Kidney disease as a complication of inflammatory bowel disease (IBD), including Crohn disease (CD) and ulcerative colitis (UC), has been the subject of case reports. However, no cases series ...examining IBD and kidney disease has been published to date. This study aimed to evaluate a large series of kidney biopsy specimens from patients with IBD to better define the spectrum and relative frequencies of IBD-associated kidney pathology.
A retrospective review of native kidney biopsy specimens obtained from March 2001 to June 2012 identified 83 patients with IBD. Standard processing of all biopsy specimens included light microscopy, immunofluorescence, and electron microscopy.
There were 45 cases of CD and 38 cases of UC represented. The most common indication for kidney biopsy was acute or chronic kidney failure (63% 52 of 83) and nephrotic-range proteinuria (16% 13 of 83). IgA nephropathy was the most common diagnosis (24% 20 of 83), followed by interstitial nephritis (19% 16 of 83), arterionephrosclerosis (12% 10 of 83), acute tubular injury (8% 7 of 83), proliferative GN (7% 6 of 83), and minimal-change disease (5% 4 of 83). When compared, the frequency of IgA nephropathy in IBD was significantly higher than in all other native renal biopsy specimens from the same time period (24% 20 of 83 versus 8% 2734 of 33,630; P<0.001). Of the 16 cases of interstitial nephritis, 9 (56%) had current or recent past exposure to aminosalicylates, including all cases of granulomatous interstitial nephritis.
IBD is associated with a spectrum of kidney diseases most commonly affecting the glomerular and tubulointerstitial compartments. IgA nephropathy is the most frequent kidney biopsy diagnosis in IBD and has a significantly higher diagnostic prevalence compared with all non-IBD kidney biopsy specimens. This may reflect a common pathogenic mechanism. Although many cases of tubulointerstitial nephritis are related to aminosalicylate exposure, the possibility of a direct relationship with IBD cannot be ruled out.
Autoantibody formation directed against phospholipase A2 receptor (PLA2R)1 is the underlying etiology in most cases of primary membranous glomerulopathy. This new understanding of the pathogenesis of ...primary membranous is in the process of transforming the way the disease is diagnosed. We validated an indirect immunofluorescence assay to examine PLA2R1 in renal biopsies utilizing a commercially available antibody and standard indirect immunofluorescence. Using this assay, we examined a total of 165 cases of membranous glomerulopathy including 85 primary and 80 secondary. We found tissue staining for PLA2R1 to have a sensitivity of 75% (95% CI 65−84%) and a specificity of 83% (95% CI 72−90%) for primary membranous glomerulopathy. Hepatitis C virus was the secondary etiology with the most number of cases staining positive for PLA2R1 (7/11, 64%) followed by sarcoidosis (3/4, 75%) and neoplasm (3/12, 25%). Autoimmune etiologies showed rare PLA2R1-positive staining (1/46, 2%). All cases of secondary membranous glomerulopathy with positive PLA2R1 showed IgG4-predominant staining, which is typically associated with primary membranous glomerulopathy. This IgG4 predominance raises the possibility that these cases are more pathogenically related to primary membranous glomerulopathy than secondary. We present the largest case series to date examining PLA2R1 involvement in membranous glomerulopathy utilizing a technique that is readily adoptable by most renal pathology laboratories.
Systemic lupus erythematosus (SLE) is a complex autoimmune disease with genetic and environmental contributions. Hallmarks of the disease are the appearance of immune complexes (IC) containing ...autoreactive Abs and TLR-activating nucleic acids, whose deposition in kidney glomeruli is suspected to promote tissue injury and glomerulonephritis (GN). Here, using a mouse model based on the human SLE susceptibility locus TNFAIP3-interacting protein 1 (TNIP1, also known as ABIN1), we investigated the pathogenesis of GN. We found that GN was driven by TLRs but, remarkably, proceeded independently of ICs. Rather, disease in 3 different mouse models and patients with SLE was characterized by glomerular accumulation of patrolling monocytes (PMos), a cell type with an emerging key function in vascular inflammation. Consistent with such function in GN, monocyte-specific deletion of ABIN1 promoted kidney disease, whereas selective elimination of PMos provided protection. In contrast to GN, PMo elimination did not protect from reduced survival or disease symptoms such as IC generation and splenomegaly, suggesting that GN and other inflammatory processes are governed by distinct pathogenic mechanisms. These data identify TLR-activated PMos as the principal component of an intravascular process that contributes to glomerular inflammation and kidney injury.
Renal pathologists and nephrologists met on February 20, 2015 to establish an etiology/pathogenesis-based system for classification and diagnosis of GN, with a major aim of standardizing the kidney ...biopsy report of GN. On the basis of etiology/pathogenesis, GN is classified into the following five pathogenic types, each with specific disease entities: immune-complex GN, pauci-immune GN, antiglomerular basement membrane GN, monoclonal Ig GN, and C3 glomerulopathy. The pathogenesis-based classification forms the basis of the kidney biopsy report. To standardize the report, the diagnosis consists of a primary diagnosis and a secondary diagnosis. The primary diagnosis should include the disease entity/pathogenic type (if disease entity is not known) followed in order by pattern of injury (mixed patterns may be present); score/grade/class for disease entities, such as IgA nephropathy, lupus nephritis, and ANCA GN; and additional features as detailed herein. A pattern diagnosis as the sole primary diagnosis is not recommended. Secondary diagnoses should be reported separately and include coexisting lesions that do not form the primary diagnosis. Guidelines for the report format, light microscopy, immunofluorescence microscopy, electron microscopy, and ancillary studies are also provided. In summary, this consensus report emphasizes a pathogenesis-based classification of GN and provides guidelines for the standardized reporting of GN.
Collapsing glomerulopathy is a devastating renal disease that primarily affects African Americans and associates with numerous etiologies, such as HIV and autoimmune disease. The presence of APOL1 ...risk alleles associates with HIV-associated collapsing glomerulopathy, but it is unknown whether these risk alleles also associate with systemic lupus erythematosus (SLE) -associated collapsing glomerulopathy. Here, re-examination of 546 renal biopsies from African-American patients with SLE identified 26 cases of collapsing glomerulopathy, which we genotyped for APOL1 risk alleles using DNA extracted from archived biopsy tissue. APOL1 strongly associated with SLE-associated collapsing glomerulopathy (P<0.001). In a recessive model, two APOL1 risk alleles conferred 5.4-fold (95% CI=2.4 to 12.1) higher odds of developing SLE-associated collapsing glomerulopathy (P<0.001). In conclusion, APOL1 genotyping of African-American patients with SLE might help identify patients at risk for collapsing glomerulopathy, an entity with a poor prognosis that is often resistant to treatment.
The renal biopsy Walker, Patrick D
Archives of pathology & laboratory medicine (1976)
133, Številka:
2
Journal Article
Recenzirano
The first renal biopsy was carried out more than a century ago, but its widespread introduction into clinical use, beginning in the 1950s, helped develop nephrology into the powerful subspecialty of ...internal medicine that it is today. In the past 25 years, the use of the spring-loaded biopsy gun, in combination with newer visualization techniques, including ultrasound and computed axial tomography scanning, has led to greater tissue yield and to a much lower risk of complication. During this same time, our understanding of renal pathology has increased many fold. Correct fixation and processing of renal biopsy tissue is critical, and the laboratory must be skilled with renal biopsy light microscopy, immunohistochemistry, and transmission electron microscopy preparation.
To provide an overview of the renal biopsy, including the techniques and its complications, and to summarize proper laboratory methods for processing renal biopsy tissue.
This article is based on a review of the literature and on the experience of the author.
The experienced nephropathologist, knowledgeable in both renal medicine and pathology and thus able to correlate subtle tissue-derived information with appropriate clinical data, remains the most important key to the development of an accurate clinicopathologic diagnosis.
Immunofluorescence studies on paraffin-embedded tissue after Pronase digestion (paraffin immunofluorescence) is used as a salvage technique in renal pathology, when frozen tissue for routine ...immunofluorescence is inadequate. We have recently found that it is also useful in rare cases in which the immune deposits are 'masked' on routine immunofluorescence, giving false-negative staining by routine immunofluorescence and positive staining by paraffin immunofluorescence. This study aims to evaluate the role of paraffin immunofluorescence in clinical practice with emphasis on its utility to avoid misdiagnosis of cases with masked immune complex deposits. Paraffin immunofluorescence was used in 304 (6.1%) of 4969 native biopsies reviewed from our files. In 207 (68.1%) cases, paraffin immunofluorescence was used as a salvage technique. It was necessary for diagnosis in 24 (11.6%) and had a significant contribution in 63 (30.4%) of these cases. Paraffin immunofluorescence was used to evaluate masked deposits in 97 (31.9%) cases. In 61 (62.9%) of these cases it was used to evaluate masked immune complex glomerular deposits, and in 36 cases (37.1%) it was used to evaluate masked paraproteins. Of the cases where immune complex deposits were sought, paraffin immunofluorescence was necessary for diagnosis in 16 (26.2%) cases and had a significant contribution in 4 (6.6%) cases. Fourteen of the 20 cases with masked deposits had C3 dominant stain by routine immunofluorescence, which could have been misdiagnosed as C3 glomerulopathy. Overall, paraffin immunofluorescence was necessary or had a significant contribution to diagnosis in >1/3 of the cases and is a valuable technique in renal pathology.
Sodium phenylbutyrate and taurursodiol have been found to reduce neuronal death in experimental models. The efficacy and safety of a combination of the two compounds in persons with amyotrophic ...lateral sclerosis (ALS) are not known.
In this multicenter, randomized, double-blind trial, we enrolled participants with definite ALS who had had an onset of symptoms within the previous 18 months. Participants were randomly assigned in a 2:1 ratio to receive sodium phenylbutyrate-taurursodiol (3 g of sodium phenylbutyrate and 1 g of taurursodiol, administered once a day for 3 weeks and then twice a day) or placebo. The primary outcome was the rate of decline in the total score on the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R; range, 0 to 48, with higher scores indicating better function) through 24 weeks. Secondary outcomes were the rates of decline in isometric muscle strength, plasma phosphorylated axonal neurofilament H subunit levels, and the slow vital capacity; the time to death, tracheostomy, or permanent ventilation; and the time to death, tracheostomy, permanent ventilation, or hospitalization.
A total of 177 persons with ALS were screened for eligibility, and 137 were randomly assigned to receive sodium phenylbutyrate-taurursodiol (89 participants) or placebo (48 participants). In a modified intention-to-treat analysis, the mean rate of change in the ALSFRS-R score was -1.24 points per month with the active drug and -1.66 points per month with placebo (difference, 0.42 points per month; 95% confidence interval, 0.03 to 0.81; P = 0.03). Secondary outcomes did not differ significantly between the two groups. Adverse events with the active drug were mainly gastrointestinal.
Sodium phenylbutyrate-taurursodiol resulted in slower functional decline than placebo as measured by the ALSFRS-R score over a period of 24 weeks. Secondary outcomes were not significantly different between the two groups. Longer and larger trials are necessary to evaluate the efficacy and safety of sodium phenylbutyrate-taurursodiol in persons with ALS. (Funded by Amylyx Pharmaceuticals and others; CENTAUR ClinicalTrials.gov number, NCT03127514.).
Juxtaglomerular cells are crucial for blood pressure and fluid-electrolyte homeostasis. The factors that maintain the life of renin cells are unknown. In vivo, renin cells receive constant ...cell-to-cell, mechanical, and neurohumoral stimulation that maintain their identity and function. Whether the presence of this niche is crucial for the vitality of the juxtaglomerular cells is unknown. Integrins are the largest family of cell adhesion molecules that mediate cell-to-cell and cell-to-matrix interactions. Of those, β1-integrin is the most abundant in juxtaglomerular cells. However, its role in renin cell identity and function has not been ascertained. To test the hypothesis that cell-matrix interactions are fundamental not only to maintain the identity and function of juxtaglomerular cells but also to keep them alive, we deleted
in vivo in cells of the renin lineage. In mutant mice, renin cells died by apoptosis, resulting in decreased circulating renin, hypotension, severe renal-vascular abnormalities, and renal failure. Results indicate that cell-to-cell and cell-to-matrix interactions via β1-integrin is essential for juxtaglomerular cells survival, suggesting that the juxtaglomerular niche is crucial not only for the tight regulation of renin release but also for juxtaglomerular cell survival-a sine qua non condition to maintain homeostasis.