scholarly journals Significance of kidney biopsy in autosomal dominant tubulointerstitial kidney disease-UMOD: is kidney biopsy truly nonspecific?

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Tamehito Onoe ◽  
Satoshi Hara ◽  
Kazunori Yamada ◽  
Takeshi Zoshima ◽  
Ichiro Mizushima ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Autosomal Dominant ◽  
Kidney Biopsy ◽  
Interstitial Fibrosis ◽  
Hereditary Disease ◽  
Basement Membranes ◽  
Pathological Findings ◽  
Tubular Atrophy ◽  
Pas Staining ◽  
Conventional Methods

Abstract 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.

What is the value of repeat kidney biopsies in patients with lupus nephritis?

Lupus ◽  
2020 ◽  
Vol 30 (1) ◽  
pp. 25-34
Author(s):  
Enrique Morales ◽  
Hernando Trujillo ◽  
Teresa Bada ◽  
Marina Alonso ◽  
Eduardo Gutiérrez ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Lupus Nephritis ◽  
Disease Progression ◽  
Kidney Biopsy ◽  
Interstitial Fibrosis ◽  
Repeat Biopsy ◽  
Vascular Lesions ◽  
Clinical Indication ◽  
Tubular Atrophy ◽  
Kidney Disease Progression

Introduction Recent studies with protocol biopsies have shown a mismatch between clinical and histological remission in lupus nephritis (LN). We aimed to evaluate histological changes in repeat kidney biopsies by clinical indication in patients with LN. Methods We analyzed 107 patients with LN in which a kidney biopsy was performed between 2008 and 2018. Of those, we included 26 (24.2%) who had ≥2 kidney biopsies. Classification was done according to the International Society of Nephrology/Renal Pathology Society. Results Mean time between biopsies was 71.5 ± 10.7 months. 73.1% of patients presented a change of class at repeat biopsy; 38.4% to a higher class and 34.6% to a lower class. A significant increase in glomerulosclerosis (% GS) (3.8% vs 18.7%, p = 0.006), interstitial fibrosis (3.8% vs 26.9%, p = 0.021), tubular atrophy (15.4% vs 57.7%, p = 0.001) and chronicity index (CI) (1 vs 3, p < 0.001) was observed at repeat biopsy. Subjects who developed chronic kidney disease progression had a lower rate of complete remission at 12 months (0% vs 37.5%, p = 0.02), higher % GS at first biopsy (7.9% vs 1.2%, p = 0.02) and higher CI (4 vs 2, p = 0.006), tubular atrophy (90% vs 37.6%, p = 0.008), interstitial fibrosis (50% vs 12.5%, p = 0.036) and vascular lesions (60% vs 18.8%, p = 0.031) at second biopsy. Conclusions Our major finding was that patients with LN showed a significant increase in % GS, interstitial fibrosis, tubular atrophy and vascular lesions in repeat biopsies performed by clinical indication. This suggest that a second kidney biopsy may provide valuable and useful information regarding kidney disease progression.

scholarly journals Should We Always Defer Treatment of Kidney Disease When There Is Extensive Interstitial Fibrosis on Biopsy?

2016 ◽  
Vol 44 (4) ◽  
pp. 286-288 ◽  
Author(s):  
Musab S. Hommos ◽  
Andrew D. Rule
Keyword(s):  
Kidney Disease ◽  
Prognostic Marker ◽  
Kidney Failure ◽  
Kidney Biopsy ◽  
Interstitial Fibrosis ◽  
Strong Predictor ◽  
Tubular Atrophy ◽  
Severe Fibrosis

Severity of interstitial fibrosis and tubular atrophy (IFTA) seen on kidney biopsy has been used by nephrologist as prognostic marker of kidney disease. While IFTA is a very strong predictor of kidney failure, some patients with severe fibrosis will still not progress to kidney failure within 5 years. Treatment of underlying kidney disease in select patients with severe IFTA should be considered when risks of treatment are reasonable despite the low potential for benefit.

scholarly journals Matrix Metalloproteinases in Diabetic Kidney Disease

2020 ◽  
Vol 9 (2) ◽  
pp. 472 ◽  
Author(s):  
Garcia-Fernandez ◽  
Jacobs-Cachá ◽  
Mora-Gutiérrez ◽  
Vergara ◽  
Orbe ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Interstitial Fibrosis ◽  
Experimental Models ◽  
Basement Membranes ◽  
Matrix Metalloproteases ◽  
Mesangial Expansion ◽  
Tubular Atrophy ◽  
Diabetic Kidney ◽  
The Matrix

Around the world diabetic kidney disease (DKD) is the main cause of chronic kidney disease (CKD), which is characterized by mesangial expansion, glomerulosclerosis, tubular atrophy, and interstitial fibrosis. The hallmark of the pathogenesis of DKD is an increased extracellular matrix (ECM) accumulation causing thickening of the glomerular and tubular basement membranes, mesangial expansion, sclerosis, and tubulointerstitial fibrosis. The matrix metalloproteases (MMPs) family are composed of zinc-dependent enzymes involved in the degradation and hydrolysis of ECM components. Several MMPs are expressed in the kidney; nephron compartments, vasculature and connective tissue. Given their important role in DKD, several studies have been performed in patients with DKD proposing that the measurement of their activity in serum or in urine may become in the future markers of early DKD. Studies from diabetic nephropathy experimental models suggest that a balance between MMPs levels and their inhibitors is needed to maintain renal homeostasis. This review focuses in the importance of the MMPs within the kidney and their modifications at the circulation, kidney and urine in patients with DKD. We also cover the most important studies performed in experimental models of diabetes in terms of MMPs levels, renal expression and its down-regulation effect.

scholarly journals Cellular Mechanisms of Tissue Fibrosis. 3. Novel mechanisms of kidney fibrosis

2013 ◽  
Vol 304 (7) ◽  
pp. C591-C603 ◽  
Author(s):  
Gabriela Campanholle ◽  
Giovanni Ligresti ◽  
Sina A. Gharib ◽  
Jeremy S. Duffield
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Interstitial Fibrosis ◽  
Kidney Injury ◽  
Innate Immune ◽  
Cellular Mechanisms ◽  
Tubular Atrophy ◽  
Kidney Fibrosis ◽  
Capillary Rarefaction ◽  
Peritubular Capillaries

Chronic kidney disease, defined as loss of kidney function for more than three months, is characterized pathologically by glomerulosclerosis, interstitial fibrosis, tubular atrophy, peritubular capillary rarefaction, and inflammation. Recent studies have identified a previously poorly appreciated, yet extensive population of mesenchymal cells, called either pericytes when attached to peritubular capillaries or resident fibroblasts when embedded in matrix, as the progenitors of scar-forming cells known as myofibroblasts. In response to sustained kidney injury, pericytes detach from the vasculature and differentiate into myofibroblasts, a process not only causing fibrosis, but also directly contributing to capillary rarefaction and inflammation. The interrelationship of these three detrimental processes makes myofibroblasts and their pericyte progenitors an attractive target in chronic kidney disease. In this review, we describe current understanding of the mechanisms of pericyte-to-myofibroblast differentiation during chronic kidney disease, draw parallels with disease processes in the glomerulus, and highlight promising new therapeutic strategies that target pericytes or myofibroblasts. In addition, we describe the critical paracrine roles of epithelial, endothelial, and innate immune cells in the fibrogenic process.

scholarly journals MO638ANEMIA IN DIABETIC PATIENTS REFLECTS SEVERE TUBULOINTERSTITIAL INJURY AND ASSISTS CLINICALLY IN PREDICTING DIAGNOSIS OF DIABETIC NEPHROPATHY

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Soichiro Yokota ◽  
Kenji Ito ◽  
Maho Watanabe ◽  
Koji Takahashi ◽  
Naoko Himuro ◽  
...  
Keyword(s):  
Renal Function ◽  
Regression Analysis ◽  
Diabetic Nephropathy ◽  
Kidney Disease ◽  
Confidence Interval ◽  
Odds Ratio ◽  
Kidney Biopsy ◽  
Renal Pathology ◽  
Diabetic Patients ◽  
Pathological Findings

Abstract Background and Aims Diabetic nephropathy (DN) is currently a leading cause of end-stage kidney disease worldwide. Kidney biopsy is generally performed in diabetic patients to discriminate between DN and non-diabetic kidney disease (NDKD), and to provide more specific treatments. In addition to conventional predicting factors of DN, recent studies suggested the predictive value of anemia in the diagnosis of DN, however detailed pathophysiology and the significance of anemia in renal pathology are not fully understood. This study aimed to investigate the impact of anemia on renal pathology and clinical course in patients who underwent kidney biopsy. Method We reviewed 81 patients (60.4 ± 13.7 years, 54 men and 27 women) with type 2 diabetes who underwent percutaneous kidney biopsy in Fukuoka University Hospital from January 2001 through March 2020. DN was diagnosed by mesangial expansion or nodular glomerulosclerosis observed under a light microscope, and immunofluorescence assisted in differentiating NDKD from DN. Anemia was defined as hemoglobin level &lt;13 g/dL in males and &lt;12 g/dL in females in accordance with the World Health Organization standards. Laboratory and pathological findings, and clinical courses were investigated. Results According to their pathological findings, patients were classified into two groups: isolated DN (DN group, n=30) and NDKD alone or concurrent DN (NDKD group, n=51). There were 11 types of NDKD. Of these, membranous nephropathy was the most common (23.5%), followed by IgA nephropathy (17.6%), and crescentic glomerulonephritis (13.7%). In multiple logistic regression analysis, absence of severe hematuria (odds ratio (OR) 11.66, 95% confidence interval (CI) 1.68 - 89.9) and presence of anemia (OR 11.38, 95% CI 2.51 - 51.52) were significantly related with the diagnosis of DN. Akaike’s information criterion (AIC) and net reclassification improvement (NRI) analyses revealed improved predictive performance by adding anemia to the conventional factors (AIC 100.152 to 91.844; NRI 27.0%). The tissues of patients in the DN group demonstrated more severe interstitial fibrosis and tubular atrophy (IF/TA) than the NDKD group (p&lt;0.05) regardless of the rate of global glomerulosclerosis (figure), and IF/TA was related to the prevalence of anemia (odds ratio: 7.31, 95% confidence interval: 2.33 - 23.00) in multivariate regression analysis. These results suggest DM-associated severe IF/TA (compared with NDKD) impaired erythropoietin production, resulting in earlier anemia, independent of glomerular injuries and renal function. Furthermore, the renal prognosis was significantly better in the NDKD group than in the DN group using Log-rank test (p&lt;0.05). Conclusion DN is associated with anemia because of severe IF/TA regardless of renal function, and anemia helps clinician discriminate clinically between isolated DN and NDKD.

scholarly journals In Patients with Membranous Lupus Nephritis, Exostosin-Positivity and Exostosin-Negativity Represent Two Different Phenotypes

2021 ◽  
pp. ASN.2020081181 ◽  
Author(s):  
Aishwarya Ravindran ◽  
Marta Casal Moura ◽  
Fernando C. Fervenza ◽  
Samih H. Nasr ◽  
Mariam P. Alexander ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Kidney Biopsy ◽  
Interstitial Fibrosis ◽  
Study Cohort ◽  
Lower Serum ◽  
Tubular Atrophy ◽  
Novel Proteins ◽  
Biopsy Specimens ◽  
Membranous Lupus Nephritis

BackgroundIn patients with secondary (autoimmune) membranous nephropathy, two novel proteins, Exostosin 1 and Exostosin 2 (EXT1/EXT2), are potential disease antigens, biomarkers, or both. In this study, we validate the EXT1/EXT2 findings in a large cohort of membranous lupus nephritis.MethodsWe conducted a retrospective cohort study of patients with membranous lupus nephritis, and performed immunohistochemistry studies on the kidney biopsy specimens against EXT1 and EXT2. Clinicopathologic features and outcomes of EXT1/EXT2-positive versus EXT1/EXT2-negative patients were compared.ResultsOur study cohort included 374 biopsy-proven membranous lupus nephritis cases, of which 122 (32.6%) were EXT1/EXT2-positive and 252 (67.4%) were EXT1/EXT2-negative. EXT1/EXT2-positive patients were significantly younger (P=0.01), had significantly lower serum creatinine levels (P=0.02), were significantly more likely to present with proteinuria ≥3.5 g/24 h (P=0.009), and had significantly less chronicity features (glomerulosclerosis, P=0.001 or interstitial fibrosis and tubular atrophy, P<0.001) on kidney biopsy. Clinical follow-up data were available for 160 patients, of which 64 (40%) biopsy results were EXT1/EXT2-positive and 96 (60%) were EXT1/EXT2-negative. The proportion of patients with class 3/4 lupus nephritis coexisting with membranous lupus nephritis was not different between the EXT1/EXT2-positive and EXT1/EXT2-negative groups (25.0% versus 32.3%; P=0.32). The patients who were EXT1/EXT2-negative evolved to ESKD faster and more frequently compared with EXT1/EXT2-positive patients (18.8% versus 3.1%; P=0.003).ConclusionsThe prevalence of EXT1/EXT2 positivity was 32.6% in our cohort of membranous lupus nephritis. Compared with EXT1/EXT2-negative membranous lupus nephritis, EXT1/EXT2-positive disease appears to represent a subgroup with favorable kidney biopsy findings with respect to chronicity indices. Cases of membranous lupus nephritis that are EXT1/EXT2-negative are more likely to progress to ESKD compared with those that are EXT1/EXT2-positive.

P0132DIAGNOSIS OF HYPEROXALURIA FROM RENAL BIOPSY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Marwa Omrane ◽  
Raja Aoudia ◽  
Mondher Ounissi ◽  
Nada Sellami ◽  
Mouna Jerbi ◽  
...  
Keyword(s):  
Renal Failure ◽  
Kidney Disease ◽  
Renal Biopsy ◽  
Kidney Biopsy ◽  
Interstitial Fibrosis ◽  
Renal Pathology ◽  
Crystal Deposition ◽  
Biopsy Specimens ◽  
Initial Symptoms ◽  
History Of

Abstract Background and Aims Crystal-induced kidney disease refers to kidney injury caused by intratubular crystal deposition. The most common forms of crystalline nephropathy encountered in renal pathology are nephrocalcinosis and oxalate nephropathy. The purpose of our study is to determine the epidemiological and clinical characteristics of hyperoxaluria diagnosed from renal biopsy. Method We retrospectively reviewed all kidney biopsy specimens evaluated at renal pathology laboratory, from 1976 to 2019. The biopsy specimens were received from multiple medical department and medical centers. We studied 8900 biopsy specimens and we were focused on patients whose diagnosis of hyperoxaluria was made from renal biopsy Results We identified 25 cases (15 children and 10 adults) with a sex ratio H / F of 0.9. Mean age at diagnosis was 17.2 years old [4 months-73 years old]. Most patients were offspring of consanguineous mating (14 of 25) with intermarriage of first-degree cousins being the most common pattern. A family history of chronic kidney disease was found in 13 patients: indeterminated nephropathy (n = 6) and renal stone (n = 5) and primary hyperoxaluria (n=2). Among our patients, five had a history of urolithiasis. One patient had a history of chronic diarrhea related to Crohn's disease and one patient had a history of cephalic pancreatectomy and ileal resection. Initial symptoms and signs were dominated by renal failure (n = 25) with mean creatinine of 789.5 μmol / l [306-1832μmol / l], associated with proteinuria in 10 patients and hematuria in 11 patients. Arterial hypertension was present in 4 patients. Oligo anuria was reported in 4 patients without dilation of the urinary excretory pathways. In our patients, the diagnosis of crystalin nephropathy was revealed by renal biopsy. In one case, the diagnosis was made after renal transplant. In 4 cases the diagnosis was made by postmortem kidney biopsy. In all cases, the kidney biopsy specimen showed extensive intratubular crystal deposition and tubulointerstitial mononuclear cell infiltration with features of tubular injury and interstitial fibrosis. Examination of histologic slides showed colorless refractile crystals of polygonal appearance. Multicolored birefringence under polarized light identified these crystals as calcium oxalate. After different investigations (genetic and biological analysis), the diagnosis of hyperoxaluria was confirmed. Hyperoxaluria was primary in 23 patients and secondary in 2 patients. Conclusion Hyperoxaluria is a rare condition, often serious, involving renal prognosis and sometimes life-threatening, especially in early-onset forms. Early diagnosis and treatment should be done as soon as possible to slow the progression to end-stage renal failure. In patients with renal insufficiency, the diagnosis of hyperoxaluria is difficult. Renal biopsy can help when clinical and radiological data are not sufficient.

scholarly journals Urinary chemokine C-X-C motif ligand 16 and endostatin as predictors of tubulointerstitial fibrosis in patients with advanced diabetic kidney disease

2019 ◽  
Author(s):  
Yu Ho Lee ◽  
Ki Pyo Kim ◽  
Sun-Hwa Park ◽  
Dong-Jin Kim ◽  
Yang-Gyun Kim ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Interstitial Fibrosis ◽  
Renal Outcome ◽  
Enzyme Linked Immunosorbent Assay ◽  
Glomerular Injury ◽  
Tubular Atrophy ◽  
Diabetic Kidney ◽  
Cytokines And Chemokines ◽  
Pathologic Features

Abstract Background Interstitial fibrosis and tubular atrophy (IFTA) is a well-recognized risk factor for poor renal outcome in patients with diabetic kidney disease (DKD). However, a noninvasive biomarker for IFTA is currently lacking. The purpose of this study was to identify urinary markers of IFTA and to determine their clinical relevance as predictors of renal prognosis. Methods Seventy patients with biopsy-proven isolated DKD were enrolled in this study. We measured multiple urinary inflammatory cytokines and chemokines by multiplex enzyme-linked immunosorbent assay in these patients and evaluated their association with various pathologic features and renal outcomes. Results Patients enrolled in this study exhibited advanced DKD at the time of renal biopsy, characterized by moderate to severe renal dysfunction [mean estimated glomerular filtration rate (eGFR) 36.1 mL/min/1.73 m2] and heavy proteinuria (mean urinary protein:creatinine ratio 7.8 g/g creatinine). Clinicopathologic analysis revealed that higher IFTA scores were associated with worse baseline eGFR (P < 0.001) and poor renal outcome (P = 0.002), whereas glomerular injury scores were not. Among measured urinary inflammatory markers, C-X-C motif ligand 16 (CXCL16) and endostatin showed strong correlations with IFTA scores (P = 0.001 and P < 0.001, respectively), and patients with higher levels of urinary CXCL16 and/or endostatin experienced significantly rapid renal progression compared with other patients (P < 0.001). Finally, increased urinary CXCL16 and endostatin were independent risk factors for poor renal outcome after multivariate adjustments (95% confidence interval 1.070–3.455, P = 0.029). Conclusions Urinary CXCL16 and endostatin could reflect the degree of IFTA and serve as biomarkers of renal outcome in patients with advanced DKD.

Sign in / Sign up

Export Citation Format

Share Document