Patient and nursing experience of flash glucose monitoring following kidney transplantation.

Flash glucose monitoring (FGM) is increasingly used for blood glucose assessment due to ease of use and is now subsidized in Australia for blood glucose measurement for patients with Type 1 Diabetes Mellitus. Dysglycaemia is common following kidney transplantation and is associated with worse outcomes and there are data to support the use of FGM post-transplant to better detect and manage changes in blood glucose levels. There is, however, no data on patient or staff perceptions of FGM, or resource implications in this setting. We prospectively evaluated patients and nursing staff experiences of FGM compared to traditional capillary glucose measurement in the immediate post-transplant setting, along with resource utilization, cost of testing, staff time taken to test and accuracy. Twenty-one kidney transplant recipients had a FGM sensor applied in the post-operative period and results compared to capillary blood glucose monitoring (CBGM) measured at least four times a day. Six-hundred-fifty-six glucose measurements were obtained, median per patient of 30 readings (IQR 10). Pearson's correlation between FGM and CBGM readings is 0.95 (p < .001). FGM readings were lower than CBGM by an average of 1.2 mmol/L (SD 0.7). Using a 5-point preference questionnaire (with ratings varying from strongly disagree-strongly agree), both patients and nurses were highly satisfied with the usability and convenience of FGM, with all preferring FGM over CBGM. Average time to perform FGM was 3.6 s versus 64 s for CBGM. In average, cost of FGM was $58 less than traditional testing per patient. FGM is an accurate, convenient and cost-effective tool that may support optimal management of glycaemic control in the post-transplant period.

Rhabdomyolysis following snapper fish consumption (Haff disease): a family affair.

This case describes the first report of Haff disease in Australia, where a family of three all presented with myalgia, after ingesting recently thawed, baked queen snapper fish, caught off the coast of Western Australia. All three members (mother, father and son) developed rhabdomyolysis; however, the son, who had a higher creatine kinase level, also developed an acute kidney injury, likely linked to his double fish consumption. All members were admitted for intravenous hydration and clinically improved. This case highlights the importance of dietary and environmental history in cases of rhabdomyolysis without an obvious aetiology in an otherwise self-limiting disease.

Tackling Dialysis Burden around the World: A Global Challenge.

CKD is a global problem that causes significant burden to the healthcare system and the economy in addition to its impact on morbidity and mortality of patients. Around the world, in both developing and developed economies, the nephrologists and governments face the challenges of the need to provide a quality and cost-effective kidney replacement therapy for CKD patients when their kidneys fail. In December 2019, the 3rd International Congress of Chinese Nephrologists was held in Nanjing, China, and in the meeting, a symposium and roundtable discussion on how to deal with this CKD burden was held with opinion leaders from countries and regions around the world, including Australia, Canada, China, Hong Kong, Singapore, Taiwan, the UK, and the USA. The participants concluded that an integrated approach with early detection of CKD, prompt treatment to slow down progression, promotion of home-based dialysis therapy like peritoneal dialysis and home HD, together with promotion of kidney transplantation, are possible effective ways to combat this ongoing worldwide challenge.

One-Time Fecal Immunochemical Screening for Advanced Colorectal Neoplasia in Patients with CKD (DETECT Study).

BACKGROUND: In patients with CKD, the risk of developing colorectal cancer is high and outcomes are poor. Screening using fecal immunochemical testing (FIT) is effective in reducing mortality from colorectal cancer, but performance characteristics of FIT in CKD are unknown. METHODS: To determine the detection rates and performance characteristics of FIT for advanced colorectal neoplasia (ACN) in patients with CKD, we used FIT to prospectively screen patients aged 35-74 years with CKD (stages 3-5 CKD, dialysis, and renal transplant) from 11 sites in Australia, New Zealand, Canada, and Spain. All participants received clinical follow-up at 2 years. We used a two-step reference standard approach to estimate disease status. RESULTS: Overall, 369 out of 1706 patients who completed FIT (21.6%) tested positive; 323 (87.5%) underwent colonoscopies. A total of 1553 (91.0%) completed follow-up; 82 (4.8%) had died and 71 (4.2%) were lost. The detection rate of ACN using FIT was 6.0% (5.6%, 7.4%, and 5.6% for stages 3-5 CKD, dialysis, and transplant). Sensitivity, specificity, and positive and negative predictive values of FIT for ACN were 0.90, 0.83, 0.30, and 0.99, respectively. Of participants who underwent colonoscopy, five (1.5%) experienced major colonoscopy-related complications, including bowel perforation and major bleeding. CONCLUSIONS: FIT appears to be an accurate screening test for patients with CKD, such that a negative test may rule out the diagnosis of colorectal cancer within 2 years. However, the risk of major complications from work-up colonoscopy are at least ten-fold higher than in the general population.

Infection Prophylaxis in Peritoneal Dialysis Patients: Results from an Australia/New Zealand Survey.

♦ BACKGROUND: Clinical practice guidelines aim to reduce the rates of peritoneal dialysis (PD)-related infections, a common complication of PD in end-stage kidney disease patients. We describe the clinical practices used by Australian and New Zealand nephrologists to prevent PD-related infections in PD patients. ♦ METHODS: A survey of PD practices in relation to the use of antibiotic and antifungal prophylaxis in PD patients was conducted of practicing nephrologists identified via the Australia and New Zealand Society of Nephrology (ANZSN) membership in 2013. ♦ RESULTS: Of 333 nephrologists approached, 133 (39.9%) participated. Overall, 127 (95.5%) nephrologists prescribed antibiotics at the time of Tenckhoff catheter insertion, 85 (63.9%) routinely screened for nasal S. aureus carriage, with 76 (88.4%) reporting they treated S. aureus carriers with mupirocin ointment. Following Tenckhoff catheter insertion, 79 (59.4%) prescribed mupirocin ointment at the exit site or intranasally, and 93 (69.9%) nephrologists routinely prescribed a course of oral antifungal agent whenever their PD patients were given a course of antibiotics. ♦ CONCLUSIONS: Although the majority of nephrologists prescribe antibiotics at the time of Tenckhoff catheter insertion, less than 70% routinely prescribe mupirocin ointment and/or prophylactic antifungal therapy. This variation in practice in Australia and New Zealand may contribute to the disparity in PD-related infection rates that is seen between units.

The Association Between Broad Antigen HLA Mismatches, Eplet HLA Mismatches and Acute Rejection After Kidney Transplantation.

BACKGROUND: Epitope matching, which evaluates mismatched amino acids within antigen-antibody interaction sites (eplets), may better predict acute rejection than broad antigen matching alone. We aimed to determine the association between eplet mismatches and acute rejection in kidney transplant recipients. METHODS: The association between eplet mismatches, broad antigen mismatches and acute rejection was assessed using adjusted Cox proportional hazard regression. Model discrimination for acute rejection was evaluated using the area under receiver operating characteristic curves. RESULTS: Of the 3,499 kidney transplant recipients from 2006 to 2011, the average (SD) number of broad antigen and eplet mismatches were 3.4 (1.7) and 22.8 (12.2), respectively. Compared with 0 to 2 eplet mismatches, the adjusted hazard ratio (HR) for acute rejection among those with 20 or greater eplet mismatches was 2.16 (95% confidence interval [CI], 1.33-3.52; P = 0.001). The adjusted area under the curve for broad antigen mismatches was 0.58 (95% CI, 0.56-0.61), similar to that for eplet mismatches (HR, 0.59; 95% CI, 0.56-0.61; P = 0.365). In recipients who were considered as low immunological risk (0-2 broad antigen HLA-ABDR mismatch), those with 20 or greater eplet mismatches experienced an increased risk of rejection compared to those with less than 20 mismatches (adjusted HR, 1.85; 95% CI, 1.11-3.08; P = 0.019). CONCLUSIONS: Increasing number of eplet mismatches is associated with acute rejection in kidney transplant recipients. Consideration of eplet HLA mismatches may improve risk stratification for acute rejection in a selected group of kidney transplant candidates.

Chronic kidney disease and the risk of cancer: an individual patient data meta-analysis of 32,057 participants from six prospective studies.

BACKGROUND: Chronic kidney disease (CKD) is an established risk factor for cardiovascular disease but the relevance of reduced kidney function to cancer risk is uncertain. METHODS: Individual patient data were collected from six studies (32,057 participants); including one population-based cohort and five randomized controlled trials. Participants were grouped into one of five CKD categories (estimated glomerular filtration rate [eGFR] ≥75 mL/min/1.73 m(2); eGFR ≥60 to <75 mL/min/1.73 m(2); eGFR ≥45 to <60 mL/min/1.73 m(2); eGFR <45 mL/min/1.73 m(2); on dialysis). Stratified Cox regression was used to assess the impact of CKD category on cancer incidence and cancer death. RESULTS: Over a follow-up period of 170,000 person-years (mean follow-up among survivors 5.6 years), 2626 participants developed cancer and 1095 participants died from cancer. Overall, there was no significant association between CKD category and cancer incidence or death. As compared with the reference group with eGFR ≥75 mL/min/1.73 m(2), adjusted hazard ratio (HR) estimates for each category of renal function, in descending order, were: 0.98 (95 % CI 0.87-1.10), 0.99 (0.88-1.13), 1.01 (0.84-1.22) and 1.24 (0.97-1.58) for cancer incidence, and 1.03 (95 % CI 0.86-1.24), 0.95 (0.78-1.16), 1.00 (0.76-1.33), and 1.58 (1.09-2.30) for cancer mortality. Among dialysis patients, there was an excess risk of cancers of the urinary tract (adjusted HR: 2.34; 95 % CI 1.10-4.98) and endocrine cancers (11.65; 95 % CI: 1.30-104.12), and an excess risk of death from digestive tract cancers (2.11; 95 % CI: 1.13-3.99), but a reduced risk of prostate cancers (0.38; 95 % CI: 0.18-0.83). CONCLUSIONS: Whilst no association between reduced renal function and the overall risk of cancer was observed, there was evidence among dialysis patients that the risk of cancer was increased (urinary tract, endocrine and digestive tract) or decreased (prostate) at specific sites. Larger studies are needed to characterise these site-specific associations and to identify their pathogenesis.

Vitamin D and cancer mortality in elderly women.

BACKGROUND: There is increasing evidence that vitamin D deficiency is a risk factor for cancer, however it remains uncertain whether vitamin D deficiency also predisposes to death from cancer. The aim of the study was to determine the association between serum 25-hydroxy-vitamin D (25 (OH) D) concentrations and cancer-specific mortality in a community-based cohort of older post-menopausal women. METHODS: Cox proportional regression analyses were conducted to examine the association between serum 25 (OH) D concentrations and the risk of overall and site-specific cancer mortality in a cohort of elderly women. RESULTS: Over a median follow-up time of 10 years, a total of 84 cancer deaths were observed. Women with lower serum 25 (OH) D concentrations were at an increased risk of cancer death, but not for incident cancer. The excess risk for cancer death was observed with serum 25 (OH) D concentration less than 64 nmol/L (the median value) [adjusted HR: 1.61 (95% CI: 1.02 - 2.54, p = 0.04]. For every 30 nmol/L reduction in serum 25 (OH) D concentrations, there was a 30% increase in the overall risk of cancer death [adjusted HR: 1.33; 95% CI: 1.03 - 1.72, p = 0.02]. The excess risk appeared to be site-specific and greatest in those with haematological cancers [adjusted HR: 2.13: 95% CI: 1.0 - 4.55, p = 0.05]. CONCLUSIONS: In elderly women, lower serum 25 (OH) D concentrations appear to be an independent risk factor for cancer-specific mortality, but not a risk factor for the development of cancer.

Diagnostic and management dilemma of a pancreas-kidney transplant recipient with aplastic anaemia.

We report a case of a 57-year-old woman with type I diabetes who had received a simultaneous pancreas-kidney (SPK) transplant maintained on tacrolimus, mycophenolic acid (MPA) and prednisolone. Her renal allograft failed 6 years post-transplant but she continued to have a normal functioning pancreatic allograft. Over the course of 5 years, she developed progressive bone marrow failure with repeat bone marrow aspirates demonstrating an evolution from erythroid hypoplasia to hypocellular marrow and eventual aplastic anaemia despite discontinuation of MPA and reduction of tacrolimus. She was transfusion-dependent and had frequent admissions for sepsis. Despite treatment with antithymocyte globulin and cyclosporine for aplastic anaemia, she developed fatal invasive pulmonary aspergillosis within 3 weeks of treatment. Even though the cause of aplastic anaemia is likely multifactorial, this case highlights the difficulty in balancing the need for versus the risk of ongoing immunosuppression in a SPK transplant recipient who continues to have normal pancreatic graft function.

The importance of genetic mutation screening to determine retransplantation following failed kidney allograft from recurrent atypical haemolytic ureamic syndrome.

We report the case of a patient with familial atypical haemolytic uraemic syndrome (aHUS) who underwent successful retransplantation 30 months following his failed first kidney allograft from recurrent aHUS. He achieved excellent graft function (creatinine 90 µmol/L), with no evidence of disease recurrence on standard maintenance immunosuppression 9 months after his second deceased donor kidney transplantation. Genetic mutation testing was not available prior to first transplant but screening prior to retransplant identified the patient as having a newly discovered mutation, c.T3566A, within exon 23 of the complement factor H (CFH) gene. Currently, public financing and subsidisation for eculizumab, a costly but effect complement (C5) inhibitor for the treatment of aHUS is not available in Australia. The decision for retransplantation must balance between the risk of disease recurrence and greater risk of death on dialysis. The absence of a more severe CFH genotype assisted in the decision for retransplantation and suggests the importance of genetic mutation screening in order to stratify the risk of disease recurrence and graft loss versus the benefit of transplantation.

Human plasmacytoid dendritic cells regulate immune responses to Epstein-Barr virus (EBV) infection and delay EBV-related mortality in humanized NOD-SCID mice.

Epstein-Barr virus (EBV) is associated with posttransplant lymphoproliferative disease (PTLD), which is a leading cause of cancer death in recipients of transplants. We investigated the role of plasmacytoid dendritic cells (PDCs) in the development of EBV infection and the onset of lymphoproliferative disease (LPD) in humanized NOD-SCID mice and studied the effect of EBV on PDC function. NOD-SCID mice reconstituted with PDC-depleted peripheral blood mononuclear cells (PBMCs) from EBV IgG+ human donors had significantly enhanced mortality from disseminated EBV infection (median survival, 43 days) compared to PBMC-only mice (median survival, 72 days; log-rank P<.05). Mice reconstituted with PDC-enriched PBMCs challenged with EBV exhibited delayed mortality from EBV-LPD (median survival, 80 days) compared to PBMC-only mice challenged with EBV (median survival, 50 days; log-rank P<.05). EBV-stimulated pDCs produced interferon alpha (IFN-alpha) and promoted the activation of natural killer cells and IFN-gamma-producing CD3+T cells. PDC activation of CD3+T cells in response to EBV stimulation was dependent on cell-to-cell contact, in part mediated by toll-like receptor 9 (TLR-9) signaling that was inhibited by chloroquine and TLR-9 inhibitory CpG. Thus, PDCs play an important role in anti-EBV cellular immune responses that may be targets for manipulation in novel strategies for the treatment of PTLD.