Maria Mesquita

Plasma osteoprotegerin is an independent risk factor for mortality and an early biomarker of coronary vascular calcification in chronic kidney disease.

Abstract Background: Cardiovascular disease is the major cause of morbidity and mortality in chronic kidney disease (CKD) and early biomarkers are required which can predict disease and death in such patients. The aim of our study was to investigate if osteoprotegerin (OPG) could be a predictor of coronary artery calcification (CAC) and mortality in CKD. Methods: A total of 77 outpatients (32 with pre-dialysis CKD and 45 undergoing hemodialysis) were followed-up during 2 years. Measurements of CAC were performed using Siemens Multidetector CT software and calcium scores were measured according to the Agatston method. Results: OPG was an independent predictor of the Agatston score for CAC and correlated with the degree of CAC in pre-dialysis patients. A two-sample t-test characterized survivors as having a better glomerular filtration rate, lower Agatston scores, and lower serum levels of OPG. Kaplan-Meier survival curves separated survivors from non-survivors at plasma OPG cut-off levels of <3.1 ng/mL. A multivariable logistic regression analysis showed that OPG was an independent predictor of mortality from all causes in CKD patients. Conclusions: OPG predicted mortality in CKD patients and could be a valuable biomarker in early detection of CAC in these patients. Clin Chem Lab Med 2009;47:339–46.

Quantitative ultrasound and dual X-ray absorptiometry measurements of the calcaneus in patients on maintenance hemodialysis.

It has been suggested that quantitative ultrasound measurements (QUS), which reflect mainly bone density, could be influenced by bone micro-architecture. The aim of the study was to assess whether the relationship of QUS to dual X-ray absorptiometry (DXA) would reflect abnormalities of bone structure observed in renal osteodystrophy. QUS and bone mineral density of the calcaneus (BMDc) were measured by DXA in 30 patients on maintenance hemodialysis and 34 age- and gender-matched controls. QUS parameters and BMDc were significantly lower in hemodialysis patients than in controls (speed of sound [SOS] and broadband ultrasound attenuation [BUA], p = 0. 030; stiffness, p = 0.003; BMDc, p = 0.006). Bone measurements were not correlated with serum parathyroid hormone (PTH). The regression lines of SOS, BUA, and stiffness to BMDc were not significantly different from that of the controls. When dividing the patients into two subgroups according to their median PTH (203 pg/mL), the slopes of the regression lines of BUA to BMDc were significantly different between these two subgroups (p = 0.052). The slope of the subgroup with PTH </= 203 pg/mL was significantly different from that of the controls (p = 0.030). In conclusion, QUS of the calcaneus can be used for bone assessment in patients on maintenance hemodialysis. The differences in the slopes of patients with a less pronounced degree of hyperparathyroidism compared with patients with a higher degree of hyperparathyroidism and to controls suggest that BUA of the calcaneus contains information on bone complementary to DXA measured at the same site. The clinical relevance of this finding is presently unclear.

RENAL BIOPSY FINDINGS IN BELGIUM: A RETROSPECTIVE SINGLE CENTER ANALYSIS

Abstract Renal biopsy is the definitive diagnostic test in patients with renal parenchymal disease. Renal biopsy registry is an important tool which can provide valuable data concerning early and correct epidemiological description and clinical correlations of renal diseases. Records of 326 adult renal biopsies performed at our hospital from January 1991 till the end of December 2006 were retrospectively examined. Overall, secondary glomerular diseases (SGD) were predominant (39.9%), followed by primary glomerular diseases (PGD) (30.4%), vascular diseases (13.2%) and TIN (6.7%). Total sclerosis of the kidney did not allow histopathological diagnosis in 5.8% of all biopsied kidneys. Focal and Segmental Glomerular Sclerosis (FSGS), IgA Nephropathy (IgAGN) and Minimal Change Disease (MCD) and Membranous Glomerulopathy (MGN) were the most common PGD, altogether representing 75.7% of all PGD. FSGS was the most frequent (30.3%), followed by IgAGN (21.2%), MCD (19.1%) and MGN in 15.1%. Vasculitis, HIVAN, diabetic nephropathy and amyloidosis were the most common SGD, altogether representing 90% of all SGD. Immune Mediated Glomerulonephritis (IMGN) were the most frequent (32.3%), followed by HIVAN (16.9%), diabetic nephropathy (14.6%) and amyloidosis (10%). Nephroangiosclerosis (benign and malignant nephroangiosclerosis) was the most frequent vascular nephropathy responsible for 79% of all vascular diseases. Thrombotic microangiopathy was seen in 9.3% and atherothrombotic disease in 7% of all vascular diseases. Concerning tubular diseases, chronic TIN accounted for 63.6% of all tubular diseases, followed by light chaincast nephropathy (22.7%) and acute TIN (13.6%). Becauseof lack of material, 3.4% of all biopsies could not be analyzed. These data demonstrate that the distribution of biopsy-proved renal diseases in a Belgian population of the Brussels area is strongly influenced by the indications of renal biopsy. Harmonization of these indications might reflect with more accuracy the actual incidence of different nephropathies in a given population. Nation and worldwide renal biopsy registers are important to follow patterns of renal diseases in different populations. This information is important not only for health organizations in order to plan health budget but also for helping clinicians to provide a better care to patients.

Osteoprotegerin and Progression of Coronary and Aortic Calcifications in Chronic Kidney Disease

Vascular calcifications (VCs) are important predictors of cardiovascular mortality in patients with chronic kidney disease (CKD). We have shown previously that osteoprotegerin (OPG), a potential early biomarker for VC, was an independent predictor of mortality in CKD patients. The aim of our study was to follow longitudinally coronary and aortic VCs. VCs were measured using Siemens 16 detector CT in a group of predialysis and hemodialyzed patients before and after a follow-up of 4 years. Some of these patients were transplanted in the meantime. Renal function, calcium, phosphate, iPTH, hs-CRP (high sensitive protein C reactive), and OPG serum levels were also compared. VCs progressed in predialysis, hemodialyzed, and transplanted patients but the progression was not the same in all arterial beds. A progression of coronary calcifications was observed in predialysis and transplanted patients, while aortic calcifications worsened significantly only in hemodialyzed patients. OPG serum levels and hs-CRP were significantly lower among transplanted patients. We concluded that VC depends on the severity of the kidney disease. Transplanted patients are not protected from VC, yet their OPG serum levels were significantly lower, suggesting that there is no link between between OPG levels and severity of VC. Longer follow-up of these patients would be necessary to assess whether a decline in OPG correlates with better survival.

First Use of Tamoxifen in an HIV Patient with Encapsulating Peritoneal Sclerosis

Encapsulating peritoneal sclerosis (EPS) is a rare but serious life-threatening complication in peritoneal dialysis patients. At present, there is no evidence-based standard therapy for EPS. Tamoxifen has been used and shown good results in non-HIV peritoneal dialysis patients with EPS. We report a case of a patient with HIV treated with antiretroviral therapy (zidovudine, lamivudine and saquinavir) for several years. He had end-stage renal disease and was treated with continuous ambulatory peritoneal dialysis (CAPD). After 11 years on CAPD, he developed EPS and was treated successfully with tamoxifen in combination with corticosteroids. No adverse effects were observed and no changes were noted in CD4 counts or HIV viral load during this therapy. These findings suggest that tamoxifen can be safely given to HIV patients with peritoneal dialysis-related EPS. Nevertheless, caution is required as tamoxifen could interact with certain antiretroviral agents.

False positive carbohydrate-deficient transferrin results in chronic hemodialysis patients related to the analytical methodology

OBJECTIVES Chronic kidney disease stage V is associated with a metabolic acidosis, a disturbance also observed in heavy alcohol consumption. Carbohydrate-deficient transferrin is considered the most accurate biomarker for identifying chronic alcohol abuse. We tested whether increased CDT results occurred in patients on dialysis therapy. DESIGN AND METHODS One hundred twenty-two samples from HD patients were analyzed by three different analytical methods and the results were compared with those obtained in 48 healthy volunteers. RESULTS On the basis of the upper 97.5th percentile, positive CDT results were found in 25.4%, 9.8% and 12.3% of the HD patients with particle-enhanced immunonephelometry, capillary electrophoresis and HPLC, respectively. A significant correlation between CDT values and transferrin concentration was found for the particle-enhanced immunonephelometric test (r: -0.311; p: 0.0009). CONCLUSIONS A high rate of positive CDT results was observed in HD patients with the particle-enhanced immunonephelometry and seems to be related to the low transferrin concentration.

Late diagnosis of extra-pulmonary tuberculosis leads to irreversible kidney failure in a non-immunocompromised patient

We report a case of extra pulmonary tuberculosis with multiple localizations including bone and kidney in a 21-year-old Pakistani immigrant living in Belgium. Late diagnosis of tuberculosis may lead to end stage renal disease and dialysis. Countries with low prevalence of tuberculosis should be vigilant towards high risk groups for tuberculosis because this preventable and curable disease may lead to devastating complications when diagnosed late.

Management of Refractory Essential Thrombocythemia With Anagrelide in a Patient Undergoing Hemodialysis

BACKGROUND Management of essential thrombocythemia (ET) in high-risk patients is difficult because high platelet numbers can lead to vascular occlusive events and bleeding. Therapeutic interventions in ET are limited to hydroxyurea and anagrelide; however, in Europe, anagrelide is contraindicated in patients with chronic renal disease. OBJECTIVE The aim of this case report was to describe the use of anagrelide in a patient with ET and renal impairment. CASE SUMMARY A 73-year-old white female patient with severe renal impairment who was diagnosed with ET was receiving treatment with hydroxyurea 1 g/d since 2001. At this time she was also receiving aspirin 80 mg/d; calcium carbonate 1 g/d; pravastatin 40 mg/d; folic acid 5 mg/d; furosemide 40 mg/d; cetirizine 10 mg/d; erythropoietin 10,000 U once monthly; a vitamin B complex, 1 tablet a day; and iron tablets 105 mg/d. In February 2007, because her white blood cell count fell to 2.1 x 10(9)/L, myelodepression was suspected and hydroxyurea was stopped. This led to enhanced platelet levels and the introduction of anagrelide at an initial dose of 0.5 mg/d that was steadily increased to 2.5 mg/d. All other treatments were continued with some dosage adjustments. Sodium bicarbonate 1 g/d and vitamin D were added to her regimen. After 18 months of anagrelide treatment, a sudden but moderate fall of platelets to 142 x 10(3)/microL with severe anemia (hemoglobin, 6.5 g/dL) was observed. The patient had anemia since 2004, but the condition worsened due to bleeding related to an ulcer at the cecal valve. The patient refused blood and platelet transfusions and surgical intervention for religious reasons. Because of hemodynamic instability, she was admitted to the intensive care unit in December 2008 and died 24 hours after admission. CONCLUSION We report a case of ET and chronic renal failure treated with anagrelide and low-dose aspirin in a patient who did not receive transfusion and surgical intervention due to religious reasons, and had a fatal outcome.

Fatal cerebritis and brain abscesses following a nontraumatic subdural hematoma in a chronic hemodialyzed patient.

Staphylococcus aureus is the leading cause of bacteremia in hemodialysis‐dependent patients that can lead to metastatic abscesses with poor outcome. We report a case of a 65‐year‐old chronic hemodialyzed male patient who developed cerebritis and brain abscesses complicating a spontaneous subdural hematoma, following Staphylococcus aureus bacteremia related to infected arteriovenous fistula. In spite of adequate antibiotherapy and several surgical brain drainages, our patient did not survive. Prevention of S. aureus is highly important in hemodialysis patients.

OPG, RANK-L, bone metabolism and BMD in patients on haemodialysis and ambulatory peritoneal dialysis

Prostate Cells Express Vitamin D-25-Hydroxylases and Can Synthesize 1α,25-Dihydroxyvitamin D3 from Vitamin D3. J. N. Flanagan*, M. V. Young*, L. W. Whitlatch*, J. S. Mathieu*, K. S. Persons*, M. F. Holick, T. C. Chen. Department of Medicine, Boston University School of Medicine, Boston, MA, USA. The biologically active form of vitamin D, 1α,25-dihydroxyvitamin D (1,25D), plays essential roles in calcium homeostasis, and regulates proliferation and differentiation of a variety of cells, including prostate cells. Two hydroxylation steps catalyzed by vitamin D25-hydroxylase (25-OHase) in the liver and 25-hydroxyvitamin D (25D)-1α-hydroxylase (1α-OHase) in the kidneys are required for the activation of vitamin D to 1,25D. Previously, we reported that 1α-OHase is also expressed in extra-renal tissues, including prostate cells, suggesting that local production of 1,25D could provide an important cell growth regulatory mechanism. Now, we present evidence that prostate cells also possess 25OHase and are capable of metabolizing vitamin D3 to 1,25D3 in the immortalized PZ-HPV7 cells derived from normal prostate tissue. Three types of 25-OHase, one mitochondrial (CYP27A1) and two microsomal (CYP3A4 and CYP2R1), have been described. Using real-time PCR we found that CYP2R1 was expressed two-fold greater in normal human prostate tissue, 3-fold greater in PZ-HPV-7 cells and 6-fold greater in LNCaP prostate cancer cells than in normal liver tissue, whereas CYP27A1 was expressed 10-fold greater in normal liver tissue than in normal prostate tissue. Very little or no expression of CYP27A1 was found in PZ-HPV-7, LNCaP and PC-3 cells. PC-3 cells also expressed very little or no CYP2R1. The presence of 25-OHase in PZ-HPV-7 cells was further supported by the use of functional assays: (1) the addition of vitamin D3 caused a dose-dependent up-regulation of 24-hydroxylase (CYP24A1) and IGF-BP3 mRNA, two genes known to be sensitive to 1,25D regulation in prostate cells, (2) vitamin D3 at 10 -6 M caused a 40% inhibition of Hthymidine incorporation into DNA. These data suggest that vitamin D3 was converted to 25D3, which in turn was further converted to 1,25D3 before exerting biological actions in prostate cells. The higher expression of CYP2R1 in prostate cells than in liver cells may have chemo-preventive relevance in prostate cancer, since CYP2R1 has been recently identified by a gene mutation analysis of a vitamin D deficient patient as a biologically relevant 25-OHase. Our results suggest that maintaining adequate levels of serum vitamin D or 25D by oral supplementation or sun exposure can be a safe and effective chemo-preventive measure to decrease the risk of prostate cancer.