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. =E2=89=A52+) 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=E2=89=A52+ 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. Copyright =C2=A9 2020 Elsevier Inc. All rights reserved.

AimRenal hyperfiltration (RHF) is a marker of early kidney injury that was recently shown to be a novel marker of mortality. However, it has no clear definition. In this study, we suggested an age- and sex-adjusted RHF definition and explored the association between RHF and mortality by sex. MethodsWe analyzed data from individuals receiving routine health examinations from 1995 to 2009. RHF was defined as an estimated glomerular filtration rate over the 95th percentile matched for age and sex. ResultsA total of 114966 individuals were included. During the 75-month of observation period, 2559 (2.2%) participants died. Among those, 71.4% were men. Because sex and RHF had a significant interaction for mortality (P for interaction<0.001), we performed survival analysis according to sex. RHF was related to lower body weight and a higher proportion of cigarette smoking in men, whereas these relationships were not found in women. In the Kaplan-Meier curve, RHF was associated with higher mortality rate than non-RHF in both sexes, but this relationship was more prominent in men. In the multivariate analysis, RHF remained as an independent risk factor for all-cause mortality even after adjustment for confounding in men (hazard ratio, 1.34; 95% confidence interval, 1.12-1.59; P=3D0.001). In women, RHF was not associated with increased mortality. ConclusionsWe demonstrated that RHF was a significant risk factor for mortality in men but not in women. The mechanisms and clinical implications of these different associations according to sex require a further clarification. Summary at a Glance Renal hyperfiltration is a risk factor for renal decline and mortality. This paper has the novel finding of only being able to demonstrate this association in men.

BackgroundWith evaluation for physical performance, measuring muscle mass is an important step in detecting sarcopenia. However, there are no methods to estimate muscle mass from blood sampling.MethodsTo develop a new equation to estimate total-body muscle mass with serum creatinine and cystatin C level, we designed a cross-sectional study with separate derivation and validation cohorts. Total body muscle mass and fat mass were measured using dual-energy x-ray absorptiometry (DXA) in 214 adults aged 25 to 84 years who underwent physical checkups from 2010 to 2013 in a single tertiary hospital. Serum creatinine and cystatin C levels were also examined.ResultsSerum creatinine was correlated with muscle mass (P < .001), and serum cystatin C was correlated with body fat mass (P < .001) after adjusting glomerular filtration rate (GFR). After eliminating GFR, an equation to estimate total-body muscle mass was generated and coefficients were calculated in the derivation cohort. There was an agreement between muscle mass calculated by the novel equation and measured by DXA in both the derivation and validation cohort (P < .001, adjusted R-2 =3D 0.829, beta =3D 0.95, P < .001, adjusted R-2 =3D 0.856, beta =3D 1.03, respectively).ConclusionThe new equation based on serum creatinine and cystatin C levels can be used to estimate total-body muscle mass.

BACKGROUND: longitudinal relationship between renal function, disability and mortality has not been evaluated.; OBJECTIVE: we investigated the temporal association between renal function and disability, and aimed to identify the influence of disability on mortality according to renal function in a cohort of older Koreans.; DESIGN/SETTING: Korean Longitudinal Study on Health and Aging is a prospective, population-based cohort.; SUBJECTS: community-dwelling Koreans =E2=89=A565 years of age.; MAIN OUTCOME MEASURES: Korean version of activities of daily living (ADL), Instrumental activities of daily living (IADL) and all-cause mortality.; RESULTS: a total of 984 participants were followed for 5 years with a 70.9% participation rate. The participants were categorized into three groups according to their baseline estimated glomerular filtration rates (eGFRs) (Group I, =E2=89=A560; Group II, 45-59; and Group III, <45 ml/min/1.73 m(2)). Baseline eGFR was higher in participants who maintained functional status compared with participants who died or had disability at follow-up examination. The incidence of ADL/IADL decline was 13, 12.5 and 29.5% in participants who showed improvement, no change, and decline in renal function, respectively (P =3D 0.01). The hazard ratio for mortality in the subgroup with IADL disability was 1.87 (95% CI: 1.10-3.20, P =3D 0.022) in Group I, and 2.53 (95% CI: 1.57-4.09, P<0.001) in Groups II and III after adjustment.; CONCLUSIONS: impaired renal function was related to disability and ADL/IADL decline. The effect of ADL/IADL disability on mortality was more prominent in participants with impaired eGFR. =C2=A9 The Author 2014. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Background. Diagnosis of acute kidney injury (AKI) has been a major concern due to its association with increased morbidity and mortality. However, the clinical implication of the urine output criterion (UOCr) in diagnosing AKI has not been fully established. Methods. We assessed the incidence of AKI among 1625 critically ill patients and analysed the overall survival rates based on the serum creatinine criterion (CrCr) and UOCr, both of which have been defined by the AKI Network (AKIN). Results. Within 7 days of admission, the risk rate of AKI was 57.0% and the rate determined by UOCr alone was 25.7%. AKI determined by the UOCr alone increased hazard ratios (HRs) for mortality; 1.81 (Stage 1), 2.96 (Stage 2) and 4.17 (Stage 3) compared to non-AKI. However, the difference in mortality between Stages 2 and 3 using the CrCr alone was not significant (P = 0.881). In patients with Stages 2 and 3 by the CrCr, the UOCr further separated the survival rates (P = 0.001 among the four UOCr stages). The diuretic dose did not alter the discriminative function of the UOCr for survival rates. However, 42.1% of non-AKI cases, as determined by the UOCr, were identified as AKI cases by the CrCr. Conclusion. Although some AKI cases were not identified by the UOCr alone, the UOCr has an additional role in AKI staging, regardless of diuretic use.

Background/Aims: The association between gestational estimated glomerular filtration rate (eGFR) and adverse pregnancy outcomes has not been fully investigated. Methods: This observational cohort study included pregnancy cases of singleton mothers whose serum creatinine levels were measured during pregnancy at two tertiary hospitals in Korea from 2000 to 2015. Those with identified substantial renal function impairment (eGFR <60 mL/min/1.73 m2 at baseline, during, or after pregnancy) were excluded. The Chronic Kidney Disease Epidemiology Collaboration equation was used for the eGFR calculation. We computed the time-averaged eGFR during gestation to determine representative values when there were multiple measurements. We studied the following three gestational complications: preterm birth (<37 weeks' gestational age), low birth weight (<2.5 kg), and preeclampsia. Results: Among the 12,899 studied pregnancies, 4,360 cases experienced one or more gestational complications. The adjusted odds ratio (aOR) and 95% confidence interval of composite gestational complications for eGFR ranges other than the reference range of 120-150 mL/ min/1.73m(2)were: 50 mL/min/1.73m(2), aOR 1.64 (1.38-1.95), P<0.001; 90-120 mL/min/1.73m(2), aOR 1.41 (1.28-1.56), P<0.001; and 60-90 mL/min/1.73m(2), aOR 2.56 (1.70-3.84), P<0.001. Incidence of preterm birth or low birth weight showed similar U-shaped association with eGFR values; otherwise, preeclampsia or small for gestational age occurred more often in mothers with a lower gestational eGFR than in those with a higher value. Conclusion: Considering the unique association between gestational eGFR and pregnancy outcomes, carefully interpreting these results may help predict obstetric complications. (C) 2018 The Author(s) Published by S. Karger AG, Basel

Purpose: We conducted a multi-center randomized double-blind study to determine the effects of 6-month therapy with sulodexide on urinary protein excretion in patients with idiopathic Immunoglobulin A (IgA) nephropathy. Materials and Methods: A total of seventy-seven patients participated in the study. They were randomly allocated to one of three groups: sulodexide 75 mg or 150 mg daily or the placebo for 6 months. The primary end point was the achievement, at 6 months, of at least 50% reduction in urine protein/creatinine ratio (UPCR) from the baseline value. Results: At 6 months, the primary end point was achieved by 12.5% of the patients assigned to the placebo, 4.0% of the patients assigned to sulodexide 75 mg daily and 21.4% of those assigned to 150 mg (p=0.308). Treatment with sulodexide 150 mg daily for 6 months significantly reduced log UPCR from 6.38 +/- 0.77 at baseline to 5.98 +/- 0.94 at 6 months (p=0.045), while treatment with sulodexide 75 mg daily and placebo did not. Conclusion: A 6-month treatment with sulodexide did not achieve 50% reduction of urinary protein excretion in IgA nephropathy patients, but showed a tendency to increase the time-dependent anti-proteinuric effect. Therefore, long-term clinical trials on a larger scale are warranted to elucidate the hypothesis that sulodexide affords renal protection in IgA nephropathy patients.

BACKGROUND: The long-term prognosis of clinically early IgA nephropathy (IgAN) patients remains to be clarified. We investigated the long-term outcomes of IgAN patients with an apparently benign presentation and evaluated prognostic factors for renal survival.; METHODS: We included patients with biopsy-proven IgAN who had estimated glomerular filtration rates (eGFR) =E2=89=A5 60 mL/min/1.73 m2, normal blood pressure, and proteinuria <0.5 g/day at the time of biopsy. The primary outcome was progression to end-stage renal disease (ESRD). The secondary outcome was a 50% increase in serum creatinine level or an increase in proteinuria to >1 g/day.; RESULTS: The analysis included 153 patients who met the inclusion criteria. At diagnosis, their median systolic blood pressure was 120 (110-130) mmHg, eGFR was 85.9 (74.9-100.1) mL/min/1.73 m2, and proteinuria was 0.25 (0.13-0.38) g/day. Of these, 4 patients died and 6 reached ESRD. The 30-year renal survival rate was 85.5%. Three patients had increased serum creatinine levels and 11 developed proteinuria. Remission was observed in 35 (22.9%) patients. A moderate or severe degree of interstitial fibrosis (adjusted odd ratio [OR] 5.93, 95% confidence interval [CI] 1.44-24.45, P=3D0.014) and hypoalbuminemia (adjusted OR 6.18, 95% CI 1.20-31.79, P=3D0.029) were independent predictors of the secondary outcome.; CONCLUSIONS: This study showed that the prognosis of early IgAN was not always favorable, even resulting in progression to ESRD in some cases. Hypoalbuminemia and interstitial fibrosis should also be considered important prognostic factors in clinically early IgAN patients.=20

Objective. To examine the level of adherence to clinical practice guidelines and its relationship to outcomes in patients with diabetes. Design. Retrospective cohort study. Setting. A tertiary teaching hospital in Korea. Participants. Patients aged >= 18 years with diabetes (n = 4994) who visited the study hospital once or more during 2004. Main Outcome Measures. The outcomes were mortality from the database of the Statistics Korea and end-stage renal disease (ESRD) incidence from ESRD registry in the Korean Society of Nephrology until December 2009. Results. Testing rates for blood pressure, eye examination, HbA1c, renal function and lipid profiles were 93.9, 32.8, 84.9, 33.5 and 45.9%, respectively. The percentage of patients achieving each treatment goal was 27.8% for blood pressure, 44.2% for HbA1c and 49.4% for low-density lipoprotein (LDL) cholesterol. There were 11.7% patients with composite outcome (death and/or ESRD). Male gender, level of HbA1c (<7%), presence of HbA1c data, checking eye examination, presence of data on urine albumin-to-creatinine ratio (UACR) and having anti-platelet medication were associated with better outcome. Conclusions. The adherence to recommendations was unsatisfactory, especially in checking eye examination, testing UACR and LDL cholesterol, and achieving a target goal for each parameter. Guideline adherence was positively related to better prognosis. Active strategies to apply the guidelines to clinical practice should be developed to improve patient outcomes.

OBJECTIVES: To investigate the nature of frontal dysfunction associated with chronic kidney disease (CKD) in people without stroke or depressive disorders.DESIGN: Cross-sectional.SETTING: Community based.PARTICIPANTS: Five hundred twenty-nine community-dwelling participants.MEASUREMENTS: Participants with CKD were classified into one of three diagnostic groups based on their estimated glomerular filtration rate (eGFR): normal (鈮�60.0 mL/min per 1.73 m(2)), mild CKD (45.0-59.9 mL/min per 1.73 m(2)), or moderate to severe CKD (<45.0 mL/min per 1.73 m(2)). Cognitive function was assessed using the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Assessment Battery, lexical fluency, digit span test, and the 64-card Wisconsin Card Sorting Test.RESULTS: Perseverative responses and perseverative errors were significantly more prevalent in the group with moderate to severe CKD than in those without CKD and those with mild CKD. The mean number of perseverative responses was 28.6 16.9 in participants with moderate to severe CKD, 19.0 11.4 in those with mild CKD, and 17.1 10.6 in those without CKD (P < .001, ANCOVA). The mean number of perseverative errors was 23.1 12.3 in participants with moderate to severe CKD, 16.2 8.3 in those with mild CKD, and 14.8 7.8 in those without CKD (P < .001, analysis of covariance). The odds ratios in the fully adjusted model for the presence of moderate to severe CKD for perseverative responses and perseverative errors were 4.82 (95% confidence interval (CI) = 2.14-10.85, P < .001) and 5.01 (95% CI = 2.22-11.28, P<.001), respectively.CONCLUSION: Frontal dysfunction, particularly perseverative errors and responses, was associated with moderate to severe CKD in the population studied. 2011, Copyright the Authors. Journal compilation 2011, The American Geriatrics Society.

Background: The inhibition of dipeptidyl peptidase (DPP) IV shows protective effects on tissue injury of the heart, lung, and kidney. Forkhead box O (FoxO) transcriptional factors regulate cellular differentiation, growth, survival, the cell cycle, metabolism, and oxidative stress. The aims of this study were to investigate whether the DPP IV inhibitor sitagliptin could attenuate kidney injury and to evaluate the status of FoxO3a signaling in the rat remnant kidney model. Methods: Rats were received two-step surgery of 5/6 renal mass reduction and fed on an oral dose of 200 mg/kg/day sitagliptin for 8 weeks. Before and after the administration of sitagliptin, physiologic parameters were measured. After 8 weeks of treatment, the kidneys were harvested. Results: The sitagliptin treatment attenuated renal dysfunction. A histological evaluation revealed that glomerulosclerosis and tubulointerstitial injury were significantly decreased by sitagliptin. Sitagliptin decreased DPP IV activity and increased the renal expression of glucagon-like peptide-1 receptor (GLP-1R). The subtotal nephrectomy led to the activation of phosphatidylinositol 3-kinase (PI3K)-Akt and FoxO3a phosphorylation, whereas sitagliptin treatment reversed these changes, resulting in PI3K-Akt pathway inactivation and FoxO3a dephosphorylation. The renal expression of catalase was increased and the phosphorylation of c-Jun N-terminal kinase (JNK) was decreased by sitagliptin. Sitagliptin treatment reduced apoptosis by decreasing cleaved caspase-3 and -9 and Bax levels and decreased macrophage infiltration. Conclusions: In rat remnant kidneys, DPP IV inhibitor attenuated renal dysfunction and structural damage. A reduction of apoptosis, inflammation and an increase of antioxidant could be suggested as a renoprotective mechanism together with the activation of FoxO3a signaling. Therefore, DPP IV inhibitors might provide a promising approach for treating CKD, but their application in clinical practice remains to be investigated.

BACKGROUNDS: Knowledge on cross-talk between the heart and kidney has been established by basic and clinical research. Nevertheless, the effects of systolic and diastolic heart dysfunctions on the development of acute kidney injury (AKI) and end-stage renal disease (ESRD) remain unresolved in hospitalized patients.; METHODS: A total of 1327 hospitalized patients who had baseline transthoracic echocardiography performed were retrospectively analyzed. Patients were categorized by the quartiles of ejection fraction (EF) and the ratio of the early transmitral blood flow velocity to early diastolic velocity of the mitral annulus (E/e'). The odds ratios (ORs) for AKI and the hazard ratios (HRs) for ESRD were calculated after adjustment of multiple covariates.; RESULTS: During hospital admission, AKI occurred in 210 (15.8%) patients. The lowest quartile of EF was associated with a risk of AKI (OR, 1.60 [1.07-2.41]) and the highest quartile of E/e' was associated with a risk of AKI (OR, 1.90 [1.26-2.41]). When two echocardiographic parameters were combined, patients with a low EF (first to second quartiles) and high E/e' (fourth quartile) showed the highest OR for AKI (OR, 2.27 [1.49-3.45]) compared with the counterpart patients. When the risk of ESRD was evaluated, E/e', but not EF, was a significant parameter of high risk (fourth vs. first quartiles: HR, 4.13 [1.17-14.64]).; CONCLUSIONS: Baseline systolic and diastolic dysfunction is related to subsequent risks of AKI and ESRD in hospitalized patients. Monitoring of these parameters may be a useful strategy to predict the risk of these adverse events in the kidney.=20

Background. The relationship between glycated haemoglobin and the incidence of end-stage renal disease (ESRD) in patients with diabetes remains uncertain, especially in those with decreased glomerular filtration rate (GFR). The aim of this study was to assess the appropriate HbA(1c) level for diabetics for minimizing the incidence of ESRD and all-cause mortality. Methods. A cohort of patients aged 25 years or older who had been treated for diabetes was generated from the Seoul National University Bundang Hospital database using diagnosis code and prescribed medication during 2004. The 4474 patients were classified into three groups according to the baseline HbA(1c) in 2004 (HbA(1c) < 6.50%, 6.50-7.49% and >= 7.50%; termed groups 1, 2 and 3, respectively). The outcomes were extracted from the database of Statistics Korea for mortality and registry in the Korean Society of Nephrology for ESRD incidence. Results. Ninety patients developed ESRD during 5.29 +/- 1.22 years of mean follow-up period. Group 1 patients showed the lowest incidence of ESRD (P = 0.003). Compared with this group, the adjusted hazard ratio of ESRD was 2.915 and 4.219 in groups 2 and 3, respectively. The incidence of ESRD increased in patients with HbA(1c) = 6.50% compared with the patients with HbA(1c) < 6.50%, regardless of GFR. However, HbA(1c) < 6.50% showed no benefit on ESRD development in patients older than 80 years and in patients with diabetic duration > 10 years. All-cause mortality was not associated with the level of HbA(1c). Conclusions. HbA(1c) > 6.50% was associated with reduced development of ESRD in all patients and later stages of chronic kidney disease.