A novel allocation strategy for the difficult-to-allocate donor: audit of deceased donor kidneys utilised for preemptive recipients within Western Australia.

Kidney donor allocation can occasionally be difficult in Australia given a small population spread over vast distances. Therefore, between 2017 and 2019 our service allowed transplantation from deceased donors into local (same-state) preemptive recipients, only if no well-matched dialysis-dependent transplant waitlist recipient was available. Transplantation using this novel allocation pathway was associated with good clinical and immunological outcomes.

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.

Matrix metalloproteinase-12 deficiency attenuates experimental crescentic anti-glomerular basement membrane glomerulonephritis.

AIM: Matrix metalloproteinase-12 (MMP-12; macrophage elastase) is an enzyme that can cleave various extracellular matrix proteins and is required for macrophage infiltration and pulmonary fibrosis in experimental emphysema. We have shown previously that MMP-12 is highly up-regulated in experimental anti-glomerular basement membrane (GBM) disease. The aim of this study was to determine whether MMP-12 is required for glomerular macrophage infiltration and crescent formation in anti-GBM glomerulonephritis. METHODS: Accelerated anti-GBM disease was induced in groups of MMP-12 gene deficient mice (MMP-12-/-) and wild-type C57BL/6J controls, which were killed 12 days after injection of anti-GBM serum. RESULTS: Wild-type and MMP-12-/- mice developed glomerular damage and glomerular tuft adhesions to Bowman's capsule. Both groups developed severe proteinuria. Wild-type mice also developed significant loss of renal function and crescents in 22% of glomeruli, which were associated with macrophage infiltration and Bowman's capsule rupture. In contrast, MMP-12-/- mice were partially protected from renal function decline, crescent formation and Bowman's capsule rupture. This was associated with reduced macrophage infiltration in both glomeruli and the interstitium, and with reduced expression of CCL2, TNF-α and iNOS mRNA in MMP-12-/- kidneys. In addition, KIM-1 mRNA levels were reduced in MMP-12-/- mice indicating less tubular damage. CONCLUSION: These data demonstrate that endogenous MMP-12 facilitates macrophage accumulation and activation in anti-GBM glomerulonephritis which is required for glomerular crescent formation, Bowman's capsule rupture, tubular damage and renal function decline.

Intravitreal Sirolimus for Noninfectious Uveitis: A Phase III Sirolimus Study Assessing Double-masKed Uveitis TReAtment (SAKURA).

PURPOSE: To evaluate the efficacy and safety of intravitreal sirolimus in the treatment of noninfectious uveitis (NIU) of the posterior segment (i.e., posterior, intermediate, or panuveitis). DESIGN: Phase III, randomized, double-masked, active-controlled, 6-month study with intravitreal sirolimus. PARTICIPANTS: Adults with active NIU of the posterior segment (intermediate, posterior, or panuveitis), defined as a vitreous haze (VH) score >1+. Subjects discontinued NIU medications before baseline, except for systemic corticosteroids, which were allowed only for those already receiving them at baseline and were rapidly tapered after baseline per protocol. METHODS: Intravitreal sirolimus assigned 1:1:1 at doses of 44 (active control), 440, or 880 µg, administered on Days 1, 60, and 120. MAIN OUTCOME MEASURES: The primary efficacy outcome was the percentage of subjects with VH 0 response at Month 5 (study eye) without use of rescue therapy. Secondary outcomes at Month 5 were VH 0 or 0.5+ response rate, corticosteroid tapering success rate (i.e., tapering to a prednisone-equivalent dosage of ≤5 mg/day), and changes in best-corrected visual acuity (BCVA). Adverse events during the double-masked treatment period are presented. RESULTS: A total of 347 subjects were randomized. Higher proportions of subjects in the intravitreal sirolimus 440 µg (22.8%; P = 0.025) and 880 µg (16.4%; P = 0.182) groups met the primary end point than in the 44 µg group (10.3%). Likewise, higher proportions of subjects in the 440 µg (52.6%; P = 0.008) and 880 µg (43.1%; P = 0.228) groups achieved a VH score of 0 or 0.5+ than in the 44 µg group (35.0%). Mean BCVA was maintained throughout the study in each dose group, and the majority of subjects receiving corticosteroids at baseline successfully tapered off corticosteroids (44 µg [63.6%], 440 µg [76.9%], and 880 µg [66.7%]). Adverse events in the treatment and active control groups were similar in incidence, and all doses were well tolerated. CONCLUSIONS: Intravitreal sirolimus 440 µg demonstrated a significant improvement in ocular inflammation with preservation of BCVA in subjects with active NIU of the posterior segment.

Macrophage infiltration and renal damage are independent of matrix metalloproteinase 12 in the obstructed kidney.

AIM: To determine whether matrix metalloproteinase-12 (MMP-12) plays a functional role in renal interstitial macrophage accumulation, interstitial fibrosis or tubular apoptosis in the unilateral ureteric obstruction (UUO) model. BACKGROUND: MMP-12 is an enzyme that can cleave a number of extracellular matrix proteins and plays a role in macrophage-mediated injury in experimental models of emphysema and antibody-dependent glomerular disease. Macrophages are thought to promote renal fibrosis and tubular damage in the obstructed kidney. Furthermore, upregulation of MMP-12 expression by infiltrating macrophages in the obstructed kidney has been described, but the potential role of MMP-12 in renal injury induced by this non-immune insult is unknown. METHODS: Groups of eight MMP-12 gene deficient (MMP-12(-/-)) and wild type (WT) C57BL/6J mice were killed 3, 7 or 14 days after UUO. RESULTS: Analysis of three different lineage markers found no difference in the degree of interstitial macrophage accumulation between MMP-12(-/-) and WT UUO groups at any time point. Examination of renal fibrosis by total collagen staining, α-SMA + myofibroblast accumulation, and TGF-ß1, PAI-1 and collagen IV mRNA levels showed no difference between MMP-12(-/-) and WT UUO groups. Finally, tubular damage (KIM-1 levels) and tubular apoptosis (cleaved caspase-3) in the obstructed kidney was not affected by MMP-12 gene deletion. CONCLUSION: In contrast to lung injury and antibody-dependent glomerular injury, MMP-12 is not required for renal interstitial macrophage accumulation, interstitial fibrosis or tubular damage in the obstructed kidney.

Folie à deux.

Folie à deux is defined as an identical or similar mental disorder affecting two or more individuals, usually the members of a close family. Two case reports of this condition are presented with a brief review of the literature. Prompt recognition of this condition is an essential step in the management. The majority of patients with folie à deux require multiple treatments including separation, antipsychotics, individual and group psychotherapy, and family therapy.