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Balkan Nephropathy

Endemic Nephropathy Balkan

Balkan nephropathy is a type of degenerative, familial, slowly progressive chronic tubulointerstitial disease that may lead to carcinomas of the renal pelvis or upper urethra. The disease is endemic to the Balkan countries like Bosnia and Herzegovina, Romania, Serbia, Croatia, and Bulgaria.


Presentation

Balkan nephropathy is clinically silent initially and occurs three times more frequently in women than men. Affected individuals are usually farmers. First symptoms are nonspecific [1], occurring usually after the patient turns 30 years old and consists of weakness, anorexia, nausea, vomiting, headache, dizziness, somnolence, muscular spasms, dyspepsia, pale skin with copper-brown discoloration of the palms and soles, weight loss, episodes of macrohematuria and mild, non-characteristic pain in the lumbar area. Blood pressure remains normal in incipient phases and becomes elevated later during illness evolution. Symptoms of chronic kidney disease (uremic syndrome) become apparent as Balkan nephropathy progresses [2] [3]. Dysuria and fever are absent. Peripheral edema is seldom seen and is due to hydroelectrolytic disturbances. Working capacity is preserved for a long time. Patients with prolonged disease evolution present with urothelial tumors or signs of chronic renal failure: pollakyuria, polydipsia, and nocturia.

Hypertensive Retinopathy
  • Only patients with hypertensive retinopathy grade 2 or more and patients with left ventricle hypertrophy diagnosed by two-dimensional echocardiography were involved.[ndt.oxfordjournals.org]
Skin Discoloration
  • At least 25,000 individuals are known to have the disease.Symptoms include weakness, a low number of red blood cells in the bloodstream (anemia), and a coppery skin discoloration.[en.wikipedia.org]
  • At least 25,000 individuals are known to have the disease. [4] Symptoms include weakness, anemia, and a coppery skin discoloration A later finding, usually after kidney failure occurs, is transitional cancer of urothelial tract.[ipfs.io]
Photosensitivity
  • Another ignored area are unstable and, particularly, photosensitive substances. Fertilizers, pesticides, analgesics, local herbs and teas have no causal relation to BN.[ncbi.nlm.nih.gov]
Suggestibility
  • 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.[ncbi.nlm.nih.gov]
  • The results of the biochemical and immunological investigations performed on these samples suggest that the tubular alteration is the first lesion.[ncbi.nlm.nih.gov]
  • It is suggested that overproduction of beta 2-microglobulin, a light-chain-like immune globulin, by the tumour cells may result in a light-chain-like nephropathy--i.e., endemic Balkan nephropathy.[ncbi.nlm.nih.gov]
  • Radioimmunoassay of the protein is sensitive enough to detect tubular proteinuria at an early stage and is suggested as a suitable screening test for the disease.[ncbi.nlm.nih.gov]
  • Coronaviruses have been isolated from pigs, and it is suggested that a slow coronavirus infection causes endemic nephropathy in man.[ncbi.nlm.nih.gov]
Kidney Failure
  • failure N17.0 Acute kidney failure with tubular necrosis N17.1 Acute kidney failure with acute cortical necrosis N17.2 Acute kidney failure with medullary necrosis N17.8 Other acute kidney failure N17.9 Acute kidney failure, unspecified Reimbursement[icd10data.com]
  • Affected individuals develop kidney damage that slowly progresses over 10 to 20 years to kidney failure . Many people with this condition also develop a type of bladder cancer known as upper urothelial carcinoma (UUC).[rarediseases.info.nih.gov]
  • CLINICAL FEATURES (1) This slowly progressive kidney failure lacks high blood pressure and protein in the urine. (2) Except for anemia, no clinical symptoms are evident early during the disease. (3) The only early abnormality could be detected by finding[silive.com]
  • ., incidence only in adults (no children affected), absence of high blood pressure, xanthochromia of palms and soles (Tanchev's sign), early hypochromic anemia, absence of proteinuria, and slow progression of kidney failure.[ipfs.io]

Workup

Tubular type proteinuria involving albumin and β2-microglobulin is initially intermittent and not accompanied by decreased serum protein levels but later becomes permanent. It is usually less than 0.5 g/24 hours. Urine concentration ability is gradually lost and followed by a decrease in the glomerular filtration rate [4] [5]. Urinary sediment detects red, white blood cells [6] and tumor cells if the disease has become complicated by a urothelial tumor [7]. Bacteriuria, glycosuria, enzymuria, and aminoaciduria (hydroxyprolinuria) have been described. Normo- or hypochromic normocytic hypo regenerative anemia is present from the initial stages of the disease and is more severe than expected based on glomerular filtration rate reduction. It is caused by urinary or digestive losses, impaired erythropoietin synthesis, and hemolysis. The erythrocyte sedimentation rate is elevated. Complement, as well as anti-tubular basal membrane and anti-glomerular basal membrane antibodies levels, remain normal. High values of urinary leucine aminopeptidase activity have been described. Tubular dysfunction leads to salt wasting, abnormal ammonia, phosphate and uric acid excretion and urine acidification abnormalities.

Balkan nephropathy progresses in a gradual manner, with several stages. Azotemia is initially absent, then asymptomatic, with stable blood urea nitrogen level and in the end clinically overt.

Ultrasonography reveals progressive, symmetrical kidney atrophy [6] [8] due to sclerosis and high echo density of the renal pelvis and parenchyma. Histology demonstrates the substratum of these findings: interstitial and periglomerular fibrosis, glomerular lesions of the endothelial and mesangial proliferative type or micro cysts. Tubular epithelium may be dystrophic or atrophic, may be affected by hydroprotidic de-generescence or pseudo cystic dilatation. Vascular lesions consist of intimal fibrous hyperplasia or intimal fibrosis and arterial hyalinosis.

Radiography and other imaging methods may reveal carcinomas that usually involve the upper ureter or renal pelvis [9]. Tumors may also be encountered in the urinary bladder, but this is a rare finding. Urography and ascending pyelography, as well as computer tomography scans are useful in tumor diagnosis. Renal biopsy is seldom indicated because patients usually present when the kidneys are already atrophied.

Xanthochromia
  • ., incidence only in adults (no children affected), absence of high blood pressure, xanthochromia of palms and soles (Tanchev's sign), early hypochromic anemia, absence of proteinuria, and slow progression of kidney failure.[en.wikipedia.org]
  • ., incidence only in adults (no children affected), lack of high blood pressure, xanthochromia of palms and soles (Tanchev's sign), early hypochromic anemia, a lack of proteinuria, and slow progression to chronic kidney failure.[wikidoc.org]
Albuminuria
  • The patients had the following common characteristics: from endemic areas; other renal ailments in the family; copper-yellow skin and orange palms and soles; normochromic anaemia; absence of acute onset, considerable albuminuria, hypertension and oedema[ncbi.nlm.nih.gov]
  • In addition, the inclusion of new markers of BEN as well as the variables known as characteristics of particular kidney diseases (albuminuria, LWM-proteinuria/albuminuria, parenchymal scars, deformation of the pyelocaliceal system, etc.) would be warranted[ndt.oxfordjournals.org]
Microalbuminuria
  • The first phase encompassed obtaining anamnestic data (demographic, personal and family history), measurement of arterial blood pressure, and urine dipstick testing (specific gravity, pH, proteins, leukocytes, glucose, ketones, and microalbuminuria).[ncbi.nlm.nih.gov]
Normocytic Anemia
  • anemia; a very high frequency of upper urinary tract tumors (UTT) in BEN patients.[uninet.edu]

Treatment

  • GOAL: Analysis of the incidence of urothelial cancer and outcome of treatment in patients with Endemic Balkan Nephropathy (EN) after renal transplantation.[ncbi.nlm.nih.gov]
  • The etiology of this disease remains unknown, and no treatment is available, although haemodialysis and kidney transplants have prolonged patients' survival.[ncbi.nlm.nih.gov]
  • Please consult your own licensed physician regarding diagnosis and treatment of any medical condition! Please see also our disclaimer . This site complies with the HONcode standard for health information: verify here . Database updated 2019-02-19.[diseasesdatabase.com]
  • There are no known treatments to slow the progression of this disease.[myvmc.com]
  • Treatment and prognosis As these tumors are bilateral, multiple and of low grade conservative management is the mainstay of treatment 1 . Promoted articles (advertising)[radiopaedia.org]

Prognosis

  • […] nephropathy endemic to the littoral regions of the Danube, occurring in the Balkans—Bulgaria, Croatia, Romania, Serbia Etiology Unknown; converging lines of evidence suggest a link to long-term consumption of food contaminated with aristolochic acid Prognosis[medical-dictionary.thefreedictionary.com]
  • Prognosis of Balkan Endemic Nephropathy (BEN) The prognosis of this condition is poor, as those who develop Balkan endemic nephropathy progressive to chronic renal failure over a period of three months to ten years.[myvmc.com]
  • Treatment and prognosis As these tumors are bilateral, multiple and of low grade conservative management is the mainstay of treatment 1 . Promoted articles (advertising)[radiopaedia.org]
  • Prognosis is generally [excellent/good/poor], and the [1/5/10year mortality/survival rate] of patients with [disease name] is approximately [#%].[wikidoc.org]

Etiology

  • Balkan endemic nephropathy and the associated urinary tract tumours: review on etiological causes, potential role of mycotoxins. Ochratoxin A in human blood in relation to Balkan endemic nephropathy and urinary tract tumours in Bulgaria.[medical-dictionary.thefreedictionary.com]
  • Abstract Endemic Balkan nephropathy (EBN) is a kidney disease of unknown etiology limited to Bulgaria, Rumania and former Yugoslavia.[ncbi.nlm.nih.gov]
  • The geographic correlation and presence of AA-DNA adducts in both BEN and associated urothelial cancer, support the speculation that these diseases share a common etiology.[ncbi.nlm.nih.gov]
  • Abstract Balkan nephropathy is a chronic kidney disease of a completely unknown etiology. Most epidemiologists believe that the disease has been caused by viruses, though all attempts to prove such a relationship have been fruitless.[ncbi.nlm.nih.gov]
  • Moreover, the paper analyzes the main etiological factors suspected to play a role in BEN: aristolochic acid (the disease has many similarities to aristolochic nephropathy caused by Chinese herbs), mycotoxins, toxic substances from pliocene lignite, genetic[ncbi.nlm.nih.gov]

Epidemiology

  • Such an explanation fits most of the existing epidemiological data.[ncbi.nlm.nih.gov]
  • , National Center for Public Health Protection, Sofia, Bulgaria. 13 Department of Epidemiology and Institute for Public Health Genetics, School of Public Health and Community Medicine University of Washington, Seattle, WA, USA. 14 School of Medicine,[ncbi.nlm.nih.gov]
  • Jelaković et al. present molecular epidemiological evidence relating urothelial carcinoma in patients with BEN to dietary exposure to AA.[ncbi.nlm.nih.gov]
  • 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.[ncbi.nlm.nih.gov]
Sex distribution
Age distribution

Pathophysiology

  • In addition, the renal pathophysiology and histopathology observed in endemic nephropathy most closely resemble the entity known as aristolochic acid nephropathy.[ncbi.nlm.nih.gov]
  • This hypothesis is supported by striking similarities between the pathophysiology of EN and the recently recognized syndrome of aristolochic acid nephropathy. Scientists based at the Univ. of Zagreb School of Medicine and Rudjer Boskovic Inst.[grantome.com]
  • Brenner/Rector remains the go-to resource for practicing and training nephrologists and internists who wish to master basic science, pathophysiology, and clinical best practices.[books.google.com]
  • Although various hypotheses had been advanced to explain the etiology of BEN/UUC none could fully explain the unique epidemiological and pathophysiological features of this disease, and its cause remained a mystery.[medicine.stonybrookmedicine.edu]
  • These results therefore provide further structural and functional insights into the possible pathophysiological effects of this missense variant in TASK-2.[journals.plos.org]

Prevention

  • Preventive nephroureterectomy is recommended.[ncbi.nlm.nih.gov]
  • A high incidence of urothelial cancer in end-stage BEN patients strongly suggests preventive nephro-ureterectomy in all end-stage patients with BEN treated with either transplantation or dialysis.[ncbi.nlm.nih.gov]
  • […] endemic nephropathy is caused by chronic dietary exposure to low concentrations of a toxin called aristolochic acid, which comes from a plant called Aristolochia clematis. [1] [2] [3] Genetics factors may also be involved. [2] [3] There is no specific prevention[rarediseases.info.nih.gov]
  • Prevention There are no primary preventive measures available for [disease name]. Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].[wikidoc.org]
  • NO SPECIFIC PREVENTION There is no specific prevention or treatment for BEN. Patients who progress to end-stage renal disease may be treated with dialysis or kidney transplantation.[silive.com]

References

Article

  1. Stefanovic V, Cukuranovic R, Miljkovic S, et al. Fifty years of Balkan endemic nephropathy: challenges of study using epidemiological method. Ren Fail. 2009;31:409–418.
  2. Djukanović L, Marić I, Marinković J, et al. Evaluation of criteria for the diagnosis of Balkan endemic nephropathy. Ren Fail. 2007;29:607–614.
  3. Cukuranovic R, Jovanovic I, Miljkovic S, et al. Hemodialysis treatment in patients with Balkan endemic nephropathy: an epidemiological study. Ren Fail. 2007;29:805–810.
  4. Alecković M, Mesić E, Trnacević S, et al. Glomerular filtration rate in examined population of Bosnian Posavina—region of Balkan Endemic Nephropathy. Bosn J Basic Med Sci. 2010;10:S68–S72.
  5. Dimitrov P, Tsolova S, Georgieva R, et al. Clinical markers in adult offspring of families with and without Balkan endemic nephropathy. Kidney Int. 2006;69:723–729.
  6. Radonić M, Radosević Z. Clinical features of Balkan endemic nephropathy. Food Chem Toxicol. 1992;30(3): 189–192.
  7. Stefanovic V, Polenakovic M, Toncheva D. Urothelial carcinoma associated with Balkan endemic nephropathy. A worldwide disease. Pathol Biol. 2011; 59(5): 286–291.
  8. Vukelic M, Sostaric B, Belicza M. Pathomorphology of Balkan endemic nephropathy. Food Chem Toxicol. 1992;30(3): 193–200.
  9. Vikram R, Sandler CM, Ng CS. Imaging and staging of transitional cell carcinoma: part 2, upper urinary tract. AJR Am J Roentgenol. 2009;192 (6): 1488-1493.

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Last updated: 2019-07-11 21:27