P0424CLINICO-PATHOLOGICAL CHARACTERISTICS AND OUTCOMES OF PATIENTS WITH DNAJB9 POSITIVE FIBRILLARY GLOMERULONEPHRITIS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Shaoshan Liang ◽  
Dandan Liang ◽  
Feng Xu ◽  
Mingchao Zhang ◽  
Fan Yang ◽  
...  
Keyword(s):  
Interstitial Fibrosis ◽  
Young Patients ◽  
Hashimoto Thyroiditis ◽  
Basement Membranes ◽  
Igg Subclasses ◽  
Tubular Atrophy ◽  
Fibrillary Glomerulonephritis ◽  
Peritubular Capillaries ◽  
Polyclonal Igg ◽  
Glomerular Deposits

Abstract Background and Aims To investigate the clinicopathological features and prognosis of DNAJB9 positive fibrillary glomerulonephritis (FGN) in a single center in China. Method Cases diagnosed as FGN by renal biopsy from January 2011 to December 2019 in Jinling Hospital were stained with anti-DNAJB9 by immunohistochemistry. The patients with DNAJB9 positive FGN were retrospective analyzed. Results DNAJB9 staining of glomerular deposits was seen in 6 cases of FGN. 1 man and 5 women with a median age of 26 years (range, 21 to 49 years) were studied. Underlying autoimmune disease of Sjogren's syndrome and Hashimoto thyroiditis was in 1 case. None of them had dysproteinemia, malignancy, hepatitis C, hepatitis B, cryoglobulinemia, or diabetes. The patients presented with hypertension and edema in 5 cases, renal insufficiency in 1 case, and proteinuria in 6 cases with the median 24-hour urine protein 2.58 g (range, 1.66 to 9.57 g), nephrotic syndrome in 3 cases, and microscopic hematuria in 2 cases. The histologic pattern was mesangial proliferative glomerulonephritis (GN) and membranoproliferative GN. A mean of 9.7% of glomeruli were globally sclerotic. Crescents were present in 1 case (10%). The degree of tubular atrophy and interstitial fibrosis were absent (2 cases) and mild (4 cases), and severe acute tubular injury was in 1 case. All 6 cases showed glomerular positivity for IgG, C3 and C1q, 5 of which were positive for IgM, and 4 of which were positive for IgA. The glomerular deposits stained for polyclonal IgG subclasses and both kappa and lambda light chains in 3 cases. In 1 case, it stained for polyclonal IgG subclasses without kappa or lambda. IgG subclasses were IgG4 dominant in 3 cases and IgG1 dominant in 1 case. In 2 cases, they stained for monoclonal IgG1-kappa and IgG1-lambda. On electron microscopy (EM), the fibrillary deposits were seen infiltrating the mesangium, subendothelial, subepithelial area in all 6 cases, and the lamina densa of the GBMs in 5 cases with diameter of 7-40nm. Combined with observation of DNAJB9 staining, immunofluorescence microscopy and EM, extraglomerular deposits were identified in vessel walls in 5 cases, tubular basement membranes in 3 cases, peritubular capillaries in 3 cases. Congo red positivity was in 4 cases. At a median time of 32.9 months (range, 1 to 68.3 months) after biopsy, 3 cases were stable, 1 case had partial renal function recovery, and 2 cases had partial remission of proteinuria. Conclusion DNAJB9 immunohistochemistry is sensitive and specific for FGN. Monoclonal IgG and light chain was observed in young patients. Extraglomerular deposits were common. Prognosis was good in this young patient’s series.

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 Microcirculation: nexus of comorbidities in diabetes

2007 ◽  
Vol 293 (2) ◽  
pp. F486-F493 ◽  
Author(s):  
Constance Temm ◽  
Jesus H. Dominguez
Keyword(s):  
Metabolic Syndrome ◽  
Large Scale ◽  
Interstitial Fibrosis ◽  
Peritubular Capillary ◽  
Tubular Atrophy ◽  
The Metabolic Syndrome ◽  
Peritubular Capillaries ◽  
Obese Rats ◽  
Capillary Dysfunction

Generalized capillary dysfunction is a morbid element in the metabolic syndrome, and it is likely involved in its complications. We tested the hypothesis that vast amounts of serum albumin previously observed in kidneys of rats with the metabolic syndrome were caused, in part, by leakage from renal peritubular capillaries. We report herein large scale leaks of plasma fluid in peritubular capillaries of rats with the metabolic syndrome. This finding was directly demonstrated in vivo, and the presence of leftover albumin residue confirmed the leak in postmortem kidney specimens. Moreover, renal interstitial fibrosis and tubular atrophy were found in a distribution similar to the leaked renal albumin in obese rats. We suggest that there is an important link between peritubular capillary damage and interstitial fibrosis, represented as tubulointerstitial disease in the metabolic syndrome. We propose that maintenance of the peritubular microcirculation may improve renal outcomes in diabetes and the metabolic syndrome.

Seropositive PLA2R-associated membranous nephropathy but biopsy-negative PLA2R staining

2020 ◽  
Author(s):  
Jiao Luo ◽  
Wang Zhang ◽  
Cailing Su ◽  
Zhanmei Zhou ◽  
Guobao Wang
Keyword(s):  
Membranous Nephropathy ◽  
Interstitial Fibrosis ◽  
Clinicopathological Characteristics ◽  
Enzyme Linked Immunosorbent Assay ◽  
Double Positive ◽  
Lower Serum ◽  
Tubular Atrophy ◽  
Phospholipase A2 Receptor ◽  
Glomerular Deposits ◽  
Paraffin Tissue

Abstract Background Serum phospholipase A2 receptor (PLA2R) antibody (SAb) and glomerular deposits of PLA2R antigen (GAg) have been tested widely in idiopathic membranous nephropathy (MN). Recently, we noticed a special form of PLA2R-associated MN with positive circulating PLA2R antibody but negative PLA2R deposits in the glomeruli by immunofluorescence on frozen tissue (IF-F). The significance of this form of PLA2R-associated MN is yet to be elucidated. This study aimed to explore the clinicopathological features of these PLA2R-associated MN patients. Methods This study enrolled 229 biopsy-proven PLA2R-associated MN patients with SAb+. SAb was measured by enzyme-linked immunosorbent assay, and GAg was detected by IF-F. These patients were divided into SAb+/GAg+ and SAb+/GAg− groups. Clinicopathological characteristics of SAb+/GAg+ and SAb+/GAg− PLA2R-associated MN patients were compared. PLA2R antigens of 19 SAb+/GAg− PLA2R-associated MN patients were verified by immunohistochemistry on paraffin tissue (IHC-P). Results Among 229 SAb+ PLA2R-associated MN patients, 210 (91.70%) were GAg+ and 19 (8.3%) were GAg−. These 19 SAb+/GAg− PLA2R-associated MN patients presented positive PLA2R deposits by IHC-P. Compared with SAb+/GAg+ PLA2R-associated MN patients, SAb+/GAg- PLA2R-associated MN patients had higher levels of serum PLA2R antibody (P = 0.004), increased proteinuria (P = 0.008), lower serum albumin (P = 0.019), more prominent chronic pathological lesions in terms of glomerulosclerosis score (P = 0.025), interstitial fibrosis score (P = 0.016), tubular atrophy score (P = 0.010) and total renal chronicity score (P = 0.010), and were more likely to be accompanied by focal segmental glomerulosclerosis (P = 0.014). Higher SAb level was associated with the total renal chronicity score (odds ratio per 100 RU/mL, 1.16; 95% confidence interval 1.01–1.33; P = 0.033). Conclusions PLA2R-associated MN patients with seropositive PLA2R antibody but negative PLA2R deposits in the glomeruli by IF-F have higher levels of SAb and worse clinicopathological manifestations compared with their double-positive counterparts. IHC-P can be an alternative technique to reveal PLA2R glomerular deposits.

scholarly journals Cisplatin-induced renal toxicity in elderly people

2020 ◽  
Vol 12 ◽  
pp. 175883592092343 ◽  
Author(s):  
ZhiYu Duan ◽  
GuangYan Cai ◽  
JiJun Li ◽  
XiangMei Chen
Keyword(s):  
Elderly Patients ◽  
Elderly People ◽  
Renal Toxicity ◽  
Enzyme Inhibitor ◽  
Interstitial Fibrosis ◽  
Angiotensin Receptor Blockers ◽  
Young Patients ◽  
Kidney Injury ◽  
The Elderly ◽  
Tubular Atrophy

Despite available prevention and treatment measures, such as hydration, diuresis, magnesium supplementation, and amifostine, renal toxicity is still one of the major dose-limiting side effects of cisplatin. The aim of this review is to discuss the issue of cisplatin-induced nephrotoxicity in the elderly. Compared with young patients, the incidences of cisplatin-induced nephrotoxicity and acute kidney injury (AKI) in elderly patients are significantly increased, and survival time may be decreased. Following cisplatin treatment of elderly patients, tubulointerstitial injuries will be significantly aggravated based on their original age, both for acute injuries due to cell necrosis and exfoliation and chronic injuries due to interstitial fibrosis, tubular atrophy, and dilatation. The high incidence of cisplatin-induced nephrotoxicity in elderly patients may be associated with renal hypoperfusion; increased comorbidities, such as chronic kidney disease (CKD), cardiovascular disease, and diabetes mellitus; increased use of combined drugs [especially non-steroidal anti-inflammatory drugs, angiotensin-converting enzyme inhibitor and angiotensin receptor blockers (ACEI/ARB), and antibiotics]; decreased clearance of cisplatin; and high plasma ultrafilterable cisplatin. Considering hemodynamic stability and water balance, short duration and low volume hydration may be more suitable for treating elderly people. With the increasing popularity of low-dose daily/weekly regimens, we do not recommend routine diuretic treatment for elderly patients. We recommend using a less nephrotoxic platinum if large doses of cisplatin (100mg/m2) are needed.

Advanced glycation end products and the kidney

2005 ◽  
Vol 289 (4) ◽  
pp. F645-F659 ◽  
Author(s):  
Jürgen M. Bohlender ◽  
Sybille Franke ◽  
Günter Stein ◽  
Gunter Wolf
Keyword(s):  
Advanced Glycation End Products ◽  
Structural Changes ◽  
Therapeutic Potential ◽  
Interstitial Fibrosis ◽  
Basement Membranes ◽  
Renal Diseases ◽  
Advanced Glycation ◽  
Tubular Atrophy ◽  
Glycation End Products ◽  
End Products

Advanced glycation end products (AGEs) are a heterogeneous group of protein and lipids to which sugar residues are covalently bound. AGE formation is increased in situations with hyperglycemia (e.g., diabetes mellitus) and is also stimulated by oxidative stress, for example in uremia. It appears that activation of the renin-angiotensin system may contribute to AGE formation through various mechanisms. Although AGEs could nonspecifically bind to basement membranes and modify their properties, they also induce specific cellular responses including the release of profibrogenic and proinflammatory cytokines by interacting with the receptor for AGE (RAGE). However, additional receptors could bind AGEs, adding to the complexity of this system. The kidney is both: culprit and target of AGEs. A decrease in renal function increases circulating AGE concentrations by reduced clearance as well as increased formation. On the other hand, AGEs are involved in the structural changes of progressive nephropathies such as glomerulosclerosis, interstitial fibrosis, and tubular atrophy. These effects are most prominent in diabetic nephropathy, but they also contribute to renal pathophysiology in other nondiabetic renal diseases. Interference with AGE formation has therapeutic potential for preventing the progression of chronic renal diseases, as shown from data of animal experiments and, more recently, the first clinical trials.

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 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.

Physical Properties of Isolated Perfused Renal Tubular Basement Membranes

1971 ◽  
Vol 29 ◽  
pp. 390-391
Author(s):  
Jared Grantham ◽  
Larry Welling
Keyword(s):  
Basement Membrane ◽  
Basement Membranes ◽  
Transport Mechanisms ◽  
Permeability Characteristics ◽  
Peritubular Capillaries ◽  
Strategic Location ◽  
Tubular Lumen ◽  
Glomerular Filtrate ◽  
Urine Formation ◽  
Renal Tubular

In the course of urine formation in mammalian kidneys over 90% of the glomerular filtrate moves from the tubular lumen into the peritubular capillaries by both active and passive transport mechanisms. In all of the morphologically distinct segments of the renal tubule, e.g. proximal tubule, loop of Henle and distal nephron, the tubular absorbate passes through a basement membrane which rests against the basilar surface of the epithelial cells. The basement membrane is in a strategic location to affect the geometry of the tubules and to influence the movement of tubular absorbate into the renal interstitium. In the present studies we have determined directly some of the mechanical and permeability characteristics of tubular basement membranes.

Identifying patients with CKD risk at the time of nephrectomy: When to initiate nephrology consult

2021 ◽  
pp. 239936932110319
Author(s):  
Yihe Yang ◽  
Zachary Kozel ◽  
Purva Sharma ◽  
Oksana Yaskiv ◽  
Jose Torres ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multivariate Analysis ◽  
Radical Nephrectomy ◽  
Mixed Model ◽  
Linear Mixed Model ◽  
Interstitial Fibrosis ◽  
Kidney Neoplasm ◽  
Tubular Atrophy ◽  
Independent Risk Factors

Introduction: The prevalence of chronic kidney disease (CKD) is high among kidney neoplasm patients because of the overlapping risk factors. Our purpose is to identify kidney cancer survivors with higher CKD risk. Methods: We studied a retrospective cohort of 361 kidney tumor patients with partial or radical nephrectomy. Linear mixed model was performed. Results: Of patients with follow-up >3 months, 84% were identified retrospectively to fulfill criteria for CKD diagnosis, although CKD was documented in only 15%. Urinalysis was performed in 205 (57%) patients at the time of nephrectomy. Multivariate analysis showed interstitial fibrosis and tubular atrophy (IFTA) >25% ( p = 0.005), severe arteriolar sclerosis ( p = 0.013), female gender ( p = 0.024), older age ( p = 0.012), BMI ⩾ 25 kg/m2 ( p < 0.001), documented CKD ( p < 0.001), baseline eGFR ⩽ 60 ml/min/1.73 m2 ( p < 0.001), and radical nephrectomy ( p < 0.001) were independent risk factors of lower eGFR at baseline and during follow-up. Average eGFR decreased within 3 months post nephrectomy. However, patients with different risk levels showed different eGFR time trend pattern at longer follow-ups. Multivariate analysis of time × risk factor interaction showed BMI, radical nephrectomy and baseline eGFR had time-dependent impact. BMI ⩾ 25 kg/m2 and radical nephrectomy were associated with steeper eGFR decrease slope. In baseline eGFR > 90 ml/min/1.73 m2 group, eGFR rebounded to pre-nephrectomy levels during extended follow-up. In partial nephrectomy patients with baseline eGFR ⩾ 90 ml/min/1.73 m2 ( n = 61), proteinuria ( p < 0.001) and BMI ( p < 0.001) were independent risk factors of decreased eGFR during follow up. Conclusions: As have been suggested by others and confirmed by our study, proteinuria and CKD are greatly under-recognized. Although self-evident as a minimum workup for nephrectomy patients to include SCr, eGFR, urinalysis, and proteinuria, the need for uniform applications of this practice should be reinforced. Non-neoplastic histology evaluation is valuable and should include an estimate of global sclerosis% (GS) and IFTA%. Patients with any proteinuria and/or eGFR ⩽ 60 at the time of nephrectomy or in follow-up with urologists, and/or >25% GS or IFTA, should be referred for early nephrology consultation.

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