Retrospective case-control study exploring pretransplant predictors for loss of kidney transplant function or death among indigenous kidney transplant recipients.

BACKGROUND: The factors affecting the outcomes among Indigenous kidney transplant recipients is not fully understood. We conducted a retrospective case control study to identify risk factors beyond those explained by the ANZDATA registry. AIM: To identify the risk factors for loss of kidney transplant function or death among Indigenous kidney transplant recipients. METHODS: Cases were defined as all Indigenous Australian kidney transplant recipients from 1 January 2005 to 31 December 2015 from the major hospitals in the Northern Territory (NT) and South Australia (SA) who experienced graft loss (including patient death) up to 2-years post-transplant. Controls (matched 4:1) were defined as all indigenous kidney transplant recipients during the same period with functioning transplants at 2-years post-transplant operation. Matching was done on gender and diabetes status. Regression analysis adjusted for age was used for comparing cases and controls. RESULTS: There were 17 cases and 68 matched controls. Among cases, the odds ratio for more than one hospital admission episode (compared with ≤1 episode) in the 2-year pretransplant period was 6.2 (95% confidence interval, 1.2-32.5). However, there were no significant differences in the frequency of comorbidities at renal replacement therapy start, cardiovascular intervention pretransplant, pretransplant infection screening, age and gender of the donors, frequency of admission episodes where an infection was documented, the total length of inpatient stay or admission to intensive care unit during pretransplant hospital admission between cases and controls. CONCLUSION: Early graft loss was associated with a higher frequency of hospital admissions in the 2-years pretransplant period. In contrast, other measured factors in the pretransplant period did not predict these adverse outcomes.

Remote Strain Activation in a Sulfate-Linked Dibenzocycloalkyne.

Cycloalkynes and their utilization in cycloaddition reactions enable modular strategies spanning the molecular sciences. Strain─imparted by deviation from linearity─enables sufficient alkyne reactivity without the need for a catalyst (e.g., copper); however, the design and synthesis of stable reagents with suitable reactivity remains an ongoing challenge. We report the incorporation of an endocyclic sulfate within a dibenzocyclononyne scaffold to generate a cyclononyne displaying remarkable reactivity and stability. Through computational analyses, we revealed that the endocyclic sulfate group shares nearly half the total strain energy, providing an activation strategy that reduces alkyne bending. Rehybridization of alkyne carbons in the formation of the heterocyclic product relieves strain both at the reactive site and in the transannular sulfate group. This mode of remote activation enables rapid reactivity while minimizing distortion─and strain─at the reactive site (the alkyne). The result: a design strategy for a new class of cycloalkynes with increased stability and reactivity.

Acceleration of 1,3-Dipolar Cycloadditions by Integration of Strain and Electronic Tuning.

The 1,3-dipolar cycloaddition between azides and alkynes provides new means to probe and control biological processes. A major challenge is to achieve high reaction rates with stable reagents. The optimization of alkynyl reagents has relied on two strategies: increasing strain and tuning electronics. We report on the integration of these strategies. A computational analysis suggested that a CH → N aryl substitution in dibenzocyclooctyne (DIBO) could be beneficial. In transition states, the nitrogen of 2-azabenzo-benzocyclooctyne (ABC) engages in an n→π* interaction with the C=O of α-azidoacetamides and forms a hydrogen bond with the N-H of α-diazoacetamides. These dipole-specific interactions act cooperatively with electronic activation of the strained π-bond to increase reactivity. We found that ABC does indeed react more quickly with α-azidoacetamides and α-diazoacetamides than its constitutional isomer, dibenzoazacyclooctyne (DIBAC). ABC and DIBAC have comparable chemical stability in a biomimetic solution. Both ABC and DIBO are accessible in three steps by the alkylidene carbene-mediated ring expansion of commercial cycloheptanones. Our findings enhance the accessibility and utility of 1,3-dipolar cycloadditions and encourage further innovation.

Nickel-Catalyzed α-Carbonylalkylarylation of Vinylarenes: Expedient Access to γ,γ-Diarylcarbonyl and Aryltetralone Derivatives.

We report a Ni-catalyzed regioselective α-carbonylalkylarylation of vinylarenes with α-halocarbonyl compounds and arylzinc reagents. The reaction works with primary, secondary, and tertiary α-halocarbonyl molecules, and electronically varied arylzinc reagents. The reaction generates γ,γ-diarylcarbonyl derivatives with α-secondary, tertiary, and quaternary carbon centers. The products can be readily converted to aryltetralones, including a precursor to Zoloft, an antidepressant drug.

Disparity of access to kidney transplantation by Indigenous and non-Indigenous Australians.

OBJECTIVE: To compare the likelihood of Indigenous and non-Indigenous Australians being placed on the waiting list for transplantation of a kidney from a deceased donor; to compare the subsequent likelihood of transplantation. DESIGN, SETTING AND PARTICIPANTS: Observational cohort study; analysis of data from the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry for patients aged 18-60 years at the start of renal replacement therapy, who commenced renal replacement therapy in Australia between 28 June 2006 and 31 December 2016. MAIN OUTCOME MEASURES: Time to wait-listing; time to kidney transplantation after wait-listing. RESULTS: 10 839 patients met the inclusion criteria, of whom 2039 (19%) were Indigenous Australians; 217 Indigenous and 3829 non-Indigenous patients were active on the waiting list at least once during the study period. The hazard ratio (HR) for wait-listing (Indigenous v non-Indigenous patients, adjusted for patient- and disease-related factors) in the first year of renal replacement therapy varied with age and remoteness (range, 0.11 [95% CI, 0.07-0.15] to 0.36 [95% CI, 0.16-0.56]); in subsequent years the adjusted HR was 0.90 (95% CI, 0.50-1.6). The adjusted HR for transplantation during the first year of wait-listing did not differ significantly from 1.0; for subsequent years of wait-listing, however, the adjusted HR was 0.40 (95% CI, 0.29-0.55). CONCLUSION: Disparities between Indigenous and non-Indigenous patients with end-stage kidney disease in access to kidney transplantation are not explained by patient- or disease-related factors. Changes in policy and practice are needed to reduce these differences.

Ni-Catalyzed Regioselective Alkylarylation of Vinylarenes via C(sp3)-C(sp3)/C(sp3)-C(sp2) Bond Formation and Mechanistic Studies.

We report a Ni-catalyzed regioselective alkylarylation of vinylarenes with alkyl halides and arylzinc reagents to generate 1,1-diarylalkanes. The reaction proceeds well with primary, secondary and tertiary alkyl halides, and electronically diverse arylzinc reagents. Mechanistic investigations by radical probes, competition studies and quantitative kinetics reveal that the current reaction proceeds via a Ni(0)/Ni(I)/Ni(II) catalytic cycle by a rate-limiting direct halogen atom abstraction via single electron transfer to alkyl halides by a Ni(0)-catalyst.

Overview of dialysis in indigenous compared to nonindigenous Australians.

INTRODUCTION: Indigenous Australians (Aboriginal and Torres Strait Islanders, ATSI) make up 3% of the total Australian population [1] and comprised ~ 10% of new patients beginning renal replacement for end-stage kidney disease (ESKD) in Australia during 2013 [2]. In this study, we examined the differences in characteristics, incidence, and prevalence of different modalities of dialysis and survival between indigenous and nonindigenous Australians. METHODS: We examined outcomes of all adults (aged ≥ 18 years at the start of renal replacement therapy (RRT)) in the ANZDATA registry who started RRT from 1st Jan 2003 to 31st Dec 2013 in Australia. Adjusted patient survival on dialysis was calculated using standard techniques. RESULTS: A total of 25,528 participants were included, of whom 2,447 (9.5%) were indigenous Australians. Use of facility hemodialysis was more common among indigenous people, odds ratio (OR) 1.79 (95% confidence interval (CI), 1.37, 2.35). Of several interactions between indigenous status and other comorbidities, the most clinically significant was one with diabetes. In fully adjusted models, compared to nonindigenous with diabetes; death risk was higher for indigenous people with diabetes, HR 1.15 (95% CI, 1.06, 1.25). There was no difference between the two groups without diabetes, HR 0.86 (95% CI, 0.73, 1.05). There was no variation in the risks associated with ethnicity over year of dialysis start. CONCLUSION: There are differences in adjusted outcomes of indigenous Australians compared to nonindigenous with ESKD. Interactions suggest that the influence of reported comorbidities may differ in this group. Further investigations will be valuable in closing the gap and improving health outcome of indigenous Australians on RRT.

Factors predicting the outcome of acute renal failure in pregnancy.

OBJECTIVE: To determine the factors predicting renal outcome in patients developing acute renal failure in pregnancy. STUDY DESIGN: Descriptive cohort study. PLACE AND DURATION OF STUDY: Study was conducted at Nephrology Unit of Sindh Institute of Urology and Transplantation, Karachi, from October 2006 to March 2007. METHODOLOGY: Patients with acute renal failure due to complications of pregnancy, with normal size of both the kidneys on ultrasound were enrolled, and followed for a period of 60 days or until recovery of renal function. Patient's age and parity, presence of antenatal care, type of complication of pregnancy, foetal outcome and duration of oliguria were compared between patients who remained dialysis dependent and those who recovered renal function. Chi-square/Fisher's exact test and student's t-test, were used for determining the association of categorical and continuous variables with dialysis dependency. RESULTS: The mean age was 29+/-6 years. Most patients came from rural areas of interior Sindh. Sixty eight percent did not have antenatal checkups. Antepartum haemorrhage (p=0.002) and prolonged duration of oliguria (35+/-15.7 days, p= < 0.001) were associated with dialysis dependency, which was observed in 50% of the study group. CONCLUSION: Ante-partum haemorrhage and prolonged oliguria were strong predictors of irreversible renal failure. This highlights the need for early recognition and referral, and the importance of trained birth attendants and antenatal care.