The Kornblum DeLaMare rearrangement in natural product synthesis: 25 years of innovation.

Covering: 1998 up to the end of 2023Since its initial disclosure in 1951, the Kornblum DeLaMare rearrangement has proved an important synthetic transformation and has been widely adopted as a biomimetic step in natural product synthesis. Utilising the base catalysed decomposition of alkyl peroxides to yield a ketone and alcohol has found use in many syntheses as well as a key strategic step, including the unmasking of furans, as a biomimetic synthetic tool, and the use of the rearrangement to install oxygen enantioselectively. Since ca. 1998, its impact as a synthetic transformation has grown significantly, especially given the frequency of use in natural product syntheses, therefore this 25 year time period will be the focus of the review.

Structures of Streptococcus pyogenes class A sortase in complex with substrate and product mimics provide key details of target recognition.

The cell wall is a critical extracellular barrier for bacteria and many other organisms. In bacteria, this structural layer consists of peptidoglycan, which maintains cell shape and structural integrity and provides a scaffold for displaying various protein factors. To attach proteins to the cell wall, Gram-positive bacteria utilize sortase enzymes, which are cysteine transpeptidases that recognize and cleave a specific sorting signal, followed by ligation of the sorting signal-containing protein to the peptidoglycan precursor lipid II (LII). This mechanism is the subject of considerable interest as a target for therapeutic intervention and as a tool for protein engineering, where sortases have enabled sortase-mediated ligation or sortagging strategies. Despite these uses, there remains an incomplete understanding of the stereochemistry of substrate recognition and ligation product formation. Here, we solved the first structures of sortase A from Streptococcus pyogenes bound to two substrate sequences, LPATA and LPATS. In addition, we synthesized a mimetic of the product of sortase-mediated ligation involving LII (LPAT-LII) and solved the complex structure in two ligand conformations. These structures were further used as the basis for molecular dynamics simulations to probe sortase A-ligand dynamics and to construct a model of the acyl-enzyme intermediate, thus providing a structural view of multiple key states in the catalytic mechanism. Overall, this structural information provides new insights into the recognition of the sortase substrate motif and LII ligation partner and will support the continued development of sortases for protein engineering applications.

Kidney outcomes and prognostic factors of myeloma associated acute kidney injury in the contemporary era.

Myeloma cast nephropathy (MCN) has historically been associated with poor kidney outcomes. We aimed to evaluate the kidney outcomes and identify prognostic factors of myeloma-associated acute kidney injury (M-AKI) in the contemporary era of anti-plasma cell therapy. Patients who received anti-myeloma therapy with M-AKI (January 2012 to June 2020) from a single centre were identified from electronic medical records. Diagnosis of MCN was either biopsy confirmed (BC) or clinically suspected (CS), the latter defined as acute kidney injury with reduced estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 and involved serum free light chains (iSFLC) >500 mg/L at diagnosis. Twenty-six patients with M-AKI were identified (BC: n = 13, CS: n = 13). Median eGFR at diagnosis was 12 (interquartile range 6-20) mL/min/1.73 m2 . All six dialysis-requiring patients achieved dialysis independence after 71 (43-208) days. The best-achieved eGFR was 47 (32-67) mL/min/1.73 m2 after 120 (63-167) days post-treatment, which was maintained at 47 (33-66) mL/min/1.73 m2 12 months post-treatment. Patients with best-achieved eGFR above the median were more likely to have achieved an iSFLC of <20 mg/L (above median group 62% versus below median group 0%; p < .001) and lower best post-treatment iSFLC (20 (12-90) versus 67 (29-146) mg/L; p < .05). Best-achieved iSFLC was a prognostic factor for superior eGFR following treatment for M-AKI. Despite low eGFR at diagnosis, contemporary anti-myeloma therapy can achieve significant recovery of kidney function.

Understanding underperformance in a high-stakes clinical-based simulation assessment in physiotherapy: a descriptive analysis.

BACKGROUND: High-stakes assessments are often used as a 'gate-keeper' activity for entry into the health professions by ensuring that the minimum core competency thresholds of the profession are met. The aim of the study was to explore if common areas of underperformance existed in international candidates assessed with a high-stakes clinical-based simulation assessment for entry into the physiotherapy profession in Australia. METHODS: A retrospective mixed methods analysis of the clinical assessments completed by international candidates over a one-month period in 2021 that were deemed as not meeting competency. The clinical assessments were completed in one of the three practice areas: cardiorespiratory, musculoskeletal, or neurological rehabilitation. Each assessment was scored by two independent assessors, who discussed the performance and then completed a moderated assessment form. The assessment form used to score competency included seven domains such as initial assessment, effective treatment, communication skills, and risk management. RESULTS: Fifty-one clinical assessments graded as not competent were analysed. Across the practice areas, a high failure rate was found in domains related to interpreting assessment findings and developing a treatment plan. This trend was also observed in the qualitative data, suggesting candidates struggled to meet competency in areas of planning and prioritisation, interpretation and implementation of the information gathered, and selection and evaluation of effective treatment. CONCLUSION: These findings align with published data on the underperformance of Australian physiotherapy students in clinical placement settings, suggesting these issues are not specific to high stakes assessment of overseas physiotherapists, and that education needs to focus on improving these skills within the profession at all levels. With the identified areas of underperformance aligning with the ability to use higher order thinking and skills integral to clinical reasoning, improvements in the education and implementation of clinical reasoning may be a place to start.

Painful temporomandibular disorders in Confucian-heritage cultures: Their inter-relationship with bodily pain, psychological well-being and distress.

BACKGROUND: Temporomandibular disorders (TMDs) are common and affect individuals negatively. OBJECTIVES: This study investigated the inter-relationship of painful TMDs with bodily pain, psychological well-being and distress in young people from a Confucian-heritage culture (CHC). METHODS: Adolescents/young adults were recruited from a polytechnic in Singapore. While the presence/severity of painful TMDs and bodily pain were established with the DC/TMD Pain Screener (TPS) and Maciel's Pain Inventory, psychological well-being and distress were evaluated with the Scales of Psychological Well-being-18 (SPWB-18) and Patient Health Questionnaire-4 (PHQ-4). Statistical explorations were conducted using chi-square/Mann-Whitney U tests, Spearman's correlation and logistic regression analyses (α = .05). RESULTS: Among the 225 participants (mean age 20.1 ± 3.9 years) examined, 11.6% had painful TMDs and 68.9% experienced multisite bodily pain. Though painful TMDs were accompanied by a higher occurrence of multisite bodily pain, the overall/discrete number of bodily pain sites did not differ substantially between the 'no TMD pain' (NT) and 'with TMD pain' (WT) groups. Besides ear pain, differences in overall/discrete bodily pain scores were also insignificant. However, significant differences in environmental mastery, overall psychological distress, depression and anxiety subscale scores were discerned between the NT and WT groups. Psychological well-being and distress were moderately and negatively correlated (rs = -.56). Multivariate analysis indicated that ear pain and psychological distress increased the prospect of painful TMDs. CONCLUSION: The prevalence of multi-site bodily pain was high in young people from CHCs irrespective of the painful TMDs' presence of painful TMDs. Enhancing environmental mastery and relieving depression/anxiety may help manage TMD pain.

Lower versus higher starting tacrolimus dosing in kidney transplant recipients.

Achieving therapeutic tacrolimus levels is an essential component of balancing immunosuppression in kidney transplantation. At our institution, the starting tacrolimus dose was reduced from .075 mg/kg BD (higher dose [HD]) to .050 mg/kg BD (lower dose [LD]), to better achieve our target level of 6-10 µg/L in the early posttransplant period. Kidney transplant recipients (KTRs) transplanted 1-year before (HD: n = 64) and after (LD: n = 63) the starting dose reduction were retrospectively compared. Achieved tacrolimus levels were significantly lower in the LD group during the first 14 days posttransplant, but not at day 21 or day 28. A higher proportion of LD KTRs achieved therapeutic levels (day 1-3: 36.1% vs. 18.8%; day 4-7: 50.8% vs. 40.6%, day 8-14: 83.6% vs. 71.7%), while the HD KTRs were more likely to have supratherapeutic levels. Tacrolimus dose was significantly lower on day 5 compared to day 0 in the HD group but similar in the LD group. Rates of delayed graft function, posttransplant diabetes, and treated rejection at 6 months and graft outcomes at 3 years were all similar. Lowering the starting tacrolimus dose increased the proportion of KTRs achieving therapeutic range and minimized dose changes early posttransplant without an impact on clinical outcomes.

Eating and Psychiatric Disorders Are Independent Risk Factors for Rumination Syndrome.

GOAL: The goal of this study was to evaluate whether a history of eating disorders (EDs) or psychiatric disorders (PDs) are risk factors for rumination syndrome (RS). BACKGROUND: RS is a disorder of gut-brain interaction characterized by an effortless postprandial retrograde flow of ingested contents. Disorder of gut-brain interactions have been associated with psychiatric and behavioral comorbidities. No prior comparative study has assessed the relationship between RS and ED or PD. METHODS: This was a case-control study of adults with RS at a tertiary center in January 2013 to January 2018. Two age-matched/gender-matched controls per RS case were identified. The Fisher exact test (categorical)/Student t test (continuous) and forward stepwise logistic regression were performed for univariate and multivariable analyses, respectively. RESULTS: Seventy-two patients (24 cases/48 controls) were included. Baseline demographics and characteristics were similar between cases and controls. Among RS patients, 9 (37.5%) had a history of ED, including 3 (12.5%) anorexia nervosa and 4 (16.7%) bulimia nervosa; and 20 (83.3%) had a PD, including 9 (37.5%) anxiety and 7 (29.2%) depression. Prevalence of ED (37.5% vs. 4.2%, P=0.0002) and PD (83.3% vs. 50.0%, P=0.0062) were higher among RS patients than controls. Specifically, the risks of anorexia nervosa (16.7% vs. 0%, P=0.005) and bulimia nervosa (21.1% vs. 0%, P=0.001) were both increased in RS patients. On multivariable analysis, ED (adjusted odds ratio=16.4, P=0.0033) and PD (adjusted odds ratio=4.47, P=0.029) remained independent predictors for RS. CONCLUSIONS: A history of ED and PD were independent risk factors for RS. Abnormal eating behaviors and psychiatric comorbidities may contribute to the pathogenesis of RS. Evaluation of RS should include a detailed history for ED and PD.

Current approaches to the diagnosis and management of amyloidosis.

Amyloidosis is a collection of diseases caused by the misfolding of proteins that aggregate into insoluble amyloid fibrils and deposit in tissues. While these fibrils may aggregate to form insignificant localised deposits, they can also accumulate in multiple organs to the extent that amyloidosis can be an immediately life-threatening disease, requiring urgent treatment. Recent advances in diagnostic techniques and therapies are dramatically changing the disease landscape and patient prognosis. Delays in diagnosis and treatment remain the greatest challenge, necessitating physician awareness of the common clinical presentations that suggest amyloidosis. The most common types are transthyretin (ATTR) amyloidosis followed by immunoglobulin light-chain (AL) amyloidosis. While systemic AL amyloidosis was previously considered a death sentence with no effective therapies, significant improvement in patient survival has occurred over the past 2 decades, driven by greater understanding of the disease process, risk-adapted adoption of myeloma therapies such as proteosome inhibitors (bortezomib) and monoclonal antibodies (daratumumab) and improved supportive care. ATTR amyloidosis is an underdiagnosed cause of heart failure. Technetium scintigraphy has made noninvasive diagnosis much easier, and ATTR is now recognised as the most common type of amyloidosis because of the increased identification of age-related ATTR. There are emerging ATTR treatments that slow disease progression, decrease patient hospitalisations and improve patient quality of life and survival. This review aims to update physicians on recent developments in amyloidosis diagnosis and management and to provide a diagnostic and treatment framework to improve the management of patients with all forms of amyloidosis.

Dental fear and anxiety in Asian youths: response components and inducing stimuli.

OBJECTIVES: This study estimated the prevalence of dental fear/anxiety (DFA) and phobia in Asian youths and investigated the fear/anxiety response components and triggers for those with DFA. MATERIALS AND METHODS: A convenience sample of youths, aged 17 to 24 years old, was recruited from a local polytechnic. The Index of Dental Anxiety and Fear-4C + (IDAF-4C +) was employed to assess the occurrence of DFA (IDAF-4C) and phobia (IDAF-P) as well as to ascertain fear/anxiety-inducing stimuli (IDAF-S). Psychological distress was determined with the Patient Health Questionnaire-4 (PHQ-4). Sociodemographic, IDAF-4C + , dental attendance patterns, and PHQ-4 data were gathered electronically. Statistical analyses were conducted with chi-square, Kruskal-Wallis, and relevant post hoc tests (α = 0.05). RESULTS: A total of 215 participants were enrolled (mean age of 18.9 ± 2.0 years; 87.4% women). Of these, 12.6/6.0% had moderate-to-high (MH)/high-to-extreme (HE) DFA and 0.9% experienced dental phobia. Significant differences in scores were observed between the HE/MH and no-to-moderate (NM) groups for all IDAF-4C components. Apart from the cost of dental treatment, IDAF-4S scores varied significantly among the three DFA groups. The two most highly rated DFA stimuli were painful/uncomfortable procedures and needles/injections for the HE group, while they were needles/injections and the cost of dental treatment for the MH and NM groups. CONCLUSIONS: Moderate-to-extreme DFA existed in 18.6% of the Asian youths examined. The emotional and physiological components of the IDAF-4C appear to contribute more to the DFA response. Dental pain including needles/injections and the cost of dental treatment troubled Asian youths the most. CLINICAL RELEVANCE: DFA is a common problem among Asian youths, and understanding its extent, nature, and triggers is central for effective interventions.

Dental environment and practitioner preferences of southeast Asian youths with dental fear/anxiety.

OBJECTIVES: This study estimated the prevalence of dental fear/anxiety (DFA) in Southeast Asian youths and established their dental environment and practitioner preferences. METHODS: A convenience sample of youths were enrolled from a local polytechnic. The Index of Dental Anxiety and Fear (IDAF-4C) was used to ascertain the presence and severity of DFA. Socio-demographic and IDAF-4C data, along with participants' dental environment and practitioner partialities were gathered electronically. Statistical evaluations were performed with Kruskal-Wallis and Chi-square tests (α = 0.05). RESULTS: Data from a total of 215 participants were appraised. The mean age of the study sample was 18.9 ± 2.0 years (87.4% women). Of these, 12.6% had moderate-to-high DFA and 6.0% had high-to-extreme DFA. As a group, Southeast Asian youths generally liked dental clinics with adorned walls, cooler temperatures, magazines/books, background music and audio-visual devices. In addition, they favoured female practitioners who are younger (≤45 years old), friendly, talkative and maintain a professional relationship. However, those with high-to-extreme DFA preferred a warmer clinic environment and to have an informal relationship with their dental practitioners (p = 0.01). CONCLUSIONS: The prevalence of moderate-to-extreme DFA in Southeast Asian youths was 18.6%. Individuals with high-to-extreme DFA may have disparate dental environment and practitioner preferences compared to those with no-to-moderate DFA.

Reflex Detection of Ciprofloxacin Resistance in Neisseria gonorrhoeae by Use of the SpeeDx ResistancePlus GC Assay.

Resistance-guided therapy (RGT) for gonorrhea may reduce unnecessary use of broad-spectrum antibiotics. When reflexed from the Aptima Combo 2 assay, the ResistancePlus GC assay demonstrated 94.8% sensitivity and 100.0% specificity for Neisseria gonorrhoeae detection. Of the 379 concordant N. gonorrhoeae-positive samples, 86.8% were found to possess the gyrA S91F mutation, which was highly predictive for ciprofloxacin resistance and stable across 3,144 publicly available N. gonorrhoeae genomes. Our work supports the feasibility of implementing RGT for gonorrhea into routine molecular workflows.

Coexisting Abnormal Esophageal Body Motility Predicts Clinical Symptoms and Bolus Transit in Patients With Esophagogastric Junction Outflow Obstruction (EGJOO).

GOAL: The goal of this study was to compare the clinical presentations of esophagogastric junction outflow obstruction (EGJOO) with coexisting abnormal esophageal body motility (EBM) to isolated EGJOO. BACKGROUND: The clinical significance and management of EGJOO remain debated, as patients may have varied to no symptoms. The effect of coexisting abnormal EBM in EGJOO is unclear. We hypothesized that a concomitant EBM disorder is associated with clinical symptoms of EGJOO. STUDY: This was a retrospective cohort study of consecutive adults diagnosed with EGJOO on high-resolution impedance-manometry (HRIM) at 2 academic centers in March 2018 to September 2018. Patients with prior treatment for achalasia, foregut surgery, or evidence of obstruction were excluded. Subjects were divided into EGJOO with abnormal EBM per Chicago classification v3.0 and isolated EGJOO. Statistical analyses were performed using Fisher-exact or Student t test (univariate) and logistic or linear regression (multivariate). RESULTS: Eighty-two patients (72% women, age 61.1±10.7 y) were included. Thirty-one (37.8%) had abnormal EBM, including 16 (19.5%) ineffective esophageal motility and 15 (18.2%) hypercontractile esophagus. Esophageal symptoms (heartburn, regurgitation, chest pain, dysphagia) were more prevalent among those with abnormal EBM (90.3% vs. 64.7%, P=0.01). On logistic regression adjusting for age, gender, body mass index, and opioid use, abnormal EBM remained predictive of esophageal symptoms (adjusted odds ratio [aOR] 7.51, P=0.007). On separate models constructed, HE was associated with chest pain (aOR 7.45, P=0.01) and regurgitation (aOR 4.06, P=0.046), while ineffective esophageal motility was predictive of heartburn (aOR 5.84, P=0.009) and decreased complete bolus transit (ß-coefficient -0.177, P=0.04). CONCLUSION: Coexisting abnormal EBM is associated with esophageal symptoms and bolus transit in patients with EGJOO.

Tissue-specific production of MicroRNA-155 inhibits melanocortin 5 receptor-dependent suppressor macrophages to promote experimental autoimmune uveitis.

Tissue-specific immune regulation is an important component of the immune response relevant to many areas of immunology. The focus of this study is on tissue-specific mechanisms that contribute to autoimmune uveitis. Precise gene regulation is necessary for the proper expression of an inflammatory or regulatory response. This precision gene regulation can be accomplished by microRNA at the level of the mRNA transcript. miR-155, in particular, has a complicated role in the immune response with positive and negative inflammatory effects. In this work, we identify a decrease in miR-155 in suppressor macrophages and further examine how tissue-specific production of miR-155 impacts experimental autoimmune uveitis. Importantly, we show that eliminating miR-155 expression by the target tissue before initiation reduces disease severity, but elimination of miR-155 after the onset of inflammation does not alter the course of disease. Additionally, expression of miR-155 by the target tissue before initiation is necessary for the induction of regulatory immunity that protects from further autoimmune disease, but not after the onset of inflammation. In summary, we find a MC5r-dependent decrease in miR-155 in postexperimental autoimmune uveitis APC, miR-155 production by the target tissue is necessary for the initiation of autoimmune uveitis, and may have a role in establishing protective regulatory immunity.

TIGIT+ A2Ar-Dependent anti-uveitic Treg cells are a novel subset of Tregs associated with resolution of autoimmune uveitis.

Regulatory T cells (Tregs) are necessary to prevent autoimmune disease. As such, stable FoxP3 expression is required for the proper function of Tregs in the control of autoimmune disease. Different Treg subsets that utilize different mechanisms of suppression have been identified. The T-cell immunoglobulin immunoreceptor tyrosine-based inhibitory motif (TIGIT) is a relatively new Treg cell marker that has a suppressive function. We have previously identified the adenosine 2A receptor (A2Ar) as a requirement for the emergence of Tregs following resolution of autoimmune disease. Using a FoxP3-GFP-Cre reporter mouse, we identify FoxP3 and 'exFoxP3' cells, show FoxP3 and not exFoxP3 cells are suppressive. We further show FoxP3 cells express TIGIT, and are induced through A2Ar in healthy volunteers, but not patients with autoimmune disease. Furthermore, we show Tregs emerge in the target tissue at the onset of autoimmune disease in an A2Ar-dependent manner. In summary, we identify a novel subset of TIGIT+ Tregs that are induced through stimulation of the A2Ar.

Baseline characteristics of patients with atypical haemolytic uraemic syndrome (aHUS): The Australian cohort in a global aHUS registry.

AIMS: To describe the baseline characteristics and treatment of Australian patients diagnosed with atypical haemolytic uraemic syndrome (aHUS) reported to the Global aHUS Registry. METHODS: Descriptive analysis of the Australian cohort with aHUS (n = 106) was undertaken for demographics, disease characteristics and prior treatment with eculizumab; comparing with the global cohort (n = 1688) for certain pre-specified disease characteristics. RESULTS: In Australia, almost two-thirds of patients diagnosed with aHUS were female and over 80% of patients were Caucasians, with similar proportions reported in the global cohort. Less than 6% of patients in the Australia and global cohorts were reported to have a history of autoimmune disease (4% vs 2%, respectively; P = .21) or cancer (5% vs 5%, respectively; P = .93), conditions that have been associated with secondary HUS. In the Australian cohort, 26% had received a kidney transplant and 68% of patients had received eculizumab. Kidneys were the most common organ involvement, followed by gastrointestinal tract (26%) and cardiovascular system (19%), with 35% of patients reported to have had at least two organs involved within 6 months prior to baseline visit or entry into the registry. Complement factor H was the most common pathogenic complement gene variant in the Australian patients. CONCLUSION: Data from the aHUS registry confirms and defines region-specific disease characteristics among a selected group of Australian children and adults with aHUS reported to the registry. Ongoing and more inclusive data will provide further information about temporal trends and treatment outcomes, representing a unique opportunity for clinicians and researchers to further develop knowledge surrounding this rare disease.

Allocation of deceased donor kidneys: A review of international practices.

The demand for kidney transplantation continues to exceed the availability of deceased donor kidneys. Balancing the overarching principles of the optimal use of (utility) and equal access to (equity) this scarce resource requires a sophisticated allocation system. This review will examine how various factors are addressed in allocation systems around the world to strike a balance between utility and equity.

Tissue typing for kidney transplantation for the general nephrologist.

Tissue typing is the process by which an individual's human leukocyte antigens (HLA) are determined. In transplantation, this vital process allows the immunologic or rejection risk of a donor-recipient pairing to be assessed through reviewing their HLA matching and whether any anti-HLA antibodies present in recipient serum are donor specific. Tissue typing has increased in sophistication over time which has allowed a deeper appreciation of the antigenically important parts of HLA and increased the complexity of determining immunologic risk.

A controlled study of the effects of ferric carboxymaltose on bone and haematinic biomarkers in chronic kidney disease and pregnancy.

Background: Intravenous (IV) iron can modulate fibroblast growth factor 23 (FGF23) concentrations and cause transient but significant hypophosphataemia. However, it is unknown what other markers might be involved, especially in different patient groups. This study aimed to determine changes in bone and haematinic biomarkers following IV ferric carboxymaltose (FCM) and to identify risk factors for hypophosphataemia in pregnant subjects and those with chronic kidney disease (CKD). Methods: Changes in bone [serum FGF23, fractional excretion of phosphate urinary fractional excretion of phosphate (FEPi), serum phosphate and serum vitamin D derivatives] and haematinic [plasma hepcidin, serum ferritin and transferrin saturation (TSAT)] biomarkers after 1 g of IV FCM were followed in iron-deficient pregnant and CKD patients and compared with controls (estimated glomerular filtration rate > 60 mL/min/1.73 m2). Data were collected at baseline and up to 42 days after infusion. Risk factors for post-FCM hypophosphataemia were also assessed. Results: Sixty-five subjects completed the study (control, n = 20; pregnant, n = 20; CKD, n = 25). A uniform but variable increase across groups was seen in intact FGF23 (peak Day 2), whereas c-terminal FGF23 varied markedly. Trough serum phosphate timed with the peak FEPi at Day 7, recovering by Day 21 in the pregnant group and Day 42 in other groups. Independent predictors of a low phosphate nadir included baseline phosphate, FEPi and weight-adjusted FCM dose. All groups showed an early and marked increase in plasma hepcidin (peak Day 2), serum ferritin and TSAT (peak Day 7 for both). Conclusions: Changes in bone and haematinic biomarkers differ between patient groups following IV FCM. For patients with lower serum phosphate concentrations, limiting the dose and measuring levels 7 days after administration may mitigate clinically significant hypophosphataemia.

Lifetime risk of end-stage kidney disease in living donors for paediatric kidney transplant recipients in Australia and New Zealand - a retrospective study.

Living kidney donors (LKD) for paediatric kidney transplant recipients (KTR) have a heightened motivation to donate for emotional reasons and the clear health benefits to the KTR. We hypothesized that the cohort of LKD for paediatric KTR (LKD-P) includes motivated young parents with a higher lifetime end-stage kidney disease (ESKD) risk compared to adult KTR (LKD-A). Data from the Australia and New Zealand Dialysis and Transplant LKD Registry (2004-2015) was analysed to compare baseline characteristics and predonation ESKD risk in LKD-P (n = 315) versus LKD-A (n = 3448). LKD-P were younger (median age 42 vs. 50 years; P < 0.001) and had a marginally higher lifetime ESKD risk (median 0.44% vs. 0.40%; P < 0.01), with a similar proportion of LKD exceeding 1% risk threshold (5.4% vs. 5.6%; P = NS). Compared to grandparents as LKD-P, parents (median age 41 vs. 59 years; P < 0.001) had a higher lifetime ESKD (0.44% vs. 0.25%; P < 0.001). Although unique benefits to paediatric KTR justify the minor increase in lifetime ESKD risk in young parents, carefully selected grandparents are an alternative LKD-P option, allowing parents to donate for subsequent transplants.

Use of a new end-stage kidney disease risk calculator in the Kidney Disease Improving Global Outcomes guideline to evaluate the impact of different living kidney donor candidate assessments.

AIM: The Kidney Disease Improving Global Outcomes (KDIGO) guideline recommends the incorporation of a new risk calculator that quantifies the end-stage kidney disease (ESKD) risk based on a composite profile of risk factors in living kidney donor candidates (LKDC). We compared the ESKD risk estimates in previously declined versus accepted LKDC to evaluate the predictive capacity and potential impact of this tool. METHODS: Baseline 15 year and lifetime ESKD risk estimates without donation were calculated using the risk calculator for LKDC assessed from two centres between 2007 and 2015. LKDC suitability based on the proposed KDIGO and the existing Caring for Australasians with Renal Impairment national guidelines was compared. RESULTS: Median 15 year ESKD risk was 0.14% (IQR 0.09-0.31%) in declined LKDC (n=59) versus 0.10% (0.07-0.14%) in accepted LKDC (n=89) (P<0.001). Lifetime risk was similar: 0.39% (0.23-0.80%) versus 0.35% (0.22-0.56%), respectively; however, declined LKDC had a higher 98% risk percentile value (8.19% vs 1.02%) and were more likely to exceed a 1% ESKD risk threshold (15% vs 1%; P<0.01). The calculator captured reasons for declining donation in only 39% of LKDC; 46.9% of LKDC with Caring for Australasians with Renal Impairment contraindications were reclassified as having an acceptable (≤1%) lifetime risk and no KDIGO contraindications, primarily related to a lower pre-donation glomerular filtration rate or controlled hypertension with obesity. CONCLUSION: Declined LKDC had a higher 15 year but similar lifetime ESKD risk. However, the calculator successfully differentiated declined LKDC with a lifetime risk >1%. This risk calculator appears to complement but not replace clinical evaluation.