Diagnosis Of Glomerular Diseases Research Articles

Associations between the concentrations of CD68, TGF-β1, renal injury index and prognosis in glomerular diseases.

The present study aimed to investigate the association between the concentrations of CD68, TGF-β1, renal injury index and prognosis in glomerular diseases. Altogether 218 patients with glomerular diseases admitted to Weifang People's Hospital from January, 2014 to March, 2017 were used as the study group. A total of 100 healthy individuals who visited Weifang People's Hospital for a physical examination during the same time period were used as the control group. The levels of CD68 in peripheral blood obtained from the 2 groups of subjects were detected by flow cytometry, and the expression of TGF-β1 in serum was detected by enzyme-linked immunosorbent assay (ELISA). The concentrations of CD68 and TGF-β1 between the 2 groups were compared. The correlation between the concentrations of CD68, TGF-β1 and renal injury indexes in the study group was analyzed, as well as prognostic significance. The diagnostic value of CD68 and TGF-β1 in patients with glomerular disease was analyzed using a ROC curve, and the recovery of the patients was observed. The serum concentrations of CD68 and TGF-β1 in the study group were higher than those in the control group (P<0.05). The concentrations of CD68 and TGF-β1 in the study group positively correlated with the renal injury indexes, such as blood urea nitrogen (BUN), serum creatinine (SCR), uric acid (UA) and the 24-h urinary protein quantity (P<0.05). ROC curve analysis revealed that the area under the curve of CD68 and TGF-β1 as regards the diagnostic value in patients with glomerular disease was 0.808 and 0.738, respectively, while the area under the combined detection curve was 0.866. Multivariate unconditional logistic regression analysis revealed that the clinical classification and the concentrations of CD68 and TGF-β1 were independent prognostic factors in the study group. On the whole, the findings of the present study demonstrate that clinical classification, and the CD68 and TGF-β1 concentrations are independent prognostic factors for patients with glomerular disease. CD68 and TGF-β1 have certain value in the diagnosis of glomerular diseases, and may thus be used as predictors of the diagnosis and recovery of glomerular disease.

37-Year-Old Woman With Bilateral Lower Extremity Edema, Proteinuria, and Microscopic Hematuria

37-Year-Old Woman With Bilateral Lower Extremity Edema, Proteinuria, and Microscopic Hematuria

Viral seroprevalence in pediatric kidney transplant recipients.

Aim:Viral infections commonly affect kidney transplant recipients and may lead to graft failure and death. The aim of this study was to evaluate the antibody seroprevalence against viral agents in kidney transplant recipients.Material and Methods:The records of children who underwent kidney transplantation between 2008 and 2018 in Akdeniz University Faculty of Medicine were retrospectively reviewed. Epstein-Barr virus, cytomegalovirus, hepatitis A virus, hepatitis B virus, varicella, measles, rubella and mumps serologies evaluated before transplantation, were recorded. The clinical characteristics of seronegative and seropositive patients were compared, and factors that affected seropositivity were investigated.Results:The study included 253 children with a mean age of 16.7±6.23 years. The mean age at transplantation was 11.4±5.01 years. The seropositivity rates for vaccine-preventable viral infections varied: hepatitis B 89.7%, hepatitis A 60.5%, measles 78.7%, rubella 88.1%, mumps 61.2%, and varicella 71.9%. Cytomegalovirus seropositivity was 92.1% and Epstein-Barr virus seropositivity was 82.2%. Hepatitis B antibody positivity was 91.8% in patients undergoing hemodialysis, 94.5% in patients undergoing peritoneal dialysis, and 84.9% in pre-emptive transplantation patients (p=0.037). The mean age at transplantation was higher in patients with seropositivity for both cytomegalovirus and Epstein-Barr virus compared with seronegative patients (p<0.001 for both). The mean age at transplantation and diagnosis of glomerular disease was found to be effective for varicella seropositivity in multivariate regression analysis (OR 0.860, 95% CI: 0.808–0.915, p<0.001 and OR 2.502, 95% CI: 1.321–4.739, p=0.005, respectively).Conclusion:It is important to screen patients with chronic kidney disease in terms of vaccine-preventable diseases to identify risky groups of patients and to immunize these patients before end-stage kidney disease develops.

Acute kidney injury associated with glomerular diseases.

This review focuses on acute kidney injury (AKI) associated with glomerular diseases and specifically the mechanisms of development of AKI in the wide spectrum of glomerulopathies. The immune system and the kidneys are closely linked. In healthy individuals, the kidneys contribute to immune homeostasis, whereas components of the immune system mediate many acute forms of kidney disease. Both crescentic and noncrescentic forms of acute glomerulonephritis can present as AKI. The diagnosis of glomerular diseases underlying AKI requires a high degree of suspicion coupled with an algorithmic approach to laboratory investigations. Renal biopsy represents the gold standard for the diagnosis of medical conditions of the kidney. The main clinical-biological presentations of glomerular diseases are acute nephritic syndrome, nephrotic syndrome and rapidly progressive glomerulonephritis (RPGN). All these presentations can be worsened by AKI both in the onset and in the clinical course. Heavy proteinuria and macroscopic hematuria can be directly involved in the development of AKI. AKI associated with glomerular diseases is not uncommon. Sometimes it represents an emergency case. The understanding of the various mechanisms underlying kidney diseases is improving, and may aid in their prevention and treatment.

Approach to native medical renal biopsy interpretation of glomerular disease

Diverse pathogenetic mechanisms and clinical manifestation of renal diseases may produce the same renal morphologic pattern or variety of renal morphologic pattern can lead to the same clinical syndrome. The primary role of the renal biopsy is to provide a diagnosis and information about disease activity and chronicity. The systematic approach to native medical renal biopsy includes evaluation of the four compartments of the kidney sequentially (glomeruli, tubules, interstitium, and blood vessels). The diagnosis in renal pathology is an integrated process in which we must analyze all clinical data, light microscopy, immunohistology, and electron microscopy studies for diagnosis. The aim of the article is to describe the handling of the renal tissue in the anatomical pathology laboratory. It also provides the guideline to renal biopsy evaluation and approach to arrive at the diagnosis of glomerular diseases with similar clinical presentations.

Evaluation of Tryptic Podocin Peptide in Urine Sediment Using LC-MS-MRM Method as a Potential Biomarker of Glomerular Injury in Dogs with Clinical Signs of Renal and Cardiac Disorders.

The early asymptomatic stage of glomerular injury is a diagnostic challenge in the course of renal and extra-renal disease, e.g., heart insufficiency. It was found that podocin, a podocyte-specific protein present in the urine, may serve as a biomarker in the diagnosis of glomerular disease in humans and animals including glomerulonephritis, glomerulosclerosis, amyloidosis, or nephropathy. Therefore, there is a need of development of the sensitive and straightforward method of urinary podocin identification. In this work, we report our extended research under the glomerular injury investigation in dogs by application of clinical examination and LC-MS-MRM method in the identification of canine podocin in urine samples. The LC-MS-MRM method is based on the identification of podocin tryptic peptide with the 218H-AAEILAATPAAVQLR-OH232 sequence. The model peptide was characterized by the highest ionization efficiency of all the proposed model podocin tryptic peptides in a canine urine sediment according to the LC-MS/MS analysis. The obtained results revealed the presence of the model peptide in 40.9% of dogs with MMVD (active glomerular injury secondary to heart disease = cardiorenal syndrome-CRS) and 33.3% dogs with chronic kidney disease. The potential applicability of the developed methodology in the analysis of podocin in canine urine sediments was confirmed.

Prognostic nomogram and score to predict renal survival of patients with biopsy-proven diabetic nephropathy

AimsBoth clinical and pathogenetic markers for accurate prediction of end-stage renal disease in diabetic nephropathy (DN) are lacking. This study aimed to establish an effective prognostic nomogram and a score for renal survival (RS) in biopsy-proven DN. MethodsAnalyses were derived from 110 DN patients who underwent renal biopsy at China-Japan Friendship Hospital between January 2006 and May 2018 with DN as the only glomerular disease diagnosis. The prognostic ability of 34 baseline clinicopathologic parameters was evaluated using univariate and multivariate Cox regression analyses. The predictive accuracy and discriminative ability of the final model were measured using the calibration curve and concordance index (C-index). Internal validation of the model was assessed using bootstrap resampling. ResultsUrinary proteinuria excretion, stages of chronic kidney disease, glomerular hyalinosis, and extracapillary hypercellularity were independent prognostic factors for RS, and all were selected into the nomogram. The calibration curve for the probability of survival showed good agreement between the prediction by nomogram and actual observation. The C-index for predicting survival was 0.79 (95% confidence interval (CI) 0.72–0.86). A high C-index value of 0.76 indicated good internal validation. The prognostic score had the potential to delineate two prognosis groups with median RS of 24 and 70 months, respectively. ConclusionsThe proposed nomogram and score provide a useful individualized risk estimate of renal prognosis in patients with DN.

Prevalence of Cardiovascular Disease Risk Factors in Childhood Glomerular Diseases.

BackgroundCardiovascular disease is a major cause of morbidity and mortality in children with chronic kidney disease. We sought to determine the prevalence of cardiovascular risk factors in children with glomerular disease and to describe current practice patterns regarding risk factor identification and management.Methods and ResultsSeven‐hundred sixty‐one children aged 0 to 17 years with any of 4 biopsy‐confirmed primary glomerular diseases (minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, and IgA nephropathy/vasculitis) were enrolled at a median of 16 months from glomerular disease diagnosis in the multicenter prospective Cure Glomerulonephropathy Network study. Prevalence of traditional (hypertension, hypercholesterolemia, and obesity) and novel (proteinuria, prematurity, and passive smoke exposure) cardiovascular risk factors were determined at enrollment and compared across glomerular disease subtypes. Frequency of screening for dyslipidemia and prescribing of lipid‐lowering or antihypertensive medications were compared across glomerular disease subtype, steroid exposure, and remission status groups. Compared with the general population, all traditional risk factors were more frequent: among those screened, 21% had hypertension, 51% were overweight or obese, and 71% had dyslipidemia. Children who were not in remission at enrollment were more likely to have hypertension and hypercholesterolemia. Fourteen percent of hypertensive children were not receiving antihypertensives. Only 49% underwent screening for dyslipidemia and only 9% of those with confirmed dyslipidemia received lipid‐lowering medications.ConclusionsChildren with primary glomerular diseases exhibit a high frequency of modifiable cardiovascular risk factors, particularly untreated dyslipidemia. Lipid panels should be routinely measured to better define the burden of dyslipidemia in this population. Current approaches to screening for and treating cardiovascular risk factors are not uniform, highlighting a need for evidence‐based, disease‐specific guidelines.

Trends of renal diseases in Germany: review of a regional renal biopsy database from 1990 to 2013.

BackgroundSeveral renal biopsy registries in Europe have shown geographical and temporal variations in the patterns of renal diseases. However, there is a lack of current data on trends of renal disease in Central Europe. MethodsAfter exclusion of transplant and re-biopsies, the renal biopsy registry of the German RWTH Aachen University Hospital included data of 1208 biopsies over a period of 24 years (1990–2013). Trends in the biopsy rate and diagnosis of glomerular diseases were analysed. ResultsThe average annual biopsy incidence was 6.1 biopsies per 100 000 population. The frequency of kidney biopsies increased significantly over the years (P < 0.001). Primary glomerulonephritis (GN) accounted for nearly two-thirds (58.4%) of all native kidney biopsies, and immunoglobulin A-nephropathy (IgAN) was the leading histological diagnosis (34.7%) followed by necrotizing GN (RPGN) at 18.7%. IgAN increased 2-fold over the study periods (+195%, P < 0.001). Focal segmental glomerulosclerosis accounted for 6.1% of all diagnoses, and its frequency rose to 3.9-fold (+388%, P < 0.001). Lupus nephritis showed a doubling in incidence (P = 0.0499), while acute tubular necrosis decreased to 3.5-fold (P = 0.0008). All other disease entities failed to exhibit linear trends over time. In children, the most common pathologies were IgAN (26.1%) and minimal change disease (21.7%), whereas RPGN (19.4%) dominated in the group of patients >60 years. ConclusionIgAN was the most common primary glomerular disease in our centre and its prevalence increased over 24 years.

New Views of the Glomerulus: Advanced Microscopy for Advanced Diagnosis.

New technologies are ready to revolutionize glomerular imaging and significantly improve or replace immunofluorescence and electron microscopy, which have driven research and diagnosis of glomerular diseases for over 50 years. Advanced forms of transmission and scanning electron microscopy have revealed the detailed spatial relationships of the glomerular basement membrane, podocytes, and endothelial cells. These may be overshadowed by super resolution microscopy (SRM), which combines the advantages of immunofluorescence and electron microscopy, offers high resolution identification of specific molecules, and images large, physiologically relevant volumes of the glomerulus. Rapidity, ease of use and low cost with some types of SRM make them potentially suitable for routine diagnosis. SRM visualizes structures below the classical diffraction limit of conventional light microscopy by adding a time variable to either the illumination of the specimen, or to the fluorescence signal emitted by it. Ensemble techniques vary illumination and include Structured Illumination Microscopy (SIM) and Stimulation Emission Depletion Microscopy (STED). Single molecule localization techniques vary the light emission by fluorescence labels in the specimen, and include Photoactivated Localization Microscopy (PALM) and Stochastic Optical Reconstruction Microscopy (STORM). Technologies such as expansion microscopy and genetic labeling can also create effective super resolution imaging by non-optical, specialized preparation techniques. All technologies require dark field fluorescence and some require computer image analysis and reconstruction. Replicating successful application in other areas of biology, SIM, STED, and STORM have visualized normal and nephrotic disease podocytes, and have confirmed their appearances to be similar to those seen by electron microscopy, but with added new information on cell configuration and protein localization. STORM has also localized podocyte cytoskeleton and adhesion proteins, and glomerular basement membrane proteins at a resolution never before possible. These pioneering efforts show the promise of super resolution microscopy, and lay the groundwork for future study and new diagnostic tools for glomerular diseases.

Development of a novel cell-based assay to diagnose recurrent focal segmental glomerulosclerosis patients

Definitive diagnosis of glomerular disease requires a kidney biopsy, an invasive procedure that may not be safe or feasible to perform in all patients. We developed a noninvasive, accurate, and economical diagnostic assay with easy commercial adaptability to detect recurrent focal segmental glomerulosclerosis (rFSGS) after kidney transplant. Since FSGS involves podocyte damage and death, our approach involved mRNA profiling of cultured podocytes treated with plasma from patients with rFSGS to identify upregulated genes involved in podocyte damage. For concept validation, three upregulated pro-apoptotic candidate genes (IL1β, BMF, and IGFBP3) were selected, and their promoter regions were cloned into a luciferase-based reporter vector and transfected into podocytes to generate stable podocyte cell lines. Strikingly, when exposed to rFSGS patient plasma, these cell lines showed increased reporter activity; in contrast, no reporter activity was noted with plasma from patients with non-recurrent FSGS or membranous nephropathy. Area under the receiver operating characteristics curves (AUCs) for models discriminating between rFSGS and other nephropathies (non-recurrent FSGS and membranous nephropathy) and between rFSGS and non-recurrent FSGS ranged from 0.81 to 0.86, respectively. Estimated sensitivities and specificities for the diagnosis of rFSGS were greater than 80% for the IL1β and BMF cell lines, and were slightly lower for the IGFBP3 cell line. Importantly, the novel approach outlined here for the diagnosis of rFSGS is widely applicable to the design of sensitive and specific diagnostic/prognostic assays for other glomerular diseases.

Expression of DENDRIN in several glomerular diseases and correlation to pathological parameters and renal failure - preliminary study

BackgroundIn glomerular injury dendrin translocates from the slit diaphragm to the podocyte nucleus, inducing apoptosis. We analyzed dendrin expression in IgA glomerulonephritis and Henoch Schönlein purpura (IgAN/HSP) versus in podocytopathies minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS), and compared it to pathohistological findings and renal function at the time of biopsy and the last follow-up.MethodsTwenty males and 13 females with median of age 35 years (min-max: 3–76) who underwent percutaneous renal biopsy and had diagnosis of glomerular disease (GD) were included in this retrospective study. Fifteen patients had IgAN/HSP and eighteen podocytopathy. Control group consisted of ten patients who underwent nephrectomy due to renal cancer. Dendrin expression pattern (membranous, dual, nuclear or negative), number of dendrin positive nuclei and proportion of dendrin negative glomeruli were analyzed.ResultsIn GD and the control group significant differences in number of dendrin positive nuclei and proportion of dendrin negative glomeruli were found (P = 0.004 and P = 0.003, respectively). Number of dendrin positive nuclei was higher in podocytopathies than in IgAN/HSP, 3.90 versus 1.67 (P = 0.028). Proportion of dendrin negative glomeruli correlated to higher rates of interstitial fibrosis (P = 0.038), tubular atrophy (P = 0.011) and globally sclerotic glomeruli (P = 0.008). Dual and nuclear dendrin expression pattern were connected with lower rate of interstitial fibrosis and tubular atrophy than negative dendrin expression pattern (P = 0.024 and P = 0.017, respectively). Proportion of dendrin negative glomeruli correlated with lower creatinine clearance (CC) at the time of biopsy and the last follow-up (P = 0.010 and P < 0.001, respectively). Dendrin expression pattern correlated to CC at the last follow-up (P = 0.009), being lower in patients with negative than nuclear or dual dendrin expression (P = 0.034 and P = 0.004, respectively).ConclusionIn this pilot study the number of dendrin positive nuclei was higher in podocytopathies than in inflammatory GD. Negative dendrin expression pattern correlated to chronic tubulointerstitial changes and lower CC, which needs to be confirmed in a larger series.

Changes in the diagnosis of glomerular diseases in east China: a 15-year renal biopsy study

Background: There have been some gradual changes in the distribution of renal biopsy pathological diagnoses during recent years. This study aimed to show changes in renal disease prevalence in China by investigating 10 patients diagnosed at our Kidney Disease Centre during the last 15 years.Methods and results: All patients aged 15-year-old or older who underwent renal biopsy at the First Affiliated Hospital, Zhejiang University, from 2001 to 2015 were enrolled. There were 5 common types of primary glomerulonephritis: IgA nephropathy (IgA N), membranous nephropathy (MN), mesangial progressive glomerulonephritis (MsPGN), minimal change disease (MCD), and focal segmental glomerulosclerosis (FSGS), which represented 50%, 16.8%, 15.9%, 8.1% and 2.5% of total cases, respectively. IgA nephropathy was the most common type of primary glomerulonephritis (PGN).Conclusions: Our results mostly showed a new trend that the diagnosis of IgA nephropathy was not increasing and the prevalence of membranous nephropathy had increased, becoming the second most common type of primary glomerulonephritis.Key POINTSDistinguished with other domestic studies, IgA nephropathy did not show a trend of continuous growth although it still had about the half proportion of PGN, whereas membranous nephropathy kept rising and became the second common PGN.Concerning SGN, LN peaked in the younger-age and middle-age groups with a significant female prevalence, DN, BANS and SV had a male predominance peaking in the middle-age and old-age groups.

Multi-radial LBP Features as a Tool for Rapid Glomerular Detection and Assessment in Whole Slide Histopathology Images

We demonstrate a simple and effective automated method for the localization of glomeruli in large (~1 gigapixel) histopathological whole-slide images (WSIs) of thin renal tissue sections and biopsies, using an adaptation of the well-known local binary patterns (LBP) image feature vector to train a support vector machine (SVM) model. Our method offers high precision (>90%) and reasonable recall (>70%) for glomeruli from WSIs, is readily adaptable to glomeruli from multiple species, including mouse, rat, and human, and is robust to diverse slide staining methods. Using 5 Intel(R) Core(TM) i7-4790 CPUs with 40 GB RAM, our method typically requires ~15 sec for training and ~2 min to extract glomeruli reproducibly from a WSI. Deploying a deep convolutional neural network trained for glomerular recognition in tandem with the SVM suffices to reduce false positives to below 3%. We also apply our LBP-based descriptor to successfully detect pathologic changes in a mouse model of diabetic nephropathy. We envision potential clinical and laboratory applications for this approach in the study and diagnosis of glomerular disease, and as a means of greatly accelerating the construction of feature sets to fuel deep learning studies into tissue structure and pathology.

Segmental Sclerosis and Extracapillary Hypercellularity Predict Diabetic ESRD.

Pathogenetic markers of diabetic kidney disease (DKD) progression to ESRD are lacking. We characterized the prognostic value of histologic findings in DKD for time to ESRD in native kidney specimens from biopsies performed from 1995 to 2011 with diabetic glomerulosclerosis as the only glomerular disease diagnosis (n=109). Biopsy specimens were analyzed according to standard methods, including determination of diabetic nephropathy class, as defined by the Renal Pathology Society. Clinical data were extracted from electronic medical records. We used competing risk models, with death as the competing risk, to estimate subdistribution hazard ratios (HRs) for ESRD. All multivariable models included age, sex, black race, baseline eGFR, and baseline proteinuria. Pathologic characteristics achieving P<0.1 were added into successively complex models. ESRD occurred in 56% of patients, and 26% of patients died before reaching ESRD. In univariate analyses, diabetic nephropathy class was not statistically significant in predicting time to ESRD. The final multivariable model (n=106) showed a borderline association between mild mesangial expansion and decreased risk for ESRD (subdistribution HR, 0.64; 95% confidence interval, 0.40 to 1.00). Poor prognostic factors in the final model included segmental sclerosis and extracapillary hypercellularity (subdistribution HR, 2.04; 95% confidence interval, 1.36 to 3.05; and subdistribution HR, 2.21; 95% confidence interval, 1.19 to 4.11, respectively). In conclusion, we identified segmental sclerosis and extracapillary hypercellularity as novel, poor prognostic indicators of time from DKD to ESRD. Whether these indicators represent a distinct pathogenetic phenotype of DKD will require a large study with a broad spectrum of disease severity.

Transcriptomics in kidney biopsy is an untapped resource for precision therapy in nephrology: a systematic review.

The diagnosis of glomerular diseases is based on the evaluation of histological lesions in renal tissue by means of light and electronic microscopy, and immunofluorescence technique. Frozen and archival formalin-fixed paraffin-embedded kidney biopsies represent a stored resource for high-throughput technologies. Transcriptomics makes it possible to study the whole gene-expression profile of cells and tissues in a specific period and/or condition. The results, whether considered alone or integrated with other omics data, could help to improve existing knowledge about the pathogenetic mechanisms of glomerulopathies. This review describes the molecular analysis of histological lesions obtained by transcriptomics in glomerular diseases, such as minimal change disease, focal and segmental glomerular sclerosis, IgA nephropathy, lupus nephritis and diabetic nephropathy. Of 716 articles obtained through database searches, 19 relevant articles were considered for the systematic review. Transcriptomics in kidney biopsy from patients with glomerular diseases have generated new insights on a few promising genes, illustrated in each disease section, which may be considered important targets for the care of these diseases. Transcriptomics is an untapped resource for precision nephrology. Moreover, the integration of transcriptomics and systems pharmacology could predict the best drug combination to revert a pathological condition by targeting disease-specific molecular networks.

Pregnancy Outcomes in Patients with Glomerular Disease Attending a Single Academic Center in North Carolina

Background: Contemporary data regarding pregnancy outcomes in US patients with primary glomerular diseases are lacking. We aimed to report fetal and maternal outcomes among women with biopsy-proven primary glomerular disease who received obstetric care at a single large academic US center. Methods: All women with a biopsy-confirmed primary glomerular disease diagnosis and without end-stage kidney disease who received obstetric care at the University of North Carolina (UNC) Hospitals (1996-2015) were identified using the Glomerular Disease Collaborative Network registry and the UNC Hospitals Perinatal Database. The primary study outcome was perinatal death (stillbirth at >20 weeks or neonatal death). Secondary outcomes included premature birth (<37 weeks), birth weight, preeclampsia, and kidney function changes (postpartum vs. baseline). Demographics, clinical characteristics, and outcomes were compared across glomerular disease subtypes. Results: Among 48 pregnancies in 43 women (IgA nephropathy n = 17, focal segmental glomerulosclerosis [FSGS] n = 16, membranous nephropathy n = 6, minimal change disease n = 4), 13% of pregnancies resulted in perinatal death and 48% of babies were born prematurely. From a maternal perspective, 33% of pregnancies were complicated by preeclampsia, 39% by a doubling of urinary protein, and 27% by a ≥50% increase in serum creatinine. Outcome differences across glomerular disease subtypes were not statistically significant, although decline in kidney function appeared most frequent in FSGS. Conclusion: Adverse pregnancy outcomes are frequently observed in women with glomerular disease. The independent influence of glomerular disease subtype on outcomes requires further study. More widespread reporting and analysis of pregnancy outcomes in women with glomerular disease are urgently needed.

Temporal and Demographic Trends in Glomerular Disease Epidemiology in the Southeastern United States, 1986-2015.

Large-scale, contemporary studies exploring glomerular disease epidemiology in the United States are lacking. We aimed to determine 30-year temporal and demographic trends in renal biopsy glomerular disease diagnosis frequencies in the southeastern United States. In this cross-sectional, observational study, we identified all patients with a native kidney biopsy specimen showing one of 18 widely recognized glomerular disease diagnoses referred to the University of North Carolina Chapel Hill Division of Nephropathology between 1986 and 2015. Biopsy era (1986-1995, 1996-2005, and 2006-2015) and demographics (age, sex, and race) were our primary and secondary predictors, respectively, and the relative frequency of each glomerular disease diagnosis was our primary outcome. Among 21,374 patients (mean age =48.3±18.3 years old; 50.8% men; 56.8% white; 38.3% black; 2.8% Latino; 1.4% Asian; 0.8% other), the frequency of diabetic glomerulosclerosis in renal biopsy specimens increased dramatically over the three decades (5.5%, 11.4%, and 19.1% of diagnoses, respectively; P for trend <0.001). The frequency of FSGS initially increased but then declined (22.6%, 27.2%, and 24.7%, respectively; P for trend =0.64). The frequencies of other common glomerular disease subtypes remained stable (IgA nephropathy and ANCA/pauci-immune GN) or declined (minimal change disease, membranous nephropathy, membranoproliferative GN, and lupus nephritis). These temporal trends were largely preserved within all demographic subgroups, although cross-sectional frequency distributions differed according to age, sex, and race. We identified significant changes in relative renal biopsy frequencies of many glomerular disease subtypes over three decades. Temporal trends were consistently observed within all major demographic groups, although relative predominance of individual glomerular disease subtypes differed according to patient age, sex, and race. We propose that exploration of behavioral and environmental exposures that likely underlie these findings should be the focus of future hypothesis-driven research.

The role of electron microscopy in renal allograft biopsy evaluation.

To review and discuss the use of electron microscopy in the examination of renal transplant biopsies, in particular its role in the diagnosis of glomerular disease and antibody-mediated rejection. Electron microscopy can detect recurrent and de-novo glomerular disease at early stages, in particular for focal and segmental glomerulosclerosis and thrombotic microangiopathy.Ultrastructural features are an integral part of the Banff definition of chronic, active antibody-mediated rejection, which has been recently modified to include ultrastructural-only glomerular double contours. In addition, the threshold of peritubular capillary basement membrane multilayering diagnostic for chronic, active antibody-mediated rejection has been changed. As an area for further investigation, ultrastructural-only glomerular and peritubular capillary features could become tools in the early detection of antibody-mediated rejection. Electron microscopy is important in the diagnosis of glomerular disease and chronic, active antibody-mediated rejection, both of which contribute to late graft loss. Early detection and treatment may help prolong graft survival. More data are needed on the early ultrastructural features of antibody-mediated injury, so that the usefulness of this technique can be compared with emerging technologies such as transcript analysis.

Role of direct immunofluorescence in the diagnosis of glomerulonephritis

Background: Immunofluorescence microscopy is a vital tool for the diagnosis of glomerular diseases. This study was carried out to study patterns of glomerulonephritis (GN) and to record the sensitivity of direct immunofluorescence (DIF) in renal lesions. The DIF findings were correlated with clinical and histopathology findings and discrepancies were analyzed. Materials and Methods: The cross-sectional analytical study was conducted during the period July 2011 to July 2013 at a tertiary care Hospital, Department of Pathology. A total of 75 renal biopsies were received for routine and immunofluorescence studies in which histopathology and clinical data were reviewed and analyzed. Results: The sensitivity of DIF was 87.9% and specificity was 70.5%. The maximum number of cases were seen in the age group 41-50 years. The pattern of GN by DIF was minimal change disease (MCD) in 24%, IgA nephropathy in 13%, focal segmental glomerulosclerosis in 9% and membranoproliferative glomerulonephritis in 8% of the cases. Twelve histopathologically proven cases of GN were negative on DIF. One case of MCD on histopathology was diagnosed as IgM nephropathy based on DIF. Conclusion: Direct immunofluorescence forms an important diagnostic tool in reaching the exact diagnosis in various types of GN presenting with overlapping clinical and histomorphological features.