Purpose of review

High-protein intake may lead to increased intraglomerular pressure and glomerular hyperfiltration. This can cause damage to glomerular structure leading to or aggravating chronic kidney disease (CKD). Hence, a low-protein diet (LPD) of 0.6-0.8 g/kg/day is often recommended for the management of CKD. We reviewed the effect of protein intake on incidence and progression of CKD and the role of LPD in the CKD management.

Recent findings

Actual dietary protein consumption in CKD patients remains substantially higher than the recommendations for LPD. Notwithstanding the inconclusive results of the 'Modification of Diet in Renal Disease' (MDRD) study, the largest randomized controlled trial to examine protein restriction in CKD, several prior and subsequent studies and meta-analyses appear to support the role of LPD on retarding progression of CKD and delaying initiation of maintenance dialysis therapy. LPD can also be used to control metabolic derangements in CKD. Supplemented LPD with essential amino acids or their ketoanalogs may be used for incremental transition to dialysis especially on nondialysis days. The LPD management in lieu of dialysis therapy can reduce costs, enhance psychological adaptation, and preserve residual renal function upon transition to dialysis. Adherence and adequate protein and energy intake should be ensured to avoid protein-energy wasting.

Summary

A balanced and individualized dietary approach based on LPD should be elaborated with periodic dietitian counseling and surveillance to optimize management of CKD, to assure adequate protein and energy intake, and to avoid or correct protein-energy wasting.

Background and objectives

There are inconsistent reports on the association of dietary protein intake with serum albumin and outcomes among patients on hemodialysis. Using a new normalized protein catabolic rate (nPCR) variable accounting for residual renal urea clearance, we hypothesized that higher baseline nPCR and rise in nPCR would be associated with higher serum albumin and better survival among incident hemodialysis patients.

Design, setting, participants, & measurements

Among 36,757 incident hemodialysis patients in a large United States dialysis organization, we examined baseline and change in renal urea clearance-corrected nPCR as a protein intake surrogate and modeled their associations with serum albumin and mortality over 5 years (1/2007-12/2011).

Results

Median nPCRs with and without accounting for renal urea clearance at baseline were 0.94 and 0.78 g/kg per day, respectively (median within-patient difference, 0.14 [interquartile range, 0.07-0.23] g/kg per day). During a median follow-up period of 1.4 years, 8481 deaths were observed. Baseline renal urea clearance-corrected nPCR was associated with higher serum albumin and lower mortality in the fully adjusted model (P_trend<0.001). Among 13,895 patients with available data, greater rise in renal urea clearance-corrected nPCR during the first 6 months was also associated with attaining high serum albumin (≥3.8 g/dl) and lower mortality (P_trend<0.001); compared with the reference group (a change of 0.1-0.2 g/kg per day), odds and hazard ratios were 0.53 (95% confidence interval, 0.44 to 0.63) and 1.32 (95% confidence interval, 1.14 to 1.54), respectively, among patients with a change of <-0.2 g/kg per day and 1.62 (95% confidence interval, 1.35 to 1.96) and 0.76 (95% confidence interval, 0.64 to 0.90), respectively, among those with a change of ≥0.5 g/kg per day. Within a given category of nPCR without accounting for renal urea clearance, higher levels of renal urea clearance-corrected nPCR consistently showed lower mortality risk.

Conclusions

Among incident hemodialysis patients, higher dietary protein intake represented by nPCR and its changes over time appear to be associated with increased serum albumin levels and greater survival. nPCR may be underestimated when not accounting for renal urea clearance. Compared with the conventional nPCR, renal urea clearance-corrected nPCR may be a better marker of mortality.

Introduction

Hypoalbuminemia is a predictor of poor outcomes in dialysis patients. Among hemodialysis patients, there has not been prior study of whether residual kidney function or decline over time impacts serum albumin levels. We hypothesized that a decline in residual kidney function is associated with an increase in serum albumin levels among incident hemodialysis patients.

Methods

In a large national cohort of 38,504 patients who initiated hemodialysis during 1/2007-12/2011, we examined the association of residual kidney function, ascertained by urine volume and renal urea clearance, with changes in serum albumin over five years across strata of baseline residual kidney function, race, and diabetes using case-mix adjusted linear mixed effects models.

Findings

Serum albumin levels increased over time. At baseline, patients with greater urine volume had higher serum albumin levels: 3.44 ± 0.48, 3.50 ± 0.46, 3.57 ± 0.44, 3.59 ± 0.45, and 3.65 ± 0.46 g/dL for urine volume groups of <300, 300-<600, 600-<900, 900-<1,200, and ≥1,200 mL/day, respectively (P_trend  < 0.001). Over time, urine volume and renal urea clearance declined and serum albumin levels rose, while the baseline differences in serum albumin persisted across groups of urinary volume. In addition, the rate of decline in residual kidney function was not associated with the rate of change in albumin.

Discussion

Hypoalbuminemia in hemodialysis patients is associated with lower residual kidney function. Among incident hemodialysis patients, there is a gradual rise in serum albumin that is independent of the rate of decline in residual kidney function, suggesting that preservation of residual kidney function does not have a deleterious impact on serum albumin levels.

Objectives

Serum albumin (sAlb) may be a strong predictor of longevity in the general population and in chronic kidney disease. This study aimed to determine the relationship between sAlb concentrations and mortality risk independent of kidney function.

Methods

This was a retrospective cohort study of 31 274 adults from the 1999-2010 National Health and Nutrition Examination Survey. The estimated glomerular filtration rate (eGFR) was examined as both a confounder and modifier of the association of sAlb with mortality risk. We examined the association of sAlb (categorized as <3.8, 3.8 to <4.0, 4.0 to <4.2, 4.2 to <4.4, 4.4 to <4.6, 4.6 to <4.8, and ≥4.8 g/dL) with mortality using Cox models. Subsequently, we conducted spline analyses to estimate the association of sAlb with all-cause mortality across varying eGFR levels.

Results

In unadjusted analyses, participants with incrementally lower sAlb concentrations of <4.6 g/dL had an increasingly higher mortality risk compared with those with sAlb levels ranging from 4.6 to <4.8 g/dL (reference), whereas those with higher sAlb levels of ≥4.8 g/dL had a lower mortality risk (hazard ratios [95% confidence interval]: 3.88 [3.26-4.62], 3.59 [3.01-4.27], 2.79 [2.37-3.29], 2.10 [1.79-2.48], 1.72 [1.45-2.03], and 0.71 [0.55-0.92] for sAlb concentrations of <3.8, 3.8 to <4.0, 4.0 to <4.2, 4.2 to <4.4, 4.4 to <4.6, and ≥4.8 g/dL, respectively). Adjusted analyses showed similar findings, although the association of higher sAlb levels of ≥4.8 g/dL with better survival was attenuated to the null. Spline analyses showed that participants with sAlb levels of <4.6 g/dL had higher mortality across all concentrations of eGFR, ranging from 30 to 120 mL/min/1.73 m² (reference: sAlb ≥ 4.6 g/dL).

Conclusions

Among a nationally representative U.S. cohort, a graded association was observed between lower sAlb concentrations and higher death risk, which was robust across varying levels of kidney function.

Background

Hyperkalemia is observed in chronic kidney disease patients and may be a risk factor for life-threatening arrhythmias and death. Race/ethnicity may be important modifiers of the potassium-mortality relationship in maintenance hemodialysis (MHD) patients given that potassium intake and excretion vary among minorities.

Methods

We examined racial/ethnic differences in baseline serum potassium levels and all-cause and cardiovascular mortality using Cox proportional hazard models and restricted cubic splines in a cohort of 102,241 incident MHD patients. Serum potassium was categorized into 6 groups: ≤3.6, >3.6 to ≤4.0, >4.0 to ≤4.5 (reference), >4.5 to ≤5.0, >5.0 to ≤5.5, and >5.5 mEq/L. Models were adjusted for case-mix and malnutrition-inflammation cachexia syndrome (MICS) covariates.

Results

The cohort was composed of 50% whites, 34% African-Americans, and 16% Hispanics. Hispanics tended to have the highest baseline serum potassium levels (mean ± SD: 4.58 ± 0.55 mEq/L). Patients in our cohort were followed for a median of 1.3 years (interquartile range 0.6-2.5). In our cohort, associations between higher potassium (>5.5 mEq/L) and higher mortality risk were observed in African-American and whites, but not Hispanic patients in models adjusted for case-mix and MICS covariates. While in Hispanics only, lower serum potassium (<3.6 mEq/L) levels were associated with higher mortality risk. Similar trends were observed for cardiovascular mortality.

Conclusions

Higher potassium levels were associated with higher mortality risk in white and African-American MHD patients, whereas lower potassium levels were associated with higher death risk in Hispanics. Further studies are needed to determine the underlying mechanisms for the differential association between potassium and mortality across race/ethnicity.

Background

Inadequate protein intake and hypoalbuminemia, indicators of protein-energy wasting, are among the strongest mortality predictors in hemodialysis patients. Hemodialysis patients are frequently counseled on dietary phosphorus restriction, which may inadvertently lead to decreased protein intake. We hypothesized that, in hypoalbuminemic hemodialysis patients, provision of high-protein meals during hemodialysis combined with a potent phosphorus binder increases serum albumin without raising phosphorus levels.

Methods

We conducted a randomized controlled trial in 110 adults undergoing thrice-weekly hemodialysis with serum albumin <4.0 g/dL recruited between July 2010 and October 2011 from eight Southern California dialysis units. Patients were randomly assigned to receive high-protein (50-55 g) meals during dialysis, providing 400-500 mg phosphorus, combined with lanthanum carbonate versus low-protein (<1 g) meals during dialysis, providing <20 mg phosphorus. Prescribed nonlanthanum phosphorus binders were continued over an 8-week period. The primary composite outcome was a rise in serum albumin of ≥0.2 g/dL while maintaining phosphorus between 3.5-<5.5 mg/dL. Secondary outcomes included achievement of the primary outcome's individual endpoints and changes in mineral and bone disease and inflammatory markers.

Results

Among 106 participants who satisfied the trial entrance criteria, 27% ( n = 15) and 12% ( n = 6) of patients in the high-protein versus low-protein hemodialysis meal groups, respectively, achieved the primary outcome (intention-to-treat P-value = 0.045). A lower proportion of patients in the high-protein versus low-protein intake groups experienced a meaningful rise in interleukin-6 levels: 9% versus 31%, respectively (P = 0.009). No serious adverse events were observed.

Conclusion

In hypoalbuminemic hemodialysis patients, high-protein meals during dialysis combined with lanthanum carbonate are safe and increase serum albumin while controlling phosphorus.

Whereas in many parts of the world a low protein diet (LPD, 0.6-0.8 g/kg/day) is routinely prescribed for the management of patients with non-dialysis-dependent chronic kidney disease (CKD), this practice is infrequent in North America. The historical underpinnings related to LPD in the USA including the non-conclusive results of the Modification of Diet in Renal Disease Study may have played a role. Overall trends to initiate dialysis earlier in the course of CKD in the US allowed less time for LPD prescription. The usual dietary intake in the US includes high dietary protein content, which is in sharp contradistinction to that of a LPD. The fear of engendering or worsening protein-energy wasting may be an important handicap as suggested by a pilot survey of US nephrologists; nevertheless, there is also potential interest and enthusiasm in gaining further insight regarding LPD's utility in both research and in practice. Racial/ethnic disparities in the US and patients' adherence are additional challenges. Adherence should be monitored by well-trained dietitians by means of both dietary assessment techniques and 24-h urine collections to estimate dietary protein intake using urinary urea nitrogen (UUN). While keto-analogues are not currently available in the USA, there are other oral nutritional supplements for the provision of high-biologic-value proteins along with dietary energy intake of 30-35 Cal/kg/day available. Different treatment strategies related to dietary intake may help circumvent the protein- energy wasting apprehension and offer novel conservative approaches for CKD management in North America.

(1) Background: Current dietary recommendations for dialysis patients suggest that high phosphorus diets may be associated with adverse outcomes such as hyperphosphatemia and death. However, there has been concern that excess dietary phosphorus restriction may occur at the expense of adequate dietary protein intake in this population. We hypothesized that higher dietary phosphorus intake is associated with higher mortality risk among a diverse cohort of hemodialysis patients. (2) Methods: Among 415 patients from the multi-center prospective Malnutrition, Diet, and Racial Disparities in Kidney Disease Study, we examined the associations of absolute dietary phosphorus intake (mg/day), ascertained by food frequency questionnaires, with all-cause mortality using multivariable Cox models. In the secondary analyses, we also examined the relationship between dietary phosphorus scaled to 1000 kcal of energy intake (mg/kcal) and dietary phosphorus-to-protein ratio (mg/g) with survival. (3) Results: In expanded case-mix + laboratory + nutrition adjusted analyses, the lowest tertile of dietary phosphorus intake was associated with higher mortality risk (ref: highest tertile): adjusted HR (aHR) (95% CI) 3.33 (1.75-6.33). In the analyses of dietary phosphorus scaled to 1000 kcal of energy intake, the lowest tertile of intake was associated with higher mortality risk compared to the highest tertile: aHR (95% CI) 1.74 (1.08, 2.80). Similarly, in analyses examining the association between dietary phosphorus-to-protein ratio, the lowest tertile of intake was associated with higher mortality risk compared to the highest tertile: aHR (95% CI) 1.67 (1.02-2.74). (4) Conclusions: A lower intake of dietary phosphorus was associated with higher mortality risk in a prospective hemodialysis cohort. Further studies are needed to clarify the relationship between specific sources of dietary phosphorus intake and mortality in this population.

Background

Incident hemodialysis patients may experience rapid weight loss in the first few months of starting dialysis. However, trends in weight changes over time and their associations with survival have not yet been characterized in this population.

Methods

In a large contemporary US cohort of 58 106 patients who initiated hemodialysis during 1 January 2007-31 December 2011 and survived the first year of dialysis, we observed trends in weight changes during the first year of treatment and then examined the association of post-dialysis weight changes with all-cause mortality.

Results

Patients' post-dialysis weights rapidly decreased and reached a nadir at the 5th month of dialysis with an average decline of 2% from baseline, whereas obese patients (body mass index ≥30 kg/m 2 ) did not reach a nadir and lost ∼3.8% of their weight by the 12th month. Compared with the reference group (-2 to 2% changes in weight), the death hazard ratios (HRs) of patients with -6 to -2% and greater than or equal to -6% weight loss during the first 5 months were 1.08 (95% confidence interval, 1.02-1.14) and 1.14 (1.07-1.22), respectively. Moreover, the death HRs with 2-6% and ≥6% weight gain during the 5th to 12th months were 0.91 (0.85-0.97) and 0.92 (0.86-0.99), respectively.

Conclusions

In patients who survive the first year of hemodialysis, a decline in post-dialysis weight is observed and reaches a nadir at the 5th month. An incrementally larger weight loss during the first 12 months is associated with higher death risk, whereas weight gain is associated with greater survival during the 5th to 12th month but not in the first 5 months of dialysis therapy.