From the Guidelines
The diagnostic criteria for Balkan nephropathy are not explicitly defined in the provided evidence, but based on the available information, a diagnosis can be made by combining clinical, laboratory, and epidemiological findings, including residence in endemic regions, tubular proteinuria, impaired concentrating ability, anemia, and absence of hypertension in early stages, as well as laboratory and imaging findings 1.
Clinical Characteristics
The provided evidence discusses Autosomal Dominant Tubulointerstitial Kidney Disease (ADTKD), which shares some similarities with Balkan nephropathy, but the diagnostic criteria for Balkan nephropathy are not directly addressed. However, some key features of ADTKD that may be relevant to Balkan nephropathy include:
- Autosomal dominant inheritance
- Progressive loss of kidney function
- Bland urinary sediment
- Absent-to-mild albuminuria/proteinuria
- No severe hypertension during early stages
- Normal or small-sized kidneys on ultrasound
- Nocturia or enuresis in children due to loss of renal concentration ability
Laboratory and Imaging Findings
Laboratory findings in ADTKD include:
- Elevated serum creatinine
- Decreased glomerular filtration rate
- Increased urinary excretion of beta2-microglobulin Imaging may reveal:
- Asymmetrically contracted kidneys with smooth outlines
- Renal histology showing interstitial fibrosis with tubular atrophy and normal glomeruli
Epidemiological Considerations
Balkan nephropathy is believed to be caused by chronic exposure to aristolochic acid from Aristolochia plants that contaminate grain fields in endemic areas, explaining its geographical distribution and gradual onset after prolonged exposure. Patients must reside or have resided in endemic regions of the Balkans for at least 15-20 years to be considered at risk 1.
Diagnostic Approach
A kidney biopsy may show extensive interstitial fibrosis with tubular atrophy and minimal glomerular changes, supporting the diagnosis of Balkan nephropathy. The diagnosis is further supported by exclusion of other causes of chronic kidney disease and an increased risk of upper urinary tract urothelial cancers. The combination of clinical, laboratory, and epidemiological findings, along with the exclusion of other causes, is essential for making a diagnosis of Balkan nephropathy.
From the Research
Diagnostic Criteria for Balkan Nephropathy
The diagnostic criteria for Balkan nephropathy are not uniformly established, with different studies and centers using various combinations of parameters and cut-off values 2. However, several studies have proposed and evaluated different criteria for diagnosing the disease.
Proposed Diagnostic Criteria
Some of the proposed diagnostic criteria for Balkan nephropathy include:
- Danilovic's criteria, which include factors such as age, sex, blood pressure, creatinine clearance, glucosuria, urine osmolality, alkaline phosphatase, alpha 1-microglobulin, fractional sodium excretion, tubular phosphate reabsorption, kidney length, and volume 3
- Proteinuria, urine alpha1-microglobulin, kidney length, and volume, which have been selected as significant predictors of Balkan nephropathy 4
- A screening procedure for Balkan endemic nephropathy in endemic settlements, which includes a combination of clinical, laboratory, and ultrasound variables 5
Evaluation of Diagnostic Criteria
Studies have evaluated the sensitivity, specificity, and predictive value of different diagnostic criteria for Balkan nephropathy. For example:
- Danilovic's criteria were found to have low sensitivity and specificity in differentiating Balkan nephropathy from other kidney diseases 3
- Proteinuria was found to have high sensitivity and specificity in differentiating Balkan nephropathy from healthy persons, but not from other kidney diseases 3, 4
- Urine alpha1-microglobulin was found to be a significant predictor of Balkan nephropathy, particularly in differentiating it from other kidney diseases 3, 4
Key Diagnostic Features
Some of the key diagnostic features of Balkan nephropathy include: