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.

Hospitalizations Among Adults With CKD in Public Renal Specialty Practices: A Retrospective Study From Queensland, Australia.

Rationale & Objective: Little is known about hospital admissions in nondialysis patients with chronic kidney disease (CKD) before death or starting kidney replacement therapy (KRT). Study Design: Retrospective observational cohort study. Setting & Participants: Hospitalizations among 7,201 patients with CKD from 10 public renal clinics in Queensland (QLD), enrolled in the CKD.QLD registry starting in May 2011, were followed for 25,496.34 person-years until they started receiving KRT or died, or until June 30, 2018. Predictors: Demographic and clinical characteristics of patients with CKD. Outcomes: Hospital admissions. Analytical Approach: We evaluated the association of demographic and clinical features with hospitalizations, length of hospital stay, and cost. Results: Approximately 81.5% of the patients were admitted at least once, with 42,283 admissions, costing Australian dollars (AUD) 231 million. The average number of admissions per person-year was 1.7, and the cost was AUD 9,060, 10 times and 2 times their Australian averages, respectively. Single (1-day) admissions constituted 59.2% of all the hospital episodes, led by neoplasms (largely chemotherapy), anemia, CKD-related conditions and eye conditions (largely cataract extractions), but only 14.8% of the total costs. Approximately 41% of admissions were >1-day admissions, constituting 85.2% of the total costs, with cardiovascular conditions, respiratory conditions, CKD-related conditions, and injuries, fractures, or poisoning being the dominant causes. Readmission within 30 days of discharge constituted >42% of the admissions and 46.8% costs. Admissions not directly related to CKD constituted 90% of the admissions and costs. More than 40% of the admissions and costs were through the emergency department. Approximately 19% of the hospitalized patients and 27% of the admissions did not have kidney disease mentioned as either principal or associate causes. Limitations: Variable follow-up times because of different dates of consent. Conclusions: The hospital burden of patients with CKD is mainly driven by complex multiday admissions and readmissions involving comorbid conditions, which may not be directly related to their CKD. Strategies to prevent these complex admissions and readmissions should minimize hospital costs and outcomes. Plain-Language Summary: We analyzed primary causes, types, and costs of hospitalizations among 7,201 patients with chronic kidney disease (CKD) from renal speciality clinics across Queensland, Australia, over an average follow-up of 3.54 years. The average annual cost per person was $9,060, and was the highest in those with more advanced CKD, higher age, and with diabetes. More than 85% of costs were driven by more complex hospitalizations with longer length of stay. Cardiovascular disease was the single largest contributor for hospitalizations, length of hospital stay, and total costs. Readmission within 30 days of discharge, particularly for the same disorder, and multiday admissions should be the main targets for mitigation of hospital costs in this population.

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.

Chronic kidney disease in public renal practices in Queensland, Australia, 2011-2018.

AIM: To describe adults with (non-dialysis) chronic kidney disease (CKD) in nine public renal practice sites in the Australian state of Queensland. METHODS: 7,060 persons were recruited to a CKD Registry in May 2011 and until start of kidney replacement therapy (KRT), death without KRT or June 2018, for a median period of 3.4 years. RESULTS: The cohort comprised 7,060 persons, 52% males, with a median age of 68 yr; 85% had CKD stages 3A to 5, 45.4% were diabetic, 24.6% had diabetic nephropathy, and 51.7% were obese. Younger persons mostly had glomerulonephritis or genetic renal disease, while older persons mostly had diabetic nephropathy, renovascular disease and multiple diagnoses. Proportions of specific renal diagnoses varied >2-fold across sites. Over the first year, eGFR fell in 24% but was stable or improved in 76%. Over follow up, 10% started KRT, at a median age of 62 yr, most with CKD stages 4 and 5 at consent, while 18.8% died without KRT, at a median age of 80 yr. Indigenous people were younger at consent and more often had diabetes and diabetic kidney disease and had higher incidence rates of KRT. CONCLUSION: The spectrum of characteristics in CKD patients in renal practices is much broader than represented by the minority who ultimately start KRT. Variation in CKD by causes, age, site and Indigenous status, the prevalence of obesity, relative stability of kidney function in many persons over the short term, and differences between those who KRT and die without KRT are all important to explore.

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.

Bilateral renal artery stenosis due to fibromuscular dysplasia presenting as superimposed pre-eclampsia.

Renal vascular hypertension is a diagnosis that needs to be entertained in the setting of refractory, otherwise unexplained hypertension in pregnancy. Conclusive diagnosis of the condition is made by the use of angiography, which confers only a low, safe dose of radiation to the fetus, especially after the first trimester. Percutaneous angioplasty is effective in treating this condition and is best performed postnatally to avoid fetal exposure to ionising radiation. While it could be managed pharmacologically, more refractory cases in pregnancy may be offered interventional treatment.

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.

A Randomized Controlled Trial to Determine the Appropriate Time to Initiate Peritoneal Dialysis after Insertion of Catheter (Timely PD Study).

BACKGROUND: The optimal time for the commencement of peritoneal dialysis (PD) after PD catheter insertion is unclear. If dialysis is started too soon after insertion, dialysate leaks and infection could occur. However, by starting PD earlier, morbidity and costs can be reduced through lesser hemodialysis requirements. This is the first randomized controlled trial to determine the safest and shortest interval to commence PD after catheter insertion. METHODS: All consecutive patients undergoing PD catheter insertion at the Royal Brisbane and Women's Hospital and Rockhampton Hospital from 1 March 2008 to 31 May 2013 who met the inclusion and exclusion criteria were invited to participate in the trial. Participants were randomized to 1 of 3 groups. Group 1 (G1) commenced PD at 1 week, group 2 (G2) at 2 weeks and group 3 (G3) at 4 weeks after PD catheter insertion. These groups were stratified by hospital and the presence of diabetes. Primary outcomes were the incidence of peritoneal fluid leaks or PD-related infection during the 4 weeks after commencement of PD. RESULTS: In total 122 participants were recruited, 39, 42, and 41 randomized to G1, G2, and G3, respectively. The primary outcome catheter leak was significantly higher in G1 (28.2%) compared with G3 (2.4%, p = 0.001) but not compared with G2 (9.5%, p = 0.044), based on intention to treat analysis. These differences were even more marked when analyzed with per protocol method: G1 had a significantly higher percentage (32.4 %) compared with G3 (3.3%, p = 0.003) but not compared with G2 (10.5%, p = 0.040). Event percentages of leak were statistically higher in G1 and occurred significantly earlier compared with other groups (p = 0.002). Amongst diabetics, technique failure was significantly higher (28.6%) in G3 compared with 0% in G1 and 7.1% in G2 (p = 0.036) and earlier in G3 at 163.2 days vs 176.8 and 175.8 (p = 0.037) for G1 and G2, respectively. CONCLUSION: Leaks were higher in participants commencing PD at 1 week after catheter insertion compared with the other 2 groups, and technique failure was higher in diabetics starting PD at 4 weeks.

Clinical and research markers of oxidative stress in chronic kidney disease.

CONTEXT: Kidney-related pathologies have increasing prevalence rates, produce a considerable financial burden, and are characterized by elevated levels of oxidative stress (OS). OBJECTIVE: This review examines relationships between chronic kidney disease (CKD) and markers of OS and antioxidant status (AS). METHODS: A systematic review of MEDLINE-indexed clinical trials, randomized controlled trials and comparative studies that examined OS and AS was performed. RESULTS AND CONCLUSION: Several markers emerged as well-suited indicators of OS and AS in CKD: malondialdehyde, F2-isoprostanes, lipid hydroperoxides, asymmetric dimethylarginine, 8-oxo-7,8-dihydro-2'-deoxyguanosine, protein carbonyls, advanced oxidation protein products and glutathione-related activity.

Randomised controlled trial to determine the appropriate time to initiate peritoneal dialysis after insertion of catheter to minimise complications (Timely PD study).

BACKGROUND: The most appropriate time to initiate dialysis after surgical insertion of Tenckhoff catheters is not clear in the literature. There is the possibility of peritoneal dialysis (PD) complications such as leakage and infection if dialysis is started too soon after insertion. However, much morbidity and expense could be saved by reducing dependency on haemodialysis (HD) by earlier initiation of PD post catheter insertion. Previous studies are observational and mostly compare immediate with delayed use. The primary objective is to determine the safest and shortest time interval between surgical placement of a Tenckhoff catheter and starting PD. METHODS/DESIGN: This is a randomised controlled trial of patients who will start PD after insertion of Tenckhoff catheter at Royal Brisbane and Women's Hospital (RBWH) or Rockhampton Base Hospital (RBH) who meet the inclusion criteria. Patients will be stratified by site and diabetic status. The patients will be randomised to one of three treatment groups. Group 1 will start PD one week after Tenckhoff catheter insertion, group 2 at two weeks and group 3 at four weeks. Nurses and physicians will be blinded to the randomised allocation. The primary end point is the complication rate (leaks and infection) after initiation of PD. DISCUSSION: The study will determine the most appropriate time to initiate PD after placement of a Tenckhoff catheter. TRIAL REGISTRATION: ACTRN12610000076077.

HIV/AIDS--dominant player in chronic kidney disease.

HIV-associated nephropathy (HIVAN) is now the third leading cause of end-stage renal disease (ESRD) in African Americans between the ages of 20 and 64 years. Statistics in the United States estimate the incidence of HIVAN to be between 3.5% and 12%. The estimated number of those living with HIV worldwide is 37.4 million, with 26 million in Africa. If the US data for HIVAN were extrapolated to Africa, between 0.9 and 3.1 million people would be predicted to have HIVAN. These figures predict an unprecedented (and possibly underestimated) burden of chronic kidney disease (CKD) in Africa, especially if we take into account the socioeconomic associations with CKD for the African continent. This potentially large number of patients poses daunting logistic, financial, and ethical issues for physicians and nephrologists practicing in Africa. Preventing chronic kidney disease due to HIV in Africa should become a major priority. This would enable early detection and treatment of HIVAN in order to prevent or delay progression to ESRD. As HIV infection is a risk factor for the development of CKD, the HIV Medicine Association of the Infectious Diseases Society of America recommends screening for CKD in HIV-infected patients; screening tests should be similar to those for patients with diabetes mellitus to detect early renal involvement. Preventive strategies need to be determined; prospective studies including antiretroviral therapy, angiotensin-converting enzyme inhibitors, and other therapeutic agents are required.