A multicentre, multinational, randomized, placebo-controlled, double-blind, phase 3 trial to evaluate the efficacy and safety of gemigliptin (LC15-0444) in patients with type 2 diabetes.

AIM: This study was designed to assess the efficacy and safety of the dipeptidyl peptidase IV inhibitor gemigliptin (LC15-0444) 50 mg versus placebo in patients with type 2 diabetes. METHODS: We conducted a 24-week, randomized, double-blind, placebo-controlled phase III trial in 182 patients (74 from Korea and 108 from India) with type 2 diabetes. After an initial 2 weeks of a diet and exercise programme followed by 2 weeks of a single-blind placebo run-in period, eligible patients were randomized to gemigliptin 50 mg or placebo, receiving the assigned treatment for 24 weeks. HbA1c and fasting plasma glucose (FPG) were measured periodically, and oral glucose tolerance test was performed at baseline and weeks 12 and 24. RESULTS: At week 24, gemigliptin treatment led to significant reductions in HbA1c measurements compared to placebo (adjust mean after subtracting the placebo effect size: -0.71%, 95% confidence interval: -1.04 to -0.37%). A significantly greater proportion of patients achieved an HbA1c <7% with gemigliptin than with placebo. The placebo-subtracted FPG change from baseline at week 24 was -19.80 mg/dl. The overall incidence rates for adverse events were similar in the gemigliptin and placebo groups. CONCLUSIONS: This study showed the efficacy and safety of gemigliptin 50 mg administered once daily as a monotherapy for type 2 diabetes patients.

Vena cava filters: a synopsis of complications and related topics.

Deep venous thrombosis and pulmonary embolism constitute common preventable causes of morbidity and mortality. The incidence of venous thromboembolism (VTE) continues to increase. Standard anticoagulation therapy may reduce the risk of fatal PE by 75% and that of recurrent VTE by over 90%. For patients who are not candidates for anticoagulation, a vena cava filter (VCF) may be beneficial. Despite a good overall safety record, significant complications related to VCF are occasionally seen. This review discusses both procedural and non-procedural complications associated with VCF placement and use. We will also discuss VCF use in the settings of pregnancy, malignancy, and the clinical need for more than one filter.

The relationship between processes and outcomes for injured older adults: a study of a statewide trauma system.

PURPOSE: Age is a risk factor for death, adverse outcomes, and health care use following trauma. The American College of Surgeons' Trauma Quality Improvement Program (TQIP) has published "best practices" of geriatric trauma care; adoption of these guidelines is unknown. We sought to determine which evidence-based geriatric protocols, including TQIP guidelines, were correlated with decreased mortality in Pennsylvania's trauma centers. METHODS: PA's level I and II trauma centers self-reported adoption of geriatric protocols. Survey data were merged with risk-adjusted mortality data for patients ≥65 from a statewide database, the Pennsylvania Trauma Systems Foundation (PTSF), to compare mortality outlier status and processes of care. Exposures of interest were center-specific processes of care; outcome of interest was PTSF mortality outlier status. RESULTS: 26 of 27 eligible trauma centers participated. There was wide variation in care processes. Four trauma centers were low outliers; three centers were high outliers for risk-adjusted mortality rates in adults ≥65. Results remained consistent when accounting for center volume. The only process associated with mortality outlier status was age-specific solid organ injury protocols (p = 0.04). There was no cumulative effect of multiple evidence-based processes on mortality rate (p = 0.50). CONCLUSIONS: We did not see a link between adoption of geriatric best-practices trauma guidelines and reduced mortality at PA trauma centers. The increased susceptibility of elderly to adverse consequences of injury, combined with the rapid growth rate of this demographic, emphasizes the importance of identifying interventions tailored to this population. LEVEL OF EVIDENCE: III. STUDY TYPE: Descriptive.

In vivo markers of inflammatory response in recent-onset schizophrenia: a combined study using [(11)C]DPA-713 PET and analysis of CSF and plasma.

Several lines of evidence suggest aberrant immune response in schizophrenia, including elevated levels of cytokines. These cytokines are thought to be produced by activated microglia, the innate immune cells of the central nervous system. However, increase in translocator protein 18 kDa (TSPO), a marker of activated glia, has not been found in patients with chronic schizophrenia using second-generation radiotracers and positron emission tomography (PET)-based neuroimaging. In this study we focused on patients with recent onset of schizophrenia (within 5 years of diagnosis). Quantified levels of TSPO in the cortical and subcortical brain regions using the PET-based radiotracer [(11)C]DPA-713 were compared between the patients and healthy controls. Markers of inflammation, including interleukin 6 (IL-6), were assessed in the plasma and cerebrospinal fluid (CSF) in these participants. We observed no significant change in the binding of [(11)C]DPA-713 to TSPO in 12 patients with recent onset of schizophrenia compared with 14 controls. Nevertheless, the patients with recent onset of schizophrenia showed a significant increase in IL-6 in both plasma (P<0.001) and CSF (P=0.02). The CSF levels of IL-6 were significantly correlated with the levels of IL-6 in plasma within the total study population (P<0.001) and in patients with recent onset of schizophrenia alone (P=0.03). Our results suggest that increased levels of IL-6 may occur in the absence of changed TSPO PET signal in the brains of medicated patients with recent onset of schizophrenia. Future development of PET-based radiotracers targeting alternative markers of glial activation and immune response may be needed to capture the inflammatory signature present in the brains of patients with early-stage disease.

Hypoxia renders hepatocytes susceptible to cell death by nitric oxide.

Under normoxic conditions, nitric oxide (NO) suppresses hepatocyte apoptosis. In contrast, NO contributes to hepatocellular injury in conditions associated with ischemia and reperfusion. To understand this paradoxical effect further, we compared the effects of various doses of NO, delivered from the chemical NO donor S-nitroso-N-acetylpenicillamine (SNAP), under both normoxic and hypoxic tissue culture conditions. We found that the cell death induced by NO under hypoxic conditions, which increased the production of reactive oxygen species, was accompanied by a necrotic morphology with a concomitant early decrease in ATP levels. The NO-induced death of hypoxic hepatocytes was reversed by co-incubation with the anti-oxidant N-acetylcysteine. We conclude that hypoxia-induced oxidative stress subsequent to ATP depletion can switch NO from an anti-apoptotic to a hepatotoxic agent. These findings may have implications for NO-induced liver damage in settings of tissue hypoxia.

Multiple pathways for protein transport to peroxisomes.

Peroxisomes are unique among the organelles of the endomembrane system. Unlike other organelles that derive most if not all of their proteins from the ER (endoplasmic reticulum), peroxisomes contain dedicated machineries for import of matrix proteins and insertion of membrane proteins. However, peroxisomes are also able to import a subset of their membrane proteins from the ER. One aspect of peroxisome biology that has remained ill defined is the role the various import pathways play in peroxisome maintenance. In this review, we discuss the available data on matrix and membrane protein import into peroxisomes.

Initial venous lactate levels in patients with isolated penetrating extremity trauma: a retrospective cohort study.

INTRODUCTION: Elevated initial lactate levels have been shown to be associated with severe injury in trauma patients, but some patients who do not appear to be in shock also presented with elevated lactate levels. We hypothesized that in hemodynamically stable patients with isolated penetrating extremity trauma, initial lactate level does not predict clinically significant bleeding. METHODS: A 5-year institutional database review was performed. Hemodynamically stable patients (HR < 101, SBP > 90) with isolated penetrating extremity trauma with an initial lactate sent were included. The exposure of interest was captured as a dichotomous variable by initial lactate level normal (N ≤ 2.2 mEq/L), elevated (E > 2.2 mEq/L). The primary outcome measurement was clinically significant bleeding, defined by need for intervention (operation, angioembolization, or transfusion) or laboratory evidence of bleeding (presenting Hg < 7 g/dL, or Hg decrease by >2 g/dL/24 h). Chi-squared and Mann-Whitney tests were used to compare variables. RESULTS: A total of 132 patients were identified. There were no differences in demographics or mechanism of injury between the N (n = 43, 7%) and E (n = 89, 14%) groups. Median lactate levels were 1.6 (IQR 1.2-1.9) mEq/dL vs. 3.8 (IQR 2.8-5.2) in the N and E groups, p < 0.001. Lactate was elevated in 89 (67%) patients but was not associated with clinically significant bleeding (37% elevated vs. 39 % not elevated p = 0.82). CONCLUSIONS: In hemodynamically stable patients with isolated penetrating trauma to the extremity, elevated initial venous lactate levels (>2.2 mEq/L) are not associated with bleeding or need for interventions. Clinical judgment remains the gold standard for evaluation and management of these patients.

Decoupling of N-acetyl-aspartate and glutamate within the dorsolateral prefrontal cortex in schizophrenia.

Aberrant function of glutamatergic pathways is likely to underlie the pathology of schizophrenia. Evidence of oxidative stress in the disease pathology has also been reported. N-Acetylaspartate (NAA) is metabolically linked to both cascades and may be a key marker in exploring the interconnection of glutamatergic pathways and oxidative stress. Several studies have reported positive correlation between the levels of NAA and Glx (the sum of glutamate and glutamine) in several brain regions in healthy subjects, by using proton magnetic resonance spectroscopy ([(1)H]MRS). Interestingly, one research group recently reported decoupling of the relationship between NAA and Glx in the hippocampus of patients with schizophrenia. Here we report levels of NAA and Glx measured using [(1)H]MRS, relative to the level of creatine (Cr) as an internal control. The dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) in 25 patients with schizophrenia and 17 matched healthy controls were studied. In DLPFC, NAA/Cr and Glx/Cr were significantly positively correlated in healthy controls after correction for the effect of age and smoking status and after correction for multiple comparisons (r= 0.627, P= 0.017). However, in patients with schizophrenia, the positive correlation between NAA/Cr and Glx/Cr was not observed even after correcting for these two variables (r= -0.330, P= 0.124). Positive correlation between NAA/Cr and Glx/Cr was not observed in the ACC in both groups. Decoupling of NAA and Glx in the DLPFC may reflect the interconnection of glutamatergic pathways and oxidative stress in the pathology of schizophrenia, and may possibly be a biomarker of the disease.

Intraabdominal sepsis down-regulates transcription of sodium taurocholate cotransporter and multidrug resistance-associated protein in rats.

Hepatic dysfunction in sepsis is characterized by hyperbilirubinemia and intrahepatic cholestasis. We hypothesize that sepsis causes decreased hepatic transcription of the bile acid transporter sodium taurocholate cotransporter (Ntcp) and the organic anion transporter multidrug resistance-associated protein (Mrp2) and that interleukin (IL)-6 is important in the down-regulation of Ntcp and Mrp2 expression. Male Sprague-Dawley rats underwent induction of mild, nonlethal sepsis by cecal ligation and single puncture (CLP) or fulminant sepsis by cecal ligation and double puncture (2CLP). Hepatic transcription of Ntcp and Mrp2 rapidly decreased after CLP or 2CLP. Seventy-two hours later, transcription was 60% of baseline in CLP and 14% of baseline in 2CLP. Serum bilirubin was elevated from 24 h onward and cholestasis was observed on fixed liver specimens at 24, 48, and 72 h after 2CLP but not after CLP. Steady-state Ntcp and Mrp2 mRNA was decreased in IL-6-treated cultured hepatocytes and in normal rats given 1 mg/kg intravenous IL-6. We conclude that 1) Ntcp and Mrp2 transcription is down-regulated transiently after CLP and persistently after 2CLP; 2) 2CLP results in hyperbilirubinemia and cholestasis, in part due to persistently decreased transcription of Ntcp and Mrp2; and 3) altered Ntcp and Mrp2 transcription is mediated in part by IL-6.

Paclitaxel-induced apoptosis in non-small cell lung cancer cell lines is associated with increased caspase-3 activity.

OBJECTIVE: Our objective was to determine whether paclitaxel-induced apoptosis in human lung cancer cells is Fas dependent. METHODS: Human lung cancer cell lines were evaluated for morphologic evidence of apoptosis, DNA fragmentation (TUNEL positivity), and caspase-3 activation after paclitaxel treatment. Human lung adenocarcinoma, squamous cell carcinoma, undifferentiated lung carcinoma, and bronchoalveolar carcinoma cell lines were each cultured in 10 micromol/L paclitaxel. RESULTS: After 24 hours of culture in paclitaxel, a 22% to 69% increase in the number of apoptotic cells was evident by means of methylene blue-azure A-eosin staining with characteristic blebbing and nuclear condensation. TUNEL assay also confirmed an increase of 19.9% to 73.0% of cells with nuclear fragmentation. Caspase-3 activity, assayed by Z-DEVD cleavage, increased from 20% to 215% (P <.05). ZB4, an antagonistic anti-Fas antibody, did not block paclitaxel induction of caspase-3 activity (155.8 vs 165.8 U, not significant). Apoptotic morphologic changes were inhibited in cells cultured in the presence of paclitaxel and Ac-DEVD-CHO, a caspase-3 inhibitor. CONCLUSIONS: Paclitaxel induces apoptosis in lung cancer cell lines, as assessed by a consistent increase in caspase-3 activity, DNA laddering, and characteristic morphologic changes. Paclitaxel-induced apoptosis in human lung cancer cells is associated with caspase-3 activation but is not Fas dependent.

Analysis of the envelope region of hepatitis G virus isolated from Korean patients.

The genetic diversity of hepatitis G virus (HGV) was investigated. By using a RT-PCR procedure, 14% of either HBV (hepatitis B virus)- or HCV (hepatitis C virus)-positive Korean hepatitis patients were proved to be HGV positives. Nucleotide sequences in the E1 region of the eight isolates from Korean patients and the six previously reported isolates were compared. Nucleotide substitutions spread uniformly throughout the E1 region. Sequence homology among the Korean isolates was 84-99% and 88-99% at the nucleotide and amino acid sequences, respectively, whereas those from different geographic areas was slightly lower at both levels. At least two genotypes might exist among the Korean HGV isolates. Compared to the corresponding region of HCV, the E1 sequence from HGV is moderately conserved. In addition, as frameshift mutations were observed in most of the Korean isolates compared to the prototype HGV sequence, the Korean isolates might not use the translational initiation site of the prototype HGV for polyprotein translation. Because a putative signal sequence of E1 for entry into endoplasmic reticulum starts from the N-terminus of the polyprotein, and capsid-like peptides composed of basic amino acids could not be detected from the upstream region of E1, the core protein of HGV is absent, or at least not present, at the region next to 5'-UTR. Therefore, HGV could be clearly distinguished from other genera of Flaviviridae.

The regulatory role of nitric oxide in apoptosis.

Nitric oxide (NO) is a multi-faceted molecule with dichotomous regulatory roles in many areas of biology. The complexity of its biological effects is a consequence of its numerous potential interactions with other molecules such as reactive oxygen species (ROS), metal ions, and proteins. The effects of NO are modulated by both direct and indirect interactions that can be dose-dependent and cell-type specific. For example, in some cell types NO can promote apoptosis, whereas in other cells NO inhibits apoptosis. In hepatocytes, NO can inhibit the main mediators of cell death-caspase proteases. Moreover, low physiological concentrations of NO can inhibit apoptosis, but higher concentrations of NO may be toxic. High NO concentrations lead to the formation of toxic reaction products like dinitrogen trioxide or peroxynitrite that induce cell death, if not by apoptosis, then by necrosis. Long-term exposure to nitric oxide in certain conditions like chronic inflammatory states may predispose cells to tumorigenesis through DNA damage, inhibition of DNA repair, alteration in programmed cell death, or activation of proliferative signaling pathways. Understanding the regulatory mechanisms of NO in apoptosis and carcinogenesis will provide important clues to the diagnosis and treatment of tissue damage and cancer. In this article we have reviewed recent discoveries in the regulatory role of NO in specific cell types, mechanisms of pro-apoptotic and anti-apoptotic induction by NO, and insights into the effects of NO on tumor biology.

Inflammatory responses and mediators.

The host response to injury is usually appropriate in degree and is self-limited. In more severe injury, the host response may persist inappropriately, leading to SIRS and MODS and possibly multiple organ failure. The initial response to injury is mediated primarily by norepinephrine, and is directed toward preservation of circulation to the heart and brain at the expense of other vascular beds. If fluid resuscitation is adequate and necrotic tissue is débrided, a hypermetabolic state ensues, mediated by epinephrine and directed toward supporting repair of injured tissue by leukocytes. Inflammatory cells are recruited to the site of injury and elaborate cytokines, which promote repair locally, but in severe injury may be systemically released and trigger remote inflammation. Cytokine biology presently is poorly understood, and simple anticytokine strategies have failed to improve survival of critically ill patients. Current therapy of SIRS and MODS is directed toward symptoms. Presently, it is unclear how an abnormal stress response arises. Cytokine spillover into the systemic circulation may occur. Selective transcriptional failure may be the cellular basis of organ dysfunction. Inappropriate production of peroxynitrite or its precursor, NO, is implicated in mediating cellular injury in SIRS and MODS.

Glomerular growth under cyclosporine treatment in childhood nephrotic syndrome.

BACKGROUND: Glomerular hypertrophy is important in children with idiopathic nephrotic syndrome in regard to diagnosis and pathogenesis. Moreover, glomerular growth may be altered by cyclosporine (CsA) treatment in these patients. METHODS: Bowman's area (BA) and the glomerular tuft area (GA) of pre- and post-treatment biopsies was measured by morphometry in 47 children with idiopathic nephrotic syndrome (39 MCD and 8 FSGS) treated with CsA and low-dose prednisolone for up to 2 years. RESULTS: BA and GA increased with age. The mean BA and GA were 1.2 times larger in FSGS than in MCD and the proportional increase was similar in both diseases after treatment. BA and GA decreased in 48.9% and 40.4% of cases after treatment, respectively, whereas tubulointerstitial lesion (TIL) developed in 27.7%. BA and GA decreased to 10.4% and 8.3%, respectively in children who developed TIL after treatment and the values were largely unchanged in those treated for more than 16 months. CONCLUSIONS: Glomerular growth is hampered by CsA nephrotoxicity, which is a more common complication than TIL. The impairment of glomerular growth is related to the duration of treatment and the development of TIL, but not to age or diagnosis.

Pediatric peritoneal dialysis in Korea: practical solutions to the problems of peritoneal dialysis for children.

PURPOSE: To find and solve the common problems of peritoneal dialysis (PD) by analyzing the clinical data of pediatric PD performed in Korea. METHODS: We looked at 264 cases of continuous ambulatory peritoneal dialysis (CAPD) and acute PD that were performed in 18 institutions of pediatric nephrology in Korea from November 1987 to October 1997. RESULTS: CAPD was performed in 114 cases. The mean age of the patients was 10.5+/-6.6 years, and the male-to-female ratio was 1.4:1. The original causes of end-stage renal disease (ESRD) were proven in 92 cases (81%). The most common renal diseases were focal segmental glomerulosclerosis (17%), reflux nephropathy (11%), and chronic glomerulonephritis (11%). Mean duration of CAPD was 20 months+/-16.9 months. Peritonitis was the most common complication, and the peritonitis incidence was 0.96 episode per patient-year. Other complications were exit-site infection in 10 cases, obstruction in 7 cases, and leakage of dialysate in 6 cases. The most common etiologic organism of peritonitis was Staphylococcus aureus and the next most common was coagulase-negative staphylococcus. Acute PD was performed in 150 cases. The most common underlying causes were congenital heart disease, hemolytic uremic syndrome, sepsis, and dehydration. The mean duration was 10.3+/-11.3 days. The most common complication was peritonitis (78.3%). The most common etiologic organisms of peritonitis were Staphylococcus aureus, coag-neg staphylococcus, Acinetobacter, and Pseudomonas. CONCLUSION: Reflux nephropathy should be emphasized in early diagnosis and treatment to prevent ESRD. Incidence of congenital anomaly (7%) as a original cause of ESRD was relatively low in Korea. Growth status was not significantly improved after CAPD. In acute PD, the incidence of peritonitis rapidly increased at 2 weeks after the start of dialysis.

Long-term results of cyclosporine-induced remission of relapsing nephrotic syndrome in children.

Twenty-nine children with nephrotic syndrome were treated with cyclosporine (CsA), 100 mg/m2/day for 6 months and prednisone, 2 mg/kg every other day for 1 month and then subsequently 1 mg/kg every other day for 5 months. A renal biopsy had shown minimal change disease (MCD) in 18 children, focal segmental glomerulosclerosis (FSGS) in 3 children, membranous glomerulonephritis (MGN) in 4 children, membranoproliferative glomerulonephritis (MPGN) in 2 children, and IgA nephropathy in 2 children. All MCD patients went into complete remission during therapy. Five out of 11 steroid-sensitive patients (45.5%) remained in complete remission, while the remaining 6 (54.5%) had 2 to 3 relapses, 19 to 47 months after CsA discontinuation. Two out of 7 steroid-resistant patients (28.6%) were still in complete remission and 5 (71.4%) had 1 to 6 relapses 25 to 49 months after CsA withdrawal. The mean number of relapses in the steroid-sensitive group before and after CsA treatment decreased more (8.5 vs 1.4) than in the steroid-resistant group (8.1 vs 2.4) (p < 0.05). At the most recent examination, 1 of 3 FSGS patients achieved complete remission and 2 had a partial response. Three of 4 MGN patients were in complete remission and 1 was in partial remission. One of 2 MPGN patients achieved complete remission and 1 showed partial remission. Two patients with IgA nephropathy were in partial remission. We compared MCD patients in sustained remission and relapse; the mean CD4/CD8 ratio decreased from 1.5 to 0.9 in the remission group, in comparison with no change in the relapsed group (p < 0.05). The posttreatment renal biopsy showed lesions of nephrotoxicity in 3 of 18 children with MCD whose renal function did not alter after CsA treatment. We concluded: 1) A 6-month treatment of CsA, in combination with a low-dose alternate-day steroid, proved to be effective in maintaining the remission of steroid-sensitive and steroid-resistant MCD patients. 2) The CD4/CD8 ratio can be used as a index to predict remission or relapse after CsA therapy.

An analysis of 2361 cases of renal biopsy in Korea.

To evaluate the distribution pattern of renal diseases based on needle biopsy, we analyzed 2361 cases of renal biopsy and necropsy material examined at the Department of Pathology from 1973 to 1988. The average age was 21.1 years for males and 23.7 years for females. The adult cases comprised 60.2% and the child cases 39.8%. The male to female ratio was 1.6: 1 in adults and 2.3:1 in children. Glomerular diseases were 97.8% of the total; primary glomerulonephritis (GN) 59.8% and secondary GN 27.6% The major glomerular diseases, in descending order of frequency, were; minimal change nephrotic syndrome (MCNS; 24.2%), IgA nephropathy (IgAN; 17.8%), benign recurrent hematuria (BRH; 8.8%), membranous GN (MGN; 7.9%), acute poststreptococcal GN (APSGN; 7.3%), mesangioproliferative GN (MspGN; 5.5%), minimal mesangiopathy (5.5%), membranoproliferative GN(4.1%), and focal segmental glomerulosclerosis (FSGS; 2.7%). GN of systemic disease included 77 cases of lupus nephritis, 157 cases of Henoch-Schönlein purpura nephritis (HSPN) and 7 cases of systemic infection excluding Hepatitis B viral hepatitis. The most common glomerular diseases were MCNS, IgAN, MGN and MspGN in adults, and MCNS, BRH, HSP-N and APSGN in children. HBs antigenemia was found in 71 cases, of which MGN and IgAN were the most frequent. HBs antigenemia-associated MGN was prevalent in male children, whereas IgAN was prevalent in adults.(ABSTRACT TRUNCATED AT 250 WORDS)

Significance of mesangial IgA deposition in minimal change nephrotic syndrome: a study of 60 cases.

We studied 60 cases of minimal change nephrotic syndrome (MCNS) with mesangial IgA deposits occurring over a 6 year period. There were 43 adults and 17 children. Hematuria occurred in 69.0% of the adults and 88.2% of the children. Two adults and six children had gross hematuria during the course of the disease. Mesangial IgA deposits were noted in 100% of the cases, and concomitant IgG or IgM deposits were found in 78.6% of adults and 73.7% of children. The fluorescent intensity of mesangial IgA deposits was trace (+/-) to 1+ in 86.1% and 70.6% of the adults and children respectively. Most of the patients showed electron microscopic findings consistent with minimal change nephrotic syndrome. We speculate that most of our cases are variants of minimal change nephrotic syndrome but are neither IgA nephropathy nor an overlapping syndrome, and that environmental or genetic factors may be related to the deposition of IgA in these MCNS patients.

An analysis of 4,514 cases of renal biopsy in Korea.

To evaluate the distribution and changing patterns of renal diseases in Korea, a total of 4,514 cases of renal biopsy collected over a 23-year period between 1973 and 1995 were reviewed. Of 4,200 cases excluding 314 unsatisfactory biopsies, adult cases comprised 59.5% and pediatric cases, 40.5%. The male to female ratio was 1.5:1 in adults and 2.2:1 in children. Glomerulonephritis (GN) comprised 80.0% of the total. The most common primary GN in adults was minimal change disease (MCD) (26.6%), followed by IgA nephropathy (IgAN) (22.1%), membranous GN (MGN) (11.8%), and membranoproliferative GN (MPGN) (5.9%). In children, the primary GN incidence rates were MCD (24.8%), IgAN (10.3%), poststreptococcal (including postinfectious) GN (PSGN) (8.6%), and focal segmental glomerulosclerosis (FSGS) (4.0%). The most common secondary GN in adults was lupus nephritis and in children Henoch-Schonlein purpura nephritis. The most common cause of nephrotic syndrome was MCD in both adults and children, followed by MGN and FSGS. The elderly, aged sixty years and older, comprised 2.7% of cases and recorded equal numbers of MCD and MGN. The proportion of the biopsies found to be seropositive for HBs antigen was 27.9%, and these showed either MGN or MPGN pattern. Repeat biopsy was performed in 168 patients, due to previous biopsy failure in 15.5%. When the primary GN cases were analyzed at 5-year intervals, the prevalence of PSGN, which was greater than 25% during the 1973-1982 period, decreased abruptly in children thereafter, whereas the prevalence of FSGS increased slowly since the 1988-1992 period in both adults and children. The decrease of PSGN and the increase of FSGS suggest a role for socioeconomic and environmental factors in Korea.