Optimizing Care Delivery in Patients with Chronic Kidney Disease in the United States: Proceedings of a Multidisciplinary Roundtable Discussion and Literature Review.

BACKGROUND: Approximately 37 million individuals in the United States (US) have chronic kidney disease (CKD). Patients with CKD have a substantial morbidity and mortality, which contributes to a huge economic burden to the healthcare system. A limited number of clinical pathways or defined workflows exist for CKD care delivery in the US, primarily due to a lower prioritization of CKD care within health systems compared with other areas (e.g., cardiovascular disease [CVD], cancer screening). CKD is a public health crisis and by the year 2040, CKD will become the fifth leading cause of years of life lost. It is therefore critical to address these challenges to improve outcomes in patients with CKD. METHODS: The CKD Leaders Network conducted a virtual, 3 h, multidisciplinary roundtable discussion with eight subject-matter experts to better understand key factors impacting CKD care delivery and barriers across the US. A premeeting survey identified topics for discussion covering the screening, diagnosis, risk stratification, and management of CKD across the care continuum. Findings from this roundtable are summarized and presented herein. RESULTS: Universal challenges exist across health systems, including a lack of awareness amongst providers and patients, constrained care team bandwidth, inadequate financial incentives for early CKD identification, non-standardized diagnostic classification and triage processes, and non-centralized patient information. Proposed solutions include highlighting immediate and long-term financial implications linked with failure to identify and address at-risk individuals, identifying and managing early-stage CKD, enhancing efforts to support guideline-based education for providers and patients, and capitalizing on next-generation solutions. CONCLUSIONS: Payers and other industry stakeholders have opportunities to contribute to optimal CKD care delivery. Beyond addressing the inadequacies that currently exist, actionable tactics can be implemented into clinical practice to improve clinical outcomes in patients at risk for or diagnosed with CKD in the US.

Preferences for and Experiences of Shared and Informed Decision Making Among Patients Choosing Kidney Replacement Therapies in Nephrology Care.

RATIONALE & OBJECTIVE: Chronic kidney disease (CKD) can progress rapidly, and patients are often unprepared to make kidney failure treatment decisions. We aimed to better understand patients' preferences for and experiences of shared and informed decision making (SDM) regarding kidney replacement therapy before kidney failure. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: Adults receiving nephrology care at CKD clinics in rural Pennsylvania. PREDICTORS: Estimated glomerular filtration rate, 2-year risk for kidney failure, duration and frequency of nephrology care, and preference for SDM. OUTCOMES: Occurrence and extent of kidney replacement therapy discussions and participants' satisfaction with those discussions. ANALYTIC APPROACH: Multivariable logistic regression to quantify associations between participants' characteristics and whether they had discussions. RESULTS: The 447 study participants had a median age of 72 (IQR, 64-80) years and mean estimated glomerular filtration rate of 33 (SD, 12) mL/min/1.73 m2. Most (96%) were White, high school educated (67%), and retired (65%). Most (72%) participants preferred a shared approach to kidney treatment decision making, and only 35% discussed dialysis or transplantation with their kidney teams. Participants who had discussions (n = 158) were often completely satisfied (63%) but infrequently discussed potential treatment-related impacts on their lives. In multivariable analyses, those with a high risk for kidney failure within 2 years (OR, 3.24 [95% CI, 1.72-6.11]; P < 0.01), longer-term nephrology care (OR, 1.12 [95% CI, 1.05-1.20] per 1 additional year; P < 0.01), and more nephrology visits in the prior 2 years (OR, 1.34 [95% CI, 1.20-1.51] per 1 additional visit; P < 0.01) had higher odds of having discussed dialysis or transplantation. LIMITATIONS: Single health system study. CONCLUSIONS: Most patients preferred sharing CKD treatment decisions with their providers, but treatment discussions were infrequent and often did not address key treatment impacts. Longitudinal nephrology care and frequent visits may help ensure that patients have optimal SDM experiences.

Integrated Digital Health System Tools to Support Decision Making and Treatment Preparation in CKD: The PREPARE NOW Study.

RATIONALE & OBJECTIVE: Digital health system tools to support shared decision making and preparation for kidney replacement treatments for patients with chronic kidney disease (CKD) are needed. STUDY DESIGN: Descriptive study of the implementation of digital infrastructure to support a patient-centered health system intervention. SETTING & PARTICIPANTS: 4 CKD clinics within a large integrated health system. EXPOSURE: We developed an integrated suite of digital engagement tools to support patients' shared decision making and preparation for kidney failure treatments. Tools included an automated CKD patient registry and risk prediction algorithm within the electronic health record (EHR) to identify and prioritize patients in need of nurse case management to facilitate shared decision making and preparation for kidney replacement treatments, an electronic patient-facing values clarification tool, a tracking application to document patients' preparation for treatments, and an EHR work flow to broadcast patients' treatment preferences to all health care providers. OUTCOMES: Uptake and acceptability. ANALYTIC APPROACH: Mixed methods. RESULTS: From July 1, 2017, through June 30, 2018, the CKD registry identified 1,032 patients in 4 nephrology clinics, of whom 243 (24%) were identified as high risk for progressing to kidney failure within 2 years. Kidney Transitions Specialists enrolled 117 (48%) high-risk patients by the end of year 1. The values tool was completed by 30/33 (91%) patients who attended kidney modality education. Nurse case managers used the tracking application for 100% of patients to document 287 planning steps for kidney replacement therapy. Most (87%) high-risk patients had their preferred kidney replacement modality documented and displayed in the EHR. Nurse case managers reported that the tools facilitated their identification of patients needing support and their navigation activities. LIMITATIONS: Single institution, short duration. CONCLUSIONS: Digital health system tools facilitated rapid identification of patients needing shared and informed decision making and their preparation for kidney replacement treatments. FUNDING: This work was supported through a Patient-Centered Outcomes Research Institute (PCORI) Project Program Award (IHS-1409-20967). TRIAL REGISTRATION: ClinicalTrials.gov NCT02722382.

Advanced CKD Care and Decision Making: Which Health Care Professionals Do Patients Rely on for CKD Treatment and Advice?

RATIONALE & OBJECTIVE: Chronic kidney disease (CKD) care is often fragmented across multiple health care providers. It is unclear whether patients rely mostly on their nephrologists or non-nephrologist providers for medical care, including CKD treatment and advice. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: Adults receiving nephrology care at CKD clinics in Pennsylvania. PREDICTORS: Frequency, duration, and patient-centeredness (range, 1 [least] to 4 [most]) of participants' nephrology care. OUTCOME: Participants' reliance on nephrologists, primary care providers, or other specialists for medical care, including CKD treatment and advice. ANALYTICAL APPROACH: Multivariable logistic regression to quantify associations between participants' reliance on their nephrologists (vs other providers) and their demographics, comorbid conditions, kidney function, and nephrology care. RESULTS: Among 1,412 patients in clinics targeted for the study, 676 (48%) participated. Among these, 453 (67%) were eligible for this analysis. Mean age was 71 (SD, 12) years, 59% were women, 97% were white, and 65% were retired. Participants were in nephrology care for a median of 3.8 (IQR, 2.0-6.6) years and completed a median of 4 (IQR, 3-5) nephrology appointments in the past 2 years. Half (56%) the participants relied primarily on their nephrologists, while 23% relied on primary care providers, 18% relied on all providers equally, and 3% relied on other specialists. Participants' adjusted odds of relying on their nephrologists were higher for those in nephrology care for longer (OR, 1.08 [95% CI, 1.02-1.15]; P = 0.02), those who completed more nephrology visits in the previous 2 years (OR, 1.16 [95% CI, 1.05-1.29]; P = 0.005), and those who perceived their last interaction with their nephrologists as more patient-centered (OR, 2.63 [95% CI, 1.70-4.09]; P < 0.001). LIMITATIONS: Single health system study. CONCLUSIONS: Many nephrology patients relied on non-nephrologist providers for medical care. Longitudinal patient-centered nephrology care may encourage more patients to follow nephrologists' recommendations.

Doxycycline-Induced Antinuclear Antibody and Antineutrophil Cytoplasmic Antibody Associated Vasculitis: A Case Report and Literature Review.

Drug-induced antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) has been increasingly recognized in the literature with numerous medications listed as causative agents in disease pathology. Doxycycline is a commonly prescribed medication within the United States which is a synthetic, broad-spectrum antibiotic with antimicrobial properties and at low doses exhibits anti-inflammatory effects. In this report, we describe a case of doxycycline-induced ANCA-associated vasculitis with laboratory and biopsy findings supporting the diagnosis, which to the best of our knowledge is the first described case of doxycycline-induced AAV in the literature. The patient was started on doxycycline for treatment of potential Lyme disease. She began to develop progressively worsening myasthenia, erythematous macular rash, anorexia, anemia, and fatigue for several weeks following the course of doxycycline with initial concern of a paraneoplastic process. Ultimately, the patient was discovered to be positive for antinuclear antibody (ANA), perinuclear antineutrophil cytoplasmic antibody (pANCA), and myeloperoxidase (MPO) antibody for which she was treated with a course of prednisone leading to complete remission of disease. A brief review of the pathogenesis of ANCA vasculitides will also be discussed within this article.

Bisphosphonates and mortality in women with CKD and the presence or absence of cardiovascular disease.

BACKGROUND AND OBJECTIVES: A modest protective association between bisphosphonate prescription and mortality among women with CKD but without clinically manifest cardiovascular disease has been shown. Whether a prior cardiovascular event (myocardial infarction, stroke, or heart failure) modifies this association is unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A cohort of adult women with stages 3 and 4 CKD receiving primary care in a rural integrated health care system during the period 2004-2011 without history of advanced malignancy or organ transplantation (n=6756, median age=74 years, median follow-up=4.3 years) was retrospectively assembled. The primary analysis compared those patients prescribed bisphosphonates (both prevalent and incident use during follow-up) with those patients not prescribed. Additional approaches were taken to account for survival and indication biases. The primary outcome was time to death by Cox multivariable regression. RESULTS: In the primary analysis, compared with women not prescribed a bisphosphonate, the hazard ratio (95% confidence interval) for death among women prescribed a bisphosphonate was 0.90 (0.78 to 1.04) if there was no history of cardiovascular event but 1.22 (1.04 to 1.42) if there was history of cardiovascular event (P for interaction=0.004). In the additional approaches, associations between bisphosphonate prescription and mortality among those patients with a prior cardiovascular history varied: hazard ratios (95% confidence intervals) were 1.25 (1.01 to 1.57), 1.48 (1.16 to 1.88), and 0.94 (0.66 to 1.34). Interaction by prior cardiovascular event history varied across these three approaches (P=0.07, P=0.22, and P=0.05). CONCLUSION: In this study of women with CKD, the association between bisphosphonate treatment and mortality risk was inconclusive across a series of analyses designed to account for various types of selection and indication bias.

Readmission after hospitalization for heart failure among patients with chronic kidney disease: a prediction model.

AIMS: 30-day readmission rates after hospitalization for heart failure (HF) approach 25%, and patients with chronic kidney disease (CKD) are disproportionately represented. A retrospective cohort study was conducted to develop a prediction tool for 30-day readmission after hospitalization for HF among those with non-dialysis dependent CKD. METHODS: Geisinger primary care patients with Stage 3 - 5 CKD hospitalized with a primary discharge diagnosis of HF during the period July 1, 2004 through February 28, 2010 were eligible. Multivariate logistic regression was employed to build models from predictors of 30-day readmission, drawn from demographic, clinical, laboratory, and pharmaceutical variables in the electronic health record. Variables were manually removed to achieve a model with satisfactory goodness-of-fit and parsimony while maximizing area under the receiver operating characteristic curve (AUC). Internal validation was performed using the bootstrap resampling method (1,000 samples) to provide a bias-corrected AUC. RESULTS: 607 patients with CKD were admitted for HF during the study period; 116 (19.1%) were readmitted within 30 days. A model incorporating 23 variables across domains of medical history, active outpatient pharmaceuticals, vital signs, laboratory tests, and recent inpatient and outpatient resource utilization yielded an AUC (95% CI) of 0.792 (0.746 - 0.838). The bias-corrected AUC was 0.743. At an estimated readmission probability of 20%, the model correctly classified readmission status for 73% of the population, with a sensitivity of 69% and a specificity of 73%. CONCLUSION: A robust electronic health record may facilitate the identification of CKD patients at risk for readmission after hospitalization for HF.

Increased risk of death and de novo chronic kidney disease following reversible acute kidney injury.

Acute kidney injury increases mortality risk among those with established chronic kidney disease. In this study we used a propensity score-matched cohort method to retrospectively evaluate the risks of death and de novo chronic kidney disease after reversible, hospital-associated acute kidney injury among patients with normal pre-hospitalization kidney function. Of 30,207 discharged patients alive at 90 days, 1610 with reversible acute kidney injury that resolved within the 90 days were successfully matched across multiple parameters with 3652 control patients who had not experienced acute kidney injury. Median follow-up was 3.3 and 3.4 years (injured and control groups, respectively). In Cox proportional hazard models, the risk of death associated with reversible acute kidney injury was significant (hazard ratio 1.50); however, adjustment for the development of chronic kidney injury during follow-up attenuated this risk (hazard ratio 1.18). Reversible acute kidney injury was associated with a significant risk of de novo chronic kidney disease (hazard ratio 1.91). Thus, a resolved episode of hospital-associated acute kidney injury has important implications for the longitudinal surveillance of patients without preexisting, clinically evident kidney disease.

Fat-free weight prediction in morbidly obese females.

PURPOSE: Precise estimation of creatinine clearance in obese individuals relies on the appropriate assessment of lean body weight (LBW). Anthropometric methods of predicting LBW have not been validated in morbidly obese populations. PATIENTS AND METHODS: Using an existing dataset of anthropometric data for a female cohort with morbid obesity who had undergone measured FFW with dual energy absorptiometry, we evaluated the performance of five previously reported estimating equations for the prediction of LBW. Linear regression was used to derive a new LBW prediction formula and was then compared with the other formulae. RESULTS: Seventy females (mean [standard deviation] age, weight, and body mass index 43.0 [11.0] years, 128.1 [13.8] kg, and 48.3 [4.8] kg/m(2), respectively) were identified. LBW as estimated by the method of Garrow and Webster correlated well (r = 0.87) with measured mass while demonstrating the highest accuracy, best precision, and smallest bias (93%, 2.1 kg, and 2.9 kg, respectively; P < 0.0001 for all comparisons). The derived formula further improved bias, precision, and accuracy. CONCLUSION: Among females with morbid obesity, most previously reported estimating equations for LBW predicted FFW poorly. These findings have important clinical implications for the assessment of kidney function and for safe and effective drug dosing.

Factors contributing to an increase in duplicate medication order errors after CPOE implementation.

OBJECTIVE: To evaluate the incidence of duplicate medication orders before and after computerized provider order entry (CPOE) with clinical decision support (CDS) implementation and identify contributing factors. DESIGN: CPOE with duplicate medication order alerts was implemented in a 400-bed Northeastern US community tertiary care teaching hospital. In a pre-implementation post-implementation design, trained nurses used chart review, computer-generated reports of medication orders, provider alerts, and staff reports to identify medication errors in two intensive care units (ICUs). MEASUREMENT: Medication error data were adjudicated by a physician and a human factors engineer for error stage and type. A qualitative analysis of duplicate medication ordering errors was performed to identify contributing factors. RESULTS: Data were collected for 4147 patient-days pre-implementation and 4013 patient-days post-implementation. Duplicate medication ordering errors increased after CPOE implementation (pre: 48 errors, 2.6% total; post: 167 errors, 8.1% total; p<0.0001). Most post-implementation duplicate orders were either for the identical order or the same medication. Contributing factors included: (1) provider ordering practices and computer availability, for example, two orders placed within minutes by different providers on rounds; (2) communication and hand-offs, for example, duplicate orders around shift change; (3) CDS and medication database design, for example confusing alert content, high false-positive alert rate, and CDS algorithms missing true duplicates; (4) CPOE data display, for example, difficulty reviewing existing orders; and (5) local CDS design, for example, medications in order sets defaulted as ordered. CONCLUSIONS: Duplicate medication order errors increased with CPOE and CDS implementation. Many work system factors, including the CPOE, CDS, and medication database design, contributed to their occurrence.

ICU nurses' acceptance of electronic health records.

OBJECTIVE: To assess intensive care unit (ICU) nurses' acceptance of electronic health records (EHR) technology and examine the relationship between EHR design, implementation factors, and nurse acceptance. DESIGN: The authors analyzed data from two cross-sectional survey questionnaires distributed to nurses working in four ICUs at a northeastern US regional medical center, 3 months and 12 months after EHR implementation. MEASUREMENTS: Survey items were drawn from established instruments used to measure EHR acceptance and usability, and the usefulness of three EHR functionalities, specifically computerized provider order entry (CPOE), the electronic medication administration record (eMAR), and a nursing documentation flowsheet. RESULTS: On average, ICU nurses were more accepting of the EHR at 12 months as compared to 3 months. They also perceived the EHR as being more usable and both CPOE and eMAR as being more useful. Multivariate hierarchical modeling indicated that EHR usability and CPOE usefulness predicted EHR acceptance at both 3 and 12 months. At 3 months postimplementation, eMAR usefulness predicted EHR acceptance, but its effect disappeared at 12 months. Nursing flowsheet usefulness predicted EHR acceptance but only at 12 months. CONCLUSION: As the push toward implementation of EHR technology continues, more hospitals will face issues related to acceptance of EHR technology by staff caring for critically ill patients. This research suggests that factors related to technology design have strong effects on acceptance, even 1 year following the EHR implementation.

Acute kidney injury in the critically ill, morbidly obese patient: diagnostic and therapeutic challenges in a unique patient population.

The growing burden of morbid obesity (body mass index >40 kg/m²) on critical care resources translates to a significant incidence of acute kidney injury (AKI) in morbidly obese (MO), critically ill patients. This article examines the literature pertinent to AKI in critically ill MO patients. After a concise review of the available epidemiologic data regarding the incidence of acute renal injury in MO individuals, the authors review the limitations and available tools for estimation of renal function in the MO population (with emphasis on the critical illness). Also described are several specific types of renal injury previously described in this population that are applicable to the critical care setting. Lastly, the authors review some of the challenges and limitations in providing renal support to critically ill MO individuals, and identify potential areas for future research in this population.

Hypernatremia in a patient treated with sodium polystyrene sulfonate.

Severe hyperkalemia requires urgent medical attention and correction in order to prevent arrhythmic complications. Sodium polystyrene sulfonate (SPS) is a cation exchange resin commonly used in the management of hyperkalemia. A recent review raised concerns regarding its effectiveness and potential adverse effects. Hypernatremia in adults in the setting of sodium polystyrene sulfonate therapy has not been described in the literature. We report the case of a woman who developed hypernatremia in the setting of excessive SPS administration and hope to increase awareness among clinicians regarding this potential side effect of SPS therapy.

Fibrillary glomerulopathy secondary to light chain deposition disease in a patient with monoclonal gammopathy.

The pathologic manifestations of renal diseases related to monoclonal plasma cell dyscrasia include light chain deposition disease, the AL type of amyloidosis, and myeloma cast nephropathy. Light chain deposit disease (LCDD) is an uncommon condition in which monoclonal light chains are deposited in the glomeruli, tubules, and vessels causing varying degree of damage. We report a case of LCDD coincident with fibrillary glomerulonephropathy (FGN) in a 73-yr-old man with a diagnosis of monoclonal gammopathy of undetermined significance who presented with progressive renal insufficiency and mild proteinuria. The serum kappa light chain level was markedly raised. Immunofluorescent stains showed IgG along with C3 and kappa staining in glomeruli, but lambda staining was negative. Electron microscopic studies revealed diffuse punctuate-type deposits along the subendothelial areas. There were also scattered randomly oriented fibrils with a mean fibril thickness of 15-25 nm seen mainly in the glomerular mesangium, consistent with FGN. The congo red stain was negative on the histologic section. The present case illustrates that LCDD can progress to develop FGN in a patient with monoclonal gammopathy.

Transplantation and 6-month follow-up of renal transplantation from a donor with systemic lupus erythematosus and lupus nephritis.

Transplantation of kidneys with pre-existing glomerulonephritis (GN) has rarely been reported. Little is known of the subsequent evolution of donor pathology in the recipient. We report a transplant using a donor with systemic lupus erythematosus (SLE) and a history of remote acute renal failure but normal renal function at death. Although the screening harvest biopsy was unremarkable, time zero post-implantation renal biopsy showed evidence of lupus nephritis (LN). Sequential protocol biopsies demonstrated gradual resolution of the donor pathology, and renal function was stable despite severe cardiac disease in the recipient. Studies examining the role of functional and biopsy data on outcomes in expanded criteria renal transplantation are reviewed, and the limits of guidance from use of this data are discussed. Pre-existing mild GN may not be an absolute donor exclusion for candidates willing to accept expanded criteria donors. Use of expanded pool kidneys should be guided by functional, biopsy and demographic information, as no single factor alone predicts outcome.

Acute cellular rejection predominated by monocytes is a severe form of rejection in human renal recipients with or without Campath-1H (alemtuzumab) induction therapy.

Campath-1H has been used successfully for induction and has resulted in a low rate of acute cellular rejection (ACR) in renal transplantation in combination with various postoperative immunosuppression regimens. This study was undertaken to investigate the extent of monocyte involvement in ACR, with or without Campath-1H induction. We found that monocytes represented the majority of inflammatory cells in grades Ib or higher ACR, but not with Ia type of ACR, regardless of the status of Campath-1H induction. Cases of ACR, following Campath-1H induction, appear to demonstrate a 'pure form' of monocytic ACR, whereas monocytes were mixed with many other types of inflammatory cells in the cases of ACR in the absence of Campath-1H induction. In addition with Campath-1H induction, the cases of monocyte-predominant ACR were found to uniformly exhibit a good response to corticosteroid treatment. We conclude that monocyte-predominate ACR may represent a severe form of rejection, with or without Campath-1H treatment.

Monocyte-mediated acute renal rejection after combined treatment with preoperative Campath-1H (alemtuzumab) and postoperative immunosuppression.

Campath-1H (alemtuzumab), a humanized monoclonal antibody against CD52, can cause more profound depletion of lymphocytes than monocytes. The resultant imbalance of lymphocytes and monocytes after Campath-1H treatment of a renal-transplant recipient may lead to an acute rejection dominated by monocytes. We report such a case of acute transplant rejection in a 49-yr-old man who received a living non-related kidney transplant and was treated with preoperative Campath-1H and postoperative immunosuppression. An initial post-transplant renal biopsy showed diffuse mild acute rejection with 95% CD68-positive monocytes, but only 5% CD3-positive T lymphocytes. Inflammatory cells in the renal biopsy were negative for CD34 and CD1a stains, suggesting non-involvement of CD34-derived dendritic cells in the acute rejection. After steroid treatment for 2 wk, the patient's serum creatinine concentration diminished to 1.5 mg/dl. The histopathological features of acute rejection were absent in a second biopsy of the transplanted kidney. In summary, this case is an instance of monocyte-mediated acute rejection of a transplanted kidney.