Karnofsky Performance Score-Failure to Thrive as a Frailty Proxy?

Among patients listed for kidney transplantation, the Karnofsky Performance Status (KPS) Scale has been used as a proxy for frailty and proposed as a predictor of long-term posttransplant outcomes. The KPS is required by the Organ Procurement and Transplantation Network for all transplants; however, the interrater reliability of KPS reporting in kidney transplant candidates has not been well investigated, and there is concern regarding limitations of using KPS that may influence transplant eligibility. METHODS: We performed an observational study using existing Scientific Registry of Transplant Recipients data from 2006 to 2020 to examine the variability, reliability, and trends in the KPS among patients on the kidney transplant waitlist. RESULTS: Our analysis included 8197 kidney transplant candidates with >1 KPS in a 3-mo period. We observed 2-7 scores per patient with an average score of 78.9 (SD = 12, 95% confidence interval, 78.8-79.1). We found substantial variability in KPS reporting, in which 27% of the patients had scores that varied widely with 20-80 points in difference. Interrater reliability in the 10-point scale was poor (30%). When using a condensed 4-category scale (disabled, requires assistance, capable of self-care, normal activity), 38% of patients experienced at least a 1-category shift in their score. CONCLUSIONS: The lack of reliability in KPS reporting raises concerns when applying the KPS as a proxy for frailty and a metric to be considered when evaluating candidacy for kidney transplantation.

Performance versus Risk Factor-Based Approaches to Coronary Artery Disease Screening in Waitlisted Kidney Transplant Candidates.

INTRODUCTION: Current screening algorithms for coronary artery disease (CAD) before kidney transplantation result in many tests but few interventions. OBJECTIVE: The aim of this study was to study the utility of 6-minute walk test (6MWT), an office-based test of cardiorespiratory fitness, for risk stratification in this setting. METHODS: We enrolled 360 patients who are near the top of the kidney transplant waitlist at our institution. All patients underwent CAD evaluation irrespective of 6MWT results. We examined the association between 6MWT and time to CAD-related events (defined as cardiac death, revascularization, nonfatal myocardial infarction, and removal from the waitlist for CAD), treating noncardiac death and waitlist removal for non-CAD reasons as competing events. RESULTS: The 6MWT-based approach designated approximately 45% of patients as "low risk," whereas a risk factor- or symptom-based approach designated 14 and 81% of patients as "low risk," respectively. The 6MWT-based approach was not significantly associated with CAD-related events within 1 year (subproportional hazard ratio [sHR] 1.00 [0.90-1.11] per 50 m) but was significantly associated with competing events (sHR 0.70 [0.66-0.75] per 50 m). In a companion analysis, removing waitlist status from consideration, 6MWT result was associated with the development of CAD-related events (sHR 0.92 [0.84-1.00] per 50 m). CONCLUSIONS: The 6MWT designates fewer patients as high risk and in need of further testing (compared to risk factor-based approaches), but its utility as a pure CAD risk stratification tool is modulated by the background waitlist removal rate. CAD screening before kidney transplant should be tailored according to a patient's actual chance of receiving a transplant.

Toward telemedicine-compatible physical functioning assessments in kidney transplant candidates.

Frailty is associated with adverse kidney transplant outcomes and can be assessed by subjective and objective metrics. There is increasing recognition of the value of metrics obtainable remotely. We compared the self-reported SF-36 physical functioning subscale score (SF-36 PF) with in-person physical performance tests (6-min walk and sit-to-stand) in a prospective cohort of kidney transplant candidates. We assessed each metric's ability to predict time to the composite outcome of waitlist removal or death, censoring at transplant. We built time-dependent receiver operating characteristic curves and calculated the area under the curve [AUC(t)] at 1 year, using bootstrapping for internal validation. In 199 patients followed for a median of 346 days, 41 reached the composite endpoint. Lower SF-36 PF scores were associated with higher risk of waitlist removal/death, with every 10-point decrease corresponding to a 16% increase in risk. All models showed an AUC(t) of 0.83-0.84 that did not contract substantially after internal validation. Among kidney transplant candidates, SF-36 PF, obtainable remotely, can help to stratify the risk of waitlist removal or death, and may be used as a screening tool for poor physical functioning in ongoing candidate evaluation, particularly where travel, increasing patient volume, or other restrictions challenge in-person assessment.

Physical Performance Testing in Kidney Transplant Candidates at the Top of the Waitlist.

RATIONALE & OBJECTIVE: Frailty and poor physical function are associated with adverse kidney transplant outcomes, but how to incorporate this knowledge into clinical practice is uncertain. We studied the association between measured physical performance and clinical outcomes among patients on kidney transplant waitlists. STUDY DESIGN: Prospective observational cohort study. SETTING & PARTICIPANTS: We studied consecutive patients evaluated in our Transplant Readiness Assessment Clinic, a top-of-the-waitlist management program, from May 2017 through December 2018 (N=305). We incorporated physical performance testing, including the 6-minute walk test (6MWT) and the sit-to-stand (STS) test, into routine clinical assessments. EXPOSURES: 6MWT and STS test results. OUTCOMES: The primary outcome was time to adverse waitlist outcomes (removal from waitlist or death); secondary outcomes were time to transplantation and time to death. ANALYTICAL APPROACH: We used linear regression to examine the relationship between clinical characteristics and physical performance test results. We used subdistribution hazards models to examine the association between physical performance test results and outcomes. RESULTS: Median 6MWT and STS results were 393 (IQR, 305-455) m and 17 (IQR, 12-21) repetitions, respectively. Clinical characteristics and Estimated Post-Transplant Survival scores accounted for only 14% to 21% of the variance in 6MWT/STS results. Physical performance test results were associated with adverse waitlist outcomes (adjusted subdistribution hazard ratio [sHR] of 1.42 [95% CI, 1.30-1.56] per 50-m lower 6MWT test result and 1.53 [95% CI, 1.33-1.75] per 5-repetition lower STS test result) and with transplantation (adjusted sHR of 0.80 [95% CI, 0.72-0.88] per 50-m lower 6MWT test result and 0.80 [95% CI, 0.71-0.89] per 5-repetition lower STS test result). Addition of either STS or 6MWT to survival models containing clinical characteristics enhanced fit (likelihood ratio test P<0.001). LIMITATIONS: Single-center observational study. Other measures of global health status (eg, Fried Frailty Index or Short Physical Performance Battery) were not examined. CONCLUSIONS: Among waitlisted kidney transplant candidates with high kidney allocation scores, standardized and easily performed physical performance test results are associated with waitlist outcomes and contain information beyond what is currently routinely collected in clinical practice.

Identification of glomerular and podocyte-specific genes and pathways activated by sera of patients with focal segmental glomerulosclerosis.

Focal segmental glomerulosclerosis (FSGS) accounts for about 40% of all nephrotic syndrome cases in adults. The presence of several potential circulating factors has been suggested in patients with primary FSGS and particularly in patients with recurrent disease after transplant. Irrespectively of the nature of the circulating factors, this study was aimed at identifying early glomerular/podocyte-specific pathways that are activated by the sera of patients affected by FSGS. Kidney biopsies were obtained from patients undergoing kidney transplantation due to primary FSGS. Donor kidneys were biopsied pre-reperfusion (PreR) and a subset 1-2 hours after reperfusion of the kidney (PostR). Thirty-one post reperfusion (PostR) and 36 PreR biopsy samples were analyzed by microarray and gene enrichment KEGG pathway analysis. Data were compared to those obtained from patients with incident primary FSGS enrolled in other cohorts as well as with another cohort to correct for pathways activated by ischemia reperfusion. Using an ex-vivo cell-based assay in which human podocytes were cultured in the presence of sera from patients with recurrent and non recurrent FSGS, the molecular signature of podocytes exposed to sera from patients with REC was compared to the one established from patients with NON REC. We demonstrate that inflammatory pathways, including the TNF pathway, are primarily activated immediately after exposure to the sera of patients with primary FSGS, while phagocytotic pathways are activated when proteinuria becomes clinically evident. The TNF pathway activation by one or more circulating factors present in the sera of patients with FSGS supports prior experimental findings from our group demonstrating a causative role of local TNF in podocyte injury in FSGS. Correlation analysis with clinical and histological parameters of disease was performed and further supported a possible role for TNF pathway activation in FSGS. Additionally, we identified a unique set of genes that is specifically activated in podocytes when cultured in the presence of serum of patients with REC FSGS. This clinical translational study supports our prior experimental findings describing a potential role of the TNF pathway in the pathogenesis of FSGS. Validation of these findings in larger cohorts may lay the ground for the implementation of integrated system biology approaches to risk stratify patients affected by FSGS and to identify novel pathways relevant to podocyte injury.

Septic thrombophlebitis of the internal jugular vein, a case of Lemierre's syndrome.

An 18-year-old gentleman with a history of recurrent tonsillitis presented to the emergency room complaining of worsening sore throat. He was found to have a peritonisillar abscess, and imaging revealed a non-occlusive left internal jugular vein thrombosis. Lemierre's syndrome is a rare, potentially fatal condition characterized by internal jugular vein thrombosis with septicemia following an acute oropharyngeal infection. While anticoagulation is the mainstay of treatment of deep venous thromboembolism (DVT) and pulmonary embolism (PE), the use of therapy is controversial in septic thrombophlebitis. This is counterintuitive since a common reported complication is pulmonary emboli. Early in the course of thrombophlebitis, while the thrombus is firmly attached, antibiotics may be all that is necessary to treat the condition.

Screening for asymptomatic carotid artery stenosis: a systematic review and meta-analysis for the U.S. Preventive Services Task Force.

BACKGROUND: Approximately 10% of ischemic strokes are caused by carotid artery stenosis (CAS). Estimated prevalence of asymptomatic CAS is 1%. PURPOSE: To evaluate evidence on screening and treating asymptomatic adults for CAS. DATA SOURCES: MEDLINE, the Cochrane Library, EMBASE, and trial registries through September 2013; MEDLINE through March 2014 for trials. STUDY SELECTION: Good- or fair-quality trials of screening, carotid endarterectomy (CEA), or stenting compared with medical therapy or of intensification of medical therapy; systematic reviews; multi-institution studies reporting harms; and externally validated risk-stratification tools. DATA EXTRACTION: Dual extraction and quality assessment. DATA SYNTHESIS: No trials compared screening with no screening or stenting with medical therapy or assessed intensification of medical therapy, and no externally validated, reliable risk-stratification tools were found. Given the specificity of ultrasonography (range, 88% to 94% for CAS ≥ 50% to ≥ 70%), its use in low-prevalence populations would yield many false-positive results. Absolute reduction of nonperioperative strokes was 5.5% (95% CI, 3.9% to 7.0%; 3 trials; 5223 participants) over approximately 5 years for CEA compared with medical therapy. The 30-day rates of stroke or death after CEA in trials and cohort studies were 2.4% (CI, 1.7% to 3.1%; 6 trials; 3435 participants) and 3.3% (CI, 2.7% to 3.9%; 7 studies; 17474 participants), respectively. Other harms of interventions included myocardial infarction, nerve injury, and hematoma. LIMITATIONS: Trials may have overestimated benefits and used highly selected surgeons. Medical therapy used in trials was outdated, and stroke rates have declined in recent decades. Harms may have been underreported. CONCLUSION: Current evidence does not establish incremental overall benefit of CEA, stenting, or intensification of medical therapy. Potential for overall benefit is limited by low prevalence and harms. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.