Su Ah Sung

Reduction of Renal Fibrosis as a Result of Liposome Encapsulated Clodronate Induced Macrophage Depletion after Unilateral Ureteral Obstruction in Rats

Background/Aim: Macrophages have been thought to play a role in renal tubulointerstitial fibrosis; recent reports have demonstrated an antifibrotic effect of macrophages in late-stage renal fibrosis. Liposome-encapsulated clodronate (LC) produces a selective and systemic depletion of phagocytic macrophages in vivo. To study the role of initial infiltrating macrophages in renal fibrosis, we compared the effects of pretreatment with LC and a liposome vehicle for control of the severity of renal fibrosis in a unilateral ureteral obstruction (UUO) rat model. Methods: One day after a single intravenous injection of LC or liposome vehicle, the rats underwent UUO. Following 1, 5, and 14 days, the kidneys were examined to evaluate macrophage infiltration and renal fibrosis. Results: LC depleted macrophages systemically and reduced renal fibrosis associated with UUO; this beneficial effect was accompanied by a decrease of transforming growth factor beta mRNA expression. The osteopontin expression was also reduced by pretreatment with LC. Conclusion: Initial interstitial infiltration of macrophages contributes to tubulointerstitial fibrosis in UUO.

Sphingosine-1-phosphate reduces hepatic ischaemia/reperfusion-induced acute kidney injury through attenuation of endothelial injury in mice

Aim:  Hepatic ischaemia/reperfusion injury (IRI) frequently complicates acute kidney injury (AKI) during the perioperative period. This study was to determine whether hepatic IRI causes AKI and the effect of the sphingosine‐1‐phosphate (S1P) on AKI.

Diagnostic value of cystatin C for predicting acute kidney injury in patients with liver cirrhosis

Background/Aims The present study aimed to determine the role of cystatin C as a prognostic factor for acute kidney injury and survival in cirrhotic patients. Methods The study investigated 53 liver cirrhosis patients. The renal function was evaluated by serum creatinine, serum and urine cystatin C, and 24-hour creatinine clearance on admission. Acute kidney injury was defined as a serum creatinine level exceeding the normal range (>1.2 mg/dl) and an increase of at least 50% from the baseline value. Multivariate analysis, receiver operating characteristic curve, and survival analysis were used to investigate prognostic factors for acute kidney injury and survival. Results Nine of the 53 cirrhotic patients (17.0%) developed acute kidney injury within 3 months. Both serum creatinine and cystatin C were predictive factors for acute kidney injury in univariate analysis, with a diagnostic accuracy of 0.735 (95% confidence interval (CI), 0.525-0.945; p=0.028) for serum cystatin C and 0.698 (95% CI, 0.495-0.901, p=0.063) for creatinine. In multivariate analysis, only serum cystatin C was an independent risk factor for acute kidney injury. The sensitivity and specificity of a serum cystatin C level of >1.23 mg/L to acute kidney injury were 66% and 86%, respectively. Serum cystatin C was positively correlated with the Model for End-Stage Liver Disease (MELD) and MELD-Na scores (r=0.346 and p=0.011, and r=0.427 and p=0.001, respectively). Comparison of the survival rates over the observation period revealed that a serum cystatin C level of >1.23 mg/L was a useful marker for short-term mortality (p<0.001). Conclusions The accuracy in predicting acute kidney injury and short-term mortality was higher for a serum cystatin C level of >1.23 mg/L than for the serum creatinine concentration in patients with cirrhosis.

Genetic Polymorphisms of Hypoxia-Inducible Factor-1 Alpha and Cardiovascular Disease in Hemodialysis Patients

Background: Hemodialysis patients are prone to ischemic events potentially aggravated by hypoxia. The key player in adaptation to hypoxia is hypoxia-inducible factor-1 alpha (HIF-1α). Therefore, we investigated the association of HIF-1α polymorphisms with ischemia/hypoxia-related events in hemodialysis patients. Methods: Patients on maintenance hemodialysis were enrolled from 4 training hospitals in Korea. Seven single nucleotide polymorphisms (SNP) of HIF-1α were genotyped. The association of these SNP with hypoxia-related clinical outcomes (ischemic diseases and anemia) and cancer was analyzed. Results: A total of 376 patients participated in the study. No significant difference in genotype distribution was found between subjects with and without the hypoxia-related events. Three sets of linkage disequilibrium blocks were made for haplotype analyses (rs2783778 and rs7148720 in 5′ upstream region; rs7143164 and rs10873142; rs2301113, rs11549465 and rs2057482). Of these, the CT haplotype in the first set was associated with both acute myocardial infarction and frequent intradialytic hypotension (acute myocardial infarction: adjusted odds ratio = 0.15, 95% CI: 0.03–0.69; frequent intradialytic hypotension: adjusted odds ratio = 0.29, 95% CI: 0.12–0.72). Conclusion: Genetic polymorphisms of HIF-1α were associated with acute myocardial infarction and intradialytic hypotension in hemodialysis patients.

Interleukin-10 and Tumor Necrosis Factor-α Polymorphisms in Vascular Access Failure in Patients on Hemodialysis: Preliminary Data in Korea

Neointimal hyperplasia causes vascular stenosis and subsequent thrombosis, which result in vascular access failure in patients undergoing hemodialysis. Interleukin-10 (IL-10) and tumour necrosis factor-α (TNF-α ) are involved in this inflammatory process. The aim of this study was to investigate the relationship between vascular accessm failure and various inflammatory markers including the genetic polymorphisms of IL-10 and TNF-α . Seventy-five patients on hemodialysis with an arteriovenous fistula in place or an artificial graft (18 with vascular access failure and 82 without failure) and 98 healthy individuals were genotyped for IL-10 and TNF-α single nucleotide polymorphisms. Clinical and laboratory data including serum IL-10 and TNF-α levels were compared. Stimulated IL-10 levels, from in vitro incubation of blood with lipopolysaccharide, were also obtained and compared. Female gender, hypoproteinemia, and hypertriglyceridemia were associated with vascular access failure. The basal TNF-α level was significantly higher in patients with access failure. The distribution of IL-10 and TNF-α genotype did not differ among patients with or without access failure. This study could not demonstrate a relationship between genetic polymorphisms and vascular access failure. However, an altered immune response and inflammation might contribute to vascular access failure.

Successful Pregnancy in a Patient with Autosomal Dominant Polycystic Kidney Disease on Long-Term Hemodialysis

Recent advances in dialysis and a multidisciplinary approach to pregnant patients with advanced chronic kidney disease provide a better outcome. A 38-yr-old female with autosomal dominant polycystic kidney disease (ADPKD) became pregnant. She was undergoing hemodialysis (HD) and her kidneys were massively enlarged, posing a risk of intrauterine fetal growth restriction. By means of intensive HD and optimal management of anemia, pregnancy was successfully maintained until vaginal delivery at 34.5 weeks of gestation. We discuss the special considerations involved in managing our patient with regard to the underlying ADPKD and its influence on pregnancy. Graphical Abstract

LOSS OF RESIDUAL RENAL FUNCTION WAS NOT ASSOCIATED WITH GLYCEMIC CONTROL IN PATIENTS ON PERITONEAL DIALYSIS

♦ Background: Better glycemic control has been reported to slow the progression of nephropathy in predialysis diabetic patients. However, the relationship between glycemic control and residual renal function (RRF) in patients on peritoneal dialysis (PD) is uncertain. ♦ Methods: 89 incident diabetic patients on PD were recruited from 5 centers. We measured glomerular filtration rate (GFR) and hemoglobin A1c (HbA1c) within 2 months (baseline) after the start of PD and at 6 and 12 months. GFR was calculated as the average of renal creatinine and urea clearances. We analyzed whether mean HbA1c was associated with change in GFR (ΔGFR) over 1 year. ♦ Results: During the first year of PD, ΔGFR was –1.7 ± 3.4 mL/min/1.73 m2 and was not affected by mean HbA1c. Acute hemodialysis before starting PD and mean arterial diastolic pressure were related to the decline of GFR in a multivariate analysis. ♦ Conclusion: Glycemic control was not associated with change in RRF in diabetic patients during the first year after starting PD.

A case of multiple organ failure due to heat stoke following a warm bath.

Heat stroke is a potentially fatal disorder thats caused by an extreme elevation in body temperature. We report here an unusual case of multiple organ failure that was caused by classical, nonexertional heat stroke due to taking a warm bath at home. A 68 year old diabetic man was hospitalized for loss of consciousness. He was presumed to have been in a warm bath for 3 hrs and his body temperature was 41℃. Despite cooling and supportive care, he developed acute renal failure, disseminated intravascular coagulation (DIC) and fulminant liver failure. Continuous venovenous hemofiltration was started on day 3 because of the progressive oligouria and severe metabolic acidosis. On day 15, septic ascites was developed and Acinetobacter baumanii and Enterococcus faecium were isolated on the blood cultures. In spite of the best supportive care, the hepatic failure and DIC combined with septic peritonitis progressed; the patient succumbed on day 25.

A Rare Case of Primary Hyperparathyroidism Associated with Primary Aldosteronism, Hürthle Cell Thyroid Cancer and Meningioma

Multiple endocrine neoplasia type 1 (MEN1) syndrome includes varying combinations of endocrine and non-endocrine tumors. There are also a considerable number of atypical MEN1 syndrome. In this case, a 68-yr-old woman was referred to the Department of Endocrinology for hypercalcemia. Five years ago, she had diagnosed as primary hyperaldosteronism and now newly diagnosed as parathyroid hyperplasia with laboratory and pathologic findings. Hürthle-cell thyroid cancer was also resected during the parathyroid exploration and small meningioma was found on brain MRI. Her general condition has markedly improved and her adrenal mass and meningioma are being closely observed now. We could find the loss of heterozygosity of the MEN1 locus in parathyroid glands, suggesting a MEN1-related tumor, but not a germline mutation. Considering a variety of phenotypic expression and a limitation of current molecular analysis, periodic follow up will be needed in patients with a MEN1-like phenotype.

Waldenstrom Macroglobulinemia with CD5+ Expression Presented as Cryoglobulinemic Glomerulonephropathy: A Case Report

Waldenstrom macroglobulinemia (WM) is a B-cell lymphoproliferative disorder associated with bone marrow involvement of lymphoplasmacytic lymphoma (LPL) and an IgM monoclonal gammopathy. Generally B-lymphocytes in LPL do not express CD5 that is important for differential diagnosis of B-cell lymphoproliferative disorders. In WM, various renal diseases and type I cryoglobulinemia are well described separately, but cryoglobulinemic glomerulonephropathy is very rarely reported. A 61-yr-old woman complained of generalized edema, cyanosis of the extremities in cold weather, visual disturbance, and pancytopenia. Bone marrow and renal biopsy showed CD5+ expressing B-cells and cryoglobulinemic glomerulonephropathy. With the diagnosis of WM, she received cyclophosphamide, doxorubicin, vincristine and prednisolone chemotherapy and got complete remission. Here, we report a rare case of WM associated with unusual expression of CD5+ B-lymphocytes and cryoglobulinemic glomerulonephropathy, and emphasize the importance of the clinical features in differentiating CD5+ B-cell lymphoproliferative disorders.