Clinicomorphological characteristics of renal disorders in patients with genetic thrombophilia


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Abstract

Aim. To characterize the course and clinicomorphological features of chronic glomerulonephritis (CGN) in patients with genetic thrombophilia.
Material and methods. A clinical picture and evidence on renal biopsy from 25 patients (12 females, mean age 32 ± 12 years and 13 males, mean age 36 ± 8.8 years) admitted to hospital with diagnosis of chronic glomerulonephritis were analysed. Mean duration of renal problem to the moment of biopsy was 37.6 ± 39 months. Renal end point was stable rise of Scr > 1.4 mg/dl for 6 months. Polymerase chain reaction defined polymorphisms of the genes MTHFR C677T; PTG G20210A; FV Leiden G1691A; FGB G455A; ITGB3 T176C L33P; PAI-1 4G/5G 675.
Results. Mutation in one gene was detected in 24% patients, a multigenic form of thrombophilia - in 76% patients. Morphologically, all the patients' renal tissue had the signs of thrombotic microangiopathy (TMA), 8 patients had a combination of acute and chronic TMA. TMA was the only histological sign of nephropathy in 3 (13%) patients, the rest patients showed TMA combination with different morphological variants of CGN. Sclerotic alterations were most severe in combined carriage of the alleles 4G PAI-1 and T MTHFR. A correlation was found between the renal end point and number of mutant alleles (r = 0.6, p < 0.05), the presence of allele 4G (r = 0.46, p = 0.05) and interstitial sclerosis (r = 0.5, p = 0.05).
Conclusion. Hereditary thrombophilia promotes induction of nephrosclerosis leading to activation of intraglomerular blood clotting which contributes to CGN progression. Patients with genetic thrombophilia may develop acute TMA as the only variant of renal damage.

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