Canagliflozin and iron metabolism in the CREDENCE trial.

BACKGROUND AND HYPOTHESIS: Studies in patients with heart failure have indicated that sodium-glucose cotransporter 2 (SGLT2) inhibitors increase iron use and enhance erythropoiesis. In this post-hoc analysis of the CREDENCE trial, we evaluated the effects of canagliflozin on iron metabolism in patients with chronic kidney disease (CKD) and whether the effects of canagliflozin on hemoglobin and cardiorenal outcomes were modified by iron deficiency. METHODS: We measured serum iron, total iron binding capacity (TIBC), transferrin saturation (TSAT) and ferritin at baseline and 12 months. The effects of canagliflozin, relative to placebo, on iron markers were assessed with analysis of covariance. Interactions between baseline iron deficiency, defined as TSAT < 20%, and the effects of canagliflozin on hemoglobin and cardiorenal outcomes were evaluated with mixed effect models and Cox regression models, respectively. RESULTS: Of 4401 participants randomized in CREDENCE, 2416 (54.9%) had iron markers measured at baseline, of whom 924 (38.2%) were iron deficient. Canagliflozin, compared to placebo, increased TIBC by 2.1% (95%CI 0.4-3.8; p = 0.014) and decreased ferritin by 11.5% (95%CI 7.1-15.7; p < 0.001) with no clear effect on serum iron or TSAT. Canagliflozin increased hemoglobin over the trial duration by 7.3 g/L (95% CI 6.2-8.5; p < 0.001) and 6.7 g/L (95% CI 5.2- 8.2; p < 0.001) in patients with and without iron deficiency, respectively (p-interaction = 0.38). The relative effect of canagliflozin on the primary outcome of doubling of serum creatinine, kidney failure or death due to cardiovascular disease or kidney failure (HR 0.70, 95%CI 0.56-0.87) was consistent regardless of iron deficiency (p-interaction 0.83), as were effects on other cardiovascular and mortality outcomes (all p-interactions ≥ 0.10). CONCLUSIONS: Iron deficiency is highly prevalent in patients with type 2 diabetes and CKD. Canagliflozin increased TIBC and decreased ferritin in patients with T2D and CKD, suggesting increased iron utilization, and improved hemoglobin levels and clinical outcomes regardless of iron deficiency.

Sacubitril/Valsartan in Patients With Heart Failure and Deterioration in eGFR to <30 mL/min/1.73 m2.

BACKGROUND: Sacubitril/valsartan is a foundational therapy for patients with heart failure. Although current U.S. Food and Drug Administration labeling does not provide guidance regarding initiation or continuation of sacubitril/valsartan in patients with worsening kidney function, guidelines identify estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 as a contraindication to therapy. OBJECTIVES: This study aims to assess the safety and efficacy of continuing sacubitril/valsartan in patients with deterioration of kidney function below an eGFR of 30 mL/min/1.73 m2. METHODS: The association between a deterioration in eGFR <30 mL/min/1.73 m2, efficacy and safety outcomes, and treatment with sacubitril/valsartan vs renin-angiotensin system inhibitor were evaluated using time updated Cox models in a post hoc parallel trial analyses of PARADIGM-HF and PARAGON-HF. RESULTS: Among 8,346 randomized patients in PARADIGM-HF and 4,746 in PARAGON-HF, 691 (8.3%) and 613 (12.9%), respectively, had an eGFR <30 mL/min/1.73 m2 at least once in follow-up. Patients experiencing such deterioration were at higher risk of the primary outcome in both PARADIGM-HF and PARAGON-HF. However, the incidence of the primary outcome remained lower with sacubitril/valsartan vs renin-angiotensin system inhibitor, regardless of deterioration in kidney function in both PARADIGM-HF (Pinteraction = 0.50) and PARAGON-HF (Pinteraction = 0.64). Rates of key safety outcomes were higher among patients experiencing eGFR deterioration; however, rates were similar between treatment groups including among those who remained on treatment. CONCLUSIONS: Patients experiencing deterioration of kidney function to a value below eGFR 30 mL/min/1.73 m2 faced high risk of cardiovascular and kidney disease outcomes. Continuation of sacubitril/valsartan was associated with persistent clinical benefit and no incremental safety risk. These data support continuation of sacubitril/valsartan for heart failure treatment even when eGFR declines below this threshold (PARADIGM-HF [Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure], NCT01035255; and PARAGON-HF [Prospective Comparison of ARNI with ARB Global Outcomes in HF with Preserved Ejection Fraction], NCT01920711).

Design and baseline characteristics of the Finerenone, in addition to standard of care, on the progression of kidney disease in patients with Non-Diabetic Chronic Kidney Disease (FIND-CKD) randomized trial.

BACKGROUND AND HYPOTHESIS: Finerenone, a non-steroidal mineralocorticoid receptor antagonist, improved kidney, and cardiovascular outcomes in patients with CKD and T2D in two Phase 3 outcome trials. The FIND-CKD study investigates the effect of finerenone in adults with CKD without diabetes. METHODS: FIND-CKD (NCT05047263 and EU CT 2023-506897-11-00) is a randomized, double-blind, placebo-controlled Phase 3 trial in patients with CKD of non-diabetic aetiology. Adults with a urinary albumin-creatinine ratio (UACR) of ≥ 200 to ≤3500 mg/g and eGFR ≥ 25 to <90 mL/min/1.73 m2 receiving a maximum tolerated dose of a renin-angiotensin-system (RAS) inhibitor were randomized 1:1 to once daily placebo or finerenone 10 or 20 mg depending on eGFR above or below 60 mL/min/1.73 m2. The primary efficacy outcome is total eGFR slope, defined as the mean annual rate of change in eGFR from baseline to Month 32. Secondary efficacy outcomes include a combined cardiorenal composite outcome comprising time to kidney failure, sustained ≥57% decrease in eGFR, hospitalization for heart failure, or cardiovascular death, as well as separate kidney and cardiovascular composite outcomes. Adverse events are recorded to assess tolerability and safety. RESULTS: Across 24 countries, 3231 patients were screened and 1584 were randomized to study treatment. The most common causes of CKD were chronic glomerulonephritis (57.0%) and hypertensive/ischaemic nephropathy (29.0%). Immunoglobulin A nephropathy was the most common glomerulonephritis (26.3% of the total population). At baseline, mean eGFR and median UACR were 46.7 mL/min/1.73 m2 and 818.9 mg/g, respectively. Diuretics were used by 282 participants (17.8%), statins by 851 (53.7%), and calcium channel blockers by 794 (50.1%). SGLT2 inhibitors were used in 16.9% of patients; these individuals had a similar mean eGFR (45.6 vs 46.8 mL/min/1.73 m2) and slightly higher median UACR (871.9 vs 808.3 mg/g) compared to those not using SGLT2 inhibitors at baseline. CONCLUSIONS: FIND-CKD is the first Phase 3 trial of finerenone in patients with CKD of non-diabetic aetiology.

Treatment effect of canagliflozin for patients on therapy for heart failure: Pooled analysis of the CANVAS program and CREDENCE trial.

BACKGROUND: Canagliflozin is a sodium-glucose cotransporter 2 inhibitor that has been shown to reduce cardiovascular events in diabetic patients with and without heart failure (HF). Whether the clinical benefits and safety profile of canagliflozin are different in those on a beta blocker and an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (BB + RAASi) is unknown. METHODS: We pooled participants with HF at baseline from the CANVAS Program and CREDENCE trial and assessed major adverse cardiovascular events and its components; hospitalization for heart failure (HHF); HHF or CV death; all-cause mortality; a renal composite; and a combined renal and CV composite. RESULTS: Of 14,543 participants, 2113 had HF at baseline, and 1280 were on BB + RAASi. In those with a history of HF, participants on BB + RAASi therapy were more likely to have coronary atherosclerotic disease (82 vs 72%, p < 0.001), history of myocardial infarction (42 vs 29%, p < 0.001), higher mean body mass index (34 vs 32 kg/m2, p < 0.001), and lower mean estimated glomerular filtration rate (67 vs 70 mL/min/1.73 m2, p < 0.01). They were also more likely to be on insulin, a statin, antithrombotic agent, and a diuretic (all p < 0.001). In unadjusted analysis and when adjusted for selected baseline factors, there was no heterogeneity in canagliflozin treatment effect except for HHF/CV death in those on baseline BB + RAASi vs. those not on baseline BB + RAASi (Pheterogeneity = 0.02). CONCLUSION: Canagliflozin mostly improved CV and kidney outcomes in participants with a history of HF irrespective of use of BB + RAASi at baseline, with possible greater benefit on HHF/CV death in participants on BB + RAASi.

Effects of dapagliflozin and dapagliflozin-saxagliptin on erythropoiesis, iron and inflammation markers in patients with type 2 diabetes and chronic kidney disease: data from the DELIGHT trial.

BACKGROUND: This post-hoc analysis of the DELIGHT trial assessed effects of the SGLT2 inhibitor dapagliflozin on iron metabolism and markers of inflammation. METHODS: Patients with type 2 diabetes and albuminuria were randomized to dapagliflozin, dapagliflozin and saxagliptin, or placebo. We measured hemoglobin, iron markers (serum iron, transferrin saturation, and ferritin), plasma erythropoietin, and inflammatory markers (urinary MCP-1 and urinary/serum IL-6) at baseline and week 24. RESULTS: 360/461 (78.1%) participants had available biosamples. Dapagliflozin and dapagliflozin-saxagliptin, compared to placebo, increased hemoglobin by 5.7 g/L (95%CI 4.0, 7.3; p < 0.001) and 4.4 g/L (2.7, 6.0; p < 0.001) and reduced ferritin by 18.6% (8.7, 27.5; p < 0.001) and 18.4% (8.7, 27.1; p < 0.001), respectively. Dapagliflozin reduced urinary MCP-1/Cr by 29.0% (14.6, 41.0; p < 0.001) and urinary IL-6/Cr by 26.6% (9.1, 40.7; p = 0.005) with no changes in other markers. CONCLUSIONS: Dapagliflozin increased hemoglobin and reduced ferritin and urinary markers of inflammation, suggesting potentially important effects on iron metabolism and inflammation. TRIAL REGISTRATION: ClinicalTrials.gov NCT02547935.

Interleukin-6 and Cardiovascular and Kidney Outcomes in Patients With Type 2 Diabetes: New Insights From CANVAS.

OBJECTIVE: The inflammatory cytokine interleukin-6 (IL-6) is associated with cardiovascular (CV) and kidney outcomes in various populations. However, data in patients with type 2 diabetes are limited. We assessed the association of IL-6 with CV and kidney outcomes in the Canagliflozin Cardiovascular Assessment Study (CANVAS) and determined the effect of canagliflozin on IL-6. RESEARCH DESIGN AND METHODS: Patients with type 2 diabetes at high CV risk were randomly assigned to canagliflozin or placebo. Plasma IL-6 was measured at baseline and years 1, 3, and 6. The composite CV outcome was nonfatal myocardial infarction, nonfatal stroke, or CV death; the composite kidney outcome was sustained ≥40% estimated glomerular filtration rate decline, end-stage kidney disease, or kidney-related death. Multivariable-adjusted Cox proportional hazards regression was used to estimate the associations between IL-6 and the outcomes. The effect of canagliflozin on IL-6 over time was assessed with a repeated-measures mixed-effects model. RESULTS: The geometric mean IL-6 at baseline, available in 3,503 (80.2%) participants, was 1.7 pg/mL. Each doubling of baseline IL-6 was associated with 14% (95% CI 4, 24) and 21% (95% CI 1, 45) increased risk of CV and kidney outcomes, respectively. Over 6 years, IL-6 increased by 5.8% (95% CI 3.4, 8.3) in the placebo group. Canagliflozin modestly attenuated the IL-6 increase (absolute percentage difference vs. placebo 4.4% [95% CI 1.3, 9.9; P = 0.01]). At year 1, each 25% lower level of IL-6 compared with baseline was associated with 7% (95% CI 1, 22) and 14% (95% CI 5, 22) lower risks for the CV and kidney outcome, respectively. CONCLUSIONS: In patients with type 2 diabetes at high CV risk, baseline IL-6 and its 1-year change were associated with CV and kidney outcomes. The effect of IL-6-lowering therapy on CV, kidney, and safety outcomes remains to be tested.

Effects of steroidal mineralocorticoid receptor antagonists on acute and chronic estimated glomerular filtration rate slopes in patients with chronic heart failure.

AIMS: Steroidal mineralocorticoid receptor antagonists (MRAs) form a cornerstone of the management of heart failure (HF), but little is known about the long-term effects of MRA therapy on kidney function. We evaluated acute and chronic estimated glomerular function (eGFR) slopes in the two largest completed trials testing steroidal MRAs in chronic HF. METHODS AND RESULTS: We conducted parallel post hoc eGFR slope analyses in two multinational, double-blind randomized, placebo-controlled trials of steroidal MRAs in chronic HF with reduced ejection fraction (EMPHASIS-HF) and preserved ejection fraction (TOPCAT Americas region). GFR was estimated using the Chronic Kidney Disease Epidemiology Collaboration equation. Annual slopes of eGFR were assessed by generalized random coefficient models. Least square mean differences in eGFR slopes between steroidal MRA and placebo arms were assessed. Median follow-up was 1.8 years (EMPHASIS-HF) and 3.3 years (TOPCAT Americas). From baseline to month 4-6 ('acute eGFR slope'), compared to placebo, MRA treatment led to an acute decline in eGFR of -2.4 ml/min/1.73 m2 (95% confidence interval [CI] -3.4 to -1.4; p < 0.001) and -2.0 ml/min/1.73 m2 (95% CI -3.0 to -1.8; p < 0.001) in EMPHASIS-HF and TOPCAT Americas, respectively. From month 4-6 to end of study, there was no difference in 'chronic eGFR slope' between MRA and placebo arms (-0.3 ml/min/1.73 m2 /year [95% CI -1.3 to 0.7; p = 0.53] and 0.1 ml/min/1.73 m2 /year [95% CI -1.4 to 1.7; p = 0.86]) in EMPHASIS-HF and TOPCAT Americas, respectively. CONCLUSIONS: Steroidal MRAs result in acute declines in eGFR but do not modify long-term kidney disease trajectories in chronic HF with reduced or preserved ejection fraction. CLINICAL TRIAL REGISTRATION: EMPHASIS-HF (ClinicalTrials.gov NCT00232180) and TOPCAT (ClinicalTrials.gov NCT00094302).

Risk factors for incident kidney disease in older adults: an Australian prospective population-based study.

BACKGROUND AND AIM: To determine risk factors for incident chronic kidney disease (CKD) in a large population-based cohort. METHODS: This prospective opt-in population-based cohort study is based on the 45 and Up Study, where New South Wales residents aged ≥45 years were randomly sampled from the Services Australia database and agreed to complete the 45 and Up Study baseline questionnaire and have their responses linked to their health data in routinely collected databases. The primary outcome was the development of incident CKD, defined as eGFR < 60 mL/min/1.73 m2 . CKD incidence was calculated using Poisson regression. Risk factors for incident CKD were assessed using Cox regression in multivariable models. RESULTS: In 39 574 participants who did not have CKD at enrolment, independent factors associated with developing CKD included: older age, regional residence (HR 1.38 (1.27-1.50) for outer regional vs major city), smoking (1.13 (1.00-1.27) for current smoker vs non-smoker), obesity (1.25 (1.16-1.35) for obese vs normal body mass index), diabetes mellitus (1.41 (1.33-1.50)), hypertension (1.53 (1.44-1.62)), coronary heart disease (1.13 (1.07-1.20)), depression/anxiety (1.16 (1.09-1.24)) and cancer (1.29 (1.20-1.39)). Migrants were less likely to develop CKD compared with people born in Australia (0.88 (0.83-0.94)). Gender, partner status and socioeconomic factors were not independently associated with developing CKD. CONCLUSIONS: This large population-based study found multiple modifiable and non-modifiable factors were independently associated with developing CKD. In the Australian setting, the risk of CKD was higher with regional residence. Differences according to socioeconomic status were predominantly explained by age, comorbidities and harmful health-related behaviours.

Association between TNF Receptors and KIM-1 with Kidney Outcomes in Early-Stage Diabetic Kidney Disease.

BACKGROUND AND OBJECTIVES: Clinical trials in nephrology are enriched for patients with micro- or macroalbuminuria to enroll patients at risk of kidney failure. However, patients with normoalbuminuria can also progress to kidney failure. TNF receptor-1, TNF receptor-2, and kidney injury marker-1 (KIM-1) are known to be associated with kidney disease progression in patients with micro- or macroalbuminuria. We assessed the value of TNF receptor-1, TNF receptor-2, and KIM-1 as prognostic biomarkers for CKD progression in patients with type 2 diabetes and normoalbuminuria. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: TNF receptor-1, TNF receptor-2, and KIM-1 were measured using immunoassays in plasma samples from patients with type 2 diabetes at high cardiovascular risk participating in the Canagliflozin Cardiovascular Assessment Study trial. We used multivariable adjusted Cox proportional hazards analyses to estimate hazard ratios per doubling of each biomarker for the kidney outcome, stratified the population by the fourth quartile of each biomarker distribution, and assessed the number of events and event rates. RESULTS: In patients with normoalbuminuria (n=2553), 51 kidney outcomes were recorded during a median follow-up of 6.1 (interquartile range, 5.8-6.4) years (event rate, 3.5; 95% confidence interval, 2.6 to 4.6 per 1000 patient-years). Each doubling of baseline TNF receptor-1 (hazard ratio, 4.2; 95% confidence interval, 1.8 to 9.6) and TNF receptor-2 (hazard ratio, 2.3; 95% confidence interval, 1.5 to 3.6) was associated with a higher risk for the kidney outcome. Baseline KIM-1, urinary albumin-creatinine ratio, and eGFR were not associated with kidney outcomes. The event rates in the highest quartile of TNF receptor-1 (≥2992 ng/ml) and TNF receptor-2 (≥11,394 ng/ml) were 5.6 and 7.0 events per 1000 patient-years, respectively, compared with 2.8 and 2.3, respectively, in the lower three quartiles. CONCLUSIONS: TNF receptor-1 and TNF receptor-2 are associated with kidney outcomes in patients with type 2 diabetes and normoalbuminuria. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: CANagliflozin cardioVascular Assessment Study (CANVAS), NCT01032629.

Effects of the SGLT2 inhibitor canagliflozin on plasma biomarkers TNFR-1, TNFR-2 and KIM-1 in the CANVAS trial.

AIMS/HYPOTHESIS: Higher plasma concentrations of tumour necrosis factor receptor (TNFR)-1, TNFR-2 and kidney injury molecule-1 (KIM-1) have been found to be associated with higher risk of kidney failure in individuals with type 2 diabetes in previous studies. Whether drugs can reduce these biomarkers is not well established. We measured these biomarkers in samples of the CANVAS study and examined the effect of the sodium-glucose cotransporter 2 inhibitor canagliflozin on these biomarkers and assessed whether the early change in these biomarkers predict cardiovascular and kidney outcomes in individuals with type 2 diabetes in the CANagliflozin cardioVascular Assessment Study (CANVAS). METHODS: Biomarkers were measured with immunoassays (proprietary multiplex assay performed by RenalytixAI, New York, NY, USA) at baseline and years 1, 3 and 6. Mixed-effects models for repeated measures assessed the effect of canagliflozin vs placebo on the biomarkers. Associations of baseline levels and the early change (baseline to year 1) for each biomarker with the kidney outcome were assessed using multivariable-adjusted Cox regression. RESULTS: In total, 3523/4330 (81.4%) of the CANVAS participants had available samples at baseline. Each doubling in baseline TNFR-1, TNFR-2 and KIM-1 was associated with a higher risk of kidney outcomes, with corresponding HRs of 3.7 (95% CI 2.3, 6.1; p < 0.01), 2.7 (95% CI 2.0, 3.6; p < 0.01) and 1.5 (95% CI 1.2, 1.8; p < 0.01), respectively. Canagliflozin reduced the level of the plasma biomarkers with differences in TNFR-1, TNFR-2 and KIM-1 between canagliflozin and placebo during follow-up of 2.8% (95% CI 3.4%, 1.3%; p < 0.01), 1.9% (95% CI 3.5%, 0.2%; p = 0.03) and 26.7% (95% CI 30.7%, 22.7%; p < 0.01), respectively. Within the canagliflozin treatment group, each 10% reduction in TNFR-1 and TNFR-2 at year 1 was associated with a lower risk of the kidney outcome (HR 0.8 [95% CI 0.7, 1.0; p = 0.02] and 0.9 [95% CI 0.9, 1.0; p < 0.01] respectively), independent of other patient characteristics. The baseline and 1 year change in biomarkers did not associate with cardiovascular or heart failure outcomes. CONCLUSIONS/INTERPRETATION: Canagliflozin decreased KIM-1 and modestly reduced TNFR-1 and TNFR-2 compared with placebo in individuals with type 2 diabetes in CANVAS. Early decreases in TNFR-1 and TNFR-2 during canagliflozin treatment were independently associated with a lower risk of kidney disease progression, suggesting that TNFR-1 and TNFR-2 have the potential to be pharmacodynamic markers of response to canagliflozin.

Chronic kidney disease.

Chronic kidney disease is a progressive disease with no cure and high morbidity and mortality that occurs commonly in the general adult population, especially in people with diabetes and hypertension. Preservation of kidney function can improve outcomes and can be achieved through non-pharmacological strategies (eg, dietary and lifestyle adjustments) and chronic kidney disease-targeted and kidney disease-specific pharmacological interventions. A plant-dominant, low-protein, and low-salt diet might help to mitigate glomerular hyperfiltration and preserve renal function for longer, possibly while also leading to favourable alterations in acid-base homoeostasis and in the gut microbiome. Pharmacotherapies that alter intrarenal haemodynamics (eg, renin-angiotensin-aldosterone pathway modulators and SGLT2 [SLC5A2] inhibitors) can preserve kidney function by reducing intraglomerular pressure independently of blood pressure and glucose control, whereas other novel agents (eg, non-steroidal mineralocorticoid receptor antagonists) might protect the kidney through anti-inflammatory or antifibrotic mechanisms. Some glomerular and cystic kidney diseases might benefit from disease-specific therapies. Managing chronic kidney disease-associated cardiovascular risk, minimising the risk of infection, and preventing acute kidney injury are crucial interventions for these patients, given the high burden of complications, associated morbidity and mortality, and the role of non-conventional risk factors in chronic kidney disease. When renal replacement therapy becomes inevitable, an incremental transition to dialysis can be considered and has been proposed to possibly preserve residual kidney function longer. There are similarities and distinctions between kidney-preserving care and supportive care. Additional studies of dietary and pharmacological interventions and development of innovative strategies are necessary to ensure optimal kidney-preserving care and to achieve greater longevity and better health-related quality of life for these patients.

Incidence and Associations of Chronic Kidney Disease in Community Participants With Diabetes: A 5-Year Prospective Analysis of the EXTEND45 Study.

OBJECTIVE: To determine the incidence of and factors associated with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 in people with diabetes. RESEARCH DESIGN AND METHODS: We identified people with diabetes in the EXamining ouTcomEs in chroNic Disease in the 45 and Up Study (EXTEND45), a population-based cohort study (2006-2014) that linked the Sax Institute's 45 and Up Study cohort to community laboratory and administrative data in New South Wales, Australia. The study outcome was the first eGFR measurement <60 mL/min/1.73 m2 recorded during the follow-up period. Participants with eGFR < 60 mL/min/1.73 m2 at baseline were excluded. We used Poisson regression to estimate the incidence of eGFR <60 mL/min/1.73 m2 and multivariable Cox regression to examine factors associated with the study outcome. RESULTS: Of 9,313 participants with diabetes, 2,106 (22.6%) developed incident eGFR <60 mL/min/1.73 m2 over a median follow-up time of 5.7 years (interquartile range, 3.0-5.9 years). The eGFR <60 mL/min/1.73 m2 incidence rate per 100 person-years was 6.0 (95% CI 5.7-6.3) overall, 1.5 (1.3-1.9) in participants aged 45-54 years, 3.7 (3.4-4.0) for 55-64 year olds, 7.6 (7.1-8.1) for 65-74 year olds, 15.0 (13.0-16.0) for 75-84 year olds, and 26.0 (22.0-32.0) for those aged 85 years and over. In a fully adjusted multivariable model incidence was independently associated with age (hazard ratio 1.23 per 5-year increase; 95% CI 1.19-1.26), geography (outer regional and remote versus major city: 1.36; 1.17-1.58), obesity (obese class III versus normal: 1.44; 1.16-1.80), and the presence of hypertension (1.52; 1.33-1.73), coronary heart disease (1.13; 1.02-1.24), cancer (1.30; 1.14-1.50), and depression/anxiety (1.14; 1.01-1.27). CONCLUSIONS: In participants with diabetes, the incidence of an eGFR <60 mL/min/1.73 m2 was high. Older age, remoteness of residence, and the presence of various comorbid conditions were associated with higher incidence.

Lupus nephritis in Indigenous Australians: a single-centre study.

BACKGROUND: The incidence, presentation and outcomes of lupus nephritis (LN) vary with geography, ethnicity, socioeconomic status and gender. There are relatively few data on LN in the non-Caucasian populations in Australia. AIMS: To describe the clinical presentation, histological features, natural history, and outcomes of a historical cohort of Aboriginal and Torres Strait Islanders people in Far North Queensland with biopsy-proven LN. METHODS: This is a retrospective observational study, and the study was conducted in Cairns and Hinterland Hospital and Health Service, Queensland, Australia. The study included Aboriginal and Torres Strait Islander patients with biopsy-proven LN treated between 1990 and 2013. The main outcome measures were renal replacement therapy and overall patient survival. RESULTS: Aboriginal and Torres Strait Islander people represented a substantial proportion (n = 16/40, 40%) of all patients diagnosed with LN during the observation period. The frequency of nephrotic range proteinuria (n = 11/14, 78.5%), estimated glomerular filtration rate <60 mL/min/1.73 m2 (n = 6/14, 42.8%) and proliferative LN (n = 13/16, 81.25%) was high at the time of presentation. Despite use of multiple immunosuppressive agents, the overall rate of remission was poor (n = 4/14, 28.5%) and incidence of end-stage kidney disease (n = 4/14, 28.5%) and death (n = 5/16, 31.25%) was high. CONCLUSIONS: The clinical presentation of LN in Aboriginal and Torres Strait Islanders in Far North Queensland is severe and the response to standard immunosuppressive therapy is unsatisfactory. Larger prospective multi-centre studies are required to better understand ethnic disparities in prognosis and response to immunosuppressive therapy in this specific population.

Clinical presentation, treatment and outcome of focal segmental glomerulosclerosis in Far North Queensland Australian adults.

AIM: The aim is to describe the clinical features, treatment and outcomes in Australian adults with focal segmental glomerulosclerosis and identify predictors of disease progression and all-cause mortality. METHODS: The study included all patients with biopsy confirmed focal segmental glomerulosclerosis between January 1997 and June 2014 at participating hospitals. Clinical factors, histopathological findings, biochemical markers and treatments were analysed and potential predictors of doubling serum creatinine, end stage kidney disease or death identified. RESULTS: A total of 98 patients were included with a median follow up of 4.3 years. Thirty-four (35%) patients were Aboriginal or Torres Strait Islander. Focal segmental glomerulosclerosis not-otherwise-specified was the most common variant. Seventeen (59%) patients initially treated with immunosuppression experienced an improvement in renal function. At the end of follow up, 43 (44%) patients had progressed to the composite outcome. Baseline tubulointerstitial scarring and lower haemoglobin predicted shorter time to doubling serum creatinine. Dual diagnosis, higher serum creatinine, lower estimated glomerular filtration rate and doubling creatinine were associated with shorter time to end stage kidney disease with remission the only protective factor. Age was the only variable associated with all-cause mortality. CONCLUSION: Focal segmental glomerulosclerosis holds serious implications for patients. Concomitant diabetic nephropathy, higher serum creatinine and lower estimated glomerular filtration rate at renal biopsy were associated with poorer renal prognosis. Indigenous people had a female predominance and are over-represented in relation to their population size, however, were not associated with poorer prognosis. Remission was the only modifiable variable and thus should be at the forefront of patient management goals and future studies.

Neutrophil-lymphocyte ratio predicts cardiovascular and all-cause mortality in hemodialysis patients.

Neutrophil-lymphocyte ratio (NLR) is a marker of systemic inflammation that has been shown to predict mortality in patients with malignancies, ischemic heart disease and peripheral vascular disease. Its prognostic value in hemodialysis patients is unclear. The aims of this study were to: (i) explore the relationship between NLR and other biochemical parameters and (ii) to examine the value of NLR as a predictor of cardiovascular and all-cause mortality in hemodialysis patients. The study included all the incident hemodialysis patients from a single center between 2007 and 2012. NLR was calculated using samples obtained 3 months after commencing hemodialysis. One hundred seventy hemodialysis patients were included with a median follow-up of 37 months. There were 54 deaths (32%). NLR was positively correlated with C-reactive protein (r = 0.24, p = 0.0023) and negatively correlated with hemoglobin (r = -0.27, p = 0.00048), albumin (r = -0.23, p = 0.0034) and total cholesterol (r = -0.17, p = 0.049) levels. In multivariate Cox regression, NLR was independently associated with both all-cause mortality (adjusted hazard ratio [HR] 1.4; 95% confidence interval [CI], 1.2-1.6; p ≤ 0.0001) and cardiovascular death (HR 1.3, 95% CI 1.1-1.6, p = 0.0032). Other predictors of all-cause mortality were age (HR 1.6 per decade; 95% CI, 1.2-2.1; p = 0.0017), body mass index (HR 0.93; 95% CI, 0.88-0.98; p = 0.0047), albumin (HR 0.91; 95% CI, 0.86-0.97; p = 0.0035) and peripheral vascular disease (HR 2.7; 95% CI, 1.4-5.1; p = 0.0023). NLR is a practical, cost-efficient and easy to use predictor of cardiovascular and all-cause mortality in incident hemodialysis patients.

Solitary jejunal metastasis from renal cell carcinoma presenting as small bowel obstruction 19 years after nephrectomy.

Metachronous metastatic disease may develop in up to 50% of patients with renal cell carcinoma (RCC) who have undergone a presumably curative radical nephrectomy. We describe a case of small bowel obstruction secondary to a solitary jejunal RCC metastasis affecting a 66-year-old man with a history of RCC, which was treated 19 years earlier by right radical nephrectomy. The patient underwent successful laparotomy and wide margin resection of the affected small bowel with end-to-end anastomosis. A subsequent staging CT revealed no other metastases. To our knowledge, only eight cases of isolated small bowel metastasis from RCC have been reported. Of these, only one previous report referred to a longer time interval to small bowel metastasis than our case. The case highlights that isolated bowel metastasis should be considered as a possible aetiology of small bowel obstruction, even in patients with a distant history of presumably curative cancer treatment.