Hemorrhagic fever with renal syndrome (HFRS) is an acute viral disease characterized by fever, hemorrhage, and renal failure. Among the various hemorrhagic complications of HFRS, the spontaneous rupture of an arteriovenous malformation of the testicular vessels with a retroperitoneal hematoma is a rare finding. Here, we report a case of HFRS complicated by a massive retroperitoneal hematoma that was treated with transcatheter arterial embolization.
Hantavirus; Arteriovenous malformations; Embolization
Although oxidized low-density lipoprotein (LDL) and lysophosphatidylcholine (LPC) have been proposed as important mediators of the atherosclerosis, the long-term contribution to the risk of cardiovascular disease (CVD) in hemodialysis patients has not been evaluated. This study investigated the relation between oxidized LDL and LPC levels with long term risk of CVD. Plasma oxidized LDL and LPC levels were determined in 69 Korean hemodialysis patients as a prospective observational study for 5 yr. During the observation period, 18 cardiovascular events (26.1%) occurred including 6 deaths among the hemodialysis patients. The low LPC level group (≤ 254 µM/L, median value) had much more increased risk of CVD compared to the high LPC level group (> 254 µM/L) (P = 0.01). However, serum levels of oxidized LDL were not significantly different between groups with and without CVD. In adjusted Cox analysis, previous CVD, (hazard ratio [HR], 5.68; 95% confidence interval [CI], 1.94-16.63, P = 0.002) and low LPC level (HR, 3.45; 95% CI, 1.04-11.42, P = 0.04) were significant independent risk factors for development of CVD. It is suggested that low LPC, but not oxidized LDL, is associated with increased risk of CVD among a group of Korean hemodialysis patients.
Renal Dialysis; Cardiovascular Disease; Lipoproteins; Oxidized LDL; Lysophosphatidylcholines
Angiotensin II type 1 receptor blocker (ARB), which is frequently prescribed in patients with glomerulonephritis (GN), is suggested to increase the risk of cancer. We registered 3,288 patients with renal biopsy and analyzed the relationship between the use of renin-angiotensin-aldosterone system (RAAS) blockade and the incidence of cancer or cancer mortality. After renal biopsy, cancer developed in 33 patients with an incidence rate of 1.0% (95% of CI for incidence: 0.7%-1.3%). There was no difference in the cancer incidence among the groups according to the use of angiotensin-converting enzyme inhibitors (ACEI) or ARB: 1.2% in the None (23/1960), 0.7% in the ARB-only (5/748), 0.4% in the ACEI-only (1/247), and 1.2% in the ACEI-ARB (4/333) (P = 0.487) groups. The cancer mortality was 2.1%, 0.4%, 0.0%, and 0.3% in None, ACEI-only, ARB-only, and ACEI-ARB group, respectively (P < 0.001). The risk of cancer mortality in patients with ARB was only 0.124 (0.034-0.445) compared to that of non-users of ARB by Cox's hazard proportional analysis. In conclusion, prescription of ACEI or ARB in patients with GN does not increase cancer incidence and recipients of ARB show rather lower rates of all-cause mortality and cancer mortality.
Glomerulonephritis; Neoplasms; Angiotensin II Type 1 Receptor Blockers
Patients with chronic kidney disease frequently show cognitive dysfunction. The association of depression and cognitive function is not well known in maintenance dialysis patients. We evaluated cognitive impairment and depression, as well as their relationship in regards to methods of dialysis, maintenance hemodialysis (MHD) and chronic peritoneal dialysis (CPD).
Materials and Methods
Fifty-six maintenance dialysis patients were recruited and their clinical and laboratory data were collected. The Korean version of the mini-mental state exam (K-MMSE) was applied to screen the patient's cognitive function, while the Korean version of the Beck Depression Inventory (K-BDI) was used for depression screening.
The average age of the participants was 54.2±10.2 years; 29 (51.8%) were female. The average dialysis vintage was 4.2±3.8 years. The CPD group showed significantly higher K-MMSE score (27.8±2.9 vs. 26.1±3.1, p=0.010) and lower K-BDI score (12.0±8.4 vs. 20.2±10.4, p=0.003) compared with the MHD group. The percentage of patients with depression symptoms was higher in the MHD group (51.7% vs. 18.5%). There was a negative correlation between cognitive function and prevalence of depressive symptoms. Depression and education level were shown to be independent predictors for cognitive impairment in multivariate analysis.
Cognitive impairment was closely correlated with depression. It is important to detect cognitive impairment and depression early in maintenance dialysis patients with simple bedside screening tools.
Cognitive impairment; depression; hemodialysis; peritoneal dialysis
In spite of higher incidence of stroke in end-stage renal disease (ESRD) patients compared to general population, the risk factor for stroke which is specific to ESRD is not fully understood. The ESRD patients who develop stroke may have certain additional risk factors compared to ESRD patients without stroke. We used registered data of Hallym Stroke Registry to elucidate the factors which affect development of ischemic stroke among the dialysis patients.
Materials and Methods
We recruited patients with acute ischemic stroke in ESRD patients undergoing maintenance dialysis. Dialysis patients without stroke were selected as control group with age and gender matching. We compared the demographic features, stroke risk factors, and laboratory findings in ESRD patients with or without ischemic stroke.
The total of 25 patients with ESRD developed ischemic stroke. Fifty ESRD patients without stroke were chosen as the control group. The mean age of acute ischemic stroke patients was 59.80±9.94 and male gender was 48%. The most common ischemic stroke subtype was small vessel occlusion (n=12), followed by large artery atherosclerosis (n=7). The patients with stroke had more frequent history of hypertension and higher systolic/diastolic blood pressure at the time of admission than the ESRD patients without stroke. Total cholesterol and LDL-cholesterol levels were significantly lower in the stroke group. In multivariate analysis, LDL-cholesterol was found to be the only risk factor for ischemic stroke.
The results of our study reveal that LDL-cholesterol is associated with greater risk for ischemic stroke in the patients on dialysis.
Cholesterol; hypertension; end-stage renal disease; ischemic stroke
Renal failure is one of the most serious complications associated with autosomal dominant polycystic kidney disease (ADPKD). To date, early markers have failed to predict renal function deterioration at the early stages. This 1-year prospective study evaluated N-acetyl-β-D-glucosaminidase (NAG) as a new surrogate marker for renal function in ADPKD.
A total of 270 patients were enrolled in the study, and we measured urinary NAG, β2-microglobulin, neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) prospectively for 1 year to compare their predictive values for renal function.
Baseline urinary NAG/Cr was negatively correlated with estimated glomerular filtration rate (GFR) (r2 = 0.153, P < 0.001) and positively correlated with total kidney volume (TKV) (r2 = 0.113, P < 0.001). Among other biomarkers, urinary NAG/Cr better discriminated patients with decreased renal function from those with conserved renal function, showing the largest area under the curve (AUC 0.794). Immunohistochemical study revealed strong staining along the cyst-lining epithelial cells as well as the nearby compressed tubular epithelial cells. However, both single and repeated measurements of urinary NAG/Cr failed to predict renal function decline in 1 year.
Urinary NAG/Cr may be a useful surrogate marker for renal function in ADPKD patients.
Autosomal dominant polycystic kidney disease; Biomarkers; Renal function
Fabry disease is an X-linked recessive and progressive disease caused by α-galactosidase A (α-GaL A) deficiency. We sought to assess the prevalence of unrecognized Fabry disease in dialysis-dependent patients and the efficacy of serum globotriaosylceramide (GL3) screening.
A total of 480 patients of 1,230 patients among 17 clinics were enrolled. Serum GL3 levels were measured by tandem mass spectrometry. Additionally, we studied the association between increased GL3 levels and cardiovascular disease, cerebrovascular disease, or left ventricular hypertrophy.
Twenty-nine patients had elevated serum GL3 levels. The α-GaL A activity was determined for the 26 patients with high GL3 levels. The mean α-GaL A activity was 64.6 nmol/hr/mg (reference range, 45 to 85), and no patient was identified with decreased α-GaL A activity. Among the group with high GL3 levels, 15 women had a α-GaL A genetics analysis. No point mutations were discovered among the women with high GL3 levels. No correlation was observed between serum GL3 levels and α-GaL A activity; the Pearson correlation coefficient was 0.01352 (p = 0.9478). No significant correlation was observed between increased GL3 levels and the frequency of cardiovascular disease or cerebrovascular disease.
Fabry disease is very rare disease in patients with end-stage renal disease. Serum GL3 measurements as a screening method for Fabry disease showed a high false-positive rate. Thus, serum GL3 levels determined by tandem mass spectrometry may not be useful as a screening method for Fabry disease in patients with end stage renal disease.
Fabry disease; Globotriaosylceramide; End-stage renal disease
Familial Juvenile hyperuricemic nephropathy (FJHN, OMIM #162000) is a rare autosomal dominant disorder characterized by hyperuricemia with renal uric acid under-excretion, gout and chronic kidney disease. In most but not all families with FJHN, genetic studies have revealed mutations in the uromodulin (UMOD) gene located on chromosome 16p11-p13. We here described a novel heterozygous missense mutation (c.1382C>A causing p.Ala461Glu) in an affected 16-year-old male with hyperuricemia, gout and chronic kidney disease. His father was also affected and the UMOD mutation was found to segregate with the disease. There has been only one case report of Korean family with FJHN, which has not been diagnosed by genetic study. This is the first report of genetically diagnosed FJHN in Korea.
Hyperuricemia; Tamm-Horsfall protein; Mutation
Connective tissue growth factor (CTGF) is known to be a profibrotic growth factor, which mediate the fibrotic effect of transforming growth factor-β (TGF-β) and to stimulate cell proliferation and matrix production. CTGF has been shown to be hypoxia-inducible in several cell types. Here we investigated the effect of hypoxia on CTGF gene expression in cultured mouse renal tubular cells (MTC). Quiescent cultures of MTC were exposed to hypoxia (1% O2) or normoxia in serum-free medium. The effects on hypoxia-induced CTGF expression were evaluated by Northern blot and real-time PCR. The roles of mitogen-activated protein kinase (MAPK) and TGF-β were also determined using specific biochemical inhibitors. Exposure of quiescent tubular cells to hypoxia for 24 hr in a conditioned medium resulted in a significant increase TGF-β. Hypoxia caused a significant increase in CTGF mRNA expression in MTC. Either JNK or ERK inhibitor did not block the hypoxia-induced stimulation of CTGF, whereas an inhibitor of p38 MAPK reduced the hypoxia-induced changes of CTGF. Although hypoxia stimulated TGF-β production, neutralizing anti-TGF-β1 antibody did not abolish the hypoxia-induced CTGF mRNA expression. The data suggest that hypoxia up-regulates CTGF gene expression, and that p38 MAPK plays a role in hypoxic-stimulation of CTGF. We also demonstrated that hypoxia induces CTGF mRNA expression via a TGF-β1-independent mechanism.
Cell Hypoxia; Connective Tissue Growth Factor; Transforming Growth Factor Beta 1; Mitogen-activated Protein Kinase
Vascular access dysfunction is an important cause of morbidity and mortality in hemodialysis (HD) patients. Recent studies have shown that a klotho gene mutation is related to endothelial dysfunction, thrombosis, and arteriosclerosis, which are regarded as causes of vascular access dysfunction. We investigated the relationship between the klotho G-395A polymorphism and early dysfunction in vascular access in HD patients.
Patients who underwent vascular access operations between 1999 and 2002 were enrolled (n=126). Genotyping was performed by allelic discrimination using a 5'-nuclease polymerase chain reaction assay. Clinical data that could be relevant to access dysfunction were obtained from medical records. Early dysfunction of vascular access was defined as the need for any angioplastic or surgical intervention to correct or replace a poorly or nonfunctioning vascular access within 1 year and at least 8 weeks after initial access placement.
Of the 126 patients, the genotype frequency of G-395A was 72.2% for GG (n=91), 24.6% for GA (n=31), and 3.2% for AA (n=4), and the frequency of minor allele was 0.155. Clinical data were similar between the two groups, divided according to the status of the A allele. Early dysfunction occurred in 34 (27.0%) of patients, but it occurred at a significantly higher rate in A allele carriers (45.7%, 16/35) than in noncarriers (19.8%, 18/91; p=0.003).
Our results suggest that the klotho G-395A polymorphism could be a risk factor for early dysfunction of vascular access in HD patients.
klotho; Arteriovenous access; Hemodialysis