Infective Endocarditis-Associated Pauci-Immune Glomerulonephritis in a Patient With Cryoglobulinemia.

Small-vessel vasculitis has a broad differential with similar clinical presentation and laboratory abnormalities, including petechial rashes, neurologic symptoms, glomerulonephritis, and abnormal inflammatory markers. Biopsy-based diagnosis is critical as the treatment varies by etiology. We report a case of a 41-year-old man with diagnosed cryoglobulinemia and hepatitis C presenting with a petechial rash, altered mental status, and acute kidney injury and ultimately found to have proteinase 3 (PR3)-antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis secondary to infective endocarditis. Skin biopsy was consistent with resolving, but nonspecific vasculitis and MRI showed foci of hemosiderin deposition concerning vasculitic lesions. Blood cultures grew Enterococcus faecalis, and he was treated with IV antibiotics. Kidney biopsy showed pauci-immune necrotizing focal segmental glomerulonephritis (GN) and diffuse acute tubular necrosis (ATN). After blood cultures cleared, he was initially treated with mycophenolate for worsening renal function. When the patient stopped antibiotics unexpectedly, his kidney function worsened and improved only after immunosuppression was stopped and antibiotics were restarted. This case highlights the importance of renal biopsy in patients with multiple potential etiologies of GN. The case resolution also reinforces that patients with infective endocarditis causing ANCA-associated GN should be treated with antibiotics in addition to, and possibly instead of, immunosuppression.

Supportive Care and Symptom Management for Patients With Immunoglobulin Light Chain (AL) Amyloidosis.

Immunoglobulin light chain (AL) amyloidosis is a disorder of clonal plasma cells characterized by deposition of amyloid fibrils in a variety of tissues, leading to end-organ injury. Renal or cardiac involvement is most common, though any organ outside the central nervous system can develop amyloid deposition, and symptomatic presentations may consequently vary. The variability and subtlety of initial clinical presentations may contribute to delayed diagnoses, and organ involvement is often quite advanced and symptomatic by the time a diagnosis is established. Additionally, while organ function can improve with plasma-cell-directed therapy, such improvement lags behind hematologic response. Consequently, highly effective supportive care, including symptom management, is essential to improve quality of life and to maximize both tolerance of therapy and likelihood of survival. Considering the systemic nature of the disease, close collaboration between clinicians is essential for effective management.

One-Year Linear Trajectories of Symptoms, Physical Functioning, Cognitive Functioning, Emotional Well-being, and Spiritual Well-being Among Patients Receiving Dialysis.

BACKGROUND: This study evaluated 1-year linear trajectories of patient-reported dimensions of quality of life among patients receiving dialysis. STUDY DESIGN: Longitudinal observational study. SETTING & PARTICIPANTS: 227 patients recruited from 12 dialysis centers. FACTORS: Sociodemographic and clinical characteristics. MEASUREMENTS/OUTCOMES: Participants completed an hour-long interview monthly for 12 months. Each interview included patient-reported outcome measures of overall symptoms (Edmonton Symptom Assessment System), physical functioning (Activities of Daily Living/Instrumental Activities of Daily Living), cognitive functioning (Patient's Assessment of Own Functioning Inventory), emotional well-being (Center for Epidemiologic Studies Depression Scale, State Anxiety Inventory, and Positive and Negative Affect Schedule), and spiritual well-being (Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale). For each dimension, linear and generalized linear mixed-effects models were used. Linear trajectories of the 5 dimensions were jointly modeled as a multivariate outcome over time. RESULTS: Although dimension scores fluctuated greatly from month to month, overall symptoms, cognitive functioning, emotional well-being, and spiritual well-being improved over time. Older compared with younger participants reported higher scores across all dimensions (all P<0.05). Higher comorbidity scores were associated with worse scores in most dimensions (all P<0.01). Nonwhite participants reported better spiritual well-being compared with their white counterparts (P<0.01). Clustering analysis of dimension scores revealed 2 distinctive clusters. Cluster 1 was characterized by better scores than those of cluster 2 in nearly all dimensions at baseline and by gradual improvement over time. LIMITATIONS: Study was conducted in a single region of the United States and included mostly patients with high levels of function across the dimensions of quality of life studied. CONCLUSIONS: Multidimensional patient-reported quality of life varies widely from month to month regardless of whether overall trajectories improve or worsen over time. Additional research is needed to identify the best approaches to incorporate patient-reported outcome measures into dialysis care.

Racial Differences in Outcomes of an Advance Care Planning Intervention for Dialysis Patients and Their Surrogates.

BACKGROUND: African Americans' beliefs about end-of-life care may differ from those of whites, but racial differences in advance care planning (ACP) outcomes are unknown. OBJECTIVE: The aim of this study was to compare the efficacy of an ACP intervention on preparation for end-of-life decision making and post-bereavement outcomes for African Americans and whites on dialysis. METHOD: A secondary analysis of data from a randomized trial comparing an ACP intervention (Sharing Patient's Illness Representations to Increase Trust [SPIRIT]) with usual care was conducted. There were 420 participants, 210 patient-surrogate dyads (67.4% African Americans), recruited from 20 dialysis centers in North Carolina. The outcomes of preparation for end-of-life decision making included dyad congruence on goals of care, surrogate decision-making confidence, a composite of the two, and patient decisional conflict assessed at 2, 6, and 12 months post-intervention. Surrogate bereavement outcomes included anxiety, depression, and post-traumatic distress symptoms assessed at 2 weeks, and at 3 and 6 months after the patient's death. RESULTS: SPIRIT was superior to usual care in improving dyad congruence (odds ration [OR] = 2.31, p = 0.018), surrogate decision-making confidence (ß = 0.18, p = 0.021), and the composite (OR = 2.19, p = 0.028) 2 months post-intervention, but only for African Americans. SPIRIT reduced patient decisional conflict at 6 months for whites and at 12 months for African Americans. Finally, SPIRIT was superior to usual care in reducing surrogates' bereavement depressive symptoms for African Americans but not for whites (ß = -3.49, p = 0.003). CONCLUSION: SPIRIT was effective in improving preparation for end-of-life decision-making and post-bereavement outcomes in African Americans.

Depressive symptom severity, contributing factors, and self-management among chronic dialysis patients.

Despite the high prevalence of depressive symptoms in patients receiving chronic dialysis, there has been inadequate attention to patient-related barriers to management of depressive symptoms, such as factors identified by these patients as contributing to their symptoms, and how they responded to the symptoms. Participants (N = 210) in an ongoing longitudinal observational study of multidimensional quality of life in patients receiving chronic dialysis completed a battery of measures monthly for 12 months. For each patient at each measurement point, an event report was generated if he or she scored outside of the normal range on the depressive symptom scale (Center for Epidemiologic Studies Depression Scale-Short Form [CESD-SF] ≥10) or expressed suicidal ideation. Of the 210 participants, 100 (47.6%) had a CESD-SF score ≥10 at least once resulting in 290 event reports. Of these 100 participants, 15 (15%) had also reported suicidal ideation in addition to having depressive symptoms. The most frequently stated contributing factors included "managing comorbid conditions and complications" (56 event reports, 19.3%), "being on dialysis" (50, 17.2%), "family or other personal issues" (37, 12.8%), and "financial difficulties" (31, 10.7%). On 11 event reports (3.8%) participants had been unaware of their depressive symptoms. On 119 event reports (41%) participants reported that they discussed these symptoms with their dialysis care providers or primary care providers, while on 171 event reports (59%) symptoms were not discussed with their health-care providers. The prevalence of depressive symptoms is high and many patients lack knowledge about effective self-management strategies.

Clinical Features of Reported Ethylene Glycol Exposures in the United States.

BACKGROUND: Ethylene glycol is highly toxic and represents an important cause of poisonings worldwide. Toxicity can result in central nervous system dysfunction, cardiovascular compromise, elevated anion gap metabolic acidosis and acute kidney injury. Many states have passed laws requiring addition of the bittering agent, denatonium benzoate, to ethylene glycol solutions to reduce severity of exposures. The objectives of this study were to identify differences between unintentional and intentional exposures and to evaluate the utility of denatonium benzoate as a deterrent. METHODS AND FINDINGS: Using the National Poison Data System, we performed a retrospective analysis of reported cases of ethylene glycol exposures from January 2006 to December 2013. Outcome classification was summed for intentionality and used as a basis for comparison of effect groups. There were 45,097 cases of ethylene glycol exposures resulting in 154 deaths. Individuals more likely to experience major effects or death were older, male, and presented with more severe symptoms requiring higher levels of care. Latitude and season did not correlate with increased exposures; however, there were more exposures in rural areas. Denatonium benzoate use appeared to have no effect on exposure severity or number. CONCLUSION: Deaths due to ethylene glycol exposure were uncommon; however, there were major clinical effects and more exposures in rural areas. Addition of denatonium benzoate was not associated with a reduction in exposures. Alternative means to deter ingestion are needed. These findings suggest the need to consider replacing ethylene glycol with alternative and less toxic agents.

Advance care planning and end-of-life decision making in dialysis: a randomized controlled trial targeting patients and their surrogates.

BACKGROUND: Few trials have examined long-term outcomes of advance care planning (ACP) interventions. We examined the efficacy of an ACP intervention on preparation for end-of-life decision making for dialysis patients and surrogates and for surrogates' bereavement outcomes. STUDY DESIGN: A randomized trial compared an ACP intervention (Sharing Patient's Illness Representations to Increase Trust [SPIRIT]) to usual care alone, with blinded outcome assessments. SETTING & PARTICIPANTS: 420 participants (210 dyads of prevalent dialysis patients and their surrogates) from 20 dialysis centers. INTERVENTION: Every dyad received usual care. Those randomly assigned to SPIRIT had an in-depth ACP discussion at the center and a follow-up session at home 2 weeks later. PRIMARY OUTCOMES: preparation for end-of-life decision making, assessed for 12 months, included dyad congruence on goals of care at end of life, patient decisional conflict, surrogate decision-making confidence, and a composite of congruence and surrogate decision-making confidence. SECONDARY OUTCOMES: bereavement outcomes, assessed for 6 months, included anxiety, depression, and posttraumatic distress symptoms completed by surrogates after patient death. PRIMARY OUTCOMES: adjusting for time and baseline values, dyad congruence (OR, 1.89; 95% CI, 1.1-3.3), surrogate decision-making confidence (ß=0.13; 95% CI, 0.01-0.24), and the composite (OR, 1.82; 95% CI, 1.0-3.2) were better in SPIRIT than controls, but patient decisional conflict did not differ between groups (ß=-0.01; 95% CI, -0.12 to 0.10). SECONDARY OUTCOMES: 45 patients died during the study. Surrogates in SPIRIT had less anxiety (ß=-1.13; 95% CI, -2.23 to -0.03), depression (ß=-2.54; 95% CI, -4.34 to -0.74), and posttraumatic distress (ß=-5.75; 95% CI, -10.9 to -0.64) than controls. LIMITATIONS: Study was conducted in a single US region. CONCLUSIONS: SPIRIT was associated with improvements in dyad preparation for end-of-life decision making and surrogate bereavement outcomes.

Patient-reported cognitive functioning and daily functioning in chronic dialysis patients.

Subjective cognitive impairment negatively affects daily functioning, health-related quality of life, and health care consumption, and is predictive of future cognitive decline in many patient populations. However, no subjective measures of multidimensional cognitive functioning have been evaluated for dialysis patients. Our purposes were to examine (1) the association between patient-reported (subjective) cognitive functioning and objective cognitive functioning and (2) the relationships between subjective and objective cognitive functioning and everyday functioning of dialysis patients. We used baseline data from an ongoing longitudinal observational study of trajectories in dialysis patients' multidimensional quality of life. One hundred thirty-five patients completed a telephone-based neuropsychological battery (Brief Test of Adult Cognition by Telephone, a measure of objective cognitive functioning), a measure of subjective cognitive functioning (Patient's Assessment of Own Functioning Inventory), and measures of everyday functioning (Activities of Daily Living [ADL] and Instrumental Activities of Daily Living [IADL] scales). After controlling for age and education, there was a modest correlation (r = 0.33, P > 0.001) between subjective and objective cognitive functioning. Multivariate logistic regression models showed subjective, but not objective, cognitive functioning was a significant predictor of both ADLs and IADLs. The findings suggest the potential clinical value of subjective measures of cognitive functioning, not to replace objective measures or diagnostic tests, but rather to optimize the meaningfulness of clinical assessment and management.

Variable clinical presentation of an MUC1 mutation causing medullary cystic kidney disease type 1.

BACKGROUND AND OBJECTIVES: The genetic cause of medullary cystic kidney disease type 1 was recently identified as a cytosine insertion in the variable number of tandem repeat region of MUC1 encoding mucoprotein-1 (MUC1), a protein that is present in skin, breast, and lung tissue, the gastrointestinal tract, and the distal tubules of the kidney. The purpose of this investigation was to analyze the clinical characteristics of families and individuals with this mutation. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Families with autosomal dominant interstitial kidney disease were referred for genetic analysis over a 14-year period. Families without UMOD or REN mutations prospectively underwent genotyping for the presence of the MUC1 mutation. Clinical characteristics were retrospectively evaluated in individuals with the MUC1 mutation and historically affected individuals (persons who were both related to genetically affected individuals in such a way that ensured that they could be genetically affected and had a history of CKD stage IV or kidney failure resulting in death, dialysis, or transplantation). RESULTS: Twenty-four families were identified with the MUC1 mutation. Of 186 family members undergoing MUC1 mutational analysis, the mutation was identified in 95 individuals, 91 individuals did not have the mutation, and111 individuals were identified as historically affected. Individuals with the MUC1 mutation suffered from chronic kidney failure with a widely variable age of onset of end stage kidney disease ranging from 16 to >80 years. Urinalyses revealed minimal protein and no blood. Ultrasounds of 35 individuals showed no medullary cysts. There were no clinical manifestations of the MUC1 mutation detected in the breasts, skin, respiratory system, or gastrointestinal tract. CONCLUSION: MUC1 mutation results in progressive chronic kidney failure with a bland urinary sediment. The age of onset of end stage kidney disease is highly variable, suggesting that gene-gene or gene-environment interactions contribute to phenotypic variability.

Management of ethical issues related to care of seriously ill dialysis patients in free-standing facilities.

CONTEXT: There are few data on the frequency and current management of clinical ethical issues related to care of seriously ill dialysis patients in free-standing dialysis facilities. OBJECTIVES: To examine the extent of clinical ethical challenges experienced by care providers in free-standing facilities and their perceptions about how those issues are managed. METHODS: A total of 183 care providers recruited from 15 facilities in North Carolina completed a survey regarding the occurrence and management of ethical issues in the past year. Care plan meetings were observed at four of the facilities for three consecutive months. Also, current policies and procedures at each of the facilities were reviewed. RESULTS: The two most frequently experienced challenges involved dialyzing frail patients with multiple comorbidities and caring for disruptive/difficult patients. The most common ways of managing ethical issues were discussions in care plan meetings (n = 47) or discussions with the clinic manager (n = 47). Although policies were in place to guide management of some of the challenges, respondents were often not aware of those policies. Also, although participants reported that ethical issues related to dialyzing undocumented immigrants were fairly common, no facility had a policy for managing this challenge. Participants suggested that all staff obtain training in clinical ethics and communication skills, facilities develop ethics teams, and there be clear policies to guide management of ethical challenges. CONCLUSION: The scope of ethical challenges was extensive, how these challenges were managed varied widely, and there were limited resources for assistance. Multifaceted efforts, encompassing endeavors at the individual, facility, organization, and national levels, are needed to support staff in improving the management of ethical challenges in dialysis facilities.

Lessons learned from the ASN Renal Educator Listserv and survey.

Nephrology ranks next to last in career choices among US medical school graduates. The American Society of Nephrology established a Workforce Committee to help address this issue. Surveys of US medical students indicate that experiences during kidney pathophysiology courses in the preclerkship years may impact their decision to consider a career in nephrology. In October of 2011, preclinical kidney physiology and pathophysiology course directors at US medical schools were surveyed about teaching methods, curricular content, resources, and institutional support for teaching to identify what worked well and what impairs their teaching efforts. A Listserv of these educators, the American Society of Nephrology Renal Educators Listserv, was used to electronically administer the survey. Course leaders from 62 of 114 (54.4%) surveyed medical schools responded. Most of these educators are nephrologists, but physiologists and other clinicians also lead courses; 60% of course directors noted that lectures are videotaped, resulting in decreased attendance. A range of resources is used: 68% use audience response systems, 16% use the simulation center, and none of the educators indicated use of social media (such as Twitter or Facebook); 50% of respondents receive no remuneration, and 68% receive no full-time equivalent for their efforts. Audience response systems, virtual microscopy, and flash animations were identified as valuable teaching tools. Course directors, during subsequent dialogue on the American Society of Nephrology Renal Educators Listserv, have cited incorporation of case scenarios and integration of clinical exposure during preclinical years as methods that inspired interest. Hopefully, adoption of such approaches will ultimately serve to stimulate interest in nephrology.

Psychological symptoms and end-of-life decision making confidencein surrogate decision-makers of dialysis patients.

This cross-sectional descriptive study explored surrogate decision-makers' psychological symptoms and their own assessment of decision-making abilities before actual involvement in end-of-life decision-making for their loved ones. One hundred-twenty dialysis patients' surrogates (79 African Americans and 41 Caucasians) completed scales measuring decision-making confidence, anxiety and depression, Post-Traumatic Symptoms (PTSS), and a sociodemographic questionnaire. Forty-two (35%) and 14 (11.7%) surrogates showed abnormal scores on anxiety and depression, respectively. Seven (5.8%) surrogates showed abnormal scores on PTSS. While surrogates decision making confidence was high (M=17.70, SD=2.88), there was no association between decision-making confidence and the three psychological variables. Surrogates' confidence was associated only with the quality of relationship with patient (r=0.33, p=0.001).

The Calcimimetic agent AMG 073 lowers plasma parathyroid hormone levels in hemodialysis patients with secondary hyperparathyroidism.

Treatment with vitamin D sterols can lower plasma parathyroid hormone (PTH) in many patients with secondary hyperparathyroidism due to end-stage renal disease, but hypercalcemia, hyperphosphatemia, or both often develop during treatment. As such, alternative therapeutic approaches to managing excess PTH secretion are needed. Calcimimetic agents directly inhibit PTH secretion by activating the calcium-sensing receptor in the parathyroid glands, but clinical experience with them is limited. Fifty-two hemodialysis patients with secondary hyperparathyroidism were given single orally administered doses of the calcimimetic agent AMG 073 ranging from 5 to 100 mg, or placebo. Plasma PTH levels decreased 2 h after 25-, 50-, 75-, or 100-mg doses, falling by a maximum of 43 +/- 29%, 40 +/- 36%, 54 +/- 28%, or 55 +/- 39%, respectively. Plasma PTH levels decreased in all patients given doses of > or =25 mg but did not change in those who received placebo. In patients treated with daily doses of 25 or 50 mg of AMG 073 for 8 d, plasma PTH levels declined for the first 3 to 4 d and remained below baseline values after 8 d of treatment. Serum calcium concentrations also decreased by 5 to 10% from pretreatment levels in patients given 50 mg of AMG 073 for 8 d, but values were unchanged in those who received lower doses. Serum phosphorus levels and values for the calcium-phosphorus ion product both decreased after treatment with AMG 073. Thus, 8 d of treatment with AMG 073 effectively lowers plasma PTH levels and improves several disturbances in mineral metabolism that have been associated with soft tissue and vascular calcification and with adverse cardiovascular outcomes in patients with end-stage renal disease.