Human proximal tubular epithelial cell-derived small extracellular vesicles mediate synchronized tubular ferroptosis in hypoxic kidney injury.

Hypoxia is the key pathobiological trigger of tubular oxidative stress and cell death that drives the transition of acute kidney injury (AKI) to chronic kidney disease (CKD). The mitochondrial-rich proximal tubular epithelial cells (PTEC) are uniquely sensitive to hypoxia and thus, are pivotal in propagating the sustained tubular loss of AKI-to-CKD transition. Here, we examined the role of PTEC-derived small extracellular vesicles (sEV) in propagating the 'wave of tubular death'. Ex vivo patient-derived PTEC were cultured under normoxia (21 % O2) and hypoxia (1 % O2) on Transwell inserts for isolation and analysis of sEV secreted from apical versus basolateral PTEC surfaces. Increased numbers of sEV were secreted from the apical surface of hypoxic PTEC compared with normoxic PTEC. No differences in basolateral sEV numbers were observed between culture conditions. Biological pathway analysis of hypoxic-apical sEV cargo identified distinct miRNAs linked with cellular injury pathways. In functional assays, hypoxic-apical sEV selectively induced ferroptotic cell death (↓glutathione peroxidase-4, ↑lipid peroxidation) in autologous PTEC compared with normoxic-apical sEV. The addition of ferroptosis inhibitors, ferrostatin-1 and baicalein, attenuated PTEC ferroptosis. RNAse A pretreatment of hypoxic-apical sEV also abrogated PTEC ferroptosis, demonstrating a role for sEV RNA in ferroptotic 'wave of death' signalling. In line with these in vitro findings, in situ immunolabelling of diagnostic kidney biopsies from AKI patients with clinical progression to CKD (AKI-to-CKD transition) showed evidence of ferroptosis propagation (increased numbers of ACSL4+ PTEC), while urine-derived sEV (usEV) from these 'AKI-to-CKD transition' patients triggered PTEC ferroptosis (↑lipid peroxidation) in functional studies. Our data establish PTEC-derived apical sEV and their intravesicular RNA as mediators of tubular lipid peroxidation and ferroptosis in hypoxic kidney injury. This concept of how tubular pathology is propagated from the initiating insult into a 'wave of death' provides novel therapeutic check-points for targeting AKI-to-CKD transition.

High risk clear cell renal cell carcinoma microenvironments contain protumour immunophenotypes lacking specific immune checkpoints.

Perioperative immune checkpoint inhibitor (ICI) trials for intermediate high-risk clear cell renal cell carcinoma (ccRCC) have failed to consistently demonstrate improved patient outcomes. These unsuccessful ICI trials suggest that the tumour infiltrating immunophenotypes, termed here as the immune cell types, states and their spatial location within the tumour microenvironment (TME), were unfavourable for ICI treatment. Defining the tumour infiltrating immune cells may assist with the identification of predictive immunophenotypes within the TME that are favourable for ICI treatment. To define the immunophenotypes within the ccRCC TME, fresh para-tumour (pTME, n = 2), low-grade (LG, n = 4, G1-G2) and high-grade (HG, n = 4, G3-G4) tissue samples from six patients with ccRCC presenting at a tertiary referral hospital underwent spatial transcriptomics sequencing (ST-seq). Within the generated ST-seq datasets, immune cell types and states, termed here as exhausted/pro-tumour state or non-exhausted/anti-tumour state, were identified using multiple publicly available single-cell RNA and T-cell receptor sequencing datasets as references. HG TMEs revealed abundant exhausted/pro-tumour immune cells with no consistent increase in expression of PD-1, PD-L1 and CTLA4 checkpoints and angiogenic genes. Additional HG TME immunophenotype characteristics included: pro-tumour tissue-resident monocytes with consistently increased expression of HAVCR2 and LAG3 checkpoints; an exhausted CD8+ T cells sub-population with stem-like progenitor gene expression; and pro-tumour tumour-associated macrophages and monocytes within the recurrent TME with the expression of TREM2. Whilst limited by a modest sample size, this study represents the largest ST-seq dataset on human ccRCC. Our study reveals that high-risk ccRCC TMEs are infiltrated by exhausted/pro-tumour immunophenotypes lacking specific checkpoint gene expression confirming that HG ccRCC TME are immunogenic but not ICI favourable.

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.

The Impact of Anaemia on Outcomes, Admissions, and Costs in Patients with Chronic Kidney Disease in Two Public Nephrology Practices in Queensland: A CKD.QLD Registry Study.

Aim: Anaemia among patients with chronic kidney disease (CKD) leads to poor overall outcomes. This study explores anaemia and its impact on nondialysis CKD (NDD-CKD) patients. Methods: 2,303 adults with CKD from two CKD.QLD Registry sites were characterised at consent and followed until start of kidney replacement therapy (KRT), death, or censor date. Mean follow-up was 3.9 (SD 2.1) years. Analysis explored the impact of anaemia on death, KRT start, cardiovascular events (CVE), admissions, and costs in these NDD-CKD patients. Results: At consent, 45.6% patients were anaemic. Males were more often anaemic (53.6%) than females, and anaemia was significantly more common over the age of 65 years. The prevalence of anaemia was highest among CKD patients with diabetic nephropathy (27.4%) and renovascular disease (29.2%) and lowest in patients with genetic renal disease (3.3%). Patients with admissions for gastrointestinal bleeding had more severe anaemia, but accounted for only the minority of cases overall. Administration of ESAs, iron infusions, and blood transfusions were all correlated with more severe degrees of anaemia. The number of hospital admissions, length of stay, and hospital costs were all strikingly higher with more severe degrees of anaemia. Adjusted hazard ratios (CI 95%) of patients with moderate and severe anaemia vs. no anaemia for subsequent CVE, KRT, and death without KRT were 1.7 (1.4-2.0), 2.0 (1.4-2.9), and 1.8 (1.5-2.3), respectively. Conclusion: Anaemia is associated with higher rates of CVE, progression to KRT and death in NDD- CKD patients, and with greater hospital utilisation and costs. Preventing and treating anaemia should improve clinical and economic outcomes.

Serum Creatinine and Tacrolimus Assessment With VAMS Finger-Prick Microsampling: A Diagnostic Test Study.

Rationale & Objective: Kidney transplant recipients require frequent venipunctures. Microsampling methods that use a finger-prick draw of capillary blood, like volumetric absorptive microsamplers (VAMS), have the potential to reduce the pain, inconvenience, and volume of blood loss associated with venipuncture. This study aimed to provide diagnostic accuracy using VAMS for measurement of tacrolimus and creatinine compared to gold standard venous blood in adult kidney transplant recipients. Study Design: Diagnostic test study. Prospective blood samples for measurement of tacrolimus and creatinine were collected using Mitra VAMS and venipuncture immediately before and 2 hours after tacrolimus dosing. Setting & Participants: A convenience sample of 40 adult kidney transplant participants in the outpatient setting. Tests Compared: Method comparison was assessed by Passing-Bablok regression and Bland-Altman analysis. The predictive performance of VAMS measurement compared to venipuncture was also assessed through estimation of the median prediction error and median absolute percentage prediction error. Results: A total of 74 tacrolimus samples and 70 creatinine samples were analyzed from 40 participants. Passing-Bablok regression showed a systematic difference between VAMS and venipuncture when measuring tacrolimus and creatinine with a slope of 1.08 (95% CI, 1.03-1.13) and a slope of 0.65 (95% CI, 0.6-0.7), respectively. These values were then corrected for the systematic difference. When used for Bland-Altman analysis, corrected values of tacrolimus and creatinine showed a bias of -0.1 µg/L and 0.04 mg/dL, respectively. Tacrolimus (corrected) and creatinine (corrected) microsampling values when compared to corresponding venipuncture values met median prediction error and median absolute percentage prediction error predefined acceptability limits of <15%. Limitations: This study was conducted in a controlled environment using a trained nurse to collect VAMS samples. Conclusions: In this study, VAMS was used to reliably measured tacrolimus and creatinine. This represents a clear opportunity for more frequent and less invasive sampling for patients.

Cellular milieu in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is globally the most prevalent renal cancer. The cells of origin in ccRCC have been identified as proximal tubular epithelial cells (PTEC); however, the transcriptomic pathways resulting in the transition from normal to malignant PTEC state have remained unclear. Immunotherapy targeting checkpoints have revolutionized the management of ccRCC, but a sustained clinical response is achieved in only a minority of ccRCC patients. This indicates that our understanding of the mechanisms involved in the malignant transition and resistance to immune checkpoint therapy in ccRCC is unclear. This review examines recent single-cell transcriptomics studies of ccRCC to clarify the transition of PTEC in ccRCC development, and the immune cell types, states, and interactions that may limit the response to targeted immune therapy, and finally suggests stromal cells as key drivers in recurrent and locally invasive ccRCC. These and future single-cell transcriptomics studies will continue to clarify the cellular milieu in the ccRCC microenvironment, thus defining actional clinical, therapeutic, and prognostic characteristics of ccRCC.

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.

Spatially Resolved Transcriptomes of Mammalian Kidneys Illustrate the Molecular Complexity and Interactions of Functional Nephron Segments.

Available transcriptomes of the mammalian kidney provide limited information on the spatial interplay between different functional nephron structures due to the required dissociation of tissue with traditional transcriptome-based methodologies. A deeper understanding of the complexity of functional nephron structures requires a non-dissociative transcriptomics approach, such as spatial transcriptomics sequencing (ST-seq). We hypothesize that the application of ST-seq in normal mammalian kidneys will give transcriptomic insights within and across species of physiology at the functional structure level and cellular communication at the cell level. Here, we applied ST-seq in six mice and four human kidneys that were histologically absent of any overt pathology. We defined the location of specific nephron structures in the captured ST-seq datasets using three lines of evidence: pathologist's annotation, marker gene expression, and integration with public single-cell and/or single-nucleus RNA-sequencing datasets. We compared the mouse and human cortical kidney regions. In the human ST-seq datasets, we further investigated the cellular communication within glomeruli and regions of proximal tubules-peritubular capillaries by screening for co-expression of ligand-receptor gene pairs. Gene expression signatures of distinct nephron structures and microvascular regions were spatially resolved within the mouse and human ST-seq datasets. We identified 7,370 differentially expressed genes (p adj < 0.05) distinguishing species, suggesting changes in energy production and metabolism in mouse cortical regions relative to human kidneys. Hundreds of potential ligand-receptor interactions were identified within glomeruli and regions of proximal tubules-peritubular capillaries, including known and novel interactions relevant to kidney physiology. Our application of ST-seq to normal human and murine kidneys confirms current knowledge and localization of transcripts within the kidney. Furthermore, the generated ST-seq datasets provide a valuable resource for the kidney community that can be used to inform future research into this complex organ.

The prevalence of Fabry disease in a statewide chronic kidney disease cohort - Outcomes of the aCQuiRE (Ckd.Qld fabRy Epidemiology) study.

BACKGROUND: Prevalence of Fabry disease amongst Chronic Kidney Disease (CKD) patients on haemodialysis has been shown to be approximately 0.2%. METHODS: We undertook a cross-sectional study employing a cascade screening strategy for Fabry Disease amongst 3000 adult, male and female patients affected by CKD stage 1-5D/T at public, specialty renal practices within participating Queensland Hospital and Health Services from October 2017 to August 2019. A multi-tiered FD screening strategy, utilising a combination of dried blood spot (DBS) enzymatic testing, and if low, then lyso-GB3 testing and DNA sequencing, was used. RESULTS: Mean (SD) age was 64.0 (15.8) years (n = 2992), and 57.9% were male. Eight participants withrew out of the 3000 who consented. Of 2992 screened, 6 (0.20%) received a diagnosis of FD, 2902 (96.99%) did not have FD, and 84 (2.81%) received inconclusive results. Of the patients diagnosed with FD, mean age was 48.5 years; 5 were male (0.29%) and 1 was female (0.08%); 4 were on kidney replacement therapy (2 dialysis and 2 transplant); 3 were new diagnoses. CONCLUSIONS: Estimated overall FD prevalence was 0.20%. Screening of the broader CKD population may be beneficial in identifying cases of FD. TRIAL REGISTRATION: The aCQuiRE Study has been prospectively registered with the Queensland Health Database of Research Activity (DORA, https://dora.health.qld.gov.au ) as pj09946 (Registered 3rd July 2017).

Promoting Plant-Based Therapies for Chronic Kidney Disease.

Chronic kidney disease (CKD) is debilitating, increasing in incidence worldwide, and a financial and social burden on health systems. Kidney failure, the final stage of CKD, is life-threatening if untreated with kidney replacement therapies. Current therapies using commercially-available drugs, such as angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers and calcium channel blockers, generally only delay the progression of CKD. This review article focuses on effective alternative therapies to improve the prevention and treatment of CKD, using plants or plant extracts. Three mechanistic processes that are well-documented in CKD pathogenesis are inflammation, fibrosis, and oxidative stress. Many plants and their extracts are already known to ameliorate kidney dysfunction through antioxidant action, with subsequent benefits on inflammation and fibrosis. In vitro and in vivo experiments using plant-based therapies for pre-clinical research demonstrate some robust therapeutic benefits. In the CKD clinic, combination treatments of plant extracts with conventional therapies that are seen as relatively successful currently may confer additive or synergistic renoprotective effects. Therefore, the aim of recent research is to identify, rigorously test pre-clinically and clinically, and avoid any toxic outcomes to obtain optimal therapeutic benefit from medicinal plants. This review may prove to be a filtering tool to researchers into complementary and alternative medicines to find out the current trends of using plant-based therapies for the treatment of kidney diseases, including CKD.

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.

Determining the association between the type of intervention for ischaemic heart disease and mortality and morbidity in patients with chronic kidney disease.

BACKGROUND: Association between chronic kidney disease (CKD) and ischaemic heart disease (IHD) is well known. Clinically, because of the use of intra-arterial contrast, coronary angiograms are sometimes not performed to avoid further deterioration in kidney function among CKD patients. AIMS: To identify whether intervention for non-ST elevation myocardial infarction (NSTEMI) is associated with increased mortality or further renal deterioration. METHODS: A retrospective observational cohort study involving 144 patients with a diagnosis of IHD in the CKD.QLD registry from May 2011 to August 2017, with a minimum of 2-years follow up, was undertaken. Patients were divided into two groups based on whether they obtained an interventional or medical management for NSTEMI. RESULTS: Fifty-nine patients had medically managed and 85 patients had intervention for IHD. Patients in the medically managed group were observed to be significantly older (median: 78 vs 69 years; P < 0.05) with worse baseline renal function (median: 31 vs 36 mL/min/1.73 m2 ; P <0.05) and higher serum urate level (median: 0.5 vs 0.4 mmol/L; P = 0.2). The interventional group had lower prevalence of diabetes, dyslipidaemia, cerebrovascular disease and peripheral vascular disease. Although this was not significant, Kaplan-Meier analysis revealed a significant decrease in mean survival of medically managed group compared with the interventional group. Furthermore, post adjustment for age and above comorbidities, the medically managed group and higher age were associated with significantly higher mortality. However, the patients in the medically managed and interventional groups had no significant difference in delta estimated glomerular filtration rate. CONCLUSIONS: In this observational study, intervention for IHD was associated with increased survival with no change in renal disease progression in comparison with medically managed patients.

Identification of factors associated with high-cost use of inpatient care in chronic kidney disease: a registry study.

OBJECTIVE: To explore factors behind inpatient admissions by high-cost users (HCUs) in pre-end-stage chronic kidney disease (CKD). DESIGN: Retrospective analysis of CKD.QLD Registry and hospital admissions of the Queensland Government Department of Health recorded between 1 July 2011 and 30 June 2016. SETTING: Queensland public and private hospitals. PARTICIPANTS: 5096 individuals with CKD who consented to the CKD.QLD Registry via 1 of 11 participating sites. MAIN OUTCOMES: Associations of HCU status with patient characteristics, pathways and diagnoses behind hospital admissions at 12 months. RESULTS: Age, advanced CKD, primary renal diagnosis, cardiovascular disease and hypertension were predictors of the high-cost outcome. HCUs were more likely than non-HCUs to be admitted by means of episode change (relative risk: 5.21; 95% CI 5.02 to 5.39), 30-day readmission (2.19; 2.13 to 2.25), scheduled readmission (1.29; 1.11 to 1.46) and emergency (1.07; 1.02 to 1.13), for diagnoses of the nervous (1.94; 1.74 to 2.15), circulatory (1.24; 1.14 to 1.34) and respiratory (1.2; 1.03 to 1.37) systems and other factors influencing health status (1.92; 1.74 to 2.09). CONCLUSIONS: The high relevance of episode change and other factors influencing health status revealed that a substantial part of excess demand for inpatient care was associated with discordant conditions often linked to frailty, decline in psychological health and social vulnerability. This suggests that multidisciplinary models of care that aim to manage discordant comorbidities and address psychosocial determinants of health, such as renal supportive care, may play an important role in reducing inpatient admissions in this population.

Heterogeneity in patterns of progression of chronic kidney disease.

BACKGROUND: Progression of kidney disease is a deceptively simple word for a complex bio-clinical process, evidenced by the number of definitions in the literature. This has led to confusion and differences in interpretation of studies. METHODS: We describe different patterns of progression, the performance of different definitions of progression and factors associated with chronic kidney disease (CKD) progression in a public renal service in Australia, in a study of patients enrolled in the CKD.QLD Registry with a minimum of 2 years' follow up. RESULTS: Nine patterns of changing estimated glomerular filtration rate (eGFR) over two consecutive 12-month periods were identified. Most common was a stable eGFR over 2 years (30%), and the least was a sustainable improvement of eGFR over both periods (2.1%). There was a lack of congruence between the several definitions of progression of CKD evaluated. More people progressed using the definition of decline of eGFR of >5 mL/min/1.73 m2 /year (year 1 = 30.2%, year 2 = 20.7%) and the least using development of end-stage renal disease (year 1 = 5.4%, year 2 = 9.9%). Age (40-59, ≥80 years), degree of proteinuria at baseline (nephrotic range) and CKD aetiology (renal vascular disease, diabetic nephropathy) were significantly associated with eGFR decline over 2 years. CONCLUSIONS: This is one of the first demonstrations of the great variations among and within individuals in the progression of CKD over even a period as short as 2 years. Findings suggest considerable potential for renal function recovery and stability while demonstrating the importance of using identical definitions for comparisons across datasets from different sources.

Bleeding Complications of Percutaneous Kidney Biopsy: Does Gender Matter?

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

Utilization and Costs of Health Care in a Kidney Supportive Care Program.

Kidney supportive care (KSC) is a patient-centered model of multidisciplinary care designed for patients with advanced chronic kidney disease (CKD) and end-stage kidney disease (ESKD). Our goal was to characterize the types, frequencies, and costs of services accessed by patients enrolled in a KSC program. We analyzed health care utilization data prospectively collected from 102 patients who enrolled in the KSC program during the first 52 weeks of its existence. The data comprised program appointments, emergency department presentations, ambulance service use, outpatient visits, inpatient episodes, and dialysis treatments made within the Brisbane area of Metro North. Costs of resource use were estimated using Queensland Health funding principles and guidelines. Analyses included descriptive statistics, correlations, and multivariate regressions. During the median program participation of 22 weeks, patients had 3975 contacts with health care, with the total value of services amounting to nearly A$3 million. Dialysis treatments accounted for 70% of visits and 49% of costs. Patients receiving dialysis had higher utilization of outpatient services and associated cost, compared to patients who were not dialyzed. The presence of diabetes and the choice of conservative pathway were both predictors of higher frequency and cost of services. Longer program participation was associated with lower weekly utilization and cost. The program attracted patients representing various characteristics, pathways, needs, and outcomes. Exploring these patterns will enable better understanding of the patient population and improved service planning, in KSC and similar programs that aim to comprehensively address the needs of patients with advanced CKD and ESKD.

Blood pressure management in hypertensive people with non-dialysis chronic kidney disease in Queensland, Australia.

BACKGROUND: High blood pressure is the most significant risk factor for the development and progression of chronic kidney disease (CKD). Lowering blood pressure is a goal to prevent CKD progression. This study of adults with CKD who have hypertension aimed to determine blood pressure control rates and the treatment patterns of hypertension and to explore factors associated with control of hypertension. METHODS: This cross-sectional study included all non-dialysis people with CKD stages 3A to 5 under nephrology care in three public renal clinics in Queensland, who joined the CKD.QLD registry from May 2011 to Dec 2015 and had a history of hypertension. Demographic information, other health conditions, laboratory markers and anti-hypertensive medications in use at consent were extracted from the registry. RESULTS: Among 1814 CKD people in these three sites in the registry who were age ≥ 18 years and had CKD stage 3A to 5, 1750 or 96% had a history of hypertension. Of these, the proportion with BP control to < 140/90 mmHg was 61.7% and to < 130/80 mmHg was 36.3%. With target BP < 140/90 mmHg or < 130/80 mmHg, participants aged ≥65 years were 1.23 (95% CI 1.06-1.42) or 1.12 (1.03-1.22) times more likely to have uncontrolled BP compared to those < 65 years old. Participants with severe albuminuria or proteinuria were 1.58 (1.32-1.87) or 1.28 (1.16-1.42, p < 0.001) more likely to have uncontrolled BP compared to those without significant albuminuria or proteinuria. Participants who had cardiovascular disease (CVD) were less likely to have uncontrolled BP compared to those without CVD (0.78, 0.69-0.89 or 0.86, 0.80-0.92). Factors associated with use of more classes of antihypertensive medicines among participants with uncontrolled BP (> 140/90 mmHg) were older age, diabetes, CVD, obesity and severe albuminuria/proteinuria (p < 0.05). Renin Angiotensin Aldosterone System inhibitors were the most frequently used medicines, regardless of the number of medicine classes an individual was prescribed. CONCLUSIONS: Blood pressure control rates in these hypertensive people with CKD was still far from optimal. People with CKD and hypertension aged 65 or older or with severe albuminuria or proteinuria, a group at risk of progression of kidney disease, have higher rates of uncontrolled BP.

BMI and its association with death and the initiation of renal replacement therapy (RRT) in a cohort of patients with chronic kidney disease (CKD).

BACKGROUND: A survival advantage associated with obesity has often been described in dialysis patients. The association of higher body mass index (BMI) with mortality and renal replacement therapy (RRT) in preterminal chronic kidney disease (CKD) patients has not been established. METHODS: Subjects were patients with pre-terminal CKD who were recruited to the CKD.QLD registry. BMI at time of consent was grouped as normal (BMI 18.5-24.9 kg/m2), overweight (BMI 25-29.9 kg/m2), mild obesity (BMI 30-34.9 kg/m2) and moderate obesity+ (BMI ≥ 35 kg/m2) as defined by WHO criteria. The associations of BMI categories with mortality and starting RRT were analysed. RESULTS: The cohort consisted of 3344 CKD patients, of whom 1777 were males (53.1%). The percentages who had normal BMI, or were overweight, mildly obese and moderately obese+ were 18.9, 29.9, 25.1 and 26.1%, respectively. Using people with normal BMI as the reference group, and after adjusting for age, socio-economic status, CKD stage, primary renal diagnoses, comorbidities including cancer, diabetes, peripheral vascular disease (PVD), chronic lung disease, coronary artery disease (CAD), and all other cardiovascular disease (CVD), the hazard ratios (HRs, 95% CI) of males for death without RRT were 0.65 (0.45-0.92, p = 0.016), 0.60 (0.40-0.90, p = 0.013), and 0.77 (0.50-1.19, p = 0.239) for the overweight, mildly obese and moderately obese+. With the same adjustments the hazard ratios for death without RRT in females were 0.96 (0.62-1.50, p = 0.864), 0.94 (0.59-1.49, p = 0.792) and 0.96 (0.60-1.53, p = 0.865) respectively. In males, with normal BMI as the reference group, the adjusted HRs of starting RRT were 1.15 (0.71-1.86, p = 0.579), 0.99 (0.59-1.66, p = 0.970), and 0.95 (0.56-1.61, p = 0.858) for the overweight, mildly obese and moderately obese+ groups, respectively, and in females they were 0.88 (0.44-1.76, p = 0.727), 0.94 (0.47-1.88, p = 0.862) and 0.65 (0.33-1.29, p = 0.219) respectively. CONCLUSIONS: More than 80% of these CKD patients were overweight or obese. Higher BMI seemed to be a significant "protective" factor against death without RRT in males but there was not a significant relationship in females. Higher BMI was not a risk factor for predicting RRT in either male or female patients with CKD.

Frequency and Consequences of Acute Kidney Injury in Patients With CKD: A Registry Study in Queensland Australia.

BACKGROUND: Acute kidney injury (AKI) contributes to and complicates chronic kidney disease (CKD). We describe AKI documented in hospital encounters in patients with CKD from the CKD Queensland registry. STUDY DESIGN: A retrospective cohort study during 2011 to 2016. SETTING & PARTICIPANTS: Participants had been admitted to a hospital in Queensland. PREDICTORS: AKI was identified from International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Australian Modification codes. OUTCOMES: All-cause mortality with or without kidney replacement therapy (KRT), start-up KRT and maintenance KRT, costs of care. ANALYTICAL APPROACH: Time to outcomes for those with versus without AKI was evaluated using Cox regression models. Mann-Whitney test was used to compare number of admissions, hospitalized days and costs by AKI status. RESULTS: Among 6,365 patients followed up for up to 5.4 years, 2,199 (35%) had 4,711 hospital encounters with an AKI diagnosis. Those with AKI were older (68 vs 64 years old), were more often men (36.7% vs 32.2%; P < 0.001), had more advanced CKD stages (stage 3b, 34%; stage 4, 35%; and stage 5, 10%), had more admissions (12 vs 5; P < 0.001), and stayed in the hospital longer (56 vs 14 days; P < 0.001) than those without AKI. Almost 90% of AKI admissions were through the emergency department. Of those with AKI, 554 (25%) subsequently died without any form of KRT and 285 (13%) started KRT, compared with 282 (6.8%) who died and 315 (7.6%) who started KRT among those without AKI; P < 0.001 for each. Adjusted for other significant factors, hazard ratios for all deaths or death without KRT were 2.95 (95% CI, 2.56-3.39; P < 0.001) and 3.02 (95% CI, 2.60-3.51; P < 0.001), respectively, in patients with AKI relative to those without AKI. The hazard ratio for all KRT was 1.40 (95% CI, 1.18-1.66; P < 0.001), and for maintenance KRT was 1.21 (95% CI, 0.98-1.48; P = 0.07). Mean total hospital cost in patients with AKI was more than triple that of patients with no AKI (A $93,042 vs A $30,778; P < 0.001). LIMITATIONS: These findings may not be generalizable to CKD populations from the general community or in other health care environments. CONCLUSIONS: AKI is associated with strikingly increased deaths, increased rates of KRT, and higher hospital costs.