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The onset of IgA nephropathy (IgAN), characterized by glomerular deposition of IgA-containing immune complexes, is often associated with synpharyngitic hematuria. Innate immune responses mediated by Toll-like receptors (TLR) may play a role in IgAN onset and/or progression. Here, we assessed the expression of TLR 4, 7, 8, and 9 in renal-biopsy specimens from patients with IgAN, with different degree of proteinuria and eGFR, compared with normal-kidney and disease-control tissues (ANCA-associated vasculitis). Renal-biopsy specimens from 34 patients with IgAN and 7 patients with ANCA-associated vasculitis were used. In addition, we used 15 healthy portions of renal-tissue specimens from kidneys after nephrectomy for cancer as control specimens. Expression of TLR 4, 7, 8, and 9 was assessed using immunohistochemical staining of paraffin-embedded renal-biopsy tissue specimens with specific antibodies and evaluated semiquantitatively by light microscopy. Linear discriminant analysis (LDA) was used to test whether intrarenal staining of TLR 4, 7, 8, and 9 distinguished patients with IgAN from controls or correlated with eGFR and/or proteinuria. eGFR was calculated using the creatinine-based formula. Moreover, the biopsies from patients with IgAN were scored according to the Oxford Classification. LDA showed that staining for TLR 4, 7, 8, and 9 was more intense in specimens from IgAN patients compared to normal kidney tissues. The intensity of intrarenal staining of TLRs discriminated four groups of IgAN patients with different eGFR and proteinuria and MEST scoring.

We have summarized the latest findings on markers for progression of immunoglobulin A (IgA) nephropathy (IgAN), the most common primary glomerulonephritis with a high prevalence among end-stage renal disease (ESRD) patients. The clinical predictors of renal outcome in IgAN nephropathy, such as proteinuria, hypertension, and decreased estimated glomerular filtration rate (eGFR) at the time of the diagnosis, are well known. The Oxford classification of IgAN identified four types of histological lesions (known as the MEST score) associated with the development of ESRD and/or a 50 % reduction in eGFR. In addition, the role of genetic risk factors associated with IgAN is being elucidated by genome-wide association studies, with multiple risk alleles described. Recently, biomarkers in serum (galactose-deficient IgA1, IgA/IgG autoantibodies against galactose-deficient IgA1, and soluble CD 89-IgA complexes) and urine (soluble transferrin receptor, interleukin-6/epidermal growth factor ratio, fractalkine, laminin G-like 3 peptide, κ light chains, and mannan-binding lectin) have been identified. Some of these biomarkers may represent candidates for the development of noninvasive diagnostic tests, that would be useful for detection of subclinical disease activity, monitoring disease progression, assessment of treatment, and at the same time circumventing the complications associated with renal biopsies. These advances, along with future disease-specific therapy, will be helpful in improving the treatment effectiveness, prognosis, and the quality of life in connection with IgAN.

Background: We describe data on 10,472 renal biopsies gathered by the Czech Registry of Renal Biopsies over a period of 18 years., Methods: We assessed the main demographic, clinical and histological data of individuals who underwent renal biopsies of native kidneys in 31 centers in the Czech Republic (population 10.3 million) during the period 1994-2011., Results: We evaluated 10,472 renal biopsies: males 57.8%, children (≤15 years) 13.6%, elderly (>60 years) 19.1%. The most frequent biopsy-proven diseases were primary (55.7%) and secondary (29.1%) glomerulonephritides (GN). Tubulointerstitial nephritis (TIN) was observed in 3.4 % and vascular diseases in 4.1%. The samples were non-diagnostic in 4.2%. Among primary GN the most frequent diagnoses were IgA nephropathy (IgAN) (37.4%), membranous GN (MGN) (13%) and focal segmental glomerulosclerosis (FSGS) (12.6%). Among secondary GN, systemic lupus erythematosus (SLE) represented 23.2%, hereditary diseases 19.8% and necrotizing vasculitis (NV) 19.4%. Among adults, mild renal insufficiency [serum creatinine (SCr) 111-200 μmol/l] was present in 24.7%, advanced renal insufficiency (SCr 201-400 μmol/l) in 15.3, and 12.3% of patients had SCr > 400 μmol/l. The most common diseases in patients with nephrotic proteinuria were minimal change disease (MCD) (39.7%) among children, IgAN (26.2%) in adults aged 16-60 years and amyloidosis (42.7%) among the elderly. The mean annual incidence (per million population) was: primary GN 30.9, secondary GN 18.1, IgAN 11.6, MGN 4.0, SLE 4.0, FSGS 3.9, MCD 3.4, NV 3.2, diabetic nephropathy 2.3, thin basement membrane glomerulopathy 2.0, mesangioproliferative GN 1.9, and TIN 1.9. Ultrasound needle guidance was used in 66.8%. The frequency of serious complications (symptomatic hematoma, gross hematuria, blood transfusion) was approximately 3.2%., Conclusions: This report provides representative population-based data on native biopsy-proven renal diseases in the Czech Republic. Over the 18 years of nationwide biopsy survey, we noted an increase of the mean age of renal biopsy cases, an increasing proportion of elderly, and a cardinal change in biopsy technique towards ultrasonography needle guidance.