High dietary protein intake may lead to increased intraglomerular pressure and glomerular hyperfiltration, which in the long-term can lead to de novo or aggravating preexisting chronic kidney disease (CKD). Hence, a low protein diet (LPD, 0.6 to 0.8 g/kg/day) is recommended for the management of CKD. There are evidences that dietary protein restriction mitigate progression of CKD and retard the initiation of dialysis or facilitate incremental dialysis. LPD is also helpful to control metabolic derangements in CKD such as metabolic acidosis and hyperphosphatemia. Recently, a growing body of evidence has emerged on the benefits of plant-dominant low-protein diet (PLADO), which composed of > 50% plant-based sources. PLADO is considered to be helpful for relieving uremic burden and metabolic complications in CKD compared to animal protein dominant consumption. It may also lead to favorable alterations in the gut microbiome, which can modulate uremic toxin generation along with reducing cardiovascular risk. Alleviation of constipation in PLADO may minimize the risk of hyperkalemia. A balanced and individualized dietary approach for good adherence to LPD utilizing various plant-based sources as patients' preference should be elaborated for the optimal care in CKD. Periodic nutritional assessment under supervision of trained dietitians should be warranted to avoid protein-energy wasting.

Chronic kidney disease (CKD) is one of the most prevalent complications of diabetes, and patients with diabetic kidney disease (DKD) have a substantially higher risk of cardiovascular disease and death compared to their non-diabetic CKD counterparts. In addition to pharmacologic management strategies, nutritional and dietary interventions in DKD are an essential aspect of management with the potential for ameliorating kidney function decline and preventing the development of other end-organ complications. Among DKD patients with non-dialysis dependent CKD, expert panels recommend lower dietary protein intake of 0.8 g/kg of body weight/day, while higher dietary protein intake (>1.2 g/kg of body weight/day) is advised among diabetic end-stage renal disease patients receiving maintenance dialysis to counteract protein catabolism, dialysate amino acid and protein losses, and protein-energy wasting. Carbohydrates from sugars should be limited to less than 10% of energy intake, and it is also suggested that higher polyunsaturated and monounsaturated fat consumption in lieu of saturated fatty acids, trans-fat, and cholesterol are associated with more favorable outcomes. While guidelines recommend dietary sodium restriction to less than 1.5-2.3 g/day, excessively low sodium intake may be associated with hyponatremia as well as impaired glucose metabolism and insulin sensitivity. As patients with advanced DKD progressing to end-stage renal disease may be prone to the "burnt-out diabetes" phenomenon (i.e., spontaneous resolution of hypoglycemia and frequent hypoglycemic episodes), further studies in this population are particularly needed to determine the safety and efficacy of dietary restrictions in this population.

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.

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.

Purpose of review

High-protein diets (HPDs) are popular but their consequences for kidney health, especially among athletes and bodybuilders who typically maintain a high protein intake for a long time, have not been investigated. This review focused on recent studies of the association of HPD with long-term kidney health and the concept of high dietary protein-related nephropathy.

Recent findings

Several long-term observational studies including large populations have reinforced the notion that HPDs are associated with a rapid decline of kidney function. An increase in renal blood flow and glomerular hyperfiltration caused by vasodilation, and increased levels of endocrine and paracrine factors (glucagon, IGF-1, prostanoids, and nitric oxide), facilitates the excretion of protein-derived nitrogenous waste. Inhibition of tubule-glomerular feedback and increased proximal tubular Na+ reabsorption after a HPD augment glomerular hyperfiltration and may trigger synthesis of proinflammatory cytokines and receptor for advanced glycation end-products (RAGE). Focal segmental glomerulosclerosis reported in association with anabolic steroid may indeed be a HPD nephropathy given that HPD results in progressive glomerulosclerosis, especially in remnant glomeruli or in diabetic kidney disease but can happen in any high-risk situation, such as solitary kidney and polycystic kidneys.

Summary

HPD among athletes and bodybuilders in an extreme way across a long-term period may pose a risk to renal health including high incidence of HPD nephropathy.

Background

It is not clear whether peritoneal dialysis (PD) and home hemodialysis (HHD) have similar outcomes, and little is known about how mortality associated with HHD versus PD differs according to the duration of dialysis.

Methods

We examined a national cohort of incident end-stage renal disease patients that was comprised of 1,993 and 16,514 patients transitioning to HHD and PD, respectively, from 2007 to 2011. The HHD patients were matched with PD patients using propensity score (PS). Demographics, comorbidities, duration of dialysis, and body mass index were adjusted for in logistic regression models using PS matching. We matched 1,915 HHD patients with 1,915 PD patients based on the PS. The patients were categorized by their vintage (duration of dialysis) at the time of the transition to HHD or PD (<3, 3 to <12, and ≥12 months).

Results

In the matched cohort, 237 and 359 deaths occurred in the HHD and PD patients, respectively (cumulative incidence 9.6 vs. 12.9/100 patient-years, p < 0.001). PD patients who transitioned within 12 months of starting dialysis had similar mortality risks, while PD patients who transitioned >12 months after starting dialysis had an 83% higher risk for mortality (hazard ratio 1.83; 95% CI 1.33-2.52).

Conclusions

Whereas there was no meaningful survival difference in the first 12 months between HHD and PD, patients who transitioned to PD after 12 months of dialysis had worse survival than their HHD counterparts. Additional studies are warranted to investigate clinical implications of these differences.

There is accumulating evidence that serum levels of non-high-density lipoprotein cholesterol (non-HDL-C) are a more accurate predictor of cardiovascular outcomes when compared with low-density lipoprotein cholesterol. However, we recently found that higher serum concentrations of triglycerides are associated with better outcomes in patients undergoing hemodialysis. Therefore, we hypothesized that the association of serum levels of non-HDL-C (which includes triglyceride-rich lipoproteins) with outcomes may also be different in patients undergoing hemodialysis when compared with other patient populations. We studied the association of baseline and time-dependent serum levels of non-HDL-C with all-cause and cardiovascular mortality using Cox proportional hazard regression models in a nationally representative cohort of 50 118 patients undergoing incident hemodialysis from January 1, 2007, to December 31, 2011. In time-dependent models adjusted for case mix and surrogates of malnutrition and inflammation, a graded inverse association between non-HDL-C level and mortality was demonstrated with hazard ratios (95% confidence intervals) of the lowest (<60 mg/dL) and highest (≥160 mg/dL) categories: 1.88 (1.72-2.06) and 0.73 (0.64-0.83) for all-cause mortality and 2.07 (1.78-2.41) and 0.75 (0.60-0.93) for cardiovascular mortality, respectively (reference, 100-115 mg/dL). In analyses using baseline values, non-HDL-C levels <100 mg/dL were also associated with significantly higher mortality risk across all levels of adjustment. Similar associations were found when evaluating non-HDL/HDL cholesterol ratio and mortality, with the highest all-cause and cardiovascular mortality being observed in patients with decreased non-HDL/HDL-C ratio (<2.5). Contrary to the general population, decrements in non-HDL-C and non-HDL/HDL cholesterol ratio were paradoxically associated with increased all-cause and cardiovascular mortality in patients undergoing incident hemodialysis. The underlying mechanisms responsible for these associations await further investigation.

Background

Arteriovenous fistulas (AVFs) are the preferred vascular access type in most hemodialysis patients. However, the optimal vascular access type in octogenarians and older (≥80 years) hemodialysis patients remains widely debated given their limited life expectancy and lower AVF maturation rates.

Methods

Among incident hemodialysis patients receiving care in a large national dialysis organization during 2007-2011, we examined patterns of vascular access type conversion in 1 year following dialysis initiation in patients <80 versus ≥80 years of age. Among a subcohort of patients ≥80 years of age, we examined the association between vascular access type conversion and mortality using multivariable survival models.

Results

In the overall cohort of 100 804 patients, the prevalence of AVF/arteriovenous graft (AVG) as the primary vascular access type increased during the first year of hemodialysis, but plateaued thereafter. Among 8356 patients ≥80 years of age and treated for >1 year, those with initial AVF/AVG use and placement of AVF from a central venous catheter (CVC) had lower mortality compared with patients with persistent CVC use. When the reference group was changed to patients who had AVF placement from a CVC in the first year of dialysis, those with initial AVF use had similar mortality. A longer duration of CVC use was associated with incrementally worse survival.

Conclusions

Among incident hemodialysis patients ≥80 years of age, placement of an AVF from a CVC within the first year of dialysis had similar mortality compared with initial AVF use. Our data suggest that initial CVC use with later placement of an AVF may be an acceptable option among elderly hemodialysis patients.

Background

The population of elderly end-stage renal disease patients initiating dialysis is rapidly growing. Although longer treatment is supposed to benefit for hemodialysis (HD) patients through more solute clearance and slower fluid removal, it is not yet clear how treatment session length affects mortality risk in octogenarians and nonagenarians.

Methods

In a cohort of 112,026 incident HD patients between 2007 and 2011, we examined the association of treatment session length with all-cause mortality, adjusting for demographics and comorbid conditions. We also used restricted spline functions for age to evaluate continuous changes in the association of short (< 210 min) and extended (≥240 min) HD treatment (vs. 210 to < 240 min) with all-cause mortality over continuous age.

Results

During the first 91 days of dialysis, patients aged ≥80 years tended to have the lowest treatment session length (median [interquartile range] 211 [193-230] min, r > 0.5). Longer treatment was associated with better survival in patients < 65 and 65 to < 80 years but not in octogenarians/nonagenarians. The association of extended treatment (≥240 min) with better survival was attenuated across age and not significant among patients aged ≥80 years with a hazard ratio of 1.10 (95% CI 0.99-1.20). Shorter treatment sessions (< 210 min) was associated with higher mortality across all age groups.

Conclusion

Extended HD was not associated with lower mortality among octogenarians and nonagenarians, while it was associated with better survival among younger patients. Further studies are needed to determine the optimal treatment session length in elderly incident HD patients.

Background

Elevated serum high-density lipoprotein cholesterol (HDL-C) has not been associated with better cardiovascular (CV) and all-cause mortality in hemodialysis patients. However, the association between change in HDL over time and mortality has not been fully examined.

Objective

In a nationally representative cohort of incident hemodialysis patients who had available HDL data at baseline and 6 months after dialysis initiation, we studied the association of change in HDL-C during the first 6 months of dialysis with all-cause and CV mortality.

Methods

Associations between HDL-C change and mortality were determined in Cox proportional hazard regression models with adjustment for multiple variables.

Results

In case-mix models, there was a J-shaped association between change in HDL-C and mortality, such that quartiles 1 (<-5 mg/dL) and 4 (≥7 mg/dL) were each associated with higher all-cause (hazard ratio, 1.32 [95% confidence interval, 1.21-1.45] and 1.09 [1.01-1.18]) and CV (1.28 [1.06-1.55] and 1.23 [1.04-1.45]) death risk, respectively. In fully adjusted models that included indices of malnutrition and inflammation, the higher death risk observed in the lowest quartile was attenuated, whereas the highest quartile continued to demonstrate significantly higher all-cause (1.11 [1.02-1.20]) and CV mortality (1.15 [1.00-1.32]). These associations persisted across various subgroups.

Conclusions

Although malnutrition and inflammation may explain the increased risk for mortality in patients with decreasing serum HDL-C concentrations over time, these indices do not mitigate the elevated risk in patients with rising serum HDL-C. We found that increasing serum HDL-C over time is paradoxically associated with worse outcomes in incident hemodialysis patients.