Symptom Science in Kidney Disease.

Physical and emotional symptoms are highly prevalent among patients with kidney disease and are directly linked to impaired health-related quality of life. Symptom science is a field of research aimed at advancing knowledge of the holistic mechanisms driving symptoms, how best to assess symptoms accurately, and developing novel and patient-centered approaches to symptom management. Patients with kidney disease have identified symptom science as a top research priority, and opportunities abound for ongoing patient engagement in symptom-related research efforts and clinical care. This review describes the burden of symptoms experienced by patients with kidney disease, explores the spectrum of patient engagement in symptom care and research, and discusses approaches for symptom assessment and management, taking into consideration the multitude of factors that may contribute to symptoms.

The Microbiome and Protein Carbamylation: Potential Targets for Protein-Restricted Diets Supplemented with Ketoanalogues in Predialysis Chronic Kidney Disease.

In chronic kidney disease (CKD), metabolic derangements resulting from the interplay between decreasing renal excretory capacity and impaired gut function contribute to accelerating disease progression and enhancing the risk of complications. To protect residual kidney function and improve quality of life in conservatively managed predialysis CKD patients, current guidelines recommend protein-restricted diets supplemented with essential amino acids (EAAs) and their ketoanalogues (KAs). In clinical studies, such an approach improved nitrogen balance and other secondary metabolic disturbances, translating to clinical benefits, mainly the delayed initiation of dialysis. There is also increasing evidence that a protein-restricted diet supplemented with KAs slows down disease progression. In the present review article, recent insights into the role of KA/EAA-supplemented protein-restricted diets in delaying CKD progression are summarized, and possible mechanistic underpinnings, such as protein carbamylation and gut dysbiosis, are elucidated. Emerging evidence suggests that lowering urea levels may reduce protein carbamylation, which might contribute to decreased morbidity and mortality. Protein restriction, alone or in combination with KA/EAA supplementation, modulates gut dysbiosis and decreases the generation of gut-derived uremic toxins associated, e.g., with cardiovascular disease, inflammation, protein energy wasting, and disease progression. Future studies are warranted to assess the effects on the gut microbiome, the generation of uremic toxins, as well as markers of carbamylation.

Nutritional vitamin D supplementation in dialysis: a randomized trial.

BACKGROUND AND OBJECTIVES: Vitamin D (25-hydroxyvitamin D; 25[OH]D) deficiency is common in patients initiating long-term hemodialysis, but the safety and efficacy of nutritional vitamin D supplementation in this population remain uncertain. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This randomized, placebo-controlled, parallel-group multicenter trial compared two doses of ergocalciferol with placebo between October 2009 and March 2013. Hemodialysis patients (n=105) with 25(OH)D levels ≤32 ng/ml from 32 centers in the Northeast United States were randomly assigned to oral ergocalciferol, 50,000 IU weekly (n=36) or monthly (n=33), or placebo (n=36) for a 12-week treatment period. The primary endpoint was the achievement of vitamin D sufficiency (25[OH]D >32 ng/ml) at the end of the 12-week treatment period. Survival was assessed through 1 year. RESULTS: Baseline characteristics were similar across all arms, with overall mean±SD 25(OH)D levels of 21.9±6.9 ng/ml. At 12 weeks, vitamin D sufficiency (25[OH]D >32 ng/ml) was achieved in 91% (weekly), 66% (monthly), and 35% (placebo) (P<0.001). Mean 25(OH)D was significantly higher in both the weekly (49.8±2.3 ng/ml; P<0.001) and monthly (38.3±2.4 ng/ml; P=0.001) arms compared with placebo (27.4±2.3 ng/ml). Calcium, phosphate, parathyroid hormone levels, and active vitamin D treatment did not differ between groups. All-cause and cause-specific hospitalizations and adverse events were similar between groups during the intervention period. Lower all-cause mortality among ergocalciferol-treated participants was not statistically significant (hazard ratio, 0.28; 95% confidence interval, 0.07 to 1.19). CONCLUSIONS: Oral ergocalciferol can increase 25(OH)D levels in incident hemodialysis patients without significant alterations in blood calcium, phosphate, or parathyroid hormone during a 12-week period.

Carbamylation of serum albumin as a risk factor for mortality in patients with kidney failure.

Urea, the toxic end product of protein catabolism, is elevated in end-stage renal disease (ESRD), although it is unclear whether or how it contributes to disease. Urea can promote the carbamylation of proteins on multiple lysine side chains, including human albumin, which has a predominant carbamylation site on Lys(549). The proportion of serum albumin carbamylated on Lys(549) (%C-Alb) correlated with time-averaged blood urea concentrations and was twice as high in ESRD patients than in non-uremic subjects (0.90% versus 0.42%). Baseline %C-Alb was higher in ESRD subjects who died within 1 year than in those who survived longer than 1 year (1.01% versus 0.77%) and was associated with an increased risk of death within 1 year (hazard ratio, 3.76). These findings were validated in an independent cohort of diabetic ESRD subjects (hazard ratio, 3.73). Decreased concentrations of serum amino acids correlated with higher %C-Alb in ESRD patients, and mice with diet-induced amino acid deficiencies exhibited greater susceptibility to albumin carbamylation than did chow-fed mice. In vitro studies showed that amino acids such as cysteine, histidine, arginine, and lysine, as well as other nucleophiles such as taurine, inhibited cyanate-induced C-Alb formation at physiologic pH and temperature. Together, these results suggest that chronically elevated urea promotes carbamylation of proteins in ESRD and that serum amino acid concentrations may modulate this protein modification. In summary, we have identified serum %C-Alb as a risk factor for mortality in patients with ESRD and propose that this risk factor may be modifiable with supplemental amino acid therapy.

Does vitamin D modulate blood pressure?

PURPOSE OF REVIEW: Both vitamin D deficiency and hypertension are highly prevalent. It is unclear whether vitamin D modulates blood pressure and therefore whether vitamin D testing and therapy should become part of routine hypertension prevention and management. This article provides an overview of the data, with special emphasis on the work published in the last 2 years. RECENT FINDINGS: Several animal studies corroborate the strong effect of vitamin D on the renin-angiotensin-aldosterone axis. Small and large observational studies have found associations between vitamin D, increased blood pressure, and the risk of developing hypertension. In contrast, recent data from randomized trials are mixed. Two randomized trials with approximately 1 year of follow-up detected no association between vitamin D treatment and blood pressure, whereas another study of active vitamin D reported a 9-mmHg decrease in systolic blood pressure. Meta-analyses have linked vitamin D levels with blood pressure, but the effect of vitamin D administration on blood pressure remains controversial. SUMMARY: Vitamin D deficiency is asociated with high blood pressure in observational studies. This effect is thought to be partly mediated through regulation of the renin-angiotensin-aldosterone axis. However, randomized clinical trials and their meta-analyses have yielded inconclusive results. Large randomized trials focusing on patients with severe vitamin D deficiency and hypertension are needed before vitamin D can be recommended for the prevention or treatment of hypertension.