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Author(s): Rhee, Connie M; Ahmadi, Seyed-Foad; Kovesdy, Csaba P; Kalantar-Zadeh, Kamyar | Abstract: BackgroundRecent data pose the question whether conservative management of chronic kidney disease (CKD) by means of a low-protein diet can be a safe and effective means to avoid or defer transition to dialysis therapy without causing protein-energy wasting or cachexia. We aimed to systematically review and meta-analyse the controlled clinical trials with adequate participants in each trial, providing rigorous contemporary evidence of the impact of a low-protein diet in the management of uraemia and its complications in patients with CKD.MethodsWe searched MEDLINE (PubMed) and other sources for controlled trials on CKD to compare clinical management of CKD patients under various levels of dietary protein intake or to compare restricted protein intake with other interventions. Studies with similar patients, interventions, and outcomes were included in the meta-analyses.ResultsWe identified 16 controlled trials of low-protein diet in CKD that met the stringent qualification criteria including having 30 or more participants. Compared with diets with protein intake of g0.8ng/kg/day, diets with restricted protein intake (l0.8ng/kg/day) were associated with higher serum bicarbonate levels, lower phosphorus levels, lower azotemia, lower rates of progression to end-stage renal disease, and a trend towards lower rates of all-cause death. In addition, very-low-protein diets (protein intake l0.4ng/kg/day) were associated with greater preservation of kidney function and reduction in the rate of progression to end-stage renal disease. Safety and adherence to a low-protein diet was not inferior to a normal protein diet, and there was no difference in the rate of malnutrition or protein-energy wasting.ConclusionsIn this pooled analysis of moderate-size controlled trials, a low-protein diet appears to enhance the conservative management of non-dialysis-dependent CKD and may be considered as a potential option for CKD patients who wish to avoid or defer dialysis initiation and to slow down the progression of CKD, while the risk of protein-energy wasting and cachexia remains minimal.

Background Chronic pain is a common condition in the general population. However, large epidemiologic studies examining the role of pain in the deterioration of kidney function, development of chronic kidney disease, and risk for death are lacking. Study Design Retrospective cohort study. Setting & Participants A nationally representative cohort of 2,360,056 US veterans with baseline estimated glomerular filtration rates (eGFRs) ≥ 60mL/min/1.73m 2 , followed up from October 2004 to September 2006. Predictor 4 pain categories were compared: none (score, 0), mild (1-4), moderate (5-6), or severe (≥7). Outcomes eGFR decline (determined by eGFR slope) and combined incident eGFR 2 or all-cause death. Measurements We examined the pain management pattern and association of reported pain with (1) rapid eGFR decline and (2) a composite outcome of incident eGFR 2 or all-cause death using logistic regression and Cox models adjusted for baseline eGFR, demographics, comorbid conditions, cardiovascular risk factors, and depression. Results ∼60% of veterans reported pain of any severity during the baseline period. The most commonly prescribed analgesics were opioids. In a dose-response relationship, veterans reporting moderate or severe pain had a higher risk for faster eGFR decline compared with those reporting none (ORs of 1.11 [95% CI, 1.09-1.14] and 1.17 [95% CI, 1.13-1.21] for moderate and severe pain, respectively). In combined analyses, veterans reporting moderate or severe pain both had 30% higher risk of the combined outcome (incident eGFR, 60 mL/min/1.73 m 2 or death) compared with those reporting none (HRs of 1.30 [95% CI, 1.28-1.31] and 1.30 [95% CI, 1.28-1.32] for moderate and severe pain, respectively). Limitations Lack of granular data regarding type and location of pain. Conclusions We observed a high prevalence of pain and analgesic prescription in the US veteran population with normal eGFRs. Pain was associated with a higher incidence of eGFRs 2 , faster kidney function decline, and higher mortality.

Obesity is a major risk factor for the development of de novo chronic kidney disease (CKD). However, once kidney disease is acquired, obesity is paradoxically linked with greater survival, especially in those with advanced CKD. This review examines current evidence for obesity as a risk factor for incident CKD, studies of obesity and mortality across various CKD populations, and potential mechanisms underlying the 'obesity paradox' in kidney disease.Large cohort studies show that overweight body habitus, especially in the context of metabolic syndrome, is associated with higher risk of incident CKD. Emerging data also suggest weight-loss interventions retard or reverse early CKD progression, whereas in hemodialysis patients weight-loss paradoxically heralds poor outcomes. Although the pathogenesis of CKD in obesity remains unclear, studies indicate that excess body fat leads to kidney disease via indirect and direct mechanisms. Meta-analyses suggest that overweight and obese BMI ranges are counterintuitively associated with lower mortality in advanced predialysis and dialysis-dependent CKD patients, whereas a pooled analysis observed that higher pretransplantation BMI was associated with higher mortality in kidney transplantation recipients.In addition to its role as a risk factor for de novo CKD, there appears to be a consistent association between obesity and lower mortality in those with established CKD, particularly among hemodialysis patients, suggesting that the reverse epidemiology of obesity is biologically plausible.

Author(s): Soohoo, Melissa; Ahmadi, Seyed-Foad; Qader, Hemn; Streja, Elani; Obi, Yoshitsugu; Moradi, Hamid; Rhee, Connie M; Kim, Tae Hee; Kovesdy, Csaba P; Kalantar-Zadeh, Kamyar | Abstract: BackgroundVitamin B12 (B12) and folate are essential vitamins that play important roles in physiological processes. In the general population, many studies have evaluated the association of these vitamins with clinical outcomes, yet this association in hemodialysis (HD) patients remains unclear.MethodsWe examined the association of serum folate and B12 with mortality in a 5-year cohort of 9517 (folate) and 12 968 (B12) HD patients using Cox models with hierarchical adjustment for sociodemographics, comorbidities, and laboratory variables associated with the malnutrition and inflammation complex syndrome. The associations of baseline B12 and folate (separately) with all-cause mortality were evaluated across five categories of B12 [l400 (reference), 400-l550, 550-l650, 650-l750 and ≥750 pg/mL] and folate [l6.2, 6.2-l8.4, 8.4-l11 (reference), 11-l14.3 and ≥14.3 ng/mL].ResultsThe study cohort with B12 measurements had a mean ± standard deviation age of 63 ± 15 years, among whom 43% were female, 33% were African-American, and 57% were diabetic. Higher B12 concentrations ≥550 pg/mL were associated with a higher risk of mortality after adjusting for sociodemographic and laboratory variables. However, only lower serum folate concentrations l6.2 ng/mL were associated with a higher risk of all-cause mortality when adjusted for sociodemographic variables [adjusted hazard ratio (95% confidence-interval): 1.18 (1.03-1.35)].ConclusionsHigher B12 concentrations are associated with higher all-cause mortality in HD patients independent of sociodemographics and laboratory variables, whereas lower folate concentrations were associated with higher all-cause mortality after accounting for sociodemographic variables. Further studies are warranted to determine the optimal B12 and folate level targets in this population.

Background Although higher body mass index (BMI) is associated with better outcomes in hemodialysis patients, the relationship in peritoneal dialysis (PD) patients is less clear. We aimed to synthesize the results from all large and high-quality studies to examine whether underweight, overweight, or obesity is associated with any significantly different risk of death in peritoneal dialysis patients. Methods We searched MEDLINE, EMBASE, Web of Science, CINAHL, and Cochrane CENTRAL, and screened 7,123 retrieved studies for inclusion. Two investigators independently selected the studies using predefined criteria and assessed each study's quality using the Newcastle-Ottawa Quality Assessment Scale. We meta-analyzed the results of the largest studies with no overlap in their data sources. Results We included 9 studies ( n = 156,562) in the systematic review and 4 studies in the meta-analyses. When examined without stratifying studies by follow-up duration, the results of the studies were inconsistent. Hence, we pooled the study results stratified based upon their follow-up durations, as suggested by a large study, and observed that being underweight was associated with higher 1-year mortality but had no significant association with 2- and 3- to 5-year mortalities. In contrast, being overweight or obese was associated with lower 1-year mortality but it had no significant association with 2-, and 3- to 5-year mortalities. Conclusion Over the short-term, being underweight was associated with higher mortality and being overweight or obese was associated with lower mortality. The associations of body mass with mortality were not significant over the long-term.

Background: Previous studies have not shown a consistent link between body mass index (BMI) and outcomes such as mortality and kidney disease progression in non-dialysis-dependent chronic kidney disease (CKD) patients. Therefore, we aimed to complete a systematic review and meta-analysis study on this subject. Methods: We searched MEDLINE, EMBASE, Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Cochrane Central Register of Controlled Trials (CENTRAL), and screened 7,123 retrieved studies for inclusion. Two investigators independently selected the studies using predefined criteria and assessed each study's quality using the Newcastle-Ottawa quality assessment scale. We meta-analyzed the results based on the BMI classification system by the WHO. Results: We included 10 studies (with a total sample size of 484,906) in the systematic review and 4 studies in the meta-analyses. The study results were generally heterogeneous. However, following reanalysis of the largest reported study and our meta-analyses, we observed that in stage 3-5 CKD, being underweight was associated with a higher risk of death while being overweight or obese class I was associated with a lower risk of death; however, obesity classes II and III were not associated with risk of death. In addition, reanalysis of the largest available study showed that a higher BMI was associated with an incrementally higher risk of kidney disease progression; however, this association was attenuated in our pooled results. For earlier stages of CKD, we could not complete meta-analyses as the studies were sparse and had heterogeneous BMI classifications and/or referent BMI groups. Conclusion: Among the group of patients with stage 3-5 CKD, we found a differential association between obesity classes I-III and mortality compared to the general population, indicating an obesity paradox in the CKD population.

Background: A higher body mass index (BMI) seems to be linked to survival advantage in maintenance hemodialysis patients. However, it is uncertain if this ‘obesity survival paradox' is also observed in kidney transplant recipients. Hence, we systematically reviewed the literature on the impact of pre-transplantation BMI on all-cause mortality in this population. Methods: We searched MEDLINE, EMBASE, Web of Science, CINAHL, and Cochrane CENTRAL for relevant studies up to July 2013. Two investigators independently selected the studies using predefined criteria, abstracted the data from the included studies, and independently assessed each study's quality using the Newcastle-Ottawa Quality Assessment Scale. In addition to the qualitative synthesis, we quantitatively pooled the results of the studies with clinical, methodological, and statistical homogeneity. Results: We screened 7,123 records, from which we included 11 studies (with a total of 305,392 participants) in this systematic review and 4 studies in the meta-analyses. In the only study that included children, obesity was linked to higher mortality in children of 6-12 years old. For adults, our meta-analyses indicated that compared to normal BMI, underweight [Hazard Ratio (HR): 1.09; 95% Confidence Interval (CI): 1.02-1.20], overweight (HR: 1.07; 95% CI: 1.04-1.12), and obese (HR: 1.20; 95% CI: 1.14-1.23) levels of BMI were associated with higher mortality. Conclusion: The presence of the obesity survival paradox is unlikely in kidney transplant recipients since both extremes of pre-transplantation BMI are linked to higher mortality in this population.