Urinary Oxalate Excretion During Pregnancy in Primary Hyperoxaluria Type 1: A Report of 4 Cases.

Primary hyperoxaluria (PH) is a rare genetic disorder characterized by excessive oxalate production because of specific gene defects. PH1 is the most prevalent type, causing recurrent kidney stone disease and often leading to chronic kidney disease and kidney failure. Our previous study suggested that pregnancy did not adversely affect kidney function in female patients with PH. In this study, we identified 4 PH1 cases with urinary oxalate (UOx) measurements during pregnancy from the Rare Kidney Stone Consortium and Oxalosis and Hyperoxaluria Foundation PH registry to investigate UOx levels during pregnancy in patients with PH1. The PH Registry is approved by the Institutional Review Board of Mayo Clinic (Rochester, MN). All 4 showed a decrease in UOx during pregnancy when compared with before pregnancy and after delivery. These findings contrast with those of the general population, in which the UOx tends to increase during pregnancy because of a simultaneous physiological increase in the glomerular filtration rate. Elucidating the mechanism underlying reduced UOx during pregnancy in PH1 could suggest novel PH therapies. These findings could also affect the clinical management and have implications regarding the safety of withholding novel PH1-directed molecular therapies that currently have uncertain safety profiles during pregnancy. We highlight the need for additional data on urinary changes in patients with PH and other populations while pregnant to clarify changes in UOx throughout pregnancy.

Telehealth versus face-to-face visits: A comprehensive outpatient perspective-based cohort study of patients with kidney disease.

BACKGROUND: Telenephrology has become an important health care delivery modality during the COVID-19 pandemic. However, little is known about patient perspectives on the quality of care provided via telenephrology compared to face-to-face visits. We aimed to use objective data to study patients' perspectives on outpatient nephrology care received via telenephrology (phone and video) versus face-to-face visits. METHODS: We retrospectively studied adults who received care in the outpatient Nephrology & Hypertension division at Mayo Clinic, Rochester, from March to July 2020. We used a standardized survey methodology to evaluate patient satisfaction. The primary outcome was the percent of patients who responded with a score of good (4) or very good (5) on a 5-point Likert scale on survey questions that asked their perspectives on access to their nephrologist, relationship with care provider, their opinions on the telenephrology technology, and their overall assessment of the care received. Wilcoxon rank sum tests and chi-square tests were used as appropriate to compare telenephrology versus face-to-face visits. RESULTS: 3,486 of the patient encounters were face-to-face, 808 phone and 317 video visits. 443 patients responded to satisfaction surveys, and 21% of these had telenephrology encounters. Established patients made up 79.6% of telenephrology visits and 60.9% of face-to-face visits. There was no significant difference in patient perceived access to health care, satisfaction with their care provider, or overall quality of care between patients cared for via telenephrology versus face-to-face. Patient satisfaction was also equally high. CONCLUSIONS: Patient satisfaction was equally high amongst those patients seen face-to-face or via telenephrology.

Oxalosis Associated With High-Dose Vitamin C Ingestion in a Peritoneal Dialysis Patient.

We report a case of systemic oxalosis involving the eyes and joints due to long-term use of high-dose vitamin C in a patient receiving maintenance peritoneal dialysis (PD). This 76-year-old woman with autosomal dominant polycystic kidney disease underwent living unrelated kidney transplantation 10 years earlier. The transplant failed 6 months before presentation, and she initiated hemodialysis therapy before transitioning to PD therapy 4 months later. During the month before presentation, the patient noted worsening arthralgias and decreased vision. Ophthalmologic examination revealed proliferative retinopathy and calcium oxalate crystals. Plasma oxalate level was markedly elevated at 187 (reference range, <1.7) µmol/L, and urine oxalate-creatinine ratio was high (0.18mg/mg). The patient reported taking up to 4g of vitamin C per day for several years. Workup for causes of primary and secondary hyperoxaluria was otherwise negative. Vitamin C use was discontinued, and the patient transitioned to daily hemodialysis for 2 weeks. Plasma oxalate level before the dialysis session decreased but remained higher (30-53µmol/L) than typical for dialysis patients. Upon discharge, the patient remained on thrice-weekly hemodialysis therapy with stabilized vision and improved joint symptoms. This case highlights the risk of high-dose vitamin C use in patients with advanced chronic kidney disease, especially when maintained on PD therapy.

End of Life, Withdrawal, and Palliative Care Utilization among Patients Receiving Maintenance Hemodialysis Therapy.

BACKGROUND AND OBJECTIVES: Withdrawal from maintenance hemodialysis before death has become more common because of high disease and treatment burden. The study objective was to identify patient factors and examine the terminal course associated with hemodialysis withdrawal, and assess patterns of palliative care involvement before death among patients on maintenance hemodialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We designed an observational cohort study of adult patients on incident hemodialysis in a midwestern United States tertiary center, from January 2001 to November 2013, with death events through to November 2015. Logistic regression models evaluated associations between patient characteristics and withdrawal status and palliative care service utilization. RESULTS: Among 1226 patients, 536 died and 262 (49% of 536) withdrew. A random sample (10%; 52 out of 536) review of Death Notification Forms revealed 73% sensitivity for withdrawal. Risk factors for withdrawal before death included older age, white race, palliative care consultation within 6 months, hospitalization within 30 days, cerebrovascular disease, and no coronary artery disease. Most withdrawal decisions were made by patients (60%) or a family member (33%; surrogates). The majority withdrew either because of acute medical complications (51%) or failure to thrive/frailty (22%). After withdrawal, median time to death was 7 days (interquartile range, 4-11). In-hospital deaths were less common in the withdrawal group (34% versus 46% nonwithdrawal, P=0.003). A third (34%; 90 out of 262) of those that withdrew received palliative care services. Palliative care consultation in the withdrawal group was associated with longer hemodialysis duration (odds ratio, 1.19 per year; 95% confidence interval, 1.10 to 1.3; P<0.001), hospitalization within 30 days of death (odds ratio, 5.78; 95% confidence interval, 2.62 to 12.73; P<0.001), and death in hospital (odds ratio, 1.92; 95% confidence interval, 1.13 to 3.27; P=0.02). CONCLUSIONS: In this single-center study, the rate of hemodialysis withdrawals were twice the frequency previously described. Acute medical complications and frailty appeared to be driving factors. However, palliative care services were used in only a minority of patients.

Acute retinal vein occlusion and cystic fibrosis.

BACKGROUND: The ocular manifestations of cystic fibrosis typically present with surface irritation or nyctalopia due to Vitamin A deficiency, however, there have been two previous reports of patients with cystic fibrosis that developed retinal vein occlusions. These reports hypothesized that either elevated fibrinogen levels due to chronic infections or elevated homocysteine levels have predisposed patients with cystic fibrosis to develop retinal vein occlusions. CASE PRESENTATION: We present a case of a 35-year-old male with cystic fibrosis complicated by chronic sinusitis with no history of organ transplantation or chronic pulmonary infections who presented with an acute branch retinal vein occlusion in his left eye with associated macular edema. Evaluation revealed an elevated fibrinogen level, while the rest of his workup was relatively unremarkable including a normal homocysteine level. His vision remained 20/20 throughout his care and he did not require treatment of his macular edema. CONCLUSIONS: Patients with cystic fibrosis are at an increased risk of developing retinal vein occlusions likely due to a variety of systemic thrombogenic factors rather than a single risk factor which had been reported previously. Elevated fibrinogen levels in these patients may not be due to chronic infections, but inherent to the cystic fibrosis.

Performance on the Nephrology In-Training Examination and ABIM Nephrology Certification Examination Outcomes.

BACKGROUND AND OBJECTIVES: Medical specialty and subspecialty fellowship programs administer subject-specific in-training examinations to provide feedback about level of medical knowledge to fellows preparing for subsequent board certification. This study evaluated the association between the American Society of Nephrology In-Training Examination and the American Board of Internal Medicine Nephrology Certification Examination in terms of scores and passing status. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The study included 1684 nephrology fellows who completed the American Society of Nephrology In-Training Examination in their second year of fellowship training between 2009 and 2014. Regression analysis examined the association between In-Training Examination and first-time Nephrology Certification Examination scores as well as passing status relative to other standardized assessments. RESULTS: This cohort included primarily men (62%) and international medical school graduates (62%), and fellows had an average age of 32 years old at the time of first completing the Nephrology Certification Examination. An overwhelming majority (89%) passed the Nephrology Certification on their first attempt. In-Training Examination scores showed the strongest association with first-time Nephrology Certification Examination scores, accounting for approximately 50% of the total explained variance in the model. Each SD increase in In-Training Examination scores was associated with a difference of 30 U (95% confidence interval, 27 to 33) in certification performance. In-Training Examination scores also were significantly associated with passing status on the Nephrology Certification Examination on the first attempt (odds ratio, 3.46 per SD difference in the In-Training Examination; 95% confidence interval, 2.68 to 4.54). An In-Training Examination threshold of 375, approximately 1 SD below the mean, yielded a positive predictive value of 0.92 and a negative predictive value of 0.50. CONCLUSIONS: American Society of Nephrology In-Training Examination performance is significantly associated with American Board of Internal Medicine Nephrology Certification Examination score and passing status.

Science of health care delivery milestones for undergraduate medical education.

BACKGROUND: The changing healthcare landscape requires physicians to develop new knowledge and skills such as high-value care, systems improvement, population health, and team-based care, which together may be referred to as the Science of Health Care Delivery (SHCD). To engender public trust and confidence, educators must be able to meaningfully assess physicians' abilities in SHCD. We aimed to develop a novel set of SHCD milestones based on published Accreditation Council for Graduate Medical Education (ACGME) milestones that can be used by medical schools to assess medical students' competence in SHCD. METHODS: We reviewed all ACGME milestones for 25 specialties available in September 2013. We used an iterative, qualitative process to group the ACGME milestones into SHCD content domains, from which SHCD milestones were derived. The SHCD milestones were categorized within the current ACGME core competencies and were also mapped to Association of American Medical Colleges' Entrustable Professional Activities (AAMC EPAs). RESULTS: Fifteen SHCD sub-competencies and corresponding milestones are provided, grouped within ACGME core competencies and mapped to multiple AAMC EPAs. CONCLUSIONS: This novel set of milestones, grounded within the existing ACGME competencies, defines fundamental expectations within SHCD that can be used and adapted by medical schools in the assessment of medical students in this emerging curricular area. These milestones provide a blueprint for SHCD content and assessment as ongoing revisions to milestones and curricula occur.

Ways to Write a Milestone: Approaches to Operationalizing the Development of Competence in Graduate Medical Education.

PURPOSE: To identify approaches to operationalizing the development of competence in Accreditation Council for Graduate Medical Education (ACGME) milestones. METHOD: The authors reviewed all 25 "Milestone Project" documents available on the ACGME Web site on September 11, 2013, using an iterative process to identify approaches to operationalizing the development of competence in the milestones associated with each of 601 subcompetencies. RESULTS: Fifteen approaches were identified. Ten focused on attributes and activities of the learner, such as their ability to perform different, increasingly difficult tasks (304/601; 51%), perform a task better and faster (171/601; 45%), or perform a task more consistently (123/601; 20%). Two approaches focused on context, inferring competence from performing a task in increasingly difficult situations (236/601; 29%) or an expanding scope of engagement (169/601; 28%). Two used socially defined indicators of competence such as progression from "learning" to "teaching," "leading," or "role modeling" (271/601; 45%). One approach focused on the supervisor's role, inferring competence from a decreasing need for supervision or assistance (151/601; 25%). Multiple approaches were often combined within a single set of milestones (mean 3.9, SD 1.6). CONCLUSIONS: Initial ACGME milestones operationalize the development of competence in many ways. These findings offer insights into how physicians understand and assess the developmental progression of competence and an opportunity to consider how different approaches may affect the validity of milestone-based assessments. The results of this analysis can inform the work of educators developing or revising milestones, interpreting milestone data, or creating assessment tools to inform milestone-based performance measures.

Echocardiography Criteria for Structural Heart Disease in Patients With End-Stage Renal Disease Initiating Hemodialysis.

BACKGROUND: Cardiovascular disease among hemodialysis (HD) patients is linked to poor outcomes. The Acute Dialysis Quality Initiative Workgroup proposed echocardiographic (ECHO) criteria for structural heart disease (SHD) in dialysis patients. The association of SHD with important patient outcomes is not well defined. OBJECTIVES: This study sought to determine prevalence of ECHO-determined SHD and its association with survival among incident HD patients. METHODS: We analyzed patients who began chronic HD from 2001 to 2013 who underwent ECHO ≤1 month prior to or ≤3 months following initiation of HD (n = 654). RESULTS: Mean patient age was 66 ± 16 years, and 60% of patients were male. ECHO findings that met 1 or more and ≥3 of the new criteria were discovered in 87% and 54% of patients, respectively. Over a median of 2.4 years, 415 patients died: 108 (26%) died within 6 months. Five-year mortality was 62%. Age- and sex-adjusted structural heart disease variables associated with death were left ventricular ejection fraction (LVEF) ≤45% (hazard ratio [HR]: 1.48; confidence interval [CI]: 1.20 to 1.83) and right ventricular (RV) systolic dysfunction (HR: 1.68; CI: 1.35 to 2.07). An additive of higher death risk included LVEF ≤45% and RV systolic dysfunction rather than neither (HR: 2.04; CI: 1.57 to 2.67; p = 0.53 for test for interaction). Following adjustment for age, sex, race, diabetic kidney disease, and dialysis access, RV dysfunction was independently associated with death (HR: 1.66; CI 1.34 to 2.06; p < 0.001). CONCLUSIONS: SHD was common in our HD study population, and RV systolic dysfunction independently predicted mortality.

Pregnancy and Parental Leave During Graduate Medical Education.

PURPOSE: To understand the pregnancy, childbirth, and parental leave plans and experiences of trainees in multiple graduate medical education (GME) programs at a single institution. METHOD: In 2013, the authors developed and deployed a voluntary, Internet-based survey of trainees in 269 residency and fellowship programs across the three sites of the Mayo School of Graduate Medical Education. The survey assessed pregnancy-related issues, including use of relevant institutional policies, changes in work due to pregnancy, and activities during pregnancy and parental leave. The authors analyzed the responses to make comparisons across groups. RESULTS: Forty-two percent (644/1,516) of trainees responded. Less than half (264; 41%) had children, and 46 (7%) were currently pregnant (themselves or their partners). Among parents, 24 (of 73; 33%) women and 28 (of 81; 35%) men planned to have another child during their current training program, and 13 (18%) women and 14 (17%) men planned to do so during their next training program. Among nonparents, 40 (of 135; 30%) women and 36 (of 111; 32%) men planned pregnancies during their current training program, and 25 (19%) women and 14 (13%) men planned pregnancies during their next training program. Of respondents eligible for parental leave, 81 (of 83; 98%) women and 89 (of 101; 88%) men had used it. CONCLUSIONS: Approximately 40% of respondents planned to have children during their GME training; most will require family leave and institutional support. GME programs should pursue policies and practices to minimize the effects of these leaves on their workforce.

Predictors of outpatient kidney function recovery among patients who initiate hemodialysis in the hospital.

BACKGROUND: Recent policy clarifications by the Centers for Medicare & Medicaid Services have changed access to outpatient dialysis care at end-stage renal disease (ESRD) facilities for individuals with acute kidney injury in the United States. Tools to predict "ESRD" and "acute" status in terms of kidney function recovery among patients who previously initiated dialysis therapy in the hospital could help inform patient management decisions. STUDY DESIGN: Historical cohort study. SETTING & PARTICIPANTS: Incident hemodialysis patients in the Mayo Clinic Health System who initiated in-hospital renal replacement therapy (RRT) and continued outpatient dialysis following hospital dismissal (2006 through 2009). PREDICTOR: Baseline estimated glomerular filtration rate (eGFR), acute tubular necrosis from sepsis or surgery, heart failure, intensive care unit, and dialysis access. OUTCOMES: Kidney function recovery defined as sufficient kidney function for outpatient hemodialysis therapy discontinuation. RESULTS: Cohort consisted of 281 patients with a mean age of 64 years, 63% men, 45% with heart failure, and baseline eGFR≥30mL/min/1.73m(2) in 46%. During a median of 8 months, 52 (19%) recovered, most (94%) within 6 months. Higher baseline eGFR (HR per 10-mL/min/1.73m(2) increase eGFR, 1.27; 95% CI, 1.16-1.39; P<0.001), acute tubular necrosis from sepsis or surgery (HR, 3.34; 95% CI, 1.83-6.24; P<0.001), and heart failure (HR, 0.40; 95% CI, 0.19-0.78, P=0.007) were independent predictors of recovery within 6 months, whereas first RRT in the intensive care unit and catheter dialysis access were not. There was a positive interaction between absence of heart failure and eGFR≥30mL/min/1.73m(2) for predicting kidney function recovery (P<0.001). LIMITATIONS: Sample size. CONCLUSIONS: Kidney function recovery in the outpatient hemodialysis unit following in-hospital RRT initiation is not rare. As expected, higher baseline eGFR is an important determinant of recovery. However, patients with heart failure are less likely to recover even with a higher baseline eGFR. Consideration of these factors at hospital discharge informs decisions on ESRD status designation and long-term hemodialysis care.

Hypothyroidism and reversible kidney dysfunction: an essential relationship to recognize.

OBJECTIVE: To report 3 cases of reversible hypothyroidism-induced kidney dysfunction and review the interaction between these commonly encountered, yet seemingly disparate, conditions. METHODS: We describe the clinical course and laboratory and physical findings of 3 patients who presented with kidney dysfunction that improved after initiating thyroid hormone replacement therapy. We also review similar cases in the literature and discuss the pathophysiologic mechanisms. RESULTS: A 68-year-old male presented with classical signs and symptoms of hypothyroidism, including fatigue, confusion, and gait imbalance. Physical exam showed bradycardia, thyromegaly, slow mentation, and cracked, thin skin; he was found to have decreased kidney function. Second, a 42-year-old previously healthy female presented with bilateral hand swelling and elevated serum creatinine with an otherwise unremarkable physical exam. The third patient was a 72-year-old male with advanced heart failure on amiodarone and stage 3 chronic kidney disease who presented with fatigue, acute kidney injury, and lower extremity edema. In all cases, serum creatinine and thyroid-stimulating hormone (TSH) were elevated at presentation (1.4-3.0 mg/dL and 94.1-184 mIU/L respectively), and free thyroxine (T4) was low (undetectable-0.4 ng/dL). The initiation or increased dose of levothyroxine normalized serum creatinine to baseline within 2 to 10 months. CONCLUSION: Hypothyroidism and kidney dysfunction are both commonly encountered clinical entities, but the interplay between the thyroid gland and kidneys may be infrequently recalled, causing the reversible relationship between these 2 disorders to be missed.

Risk factors for hospitalization among older, incident haemodialysis patients.

AIMS: The number of elderly persons with end-stage renal disease is increasing with many requiring hospitalizations. This study examines the causes and predictors of hospitalization in older haemodialysis patients. METHODS: We reviewed hospitalizations of older (≥65 years) incident chronic haemodialysis patients initiating therapy between 1 January 2007 and 31 December 2009 under the care of a single Midwestern United States dialysis provider. RESULTS: Of 125 patients, the mean age was 76 ± 7 years and 72% were male. At first dialysis, 68% used a central venous catheter (CVC) and 51% were in the hospital. Mean follow-up was 1.8 ± 1.0 years. At least one hospitalization occurred in 89 (71%) patients and half of all patients were hospitalized once within the first 223 days. Total hospital admission rate was 1.48 per patient year with hospital days totalling 8.54 days per patient year. The three most common reasons for first admission were cardiac (33%), infection (18%) and gastrointestinal (12%). Predictors of future hospitalization included the first dialysis occurring in hospital (hazard ratios (HR) 2.1, 95% CI 1.4-3.3, P = 0.0005) and the use of a CVC at first haemodialysis (HR 2.6, CI 1.6-4.4, P < 0.0001). CONCLUSION: Hospitalizations are common in older incident haemodialysis patients. Access preparation and overall burden of illness leading to the initial hospitalization appear to play a role. Identification of additional factors associated with hospitalization will allow for focused interventions to reduce hospitalization rates and increase the value of care.

Differentiating scleroderma renal crisis from other causes of thrombotic microangiopathy in a postpartum patient.

Thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS), and scleroderma renal crisis (SRC) all present with features of thrombotic microangiopathy. Distinguishing among these entities is critical, however, as treatments differ and may be mutually exclusive. We describe the case of a 25-year-old woman with an undefined mixed connective tissue disease who presented 6 weeks post-partum with fever, transient aphasia, thrombocytopenia, hemolytic anemia, and acute kidney injury eventually requiring initiation of hemodialysis. Renal biopsy revealed thrombotic microangiopathy. Renal function did not improve despite immediate initiation of plasma exchange, and an angiotensin-converting enzyme (ACE) inhibitor was initiated following discontinuation of plasma exchange. At last follow up, she remained dialysis dependent. Due to the myriad causes of thrombotic microangiopathy and potential for diagnostic uncertainty, the patient's response to therapy should be closely monitored and used to guide modification of therapy.

Mentorship programs for gastroenterology program directors: is there an unmet need?

GOALS: The purpose of this study was to determine whether a need exists for mentorship programs among gastroenterology (GI) fellowship program directors (PDs), to investigate specific areas where mentoring would be helpful, and to assess the willingness to establish mentoring relationships. BACKGROUND: There is no research regarding mentorship for GI fellowship PDs or associate/assistant program directors (APDs). Although some mentoring resources currently exist, it is not clear whether they fulfill the needs of PDs and APDs. STUDY: Mentorship needs were assessed using an electronic survey sent to GI PDs and APDs who subscribe to the American Gastroenterological Association PDs' list server. RESULTS: Fifty-nine GI PDs (47.6% completion rate) and 18 APDs returned the survey. Seventy-five percent of PDs and 78% of APDs thought a formal mentorship program would be beneficial to those starting their role. Content areas were identified where a mentor would be most helpful included Accreditation Council for Graduate Medical Education competencies, accreditation requirements, curriculum development, and site visit preparation. CONCLUSIONS: Current GI PDs and APDs felt a mentoring program would be beneficial, despite the availability of several resources including web sites and meetings. Our results suggest that there remains an unmet need for mentorship resources among GI PDs and APDs.