Harin Rhee

Serum Cystatin C Is Related to Pulse Wave Velocity Even in Subjects with Normal Serum Creatinine

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, r2=0.056, p<0.001) was found in males. Stepwise multivariate regression analysis in males showed that age, waist circumference, heart rate, cystatin C level, triglyceride level, and fasting glucose were independent contributors to baPWV. In females, a positive relationship between baPWV and serum cystatin C (Y=1035.7828+402.2970X, r2=0.090, p<0.001) was found. Stepwise multivariate regression analysis showed that age, heart rate, cystatin C level, fasting glucose and insulin level were independent contributors to baPWV. Age, heart rate, fasting glucose and serum cystatin C were the significant variables in both genders that contributed to baPWV. In conclusion, this study confirmed that serum cystatin C was related to pulse wave velocity even in subjects with normal serum creatinine. This finding suggested that cystatin C could be a more predictable marker of arterial stiffness than serum creatinine and creatinine-based GFR.

Pandemic H1N1 influenza A viral infection complicated by atypical hemolytic uremic syndrome and diffuse alveolar hemorrhage.

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.

Decreased Renal Function Is an Independent Predictor of Severity of Coronary Artery Disease: An Application of Gensini Score

Coronary artery disease (CAD) is the leading cause of death in patients with chronic kidney disease (CKD).Although many studies have shown a higher prevalence of CAD among these patients, the association between the spectrum of renal dysfunction and severity of CAD remains unclear. In this study, we investigate the association between renal function and the severity of CAD. We retrospectively reviewed the medical records of 1,192 patients who underwent elective coronary angiography (CAG). The severity of CAD was evaluated by Gensini score according to the degree of luminal narrowing and location(s) of obstruction in the involved main coronary artery. In all patients, the estimated glomerular filtration rate (eGFR) was independently associated with Gensini score (β=-0.27, P < 0.001) in addition to diabetes mellitus (β=0.07, P = 0.02), hypertension (β=0.12, P < 0.001), low density lipoprotein (LDL)-cholesterol (β=0.08, P = 0.003), and hemoglobin (β=-0.07, P = 0.03) after controlling for other confounding factors. The result of this study demonstrates that decreased renal function is associated not only with the prevalence, but also the severity, of CAD.

Use of Multifrequency Bioimpedance Analysis in Male Patients with Acute Kidney Injury Who Are Undergoing Continuous Veno-Venous Hemodiafiltration

Introduction Fluid overload is a well-known predictor of mortality in patients with acute kidney injury (AKI). Multifrequency bioimpedance analysis (MF-BIA) is a promising tool for quantifying volume status. However, few studies have analyzed the effect of MF-BIA-defined volume status on the mortality of critically ill patients with AKI. This retrospective medical research study aimed to investigate this issue. Methods We retrospectively reviewed the medical records of patients with AKI who underwent continuous veno-venous hemodiafiltration (CVVHDF) from Jan. 2013 to Feb. 2014. Female patients were excluded to control for sex-based differences. Volume status was measured using MF-BIA (Inbody S20, Seoul, Korea) at the time of CVVHDF initiation, and volume parameters were adjusted with height squared (H2). Binary logistic regression analyses were performed to test independent factors for prediction of in-hospital mortality. Results A total of 208 male patients were included in this study. The mean age was 65.19±12.90 years. During the mean ICU stay of 18.29±27.48 days, 40.4% of the patients died. The in-hospital mortality rate increased with increasing total body water (TBW)/H2 quartile. In the multivariable analyses, increased TBW/H2 (OR 1.312(1.009-1.705), p=0.043) and having lower serum albumin (OR 0.564(0.346-0.919, p=0.022) were independently associated with higher in-hospital mortality. When the intracellular water (ICW)/H2 or extracellular water (ECW)/H2 was adjusted instead of the TBW/H2, only excess ICW/H2 was independently associated with increased mortality (OR 1.561(1.012-2.408, p=0.044). Conclusions MF-BIA-defined excess TBW/H2 and ICW/H2 are independently associated with higher in-hospital mortality in male patients with AKI undergoing CVVHDF.

Glycated albumin is a more accurate glycemic indicator than hemoglobin A1c in diabetic patients with pre-dialysis chronic kidney disease.

Glycated albumin (GA) has been reported to be a more reliable glycaemic indicator than haemoglobin A1c (HbA1c) in patients with diabetes on dialysis. However, the significance of these assays has been less evaluated in patients with diabetes and pre‐dialysis chronic kidney disease (CKD).

A case of severe acute kidney injury by near-drowning.

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.

Fluid overload and survival in critically ill patients with acute kidney injury receiving continuous renal replacement therapy

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.

Enhanced expression of two discrete isoforms of matrix metalloproteinase-2 in experimental and human diabetic nephropathy

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.

Short- and Long-Term Mortality Rates of Elderly Acute Kidney Injury Patients Who Underwent Continuous Renal Replacement Therapy.

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<0.001), the old-old cohort (HR 4.40(1.20–16.10), p = 0.025), a lower BMI, the presence of liver cirrhosis, the presence of congestive heart failure and a history of sepsis were independent risk factors for the prediction of long-term mortality. Conclusion Compared with the middle-aged cohort, the middle-old and the old-old cohort showed an increased short-term and long-term mortality rate. However, in the young-old cohort, neither the short-term nor the long-term mortality rate was increased.

High serum and urine neutrophil gelatinase-associated lipocalin levels are independent predictors of renal progression in patients with immunoglobulin A nephropathy

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.