Faculty Bibliography

Cystic fibrosis (CF) may predispose patients to urinary stone disease (USD), but reported prevalence of USD in patients with CF in previous small studies is variable. To date, analysis of risk factors for USD within the CF population has been limited. We studied 29,396 patients in the Cystic Fibrosis Foundation Patient Registry to calculate age and sex-stratified prevalence of USD. For adult patients, we examined age and multivariable-adjusted cross-sectional associations between demographic and clinical factors, CFTR mutation class, and prevalent USD. Prevalence of USD was 0.4% (95% CI 0.3-0.5%) under age 18 years, 3.1% (2.7-3.6%) at 18-24 years, 6.4% (5.8-7.1%) at 25-34 years, 7.5% (6.5-8.5%) at 35-44 years, and 6.7% (5.8-7.8%) at 45 years and older. Prevalence for women was higher than men at younger (< 45 years) but not older ages (P value for interaction < 0.0005). Multivariable odds of prevalent USD were significantly increased for severe CFTR mutations, OR 1.53 (1.14-2.06), diabetes, OR 1.24 (1.03-1.50), hypertension, OR 1.58 (1.29-1.93), and chronic macrolide therapy, OR 1.27 (1.07-1.52). BMI was not associated with USD. USD prevalence in CF is similar to that in the general population. With the exception of BMI, known risk factors for USD in the general population also appear to be important for patients with CF. We identified several novel associations in CF patients, including greater prevalence of USD in individuals with severe CFTR mutations and among young women.

The incidence of kidney stones is increasing in the US population. Oxalate, a major factor for stone formation, is degraded by gut bacteria reducing its intestinal absorption. Intestinal O. formigenes colonization has been associated with a lower risk for recurrent kidney stones in humans. In the current study, we used a clinical trial of the eradication of Helicobacter pylori to assess the effects of an antibiotic course on O. formigenes colonization, urine electrolytes, and the composition of the intestinal microbiome. Of 69 healthy adult subjects recruited, 19 received antibiotics for H. pylori eradication, while 46 were followed as controls. Serial fecal samples were examined for O. formigenes presence and microbiota characteristics. Urine, collected serially fasting and following a standard meal, was tested for oxalate and electrolyte concentrations. O. formigenes prevalence was 50%. Colonization was significantly and persistently suppressed in antibiotic-exposed subjects but remained stable in controls. Urinary pH increased after antibiotics, but urinary oxalate did not differ between the control and treatment groups. In subjects not on antibiotics, the O. formigenes-positive samples had higher alpha-diversity and significantly differed in Beta-diversity from the O. formigenes-negative samples. Specific taxa varied in abundance in relation to urinary oxalate levels. These studies identified significant antibiotic effects on O. formigenes colonization and urinary electrolytes and showed that overall microbiome structure differed in subjects according to O. formigenes presence. Identifying a consortium of bacterial taxa associated with urinary oxalate may provide clues for the primary prevention of kidney stones in healthy adults.

BACKGROUND:Chronic kidney disease (CKD) is often complicated by anaemia, which is associated with disease progression and increased hospital visits, decreased quality of life, and increased mortality. METHODS:A comprehensive literature search of English language peer-reviewed articles in PubMed/MedLine published between 1998 and 2020 related to the treatment of anaemia of CKD was conducted. The United States Renal Database System and Dialysis Outcomes and Practice Patterns Study (DOPPS) data reports, the Centers for Disease Control and Prevention and the US Food and Drug Administration websites, and published congress abstracts in 2020 were surveyed for relevant information. RESULTS:Subgroups of patients with anaemia of CKD present a clinical challenge throughout the disease spectrum, including those with end-stage kidney disease, advanced age or resistance to or ineligibility for current standards of care (ie, oral or intravenous iron supplementation, erythropoietin-stimulating agents and red blood cell transfusions). In addition, those with an increased risk of adverse events because of comorbid conditions, such as cardiovascular diseases or diabetes, comprise special populations of patients with an unmet need for interventions to improve clinical outcomes. These comorbidities must be managed in parallel and may have a synergistic effect on overall disease severity. CONCLUSIONS:Several therapies provide promising opportunities to address gaps with a standard of care, including hypoxia-inducible factor prolyl hydroxylase inhibitors, which stimulate haematopoiesis through promoting modest increases in serum erythropoietin and improved iron homeostasis. The critical issues in the management of anaemia of CKD in these challenging phenotypes and the clinical utility of new therapeutic agents in development for the treatment of anaemia of CKD should be assessed and the information should be made available to healthcare providers.

OBJECTIVE:The objective of the study was to evaluate the feasibility and acceptability of mobile health (mHealth) phosphorus management programs in hemodialysis (HD) patients. METHODS:Patients receiving thrice-weekly HD who had 3-month average serum phosphorus of >5.5 mg/dL were randomized to one of the three self-directed phosphorus management programs delivered using tablet PCs: (1) educational videos and handouts (Education), (2) education intervention plus mobile self-monitoring with email feedback (Monitoring), or (3) education and monitoring interventions plus social cognitive theory-based behavioral videos (Combined). Feasibility and acceptability were assessed based on enrollment and retention and training needs (feasibility) and adherence to self-monitoring and reported satisfaction (acceptability). RESULTS:Of 312 patients, 56 expressed interest, and 40 were enrolled. The majority of participants (80%) completed the 6-month study; none withdrew for intervention-related reasons. The Monitoring and Combined groups received 44 ± 15 minutes of technology training, which was considered adequate by most (75%). Self-monitoring rates were initially high, with 78% and 71% of the participants recording at least one meal and phosphate binder in week 1, respectively, but decreased over time to 15% and 9% in the final week. Most participants reported that self-monitoring helped them stay motivated (64%), track nutrients (80%), and understand how to change diet (76%), and nearly two-thirds of participants (64%) stated that they would like to continue using the tablet PC to manage their health. However, few participants (16%) indicated that self-monitoring was worth the effort. The Monitoring and Combined groups did not differ from the Education group in study outcomes. CONCLUSION/CONCLUSIONS:Although the mHealth programs were generally well received, self-monitoring rates decreased substantially over time and were unaffected by social cognitive theory-based videos. Self-directed mHealth programs may be a useful adjunct to standard care but should be compared to more resource intensive programs (e.g., involving more "live" contact with a dietitian) to determine overall cost-effectiveness and role in HD care.

INTRODUCTION/BACKGROUND:The term "lactic acidosis" reinforces the misconception that lactate contributes to acidemia. Although it is common to discover an anion gap acidosis with a concomitant elevated lactate concentration, the two are not mutually dependent. CASE REPORT/METHODS:Here we describe two patients exhibiting high lactate concentrations in the setting of metabolic alkalemia. CONCLUSION/CONCLUSIONS:Lactate is not necessarily the direct cause of acid-base disturbances, and there is no fixed relationship between lactate and the anion gap or between lactate and pH. The term "metabolic acidosis with hyperlactatemia" is more specific than "lactic acidosis" and thus more appropriate.

BACKGROUND: Primary hyperoxaluria (PH) is a family of rare genetic disorders affecting 1-3 per 1 million persons globally. PH causes hepatic oxalate overproduction leading to increased urinary oxalate excretion, that can result in frequent kidney stone events, progression to end-stage kidney disease (ESKD) and then other systemic morbidities.
OBJECTIVE(S): To assess the burden of PH among patients and caregivers with respect to healthcare resource utilization (HRU), quality of life (QoL) and work productivity.
METHOD(S): An IRB-approved web survey was conducted among adults (>= 18 years) with PH, and caregivers of children (< 17 years) with PH in the US. Participants were asked about their or their child's medical care, HRU and QoL. The Kidney Disease Quality of Life (KDQOL-36TM: range 0-100, higher score = better QOL) and Work Productivity and Activity Impairment (WPAI: range 0-100%, higher score = more impairment) questionnaires were administered. Descriptive statistics summarized the responses.
RESULT(S): Patient sample (n = 21) comprised 7 adults (median age 42 years) and 14 children (median age 8 years). Patients' HRU consisted of visits to nephrologists (81%), urologists (67%) and ophthalmologists (10%). 33% visited the emergency room and 29% were hospitalized. Patients on dialysis (n = 5) spent a median of 24 hours per week receiving dialysis. PH complications included kidney stone events (95%), pain (71%, nearly all moderate-severe) and nephrocalcinosis (48%). 48% of all patients experienced PH-related anxiety. Adult patients' mean KDQOL-36TM domain scores (burden, symptoms/problems and effects of kidney disease) were 38 (SD = 23), 77 (SD = 23) and 65 (SD = 26), respectively. Employed adult patients (n = 4) reported 25% presenteeism (reduced productivity at work) on average based on the WPAI. Children missed a median of 15 hours/month of school due to their PH. Caregivers (n = 13) experienced moderate-severe anxiety about the possibility of future PH-related outcomes (i.e., kidney stones [54%], kidney disease progression [62%] and ESKD [62%]) for their child. Employed caregivers (n = 9) reported 28% presenteeism on average based on the WPAI.
CONCLUSION(S): This research quantifies the burden of PH in terms of HRU, QoL and productivity for patients and caregivers. Patients experienced considerable clinical sequalae associated with PH, such as kidney stones and pain, which appear to negatively affect these outcomes. Numerous clinician visits indicated an intensive level of care. Further, PH burden goes beyond the patient, as evidenced by caregiver burden, including anxiety and impact on work productivity

PURPOSE OF REVIEW:Respiratory acidosis is commonly present in patients with respiratory failure. The usual treatment of hypercapnia is to increase ventilation. During the recent surge of COVID-19, respiratory acidosis unresponsive to increased mechanical ventilatory support was common. Increasing mechanical ventilation comes at the expense of barotrauma and hemodynamic compromise from increasing positive end-expiratory pressures or minute ventilation. Treating acute respiratory acidemia with sodium bicarbonate remains controversial. RECENT FINDINGS:There are no randomized controlled trials of administration of sodium bicarbonate for respiratory acidemia. A recent review concluded that alkali therapy for mixed respiratory and metabolic acidosis might be useful but was based on the conflicting and not conclusive literature regarding metabolic acidosis. This strategy should not be extrapolated to treatment of respiratory acidemia. Low tidal volume ventilation in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) has beneficial effects associated with permissive hypercapnia. Whether the putative benefits will be negated by administration of alkali is not known. Hypercapnic acidosis is well tolerated, with few adverse effects as long as tissue perfusion and oxygenation are maintained. SUMMARY:There is a lack of clinical evidence that administration of sodium bicarbonate for respiratory acidosis has a net benefit; in fact, there are potential risks associated with it.

OBJECTIVE:To assess the effectiveness of an empiric approach to metabolic stone prevention. METHODS:Using medical claims from a cohort of working age adults with kidney stone diagnoses (2008-2017), we identified the subset who were prescribed thiazides, alkali therapy, or allopurinol-collectively known as preventive pharmacologic therapy (PPT). We distinguished between those who had 24-hour urine testing prior to initiating PPT (selective therapy) from those without it (empiric therapy). We conducted a survival analysis for time to first recurrence for stone-related events, including ED visits, hospitalizations, and surgery, up to 2 years after initiating PPT. RESULTS:Of 10,125 patients identified, 2744 (27%) and 7381 (73%) received selective and empiric therapy, respectively. The overall frequency of any stone-related event was 11%, and this did not differ between the 2 groups on bivariate analysis (P = .29). After adjusting for sociodemographic factors, comorbidities, medication class, and adherence, there was no difference in the hazard of a stone-related event between the selective and empiric therapy groups (hazard ratio, 0.97; 95% confidence interval, 0.84-1.12). When considered individually, the frequency of ED visits, hospitalizations, and surgeries did not differ between groups. Greater adherence to PPT and older age were associated with a lower hazard of a stone-related event (both P < .05). CONCLUSION/CONCLUSIONS:Compared to empiric therapy, PPT guided by 24-hour urine testing, on average, is not associated with a lower hazard of a stone-related event. These results suggest a need to identify kidney stone patients who benefit from 24-hour urine testing.

The Consensus Group deliberated on a number of questions concerning urine and stone analysis over a period of months, and then met to develop consensus. The Group concluded that analyses of urine and stones should be routine in the diagnosis and treatment of urinary stone diseases. At present, the 24-h urine is the most useful type of urine collection, and accepted methods for analysis are described. Patient education is also important for obtaining a proper urine sample. Graphical methods for reporting urine analysis results can be helpful both for the physician and for educating the patient as to proper dietary changes that could be beneficial. Proper analysis of stones is also essential for diagnosis and management of patients. The Consensus Group also agreed that research has shown that evaluation of urinary crystals could be very valuable, but the Group also recognizes that existing methods for assessment of crystalluria do not allow this to be part of stone treatment in many places.