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Objective To determine whether surge conditions were associated with increased mortality. Design Multicenter cohort study. Setting U.S. ICUs participating in STOP-COVID. Patients Consecutive adults with COVID-19 admitted to participating ICUs between March 4 and July 1, 2020. Interventions None Measurements and Main Results The main outcome was 28-day in-hospital mortality. To assess the association between admission to an ICU during a surge period and mortality, we used two different strategies: (1) an inverse probability weighted difference-in-differences model limited to appropriately matched surge and non-surge patients and (2) a meta-regression of 50 multivariable difference-in-differences models (each based on sets of randomly matched surge- and non-surge hospitals). In the first analysis, we considered a single surge period for the cohort (March 23 – May 6). In the second, each surge hospital had its own surge period (which was compared to the same time periods in matched non-surge hospitals). Our cohort consisted of 4342 ICU patients (average age 60.8 [sd 14.8], 63.5% men) in 53 U.S. hospitals. Of these, 13 hospitals encountered surge conditions. In analysis 1, the increase in mortality seen during surge was not statistically significant (odds ratio [95% CI]: 1.30 [0.47-3.58], p = .6). In analysis 2, surge was associated with an increased odds of death (odds ratio 1.39 [95% CI, 1.34-1.43], p Conclusions Admission to an ICU with COVID-19 in a hospital that is experiencing surge conditions may be associated with an increased odds of death. Given the high incidence of COVID-19, such increases would translate into substantial excess mortality.

Rationale: Neurofibromatosis type 1 (NF-1) is an autosomal-dominant neurocutaneous disorder that affects the skin, bones, and nervous system. The most common manifestation of kidney involvement is renal artery stenosis; glomerulonephritis is extremely rare. In this case report, we present a patient with NF-1 and immunoglobulin A nephropathy (IgAN). Patient concerns: A 51-year-old Korean man previously diagnosed with NF-1 presented with persistent proteinuria and hematuria identified during a routine medical check-up. He had no history of hypertension or diabetes, and denied a history of alcohol use or smoking. Diagnosis: The contrast-enhanced computed tomography scan revealed normal-sized kidneys and no evidence of renal artery stenosis. On the day of the kidney biopsy, laboratory tests showed a serum creatinine level of 1.1 mg/dL, urine protein/creatinine ratio of 1.3 g/g, and urine red blood cell count of >10 to 15/HPF. The kidney biopsy sample revealed IgAN grade III, according to Lee glomerular grading system. Intervention: The patient was advised to take 4 mg of perindopril. Outcome: Three months after the treatment, the urine protein/creatinine ratio decreased to 0.6 g/g, with no change in the serum creatinine level (1.03 mg/dL). Lessons: A genetic link between NF-1 and IgAN or other glomerular diseases is not established. However, activation of the mTOR pathway may explain this association.

Variation in hospital mortality has been described for coronavirus disease 2019 (COVID-19), but the factors that explain these differences remain unclear.Our objective was to utilize a large, nationally representative dataset of critically ill adults with COVID-19 to determine which factors explain mortality variability.In this multicenter cohort study, we examined adults hospitalized in intensive care units with COVID-19 at 70 United States hospitals between March and June 2020. The primary outcome was 28-day mortality. We examined patient-level and hospital-level variables. Mixed-effects logistic regression was used to identify factors associated with interhospital variation. The median odds ratio (OR) was calculated to compare outcomes in higher- vs. lower-mortality hospitals. A gradient boosted machine algorithm was developed for individual-level mortality models.A total of 4,019 patients were included, 1537 (38%) of whom died by 28 days. Mortality varied considerably across hospitals (0-82%). After adjustment for patient- and hospital-level domains, interhospital variation was attenuated (OR decline from 2.06 [95% CI, 1.73-2.37] to 1.22 [95% CI, 1.00-1.38]), with the greatest changes occurring with adjustment for acute physiology, socioeconomic status, and strain. For individual patients, the relative contribution of each domain to mortality risk was: acute physiology (49%), demographics and comorbidities (20%), socioeconomic status (12%), strain (9%), hospital quality (8%), and treatments (3%).There is considerable interhospital variation in mortality for critically ill patients with COVID-19, which is mostly explained by hospital-level socioeconomic status, strain, and acute physiologic differences. Individual mortality is driven mostly by patient-level factors. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Summary: Many US states published crisis standards of care (CSC) guidelines for allocating scarce critical care resources during the COVID-19 pandemic. However, the performance of these guidelines in maximizing their population benefit has not been well tested. In 2,272 adults with COVID-19 requiring mechanical ventilation drawn from the Study of the Treatment and Outcomes in Critically Ill Patients with COVID-19 (STOP-COVID) multicenter cohort, we test the following three approaches to CSC algorithms: Sequential Organ Failure Assessment (SOFA) scores grouped into ranges, SOFA score ranges plus comorbidities, and a hypothetical approach using raw SOFA scores not grouped into ranges. We find that area under receiver operating characteristic (AUROC) curves for all three algorithms demonstrate only modest discrimination for 28-day mortality. Adding comorbidity scoring modestly improves algorithm performance over SOFA scores alone. The algorithm incorporating comorbidities has modestly worse predictive performance for Black compared to white patients. CSC algorithms should be empirically examined to refine approaches to the allocation of scarce resources during pandemics and to avoid potential exacerbation of racial inequities.

Hypercoagulability may be a key mechanism of death in patients with COVID-19. This cohort study evaluated the incidence of venous thromboembolism and major bleeding in critically ill patients with COVID-19 and examined the observational effect of early therapeutic anticoagulation on survival., Visual Abstract. Early Anticoagulation in COVID-19 Hypercoagulability may be a key mechanism of death in patients with COVID-19. This cohort study evaluated the incidence of venous thromboembolism and major bleeding in critically ill patients with COVID-19 and examined the observational effect of early therapeutic anticoagulation on survival. Visual Abstract. Early Anticoagulation in COVID-19 Hypercoagulability may be a key mechanism of death in patients with COVID-19. This cohort study evaluated the incidence of venous thromboembolism and major bleeding in critically ill patients with COVID-19 and examined the observational effect of early therapeutic anticoagulation on survival., Background: Hypercoagulability may be a key mechanism of death in patients with coronavirus disease 2019 (COVID-19). Objective: To evaluate the incidence of venous thromboembolism (VTE) and major bleeding in critically ill patients with COVID-19 and examine the observational effect of early therapeutic anticoagulation on survival. Design: In a multicenter cohort study of 3239 critically ill adults with COVID-19, the incidence of VTE and major bleeding within 14 days after intensive care unit (ICU) admission was evaluated. A target trial emulation in which patients were categorized according to receipt or no receipt of therapeutic anticoagulation in the first 2 days of ICU admission was done to examine the observational effect of early therapeutic anticoagulation on survival. A Cox model with inverse probability weighting to adjust for confounding was used. Setting: 67 hospitals in the United States. Participants: Adults with COVID-19 admitted to a participating ICU. Measurements: Time to death, censored at hospital discharge, or date of last follow-up. Results: Among the 3239 patients included, the median age was 61 years (interquartile range, 53 to 71 years), and 2088 (64.5%) were men. A total of 204 patients (6.3%) developed VTE, and 90 patients (2.8%) developed a major bleeding event. Independent predictors of VTE were male sex and higher D-dimer level on ICU admission. Among the 2809 patients included in the target trial emulation, 384 (11.9%) received early therapeutic anticoagulation. In the primary analysis, during a median follow-up of 27 days, patients who received early therapeutic anticoagulation had a similar risk for death as those who did not (hazard ratio, 1.12 [95% CI, 0.92 to 1.35]). Limitation: Observational design. Conclusion: Among critically ill adults with COVID-19, early therapeutic anticoagulation did not affect survival in the target trial emulation. Primary Funding Source: None.

Acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT) is the most severe form of AKI associated with poor short- and long-term patient outcomes. The aim of this study was to evaluate the variables associated with long-term patient survival in our clinic. This was a single-center retrospective study with AKI survivors who received CRRT from March 2011 to February 2015. During the study period, all consecutive AKI survivors who underwent CRRT were included. Patients on maintenance dialysis prior to CRRT were excluded. Data were collected by reviewing the patients’ medical charts. Long-term follow-up data were gathered through February 2018. A total of 430 patients were included, and 62.8% of the patients were male. The mean age of the patients was 63.4 ± 14.6 years. The mean serum creatinine level at the time of CRRT initiation was 3.5 ± 2.5 mg/dL. At the time of discharge, the mean eGFR and serum creatinine levels were 58.4 ± 46.7 and 1.7 ± 1.6 mg/dL, respectively. After 3 years, 44.9% of the patients had survived. When we investigated the factors associated with long-term patient mortality, a longer stay in the ICU [OR 1.034 (1.016–1.053), p

Background The level of serum uric acid (SUA) has been reported to be associated with left ventricular hypertrophy (LVH) and left ventricular diastolic dysfunction (LVDD). However, this association remains unclear in patients with chronic kidney disease (CKD). Methods A total of 1025 patients with pre-dialysis CKD with preserved left ventricular systolic function were enrolled in this cross-sectional study. The LVH and LVDD were assessed using two-dimensional echocardiography and tissue Doppler imaging. The associations of LVH/LVDD with clinical and laboratory variables were investigated using univariable and multivariable logistic regression analyses. Results In a multivariable analysis, the SUA level was an independent predictor of LVH (odds ratio [OR]: 1.40, 95% confidence interval [CI]: 1.31–1.50, P < 0.001). In addition, patient age, systolic blood pressure, intact parathyroid hormone levels, and left atrial volume index levels were independent predictors of LVH. The SUA level was also an independent predictor of LVDD (OR: 1.93, 95% CI: 1.53–2.43, P < 0.001). Furthermore, systolic blood pressure and left atrial volume index levels were an independent predictor of LVDD. Receiver-operating characteristic curve analysis showed that the best cutoff values of SUA levels for identifying LVH and LVDD were ≥ 7.5 mg/dL and ≥ 6.3 mg/dL, respectively. Conclusion The SUA level was an independent predictor of LVD and LVDD in patients with CKD, suggesting that SUA could be a biomarker for LVH and LVDD.

Iron deficiency anemia is common in patients with chronic kidney disease (CKD). Neutrophil gelatinase-associated lipocalin (NGAL), a biomarker of acute kidney injury, is known to be associated with iron metabolism. We investigated whether plasma NGAL level is associated with iron status in pre-dialysis CKD patients with anemia. This study included 419 patients who had anemia. The subjects were into categorized into a pre-dialysis group (estimated glomerular filtration rate [eGFR] 60 ml/min/1.73 m2, n = 131). The associations between plasma NGAL and iron status (serum ferritin and transferrin saturation [TSAT]), eGFR, albumin, uric acid, total cholesterol, calcium, phosphate, and C-reactive protein (CRP) were assessed. In non-CKD group, plasma NGAL was not associated with any baseline variables including iron indices (TSAT and serum ferritin). In pre-dialysis group, univariate analysis showed plasma NGAL correlated with eGFR, CRP, TSAT, and serum ferritin. In multivariate analysis, plasma NGAL was independently associated with TSAT. However, serum ferritin lost its association with plasma NGAL. In ROC analysis for identifying iron deficiency, the plasma NGAL (best cut-off value ≤394 ng/ml) was superior to the serum ferritin (suggested cut-off value ≤500 ng/ml) in both sensitivity and specificity. Plasma NGAL is associated with iron status in anemic patients with pre-dialysis CKD. Further studies are needed to demonstrate the role of plasma NGAL in assessing the iron deficiency and in guiding the iron therapy for pre-dialysis CKD patients.

BackgroundWe recently reported on the enhanced tubular expression of two discrete isoforms of the MMP-2 (full length and N-terminal truncated, FL-MMP-2, NTT-MMP-2) in a murine model and human diabetic kidneys. In the present study, we examined in more detail the temporal and spatial distributions of MMP-2 isoform expression in murine models of Type 1 and Type 2 diabetes mellitus.MethodsDiabetic models were streptozotocin (STZ)-induced diabetes (Type 1 diabetes mellitus) and db/db mice (Type 2 diabetes mellitus). We quantified the abundance of two isoforms of MMP-2 transcripts by qPCR. A spatial distribution of two isoforms of MMP-2 was analyzed semi-quantitatively according to time after injection of STZ and with increasing age of db/db mice. Furthermore, immunohistochemistry for nitrotyrosine was performed to examine a potential association between oxidative stress and MMP-2 isoform expression.ResultsBoth isoforms of MMP-2 were upregulated in whole kidneys from STZ and db/db mice. In the case of FL-MMP-2, mRNA levels significantly increased at 12 and 24weeks in STZ mice, while the isoform expression was significantly increased only at 16weeks, in the db/db mice. FL-MMP-2 protein levels increased in the cortices and outer medullae of both STZ and db/db mice as a function of the duration of diabetes. For NTT-MMP-2, mRNA levels increased earlier at 4weeks in STZ mice and at 10weeks of age in db/db mice. The expression of NTT-MMP-2 also increased, primarily in the cortices of STZ and db/db mice, as a function of the duration of diabetes. Quantitatively, these findings were consistent with the qPCR results in the case of NTT-MMP-2, respectively (STZ 24weeks, 3.24 ± 3.70 fold; 16weeks db/db, 4.49 ± 0.55 fold). In addition, nitrotyrosine was expressed primarily in cortex as compared to medulla as a function of the duration of diabetes similar to NTT-MMP-2 expression.ConclusionsTwo isoforms of MMP-2 are highly inducible in two diabetic murine models and become more abundant as a function of time. As the expression patterns were not the same in the two isoforms of MMP-2, it is possible that each isoform has a discrete role in the development of diabetic renal injury.

Erythropoietin (EPO) deficiency and resistance to endogenous EPO is an important pathophysiological feature in anemia of chronic kidney disease (CKD). Low 1,25 dihydroxyvitamin D [1,25(OH)2D] level is known to contribute to anemia of CKD. We aimed to investigate the associations between serum 1,25(OH)2D and anemia, EPO deficiency, and endogenous EPO resistance in patients with CKD. This study included 409 patients with CKD [glomerular filtration rate (GFR)

Kidney transplant recipients are at increased risk of cardiovascular morbidity and malignant neoplasm, and meticulous evaluation of potential recipients is needed to minimize risks of complications after transplantation. The purpose of this study was to analyze the results of preoperative assessments and document the importance of timed and detailed examinations. Methods Medical records of patients evaluated as kidney transplant candidates from January 2015 to September 2017 were retrospectively collected and analyzed. Results Of the 216 patients evaluated during the study period, 135 (62.5%) were male, 112 (51.9%) had diabetes mellitus, 163 (75.5%) had hypertension, 31 (14.4%) had a cardiovascular event history, and 7 (3.2%) had previous history of malignant neoplasms. Mean (SD) patient age was 50.7 (10.8) years. All 216 recipient candidates underwent echocardiography. Mean (SD) ejection fraction was 57.8% (5.9%), and 48 candidates (22.2%) showed regional wall motional abnormality. Coronary angiography was performed on 81 candidates, and in 57 (70.4%) of these, coronary artery disease was detected. Malignant neoplasms were detected in 10 (4.6%) candidates. Kidney transplantation was performed on 55 candidates. One recipient died of Pneumocystis jirovecii pneumonia at 15 months after kidney transplant, but there was no death-censored graft failure, newly detected malignant neoplasm, or cardiovascular event over a mean (SD) follow-up duration of 15.5 (8.6) months. Conclusion Evaluation of kidney transplant candidates resulted in diagnoses of malignant neoplasms in 4.6% of patients and coronary artery disease in 26.4% of patients. The results of this study demonstrate candidates for kidney transplant should undergo detailed preoperative evaluation.

Background Cardiovascular disease (CVD) is a leading cause of death in patients with chronic kidney disease (CKD). Left ventricular hypertrophy (LVH) and left ventricular diastolic dysfunction (LVDD) are known as predictors of CVD in these patients. Neutrophil gelatinase-associated lipocalin (NGAL) is a biomarker of acute kidney injury. Recently, elevated NGAL levels have been reported in patients with CVD. This study aimed to evaluate the association between plasma NGAL levels and LVH/LVDD in patients with CKD. Methods This study included 332 patients with pre-dialysis CKD (estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m2). Two-dimensional echocardiography was performed to measure the left ventricular mass index (LVMI). Tissue Doppler imaging was used to measure early mitral inflow velocity (E) and the peak early mitral annular velocity (E'). Diastolic function was estimated using E' and the ratio of E to E' (E/E'). The associations of echocardiographic index with clinical and laboratory variables (age, sex, diabetes, hypertension, eGFR, albumin, uric acid, calcium, phosphate, total cholesterol, hemoglobin, C-reactive protein, intact parathyroid hormone (PTH), the inferior vena cava collapse index (IVCCI) < 50%, and plasma NGAL) were investigated using univariate and multivariate analyses. Results In multivariate logistic regression analysis, plasma NGAL was an independent predictor of LVH (OR: 1.02, 95% CI: 1.01–1.02), P < 0.001). In addition, hypertension, intact PTH, and IVCCI < 50% were independent predictors of LVH. Plasma NGAL (OR: 1.02, 95% CI: 1.01–1.02, P < 0.001) was also an independent factor of LVDD. Furthermore, hypertension, intact PTH, and IVCCI < 50% were independent predictors of LVDD. Receiver operating characteristic curve analysis (area under the curve: 0.835, 95% CI: 0.792–0.879) showed the best cutoff value of plasma NGAL for identifying LVDD was ≥ 258 ng/ml with an associated sensitivity of 77.6% and a specificity of 87.6%. Conclusion Plasma NGAL levels were independent predictors of LVH and LVDD in patients with pre-dialysis CKD, suggesting that plasma NGAL could be a biomarker for LVH and LVDD in these patients.

Glomerular filtration rate (GFR) has been reported to decrease after unilateral adrenalectomy in patients with primary aldosteronism (PA). The aim of this study was to identify clinical predictors for decreased GFR after adrenalectomy in patients with PA. The records of 187 patients (98 patients with PA and 89 with non-PA adrenal disease) who were followed up for at least 6 months after unilateral adrenalectomy were retrospectively analyzed. Estimated GFR (eGFR) was investigated at 1, 3, and 6 months postoperatively. Preoperative risk factors for eGFR% decline at 1 month ([preoperative eGFR−eGFR at 1 month]/preoperative eGFR × 100) and postoperative CKD development were investigated. The eGFR decreased significantly at 1 month and remained stable in the PA group. However, there were no significant changes in eGFR in the non-PA group over the 6-month period. In the PA group, a high preoperative eGFR and high aldosterone to renin ratio (ARR) were independently associated with eGFR% decline at 1 month. In patients with PA but without preoperative CKD (n = 68), a low preoperative eGFR and high ARR were independent risk factors for developing postoperative CKD. The best preoperative cut-off values of eGFR and ARR for predicting the development of postoperative CKD were ≤ 102 ml/min/1.73 m2 and ≥ 448 ng/dl:ng/ml/h, respectively. Renal function deteriorated significantly after unilateral adrenalectomy in patients with PA. Clinicians must pay attention to postoperative renal function in PA patients at elevated risk of developing decreased kidney function.

The bacterial colonization of hemodialysis catheter occurs frequently and reaches to the catheter-related bloodstream infections (CRBSIs). We hypothesized bacterial colonization promotes inflammation and that might be associated with renal outcome. The aim of this study was to investigate the colonization status for tunneled cuffed dialysis catheter (TCC) and the factors for contributing to the catheter colonization and explore whether bacterial colonization would be related with declining of residual renal function (RRF). 115 patients who received TCC removal operation and underwent catheter tip culture from January 2005 to June 2014 were enrolled. The follow-up data such as urine output (UO), time to anuria and patients’ survival were collected from the patients or their family members by telephone in June, 2014. There were nineteen patients (16.5 %, 19/115) with positive tip culture (colonization group). In the analysis of demographic and biochemical parameters, there were no significant differences between both groups. Fifty of all the subjects responded to the telephone survey and ten patients (20.0 %, 10/50) belonged to colonization group. The monthly decreasing rate of UO was significantly more rapid in colonization group (p = 0.001). The survival analysis showed that colonization group had worse estimated anuria-free survival than non-colonization group (p

BACKGROUND/AIMS Tubulointerstitial injury plays an important role in the progression of immunoglobulin A nephropathy (IgAN), and neutrophil gelatinase-associated lipocalin (NGAL) is among the most sensitive tubular biomarkers. We investigated whether serum or urine NGAL predicts prognosis in patients with IgAN. METHODS The present study enrolled patients with biopsy-proven IgAN from January 2005 to December 2010, whose serum and urine samples at the time of kidney biopsy were preserved by freezing. We retrospectively reviewed patient clinical data and followed patients until October 2012. Serum and urine NGAL levels were measured using an enzyme-linked immunosorbent assay kit. Renal progression was defined as an estimated glomerular filtration rate decline by > 50% or progression to end-stage renal disease. RESULTS There were 121 patients enrolled in this study. During the median follow-up period of 41.49 months, renal progression was found in nine patients (7.4%). Serum or urine NGAL alone could not predict renal progression; however, when serum and urine NGAL levels were combined, belonging to the high NGAL group independently predicted renal progression (hazard ratio [HR], 5.56; 95% confidence interval [CI], 1.42 to 21.73; p = 0.014), along with tubular damage graded according to the Oxford classification as T2 (HR, 8.79; 95% CI, 2.01 to 38.51; p = 0.004). In addition, a Kaplan-Meier curve of renal survival showed significantly higher renal progression in patients in the high NGAL group (log rank, p = 0.004). CONCLUSIONS In patients with IgAN, high serum and urine NGAL levels at the time of kidney biopsy predict renal progression.

Background The requirement of continuous renal replacement therapy (CRRT) is increasing with the growing incidence of acute kidney injury (AKI). The decision to initiate CRRT is not difficult if an adequate medical history is obtained. However, the handling and maintenance of CRRT constitute a labor-intensive intervention that requires specialized skills. For these reasons, our center organized a specialized CRRT team in March 2013. The aim of this study is to report on the role of a specialized CRRT team and to evaluate the team’s outcome. Methods This retrospective single-center study evaluated AKI patients who underwent CRRT in the intensive care unit (ICU) from March 2011 to February 2015. Patients were divided into two groups based on whether they received specialized CRRT team intervention. We collected information on demographic characteristics, laboratory parameters, SOFA score, CRRT initiation time, actual delivered dose and CRRT down-time. In-hospital mortality was defined by medical chart review. Binary logistic regression analysis was used to define factors associated with in-hospital mortality. Results A total of 1104 patients were included in this study. The mean patient age was 63.85 ± 14.39 years old, and 62.8% of the patients were male. After the specialized CRRT team intervention, there was a significant reduction in CRRT initiation time (5.30 ± 13.86 vs. 3.60 ± 11.59 days, p = 0.027) and CRRT down-time (1.78 ± 2.23 vs. 1.38 ± 2.08 h/day, p = 0.002). The rate of in-hospital mortality decreased after the specialized CRRT team intervention (57.5 vs. 49.2%, p = 0.007). When the multivariable analysis was adjusted, delayed CRRT initiation (HR 1.054(1.036–1.072), p

Background We recently reported on the enhanced expression of two isoforms of matrix metalloproteinase-2 (MMP-2) in human renal transplantation delayed graft function. These consist of the conventional secreted, full length MMP-2 isoform (FL-MMP-2) and a novel intracellular N-Terminal Truncated isoform (NTT-MMP-2) generated by oxidative stress-mediated activation of an alternate promoter in the MMP-2 first intron. Here we evaluated the effect of hyperglycemia and diabetes mellitus on the in vitro and in vivo expression of the two MMP-2 isoforms. Methods We quantified the abundance of the FL-MMP-2 and NTT-MMP-2 transcripts by qPCR in HK2 cells cultured in high glucose or 4-hydroxy-2-hexenal (HHE) and tested the effects of the NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC). The streptozotocin (STZ) murine model of Type I diabetes mellitus and renal biopsies of human diabetic nephropathy were used in this study. Results Both isoforms of MMP-2 in HK2 cells were upregulated by culture in high glucose or with HHE. PDTC treatment did not suppress high glucose-mediated FL-MMP-2 expression but potently inhibited NTT-MMP-2 expression. With STZ-treated mice, renal cortical expression of both isoforms was increased (FL-MMP-2, 1.8-fold; NTT-MMP-2, greater than 7-fold). Isoform-specific immunohistochemical staining revealed low, but detectable levels of the FL-MMP-2 isoform in controls, while NTT-MMP-2 was not detected. While there was a modest increase in tubular epithelial cell staining for FL-MMP-2 in STZ-treated mice, NTT-MMP-2 was intensely expressed in a basolateral pattern. FL-MMP-2 and NTT-MMP-2 isoform expression as quantified by qPCR were both significantly elevated in renal biopsies of human diabetic nephropathy (12-fold and 3-fold, respectively). Conclusions The expression of both isoforms of MMP-2 was enhanced in an experimental model of diabetic nephropathy and in human diabetic nephropathy. Selective MMP-2 isoform inhibition could offer a novel approach for the treatment of diabetic renal disease.

Acute renal infarct (ARI) is a common renovascular disease caused by the abrupt interruption of renal blood flow. Since the presenting symptoms are often non-specific, a major concern in ARI has been prompt diagnosis, and its long-term outcome has never been studied. From January 2000 through to December 2009, adult patients with ARI were enrolled in this study. We retrospectively reviewed their clinical data, and followed them up until July 2011. Renal outcome and all-cause mortality were measured. A total of 67 patients were finally enrolled in this study. Their mean age was 56.1 ± 16.4 years, and 52.2% of them were male. Over 76% of patients were identified to have more than one comorbidity and concurrent thromboembolic events occurred in 16.4% of the patients. Although, acute kidney injury (AKI) was present in 40.7% of the patients, long-term renal outcome was relatively good. In all cases, AKI was resolved within a month, and renal loss was found in only one patient. In-hospital mortality was 8.9% and during the median follow-up period of 40.6 months, long-term mortality was 19.7%. Independent risk factors for mortality were age, atrial fibrillation, myocardial infarction and hematuria [hazard ratio (HR) 1.051, 95% confidence interval (CI) 1.008–1.096; HR 3.322, 95% CI 1.119–9.860; HR 9.315, 95% CI 1.555–55.796 and HR 7.745, 95% CI 1.606–37.353, respectively]. Our study suggested that in-hospital and long-term outcomes of ARI were closely related to the comorbidities or underlying disease of ARI, rather than the disease itself.

Despite remarkable medical progress, the main pathogenetic mechanisms of focal segmental glomerulosclerosis (FSGS) have not been fully delineated and its prognosis is poor at present. Recently, it was revealed that the receptor for advanced glycation endproducts (RAGE) was highly expressed at the base of podocytes with an up-regulation mainly in diabetic nephropathy. However, there is no report about the association between glomerulonephritis and RAGE. The aims of the current study were to explore the relationships between several clinical parameters and circulating soluble RAGE in primary FSGS and compare serum levels in primary FSGS with immunoglobulin A nephropathy (IgAN) and controls. A total of 35 subjects aged >18 years were enrolled. Thirty-five subjects consisted of three groups: primary FSGS (N = 15), IgAN (N = 10), and normal controls (N = 10). Laboratory measurements of serum carboxymethyl-lysin (CML), soluble RAGE (sRAGE), and endogenous secretory RAGE (esRAGE) were performed. Serum esRAGE level in the FSGS group was higher than that in the IgAN group (0.55 ± 0.32 ng/mL vs. 0.27 ± 0.11 ng/mL, p = 0.013). There was no statistical difference between sRAGE and CML among the three groups. Within the FSGS group, esRAGE, but not sRAGE, was positively correlated with 24-h urinary protein (r = 0.553, p = 0.033) and negatively correlated with body mass index (r = −0.623, p = 0.013). In stepwise multiple regression analysis, body mass index and 24-h urinary protein were significant contributors to esRAGE within the FSGS group. This study showed that only the serum level of esRAGE, not sRAGE, was higher in the FSGS group than in the IgAN and control groups. The amount of 24-h proteinuria was also related to the serum level of esRAGE in the FSGS group.

We hypothesized that serum cystatin C can be a more predictable marker of arterial stiffness than serum creatinine and creatinine-based glomerular filtration rate (GFR). The aim of this study is to evaluate whether serum cystatin C is related to arterial stiffness independently of serum creatinine in subjects for whom serum creatinine is normal. A total of 2,018 individuals (1,120 males, 898 females) were enrolled. Mean brachial-ankle pulse wave velocity (baPWV) was used as a marker of arterial stiffness and sex-specific analysis was performed. A positive relationship between baPWV and serum cystatin C (Y=1109.0548+329.9102X, r(2)=0.056, p

In chronic peritoneal dialysis patients, preservation of residual renal function (RRF) is a major determinant of patient survival, and maintaining sufficient intravascular volume has been hypothesized to be beneficial for the preservation of RRF. The present study aimed to test this hypothesis using multifrequency bioimpedence analyzer (MFBIA), in Korean peritoneal dialysis patients.A total of 129 patients were enrolled in this study. The baseline MFBIA was checked, and the patients were divided into the following two groups: group 1, extracellular water per total body water (ECW/TBW) median, group 2, ECW/TBW median. We followed up the patients, and then we analyzed the changes in the urine output (UO) and the solute clearance (weekly uKt/V) in each group. Data associated with patient and technical survivor were collected by medical chart review. The volume measurement was made using Inbody S20 equipment (Biospace, Seoul, Korea). We excluded the anuric patients at baseline.The median value of ECW/TBW was 0.396. The mean patient age was 49.74 ± 10.01 years, and 62.1 % of the patients were male; most of the patients were on continuous ambulatory peritoneal dialysis (89.1 %). The mean dialysis vintage was 26.20 ± 28.71 months. All of the patients were prescribed hypertensive medication, and 48.5 % of the patients had diabetes. After 25.47 ± 6.86 months of follow up, ΔUO and Δweekly Kt/V were not significantly different in the two groups as follows: ΔUO (-236.07 ± 185.15 in group 1 vs -212.21 ± 381.14 in group 2, p = 0.756); Δ weekly Kt/v (-0.23 ± 0.43 in group 1 vs -0.29 ± 0.49 in group 2, p = 0.461). The patient and technical survivor rate was inferior in the group 2, and in the multivariable analysis, initial hypervolemia was an independent factor that predicts both of the patient mortality [HR 1.001 (1.001-1.086), p = 0.047] and the technical failure [HR 1.024 (1.001-1.048), p = 0.042].Extracellular volume expansion, measured by MFBIA, does not help preserve residual renal function, and is harmful for the technical and patient survival in Korean peritoneal dialysis patients.

The RIFLE classification is widely used to assess the severity of acute kidney injury (AKI), but its application to geriatric AKI patients complicated by medical problems has not been reported. We investigated 256 geriatric patients (≥65 years old; mean age, 74.4 ± 6.3 years) who developed AKI in the intensive care unit (ICU) according to the RIFLE classification. Etiologic, clinical, and prognostic variables were analyzed. They were categorized into RIFLE-R (n = 53), RIFLE-I (n = 102), and RIFLE-F (n = 101) groups. The overall in-hospital mortality was 39.8 %. There were no significant differences in RIFLE category between survivors and non-survivors. Survivors had significantly less needs for a ventilator and vasopressor, and lower number of failing organs. Survivors had higher systolic blood pressure, hemoglobin level, and serum albumin levels. We performed a logistic regression analysis to identify the independent predictors of in-hospital mortality. In a univariate analysis, hypertension, chronic kidney disease, RIFLE classification, number of failing organs, need for a ventilator and vasopressor, systolic blood pressure, hemoglobin level, and serum albumin levels were identified as prognostic factors of in-hospital mortality. However, in a multivariate analysis, hypertension, chronic kidney disease, number of failing organs, and serum albumin levels were independent risk factors, with no significant difference for in-hospital mortality with the RIFLE classification. The RIFLE classification might not be associated with mortality in geriatric AKI patients in the ICU. In geriatric patients with AKI, various factors besides severity of AKI should be considered to predict mortality.

Background Fluid overload is known to be associated with increased mortality in patients with acute kidney injury (AKI) who are critically ill. In this study, we intended to uncover whether the adverse effect of fluid overload on survival could be applied to all of the patients with AKI who received continuous renal replacement therapy (CRRT). Methods We analyzed 341 patients with AKI who received CRRT in our intensive care units. The presence of fluid overload was defined as a minimum 10% increase in body weight from the baseline. Demographics, comorbid diseases, clinical data, severity of illness [the sequential organ failure assessment (SOFA) score, number of vasopressors, diagnosis of sepsis, use of ventilator] upon ICU admission, fluid overload status, and time elapsed from AKI diagnosis until CRRT initiation were reviewed from the medical charts. Results Patients with total fluid overload from 3 days before CRRT initiation to ICU discharge had a significantly lower survival rate after ICU admission, as compared to patients with no fluid overload (P < 0.001). Among patients with sepsis (P < 0.001) or with high SOFA scores (P < 0.001), there was a significant difference in survival of the patients with and without fluid overload. In patients without sepsis or with low SOFA score, there was no significant difference in survival of patients irrespective of fluid overload. Conclusion Our study demonstrates that the adverse effect of fluid overload on survival is more evident in patients with sepsis or with more severe illness, and that it might not apply to patients without sepsis or with less severe illness.

Cardiac valve calcification is common in chronic kidney disease (CKD) patients. Coronary artery disease (CAD) is the one of major causes for increased cardiovascular mortality in CKD patients. We hypothesized that cardiac valve calcification is associated with the presence and the severity of CAD in pre-dialysis CKD patients. This study included 1166 patients who underwent transthoracic echocardiography for assessment of cardiac valve calcification and coronary angiography for assessment of CAD. The patients were divided into two groups according to estimated glomerular filtration rate (eGFR): pre-dialysis CKD group (n = 215, eGFR

Background The world’s population is aging faster and the incidence of acute kidney injury (AKI) needing continuous renal replacement therapy (CRRT) is increasing in elderly population. The outcome of AKI needing CRRT in elderly patients is known to be poor. However, the definitions of elderly used in the previous literatures were diverse and, there were few data that compared the long-term mortality rates of these patients with middle aged patients. This study was aimed to evaluate this issue. Methods This study was a single-center, retrospective cohort study of patients who underwent CRRT from January 2013 to December 2015. The patients were divided into the following four age cohorts: middle-aged (55–64), young-old (65–74), middle-old (75–84), and old-old (≥85). The short- and long-term mortality rates for each age cohort were compared. Results A total of 562 patients met the inclusion criteria. The short-term mortality rate was 57.3% in the entire cohort. Compared with the middle-aged cohort, the middle-old cohort (HR 1.48 (1.09–2.02), p = 0.012) and the old-old cohort (HR 2.33 (1.30–4.19), p = 0.005) showed an increased short-term mortality rate along with an increased SOFA score, acidemia and a prolonged prothrombin time. When we analyzed the long-term mortality rate of the 238 survived patients, the middle-old cohort (HR 3.76 (1.84–7.68), p

Gongjin-dan (GJD) is a traditional formula that is widely used in Korea and China, and it has been used from 1345 AD in China to improve the circulation between the kidneys and the heart and to prevent all diseases. However, its adverse effects have not yet been reported. We present a patient with minimal change disease and focal tubulointerstitial nephritis associated with GJD. A 72-year-old man visited the clinic for generalized edema 20 days after starting GJD. His serum albumin level was low and nephrotic-range proteinuria was detected. A kidney biopsy showed minimal change disease and acute tubulointerstitial nephritis. After stopping GJD, a spontaneous complete remission was achieved. We discuss the possible pathogenesis of GJD-induced minimal change disease and review the adverse effects of GJD's ingredients and traditional Chinese medicines that can induce proteinuria. We report a new adverse effect of GJD, which might induce increased IL-13 production and an allergic response, leading to minimal change disease and focal tubulointerstitial nephritis.

Bladder rupture in patients undergoing renal transplant is rare. A 26-year-old man underwent a deceased-donor renal transplant. Postoperatively, he showed a good clinical course, but after removal of the urethral catheter, he complained of pain in the lower aspect of the abdomen and in the left flank. Findings of abdominal computed tomography and retrograde cystography revealed an extraperitoneal bladder rupture. We did not identify specific causes for this condition and believe that the bladder rupture was spontaneous. However, we could not rule out the possibility of traumatic rupture by the double-J ureteral stent. We decided to manage this case conservatively, with an indwelling urethral catheter and antibiotics, instead of by surgical repair. Results of repeated serial cystography during the treatment showed decreased contrast extravasation, and cystographic findings at 6 weeks showed no leakage of contrast medium. We confirmed complete healing of the ruptured bladder and removed the urethral catheter. Since then, the patient has maintained good renal function without any complications.

There has been no study to investigate whether cystatin C could predict cardiovascular events in incident dialysis patients. We aimed to delineate the role of serum cystatin C and cystatin C-based estimated glomerular filtration rate (eGFR(cysC)) for prediction of cardiovascular events.This study included 66 end-stage renal disease patients who survived for3 months after the start of dialysis, and serum cystain C levels were measured at the point of dialysis initiation.Serum cystatin C was correlated with blood urea nitrogen (r = 0.537, p0.001), serum creatinine (r = 0.480, p0.001) and smoking (r = 0.284, p = 0.021). Cystatin C was inversely correlated with age (r = -0.316, p = 0.01) and eGFR(Cr) by modification of diet in renal disease (r = -0.533, p0.001). Kaplan-Meier analysis for cardiovascular events revealed that patients in the group with lower cystatin C levels (4.14 mg/L) had a better event-free survival rate than patients in the group with higher cystatin C levels (≥4.14 mg/L) (p = 0.039). In univariate analysis, cystatin C (hazard ratio (HR) 2.62, p = 0.011) and eGFR(cysC) (HR 0.64, p = 0.004) were significant factors for the prediction of cardiovascular events. After multivariate adjustment, serum cystatin C and eGFR(cysC) were independent determinants of cardiovascular events (HR 3.952, p = 0.001 and HR 0.640, p = 0.004, respectively).Serum cystatin C might be an independent marker of cardiovascular events in incident dialysis patients. Furthermore, eGFR(cysC) based on measured serum cystatin C could have a new role in predicting cardiovascular events beyond the estimation of true GFR.

We report a case of relapse of minimal change disease following infection with the influenza A (H1N1) virus responsible for the 2009 pandemic. A 22-year-old man who had been diagnosed with minimal change disease presented with systemic edema. He had achieved complete remission with an oral steroid (prednisolone 1 mg/kg/day) by the 17th day of administration. On the 27th day of prednisolone administration, he presented with a new onset of generalized edema after several days of productive coughing. His urine showed proteinuria (4+) with a protein/creatinine ratio (PCR) of 2852.1 mg/g. His nasal swab sample was positive for the 2009 pandemic influenza (H1N1) virus by real-time reverse-transcriptase polymerase chain reaction (RT-PCR). He received oseltamivir (150 mg/day) for 5 days. A day after completing the oseltamivir therapy, his proteinuria returned to a normal range; urinalysis was negative for protein with PCR 79.2 mg/g. One month later, the patient remained normal with no proteinuria.

Recent observational studies have found that low intact parathyroid hormone (iPTH) is related with mortality in hemodialysis patients and these findings may be considered to be the result of accelerated cardiovascular calcifications in adynamic bone disease. This study was aimed to determine the relationship between persistently low iPTH and aortic arch calcification (AAC) in incident hemodialysis patients.From January 2004 to December 2008, a total of 94 incident hemodialysis patients were enrolled in this study. They were divided into three groups according to the changing patterns of iPTH during the first year of hemodialysis. ACC was scored on posterior-anterior plain chest X-rays using a specific scale at the initiation of dialysis and followed till May 2011.The median follow-up periods were 46.9 months. The prevalence of baseline AAC and its progression were the highest in the persistently low iPTH group. Also, all-cause mortality was the highest in this group. Age, baseline calcification score and persistently low iPTH independently contributed to the progression of calcification by multivariate logistic regression analyses (HR 1.083, 95% CI 1.023-1.147, P = 0.006; HR 3.320, 95% CI 1.023-10.789, P = 0.046; HR 5.207, 95% CI 1.027-26.412, P = 0.046, respectively). Also, mortality was relatively higher in calcification progressor compared to non-progressor (39.3, 18.2%, P = 0.030).Persistently low iPTH was an independent risk factor for both AAC and mortality in incident hemodialysis patients.

We report here on a case of a 27-year-old man with atypical hemolytic uremic syndrome and diffuse alveolar hemorrhage associated with influenza A H1N1 infection. Treatment with oseltamivir, plasma exchange and hemodiafiltration for the hemolytic uremic syndrome and meticulous supportive care with steroid pulse therapy for the pulmonary alveolar hemorrhage was successful in this case. We discuss the relationship between hemolytic uremic syndrome and influenza A and the underlying immunologic factors that should be tested in a patient with atypical hemolytic uremic syndrome. We also discuss using steroid therapy for patients with H1N1-related diffuse alveolar hemorrhage.

Acute kidney injury (AKI) secondary to near-drowning is rarely described and poorly understood. Only few cases of severe isolated AKI resulting from near-drowning exist in the literature. We report a case of near-drowning who developed to isolated AKI due to acute tubular necrosis (ATN) requiring dialysis. A 21-yr-old man who recovered from near-drowning in freshwater 3 days earlier was admitted to our hospital with anuria and elevated level of serum creatinine. He needed five sessions of hemodialysis and then renal function recovered spontaneously. Renal biopsy confirmed ATN. We review the existing literature on near-drowning-induced AKI and discuss the possible pathogenesis.