Marica Miletić-Medved

Consensus statement on screening, diagnosis, classification and treatment of endemic (Balkan) nephropathy

Currently used diagnostic criteria in different endemic (Balkan) nephropathy (EN) centers involve different combinations of parameters, various cut-off values and many of them are not in agreement with proposed international guidelines. Leaders of EN centers began to address these problems at scientific meetings, and this paper is the outgrowth of those discussions. The main aim is to provide recommendations for clinical work on current knowledge and expertise. This document is developed for use by general physicians, nephrologists, urologist, public health experts and epidemiologist, and it is hoped that it will be adopted by responsible institutions in countries harboring EN. National medical providers should cover costs of screening and diagnostic procedures and treatment of EN patients with or without upper urothelial cancers.

Angiotensin-converting enzyme gene polymorphism and N-Acetyl-β-D-glucosaminidase excretion in endemic nephropathy.

Background: Tubular proteinuria and enzymuria are hallmarks of endemic nephropathy (EN). The role of I/D angiotensin convertase (ACE) gene polymorphism has not yet been elucidated in this peculiar chronic tubulointerstitial nephritis, and our aim was to investigate the role of this polymorphism in EN focusing on the urinary N-acetyl-β-D-glucosaminidase (NAG) excretion, a biomarker of proximal tubular damage. Methods:ACE genotype and allele frequencies were determined in 229 farmers (147 women and 82 men) from an endemic Croatian village. The farmers were stratified according to the WHO criteria into the following subgroups: those ‘at risk’ for EN (n = 37), ‘suspected of having EN’ (n = 57), and ‘others’ (n = 135). Results: There were 74 (32.3%) subjects homozygous for the D allele, 99 (43.2%) heterozygous (ID genotype) and 56 (24.4%) homozygous for the I allele. No differences in allele frequency were found between the established WHO subgroups (p > 0.05). In the whole group, DD subjects had significantly higher values of diastolic blood pressure (p = 0.003) and urinary NAG than subjects with ID and II genotype (5.5 ± 1.2 vs. 4.0 ± 3.0 vs. 3.8 ± 4.2, respectively; p = 0.023). The highest values of serum creatinine (p = 0.02), proteinuria (p = 0.03) and urinary NAG (6.0 ± 3.7 vs. 3.7 ± 2.1 vs. 3.0 ± 1.6, respectively; p = 0.008) were observed in those suspected of having EN group with the DD genotype. Conclusion:ACE gene polymorphism is not a risk factor for EN. However, it might influence the clinical course of EN, and increased excretion of NAG might be a prognostic marker of this chronic tubulointerstitial nephritis.

METABOLIC SYNDROME AND EARLY KIDNEY DAMAGE IN RURAL POPULATION: PP.34.388

Objective: To analyze prevalence of metabolic syndrome (MS) in early phases of chronic kidney disease (CKD) and effect of its components on early renal impairment. Design and Method: In this survey 1003 farmers from continental, rural part of Croatia were enrolled (386 men; 617 women; average age 52(30-95); females were older(Mann-Whitney test:z=3,6;p < 0,001). After extended questionnaire and clinical exam, fasting blood was drawn and second morning urine sample was collected (for microalbuminuria (MA) and alpha1 microglobulinuria (α1MG). Blood pressure (BP) was measured following the ESH/ESC guidelinies, metabolic syndrome (MS) was defined according to the NCEP ATP III recommendations. Subjects were classified into the CKD stages groups according to the KDOQI classification. Results: In general rural population prevalence of MS was 22,6% (30% men, 70% women; p = 0,045). Prevalence of MS was significantly higher in subjects with CKD stage 3 as compared to the CKD stage 1 (χ2 = 4;p = 0,045) as well as in subjects with MA compared to those with normal values (χ2 = 5,85;p = 0,016), while there was no difference between subjects with elevated and normal values of α1MG (χ2 = 0,19;p = 0,662). We observed significant difference between stages CKD 1 and 3 in BP (χ2 = 15,6;p < 0,001), waist circumference (WC) (χ2 = 26,8;p < 0,001), fasting blood glucose (FBG) (χ2 = 22;p < 0,001), triglycerdies (TG) (χ2 = 7,4;p = 0,024) and HDL level (χ2 = 0,621;p < 0,001). Significant differences in BP, FBG, WC and TG were observed between subjects with MA in comparison with normal values (χ2 = 8,1;p = 0,004; χ2 = 23,2;p < 0,001; χ2 = 6,85;p = 0,009; χ2 = 9,0;p = 0,003, respectively). Multivariate age-adjusted OR for development of MA was significant for FBG and TG (OR 2(1,43–2,8);p < 0,001; OR 1,59(1,02–2,5);p = 0,043, respectively). Only systolic BP was significantly associated with α1MG(χ2 = 2,59;p < 0,001) with multivariate age-adjusted OR for development of α1MG of 1,52 (1,01–2,28);p = 0,043. Conclusions: Prevalence of MS and its components increase with CKD stage. MS, and especially FBG and TG are risk factors for MA while systolic BP is a risk factor for proximal tubule damage i.e. α1MG.

WHITE BLOOD CELL COUNT IS RELATED TO BLOOD PRESSURE VALUES ONLY IN ADVANCED HYPERTENSION: PP.19.240

Objective: The question whether inflammation is an initial event in hypertension or rather a consequence of endothelial damage is still opened, as well as whether white blood cell count (WBC) could be a marker of it. Our aim was to analyze the relation between WBC and blood pressure (BP) in our group of 1375 subjects (587 men and 788 women). Design and Method: After an extended questionnaire and clinical exam BP was measured following the ESH/ESC guidelines and subjects were classified in groups with optimal BP (OBP), normal BP (NBP), high normal BP (HNBP), stage1, 2, 3 and isolated systolic hypertension (ISH). Fasting blood was drawn and WBC count, number of neutrophils, lymphocytes and other WBC were determined. Subjects treated with anti-inflammatory drugs and antibiotics were excluded. Results: In our group OBP, NBP, HNBP, strage1, 2, 3 and ISH were diagnosed in 16.2%, 12.6%, 11.1%, 12.9%, 9.4%, 5.9% and 21.2% subjects, respectively. BP categories were significantly related to the WBC count (χ2 = 14,2; p = 0,027). Significant differences in WBC were observed between stage 3 vs. OB, NBP and HNBP (p = 0.008, 0.002, 0.001, respectively) and stage 2 vs. HNBP (p = 0.01). Similar results were observed with neutrophils (χ2 = 18,1; p = 0,006), and again significant differences between stage 3 vs. OB, NBP, HNBP (p < 0.01) were determined. There were no differences in lymphocytes and other WBC between BP categories (p > 0.05). Interestingly, we failed to find differences in WBC count and neutrophiles between OBP vs. NBP vs. HNBP (p > 0.05). Conclusions: WBC, i.e. neutrophiles are related to BP values only in advanced phases of hypertension. We failed to find differences in WBC between subjects with OBP and HNBP what could lead to the conclusion that inflammation is not a characteristic of prehypertension, but also, it might be that WBC is not a sufficiently sensitive biomarker.