Impact of Prior Abdominal Procedures on Peritoneal Dialysis Catheter Outcomes: Findings From the North American Peritoneal Dialysis Catheter Registry.

RATIONALE & OBJECTIVE: A history of prior abdominal procedures may influence the likelihood of referral for peritoneal dialysis (PD) catheter insertion. To guide clinical decision making in this population, this study examined the association between prior abdominal procedures and outcomes in patients undergoing PD catheter insertion. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Adults undergoing their first PD catheter insertion between November 1, 2011, and November 1, 2020, at 11 institutions in Canada and the United States participating in the International Society for Peritoneal Dialysis North American Catheter Registry. EXPOSURE: Prior abdominal procedure(s) defined as any procedure that enters the peritoneal cavity. OUTCOMES: The primary outcome was time to the first of (1) abandonment of the PD catheter or (2) interruption/termination of PD. Secondary outcomes were rates of emergency room visits, hospitalizations, and procedures. ANALYTICAL APPROACH: Cumulative incidence curves were used to describe the risk over time, and an adjusted Cox proportional hazards model was used to estimate the association between the exposure and primary outcome. Models for count data were used to estimate the associations between the exposure and secondary outcomes. RESULTS: Of 855 patients who met the inclusion criteria, 31% had a history of a prior abdominal procedure and 20% experienced at least 1 PD catheter-related complication that led to the primary outcome. Prior abdominal procedures were not associated with an increased risk of the primary outcome (adjusted HR, 1.12; 95% CI, 0.68-1.84). Upper-abdominal procedures were associated with a higher adjusted hazard of the primary outcome, but there was no dose-response relationship concerning the number of procedures. There was no association between prior abdominal procedures and other secondary outcomes. LIMITATIONS: Observational study and cohort limited to a sample of patients believed to be potential candidates for PD catheter insertion. CONCLUSION: A history of prior abdominal procedure(s) does not appear to influence catheter outcomes following PD catheter insertion. Such a history should not be a contraindication to PD. PLAIN-LANGUAGE SUMMARY: Peritoneal dialysis (PD) is a life-saving therapy for individuals with kidney failure that can be done at home. PD requires the placement of a tube, or catheter, into the abdomen to allow the exchange of dialysis fluid during treatment. There is concern that individuals who have undergone prior abdominal procedures and are referred for a catheter might have scarring that could affect catheter function. In some institutions, they might not even be offered PD therapy as an option. In this study, we found that a history of prior abdominal procedures did not increase the risk of PD catheter complications and should not dissuade patients from choosing PD or providers from recommending it.

Unusual cases of peritonitis: A case series of five patients.

INTRODUCTION: Peritonitis is a complication in patients on peritoneal dialysis that frequently results from touch contamination. Most cases of peritoneal dialysis-related peritonitis are caused by skin organisms. Herein, we are presenting a series of peritonitis cases with unusual organisms in a single home dialysis center at an academic hospital in New York City. METHODS: The records of five patients with an unusual cause of peritonitis were reviewed by a clinician. We have chronologically tabulated the cell count of the dialysate, microbiologic cultures, and antibiotics received by each patient. Additionally, both a table and figure detail the microbiologic organisms that our dialysis unit encountered over the 3-year period concurrent with the infections reported. RESULTS: The first patient presented with refractory polymicrobial peritonitis due to a liver abscess. Another patient presented with diverticulitis and developed enteric peritonitis with various organisms. The following patient had peritonitis in the setting of bowel pathologies and from Rhizobium after exposure to plants. The next patient developed Pasteurella peritonitis from his cat. The final patient developed multiple episodes of peritonitis from organisms including flora native to soil and water. CONCLUSION: These uncommon cases of peritonitis with unusual circumstances bring awareness to various elements that can lead to peritonitis.

Molecular mechanisms and therapeutic targets for diabetic kidney disease.

Diabetic kidney disease has a high global disease burden and substantially increases the risk of kidney failure and cardiovascular events. Despite treatment, there is substantial residual risk of disease progression with existing therapies. Therefore, there is an urgent need to better understand the molecular mechanisms driving diabetic kidney disease to help identify new therapies that slow progression and reduce associated risks. Diabetic kidney disease is initiated by diabetes-related disturbances in glucose metabolism, which then trigger other metabolic, hemodynamic, inflammatory, and fibrotic processes that contribute to disease progression. This review summarizes existing evidence on the molecular drivers of diabetic kidney disease onset and progression, focusing on inflammatory and fibrotic mediators-factors that are largely unaddressed as primary treatment targets and for which there is increasing evidence supporting key roles in the pathophysiology of diabetic kidney disease. Results from recent clinical trials highlight promising new drug therapies, as well as a role for dietary strategies, in treating diabetic kidney disease.

Beyond the Urine Anion Gap: In Support of the Direct Measurement of Urinary Ammonium.

Ammonium is a major urinary buffer that is necessary for the normal excretion of the daily acid load. Its urinary rate of excretion (UNH4) may be increased several fold in the presence of extrarenal metabolic acidosis. Therefore, measurement of UNH4 can provide important clues about causes of metabolic acidosis. Because UNH4 is not commonly measured in clinical laboratories, the urinary anion gap (UAG) was proposed as its surrogate about 4 decades ago, and it is still frequently used for that purpose. Several published studies strongly suggest that UAG is not a good index of UNH4 and support the concept that direct measurement of UNH4 is an important parameter to define in clinical nephrology. Low UNH4 levels have recently been found to be associated with a higher risk of metabolic acidosis, loss of kidney function, and death in persons with chronic kidney disease, while surrogates like the UAG do not recapitulate this risk. In order to advance the field it is necessary for the medical community to become more familiar with UNH4 levels in a variety of clinical settings. Herein, we review the literature, searching for available data on UNH4 under normal and various pathological conditions, in an attempt to establish reference values to interpret UNH4 results if and when UNH4 measurements become available as a routine clinical test. In addition, we present original data in 2 large populations that provide further evidence that the UAG is not a good predictor of UNH4. Measurement of urine NH4 holds promise to aid clinicians in the care of patients, and we encourage further research to determine its best diagnostic usage.

Prevalence and Outcomes Associated with Hyperuricemia in Hospitalized Patients with COVID-19.

INTRODUCTION: Coronavirus 2019 (COVID-19) can increase catabolism and result in hyperuricemia. Uric acid (UA) potentially causes kidney damage by alteration of renal autoregulation, inhibition of endothelial cell proliferation, cell apoptosis, activation of the pro-inflammatory cascade, and crystal deposition. Hyperuricemia in patients with COVID-19 may contribute to acute kidney injury (AKI) and poor outcomes. METHODS: We included 834 patients with COVID-19 who were >18 years old and hospitalized for >24 h in the Mount Sinai Health System and had at least 1 measurement of serum UA. We examined the association between the first serum UA level and development of acute kidney injury (AKI, defined by KDIGO criteria), major adverse kidney events (MAKE, defined by a composite of all-cause in-hospital mortality or dialysis or 100% increase in serum creatinine from baseline), as well as markers of inflammation and cardiac injury. RESULTS: Among the 834 patients, the median age was 66 years, 42% were women, and the median first serum UA was 5.9 mg/dL (interquartile range 4.5-8.8). Overall, 60% experienced AKI, 52% experienced MAKE, and 32% died during hospitalization. After adjusting for demographics, comorbidities, and laboratory values, a doubling in serum UA was associated with increased AKI (odds ratio [OR] 2.8, 95% confidence interval [CI] 1.9-4.1), MAKE (OR 2.5, 95% CI 1.7-3.5), and in-hospital mortality (OR 1.7, 95% CI 1.3-2.3). Higher serum UA levels were independently associated with a higher level of procalcitonin (ß, 0.6; SE 0.2) and troponin I (ß, 1.2; SE 0.2) but were not associated with serum ferritin, C-reactive protein, and interleukin-6. CONCLUSION: In patients admitted to the hospital for COVID-19, higher serum UA levels were independently associated with AKI, MAKE, and in-hospital mortality in a dose-dependent manner. In addition, hyperuricemia was associated with higher procalcitonin and troponin I levels.

Comparing the effect of peritoneal dialysis cycler type on patient-reported satisfaction, support needs and treatments.

BACKGROUND: Most patients on peritoneal dialysis (PD) in the United States choose automated PD via cyclers. Cyclers have evolved considerably over time with older versions (e.g. HomeChoice Pro) replaced by more sophisticated and technologically advanced versions (e.g. Amia). Understanding the effect that different cyclers and their features have on patient treatments and support needs is important.  METHODS: Single center study with retrospective and prospective arms. Retrospective arm: Patients > 18 years old, on Amia or HomeChoice Pro (HC) for ≥ 3 months between 8/1/17 and 1/31/18. Number of office/telephone encounters, PD-related emergency room visits/hospitalizations, PD training days, and dialysis adequacy (Kt/V) were recorded. Prospective arm: Patients > 18 years old, on Amia or HC for ≥ 3 months between 9/1/19 and 2/29/20 were surveyed on their comfort, troubleshooting, satisfaction and reported assistance needed with their cyclers. RESULTS: Retrospective arm: 43 patients on AMIA and 27 patients on HC. Number of PD training days, Kt/Vs achieved, PD-related telephone/office encounters, and PD-related emergency room visits/hospitalizations were all similar. Prospective Arm: 32 patients on AMIA and 6 patients on HC. Higher rate of patient comfort with AMIA, but similar overall patient satisfaction with both cyclers. No difference in terms of patient-reported troubleshooting issues requiring assistance. CONCLUSIONS: Despite the difference in features provided between the 2 cyclers, patient overall satisfaction rates were high irrespective of the PD cycler. The HomeChoice Pro and AMIA cycler patients had a similar number of PD training days, PD-related telephone/office encounters, and PD-related emergency room visits/hospitalizations. TRIAL REGISTRATION: This study was approved by the Icahn School of Medicine at Mount Sinai Institutional Review Board (IRB-17-02704).

The Urine Anion Gap: Common Misconceptions.

Two papers, one in 1986 and another one in 1988, reported a strong inverse correlation between urinary anion gap (UAG) and urine ammonia excretion (UNH4) in patients with metabolic acidosis and postulated that UAG could be used as an indirect measure of UNH4 This postulation has persisted until now and is widely accepted. In this review, we discuss factors regulating UAG and examine published evidence to uncover errors in the postulate and the design of the original studies. The essential fact is that, in the steady state, UAG reflects intake of Na, K, and Cl. Discrepancy between intake and urinary output of these electrolytes (i.e, UAG) indicates selective extrarenal loss of these electrolytes or nonsteady state. UNH4 excretion, which depends, in the absence of renal dysfunction, mainly on the daily acid load, has no consistent relationship to UAG either theoretically or in reality. Any correlation between UAG and UNH4, when observed, was a fortuitous correlation and cannot be extrapolated to other situations. Furthermore, the normal value of UAG has greatly increased over the past few decades, mainly due to increases in dietary intake of potassium and widespread use of sodium salts with anions other than chloride as food additives. The higher normal values of UAG must be taken into consideration in interpreting UAG.

Use of peritoneal dialysis for acute kidney injury during the COVID-19 pandemic in New York City: a multicenter observational study.

To demonstrate feasibility of acute peritoneal dialysis (PD) for acute kidney injury during the coronavirus disease 2019 (COVID-19) pandemic, we performed a multicenter, retrospective, observational study of 94 patients who received acute PD in New York City in the spring of 2020. Patient comorbidities, severity of disease, laboratory values, kidney replacement therapy, and patient outcomes were recorded. The mean age was 61 ± 11 years; 34% were women; 94% had confirmed COVID-19; 32% required mechanical ventilation on admission. Compared to the levels prior to initiation of kidney replacement therapy, the mean serum potassium level decreased from 5.1 ± 0.9 to 4.5 ± 0.7 mEq/L on PD day 3 and 4.2 ± 0.6 mEq/L on day 7 (P < 0.001 for both); mean serum bicarbonate increased from 20 ± 4 to 21 ± 4 mEq/L on PD day 3 (P = 0.002) and 24 ± 4 mEq/L on day 7 (P < 0.001). After a median follow-up of 30 days, 46% of patients died and 22% had renal recovery. Male sex and mechanical ventilation on admission were significant predictors of mortality. The rapid implementation of an acute PD program was feasible despite resource constraints and can be lifesaving during crises such as the COVID-19 pandemic.

Increased advanced glycation end product and meat consumption is associated with childhood wheeze: analysis of the National Health and Nutrition Examination Survey.

We examined 4388 children from the 2003 to 2006 National Health and Nutrition Examination Survey and used survey-design-adjusted multivariable logistic regression to evaluate associations between dietary advanced glycation end product (AGE) and meat consumption frequencies and respiratory symptoms. Higher AGE intake was significantly associated with increased odds of wheezing (adjusted OR 1.18; 95% CI 1.02 to 1.36), wheeze-disrupted sleep (1.26; 95% CI 1.05 to 1.51) and exercise (1.34; 95% CI 1.08 to 1.67) and wheezing requiring prescription medication (1.35; 95% CI 1.13 to 1.63). Higher intake of non-seafood meats was associated with wheeze-disrupted sleep (2.32; 95% CI 1.11 to 4.82) and wheezing requiring prescription medication (2.23; 95% CI 1.10 to 4.54).

State-of-the-Art Management of Hyperphosphatemia in Patients With CKD: An NKF-KDOQI Controversies Perspective.

Phosphate binders are among the most common medications prescribed to patients with kidney failure receiving dialysis and are often used in advanced chronic kidney disease (CKD). In patients with CKD glomerular filtration rate category 3a (G3a) or worse, including those with kidney failure who are receiving dialysis, clinical practice guidelines suggest "lowering elevated phosphate levels towards the normal range" with possible strategies including dietary phosphate restriction or use of binders. Additionally, guidelines suggest restricting the use of oral elemental calcium often contained in phosphate binders. Nutrition guidelines in CKD suggest<800-1,000mg of calcium daily, whereas CKD bone and mineral disorder guidelines do not provide clear targets, but<1,500mg in maintenance dialysis patients has been previously recommended. Many different classes of phosphate binders are now available and clinical trials have not definitively demonstrated the superiority of any class of phosphate binders over another with regard to clinical outcomes. Use of phosphate binders contributes substantially to patients' pill burden and out-of-pocket costs, and many have side effects. This has led to uncertainty regarding the use and best choice of phosphate binders for patients with CKD or kidney failure. In this controversies perspective, we discuss the evidence base around binder use in CKD and kidney failure with a focus on comparisons of available binders.

Healthy eating recommendations: good for reducing dietary contribution to the body's advanced glycation/lipoxidation end products pool?

The present review aims to give dietary recommendations to reduce the occurrence of the Maillard reaction in foods and in vivo to reduce the body's advanced glycation/lipoxidation end products (AGE/ALE) pool. A healthy diet, food reformulation and good culinary practices may be feasible for achieving the goal. A varied diet rich in fresh vegetables and fruits, non-added sugar beverages containing inhibitors of the Maillard reaction, and foods prepared by steaming and poaching as culinary techniques is recommended. Intake of supplements and novel foods with low sugars, low fats, enriched in bioactive compounds from food and waste able to modulate carbohydrate metabolism and reduce body's AGE/ALE pool is also recommended. In conclusion, the recommendations made for healthy eating by the Spanish Society of Community Nutrition (SENC) and Harvard University seem to be adequate to reduce dietary AGE/ALE, the body's AGE/ALE pool and to achieve sustainable nutrition and health.

Home Dialysis: A Majority Chooses It, a Minority Gets It.

INTRODUCTION: When choosing a modality for outpatient renal replacement therapy, patients and medical providers have 3 options to choose from in-center hemodialysis (HD), home HD (HHD), and peritoneal dialysis (PD). In 2017, just over 10% of incident ESKD patients were on a home dialysis modality. We set out to determine outcomes of dialysis modality education in both pre-dialysis and dialysis patients. Moreover, we examined barriers that preclude patients from choosing home dialysis. METHODS: This was a single-center, retrospective study looking at patients who were referred to the CKD educator for dialysis modality education between January 1, 2019, and March 31, 2020. Patient demographics, preferred language of communication, stage of renal disease, and reasons for patients' refusal to undertake a home dialysis modality were recorded. Patients' average household income and driving distance to our home dialysis unit were calculated using their home zip code. RESULTS: 167 patients were referred for CKD education. Mean age was 60 years, and 59% male, 42% African American, 22% White, 7% Asian, and 28% were Hispanic or Latino. Only 23% of the total cohort chose in-center HD, while 74% chose a home dialysis modality (59% PD and 15% HHD), and the remaining patients remained undecided. 56% of in-center HD patients chose a home dialysis modality. The most commonly cited barriers to home dialysis were lack of a care partner, lack of home space, and patient preference. LIMITATIONS: Over 90% of our patients reside in NY City where home space is limited. We require in our home HD program that patients have a trained care partner present during their treatments. We cannot assume that all CKD stage-4 patients or higher were either referred for CKD education or followed through on the referral. CONCLUSIONS: A large discrepancy between informed patients' choices and the reality of the current dialysis landscape. Absence of a care partner, lack of home space, and patients not deemed appropriate surgical candidates were the main driving forces in their not opting for a home modality.

Chronic kidney disease and kidney stones.

PURPOSE OF REVIEW: Both chronic kidney disease (CKD) and kidney stones are major public health problems, which are closely interrelated. Recurrent kidney stones predispose to CKD although CKD seems to decrease risk of further kidney stone formation. Herein, we review new information of this interrelationship. RECENT FINDINGS: Several epidemiological studies in the past have shown an association between history of kidney stones and risk for CKD and CKD progression. Recent literature supports this concept and it is reviewed in this article. The issue of whether CKD protects against new kidney stone formation remains unsettled and there is no recent literature addressing it. In relation to stone risk factors in CKD, there are several interesting new articles that discuss mechanisms of hypocitraturia in early CKD before overt metabolic acidosis. Since hypocitraturia is an important risk factor for kidney stone formation we addressed these new data in detail. There are also new data supporting urinary oxalate excretion as a predictor of CKD progression. SUMMARY: It seems clear that recurrent kidney stones should be avoided not only because of their immediate clinical manifestations but also because of their long-term predisposition to CKD progression. Mechanisms leading to hypocitraturia in early CKD still remain controversial.

Adverse Effects of Autoclaved Diets on the Progression of Chronic Kidney Disease and Chronic Kidney Disease-Mineral Bone Disorder in Rats.

BACKGROUND: Autoclaving rodent diets is common in laboratory animals, but autoclaving increases the formation of dietary advanced glycation end-products (AGE). We studied the effect of autoclaved (AC) diet alone or in combination with a diet high in bioavailable phosphorus on biochemistries of chronic kidney disease-mineral and bone disorder (CKD-MBD), intestinal gene expression, and oxidative stress. METHODS: Male CKD rats (Cy/+) and normal littermates were fed 1 of 3 diets: AC 0.7% phosphorus grain-based diet for 28 weeks (AC); AC diet for 17 weeks followed by non-autoclaved (Non-AC) 0.7% phosphorus casein diet until 28 weeks (AC + Casein); or Non-AC diet for 16 weeks followed by a Non-AC purified diet until 30 weeks (Non-AC + Casein). RESULTS: AC diets contained ~3× higher AGEs and levels varied depending on the location within the autoclave. Rats fed the AC and AC + Casein diets had higher total AGEs and oxidative stress, irrespective of kidney function. Kidney function was more severely compromised in CKD rats fed AC or AC + Casein compared to Non-AC + Casein. There was a disease-by-diet interaction for plasma phosphorus, parathyroid hormone, and c-terminal fibroblast growth factor-23, driven by high values in the CKD rats fed the AC + Casein diet. Compared to Non-AC + Casein, AC and AC + Casein-fed groups had increased expression of receptor of AGEs and intestinal NADPH oxidase dual oxidase-2, independent of kidney function. CONCLUSIONS: Autoclaving rodent diets impacts the progression of CKD and CKD-MBD, highlighting the critical importance of standardizing diets in experiments.

Utilization of peritoneal dialysis in the United States: Reasons for underutilization, specifically in New York State and the boroughs of New York City.

Peritoneal dialysis (PD) is currently underutilized in the United States (US), even within resource-rich neighborhoods. We analyzed data from US Renal Data Service to determine PD utilization within the US, New York State (NYS), selected boroughs within New York City (NYC), and Boston, Massachusetts. We then compared the odds of selecting PD with hemodialysis (HD) and analyzed how diabetes mellitus status, age >65 years, gender, and race influenced PD utilization between 2010 and 2016. We then compared a high-volume PD center (HVC) with a low-volume PD center (LVC). The odds of starting PD vs HD were as follows: Brooklyn 0.30 (0.25-0.36; <0.0001), Bronx 0.56 (0.47-0.67; <0.0001), Queens 0.66 (0.54-0.80; <0.0001), and Manhattan 0.61 (0.52-0.71; <0.0001). In 2016, the odds of starting PD compared with the rest of the US were as follows: Brooklyn 0.14 (0.08-0.22; <0.0001), Bronx 0.39 (0.27-0.56; <0.0001), Queens 0.32 (0.23-0.45; <0.0001), Manhattan 0.54 (0.36-0.79; 0.002), and Boston 0.89 (0.58-1.4; 0.624). Analysis of influencing factors showed that only age >65 significantly (<0.0001) influenced PD modality selection in Brooklyn and Boston. Differences between HVC and LVC in terms of modality transition, peritonitis rate, or provider:patient ratio were not statistically significant. Factors that influence PD utilization in urban neighborhoods are discussed and remediation measures are proposed.

Implementation of a quality improvement strategy to increase outpatient kidney transplant referrals.

BACKGROUND: Kidney transplantation remains the optimal therapy for patients with end stage kidney disease (ESKD), though a small fraction of patients on dialysis are on organ waitlists. An important barrier to both preemptive kidney transplantation and successful waitlisting is timely referral to a kidney transplant center. We implemented a quality improvement strategy to improve outpatient kidney transplant referrals in a single center academic outpatient nephrology clinic. METHODS: Over a 3 month period (July 1-September 30, 2016), we assessed the baseline kidney transplantation referral rate at our outpatient nephrology clinic for patients 18-75 years old with an estimated glomerular filtration rate (eGFR) of less than 20 mL/min/1.73m2 (2 values over 90 days apart). Charts were manually reviewed by two reviewers to look for kidney transplant referrals and documentation of discussions about kidney transplantation. We then performed a root cause analysis to explore potential barriers to kidney transplantation. Our intervention began on July 1, 2017 and included the implementation of a column in the electronic medical record (EMR) which displayed the patient's last eGFR as part of the clinic schedule. In addition, physicians were given a document listing their patients to be seen that day with an eGFR of < 20 mL/min/1.73m2. Annual education sessions were also held to discuss the importance of timely kidney transplant referral. RESULTS: At baseline, 54 unique patients with eGFR ≤20 ml/min/1.73 m2 were identified who were seen in the Clinic between July 1, 2016 and September 30, 2016. 29.6% (16) eligible patients were referred for kidney transplantation evaluation. 69.5% (37) of these patients were not referred for kidney transplant evaluation. 46.3% (25) did not have documentation regarding kidney transplant in the EMR. nephrologist's most recent note. Following the intervention, 66 unique patients met criteria for eligibility for kidney transplant evaluation. Kidney transplant referrals increased to 60.6% (p <  0.001). CONCLUSIONS: Our pilot implementation study of a strategy to improve outpatient kidney transplant referrals showed that a free, simple, scalable intervention can significantly improve kidney transplant referrals in the outpatient setting. This intervention targeted the nephrologist's role in the transplant referral, and facilitated the process of patient recognition and performing the referral itself without significantly interrupting the workflow. Next steps include further investigation to study the impact of early referral to kidney transplant centers on preemptive and living donor kidney transplantation as well as successful waitlisting.

Advanced glycation end products are elevated in estrogen receptor-positive breast cancer patients, alter response to therapy, and can be targeted by lifestyle intervention.

PURPOSE: Lifestyle factors associated with personal behavior can alter tumor-associated biological pathways and thereby increase cancer risk, growth, and disease recurrence. Advanced glycation end products (AGEs) are reactive metabolites produced endogenously as a by-product of normal metabolism. A Western lifestyle also promotes AGE accumulation in the body which is associated with disease phenotypes through modification of the genome, protein crosslinking/dysfunction, and aberrant cell signaling. Given the links between lifestyle, AGEs, and disease, we examined the association between dietary-AGEs and breast cancer. METHODS: We evaluated AGE levels in bio-specimens from estrogen receptor-positive (ER+) and estrogen receptor-negative (ER-) breast cancer patients, examined their role in therapy resistance, and assessed the ability of lifestyle intervention to reduce circulating AGE levels in ER+ breast cancer survivors. RESULTS: An association between ER status and AGE levels was observed in tumor and serum samples. AGE treatment of ER+ breast cancer cells altered ERα phosphorylation and promoted resistance to tamoxifen therapy. In a proof of concept study, physical activity and dietary intervention was shown to be viable options for reducing circulating AGE levels in breast cancer survivors. CONCLUSIONS: There is a potential prognostic and therapeutic role for lifestyle derived AGEs in breast cancer. Given the potential benefits of lifestyle intervention on incidence and mortality, opportunities exist for the development of community health and nutritional programs aimed at reducing AGE exposure in order to improve breast cancer prevention and treatment outcomes.

Dietary Phosphate and the Forgotten Kidney Patient: A Critical Need for FDA Regulatory Action.

Careful dietary management that reduces high phosphate intake is recommended to slow the progression of chronic kidney disease (CKD) and prevent complications of CKD and may help reduce chronic disease risks such as incident CKD associated with high phosphate intake in the healthy general population. For patients treated with maintenance dialysis, control of serum phosphorus levels is considered a marker of good care and requires a coordinated plan that limits dietary phosphate intake, uses oral phosphate binders, and provides an adequate dialysis prescription. Even with traditional thrice-weekly hemodialysis or peritoneal dialysis, use of phosphate binders, and a concerted effort to limit dietary phosphate intake, adequately controlled serum phosphorus levels are not possible in all dialysis patients. Efforts to limit phosphate intake are thwarted by the underestimated and unquantified phosphate content of processed foods and some medications due to the hidden presence of phosphate additives or excipients added during processing or drug formulation. Effectively limiting phosphate intake could potentially be achieved through simple US Food and Drug Administration regulatory actions. Mandatory labeling of phosphate content on all packaged foods and drugs would enable identification of healthy low-phosphate foods and medications and permit critically important control of total phosphate intake. Simple changes in regulatory policy and labeling are warranted and would enable better management of dietary intake of phosphate at all stages of kidney disease, as well as potentially reduced health risks in the general population.

Alkali delivery in chronic hemodialysis: Would more acetate be helpful?

The dialysate alkali used in hemodialysis to replace low body alkali levels in end stage renal disease (ESRD) patients has changed over time from bicarbonate to acetate and finally back to bicarbonate with a small addition of acetate. The ideal way to replace alkali in dialysis patients remains uncertain. Elsewhere in this issue of the journal, Sargent and Gennari, who have contributed greatly to our understanding of dialysis and acid-base kinetics, suggest that decreasing the currently used concentration of bicarbonate while increasing concentration of acetate in the dialysate may be a much more physiological approach to alkali delivery during hemodialysis. These recommendations are based on results from a series of hemodialysis simulations using mathematical theoretical methods, with the assumption that acetate metabolism will be sufficiently delayed with the higher acetate dialysate and reduce the rate of correction of metabolic acidosis during dialysis. Although valuable in calling attention to the issues surrounding alkali repletion during hemodialysis, these postulations should be tested in clinical trials. We believe, however, that the available evidence suggests that the rate of gain of bicarbonate during dialysis with the higher acetate dialysate would not be slower and that the replacement of some dialysate bicarbonate with acetate will not alter alkali accretion or intradialytic pH.