Umit Saatci

Mutation frequency of Familial Mediterranean Fever and evidence for a high carrier rate in the Turkish population

Familial Mediterranean Fever (FMF) is a recessive disorder characterised by episodes of fever and neutrophil-mediated serozal inflammation. The FMF gene (MEFV) was recently identified and four common mutations characterised. The aim of this study was to determine the carrier rate in the Turkish population and the mutation frequency in the clinically diagnosed FMF patients. We found a high frequency of carriers in the healthy Turkish population (20%). The distribution of the five most common MEFV mutations among healthy individuals (M694V 3%, M680I 5%, V726A 2%, M694I 0% and E148Q 12%) was significantly different (P<0.005) from that found in patients (M694V 51.55%, M680I 9.22%, V726A 2.88%, M694I 0.44% and E148Q 3.55%).

Implications of certain genetic polymorphisms in scarring in vesicoureteric reflux: Importance of ace polymorphism

Polymorphisms of the renin-angiotensin system (RAS) have been shown to affect renal prognosis in a number of diseases. We examined the influence of deletion (D) and insertion (I) polymorphism in the angiotensin I-converting enzyme (ACE) gene and the other polymorphic markers of RAS, and that of plasminogen-activator inhibitor-1 (PAI-1) on renal scarring in reflux nephropathy. Ninety-four children with third- or fourth-degree reflux were the subject of the study. They were stratified into two groups according to the technetium-99m-dimercaptosuccinic acid (DMSA) findings: the first group consisted of 41 patients with no scar formation. In the second group (n = 53), there was significant scar formation in the refluxing units. ACE levels, ACE gene, angiotensin-1 receptor (AT1) A1166C, angiotensinogen (ATG) M235T, and PAI-1 4G/5G polymorphisms were studied. In the second group with scarred kidneys, 18 patients had decreased renal function. The frequency of patients homozygous for the D allele was significantly greater in the second group with scar formation in the refluxing units compared with the first group of patients (P < 0.005). On multivariate analysis, the DD genotype was the only factor that had a significant impact on renal scar formation, introducing a 4.9-fold risk (P < 0.05, 95% confidence interval). We were unable to find any correlation with the presence ofDD genotype and hypertension, decreased renal function, proteinuria, or sex of the patient. DDgenotype correlated with the serum ACE levels (P < 0.005). AT1and ATGpolymorphisms and PAI-1 polymorphism did not correlate with scar formation or any of the parameters. This study provides evidence that the DDgenotype of ACE may be a genetic susceptibility factor contributing to adverse renal prognosis in reflux nephropathy; namely, scar formation. The role of the synergism between the aforementioned genetic polymorphisms can be enlightened with larger patient groups, possibly through multicenter studies.

Effect of Congenital Heart Disease on Renal Function in Childhood

Background: Nephropathy is a well-known complication of congenital heart disease (CHD), and the risk of developing renal impairment is particularly high in patients with cyanotic CHD. Most investigations of renal impairment in CHD have involved patients 20 years and older. This study investigated renal tubule function in pediatric patients with CHD, and compared findings in cyanotic and acyanotic groups. Methods: Twenty children with acyanotic CHD, 23 children with cyanotic CHD, and 13 healthy children were enrolled. Blood and early morning urine samples were collected from each subject to measure urinary concentrations of sodium, microalbumin, creatinine, β2-microglobulin, and N-acetyl-β-D-glucosaminidase (NAG). Results: The age and sex distributions in the three groups were similar. Median fractional excretion of sodium (FeNa) and urinary NAG/creatinine were significantly higher in the cyanotic group than in the control group (p = 0.022 and p = 0.002, respectively). There were no statistically significant differences among the groups with respect to urinary β2-microglobulin/creatinine, urinary microalbumin/creatinine or glomerular filtration rate. Conclusion: Tubular injury can be detected before glomerular injury occurs even within the first decade of life in patients with cyanotic CHD.

Serum concentration and urinary excretion of beta 2-microglobulin and microalbuminuria in familial Mediterranean fever.

Familial Mediterranean fever is characterised by recurrent and self limited attacks of fever and polyserositis and its devastating complication is the development of renal amyloidosis. In order to detect the presence of early glomerular and tubular damage in patients with familial Mediterranean fever and to assess the possible role of beta 2-microglobulin in the inflammatory attacks of this disease, serum and urine beta 2-microglobulin concentrations and microalbuminuria were evaluated in these patients. A total of 20 patients with familial Mediterranean fever were studied on and off colchicine treatment; seven of these patients developed a familial Mediterranean fever attack when they were off treatment. During the familial Mediterranean fever attacks serum beta 2-microglobulin concentrations decreased, whereas fractional excretion of beta 2-microglobulin, urine beta 2-microglobulin creatinine, and urine albumin/creatinine ratios increased. We conclude that glomerular and tubular functions deteriorate during the attacks. Further studies are needed to discover the effector(s) causing these transient glomerular and tubular disorders.

Autoimmune thyroiditis with associated proteinuria: report of two patients.

The association of renal disease and autoimmune thyroid disorders has been reported previously. Renal findings associated with autoimmune thyroiditis present more commonly as proteinuria ranging from mild to nephrotic levels. We report here two adolescent girls with hyperthyroidism associated with transient proteinuria correlated with thyroid hormone levels. They had positive antithyroid peroxidase and antithyroglobulin antibodies. Ultrasonographic and scintigraphic findings of the thyroid gland were consistent with Graves disease in both. Their renal functions were normal except proteinuria (daily protein excretion of 13.5 mg/m2/h in patient 1 and 11 mg/m2/h in patient 2). When they became euthyroid on antithyroid treatment, proteinuria decreased without associated hematuria and/or hypertension. In conclusion, patients with autoimmune thyroid disease should be assessed for the possibility of proteinuria and the etiological investigation of proteinuria should include evaluation of thyroid functions.

Urinary glycosaminoglycans in the course of familial Mediterranean fever

Familial Mediterranean fever (FMF) is characterised by recurrent fever and serositis. The most important complication of the disease is amyloidosis. Cheap and non-invasive methods would be important in predicting or establishing the early diagnosis of amyloidosis. For this purpose, we studied the role of urinary glycosaminoglycans (GAG). The study group included 123 FMF patients without an attack and 11 patients with FMF associated amyloidosis. Ten healthy children and ten patients with primary nephrotic syndrome served as controls. In patients with amyloidosis, urinary GAG were lower than in patients with FMF, patients with nephrotic syndrome and controls (median and range: 8.54xa0mg hexuronic acid/g creatinine (1.87–25.5), 5.8 (1.7-17.26), 23.12 (8.74–28.06) and 19.25 (14.2–26.9) respectively, P<0.01). There was a significant negative correlation between the duration of the disease and urinary GAG (r= -043, P=0.002). In 49 FMF patients with a low GAG , urinary GAG increased significantly after an increase in the colchicine dose (median and range: 6.64xa0mg hexuronic acid/g creatinine (1.77–19.39) and 9.45xa0mg hexuronic acid/g creatinine (2.36–28.9), P<0.01). Conclusion: These results suggest that urinary glycosaminoglycan levels may be a predictor of amyloidosis in patients with familial Mediterranean fever. We also suggest that effective colchicine doses may be monitored by following urinary glycosaminoglycan excretion.

Low-Dose Intranasal Desmopressin (DDAVP) for Uremic Bleeding

Dr. Seza Ozen, Kuleli sok. 9/2, GaziOsmanPasa, TR-06700 Ankara (Turkey) Table 1. Effect of low-dose DDAVP Dear Sir, In children with advanced chronic renal failure, bleeding is a frequent complication which contributes to morbidity and even mortality. In the last decade, desmopressin (l-deamino-8-/Jarginine vasopressin; DDAVP), a synthetic analogue of antidiuret-ic hormone, has been used to treat uremic bleeding. The exact mechanism by which DDAVP corrects uremic bleeding is still not clear; DDAVP-induced release of large von Willebrand factor (vWF) multimers or release of serotonin from uremic platelets has been among the suggested mechanisms [1, 2]. Although DDAVP has usually been administered parenterally in uremic patients, this route of application requires a physician and is not very feasible for children. Intranasal DDAVP at high doses has also been put into use in uremic patients [3]. In the presented study, we have examined the effect of low-dose (10 and 20 μg) intranasal DDAVP (Minirin) on bleeding time, factor VIII procoagulant activity (FVIIl·C), vWF, protein C (PC) activity, plasminogen activator inhibitor-3 (PAI-3), αi-antitrypsin and thrombomodulin in our uremic children on maintenance hemodialy-sis. We have thus attempted to investigate the mode of action of low-dose intranasal DDAVP and clarify its action in potentiating hemostasis. The patient group consisted of 11 children hemodialyzed thrice weekly with cuprophane membranes. The age range was 12-21 years (median 16). Six of them had clinical signs of bleeding diathesis in the form of dysmenorrhea, or oral or nasal/naso-pharyngeal bleeding and/or gastrointestinal bleeding, or in the form of spontaneous ec-chymotic skin lesions. DDAVP was administered intranasally at a dose of 10 μg at the first phase of the study (44 h after the termination of the previous dialysis session). At the second phase of the study, 2 days later, 20 μg DDAVP was given by the same route. In only 1 patient (No. 2), who developed heparin-induced thrombocytopenia, a third dose of DDAVP was administered intravenously (0.3 μg · kg-’). Ivy bleeding times were measured before and 2 h after DDAVP administration by a medical person who was blinded to the aim of the procedure and the medications given to the study

DMSA renal scanning versus urography for detecting renal scars in vesicoureteral reflux.

32 children admitted to Hacettepe University Hospital for surgical treatment of vesicoureteral reflux (VUR) between 1987 and 1988 were included in this prospective double-blind study. All patients underwent intravenous urography (IVU), voiding cystouretrography and 99mTc DMSA renal scanning. The sensitivity and specificity of the DMSA scan and IVU for detecting renal scarring were investigated. With regard to the presence of renal scarring, the sensitivity and specificity of IVU and DMSA were not found to be statistically different. But when the scars were scored, DMSA was found to have a higher scoring index compared to IVU. In patients who were candidates for surgical management of VUR, renal scars could be detected both by IVU and DMSA scan but, for the follow-up, the DMSA scan was found to be the investigation of choice.

Clinical review of idiopathic versus hepatitis B surface antigen related forms of membranous glomerulonephritis.

Clinical features and therapeutical approaches in 10 cases of membranous glomerulonephritis (MGN) have been reviewed in an attempt to identify predictive indices of prognosis, and features distinguishing between idiopathic and hepatitis B surface antigen (HBsAg) related forms of glomerulopathy. Five of these children (age range 8-10 years) had HBsAg associated MGN and the other five (age range 12-16) lacking this antigen were defined as idiopathic MGN. The follow up was nine months to 10 years (mean 4.3 years). All had nephrotic syndrome during the course of their disease. There were no distinguishing clinical features nor any difference in the outcome between these two groups. None of the clinical findings including the presence of HBsAg, adversely affected outcome. All patients in the idiopathic group and three of the five in the HBsAg related group received immunosuppressive treatment. Overall complete remission was achieved in four of the five HBsAg associated patients and in three of the idiopathic patients plus partial remission in one of each group. Immunosuppressive treatment caused no complications, and beneficial results of the treatment particularly in the idiopathic MGN group were observed.

Effect of obesity on inflammatory markers and renal functions: Inflammatory markers and renal functions in obesity

Aim: To examine the relationship between inflammation criteria and body mass index in otherwise‐healthy obese schoolchildren and to evaluate the effect of obesity on renal functions. Methods: Sixty‐five otherwise‐healthy obese children (median age 10.8 y, range 7.1–16.5 y; median body mass index 26.8 kg/m2, range 19.9–38.7 kg/m2) and 20 healthy controls (median age 12.4 y, range 10.1–17.1 y; median body mass index 18.8 kg/m2, range 17.3–23.1 kg/m2) were included. Blood and urine samples were taken from every child. Results: Children in the obese and control groups had similar age and sex distributions (p>0.05). Inflammatory mediators were higher in obese children (p<0.05). A significant positive correlation was found between glomerular filtration rate and body mass index in the whole study group (r=0.39, p=0.001). A positive correlation was found between body mass index standard deviation and inflammatory mediators and glomerular filtration rate. No significant difference existed regarding protein and microalbumin excretion in the urine.