Diagnostic accuracy of ANCA serology in ANCA-associated vasculitis with renal involvement.

BACKGROUND: Pauci-immune glomerulonephritis (GN) due to antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a common cause of crescentic GN. Despite advances in treatment, rates of mortality and progression to end-stage kidney disease remain high. Renal involvement is diagnosed by histological examination of kidney tissue. Serum ANCAs play a significant role in AAV; however, the value of serum ANCA quantification to predict renal involvement is not well-established. AIM: We aimed to evaluate the diagnostic accuracy of serum ANCA titres in diagnosing AAV with renal involvement. METHODS: We conducted a retrospective study of consecutive native kidney biopsies reported at our centre from 2016 to 2021. We included all adults who had both a kidney biopsy and ANCA serology. ANCA serology was tested using indirect immunofluorescence with reporting of titres. Antibodies to proteinase 3 and myeloperoxidase were measured using a chemiluminescent immunoassay. RESULTS: Eight hundred and forty-eight native kidney biopsies were reported during the study period. Five hundred and seven cases were included. The biopsy prevalence of pauci-immune GN in paired samples was 41/507 (8.1%). Most of the cohort had haematuria (66.6%), proteinuria (93.4%) and/or acute kidney injury (65.0%). A positive ANCA at any titre demonstrated a sensitivity of 97.6% and a specificity of 71.2% for a diagnosis of pauci-immune GN. The area under the curve for the receiver operator characteristic was 0.93 (95% confidence interval [CI]: 0.89-0.97). A cutoff ANCA titre of 1:160 provided the optimum balance between a sensitivity of 75.6% (95% CI: 59.7%-87.6%) and a specificity of 94.0% (95% CI: 91.6%-96.0%). CONCLUSIONS: ANCA titres are highly predictive of pauci-immune GN in the appropriate context. While serum ANCA quantitation may not replace renal biopsy, reporting will assist in the decision to start treatment early for patients with organ or life-threatening disease.

Economic Evaluation of Screening for Polyomavirus Infection in Kidney Transplant Recipients: A Cost-Utility Analysis.

Screening for polyomavirus infection after kidney transplantation is recommended by clinical practice guidelines, but cost-effectiveness of this strategy is uncertain. The aim of this study was to estimate the incremental costs and benefits of routine screening for polyomavirus infection compared with no screening in kidney transplant recipients. Methods: Probabilistic Markov models were constructed to compare the health and economic benefits of routine screening for polyomavirus infection using real-time polymerase chain reaction assay. A series of 1-way and probabilistic sensitivity analyses were conducted to define the most influential variables in the model. Results: Monthly screening for 6 mo followed by 3 monthly screenings until 12 mo after transplant was dominant (lower costs and improved outcomes). Compared with no screening, the incremental benefits of screening were 0.294 life-years saved and 0.232 quality-adjusted life-years saved. Total savings from screening were $6986 Australian dollars ($5057 US dollars). The cost-effectiveness ratios were most sensitive to the costs of transplantation and dialysis, age of transplantation, prevalence of viremia, and probability of death in patients with a history of polyomavirus-associated nephropathy. Probabilistic sensitivity analysis indicated that screening (compared with no screening) was the dominant strategy across all plausible ranges of transition probabilities. Conclusions: Screening for polyomavirus infections 1 year following transplantation appears to save money, improves survival, and improves quality of life in kidney transplant recipients.

Polyoma BK Virus in Kidney Transplant Recipients: Screening, Monitoring, and Management.

Polyomavirus BK virus (BKPyV) infection is an important complication of kidney transplantation and allograft failure. The prevalence of viremia is 10%-15%, compared with BK-associated nephropathy (BKPyVAN) at 3%-5%. Given that there are no effective antiviral prophylaxis or treatment strategies for BKPyVAN, active screening to detect BKPyV viremia is recommended, particularly during the early posttransplant period. Immunosuppression reduction to allow viral clearance may avoid progression to severe and irreversible allograft damage. The frequency and duration of screening are highly variable between transplant centers because the evidence is reliant largely on observational data. While the primary treatment goals center on achieving viral clearance through immunosuppression reduction, prevention of subsequent acute rejection, premature graft loss, and return to dialysis remain as major challenges. Treatment strategies for BKPyV infection should be individualized to the recipient's underlying immunological risk and severity of the allograft infection. Efficacy data for adjuvant therapies including intravenous immunoglobulin and cidofovir are sparse. Future well-powered and high-quality randomized controlled trials are needed to inform evidence-based clinical practice for the management of BKPy infection.

Measurement properties of all versions of the Stroke Specific Quality of Life Scale (SS-QOL) 2.0: a systematic review protocol.

OBJECTIVE: The aim of this review is to critically appraise and summarize the quality of the measurement properties of all versions of the Stroke Specific Quality of Life Scale (SS-QOL) version 2.0. INTRODUCTION: The Stroke Specific Quality of Life Scale version 2.0 was developed as a comprehensive measure in assessing the quality of life of stroke survivors. The shortened version and cross-culturally translated versions are further developed in different countries. A systematic review will clarify the levels of reliability and validity of all versions. INCLUSION CRITERIA: The population of interest for this review will include adult stroke survivors of either sex diagnosed with a stroke (ischemic or hemorrhagic) who have no other comorbidities affecting their quality of life. The SS-QOL version 2.0 will be the specific instrument of interest, and the quality of life of stroke survivors will be the construct of interest in this review. The measures of reliability, validity, and responsiveness will be assessed as outcomes. Only the studies evaluating the reliability, validity, and responsiveness of all versions of the SS-QOL 2.0 will be included in the review. METHODS: A literature search will be conducted for published studies in MEDLINE and Embase, and unpublished data in Google Scholar and ProQuest Dissertations and Theses. After a three-step search strategy, study selection will be done by two reviewers independently. Then, the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) methodology will be applied for assessment of methodological quality, data extraction, and synthesis. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42020211727.

Tests for latent tuberculosis in candidates for solid organ transplantation: A systematic review and meta-analysis.

Reactivation of latent tuberculosis following solid organ transplantation has serious consequences for the recipient. The most useful diagnostic test for latent TB is not clear. We conducted a systematic review and meta-analysis to assess the relative test performance of interferon gamma release assays (IGRAs) and the tuberculin skin test (TST) in people undergoing solid organ transplantation. The clinical or radiological risk factors were used as the proxy reference standard. Test performance was expressed as an odd ratio (OR). We identified 24 studies (N = 7811), 12 studies compared IGRAs with TST directly, nine studies evaluated only TST and three studies only IGRAs. Direct comparison between tests and clinical risk factors indicated both tests were strongly associated with the presence of clinical risk factors for TB (TST: OR 3.17; 95%CI 1.55-6.48, IGRA: OR 2.78; 95%CI 1.55-5.01), and radiological evidence of past TB (TST: OR 3.26; 95%CI 1.85-5.73, IGRA: OR 3.85; 95%CI 2.16-6.86). Relative comparison indicated IGRAs positivity was more strongly associated with presence of radiological evidence of TB than TST (relative OR: 3.24; 95%CI 1.10-9.56). While there is no strong evidence in supporting use of IGRAs over TST for diagnosing latent TB, IGRAs positivity is more associated with the presence of radiological evidence of previous TB.

Treatments to slow progression of autosomal dominant polycystic kidney disease: systematic review and meta-analysis of randomized trials.

AIM: Autosomal dominant polycystic kidney disease (ADPKD) is a monogenetic disorder that leads to kidney failure. Our aim was to undertake a meta-analysis of randomized trials of interventions that have been hypothesized to reduce the progression of total kidney volume (TKV) and renal function in ADPKD. METHODS: Relevant trials were identified, and outcomes were: change in TKV, total cyst volume (TCV), renal function and adverse events. Meta-analysis used random effects, with results expressed as mean difference and risk ratio both with 95% confidence intervals (CI). RESULTS: Eleven trials (2262 patients) were included. Compared with placebo, Target of Rapamycin complex 1 (TORC1) inhibitors (5 trials, n = 619), showed no significant change in TKV (P = 0.21), TCV (P = 0.06) or eGFR (P = 0.22). Somatostatin analogues (3 trials, n = 157) reduced TKV by 9% (95% CI -10.33 to -7.58%) but did not alter eGFR. The vasopressin receptor antagonist (n = 1455) attenuated TKV increase to 3%/year (95% CI -3.48 to -2.52) and slowed kidney function decline over a 3-year period. A single trial (n = 41) of eicosapentaenoic acid did not alter the progression of either TKV (P = 0.9) or renal dysfunction (P = 0.78). Adverse events were significant for interventions in all trials compared with placebo. CONCLUSION: These data suggest that somatostatin analogues and vasopressin receptor antagonists attenuate TKV increase. The neutral effects of TORC1 inhibitors on TKV could be true, or due to heterogeneity in study population, drug efficacy and follow-up duration. In the future, further well-designed and powered trials of longer duration using new biomarkers or therapeutic agents with better tolerance are required.

Health-related quality of life of patients awaiting kidney and simultaneous pancreas-kidney transplants.

AIM: Patients undergoing kidney and simultaneous pancreas-kidney (SPK) transplants are younger and fitter than the general dialysis population. Intuitively these patients might have better quality of life (QOL) than the general dialysis population, but their QOL scores are not well characterized. The aim of this study was to compare QOL of patients about to undergo kidney or SPK transplants with Australian dialysis outcomes and practice patterns (DOPPS) data and multiple comorbidity and age-adjusted general population data. METHODS: Patients attending Westmead Hospital for transplants from August 2009 to December 2011 were invited to complete the Kidney Disease QOL-SF(™) 1.3 (KDQOL-SF(™) 1.3) questionnaire regarding their immediate pretransplant QOL. This QOL instrument is predictive of hospitalizations and mortality. The questionnaire was completed within 4 weeks of transplantation. RESULTS: Of 180 patients seen within 4 weeks of transplantation 95 (53%) responded, with no differences from non-responders in age, sex, comorbidities or perioperative complications. Compared with DOPPS, these patients had better physical function and less pain, but significantly lower scores for role physical (CI: -19 to -4, P=0.004) and role emotional (CI: -17 to -2, P=0.018). Patients undergoing SPK transplants reported even poorer general health, energy, social support and function. Patients had lower emotional and social function than people with multiple comorbidities, with whom they shared poor general and mental health and vitality. Scores were markedly lower than the general population except for bodily pain (female). CONCLUSION: Younger, fitter patients are more vulnerable to effects of their illness on social, emotional and physical interactions and may benefit from targeted support.