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Background The impact of contrast-induced acute kidney injury (CI-AKI) on long-term major adverse cardiovascular events (MACE) remains controversial. Method This was a retrospective cohort study from 14 hospitals under the Hospital Authority of Hong Kong between 2004 and 2017. Severe CI-AKI was defined as an increase in serum creatinine of >50% from the baseline value, an absolute increase of >1 mg/dL (88 μmol/L) or requiring dialysis after percutaneous coronary intervention (PCI). Mild CI-AKI was defined as an increase in serum creatinine of >25% from the baseline value or an absolute increase of >0.5 mg/dL (44 μmol/L) after PCI but not fulfilling the criteria for severe CI-AKI. The primary endpoint was MACE, defined as a composite outcome of all-cause mortality, non-fatal myocardial infarction after hospital discharge, stroke or any unplanned coronary revascularization, in a time-to-first-event analysis up to 5 years after PCI. The secondary endpoints were individual components of MACE and cardiovascular mortality. Results A total of 34 576 patients were analysed. After adjustment for cardiovascular risk factors, procedural characteristics and medication use, the risk of MACE at 5 years was significantly higher with mild CI-AKI {hazard ratio [HR], 1.18 [95% confidence interval (CI) 1.12–1.26); P Conclusions Among patients undergoing a first-ever PCI, CI-AKI of any severity was associated with a higher adjusted risk of MACE at 5 years. Severe CI-AKI has a stronger association with MACE and its individual components, with an excess of early and late events.

Background Health claims data may be an efficient and easily accessible source to study chronic kidney disease (CKD) prevalence in a nationwide population. Our aim was to study Dutch claims data for their ability to identify CKD patients in different subgroups. Methods From a laboratory database, we selected 24 895 adults with at least one creatinine measurement in 2014 ordered at an outpatient clinic. Of these, 15 805 had ≥2 creatinine measurements at least 3 months apart and could be assessed for the chronicity criterion. We estimated the validity of a claim-based diagnosis of CKD and advanced CKD. The estimated glomerular filtration rate (eGFR)-based definitions for CKD (eGFR Results In general, sensitivity of claims data was highest in the population with the chronicity criterion as reference group. Sensitivity was higher in advanced CKD patients than in CKD patients {51% [95% confidence interval (CI) 47–56%] versus 27% [95% CI 25–28%]}. Furthermore, sensitivity was higher in young versus elderly patients. In patients with advanced CKD, sensitivity was 72% (95% CI 62–83%) for patients aged 20–59 years and 43% (95% CI 38–49%) in patients ≥75 years. The specificity of CKD and advanced CKD was ≥99%. Positive predictive values ranged from 72% to 99% and negative predictive values ranged from 40% to 100%. Conclusion When using health claims data for the estimation of CKD prevalence, it is important to take into account the characteristics of the population at hand. The younger the subjects and the more advanced the stage of CKD the higher the sensitivity of such data. Understanding which patients are selected using health claims data is crucial for a correct interpretation of study results.

Background The diagnostic status of chronic kidney disease (CKD) and its underlying reasons provide evidence that can improve CKD management. However, the situation in developing countries remains under-investigated. Methods Adults with electronic health records (EHRs; 2008–19) in Yinzhou, China were included. The gold standard for CKD was defined as having persistently reduced estimated glomerular filtration rate (eGFR), albuminuria/proteinuria, haematuria or a history of CKD. CKD stages (G1–G5) were defined by eGFR. Clinical diagnosis of CKD in the real world setting was evaluated using International Classification of Diseases (ICD)-10 codes related to primary cause or stages of CKD. The specialty of doctors who administered the serum creatinine (SCr) tests and who made the primary-cause/CKD-staging diagnoses was analysed. The accuracy of CKD-staging codes was assessed. Results Altogether, 85 519 CKD patients were identified from 976 409 individuals with EHRs. Of them, 10 287 (12.0%) having persistent urinary abnormalities or labelled with CKD-related ICD codes did not receive SCr tests within 12 months before or after the urine tests. Among 75 147 patients who received SCr tests, 46 150 (61.4%) missed any CKD-related codes, 6857 (35.7%) were merely labelled with primary-cause codes, and only 2140 (2.9%) were labelled with CKD-staging codes. The majority of CKD patients (51.6–91.1%) received SCr tests from non-nephrologists, whereas CKD-staging diagnoses were mainly from nephrologists (52.3–64.8%). Only 3 of 42 general hospitals had nephrologists. The CKD-staging codes had high specificity (>99.0%) but low sensitivity (G3–G4: Conclusions Under-perception of CKD among doctors, rather than unsatisfactory health-seeking behaviour or low detection rates, was the main cause of under-diagnosis of CKD in China. Intensification of CKD education among doctors with different specialties might bring about immediate effective improvement in the diagnosis and awareness of CKD.

Background Disordered mineral and bone metabolism is a common complication of chronic kidney disease (CKD). Bone biopsy remains the gold standard tool for evaluating renal osteodystrophy (ROD), but it is an invasive procedure. Despite a growing interest in the ability of newer bone biomarkers to discriminate between different forms of ROD, data on pre-dialysis patients are scarce. Methods A cross-sectional study was conducted in a cohort of 56 patients with CKD Stages 3 and 4. Participants underwent a transiliac bone biopsy after a course of double tetracycline labelling. Circulating levels of Wnt signalling inhibitors sclerostin and Dickkopf-1 (DKK1), soluble receptor activator of nuclear factor-κB ligand (sRANKL) and osteoprotegerin were measured and correlated with histomorphometric analysis results. Results Most patients had abnormal bone histology and low-turnover bone disease was the predominant form of ROD. Characteristics associated with high bone turnover were worse renal function, lower serum calcium and higher intact parathyroid hormone and fibroblast growth factor-23 levels. Patients with low bone turnover, on the other hand, presented with higher sclerostin along with lower DKK1 and sRANKL levels. In the multivariable logistic regression analysis, sclerostin and DKK1 levels were independently associated with low-turnover bone disease. Conclusions Our results suggest that circulating levels of Wnt signalling inhibitors sclerostin and DKK1 are predictive of low-turnover bone disease in patients not yet on dialysis. Further research is needed to assess the performance of these bone turnover biomarkers, compared with histomorphometric analysis, in the diagnosis and treatment monitoring of ROD., Graphical Abstract Graphical Abstract

Background Chronic kidney disease (CKD) is common among people with type 2 diabetes (T2D), and increases the risk of kidney failure and cardiovascular diseases. Shorter leukocyte telomere length (LTL) is associated with CKD in patients with T2D. We previously reported single-nucleotide polymorphisms (SNPs) associated with LTL in an Asian population. In this study, we elucidated the association of these SNPs with CKD in patients with T2D using the Mendelian randomization (MR) approach. Methods The cross-sectional association of 16 LTL SNPs with CKD, defined as an estimated glomerular filtration rate of Results Genetically determined shorter LTL was associated with increased risk of CKD in patients with T2D (meta-IVW adjusted odds ratio = 1.51, 95% confidence interval 1.12–2.12, P = 0.007, Phet = 0.547). Similar results were obtained following sensitivity analysis. MR-Egger analysis (intercept) suggested no evidence of horizontal pleiotropy (β = 0.010, P = 0.751). Conclusions Our findings suggest that genetically determined LTL is associated with CKD in patients with T2D. Further studies are warranted to elucidate the causal role of telomere length in CKD progression.

Background Acute kidney injury (AKI) may develop in COVID-19 patients and may be associated with a worse outcome. The aim of this study is to describe AKI incidence during the first 45 days of the SARS-CoV2 pandemic in Spain, its reversibility and the association with mortality. Methods Observational retrospective case-control study based on patients hospitalized between March 1 and April 15, 2020 with SARS-CoV2 infection and AKI. Confirmed AKI cases were compared with stable kidney function patients for baseline characteristics, analytical data, treatment and renal outcome. Patients with end-stage kidney disease were excluded. Results AKI incidence was 17.22% among 3182 admitted COVID-19 patients and acute kidney disease (AKD) incidence was 6.82%. The most frequent causes of AKI were prerenal (68.8%) and sepsis (21.9%). Odds ratio for AKI was increased in patients with pre-existent hypertension (OR 2.58, 95% CI 1.71-3.89) and chronic kidney disease (OR 2.14, 95% CI 1.33-3.42) and in those with respiratory distress (OR 2.37, 95% CI 1.52-3.70). Low arterial pressure at admission increased the risk for stage 3 AKI (OR 1.65, 95% CI 1.09-2.50). Baseline kidney function was not recovered in 45.73% of overall AKI cases and in 52.75% of AKI patients with prior chronic kidney disease. Mortality was 38.5% compared to 13.4% of the overall sample population. AKI increased mortality risk at any time of hospitalization (HR 1.45, 95% CI 1.09-1.93). Conclusions AKI is frequent in COVID-19 patients and is associated to mortality, independently from acute respiratory distress syndrome. AKD was also frequent and merits adequate follow-up., Graphical Abstract Graphical Abstract

Background Accelerated senescence of renal tubular epithelial cells (RTECs) might contribute to immunoglobulin A nephropathy (IgAN) progression. This study aimed to determine whether the RTEC senescence marker, decoy receptor 2 (DcR2), could predict prognosis in IgAN. Methods We included a retrospective cohort of 105 patients with biopsy-proven IgAN. Tubular DcR2 expression was assessed at renal biopsy and the Oxford histological MEST-C score [mesangial hypercellularity (M), endocapillary proliferation (E), segmental sclerosis (S), interstitial fibrosis/tubular atrophy (T) and crescents (C)] defined disease severity. IgAN progression was defined as a composite of end-stage renal disease or a 30% decline in the estimated glomerular filtration rate (eGFR), analyzed using Kaplan–Meier and Cox regression analyses. Results Tubular DcR2 was overexpressed in IgAN. Numbers of DcR2 and p16 double-positive RTECs increased with increasing severity of tubular atrophy/interstitial fibrosis (T lesion). Patients with ≥25% tubular DcR2 expression experienced worse proteinuria, T lesions and a lower eGFR. Cumulative renal survival was significantly lower in patients with ≥25% DcR2 positivity. Multivariate regression analyses showed that ≥25% tubular DcR2 expression was significantly associated with worse eGFR slopes (the rate of renal function decline; P = 0.003) and the incidence of the composite outcome (P = 0.001) in IgAN. The addition of tubular DcR2 to a model with clinical data at biopsy (mean arterial pressure, proteinuria and eGFR) or MEST-C score significantly improved the 5-year risk prediction of IgAN progression, as confirmed by receiver operating characteristic curve analyses. Conclusions Tubular DcR2 expression detected at biopsy was a strong independent predictor for IgAN progression and might have prognostic value in addition to established risk markers.

Background Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common monogenetic disorders in humans and is characterized by numerous fluid-filled cysts that grow slowly, resulting in end-stage renal disease in the majority of patients. Preclinical studies have indicated that treatment with low-dose thiazolidinediones, such as pioglitazone, decrease cyst growth in rodent models of PKD. Methods This Phase 1b cross-over study compared the safety of treatment with a low dose (15 mg) of the peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist pioglitazone or placebo in PKD patients, with each treatment given for 1 year. The study monitored known side effects of PPAR-γ agonist treatment, including fluid retention and edema. Liver enzymes and risk of hypoglycemia were assessed throughout the study. As a secondary objective, the efficacy of low-dose pioglitazone was followed using a primary assessment of total kidney volume (TKV), blood pressure (BP) and kidney function. Results Eighteen patients were randomized and 15 completed both arms. Compared with placebo, allocation to pioglitazone resulted in a significant decrease in total body water as assessed by bioimpedance analysis {mean difference 0.16 Ω [95% confidence interval (CI) 0.24–2.96], P = 0.024} and no differences in episodes of heart failure, clinical edema or change in echocardiography. Allocation to pioglitazone led to no difference in the percent change in TKV of −3.5% (95% CI −8.4–1.4, P = 0.14), diastolic BP and microalbumin:creatinine ratio. Conclusions In this small pilot trial in people with ADPKD but without diabetes, pioglitazone 15 mg was found to be as safe as placebo. Larger and longer-term randomized trials powered to assess effects on TKV are needed.

Background We aimed to update information on the prevalence of chronic kidney disease (CKD) in Japan. We also explored whether CKD was properly recognized and managed. Methods We used data from annual health checkups in 2017, compiling records for 5 million persons. These included laboratory results and were linked to healthcare utilization records via personal identifiers. CKD was defined as an estimated glomerular filtration rate Results Of the 761 565 records [median age 46 years (interquartile range 50–62)], CKD was found in 50 091 persons; the crude and age-adjusted prevalences were 63.1 and 71.8 per 1000 persons, respectively. CKD prevalence was significantly higher in 2017 than in 2005, with an increase of 14.1 per 1000 persons. Among persons with CKD, >95% sought medical services and 64.6% received laboratory tests within 180 days of the checkup. However, the diagnostic code suggestive of CKD was recorded in only 23.2% of patients and prescriptions for DM and HT were found in 31.2% (1590/5096) and 36.7% (8081/22 019) of comorbid persons, respectively. Conclusions The prevalence of CKD in Japan has increased over the past decade. However, recognition of CKD is likely suboptimal and there is room to improve the management of comorbid DM and HT.

Background Nephrotic-range proteinuria (NRP) is associated with rapid kidney function loss and increased cardiovascular (CV) disease risk. We assessed the effects of linagliptin (LINA) on CV and kidney outcomes in people with Type 2 diabetes (T2D) with or without NRP. Methods Cardiovascular and renal microvascular outcome study with LINA randomized participants with T2D and CV disease and/or kidney disease to LINA 5 mg or placebo (PBO). The primary endpoint [time to first occurrence of 3-point major adverse cardiac events (3P-MACE)], and kidney outcomes, were evaluated by NRP status [urinary albumin:creatinine ratio (UACR) ≥2200 mg/g] at baseline (BL) in participants treated with one or more dose of study medication. Results NRP was present in 646/6979 [9.3% (LINA/PBO n = 317/n = 329); median UACR 3486 (Q1: 2746/Q3: 4941) mg/g] participants, who compared with no-NRP were younger (62.3/66.1 years) and had lower estimated glomerular filtration rate (eGFR) (39.9/56.1 mL/min/1.73 m2). Over a median of 2.2 years, 3P-MACE occurred with a 2.0-fold higher rate in NRP versus no-NRP (PBO group), with a neutral LINA effect, regardless of NRP. The composite of time to renal death, end-stage kidney disease (ESKD) or decrease of ≥40 or ≥50% in eGFR, occurred with 12.3- and 13.6-fold higher rate with NRP (PBO group); evidence of heterogeneity of effects with LINA was observed for the former [NRP yes/no: hazard ratio 0.80 (0.63–1.01)/1.25 (1.02–1.54); P-interaction 0.005], but not the latter [0.83 (0.64–1.09)/1.17 (0.91–1.51), P-interaction 0.07]. No heterogeneity was observed for renal death or ESKD [0.88 (0.64–1.21)/0.94 (0.67–1.31), P-interaction 0.79]. Glycated haemoglobin A1c (HbA1c) was significantly reduced regardless of NRP, without increasing hypoglycaemia risk. Regression to normoalbuminuria [1.20 (1.07–1.34)] and reduction of UACR ≥50% [1.15 (1.07–1.25)] from BL, occurred more frequently with LINA, regardless of NRP status (P-interactions >0.05). Conclusions Individuals with T2D and NRP have a high disease burden. LINA reduces their albuminuria burden and HbA1c, without affecting CV or kidney risk., Graphical Abstract

Background Randomized trials can provide evidence to inform decision-making but this may be limited if the outcomes of importance to patients and clinicians are omitted or reported inconsistently. We aimed to assess the scope and heterogeneity of outcomes reported in trials in peritoneal dialysis (PD). Methods We searched the Cochrane Kidney and Transplant Specialized Register for randomized trials in PD. We extracted all reported outcome domains and measurements and analyzed their frequency and characteristics. Results From 128 reports of 120 included trials, 80 different outcome domains were reported. Overall, 39 (49%) domains were surrogate, 23 (29%) patient-reported and 18 (22%) clinical. The five most commonly reported domains were PD-related infection [59 (49%) trials], dialysis solute clearance [51 (42%)], kidney function [45 (38%)], protein metabolism [44 (37%)] and inflammatory markers/oxidative stress [42 (35%)]. Quality of life was reported infrequently (4% of trials). Only 14 (12%) trials included a patient-reported outcome as a primary outcome. The median number of outcome measures (defined as a different measurement, aggregation and metric) was 22 (interquartile range 13–37) per trial. PD-related infection was the most frequently reported clinical outcome as well as the most frequently stated primary outcome. A total of 383 different measures for infection were used, with 66 used more than once. Conclusions Trials in PD include important clinical outcomes such as infection, but these are measured and reported inconsistently. Patient-reported outcomes are infrequently reported and nearly half of the domains were surrogate. Standardized outcomes for PD trials are required to improve efficiency and relevance.

Background Chronic kidney disease (CKD), one of the most common complications of type 2 diabetes (T2D), is associated with poor health outcomes and high healthcare expenditures. As the CKD population increases, a better understanding of the prevalence and progression of CKD is critical. However, few contemporary studies have explored the progression of CKD relative to its onset in T2D patients using established markers derived from real-world care settings. Methods This retrospective, population-based cohort study assessed CKD progression among adults with T2D and with newly recognized CKD identified from US administrative claims data between 1 January 2008 and 30 September 2018. Included were patients with T2D and laboratory evidence of CKD as indicated by the established estimated glomerular filtration rate (eGFR) and urine albumin:creatinine ratio (UACR) criteria. Disease progression was described as transitions across the eGFR- and UACR-based stages. Results A total of 65 731 and 23 035 patients with T2D contributed to the analysis of eGFR- and UACR-based CKD stage progression, respectively. CKD worsening was observed in approximately 10–17% of patients over a median follow-up of 2 years. Approximately one-third of patients experienced an increase in eGFR values or a decrease in UACR values during follow-up. Conclusions A relatively high proportion of patients were observed with disease progression over a short period of time, highlighting the need for better identification of patients at risk of rapidly progressive CKD. Future studies are needed to determine the clinical characteristics of these patients to inform earlier diagnostic and therapeutic interventions aimed at slowing disease progression., Graphical Abstract

Objectives Idiopathic focal segmental glomerulosclerosis (FSGS) has been linked to immunological and inflammatory response dysregulations. The aim of this study was to find endotypes of FSGS patients using a cluster (CL) analysis based on inflammatory and immunological variables, and to analyse whether a certain endotype is associated with response to treatment with corticosteroids. Methods This prospective observational study included patients with idiopathic FSGS diagnosed by kidney biopsy. Serum levels of soluble interleukin (IL)-1 receptor, tumoural necrosis factor alpha, Interferon gamma (IFNγ), IL-6, IL-17, IL-12, IL-23, IL-13, IL-4, IL-5, IL-6, haemopexin (Hx), haptoglobin (Hgl), soluble urokinase-type plasminogen activator receptor (suPAR) and urinary CD80 (uCD80) were measured with enzyme-linked immunosorbent assay or nephelometry. T-helper lymphocyte populations and T-regulatory lymphocytes were analysed by flow cytometry. A factorial analysis followed by a k-means CL analysis was performed. Results A total of 79 FSGS patients were included. Three CLs were identified. CL1 (27.8%) included IL-12, IL-17, IL-23 and a T helper 17 (Th17) pattern. CL2 (20.2%) included IL-4, IL-5, IL-13, immunoglobulin E and Th2 pattern. CL3 (51.8%) included IL-6, Hx, Hgl, suPAR and uCD80. There were no differences in age, gender, kidney function, albumin or proteinuria among CLs. About 42/79 patients (53.1%) showed cortico-resistance. The prevalence of cortico-resistance was significantly lower in CL2 (4/16, 25%) than in CL1 (16/26, 72.7%) and CL3 (22/41, 53.7%) (P = 0.018), with no significant differences between CLs 1 and 3 (P = 0.14). Conclusions Patients with FSGS and indistinguishable clinical presentation at diagnosis were classified in three distinct CLs according to predominant Th17, Th2 and acute inflammatory responses that display differences in clinical response to treatment with corticosteroids., Graphical Abstract

Background Glomerular filtration rate (GFR) decline ≥30% over 2 years can substitute for the conventional ‘doubling of serum creatinine’ to predict end-stage renal disease in patients with native kidneys. While chronic kidney disease trajectory is less predictable in transplanted patients, recent data have suggested that similar GFR decline might be an acceptable surrogate for long-term transplant outcome. We sought (i) to confirm the prognostic value of an early GFR decline in kidney transplant recipients and (ii) to determine whether using direct measurement of GFR with inulin improves the performance of this surrogate. Methods We retrospectively analysed all recipients transplanted between 1989 and 2000 in our centre, with inulin-measured and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)-estimated GFR at 1 and 5 years post-transplant, and evaluated the performance [time-dependent area under the receiver operating characteristic curve (ROC AUC) and subdistribution hazard ratio (sdHR) with competing risk model] of GFR change to predict graft failure and all-cause mortality. Results Out of 417 kidney transplant recipients, 116 patients had lost their graft and 77 had died 16 years after transplantation. While being significantly associated with graft failure [sdHR = 2.37 (95% confidence interval 1.47–3.83)], CKD-EPI-GFR decline ≥30% failed to appropriately predict long-term graft survival (C-statistics of 0.63). Concordance between inulin-GFR and CKD-EPI-GFR to detect similar GFR change was only 53%. Inulin-GFR change was, however, not a better predictor (C-statistics of 0.59). Comparable results were observed for mortality. Conclusions Our data suggest that early GFR decline is a poor surrogate for long-term transplant outcome, even when change in GFR is directly measured by a reference method.

Background The effect of early initiation of dialysis on outcomes of patients with end-stage renal disease (ESRD) remains controversial. We conducted this study to investigate the association between the timing of peritoneal dialysis (PD) initiation and mortality in different age groups. Methods In this single-centre cohort study, incident patients receiving PD from 1 January 2006 to 31 December 2016 were enrolled. Patients were categorized into three groups according to the estimated glomerular filtration rate (eGFR) at the initiation of PD, with early, mid and late initiation of PD defined as eGFR ≥7.5, 5–7.5 and Results A total of 2133 incident patients receiving PD were enrolled with a mean age of 47.1 years, 59.6% male and 25.3% with diabetes, of whom 1803 were young (age Conclusions No significant difference in mortality risk was found among the three levels of eGFR at PD therapy initiation in young patients, while early initiation of PD was associated with a higher risk of overall and CV mortality among elderly patients.

Background Dyslipidemia is an essential parameter in the prediction of cardiovascular disease (CVD). We aimed to explore whether lipid profiles could predict major outcomes in patients with advanced chronic kidney disease (CKD). Methods We retrospectively reviewed the National Health Insurance Service database for people who received nationwide health screening in 2009. All subjects exposed to a lipid-lowering agent before screening were excluded. The population was divided into control, early [estimated glomerular filtration rate (eGFR) 45–59 mL/min/1.73 m2] and advanced (eGFR Results A total of 3 634 873 participants were included in this study, with 404 298 (11.1%) and 66 805 (1.8%) having early and advanced CKD, respectively. For all populations, levels of triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) showed a linear association with major cardiovascular and cerebrovascular events (MACCEs) and all-cause mortality, while low-density lipoprotein cholesterol (LDL-C) showed a different pattern of association with MACCEs (linear association) from all-cause mortality (U-shaped association). The significance between the levels of LDL-C and outcomes was attenuated in the advanced CKD group. For TG/HDL-C, although the significance was decreased, the linear patterns with both MACCEs and all-cause mortality were maintained in the advanced CKD group. Conclusions The pattern and significance of lipid profiles were different according to the grade of kidney function. TG/HDL-C should be additionally considered as a predictive marker for CVD and mortality along with LDL-C in patients with CKD.

Background We aimed to describe the characteristics of immunoglobulin A nephropathy (IgAN) in Korea with assessment for time trends. Methods We performed a multicenter retrospective observational cohort study including biopsy-confirmed native IgAN cases from four tertiary hospitals in Korea. Time eras of diagnosis were stratified into 1979–2003, 2004–9 and 2010–17. The prognostic variable was progression to end-stage kidney disease (ESKD) analyzed by multivariable Cox regression analysis. Results We included 1366 (from 1979 to 2003), 1636 (from 2004 to 2009) and 1442 (from 2010 to 2017) IgAN patients in this study. In the recent periods, IgAN had relatively better clinical characteristics, as patients had higher estimated glomerular filtration rates and lower baseline blood pressures than before. The use of renin–angiotensin–aldosterone system (RAAS) blockers increased from 57.7% in 1979–2003 to 80.0% in 2010–17. During a median follow-up duration of 11.3 years, 722 patients progressed to ESKD with an incidence rate of 12.5 per 1000 person-years. The 10-year risk of progression to ESKD was lower in 2010–17 compared with that of 1979–2003 [adjusted hazard ratio 0.692 (95% confidence interval 0.523–0.915)], even after adjustment for multiple clinicopathologic characteristics. The use of RAAS blockers was a significant mediator (P < 0.001) for the association between time trends and lower 10-year ESKD risk. Conclusions Clinicopathologic characteristics of IgAN in Korea have changed over time. Although the limitation of a retrospective observational study remains, the result showed that the prognosis of IgAN has improved over the study period, possibly related to increased prescription of RAAS blockers.

BackgroundThe relationships of sodium intake to kidney function within the population have been poorly investigated and are the objective of the study.MethodsThis observational, population-based, cross-sectional and longitudinal study targeted 4595 adult participants of the Gubbio study with complete data at baseline exam. Of these participants, 3016 participated in the 15-year follow-up (mortality-corrected response rate 78.4%). Baseline measures included sodium:creatinine ratio in timed overnight urine collection, used as an index of sodium intake, together with serum creatinine, sex, age and other variables. Follow-up measures included serum creatinine and other variables. Estimated glomerular filtration rate (eGFR, mL/min/1.73 m2) was calculated using serum creatinine, sex and age and was taken as an index of kidney function.ResultsThe study cohort was stratified in sex- and age-controlled quintiles of baseline urine sodium:creatinine ratio. A higher quintile associated with higher baseline eGFR (P ConclusionsWithin the general population, an index of higher sodium intake associated cross-sectionally with higher kidney function but longitudinally with greater kidney function decline.

Objective Nephrectomy, the standard of care for localized renal cell carcinoma (RCC), may lead to kidney function loss. Our goal was to identify prognostic biomarkers of postoperative renal function using metabolomics. Methods Metabolomics data from benign kidney parenchyma were collected prospectively from 138 patients with RCC who underwent nephrectomy at a single institution. The primary endpoint was the difference between the postoperative and preoperative estimated glomerular filtration (eGFR) rate divided by the elapsed time (eGFR slope). eGFR slope was calculated ∼2 years post-nephrectomy (GFR1), and at last follow-up (GFR2). A multivariate regularized regression model identified clinical characteristics and abundance of metabolites in baseline benign kidney parenchyma that were significantly associated with eGFR slope. Findings were validated by associating gene expression data with eGFR slope in an independent cohort (n = 58). Results Data were compiled on 78 patients (median age 62.6 years, 65.4% males). The mean follow-up was 25 ± 3.4 months for GFR1 and 69.5 ± 23.5 months for GFR2 and 17 (22%) and 32 (41%) patients showed eGFR recovery, respectively. Nephrectomy type, blood lipids, gender and 23 metabolites from benign parenchyma were significantly associated with eGFR slope. Some metabolites associated with eGFR slope overlapped with previously reported chronic kidney disease-related processes. Subgroup analysis identified unique ‘metabolite signatures’ by older age, nephrectomy type and preoperative eGFR. Conclusions Nephrectomy type, gender, blood lipids and benign parenchyma metabolites at nephrectomy were associated with long-term kidney function. On further study, these metabolites may be useful as potential biomarkers and to identify novel therapeutic targets for malignancy-associated renal disease.

Nephrologists are familiar with severe cases of anti-neutrophil cytoplasmic antibodies-associated vasculitis (AAV) presenting as rapidly progressive glomerulonephritis. However, less is known about AAV with slowly progressive renal involvement. While its existence is acknowledged in textbooks, much remains unknown regarding its relative frequency versus more aggressive cases as well as about the optimal therapeutic approach and response to therapy. Moreover, this uncommon presentation may be underdiagnosed, given the scarce familiarity of physicians. In this issue of Clinical Kidney Journal, Trivioli et al. report the largest series to date and first systematic assessment of patients with AAV and slowly progressive renal involvement, defined as a reduction in estimated glomerular filtration rate (eGFR) of 25–50% in the 6 months prior to diagnosis after excluding secondary causes. Key findings are that slowly progressive AAV may be less common than previously thought, although it still represents the second most common presentation of renal AAV, it usually has a microscopic polyangiitis, anti-myeloperoxidase, mainly renal phenotype in elderly individuals, diagnosis may be late (over one-third of patients had end-stage kidney disease at diagnosis), clearly identifying an unmet need for physician awareness about this presentation, but those not needing renal replacement therapy at diagnosis still responded to immunosuppression.

The incidence of acute kidney injury (AKI) has increased in the past decades. AKI complicates up to 15% of hospitalizations and can reach up to 50–60% in critically ill patients. Besides the short-term impact of AKI in patient outcomes, several studies report the association between AKI and adverse long-term outcomes, such as recurrent AKI episodes in 25–30% of cases, hospital re-admissions in up to 40% of patients, an increased risk of cardiovascular events, an increased risk of progression of chronic kidney disease (CKD) after AKI and a significantly increased long-term mortality. Despite the long-term impact of AKI, there are neither established guidelines on the follow-up care of AKI patients, nor treatment strategies to reduce the incidence of sequelae after AKI. Only a minority of patients have been referred to nephrology post-discharge care, despite the evidence of improved outcomes associated with nephrology referral by addressing cardiovascular risk and risk of progression to CKD. Indeed, AKI survivors should have specialized nephrology follow-up to assess kidney function after AKI, perform medication reconciliation, educate patients on nephrotoxic avoidance and implement strategies to prevent CKD progression. The authors provide a comprehensive review of the transition from AKI to CKD, analyse the current evidence on the long-term outcomes of AKI and describe predisposing risk factors, highlight the importance of follow-up care in these patients and describe the current therapeutic strategies which are being investigated on their impact in improving patient outcomes.

Acute kidney injury (AKI) is the clinical term used for decline or loss of renal function. It is associated with chronic kidney disease (CKD) and high morbidity and mortality. However, not all causes of AKI lead to severe consequences and some are reversible. The underlying pathology can be a guide for treatment and assessment of prognosis. The Kidney Disease: Improving Global Outcomes guidelines recommend that the cause of AKI should be identified if possible. Renal biopsy can distinguish specific AKI entities and assist in patient management. This review aims to show the pathology of AKI, including glomerular and tubular diseases.

Sodium–glucose co-transporter-2 (SGLT2) inhibitors decreased cardiovascular (CV) events and improved renal outcomes in CV safety studies in type 2 diabetes melitus (T2DM) patients at high CV risk. Canagliflozin also improved kidney outcomes in diabetic kidney disease in the Canagliflozin and Renal Events in Diabetes and Nephropathy Clinical Evaluationtrial. More recently, the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) trial showed that dapagliflozin improved CV outcomes in patients with HF with or without diabetes. Protection from HF in non-diabetics was confirmed for empagliflozin in the EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction (EMPEROR-Reduced) trial. A meta-analysis of DAPA-HF and EMPEROR-Reduced confirmed reductions in all-cause and CV death and the combined risk of CV death or worsening HF, as well as in the composite renal endpoint {hazard ratio [HR] 0.62 [95% confidence interval (CI) 0.43–0.90]} without differences based on the presence of diabetes or baseline estimated glomerular filtration rate (eGFR). Moreover, the Study to Evaluate the Effect of Dapagliflozin on Renal Outcomes and Cardiovascular Mortality in Patients With Chronic Kidney Disease (DAPA-CKD) showed that dapagliflozin as an add-on over renin–angiotensin system blockade in patients with chronic kidney disease (CKD; with or without T2DM) reduced the HR for the primary endpoint (time to the first occurrence of ≥50% eGFR decline, end-stage kidney disease or renal or CV death) to 0.61 (95% CI 0.51–0.72) and for the secondary endpoints of worsening renal function or death from kidney failure [HR 0.56 (95% CI 0.45–0.68)], hospitalization for HF or CV death [HR 0.71 (95% CI 0.55–0.92)] and all-cause mortality [HR 0.69 (95% CI 0.53–0.88)]. These beneficial effects were consistent in patients with and without T2DM. In conclusion, SGLT2 inhibitors offer CV and kidney protection in both diabetic and non-diabetic CKD and, additionally, improve glycaemic control in T2DM, making them first-line therapy for CKD independent from diabetic status.

Hyperuricaemia is frequent in chronic kidney disease (CKD). Observational studies have shown an association with adverse outcomes and acquired hyperuricaemia (meaning serum urate levels as low as 1.0 mg/dL) in animal models induces kidney injury. This evidence does not justify the widespread use of urate-lowering drugs for asymptomatic hyperuricaemia in CKD. However, promising results from small, open-label studies led some physicians to prescribe urate-lowering drugs to slow CKD progression. Two recent, large, placebo-controlled trials (CKD-FIX and PERL) showed no benefit from urate lowering with allopurinol on the primary endpoint of CKD progression, confirming prior negative results. Despite these negative findings, it was still argued that the study population could be optimized by enrolling younger non-proteinuric CKD patients with better preserved glomerular filtration rate (GFR). However, in these low-risk patients, GFR may be stable under placebo conditions. Additionally, the increased mortality trends already identified in gout trials of urate-lowering therapy were also observed in CKD-FIX and PERL, sending a strong safety signal: 21/449 (4.7%) and 10/444 (2.2%) patients died in the combined allopurinol and placebo groups, respectively [chi-squared P-value 0.048; relative risk 2.07 (95% CI 0.98-4.34); P = 0.06]. Given the absent evidence of benefit in multiple clinical trials and the potentially serious safety issues, the clear message should be that urate-lowering therapy should not be prescribed for the indication of slowing CKD progression. Additionally, regulatory agencies should urgently reassess the safety of chronic prescription of urate-lowering drugs for any indication., FIS/Fondos FEDER; ERAPerMed-JTC2018; European Commission; European Union (EU); Horizon 2020; Comunidad de Madrid en Biomedicina; Sociedad Espanola de Nefrologia; FRIAT

Background Acute kidney injury (AKI) is frequent during hospitalization and may contribute to adverse short- and long-term consequences. Acute kidney disease (AKD) reflects the continuing pathological processes and adverse events developing after AKI. We aimed to evaluate the association of AKD, long-term adverse renal function and mortality in a cohort of patients with sepsis. Methods We performed a retrospective analysis of adult patients with septic AKI admitted to the Division of Intensive Medicine of the Centro Hospitalar Lisboa Norte (Lisbon, Portugal) between January 2008 and December 2014. Patients were categorized according to the development of AKI using the Kidney Disease: Improving Global Outcomes (KDIGO) classification. AKI was defined as an increase in absolute serum creatinine (SCr) ≥0.3 mg/dL or by a percentage increase in SCr ≥50% and/or by a decrease in urine output to 6 h. AKD was defined as presenting at least KDIGO Stage 1 criteria for >7 days after an AKI initiating event. Adverse renal outcomes (need for long-term dialysis and/or a 25% decrease in estimated glomerular filtration rate after hospital discharge) and mortality after discharge were evaluated. Results From 256 selected patients with septic AKI, 53.9% developed AKD. The 30-day mortality rate was 24.5% (n = 55). The mean long-term follow-up was 45.9 ± 43.3 months. The majority of patients experience an adverse renal outcome [n = 158 (61.7%)] and 44.1% (n = 113) of patients died during follow-up. Adverse renal outcomes, 30-day mortality and long-term mortality after hospital discharge were more frequent among AKD patients [77.5 versus 43.2% (P Conclusions AKD after septic AKI was independently associated with the risk of long-term need for dialysis and/or renal function decline and with the risk of death after hospital discharge.

Diabetis mellitus; Malaltia renal diabètica; Atenció multidisciplinària Diabetes mellitus; Diabetic kidney disease; Multidisciplinary care Diabetes mellitus; Enfermedad renal diabética; Atención multidisciplinaria Age-standardized rates of diabetes mellitus (DM)-related complications, such as acute myocardial infarction, stroke or amputations, have decreased in recent years, but this was not associated with a clear reduction of the incidence of advanced chronic kidney disease (CKD) requiring renal replacement therapy. The early detection of diabetic kidney disease (DKD) is a key to reduce complications, morbidity and mortality. Consensus documents and clinical practice guidelines recommend referral of DM patients to nephrology when the estimated glomerular filtration rate falls below 30 mL/min/1.73 m2 or when albuminuria exceeds 300 mg/g urinary creatinine. Conceptually, it strikes as odd that patients with CKD are referred to the specialist caring for the prevention and treatment of CKD only when >70% of the functioning kidney mass has been lost. The increasing global health burden of CKD, driven in large part by DKD, the suboptimal impact of routine care on DKD outcomes as compared with other DM complications, the realization that successful therapy of CKD requires early diagnosis and intervention, the advances in earlier diagnosis of kidney injury and the recent availability of antidiabetic drugs with a renal mechanism of action and lack of hypoglycaemia risk, which additionally are cardio- and nephroprotective, all point towards a paradigm shift in the care for DM patients in which they should be referred earlier to nephrology as part of a coordinated and integrated care approach. Sources of support: FIS/Fondos FEDER PI18/01386, PI19/00588, PI19/00815, DTS18/00032, ERA-PerMed-JTC2018 (KIDNEY ATTACK AC18/00064 and PERSTIGAN AC18/00071, ISCIII-RETIC REDinREN RD016/0009), Sociedad Española de Nefrología, FRIAT, Comunidad de Madrid en Biomedicina B2017/BMD-3686 CIFRA2-CM.

Background Improving recognition of patients at increased risk of acute kidney injury (AKI) in the community may facilitate earlier detection and implementation of proactive prevention measures that mitigate the impact of AKI. The aim of this study was to develop and externally validate a practical risk score to predict the risk of AKI in either hospital or community settings using routinely collected data. Methods Routinely collected linked datasets from Tayside, Scotland, were used to develop the risk score and datasets from Kent in the UK and Alberta in Canada were used to externally validate it. AKI was defined using the Kidney Disease: Improving Global Outcomes serum creatinine–based criteria. Multivariable logistic regression analysis was performed with occurrence of AKI within 1 year as the dependent variable. Model performance was determined by assessing discrimination (C-statistic) and calibration. Results The risk score was developed in 273 450 patients from the Tayside region of Scotland and externally validated into two populations: 218 091 individuals from Kent, UK and 1 173 607 individuals from Alberta, Canada. Four variables were independent predictors for AKI by logistic regression: older age, lower baseline estimated glomerular filtration rate, diabetes and heart failure. A risk score including these four variables had good predictive performance, with a C-statistic of 0.80 [95% confidence interval (CI) 0.80–0.81] in the development cohort and 0.71 (95% CI 0.70–0.72) in the Kent, UK external validation cohort and 0.76 (95% CI 0.75–0.76) in the Canadian validation cohort. Conclusion We have devised and externally validated a simple risk score from routinely collected data that can aid both primary and secondary care physicians in identifying patients at high risk of AKI., Graphical Abstract Graphical Abstract

Background Hypothyroidism and low free triiodothyronine (FT3) syndrome [low FT3 levels with normal thyroid-stimulating hormone (TSH)] have been associated with reduced kidney function cross-sectionally in chronic kidney disease (CKD) patients with severely reduced estimated glomerular filtration rate (eGFR) or end-stage kidney disease (ESKD). Results on the prospective effects of impaired thyroid function on renal events and mortality for patients with severely reduced eGFR or from population-based cohorts are conflicting. Here we evaluated the association between thyroid and kidney function with eGFR (cross-sectionally) as well as renal events and mortality (prospectively) in a large, prospective cohort of CKD patients with mild to moderately reduced kidney function. Methods Thyroid markers were measured among CKD patients from the German Chronic Kidney Disease study. Incident renal endpoints (combined ESKD, acute kidney injury and renal death) and all-cause mortality were abstracted from hospital records and death certificates. Time to first event analysis of complete data from baseline to the 4-year follow-up (median follow-up time 4.04 years) of 4600 patients was conducted. Multivariable linear regression and Cox proportional hazards models were fitted for single and combined continuous thyroid markers [TSH, free thyroxine (FT4), FT3] and thyroid status. Results Cross-sectionally, the presence of low-FT3 syndrome showed a significant inverse association with eGFR and continuous FT3 levels alone showed a significant positive association with eGFR; in combination with FT4 and TSH, FT3 levels also showed a positive association and FT4 levels showed a negative association with eGFR. Prospectively, higher FT4 and lower FT3 levels were significantly associated with a higher risk of all-cause mortality (Nevents = 297). Per picomole per litre higher FT3 levels the risk of reaching the composite renal endpoint was 0.73-fold lower (95% confidence interval 0.65–0.82; Nevents = 615). Compared with euthyroid patients, patients with low-FT3 syndrome had a 2.2-fold higher risk and patients with hypothyroidism had a 1.6-fold higher risk of experiencing the composite renal endpoint. Conclusions Patients with mild to moderate CKD suffering from thyroid function abnormalities are at an increased risk of adverse renal events and all-cause mortality over time.

Background Fabry disease is a rare, X-linked genetic disorder that, if untreated in patients with the Classic phenotype, often progresses to end-stage kidney disease. This meta-analysis determined the effect of agalsidase beta on loss of estimated glomerular filtration rate (eGFR) in the Classic phenotype using an expansive evidence base of individual patient-level data. Methods The evidence base included four Sanofi-Genzyme studies and six studies from a systematic literature review. These were restricted to Classic Fabry patients meeting the eligibility criteria from Phases III and IV agalsidase beta trials, including 315 patients (161 treated). Linear regression was first used to model annual change in eGFR for each patient and the resulting annualized eGFR slopes were modelled with treatment and covariates using quantile regression. These results were then used to estimate median annualized eGFR change in agalsidase beta treated versus untreated groups. Results Imbalances across treatment groups were found in baseline age, sex and proteinuria, but not in the use of renin–angiotensin system blockers. The adjusted model suggests that treated (agalsidase beta) patients experienced a slower median eGFR decrease [2.46 mL/min/1.73 m2/year slower; 95% confidence interval (CI) 0.63–4.29; P = 0.0087] than comparable untreated patients. The median eGFR decrease was 2.64 mL/min/1.73 m2/year slower (95% CI 0.53–4.78; P = 0.0141) in treated Classic males. Conclusions Using an expansive evidence base and robust modelling approach, these data indicate that agalsidase beta-treated patients with the Classic phenotype conserve their renal function better than untreated patients.

Nephrolithiasis is one of the most common urological conditions with a huge socio-economic impact. About 50% of recurrent stone-formers have just one lifetime recurrence and >10% of patients present with a high recurrent disease requiring subsequent and sometimes multiple surgical interventions. The advent of new technology has made endourological procedures the pinnacle of stone treatment, including procedures like percutaneous nephrolithotomy (PCNL), retrograde intrarenal surgery and miniaturized PCNL procedures. Researchers have primarily focused on comparisons with respect to stone-free rates, procedure parameters and post-operative complications. However, the effect of these three procedures on renal function or indexes of renal injury has not been sufficiently examined. This was only reported in a few studies as a secondary objective with the use of common and not the appropriate and detailed renal parameters. This review presents current literature regarding the use of novel and highly predictive biomarkers for diagnosing acute kidney injury, discusses potential mechanisms through which endourological procedures for renal stone treatment may affect renal function and proposes areas with open questions where future research efforts in the field should focus.

Background Kidney disease is a frequent but underestimated complication in patients suffering from intestinal failure (IF) treated by long-term home parenteral nutrition (HPN). The evolution in glomerular filtration rate (GFR) over time is poorly characterized. The current equations for estimating GFR have limited precision. No study has specifically investigated the reliability of recent creatinine-based estimated GFR (eGFR) equations in this population. The aim of this study was to evaluate the renal function decline under home parenteral nutrition (HPN) with a gold standard method and compare the performances of routinely used eGFR equations. Methods Forty patients with HPN and two or more GFR measurements were retrospectively studied. The renal function decline was calculated by the slope drawn between the successive measured GFRs (mGFRs). The performances of the Modification of Diet in Renal Disease, Chronic Kidney Disease Epidemiology Collaboration, full age spectrum and revised Lund–Malmö equations were compared with reference methods (inulin or iohexol clearance). Results The mean mGFR was 78 ± 28 mL/min/1.73 m2. The annual decline of mGFR was −1.9 mL/min/1.73 m2/year. No predisposing factor was identified to predict impairment in renal function. eGFR formulas grossly overestimated mGFR and had a low level of accuracy. Conclusions Patients with IF are at significant risk for impaired renal function. In this population, the tested eGFR equations were inaccurate. However, monitoring kidney function with mGFR remains important in these patients, as their GFR regularly declines and no specific risk factor has yet been identified.

Background The incidence of acute tubulointerstitial nephritis (ATIN) related to drugs has dramatically increased over recent years. A new subtype of ATIN, apparently different from classical drug-related ATIN, has emerged that has been related to the administration of immune checkpoint inhibitors (ICIs). We investigated these differences between ICI-related ATIN (ICI ATIN) and non-ICI-related ATIN in terms of clinical features, response to treatment with steroids and the evolution of kidney function. Methods A total of 47 patients diagnosed with ATIN from two centres were recruited. Of these, 13 patients presented with ATIN during ICI treatment and 34 were diagnosed with ATIN attributed to other drugs. The main demographic, clinical and analytical variables such as gender, age and current medication were recorded. The type of malignancy, oncological treatment, ICI dose and presence of extrarenal immune-related adverse events were also reviewed. Renal biopsy diagnosis, time to drug withdrawal and ATIN-specific treatment, as well as laboratory data during follow-up, were also studied. Results Patients diagnosed with ICI ATIN presented with lower creatinine (ICI ATIN 3.8 ± 1.03 versus classical ATIN 5.98 ± 4.15 mg/dL, P = 0.007) at diagnosis and higher urinary leucocyte counts (ICI ATIN 263.2 ± 418.04 versus classical ATIN 133.55 ± 284.62, P = 0.048) compared with patients with non-ICI-related ATIN. Time from initiation of the culprit drug to ATIN diagnosis was longer in patients with ICI ATIN than in those with classical ATIN (197.07 ± 184.99 versus 114.4 ± 352.16 days, P = 0.006). In addition, during follow-up, the slope of decreasing creatinine over time was lower for ICI ATIN compared with non-ICI-related ATIN. Conclusions In this study, we analysed differences between ICI ATIN and classical ATIN. We found that patients with ICI ATIN presented with a larger latency period after culprit drug initiation, milder acute kidney injury and slower creatinine amelioration compared with those with classical ATIN. These results may, in part, be ascribed to potential differences in the pathological mechanisms involved in ATIN development, suggesting that ICI and classical ATIN may be different diseases with similar renal histologies.

Ifosfamide is a commonly used chemotherapeutic known to have numerous adverse kidney manifestations. In this issue of Clinical Kidney Journal, Ensergueix et al. report a multicentric observational retrospective French study on 34 adult patients with tubular dysfunction and /or kidney dysfunction following ifosfamide treatment. Of these patients, 18% had isolated proximal tubular dysfunction, 14% had isolated acute kidney injury (AKI), 18% had isolated chronic kidney disease (CKD) and 50% had a combination of proximal tubular dysfunction and AKI. Concomitant treatment with cisplatin was identified as a risk factor for the development of AKI, and cisplatin and age were associated with estimated glomerular filtration rate at last follow-up. Interestingly, the cumulative dose of ifosfamide was not associated with renal outcomes. This report highlights the need for additional studies on the prevalence, spectrum and management of ifosfamide-associated nephrotoxicity and clearly demonstrates that patients who received ifosfamide should be followed long term to detect proximal tubular dysfunction and CKD early. ispartof: CLINICAL KIDNEY JOURNAL vol:13 issue:4 pages:500-503 ispartof: location:England status: published

BackgroundNephropathy related to obesity lacks a pathophysiological understanding and definite diagnostic pathways by biomarkers.MethodsIn this study we investigated the association between urinary peptides and body mass index (BMI) and renal function in proteome data sets from 4015 individuals.ResultsA total of 365 urinary peptides were identified to be significantly associated with BMI. The majority of these peptides were collagen fragments. In addition, most of the peptides also demonstrated a significant concordant association with estimated glomerular filtration rate (eGFR) in the investigated cohort, with the presence of diabetes exhibiting no significant association. A new classifier was developed, based on 150 urinary peptides, that enabled the distinction of non-obese subjects with preserved kidney function from obese, non-diabetic subjects with eGFR >45 mL/min/1.73 m2 in an independent cohort, with an area under the curve of 0.93.ConclusionsOn a molecular level, the data strongly suggest a link between obesity and fibrosis, which may be a major cause of obesity-related nephropathy.

Background Mild cases of acute kidney injury (AKI) are identified by a small rise in serum creatinine (SCr) according to the KDIGO AKI definition. The aim of this study was to examine the long-term outcomes of individuals with mild AKI. Methods. This was a retrospective cohort study of all adult patients who underwent abdominal, cardiothoracic, vascular or orthopaedic surgery at Landspitali–The National University Hospital of Iceland in 1998–2015. Incident chronic kidney disease (CKD), progression of pre-existing CKD and long-term survival were compared between patients with mild Stage 1 AKI (defined as a rise in SCr of ≥26.5 μmol/L within 48 h post-operatively without reaching 1.5× baseline SCr within 7 days), and a propensity score-matched control group without AKI stratified by the presence of CKD. Results Pre- and post-operative SCr values were available for 47 333 (42%) surgeries. Of those, 1161 (2.4%) had mild Stage 1 AKI and 2355 (5%) more severe forms of AKI. Mild Stage 1 AKI was associated with both incident CKD and progression of pre-existing CKD (P Conclusions. Mild Stage 1 AKI is associated with development and progression of CKD, but not with inferior 1-year survival. These findings support the inclusion of a small absolute increase in SCr in the definition of AKI.

Background Patients who survive an episode of acute kidney injury (AKI) are more likely to have further episodes of AKI. AKI is associated with increased mortality, with a further increase with recurrent episodes. It is not clear whether this is due to AKI or as a result of other patient characteristics. The aim of this study was to establish whether recurrence of AKI is an independent risk factor for mortality or if excess mortality is explained by other factors. Methods This observational cohort study included adult people from the Tayside region of Scotland, with an episode of AKI between 1 January 2009 and 31 December 2009. AKI was defined using the creatinine-based Kidney Disease: Improving Global Outcomes definition. Associations between recurrent AKI and mortality were examined using a Cox proportional hazards model. Results Survival was worse in the group identified to have recurrent AKI compared with those with a single episode of AKI [hazard ratio = 1.49, 95% confidence interval (CI) 1.37–1.63; P Conclusions Recurrent AKI is associated with increased mortality. After adjusting for patient characteristics, the increase in mortality is independently associated with recurrent AKI and is not solely explained by other risk factors.

Background Acute kidney injury (AKI) is a common complication in patients during intensive care unit (ICU) admission. AKI is defined as an increase in serum creatinine (SCr) and/or a reduction in urine output. SCr is a marker of renal function with several limitations, which led to the search for biomarkers for earlier AKI detection. Our aim was to study the predictive value of plasma neutrophil gelatinase-associated lipocalin (NGAL) at admission as a biomarker for AKI progression during the first 48 h of ICU admission in an unselected, heterogeneous ICU patient population. Methods We conducted a prospective observational study in an academic tertiary referral ICU population. We recorded AKI progression in all ICU patients during the first 48 h of ICU admission in a 6-week period. Plasma NGAL was measured at admission but levels were not reported to the attending clinicians. As possible predictors of AKI progression, pre-existing AKI risk factors were recorded. We examined the association of clinical parameters and plasma NGAL levels at ICU admission with the incidence and progression of AKI within the first 48 h of the ICU stay. Results A total of 361 patients were included. Patients without AKI progression during the first 48 h of ICU admission had median NGAL levels at admission of 115 ng/mL [interquartile range (IQR) 81–201]. Patients with AKI progression during the first 48 h of ICU admission had median NGAL levels at admission of 156 ng/mL (IQR 97–267). To predict AKI progression, a multivariant model with age, sex, diabetes mellitus, body mass index, admission type, Acute Physiology and Chronic Health Evaluation score and SCr at admission had an area under the receiver operating characteristics (ROC) curve of 0.765. Adding NGAL to this model showed a small increase in the area under the ROC curve to 0.783 (95% confidence interval 0.714–0.853). Conclusions NGAL levels at admission were higher in patients with progression of AKI during the first 48 h of ICU admission, but adding NGAL levels at admission to a model predicting this AKI progression showed no significant additive value.

Background Respiratory tract infections (RTIs) are a common reason for people to seek medical care. RTIs are associated with high short-term mortality. Inconsistent evidence exists in the association between the presence of kidney disease and the risk of death in patient with RTIs. Methods We searched the PubMed, Cochrane Library and Embase databases from inception through April 2019 for cohort and case–control studies investigating the presence of kidney disease (defined as medical diagnosis of kidney disease, reduced estimated glomerular filtration rate or creatinine clearance, elevated serum creatinine and proteinuria) on mortality in adults with RTIs in different settings including community, inpatient and intensive care units. We assessed the quality of the included studies using Cochrane Collaboration’s tool and conducted a meta-analysis on the relative risk (RR) of death. Results Of 5362 records identified, 18 studies involving 16 676 participants met the inclusion criteria, with 15 studies investigating pneumonia and 3 studies exploring influenza. The risk of bias in the available evidence was moderate. Most [17/18 (94.5%)] of studies reported positive associations of underlying chronic kidney disease with mortality. The pooled adjusted risk for all-cause mortality in patients with RTIs almost doubled [RR 1.96 (95% confidence interval 1.48–2.59)] in patients with kidney disease. Associations were consistent across different timings of kidney disease assessment and provenances of RTIs (community-acquired or healthcare-associated). Conclusions The presence of kidney disease is associated with higher mortality among people with RTIs, especially in those with pneumonia. The presence of kidney disease might be taken into account when considering admission for patients who present with RTIs.

Chronic kidney disease (CKD) patients are at an increased risk of cardiovascular disease (CVD) and statins may not be protective in advanced CKD. The reasons for the limited efficacy of statins in advanced CKD are unclear, but statins may increase plasma levels of the highly atherogenic molecule lipoprotein(a), also termed Lp(a), as well as PCSK9 (protein convertase subtilisin/kexin type 9) levels. Lp(a) has also been linked to calcific aortic stenosis, which is common in CKD. Moreover, circulating Lp(a) levels increase in nephrotic syndrome with declining renal function and are highest in patients on peritoneal dialysis. Thus, the recent publication of the Phase 2 randomized controlled trial of pelacarsen [also termed AKCEA-APO(a)-LRx and TQJ230], a hepatocyte-directed antisense oligonucleotide targeting the LPA gene messenger RNA, in persons with CVD should be good news for nephrologists. Pelacarsen safely and dose-dependently decreased Lp(a) levels by 35–80% and a Phase 3 trial [Lp(a)HORIZON, NCT04023552] is planned to run from 2020 to 2024. Unfortunately, patients with estimated glomerular filtration rate 100 mg/g were excluded from Phase 2 trials and those with ‘significant kidney disease’ will be excluded from the Phase 3 trial. Optimized exclusion criteria for Lp(a)HORIZON would provide insights into the role of Lp(a) in CVD in CKD patients.

Background Serum anti-Müllerian hormone (AMH) is a biomarker of ovarian reserve. There are limited data to guide the clinical interpretation of AMH in women with chronic kidney disease (CKD). The purpose of this study was to examine AMH concentrations in women with CKD compared with women without CKD. Methods We conducted a prospective cohort study of serum AMH concentrations in 163 non-pregnant women with CKD. Serum AMH concentrations were compared with age-specific AMH centiles from 887 healthy female controls. Results Participants included 30 women with Stage 1 CKD, 37 women with Stage 2 CKD, 26 women with Stage 3a CKD, 31 women with Stage 3b CKD and 39 women with Stages 4 and 5 CKD. The median estimated glomerular filtration rate (eGFR) was 51 (interquartile range 31–80) mL/min/1.73 m2. Serum AMH concentrations were lower in all CKD stages compared with women without CKD. Women ages 20–24 years with CKD had comparable serum AMH concentrations (median 1.959 ng/mL) to women ages 35–39 years without CKD (median 1.995 ng/mL). There was no evidence that eGFR was an independent modifier of serum AMH concentrations. More than half of women with CKD (58%) were predicted to have a low response to gonadotrophin stimulation. Conclusions Women with CKD have a lower ovarian reserve and are predicted to have a lower ovarian response to gonadotrophin stimulation compared with women without CKD of a similar age. Women with CKD who fail to conceive within 6 months of regular unprotected intercourse should be considered for fertility assessment and intervention.