Table 2.
Characteristics of the included systematic reviews
| Author, year | Study type, study period | Study population | Exposition | Protein intake | Outcome | Effect estimates | Heterogeneity estimators | NutriGrade rating | AMSTAR 2 rating |
|---|---|---|---|---|---|---|---|---|---|
| Asoudeh 2022 [22] |
SR with MA of cohort studies Published until July 2021 Study duration: 6–26 yrs |
Both sexes General population Aged ≥ 20 yrs |
NP | Risk of kidney stones | Pooled RR (95% CI), random/fixed effect model | Moderate | |||
| 2 cohort studies |
n = 154,221 n = 2,982 cases |
Total protein |
Fixed effect model: 1.04 (0.92, 1.18) Dose-response analysis: 0.99 (0.98, 1.01) per 10g/d increase Pnonlinearity = 0.11 |
I2 = 68% P = 0.08 I2 = 44.7% P = 0.18 |
Low: 4.0 | ||||
| 6 cohort studies |
n = 466,109 n = 8,494 cases |
Animal protein | Random effect model: 1.00 (0.89–1.14) |
I2 = 62% P = 0.02 |
Low: 4.9 | ||||
| 5 cohort studies |
n = 387,816 n = 6,542 cases |
Dose–response analysis: 0.99 (0.97, 1.02) per 10 g/d increase Pnonlinearity = 0.26 |
I2 = 72% P < 0.01 |
||||||
| 2 cohort studies |
n = 320,896 n = 8,971 cases |
Nondairy animal protein |
Fixed effect model: 1.11 (1.03, 1.20) Dose–response analysis: 1.01 (1.00, 1.02) per 10 g/d increase Pnonlinearity = 0.38 |
I2 = 0% P = 0.47 I2 = 42% P = 0.16 |
Low: 5.0 | ||||
| 2 cohort studies |
n = 320,896 n = 8,971 cases |
Dairy protein |
Fixed effect model: 0.91 (0.84, 0.99) Dose-response analysis: 0.96 (0.93, 0.99) per 10g/d increase Pnonlinearity = 0.86 |
I2 = 0% P = 0.55 I2 = 0% P = 0.57 |
Moderate. 6.0 | ||||
| Hengeveld 2022 [23] |
SR without MA of RCTs Published before 04/2020 Study duration: 12 wks to 18 mos |
Both sexes Relatively healthy and/or people with (moderate) physical function limitations, overweight, obesity and/or (pre-)frailty Aged ≥ 65 yrs |
High vs low animal protein intake (2 RCTs with concomitant exercise in control and intervention group) | 1.06–1.4 g/kg BW/d vs. 0.81-1.05 g/kg BW/d | NA | Moderate | |||
| 4 RCTs | n = 347–361 | Serum creatinine | 3 out of 4 RCTs reported no significant effect of increased protein | Low: 4.5 | |||||
| 5 RCTs | n = 622 | eGFR | None of the RCTs reported a significant effect of increased protein | Moderate: 5.5 | |||||
| 1 RCT | n = 111 | Albumin/creatinine ratio | The RCT reported no significant effect of increased protein | Low: 4.5 | |||||
| Kelly 2021 [21] |
SR with MA of cohort studies Published until June 2019 Follow-up: 5.5–21 yrs |
Both sexes General population, partly people with T2D, hypertension, dyslipidaemia and/or CVD Aged 30–67 yrs |
Higher vs. lower protein intake | NP | OR (95% CI), random effects model | High | |||
| 3 cohort studies | n = 19,835 | Incident CKD |
1.08 (0.91, 1.28) P = 0.36 |
I2 = 47% Chi2 = 3.75 tau2 = 0.01 df = 2 P = 0.15 |
Very low: 3.0 | ||||
| 5 cohort studies | n = 18,507 | GFR decline | 1.07 (0.96, 1.19) P = 0.25 |
I2 = 42% Chi2 = 12.16 tau2 = 0.01 df = 7 P = 0.10 |
Very low: 3.5 | ||||
| Lin 2020 [20] |
SR with MA of 4 cohort studies Published until May 2019 follow-up: 20–26 yrs |
Both sexes Aged 25–79 yrs n = 271,969 |
High vs. low animal protein intake | NP | Nephrolithiasis (incident stones) |
RR (95% CI), random effects model 1.1 (1.02–1.19) P = NP |
No heterogeneity | Low: 4.5 | High |
| Devries 2018 [16] |
SR with MA of RCTs Published from 1975 until 2016 Intervention duration: 4 d–104 wks |
Both sexes Healthy and/or people with obesity and/or hypertension Aged ≥ 18 yrs |
High vs. normal/low protein intake |
1.2–3.3 g/kg BW/d vs. 0.3–2.6 g/kg BW/d 20–40 En% vs. 12–24 En% 123–150 g/d vs. 46–75 g/d |
SMD (95% CI), random effects model | Moderate | |||
| 28 RCTs | n = 1409 | GFR |
0.19 (0.07, 0.31) P = 0.002 Dose–response analysis (linear) protein intake (g/kg BW/d) r = 0.332, P = 0.03 |
I2 = 0% Chi2 = 15.77 tau2 = 0.00 df = 29 P = 0.98 |
Moderate: 7.05 | ||||
| 14 RCTs | n = 1307 | ΔGFR |
0.11 ( – 0.05, 0.27) P = 0.16 Dose–response analysis (linear) protein intake (g/kg BW/d) r = 0.184, P = 0.33 |
I2 = 44% Chi2 = 30.26 tau2 = 0.05 df = 17 P = 0.02 |
Moderate: 6.35 | ||||
| Van Elswyk 2018 [15] |
SR without MA of RCTs and cohort studies Published before 08/2017 Intervention duration: 4 d–8 wks Follow-up: 15–21 yrs |
Both sexes Healthy and/or people with metabolic risk factors Aged ≥ 18 yrs |
Protein intake consistent with the US RDA (≥ 0.8 g/kg BW/d or 10–15 En%) or higher protein intake (20–35 En% or 10% higher than comparison intake) | 1.8–2.5 g/kg BW/d vs. 0.7–1.5 g/kg BW/d | NA | Low | |||
| 1 cohort study | n = 3798 | Total protein, animal protein, plant protein | eGFR | “Intake of total, plant, and animal protein are not associated with changes in eGFR over time.” | Low: 4.0 | ||||
| 13 RCTs | n = 235 | Total protein, animal protein, plant protein | GFR |
8 of 11 RCTs reported Significantly higher GFR in response to increased protein intake |
Very low: 2.0 | ||||
| 4 RCTs | n = 60 | Total protein, animal protein, plant protein | Uric acid | 3 of 4 RCTs reported elevated uric acid in response to increased protein intake | Very low: 3.0 | ||||
| Schwingshackl 2014 [18] |
SR with MA of RCTs Published until 02/2014 Intervention duration: 1 wk–24 mos |
Both sexes Generally healthy and/or people with overweight, obesity and/or T2D - Mean age: 22.3–67 yrs |
High vs. normal/low protein diet (≥ 5% difference in total energy intake) | 12.5–40 En% vs. 5.4–24 En% or 1.0–2.4 g/kg BW/d vs. 0.5–1.2 g/kg BW/d | Pooled WMD (95% CI), random effects model | Moderate | |||
| 21 RCTs | n = 1599 | GFR | 7.18 ml/min/1.73 m2 (4.45, 9.91) P = < 0.001 |
I2 = 52% tau2 = 16.53 Chi2 = 47.76 df = 23 P = 0.002 |
Moderate: 6.6 | ||||
| 22 RCTs | n = 1764 | Serum creatinine |
– 1.42 µmol/l ( – 3.50, 0.65) P = 0.18 |
I2 = 57% tau2 = 10.13 Chi2 = 51.42 df = 22 P = 0.0004 |
Low: 5.6 | ||||
| 13 RCTs | n = 910 | Serum urea |
1.75 mmol/l (1.13, 2.37) P = < 0.00001 |
I2 = 88% tau2 = 1.13 Chi2 = 112.57 df = 13 P < 0.00001 |
Moderate: 6.6 | ||||
| 8 RCTs | n = 295 | Serum uric acid |
0.18 µmol/l ( – 0.08, 0.44) P = 0.17 |
I2 = 3% tau2 = 0.00 Chi2 = 7.25 df = 7 P = 0.40 |
Low: 5.4 | ||||
| 7 RCTs | n = 210 | Urinary pH |
– 0.39 ( – 0.82, 0.03) P = 0.07 |
I2 = 95% tau2 = 0.33 Chi2 = 148.51 df = 7 P < 0.00001 |
Low: 5.3 | ||||
| 11 RCTs | n = 783 | Urinary albumin/protein |
0.50 mg/24 h ( – 2.83, 3.82) P = 0.77 |
I2 = 63% tau2 = 13.51 Chi2 = 32.58 df = 12 P = 0.001 |
Low: 5.8 | ||||
| 10 RCTs | n = 708 | Urinary calcium excretion |
25.43 mg/24 h (13.62, 37.24) P < 0.001 |
I2 = 90% tau2 = 172.58 Chi2 = 100.09 df = 10 P < 0.00001 |
Moderate: 6.6 | ||||
| Pedersen 2013 [17] |
SR without MA of RCTs and cohort studies Published between 01/2000 and 12/2011 Intervention duration: 7d–3 wks follow-up: 7–10 yrs |
Both sexes Generally healthy and/or people with overweight or obesity Mean age: 24–70 yrs |
RCTs: high vs. normal/low protein intake Cohort studies: En% from protein or total protein intake (in kcal or servings) |
1–1.5 g/kg BW/d vs. 2–3 g/kg BW/d | NA | Moderate | |||
| 2 RCTs | n = 48 | Total protein, animal protein | GFR | "The evidence is assessed as inconclusive regarding the relation of protein intake to renal function based on GFR.” | low: 5.0 | ||||
| 2 cohort studies | n = 10,216 | Total protein | eGFR | Low: 3.0 | |||||
| 2 RCTs | n = 48 | Total protein | Microalbuminuria | "The evidence is assessed as inconclusive regarding the relation of protein intake to renal function based on microalbuminuria.” | Low: 4.5 | ||||
| Animal protein | Low: 5.0 | ||||||||
| 2 cohort studies | n = 10,216 | Total protein | Low: 3.0 | ||||||
| 2 cohort studies | n = 141,864 | Animal protein | Kidney stones | "The evidence is assessed as inconclusive regarding the relation of protein intake to risk of kidney stones” | Low: 3.0 | ||||
| Santesso 2012 [19] |
SR with MA of 2 RCTs Published before 08/2011 Intervention duration: 84 d |
Both sexes People with overweight or obesity Mean age: 46–58 yrs n = 67 |
High vs. low protein (≥ 5% difference in total energy intake) |
Median: 27 En% vs. 18 En% Range: 16–45 En% vs. 5–23 En% |
Serum creatinine |
Pooled SMD (95% CI), random effects model 6.14 (2.49, 9.79) P = 0.001 |
I2 = 0% tau2 = 0.00 Chi2 = 0.10 df = 2 P = 0.95 |
Very low: 2.0 | High |
AMSTAR 2, A Measurement Tool to Assess Systematic Reviews; BW, body weight; CI, confidence interval; d, day(s); eGFR, estimated glomerular filtration rate; En%, energy percentage; GFR, glomerular filtration rate; MA, meta-analysis; MD, mean difference; mo, month; NA, not applicable; NP, not provided; OR, odds ratio; RCT, randomised controlled trial; RR, relative risk; SMD, standardised mean difference; SR, systematic review; T2D, type 2 diabetes mellitus; wk, week; WMD, weighted mean difference; yr, year