Aim. The aim of this study was to compare urinary alpha 1 microglobulin (A1MG) in healthy individuals with and without family burden for Balkan endemic nephropathy (BEN) in an endemic village. Methods. Otherwise healthy inhabitants with microalbuminuria or proteinuria were divided into two groups: with ( ) and without ( ) family BEN burden and screened for urinary A1MG and A1MG/urine creatinine ratio. Results. Average value of urinary A1MG was ？mg/L in group with and ？mg/L in group without family history for BEN (NS, ). A1MG was higher than 10？mg/L in eight (33.33%) inhabitants with family history and in 12 (37.5%) without (NS, ). Average values of urinary A1MG/creatinine ratio were and in group with and group without family BEN history (NS, , resp.). Elevated values of this ratio were found in 13 (54.17%) inhabitants with and 14 (43.75%) without family history for BEN (NS, ). Conclusion. We did not find statistically significant difference in the examined markers between healthy individuals with and without family burden for BEN. We concluded that these markers are not predictive of risk for BEN. 1. Introduction Balkan endemic nephropathy (BEN) is chronic irreversible tubulointerstitial nephritis that is diagnosed in agrarian regions of the Balkan (Bosnia and Herzegovina, Bulgaria, Croatia, Romania, and Serbia). BEN has never been documented in children and adolescents, has insidious onset, and is usually diagnosed in the fifth decade with terminal renal failure developing in sixth and seventh decade of life. The disease is also characterized by frequent occurrence of tumours of the renal pelvis and urethers. Majority of endemic villages are located at the alluvial valleys of Danube and its tributary rivers. There have been no significant changes in the geographic distribution of BEN since its first descriptions in 1950s [1, 2]. During the past half century, numerous dilemmas and conflicting opinions regarding BEN aetiology have been proposed and the theory that BEN is caused by chronic poisoning with aristolochic acid ingested by food in people with genetic predisposition has gained credence [3]. Based on these reports, BEN is proposed to be categorized as a toxic tubulointerstitial nephropathy, with clinical picture and disease progression not different from other tubulointerstitial nephropathies, but with BEN having an insidious and gradual progression to end stage renal disease. Despite this encouraging leads to the explanation of its aetiology, this endemic kidney disease remains a mystery since its focal and stable distribution for more than 50
References
[1]
V. Batuman, “Fifty years of Balkan endemic nephropathy: daunting questions, elusive answers,” Kidney International, vol. 69, no. 4, pp. 644–646, 2006.
[2]
G. Bamias and J. Boletis, “Balkan nephropathy: evolution of our knowledge,” American Journal of Kidney Diseases, vol. 52, no. 3, pp. 606–616, 2008.
[3]
M. E. De Broe, “Chinese herbs nephropathy and Balkan endemic nephropathy: toward a single entity, aristolochic acid nephropathy,” Kidney International, vol. 81, no. 6, pp. 513–515, 2012.
[4]
S. Raicevic, S. Trnacevic, J. Hranisavljevic, and D. Vucelic, “Renal function, protein excretion, and pathology of Balkan endemic nephropathy. II. Protein excretion,” Kidney International, vol. 40, supplement 34, pp. S-52–S-56, 1991.
[5]
M. Ikeda, T. Ezaki, T. Tsukahara et al., “Reproducibility of urinary cadmium, alpha1-microglobulin, and beta2-microglobulin levels in health screening of the general population,” Archives of Environmental Contamination and Toxicology, vol. 48, no. 1, pp. 135–140, 2005.
[6]
J. Kos, M. Miletic-Medved, D. Cvoriscec, et al., “Characteristics of the population from a Croatian focus of endemic nephropathy,” Collegium Antropologicum, vol. 30, supplement 1, p. 51, 2006.
[7]
E. Me？i？, “Early detection of Balkan endemic nephropathy in Bosanska Posavina,” Bosnian Journal of Basic Medical Sciences, vol. 10, supplement 1, pp. S83–S90, 2010.
[8]
Anonymous, “Consensus statement,” in Proceedings of the International Workshop on Screening, Diagnosis, Classification and Treatment of Endemic (Balkan) Nephropathy, Island of Brac, Croatia, April 2008.
[9]
L. Andersson, B. Haraldsson, C. Johansson, and L. Barregard, “Methodological issues on the use of urinary alpha-1-microglobuline in epidemiological studies,” Nephrology Dialysis Transplantation, vol. 23, no. 4, pp. 1252–1256, 2008.
[10]
J. Tencer, H. Thysell, and A. Grubb, “Analysis of proteinuria: reference limits for urine excretion of albumin, protein HC, immunoglobulin G, κ- and λ-immunoreactivity, orosomucoid and α1-antitrypsin,” Scandinavian Journal of Clinical and Laboratory Investigation, vol. 56, no. 8, pp. 691–700, 1996.
[11]
L. Djukanovi？, J. Marinkovi？, I. Mari？ et al., “Contribution to the definition of diagnostic criteria for Balkan endemic nephropathy,” Nephrology Dialysis Transplantation, vol. 23, no. 12, pp. 3932–3938, 2008.
[12]
G. P. Vyssoulis, D. Tousoulis, C. Antoniades, S. Dimitrakopoulos, A. Zervoudaki, and C. Stefanadis, “α-1 microglobulin as a new inflammatory marker in newly diagnosed hypertensive patients,” American Journal of Hypertension, vol. 20, no. 9, pp. 1016–1021, 2007.
[13]
V. Danilovic, “Diagnosis of endemic nephropathy,” Radovi XLVIII AN BiH, vol. 17, pp. 53–64, 1973.
[14]
A. Levey, K. U. Eckardt, Y. Tsukamoto et al., “Definition and classification of chronic kidney disease: a position statement from kidney disease: improving global outcomes (KDIGO)z,” Kidney International, vol. 67, no. 6, pp. 2089–2100, 2005.
[15]
A. Schiller, P. Gusbeth-Tatomir, N. Pavlovic, D. Ferluga, G. Spasovski, and A. Covic, “Balkan endemic nephropathy: a still unsolved puzzle,” Journal of Nephrology, vol. 21, no. 5, pp. 673–680, 2008.
[16]
J. Gaon, B. Pokrajcic, and E. Duric, “Uticaj nekih faktora spoljne sredine na odrzavanje endemske nefropatije i prijedlog za primjenu nekih preventivnih mjera,” Acta Medica Saliniana, vol. 5, no. 2, pp. 109–118, 1976.
[17]
Z. Radovanovi？, “Epidemiology and etiology of endemic nephropathy,” in Endemic Nephropathy, Z. Radovanovi？, M. Sin？i？, M. Polenakovi？, L. Djukanovi？, and V. Petroni？, Eds., pp. 22–135, Zavod za ud？benike i nastavna sredstva, Belgrade, Serbia, 2002.
[18]
K. Hanjangsit, W. Karmaus, P. Dimitrov et al., “The role of a parental history of Balkan endemic nephropathy in the occurrence of BEN: a prospective study,” International Journal of Nephrology and Renovascular Disease, vol. 5, pp. 61–68, 2012.
[19]
P. Dimitrov, S. Tsolova, R. Georgieva et al., “Clinical markers in adult offspring of families with and without Balkan Endemic Nephropathy,” Kidney International, vol. 69, no. 4, pp. 723–729, 2006.
[20]
K. Hanjangsit, P. Dimitrov, W. Karmaus et al., “Reduced kidney size in adult offspring of balkan endemic nephropathy patients and controls: a prospective study,” American Journal of the Medical Sciences, vol. 340, no. 2, pp. 94–102, 2010.
[21]
M. Radonic and Z. Radosevic, “Clinical features of Balkan endemic nephropathy,” Food and Chemical Toxicology, vol. 30, no. 3, pp. 189–192, 1992.
[22]
S. Trnacevic, A. Halilbasic, D. Ferluga et al., “Renal function, protein excretion and pathology of Balkan endemic nephropathy. I. Renal function,” Kidney International, vol. 40, no. 34, pp. S49–S51, 1991.
[23]
M. Aleckovi？, E. Me？i？, S. Trnacevi？, ？. Stipanci？, D. Hamidovi？, and E. Hasanovi？, “Glomerular filtration rate in examined population of Bosnian Posavina-region of balkan endemic nephropathy,” Bosnian Journal of Basic Medical Sciences, vol. 10, supplement 1, pp. S68–S72, 2010.
[24]
V. Stefanovic, M. Mitic-Zlatkovic, R. Cukuranovic, P. Miljkovic, N. M. Pavlovic, and P. Vlahovic, “β2-microglobulin in patients with Balkan nephropathy and in healthy members of their families,” Kidney International, vol. 40, supplement 34, pp. S-21–S-26, 1991.
[25]
L. Andersson, B. Haraldsson, C. Johansson, and L. Barregard, “Methodological issues on the use of urinary alpha-1-microglobuline in epidemiological studies,” Nephrology Dialysis Transplantation, vol. 23, no. 4, pp. 1252–1256, 2008.
[26]
A. Arsenovi？, D. Bukvi？, S. Trbojevi？, I. Mari？, and L. Djukanovi？, “Detection of renal dysfunctions in family members of patients with Balkan endemic nephropathy,” American Journal of Nephrology, vol. 25, no. 1, pp. 50–54, 2005.
[27]
G. Imamovic, V. Batuman, O. Sinanovic et al., “Microalbuminuria as a possible marker of risk of Balkan endemic nephropathy,” Nephrology, vol. 13, no. 7, pp. 616–621, 2008.
[28]
L. Djukanovic, D. Bukvic, and I. Maric, “Creatinine clearance and kidney size in Balkan endemic nephropathy patients,” Clinical Nephrology, vol. 61, no. 6, pp. 384–386, 2004.
[29]
V. Batuman, “Possible pathogenetic role of low-molecular-weight proteins in Balkan nephropathy,” Kidney International, vol. 40, supplement 34, pp. S89–S92, 1991.
[30]
P. S. Dimitrov, V. A. Simeonov, V. S. Ganev, and W. J. J. Karmaus, “Is the incidence of Balkan endemic nephropathy decreasing?” Pathologie Biologie, vol. 50, no. 1, pp. 38–41, 2002.
[31]
Z. Radovanovi？, “Epidemiology and etiology of endemic nephropathy,” in Endemic Nephropathy, Z. Radovanovi？, M. ？indji？, M. Polenakovi？, L. Djukanovi？, and V. Petroni？, Eds., pp. 22–152, Office for Textbooks and Teaching Aids, Belgrade, Serbia, 2000.
