Glomerular crescents are associated with the risk of type 2 diabetic kidney disease progression: a retrospective cohort study.

BACKGROUND: Diabetic kidney disease (DKD) stands as the predominant cause of chronic kidney disease and end-stage kidney disease. Its diverse range of manifestations complicates the treatment approach for patients. Although kidney biopsy is considered the gold standard for diagnosis, it lacks precision in predicting the progression of kidney dysfunction. Herein, we addressed whether the presence of glomerular crescents is linked to the outcomes in patients with biopsy-confirmed type 2 DKD. METHODS: We performed a retrospective evaluation, involving 327 patients diagnosed with biopsy-confirmed DKD in the context of type 2 diabetes, excluding cases with other glomerular diseases, from nine tertiary hospitals. Hazard ratios (HRs) were calculated using a Cox regression model to assess the risk of kidney disease progression, defined as either ≥ 50% decrease in estimated glomerular filtration rates or the development of end-stage kidney disease, based on the presence of glomerular crescents. RESULTS: Out of the 327 patients selected, ten patients had glomerular crescents observed in their biopsied tissues. Over the follow-up period (median of 19 months, with a maximum of 18 years), the crescent group exhibited a higher risk of kidney disease progression than the no crescent group, with an adjusted HR of 2.82 (1.32-6.06) (P = 0.008). The presence of heavy proteinuria was associated with an increased risk of developing glomerular crescents. CONCLUSION: The presence of glomerular crescents is indeed linked to the progression of type 2 DKD. Therefore, it is important to determine whether there is an additional immune-mediated glomerulonephritis requiring immunomodulation, and it may be prudent to monitor the histology and repeat a biopsy.

Air quality and kidney health: Assessing the effects of PM10, PM2.5, CO, and NO2 on renal function in primary glomerulonephritis.

BACKGROUND: While extensive studies have elucidated the relationships between exposure to air pollution and chronic diseases, such as cardiovascular disorders and diabetes, the intricate effects on specific kidney diseases, notably primary glomerulonephritis (GN)-an immune-mediated kidney ailment-are less well understood. Considering the escalating incidence of GN and conspicuous lack of investigative focus on its association with air quality, investigation is dedicated to examining the long-term effects of air pollutants on renal function in individuals diagnosed with primary GN. METHODS: This retrospective cohort analysis was conducted on 1394 primary GN patients who were diagnosed at Seoul National University Bundang Hospital and Seoul National University Hospital. Utilizing time-varying Cox regression and linear mixed models (LMM), we examined the effect of yearly average air pollution levels on renal function deterioration (RFD) and change in estimated glomerular filtration rate (eGFR). In this context, RFD is defined as sustained eGFR of less than 60 mL/min per 1.73 m2. RESULTS: During a mean observation period of 5.1 years, 350 participants developed RFD. Significantly, elevated interquartile range (IQR) levels of air pollutants-including PM10 (particles ≤10 micrometers, HR 1.389, 95 % CI 1.2-1.606), PM2.5 (particles ≤2.5 micrometers, HR 1.353, 95 % CI 1.162-1.575), CO (carbon monoxide, HR 1.264, 95 % CI 1.102-1.451), and NO2 (nitrogen dioxide, HR 1.179, 95 % CI 1.021-1.361)-were significantly associated with an increased risk of RFD, after factoring in demographic and health variables. Moreover, exposure to PM10 and PM2.5 was associated with decreased eGFR. CONCLUSIONS: This study demonstrates a substantial link between air pollution exposure and renal function impairment in primary GN, accentuating the significance of environmental determinants in the pathology of immune-mediated kidney diseases.

The Impact of Obesity on Kidney Disease: Observational Cohort Study Analyzing 14,492 Kidney Biopsy Cases.

BACKGROUND: The obesity epidemic is associated with the emergence of new kidney diseases including obesity-related glomerulopathy (ORG) and metabolic syndrome-associated disorders. However, the effects of obesity on prevalence and outcome of biopsy-proven kidney disease are not well known. METHODS: We analyzed 14,492 kidney biopsies in 18 hospitals from 1979 to 2018 in Korea. Obesity was defined as a body mass index value of ≥ 30 kg/m². RESULTS: The most common disease was IgA nephropathy (IgAN) in both obese and non-obese participants (33.7% vs. 38.9%). Obesity was associated with a higher risk of focal segmental glomerulosclerosis (FSGS) and hypertensive nephropathy (HT-N) (odds ratio [OR], 1.72, 95% confidence interval [CI], 1.37-2.17; OR, 1.96, 95% CI, 1.21-3.19) and a lower risk of IgAN (OR, 0.74, 95% CI, 0.62-0.88). During the median follow up of 93.1 ± 88.7 months, obesity increased the risk of end-stage kidney disease (ESKD) in patients with IgAN (relative risk [RR], 1.49, 95% CI, 1.01-2.20) and lupus nephritis (LN) (RR, 3.43, 95% CI, 1.36-8.67). Of 947 obese individuals, ORG was detected in 298 (31.5%), and 230 participants had other kidney diseases, most commonly, IgAN (40.9%) followed by diabetic nephropathy (15.2%). Participants with ORG, when combined with other renal diseases, showed higher risks for developing ESKD compared to those with ORG alone (RR, 2.48, 95% CI, 1.09-5.64). CONCLUSION: Obesity is associated with an increased risk of FSGS and HT-N, and also increase the ESKD risk in IgAN and LN patients. ORG in obese participants may have favorable renal outcomes if it occurs alone without any other renal disease.

Characterizing Glomerular Barrier Dysfunction with Patient-Derived Serum in Glomerulus-on-a-Chip Models: Unveiling New Insights into Glomerulonephritis.

Glomerulonephritis (GN) is characterized by podocyte injury or glomerular filtration dysfunction, which results in proteinuria and eventual loss of kidney function. Progress in studying the mechanism of GN, and developing an effective therapy, has been limited by the absence of suitable in vitro models that can closely recapitulate human physiological responses. We developed a microfluidic glomerulus-on-a-chip device that can recapitulate the physiological environment to construct a functional filtration barrier, with which we investigated biological changes in podocytes and dynamic alterations in the permeability of the glomerular filtration barrier (GFB) on a chip. We also evaluated the potential of GN-mimicking devices as a model for predicting responses to human GN. Glomerular endothelial cells and podocytes successfully formed intact monolayers on opposite sides of the membrane in our chip device. Permselectivity analysis confirmed that the chip was constituted by a functional GFB that could accurately perform differential clearance of albumin and dextran. Reduction in cell viability resulting from damage was observed in all serum-induced GN models. The expression of podocyte-specific marker WT1 was also decreased. Albumin permeability was increased in most models of serum-induced IgA nephropathy (IgAN) and membranous nephropathy (MN). However, sera from patients with minimal change disease (MCD) or lupus nephritis (LN) did not induce a loss of permeability. This glomerulus-on-a-chip system may provide a platform of glomerular cell culture for in vitro GFB in formation of a functional three-dimensional glomerular structure. Establishing a disease model of GN on a chip could accelerate our understanding of pathophysiological mechanisms of glomerulopathy.

Economic Impact of Donating a Kidney on Living Donors: A Korean Cohort Study.

RATIONALE & OBJECTIVE: Although existing studies have reported adverse health outcomes after kidney donation, its socioeconomic impact on living donors requires further study. STUDY DESIGN: A retrospective observational cohort study including a matched comparison group. SETTING & PARTICIPANTS: 1,285 living kidney donors from 7 tertiary hospitals between 2003 and 2016, and a matched comparison group consisting of the same number of health screening examinees with similar baseline clinical characteristics and socioeconomic status. All participants were receiving Korean national health insurance. EXPOSURE: Kidney donation as reflected in the Korean National Health Insurance System (NHIS) database. OUTCOME: Changes in household economic status estimated by Korean national health insurance fees and changes in employment status reflected in the NHIS database. ANALYTICAL APPROACH: The outcomes of the donor group and matched control group were compared annually using multivariable logistic regression analyses adjusted for clinical and demographic characteristics. RESULTS: The median ages of the donors and matched controls were 45 and 46 years, respectively; 44.6% of both groups were male. Compared to the comparison group, living donors were at higher risk of being unemployed or losing employment during the first 2 years after donation (eg, first-year loss of employment: odds ratio (OR), 2.27 [95% CI, 1.55-3.33]); however, this association did not persist. Donors also had a significantly lower odds of improvement in economic status (OR, 0.57 [95% CI, 0.47-0.71]) and a higher odds of deterioration in financial status (OR, 1.54 [95% CI, 1.23-1.93]) in the first year after transplantation and subsequently. LIMITATIONS: Unmeasured differences between donors and matched controls creating residual selection bias and confounding. CONCLUSIONS: Living kidney donors may suffer loss of employment and poor economic status after their voluntary donation. The socioeconomic impact on these donors should be considered in conjunction with the potential long-term adverse health outcomes after donation.

Comparison of the Efficacy and Safety of Tacrolimus and Low-Dose Corticosteroid with High-Dose Corticosteroid for Minimal Change Nephrotic Syndrome in Adults.

BACKGROUND: Tacrolimus is used as a steroid-sparing immunosuppressant in adults with minimal change nephrotic syndrome. However, combined treatment with tacrolimus and low-dose steroid has not been compared with high-dose steroid for induction of clinical remission in a large-scale randomized study. METHODS: In this 24-week open-label noninferiority study, we randomized 144 adults with minimal change nephrotic syndrome to receive 0.05 mg/kg twice-daily tacrolimus plus once-daily 0.5 mg/kg prednisolone, or once-daily 1 mg/kg prednisolone alone, for up to 8 weeks or until achieving complete remission. Two weeks after complete remission, we tapered the steroid to a maintenance dose of 5-7.5 mg/d in both groups until 24 weeks after study drug initiation. The primary end point was complete remission within 8 weeks (urine protein: creatinine ratio <0.2 g/g). Secondary end points included time until remission and relapse rates (proteinuria and urine protein: creatinine ratio >3.0 g/g) after complete remission to within 24 weeks of study drug initiation. RESULTS: Complete remission within 8 weeks occurred in 53 of 67 patients (79.1%) receiving tacrolimus and low-dose steroid and 53 of 69 patients (76.8%) receiving high-dose steroid; this difference demonstrated noninferiority, with an upper confidence limit below the predefined threshold (20%) in both intent-to-treat (11.6%) and per-protocol (17.0%) analyses. Groups did not significantly differ in time until remission. Significantly fewer patients relapsed on maintenance tacrolimus (3-8 ng/ml) plus tapered steroid versus tapered steroid alone (5.7% versus 22.6%, respectively; P=0.01). There were no clinically relevant safety differences. CONCLUSIONS: Combined tacrolimus and low-dose steroid was noninferior to high-dose steroid for complete remission induction in adults with minimal change nephrotic syndrome. Relapse rates were significantly lower with maintenance tacrolimus and steroid compared with steroid alone. No clinically-relevant differences in safety findings were observed.

Renal outcomes in adult patients with horseshoe kidney.

BACKGROUND: Horseshoe kidney (HSK) is a congenital disorder that is usually asymptomatic, but that increases the risks of kidney stones and infectious disease. However, renal outcomes such as end-stage renal disease (ESRD) in patients with HSK remain unclear. METHODS: In total, 146 patients with HSK (age of ≥20 years) from two tertiary hospitals were included in this study. Control individuals who underwent medical check-ups were selected by matching for age, sex, serum creatinine level, hypertension and diabetes. The hazard ratios (HRs) for the risks of ESRD and all-cause mortality were calculated after adjustment for multiple variables. RESULTS: The proportions of HSK-related complications for obstruction, kidney stones, urinary tract infection and urogenital cancer were 26, 25, 19 and 4%, respectively. During the median follow-up period of 9 years (maximum 32 years), the incidence of ESRD was 2.6/10 000 person-years. The risk of ESRD in patients with HSK was higher than in control individuals [adjusted HR = 7.6; 95% confidence interval (CI) 1.14-50.47]. All-cause mortality did not differ between the two groups (adjusted HR = 0.6; 95% CI 0.08-4.29). CONCLUSIONS: Patients with HSK are at risk of ESRD, which may be attributable to the high prevalence of complications. Accordingly, these patients should be regarded as having chronic kidney disease and require regular monitoring of both kidney function and potential complications.

Real-Time Clinical Decision Support Based on Recurrent Neural Networks for In-Hospital Acute Kidney Injury: External Validation and Model Interpretation.

BACKGROUND: Acute kidney injury (AKI) is commonly encountered in clinical practice and is associated with poor patient outcomes and increased health care costs. Despite it posing significant challenges for clinicians, effective measures for AKI prediction and prevention are lacking. Previously published AKI prediction models mostly have a simple design without external validation. Furthermore, little is known about the process of linking model output and clinical decisions due to the black-box nature of neural network models. OBJECTIVE: We aimed to present an externally validated recurrent neural network (RNN)-based continuous prediction model for in-hospital AKI and show applicable model interpretations in relation to clinical decision support. METHODS: Study populations were all patients aged 18 years or older who were hospitalized for more than 48 hours between 2013 and 2017 in 2 tertiary hospitals in Korea (Seoul National University Bundang Hospital and Seoul National University Hospital). All demographic data, laboratory values, vital signs, and clinical conditions of patients were obtained from electronic health records of each hospital. We developed 2-stage hierarchical prediction models (model 1 and model 2) using RNN algorithms. The outcome variable for model 1 was the occurrence of AKI within 7 days from the present. Model 2 predicted the future trajectory of creatinine values up to 72 hours. The performance of each developed model was evaluated using the internal and external validation data sets. For the explainability of our models, different model-agnostic interpretation methods were used, including Shapley Additive Explanations, partial dependence plots, individual conditional expectation, and accumulated local effects plots. RESULTS: We included 69,081 patients in the training, 7675 in the internal validation, and 72,352 in the external validation cohorts for model development after excluding cases with missing data and those with an estimated glomerular filtration rate less than 15 mL/min/1.73 m2 or end-stage kidney disease. Model 1 predicted any AKI development with an area under the receiver operating characteristic curve (AUC) of 0.88 (internal validation) and 0.84 (external validation), and stage 2 or higher AKI development with an AUC of 0.93 (internal validation) and 0.90 (external validation). Model 2 predicted the future creatinine values within 3 days with mean-squared errors of 0.04-0.09 for patients with higher risks of AKI and 0.03-0.08 for those with lower risks. Based on the developed models, we showed AKI probability according to feature values in total patients and each individual with partial dependence, accumulated local effects, and individual conditional expectation plots. We also estimated the effects of feature modifications such as nephrotoxic drug discontinuation on future creatinine levels. CONCLUSIONS: We developed and externally validated a continuous AKI prediction model using RNN algorithms. Our model could provide real-time assessment of future AKI occurrences and individualized risk factors for AKI in general inpatient cohorts; thus, we suggest approaches to support clinical decisions based on prediction models for in-hospital AKI.

Role of Human Primary Renal Fibroblast in TGF-ß1-Mediated Fibrosis-Mimicking Devices.

Renal fibrosis is a progressive chronic kidney disease that ultimately leads to end-stage renal failure. Despite several approaches to combat renal fibrosis, an experimental model to evaluate currently available drugs is not ideal. We developed fibrosis-mimicking models using three-dimensional (3D) co-culture devices designed with three separate layers of tubule interstitium, namely, epithelial, fibroblastic, and endothelial layers. We introduced human renal proximal tubular epithelial cells (HK-2), human umbilical-vein endothelial cells, and patient-derived renal fibroblasts, and evaluated the effects of transforming growth factor-ß (TGF-ß) and TGF-ß inhibitor treatment on this renal fibrosis model. The expression of the fibrosis marker alpha smooth muscle actin upon TGF-ß1 treatment was augmented in monolayer-cultured HK-2 cells in a 3D disease model. In the vascular compartment of renal fibrosis models, the density of vessels was increased and decreased in the TGF-ß-treated group and TGF-ß-inhibitor treatment group, respectively. Multiplex ELISA using supernatants in the TGF-ß-stimulating 3D models showed that pro-inflammatory cytokine and growth factor levels including interleukin-1 beta, tumor necrosis factor alpha, basic fibroblast growth factor, and TGF-ß1, TGF-ß2, and TGF-ß3 were increased, which mimicked the fibrotic microenvironments of human kidneys. This study may enable the construction of a human renal fibrosis-mimicking device model beyond traditional culture experiments.

Predictive value of mesangial C3 and C4d deposition in IgA nephropathy.

We aimed to determine the relative contribution of each complement (C3 and C4d) deposition to the progression of IgA nephropathy (IgAN). We enrolled a total of 380 patients with biopsy-confirmed IgAN. Mesangial deposition of C3(<2+ vs. ≥2+) and C4d(positive vs. negative) was evaluated by immunofluorescence staining and immunohistochemistry, respectively. Study endpoint was the composite of a 30% decline in eGFR or ESRD. The risk of reaching the primary outcome was significantly higher in patients having C3 ≥ 2+ and C4d(+) than in corresponding counterparts. Adding C3 deposition to clinical data acquired at kidney biopsy modestly increased the area under the receiver-operating characteristic curve, net reclassification improvement, and integrated discrimination improvement (IDI); adding C4d increased IDI only. In conclusion, mesangial C3 and C4d deposition was an independent risk factor for progression of IgAN. C3 showed better predictability than C4d, suggesting that lectin pathway alone has limited clinical prognostic value.

Relationship between complement deposition and the Oxford classification score and their combined effects on renal outcome in immunoglobulin A nephropathy.

BACKGROUND: Complement activation has been highlighted in immunoglobulin (Ig) A nephropathy pathogenesis. However, whether the complement system can affect the downstream phenotype of IgA nephropathy remains unknown. Herein, we investigated the association of mesangial C3 deposition with the Oxford classification and their joint effects on worsening kidney function. METHODS: We investigated 453 patients with biopsy-proven IgA nephropathy. C3 deposition was defined as an immunofluorescence intensity of C3 ≥2+ within the mesangium. The subjects were classified according to the combination of C3 deposition and Oxford classification lesions. The primary endpoint was a composite of ≥30% decline in the estimated glomerular filtration rate or an increase in proteinuria ≥3.5 g/g during follow-up. RESULTS: Among the Oxford classification lesions, mesangial hypercellularity (M1), segmental glomerulosclerosis (S1) and tubulointerstitial fibrosis (T1-2) and crescentic lesion significantly correlated with C3 deposition. During a median follow-up of 33.0 months, the primary endpoint occurred more in patients with M1, S1, T1-2 and mesangial C3 deposition than in those without. In individual multivariable-adjusted Cox analyses, the presence of M1, S1, T1-2 and C3 deposition was significantly associated with higher risk of reaching primary endpoint. In the combined analyses of C3 deposition and the Oxford classification lesions, the hazard ratios for the composite outcome were significantly higher in the presence of C3/M1, C3/S1 and C3/crescent than in the presence of each lesion alone. CONCLUSIONS: Complement deposition can strengthen the significance of the Oxford classification, and the presence of both components portends a poorer prognosis in IgA nephropathy.

Cancer development and mortality differences in patients with glomerulonephritis after renal biopsy: a single center retrospective cohort study.

BACKGROUND: The association between glomerulonephritis (GN) and cancer has been well known for decades. However, studies evaluating long-term de novo cancer development in patients with GN are limited. This study aimed to evaluate the incidence of cancer development among patients with renal biopsy-proven GN during post-biopsy follow-up and the differences in outcomes according to cancer occurrence. METHODS: We conducted a retrospective cohort study of adult patients who underwent renal biopsy at Seoul National Bundang Hospital between 2003 and 2017. After excluding 778 patients with age < 18 years, cancer diagnosis before or within 6 months after renal biopsy, immunosuppressant therapy before renal biopsy, or pathologic diagnoses other than GN, 822 patients were included in the analysis. Data on baseline clinical characteristics, renal biopsy results, and types and doses of immunosuppressant agents were collected from electronic medical records. The incidence of cancer was censored on the date when the first cancer was diagnosed. We evaluated rates of mortality and end-stage renal disease (ESRD) development during follow-up. RESULTS: During a mean follow-up period of 58.9 ± 44.5 months, 45 subjects (5.5%) developed de novo cancer. A comparison of clinical characteristics between subjects who did and did not develop cancer revealed that cancer patients were older and had higher comorbidities and immunosuppressant use. Overall, patients with GN had an elevated standardized incidence ratio (SIR) of 7.16 (95% confidence interval (CI): 5.22-9.61) relative to the age- and sex-matched general population. In particular, the SIR was significantly higher in GNs such as membranous nephropathy (MN), IgA nephropathy, lupus nephritis, and focal segmental glomerulosclerosis. Multivariable Cox proportional hazard model revealed that patients with MN had an increased risk of cancer development, with a hazard ratio of 2.30 [95% CI: 1.06-4.98]. Patients with MN who developed cancer had a significantly higher risk of mortality (hazard ratio: 6.59; 95% CI: 1.22-35.56, P = 0.03) than those without cancer, but there was a non-significant difference in ESRD development. CONCLUSIONS: Patients with GN without concurrent cancer, particularly those with MN, have significantly higher risks of cancer development and subsequent mortality and should remain aware of the potential development of malignancy during follow-up.

Association between Serum Uric Acid Level and ESRD or Death in a Korean Population.

BACKGROUND: Serum uric acid (SUA) is recognized as a risk factor for chronic kidney disease (CKD) and mortality. However, there is controversy as to whether a high or low level of SUA is related to the risk of CKD progression or death, and whether it differs between males and females. METHODS: We included 143,762 adults who underwent voluntary health screening between 1995 and 2009 in Korea. For each sex, we divided participants into sex-specific quintiles according to SUA levels and compared end-stage renal disease (ESRD) incidence and mortality between the groups with low and high SUA levels and those with middle SUA levels. Sex-specific Cox proportional hazard analyses were performed for ESRD and all-cause mortality. RESULTS: Among the 143,762 participants, 0.2% (n = 272) developed ESRD. The hazard ratio (HR) of ESRD was higher in the highest (adjusted HR, 2.13; 95% confidence interval [CI], 1.18-3.84) and lowest (adjusted HR, 1.90; 95% CI, 1.02-3.51) SUA quintiles than in the middle SUA quintile in males and the highest SUA quintile in females (adjusted HR, 2.31; 95% CI, 1.10-4.84). Four-point three percent (n = 6,215) of participants died during a mean follow-up period of 157 months. The hazard ratio (HR) of all-cause mortality was higher in the highest SUA quintile than in the middle SUA quintile in males (adjusted HR, 1.15; 95% CI, 1.03-1.28) and females (adjusted HR, 1.17; 95% CI, 1.01-1.35). CONCLUSION: Elevated levels of SUA are associated with increased risk for ESRD and all-cause mortality in both sexes. Low levels of SUA might be related to ESRD and death only in males, showing U-shaped associations. Our findings suggest sex-specific associations between SUA levels and ESRD development and mortality.

Long-term Renal Outcome of Biopsy-proven Acute Tubular Necrosis and Acute Interstitial Nephritis.

BACKGROUND: Although emerging evidence suggest acute kidney injury (AKI) progress to chronic kidney disease (CKD), long-term renal outcome of AKI still remains unclear. Acute tubular necrosis (ATN) is the most common cause of AKI due to ischemia, toxin or sepsis. Acute interstitial nephritis (AIN), caused by drugs or autoimmune diseases is also increasingly recognized as an important cause of AKI. Unlike glomerular diseases, AKI is usually diagnosed in the clinical context without kidney biopsies, and lack of histology might contribute to this uncertainty. METHODS: Among 8,769 biopsy series, 253 adults who were histologically diagnosed with ATN and AIN from 1982 to 2018 at five university hospitals were included. Demographic and pathological features that are associated with the development of end stage renal disease (ESRD) were also examined. RESULTS: Rate of non-recovery of renal function at 6 month was significantly higher in the AIN (ATN vs AIN 49.3 vs 69.4%, P = 0.007) with a 2.71-fold higher risk of non- recovery compared to ATN (95% confidence interval [CI], 1.20-6.47). During the mean follow up of 76.5 ± 91.9 months, ESRD developed in 39.4% of patients with AIN, and 21.5% patients of ATN. The risk of ESRD was significantly higher in AIN (23.05; 95% CI, 2.42-219.53) and also in ATN (12.14; 95% CI, 1.19-24.24) compared to control with non-specific pathology. Older age, female gender, renal function at the time of biopsy and at 6 months, proteinuria and pathological features including interstitial inflammation and fibrosis, tubulitis, vascular lesion were significantly associated with progression to ESRD. CONCLUSION: Our study demonstrated that patients with biopsy proven ATN and AIN are at high risk of developing ESRD. AIN showed higher rate of non-renal recovery at 6 month than ATN.

Simple Postoperative AKI Risk (SPARK) Classification before Noncardiac Surgery: A Prediction Index Development Study with External Validation.

BACKGROUND: Researchers have suggested models to predict the risk of postoperative AKI (PO-AKI), but an externally validated risk index that can be practically implemented before patients undergo noncardiac surgery is needed. METHODS: We performed a retrospective observational study of patients without preexisting renal failure who underwent a noncardiac operation (≥1 hour) at two tertiary hospitals in Korea. We fitted a proportional odds model for an ordinal outcome consisting of three categories: critical AKI (defined as Kidney Disease Improving Global Outcomes AKI stage ≥2, post-AKI death, or dialysis within 90 days after surgery), low-stage AKI (defined as PO-AKI events not fulfilling the definition of critical AKI), and no PO-AKI. RESULTS: The study included 51,041 patients in a discovery cohort and 39,764 patients in a validation cohort. The Simple Postoperative AKI Risk (SPARK) index included a summation of the integer scores of the following variables: age, sex, expected surgery duration, emergency operation, diabetes mellitus, use of renin-angiotensin-aldosterone inhibitors, baseline eGFR, dipstick albuminuria hypoalbuminemia, anemia, and hyponatremia. The model calibration plot showed tolerable distribution of observed and predicted probabilities in both cohorts. The discrimination power of the SPARK index was acceptable in both the discovery (c-statistic 0.80) and validation (c-statistic 0.72) cohorts. When four SPARK classes were defined on the basis of the sum of the risk scores, the SPARK index and classes fairly reflected the risks of PO-AKI and critical AKI. CONCLUSIONS: Clinicians may consider implementing the SPARK index and classifications to stratify patients' PO-AKI risks before performing noncardiac surgery.

Relationships between the National Early Warning Score 2, clinical worry and patient outcome at discharge: Retrospective observational study.

AIMS AND OBJECTIVES: To examine the performance of the National Early Warning Score 2 and composite score for clinical worry in identifying patients at risk of clinical deterioration, and to determine relationships between National Early Warning Score 2, clinical worry score and patient outcome at discharge. BACKGROUND: The efficacy of early warning systems depends on patient population and care settings. Based on a theoretical framework on factors affecting clinical deterioration and patient outcomes, studies exploring the relationship between early warning systems and patient outcomes at discharge are sparse. DESIGN: Retrospective observational study. METHODS: A random sample of 732 medical records were reviewed. The area under the receiver operating characteristic curve was calculated to evaluate predictive abilities regarding the events of unanticipated in-hospital mortality, unplanned intensive care unit/ higher dependency bed admission and cardiac arrest. Multiple logistic regression analyses were performed to determine relationships between National Early Warning Score 2, clinical worry score and patient outcome. Reporting followed the STROBE checklist. RESULTS: National Early Warning Score 2 and clinical worry score significantly predicted the events within 24 hr of the assessment. After controlling for other patient, treatment and organisational characteristics, National Early Warning Score 2 was a significant factor associated with patient outcome, but clinical worry score was not. Specifically, patients at high risk based on National Early Warning Score 2 were less likely to have improved outcome. CONCLUSIONS: National Early Warning Score 2 and clinical worry score performed well for predicting deteriorating condition of patients. National Early Warning Score 2 was significantly associated with patient outcome. It can be used for efficient patient management for safe, quality care. RELEVANCE TO CLINICAL PRACTICE: National Early Warning Score 2 can be used for early assessment of not only clinical deterioration but also patient outcome and provide timely intervention, when coupled with clinical worry score.

Long-Term Effects of Intensive Low-Salt Diet Education on Deterioration of Glomerular Filtration Rate among Non-Diabetic Hypertensive Patients with Chronic Kidney Disease.

BACKGROUND: Diet modification, especially a decrease in salt intake, might be an important non-pharmacological strategy to improve chronic kidney disease (CKD) prognosis. OBJECTIVES: We conducted a prospective cohort study to investigate whether an intensive low-salt diet education program effectively attenuated the rate of renal function decline in hypertensive patients with CKD. METHODS: This cohort study recruited 171 participants from a previous open-labelled, case-controlled, randomized clinical trial that originally consisted of 245 hypertensive CKD patients who were assigned to two groups, intensive low-salt diet or conventional education. We evaluated the renal outcomes, which included the rate of change in estimated glomerular filtration rate (eGFR) per year, the increase in serum creatinine ≥50%, the decrease in eGFR ≥30%, and the percent change in albuminuria throughout the entire study period. RESULTS: The baseline characteristics of the cohort participants between the two groups were similar at the time of trial phase randomization. During the whole study period, the rate of renal function decline was significantly faster in the conventional group (0.11 ± 4.63 vs. -1.53 ± 3.04 mL/min/1.73 m2/year, p = 0.01). The percent of incremental change in serum creatinine ≥50% was 1.1% in the intensive group and 8.2% in the conventional group (p = 0.025), and the percent of decremental change in eGFR ≥30% was 3.3% in the intensive group and 11.1% in the conventional group (p= 0.048). With logistic regression analysis adjusted for related factors, we found that the conventional group showed a higher risk for deterioration in serum creatinine and eGFR during the entire study period. Especially, we found that the intensive education program preserved eGFR in participants with one, several, or all of the following characteristics at the time of randomization: older age, female, obese, had higher protein intake, higher amounts of albuminuria, higher salt intake. CONCLUSION: This cohort study demonstrated that an intensive low-salt diet education program attenuated the rate of renal function decline in hypertensive CKD patients independent of its effect on lowering salt intake or albuminuria during the 36 months of follow-up.

Clinical Significance of Crescent Formation in IgA Nephropathy - a Multicenter Validation Study.

BACKGROUND/AIMS: Additional validation study was warranted to confirm the clinical significance of C score, which was recently added to the Oxford classification for immunoglobulin A nephropathy (IgAN). METHODS: We performed a multicenter retrospective cohort study in four hospitals in Korea. Patients who had biopsied glomeruli less than eight or inadequate follow-up information were excluded. Clinicopathologic parameters, including the degree of cellular or fibrocellular crescents, were collected and included in multivariable models for Cox regression analysis. The main outcome was a composite renal outcome, defined as a merge of progression to end-stage renal disease (ESRD) and halving of estimated glomerular filtration rate (eGFR) from baseline. RESULTS: Among included 3,380 biopsy-confirmed IgAN patients, there were 664 (19.6%) patients with C1 and 60 (1.8%) patients with C2 scores in the study population. Although C0 and C1 patients shared similar baseline characteristics, C2 patients frequently had more clinicopathologic risk factors for poor prognosis of IgAN. Both C1 [adjusted HR 1.33 (1.11-1.58), P=0.002] and C2 [adjusted HR 2.24 (1.46-3.43), P< 0.001] scores were associated with an increased risk of the composite outcome. C2 was a strong predictive parameter associated with both progression to ESRD and halving of eGFR, whereas C1 was mainly associated with the increased risk of halving of eGFR. Notably, the proportion of crescent showed a linear association with the risk of adverse renal outcome. CONCLUSION: The C score in the Oxford classification is a valid predictive parameter for IgAN prognosis. Additional clinical attention is necessary for IgAN patients with identified cellular or fibrocellular crescents.

Hyperuricemia is associated with acute kidney injury and all-cause mortality in hospitalized patients.

AIM: Hyperuricemia is a risk factor for high morbidity and mortality in several diseases. However, the relationship between uric acid (UA) and the risk of acute kidney injury (AKI) and mortality remain unresolved in hospitalized patients. METHODS: Data from 18 444 hospitalized patients were retrospectively reviewed. The odds ratio (OR) for AKI and the hazard ratio (HR) for all-cause mortality were calculated based on the UA quartiles after adjustment for multiple variables. All analyses were performed after stratification by sex. RESULTS: The fourth quartile group (male, UA > 6.7 mg/dL; female, UA > 5.4 mg/dL) showed a higher risk of AKI compared with the first quartile group (male, UA < 4.5 mg/dL; female, UA < 3.6 mg/dL), with the following OR: 3.2 (2.55-4.10) in males (P < 0.001); and 3.1 (2.40-4.19) in females (P < 0.001). There were more patients who did not recover from AKI in the fourth quartile compared with the first quartile, with the following OR: 2.0 (1.32-3.04) in males (P = 0.001) and 2.4 (1.43-3.96) in females (P = 0.001). The fourth quartile group had a higher risk of all-cause mortality compared with the first quartile group, with the following HR: 1.4 (1.20-1.58) in males (P < 0.001) and 1.2 (1.03-1.46) in females (P = 0.019). The in-hospital mortality risk was also higher in the fourth quartile compared with the first quartile, which was significant only in males (OR, 2.1 (1.33-3.31) (P = 0.002)). CONCLUSION: Hyperuricemia increases the risks of AKI and all-cause mortality in hospitalized patients.

Development of a new mortality scoring system for acute kidney injury with continuous renal replacement therapy.

AIM: On the basis of the worst outcomes of patients undergoing continuous renal replacement therapy (CRRT) in intensive care unit, previously developed mortality prediction model, Acute Physiologic Assessment and Chronic Health Evaluation II (APACHE II) and the Sequential Organ Failure Assessment (SOFA) needs to be modified. METHODS: A total of 828 patients who underwent CRRT were recruited. Mortality prediction model was developed for the prediction of death within 7 days after starting the CRRT. Based on regression analysis, modified scores were assigned to each variable which were originally used in the APACHE II and SOFA scoring models. Additionally, a new abbreviated Mortality Scoring system for AKI with CRRT (MOSAIC) was developed after stepwise selection analysis. RESULTS: We used all the variables included in the APACHE II and SOFA scoring models. The prediction powers indicated by C-statistics were 0.686 and 0.683 for 7-day mortality by the APACHE II and SOFA systems, respectively. After modification of these models, the prediction powers increased up to 0.752 for the APACHE II and 0.724 for the SOFA systems. Using multivariate analysis, seven significant variables were selected in the MOSAIC model wherein its C-statistic value was 0.772. These models also showed good performance with 0.720, 0.734 and 0.773 of C-statistics in the modified APACHE II, modified SOFA and MOSAIC scoring models in the external validation cohort (n = 497). CONCLUSION: The modified APACHE II/SOFA and newly developed MOSAIC models could be more useful tool for predicting mortality for patients receiving CRRT.