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Pathogenesis, Clinical Diagnosis, Treatments and Complications of Glomerular Diseases

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Nephrology & Urology".

Deadline for manuscript submissions: closed (31 December 2020) | Viewed by 28293

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Special Issue Editors

Dr. Andreas Kronbichler

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Department of Internal Medicine IV (Nephrology and Hypertension), Anichstrasse 35, 6020 Innsbruck, Austria
Interests: vasculitis; nephrotic syndrome; glomerular disease; contrast-associated acute kidney injury; systemic lupus erythematosus
Special Issues, Collections and Topics in MDPI journals

Dr. Jiwon M. Lee

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Department of Pediatrics, Chungnam National University Hospital, Daejeon 35015, Korea
Interests: nephrotic syndrome; glomerular disease; systemic lupus erythematosus

Prof. Dr. Jae Il Shin

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Guest Editor

Department of Pediatrics, Yonsei University College of Medicine, Seoul 03722, Korea
Interests: evidence-based medicine; meta-analysis; meta-research; reproducibility crisis; bias
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The area of glomerular diseases is changing and research that aims to gain insight into the pathogenesis, diagnosis, and complications of, treatment approaches to, or therapeutic measures for the underlying disease is on the increase.

This Special Issue welcomes articles either highlighting recent developments in or providing new experimental (in vitro or animal model) or clinical (human) data related to glomerular diseases. We would appreciate it if the authors provided a brief section in their manuscript indicating the novelty of their findings or, in the case of review articles, provided personal views on a particular topic (e.g., treatment of recurrent glomerulonephritis after kidney transplantation).

In summary, we are happy to host this Special Issue and welcome solicited and unsolicited submissions that will contribute to its success.

With kind regards,

Dr. Andreas Kronbichler
Dr. Jiwon M. Lee
Prof. Jae Il Shin
Guest Editors

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

glomerulonephritis
recurrence
treatment
diagnosis
pathogenesis
kidney disease
glomerular disease
vasculitis
systemic lupus erythematosus
nephrotic syndrome

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Published Papers (9 papers)

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Research

16 pages, 5591 KiB

Open AccessArticle

Agonism of Prostaglandin E2 Receptor 4 Ameliorates Tubulointerstitial Injury in Nephrotoxic Serum Nephritis in Mice

by Ida Aringer, Katharina Artinger, Corinna Schabhüttl, Thomas Bärnthaler, Agnes A. Mooslechner, Andrijana Kirsch, Marion Pollheimer, Philipp Eller, Alexander R. Rosenkranz, Akos Heinemann and Kathrin Eller

J. Clin. Med. 2021, 10(4), 832; https://doi.org/10.3390/jcm10040832 - 18 Feb 2021

Cited by 4 | Viewed by 2400

Abstract

Selectively targeting the E-type prostanoid receptor 4 (EP4) might be a new therapeutic option in the treatment of glomerulonephritis (GN), since the EP4 receptor is expressed on different immune cells, resident kidney cells, and endothelial cells, which are all involved in the pathogenesis of immune-complex GN. This study aimed to evaluate the therapeutic potential and to understand the mode of action of EP4 agonist in immune-complex GN using the murine model of nephrotoxic serum nephritis (NTS). In vivo, NTS mice were treated two times daily with two different doses of an EP4 agonist ONO AE1-329 or vehicle for 14 days total. The effect of PGE2 and EP4 agonism and antagonism was tested on murine distal convoluted tubular epithelial cells (DCT) in vitro. In vivo, the higher dose of the EP4 agonist led to an improved NTS phenotype, including a reduced tubular injury score and reduced neutrophil gelatinase-associated lipocalin (NGAL) and blood urea nitrogen (BUN) levels. EP4 agonist treatment caused decreased CD4⁺ T cell infiltration into the kidney and increased proliferative capacity of tubular cells. Injection of the EP4 agonist resulted in dose-dependent vasodilation and hypotensive episodes. The low-dose EP4 agonist treatment resulted in less pronounced episodes of hypotension. In vitro, EP4 agonism resulted in cAMP production and increased distal convoluted tubular (DCT) proliferation. Taken together, EP4 agonism improved the NTS phenotype by various mechanisms, including reduced blood pressure, decreased CD4⁺ T cell infiltration, and a direct effect on tubular cells leading to increased proliferation probably by increasing cAMP levels. Full article

(This article belongs to the Special Issue Pathogenesis, Clinical Diagnosis, Treatments and Complications of Glomerular Diseases)

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18 pages, 3341 KiB

Open AccessArticle

The Effect of Interleukin-4 and Dexamethasone on RNA-Seq-Based Transcriptomic Profiling of Human Podocytes: A Potential Role in Minimal Change Nephrotic Syndrome

by Jiwon M. Lee, Younhee Ko, Chul Ho Lee, Nara Jeon, Keum Hwa Lee, Jun Oh, Andreas Kronbichler, Moin A. Saleem, Beom Jin Lim and Jae Il Shin

J. Clin. Med. 2021, 10(3), 496; https://doi.org/10.3390/jcm10030496 - 1 Feb 2021

Cited by 3 | Viewed by 3046

Abstract

Interleukin-4 (IL-4) expression is implicated in the pathogenesis of nephrotic syndrome (NS). This study aimed to investigate the changes in the transcriptomes of human podocytes induced by IL-4 treatment and to analyze whether these changes could be affected by simultaneous steroid treatment. Three groups of human podocytes were treated with control, IL-4, and IL-4 plus dexamethasone (DEX), respectively. We performed whole-transcriptome sequencing to identify differentially expressed genes (DEGs) between the groups. We investigated relevant biological pathways using Gene Ontology (GO) enrichment analyses. We also attempted to compare and validate the DEGs with the genes listed in PodNet, a literature-based database on mouse podocyte genes. A total of 176 genes were differentially expressed among the three groups. GO analyses showed that pathways related to cytoskeleton organization and cell signaling were significantly enriched. Among them, 24 genes were listed in PodNet, and 12 of them were previously reported to be associated with IL-4-induced changes in human podocytes. Of the 12 genes, the expression levels of BMP4, RARB, and PLCE1 were reversed when podocytes were simultaneously treated with DEX. In conclusion, this study explored changes in the transcriptome profiles of human podocytes treated with IL-4. Few genes were reported in previous studies and were previously validated in experiments with human podocytes. We speculate that IL-4 may exert pathogenic effects on the transcriptome of human podocytes, and a few genes may be involved in the pathogenesis. Full article

(This article belongs to the Special Issue Pathogenesis, Clinical Diagnosis, Treatments and Complications of Glomerular Diseases)

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11 pages, 1286 KiB

Open AccessArticle

Clinical Relevance of Serum Galactose Deficient IgA1 in Patients with IgA Nephropathy

by Jin Sug Kim, Hyeon Seok Hwang, Sang Ho Lee, Yang Gyun Kim, Ju-Young Moon, Ji Yoon Kong and Kyung Hwan Jeong

J. Clin. Med. 2020, 9(11), 3549; https://doi.org/10.3390/jcm9113549 - 4 Nov 2020

Cited by 17 | Viewed by 2645

Abstract

New biomarkers of IgA nephropathy (IgAN) are needed for non-invasive diagnosis and appropriate treatment. There is emerging evidence that galactose deficient IgA1 (Gd-IgA1) is a pivotal molecule in the pathogenesis of IgAN. However, few studies have investigated the role of Gd-IgA1 as a biomarker in IgAN. In this study, we investigated the clinical relevance of serum Gd-IgA1 levels in patients with IgAN. Two hundred and thirty biopsy-proven IgAN patients, 74 disease controls (patients with non-IgAN nephropathy), and 15 healthy controls were enrolled in this study. Levels of serum Gd-IgA1 were measured using an ELISA kit in serum samples obtained the day of renal biopsy. We compared levels of serum Gd-IgA1 according to the type of glomerular disease and analyzed the association between Gd-IgA1 levels and clinical and pathological parameters in patients with IgAN. We then divided IgAN patients into two groups according to Gd-IgA1 level and investigated the predictive value of Gd-IgA1 for progression of chronic kidney disease (CKD). Serum Gd-IgA1 levels were significantly higher in IgAN patients than disease controls and healthy controls. In patients with IgAN, serum Gd-IA1 levels were significantly correlated with estimated glomerular filtration rate, serum IgA level, and tubular atrophy/interstitial fibrosis. CKD progression was more frequent in IgAN patients with higher serum Gd-IgA1 levels than in those with lower serum Gd-IgA1 levels. Cox proportional hazard models showed that high GdIgA1 level was an independent risk factor for CKD progression after adjusting for several confounders. Our results suggest that serum Gd-IgA1 level is a useful diagnostic and prognostic marker in IgAN patients. Further studies with a larger sample size and longer follow-up duration are needed. Full article

(This article belongs to the Special Issue Pathogenesis, Clinical Diagnosis, Treatments and Complications of Glomerular Diseases)

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11 pages, 1279 KiB

Open AccessArticle

Characterization of IgA Deposition in the Kidney of Patients with IgA Nephropathy and Minimal Change Disease

by Won-Hee Cho, Seon-Hwa Park, Seul-Ki Choi, Su Woong Jung, Kyung Hwan Jeong, Yang-Gyun Kim, Ju-Young Moon, Sung-Jig Lim, Ji-Youn Sung, Jong Hyun Jhee, Ho Jun Chin, Bum Soon Choi and Sang-Ho Lee

J. Clin. Med. 2020, 9(8), 2619; https://doi.org/10.3390/jcm9082619 - 12 Aug 2020

Cited by 10 | Viewed by 3623

Abstract

Approximately 5% of patients with IgA nephropathy (IgAN) exhibit mild mesangial lesions with acute onset nephrotic syndrome and diffuse foot process effacement representative of minimal change disease (MCD). It is not clear whether these unusual cases of IgAN with MCD (IgAN-MCD) are variant types of IgAN or coincidental deposition of IgA in patients with MCD. In a retrospective multicenter cohort study of 18 hospitals in Korea, we analyzed 46 patients with IgAN-MCD. Patients with endocapillary proliferation, segmental sclerosis, and crescent were excluded, and the clinical features and prognosis of IgAN-MCD were compared with those of pure MCD. In addition, we performed galactose-deficient IgA1 (KM55) staining to characterize IgAN-MCD. Among the 21,697 patients with glomerulonephritis enrolled in the database, 46 patients (0.21%) were diagnosed with IgAN-MCD, and 1610 patients (7.4%) with pure MCD. The 46 patients with IgAN-MCD accounted for 0.6% of primary IgAN patients (n = 7584). There was no difference in prognosis between patients with IgAN-MCD and those with only MCD. IgA and KM55 showed double positivity in all patients with IgAN-MCD (n = 4) or primary IgAN (n = 5) under double immunofluorescent staining. However, in four patients with lupus nephritis, mesangial IgA was deposited, but galactose-deficient-IgA1 (Gd-IgA1) was not. These findings suggest that IgAN-MCD is a dual glomerulopathy in which MCD was superimposed on possibly indolent IgAN. We confirmed by KM55 staining that IgAN-MCD is true IgAN, enabling better characterizations of the disease. Furthermore, IgAN-MCD shows a good prognosis when treated according to the usual MCD treatment modality. Full article

(This article belongs to the Special Issue Pathogenesis, Clinical Diagnosis, Treatments and Complications of Glomerular Diseases)

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17 pages, 1645 KiB

Open AccessArticle

Remission of Proteinuria May Protect against Progression to Chronic Kidney Disease in Pediatric-Onset IgA Nephropathy

by Jin-Soon Suh, Kyung Mi Jang, Hyesun Hyun, Myung Hyun Cho, Joo Hoon Lee, Young Seo Park, Jae Hyuk Oh, Ji Hong Kim, Kee Hwan Yoo, Woo Yeong Chung, Seong Heon Kim, Keehyuck Kim, Dae Yeol Lee, Jung Won Lee, Min Hyun Cho, Hyewon Park, Ja Wook Koo, Kyoung Hee Han, Eun Mi Yang, Keum Hwa Lee, Jae Il Shin, Heeyeon Cho, Kyo Soon Kim, Il-Soo Ha, Yong Hoon Park and Hee Gyung Kang Show full author list Hide full author list

J. Clin. Med. 2020, 9(7), 2058; https://doi.org/10.3390/jcm9072058 - 30 Jun 2020

Cited by 12 | Viewed by 3500

Abstract

Immunoglobulin A nephropathy (IgAN) is one of the most common primary glomerulopathies diagnosed in children and adolescents. This study aimed to evaluate the clinical features in and outcomes of pediatric IgAN over the last 30 years. Patients who were diagnosed before age of 18 at 20 centers in Korea were evaluated retrospectively. Of the 1154 patients (768 males, 386 females) with a median follow-up of 5 years, 5.6% (n = 65) progressed to stage 3–5 chronic kidney disease (CKD). The 10- and 20-year CKD-free survival rates were 91.2% and 75.6%, respectively. Outcomes did not differ when comparing those in Korea who were diagnosed prior to versus after the year 2000. On multivariate analysis, combined asymptomatic hematuria and proteinuria as presenting symptoms and decreased renal function at the time of biopsy were associated with progression to CKD, while remission of proteinuria was negatively associated with this outcome. Patients who presented with gross hematuria or nephrotic syndrome tended toward positive outcomes, especially if they ultimately achieved remission. While remission of proteinuria might imply that the disease is inherently less aggressive, it also can be achieved by management. Therefore, more aggressive management might be required for pediatric-onset IgAN. Full article

(This article belongs to the Special Issue Pathogenesis, Clinical Diagnosis, Treatments and Complications of Glomerular Diseases)

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12 pages, 1326 KiB

Open AccessArticle

Serum Uric Acid is Associated with Renal Prognosis of Lupus Nephritis in Women but not in Men

by Tae Ryom Oh, Hong Sang Choi, Chang Seong Kim, Dong-Ryeol Ryu, Sun-Hee Park, Shin Young Ahn, Soo Wan Kim, Eun Hui Bae and Seong Kwon Ma

J. Clin. Med. 2020, 9(3), 773; https://doi.org/10.3390/jcm9030773 - 12 Mar 2020

Cited by 10 | Viewed by 3128

Abstract

Lupus nephritis (LN) is a major complication of systemic lupus erythematosus. Early intervention in lupus nephritis improves prognosis. There is an association between hyperuricemia and lupus nephritis; nevertheless, the sex-specific role of uric acid in lupus nephritis remains unclear. We retrospectively analyzed 578 patients diagnosed with LN by renal biopsy. We determine the relationship of serum uric acid to progression of LN using Kaplan–Meier survival analyses and Cox proportional hazards models. The primary end point was LN progression defined as the initiation of dialysis or kidney transplantation. Men had higher mean serum uric acid levels than did women. Every 1 mg/dL increase in baseline uric acid level increased the risk of LN progression by 15.1%. The serum uric acid level was an independent risk factor for LN progression in women (hazard ratio [HR], 1.158; confidence interval [CI], 1.018–1.317; p = 0.028) but not in men (HR, 1.499; CI, 0.964–2.331; p = 0.072). Sensitivity analysis involving serum uric acid terciles generated consistent and robust results. Serum uric acid level was an independent risk factor for LN progression in women but not in men. Full article

(This article belongs to the Special Issue Pathogenesis, Clinical Diagnosis, Treatments and Complications of Glomerular Diseases)

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14 pages, 3959 KiB

Open AccessArticle

Severe Infection in Anti-Glomerular Basement Membrane Disease: A Retrospective Multicenter French Study

by Pauline Caillard, Cécile Vigneau, Jean-Michel Halimi, Marc Hazzan, Eric Thervet, Morgane Heitz, Laurent Juillard, Vincent Audard, Marion Rabant, Alexandre Hertig, Jean-François Subra, Vincent Vuiblet, Dominique Guerrot, Mathilde Tamain, Marie Essig, Thierry Lobbedez, Thomas Quemeneur, Jean-Michel Rebibou, Alexandre Ganea, Marie-Noëlle Peraldi, François Vrtovsnik, Maïté Daroux, Adnane Lamrani, Raïfah Makdassi, Gabriel Choukroun and Dimitri Titeca-Beauport Show full author list Hide full author list

J. Clin. Med. 2020, 9(3), 698; https://doi.org/10.3390/jcm9030698 - 4 Mar 2020

Cited by 7 | Viewed by 4025

Abstract

In patients presenting with anti-glomerular basement membrane (GBM) disease with advanced isolated kidney involvement, the benefit of intensive therapy remains controversial due to adverse events, particularly infection. We aim to describe the burden of severe infections (SI) (requiring hospitalization or intravenous antibiotics) and identify predictive factors of SI in a large cohort of patients with anti-GBM disease. Among the 201 patients (median [IQR] age, 53 [30–71] years) included, 74 had pulmonary involvement and 127 isolated glomerulonephritis. A total of 161 SI occurred in 116 patients during the first year after diagnosis. These infections occurred during the early stage of care (median [IQR] time, 13 [8–19] days after diagnosis) with mainly pulmonary (45%), catheter-associated bacteremia (22%) and urinary tract (21%) infections. In multivariable analysis, positive ANCA (HR [95% CI] 1.62 [1.07−2.44]; p = 0.02) and age at diagnosis (HR [95% CI] 1.10 [1.00–1.21]; p = 0.047) remained independently associated with SI. Age-adjusted severe infection during the first three months was associated with an increased three-year mortality rate (HR [95% CI] 3.13 [1.24–7.88]; p = 0.01). Thus, SI is a common early complication in anti-GBM disease, particularly in the elderly and those with positive anti-neutrophil cytoplasmic antibodies (ANCA). No significant association was observed between immunosuppressive strategy and occurrence of SI. Full article

(This article belongs to the Special Issue Pathogenesis, Clinical Diagnosis, Treatments and Complications of Glomerular Diseases)

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19 pages, 3994 KiB

Open AccessArticle

TLR2 Expression on Select Lymphocyte Subsets as a New Marker in Glomerulonephritis

by Sebastian Mertowski, Ewelina Grywalska, Krzysztof Gosik, Iwona Smarz-Widelska, Anna Hymos, Grzegorz Dworacki, Paulina Niedźwiedzka-Rystwej, Bartłomiej Drop, Jacek Roliński and Wojciech Załuska

J. Clin. Med. 2020, 9(2), 541; https://doi.org/10.3390/jcm9020541 - 17 Feb 2020

Cited by 5 | Viewed by 2581

Abstract

Toll-like receptor (TLR) signaling may be involved in autoimmune kidney disorders and has been implicated in proliferative and non-proliferative glomerulonephritis (PGN and NPGN). In this study, we investigated the expression of TLR2 on T and B lymphocytes in relation to selected clinical parameters in patients with PGN and NPGN. We collected peripheral blood from the ulnar vein of patients with PGN (n = 15) or NPGN (n = 22) and healthy volunteers (n = 20). The percentage of peripheral blood mononuclear cells expressing TLR2 was determined with flow cytometry. TLR2 expression on T and B lymphocytes was increased in PGN patients compared with NPGN patients and controls (p ≤ 0.001). In patients with PGN, TLR2 expression correlated negatively with the serum concentrations of IgG and albumin and positively with urine protein excretion. Receiver operating characteristic (ROC) analysis indicated that TLR2 expression is a highly specific marker to distinguish PGN patients from NPGN patients and controls, especially on CD4+ T lymphocytes. Its use as a non-invasive marker of disease should be further investigated. Full article

(This article belongs to the Special Issue Pathogenesis, Clinical Diagnosis, Treatments and Complications of Glomerular Diseases)

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12 pages, 1067 KiB

Open AccessArticle

Minor Glomerular Abnormalities are Associated with Deterioration of Long-Term Kidney Function and Mitochondrial Injury

by Byung Chul Yu, Nam-Jun Cho, Samel Park, Hyoungnae Kim, Hyo-Wook Gil, Eun Young Lee, Soon Hyo Kwon, Jin Seok Jeon, Hyunjin Noh, Dong Cheol Han, Ahrim Moon, Su Jung Park, Jin Kuk Kim, Seung Duk Hwang, Soo Jeong Choi and Moo Yong Park

J. Clin. Med. 2020, 9(1), 33; https://doi.org/10.3390/jcm9010033 - 22 Dec 2019

Cited by 8 | Viewed by 2446

Abstract

Minor glomerular abnormalities (MGAs) are unclassified glomerular lesions indicated by the presence of minor structural abnormalities that are insufficient for a specific pathological diagnosis. The long-term clinical outcomes and pathogenesis have not been examined. We hypothesized that MGAs would be associated with the deterioration of long-term kidney function and increased urinary mitochondrial DNA (mtDNA) copy numbers. We retrospectively enrolled patients with MGAs, age-/sex-/estimated glomerular filtration rate (eGFR)-matched patients with immunoglobulin A nephropathy (IgAN), and similarly matched healthy controls (MHCs; n = 49 each). We analyzed the time × group interaction effects of the eGFR and compared mean annual eGFR decline rates between the groups. We prospectively enrolled patients with MGAs, age- and sex-matched patients with IgAN, and MHCs (n = 15 each) and compared their urinary mtDNA copy numbers. Compared to the MHC group, the MGA and IgAN groups displayed differences in the time × group effects of eGFR, higher mean annual rates of eGFR decline, and higher urinary mtDNA copy numbers; however, these groups did not significantly differ from each other. The results indicate that MGAs are associated with deteriorating long-term kidney function, and mitochondrial injury, despite few additional pathological changes. We suggest that clinicians conduct close long-term follow-up of patients with MGAs. Full article

(This article belongs to the Special Issue Pathogenesis, Clinical Diagnosis, Treatments and Complications of Glomerular Diseases)

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