Single nucleotide polymorphisms near IL28B gene and response to treatment of chronic hepatitis C in hemodialysis patients.

BACKGROUND: It has been shown that single nucleotide polymorphisms (SNPs) near the interleukin 28B (IL28B) gene were associated with sustained virological response following standard antivirological treatment of chronic hepatitis C. OBJECTIVES: The aim of the study was to evaluate the association between SNPs near the IL28B gene and response to the treatment of chronic hepatitis C in hemodialysis patients. PATIENTS AND METHODS: The study group included 24 hemodialysis patients with chronic hepatitis C routinely treated with pegylated interferon α-2 a. HCV genotype 1 was the cause of chronic hepatitis C in all study participants. Sustained virological response was determined by an assay with a sensitivity of 20 IU/mL, 6 months after completion of the antivirological treatment. The genotyping of the three most widely studied IL28B gene polymorphisms (rs12979860, rs8099917, and rs12980275) was performed in all study participants. RESULTS: Sustained virological response was achieved in 50% of the treated patients. The treatment response was significantly associated with the CC genotype of rs12979860, TT genotype of rs8099917, and AA genotype of rs12980275 (p = 0.003, p = 0.009, and p = 0.012, respectively). CONCLUSIONS: The three most widely studied SNPs near the IL28B gene were associated with sustained virological response following antivirological treatment of chronic hepatitis C in hemodialysis patients.

Review: Occult hepatitis C virus infection: still remains a controversy.

Occult hepatitis C virus (HCV) infection is characterized by the presence of HCV RNA in the liver cells or peripheral blood mononuclear cells of the patients whose serum samples test negative for HCV RNA, with or without presence of HCV antibodies. The present study reviews the existing literature on the persistence of occult hepatitis C virus infection, with description of the clinical characteristics and methods for identification of occult hepatitis C. Occult hepatitis C virus infection was detected in patients with abnormal results of liver function tests of unknown origin, with HCV antibodies and HCV RNA negativity in serum, and also in patients with spontaneous or treatment-induced recovery from hepatitis C. The viral replication in the liver cells and/or peripheral blood mononuclear cells was present in all clinical presentations of occult hepatitis C. The peripheral blood mononuclear cells represent an extra-hepatic site of HCV replication. The reason why HCV RNA was not detectable in the serum of patients with occult hepatitis C, could be the low number of circulating viral particles not detectable by the diagnostic tests with low sensitivity. It is uncertain whether occult hepatitis C is a different clinical entity or just a form of chronic hepatitis C virus infection. Data accumulated over the last decade demonstrated that an effective approach to the diagnosis of HCV infection would be the implementation of more sensitive HCV RNA diagnostic assays, and also, examination of the presence of viral particles in the cells of the immune system.

Successful Kidney Transplantation Using Elderly Living Donor with Extremely Large Renal Cyst and Double Arteries.

The authors describe a kidney transplant procedure using a living donor with a large cyst and double arteries. Due to the lack of regular transplant activity from a deceased donors, we decided to use the, so called, expanded criteria living donors, which means older age (more than 65 years), hypertension, some structural anomalies of the kidneys (cysts, multiple renal arteries), ABO incompatible kidney transplant, etc. The surgical procedure was the unroofing of a large cyst and wadding with perirenal fat. The 10 years survival rate is quite successful and we can recommend it.

Case report: First diagnosis of Fabry disease in North Macedonia in a patient presenting with kidney failure on hemodialysis.

Introduction: Fabry disease is a rare X-linked lysosomal storage disorder caused by α-galactosidase A (α-Gal A) deficiency. Reduced or absent enzyme activity causes progressive lysosomal accumulation of globotriaosylceramide (Lyso-Gb3) in various cells throughout the body to trigger inflammation and fibrosis. Case description: We present the first familial case of Fabry Disease in North Macedonia identified based on clinical manifestations and confirmed through enzyme, biomarker, and genetic tests. The index case in the family was a 45-year-old male undergoing hemodialysis therapy. He has had chronic burning uncontrolled limb pain since childhood, intermittent abdominal cramps, anhidrosis, and hypertension. The constellation of clinical presentations accompanied by similar symptoms in close family members prompted the enzyme, biomarker, and genetic analyses for Fabry disease. Genetic testing identified a known pathogenic GLA missense variant c.443G>A or p.(Ser148Asn) in the hemizygous state. Subsequent family studies allowed identification of another hemizygous male and five heterozygous female carriers affected by this X-linked disorder. Conclusion: We report identification of the first familial case of Fabry disease in North Macedonia and describe the phenotype associated with the Ser148Asn GLA variant. Greater awareness of this rare disease linked to continuous medical education is crucial for timely diagnosis and treatment.

Percutaneous Onsite Insertion of Catheter for Peritoneal Dialysis - A New Method Introduction in the Country.

Peritoneal dialysis (PD) is one of the options for renal replacement therapy (RRT) in the end stage renal disease (ESRD) patients. Compared to hemodialysis (HD), patients on PD experience a greater sense of well-being, an improved steady state in terms of extracellular fluid volume shifts and hemodynamics and it is preferred method for patients with problematic vascular access, bleeding tendencies, heart failure and elderly patients. In order to perform PD, a tunneled catheter should be placed through the abdominal wall and into peritoneal space, with positioning of the catheter within the most dependent portion of pelvis. Currently, there are several techniques available for PD catheter placement: open surgery, laparoscopic and percutaneous. We present for the first time in our country a case of 65 year old male patient to whom percutaneous onsite insertion of peritoneal catheter was performed. The idea is to emphasize that sometimes this should be a method of choice for RRT, especially in patients where general anesthesia should be avoid. Compared to other methods, percutaneous insertion is a simple procedure with no need for general anesthesia, and the benefits of quick recovery, earlier ambulation, and less delay in catheter placement.

Celiac-Like Duodenopathy Associated With Enteric-Coated Mycophenolate Sodium Immunosuppression in Renal Transplant Recipients: Report of 4 Cases.

Celiac-like disease and celiac sprue associated with widespread use of mycophenolic acid are among the most frequent complications of renal transplant. Most cases have been observed in patients receiving mycophenolate mofetil; however, there have been rare instance after administration of enteric-coated mycophenolate sodium. Here, we describe 4 renal transplant recipients with celiac-like duodenopathy that occurred in association with enteric-coated mycophenolate sodium treatment in a time period of 14 to 19 years after living donor kidney transplant. Three of 4 patients had diarrhea, and all 4 patients had marked loss of body weight. Esophago-gastroduodenoscopy was not diagnostically helpful; however, randomly performed duodenal biopsies showed mild villous atrophy and intraepithelial lymphocytosis. Replacement of enteric-coated mycophenolate sodium with azathioprine was successful with stopping diarrhea, allowing regained body weight, and stabilization of renal function. This potential complication in kidney transplant recipients can occur more than a decade after transplant. Diagnosis and treatment initiation are urgent to cure this disease.

Immunotactoid Glomerulopathy: A Rare Glomerular Disease Case Study.

Immunotactoid glomerulopathy (ITG) is a rare glomerular disease with variable responsiveness to the immunosuppressive therapy and with uncertain prognosis. ITG was diagnosed in two patients with type 2 diabetes mellitus with nephrotic syndrome and chronic kidney disease. The absence of diabetic retinopathy in the first case and the recent onset of diabetes in the second case accompanied with sudden increase in the 24-hour proteinuria and rapid decline in kidney function, prompted us to perform kidney biopsy. The electron microscopy set the diagnosis of ITG in both cases. There is no consensus for the treatment of ITG. The first patient was treated with combination of steroids and mycophenolate mofetil with reduction of the 24-hour proteinuria, but with persistence of the chronic kidney disease. The second patient received high doses of steroids with continuous deterioration of kidney function with the need of hemodialysis treatment.

Glomerulopathies with Fibrillary Deposits.

The glomerulopathies associated with the deposition of extracellular fibrils in the glomeruli are subdivided into Congo red positive (amyloidosis) and Congo red negative (non-amyloidotic glomerulopathies) based on Congo red staining. The non-amyloidotic glomerulopathies are divided into immunoglobulin-derived and non-immunoglobulin-derived glomerulopathies. The immunoglobulin-derived glomerulopathies: fibrillary glomerulopathy (FGn) and immunotactoid glomerulopathy (ITG) are rare glomerulopathies. The diagnosis of fibrillary-immunotactoid glomerulopathy depends on electron microscopy, which shows the presence of microfibrils in the glomeruli. The microfibrils in FGn are randomly arranged with diameters less than 30 nm. The microfibrils in ITG are larger than 30 nm with a visible lumen (microtubules), focally arranged in parallel bundles. Patients with fibrillary-immunotactoid glomerulopathy present with proteinuria (usually in the nephrotic range), microscopic hematuria, arterial hypertension, and chronic kidney disease that progresses to kidney failure over months to years. Currently, there are no guidelines for the treatment of fibrillary-immunotactoid glomerulopathy, although immunotactoid glomerulopathy could be associated with underlying hematologic disorders with the need for clone-directed therapy.

Using a Catheter for Hemodialysis Placed in the Inferior Vena Cava for the First Time in N. Macedonia - Translumbar Approach.

Maintenance of vascular access for hemodialysis remains a challenge for every doctor. Exhausted conventional vascular access is the cause for the placement of the central venous catheter in unconventional sites such as enlarged collateral vessels, hepatic veins, hemiazygos, azygos, renal veins, and the inferior vena cava. The percutaneous translumbar catheter for hemodialysis in the inferior vena cava was described over 20 years ago. In this article, we report on the procedure and complications arising from the percutaneous translumbar approach of a hemodialysis catheter. This was done for the first time in N. Macedonia. This approach is a potential option in adults and children when conventional approaches are limited.

The blood flow rate on the first day after arteriovenous fistula creation is a predictor of successful fistula maturation.

BACKGROUND: The determination of blood flow rate (BFR) is a useful tool for assessing the function of arteriovenous fistula (AVF). METHODS: Eighty patients with a newly created radio cephalic AVF were analyzed. Hemodynamics and morphological characteristics of the blood vessels were assessed by Doppler ultrasound. RESULTS: The mean age of patients was 59.9 ± 13.5 years. A successful rate of AVF maturation was 62.5% at 8 weeks. Six adjusted models of multivariate analysis showed that BFR at Day 1 was a predictor for AVF maturation both at 4 weeks (p < 0.001) and 8 weeks (p < 0.001). Receiver operating characteristic analysis showed an optimal cut-off point for BFR at Day 1 of 395 ml/min for successful maturation at 4 weeks (sensitivity 0.714, specificity 0.889) and 344 ml/min for successful maturation at 8 weeks (sensitivity 0.860, specificity 0.867). CONCLUSION: BFR at Day 1 is a powerful predictor for successful AVF maturation at 4 and 8 weeks.

Lanthanum carbonate, like sevelamer-HCl, retards the progression of vascular calcification and atherosclerosis in uremic apolipoprotein E-deficient mice.

BACKGROUND: Atherosclerosis and vascular calcification (VC) progression in chronic kidney disease is favored by disturbances of mineral metabolism. We compared the effect of phosphate binder lanthanum (La) carbonate with sevelamer-HCl on atherosclerosis, VC and bone structure and function in mice with chronic renal failure (CRF). METHODS: Apolipoprotein E-deficient (apoE(-/-)) mice were randomized to one non-CRF and three CRF groups, fed with standard diet (one non-CRF and one CRF) or diet supplemented with either 3% lanthanum carbonate (La3%) or 3% sevelamer-HCl (Sev3%). RESULTS: Both La3% and Sev3% supplemented CRF mice displayed a decrease of serum phosphorus, calcification at both intimal and medial aortic sites and atherosclerosis. This was associated with a reduction of plaque Type I collagen expression by both binders and of positive nitrotyrosine staining in response to sevelamer-HCl only. Increased mineral apposition and bone formation rates in unsupplemented CRF mice were reduced by Sev3% but not by La3%. CONCLUSIONS: The beneficial effects of La carbonate and sevelamer-HCl on the progression of VC and atherosclerosis in CRF mice could be mainly due to a decrease in phosphate retention and likewise a reduction of arterial Type I collagen expression. The effect of La carbonate differed from that of sevelamer-HCl in that it did not appear to exert its vascular effects via changes in oxidative stress or bone remodeling in the present model.

Percutaneous Nephrostomy in the Treatment of Hydronephrosis in Renal Transplant Patients - Case Report.

Percutaneous nephrostomy is a first-line minimal invasive treatment option for ureteral obstruction following kidney transplantation, with high effectiveness and a low complication rate. Percutaneous nephrostomy might be used as a temporary salvage therapy, providing acute decompression of the kidney collecting system and preventing graft loss. It can also function as a permanent and sometimes only possible option in transplant patients with frequent recurrences of ureteral stenosis who either fail an open surgical reconstruction or who are not good candidates for these procedures. We present two patients with acute decline in urine output after renal transplantation with radiologically verified hydroureteronephrosis of the transplanted kidney (graft) caused by stenosis of distal ureter. In both cases, nephrostomy was placed within 48 hours as a temporary salvage treatment that ameliorates renal function and prevents graft loss. The permanent nephrostomy was the only possible solution for the preservation of the graft's function in the first case because of the recurrences of ureteral stenosis after several percutaneous interventions and open-surgery ureteral reconstruction. A few episodes of nephrostomy tube-related infections were resolved with antibiotics in the first case. The second case was treated with open ureteroneocystostomy with resection of stenotic segment and reinsertion of the ureter into the bladder (ureterocystoneostomy) because of the length of the involved ureteral segment. Both patients had stable graft function in the follow-up period.

Calcification of the cavernosal bodies may be responsible for development of erectile dysfunction in uremic apolipoprotein E deficient (apoE-/-) mice.

INTRODUCTION AND OBJECTIVE: Erectile dysfunction's physiopathology in uremia is complex and multifactorial, involving a combination of classical risk factors and specific uremia-related risk factors such as increased oxidative stress, endothelial dysfunction and inflammation. The aim of the study is to investigate the effect of chronic kidney disease (CKD) on vascular calcification and endothelial function of cavernosal bodies in apolipoprotein E deficient (apoE-/-) mice, a well known model of erectile dysfunction. MATERIALS AND METHODS: Eight-week-old male apoE-/- mice were randomly assigned to the following 3 groups: (i) subtotally nephrectomised (SNX apoE-/-, 12 mice), (ii) uninephrectomised (UNX apoE-/-, 11 mice) or (iii) sham operated (sham-op apoE-/-, 15 mice). At 16 weeks after surgery, aortas and penile erectile tissues were harvested for histological studies to assess atherosclerosis, vascular calcification, nitrotyrosine staining, total collagen content and macrophage staining. RESULTS: At sacrifice, SNX and UNX mice had significantly higher serum urea, total cholesterol, and triglyceride concentrations than sham-op controls. Atherosclerotic lesions in thoracic aorta were significantly larger in uremic apoE-/- mice than in controls. There were no atheromatous lesions in cavernosal bodies or penile artery observed in any group. However, SNX and UNX animals showed a significant increase in calcification score, collagen content and nitrotyrosine staining in cavernosal bodies when compared with controls. The degree of macrophage infiltration was comparable between the 3 groups. CONCLUSION: In conclusion, even mild renal dysfunction, i.e., after uninephrectomy increases calcification score and aggravates endothelial function of cavernosal bodies in apoE-/- mice and this effect might be linked to increased oxidative stress in penile endothelium.

COVID 19 Pneumonia and a Rare Form of Fungal Peritonitis in a Patient Survivor on Peritoneal Dialysis.

Peritoneal dialysis (PD) related peritonitis is usually caused by bacteria, but viruses and fungi could also affect the peritoneal membrane and cause cloudy effluent with negative bacterial cultures. We present a case of a PD patient who survived fungal peritonitis caused by Geotrichum klebahnii (March 2015) and COVID-19 pneumonia (April 2021) with peritonitis probably caused by the SARS-CoV-2 virus. The fungal peritonitis followed one episode of exit-site infection and two episodes of bacterial peritonitis treated with a wide-spectrum antibiotic. The patient's PD catheter was removed immediately upon the diagnosis of fungal peritonitis, and an antifungal treatment was continued for 3 weeks after catheter removal. The new peritoneal catheter was reinserted 8 weeks after complete resolution of peritonitis, and the patient continued treatment with PD. The patient developed severe Covid-19 pneumonia with a sudden appearance of cloudy peritoneal effluent. There was no bacterial or fungal growth on the effluent culture. A PCR test for SARS-CoV-2 in peritoneal effluent was not performed. The peritoneal effluent became transparent with the resolution of the severe symptoms of Covid-19 pneumonia.

Peritoneal Dialysis-Related Peritonitis: Rate, Clinical Outcomes and Patient Survival.

Peritoneal dialysis-related peritonitis remains the major complication and primary challenge to the long-term success of peritoneal dialysis (PD). The study aimed to analyze the peritonitis rate, the cause, the outcomes, and the association of peritonitis with the survival of patients on peritoneal dialysis. Patient data were collected retrospectively from medical charts. A total of 96 patients received peritoneal dialysis in the PD center from 1 January 1999 to 31 December 2018. Episodes of peritonitis (n=159) were registered in 54 (56.3%) patients. The study population was divided into two groups, a group of patients (n=54) who experienced peritonitis and a group of patients free of peritonitis (n=42). The peritonitis rate was 0.47 episodes per patient year. The majority of causative microorganisms were gram-positive bacteria (53.5%). Outcomes of the episodes of peritonitis were resolved infection in 84.9% of episodes, catheter removal in 11.3% of episodes, and death in 3.8% of the episodes of peritonitis. A Kaplan-Meier analysis and log-rank test revealed that the group with peritonitis tended to survive significantly longer than the peritonitis-free group. A 67% reduction rate in the risk of patient mortality was observed for the peritonitis group compared with the peritonitis-free group (hazard ratio: 0.33, 95% CI 0.19-0.57, P=0.000). The prevention and management of PD-related infections, resulted in their worldwide reduction, supporting the use of PD as a first-line dialysis modality.

Impact of preoperative arterial and venous diameter on achievement of the adequate blood flow in arteriovenous fistula for hemodialysis.

An arteriovenous fistula (AVF) remains the best choice of vascular access (VA) for hemodialysis (HD). The aim of the study was to determine the factors associated with the achievement of adequate blood flow (BF) of AVFs at the 4th week after creation. Created AVFs in 63 patients with chronic kidney disease (CKD) stage 4/5 and CKD stage 5 on hemodialysis (CKD5D) were analyzed in a prospective study. Doppler ultrasound (DUS) was used for measuring the diameter of the radial artery, the brachial artery and the cephalic vein before AVF creation. The BF of AVF was calculated by DUS at the 4th week after creation and adequate BF was defined as ≥ 600 mL/min. The average age of patients was 61.31 ± 12.9 years. An adequate BF of AVF at the 4th week after creation was achieved in 43.54% of patients. The BF of AVF measured in male patients was significantly higher compared to the BF of AVF obtained in females (576.03 mL/min vs 375.12 mL/min, P = 0.004). The diameter of the blood vessels with achieved adequate BF was significantly larger compared to the diameter of the blood vessels without adequate BF (radial artery: 2.45 mm vs 2.03 mm, P = 0.000; brachial artery: 4.78 mm vs 4.06 mm, P = 0.001 and cephalic vein: 3.12 mm vs 2.83 mm P = 0.018). The gender and the diameter of the blood vessels before AVF creation were significantly associated with achievement of adequate BF of AVF at the 4th week of creation.

Tissue accumulation of lanthanum as compared to aluminum in rats with chronic renal failure--possible harmful effects after long-term exposure.

BACKGROUND: Lanthanum (La) carbonate is a new treatment for hyperphosphatemia. We tested the effects of oral La carbonate and aluminum hydroxide, respectively, on tissue accumulation and liver function in rats with chronic renal failure (CRF). METHODS: Adult male non-CRF and CRF rats were randomly assigned to 3 groups receiving either standard diet (St.D), or the same diet supplemented with 3% La carbonate (non-CRF La vs. CRF La) or 3% aluminum hydroxide (non-CRF Al vs. CRF Al). RESULTS: After 12 weeks, serum phosphorus was decreased in both CRF La and Al groups. Urinary La and Al excretion was increased in these two groups, and so was liver and bone La content, and liver Al content. Both total body and liver weight were decreased in CRF La and CRF Al rats. Liver cell proliferation was decreased in these groups, while plasma total alkaline phosphatases and alanine aminotransferase were increased. Hepatic total cytochrome p450 content was reduced in CRF La, but not in CRF Al rats. CONCLUSION: Long-term oral La overload in rats with CRF was associated with a decrease in liver (and total body) weight and mild alterations of liver function, as was Al overload, possibly as a consequence of trace element accumulation.

Impact of disturbances of calcium and phosphate metabolism on vascular calcification and clinical outcomes in patients with chronic kidney disease.

Chronic kidney disease (CKD) is frequently complicated by arterial calcification. The latter is part of the associated mineral and bone disorder (CKD-MBD). Hypercalcemia and hyperphosphatemia have long been known to play a major role in the occurrence of vascular and other soft tissue calcification in patients with CKD, together with endocrine disturbances including vitamin D, parathyroid hormone, fibroblast growth factor-23, and klotho. In addition, many other systemic and local promoters, including inflammation and uremic toxins, contribute to the occurrence of vascular calcification, despite a powerful defense system made up of systemic and local inhibitors, as demonstrated in elegant experimental studies done in vitro and in vivo. Most importantly, several reports have shown that both hyperphosphatemia and hypophosphatemia, and to a lesser degree hypercalcemia and hypocalcemia, are associated with an increased relative risk of mortality in patients with CKD. However, all these reports were observational in nature and must therefore be considered as hypothesis generating. It remains to be demonstrated in prospective randomized trials whether normalization of serum phosphorus and/or calcium leads to better patient outcome. In order to improve outcome in patients with CKD-MBD, early medical intervention is of utmost importance.

Complications and Risks of Percutaneous Renal Biopsy.

BACKGROUND: Renal biopsy performed in native and transplant kidneys is generally considered a safe procedure. AIM: In this study, we evaluated renal biopsy complications and risk factors in one nephrology facility. MATERIAL AND METHODS: We conducted a three-year retrospective study on patients who underwent renal biopsy between January 2014 and December 2016. Strict written biopsy protocol was followed. Clinical and laboratory data were obtained from medical charts. Complications were categorised as minor and major, according to the need for intervention. Minor complications included macrohematuria and/or hematoma that did not require intervention. Major complications included hematuria or hematoma with fall of hematocrit that required a blood transfusion, surgery or caused death. A binary logistic regression model was used to analyse the possible factors associated with complications after the biopsy. RESULTS: We analysed 345 biopsies; samples were taken from patients aged from 15-81 years, of whom 61% were men. A total of 21 (6%) patients developed a complication, 4.4% minor and 1.7% major complications. There were no nephrectomy or death due to biopsy intervention. Overweight patients, as well as those with higher creatinine, lower hemoglobin, higher blood pressure and biopsy due to AKI had higher chances to develop complications (p = 0.037, p = 0.023, p = 0.032, p = 0.002, p = 0.002, respectively). The patients' age, gender, kidney dimension, number of passes and uninterrupted aspirin therapy were not found as significant predictors of complications. In the multivariate logistic model, body weight (OR = 1.031, 95%CI = 1.002-1.062), lower hemoglobin (OR = 0.973, 95%CI = 0.951-0.996) and hypertension (OR = 1.025, 95%CI = 1.007-1.044) increased the risk of complications in biopsied patients. CONCLUSION: Renal biopsy is a safe procedure with a low risk of complications when strict biopsy protocol is observed. Correction of anaemia and blood pressure is to be considered before the biopsy.

Effect of simvastatin in apolipoprotein E deficient mice with surgically induced chronic renal failure.

PURPOSE: Patients with a surgically reduced renal mass are at increased risk for progressive renal failure, which often requires renal replacement therapy or kidney transplantation. We investigated the effects of simvastatin supplementation on uremia enhanced atherosclerosis and vascular calcification in apoE(-/-) (apolipoprotein E deficient) mice (Charles Rivers Laboratories, Wilmington, Massachusetts) with or without superimposed chronic kidney disease. MATERIALS AND METHODS: The mice were randomly assigned to 4 groups, including 2 groups with normal renal function (simvastatin vs control in 13 mice) and the other 2 with surgically created chronic kidney disease (simvastatin vs control in 18). Simvastatin (100 mg/kg) was administered by daily oral gavage for 4 weeks. RESULTS: Simvastatin treatment did not prevent uremia accelerated atherosclerosis in chronic kidney disease apoE(-/-) mice, nor did it retard atherosclerosis progression in control nonchronic kidney disease mice. However, aortic plaques in simvastatin treated chronic kidney disease mice showed significantly less calcification than those in controls with chronic kidney disease (p <0.03). In addition, the increase of aortic nitrotyrosine staining in mice with chronic kidney disease was prevented by simvastatin treatment (p <0.02). Serum total cholesterol was increased to a similar extent in the 2 chronic kidney disease groups compared with that in the nonchronic kidney disease groups. The beneficial effect of simvastatin on uremia enhanced vascular calcification in apoE(-/-) mice with chronic kidney disease was observed despite the absence of changes in uremia accelerated atherosclerosis progression, serum total cholesterol levels or osteopontin and alkaline phosphatase expression. CONCLUSIONS: Our observation opens the possibility of a cholesterol independent action of statins on vascular calcification via a decrease in oxidative stress.