Identifying biochemical changes in the kidney using proton nuclear magnetic resonance in an adenine diet chronic kidney disease mouse model.

This study aimed to investigate the metabolic changes in the kidneys in a murine adenine-diet model of chronic kidney disease (CKD). Kidney fibrosis is the common pathological manifestation across CKD aetiologies. Sustained inflammation and fibrosis cause changes in preferred energy metabolic pathways in the cells of the kidney. Kidney cortical tissue from mice receiving a control or adenine-supplemented diet for 8 weeks (late inflammation and fibrosis) and 12 weeks (8 weeks of treatment followed by 4 weeks recovery) were analysed by 2D-correlated nuclear magnetic resonance spectroscopy and compared with histopathology and biomarkers of kidney damage. Tissue metabolite and lipid levels were assessed using the MestreNova software. Expression of genes related to inflammation, fibrosis, and metabolism were measured using quantitative polymerase chain reaction. Animals showed indicators of severely impaired kidney function at 8 and 12 weeks. Significantly increased fibrosis was present at 8 weeks but not in the recovery group suggesting some reversal of fibrosis and amelioration of inflammation. At 8 weeks, metabolites associated with glycolysis were increased, while lipid signatures were decreased. Genes involved in fatty acid oxidation were decreased at 8 weeks but not 12 weeks while genes associated with glycolysis were significantly increased at 8 weeks but not at 12 weeks. In this murine model of CKD, kidney fibrosis was associated with the accumulation of triglyceride and free lactate. There was an up-regulation of glycolytic enzymes and down-regulation of lipolytic enzymes. These metabolic changes reflect the energy demands associated with progressive kidney disease where there is a switch from fatty acid oxidation to that of glycolysis.

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.

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.

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.

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.

Predictors of new-onset chronic kidney disease in patients managed surgically for T1a renal cell carcinoma: An Australian population-based analysis.

BACKGROUND: New-onset chronic kidney disease (CKD) following surgical management of kidney tumors is common. This study evaluated risk factors for new-onset CKD after nephrectomy for T1a renal cell carcinoma (RCC) in an Australian population-based cohort. METHODS: There were 551 RCC patients from the Australian states of Queensland and Victoria included in this study. The primary outcome was new-onset CKD (eGFR <60 mL/min per 1.73 m2 ) and the secondary outcome was new-onset moderate-severe CKD (<45 mL/min per 1.73 m2 ). Multivariable logistic regression was used to evaluate associations between patient, tumor and health-service characteristics and these outcomes. RESULTS: Forty percent (219/551) of patients developed new-onset CKD, and 12% (68/551) experienced new-onset moderate-severe CKD. Risk factors for new-onset CKD were age, lower preoperative eGFR, tumor size >20 mm, radical nephrectomy, lower hospital caseloads (<20 cases/year), and rural place of residence. The associations between rural place of residence and low center volume were a consequence of higher radical nephrectomy rates. CONCLUSION: Risk factors for CKD after nephrectomy generally relate to worse baseline health, or likelihood of undergoing radical nephrectomy. Surgeons in rural centres and hospitals with low caseloads may benefit from formalized integration with specialist centers for continued professional development and case-conferencing, to assist in management decisions.

Indoxyl Sulfate Induces Apoptosis and Hypertrophy in Human Kidney Proximal Tubular Cells.

Indoxyl sulfate (IS) is a protein-bound uremic toxin that accumulates in patients with declining kidney function. Although generally thought of as a consequence of declining kidney function, emerging evidence demonstrates direct cytotoxic role of IS on endothelial cells and cardiomyocytes, largely through the expression of pro-inflammatory and pro-fibrotic factors. The direct toxicity of IS on human kidney proximal tubular epithelial cells (PTECs) remains a matter of debate. The current study explored the effect of IS on primary cultures of human PTECs and HK-2, an immortalized human PTEC line. Pathologically relevant concentrations of IS induced apoptosis and increased the expression of the proapoptotic molecule Bax in both cell types. IS impaired mitochondrial metabolic activity and induced cellular hypertrophy. Furthermore, statistically significant upregulation of pro-fibrotic (transforming growth factor-ß, fibronectin) and pro-inflammatory molecules (interleukin-6, interleukin-8, and tumor necrosis factor-α) in response to IS was observed. Albumin had no influence on the toxicity of IS. The results of this study suggest that IS directly induced a pro-inflammatory and pro-fibrotic phenotype in proximal tubular cells. In light of the associated apoptosis, hypertrophy, and metabolic dysfunction, this study demonstrates that IS may play a role in the progression of chronic kidney disease.

Optimising assessment of kidney function when managing localised renal masses.

Increased early and incidental detection, improved surgical techniques and technological advancement mean that the management of renal mass lesions is constantly evolving. The treatment of choice for renal mass lesions has historically been radical nephrectomy. Partial nephrectomy is now recommended for localised renal masses, owing to favourable renal functional outcomes. Ablative renal surgery confers a significant risk of chronic kidney disease. There are few studies assessing long term outcomes of nephrectomy on renal outcomes, and virtually no studies assessing long term outcomes for less invasive therapies such as ablation. Unless a renal mass is clearly benign on imaging, management decisions will be made with an assumption of malignancy. The content of this review applies to both benign and malignant renal mass lesions. We advocate for improved strategies for kidney function assessment and risk stratification, early targeted referral, and regular screening for chronic kidney disease for all patients after surgery.

Indoxyl sulphate and kidney disease: Causes, consequences and interventions.

In the last decade, chronic kidney disease (CKD), defined as reduced renal function (glomerular filtration rate (GFR) < 60 mL/min per 1.73 m(2) ) and/or evidence of kidney damage (typically manifested as albuminuria) for at least 3 months, has become one of the fastest-growing public health concerns worldwide. CKD is characterized by reduced clearance and increased serum accumulation of metabolic waste products (uremic retention solutes). At least 152 uremic retention solutes have been reported. This review focuses on indoxyl sulphate (IS), a protein-bound, tryptophan-derived metabolite that is generated by intestinal micro-organisms (microbiota). Animal studies have demonstrated an association between IS accumulation and increased fibrosis, and oxidative stress. This has been mirrored by in vitro studies, many of which report cytotoxic effects in kidney proximal tubular cells following IS exposure. Clinical studies have associated IS accumulation with deleterious effects, such as kidney functional decline and adverse cardiovascular events, although causality has not been conclusively established. The aims of this review are to: (i) establish factors associated with increased serum accumulation of IS; (ii) report effects of IS accumulation in clinical studies; (iii) critique the reported effects of IS in the kidney, when administered both in vivo and in vitro; and (iv) summarize both established and hypothetical therapeutic options for reducing serum IS or antagonizing its reported downstream effects in the kidney.

Lowered parasympathetic activity in apparently healthy subjects with self-reported symptoms of pain: preliminary results from a pilot study.

OBJECTIVES: The aim was to evaluate differences in the autonomic nervous system (ANS) activity, indexed by heart rate variability (HRV) in apparently healthy subjects with self-reported symptoms of pain (SRSP) within an exploratory analysis. METHODS: HRV data from 14 apparently healthy male individuals were analyzed to address potential differences in subjects with and without SRSP. SRSP was assessed using the four pain-related items from the symptom checklist (SCL-90R). Subjects were stratified based on the presence of SRSP. RESULTS: Parasympathetic activity, indexed by pNN50, RMSSD, and high frequency (HF) spectrum of HRV, was lower in subjects with SRSP. Low frequency (LF) HRV and the LF/HF ratio were greater in subjects with SRSP. However, analysis of variance revealed no significant differences between the groups. Pearson correlations showed a correlation of pNN50, HF, LF, and LF/HF ratio and the presence and frequency of SRSP. Measures of parasympathetic activity (pNN50 and HF) were inversely associated with more SRSP, indicating that subjects with more frequent SRSP show decreased parasympathetic activity. CONCLUSIONS: Consistent with evidence on changes in HRV in patients with clinical conditions of chronic or recurrent pain, this is the first study to show that healthy individuals who report symptoms of pain may have lower parasympathetic activity revealed by measures of HRV.

Two-week test-retest stability of the cold pressor task procedure at two different temperatures as a measure of pain threshold and tolerance.

BACKGROUND: The cold pressor task (CPT) was originally developed as a clinically indicative cardiovascular test, and quantifies vascular response and pulse excitability when a subject's hand is immersed into ice water. Since the test procedure results in a gradually increasing cold pain, the CPT has been widely used as a nociceptive stimulus in experimental studies on adults and children. AIM: To evaluate the test-retest stability of response patterns using the CPT as a measure of pain threshold and pain tolerance. MATERIALS AND METHODS: In the present study, sixty-one undergraduate students received painful stimulation using the CPT either at 4°C or 6°C. Measurements of pain threshold, pain tolerance and pain intensity ratings using the short form of the McGill pain questionnaire (SF-MPQ), were derived. The assessment was repeated twice over an interval of 2 weeks. Test-Retest stability was assessed within a three-layered approach, using ANOVAs, interclass correlation coefficients and standard error of the mean. A Bland-Altman analysis was also performed. Possible predictors of pain threshold and pain tolerance were assessed using random effect panel regression models. RESULTS: No significant differences emerged as a function of temperature (4°C or 6°C) on pain threshold, pain tolerance, and pain ratings. Environmental variables (room temperature and humidity) show no impact on measures of pain threshold and pain tolerance. CONCLUSION: Consistent with previous findings, regression analysis reveals that age is significantly associated with pain tolerance. The CPT procedure shows excellent 2 week test-retest stability to assess pain threshold and pain tolerance within a student population.

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.

Training-mediated leftward asymmetries during music processing: a cross-sectional and longitudinal fMRI analysis.

Practicing a musical instrument has a profound impact on the structure and function of the human brain. The present fMRI study explored how relative hemispheric asymmetries in task-related activity during music processing (same/different discrimination) are shaped by musical training (quantified as cumulative hours of instrument practice), using both a large (N=84) cross-sectional data set of children and adults, and a smaller (N=20) two time-point longitudinal data set of children tracked over 3 to 5 years. The cross-sectional analysis revealed a significant leftward asymmetry in task-related activation, with peaks in Heschl's gyrus and supramarginal gyrus (SMG). The SMG peak was further characterized by a leftward asymmetry in the partial correlation strength with subjects' cumulative hours of practice, controlling for subjects' age and task performance. This SMG peak was found to exhibit a similar pattern of response in the longitudinal data set (in this case, with subjects' cumulative hours of practice over the course of the study), controlling for age, scan interval, and amount of instrument practice prior to the first scan. This study presents novel insights into the ways musical instrument training shapes task-related asymmetries in neural activity during music processing.

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.

Differentiating maturational and training influences on fMRI activation during music processing.

Two major influences on how the brain processes music are maturational development and active musical training. Previous functional neuroimaging studies investigating music processing have typically focused on either categorical differences between "musicians versus nonmusicians" or "children versus adults." In the present study, we explored a cross-sectional data set (n=84) using multiple linear regression to isolate the performance-independent effects of age (5 to 33 years) and cumulative duration of musical training (0 to 21,000 practice hours) on fMRI activation similarities and differences between melodic discrimination (MD) and rhythmic discrimination (RD). Age-related effects common to MD and RD were present in three left hemisphere regions: temporofrontal junction, ventral premotor cortex, and the inferior part of the intraparietal sulcus, regions involved in active attending to auditory rhythms, sensorimotor integration, and working memory transformations of pitch and rhythmic patterns. By contrast, training-related effects common to MD and RD were localized to the posterior portion of the left superior temporal gyrus/planum temporale, an area implicated in spectrotemporal pattern matching and auditory-motor coordinate transformations. A single cluster in right superior temporal gyrus showed significantly greater activation during MD than RD. This is the first fMRI which has distinguished maturational from training effects during music processing.

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.

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.

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.