Analysis of risk factors for late arteriovenous fistula failure and patency rates after angioplasty in hemodialysis patients: a retrospective cohort study.

Background: The incidence of chronic kidney disease (CKD) and end-stage kidney disease (ESKD) is increasing worldwide. Hemodialysis (HD) is the mainstay of renal replacement therapy for patients with ESKD. Risk factors associated with late arteriovenous fistula (AVF) failure in HD patients are poorly investigated. Therefore, the aim of this study was to identify factors associated with late AVF failure in HD patients. Methods: Patients with end-stage renal disease (ESRD) who underwent forearm or upper arm AVF angioplasty at Second Affiliated Hospital of Chongqing Medical University between September 2009 and August 2018 were included. Patients were followed up for 36 months. Baseline characteristics were collected using electronic medical records (EMRs). Variables associated with late AVF failure were identified using Cox proportional hazards models. Results: There were 137 patients (64% male, 36% female) included in this study, with 50 (36.5%) experiencing AVF failure. Univariable log-rank analysis showed that age, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), intact parathyroid hormone (iPTH), albumin (ALB), and AVF patency rate were significantly different between patients who did and did not experience AVF failure. Cox regression analysis showed that CRP [P=0.002, hazard ratio (HR) =2.719, 95% confidence interval (CI) for HR: 1.432-5.164], ESR (P=0.030, HR =2.431, 95% CI: 1.088-5.434), iPTH (P=0.013, HR =0.325, 95% CI: 0.133-0.793), and ALB (P=0.040, HR =0.539, 95% CI: 0.299-0.972) were independently associated with AVF failure. Kaplan-Meier survival analysis showed that the cumulative patency rates of AVF at 6, 12, 18, 24, 30, and 36 months were 84%, 74%, 69%, 64%, 64%, and 64%, respectively. Conclusions: CRP, ESR, iPTH, and ALB were associated with AVF failure and should be used as reference in clinical practice.

Relationship between cortical and medullary thickness and glomerular filtration rate among living kidney donors.

The relationship between the kidney cortex and medulla is not well understood in healthy populations. This study characterised the relationship between cortical/medullary thickness and measured glomerular filtration rate (GFR) in 390 living kidney donors. A positive relationship was observed between medullary, but not cortical, thickness and GFR. We propose that this reflects a correlation between juxtamedullary nephron number and GFR.

Factors associated with hospitalisations and deaths of residential aged care residents with COVID-19 during the Omicron (BA.1) wave in Queensland.

OBJECTIVE: To identify characteristics associated with the hospitalisation and death of people with COVID-19 living in residential aged care facilities (RACFs). DESIGN: Retrospective cohort study. SETTING, PARTICIPANTS: All confirmed (polymerase chain reaction testing) or probable SARS-CoV-2 infections (rapid antigen tests) in residents of the 86 RACFs in the Metro South Hospital and Health Service area (southeast Queensland), 13 December 2021 - 24 January 2022. MAIN OUTCOME MEASURES: Hospitalisation within 14 days or death within 28 days of COVID-19 diagnosis. RESULTS: Of 1071 RACF residents with COVID-19, 151 were hospitalised within 14 days and 126 died within 28 days of diagnosis. Likelihood of death increased with age (per five years: adjusted odds ratio [aOR], 1.38; 95% confidence interval [CI], 1.21-1.57), but not that of hospitalisation. Men were more likely to be hospitalised (aOR, 1.7; 95% CI, 1.2-2.4) or die (aOR, 2.5; 95% CI, 1.7-3.6) than women. The likelihood of hospitalisation was greater for those with dementia (aOR, 1.9; 95% CI, 1.2-3.0), heart failure (aOR, 1.7; 95% CI, 1.1-2.7), chronic kidney disease (aOR, 1.7; 95% CI, 1.1-2.5), or asthma (aOR, 2.2; 95% CI, 1.2-3.8). The likelihood of death was greater for residents with dementia (aOR, 2.2; 95% CI, 1.3-3.7), diabetes mellitus (aOR, 1.9; 95% CI, 1.3-3.0), heart failure (aOR, 2.0; 95% CI, 1.1-3.3), or chronic lung disease (aOR, 1.7; 95% CI, 1.1-2.7). The likelihood of hospitalisation and death were each higher for residents who had received two or fewer vaccine doses than for those who had received three doses. CONCLUSIONS: Most characteristics that influenced the likelihood of hospitalisation or death of RACF residents with COVID-19 were non-modifiable factors linked with frailty and general health status. Having received three COVID-19 vaccine doses was associated with much lower likelihood of hospitalisation or death.

Combination Dabrafenib and Trametinib Versus Combination Nivolumab and Ipilimumab for Patients With Advanced BRAF-Mutant Melanoma: The DREAMseq Trial-ECOG-ACRIN EA6134.

PURPOSE: Combination programmed cell death protein 1/cytotoxic T-cell lymphocyte-4-blockade and dual BRAF/MEK inhibition have each shown significant clinical benefit in patients with BRAFV600-mutant metastatic melanoma, leading to broad regulatory approval. Little prospective data exist to guide the choice of either initial therapy or treatment sequence in this population. This study was conducted to determine which initial treatment or treatment sequence produced the best efficacy. PATIENTS AND METHODS: In a phase III trial, patients with treatment-naive BRAFV600-mutant metastatic melanoma were randomly assigned to receive either combination nivolumab/ipilimumab (arm A) or dabrafenib/trametinib (arm B) in step 1, and at disease progression were enrolled in step 2 to receive the alternate therapy, dabrafenib/trametinib (arm C) or nivolumab/ipilimumab (arm D). The primary end point was 2-year overall survival (OS). Secondary end points were 3-year OS, objective response rate, response duration, progression-free survival, crossover feasibility, and safety. RESULTS: A total of 265 patients were enrolled, with 73 going onto step 2 (27 in arm C and 46 in arm D). The study was stopped early by the independent Data Safety Monitoring Committee because of a clinically significant end point being achieved. The 2-year OS for those starting on arm A was 71.8% (95% CI, 62.5 to 79.1) and arm B 51.5% (95% CI, 41.7 to 60.4; log-rank P = .010). Step 1 progression-free survival favored arm A (P = .054). Objective response rates were arm A: 46.0%; arm B: 43.0%; arm C: 47.8%; and arm D: 29.6%. Median duration of response was not reached for arm A and 12.7 months for arm B (P < .001). Crossover occurred in 52% of patients with documented disease progression. Grade ≥ 3 toxicities occurred with similar frequency between arms, and regimen toxicity profiles were as anticipated. CONCLUSION: Combination nivolumab/ipilimumab followed by BRAF and MEK inhibitor therapy, if necessary, should be the preferred treatment sequence for a large majority of patients.

Two-dimensional correlated spectroscopy distinguishes clear cell renal cell carcinoma from other kidney neoplasms and non-cancer kidney.

Background: Routinely used clinical scanners, such as computed tomography (CT), magnetic resonance imaging (MRI) and ultrasound (US), are unable to distinguish between aggressive and indolent tumor subtypes in masses localized to the kidney, often leading to surgical overtreatment. The results of the current investigation demonstrate that chemical differences, detected in human kidney biopsies using two-dimensional COrrelated SpectroscopY (2D L-COSY) and evaluated using multivariate statistical analysis, can distinguish these subtypes. Methods: One hundred and twenty-six biopsy samples from patients with a confirmed enhancing kidney mass on abdominal imaging were analyzed as part of the training set. A further forty-three samples were used for model validation. In patients undergoing radical nephrectomy, biopsies of non-cancer kidney cortical tissue were also collected as a non-cancer control group. Spectroscopy data were analyzed using multivariate statistical analysis, including principal component analysis (PCA) and orthogonal projection to latent structures with discriminant analysis (OPLS-DA), to identify biomarkers in kidney cancer tissue that was also classified using the gold-standard of histopathology. Results: The data analysis methodology showed good separation between clear cell renal cell carcinoma (ccRCC) versus non-clear cell RCC (non-ccRCC) and non-cancer cortical tissue from the kidneys of tumor-bearing patients. Variable Importance for the Projection (VIP) values, and OPLS-DA loadings plots were used to identify chemical species that correlated significantly with the histopathological classification. Model validation resulted in the correct classification of 37/43 biopsy samples, which included the correct classification of 15/17 ccRCC biopsies, achieving an overall predictive accuracy of 86%, Those chemical markers with a VIP value >1.2 were further analyzed using univariate statistical analysis. A subgroup analysis of 47 tumor tissues arising from T1 tumors revealed distinct separation between ccRCC and non-ccRCC tissues. Conclusions: This study provides metabolic insights that could have future diagnostic and/or clinical value. The results of this work demonstrate a clear separation between clear cell and non-ccRCC and non-cancer kidney tissue from tumor-bearing patients. The clinical translation of these results will now require the development of a one-dimensional (1D) magnetic resonance spectroscopy (MRS) protocol, for the kidney, using an in vivo clinical MRI scanner.

Kidney failure, CKD progression and mortality after nephrectomy.

PURPOSE: This study tested the hypothesis that progression of chronic kidney disease (CKD) is less aggressive in patients whose primary cause of CKD was nephrectomy, compared with non-surgical causes. METHODS: A sample of 5983 patients from five specialist nephrology practices was ascertained from the Queensland CKD Registry. Rates of kidney failure/death were compared on primary aetiology of CKD using multivariable Cox proportional hazards models. CKD progression was compared using multivariable linear and logistic regression analyses. RESULTS: Of 235 patients with an acquired single kidney as their primary cause of CKD, 24 (10%) and 38 (17%) developed kidney failure or died at median [IQR] follow-up times of 12.9 [2.5-31.0] and 33.6 [18.0-57.9] months after recruitment. Among patients with an eGFR < 45 mL/min per 1.73m2 at recruitment, patients with diabetic nephropathy and PCKD had the highest rates (per 1000 person-years) of kidney failure (107.8, 95% CI 71.0-163.8; 75.5, 95% CI 65.6-87.1); whereas, patients with glomerulonephritis and an acquired single kidney had lower rates (52.9, 95% CI 38.8-72.1; 34.6, 95% CI 20.5-58.4, respectively). Among patients with an eGFR ≥ 45 mL/min per 1.73m2, those with diabetic nephropathy had the highest rates of kidney failure (16.6, 95% CI 92.5-117.3); whereas, those with glomerulonephritis, PCKD and acquired single kidney had a lower risk (11.3, 95% CI 7.1-17.9; 11.7, 95% CI 3.8-36.2; 10.7, 95% CI 4.0-28.4, respectively). CONCLUSION: Patients who developed CKD after nephrectomy had similar rates of adverse events to most other causes of CKD, except for diabetic nephropathy which was consistently associated with worse outcomes. While CKD after nephrectomy is not the most aggressive cause of kidney disease, it is by no means benign, and is associated with a tangible risk of kidney failure and death, which is comparable to other major causes of CKD.

Thrombotic Microangiopathy Associated with Pazopanib in a Kidney Transplant Recipient.

Thrombotic microangiopathy (TMA) is characterised by abnormalities in the walls of arterioles and capillaries, precipitated by hereditary or acquired characteristics, and culminating in microvascular thrombosis because of dysregulated complement activity. A number of drugs can precipitate TMA, including vascular endothelial growth factor (VEGF) inhibitors, because of their effects on endothelial repair. Pazopanib is a VEGF inhibitor used for the treatment of renal cell carcinoma (RCC); it is uncommonly associated with TMA. A 52-year-old male, 5 years post his second kidney transplant secondary to immunoglobulin (Ig) A nephropathy, presented with hypertension, fluid overload, and worsening graft function (peak creatinine 275 µmol/L, baseline 130-160 µmol/L) and nephrotic range proteinuria 2 months after commencing pazopanib for metastatic RCC. His maintenance immunosuppression included ciclosporin, mycophenolate, and prednisolone. Haematological parameters were unremarkable. Allograft biopsy demonstrated glomerular and arteriolar changes consistent with chronic active TMA, with overlying features of borderline cellular rejection. He was treated with intravenous methylprednisolone 250 mg for 3 days and commenced on irbesartan 75 mg daily. Drug-induced TMA from pazopanib was suspected, particularly given the documented association with other tyrosine kinase inhibitors (TKIs). In consultation with his medical oncologist, pazopanib was ceased, and an alternate TKI cabozantinib was commenced. Serum creatinine remained <200 µmol/L 3 months after admission. This is the first reported biopsy-proven case of TMA attributed to pazopanib in a kidney transplant recipient. With increasing clinical indications for and availability of TKIs, clinicians need to be aware of their association with TMA events in kidney transplant recipients, who are already susceptible to TMA due to abnormal vasculature, infectious triggers, ischaemia-reperfusion injury, and use of calcineurin inhibitor.

Allograft failure in kidney transplant recipients who developed kidney failure secondary to ANCA-associated vasculitis.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides are uncommon causes of kidney failure. In kidney transplant recipients who developed kidney failure secondary to ANCA-associated vasculitis, disease recurrence is unlikely due to ongoing immunosuppression, and patients generally have good immunological outcomes. This study compared transplant outcomes between ANCA-associated vasculitis and other etiologies of kidney disease. All 18 901 adult kidney transplant recipients (1990-2018) were ascertained from the ANZDATA Registry. Cox proportional hazards models were used to compare allograft failure between etiologies of kidney disease. Of 254 participants whose primary disease was ANCA-associated vasculitis, 95 (37%) developed allograft failure; of those who developed graft failure, 62 (65%) died with a functioning allograft. Compared with patients with IgA nephropathy, those with ANCA-associated vasculitis had higher rates of all-cause allograft failure (HR: 1.4, 95% CI: 1.2-1.7); however, rates of death-censored allograft failure were similar (HR: 1.0, 95% CI: 0.7-1.4). The most frequent causes of death in the ANCA-vasculitis group who died with a functioning graft were infection (23%) and malignancy (36%). Kidney transplant recipients who developed kidney failure secondary to ANCA-associated vasculitis may have had a higher risk of dying due to complications of immunosuppression compared with most other causes of kidney failure; however, they also had lower risks of disease recurrence and rejection.

Variability in surgical management of kidney cancer between urban and rural hospitals in Queensland, Australia: a population-based analysis.

BACKGROUND: International guidelines recommend partial over radical nephrectomy for management of kidney tumours, due to perceived advantages of kidney function preservation. In Queensland, oncological nephrectomy is performed in both metropolitan and rural hospitals. Previous studies have shown that patients from rural areas with kidney tumours are less likely to undergo partial nephrectomy compared with those in major cities. The aim of this study was to investigate patterns of partial nephrectomy according to geographical area, and to identify patient- and health-service-level characteristics associated with partial nephrectomy. METHODS: All 3,799 incident kidney cancer cases in Queensland (Jan 2009 to Dec 2014) were ascertained. Patients aged <18 yrs (n=47), who did not receive surgery (n=988), or had end-stage kidney disease (ESKD) before surgery (n=17) were excluded. The final sample included 2,747 patients. Data were analysed using multivariable logistic regression in order to identify associations with partial nephrectomy. RESULTS: Of 2,747 patients, 637 (25%) underwent partial nephrectomy. The likelihood of undergoing partial nephrectomy increased with more recent year of surgery (P<0.001) and higher socioeconomic status (P<0.001). The likelihood of undergoing partial nephrectomy decreased for patients managed in lower-volume centres (P=0.004), with increasing age (P<0.001), and hospital location outside of a major city (P<0.001). Overall, the number of nephrectomies, and proportion/number of partial nephrectomies, performed in rural hospitals has increased over the study period. CONCLUSIONS: Our results suggest that, although patients who are managed in major cities are more likely to undergo partial nephrectomy, likelihood of undergoing partial nephrectomy in rural centres is increasing, consistent with international best practice.

A Simple Clinical Tool for Stratifying Risk of Clinically Significant CKD after Nephrectomy: Development and Multinational Validation.

BACKGROUND: Clinically significant CKD following surgery for kidney cancer is associated with increased morbidity and mortality, but identifying patients at increased CKD risk remains difficult. Simple methods to stratify risk of clinically significant CKD after nephrectomy are needed. METHODS: To develop a tool for stratifying patients' risk of CKD arising after surgery for kidney cancer, we tested models in a population-based cohort of 699 patients with kidney cancer in Queensland, Australia (2012-2013). We validated these models in a population-based cohort of 423 patients from Victoria, Australia, and in patient cohorts from single centers in Queensland, Scotland, and England. Eligible patients had two functioning kidneys and a preoperative eGFR ≥60 ml/min per 1.73 m2. The main outcome was incident eGFR <45 ml/min per 1.73 m2 at 12 months postnephrectomy. We used prespecified predictors-age ≥65 years old, diabetes mellitus, preoperative eGFR, and nephrectomy type (partial/radical)-to fit logistic regression models and grouped patients according to degree of risk of clinically significant CKD (negligible, low, moderate, or high risk). RESULTS: Absolute risks of stage 3b or higher CKD were <2%, 3% to 14%, 21% to 26%, and 46% to 69% across the four strata of negligible, low, moderate, and high risk, respectively. The negative predictive value of the negligible risk category was 98.9% for clinically significant CKD. The c statistic for this score ranged from 0.84 to 0.88 across derivation and validation cohorts. CONCLUSIONS: Our simple scoring system can reproducibly stratify postnephrectomy CKD risk on the basis of readily available parameters. This clinical tool's quantitative assessment of CKD risk may be weighed against other considerations when planning management of kidney tumors and help inform shared decision making between clinicians and patients.

Haemodialysis withdrawal in Australia and New Zealand: a binational registry study.

BACKGROUND: Withdrawal from dialysis is an increasingly common cause of death in patients with end-stage kidney disease (ESKD). As most published reports of dialysis withdrawal have been outside the Oceania region, the aims of this study were to determine the frequency, temporal pattern and predictors of dialysis withdrawal in Australian and New Zealand patients receiving chronic haemodialysis. METHODS: This study included all people with ESKD in Australia and New Zealand who commenced chronic haemodialysis between 1 January 1997 and 31 December 2016, using data from the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry. Competing risk regression models were used to identify predictors of dialysis withdrawal mortality, using non-withdrawal cause of death as the competing risk event. RESULTS: Among 40 447 people receiving chronic haemodialysis (median age 62 years, 61% male, 9% Indigenous), dialysis withdrawal mortality rates increased from 1.02 per 100 patient-years (11% of all deaths) during the period 1997-2000 to 2.20 per 100 patient-years (32% of all deaths) during 2013-16 (P < 0.001). Variables that were significantly associated with a higher likelihood of haemodialysis withdrawal were older age {≥70 years subdistribution hazard ratio [SHR] 1.77 [95% confidence interval (CI) 1.66-1.89]; reference 60-70 years}, female sex [SHR 1.14 (95% CI 1.09-1.21)], white race [Asian SHR 0.56 (95% CI 0.49-0.65), Aboriginal and Torres Strait Islander SHR 0.83 (95% CI 0.74-0.93), Pacific Islander SHR 0.47 (95% CI 0.39-0.68), reference white race], coronary artery disease [SHR 1.18 (95% CI 1.11-1.25)], cerebrovascular disease [SHR 1.15 (95% CI 1.08-1.23)], chronic lung disease [SHR 1.13 (95% CI 1.06-1.21)] and more recent era [2013-16 SHR 3.96 (95% CI 3.56-4.48); reference 1997-2000]. CONCLUSIONS: Death due to haemodialysis withdrawal has become increasingly common in Australia and New Zealand over time. Predictors of haemodialysis withdrawal include older age, female sex, white race and haemodialysis commencement in a more recent era.

Utility of cytokeratin 7, S100A1 and caveolin-1 as immunohistochemical biomarkers to differentiate chromophobe renal cell carcinoma from renal oncocytoma.

BACKGROUND: Differentiation of chromophobe renal cell carcinoma (chRCC) from benign renal oncocytoma (RO) can be challenging especially when there are overlapping histological and morphological features. In this study we have investigated immunohistochemical biomarkers (cytokeratin 7/CK7, Caveolin-1/Cav-1 and S100 calcium-binding protein A1/S100A1) to aid in this difficult differentiation and attempted to validate their use in human renal tumour tissue to assess their discriminatory ability, particularly for chRCC and RO, in an Australian cohort of patients. METHODS: Retrospective study was carried out of archived formalin-fixed paraffin-embedded renal tumours from tumour nephrectomy specimens of 75 patients: 30 chRCC, 15 RO and 30 clear cell RCC (ccRCC). Sections were cut and immunostained with specific polyclonal antibodies of CK7, Cav-1 and S100A1. Morphometry was used to determine expression patterns of the biomarkers using Aperio ImageScope. Results were assessed with student t-test and ANOVA with significance at P<0.05. RESULTS: From this cohort, male-to-female ratio was 1.9:1. Median age was 64 (45-88 years) and median tumour size was 3.8 cm (range, 1.2-18 cm). There were 47 (62.7%) T1, 7 T2, 20 T3 and one T4 stage of RCC; with 2 patients presenting with M1 stage. There was significantly higher CK7 expression in chRCC compared to RO (P=0.03), and chRCC also had a different staining pattern and higher expression of Cav-1 compared to RO. There was higher expression of S100A1 in RO compared to chRCC. CONCLUSIONS: Immunohistochemical staining and standard morphometry of CK7, Cav-1 and S100A1 can aid in the differentiation of chRCC and RO. This may guide clinicians in management of patients when faced with difficult diagnostic histological distinction between the two tumour subtypes.

Chronic kidney disease after nephrectomy: a clinically-significant entity?

Worldwide, the kidney is the ninth and 14th most common primary site of cancer in men and women respectively. Surgical management with either radical or partial nephrectomy is the mainstay of treatment. Surgical resection of functional kidney parenchyma is associated with reductions in glomerular filtration rate, and can lead to the development of chronic kidney disease (CKD); however, there is currently debate as to whether CKD secondary to surgical removal of a kidney is of clinical significance. Here, it will be argued that CKD is of clinical significance regardless of aetiology, due to the higher cardiovascular and mortality risk which is associated with low glomerular filtration rate.

Kidney cancer biobanking: considerations for a single institutional biorepository.

The Princess Alexandra Hospital Kidney Cancer Biobank, housed at the Translational Research Institute in Brisbane, is an Australian biorepository which contains fixed and fresh-frozen cancer and non-cancer kidney tissue, perinephric fat, urine and peripheral blood. The patient samples are linked to de-identified clinical information via a secure database. Participants undergoing nephrectomy for suspected renal malignancy are recruited prospectively. Recruitment began in 2013 and the biobank currently contains biofluids, tissue and clinical information for more than 330 participants. This biobank contains linked de-identified clinical data, which provide comprehensive information about biospecimens, and information about clinical outcomes.

Tumor size and postoperative kidney function following radical nephrectomy.

Background: Chronic kidney disease (CKD) following nephrectomy for kidney tumors is common, and both patient and tumor characteristics may affect postoperative kidney function. Several studies have reported that surgery for large tumors is associated with a lower likelihood of postoperative CKD, but others have reported CKD to be more common before surgery in patients with large tumors. Objective: The aim of this study was to clarify inconsistencies in the literature regarding the prognostic significance of tumor size for postoperative kidney function. Study design and setting: We analyzed data from 944 kidney cancer patients managed with radical nephrectomy between January 2012 and December 2013, and 242 living kidney donors who underwent surgery between January 2011 and December 2014 in the Australian states of Queensland and Victoria. Multivariable logistic regression was used to assess the primary outcome of CKD upstaging. Structural equation modeling was used to evaluate causal models, to delineate the influence of patient and tumor characteristics on postoperative kidney function. Results: We determined that a significant interaction between age and tumor size (P=0.03) led to the observed inverse association between large tumor size and CKD upstaging, and was accentuated by other forms of selection bias. Subgrouping patients by age and tumor size demonstrated that all patients aged ≥65 years were at increased risk of CKD upstaging, regardless of tumor size. Risk of CKD upstaging was comparable between age-matched living donors and kidney cancer patients. Conclusion: Larger tumors are unlikely to confer a protective effect with respect to postoperative kidney function. The reason for the previously reported inconsistency is likely a combination of the analytical approach and selection bias.

Incident Chronic Kidney Disease After Radical Nephrectomy for Renal Cell Carcinoma.

BACKGROUND: Chronic kidney disease (CKD) after surgery for kidney cancer is common, and is associated with increased morbidity and mortality. This study aimed to identify factors associated with incident CKD in patients managed with radical nephrectomy. PATIENTS AND METHODS: All patients diagnosed with renal cell carcinoma between January 2012 and December 2013 were ascertained from state-based cancer registries in Queensland and Victoria. Information on patient, tumor, and health service characteristics was obtained via chart review. Multivariable logistic regression was used to evaluate exposures associated with incident CKD (estimated glomerular filtration rate [eGFR] <60 mL per minute per 1.73 m2) at 12 months after nephrectomy. RESULTS: Older age (adjusted odds ratio [aOR] per 5-year increase, 1.5; 95% confidence interval [CI], 1.4-1.6), male sex (aOR, 1.4; 95% CI, 1.0-2.0), obese compared with not obese (aOR, 1.8; 95% CI, 1.2-2.7), rural compared with urban place of residence (aOR, 1.8; 95% CI, 1.1-3.0) were associated with a higher risk of incident CKD. Lower preoperative eGFR was also associated with a higher risk of incident CKD. Management in private compared with public hospitals was also associated with a higher risk of CKD (aOR, 1.6; 95% CI, 1.2-2.2). Factors related to tumor size and cancer severity were also associated with worse postoperative kidney function, although it is likely this was a consequence of selection bias. CONCLUSION: Patient characteristics have the strongest associations with incident CKD after radical nephrectomy. Potential risk factors were reasonably similar to recognized CKD risk factors for the general population. Patients who undergo nephrectomy who have CKD risk factors might benefit from ongoing postoperative screening for deterioration of kidney function.

GRP78 expression in tumor and perinephric adipose tissue is not an optimal risk stratification marker for clear cell renal cell carcinoma.

OBJECTIVE: Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancer, which is difficult to treat and lacks a reliable prognostic marker. A previous study showed that the endoplasmic reticulum stress marker, glucose-regulated-protein-78 (GRP78), is a potential prognostic marker for ccRCC. The present study aimed to: (1) examine whether GRP78 was upregulated in ccRCC compared with matched non-neoplastic renal tissue; and (2) investigate whether GRP78 expression in ccRCC tissue or perinephric adipose tissue has any association with ccRCC aggressiveness. METHODS: A retrospective cross-sectional study of 267 patients who underwent nephrectomy for renal tumors between June 2013 and October 2017 was conducted at Princess Alexandra Hospital, Brisbane, Australia. Software-assisted quantification of average grey value of staining intensity (staining intensity method) and proportion of positive pixels (positive pixel method) was applied to measure expression of GRP78 in archived specimens of renal tumor tissues (n = 114), adjacent non-neoplastic renal tissues (n = 68), and perinephric adipose tissues (n = 60) in participants diagnosed with ccRCC. RESULTS: GRP78 was not upregulated in renal tumor tissue compared with paired normal renal tissue. In tumor tissue, GRP78 expression did not show any association with ccRCC aggressiveness using either quantification method. In adipose tissue, downregulation of GRP78 demonstrated poor correlation with increased probability of metastasis, with one unit increase in average grey value of GRP78 staining weakly correlating with a 17% increase in the odds ratio of metastasis (95% confidence interval: 0.99 to 1.38, p = 0.07). CONCLUSION: GRP78 is not valuable as a risk stratification marker for ccRCC.

Outcome Measures Used to Report Kidney Function in Studies Investigating Surgical Management of Kidney Tumours: A Systematic Review.

CONTEXT: Most practice decisions relevant to preserving kidney function in patients managed surgically for kidney tumours are driven by observational studies. A wide range of outcome measures are used in these studies, which reduces comparability and increases the risk of reporting bias. OBJECTIVE: To comprehensively and succinctly describe the outcomes used to evaluate kidney function in studies evaluating surgical management of kidney tumours. EVIDENCE ACQUISITION: Electronic search of the PubMed database was conducted to identify studies with at least one measure of kidney function in patients managed surgically for kidney tumours, published between January 2000 and September 2017. Abstracts were initially screened for eligibility. Full texts of articles were then evaluated in more detail for inclusion. A narrative synthesis of the evidence was conducted. EVIDENCE SYNTHESIS: A total of 312 studies, involving 127905 participants, were included in this review. Most were retrospective (n=274) studies and conducted in a single centre (n=264). Overall, 78 unique outcome measures were identified, which were grouped into six outcome categories. Absolute postoperative kidney function (n=187), relative kidney function (n=181), and postoperative chronic kidney disease (n=131) were most frequently reported. Kidney function was predominantly quantified using estimated glomerular filtration rate or creatinine clearance (n=255), most using the modification of diet in renal disease equation (n=182). Only 70 studies provided rationale for specific outcome measures used. CONCLUSIONS: There is significant variability in the reporting and quantification of kidney function in studies evaluating patients managed surgically for kidney tumours. A standardised approach to measuring and reporting kidney function will increase the effectiveness of outcomes reported and improve relevance of research findings within a clinical context. PATIENT SUMMARY: Although we know that the removal of a kidney can reduce kidney function, clinical significance of various approaches is a matter of debate. This article demonstrates significant variability in the way kidney function was reported across all studies of patients with kidney cancer undergoing surgery, indicating a need for standardisation.

Chronic kidney cortical damage is associated with baseline kidney function and albuminuria in patients managed with radical nephrectomy for kidney tumours.

This study evaluated the relationship between histological markers of chronic kidney damage in patients undergoing radical nephrectomy for kidney tumours and preoperative kidney function, degree of albuminuria, and changes in glomerular volume. A schema to grade chronic kidney damage could be used to identify patients at risk of developing CKD following nephrectomy. Non-neoplastic cortical tissue was sourced from 150 patients undergoing radical nephrectomy for suspected kidney cancer. This tissue was evaluated for indicators of chronic damage, specifically: glomerulosclerosis, arteriosclerosis, interstitial fibrosis, and tubular atrophy. Glomerular volume was determined using the Weibel and Gomez method. Associations between these parameters and both estimated glomerular filtration rate (eGFR) and albumin-creatinine ratio (ACR) were determined using either a Mann-Whitney U-test or a Kruskal-Wallis ANOVA. Associations between both eGFR and ACR and glomerular volume were assessed using linear regression. eGFR was inversely associated with the degree of glomerulosclerosis (p < 0.001), vascular narrowing (p = 0.002), tubular atrophy (p < 0.001), and interstitial fibrosis (p < 0.001). ACR was associated only with the degree of interstitial fibrosis (p = 0.02) and tubular atrophy (p = 0.02). Glomerular volume was greater for males, diabetics, hypertensive patients, and patients with a greater degree of interstitial fibrosis. Glomerular volume was positively associated with ACR. A schema to grade chronic damage was developed. The proposed schema is associated with baseline clinical indices of kidney function and damage. Longitudinal validation is necessary to determine the prognostic utility of this schema.

Cabozantinib for the Management of Metastatic Clear Cell Renal Cell Carcinoma.

Cabozantinib is a multi-tyrosine kinase inhibitor used for the treatment of various solid-organ tumours. It was recently approved as a first- and second-line therapeutic for the management of advanced/metastatic renal cell carcinoma based on the results of two randomised controlled trials. The phase III METEOR trial compared cabozantinib against everolimus as a second- or greater line therapy and found benefits in progression-free and overall survival, and the phase II CABOSUN trial compared cabozantinib against sunitinib as a first-line therapeutic and found benefits in terms of progression-free survival. This review briefly summarises how cabozantinib fits into current treatment paradigms for the management of advanced renal cell carcinoma.