Real world evaluation of kidney failure risk equations in predicting progression from chronic kidney disease to kidney failure in an Australian cohort.

BACKGROUND: Chronic kidney disease progression to kidney failure is diverse, and progression may be different according to genetic aspects and settings of care. We aimed to describe kidney failure risk equation prognostic accuracy in an Australian population. METHODS: A retrospective cohort study was undertaken in a public hospital community-based chronic kidney disease service in Brisbane, Australia, which included a cohort of 406 adult patients with chronic kidney disease Stages 3-4 followed up over 5 years (1/1/13-1/1/18). Risk of progression to kidney failure at baseline using Kidney Failure Risk Equation models with three (eGFR/age/sex), four (add urinary-ACR) and eight variables (add serum-albumin/phosphate/bicarbonate/calcium) at 5 and 2 years were compared to actual patient outcomes. RESULTS: Of 406 patients followed up over 5 years, 71 (17.5%) developed kidney failure, while 112 died before reaching kidney failure. The overall mean difference between observed and predicted risk was 0.51% (p = 0.659), 0.93% (p = 0.602), and - 0.03% (p = 0.967) for the three-, four- and eight-variable models, respectively. There was small improvement in the receiver operating characteristic-area under the curve from three-variable to four-variable models: 0.888 (95%CI = 0.819-0.957) versus 0.916 (95%CI = 0.847-0.985). The eight-variable model showed marginal receiver operating characteristic-area under the curve improvement: 0.916 (95%CI = 0.847-0.985) versus 0.922 (95%CI = 0.853-0.991). The results were similar in predicting 2 year risk of kidney failure. CONCLUSIONS: The kidney failure risk equation accurately predicted progression to kidney failure in an Australian chronic kidney disease population. Younger age, male sex, lower estimated glomerular filtration rate, higher albuminuria, diabetes mellitus, tobacco smoking and non-Caucasian ethnicity were associated with increased risk of kidney failure. Cause-specific cumulative incidence function for progression to kidney failure or death, stratified by chronic kidney disease stage, demonstrated differences within different chronic kidney disease stages, highlighting the interaction between comorbidity and outcome.

Calciphylaxis, beware the ophthalmic mimic: A case series.

PURPOSE: We present two atypical cases of calciphylaxis presenting with ocular ischemic pathology - both without the hallmark cutaneous manifestations - to raise awareness of this rare yet highly disabling condition. OBSERVATIONS: We report two cases of ophthalmic calciphylaxis presenting as (1) anterior ischemic optic neuropathy (AION) and cilioretinal artery occlusion in a 76-year-old woman with pre-dialysis kidney failure, and (2) AION with contralateral central retinal artery occlusion (CRAO) in a 44-year-old man on hemodialysis. CONCLUSION AND IMPORTANCE: These cases highlight the need for judicious clinical suspicion of calciphylaxis in patients with kidney failure, presenting with microvascular ischemic ophthalmic pathology such as AION or CRAO. Confirmation with temporal artery biopsy is essential to direct targeted individualized multi-disciplinary treatment of calciphylaxis and avoid unnecessary steroid exposure in cases masquerading as giant cell arteritis (GCA).

T-cell adoptive immunotherapy for BK nephropathy in renal transplantation.

INTRODUCTION: BK virus (BKPyV) nephropathy occurs in 1%-10% of kidney transplant recipients, with suboptimal therapeutic options. CASE: A 54-year-old woman received a transplant in March 2017. BKPyV was detected at 1.5 × 102  copies/mL within a month, necessitating halving of mycophenolate and addition of leflunomide. Allograft histology in December showed polyomavirus nephropathy treated with intravenous immunoglobulin and cessation of mycophenolate. In February 2018, cidofovir and ciprofloxacin were commenced. In April, tacrolimus was reduced while introducing everolimus. A second graft biopsy in August showed increasing polyoma virus infection and a subsequent biopsy in September for worsening renal function showed 30% of tubular reactivity for simian virus 40 (SV40). Allogeneic BKPyV-reactive T cells were generated from the patient's daughter and infused over 10 sessions starting late September. The fourth allograft biopsy in November 2018 demonstrated involvement of BKPyV in 50% of tubules. Allograft function continued to decline, requiring hemodialysis from December 2018. Allograft nephrectomy after 6 months showed <1% SV40 in preserved tubules and 80% interstitial fibrosis. DISCUSSION: We conclude that the T-cell adoptive immunotherapy reduced BKPyV load significantly despite extensive infection, but attendant fibrosis and tubular atrophy led to graft failure. Early intervention with T-cell therapy may prove efficacious in BKPyV nephropathy.

Prevalence of Fabry disease in dialysis patients: Western Australia Fabry disease screening study - the FoRWARD study.

AIM: To determine the prevalence of undiagnosed Fabry Disease (FD) in Western Australian (WA) patients undergoing dialysis. BACKGROUND: FD is a multisystem X-linked lysosomal storage disease caused by deficient activity of alpha-galactosidase-A (α-GAL-A). Affected individuals are at risk of developing small-fibre neuropathy, rash, progressive kidney disease, hypertrophic cardiomyopathy and ischaemic stroke. Diagnosis is often delayed by years or even decades. Screening high risk population such as dialysis patients may identify patients with undiagnosed Fabry disease. METHODS: A cross-sectional study was undertaken of all adult patients receiving dialysis in WA, without previously known FD. After informed consent they were screened for α-GAL-A activity by dried blood spot samples. Low or inconclusive activity were repeated via Centogene in Rostock, Germany with GLA genetic analysis. Ethics approval was granted by Royal Perth Hospital Human Research Ethic Committee REG 14-136; site-specific approval was granted from appropriate authorities; ANZ Clinical Trials Registry U1111-1163-7629. RESULTS: Between February 2015 & September 2017, α-GAL-A activity was performed on 526 patients at 16 dialysis sites. Twenty-nine patients had initial low α-GAL-A; repeat testing & GLA genotyping showed no confirmed FD cases. The causes of false positive rates were thought to be secondary to impaired protein synthesis due to patient malnutrition and chronic inflammation, which is common among dialysis patients, in addition to poor sampling handling. CONCLUSION: Analysis of this dialysis population has shown a prevalence of 0% undiagnosed FD. False positives results may occur through impaired protein synthesis and sample handling.