Primary Versus Secondary Prevention of Chronic Kidney Disease: The Case of Dietary Protein

Abstract

Related Articles, p. 235 and p. 245The proclamation that “the greatest medicine of all is to teach people how not to need it” (Hippocrates. 460-370 BC, Greece) is the basic principle of primary disease prevention, which aims to prevent disease before it ever occurs. Preventing exposures to hazards that cause disease, such as altering unhealthy behaviors, is one example of primary disease prevention. Secondary or tertiary disease prevention, however, refers to reducing the impact of a disease that has already occurred, or limiting the impact of an ongoing illness that has lasting effects, respectively. Salutary diets or lifestyles for primary versus secondary/tertiary disease prevention may not necessarily align. Related Articles, p. 235 and p. 245 In patients with manifest chronic kidney disease (CKD), a low-protein diet remains the first line of nutrition therapy for secondary prevention of CKD.1Kopple J.D. Fouque D. Pro: the rationale for dietary therapy for patients with advanced chronic kidney disease.Nephrol Dial Transplant. 2018; 33: 373-378Crossref PubMed Scopus (17) Google Scholar, 2Woodrow G. Con: the role of diet for people with advanced Stage 5 CKD.Nephrol Dial Transplant. 2018; 33: 380-384Crossref PubMed Scopus (4) Google Scholar Potential effects of low-protein diets are the preservation of residual renal function, better control of uremia, reduced kidney stone formation, hyperphosphatemia, or gut-derived uremic toxins.3Kovesdy C.P. Traditional and novel dietary interventions for preventing progression of chronic kidney disease.J Ren Nutr. 2013; 23: 241-245Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar, 4Black A.P. Anjos J.S. Cardozo L. et al.Does low-protein diet influence the uremic toxin serum levels from the gut microbiota in nondialysis chronic kidney disease patients?.J Ren Nutr. 2018; 28: 208-214Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar However, there remains conflicting data on the benefits of low-protein diets in retarding the progression to end-stage kidney disease5Klahr S. Levey A.S. Beck G.J. et al.The effects of dietary protein restriction and blood-pressure control on the progression of chronic renal disease. Modification of Diet in Renal Disease Study Group.N Engl J Med. 1994; 330: 877Crossref PubMed Scopus (2057) Google Scholar or lowering the risk of mortality,6Fouque D. Laville M. Boissel J. Low protein diets for chronic kidney disease in non diabetic adults.Cochrane Database Syst Rev. 2009; : 3Google Scholar and the potential to promote undernutrition in the elderly.2Woodrow G. Con: the role of diet for people with advanced Stage 5 CKD.Nephrol Dial Transplant. 2018; 33: 380-384Crossref PubMed Scopus (4) Google Scholar It is possible that conflicting evidence is explained by patient-centered experiences following this restrictive dietary approach.7Kelly J.T. Campbell K.L. Hoffmann T. Reidlinger D.P. Patient experiences of dietary management in chronic kidney disease: a focus group study.J Ren Nutr. 2017; (in press)Abstract Full Text Full Text PDF Scopus (21) Google Scholar In fact, compliance to a low-protein diet is commonly between 14% and 50% in CKD trials,2Woodrow G. Con: the role of diet for people with advanced Stage 5 CKD.Nephrol Dial Transplant. 2018; 33: 380-384Crossref PubMed Scopus (4) Google Scholar and approximately, 70% of nephrologists report hesitation in prescribing it.8Kalantar-Zadeh K. Moore L.W. Tortorici A.R. et al.North American experience with low protein diet for non-dialysis-dependent chronic kidney disease.BMC Nephrol. 2016; 17: 90Crossref PubMed Scopus (54) Google Scholar In contrast to the low-protein diet advice in CKD, a high protein, low carbohydrate diet has been touted as a quick fix solution to today's epidemics of obesity and type 2 diabetes. Commentary has followed related to its safety, with several reports, and lay media raising concern that such diets in the general population may be detrimental to the healthy kidney.9Marckmann P. Osther P. Pedersen A.N. Jespersen B. High-protein diets and renal health.J Ren Nutr. 2015; 25: 1-5Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar, 10Delimaris I. Adverse effects associated with protein intake above the recommended dietary allowance for adults.ISRN Nutr. 2013; 2013: 6Crossref Google Scholar, 11Manninen A.H. High-protein diets are not hazardous for the healthy kidneys.Nephrol Dial Transplant. 2005; 20 (author reply 658): 657-658Crossref PubMed Scopus (2) Google Scholar, 12Luyckx V.A. Mardigan T.A. High protein diets may be hazardous for the kidneys.Nephrol Dial Transplant. 2004; 19: 2678-2679Crossref PubMed Scopus (3) Google Scholar Yet, the current state of the evidence is uncertain, with little to no evidence to support these claims. To date, randomized controlled trials of a high-protein diet in individuals free from CKD have generally observed no adverse effect on renal function decline (Table 1). Existing studies are nonetheless too short in duration to meaningfully detect estimated glomerular filtration rate (eGFR) changes (<2 years), often include younger participants, and choose creatinine-based eGFR as a study outcome, which may be compromised when intervening on protein intake.23Inker L.A. Schmid C.H. Tighiouart H. et al.Estimating glomerular filtration rate from serum creatinine and cystatin C.N Engl J Med. 2012; 367: 20-29Crossref PubMed Scopus (2507) Google Scholar Similar conclusions were reached in a recent meta-analysis of randomized controlled trials that showed that a high-protein diet in populations free from CKD stimulated the renal reserve causing increases in eGFR, but no evidence of renal damage or eGFR decline was found.24Schwingshackl L. Hoffmann G. Comparison of high vs. normal/low protein diets on renal function in subjects without chronic kidney disease: a systematic review and meta-analysis.PLoS One. 2014; 9: e97656Crossref PubMed Scopus (75) Google Scholar Observational evidence also points to a lack of a clear association between a high-protein diet and renal function in the general population (Table 2). Finally, real-world examples support this contention, within the body-building community11Manninen A.H. High-protein diets are not hazardous for the healthy kidneys.Nephrol Dial Transplant. 2005; 20 (author reply 658): 657-658Crossref PubMed Scopus (2) Google Scholar and in historical accounts of extreme protein intakes (e.g., men in the famous Lewis and Clark expedition across America in 1804 reportedly ate as much as nine pounds of buffalo meat (>600 g protein) each day with no ill effects32Anderson S. Brenner B.M. The aging kidney: structure, function, mechanisms, and therapeutic implications.J Am Geriatr Soc. 1987; 35: 590-593Crossref PubMed Scopus (39) Google Scholar).Table 1Results of Studies Examining High Protein Intake and Renal Outcomes in Randomized Controlled Trials Conducted in Populations Free From CKD With Study Durations Greater Than 3 MonthsStudy CitationPopulationDurationProtein ExposureHigh Protein Intake and Change in Renal FunctionRandomized controlled trials Campos-Nonato et al. 201713Campos-Nonato I. Hernandez L. Barquera S. Effect of a high-protein diet versus standard-protein diet on weight loss and biomarkers of metabolic syndrome: a randomized clinical trial.Obes Facts. 2017; 10: 238-251Crossref PubMed Scopus (44) Google ScholarMexican adults; 20-60 y; BMI 25-45 kg/m2; metabolic syndrome; n = 1186 moHigh protein: 1.3 g/kgLow protein: 0.8 g/kgNo significant change in renal function Freidman et al. 201214Friedman A.N. Ogden L.G. Foster G.D. et al.Comparative effects of low-carbohydrate high-protein versus low-fat diets on the kidney.Clin J Am Soc Nephrol. 2012; 7: 1103-1111Crossref PubMed Scopus (70) Google ScholarAdults; 18-65 y; BMI 27-40 kg/m2; n = 30724 moHigh protein: >15%Low protein: 15%No significant change in renal function Krebs et al. 201215Krebs J. Elley C. Parry-Strong A. et al.The Diabetes Excess Weight Loss (DEWL) Trial: a randomised controlled trial of high-protein versus high-carbohydrate diets over 2 years in type 2 diabetes.Diabetologia. 2012; 55: 905-914Crossref PubMed Scopus (100) Google ScholarAdults; 30-75 y; type 2 diabetes; BMI >27 kg/m2; n = 41924 moHigh protein: 30%Low protein: 15%No significant change in renal function Larsen et al. 201116Larsen R.N. Mann N.J. Maclean E. Shaw J. The effect of high-protein, low-carbohydrate diets in the treatment of type 2 diabetes: a 12 month randomised controlled trial.Diabetologia. 2011; 54: 731-740Crossref PubMed Scopus (136) Google ScholarAdults; type 2 diabetes; BMI 27-40 kg/m2; n = 9912 moHigh protein: 30%Low protein: 15%No significant change in renal function Li et al. 201017Li Z. Treyzon L. Chen S. Yan E. Thames G. Carpenter C.L. Protein-enriched meal replacements do not adversely affect liver, kidney or bone density: an outpatient randomized controlled trial.Nutr J. 2010; 9: 72Crossref PubMed Scopus (34) Google ScholarAdults; >30 y; BMI 27-40 kg/m2; n = 10012 moHigh protein: 30%; 2.2 g/kgLow protein: 15%; 1.1 g/kgNo significant change in renal function Noakes et al. 200518Noakes M. Keogh J.B. Foster P.R. Clifton P.M. Effect of an energy-restricted, high-protein, low-fat diet relative to a conventional high-carbohydrate, low-fat diet on weight loss, body composition, nutritional status, and markers of cardiovascular health in obese women.Am J Clin Nutr. 2005; 81: 1298-1306Crossref PubMed Scopus (369) Google ScholarAdults; 20-65 y; BMI 27-40 kg/m2; n = 1003 moHigh protein: 37%Low protein: 17%No significant change in renal function Skov et al. 199919Skov A.R. Toubro S. Bulow J. Krabbe K. Parving H.H. Astrup A. Changes in renal function during weight loss induced by high vs low-protein low-fat diets in overweight subjects.Int J Obes Relat Metab. 1999; 23: 1170-1177Crossref PubMed Scopus (131) Google ScholarAdults; BMI 25-34 kg/m2; n = 656 moHigh protein: 25%Low protein: 12%Increase in GFR of 5 mL/minNo adverse renal effects reported Tay et al. 201520Tay J. Thompson C.H. Luscombe-Marsh N.D. et al.Long-term effects of a very low carbohydrate compared with a high carbohydrate diet on renal function in individuals with type 2 diabetes: a randomized trial.Medicine. 2015; 94: e2181Crossref PubMed Scopus (21) Google ScholarAdults; type 2 diabetes; n = 11512 moHigh protein: 28%Low protein: 17%No significant change in renal function Tirosh et al. 201321Tirosh A. Golan R. Harman-Boehm I. et al.Renal function following three distinct weight loss dietary strategies during 2 years of a randomized controlled trial.Diabetes Care. 2013; 36: 2225-2232Crossref PubMed Scopus (63) Google ScholarAdults; 40–65 y; BMI >27 kg/m2; n = 31824 moHigh protein: 22%Low protein: 19%High protein increased eGFR by 5%Albuminuria decreased in the low protein intervention.No adverse renal effects reported Wycherley et al. 201222Wycherley T. Brinkworth G. Clifton P. Noakes M. Comparison of the effects of 52 weeks weight loss with either a high-protein or high-carbohydrate diet on body composition and cardiometabolic risk factors in overweight and obese males.Nutr Diabetes. 2012; 2: e40Crossref PubMed Scopus (42) Google ScholarAdults; 20-65 y; BMI 27-40 kg/m2; n = 6812 monthsHigh protein: 35%; 1.2 g/kgLow protein: 17%; 0.8 g/kgNo significant change in renal functionBMI, body mass index; CKD, chronic kidney disease. Open table in a new tab Table 2Results of Studies Examining High Protein Intake and Renal Outcomes in Observational Studies Conducted in Populations Free From CKDStudy CitationPopulationDurationProtein ExposureHigh Protein Intake and Change in Renal FunctionDunkler et al. 201325Dunkler D. Dehghan M. Teo K.K. et al.Diet and kidney disease in high-risk individuals with type 2 diabetes mellitus.JAMA Intern Med. 2013; 173: 1682-1692PubMed Google ScholarONTARGET cohort; n = 6,1235.5 yProtein intake analyzed across tertilesHigh protein: 1 g/kgLow protein: 0.4 g/kgLowest tertile of total and animal protein intake had an increased risk of CKD compared with participants in the highest tertileHalbesma et al. 200926Halbesma N. Bakker S.J. Jansen D.F. et al.High protein intake associates with cardiovascular events but not with loss of renal function.J Am Soc Nephrol. 2009; 20: 1797-1804Crossref PubMed Scopus (66) Google ScholarPREVEND cohort; n = 8,4616.4 yProtein intake analyzed across quintiles.High protein quintile = 3.3 g/kgNo significant change observed in renal functionHaring et al.27Haring B. Selvin E. Liang M. et al.Dietary protein sources and risk for incident chronic kidney disease: results from the Atherosclerosis Risk in Communities (ARIC) Study.J Ren Nutr. 2017; 27: 233-242Abstract Full Text Full Text PDF PubMed Scopus (118) Google ScholarARIC cohort; n = 11,95223 yProtein intake analyzed across quintiles.High protein quintile: 110 g/dNo significant change observed in renal for total protein intakeRed and processed meat consumption associated with risk of CKDProtective associations from plant, egg, and fish protein sourcesKnight et al. 200328Knight E.L. Stampfer M.J. Hankinson S.E. Spiegelman D. Curhan G.C. The impact of protein intake on renal function decline in women with normal renal function or mild renal insufficiency.Ann Intern Med. 2003; 138: 460-467Crossref PubMed Scopus (306) Google ScholarNurses' Health Study cohort; n = 1,62411 yProtein intake analyzed across quintiles.High protein quintile: 93 g/dNo significant change observed in renal function in non-CKDSignificant association to renal function decline in those with established CKDLew et al. 201629Lew Q.-L.J. Jafar T.H. Koh H.W.L. et al.Red meat intake and risk of ESRD.J Am Soc Nephrol. 2016; 28: 304-312Crossref PubMed Scopus (116) Google ScholarSingapore Chinese Health Study cohort; n = 63,25715.5 yProtein intake analyzed across quartiles of animal, poultry, fish, and plant sourcesHigh protein quintile: 64 g/dLow protein quintile: 53 g/dRed meat consumption associated with risk of ESRDProtective associations from plant, egg, and fish protein sourcesCirillo et al. 201830Cirillo M. Cavallo P. Bilancio G. Lombardi C. Vagnarelli O.T. Laurenzi M. Low protein intake in the population: low risk of kidney function decline but high risk of mortality.J Ren Nutr. 2018; 28: 235-244Abstract Full Text Full Text PDF PubMed Scopus (13) Google ScholarGubbio study cohort; n = 4,67915.9 yLowest protein: 20% of the sample's UUN distributionNo significant change observed in renal function in non-CKDSignificant association to renal function decline in those with established CKDMalhotra et al. 201831Malhotra R. Lipworth L. Cavanaugh K.L. et al.Protein intake and long-term change in glomerular filtration rate in the Jackson Heart study.J Ren Nutr. 2018; 28: 245-250Abstract Full Text Full Text PDF PubMed Scopus (25) Google ScholarJackson Heart study cohort; n = 3,1658 yProtein intake analyzed across quartilesHigh protein quintile: 19%; 1 g/kgLow protein quintile: 10%; 0.6 g/kgNo significant change observed in renal function in non-CKDSignificant association to renal function decline in those with uncontrolled diabetesCKD, chronic kidney disease; ARIC, Atherosclerosis Risk in Communities; ONTARGET, The Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial; PREVEND, Prevention of Renal and Vascular End-Stage Disease; ESRD, end-stage renal disease; UUN, urine urea nitrogen. Open table in a new tab BMI, body mass index; CKD, chronic kidney disease. CKD, chronic kidney disease; ARIC, Atherosclerosis Risk in Communities; ONTARGET, The Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial; PREVEND, Prevention of Renal and Vascular End-Stage Disease; ESRD, end-stage renal disease; UUN, urine urea nitrogen. In this issue of JREN, we are presented with two studies examining the effects of dietary protein on the healthy kidney. Cirillo et al.30Cirillo M. Cavallo P. Bilancio G. Lombardi C. Vagnarelli O.T. Laurenzi M. Low protein intake in the population: low risk of kidney function decline but high risk of mortality.J Ren Nutr. 2018; 28: 235-244Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar present a post hoc analysis of the Gubbio study, an Italian population-based study of 4,679 adults. Dietary protein intake was measured from overnight urine urea nitrogen (UUN), with low protein intake defined as the lowest quartile of UUN distribution. CKD progression was defined as an eGFR reduction of less than or equal to 1 standard deviation from baseline. Over 16 years of follow-up, they found no association between low UUN and the odds of eGFR decline. Interestingly, when the analysis was restricted for those participants with reduced renal function at baseline (defined as eGFR decline from equal to or below a Z-score of -1 baseline eGFR), a low protein intake was significantly associated with lower odds of eGFR decline (odds ratio: 0.44 [95% confidence interval 0.22, 0.85]). Also in this issue, Malhotra et al.31Malhotra R. Lipworth L. Cavanaugh K.L. et al.Protein intake and long-term change in glomerular filtration rate in the Jackson Heart study.J Ren Nutr. 2018; 28: 245-250Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar present another observational analysis based on 3,165 participants from the Jackson Heart study. The sample included African–American adults who were mostly female (65%) and had dietary protein intake ascertained at baseline from food frequency questionnaires. Change in GFR was calculated as the final visit GFR minus the baseline GFR, using the CKD Epidemiology Collaboration equation. The primary finding of this study was a lack of significant association between protein intake and GFR decline over 8 years of observation. However, when the analysis was stratified by diabetes status, participants with diabetes had a higher incidence of eGFR decline across the lowest (−20.0 ± 1.7 mL/min/1.73 m2) and highest (−15.9 ± 2.8 mL/min/1.73 m2) quintiles of protein intake, as compared to those with middle quintile (−12 ± 1.6 mL/min/1.73 m2). These 2 studies add to the body of evidence that restricting protein intake may not be beneficial in the primary prevention of CKD. Nonetheless, they also suggest that a lower protein intake may be beneficial in some high-risk populations, including those with some mild degree of renal impairment or diabetes. This agrees with preceding observational reports, such as the Nurses' Health study, where an association of low protein intake with less rapid decline of kidney function over time was only observed in the subgroup of 489 participants with established mild renal impairment.28Knight E.L. Stampfer M.J. Hankinson S.E. Spiegelman D. Curhan G.C. The impact of protein intake on renal function decline in women with normal renal function or mild renal insufficiency.Ann Intern Med. 2003; 138: 460-467Crossref PubMed Scopus (306) Google Scholar There is also the suggestion that quality of the ingested protein (animal vs. plant-based) within an overall healthy dietary pattern, may be more important than the total protein ingested.33Kelly J.T. Carrero J.J. Dietary sources of protein and chronic kidney disease progression: the proof may be in the pattern.J Ren Nutr. 2017; 27: 221-224Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar Indeed, acute laboratory studies suggest that animal protein stimulates the renal reserve more so than plant-based proteins.34Hostetter T.H. Troy J.L. Brenner B.M. Glomerular hemodynamics in experimental diabetes mellitus.Kidney Int. 1981; 19: 410-415Abstract Full Text PDF PubMed Scopus (707) Google Scholar As recently shown in JREN,27Haring B. Selvin E. Liang M. et al.Dietary protein sources and risk for incident chronic kidney disease: results from the Atherosclerosis Risk in Communities (ARIC) Study.J Ren Nutr. 2017; 27: 233-242Abstract Full Text Full Text PDF PubMed Scopus (118) Google Scholar people consuming the highest quartile of vegetable protein had a 24% reduced risk of incident CKD over a 23-year follow-up period, but the analysis of overall protein intake yielded no association. When the analysis targeted individual food items, there was an increased CKD risk for those who consumed more protein from red and processed meats (HR 1.23; P < .01), and a reduced CKD risk for those who consumed more protein from dairy products, nuts, and legumes. While an important limitation of all these studies is their observational nature because of the lack of adequately powered and well-designed intervention trials. Such evidence forms the basis for many nutrition guidelines in primary and secondary prevention. The Science of Nutrition is a science of “virtue in moderation”, where any excess nutrient intake or deficit is a risk for more harm than good. Concerns relating to a high-protein diet are likely because of harmful effects other than kidney damage. Some of the adverse effects attributed to excessive protein intake include disorders of bone and calcium homeostasis, renal stone formation, possible increased risk of cancer, disorders of liver function, hypertension, and coronary artery disease.10Delimaris I. Adverse effects associated with protein intake above the recommended dietary allowance for adults.ISRN Nutr. 2013; 2013: 6Crossref Google Scholar, 35Golzarand M. Bahadoran Z. Mirmiran P. Azizi F. Protein foods group and 3-year incidence of hypertension: a prospective study from Tehran Lipid and Glucose study.J Ren Nutr. 2016; 26: 219-225Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar It is interesting, in this sense, that Malhotra et al.31Malhotra R. Lipworth L. Cavanaugh K.L. et al.Protein intake and long-term change in glomerular filtration rate in the Jackson Heart study.J Ren Nutr. 2018; 28: 245-250Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar observed a U-shape association between protein intake and mortality. Neither too little nor too much protein intake may be good for health, as it was similarly shown in other population-based studies.26Halbesma N. Bakker S.J. Jansen D.F. et al.High protein intake associates with cardiovascular events but not with loss of renal function.J Am Soc Nephrol. 2009; 20: 1797-1804Crossref PubMed Scopus (66) Google Scholar, 28Knight E.L. Stampfer M.J. Hankinson S.E. Spiegelman D. Curhan G.C. The impact of protein intake on renal function decline in women with normal renal function or mild renal insufficiency.Ann Intern Med. 2003; 138: 460-467Crossref PubMed Scopus (306) Google Scholar These two interesting studies leave us with two conclusions. First, they align with current evidence, which does not support the assertion that a high-protein diet leads to incident CKD in the community, at least in those with normal renal function. Interestingly however, is a call for caution about prescribing high-protein diets in populations at high risk of CKD, such as those with minimal renal impairment or diabetes. There is a need to better understand lifestyle advice for the primary prevention of CKD separately from secondary prevention, preferably in randomized controlled trials. Second, these studies make us realize that although a healthy diet is likely to be effective for primary CKD prevention,36Kelly J.T. Palmer S.C. Wai S.N. et al.Healthy dietary patterns and risk of mortality and ESRD in CKD: a meta-analysis of cohort studies.Clin J Am Soc Nephrol. 2016; 12: 272-279Crossref PubMed Scopus (155) Google Scholar the characteristics of such a diet are, to date, poorly defined.37Campbell K.L. Carrero J.J. Diet for the management of patients with chronic kidney disease; it is not the quantity, but the quality that matters.J Ren Nutr. 2016; 26: 279-281Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar The case of dietary protein and CKD illustrated in these 2 studies is an excellent example that primary and secondary prevention strategies are not always aligned. There is still much to be learned in the case of dietary protein, and more improvement is needed for effective strategies to minimize the burden of CKD in the community. After all, CKD afflicts 1 in 10 adults and causes as many deaths as diabetes.38Global, regional, and national age-sex specific mortality for 264 causes of death, 1980-2016: a systematic analysis for the Global Burden of Disease Study 2016.Lancet. 2017; 390: 1151-1210Abstract Full Text Full Text PDF PubMed Scopus (2981) Google Scholar, 39Thomas B. Matsushita K. Abate K.H. et al.Global cardiovascular and renal outcomes of reduced GFR.J Am Soc Nephrol. 2017; 28: 2167-2179Crossref PubMed Scopus (137) Google Scholar Protein Intake and Long-term Change in Glomerular Filtration Rate in the Jackson Heart StudyJournal of Renal NutritionVol. 28Issue 4PreviewDietary protein intake could have deleterious renal effects in populations at risk for chronic kidney disease. Here, we examined whether higher protein intake (≥80th percentile of energy from protein) is associated with decline in kidney function and whether this decline varies by diabetes status. Full-Text PDF Low Protein Intake in the Population: Low Risk of Kidney Function Decline but High Risk of MortalityJournal of Renal NutritionVol. 28Issue 4PreviewThis population-based study investigated low protein intake, mortality, and kidney function decline. Full-Text PDF