Association of HIV and viral suppression status with hospital acute kidney injury in the era of antiretroviral therapy.

In the modern era, it is unknown if people that are virally suppressed with HIV (PWH) are at increased risk for acute kidney injury (AKI) compared to people without HIV and no studies have compared the risk of AKI by viral suppression status. Here, we determined the associations of HIV status and AKI among PWH with and without viral suppression compared to people without HIV. An observational cohort study of PWH and people without HIV hospitalized in a large New York City health system between 2010-2019 was conducted. Multivariable Cox proportional hazards models were used to determine associations between HIV status and risk of AKI, severe AKI and development of chronic kidney disease (CKD). Among 173,884 hospitalized patients, 4,718 had HIV; 2,532 (53.7%) were virally suppressed and 2,186 (46.3%) were not suppressed. Compared to people without HIV, PWH with and without viral suppression were at increased risk of AKI (adjusted hazard ratio 1.27, 95% confidence interval 1.15, 1.40 and 1.73, 1.58, 1.90, respectively) and AKI requiring kidney replacement therapy (1.89, 1.27, 2.84 and 1.87, 1.23, 2.84, respectively). Incremental, graded associations were observed between HIV status and Stage 2 or 3 AKI, and among AKI survivors, and incident CKD. The elevated risk of AKI across ages of PWH was similar in magnitude to older people without HIV. Thus, regardless of virologic control, HIV is an independent risk factor for AKI among hospitalized patients. Future studies should determine the mechanisms by which HIV increases susceptibility to AKI and identify strategies to prevent AKI in PWH.

Metabolic acidosis in pediatric kidney transplant recipients.

BACKGROUND: Metabolic acidosis is a risk factor for faster kidney function decline in chronic kidney disease (CKD) and in adult kidney transplant recipients (KTRs). We hypothesized that metabolic acidosis would be highly prevalent and associated with worse allograft function in pediatric KTRs. METHODS: Pediatric KTRs at Montefiore Medical Center from 2010 to 2018 were included. Metabolic acidosis was defined as serum bicarbonate < 22 mEq/L or receiving alkali therapy. Regression models were adjusted for demographic factors and donor/recipient characteristics. RESULTS: Sixty-three patients were identified with a median age at transplant of 10.5 (interquartile range (IQR) 4.4-15.2) years and post-transplant follow-up of 3 (IQR 1-5) years. Baseline serum bicarbonate was 21.7 ± 2.4 mEq/L, serum bicarbonate < 22 mEq/L was present in 28 (44%), and 44% of all patients were receiving alkali therapy. The prevalence of acidosis ranged from 58 to 70% during the first year of follow-up. At baseline, each 1-year higher age at transplant and every 10 ml/min/1.73 m2 higher eGFR were associated with 0.16 mEq/L (95% CI: 0.03-0.3) and 0.24 mEq/L (95% CI: 0.01-0.5) higher serum bicarbonate, respectively. Older age at transplant was associated with lower odds of acidosis (OR: 0.84; 95% CI: 0.72-0.97). During follow-up, metabolic acidosis was independently associated with 8.2 ml/min/1.73 m2 (95% CI 4.4-12) lower eGFR compared to not having acidosis; furthermore, eGFR was significantly lower among KTRs with unresolved acidosis compared with resolved acidosis. CONCLUSIONS: Among pediatric KTRs, metabolic acidosis was highly prevalent in the first year post-transplantation and was associated with lower eGFR during follow-up. A higher resolution version of the Graphical abstract is available as Supplementary information.

Association of Dietary Potassium Intake With Abdominal Aortic Calcification and Pulse Pressure in US Adults.

OBJECTIVES: Arterial calcification contributes to cardiovascular mortality. Based on a recent animal study, we hypothesized that higher dietary potassium intake was associated with less abdominal aortic calcification (AAC) and lower arterial stiffness among adults in the United States. METHODS: Cross-sectional analyses were performed on participants over 40 years old from the National Health and Nutrition Examination Survey 2013-2014. Dietary potassium intake was categorized into quartiles (Q1: <1911, Q2: 1911-2461, Q3: 2462-3119, and Q4: >3119 mg/d). Primary outcome AAC was quantified using the Kauppila scoring system. AAC scores were categorized into no AAC (AAC = 0, reference group), mild/moderate (AAC >0 to ≤ 6), and severe AAC (AAC >6). Pulse pressure was used as a surrogate for arterial stiffness and examined as a secondary outcome. RESULTS: Among 2,418 participants, there was not a linear association between dietary potassium intake and AAC. Higher dietary potassium intake was associated with less severe AAC when comparing dietary potassium intake in Q2 with Q1 (odds ratio 0.55; 95% confidence interval: 0.34 to 0.92; P = .03). Higher dietary potassium intake was significantly associated with lower pulse pressure (P = .007): per 1000 mg/d higher dietary potassium intake, pulse pressure was 1.47 mmHg lower in the fully adjusted model. Compared to participants with dietary potassium intake in Q1, pulse pressure was 2.84 mmHg lower in Q4 (P = .04). CONCLUSIONS: We did not find a linear association between dietary potassium intake and AAC. Dietary potassium intake was negatively associated with pulse pressure.

Step length and fall risk in adults with chronic kidney disease: a pilot study.

BACKGROUND: Patients with chronic kidney disease commonly experience gait abnormalities, which predispose to falls and fall-related injuries. An unmet need is the development of improved methods for detecting patients at high risk of these complications, using tools that are feasible to implement in nephrology practice. Our prior work suggested step length could be such a marker. Here we explored the use of step length as a marker of gait impairment and fall risk in adults with chronic kidney disease. METHODS: We performed gait assessments in 2 prospective studies of 82 patients with stage 4 and 5 chronic kidney disease (n = 33) or end-stage renal disease (ESRD) (n = 49). Gait speed and step length were evaluated during the 4-m walk component of the Short Physical Performance Battery (SPPB). Falls within 6 months prior to or following enrollment were identified by questionnaire. Associations of low step length (≤47.2 cm) and slow gait speed (≤0.8 m/s) with falls were examined using logistic regression models adjusted for demographics and diabetes and peripheral vascular disease status. RESULTS: Assessments of step length were highly reproducible (r = 0.88, p < 0.001 for duplicate measurements at the same visit; r = 0.78, p < 0.001 between baseline and 3-month evaluations). Patients with low step length had poorer physical function, including lower SPPB scores, slower gait speed, and lower handgrip strength. Although step length and gait speed were highly correlated (r = 0.73, p < 0.001), one-third (n = 14/43) of patients with low step length did not have slow gait speed. Low step length and slow gait speed were each independently associated with the likelihood of falls (odds ratio (OR) 3.90 (95% confidence interval (CI) 1.05-14.60) and OR 4.25 (95% CI 1.24-14.58), respectively). Compared with patients who exhibited neither deficit, those with both had a 6.55 (95% CI 1.40-30.71) times higher likelihood of falls, and the number of deficits was associated with a graded association with falls (p trend = 0.02). Effect estimates were similar after further adjustment for ESRD status. CONCLUSIONS: Step length and gait speed may contribute additively to the assessment of fall risk in a general adult nephrology population.

AKI in Hospitalized Patients with and without COVID-19: A Comparison Study.

BACKGROUND: Reports from centers treating patients with coronavirus disease 2019 (COVID-19) have noted that such patients frequently develop AKI. However, there have been no direct comparisons of AKI in hospitalized patients with and without COVID-19 that would reveal whether there are aspects of AKI risk, course, and outcomes unique to this infection. METHODS: In a retrospective observational study, we evaluated AKI incidence, risk factors, and outcomes for 3345 adults with COVID-19 and 1265 without COVID-19 who were hospitalized in a large New York City health system and compared them with a historical cohort of 9859 individuals hospitalized a year earlier in the same health system. We also developed a model to identify predictors of stage 2 or 3 AKI in our COVID-19. RESULTS: We found higher AKI incidence among patients with COVID-19 compared with the historical cohort (56.9% versus 25.1%, respectively). Patients with AKI and COVID-19 were more likely than those without COVID-19 to require RRT and were less likely to recover kidney function. Development of AKI was significantly associated with male sex, Black race, and older age (>50 years). Male sex and age >50 years associated with the composite outcome of RRT or mortality, regardless of COVID-19 status. Factors that were predictive of stage 2 or 3 AKI included initial respiratory rate, white blood cell count, neutrophil/lymphocyte ratio, and lactate dehydrogenase level. CONCLUSIONS: Patients hospitalized with COVID-19 had a higher incidence of severe AKI compared with controls. Vital signs at admission and laboratory data may be useful for risk stratification to predict severe AKI. Although male sex, Black race, and older age associated with development of AKI, these associations were not unique to COVID-19.

Intradialytic acid-base changes and organic anion production during high versus low bicarbonate hemodialysis.

The use of high dialysate bicarbonate for hemodialysis in end-stage renal disease is associated with increased mortality, but potential physiological mediators are poorly understood. Alkalinization due to high dialysate bicarbonate may stimulate organic acid generation, which could lead to poor outcomes. Using measurements of ß-hydroxybutyrate (BHB) and lactate, we quantified organic anion (OA) balance in two single-arm studies comparing high and low bicarbonate prescriptions. In study 1 (n = 10), patients became alkalemic using 37 meq/L dialysate bicarbonate; in contrast, with the use of 27 meq/L dialysate, net bicarbonate loss occurred and blood bicarbonate decreased. Total OA losses were not higher with 37 meq/L dialysate bicarbonate (50.9 vs. 49.1 meq using 27 meq/L, P = 0.66); serum BHB increased in both treatments similarly (P = 0.27); and blood lactate was only slightly higher with the use of 37 meq/L dialysate (P = 0.048), differing by 0.2 meq/L at the end of hemodialysis. In study 2 (n = 7), patients achieved steady state on two bicarbonate prescriptions: they were significantly more acidemic when dialyzed against a 30 meq/L bicarbonate dialysate compared with 35 meq/L and, as in study 1, became alkalemic when dialyzed against the higher bicarbonate dialysate. OA losses were similar to those in study 1 and again did not differ between treatments (38.9 vs. 43.5 meq, P = 0.42). Finally, free fatty acid levels increased throughout hemodialysis and correlated with the change in serum BHB (r = 0.81, P < 0.001), implicating upregulation of lipolysis as the mechanism for increased ketone production. In conclusion, lowering dialysate bicarbonate does not meaningfully reduce organic acid generation during hemodialysis or modify organic anion losses into dialysate.

Effects of Sodium Bicarbonate in CKD Stages 3 and 4: A Randomized, Placebo-Controlled, Multicenter Clinical Trial.

RATIONALE & OBJECTIVE: Metabolic acidosis associated with chronic kidney disease (CKD) may contribute to muscle dysfunction and bone disease. We aimed to test whether treatment with sodium bicarbonate improves muscle and bone outcomes. STUDY DESIGN: Multicenter, randomized, placebo-controlled, clinical trial. SETTING & PARTICIPANTS: 149 patients with CKD stages 3 and 4 between July 2011 and April 2016 at 3 centers in Cleveland, OH, and the Bronx, NY. INTERVENTION: Sodium bicarbonate (0.4 mEq per kg of ideal body weight per day) (n=74) or identical-appearing placebo (n=75). OUTCOMES: Dual primary outcomes were muscle function assessed using sit-to-stand test and bone mineral density. Muscle biopsies were performed at baseline and 2 months. Participants were seen at baseline and 2, 6, 12, and 24 months. RESULTS: Mean baseline serum bicarbonate level was 24.0±2.2 (SD) mEq/L and mean baseline estimated glomerular filtration rate was 36.3±11.2mL/min/1.73m2. Baseline characteristics did not differ between groups. Mean serum bicarbonate levels in the intervention arm during follow-up were 26.4±2.2, 25.5±2.3, 25.6±2.6, and 24.4±2.8 mEq/L (at 2, 6, 12, and 24 months). These were significantly higher than in the placebo group (P<0.001). Compared to the placebo group, participants randomly assigned to sodium bicarbonate treatment had no significant differences in sit-to-stand time (5 repetitions: P=0.1; and 10 repetitions P=0.07) or bone mineral density (P=0.3). Sodium bicarbonate treatment caused a decrease in serum potassium levels that was of borderline statistical significance (P=0.05). There were no significant differences in estimated glomerular filtration rates, blood pressure, weight, serious adverse events, or levels of muscle gene expression between the randomly assigned groups. LIMITATIONS: Initial mean serum bicarbonate level was in the normal range. CONCLUSIONS: Sodium bicarbonate therapy in patients with CKD stages 3 and 4 significantly increases serum bicarbonate and decreases potassium levels. No differences were found in muscle function or bone mineral density between the randomly assigned groups. Larger trials are required to evaluate effects on kidney function. FUNDING: National Institutes of Health grant. TRIAL REGISTRATION: Registered at ClinicalTrials.gov with study number NCT01452412.

Association between dietary zinc intake and abdominal aortic calcification in US adults.

BACKGROUND: In animal studies, zinc supplementation inhibited phosphate-induced arterial calcification. We tested the hypothesis that higher intake of dietary zinc was associated with lower abdominal aortic calcification (AAC) among adults in the USA. We also explored the associations of AAC with supplemental zinc intake, total zinc intake and serum zinc level. METHODS: We performed cross-sectional analyses of 2535 participants from the National Health and Nutrition Examination Survey 2013-14. Dietary and supplemental zinc intakes were obtained from two 24-h dietary recall interviews. Total zinc intake was the sum of dietary and supplemental zinc. AAC was measured using dual-energy X-ray absorptiometry in adults ≥40 years of age and quantified using the Kauppila score system. AAC scores were categorized into three groups: no AAC (AAC = 0, reference group), mild-moderate (AAC >0-≤6) and severe AAC (AAC >6). RESULTS: Dietary zinc intake (mean ± SE) was 10.5 ± 0.1 mg/day; 28% had AAC (20% mild-moderate and 8% severe), 17% had diabetes mellitus and 51% had hypertension. Higher intake of dietary zinc was associated with lower odds of having severe AAC. Per 1 mg/day higher intake of dietary zinc, the odds of having severe AAC were 8% lower [adjusted odds ratio 0.92 (95% confidence interval 0.86-0.98), P = 0.01] compared with those without AAC, after adjusting for demographics, comorbidities and laboratory measurements. Supplemental zinc intake, total zinc intake and serum zinc level were not associated with AAC. CONCLUSIONS: Higher intake of dietary zinc was independently associated with lower odds of having severe AAC among noninstitutionalized US adults.

Advances in management of chronic metabolic acidosis in chronic kidney disease.

PURPOSE OF REVIEW: Chronic metabolic acidosis is a common complication of chronic kidney disease (CKD) and is associated with adverse consequences, such as CKD progression and muscle wasting. We review the findings from recent clinical trials that have examined the effects of sodium bicarbonate therapy and veverimer in patients with CKD and chronic metabolic acidosis. RECENT FINDINGS: There are four recent clinical trials on chronic metabolic acidosis of CKD. In a pilot, cross-over study, 6 weeks of sodium bicarbonate therapy improved vascular endothelial function, measured by brachial artery flow-mediated dilation. In a single-center, randomized, open-label study, 6 months of sodium bicarbonate therapy increased muscle mass and lean body mass, and preserved kidney function. The other two clinical trials (phase 1/2 and phase 3 studies) examined the effects of veverimer, which is a hydrochloric acid binder. The phase 3 study showed that 12-weeks of veverimer increased serum bicarbonate levels and might improve physical function. The effects of veverimer on CKD progression, physical function and cardiovascular endpoints as well as its long-term safety are yet to be determined. SUMMARY: Recent studies suggest that sodium bicarbonate therapy may improve vascular endothelial function and muscle mass, and preserve renal function. Veverimer increases serum bicarbonate level and could be a potential new therapeutic option for treating chronic metabolic acidosis.

Patients with advanced chronic kidney disease and vascular calcification have a large hydrodynamic radius of secondary calciprotein particles.

BACKGROUND: The size of secondary calciprotein particles (CPP2) and the speed of transformation (T50) from primary calciprotein particles (CPP1) to CPP2 in serum may be associated with vascular calcification (VC) in patients with chronic kidney disease (CKD). METHODS: We developed a high throughput, microplate-based assay using dynamic light scattering (DLS) to measure the transformation of CPP1 to CPP2, hydrodynamic radius (Rh) of CPP1 and CPP2, T50 and aggregation of CPP2. We used this DLS assay to test the hypothesis that a large Rh of CPP2 and/or a fast T50 are associated with VC in 45 participants with CKD Stages 4-5 (22 without VC and 23 with VC) and 17 healthy volunteers (HV). VC was defined as a Kauppila score >6 or an Adragao score ≥3. RESULTS: CKD participants with VC had larger cumulants Rh of CPP2 {370 nm [interquartile range (IQR) 272-566]} compared with CKD participants without VC [212 nm (IQR 169-315)] and compared with HV [168 nm (IQR 145-352), P < 0.01 for each]. More CPP2 were in aggregates in CKD participants with VC than those without VC (70% versus 36%). The odds of having VC increased by 9% with every 10 nm increase in the Rh of CPP2, after adjusting for age, diabetes, serum calcium and phosphate [odds ratio 1.09, 95% confidence interval (CI) 1.03, 1.16, P = 0.005]. The area under the receiver operating characteristic curve for VC of CPP2 size was 0.75 (95% CI 0.60, 0.90). T50 was similar in CKD participants with and without VC, although both groups had a lower T50 than HV. CONCLUSIONS: Rh of CPP2, but not T50, is independently associated with VC in patients with CKD Stages 4-5.

Skeletal muscle fibrosis is associated with decreased muscle inflammation and weakness in patients with chronic kidney disease.

Muscle dysfunction is an important cause of morbidity among patients with chronic kidney disease (CKD). Although muscle fibrosis is present in a CKD rodent model, its existence in humans and its impact on physical function are currently unknown. We examined isometric leg extension strength and measures of skeletal muscle fibrosis and inflammation in vastus lateralis muscle from CKD patients ( n = 10) and healthy, sedentary controls ( n = 10). Histochemistry and immunohistochemistry were used to assess muscle collagen and macrophage and fibro/adipogenic progenitor (FAP) cell populations, and RT-qPCR was used to assess muscle-specific inflammatory marker expression. Muscle collagen content was significantly greater in CKD compared with control (18.8 ± 2.1 vs. 11.7 ± 0.7% collagen area, P = 0.008), as was staining for collagen I, pro-collagen I, and a novel collagen-hybridizing peptide that binds remodeling collagen. Muscle collagen was inversely associated with leg extension strength in CKD ( r = -0.74, P = 0.01). FAP abundance was increased in CKD, was highly correlated with muscle collagen ( r = 0.84, P < 0.001), and was inversely associated with TNF-α expression ( r = -0.65, P = 0.003). TNF-α, CD68, CCL2, and CCL5 mRNA were significantly lower in CKD than control, despite higher serum TNF-α and IL-6. Immunohistochemistry confirmed fewer CD68+ and CD11b+ macrophages in CKD muscle. In conclusion, skeletal muscle collagen content is increased in humans with CKD and is associated with functional parameters. Muscle fibrosis correlated with increased FAP abundance, which may be due to insufficient macrophage-mediated TNF-α secretion. These data provide a foundation for future research elucidating the mechanisms responsible for this newly identified human muscle pathology.

Bicarbonate Balance and Prescription in ESRD.

The optimal approach to managing acid-base balance is less well defined for patients receiving hemodialysis than for those receiving peritoneal dialysis. Interventional studies in hemodialysis have been limited and inconsistent in their findings, whereas more compelling data are available from interventional studies in peritoneal dialysis. Both high and low serum bicarbonate levels associate with an increased risk of mortality in patients receiving hemodialysis, but high values are a marker for poor nutrition and comorbidity and are often highly variable from month to month. Measurement of pH would likely provide useful additional data. Concern has arisen regarding high-bicarbonate dialysate and dialysis-induced alkalemia, but whether these truly cause harm remains to be determined. The available evidence is insufficient for determining the optimal target for therapy at this time.

Hidden Obesity in Dialysis Patients: Clinical Implications.

While body-mass index (BMI) is used to diagnose obesity in the general population, its application in the end-stage renal disease (ESRD) population is fraught with difficulty. A major limitation is its inability to distinguish muscle mass from fat mass, thereby leading to misclassification of individuals with poor muscle mass but excess adipose tissue as non-obese (i.e. BMI <30 kg/m(2) ). As muscle wasting is common among ESRD patients, this is an important problem. A substantial proportion of ESRD patients have levels of BMI in the normal range, yet excess adiposity based on other measures. The importance of this "hidden" obesity remains to be determined, but it must be recognized in order for obesity interventions to be appropriately targeted and tested in the ESRD population.

Effect of oral sodium bicarbonate on fibroblast growth factor-23 in patients with chronic kidney disease: a pilot study.

BACKGROUND: The regulation of fibroblast growth factor-23 (FGF23) secretion in patients with chronic kidney disease (CKD) is incompletely understood. An in vitro study showed that metabolic acidosis increased FGF23 in mouse bone. The objective of this study is to evaluate the effect of oral sodium bicarbonate on circulating FGF23 levels in patients with CKD. METHODS: This was a single-blind pilot study. Twenty adults with estimated glomerular filtration rate between 15-45 mL/min/1.73 m(2) and serum bicarbonate between 20-24 mEq/L were treated with placebo for 2 weeks, followed by increasing doses of oral sodium bicarbonate (0.3, 0.6 and 1.0 mEq/kg/day) in 2 week intervals for a total of 6 weeks. C-terminal FGF23 levels were measured at the initial visit, after 2 weeks of placebo and after 6 weeks of bicarbonate therapy. Wilcoxon matched-pairs signed-rank test was used to compare FGF23 before and after sodium bicarbonate. RESULTS: After 6 weeks of oral sodium bicarbonate, the median FGF23 increased significantly from 150.9 RU/mL (IQR 107.7-267.43) to 191.4 RU/mL (IQR 132.6-316.9) (p = 0.048) and this persisted after excluding participants who received activated vitamin D. CONCLUSIONS: FGF23 increased after short-term oral sodium bicarbonate therapy in patients with CKD and mild metabolic acidosis. It is unclear whether this was due to the alkalinizing effect of sodium bicarbonate or other factors. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov ( NCT00888290 ) on April 23, 2009.

Serum bicarbonate and bone mineral density in US adults.

BACKGROUND: Chronic metabolic acidosis leads to bone mineral loss and results in lower bone mineral density (BMD), which is a risk factor for osteoporosis-related fractures. The effect of low-level metabolic acidosis on bone density in the general population is unknown. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: 9,724 nationally representative adults 20 years or older in NHANES (National Health and Nutrition Examination Survey) 1999-2004. FACTOR: Serum bicarbonate level. OUTCOMES: Lumbar and total BMD, as well as low lumbar and total bone mass, defined as 1.0 SD below the sex-specific mean value of young adults. MEASUREMENTS: BMD was measured by dual-energy x-ray absorptiometry and serum bicarbonate was measured in all participants. RESULTS: Both men and women with lower serum bicarbonate levels were more likely to be current smokers and had higher body mass index and estimated net endogenous acid production. There was a significant linear trend across quartiles of serum bicarbonate with lumbar BMD in the total population, as well as in sex-specific models (P=0.02 for all 3 models, P=0.1 for interaction). For total BMD, a significant association was seen with serum bicarbonate level for women but not men (P=0.02 and P=0.1, respectively; P=0.8 for interaction), and a significant association was seen for postmenopausal women but not premenopausal women (P=0.02 and P=0.2, respectively; P=0.5 for interaction). Compared with women with serum bicarbonate levels <24mEq/L, those with serum bicarbonate levels ≥27mEq/L had 0.018-g/cm(2) higher total BMD (95% CI, 0.004-0.032; P=0.01) and 31% lower odds of having low total bone mass (OR, 0.68; 95% CI, 0.46-0.99; P=0.049). LIMITATIONS: Cross-sectional study using a single measurement of serum bicarbonate. Subgroup differences are not definitive. CONCLUSIONS: Lower serum bicarbonate levels are associated with lower BMD in US adults. Further studies should examine whether serum bicarbonate levels should be incorporated into the diagnostic assessment and management of osteoporosis.

Net endogenous acid production and mortality in NHANES III.

AIM: Low serum bicarbonate is a strong mortality risk factor in people with low estimated glomerular filtration rate (eGFR). It may also raise mortality risk in people with normal eGFR. This study investigated whether higher net endogenous acid production (NEAP), an estimate of net dietary acid intake and a risk factor for chronic kidney disease (CKD) progression, associates with higher mortality in people with and without low eGFR. METHODS: NEAP was calculated among adult participants in the Third National Health and Nutrition Examination Survey as -10.2 + 54.5 x (protein intake in grams per day/potassium intake in milliequivalent per day). Cox models were performed in the (i) total population and (ii) low eGFR and (iii) normal eGFR subgroups using the lowest NEAP quartile as the reference. RESULTS: Sixteen thousand nine hundred six participants were included in the analysis. The mortality hazard ratios (95% confidence interval) for the highest NEAP quartile (72-145 mEq/day) were: (i) 0.75 (0.62-0.90) in the total population; (ii) 0.77 (0.51-1.17) in the low eGFR subgroup; and (iii) 0.75 (0.61-0.93) in the normal eGFR subgroup after adjusting for demographics, serum bicarbonate, eGFR, albuminuria and comorbidities. The mortality hazard ratios in the second and third NEAP quartiles were similar to the lowest (reference) NEAP quartile in the total population and low and normal eGFR subgroups. CONCLUSIONS: Higher NEAP is not associated with higher mortality in people with low or normal eGFR. Future studies should consider the effect of modifying dietary acid and alkali intake on mortality and CKD progression in people with reduced eGFR.

Variability in monthly serum bicarbonate measures in hemodialysis patients: a cohort study.

BACKGROUND: Some nephrologists have advocated an individualized approach to the prescription of bicarbonate hemodialysis. However, the utility of monthly serum bicarbonate levels for guiding and evaluating such treatment decisions has not been evaluated. We sought to define the variability of these measurements and to determine factors that are associated with month-to-month variability in pre-dialysis serum bicarbonate. METHODS: We examined the monthly variability in serum bicarbonate measurements among 181 hemodialysis patients admitted to a free-standing dialysis unit in the Bronx, NY from 1/1/2008-6/30/2012. All patients were treated with a uniform bicarbonate dialysis prescription (bicarbonate 35 mEq/L, acetate 8 mEq/L). Pre-dialysis serum bicarbonate values were obtained from monthly laboratory reports. Month-to-month variability was defined using a rolling measurement for each time point. RESULTS: Only 34 % of high serum bicarbonate values (>26 mEq/L) remained high in the subsequent month, whereas 60 % converted to normal (22-26 mEq/L). Of all low values (<22 mEq/L), 41 % were normal the following month, while 58 % remained low. Using the mean 3-month bicarbonate, only 29 % of high values remained high in the next 3-month period. In multivariable-adjusted longitudinal models, both low and high serum bicarbonate values were associated with greater variability than were normal values (ß = 0.12 (95 % CI 0.09-0.15) and 0.24 (0.18 to 0.29) respectively). Variability decreased with time, and was significantly associated with age, phosphate binder use, serum creatinine, potassium, and normalized protein catabolic rate. CONCLUSIONS: Monthly pre-dialysis serum bicarbonate levels are highly variable. Even if a clinician takes no action, approximately 50 % of bicarbonate values outside a normal range of 22-26 mEq/L will return to normal in the subsequent month. The decision to change the bicarbonate dialysis prescription should not be based on a single bicarbonate value, and even a 3-month mean may be insufficient.

Treatment of metabolic acidosis in patients with CKD.

Metabolic acidosis is a common complication of chronic kidney disease and is believed to contribute to a number of sequelae, including bone disease, altered protein metabolism, skeletal muscle wasting, and progressive glomerular filtration rate loss. Small trials in animal models and humans suggest a role for alkali therapy to lessen these complications. Recent studies support this notion, although more definitive evidence is needed on the long-term benefits of alkali therapy and the optimal serum bicarbonate level. The role of dietary modification also should be given greater consideration. In addition, potential adverse effects of alkali treatment must be taken into consideration, including sodium retention and the theoretical concern of promoting vascular calcification. This teaching case summarizes the rationale for and benefits and complications of base therapy in patients with chronic kidney disease.