Comparison of skin cancer risk between renal transplant recipients and patients with glomerular diseases in rural Queensland.

INTROUDCTION: There is increased risk of skin cancer in patients with gloermular disease or those with renal transplant. OBJECTIVES: To compare the risk of skin cancer between kidney recipients (KTRs) and patients with glomerular disease (GD). DESIGN: The cohort comprised patients with KTRs (n = 61) and GD (n = 51) in Central and Central West Queensland, Australia. A quantitative cohort study was undertaken to study the risk of skin cancer in rural communities between two subgroups of patients with kidney diseases in relationship to immunosuppression. Statistical analyses of the differences in incidence of skin cancers between the two groups were done by chi-square test, Fisher's exact test, independent t-test and McNemar's test. FINDINGS: KTRs with non-melanoma skin carcinoma (NMSC) increased significantly after treatment with immunosuppressants (pre-transplantation, n = 11 [18.0%], post-transplantation, n = 28 [45.9%]; p < 0.001). There were no differences in number of patients with NMSC observed in the GD group (pre-diagnosis, n = 6 [11.8%], post-diagnosis, n = 7 [13.7%]; p = 1.000). Compared to the risks at 1 year post-immunosuppressants, the incidence of NMSC of KTRs increased significantly at 3 years (20.3% vs. 35.4%, p < 0.001) and 5 years (20.3% vs. 62.2%, p < 0.001) post-immunosuppressants, whereas the increased incidence of NMSC was observed only at 5 years (2.1% vs. 11.8%, p = 0.012) in the GD cohort. The mean cumulative number of NMSC in KTRs increased significantly at 3 years (p = 0.011), and 5 years (p = 0.001) post-immunosuppressants, compared to the risks at 1 year post-immunosuppressants, however, no differences were noted in the GD cohort. DISCUSSION: Immunosuppressants increased the risk of NMSC in KTRs. The increased risk is likely dependent on the intensity and duration of immunosuppressants. CONCLUSION: In patients with a high risk of NMSC, reducing skin cancer risk should be considered in conjunction with the optimisation of treatment.

Rituximab versus azathioprine for maintenance of remission for patients with ANCA-associated vasculitis and relapsing disease: an international randomised controlled trial.

OBJECTIVE: Following induction of remission with rituximab in anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) relapse rates are high, especially in patients with history of relapse. Relapses are associated with increased exposure to immunosuppressive medications, the accrual of damage and increased morbidity and mortality. The RITAZAREM trial compared the efficacy of repeat-dose rituximab to daily oral azathioprine for prevention of relapse in patients with relapsing AAV in whom remission was reinduced with rituximab. METHODS: RITAZAREM was an international randomised controlled, open-label, superiority trial that recruited 188 patients at the time of an AAV relapse from 29 centres in seven countries between April 2013 and November 2016. All patients received rituximab and glucocorticoids to reinduce remission. Patients achieving remission by 4 months were randomised to receive rituximab intravenously (1000 mg every 4 months, through month 20) (85 patients) or azathioprine (2 mg/kg/day, tapered after month 24) (85 patients) and followed for a minimum of 36 months. The primary outcome was time to disease relapse (either major or minor relapse). RESULTS: Rituximab was superior to azathioprine in preventing relapse: HR 0.41; 95% CI 0.27 to 0.61, p<0.001. 19/85 (22%) patients in the rituximab group and 31/85 (36%) in the azathioprine group experienced at least one serious adverse event during the treatment period. There were no differences in rates of hypogammaglobulinaemia or infection between groups. CONCLUSIONS: Following induction of remission with rituximab, fixed-interval, repeat-dose rituximab was superior to azathioprine for preventing disease relapse in patients with AAV with a prior history of relapse. TRIAL REGISTRATION NUMBER: NCT01697267; ClinicalTrials.gov identifier.

Clinical and economic burden of benign and malignant skin lesions in renal transplant recipients.

BACKGROUND: Studies evaluating the economic burden of dermatological care in the transplant setting are currently not available in Australia. AIMS: To evaluate the clinical and economic burden of benign and malignant skin lesions in renal transplant recipients in Central Queensland. METHODS: A bottom-up approach was used to determine the clinical burden and direct costs from patient-level Medicare data obtained from Service Australia for skin lesions. RESULTS: Seventy-six percent of the renal transplant population in Central Queensland participated in this study. The median age was 57.0 years (standard deviation ± 13.6) and the majority (61.8%) of participants were men. The mean duration after transplant surgery was 99.9 months (interquartile range, 73.2-126.6 months). During a 2-year follow-up, 22 (40%) patients were diagnosed with benign skin lesions, 21 (38%) with nonmelanoma skin carcinoma (NMSC) and one (2%) with melanoma. There was a total of 231 visits to clinicians for diagnostic and therapeutic skin procedures and the direct costs to Medicare was $48 806 Australian Dollars (AUD) or $30 427 US Dollars (USD). Approximately 86% of the total direct costs was spent for nonNMSC and mean direct costs for NMSC was $763 AUD (or $476 USD). CONCLUSION: This Medicare data-based study provides further insight into the burgeoning clinical and economic burden of the care for benign and malignant skin lesions in the renal transplantation setting in Australia.

An integrated skin cancer education program in renal transplant recipients and patients with glomerular disease.

Sun-protective strategies focusing on skin cancer awareness are needed in immunosuppressed patients at risk of skin cancers. The study aims to determine the effect of an integrated skin cancer education program on skin cancer awareness and sun-protective behaviours in renal transplant recipients (RTRs) and patients with glomerular disease (GD) treated with long-term immunosuppressants. A pilot prospective cohort study in Central Queensland, Australia was undertaken among adult RTRs and patients with GD, who completed survey questionaries on skin cancer and sun-health knowledge (SCSK), sun-protection practices and skin examination pre- and post-education. Fifty patients (25 RTRs, 25 patients with GD) participated in the study. All of them completed questionnaires at pre-, 3-month post-education and 92%(n = 46) at 6-month post-education. There was a significant increase in SCSK scores from baseline at 3-months (p < 0.001) and 6-months post-intervention (p < 0.01). Improved knowledge was retained for 6 months after education. There were changes in 2 of 8 photoprotective behaviours at 6 months. Interventional education enhanced regular self-skin examination rate (p < 0.001) as well as the frequency of full skin checks by general practitioners (GPs) (p < 0.001). Overall, RTRs had better compliance with sun-protective methods and higher skin examination rates by themselves and/ or GPs before and after the intervention of education compared to patients with GD. To conclude, an integrated skin cancer education program improved knowledge of skin cancer and skin health as well as the frequency of self-skin examination and formal skin assessments. However, improvement in patient compliance did not extend to other sun-protective practices.

Critical evaluation of cancer risks in glomerular disease.

The increased cancer incidence in patients with glomerular disease can be secondary to an intrinsic immune dysfunction associated with the disease or/and extrinsic factors, especially immunosuppressants. The treatment for paraneoplastic glomerulopathy is different from primary glomerular disease. Immunosuppressive therapy often used for primary glomerulopathy may aggravate concomitant cancers in patients with paraneoplastic glomerulopathy. In membranous nephropathy (MN), measurement of serum circulating autoantibodies against podocyte transmembrane glycoprotein M-type phospholipase A2 receptor (PLA2R) and thrombospondin type 1 domain-containing 7A (THSD7A), immunohistochemical staining of kidney tissue for glomerular PLA2R, THSD7A, neural epidermal growth factor-like 1 protein (NELL-1) and specific types of immunoglobulin G (IgG) may be useful adjuncts when screening for underlying malignancies. This review addresses overall cancer risks in individuals with glomerular diseases and employment of biomarkers available for MN. We propose a scheme of screening of cancers frequently reported in the setting of glomerular disease.

Reducing non-melanoma skin cancer risk in renal transplant recipients.

With an increasing number of renal transplant recipients (RTRs) and improving patient survival, a higher incidence of non-melanoma skin cancer (NMSC) has been observed. NMSC in RTRs are often more numerous and biologically more aggressive than the general population, thus contributing towards an increase in morbidity and to a lesser degree, mortality. The resultant cumulative health and financial burden is a recognized concern. Proposed strategies in mitigating risks of developing NMSC and early therapeutic options thereof include tailored modification of immunosuppressants in conjunction with sun protection in all transplant patients. This review highlights the clinical and financial burden of transplant-associated skin cancers, carcinogenic mechanisms in association with immunosuppression, importance of skin cancer awareness campaign and integrated transplant skin clinic, and the potential role of chemoprotective agents. A scheme is proposed for primary and secondary prevention of NMSC based on the available evidence.

Comparison of skin cancer awareness and sun protection behaviours between renal transplant recipients and patients with glomerular disease treated with immunosuppressants.

BACKGROUND: There is no previous study that compare skin cancer awareness and photoprotective behaviours between renal transplant recipients (RTR) and patients with glomerular disease (GD). OBJECTIVES/METHODS: Sixty-one RTR and 51 patients with GD were given a self-reported questionnaire to evaluate skin cancer awareness and photoprotective behaviours in this cross-sectional study. The former group received a formal education on skin cancer and the latter an informal session prior to immunosuppressant use. RESULTS: Ninety-three percent (n = 57) of RTRs and 88% (n = 45) of patients with GD responded to the survey. Majority of participants from both groups were aware that ultraviolet radiation could play a role in the occurrence of skin cancers and the awareness increased in participants with higher education (odds ratio [OR] = 1.50, 95% confidence interval [CI] = 1.15-1.95, P = .003). Ninety-eight percent vs 71% were aware that immunosuppressants can increase the risk of developing cancer (P < .001) and higher awareness was noted in younger participants (OR = 0.92, 95% CI = 0.87-0.97, P = .003). Suboptimal photoprotective behaviours (sun avoidance, sunscreen usage and sun-protective clothing) were noted in both cohorts and slightly lower sun protection rates were reported in RTR when compared with patients having GD. The level of sun protective measures in RTR based on high, moderate and minimal use of photoprotective measures were 21%, 46% and 33%, respectively. In terms of patients with GD, the latter practices were 13%, 50% and 37%, respectively (P = .560). Higher educational status was significantly associated with better sunscreen usage in RTR (P = .017) whereas this finding was not observed in patients with GD. CONCLUSION: Patients with GD and RTR should have formal education on the risks of skin cancers before starting immunosuppressants. Follow-up education and surveillance is required to improve skin protective practices in these patients.

Bleeding Complications of Percutaneous Kidney Biopsy: Does Gender Matter?

The incidence of bleeding complications after percutaneous kidney biopsies is low.Female sex may be associated with a greater risk for bleeding complications after percutaneous kidney biopsies.This association and the plausible mechanisms require further evaluation in prospective study.

Protocol and establishment of a Queensland renal biopsy registry in Australia.

BACKGROUND: Renal biopsy is often required to obtain information for diagnosis, management and prognosis of kidney disease that can be broadly classified into acute kidney injury (AKI) and chronic kidney disease (CKD). The most common conditions identified on renal biopsy are glomerulonephritis and tubulo-interstitial disorders. There is a paucity of information on management strategies and therapeutic outcomes in AKI and CKD patients. A renal biopsy registry will provide information on biopsy-proven kidney disorders to improve disease understanding and tracking, healthcare planning, patient care and outcomes. METHODS: A registry of patients, that includes biopsy-proven kidney disease, was established through the collaboration of nephrologists from Queensland Hospital and Health Services and pathologists from Pathology Queensland services. The registry is in keeping with directions of the Advancing Kidney Care 2026 Collaborative, established in September 2018 as a Queensland Health initiative. Phase 1 of the registry entailed retrospective acquisition of data from all adult native kidney biopsies performed in Queensland, Australia, from 2002 to 2018. Data were also linked with the existing CKD.QLD patient registry. From 2019 onwards, phase 2 of the registry involves prospective collection of all incident consenting patients referred to Queensland public hospitals and having a renal biopsy. Annual reports on patient outcomes will be generated and disseminated. DISCUSSION: Establishment of the Queensland Renal Biopsy Registry (QRBR) aims to provide a profile of patients with biopsy-proven kidney disease that will lead to better understanding of clinico-pathological association and facilitate future research. It is expected to improve patient care and outcomes.

Rituximab as therapy to induce remission after relapse in ANCA-associated vasculitis.

OBJECTIVES: Evaluation of rituximab and glucocorticoids as therapy to induce remission after relapse in ANCA-associated vasculitis (AAV) in a prospective observational cohort of patients enrolled into the induction phase of the RITAZAREM trial. METHODS: Patients relapsing with granulomatosis with polyangiitis or microscopic polyangiitis were prospectively enrolled and received remission-induction therapy with rituximab (4×375 mg/m2) and a higher or lower dose glucocorticoid regimen, depending on physician choice: reducing from either 1 mg/kg/day or 0.5 mg/kg/day to 10 mg/day by 4 months. Patients in this cohort achieving remission were subsequently randomised to receive one of two regimens to prevent relapse. RESULTS: 188 patients were studied: 95/188 (51%) men, median age 59 years (range 19-89), prior disease duration 5.0 years (range 0.4-34.5). 149/188 (79%) had previously received cyclophosphamide and 67/188 (36%) rituximab. 119/188 (63%) of relapses had at least one major disease activity item, and 54/188 (29%) received the higher dose glucocorticoid regimen. 171/188 (90%) patients achieved remission by 4 months. Only six patients (3.2% of the study population) did not achieve disease control at month 4. Four patients died in the induction phase due to pneumonia (2), cerebrovascular accident (1), and active vasculitis (1). 41 severe adverse events occurred in 27 patients, including 13 severe infections. CONCLUSIONS: This large prospective cohort of patients with relapsing AAV treated with rituximab in conjunction with glucocorticoids demonstrated a high level of efficacy for the reinduction of remission in patients with AAV who have relapsed, with a similar safety profile to previous studies.

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.

Cancer risks along the disease trajectory in antineutrophil cytoplasmic antibody associated vasculitis.

This review appraises the current literature on carcinogenic risks in anti-neutrophilic cytoplasmic autoantibody (ANCA) associated vasculitis (AAV). Patients with AAV are often at increased risk of developing non-melanoma skin carcinomas (NMSCs), haematological malignancies, bladder, breast, lung, prostate, and colorectal carcinomas. Reported cancer incidence in these patients ranged from 10 to 26%. Cancer risks at the time of diagnosis of AAV and disease outcomes along the trajectory of AAV that may lead to chronic kidney disease (CKD); dialysis and transplantation are summarized. Inherent carcinogenic risks as part of immunosuppressive treatment in AAV are further detailed with considerations on specific malignancy risks of therapeutic agents used. Challenges that contribute to malignancy risk include a high relapse rate of AAV and prolonged exposure to immunosuppressants. The incidence of malignancy increases significantly after 5 years of immunosuppressant exposure though risks in the earlier years have also been described. Following renal transplantation, there is limited information available on risk of malignancy. Thoughtful use of immunosuppressants, modification of lifestyle, and environmental factors, as well as adopting appropriate cancer screening will likely influence malignancy risk in individuals with AAV.

Adalimumab-induced IgA nephropathy.

Immunoglobulin A nephropathy (IgAN) is the most commonly diagnosed glomerulonephritis worldwide. It is usually idiopathic and may be associated with many other diseases. Recently, biological agents including tumour necrosis factor alpha (TNFα) inhibitors have been identified as a potential cause for IgAN. We report the case of a 39-year-old woman who presented with renal dysfunction and visible haematuria. She had a background of Crohn's disease (CD) and had been on adalimumab for 4 years following a right hemicolectomy. Subsequently, she underwent a renal biopsy that demonstrated IgAN and adalimumab was ceased. Following a flare in her CD, she was commenced on infliximab, which led to remission of the IgAN and CD. This is the first case to demonstrate the occurrence of IgAN as a complication of a TNFα inhibitor (adalimumab) that remained in remission despite the commencement of a second TNFα inhibitor (infliximab).

Radiological Tenckhoff catheter insertion for peritoneal dialysis: A cost-effective approach.

INTRODUCTION: Radiological insertion of Tenckhoff catheters can be an alternative option for peritoneal dialysis access creation, as compared to surgical catheter insertion. This study will review the outcomes and complications of radiological Tenckhoff catheter insertion in a metropolitan renal service and compare costs between surgical and radiological insertion. METHODS: Data were collected prospectively for all patients who had a Tenckhoff catheter insertion for peritoneal dialysis (PD) under radiological guidance at our hospital from May 2014 to November 2016. The type of catheter used and complications, including peri-catheter leak, exit site infection and peritonitis were reviewed. Follow-up data were also collected at points 3, 6 and 12 months from catheter insertion. Costing data were obtained from Queensland Health Electronic Reporting System (QHERS) data, average staff salaries and consumable contract price lists. RESULTS: In the 30-month evaluation period, 70 catheters were inserted. Two patients had an unsuccessful procedure due to the presence of abdominal adhesions. Seven patients had an episode of peri-catheter leak, and four patients had an exit site infection following catheter insertion. Peritonitis was observed in nine patients during the study period. The majority of patients (90%) remained on peritoneal dialysis at 3-month follow-up. The average costs of surgical and radiological insertion were noted to be AUD$7788.34 and AUD$1597.35, respectively. CONCLUSION: Radiological Tenckhoff catheter insertion for peritoneal dialysis appears to be an attractive and cost-effective option given less waiting periods for the procedure, the relatively low cost of insertion and comparable rates of complications.

Phentermine induced acute interstitial nephritis.

Acute interstitial nephritis (AIN) has a number of medication-related aetiologies. Antibiotics, proton pump inhibitors and non-steroidal anti-inflammatory drugs are common causes; however, any medication has the potential to cause drug-induced AIN. We report the first case of phentermine-induced AIN. A Caucasian woman aged 43 years presented with a 5-week history of lethargy, left-sided lower abdominal pain, nausea and vomiting. She had been taking phentermine for weight loss for 9 months and had recently ceased the medication. The patient underwent a renal biopsy that showed a predominantly lymphohistiocytic interstitial infiltrate with a moderate number of eosinophils consistent with AIN. Phentermine is increasingly used for weight loss in obese patients. This is the first case implicating phentermine as the causative agent for drug-induced AIN. While rare, phentermine-induced AIN is a possible adverse reaction of phentermine. Physicians and patients need to be aware of this risk.

Epidemiology of biopsy-proven glomerulonephritis in Queensland adults.

AIM: There is a paucity of data pertaining to the incidence of biopsy-proven glomerulonephritis (GN) in Australia. This retrospective study aims to review the data from all adult native renal biopsies performed in the state of Queensland from 2002 to 2011--comparing results with centres from across the world. METHODS: Pathology reports of 3697 adult native kidney biopsies were reviewed, of which 2048 had GN diagnoses. Age, gender, clinical indication and histopathology findings were compared. RESULTS: The average age at biopsy was 48 ± 17 years. Male preponderance was noted overall (∼60%), with lupus nephritis being the only individual GN with female predilection. The average rate of biopsy was 12.04 per hundred thousand people per year (php/yr). Nephrotic and nephritic syndromes comprised approximately 75% of all clinical indications that lead to GN diagnoses. IgA nephropathy (1.41 php/yr) was the most common primary GN followed by focal segmental glomerulosclerosis (1.02 php/yr) and crescentic GN (0.73 php/yr). Diabetic nephropathy (0.84 php/yr), lupus nephritis (0.69 php/yr) and amyloidosis (0.19 php/yr) were the most commonly identified secondary GN. CONCLUSION: IgA nephropathy is the predominant primary GN in Queensland, and nephrotic syndrome the most common indication for a renal biopsy. While crescentic GN incidence has significantly increased with time, focal segmental glomerulosclerosis incidence has not shown any trend. Incidence of GN overall appears to increase with age. The annual rate of biopsy in this study appears lower than previously published in an Australian population.