Significance of kidney biopsy in autosomal dominant tubulointerstitial kidney disease-UMOD: is kidney biopsy truly nonspecific?
| Autor: | Tadashi Konoshita, Junko Imura, Hiroaki Muramoto, Michihiro Mitobe, Kiyoaki Ito, Ichiro Mizushima, Hiroaki Tsuruta, Mitsuhiro Kawano, Akira Iguchi, Shoichiro Daimon, Tamehito Onoe, Satoshi Hara, Takeshi Zoshima, Takayasu Mori, Nao Kishimoto, Akihiro Kuma, Maki Shimizu, Kazunori Yamada, Yoshifumi Ubara |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Adult
Male 0301 basic medicine Nephrology medicine.medical_specialty Pathology Tamm–Horsfall protein Adolescent Biopsy Tamm-Horsfall protein Kidney biopsy 030232 urology & nephrology Autosomal dominant tubulointerstitial kidney disease Gene mutation Kidney lcsh:RC870-923 Sensitivity and Specificity Young Adult 03 medical and health sciences 0302 clinical medicine Internal medicine Uromodulin medicine Humans biology medicine.diagnostic_test business.industry Glomerulosclerosis Middle Aged Polycystic Kidney Autosomal Dominant lcsh:Diseases of the genitourinary system. Urology medicine.disease Kidney Tubules 030104 developmental biology medicine.anatomical_structure Mutation biology.protein Tubulointerstitial fibrosis Female business Research Article Kidney disease |
| Zdroj: | BMC Nephrology, Vol 22, Iss 1, Pp 1-11 (2021) BMC Nephrology |
| ISSN: | 1471-2369 |
| Popis: | Background Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a rare hereditary disease caused by a variety of genetic mutations. Carriers of a mutation in the responsible genes are at risk of reaching end-stage kidney disease typically in middle age. The frequency of this disease is assumed to be underestimated because of a lack of disease-specific signs. Pathological findings obtained from kidney of uromodulin related ADTKD (ADTKD-UMOD) patients are regarded as non-specific and less-informative for its diagnosis. This research was undertaken to evaluate the significance of kidney biopsy in ADTKD-UMOD patients. Methods Thirteen patients from 10 families with nine identified uromodulin (UMOD) gene mutations who underwent kidney biopsy in the past were studied. Their kidney tissues were stained with anti-UMOD antibody in addition to conventional methods such as PAS staining. When positive, the numbers of tubules with visible UMOD protein accumulations were calculated based on the total numbers of UMOD expressing tubules. Pathological findings such as tubulointerstitial fibrosis, atrophy, inflammation and glomerulosclerosis were also evaluated and analyzed. Results Interstitial fibrosis and tubular atrophy were present in all 13 patients. Most atrophic tubules with thickening and lamellation of tubular basement membranes showed negative UMOD staining. In all but two patients with C94F mutations, massive accumulation of UMOD proteins was observed in the renal endoplasmic reticulum. UMOD accumulations were also detectable by PAS staining as polymorphic unstructured materials in the 11 patients at frequencies of 2.6–53.4%. 80.4% of the UMOD accumulations were surrounded by halos. The detection rate of UMOD accumulations positively correlated with eGFR. Glomerulosclerosis was detected in 11/13 patients, with a frequency of 20.0 to 61.1%, while no cystic dilatations of glomeruli were detected. Conclusions Massively accumulated UMOD proteins in ADTKD-UMOD kidneys are detectable not only by immunostaining using anti-UMOD antibody but also by conventional methods such as PAS staining, although their detection is not easy. These findings can provide important clues to the diagnosis of ADTKD-UMOD. Kidney biopsy in ADTKD-UMOD may be more informative than assumed previously. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink