Abstract
There are unexplained geographical variations in the incidence of kidney cancer with the high rates reported in Baltic countries, as well as eastern and central Europe. Having access to a large and well-annotated collection of “tumor/non-tumor” pairs of kidney cancer patients from the Czech Republic, Romania, Serbia, UK, and Russia, we aimed to analyze the morphology of non-neoplastic renal tissue in nephrectomy specimens. By applying digital pathology, we performed a microscopic examination of 1012 frozen non-neoplastic kidney tissues from patients with renal cell carcinoma. Four components of renal parenchyma were evaluated and scored for the intensity of interstitial inflammation and fibrosis, tubular atrophy, glomerulosclerosis, and arterial wall thickening, globally called chronic renal parenchymal changes. Moderate or severe changes were observed in 54 (5.3%) of patients with predominance of occurrence in Romania (OR = 2.67, CI 1.07–6.67) and Serbia (OR = 4.37, CI 1.20–15.96) in reference to those from Russia. Further adjustment for comorbidities, tumor characteristics, and stage did not change risk estimates. In multinomial regression model, relative probability of non-glomerular changes was 5.22 times higher for Romania and Serbia compared to Russia. Our findings show that the frequency of chronic renal parenchymal changes, with the predominance of chronic interstitial nephritis pattern, in kidney cancer patients varies by country, significantly more frequent in countries located in central and southeastern Europe where the incidence of kidney cancer has been reported to be moderate to high. The observed association between these pathological features and living in certain geographic areas requires a larger population-based study to confirm this association on a large scale.
Highlights
Worldwide, kidney cancer was reported as the 9th most common malignancy in men and 14th in women in 2018, with an estimated 136,515 and 67,424 new cases in Europe and North America respectively
Through examination of non-neoplastic renal parenchymal changes in 110 cancer-related nephrectomy specimens, Bijol et al showed that only 10% of the cases have unremarkable parenchyma and those with considerable pathological changes such as severe parenchymal scarring and more than 20% glomerulosclerosis had progressive worsening of renal function in 6-month follow-up after radical nephrectomy [6]
Since medical conditions such as hypertension and diabetes mellitus are common in Renal cell carcinoma (RCC) patients and could lead to morphological changes in renal parenchyma, we evaluated the association of the observed chronic renal parenchymal changes (CRPC) with medical conditions and risk factors for RCC
Summary
Kidney cancer was reported as the 9th most common malignancy in men and 14th in women in 2018, with an estimated 136,515 and 67,424 new cases in Europe and North America respectively. It is shown that 5 to 25% of RCC patients have varying pathologies of chronic kidney disease and those with normal renal function are more likely to develop chronic kidney disease after nephrectomy. Such changes may cause impairment of renal function and reduce the patient’s quality of life [2,3,4,5]. Through examination of non-neoplastic renal parenchymal changes in 110 cancer-related nephrectomy specimens, Bijol et al showed that only 10% of the cases have unremarkable parenchyma and those with considerable pathological changes such as severe parenchymal scarring and more than 20% glomerulosclerosis had progressive worsening of renal function in 6-month follow-up after radical nephrectomy [6]. On the other hand, understanding molecular events such as somatic mutations in non-neoplastic cells is central to understand cancer development and is taking a considerable place in research on cancer [9, 10]
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