Zeki Aydin

Role of Plasmapheresis Performed in Hemodialysis Units for the Treatment of Anti‐Neutrophilic Cytoplasmic Antibody‐Associated Systemic Vasculitides

Anti‐neutrophilic cytoplasmic antibody (ANCA) positivity is seen in some systemic necrotizing vasculitides. Wegeners granulomatosis and microscopic polyangiitis are among the ANCA‐associated systemic vasculitides (AASV) and mortality is very high when renal failure occurs together with alveolar hemorrhage. The role of plasmapheresis in the treatment of these diseases has been studied retrospectively. Twelve patients with AASV who had plasmapheresis together with immunosuppressive medications have been involved. Primary diseases, immunosuppressive protocols, the number of plasmapheresis sessions, the amount of plasma that has been exchanged, urea and creatinine levels before and after treatment, pulmonary findings, the need for hemodialysis, and the outcome of patients were recorded. The mean age of patients was 52.9 ± 18.2 years. Wegeners granulomatosis was diagnosed in seven (58.3%) and microscopic polyangiitis in five (41.7%) patients. All patients had pulse cyclophosphamide and methylprednisolone followed by maintenance doses and plasmapheresis. Seven patients had hemodialysis at the beginning, and hemodialysis needed to be continued in three patients. Partial and complete remission was seen in 6 (50%) and 3 (25%) patients, respectively, and pulmonary findings regressed in all patients. End‐stage renal disease develops generally in AASV due to rapidly progressive glomerulonephritis causing severe irreversible glomerular damage. The mortality rate rises to 50% in cases of renal failure with diffuse alveolar hemorrhage; therefore, pulse immunosuppressive treatment with plasmapheresis may be life‐saving, as shown in our study.

A novel frameshift deletion in the albumin gene causes analbuminemia in a young Turkish woman.

BACKGROUND Analbuminemia is a rare autosomal recessive disorder manifested by the absence, or severe reduction, of circulating serum albumin. The analbuminemic trait was diagnosed in a young Turkish woman on the basis of her clinical symptoms (bilateral lower limb edema) and biochemical findings (minimal albumin amount and variable increases in other protein fractions). METHODS Total DNA from the analbuminemic proband and her parents was PCR-amplified using oligonucleotide primers designed to amplify the 14 exons of the albumin gene (ALB) and the flanking intron regions. The products were screened for mutations by single-strand conformation polymorphism (SSCP) and heteroduplex analyses (HA). RESULTS HA allowed the identification of the mutation site in exon 12. Direct DNA sequencing of this abnormal fragment revealed that the analbuminemic trait was caused by a homozygous CA deletion at nucleotide positions c. 1614-1615 in the codons for Cys538 and Thr539. The subsequent frameshift should give rise to a putative truncated albumin variant in which the sequence Cys(538)-Thr-Leu-Ser has been changed to Cys(538)-Thr-Phe-Stop. The parents were heterozygous for the same mutation. CONCLUSIONS Gel-based mutation detection and DNA sequencing substantiate the clinical diagnosis of congenital analbuminemia in our patient and show that the condition is caused by a novel mutation within the ALB gene. These results contribute to shed light on the molecular basis of this rare condition.

The effect of different doses and types of intravenous iron on oxidative stress and inflammation in hemodialysis patients

BACKGROUND Although intravenous iron (IVI) is thought to have potential inflammatory and atherogenic effects, there are not enough studies comparing these effects in chronic hemodialysis (HD) patients. In this study, different doses and types of IVI were examined for effects on inflammation and oxidative stress. METHODS Chronic HD patients (n=101) were grouped into those not receiving IVI (group 1, n=29), those getting intermittent iron sucrose (group 2, n=25), those receiving intermittent iron dextran (group 3, n=24) and those getting a once monthly total dose of iron dextran (group 4, n=23). Malondialdehyde (MDA), advanced oxidation protein product (AOPP), C-reactive protein (CRP) and TNF-α levels were measured on days 0, 2, 7 and 28. RESULTS Groups were similar regarding age, sex, hemoglobin, iron indices and total amount of IVI given monthly. Although MDA levels at days 7 and 28, AOPP levels at days 0 and 28, CRP levels at day 28 and TNF-α level at day 7 were higher than at other days, there were no significant differences between the IVI groups on statistical analysis. CONCLUSION The different types and doses (intermittent or once monthly total dose) of IVI treatments are well tolerated without negative effects on the markers of lipid and protein oxidation and inflammatory indices in chronic HD patients.

The relationship of Prohepcidin levels with anemia and inflammatory markers in non-diabetic uremic patients: a controlled study.

Abstract Introduction: Hepcidin, a small peptide hormone synthesized in the liver, plays central role in regulation of iron metabolism. Hepcidin generation in chronic kidney disease (CKD) is dependent on iron status, anemia, inflammation, and hypoxia and erythropoietin levels. In our study, the relationship between Prohepcidin levels and inflammation and iron indices in non-diabetic uremic patients was investigated. Methods: This study has a cross-sectional design which includes four groups: Non-diabetic 21 patients with stage 4 CKD (predialysis), 20 hemodialysis (HD) and 21 peritoneal dialysis (PD) patients and 17 healthy volunteers as the control group. Complete blood count, iron, total iron binding capacity (TIBC), ferritin, high-sensitive C-reactive protein (hsCRP), fibrinogen, parathyroid hormone, interleukin (IL)-6 and Prohepcidin levels were recorded. Results: Serum Prohepcidin levels in the predialysis, HD, PD and the control groups were 119.6 ± 45.1 ng/mL, 140.2 ± 41.8 ng/mL, 148.2 ± 35.0 ng/mL and 93.8 ± 21.9 ng/mL, respectively (p < 0.001). Prohepcidin was positively correlated with urea (r = 0.345, p = 0.002), creatinine (r = 0.465, p < 0.001), phosphorus (r = 0.253, p = 0.025), hsCRP (r = 0.275, p = 0.019), duration of dialysis treatment (r = 0.443, p < 0.001), fibrinogen (r = 0.467, p < 0.001) and IL-6 (r = 0.615, p < 0.001) levels. A negative correlation was detected between Prohepcidin levels and albumin (r = −0.286, p < 0.001), TIBC (r = −0.573, p < 0.001), GFR (r = −0.473, p < 0.001), hemoglobin (r = −0.351, p = 0.002) and hematocrit (r = −0.342, p = 0.002) levels. Discussion: Prohepcidin levels increase with deepening anemia and show positive correlation with inflammatory markers. Therapeutic interventions regarding Prohepcidin action on inflammatory status may play a role in the treatment of anemia due to inflammation. Functional iron deficiency is frequent in uremic patients. It may be beneficial to measure Prohepcidin level together with ferritin among these patients.

Placement of Hemodialysis Catheters with a Technical, Functional, and Anatomical Viewpoint

Aims. Vascular access is of prime importance for hemodialysis patients. We aimed to study early complications of hemodialysis catheters placed in different central veins in patients with acute or chronic renal failure with or without ultrasound (US ) guidance. Material and Methods. Patients who were admitted to our unit between March 2008 and December 2010 with need for vascular access have been included. 908 patients were examined for their demographic parameters, primary renal disease, and indication for catheterization, type and location of the catheter, implantation technique, and acute complications. Results. The mean age of the patients was 60.6 ± 16.0 years. 643 (70.8 %) of the catheters were temporary while 265 (29.2%) were permanent. 684 catheters were inserted to internal jugular veins, 213 to femoral, and 11 to subclavian veins. Arterial puncture occurred in 88 (9.7%) among which 13 had resultant subcutaneous hematoma. No patient had lung trauma and there had been no need for removal of the catheter or a surgical intervention for complications. US guidance in jugular vein and experience of operator decreased arterial puncture rate. Conclusion. US-guided replacement of catheter to internal jugular vein would decrease complication rate. Referral to invasive nephrologists may decrease use of subclavian vein. Experience improves complication rates even under US guidance.

Tuberculosis in patients on hemodialysis in an endemic region.

Clinical presentation of tuberculosis is different in hemodialysis patients than in the general population. This study aimed to analyze hemodialysis patients with tuberculosis in Istanbul. Patients who were on a chronic hemodialysis program in Istanbul for more than 3 months and diagnosed to have tuberculosis at least 3 months after the start of hemodialysis were included. To discard the effect of immigration from other cities, we included only patients who had started their dialysis program in Istanbul. Their demographic and clinical data were analyzed using Statistical Package for Social Sciences for Windows ver. 13.0. Of the 925 patients screened from 7 different centers, 31 (3.35%) were found to have tuberculosis. The mean age was 52.3±13.5 years. The male/female ratio was 18/13. The mean duration of dialysis therapy and the duration of dialysis till the diagnosis of tuberculosis were 62.6±54.3 and 21.7±25.7 months, respectively. Extrapulmonary tuberculosis constituted 48.39%. Treatment ended with a cure in 18 (58.05%); was still ongoing in 12 (38.70%) patients; and 1 (3.25%) died of pulmonary tuberculosis. The lower incidence of tuberculosis compared with previous reports may be related to the differences in the diagnostic criteria and the decrease in the rate of tuberculosis during recent years. The demographic and clinical parameters of the patients were quite similar to the average dialysis population in Turkey. Hence, we cannot address a subpopulation with additional risk. It is important to prevent tuberculosis in hemodialysis patients due to difficulties in the diagnosis and treatment. Thus we recommend routine screening of hemodialysis patients and effective isolation and treatment of infected patients.

Primary hyperoxaluria in an adult presenting with end-stage renal failure together with hypercalcemia and hypothyroidism

Primary hyperoxaluria (PH) is a rare genetic disorder characterized by overproduction of oxalate due to specific enzyme deficiencies in glyoxylate metabolism. The primary clinical presentation is in the form of recurrent urolithiasis, progressive nephrocalcinosis, end‐stage renal disease, and systemic oxalosis. Herein, we present a case of PH who was diagnosed at 47 years of age after 6 years on hemodialysis. He presented with fatigue, anorexia, weight loss, and was found to have cachexia, diffuse edema, hepatomegaly, ascites, hypercalcemia, hyperphosphatemia, hypoalbuminemia, low parathyroid hormone levels, lytic and resorptive areas in the vertebrae, diffusely increased echogenity of the liver, multiple renal stones, and bilateral nephrocalcinosis. Bone marrow biopsy showed calcium oxalate crystals and crystal granulomas. The liver biopsy could not be performed. The absence of an identifiable reason for secondary forms, the severity of the clinical presentation, and pathological findings led to the diagnosis of PH2. He died while waiting for a potential liver and kidney donor. The presented case is consistent with the literature as he had renal stone disease in the third decade and end‐stage renal disease in the fifth decade. Hypercalcemia was thought to be due to osteoclast‐stimulating activity of macrophages constituting the granuloma. Erythropoietin‐resistant anemia and hypothyroidism were thought to be due to accumulation of oxalate in the bone marrow and thyroid gland, respectively. It is very important to keep in mind the possibility of PH when faced with a patient with nephrocalcinosis and oxalate stone disease.

Volume Status in Patients on Peritoneal Dialysis: The Role of Apelin and Bio-Impedance Spectroscopy

One of the main factors determining the survival of peritoneal dialysis (PD) patients is volume status. We aimed to investigate hydration status of PD patients by bio-impedance spectroscopy (BIS) and echocardiography and to study the relation of them with apelin, which has effects related with volume status like vasodilation, positive inotropism, and inhibition of ADH release and RAS antagonism. Chronic PD patients without active cardiac disease or clinically prominent hypervolemia were included. Besides the demographic, clinical, and laboratory data, BIS and echocardiographic findings together with apelin levels were recorded. The study included 21 patients. Of them, eight patients were euvolemic, one patient was hypovolemic, and others have some degree of overhydration (1.1–6.8 L) with BIS, although all were euvolemic clinically. Mean apelin level was 1.49 ± 0.49 ng/mL. Apelin level was positively correlated with ejection fraction and negatively with total body water (TBW), intracellular and extracellular water, lean tissue mass, and left atrium diameter. On linear regression model, TBW was the major determinant of apelin. Although apelin is expected to increase in hypervolemic patients, the negative correlation with body water in this study may be related with yet unknown role of apelin in dialyzed patients. They may have important roles in volume status in future.

Male pseudohermaphroditism as a cause of secondary hypertension: a case report

Seventeen alpha-hydroxylase deficiency (17OHD) syndrome is a rare genetic disorder of steroid biosynthesis causing decreased production of glucocorticoids and sex steroids and increased synthesis of mineralocorticoid precursors. There are only 130 cases reported worldwide with documented severe 17OHD. Here, we describe the clinical, hormonal, and molecular genetic characteristics of a Turkish patient with 17OHD, who presented to our clinic due to high blood pressure. A 29-year-old girl with 46,XY genotype was admitted to our nephrology clinic due to uncontrolled hypertension and hypokalemia. The diagnosis was suspected because of primary amenorrhea, absence of sexual maturation, hypertension, and hypokalemia. Endocrine investigation revealed low basal levels of all steroid hormones which require 17-hydroxylation for biosynthesis. Plasma concentrations of ACTH, FSH, and LH were elevated. Imaging did not reveal uterus or adnexial structures. The patient’s hypertension and hypokalemia resolved after glucocorticoid replacement and treatment with potassium-sparing diuretics. 17OHD is a rare form of congenital adrenal hyperplasia in which defects in the biosynthesis of cortisol and sex steroids result in mineralocorticoid excess, hypokalemic hypertension, and sexual abnormalities such as pseudohermaphroditism in males, and sexual infantilism in females. 17OHD should be suspected in patients with hypokalemic hypertension and lack of secondary sexual development so that appropriate therapy can be implemented.

CITROBACTER PERITONITIS: TWO CASES AND REVIEW OF THE LITERATURE

One of the uncommon gram negative organisms causing peritonitis in peritoneal dialysis patients is Citrobacter. Because of this organisms resistant nature, treatment for Citrobacter peritonitis may be difficult, and removal of the catheter may be necessary in refractory cases. Here we present 2 cases of peritonitis caused by this organism and fully treated with antibiotics. The literature contains only a limited number of reports on Citrobacter peritonitis, mostly case reports or portions of general papers about the microbiological spectrum of peritonitis in the relevant units. Until enough data about this micro-organism have been accumulated to map out an approach, it is wise to individualize treatment by watching the response of the patient during the wait for the antibiogram result and not to hesitate to remove the catheter if the clinical situation deteriorates.