Didem TURGUT, Fatih DEDE, Simal KÖKSAL CEVHER, Aysel ÇOLAK, Ezgi COŞKUN YENİGÜN

Primer Glomerülonefritlerde Glomerül Alanın Dijital Patoloji Yazılımı ile Değerlendirilmesi

Giriş: Böbrek biyopsisi, altta yatan böbrek hastalığını ve progresyona sebep olabilecek risk faktörlerini belirlemek içingereklidir. Glomerüler morfometri basit ancak kullanılmayan, uzun dönem böbrek fonksiyonları hakkında nitel bilgiveren bir yöntemdir. Ancak altta yatan glomerülonefrit tipine göre glomerüler morfometrinin değişip değişmediği bilinmemektedir. Güvenilir değerlendirme için de ölçümlerin standart olması gereklidir. Biz bu çalışmada, primerglomerüler hastalıklarda glomerül morfometresini dijital ortamda, standart bir şekilde, glomerüler alan ölçerekdeğerlendirmeyi hedefledik.Yöntemler: 2017-2019 yılları arasında nefrotik sendrom tanısı ile böbrek biyopsisi yapılmış 198 hasta restrospektifolarak değerlendirildi. Dışlama kriterleri sonrasında 48 hasta çalışmaya dahil edildi. Glomerül alanı, maksimum,minimum ve ortalama alan ölçümü olarak bilgisayar programı kullanılarak tüm seri kesitlerde incelendi. Bulgular: Kırksekiz böbrek biyopsinde, % 37,5 hastada IgA nefropatisi, % 33,3 memranöz glomerulonefrit, % 29,2hastada fokal segmental glomeruloskleroz tespit edildi. Üç grup arasında maksimum, minimum ve ortalama glomerülalanları benzerdi. Maksimum glomerül alanı tanı anındaki serum albumin ile negatif, 24 saatlik idrar protein miktarı ilepozitif korele bulundu (r= - 0,592, p=0,044 ve r=0,531, p=0,022). Tedavi sonrası birinci yılda, maksimum glomerül alanıserum kreatinin ile pozitif (r=0.385, p=0.019), GFR ile negatif korele bulundu (r=0,493, p=0,043).Sonuç: Glomerüler hastalıklarda tanı anındaki patolojik değerlendirmede maksimum glomerül alan ölçülmesi, böbreğinaltyapısı ve hastalığın klinik gidişatı hakkında tahminde bulunmak için ek belirteç olabilir.

Measurement of Glomerular Area in Primary Glomerular DiseasesWith a Digital Pathology Software

Objective: Kidney biopsy is essential to evaluate the activity of underlying kidney disease and the risk factors related to kidney disease progression. Glomerular morphometry is a simple but uncommonly used qualitative predictor of longterm kidney function. But it is mysterious if glomerular morphometry changes due to underlying glomerulonephritis. Measurement quantification is also necessary for reliable interpretation. We aimed to evaluate glomerular morphometry with glomerular area measurements quantitatively with digitally scanned slides in the primary glomerular diseases.Methods: We retrospectively analyzed 198 patients with nephrotic syndrome that underwent kidney biopsy between 2017 and 2019. 48 patients enrolled into the study after the exclusion criteria. We measured the glomerular area as maximum, minimum, and mean areas, using image analysis software. Results: Forty-eight kidney biopsies were analyzed retrospectively under three primary glomerular disease groups as IgA nephropathy (37.5%), focal segmental glomerulosclerosis (29.2%), and membranous glomerulonephritis (33.3%). The glomerular area measured as maximum, minimum, and mean, were similar between 3 groups. The maximum glomerular area was negatively correlated with serum albumin and positively correlated with 24hr proteinuria (r= - 0.592, p=0.044, and r=0.531, p=0.022) at the time of diagnosis. At the end of one year, maximum glomerular area was positively correlated with serum creatinine (r=0.385, p=0.019) and negatively correlated with eGFR (r= - 0.493, p=0.043). Conclusions: At the time of diagnosis of glomerular diseases, maximum glomerular area measurement during the pathological assessment might be an additional marker to estimate the ultrastructure of the kidney and the clinical course of the disease.

PDF

___

1. Aydin E, Aydin F.Y, Yilmaz E.D, Alabalik U. Böbrek Biyopsilerinin Histopatolojik Değerlendirilmesi: Tek Merkez Yedi Yıllık Deneyim. Dicle Tıp Dergisi. 2020; 47: 417–22.
2. Floege J, Barbour J.B, Cattran D. C et al. Management and treatment of glomerular diseases (part 1): conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int. 2019; 95: 268–80.
3. Pagtalunan ME, Drachman JA, Meyer TW. Methods for estimating the volume of individual glomeruli. Kidney Int. 2000; 57: 2644–49.
4. Lemley KV, Bagnasco SM, Nast CC, et al. Morphometry Predicts Early GFR Change in Primary Proteinuric Glomerulopathies: A Longitudinal Cohort Study Using Generalized Estimating Equations. PLoS ONE. 2016; 11: e0157148.
5. Lemley KV, Lafayette RA, Derby G, et al. Prediction of early progression in recently diagnosed IgA nephropathy. Nephrol Dial Transplant. 2008; 23: 213–22.
6. Tsuboi N, Kawamura T, Miyazaki Y, et al. Low glomerular density is a risk factor for progression in idiopathic membranous nephropathy. Nephrol Dial Transplant. 2011; 26:3555–60.
7. Fogo AB. Glomerular hypertension, glomerular growth and progression of renal diseases. Kidney Int. 2000; 57: 15-21.
8. Kroustrup J.P, Gundersen H.G.J, and Osterby R. Glomerular Size and Structure in Diabetes Mellitus Il, Early Enlargement of the Capillary Surface. Diabetologia. 1977; 13: 207-10.
9. Kelepouris E, Rovin BH. Overview of heavy proteinuria and the nephrotic syndrome. UpToDate. Retrieved August 28, 2019.
10. Kidney Disease: Improving Global Outcomes (KDIGO) Glomerulonephritis Work Group. KDIGO clinical practice guideline for glomerulonephritis. Kidney Int Suppl. 2012; 2: 139–274.
11. Shea SM, Raskova J, Morrison AB. A stereologic study of glomerular hypertrophy in the subtotally nephrectomized rat. Am J Pathol. 1978; 90: 201-10.
12. Kambham N, Markowitz GS, Valeri AM, et al. Obesity-related glomerulopathy: an emerging epidemic. Kidney Int. 2001; 59: 1498-509.
13. Wu Y, Liu Z, Xiang Z, et al. Obesity-related glomerulopathy: insights from gene expression profiles of the glomeruli derived from renal biopsy samples. Endocrinology. 2006; 147: 44-50.
14. Fries JWU, Sandstrom DJ, Meyer TW, et al. Glomerular hypertrophy and epithelial cell injury modulate progressive glomerulosclerosis in the rat. Lab Invest. 1989; 60: 205–18.
15. Daniels BS, Hostetter TH: Adverse effects of growth in the glomerular microcirculation. Am J Physiol. 1990; 258: 1409–16.
16. Grond J, Beukers JYB, Schilthuis MS, et al. Analysis of renal structural and functional features in two rat strains with a different susceptibility to glomerular sclerosis. Lab Invest. 1986; 4: 77–85.
17. Fogo A, Ichikawa I: Evidence for a pathogenic linkage between glomerular hypertrophy and sclerosis. Am J Kidney Dis. 1991; 17: 666–9.
18. Brenner, BM. Nephron adaptation to renal injury or ablution. Am. J. Physiol. 1985; 49: 324-37.
19. Olson JL, Heptinstall RH. Nonimmunologic mechanisms of glomerular injury. Lab Invest. 1988 Nov; 59: 564-78.
20. Kataoka H, Mochizuki T, Nitta K. Large Renal Corpuscle: Clinical Significance of Evaluation of the Largest Renal Corpuscle in Kidney Biopsy Specimens. Contrib Nephrol. 2018; 195: 20-30.
21. Hoy WE, Douglas-Denton RN, Hughson MD, et al. stereological study of glomerular number and volume: preliminary findings in a multiracial study of kidneys at autopsy. Kidney Int Suppl. 2003; 2: 31- 7.
22. Weibel ER, Gomez DM. A principle for counting tissue structures on random sections. J Appl Physiol. 1962; 3; 17:343-8.
23. Kataoka H, Ohara M, Honda K, et al. Maximal glomerular diameter as a 10-year prognostic indicator for IgA nephropathy. Nephrol Dial Transplant. 2011; 0: 1–7.
24. D. Hughson M, Johnson K, J. Young R, et al. Bertram. Glomerular Size and Glomerulosclerosis: Relationships to Disease Categories, Glomerular Solidification, and Ischemic Obsolescence. Am J Kidney Dis. 2002; 39: 679-88.
25. Kataoka H, Moriyama T, Manabe S, et al. Maximum Glomerular Diameter and Oxford MEST-C Score in IgA Nephropathy: The Significance of Time Series Changes in Pseudo-R2 Values in Relation to Renal Outcomes. J Clin Med. 2019; 2; 8. E2105. doi: 10.3390/jcm8122105.
26. Tsuboi N, Kawamura T, Koike K, et al. Glomerular density in renal biopsy specimens predicts the long term prognosis of IgA nephropathy. Clin J Am Soc Nephrol. 2010; 5: 39-44.