Randal Detwiler

High Prevalence of Unlabeled Chronic Kidney Disease Among Inpatients at a Tertiary-Care Hospital

Background:Although awareness of chronic kidney disease (CKD) is low in outpatient settings, the prevalence of unrecognized CKD in the inpatient setting is unknown. Methods:We examined the extent of unlabeled CKD among adults admitted to a tertiary-care hospital in North Carolina, based upon a combination of web-based medical record review, chart review, ICD-9 codes and laboratory information from 2000 to 2005. Results:A total of 9772 patients had 2 or more serum creatinine measures at least 6 months apart and demographic variables for race and sex; 431 met criteria for stage 5 CKD (estimated glomerular filtration rate <15 mL/min/1.73 m2) and 6851 patients had stage 2 to 4 CKD (estimated glomerular filtration rate between 15 and 89 mL/min/1.73 m2). Within the latter groups, 3002 had stage 3 to 4 CKD, and 3849 had stage 2 CKD. Forty-three percent were male, 37% had a minority race/ethnicity. The number of patients not labeled as having CKD by ICD-9 code was 2176 (72.5%). Women and whites were less likely than men and minorities to be labeled as having CKD by ICD-9 codes. Medical record review of 600 randomly selected patients identified 399 patients with stage 3 or 4 CKD diagnosis. ICD-9 codes had a sensitivity of 0.50, specificity of 0.88, and positive predictive value of 0.39. Conclusions:A large proportion of individuals with CKD are going unrecognized in the hospital setting. Automatic laboratory reporting of GFR and education about CKD may help increase awareness in both the inpatient settings.

Risk assessment for polyomavirus nephropathy using urine cytology and the detection of decoy cells: cheap and efficient.

Iapplaud the important ethical analysis by Quigley et al. (1) of Israel’s innovative scheme to give priority to people who are associated with an intention to donate should they ever themselves require to be recipients of organs for transplantation. However, it is not quite accurate to suggest that the objection to the use of brain stem death (BSD) to define organismal death is erroneous in how it represents Jewish principles (2). Although many respected rabbinic authorities clearly do accept BSD as death, many require total cessation of cardiorespiratory function before declaring life to be over. It is important to be aware of this for two reasons: first, a significant number of potential donors (or their families) may accurately cite well-respected rabbinic authorities who would suggest that a BSD person is not dead according to traditional Jewish law; second, those wishing to promote organ donation need accurately to understand the cultural and religious norms in the communities they approach. In addition, Quigley et al. (1) suggest that other objections are focused on superstitions, such as the invocation of bad luck. In fact, there are several other Jewish legal objections that are much more commonly (but erroneously) suggested (such as the need to treat a body respectfully and bury it rapidly without the interference necessitated by the donation process). There is unanimity among Jewish authorities in stating that although these principles are important, they must all be set aside given the opportunity to save another’s life.

Ecological Factors Predict Transition Readiness/Self-Management in Youth With Chronic Conditions

PURPOSE Health care transition readiness or self-management among adolescents and young adults (AYA) with chronic conditions may be influenced by factors related to their surrounding environment. METHODS Study participants were AYA diagnosed with a chronic condition and evaluated at pediatric- and adult-focused subspecialty clinics at the University of North Carolina Hospital Systems. All participants were administered a provider-administered self-management/transition-readiness tool, the UNC TRxANSITION Scale. Geographic area and associated characteristics (ecological factors) were identified for each participants ZIP code using the published U.S. Census data. The Level 1 model of the hierarchical linear regression used individual-level predictors of transition readiness/self-management. The Level 2 model incorporated the ecological factors. RESULTS We enrolled 511 AYA with different chronic conditions aged 12-31 years with the following characteristics: mean age of 20± 4 years, 45% white, 42% black, and 54% female. Participants represented 214 ZIP codes in or around North Carolina, USA. The Level 1 model showed that age, gender, and race were significant predictors of transition readiness/self-management. On adding the ecological factors in the Level 2 model, race was no longer significant. Participants from a geographic area with a greater percentage of females (β = .114, p = .005) and a higher median income (β = .126, p = .002) had greater overall transition readiness. Ecological factors also predicted subdomains of transition readiness/self-management. CONCLUSIONS In this cohort of adolescents and young adults with different chronic conditions, ecological disparities such as sex composition, median income, and language predict self-management/transition readiness. It is important to take ecological risk factors into consideration when preparing patients for health self-management or transition.

Renal Survival in Patients with Collapsing Compared with Not Otherwise Specified FSGS

BACKGROUND AND OBJECTIVES Idiopathic collapsing FSGS has historically been associated with poor renal outcomes. Minimal clinical data exist on the efficacy of immunosuppressive therapy. Our study sought to provide a comprehensive description of renal survival in patients with collapsing and not otherwise specified FSGS after controlling for factors affecting renal prognosis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We performed a retrospective analysis of an inception cohort study of patients diagnosed between 1989 and 2012. All potential patients with collapsing FSGS fulfilling the inclusion criteria were identified and compared with patients with not otherwise specified FSGS (approximately 1:2 ratio) on the basis of biopsy report and record availability. Time to ESRD was analyzed using Cox proportional hazards models. RESULTS In total, 187 patients were studied (61 collapsing and 126 not otherwise specified), with a mean follow-up of 96 months. At baseline, patients with collapsing FSGS had higher median proteinuria (12.2 [5.6-14.8] versus 4.4 [2.3-8.1] g/d, respectively; P<0.001), lower median albuminemia (2.4 [1.9-3.0] versus 2.9 [1.8-3.7] g/dl, respectively; P=0.12), and lower median eGFR (48 [26-73] versus 60 [42-92] ml/min per 1.73 m2, respectively; P=0.01) than patients with not otherwise specified FSGS. The proportion of patients with remission of proteinuria was similar in patients with collapsing FSGS and patients with not otherwise specified FSGS (65.7% [23 of 35] versus 63.2% [72 of 114], respectively; P=0.84). The overall renal outcome (ESRD defined as eGFR<15 ml/min per 1.73 m2, dialysis, or transplantation) of patients with collapsing FSGS was not poorer than that of patients with not otherwise specified FSGS in multivariate analyses after adjusting for baseline characteristics and immunotherapy (hazard ratio, 1.78; 95% confidence interval, 0.92 to 3.45). CONCLUSIONS Compared with not otherwise specified FSGS, idiopathic collapsing FSGS presented with more severe nephrotic syndrome and lower eGFR but had a similar renal survival after controlling for exposure to immunosuppressive treatment. These results highlight the importance of early diagnosis and institution of immunosuppressive therapy in patients with collapsing FSGS.

Evaluation of renal transplant status using viscoelastic response (VisR) ultrasound: A pilot clinical study

The current gold standard for monitoring renal transplant status is invasive biopsy, which is controversial due to its associated risk for morbidity and costs. A relevant biopsy alternative could be an imaging technique that exploits the viscoelastic properties of tissue given that renal disease may result in altered viscoelastic relationships between pelvis and parenchyma. Tissue viscoelasticity is delineated by VisR ultrasound, an acoustic radiation force (ARF)-based imaging method, by fitting displacements induced by two ARF impulses to the Mass Spring Damper (MSD) model. We hypothesize that VisR measures are relevant for noninvasively distinguishing biopsied and non-biopsied allografts by assessing viscoelastic similarity between pelvis and parenchyma in renal transplant patients. VisR derived metrics: τ, relative elasticity (RE), and relative viscosity (RV) were calculated in the regions of interest (ROI): outer, center, and inner parenchyma and outer and inner pelvis. The ratios of a given VisR measure for all possible ROI combinations were compared (Wilcoxon rank sum) between biopsied and non-biopsied patients. VisR τ, RE, and RV distinguished chronic allograft nephropathy, glomerulonephritis, vascular disease, and tubular and/or interstitial scarring in biopsied versus non-biopsied allografts (p <; 0.05). These results suggest that VisR measures may be relevant metrics for noninvasively monitoring renal transplant health.

Lithium use for bipolar disorder post renal transplant: Is mood stabilization without toxicity possible?

Chronic lithium exposure is predominantly associated with chronic tubulointerstitial nephropathy (CTN), characterized by lesions of interstitial fibrosis, thickened tubular basement membranes, and renal cysts from the distal tubule and collecting duct (1, 2). Molecular studies suggest accumulation in distal tubules and inhibition of cellular activity involving glycogen synthase kinase-3A and inositol monophosphate (3Y5). Reduced GFR develops in 15% to 20% of patients over 10 to 20 years of drug exposure (3, 6). Predisposing risk factors to developing nephropathy are long-term administration, high cumulative lithium exposure, episodes of acute toxicity, hypertension, and diabetes mellitus (2, 3). Individuals with CTN are at risk for progression to ESRD despite lithium discontinuation (1). Lithium clearance is directly proportional to GFR and its cations freely diffuse across glomerular membranes to the same extent as sodium and water (7, 8). Elimination half-life of lithium is dependent on duration of therapy. Pharmacokinetic studies during prolonged use demonstrate a two-fold increase in halflife (7). Reduced clearance combined with chronic exposure gradually increases lithium concentrations, leading to chronic toxicity (8). Maintenance treatment of bipolar disorder targets concentrations of 0.6 to 1.2 mEq/L with acceptable variation range of 0.5 to 1.5 mEq/L (7, 9). Symptoms associated with toxicity include nausea, vomiting, altered mental status, confusion, tremor, weakness, apathy, hyperreflexia, slurred speech, memory deficits, seizure, and coma (7). Chronic toxicity may occur with modest lithium elevations in patients receiving long-term therapy. Symptom severity does not correlate with serum concentration, and toxicity is frequently reported when concentrations are well within recommended range (9).

Implantation of Autologous Selected Renal Cells in Diabetic Chronic Kidney Disease Stages 3 and 4—Clinical Experience of a “First in Human” Study

Introduction Animal models of chronic kidney disease demonstrate that a redundant population of therapeutically bioactive selected renal cells (SRCs) can be delivered to the kidney through intraparenchymal injection and arrest disease progression. Direct injection of SRCs has been shown to attenuate nuclear factor−κB, which is known to drive tissue inflammation, as well as the transforming growth factor−β−mediated plasminogen activator inhibitor−1 response that drives tissue fibrosis. Methods We present experience from the first-in-human clinical study with SRCs. Seven male type 2 diabetic patients (63 ± 2 years of age) with chronic kidney disease stage 3 to 4 (estimated glomerular filtration rate 25 ± 2 ml/min) were recruited. After blood and urine sampling, iohexol clearance, magnetic resonance imaging, and renal scintigraphy, patients underwent ultrasound-guided renal biopsy. Two cores of renal tissue were shipped to the manufacturing plant for cell isolation, culture, and product preparation. Formulated SRCs were transported back to study sites (range 59–87 days after biopsy) for intracortical injection using a retroperitoneoscopic technique. Results Laparoscopically assisted implantation of SRCs was uneventful in all patients. However, postoperative complications were common and suggest that other techniques of SRC delivery should be used. Kidney volume, split function, and glomerular filtration rate did not change during 12 months of follow-up. An extended 24-month follow-up in 5 of the patients showed a decline in estimated glomerular filtration rate (cystatin C). Discussion Postoperative complications following retroperitoneoscopic implantation of SRC in the kidney cortex seem to be related to the surgical procedure rather than to injection of the cell product. No changes in renal function were observed during the original 12-month protocol. Beyond the first 12 months after cell implantation, individual renal function began to deteriorate during further follow-up.

Evaluating Renal Transplant Status Using Viscoelastic Response (VisR) Ultrasound

Chronic kidney disease is most desirably and cost-effectively treated by renal transplantation, but graft survival is a major challenge. Although irreversible graft damage can be averted by timely treatment, intervention is delayed when early graft dysfunction goes undetected by standard clinical metrics. A more sensitive and specific parameter for delineating graft health could be the viscoelastic properties of the renal parenchyma, which are interrogated non-invasively by Viscoelastic Response (VisR) ultrasound, a new acoustic radiation force (ARF)-based imaging method. Assessing the performance of VisR imaging in delineating histologically confirmed renal transplant pathologies in vivo is the purpose of the study described here. VisR imaging was performed in patients with (n = 19) and without (n = 25) clinical indication for renal allograft biopsy. The median values of VisR outcome metrics (τ, relative elasticity [RE] and relative viscosity [RV]) were calculated in five regions of interest that were manually delineated in the parenchyma (outer, center and inner) and in the pelvis (outer and inner). The ratios of a given VisR metric for all possible region-of-interest combinations were calculated, and the corresponding ratios were statistically compared between biopsied patients subdivided by diagnostic categories versus non-biopsied, control allografts using the two-sample Wilcoxon test (p <0.05). Although τ ratios non-specifically differentiated allografts with vascular disease, tubular/interstitial scarring, chronic allograft nephropathy and glomerulonephritis from non-biopsied control allografts, RE distinguished only allografts with vascular disease and tubular/interstitial scarring, and RV distinguished only vascular disease. These results suggest that allografts with scarring and vascular disease can be identified using non-invasive VisR RE and RV metrics.

Longitudinal Self-Management and/or Transition Readiness per the TRANSITION Index among Patients with Chronic Conditions in Pediatric or Adult Care Settings

Objective To evaluate the roles of key individual, family, and illness characteristics on the levels of and gains in longitudinal healthcare transition (HCT) readiness in the pediatric setting and/or self‐management skills (SMS) in the adult‐focused setting, we used a large dataset with longitudinal measurements from 2006 to 2015. Study Design This longitudinal observational study followed 566 adolescents and young adults with chronic conditions at University of North Carolina Hospitals. TRxANSITION Index measurements, which represent learning outcomes rather than health outcomes, were collected multiple times per patient and analyzed using a novel application of an education‐based approach. Results Levels of and gains in HCT/SMS scores increased with age (P < .001) with smaller increases at older ages. Mastery of skills varied by age with self‐management achieved after 20 years of age. Scores varied positively by fathers education and negatively by mothers education and duration of diagnosis. Gains in scores further varied positively with private insurance and negatively with mothers education and duration of diagnosis. Conclusions We found diminishing positive increases in HCT/SMS scores as patients become older and smaller levels of and gains in readiness among younger patients with more educated mothers. Risk factors for absolute level of HCT/SMS readiness and inadequate longitudinal gains are not always the same, which motivates a deeper understanding of this dynamic process through additional research. This information can guide providers to focus HCT/SMS preparation efforts on skills mastered at particular ages and to identify patients at risk for inadequate development of HCT/SMS skills.

In vivo mechanical anisotropy assessment in renal cortex using ARFI peak displacement

The kidney is an anisotropic organ, with higher elasticity along versus across nephrons. The degree of elastic anisotropy in kidney may be diagnostically relevant if properly exploited; however, if improperly controlled, anisotropy may confound stiffness measurements. The purpose of this study is to demonstrate a novel method for selectively exploiting or obviating elastic anisotropy in kidney using Acoustic Radiation Force Impulse (ARFI)-induced peak displacement (PD). The kidneys of three pigs were imaged in vivo at baseline, with venous ligation, and with arterial ligation, and then kidneys were extracted and imaged ex vivo. Imaging was performed with ARF excitation impulses having F/1.5 or F/5.0 focal configurations, and data were acquired with the transducer oriented along and across nephrons alignment in the renal cortex. In addition to ARFI PD, shear wave velocity was measured along and across nephrons to estimate longitudinal and transverse shear elastic moduli. Elastic anisotropy was then assessed as the ratio of PD across versus along nephrons, and as the ratio of shear moduli along versus across nephrons. PD ratio using the F/1.5 ARF linearly correlated with shear moduli ratio (R2 = 0.95). However, PD ratio using the F/5.0 ARF was approximately 1.0 and had weak correlation to shear moduli ratio (R2= 0.56). Further, the average difference in PD measured along versus across nephrons was 2.91 μm for the F/1.5 ARF but was 0.2 μm for the F/5.0 ARF. These results suggest that the F/1.5 ARF excitation exploited elastic anisotropy in the renal cortex, while the F/5.0 ARF excitation obviated it.