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.

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.

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.

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.

Acute Tubulointerstitial Nephritis as a Sole Manifestation of Immunoglobulin G4-Related Disease.

This is a case report of a patient who developed severe acute kidney disease with kidney biopsy showing interstitial nephritis, plasma cell infiltration and immunoglobulin G4 (IgG4) expression consistent with IgG4-related kidney disease. There were no other systemic features of IgG4-related disease. The patient was treated with corticosteroids and mycophenolate. This case highlights the need to consider IgG4-related kidney disease even in the absence of other systemic features. Isolated renal involvement is underrecognized and can lead to missed diagnosis. It also illustrates that mycophenolate can be used as a steroid sparing agent in this condition; an observation that adds to the limited literature in this field.

A Case of Intestinal Microsporidiosis in a Renal Transplant Recipient.

Post-renal transplant diarrhea is a common clinical presentation. An extensive list of potential etiology adds to the diagnostic dilemma. In cases of prolonged or intractable diarrhea, invasive tests are often performed. Intestinal microsporidia can be diagnosed with simple non-invasive stool polymerase chain reaction (PCR). Based on this case, we propose an easy to follow flow chart and present a literature review on post-renal transplant diarrhea. Further multicenter validation testing is required for the proposed flow chart.

Differential effects of phosphate binders on pre-dialysis serum bicarbonate in end-stage kidney disease patients on maintenance haemodialysis.

BACKGROUND: Phosphate binders' constituents have alkalotic or acidotic properties and may contribute to acid base balance in haemodialysis patients. This study aimed to investigate the differential effects of phosphate binders on pre-dialysis serum bicarbonate in End Stage Kidney Disease patients on maintenance haemodialysis. METHODS: Stable out-patients having satellite haemodialysis for at least 3 months were retrospectively studied for 18 months, excluding those with other medical causes for metabolic acidosis. Blood results were censored for inpatient episodes, at the time of death, renal transplant or dialysis modality change. Multivariable multilevel mixed-effects linear regression was used and five groups of phosphate binders were compared: Group A(Calcium (Ca) and/or Aluminium (Al) binders); B(Sevelamer hydrochloride (SH) alone); C(lanthanum carbonate (LC) alone); D(SH and Ca/Al), E(LC and Ca/Al). RESULTS: Of 320 patients, 292 were eligible for analysis with a mean follow-up of 15.54 (standard deviation, SD 3.98) months. Similar mean pre-dialysis serum levels of bicarbonate were observed at all 6 month-interval analyses. At 18(th) months, observed mean serum bicarbonate levels in mmol/L were Group B: 21.58 (SD 2.82, P<0.001), C: 23.29 (SD 2.80, P=0.02), D: 21.56 (SD 3.00, P<0.001), and E: 21.29 (SD 3.62, P=0.92) compared with Group A: 22.98 (SD 2.77). Mean serum bicarbonate was related to total SH dose in mmol/L: 22.34 (SD 2.56) for SH <2.5 g/day, 21.61 (SD 2.62) for SH 2.5-4.8 g/day, 21.04 (SD 3.31) for SH >4.8 g/day compared with 22.85 (SD 2.91) for non-users; P-trend<0.001. CONCLUSIONS: Phosphate binders' constituents may contribute to/protect against a predisposition to pre-dialysis metabolic acidosis. This may be dose dependant in patients taking Sevelamer Hydrochloride.

Atrial fibrillation and warfarin use in haemodialysis patients: an individualized holistic approach is important in stroke prevention.

Incidence and prevalence of atrial fibrillation (AF) is higher in haemodialysis (HD) population than general population. AF is associated with higher morbidity and mortality than sinus rhythm in this population. The purpose of this review is to summarize all available evidence regarding use of warfarin in HD patients with AF for stroke prevention. The enormous heterogeneity of available studies does not allow pooling of the data in the form of meta-analysis or systematic review. Current evidence regarding use of warfarin for AF in terms of risk benefit ratio in this population is limited and conflicting. Randomized control trials evaluating the safety and efficacy of anticoagulation in this population by means of risk/benefit assessment tools are urgently needed. However, suitable HD patients with AF should be counselled on their likelihood of reduction of stroke risk and experiencing side-effects before initiating anticoagulant therapy. It is particularly important to incorporate the patient's preferences and willingness to trade off benefit and risk in stroke prevention. An individualized holistic approach optimizing all potential risk factors of bleeding and ischemic stroke in HD patients with AF is recommended.