Uptake and Outcomes of Peritoneal Dialysis among Aboriginal and Torres Strait Islander People: Analysis of Registry Data.

Introduction: Peritoneal dialysis (PD) enables people to use kidney replacement therapy (KRT) outside of healthcare-dependent settings, a strong priority of Aboriginal and Torres Strait Islander people. Methods: We undertook an observational study analyzing registry data to describe access to PD and its outcome as the first KRT among Aboriginal and Torres Strait Islander people between January 1, 2004 and December 31 2020. Results: Out of 4604 Aboriginal and Torres Strait Islander people, reflecting 10.4% of all Australians commencing KRT, PD was the first KRT modality among 665 (14.4%). PD utilization was 17.2% in 2004 to 2009 and 12.7% in 2016 to 2020 (P = 0.002); 1105 episodes of peritonitis were observed in 413 individuals, median of 3 (interquartile range [IQR], 2-5) episodes/patient. The crude peritonitis rate was 0.53 (95% confidence interval [CI], 0.50-0.56) episodes/patient-years without any significant changes over time. The median time to first peritonitis was 1.1 years. A decrease in the peritonitis incidence rate ratio (IRR) was observed in 2016 to 2020 (IRR, 0.63 [95% CI, 0.52-0.77], P < 0.001) compared to earlier eras (2010-2015: IRR, 0.90 [95% CI, 0.76-1.07], P = 0.23; Ref: 2004-2009). The cure rates decreased from 80.0% (n = 435) in 2004 to 2009, to 70.8% (n = 131) in 2016 to 2020 (P < 0.001). Conclusion: Aboriginal and Torres Strait Islander people who utilized PD as their first KRT during 2004 to 2020 recorded a higher peritonitis rate than the current benchmark of 0.4 episodes/patient-years. The cure rates have worsened recently, which should be a big concern. There is an exigent need to address these gaps in kidney care for Aboriginal and Torres Strait Islander people.

PD peritonitis in patients undergoing capsule endoscopy: A descriptive study.

Peritoneal dialysis (PD) patients who undergo gastroendoscopy and colonoscopy are at increased risk of peritoneal dialysis-associated peritonitis (PD peritonitis) following the procedure (defined as occurring within 7 days of intervention). As per current International Society for PD (ISPD) guidelines, antibiotic prophylaxis is currently recommended pre-colonoscopy in PD patients given the risk of post-colonoscopy PD peritonitis. The risk of PD peritonitis in patients undergoing capsule endoscopy (CE) is unknown. This binational data-linkage study between the Australia and New Zealand Dialysis and Transplant Registry and all hospital admission data sets in Australia and New Zealand evaluated all patients with PD who underwent CE between 2006 and 2015. The objective of the study was to assess the risk of PD peritonitis in patients undergoing CE. Descriptive statistics were used to describe patient characteristics and clinical outcomes. Overall, 23 patients with PD underwent CE. Twelve patients underwent CE alone (i.e. no other concomitant procedures) and none of these patients experienced an episode of PD peritonitis. The remaining 11 patients underwent CE and other invasive endoscopic/abdominal surgical procedures, of whom 2 suffered PD peritonitis. CE is likely a relatively safe procedure in PD patients. PD patients undergoing CE may not require prior antibiotic prophylaxis. Given their relative safety, CE may be an appealing diagnostic tool in a select group of PD patients for the investigation of gastrointestinal disease.

Postoperative Outcomes After Gastrointestinal Surgery in Patients Receiving Chronic Kidney Replacement Therapy: A Population-based Cohort Study.

OBJECTIVE: This study evaluated the postoperative mortality and morbidity outcomes following the different subtypes of gastrointestinal (GI) surgery over a 15-year period. BACKGROUND: Patients receiving chronic kidney replacement therapy (KRT) experience higher rates of general surgery compared with other surgery types. Contemporary data on the types of surgeries and their outcomes are lacking. KRT was defined as patients requiring chronic dialysis (hemodialysis or peritoneal dilaysis) or having a functioning kidney transplant long-term. METHODS: All incident and prevalent patients aged greater than 18 years identified in the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry as receiving chronic KRT were linked with jurisdictional hospital admission datasets between January 1, 2000 until December 31, 2015. Patients were categorized by their KRT modality [hemodialysis (HD), peritoneal dialysis (PD), home hemodialysis (HHD), and kidney transplant (KT)]. GI surgeries were categorized as upper gastrointestinal (UGI), bowel (small and large bowel), anorectal, hernia surgery, cholecystectomy, and appendicectomy. The primary outcome was the rates of the different surgeries, estimated using Poisson models. Secondary outcomes were risks of 30-day/in-hospital postoperative mortality risk and nonfatal outcomes and were estimated using logistic regression. Independent predictors of 30-day mortality were examined using comorbidity-adjusted Cox models. RESULTS: Overall, 46,779 patients on chronic KRT were linked to jurisdictional hospital datasets, and 9,116 patients were identified as having undergone 14,540 GI surgeries with a combined follow-up of 76,593 years. Patients on PD had the highest rates of GI surgery (8 per 100 patient years), with hernia surgery being the most frequent. Patients on PD also had the highest risk of 30-day postoperative mortality following the different types of GI surgery, with the risk being more than 2-fold higher after emergency surgery compared with elective procedures. Infective postoperative complications were more common than cardiac complications. This study also observed a U-shaped association between body mass index (BMI) and mortality, with a nadir in the 30 to 35 kg/m 2 group. CONCLUSIONS: Patients on chronic KRT have high rates of GI surgery and morbidity, particularly in those who receive PD, are older, or are either underweight or moderately obese.

Kidney Transplant Outcomes in elderly Recipients: An Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry Study.

BACKGROUND: There is an increase in elderly patients receiving kidney transplant internationally. This study describes elderly kidney transplant recipient outcomes in Australia and New Zealand. METHODS: The study included all adult first kidney transplant recipients in Australia and New Zealand from 2000 to 2015. Survival and graft outcomes were compared between elderly (≥70 years) and younger (18-69 years) recipients using Cox proportional hazards regression. RESULTS: Overall, 10651 kidney transplant recipients were included, of which 279 (2.6%) were elderly adults. The proportion of elderly recipients increased from 0.6 to 4.4% from 2000 to 2015. Compared with younger recipients, elderly recipients were more likely to receive kidneys from deceased donors, elderly donors, and expanded criteria donors. Elderly recipients experienced poorer patient survival with 1- and 5-year survival ranging from 96% to 97% and 79% to 81%, respectively, compared with 97% to 99% and 90% 95% in younger recipients, respectively. Elderly recipients experienced comparable rates of delayed graft function and, in living donor kidney recipients, lower rates of acute rejection. CONCLUSIONS: Kidney transplantation in the elderly population is increasing. Although elderly recipients had inferior survival and graft outcomes, elderly recipients generally received poorer quality kidneys. The outcomes achieved in this cohort of elderly adults are encouraging, and improving elderly recipient outcomes should be an important focus for research.

Morbidity after elective surgery in patients on chronic dialysis: a systematic review and meta-analysis.

BACKGROUND: Patients on chronic dialysis are at increased risk of postoperative mortality following elective surgery compared to patients with normal kidney function, but morbidity outcomes are less often reported. This study ascertains the excess odds of postoperative cardiovascular and infection related morbidity outcomes for patients on chronic dialysis. METHODS: Systematic searches were performed using MEDLINE, Embase and the Cochrane Library to identify relevant studies published from inception to January 2020. Eligible studies reported postoperative morbidity outcomes in chronic dialysis and non-dialysis patients undergoing major non-transplant surgery. Risk of bias was assessed using the Newcastle-Ottawa Scale and the certainty of evidence was summarised using GRADE. Random effects meta-analyses were performed to derive summary odds estimates. Meta-regression and sensitivity analyses were performed to explore heterogeneity. RESULTS: Forty-nine studies involving 10,513,934 patients with normal kidney function and 43,092 patients receiving chronic dialysis were included. Patients on chronic dialysis had increased unadjusted odds of postoperative cardiovascular and infectious complications within each surgical discipline. However, the excess odds of cardiovascular complications was attenuated when odds ratios were adjusted for age and comorbidities; myocardial infarction (general surgery, OR 1.83 95% 1.29-2.36) and stroke (general surgery, OR 0.95, 95%CI 0.84-1.06). The excess odds of infectious complications remained substantially higher for patients on chronic dialysis, particularly sepsis (general surgery, OR 2.42, 95%CI 2.12-2.72). CONCLUSION: Patients on chronic dialysis are at increased odds of both cardiovascular and infectious complications following elective surgery, with the excess odds of cardiovascular complications attributable to being on dialysis being highest among younger patients without comorbidities. However, further research is needed to better inform perioperative risk assessment.

Assessment of cardiac structure and function in kidney failure: understanding echocardiography and magnetic resonance imaging for the nephrologist.

Cardiovascular disease is the leading cause of death in patients with kidney failure or on chronic dialysis. Patients on chronic dialysis have a 10- to 50-fold increased risk of sudden cardiac death compared to patients with normal kidney function. Adverse changes in cardiac structure and function may not manifest with clinical symptoms in patients with kidney failure and, therefore, pose a challenge in identifying cardiac dysfunction early. Fortunately, there are multi-modality cardiac imaging techniques available, including echocardiography and cardiac magnetic resonance imaging, that can help our understanding of the pathophysiology of cardiac dysfunction in kidney failure. This review describes the benefits and limitations of these two commonly available cardiac imaging modalities to assess cardiac structure and function, thereby aiding nephrologists in choosing the most appropriate investigative tool based on individual clinical circumstances. For the purposes of this review, cardiac imaging for detection of coronary artery disease has been omitted.

Effect of probiotics and synbiotics consumption on serum concentrations of liver function test enzymes: a systematic review and meta-analysis.

PURPOSE: The gut-liver interaction suggests that modification of gut bacterial flora using probiotics and synbiotics may improve liver function. This systematic review and meta-analysis aimed to clarify the effect of probiotics and synbiotics consumption on the serum concentration of liver function enzymes. METHODS: PubMed (MEDLINE), Cumulative Index to Nursing and Allied Health Literature, and Cochrane Library (Central) were searched from 1980 to August 2017 for studies where adults consumed probiotics and/or synbiotics in controlled trials and changes in liver function enzymes were examined. RESULTS: A total of 17 studies (19 trials) were included in the meta-analysis. Random effects meta-analyses were applied. Probiotics and synbiotics significantly reduced serum alanine aminotransferase [- 8.05 IU/L, 95% confidence interval (CI) - 13.07 to - 3.04; p = 0.002]; aspartate aminotransferase (- 7.79 IU/L, 95% CI: - 13.93 to - 1.65; p = 0.02) and gamma-glutamyl transpeptidase (- 8.40 IU/L, 95% CI - 12.61 to - 4.20; p < 0.001). Changes in the serum concentration of alkaline phosphatase and albumin did not reach a statistically significant level. Changes to bilirubin levels were in favour of the control group (0.95 µmol/L, 95% CI 0.48-1.42; p < 0.001). Subgroup analysis suggested the existence of liver disease at baseline, synbiotics supplementation and duration of supplementation ≥ 8 weeks resulted in more pronounced improvement in liver function enzymes than their counterparts. CONCLUSIONS: Probiotics and synbiotics may be suggested as supplements to improve serum concentration of liver enzymes, especially when synbiotics administered for a period ≥ 8 weeks and in individuals with liver disease.

Silibinin--a promising new treatment for cancer.

Silymarin and its major constituent, Silibinin, are extracts from the medicinal plant Silybum marianum (milk thistle) and have traditionally been used for the treatment of liver diseases. Recently, these orally active, flavonoid agents have also been shown to exert significant anti-neoplastic effects in a variety of in vitro and in vivo cancer models, including skin, breast, lung, colon, bladder, prostate and kidney carcinomas. The aim of the present review is to examine the pharmacokinetics, mechanisms, effectiveness and adverse effects of silibinin's anti-cancer actions reported to date in pre-clinical and clinical trials. The review will also discuss the results of current research efforts seeking to determine the extent to which the effectiveness of silibinin as an adjunct cancer treatment is influenced by such factors as histologic subtype, hormonal status, stromal interactions and drug metabolising gene polymorphisms. The results of these studies may help to more precisely target and dose silibinin therapy to optimise clinical outcomes for oncology patients.

Therapeutic monitoring of mycophenolate in transplantation: is it justified?

Mycophenolate mofetil (MMF) is the preferred antimetabolite in solid organ transplantation. It is a prodrug that undergoes pre-systemic metabolism to mycophenolic acid (MPA), the active drug moiety. MMF is typically administered as a fixed dose without routine monitoring of MPA concentrations. However, a role for therapeutic drug monitoring (TDM) of MPA has been suggested based on the drug's narrow therapeutic window and considerable between-subject variability. Dose-normalized MPA area under the concentration-time curve (AUC) has been observed to vary >/=10-fold. Some of this variability may be accounted for by patient variability in renal and liver function, serum albumin and haemoglobin levels, body mass, concomitant medication exposure and genetic polymorphisms in enzymes responsible for drug metabolism and transport, but much is unexplained. Widespread adoption of MPA TDM has been limited by the impracticality of full 0 to 12 hour AUC measurement (AUC(0-12)), poor correlation between pre-dose MPA concentration and AUC(0-12), ongoing questions regarding the utility of free versus total MPA measurements and lack of evidence correlating MPA exposure with clinical outcomes. Two recent randomized studies evaluating the role of MPA TDM in renal transplant recipients have reported conflicting results. Promising areas of ongoing study include use of Bayesian forecasting to predict MPA dosage and measurement of inosine monophosphate dehydrogenase activity. This review provides an overview of the pharmacokinetics of MMF in solid organ transplantation, and discusses the benefits and limitations of MPA monitoring. Areas that require additional research are identified.

Oxpentifylline versus placebo in the treatment of erythropoietin-resistant anaemia: a randomized controlled trial.

BACKGROUND: The main hypothesis of this study is that Oxpentifylline administration will effectively treat erythropoietin- or darbepoietin-resistant anaemia in chronic kidney disease patients. METHODS/DESIGN: Inclusion criteria are adult patients with stage 4 or 5 chronic kidney disease (including dialysis patients) with significant anaemia (haemoglobin or= 200 IU/kg/week) or darbepoetin (>or= 1 microg/kg/week). Patients will be randomized 1:1 to receive either placebo (1 tablet daily) or oxpentifylline (400 mg daily) per os for a period of 4 months. During this 4 month study period, haemoglobin measurements will be performed monthly. The primary outcome measure will be the difference in haemoglobin level between the 2 groups at the end of the 4 month study period, adjusted for baseline values. Secondary outcome measures will include erythropoiesis stimulating agent dosage, Key's index (erythropoiesis stimulating agent dosage divided by haemoglobin concentration), and blood transfusion requirement. DISCUSSION: This investigator-initiated multicentre study has been designed to provide evidence to help nephrologists and their chronic kidney disease patients determine whether oxpentifylline represents a safe and effective strategy for treating erythropoiesis stimulating agent resistance in chronic kidney disease.

Pure red cell aplasia induced by erythropoiesis-stimulating agents.

Pure red cell aplasia in patients who are treated for anemia of chronic kidney disease with erythropoiesis-stimulating agents such as epoetin was first reported in 1998. Although the incidence of pure red cell aplasia peaked in 2002, it remains important for nephrologists to know how to investigate a suspected case of pure red cell aplasia and how to identify other causes of hyporesponsiveness to erythropoiesis-stimulating agents, which account for the vast majority of such cases. The authors reviewed the current status of information in the literature and drew on their personal experiences with patients regarding the diagnosis and management of epoetin-induced pure red cell aplasia. The mechanism for development of epoetin-induced pure red cell aplasia remains unconfirmed. It generally occurs after the production of neutralizing anti-erythropoietin antibodies. Elucidation of a suspected pure red cell aplasia case requires a systematic approach, beginning with simple measurements such as blood cell counts, because most cases of erythropoiesis-stimulating agent hyporesponsiveness are attributable to other causes. If these criteria indicate that the patient's response to erythropoiesis-stimulating agent therapy is very poor, then bone marrow examination and measurement of anti-erythropoietin antibodies is justified. If pure red cell aplasia is confirmed, then cessation of erythropoiesis-stimulating agent therapy and initiation of immunosuppressive therapy are recommended. Continued study of epoetin-induced pure red cell aplasia is needed to help nephrologists prevent or manage future cases and will have implications for the use of other protein-based therapeutic agents.

Randomized, controlled trial of topical exit-site application of honey (Medihoney) versus mupirocin for the prevention of catheter-associated infections in hemodialysis patients.

The clinical usefulness of hemodialysis catheters is limited by increased infectious morbidity and mortality. Topical antiseptic agents, such as mupirocin, are effective at reducing this risk but have been reported to select for antibiotic-resistant strains. The aim of the present study was to determine the efficacy and the safety of exit-site application of a standardized antibacterial honey versus mupirocin in preventing catheter-associated infections. A randomized, controlled trial was performed comparing the effect of thrice-weekly exit-site application of Medihoney versus mupirocin on infection rates in patients who were receiving hemodialysis via tunneled, cuffed central venous catheters. A total of 101 patients were enrolled. The incidences of catheter-associated bacteremias in honey-treated (n = 51) and mupirocin-treated (n = 50) patients were comparable (0.97 versus 0.85 episodes per 1000 catheter-days, respectively; NS). On Cox proportional hazards model analysis, the use of honey was not significantly associated with bacteremia-free survival (unadjusted hazard ratio, 0.94; 95% confidence interval, 0.27 to 3.24; P = 0.92). No exit-site infections occurred. During the study period, 2% of staphylococcal isolates within the hospital were mupirocin resistant. Thrice-weekly application of standardized antibacterial honey to hemodialysis catheter exit sites was safe, cheap, and effective and resulted in a comparable rate of catheter-associated infection to that obtained with mupirocin (although the study was not adequately powered to assess therapeutic equivalence). The effectiveness of honey against antibiotic-resistant microorganisms and its low likelihood of selecting for further resistant strains suggest that this agent may represent a satisfactory alternative means of chemoprophylaxis in patients with central venous catheters.

Elevated white cell count at commencement of peritoneal dialysis predicts overall and cardiac mortality.

BACKGROUND: Higher total white blood cell counts (WCC) have been shown in the general population to be strongly and independently predictive of coronary heart disease and all-cause mortality. The aim of the present study was to evaluate the prognostic value of WCC in patients commencing peritoneal dialysis (PD). METHODS: A cohort of 323 patients (mean age 55.1 +/- 17.7 years, 54% male, 81% Caucasian) commencing PD at the Princess Alexandra Hospital between January 1, 1998 and March 31, 2003 were prospectively followed until death, completion of PD therapy, or otherwise to the end of the study (January 2, 2004), at which point data were censored. Individuals with failed renal transplants (N= 17) and those with acute infections at the time of PD onset (N= 12) were not included. A multivariate Cox's proportional hazards model was applied to calculate hazard ratios and adjusted survival curves for time to death or cardiac death, adjusting for baseline demographic, clinical, and laboratory characteristics. RESULTS: Median actuarial patient survival was 3.9 years [95% confidence interval (CI) 3.2-4.7 years]. The highest quartile of WCC (>9.4 x 10(9)/L) was significantly and independently associated with increased risks of both death from all causes [adjusted hazard ratio (HR) 2.27, 95% CI 1.09-4.74, P < 0.05] and cardiac death (HR 3.75, 95% CI 1.2-11.8, P < 0.05). Other adverse risk factors included older age, lower serum albumin, and the presence of coronary artery disease. Similar associations were found between mortality and PMN count, but not lymphocyte count. CONCLUSION: Elevated baseline WCC or PMN count at the commencement of PD (in the absence of acute infection) strongly predicts all-cause and cardiovascular mortality. These data suggest that new PD patients with higher WCC may warrant closer monitoring and extra attention to modifiable cardiovascular risk factors.

A randomized controlled trial of topical exit site mupirocin application in patients with tunnelled, cuffed haemodialysis catheters.

BACKGROUND: Central venous catheters are frequently needed for the provision of haemodialysis, but their clinical usefulness is severely limited by infectious complications. The risk of such infections can be reduced by topical application of mupirocin to the exit sites of non-cuffed catheters or by the use of tunnelled, cuffed catheters. Whether mupirocin offers any additional protection against infection in patients with tunnelled, cuffed haemodialysis catheters has not been studied. METHODS: An open-label, randomized controlled trial was performed comparing the effect of thrice-weekly exit site application of mupirocin (mupirocin group) vs no ointment (control group) on infection rates and catheter survival in patients receiving haemodialysis via a newly inserted, tunnelled, cuffed central venous catheter. All patients were followed until catheter removal and were monitored for the development of exit site infections and catheter-associated bacteraemias. RESULTS: Fifty patients were enrolled in the study. Both the mupirocin (n=27) and control (n=23) groups were similar at baseline with respect to demographic characteristics, comorbid illnesses and causes of renal failure. Compared with controls, mupirocin-treated patients experienced significantly fewer catheter-related bacteraemias (7 vs 35%, P<0.01) and a longer time to first bacteraemia (log rank score 8.68, P<0.01). The beneficial effect of mupirocin was entirely attributable to a reduction in staphylococcal infection (log rank 10.69, P=0.001) and was still observed when only patients without prior nasal Staphylococcus aureus carriage were included in the analysis (log rank score 6.33, P=0.01). Median catheter survival was also significantly longer in the mupirocin group (108 vs 31 days, log rank score 5.9, P<0.05). Mupirocin use was not associated with any adverse patient effects or the induction of antimicrobial resistance. CONCLUSIONS: Thrice-weekly application of mupirocin to tunnelled, cuffed haemodialysis catheter exit sites is associated with a marked reduction in line-related sepsis and a prolongation of catheter survival.

Is C-reactive protein a useful predictor of outcome in peritoneal dialysis patients?

An elevated C-reactive protein (CRP) has recently been shown to be strongly predictive of mortality in hemodialysis patients. However, its predictive value in peritoneal dialysis (PD) patients has not been assessed. A cohort of 50 PD patients was followed prospectively for a 3-yr period, after initial determination of CRP. Patients with an elevated CRP (>6 mg/L; n = 29) had significantly reduced plasma prealbumin (0.36 +/- 0.02 versus 0.44 +/- 0.03 g/L; P: < 0.05), decreased total weekly creatinine clearance (C(Cr); 52.5 +/- 2.3 versus 63.1 +/- 3.2 L/1.73 m(2); P: < 0.01), and increased left ventricular thickness (1.24 +/- 0.05 versus 1.08 +/- 0.06 cm; P: < 0.05) at baseline compared with those who had a normal CRP (< or =6 mg/L; n = 21). Baseline CRP (log-transformed) correlated weakly with baseline Kt/V, C(Cr), and pre-albumin. With the use of a multivariate Cox's proportional hazards model to adjust for potential confounding factors, an elevated CRP was predictive of myocardial infarction (adjusted hazard ratio, 4.8; 95% confidence interval [CI], 1.0 to 23; P: = 0.048) and tended to be predictive of fatal myocardial infarction (adjusted hazard ratio, 6.0; 95% CI, 0.8 to 43; P: = 0.07). However, CRP was not significantly associated with all-cause mortality (adjusted hazard ratio, 2.1; 95% CI,0.8 to 5.4; P: = 0.15). In conclusion, CRP elevation occurs in a substantial proportion of PD patients and is independently predictive of future myocardial infarction. Such patients may warrant closer monitoring and attention to modifiable cardiovascular risk factors.