Detection of Renal Dysfunctions in Family Members of Patients with Balkan Endemic Nephropathy

Arsenović, Aleksandra; Bukvić, Danica; Trbojević, S; Marić, Ivko; Djukanović, Ljubica

doi:10.1159/000084105

Cited by 25 publications

(25 citation statements)

References 17 publications

(14 reference statements)

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“…However, in two endemic municipalities of the outer Belgrade area (i.e., Barajevo and Lazarevac), the number of incident BEN cases did not change over the previous three decades. [5,6] One of its most peculiar characteristics is a strong association with upper urothelial cancer (UUC). [7] BENrelated UUC has the same histological features as other forms of UUC in general, but is more frequently bilateral, less frequently affects the bladder, and has a sex ratio close to 1. Living in an endemic settlement is a prerequisite for BEN diagnosis.…”

Section: Introductionmentioning

confidence: 99%

Fifty Years of Balkan Endemic Nephropathy: Challenges of Study Using Epidemiological Method

et al. 2009

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Balkan endemic nephropathy (BEN) is a chronic tubulointerstitial disease associated with urothelial cancer, which affects people living in the alluvial plains along the tributaries of the Danube River. Challenges of studying BEN using the epidemiological method are multiple. The natural history from exposure to occurrence of the disease may take many years. The early stages of BEN are not easily detectable clinically, as the disease is asymptomatic until a significant decline in function occurs, and even then symptoms are usually non-specific. The natural history of BEN is complex, possibly with multiple risk factors operating both at the stage of initiation of renal damage and in its progression. In BEN, genetic susceptibility is due to multiple genes of small effects, gene-gene interactions, and gene-environment interactions of complex nature that are difficult to assess with current study designs. BEN is now kidney disease of the old people, and many risk factors for disease such as smoking, alcohol consumption, obesity, and diabetes could contribute to the kidney damage. Evidence is presented that environmental rather than genetic factors play a decisive role in the etiopathogenesis of BEN. Aristolochic acid, described as a culprit of BEN in 1959, is confirmed in 2007 by the molecular biology methods. Mycotoxins and polycyclic aromatic hydrocarbons, leached from lignites and found in the vicinity of endemic settlements, deserve further investigation. Despite advances in understanding the epidemiology of BEN, more research is needed on the patterns of BEN over time and between places, and on identifying the contributions of modifiable risk factors in initiating and hastening progression of BEN in order to improve the scope for preventing BEN. Primary prevention is still at the beginning. Knowledge accumulated in the fifty years of BEN research and new data about prevention and treatment of chronic kidney disease reveal several effective methods in secondary and tertiary prevention of BEN. Genetic epidemiology could establish the relative size of the genetic effect in relation to other sources of variation in disease risk (i.e., environmental effects such as intrauterine environment, physical and chemical effects, as well as behavioral and social aspects). Public health authorities in the several countries having aristolochic acid nephropathy should take immediate measures for reducing dietary exposure of residents to Aristolochia.

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Section: Introductionmentioning

confidence: 99%

Fifty Years of Balkan Endemic Nephropathy: Challenges of Study Using Epidemiological Method

et al. 2009

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“…[5] However, it has recently been reported that the prevalence of hypertension in endemic villages was high, although it is the same as in nonendemic rural parts. [21,22] Hypertension was found in 43% of BEN and 35% of non-BEN family members. [21] In the endemic villages, the prevalence of hypertension was the same as in control (51.7% vs 49.2%).…”

Section: Hypertensionmentioning

confidence: 99%

“…[21,22] Hypertension was found in 43% of BEN and 35% of non-BEN family members. [21] In the endemic villages, the prevalence of hypertension was the same as in control (51.7% vs 49.2%). [22] It was suggested that the higher prevalence of hypertension is likely due, in addition to older age, to the fact that that this group contains the greatest number of obese individuals.…”

Section: Hypertensionmentioning

confidence: 99%

“…The normal mean (standard deviation) GFR in young adults is approximately 120-130 (20)(21)(22)(23)(24)(25) The fraction of elderly individuals with decreased GFR who truly have chronic kidney disease has not been systematically studied. Moreover, the health outcomes of decreased GFR in the elderly, with or without chronic kidney disease, are also not known.…”

Section: Measurement Of Renal Functionmentioning

confidence: 99%

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Diagnostic Criteria for Balkan Endemic Nephropathy: Proposal by an International Panel

Stefanović¹,

Jelaković²,

Čukuranović³

et al. 2007

Renal Failure

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Balkan endemic nephropathy (BEN) is a familial chronic tubulointerstitial disease with insidious onset and slow progression to terminal renal failure. Diagnostic criteria for BEN have been described more than 40 years ago. Research groups on BEN use one of at least three described lists of criteria. Comparison of studies using such criteria is difficult, and a recent meeting of investigators (Zagreb, October 2006) has suggested that unified criteria have to be elaborated. In this paper, an International Panel of BEN Investigators agreed on criteria appropriate to epidemiologic studies and clinical investigations of BEN. A screening procedure of BEN in endemic settlements is proposed.

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“…2,8 Existing literature and prior studies have demonstrated that increased β 2 -microglobulin and reduced kidney length were associated with both BEN patients and their healthy offspring. [9][10][11][12][13][14][15] Moreover, increased C-reactive protein (CRP) and narrow kidney cortex width were related to a parental history of BEN (PHB) before the disease manifestation. A reduced CCr was connected to both BEN patients and offspring, and it was inversely correlated with kidney sizes in BEN patients.…”

Section: Introductionmentioning

confidence: 99%

The role of a parental history of Balkan endemic nephropathy in the occurrence of BEN: a prospective study

Hanjangsit¹,

Karmaus²,

Dimitrov³

et al. 2012

IJNRD

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Balkan endemic nephropathy (BEN) is a chronic kidney disease that affects persons living in the Balkans. Despite the unique geographical specificity of this disease, its etiology has remained unclear. Even if a positive family history of BEN has been identified, it is still uncertain how the disease develops in offspring. In this paper, we examine clinical mechanisms related to the onset of BEN in individuals who have a parental history of BEN to identify early detection of the disease and formulate interventions. We conducted a 5-year prospective study, using markers in years one and three to predict new cases of BEN in year five. New cases of BEN were defined based on three criteria: parental history of BEN, reduced kidney size, and reduced kidney function. Incident cases were divided into (1) probable, (2) definite, and (3) combined labeled total incidence. We evaluated parental history in relation to BEN and tested the potentially intervening effects of kidney length, kidney cortex width, β 2 -microglobulin, C-reactive protein, and creatinine clearance, using path analyses. The findings of the path analyses suggested that parental history of BEN had both direct and indirect effects. The direct effect was significant for all three modes of parental history (biparental, maternal, and paternal; odds ratios 71.5, 52.3, and 50.1, respectively). The indirect effects of maternal BEN acted via kidney length and creatinine clearance. Biparental BEN was mediated by (1) kidney length and creatinine clearance, and (2) creatinine clearance alone. Paternal BEN had three indirect effects: (1) through kidney length and creatinine clearance, (2) via kidney cortex width and creatinine clearance, and (3) via kidney cortex width only. In conclusion, a family history of BEN led to reduced kidney length and cortex width, and a decline in creatinine clearance, which in turn predicted the onset of BEN.

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Detection of Renal Dysfunctions in Family Members of Patients with Balkan Endemic Nephropathy

Cited by 25 publications

References 17 publications

Fifty Years of Balkan Endemic Nephropathy: Challenges of Study Using Epidemiological Method

Fifty Years of Balkan Endemic Nephropathy: Challenges of Study Using Epidemiological Method

Diagnostic Criteria for Balkan Endemic Nephropathy: Proposal by an International Panel

The role of a parental history of Balkan endemic nephropathy in the occurrence of BEN: a prospective study

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