groups. High protein intake was not correlated with glomerulotubular injury.


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