Comparison of dominant and nondominant C3 deposition in primary glomerulonephritis

Alternative complement pathway dysregulation plays a key role in glomerulonephritis (GN) and is associated with C3 deposition. Herein, we examined pathological and clinical differences between cases of primary GN with C3-dominant (C3D-GN) and nondominant (C3ND-GN) deposition. Methods: We extracted primary GN data from the Korean GlomeruloNEphritis sTudy (KoGNET). C3D-GN was defined as C3 staining two grades greater than C1q, C4, and immunoglobulin via immunofluorescence analysis. To overcome a large difference in the number of patients between the C3D-GN and C3ND-GN groups (31 vs. 9,689), permutation testing was used for analysis. Results: The C3D-GN group exhibited higher serum creatinine (p ≤ 0.001), a greater prevalence of estimated glomerular filtration rate of <60 mL/min/1.72 m2 (p ≤ 0.001), higher (but not significantly so) C-reactive protein level, and lower serum C3 level (p ≤ 0.001). Serum albumin, urine protein/creatinine ratio, number of patients who progressed to end-stage renal disease, and all-cause mortality were comparable between groups. Interstitial fibrosis and mesangial cellularity were greater in the C3D-GN group (p = 0.04 and p = 0.01, respectively) than in the C3ND-GN group. C3 deposition was dominant in the former group (p < 0.001), in parallel with increased subendothelial deposition (p ≤ 0.001). Conclusion: Greater progression of renal injury and higher mortality occurred in patients with C3D-GN than with C3ND-GN, along with pathologic differences in interstitial and mesangial changes.

Effect of Active Surgical Co-Management by Medical Hospitalists in Urology Inpatient Care:A Retrospective Cohort Study

Purpose@#This study aimed to evaluate the use of active surgical co-management (SCM) by medical hospitalists for urology inpatient care. @*Materials and Methods@#Since March 2019, a hospitalist-SCM program was implemented at a tertiary-care medical center, and a retrospective cohort study was conducted among co-managed urology inpatients. We assessed the clinical outcomes of urology inpatients who received SCM and compared passive SCM (co-management of patients by hospitalists only on request; March 2019 to June 2020) with active SCM (co-management of patients based on active screening by hospitalists; July 2020 to October 2021). We also evaluated the perceptions of patients who received SCM toward inpatient care quality, safety, and subjective satisfaction with inpatient care at discharge or when transferred to other wards. @*Results@#We assessed 525 patients. Compared with the passive SCM group (n=205), patients in the active SCM group (n=320) required co-management for a significantly shorter duration (p=0.012) and tended to have a shorter length of stay at the urology ward (p=0.062) and less frequent unplanned readmissions within 30 days of discharge (p=0.095) while triggering significantly fewer events of rapid response team activation (p=0.002). No differences were found in the proportion of patients transferred to the intensive care unit, in-hospital mortality rates, or inpatient care questionnaire scores. @*Conclusion@#Active surveillance and co-management of urology inpatients by medical hospitalists can improve the quality and efficacy of inpatient care without compromising subjective inpatient satisfaction.

Role of bicarbonate and volume therapy in the prevention of acute kidney injury in rhabdomyolysis: a retrospective propensity score-matched cohort study

Although bicarbonate has traditionally been used to treat patients with rhabdomyolysis at high risk of acute kidney injury (AKI), it is unclear whether this is beneficial. This study compared bicarbonate therapy to non-bicarbonate therapy for the prevention of AKI and mortality in rhabdomyolysis patients. Methods: In a propensity score-matched cohort study, patients with a creatine kinase (CK) level of >1,000 U/L during hospitalization were divided into bicarbonate and non-bicarbonate groups. Patients were subgrouped based on low-volume (<3 mL/kg/hr) or high-volume (≥3 mL/kg/hr) fluid resuscitation in the first 72 hours. Logistic regression analyses were used to identify the impacts of bicarbonate use and fluid resuscitation on AKI risk and need for dialysis. The Kaplan-Meier method was used to estimate survival. Volume overload and electrolyte imbalances were assessed. Results: Among 4,077 patients, we assembled a cohort of 887 pairs of patients treated with and without bicarbonate. Bicarbonate group had a higher incidence of AKI, higher rate of dialysis dependency, higher 30-day mortality, and longer hospital stay than the non-bicarbonate group. Further, patients who received high-volume fluid therapy had worse renal outcomes and a higher mortality than those who received low-volume fluids regardless of bicarbonate use. Bicarbonate use, volume overload, and AKI were associated with higher mortality. Volume overload was significantly higher in the bicarbonate group than in the non-bicarbonate group. Conclusion: Bicarbonate or high-volume fluid therapy for patients with rhabdomyolysis did not reduce AKI or improve mortality compared to non-bicarbonate or low-volume fluid therapy. Limited use of bicarbonate and adjustment of fluid volume may improve the short- and long-term outcomes of patients with rhabdomyolysis.

Effect of the Concomitant Use of Subcutaneous Basal Insulin and Intravenous Insulin Infusion in the Treatment of Severe Hyperglycemic Patients

Background@#No consensus exists regarding the early use of subcutaneous (SC) basal insulin facilitating the transition from continuous intravenous insulin infusion (CIII) to multiple SC insulin injections in patients with severe hyperglycemia other than diabetic ketoacidosis. This study evaluated the effect of early co-administration of SC basal insulin with CIII on glucose control in patients with severe hyperglycemia. @*Methods@#Patients who received CIII for the management of severe hyperglycemia were divided into two groups: the early basal insulin group (n=86) if they received the first SC basal insulin 0.25 U/kg body weight within 24 hours of CIII initiation and ≥4 hours before discontinuation, and the delayed basal insulin group (n=79) if they were not classified as the early basal insulin group. Rebound hyperglycemia was defined as blood glucose level of >250 mg/dL in 24 hours following CIII discontinuation. Propensity score matching (PSM) methods were additionally employed for adjusting the confounding factors (n=108). @*Results@#The rebound hyperglycemia incidence was significantly lower in the early basal insulin group than in the delayed basal insulin group (54.7% vs. 86.1%), despite using PSM methods (51.9%, 85.2%). The length of hospital stay was shorter in the early basal insulin group than in the delayed basal insulin group (8.5 days vs. 9.6 days, P=0.027). The hypoglycemia incidence did not differ between the groups. @*Conclusion@#Early co-administration of basal insulin with CIII prevents rebound hyperglycemia and shorten hospital stay without increasing the hypoglycemic events in patients with severe hyperglycemia.

Renal outcomes of laparoscopic versus open surgery in patients with rectal cancer: a propensity score analysis

Background@#A laparoscopic approach is widely used in abdominal surgery. Although several studies have compared surgical and oncological outcomes between laparoscopic surgery (LS) and open surgery (OS) in rectal cancer patients, there have been few studies on postoperative renal outcomes. @*Methods@#We conducted a retrospective cohort study involving 1,633 patients who underwent rectal cancer surgery between 2003 and 2017. Postoperative acute kidney injury (AKI) was diagnosed according to the serum creatinine criteria of the Kidney Disease: Improving Global Outcomes classification. @*Results@#Among the 1,633 patients, 1,072 (65.6%) underwent LS. After matching propensity scores, 395 patients were included in each group. The incidence of postoperative AKI in the LS group was significantly lower than in the OS group (9.9% vs. 15.9%; p = 0.01). Operation time, estimated blood loss, and incidence of transfusion in the LS group were significantly lower than those in the OS group. Cox proportional hazard models revealed that LS was associated with decreased risk of postoperative AKI (hazard ratio [HR], 0.599; 95% confidence interval [CI], 0.402–0.893; p = 0.01) and postoperative transfusion was associated with increased risk of AKI (HR, 2.495; 95% CI, 1.529–4.072; p < 0.001). In the subgroup analysis, the incidence of postoperative AKI in patients with middle or high rectal cancer who underwent LS was much lower than in those who underwent OS (HR, 0.373; 95% CI, 0.197–0.705; p = 0.002). @*Conclusion@#This study showed that LS may have a favorable effect on the development of postoperative AKI in patients with rectal cancer.

Seropositive rate of the anti-hepatitis A immunoglobulin G antibody in maintenance hemodialysis subjects from two hospitals in Korea

BACKGROUND/AIMS@#Hepatitis A virus (HAV) is a self-limiting infectious disease, but 1% of subjects develop fulminant hepatitis. The prevalence of the anti-HAV immunoglobulin G (IgG) antibody in hemodialysis subjects in Korea remains unknown. The purpose of this study was to describe and compare the seropositive rate of anti-HAV antibody among hemodialysis subjects in two hospitals according to age group.@*METHODS@#A total of 170 hemodialysis subjects were evaluated for the seropositive rate of the anti-HAV IgG antibody and its titer.@*RESULTS@#Of the 170 maintenance hemodialysis subjects in two hospitals (Kangnam 92 vs. Chuncheon 78), 79 (46.5%) were male. The mean age was 53.2 years old, and 94.1% of the subjects were over 40 years old. The median vintage of hemodialysis was 29.0 months. Anti-HAV antibody was found in 163 subjects (95.9%), with no significant difference between the two areas (Kangnam 97.8% [n = 90] vs. Chuncheon 93.6% [n = 73]). Subjects younger than 40 years old showed a seropositive rate of 50%, while the seropositive rate increased with age for subjects aged 40 or older (p for trend < 0.001). Seropositive subjects from Kangnam showed a higher anti-HAV antibody titer than those from Chuncheon (median: Kangnam 14.2 vs. Chuncheon 11.7). Only age influenced seropositivity. The only factor that influenced the antibody level was the location of hospital (p < 0.001).@*CONCLUSIONS@#The seropositive rate of the anti-HAV antibody in hemodialysis subjects was 95%, which is similar to findings in the general population. Active immunization against hepatitis A is strongly recommended for hemodialysis subjects under 40 years of age after anti-HAV testing.

Time points for obtaining representative values of 24-hour blood pressure in chronic kidney disease

BACKGROUND/AIMS: Ambulatory blood pressure (BP) monitoring has been widely recommended for evaluating the status of BP, but is lacking in practicality. Determination of the specific time points for BP measurement that are representative of 24-hour mean BP could be useful and convenient in hypertensive patients with chronic kidney disease (CKD). METHODS: A total of 1,317 patients for whom 24-hour ambulatory BP monitoring was performed were enrolled in a multicenter study on hypertensive CKD. We analyzed the time points at which systolic blood pressure (SBP) values exhibited the smallest differences from 24-hour mean SBP (mSBP). We included office mSBP and analyzed the relationships between SBPs at the office and the time points with the smallest differences from 24-hour mSBP using several methods. RESULTS: The time points with the smallest differences from 24-hour mSBP were 7:00 AM, 2:00 PM, and 9:30 PM. In regression analysis, SBPs at 7:00 AM and 9:30 PM were better correlated with 24-hour mSBP than SBPs at 2:00 PM and the office. The proportions of patients with SBPs within 30% of 24-hour mSBP were higher at 7:00 AM and 9:30 PM. The best consistency between the uncontrolled hypertensive groups, defined as > or = 135 mmHg of 24-hour mSBP and higher values of SBPs corresponding to 135 mmHg of 24-hour mSBP, were observed at the 7:00 AM and 9:30 PM time points. CONCLUSIONS: The specific time points for SBPs that correlated well with 24-hour mSBP in hypertensive CKD patients were 7:00 AM and 9:30 PM.

The Clinical Association of the Blood Pressure Variability with the Target Organ Damage in Hypertensive Patients with Chronic Kidney Disease

It is known that blood pressure variability (BPV) can independently affect target organ damage (TOD), even with normal blood pressure. There have been few studieson chronic kidney disease (CKD) patients. We evaluated the relationship between BPV and TOD in a cross-sectional, multicenter study on hypertensive CKD patients. We evaluated 1,173 patients using 24-hr ambulatory blood pressure monitoring. BPV was defined as the average real variability, with a mean value of the absolute differences between consecutive readings of systolic blood pressure. TOD was defined as left ventricular hypertrophy (LVH) (by the Romhilt-Estes score > or =4 in electrocardiography) and kidney injury (as determined from an estimated glomerular filtration rate [eGFR]<30 mL/min/1.73 m2 and proteinuria).The mean BPV of the subjects was 15.9+/-4.63 mmHg. BPV displayed a positive relationship with LVH in a univariate analysis and after adjustment for multi-variables (odds ratio per 1 mmHg increase in BPV: 1.053, P=0.006). In contrast, BPV had no relationship with kidney injury. These data suggest that BPV may be positively associated with LVH in hypertensive CKD patients.

O-GlcNAc modification on IRS-1 and Akt2 by PUGNAc inhibits their phosphorylation and induces insulin resistance in rat primary adipocytes

It has been known that O-linked beta-N-acetylglucosamine (O-GlcNAc) modification of proteins plays an important role in transcription, translation, nuclear transport and signal transduction. The increased flux of glucose through the hexosamine biosynthetic pathway (HBP) and increased O-GlcNAc modification of protein have been suggested as one of the causes in the development of insulin resistance. However, it is not clear at the molecular level, how O-GlcNAc protein modification results in substantial impairment of insulin signaling. To clarify the association of O-GlcNAc protein modification and insulin resistance in rat primary adipocytes, we treated the adipocytes with O-(2-acetamido-2deoxy-D-glucopyranosylidene)amino-N-phenylcarbamate (PUGNAc), a potent inhibitor of O-GlcNAcase that catalyzes removal of O-GlcNAc from proteins. Prolonged treatment of PUGNAc (100 micrometer for 12 h) increased O-GlcNAc modification on proteins in adipocytes. PUGNAc also drastically decreased insulin-stimulated 2-deoxyglucose (2DG) uptake and GLUT4 translocation in adipocytes, indicating that PUGNAc developed impaired glucose utilization and insulin resistance in adipocytes. Interestingly, the O-GlcNAc modification of IRS-1 and Akt2 was increased by PUGNAc, accompanied by a partial reduction of insulin-stimulated phosphorylations of IRS-1 and Akt2. The PUGNAc treatment has no effect on the expression level of GLUT4, whereas O-GlcNAc modification of GLUT4 was increased. These results suggest that the increase of O-GlcNAc modification on insulin signal pathway intermediates, such as IRS-1 and Akt2, reduces the insulin-stimulated phosphorylation of IRS-1 and Akt2, subsequently leading to insulin resistance in rat primary adipocytes.