Glomerular diseases最新文献

Background: Glomerular diseases (GD) are chronic conditions that often involve immune dysfunction and require immunosuppressive therapy (IST) to control underlying pathogenesis. Unfortunately, such diseases appear to heighten risks of severe outcomes in COVID-19 and predispose to other infections that may be life-threatening. Thus, averting preventable infections is imperative in GD patients.

Summary: The advent of vaccines demonstrated to be safe and efficacious against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has favorably impacted the COVID-19 pandemic epidemiology. However, patients on ISTs were excluded from initial vaccine clinical trials. Thus, only limited and incomplete data are available currently regarding the potential impact of immunosuppression on immune response to or efficacy of the SARS-CoV-2 vaccines. However, new insights are emerging from SARS-CoV-2 vaccine studies, and impacts of ISTs on conventional vaccines are useful to consider. Mechanisms of immunosuppressive agents commonly used in the treatment of GD are reviewed with respect to implications for immune responses induced by SARS-CoV-2 vaccines. ISTs discussed include corticosteroids; alkylating agents; antimetabolites; calcineurin or mammalian target of rapamycin inhibitors; CD38+, CD20+, or CD19+ cell depletion; and complement protein C5 inhibition.

Key messages: Many immunosuppressive therapies may potentially attenuate or impair protective immunity of the SARS-CoV-2 vaccines. However, as vaccines currently in use employ mRNA or nonreplicative viral vectors, they appear to be safe in patients on immunosuppression, further favoring vaccination. Moreover, predominant SARS-CoV-2 vaccines are likely to afford at least partial protective immunity through one or more immune mechanisms even in patients on IST. Guidelines and emerging strategies are also considered to optimize vaccine protection from COVID-19.

Background: De novo glomerular diseases comprising those both common and unique to transplant may develop in the renal allograft leading to posttransplant proteinuria, hematuria, or allograft failure. Electron microscopy (EM) is a useful adjunct to the standard light and immunofluorescence microscopy for accurately diagnosing these diseases and subsequently aiding the clinician in initiating appropriate treatments.

Summary: De novo diseases are those new-onset diseases in renal transplantation that are unrelated to the original kidney disease in the recipient. They include virtually any primary or secondary glomerular, tubulointerstitial, or vascular diseases, ranging from subclinical to clinically overt, having acute, subacute, or chronic clinical presentations. This review focuses on common or significant, mainly glomerular, entities, with particular attention to the EM findings. The time of onset, stage, and severity of these diseases may often be modified by the current immunosuppressive protocols and other donor and recipient predisposing characteristics.

Key messages: A renal allograft biopsy not only improves our understanding of the pathophysiology but also provides diagnostic accuracy prognostic information, and potential for reversibility. In some cases, the biopsy leads to detection of unsuspected or clinically asymptomatic de novo diseases in the setting of other concomitant rejection processes, infection, or toxicity, which can dictate appropriate therapy. Routine EM in transplant kidney biopsies is a valuable modality in recognizing fully developed or early/subtle features of evolving de novo diseases, often during the subclinical phases, in "for cause" or surveillance/protocol allograft biopsies.

Aims: Glomerulonephritis is one of the leading causes of progressive chronic kidney disease worldwide and treatment requires shared decision-making to improve self-care and plan immunosuppressant therapy. However, information on health literacy (HL) in patients with glomerulonephritis is scanty. We aimed to assess HL in our multiethnic population with glomerulonephritis.

Methods: Single-center cross-sectional study of patients with glomerulonephritis receiving induction immunosuppressants at the ambulatory nephrology clinic and who completed the anonymized self-administered HLS-EU-47 questionnaire. The standardized HL index and domain item mean scores were compared with participant sociodemographic characteristics.

Results: Among 65 patients who attend the clinics over a month, 27 agreed to participate in the survey. After excluding responses with significant missing information, we included 23 participants (16 Chinese, 4 Malay, 2 Indian, and 1 other ethnicity) in the analysis. The median age was 39 (interquartile range 27, 60 years). The median general HL index was 26.2 (19.8, 29.8). The item mean scores were 2.64 (2.43, 2.77), 2.45 (2.09, 2.72), 2.33 (2.17, 2.58), and 2.50 (2.25, 2.75) for the domains of accessing, understanding, appraising, and applying health-care-related information, respectively. Male patients had significantly higher HL indices and higher scores for accessing and appraising health information, while higher personal income was significantly associated with higher score for applying health knowledge.

Conclusion: Patients with glomerulonephritis had lowest HL in the domain of appraising health information. Further research on targeted interventions to improve the HL in appraising treatment options and vaccinations in patients with glomerulonephritis is required.

Introduction: Disparities in health-related quality of life (HRQOL) have been inadequately studied in patients with glomerular disease. The aim of this study was to identify relationships between race/ethnicity, socioeconomic status, disease severity, and HRQOL in an ethnically and racially diverse cohort of patients with glomerular disease.

Methods: Cure Glomerulonephropathy (CureGN) is a multinational cohort study of patients with biopsy-proven glomerular disease. Associations between race/ethnicity and HRQOL were determined by the following: 1. Missed school or work due to kidney disease; 2. Responses to Patient Reported Outcomes Measurement Information System (PROMIS) questionnaires. We adjusted for demographics, socioeconomic status, and disease characteristics using multivariable logistic and linear regression.

Results: Black and Hispanic participants had worse socioeconomic status and more severe glomerular disease than White or Asian participants. Black adults missed work or school most frequently due to kidney disease (30% versus 16-23% in the other three groups, p=0.04), and had the worst self-reported global physical health (median score 44.1 versus 48.0-48.2, p<0.001) and fatigue (53.8 versus 48.5-51.1, p=0.002), compared to other racial/ethnic groups. However, these findings were not statistically significant with adjustment for socioeconomic status and disease severity, both of which were strongly associated with HRQOL in adults. Among children, disease severity but not race/ethnicity or socioeconomic status were associated with HRQOL.

Conclusions: Among patients with glomerular disease enrolled in CureGN, the worse HRQOL reported by Black adults was attributable to lower socioeconomic status and more severe glomerular disease. No racial/ethnic differences in HRQOL were observed in children.

Introduction: Patients with chronic health conditions, particularly chronic kidney disease, are at heightened risk for psychiatric disorders; yet, there are limited data on those with primary glomerular disease.

Methods: This study included patients with glomerular disease enrolled in the kidney research network multisite patient registry. Registry data include encounter, diagnoses, medication, laboratory, and vital signs data extracted from participants' electronic health records. ICD-9/10 diagnosis codes were used to identify a subset of psychiatric disorders focused on anxiety, mood, and behavioral disorders. Time-varying Cox proportional hazard models were used to analyze time from the onset of kidney disease to diagnosis of psychiatric disorder. Adjusted models retained significant covariates from the full list of potential confounders, including age, sex, race, ethnicity, time-varying treatment, the estimated glomerular filtration rate, and proteinuria (urine protein-to-creatinine ratio [UPCR]). Analogous models examined diagnosis of psychiatric disorder as a predictor of time to end-stage kidney disease (ESKD).

Results: Data were available for 950 participants, with a median of 58 months of follow-up. 110 (12%) participants were diagnosed with psychiatric disorder during the follow-up. The estimated rate of psychiatric diagnosis after kidney disease was 14.7 cases per 1,000 person-years and was highest among those of adolescent age at the time of kidney disease diagnosis. Adjusted analyses found adolescent age (vs. adult, hazard ratio [HR] = 3.11, 95% confidence interval [CI] 1.87-5.17) and Asian race (vs. white, HR = 0.34, 95% CI 0.16-0.71) were associated with psychiatric diagnosis. A higher UPCR per 1 log unit (HR 1.13, 95% CI 1.01-1.27) and a higher total number of oral medications were associated with psychiatric disorder (p < 0.001). Psychiatric diagnosis was also associated with progression to ESKD (HR = 2.45, 95% CI 1.53-3.92) in adjusted models.

Discussion/conclusion: Psychiatric disorders were documented in approximately one-eighth of patients with glomerular disease and correlated with clinical disease characteristics such as age, race, proteinuria, and oral medication burden. These findings suggest mental health screening is warranted in patients of all ages with glomerular disease.

Background: For the better part of the past 6 decades, transmission electron microscopy (EM), together with routine light microscopy and immunofluorescence and/or immunohistochemistry (IHC), has been an essential component of the diagnostic workup of medical renal biopsies, particularly native renal biopsies, with increasing frequency in renal allograft biopsies as well. Studies performed prior to the year 2000 have indeed shown that a substantial fraction of renal biopsies cannot be accurately diagnosed without EM. Still, EM remains costly and labor-intensive, and with increasing pressure to reduce healthcare costs, some centers are de-emphasizing diagnostic EM. This trend has been coupled with advances in IHC and other methods in renal biopsy diagnosis over the past 2-3 decades.

Summary: Nonetheless, it has been our experience that the diagnostic value of EM in the comprehensive evaluation of renal biopsies remains similar to what it was 20-30 years ago. In this review, we provide several key examples from our practice where EM was essential in making the correct renal biopsy diagnosis, ranging from relatively common glomerular lesions to rare diseases.

Key messages: EM remains an important component of the diagnostic evaluation of medical renal biopsies. Failure to perform EM in certain cases will result in an incorrect diagnosis, with possible clinical consequences. We strongly recommend that tissue for EM be taken and stored in an appropriate fixative and ultrastructural studies be performed for all native renal biopsies, as well as appropriate renal allograft biopsies as recommended by the Banff consortium.

Hereditary nephritis (HN) and thin glomerular basement membrane (GBM) lesion share a common clinical presentation of persistent hematuria, thin GBM by kidney biopsy electron microscopic examination, and a mutation in type IV collagen. However, the clinical course and treatment for these entities are different with varying patterns of heredity. Ultrastructural examination of a renal biopsy specimen is essential for the morphologic diagnosis of HN and thin GBM lesion, whereas light microscopy may only give limited diagnostic clues. Additional workup including immunostaining for subtypes of type IV collagen may provide further information on underlying genetic mutations. The diagnosis of HN may lead to treatment with renin-angiotensin system blockade in patients at risk of early-onset renal failure to delay progression to end-stage renal disease. Additionally, patients with isolated microscopic hematuria and thin GBM lesion are at increased risk for chronic kidney disease when associated with other comorbidities; those patients should receive regular clinical assessment to prevent renal function decline.

Background: Renal disease in cryoglobulinemia is difficult to grasp and diagnose because it is rare, serological testing is challenging and prone to artifacts, and its morphology is shared by other renal diseases resulting in a spectrum of differential diagnoses. On occasion, a definitive diagnosis cannot even be rendered after immunofluorescence and electron microscopic studies.

Summary: Based on kidney biopsies seen in our routine diagnostic and referral practice, we discuss and illustrate various morphological patterns of renal injury associated with cryoglobulins. We outline key pathophysiologic and clinical aspects associated with cryoglobulinemia induced renal disease and describe morphologic changes with a focus on electron microscopy. We present our practical, morphology-based approach to diagnostic decision-making with special consideration of differential diagnoses and disease mimickers. Since cryoglobulins are rarely tested for prior to kidney biopsy, pathologists and clinicians alike must have a high level of suspicion when interpreting renal biopsies and managing patients.

Key messages: Cryoglobulinemia-associated glomerulonephritis (GN) is a multifactorial disease which is important to recognize for clinical practice. Morphological features suggestive of cryoglobulinemia-associated GN include a pattern of membranoproliferative GN with abundance of monocytes and the presence of (pseudo)thrombi. By electron microscopy, the main diagnostic features are a prominent infiltration of monocytes/macrophages and the presence of mesangial and subendothelial deposits with frequently curved microtubular/cylindrical and annular substructures.

Background: Transplant glomerulopathy (TG) is a morphologic alteration in glomeruli of renal allografts, characterized by glomerular basement membrane reduplications.

Summary: TG is associated with progressive chronic allograft dysfunction and proteinuria and is a diagnostic feature of chronic antibody-mediated rejection (ABMR) in patients positive for donor-specific antibodies, according to the Banff schema for renal allograft pathology. It is a definitive endpoint in clinical trials and interventional studies for ABMR, but the lesion can also occur in the absence of definitive alloimmune injury, as a consequence of chronic thrombotic microangiopathy, and in some cases in association with hepatitis C infection. This review discusses the pathophysiology and clinical presentation of TG, the diagnostic features by light microscopy, and focuses on the sequential ultrastructural stages of the lesion. The differential diagnosis of TG, and Banff grading of the lesion, are reviewed. Clinicopathological indications for performing routine ultrastructural examination of renal allograft biopsies are discussed.

Key messages: TG can be diagnosed at an early stage by electron microscopy, before histological features are apparent, emphasizing the importance of ultrastructural examination of renal allograft biopsies for an early diagnosis, when therapeutic intervention may be beneficial.

Background: There has been a long, storied relationship between various bacterial infections and glomerular injury, which is now encompassed under the term of infection-related glomerulonephritis (GN). The clinical and pathologic manifestations vary depending on the duration, magnitude, and underlying pathogen associated with the inciting infectious process. A brief and acute episode may lead to a self-limiting glomerular manifestation while a chronic or repetitive infection can result in persistent and irreversible injury. In this review, we will discuss the clinical and pathologic findings associated with the infection-related glomerulonephritides.

Summary: An acute exudative GN with an influx of neutrophils is the most characteristic morphologic alteration associated with infection-related glomerular injury. The immunofluorescence staining pattern often reveals prominent complement component C3 deposition in both capillary walls and mesangial regions with or without accompanying immunoglobulin. Large subepithelial electron-dense deposits known as "humps" are the hallmark ultrastructural finding; however, these features can also be present in C3 glomerulopathies, which are often triggered by infections and may have similar underlying abnormalities in alternative pathway complement activation. In addition, other glomerular injuries can simultaneously be present along with infection-related GN, such as diabetic nephropathy, lupus nephritis, or immunoglobulin A nephropathy, constituting a true diagnostic challenge for the pathologist.

Key messages: Bacterial infection-related GN represents a spectrum of glomerular injury with variable clinical and pathologic presentations. The pathologic findings can show overlap with other glomerular diseases, and different forms of infection-related GN vary in terms of prognosis and treatment approach.