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Kaneko S, Murata R, Hoshimoto A, Hisada R, Harano M, Anno E, Hagiwara S, Imai E, Nagata M. Macroscopic hematuria-associated severe acute kidney injury triggered by kidney stone formation in a patient with thin basement membrane and no history of microscopic hematuria. CEN Case Rep 2024:10.1007/s13730-024-00942-7. [PMID: 39417987 DOI: 10.1007/s13730-024-00942-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Accepted: 10/07/2024] [Indexed: 10/19/2024] Open
Abstract
Macroscopic hematuria (MH)-associated acute kidney injury (AKI) is a rare condition that causes acute tubular damage due to severe glomerular bleeding with MH. A 66-year-old Japanese woman with no significant past medical history was referred for severe kidney injury with oliguric MH. Her prior medical checkup results showed no occult blood in her urine. Seven days earlier, she had experienced transient severe acute right lumbar back pain. On admission, her serum urea nitrogen was 147 mg/dL, serum creatinine (sCr) 18.3 mg/dL, urinary red blood cells (RBCs) > 100/hpf, urinary protein 28.8 g/gCr, with no hydronephrosis in either kidney, but two stones were found in the right kidney and right ureteropelvic junction. At the start of her hemodialysis, the patient was treated with high-dose steroids because of suspected rapidly progressive glomerulonephritis. A renal biopsy of the left kidney showed acute tubular injury with massive RBC casts filling the tubular lumen. Glomerulitis was not detected, but electron microscopy revealed diffuse glomerular thin basement membrane (TBM). Despite immediate steroid discontinuation, the patient's renal function and MH improved, and she was weaned from hemodialysis. The stones resolved 2 months after onset, but microscopic hematuria persisted for 7 months post-onset. The sCr level was fixed at 1.1 mg/dL 20 months post-onset. This is the first report of MH-AKI in a TBM without the risk of MH-AKI development, such as bleeding tendency or iron overload. In this TBM, a colic attack of the renal urinary tract induced glomerular bleeding, and intolerance to hematuria may have caused severe tubular damage.
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Affiliation(s)
- Shuzo Kaneko
- Department of Nephrology, Itabashi Chuo Medical Center, Itabashi, Tokyo, 174-0051, Japan.
| | - Ririko Murata
- Department of Nephrology, Itabashi Chuo Medical Center, Itabashi, Tokyo, 174-0051, Japan
| | - Ainori Hoshimoto
- Department of Nephrology, Itabashi Chuo Medical Center, Itabashi, Tokyo, 174-0051, Japan
| | - Rina Hisada
- Department of Nephrology, Itabashi Chuo Medical Center, Itabashi, Tokyo, 174-0051, Japan
| | - Makiko Harano
- Department of Nephrology, Itabashi Chuo Medical Center, Itabashi, Tokyo, 174-0051, Japan
| | - Emi Anno
- Department of Nephrology, Itabashi Chuo Medical Center, Itabashi, Tokyo, 174-0051, Japan
| | - So Hagiwara
- Department of Nephrology, Itabashi Chuo Medical Center, Itabashi, Tokyo, 174-0051, Japan
| | - Eri Imai
- Department of Nephrology, Itabashi Chuo Medical Center, Itabashi, Tokyo, 174-0051, Japan
| | - Michio Nagata
- Department of Pathology, Itabashi Chuo Medical Center, Itabashi, Japan
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Ishimori S, Horinouchi T, Yamamura T, Fujimura J, Kamiyoshi N, Kaito H, Tanaka Y, Matsukura H, Shimabukuro W, Shima Y, Kawaguchi A, Araki Y, Nakanishi K, Hara S, Nozu K. Role of Iron in Children With Immunoglobulin A Nephropathy and Macrohematuria-Induced Acute Kidney Injury. Kidney Int Rep 2024; 9:1664-1673. [PMID: 38899207 PMCID: PMC11184247 DOI: 10.1016/j.ekir.2024.03.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Revised: 02/29/2024] [Accepted: 03/04/2024] [Indexed: 06/21/2024] Open
Abstract
Introduction The role of iron in, and the prognosis of, pediatric Immunoglobulin A nephropathy (IgAN) with macrohematuria (MH)-induced acute kidney injury (AKI) (MH-AKI) have not been evaluated. Thirty percent of adults with MH-AKI, and especially those who are older, show progression to chronic kidney disease. Methods We evaluated the immunohistopathologic characteristics of renal biopsy samples from pediatric patients with MH-AKI IgAN and controls, using Berlin Blue to identify iron, CD163 (a hemoglobin-scavenging receptor), and CD68 (a total macrophage marker), then compared the findings against the clinical characteristics of the patients. Results We enrolled 44 children as follows: 19 with IgAN but no MH or AKI; 5 with IgAN and MH but no AKI (MH(+)AKI(-) IgAN); 11 with MH-AKI IgAN; and 9 with no IgAN, MH, or AKI, according to a renal biopsy. Berlin Blue staining was detected predominantly at the injured tubulointerstitium, and the areas of staining in children with MH(+)AKI(-) and MH-AKI IgAN were significantly more extensive. The areas of Berlin Blue and CD163 staining did not perfectly match; however, areas of Berlin Blue were surrounded by immunopositivity for CD163. No children with MH-AKI IgAN showed decreased renal function at their last visit. Conclusion Children with IgAN and MH, with or without AKI, showed considerable iron deposition in their renal tubules. CD163-positive cells might scavenge hemoglobin in patients with MH-AKI IgAN, but not their roles as macrophages. The renal prognosis of pediatric MH-AKI IgAN is good.
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Affiliation(s)
- Shingo Ishimori
- Department of Pediatrics, Takatsuki General Hospital, Takatsuki, Japan
| | - Tomoko Horinouchi
- Department of Pediatrics, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Japan
| | - Tomohiko Yamamura
- Department of Pediatrics, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Japan
| | - Junya Fujimura
- Department of Pediatrics, Kakogawa Central City Hospital, Kakogawa-cho, Kakogawa, Japan
| | | | - Hiroshi Kaito
- Department of Nephrology, Hyogo Prefectural Kobe Children’s Hospital, Chuo-ku, Kobe, Japan
| | - Yuriko Tanaka
- Department of Pediatrics, Dokkyo Medical University Saitama Medical Center, Koshigaya, Saitama, Japan
| | - Hiroyoshi Matsukura
- Department of Pediatrics, Saiseikai Takaoka Hospital, Takaoka, Toyama, Japan
| | - Wataru Shimabukuro
- Department of Child Health and Welfare, Graduate School of Medicine, University of the Ryukyus, Nishihara-cho, Nakagami-gun, Okinawa, Japan
| | - Yuko Shima
- Department of Pediatrics, Wakayama Medical University, Wakayama, Japan
| | - Azusa Kawaguchi
- Department of Pediatrics, National Hospital Organization Hokkaido Medical Center, Nishi-ku, Sapporo, Hokkaido, Japan
| | - Yoshinori Araki
- Department of Pediatrics, National Hospital Organization Hokkaido Medical Center, Nishi-ku, Sapporo, Hokkaido, Japan
| | - Koichi Nakanishi
- Department of Child Health and Welfare, Graduate School of Medicine, University of the Ryukyus, Nishihara-cho, Nakagami-gun, Okinawa, Japan
| | - Shigeo Hara
- Department of Diagnostic Pathology, Kobe City Medical Center General Hospital, Chuo-ku, Kobe, Japan
| | - Kandai Nozu
- Department of Pediatrics, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Japan
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Stamellou E, Seikrit C, Tang SCW, Boor P, Tesař V, Floege J, Barratt J, Kramann R. IgA nephropathy. Nat Rev Dis Primers 2023; 9:67. [PMID: 38036542 DOI: 10.1038/s41572-023-00476-9] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/26/2023] [Indexed: 12/02/2023]
Abstract
IgA nephropathy (IgAN), the most prevalent primary glomerulonephritis worldwide, carries a considerable lifetime risk of kidney failure. Clinical manifestations of IgAN vary from asymptomatic with microscopic or intermittent macroscopic haematuria and stable kidney function to rapidly progressive glomerulonephritis. IgAN has been proposed to develop through a 'four-hit' process, commencing with overproduction and increased systemic presence of poorly O-glycosylated galactose-deficient IgA1 (Gd-IgA1), followed by recognition of Gd-IgA1 by antiglycan autoantibodies, aggregation of Gd-IgA1 and formation of polymeric IgA1 immune complexes and, lastly, deposition of these immune complexes in the glomerular mesangium, leading to kidney inflammation and scarring. IgAN can only be diagnosed by kidney biopsy. Extensive, optimized supportive care is the mainstay of therapy for patients with IgAN. For those at high risk of disease progression, the 2021 KDIGO Clinical Practice Guideline suggests considering a 6-month course of systemic corticosteroid therapy; however, the efficacy of systemic steroid treatment is under debate and serious adverse effects are common. Advances in understanding the pathophysiology of IgAN have led to clinical trials of novel targeted therapies with acceptable safety profiles, including SGLT2 inhibitors, endothelin receptor blockers, targeted-release budesonide, B cell proliferation and differentiation inhibitors, as well as blockade of complement components.
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Affiliation(s)
- Eleni Stamellou
- Department of Nephrology, School of Medicine, University of Ioannina, Ioannina, Greece
- Department of Nephrology and Clinical Immunology, RWTH Aachen University Hospital, Aachen, Germany
| | - Claudia Seikrit
- Department of Nephrology and Clinical Immunology, RWTH Aachen University Hospital, Aachen, Germany
| | - Sydney C W Tang
- Division of Nephrology, Department of Medicine, University of Hong Kong, Hong Kong, China
| | - Peter Boor
- Department of Nephrology and Clinical Immunology, RWTH Aachen University Hospital, Aachen, Germany
- Department of Pathology, RWTH Aachen University, Aachen, Germany
| | - Vladimir Tesař
- Department of Nephrology, 1st Faculty of Medicine and General University Hospital, Charles University, Prague, Czech Republic
| | - Jürgen Floege
- Department of Nephrology and Clinical Immunology, RWTH Aachen University Hospital, Aachen, Germany
| | - Jonathan Barratt
- Department of Cardiovascular Sciences, University of Leicester, Leicester, UK
| | - Rafael Kramann
- Department of Nephrology and Clinical Immunology, RWTH Aachen University Hospital, Aachen, Germany.
- Department of Internal Medicine, Nephrology and Transplantation, Erasmus Medical Center, Rotterdam, Netherlands.
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Sevillano AM, Caravaca-Fontán F, Cordero Garcia-Galan L, Fernandez-Juarez G, Lopez-Revuelta K, Guzmán DA, Martín-Reyes G, Quintana LF, Rodas LM, Sanchez de la Nieta MD, Rabasco C, Espinosa M, Diaz-Encarnación M, San Miguel L, Barrios C, Rodriguez E, Garcia P, Valera A, Peña JK, Shabaka A, Velo M, Sierra M, Gonzalez F, Fernandez-Reyes MJ, Heras M, Delgado P, Gutierrez E, Moreno JA, Praga M. Effect of Immunosuppressive Treatments on Kidney Outcomes After Gross Hematuria-Related Acute Kidney Injury in Older Patients With IgA Nephropathy. Kidney Int Rep 2023; 8:1596-1604. [PMID: 37547537 PMCID: PMC10403672 DOI: 10.1016/j.ekir.2023.05.027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Revised: 05/18/2023] [Accepted: 05/28/2023] [Indexed: 08/08/2023] Open
Abstract
Introduction Macroscopic hematuria (MH) bouts, frequently accompanied by acute kidney injury (AKI-MH) are one of the most common presentations of IgA nephropathy (IgAN) in the elderly. Immunosuppressive therapies are used in clinical practice; however, no studies have analyzed their efficacy on kidney outcomes. Methods This is a retrospective, multicenter study of a cohort of patients aged ≥50 years with biopsy-proven IgAN presenting with AKI-MH. Outcomes were complete, partial, or no recovery of kidney function at 1 year after AKI-MH, and kidney survival at 1, 2, and 5 years. Propensity score matching (PSM) analysis was applied to balance baseline differences between patients treated with immunosuppression and those not treated with immunosuppression. Results The study group consisted of 91 patients with a mean age of 65 ± 15 years, with a mean follow-up of 59 ± 36 months. Intratubular red blood cell (RBC) casts and acute tubular necrosis were found in all kidney biopsies. The frequency of endocapillary hypercellularity and crescents were low. Immunosuppressive therapies (corticosteroids alone or combined with mycophenolate mofetil or cyclophosphamide) were prescribed in 52 (57%) patients, whereas 39 (43%) received conservative treatment. There were no significant differences in the proportion of patients with complete, partial, or no recovery of kidney function at 1 year between patients treated with immunosuppression and those not treated with immunosuppression (29% vs. 36%, 30.8% vs. 20.5% and 40.4 % vs. 43.6%, respectively). Kidney survival at 1, 3, and 5 years was similar among treated and untreated patients (85% vs. 81%, 77% vs. 76% and 72% vs. 66%, respectively). Despite the PSM analysis, no significant differences were observed in kidney survival between the two groups. Fourteen patients (27%) treated with immunosuppression had serious adverse events. Conclusions Immunosuppressive treatments do not modify the unfavorable prognosis of patients with IgAN who are aged ≥50 years presenting with AKI-MH, and are frequently associated with severe complications.
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Affiliation(s)
- Angel M. Sevillano
- Department of Nephrology, Hospital Universitario 12 de Octubre, Madrid, Spain
| | - Fernando Caravaca-Fontán
- Department of Nephrology, Instituto de Investigación Hospital 12 de Octubre (imas12), Madrid, Spain
| | | | - Gema Fernandez-Juarez
- Department of Nephrology, Hospital Universitario Fundación Alcorcón, Alcorcón, Spain
| | - Katia Lopez-Revuelta
- Department of Nephrology, Hospital Universitario Fundación Alcorcón, Alcorcón, Spain
| | - Diomaris A. Guzmán
- Department of Nephrology, Hospital Regional Universitario de Málaga, Malaga, Spain
| | | | - Luis F. Quintana
- Department of Nephrology, Hospital Clinic de Barcelona, Barcelona, Spain
| | - Lida M. Rodas
- Department of Nephrology, Hospital Clinic de Barcelona, Barcelona, Spain
| | | | - Cristina Rabasco
- Department of Nephrology, Hospital Universitario Reina Sofia, Cordoba, Spain
| | - Mario Espinosa
- Department of Nephrology, Hospital Universitario Reina Sofia, Cordoba, Spain
| | | | - Luz San Miguel
- Department of Nephrology, Fundación Puigvert, Barcelona, Spain
| | - Clara Barrios
- Department of Nephrology, Hospital del Mar, Barcelona, Spain
| | - Eva Rodriguez
- Department of Nephrology, Hospital del Mar, Barcelona, Spain
| | - Patricia Garcia
- Department of Nephrology, Hospital Virgen de la Victoria, Malaga, Spain
| | - Alfonso Valera
- Department of Nephrology, Hospital Virgen de la Victoria, Malaga, Spain
| | - Jessy-Korina Peña
- Department of Nephrology, Hospital Universitario Príncipe de Asturias, Alcalá de Henares, Spain
| | - Amir Shabaka
- Department of Nephrology, Hospital Universitario Fundación Alcorcón, Alcorcón, Spain
| | - Mercedes Velo
- Department of Nephrology, Hospital Clínico San Carlos, Madrid, Spain
| | - Milagros Sierra
- Department of Nephrology, Hospital San Pedro, Logroño, Spain
| | - Fayna Gonzalez
- Department of Nephrology, Hospital Universitario Dr. Negrin, Gran Canaria, Spain
| | | | - Manuel Heras
- Department of Nephrology, Hospital General de Segovia, Segovia, Spain
| | - Patricia Delgado
- Department of Nephrology, Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain
| | - Eduardo Gutierrez
- Department of Nephrology, Hospital Universitario 12 de Octubre, Madrid, Spain
| | - Juan Antonio Moreno
- Department of Cell Biology, Physiology and Immunology, University of Cordoba, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), UGC Nefrología, Hospital Universitario Reina Sofía, Córdoba, Spain
| | - Manuel Praga
- Department of Nephrology, Instituto de Investigación Hospital 12 de Octubre (imas12), Madrid, Spain
- Medicine Department, Universidad Complutense de Madrid, Madrid, Spain
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Liu Y, Gong Y, Xu G. The role of mononuclear phagocyte system in IgA nephropathy: pathogenesis and prognosis. Front Immunol 2023; 14:1192941. [PMID: 37529043 PMCID: PMC10390225 DOI: 10.3389/fimmu.2023.1192941] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Accepted: 06/12/2023] [Indexed: 08/03/2023] Open
Abstract
Although the "multiple hits" theory is a widely accepted pathogenesis in IgA nephropathy (IgAN), increasing evidence suggests that the mononuclear/macrophage system plays important roles in the progression of IgAN; however, the exact mechanism is unclear. In the present study, we explored 1,067 patients in 15 studies and found that the number of macrophages per glomerulus was positively related with the degree of hematuria, and the macrophages in the glomeruli were mainly related to mesangial proliferation (M) in renal biopsy. In the tubulointerstitium, macrophages were significantly paralleled to tubulointerstitial α-SMA and NF-kB expression, tubulointerstitial lesion, tubule atrophy/interstitial fibrosis (T), and segmental glomerulosclerosis (S). In the glomeruli and tubulointerstitium, M1 accounted for 85.41% in the M classification according to the Oxford MEST-C, while in the blood, M1 accounted for 100%, and the patients with low CD89+ monocyte mean fluorescence intensity displayed more severe pathological characteristics (S1 and T1-2) and clinical symptoms. M1 (CD80+) macrophages were associated with proinflammation in the acute phase; however, M2 (CD163+) macrophages participated in tissue repair and remodeling, which correlated with chronic inflammation. In the glomeruli, M2 macrophages activated glomerular matrix expansion by secreting cytokines such as IL-10 and tumor necrosis factor-β (TGF-β), and M0 (CD68+) macrophages stimulated glomerular hypercellularity. In the tubulointerstitium, M2 macrophages played pivotal roles in renal fibrosis and sclerosis. It is assumed that macrophages acted as antigen-presenting cells to activate T cells and released diverse cytokines to stimulate an inflammatory response. Macrophages infiltrating glomeruli destroy the integrity of podocytes through the mesangio-podocytic-tubular crosstalk as well as the injury of the tubule.
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Affiliation(s)
- Yiwen Liu
- Department of Nephrology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- The Second Clinical Medical College of Nanchang University, Nanchang, Jiangxi, China
| | - Yan Gong
- Department of Neurosurgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Gaosi Xu
- Department of Nephrology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
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Yokote S, Tsuboi N, Shimizu A, Okabe M, Haruhara K, Sasaki T, Ueda H, Yokoo T. Predictors of Gross Hematuria After SARS-CoV-2 mRNA Vaccination in Patients with IgA Nephropathy. KIDNEY360 2023; 4:943-950. [PMID: 37291717 PMCID: PMC10371300 DOI: 10.34067/kid.0000000000000192] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Accepted: 06/02/2023] [Indexed: 06/10/2023]
Abstract
Key Points Little is known about the clinical characteristics of patients with immunoglobulin A nephropathy (IgAN) who present with gross hematuria in relation to SARS-CoV-2 mRNA vaccination. The relationship between the clinical features in patients with IgAN at the time of SARS-CoV-2 mRNA vaccination and the subsequent appearance of gross hematuria was investigated. This study demonstrates the clinical significance of microscopic hematuria in patients with IgAN as a predictor of gross hematuria after SARS-CoV-2 mRNA vaccination. Background There have been several reports of immunoglobulin A nephropathy (IgAN) patients with gross hematuria and acute deterioration of urinary findings and kidney function after severe acute respiratory syndrome coronavirus 2 mRNA vaccination. Recent case series studies have indicated a possible link between the status of urinary findings at the time of vaccination and the subsequent appearance of gross hematuria. In this study, we aimed to determine whether the status of prevaccination urinary findings was associated with postvaccination gross hematuria in patients already diagnosed with IgAN. Methods Outpatients with IgAN who had been followed up before vaccination were included. We analyzed the association between the remission of prevaccination microscopic hematuria (urine sediment <5 red blood cells/high-power field) or proteinuria (<0.3 g/gCr) and postvaccination gross hematuria. Results A total of 417 Japanese patients with IgAN (median age, 51 years; 56% female; eGFR, 58 ml/min per 1.73 m2) were included. The frequency of gross hematuria after vaccination was higher in 20 of 123 patients (16.3%) with microscopic hematuria than in 5 of 294 patients (1.7%) without microscopic hematuria before vaccination (P < 0.001). There was no association between prevaccination proteinuria and postvaccination gross hematuria. After adjusting for potential confounders, such as sex (female), age (younger than 50 years), eGFR (≥60 ml/min per 1.73 m2), and histories of tonsillectomy and corticosteroid therapy, prevaccination microscopic hematuria was still associated with postvaccination gross hematuria (odds ratio, 8.98; P < 0.001). As the severity of prevaccination microscopic hematuria increased, the incidence of postvaccination gross hematuria increased (P < 0.001). Conclusions Prevaccination microscopic hematuria in patients with IgAN is a major predictor of postvaccination gross hematuria, regardless of potential confounders, including previous treatments of IgAN.
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Affiliation(s)
- Shinya Yokote
- Division of Nephrology and Hypertension, Department of Internal Medicine, Jikei University Katsushika Medical Center, Tokyo, Japan
| | - Nobuo Tsuboi
- Division of Nephrology and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan
| | - Akihiro Shimizu
- Division of Nephrology and Hypertension, Department of Internal Medicine, Jikei University Kashiwa Hospital, Chiba, Japan
| | - Masahiro Okabe
- Division of Nephrology and Hypertension, Department of Internal Medicine, Jikei University Daisan Hospital, Tokyo, Japan
| | - Kotaro Haruhara
- Division of Nephrology and Hypertension, Department of Internal Medicine, Jikei University Kashiwa Hospital, Chiba, Japan
| | - Takaya Sasaki
- Division of Nephrology, Kawaguchi Municipal Medical Center, Kawaguchi, Japan
| | - Hiroyuki Ueda
- Division of Nephrology and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan
| | - Takashi Yokoo
- Division of Nephrology and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan
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Petrou D, Kalogeropoulos P, Liapis G, Lionaki S. IgA Nephropathy: Current Treatment and New Insights. Antibodies (Basel) 2023; 12:40. [PMID: 37366657 PMCID: PMC10294861 DOI: 10.3390/antib12020040] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Revised: 05/23/2023] [Accepted: 06/09/2023] [Indexed: 06/28/2023] Open
Abstract
IgA Nephropathy (IgAN) is the most common cause of primary glomerulonephritis worldwide. Despite the histopathologic hallmark of mesangial IgA deposition, IgAN is a heterogenous autoimmune disease not only in terms of clinical presentation but also in long-term disease progression. The pathogenesis of the disease is complex and includes the generation of circulating IgA immune complexes with chemical and biological characteristics that favor mesangial deposition and reaction to mesangial under-glycosylated IgA1 accumulation, which leads to tissue injury with glomerulosclerosis and interstitial fibrosis. Patients with proteinuria over 1 g, hypertension, and impaired renal function at diagnosis are considered to be at high risk for disease progression and end-stage kidney disease (ESKD). Glucocorticoids have been the mainstay of treatment for these patients for years, but without long-term benefit for renal function and accompanied by several adverse events. A better understanding of the pathophysiology of IgAN in recent years has led to the development of several new therapeutic agents. In this review, we summarize the current therapeutic approach for patients with IgAN as well as all novel investigational agents.
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Affiliation(s)
- Dimitra Petrou
- Department of Nephrology, Second Department of Propaedeutic Internal Medicine, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece;
| | - Petros Kalogeropoulos
- Department of Nephrology, Second Department of Propaedeutic Internal Medicine, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece;
| | - George Liapis
- Department of Pathology, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
| | - Sophia Lionaki
- Department of Nephrology, Second Department of Propaedeutic Internal Medicine, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece;
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Abstract
Gross hematuria after upper respiratory tract infections is a well-known characteristic symptom of immunoglobulin A nephropathy (IgAN). In recent years, there have been several reports of existing or newly diagnosed patients with IgAN susceptible to gross hematuria after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. However, reports of patients with IgAN and gross hematuria after SARS-CoV-2 infection are extremely rare despite a considerable number of patients with coronavirus disease 2019 (COVID-19) who preferentially present with upper respiratory symptoms. Here, we report the cases of 5 Japanese patients with IgAN who developed gross hematuria associated with SARS-CoV-2 infection. These patients presented with fever and other COVID-19-related symptoms, followed by the appearance of gross hematuria within 2 days, which lasted for 1-7 days. Acute kidney injury occurred after gross hematuria in 1 case. In all cases, microhematuria was identified before gross hematuria associated with SARS-CoV-2 infection, and it persisted after the gross hematuria episode. Because repeated gross hematuria and persistent microhematuria may lead to irreversible kidney injury, the clinical manifestations of patients with IgAN during the COVID-19 pandemic should be carefully monitored.
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Weng M, Lin J, Chen Y, Zhang X, Zou Z, Chen Y, Cui J, Fu B, Li G, Chen C, Wan J. Time-Averaged Hematuria as a Prognostic Indicator of Renal Outcome in Patients with IgA Nephropathy. J Clin Med 2022; 11:jcm11226785. [PMID: 36431262 PMCID: PMC9694958 DOI: 10.3390/jcm11226785] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Revised: 11/11/2022] [Accepted: 11/15/2022] [Indexed: 11/19/2022] Open
Abstract
We aim to investigate the association of time-averaged hematuria (TA-hematuria) with the progression of IgA nephropathy (IgAN). Based on TA-hematuria during follow-up, 152 patients with IgAN were divided into a hematuria remission group (≤28 red blood cells [RBCs]/μL) and a persistent hematuria group (>28 RBCs/μL). The persistent hematuria group had a higher percentage of patients with macroscopic hematuria, lower levels of hemoglobin and TA-serum albumin, and more severe renal pathologic lesions. The composite endpoint is defined as a doubling of the baseline SCr level (D-SCr), or the presence of ESRD. During the mean follow-up of 58.08 ± 23.51 months, 15 patients (9.9%) reached the primary outcome of ESRD and 19 patients (12.5%) reached the combined renal endpoint. Kaplan-Meier analysis showed that the persistent hematuria group had a lower renal survival rate. The persistent hematuria patients who were incorporated with proteinuria (≥1.0 g/day) and low TA-serum albumin (<40 g/L) had the worst renal outcomes. Multivariate Cox regression indicated that TA-hematuria (hazard ratio [HR] = 0.004, 95% CI: 0.001, 0.008; p = 0.010) was independently associated with the progression of IgAN. Receiver operating characteristic analysis indicated the optimal TA-hematuria cutoff value for predicting the progression of IgAN was 201.21 RBCs/μL in females and 37.25 RBCs/μL in males.
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Affiliation(s)
- Mengjie Weng
- Department of Nephrology, Blood Purification Research Center, The First Affiliated Hospital of Fujian Medical University, Chazhong Road 20, Fuzhou 350005, China
- Fujian Clinical Research Center for Metabolic Chronic Kidney Disease, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, China
| | - Jiaqun Lin
- Department of Nephrology, Blood Purification Research Center, The First Affiliated Hospital of Fujian Medical University, Chazhong Road 20, Fuzhou 350005, China
- Fujian Clinical Research Center for Metabolic Chronic Kidney Disease, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, China
| | - Yumei Chen
- Department of Nephrology, Blood Purification Research Center, The First Affiliated Hospital of Fujian Medical University, Chazhong Road 20, Fuzhou 350005, China
- Fujian Clinical Research Center for Metabolic Chronic Kidney Disease, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, China
| | - Xiaohong Zhang
- Department of Nephrology, Blood Purification Research Center, The First Affiliated Hospital of Fujian Medical University, Chazhong Road 20, Fuzhou 350005, China
- Fujian Clinical Research Center for Metabolic Chronic Kidney Disease, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, China
| | - Zhenhuan Zou
- Department of Nephrology, Blood Purification Research Center, The First Affiliated Hospital of Fujian Medical University, Chazhong Road 20, Fuzhou 350005, China
- Fujian Clinical Research Center for Metabolic Chronic Kidney Disease, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, China
| | - Yi Chen
- Department of Nephrology, Blood Purification Research Center, The First Affiliated Hospital of Fujian Medical University, Chazhong Road 20, Fuzhou 350005, China
- Fujian Clinical Research Center for Metabolic Chronic Kidney Disease, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, China
| | - Jiong Cui
- Department of Nephrology, Blood Purification Research Center, The First Affiliated Hospital of Fujian Medical University, Chazhong Road 20, Fuzhou 350005, China
- Fujian Clinical Research Center for Metabolic Chronic Kidney Disease, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, China
| | - Binbin Fu
- Department of Nephrology, Blood Purification Research Center, The First Affiliated Hospital of Fujian Medical University, Chazhong Road 20, Fuzhou 350005, China
- Fujian Clinical Research Center for Metabolic Chronic Kidney Disease, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, China
| | - Guifen Li
- Department of Nephrology, Blood Purification Research Center, The First Affiliated Hospital of Fujian Medical University, Chazhong Road 20, Fuzhou 350005, China
- Fujian Clinical Research Center for Metabolic Chronic Kidney Disease, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, China
| | - Caiming Chen
- Department of Nephrology, Blood Purification Research Center, The First Affiliated Hospital of Fujian Medical University, Chazhong Road 20, Fuzhou 350005, China
- Fujian Clinical Research Center for Metabolic Chronic Kidney Disease, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, China
| | - Jianxin Wan
- Department of Nephrology, Blood Purification Research Center, The First Affiliated Hospital of Fujian Medical University, Chazhong Road 20, Fuzhou 350005, China
- Fujian Clinical Research Center for Metabolic Chronic Kidney Disease, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, China
- Correspondence:
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10
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Wang X, Guo Z, Huang B, Xie M, Ren J, Zhu Y, Guo H, Wang Y, Yu D, Zhang J, Zhang L. IgA nephropathy with acute kidney disease: Characteristics, prognosis, and causes. Eur J Intern Med 2022; 105:46-53. [PMID: 35778354 DOI: 10.1016/j.ejim.2022.05.021] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Revised: 04/20/2022] [Accepted: 05/18/2022] [Indexed: 01/20/2023]
Abstract
BACKGROUND The clinical manifestations and prognosis of IgA nephropathy (IgAN) are diverse. Some patients may present with kidney dysfunction lasting shorter than 3 months and meet the acute kidney disease (AKD) criteria. This study aimed to investigate the clinicopathological features, causes and prognosis of newly diagnosed cases of IgAN with AKD. METHODS 1320 IgAN patients diagnosed via kidney biopsy between January 2012 and June 2018 were included in this retrospective study, with a median follow-up period of 35 months. We analyzed the clinicopathological, etiological variables, as well as short-term and long-term prognosis. The main outcome was a composite event of 40% decline in eGFR, kidney failure or death. RESULTS Incidence of AKD was 8.8% in the newly diagnosed IgAN patients, and was found to be an independent risk factor affecting the short-term (HR, 7.1; 95% CI, 2.3-22.2; P = 0.001) and long-term (HR, 1.8; 95% CI, 1.2-2.6; P = 0.006) prognosis, respectively. The most common cause of AKD was malignant hypertension-related AKD (MHT-AKD; 24.1%), followed by hematuria-related AKD (H-AKD; 12.9%), nephrotoxic-drug-exposure-related AKD (NTDE-AKD; 12.1%) and crescents-related AKD (C-AKD; 11.2%). The patients in AKD group had more severe clinicopathological characteristics and poor short-term and long-term prognosis than non-AKD group. In subgroup analysis, the MHT-AKD had the worst 5 years survival rate, followed by NTDE-AKD and C-AKD, whereas H-AKD had the best survival rate. CONCLUSIONS AKD is not rare among IgAN patients, and is an independent risk factor for short-term and long-term prognosis. IgAN patients with AKD resulting from different causes have different prognosis.
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Affiliation(s)
- Xutong Wang
- Department of Nephropathy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
| | - Zuishuang Guo
- Department of Nephropathy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
| | - Bo Huang
- Department of Nephropathy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
| | - Minhua Xie
- Department of Nephropathy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
| | - Jingjing Ren
- Department of Nephropathy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
| | - Yuze Zhu
- Department of Nephropathy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
| | - Haonan Guo
- Department of Nephropathy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
| | - Yongli Wang
- Department of Nephropathy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
| | - Dan Yu
- Department of Nephropathy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
| | - Junjun Zhang
- Department of Nephropathy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
| | - Linqi Zhang
- Department of Nephropathy, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou 450052, China.
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11
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An evaluation of the roles of hematuria and uric acid in defining the prognosis of patients with IgA nephropathy. Pediatr Nephrol 2022; 37:947-958. [PMID: 33982147 DOI: 10.1007/s00467-021-05092-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2020] [Revised: 04/01/2021] [Accepted: 04/21/2021] [Indexed: 10/21/2022]
Abstract
In recent years, many significant advances have been made in determining which clinical manifestations and pathologic lesions can provide prognostic information for patients with IgA nephropathy (IgAN). However, some important questions remain, including the long-term consequences of hematuria, both macroscopic (MH) and microscopic (mH), in patients with IgAN. The importance of distinguishing patients who have a single episode of MH of long duration from those with recurrent episodes of short duration and the prognostic importance of the episodes of acute kidney injury (AKI) that sometimes accompany episodic MH will be discussed. Studies that have evaluated the mechanisms that may be responsible for recurrent MH and the toxic effects of red blood cells (RBCs), or their constituents, on kidney tubules will also be addressed. In the last section, I will review the evidence that hyperuricemia (HU) may be a significant independent risk factor for progressive kidney disease in patients with IgAN.
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12
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Wang C, Wang F, Zhao B, Xu L, Liu B, Guo Q, Yang X, Wang R. Coexisting nutcracker phenomenon and superior mesenteric artery syndrome in a patient with IgA nephropathy: A case report. Medicine (Baltimore) 2021; 100:e26611. [PMID: 34260546 PMCID: PMC8284758 DOI: 10.1097/md.0000000000026611] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2021] [Accepted: 06/22/2021] [Indexed: 01/04/2023] Open
Abstract
RATIONALE Nutcracker and superior mesenteric artery (SMA) syndrome share the same pathogenesis, but the simultaneous occurrence of both diseases is quite rare. A combination of the nutcracker syndrome and IgA nephropathy has previously been reported. Herein, we report what we believe is the first case of coexisting nutcracker and SMA syndrome in a patient with IgA nephropathy. PATIENT CONCERNS A 15-year-old Chinese boy who was diagnosed with IgA nephropathy at 8 years of age presented with gross hematuria, fatigue, anorexia, nausea, and recurrent abdominal distension for 1 week without any obvious evidence of preceding infection. Laboratory data showed macroscopic hematuria, heavy proteinuria, and relatively normal renal function. Doppler ultrasonography and upper gastrointestinal gastrografin study were performed, respectively. Since his renal function deteriorated after admission, repeated renal biopsy was performed. DIAGNOSES IgA nephropathy with nutcracker phenomenon and SMA syndrome. INTERVENTION Immunosuppressive therapy combined with conservative therapy for superior mesenteric artery syndrome. OUTCOMES One month later, his abdomen symptoms such as anorexia and abdominal distension eased a lot with body weight increase of about 3 kg. After 6 months of follow-up, his body weight increased to 57 kg, serum creatinine decreased to 63 μmol/L, and urine microscopy showed 75.5 RBC/high-power field with 0.3 g urine protein per day. LESSONS Although the association between vascular compression and IgA nephropathy (IgAN) has not been elucidated yet, combination of nutcracker syndrome and SMA syndrome should be considered in patients with IgAN. The combination may increase the complexity of the disease, and renal biopsy should not be hesitated for differential diagnosis.
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Affiliation(s)
- Chenghua Wang
- Department of Emergency center, Provincial Hospital affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Fengmei Wang
- Department of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing, Jiangsu, China
| | - Bing Zhao
- Department of Nephrology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China
| | - Liang Xu
- Department of Nephrology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China
| | - Bing Liu
- Department of Nephrology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China
| | - Qi Guo
- Department of Nephrology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China
| | - Xiaowei Yang
- Department of Nephrology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China
| | - Rong Wang
- Department of Nephrology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China
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13
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Taguchi S, Hidaka S, Yanai M, Ishioka K, Matsui K, Mochida Y, Moriya H, Ohtake T, Kobayashi S. Renal hemosiderosis presenting with acute kidney Injury and macroscopic hematuria in Immunoglobulin A nephropathy: a case report. BMC Nephrol 2021; 22:132. [PMID: 33858363 PMCID: PMC8048362 DOI: 10.1186/s12882-021-02334-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2020] [Accepted: 04/02/2021] [Indexed: 11/19/2022] Open
Abstract
Background Macroscopic hematuria-associated acute kidney injury (AKI) is a well-known complication of immunoglobulin A (IgA) nephropathy. In such cases, intratubular obstruction by red blood cell (RBC) casts and acute tubular necrosis are mainly observed pathologically. Herein, we report the case of a patient with IgA nephropathy presenting with AKI following an episode of macrohematuria. The patient presented with severe renal tubular hemosiderosis and acute tubular necrosis and without any obvious obstructive RBC casts. Case presentation A 68-year-old woman, who was diagnosed with IgA nephropathy on renal biopsy 6 years ago, was admitted to our hospital after an episode of macroscopic glomerular hematuria and AKI following upper respiratory tract infection. Renal biopsy showed mesangial proliferation of the glomeruli, including crescent formation in 17 % of the glomeruli, and acute tubular necrosis without obvious hemorrhage or obstructive RBC casts. The application of Perls’ Prussian blue stain showed hemosiderin deposition in the renal proximal tubular cells. Immunofluorescence showed granular mesangial deposits of IgA and C3. Based on these findings, she was diagnosed with acute tubular necrosis with a concurrent IgA nephropathy flare-up. Moreover, direct tubular injury by heme and iron was considered to be the cause of AKI. She was treated with intravenous pulse methylprednisolone followed by oral prednisolone. Thereafter, the gross hematuria gradually faded, and her serum creatinine levels decreased. Conclusions IgA nephropathy presenting with acute kidney injury accompanied by macrohematuria may cause renal hemosiderosis and acute tubular necrosis without obstructive RBC casts. Hemosiderosis may be a useful indicator for determining the pathophysiology of macroscopic hematuria-associated AKI. However, renal hemosiderosis may remain undiagnosed. Thus, Perls’ Prussian blue iron staining should be more widely used in patients presenting with hematuria.
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Affiliation(s)
- Shinya Taguchi
- Kidney Disease and Transplant Center, Shonan Kamakura General Hospital, 1370-1 Okamoto, 247-8553, Kamakura, Kanagawa, Japan. .,Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, 236-0004, Yokohama, Japan.
| | - Sumi Hidaka
- Kidney Disease and Transplant Center, Shonan Kamakura General Hospital, 1370-1 Okamoto, 247-8553, Kamakura, Kanagawa, Japan
| | - Mitsuru Yanai
- Department of Pathology, Sapporo Tokushukai Hospital, 1-1-1 Oyachi-higashi, Atsubetsu-ku, 004-0041, Sapporo, Hokkaido, Japan.,Hokkaido Renal Pathology Center, IT-FRONTBuilding, 28-196, N9W15, Chuo-ku, 060-0009, Sapporo, Hokkaido, Japan
| | - Kunihiro Ishioka
- Kidney Disease and Transplant Center, Shonan Kamakura General Hospital, 1370-1 Okamoto, 247-8553, Kamakura, Kanagawa, Japan
| | - Kenji Matsui
- Kidney Disease and Transplant Center, Shonan Kamakura General Hospital, 1370-1 Okamoto, 247-8553, Kamakura, Kanagawa, Japan
| | - Yasuhiro Mochida
- Kidney Disease and Transplant Center, Shonan Kamakura General Hospital, 1370-1 Okamoto, 247-8553, Kamakura, Kanagawa, Japan
| | - Hidekazu Moriya
- Kidney Disease and Transplant Center, Shonan Kamakura General Hospital, 1370-1 Okamoto, 247-8553, Kamakura, Kanagawa, Japan
| | - Takayasu Ohtake
- Kidney Disease and Transplant Center, Shonan Kamakura General Hospital, 1370-1 Okamoto, 247-8553, Kamakura, Kanagawa, Japan
| | - Shuzo Kobayashi
- Kidney Disease and Transplant Center, Shonan Kamakura General Hospital, 1370-1 Okamoto, 247-8553, Kamakura, Kanagawa, Japan
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Rajasekaran A, Julian BA, Rizk DV. IgA Nephropathy: An Interesting Autoimmune Kidney Disease. Am J Med Sci 2021; 361:176-194. [PMID: 33309134 PMCID: PMC8577278 DOI: 10.1016/j.amjms.2020.10.003] [Citation(s) in RCA: 97] [Impact Index Per Article: 24.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2020] [Revised: 08/19/2020] [Accepted: 10/05/2020] [Indexed: 12/27/2022]
Abstract
Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. It is a leading cause of chronic kidney disease and progresses to end-stage kidney disease in up to 40% of patients about 20 years after diagnosis. Additionally, IgAN is associated with significant mortality. The diagnosis currently necessitates a kidney biopsy, as no biomarker sufficiently specific and sensitive is available to supplant the procedure. Patients display significant heterogeneity in the epidemiology, clinical manifestations, renal progression, and long-term outcomes across diverse racial and ethnic populations. Recent advances in understanding the underlying pathophysiology of the disease have led to the proposal of a four-hit hypothesis supporting an autoimmune process. To date, there is no disease-specific treatment but, with a better understanding of the disease pathogenesis, new therapeutic approaches are currently being tested in clinical trials. In this review, we examine the multiple facets and most recent advances of this interesting disease.
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Affiliation(s)
- Arun Rajasekaran
- Division of Nephrology, Department of Internal Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
| | - Bruce A Julian
- Division of Nephrology, Department of Internal Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
| | - Dana V Rizk
- Division of Nephrology, Department of Internal Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
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15
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Huang Y, Li XJ, Li YQ, Dai W, Shao T, Liu WY, Han M, Xu G, Liu L. Clinical and pathological findings of SARS-CoV-2 infection and concurrent IgA nephropathy: a case report. BMC Nephrol 2020; 21:504. [PMID: 33234164 PMCID: PMC7685298 DOI: 10.1186/s12882-020-02163-3] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Accepted: 11/11/2020] [Indexed: 12/15/2022] Open
Abstract
Background Since the Coronavirus Disease 2019 (COVID-19) outbreak, there is accumulating data on the clinical characteristics, treatment strategies and prognosis of COVID-19 in patients with concurrent renal disease. Postmortem investigations reveal renal involvement in COVID-19, and most recently, several biopsy researches reveal that acute tubular injury, as well as glomerular nephropathy such as collapsing glomerulopathy were common histological findings. However, to our best knowledge, there is limited data regarding IgA nephropathy in the setting of COVID-19. Case presentation In the present case, we report a 65-year old Chinese woman who presented with dark-colored urine, worsening proteinuria and decreased renal function after COVID-19 infection. She received a renal biopsy during COVID-19 infection. The renal biopsy revealed IgA nephropathy without any evidence for SARS-Cov-2. The findings suggest that the renal abnormalities were a consequence of exacerbation of this patient’s underlying glomerular disease after COVID-19 infection. After a regimen of 3-day course of glucocorticoid and angiotensin II receptor blocker therapy, the patient recovered and remained stable upon follow-up. Conclusions It is important to consider the underlying glomerular disease exacerbation as well as virus induced injury when dealing with renal abnormalities in patients with COVID-19. A kidney biopsy may be indicated to exclude a rapidly progressive glomerular disease.
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Affiliation(s)
- Yi Huang
- Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, P.R. China
| | - Xiao-Juan Li
- Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, P.R. China
| | - Yue-Qiang Li
- Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, P.R. China
| | - Wei Dai
- Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, P.R. China
| | - Tiffany Shao
- Department of Pathology & Laboratory Medicine, University of Calgary, Alberta Precision Laboratories, Calgary, AB, Canada
| | - Wei-Yong Liu
- Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Min Han
- Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, P.R. China
| | - Gang Xu
- Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, P.R. China
| | - Liu Liu
- Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, P.R. China.
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16
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Sumnu A, Turkmen K, Cebeci E, Turkmen A, Eren N, Seyahi N, Oruc A, Dede F, Derici Ü, Basturk T, Şahin G, Sipahioglu M, Sahin GM, Tatar E, Dursun B, Sipahi S, Yılmaz M, Suleymanlar G, Ulu S, Gungor O, Kutlay S, Bahçebaşı ZB, Sahin İ, Kurultak I, Sevinc C, Yilmaz Z, Kazancioglu RT, Cavdar C, Candan F, Aydin Z, Oygar D, Gul B, Altun B, Paydas S, Uzun S, Istemihan Z, Ergul M, Dincer MT, Gullulu M, Piskinpasa S, Akcay OF, Unsal A, Koyuncu S, Gok M, Ozturk S. Characteristics of primary glomerular diseases patients with hematuria in Turkey: the data from TSN-GOLD Working Group. Int Urol Nephrol 2020; 53:945-954. [PMID: 33155086 DOI: 10.1007/s11255-020-02690-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Accepted: 10/27/2020] [Indexed: 10/23/2022]
Abstract
PURPOSE Hematuria is one of the most common laboratory findings in nephrology practice. To date, there is no enough data regarding the clinical and histopathologic characteristics of primary glomerular disease (PGD) patients with hematuria in our country. METHODS Data were obtained from national multicenter (47 centers) data entered into the Turkish Society of Nephrology Glomerular Diseases (TSN-GOLD) database between May 2009 and June 2019. The data of all PGD patients over the age of 16 years who were diagnosed with renal biopsy and had hematuria data were included in the study. Demographic characteristics, laboratory and biopsy findings were also recorded. RESULTS Data of 3394 PGD patients were included in the study. While 1699 (50.1%) patients had hematuria, 1695 (49.9%) patients did not have hematuria. Patients with hematuria had statistically higher systolic blood pressure, serum blood urea nitrogen, creatinine, albumin, levels and urine pyuria. However, these patients had statistically lower age, body mass index, presence of hypertension and diabetes, eGFR, 24-h proteinuria, serum total, HDL and LDL cholesterol, and C3 levels when compared with patients without hematuria. Hematuria was present 609 of 1733 patients (35.8%) among the patients presenting with nephrotic syndrome, while it was presented in 1090 of 1661 (64.2%) patients in non-nephrotics (p < 0.001). CONCLUSION This is the first multicenter national report regarding the demographic and histopathologic data of PGD patients with or without hematuria. Hematuria, a feature of nephritic syndrome, was found at a higher than expected in the PGDs presenting with nephrotic syndrome in our national database.
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Affiliation(s)
- Abdullah Sumnu
- Department of Nephrology, Medical Faculty, Medipol Mega Hastanesi, Medipol University, Göztepe Mahallesi Metin Sk. No: 4, Bağcılar, Istanbul, Turkey.
| | - Kultigin Turkmen
- Nephrology, Meram Medical Faculty, Necmettin Erbakan University, Konya, Turkey
| | - Egemen Cebeci
- Nephrology, Haseki Training and Research Hospital, Istanbul, Turkey
| | - Aydin Turkmen
- Nephrology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey
| | - Necmi Eren
- Nephrology Medical Faculty, Kocaeli University, İzmit, Kocaeli, Turkey
| | - Nurhan Seyahi
- Nephrology, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey
| | - Aysegul Oruc
- Nephrology, Medical Faculty, Uludag University, Bursa, Turkey
| | - Fatih Dede
- Nephrology, Ankara Numune Training and Research Hospital, Ankara, Turkey
| | - Ülver Derici
- Nephrology, Medical Faculty, Gazi University, Ankara, Turkey
| | - Taner Basturk
- Nephrology, Hamidiye Sisli Etfal Training and Research Hospital, Istanbul, Turkey
| | - Garip Şahin
- Nephrology, Medical Faculty, Eskisehir Osmangazi University, Eskisehir, Turkey
| | - Murat Sipahioglu
- Nephrology, Medical Faculty, Erciyes University, Kayseri, Turkey
| | - Gulizar Manga Sahin
- Nephrology, Sultan Abdulhamit Han Research and Training Hospital, Istanbul, Turkey
| | - Erhan Tatar
- Nephrology, Bozyaka Training and Research Hospital, Izmır, Turkey
| | - Belda Dursun
- Nephrology, Medical Faculty, Pamukkale University, Denizli, Turkey
| | - Savas Sipahi
- Nephrology, Medical Faculty, Sakarya University, Sakarya, Turkey
| | - Mürvet Yılmaz
- Nephrology, Bakirkoy Sadi Konuk Training and Research Hospital, Istanbul, Turkey
| | | | - Sena Ulu
- Nephrology, Medical Faculty, Afyon University, Afyon, Turkey
| | - Ozkan Gungor
- Nephrology, Medical Faculty, Sutcu İmam University, Kahramanmaras, Turkey
| | - Sim Kutlay
- Nephrology, İbni Sina Hospital, Medical Faculty, Ankara University, Ankara, Turkey
| | | | - İdris Sahin
- Nephrology, Medical Faculty, Inonu University, Malatya, Turkey
| | - Ilhan Kurultak
- Nephrology, Medical Faculty, Trakya University, Edirne, Turkey
| | - Can Sevinc
- Nephrology, Medical Faculty, Ataturk University, Erzurum, Turkey
| | | | | | - Caner Cavdar
- Nephrology, Medical Faculty, Dokuz Eylul University, Izmir, Turkey
| | - Ferhan Candan
- Nephrology, Medical Faculty, Cumhuriyet University, Sivas, Turkey
| | - Zeki Aydin
- Nephrology, Darica Farabi Training and Research Hospital, Darıca, Kocaeli, Turkey
| | - Deren Oygar
- Nephrology, Burhan Nalbantoglu State Hospital, Lefkosa, Cyprus
| | - Bulent Gul
- Nephrology, Bursa Yuksek Ihtisas Training and Research Hospital, Nilüfer, Bursa, Turkey
| | - Bulent Altun
- Nephrology, Medical Faculty, Hacettepe University, Ankara, Turkey
| | - Saime Paydas
- Nephrology, Medical Faculty, Cukurova University, Adana, Turkey
| | - Sami Uzun
- Nephrology, Haseki Training and Research Hospital, Istanbul, Turkey
| | - Zulal Istemihan
- Internal Medicine, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey
| | - Metin Ergul
- Nephrology Medical Faculty, Kocaeli University, İzmit, Kocaeli, Turkey
| | - Mevlut Tamer Dincer
- Nephrology, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey
| | - Mustafa Gullulu
- Nephrology, Medical Faculty, Uludag University, Bursa, Turkey
| | - Serhan Piskinpasa
- Nephrology, Ankara Numune Training and Research Hospital, Ankara, Turkey
| | | | - Abdulkadir Unsal
- Nephrology, Hamidiye Sisli Etfal Training and Research Hospital, Istanbul, Turkey
| | - Sumeyra Koyuncu
- Nephrology, Medical Faculty, Erciyes University, Kayseri, Turkey
| | - Mahmut Gok
- Nephrology, Sultan Abdulhamit Han Research and Training Hospital, Istanbul, Turkey
| | - Savas Ozturk
- Nephrology, Haseki Training and Research Hospital, Istanbul, Turkey
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17
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Gutiérrez E, Carvaca-Fontán F, Luzardo L, Morales E, Alonso M, Praga M. A Personalized Update on IgA Nephropathy: A New Vision and New Future Challenges. Nephron Clin Pract 2020; 144:555-571. [PMID: 32818944 DOI: 10.1159/000509997] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2020] [Accepted: 07/08/2020] [Indexed: 11/19/2022] Open
Abstract
IgA nephropathy (IgAN) is the most common primary glomerulonephritis in the world among patients undergoing renal biopsy. Approximately 30% of patients with IgAN develop end-stage kidney disease 20 years after renal biopsy. It is a glomerulopathy with a very broad clinical presentation, making it difficult to stratify and treat. IgAN is characterized by dysregulation of the immune system, which causes an abnormal synthesis of IgA1 that is deglycosylated causing its mesangial deposition. IgAN pathogenesis is incompletely understood; the current multi-hit hypothesis of IgAN pathogenesis does not explain the range of glomerular inflammation and renal injury associated with mesangial IgA deposition. Although associations between IgAN and glomerular and circulating markers of complement activation are established, the mechanism of complement activation and contribution to glomerular inflammation and injury are not defined. On the other hand, the renal-gut connection can also play an important role in the pathogenesis of IgAN with possible therapeutic implications. In order to standardize the histological findings, the Oxford Classification has allowed clarifying renal lesions that confer potential risk of progression. Currently, except for the blockade of the renin-angiotensin-aldosterone system, no other therapies are available in clinical setting for the treatment of IgAN, although the range of new drugs under investigation is extensive. The incorporation in the next trials of clinical parameters such as the amount of hematuria and histological lesions may allow more personalized therapeutic approaches. To summarize, in recent years, several important efforts have taken place in the understanding of IgAN, but still, further studies are warranted to elucidate the best therapeutic strategies according to the risk to improve the prognosis of this entity.
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Affiliation(s)
- Eduardo Gutiérrez
- Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain, .,Department of Nephrology, Hospital Universitario 12 de Octubre, Madrid, Spain,
| | - Fernando Carvaca-Fontán
- Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain.,Department of Medicine, Universidad Complutense de Madrid, Madrid, Spain
| | - Leonella Luzardo
- Department of Nephrology and Pathophysiology, School of Medicine, Universidad de la República, Montevideo, Uruguay
| | - Enrique Morales
- Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain.,Department of Medicine, Universidad Complutense de Madrid, Madrid, Spain
| | - Marina Alonso
- Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain.,Department of Pathological Anatomy, Hospital Universitario 12 de Octubre, Madrid, Spain
| | - Manuel Praga
- Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain.,Department of Medicine, Universidad Complutense de Madrid, Madrid, Spain
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18
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Suh JS, Jang KM, Hyun H, Cho MH, Lee JH, Park YS, Oh JH, Kim JH, Yoo KH, Chung WY, Kim SH, Kim K, Lee DY, Lee JW, Cho MH, Park H, Koo JW, Han KH, Yang EM, Lee KH, Shin JI, Cho H, Kim KS, Ha IS, Park YH, Kang HG. Remission of Proteinuria May Protect against Progression to Chronic Kidney Disease in Pediatric-Onset IgA Nephropathy. J Clin Med 2020; 9:jcm9072058. [PMID: 32629965 PMCID: PMC7408672 DOI: 10.3390/jcm9072058] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Revised: 06/24/2020] [Accepted: 06/27/2020] [Indexed: 01/25/2023] Open
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.
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Affiliation(s)
- Jin-Soon Suh
- Departments of Pediatrics, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Bucheon 14647, Korea;
| | - Kyung Mi Jang
- Yeungnam University Hospital, Daegu 42415, Korea; (K.M.J.); (Y.H.P.)
| | - Hyesun Hyun
- St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon 16247, Korea;
| | - Myung Hyun Cho
- Hallym University Sacred Heart Hospital, Anyang 14068, Korea;
| | - Joo Hoon Lee
- Asan Medical Center Children’s Hospital, University of Ulsan College of Medicine, Seoul 05505, Korea; (J.H.L.); (Y.S.P.)
| | - Young Seo Park
- Asan Medical Center Children’s Hospital, University of Ulsan College of Medicine, Seoul 05505, Korea; (J.H.L.); (Y.S.P.)
| | - Jae Hyuk Oh
- Ajou University Hospital, School of Medicine, Suwon 16499, Korea;
| | - Ji Hong Kim
- Department of Pediatrics, Yonsei University College of Medicine, Seoul 03722, Korea; (J.H.K.); (K.H.L.); (J.I.S.)
| | - Kee Hwan Yoo
- Korea University Guro Hospital, Seoul 08308, Korea;
| | - Woo Yeong Chung
- Busan Paik Hospital, College of Medicine, Inje University, Busan 47392, Korea;
| | - Seong Heon Kim
- Pusan National University Children’s Hospital, Yangsan 50612, Korea;
| | - Keehyuck Kim
- National Health Insurance Service Ilsan Hospital, Goyang 10444, Korea;
| | - Dae Yeol Lee
- Jeonbuk National University Hospital, Jeonju 54907, Korea;
| | - Jung Won Lee
- Ewha Womans University Seoul Hospital, Seoul 07804, Korea;
| | - Min Hyun Cho
- School of Medicine, Kyungpook National University, Daegu 41944, Korea;
| | - Hyewon Park
- Seoul National University Bundang Hospital, Seongnam 13620, Korea;
| | - Ja Wook Koo
- Inje University Sanggye Paik Hospital, Seoul 01757, Korea;
| | - Kyoung Hee Han
- Jeju National University School of Medicine, Jeju 63243, Korea;
| | - Eun Mi Yang
- Chonnam National University Hospital and Medical School, Hwasun 58128, Korea;
| | - Keum Hwa Lee
- Department of Pediatrics, Yonsei University College of Medicine, Seoul 03722, Korea; (J.H.K.); (K.H.L.); (J.I.S.)
| | - Jae Il Shin
- Department of Pediatrics, Yonsei University College of Medicine, Seoul 03722, Korea; (J.H.K.); (K.H.L.); (J.I.S.)
| | - Heeyeon Cho
- Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea;
| | | | - Il-Soo Ha
- Seoul National University College of Medicine and Seoul National University Children’s Hospital, Seoul 03080, Korea;
| | - Yong Hoon Park
- Yeungnam University Hospital, Daegu 42415, Korea; (K.M.J.); (Y.H.P.)
| | - Hee Gyung Kang
- Seoul National University College of Medicine and Seoul National University Children’s Hospital, Seoul 03080, Korea;
- Correspondence:
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19
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Qvigstad C, Tait RC, de Moerloose P, Holme PA. Hematuria in aging men with hemophilia: Association with factor prophylaxis. Res Pract Thromb Haemost 2020; 4:309-317. [PMID: 32110762 PMCID: PMC7040553 DOI: 10.1002/rth2.12298] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2019] [Revised: 11/17/2019] [Accepted: 11/22/2019] [Indexed: 12/14/2022] Open
Abstract
INTRODUCTION Macroscopic hematuria is considered a significant risk factor for urologic disease, and it is highly prevalent in people with hemophilia. AIM To determine whether prophylactic factor replacement therapy is associated with reduced occurrence of macroscopic hematuria in people with hemophilia in a post hoc analysis using data from a cross-sectional study conducted by the Age-Related Developments and Comobordities in Hemophilia (ADVANCE) Working Group that included males with hemophilia ≥40 years of age. METHODS Data from 16 contributing centers, in 13 European countries and Israel, were analyzed using logistic regression. Of 532 recruited individuals, this analysis included 370 patients with moderate or severe hemophilia who received on-demand or prophylactic therapy. RESULTS For patients with a history of macroscopic hematuria, we analyzed the association between prophylaxis and reoccurrence of macroscopic hematuria within the past 5 years (n = 235 patients). Frequent (≥3 times/wk) prophylaxis was negatively associated with a recent episode of macroscopic hematuria (odds ratio [OR], 0.38; 95% confidence interval [CI], 0.18-0.76). We also analyzed whether prophylaxis corresponded to a lower lifetime number of macroscopic hematuria episodes (n = 285 patients). Frequent prophylaxis for >15 years was associated with a lower number of episodes compared to on-demand treatment (OR, 0.29; 95% CI, 0.16-0.54), whereas nonsteroidal anti-inflammatory drugs (NSAIDs) and severe hemophilia were associated with a higher number. There was no association of prophylaxis <3 times/wk with hematuria. CONCLUSION Frequent prophylaxis was negatively associated with the number of episodes of macroscopic hematuria in people with hemophilia. Prevalence of macroscopic hematuria was higher among individuals with severe hemophilia and those regularly using NSAIDs.
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Affiliation(s)
- Christian Qvigstad
- Department of HaematologyOslo University HospitalOsloNorway
- Institute of Clinical MedicineUniversity of OsloOsloNorway
| | | | | | - Pål Andre Holme
- Department of HaematologyOslo University HospitalOsloNorway
- Institute of Clinical MedicineUniversity of OsloOsloNorway
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20
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Ikeda M, Tanaka M, Shimoda S, Saita H, Nishikawa S, Shimada H, Taniguchi K, Hagihara K, Iwanari S, Takeoka H. Dabigatran-induced anticoagulant-related nephropathy with undiagnosed IgA nephropathy in a patient with normal baseline renal function. CEN Case Rep 2019; 8:292-296. [PMID: 31347098 PMCID: PMC6820621 DOI: 10.1007/s13730-019-00410-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2019] [Accepted: 07/16/2019] [Indexed: 12/29/2022] Open
Abstract
Occasionally, over-anticoagulation with warfarin induces acute kidney injury (AKI) characterized by glomerular hemorrhage with tubular obstruction by red blood cell casts, which is widely acknowledged as warfarin-related nephropathy. Owing to extensive use of direct oral anticoagulants, similar AKI cases have been reported among patients treated with dabigatran. Dabigatran is primarily excreted by the kidneys; thus, renal impairment is one of the risk factors for dabigatran-induced bleeding complications. Nevertheless, risk factors for dabigatran-induced anticoagulant-related nephropathy (ARN) remain partially clarified. Here, we report a histologically established case of dabigatran-induced ARN with undiagnosed IgA nephropathy in a patient with normal baseline renal function. In addition, we summarize previously published cases of biopsy-proven, dabigatran-related ARN. A 67-year-old female with normal preexisting renal function developed macrohematuria and AKI. She had been treated with dabigatran for deep vein thrombosis. A renal biopsy diagnosed ARN with inactive IgA nephropathy. After dabigatran withdrawal, her macrohematuria and renal function improved. This report demonstrates that ARN could occur in patients with normal baseline renal function. Our case and prior reports suggest that IgA nephropathy could be a risk factor for dabigatran-induced ARN.
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Affiliation(s)
- Masaki Ikeda
- Department of Nephrology and Dialysis, Hyogo Prefectural Amagasaki General Medical Center, 2-17-77 Higashinaniwa-cho, Hyogo, Amagasaki, 660-8550, Japan.
| | - Mari Tanaka
- Department of Nephrology and Dialysis, Hyogo Prefectural Amagasaki General Medical Center, 2-17-77 Higashinaniwa-cho, Hyogo, Amagasaki, 660-8550, Japan
| | - Saeko Shimoda
- Department of Nephrology and Dialysis, Hyogo Prefectural Amagasaki General Medical Center, 2-17-77 Higashinaniwa-cho, Hyogo, Amagasaki, 660-8550, Japan
| | - Hirona Saita
- Department of Nephrology and Dialysis, Hyogo Prefectural Amagasaki General Medical Center, 2-17-77 Higashinaniwa-cho, Hyogo, Amagasaki, 660-8550, Japan
| | - Seira Nishikawa
- Department of Nephrology and Dialysis, Hyogo Prefectural Amagasaki General Medical Center, 2-17-77 Higashinaniwa-cho, Hyogo, Amagasaki, 660-8550, Japan
| | - Hiroki Shimada
- Department of Nephrology and Dialysis, Hyogo Prefectural Amagasaki General Medical Center, 2-17-77 Higashinaniwa-cho, Hyogo, Amagasaki, 660-8550, Japan
| | - Keisuke Taniguchi
- Department of Nephrology and Dialysis, Hyogo Prefectural Amagasaki General Medical Center, 2-17-77 Higashinaniwa-cho, Hyogo, Amagasaki, 660-8550, Japan
| | - Koichiro Hagihara
- Department of Nephrology and Dialysis, Hyogo Prefectural Amagasaki General Medical Center, 2-17-77 Higashinaniwa-cho, Hyogo, Amagasaki, 660-8550, Japan
| | - Sachio Iwanari
- Department of Nephrology and Dialysis, Hyogo Prefectural Amagasaki General Medical Center, 2-17-77 Higashinaniwa-cho, Hyogo, Amagasaki, 660-8550, Japan
| | - Hiroya Takeoka
- Department of Nephrology and Dialysis, Hyogo Prefectural Amagasaki General Medical Center, 2-17-77 Higashinaniwa-cho, Hyogo, Amagasaki, 660-8550, Japan
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21
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¿Es posible predecir la evolución de la nefropatia IgA? Validamos la calculadora de progresión de nefropatia IgA y su relación con Oxford score en nuestra población. Nefrologia 2019; 39:523-530. [DOI: 10.1016/j.nefro.2018.10.015] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2018] [Revised: 08/23/2018] [Accepted: 10/31/2018] [Indexed: 12/27/2022] Open
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22
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Gutiérrez E, Praga M, Rivera F, Sevillano A, Yuste C, Goicoechea M, López-Gómez JM. Changes in the clinical presentation of immunoglobulin A nephropathy: data from the Spanish Registry of Glomerulonephritis. Nephrol Dial Transplant 2019; 33:472-477. [PMID: 28460086 DOI: 10.1093/ndt/gfx058] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2016] [Accepted: 03/06/2017] [Indexed: 01/31/2023] Open
Abstract
Background Immunoglobulin A nephropathy (IgAN) is the most common glomerulonephritis in the world, but there is little epidemiological data about possible changes in its presentation over the years. Available information about the influence of age on the form of clinical presentation is also scarce. Methods The aim of the study was to analyse all renal biopsies performed between 1994 and 2013 and recorded in the Spanish Registry of Glomerulonephritis with a histological diagnosis of IgAN. The study was divided into five 4-year periods (1994-97, 1998-2001, 2002-05, 2006-09 and 2010-13) and patients were divided into four age groups: ≤16, 17-44, 45-64 and ≥65 years. Results From 20.974 renal biopsies recorded, 2961 (14.1%) corresponded to IgAN. The prevalence of IgAN remained stable, but a significant increase in age [from 37.6 (SD 17.7) in 1994-97 to 44.9 (SD 16.8) years in 2010-13; P = 0.001] and worse renal function at presentation [from serum creatinine (SCr) 1.9 (SD 1.9) in 1994-97 to 2.3 (SD 2.1) mg/dL in 2010-13; P = 0.001] were observed over the years. Nephrotic-range proteinuria and acute kidney injury (AKI) as forms of presentation were significantly more common among patients ≥65 years (17.7% and 43.2%, respectively) as compared with the other age groups [≤16 (11.4% and 13.1%, respectively), 17-44 (13.1% and 13%, respectively) and 45-64 (12.1% and 21.3%, respectively)]. Blood pressure, SCr and proteinuria were also significantly higher at presentation among elderly patients. Conclusions Although the prevalence of IgAN in Spain has remained stable over the years, patients are significantly older and present with significantly worse renal function in the last years. The incidence of nephrotic-range proteinuria (17.7%) and AKI (43.2%) as forms of presentation is remarkable among patients ≥65 years of age.
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Affiliation(s)
- Eduardo Gutiérrez
- Department of Nephrology and Research Institute, University Hospital 12 de Octubre, Madrid, Spain
| | - Manuel Praga
- Department of Nephrology and Research Institute, University Hospital 12 de Octubre, Madrid, Spain.,Department of Medicine, Complutense University, Madrid, Spain
| | - Francisco Rivera
- Department of Nephrology, General Hospital of Ciudad Real, Ciudad Real, Spain
| | - Angel Sevillano
- Department of Nephrology and Research Institute, University Hospital 12 de Octubre, Madrid, Spain
| | - Claudia Yuste
- Department of Nephrology and Research Institute, University Hospital 12 de Octubre, Madrid, Spain
| | - Marian Goicoechea
- Department of Nephrology, University General Hospital Gregorio Marañón, Madrid, Spain
| | - Juan M López-Gómez
- Department of Nephrology, University General Hospital Gregorio Marañón, Madrid, Spain
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23
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Tortajada A, Gutierrez E, Pickering MC, Praga Terente M, Medjeral-Thomas N. The role of complement in IgA nephropathy. Mol Immunol 2019; 114:123-132. [PMID: 31351413 DOI: 10.1016/j.molimm.2019.07.017] [Citation(s) in RCA: 82] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2019] [Revised: 07/16/2019] [Accepted: 07/16/2019] [Indexed: 12/22/2022]
Abstract
IgA nephropathy (IgAN) is common and often progresses to end stage renal disease. IgAN encompasses a wide range of histology and clinical features. IgAN pathogenesis is incompletely understood; the current multi-hit hypothesis of IgAN pathogenesis does not explain the range of glomerular inflammation and renal injury associated with mesangial IgA deposition. Although associations between IgAN and glomerular and circulating markers of complement activation are established, the mechanism of complement activation and contribution to glomerular inflammation and injury are not defined. Recent identification of specific complement pathways and proteins in severe IgAN cases had advanced our understanding of complement in IgAN pathogenesis. In particular, a growing body of evidence implicates the complement factor H related proteins 1 and 5 and lectin pathway as pathogenic in a subset of patients with severe disease. These data suggest complement deregulation and activity may be dominant drivers of renal injury in IgAN. Thereby, markers of complement activation may identify IgAN patients likely to progress to significant renal impairment and complement inhibition may emerge as an effective method of preventing and reducing glomerular injury in IgAN.
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Affiliation(s)
- Agustin Tortajada
- Department of Immunology, Ophthalmology and ENT, Complutense University School of Medicine and 12 de Octubre Health Research Institute (imas12), Madrid, Spain
| | - Eduardo Gutierrez
- Department of Nephrology, Research Institute Universitary Hospital 12 de Octubre (imas12), Madrid, Spain
| | | | - Manuel Praga Terente
- Department of Nephrology, Research Institute Universitary Hospital 12 de Octubre (imas12), Madrid, Spain
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24
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Sevillano AM, Diaz M, Caravaca-Fontán F, Barrios C, Bernis C, Cabrera J, Calviño J, Castillo L, Cobelo C, Delgado-Mallén P, Espinosa M, Fernandez-Juarez G, Fernandez-Reyes MJ, Garcia-Osuna R, Garcia P, Goicoechea M, Gonzalez-Cabrera F, Guzmán DA, Heras M, Martín-Reyes G, Martinez A, Olea T, Peña JK, Quintana LF, Rabasco C, López Revuelta K, Rodas L, Rodriguez-Mendiola N, Rodriguez E, San Miguel L, Sanchez de la Nieta MD, Shabaka A, Sierra M, Valera A, Velo M, Verde E, Ballarin J, Noboa O, Moreno JA, Gutiérrez E, Praga M. IgA Nephropathy in Elderly Patients. Clin J Am Soc Nephrol 2019; 14:1183-1192. [PMID: 31311818 PMCID: PMC6682823 DOI: 10.2215/cjn.13251118] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2018] [Accepted: 05/01/2019] [Indexed: 12/16/2022]
Abstract
BACKGROUND AND OBJECTIVES Some studies suggest that the incidence of IgA nephropathy is increasing in older adults, but there is a lack of information about the epidemiology and behavior of the disease in that age group. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS In this retrospective multicentric study, we analyzed the incidence, forms of presentation, clinical and histologic characteristics, treatments received, and outcomes in a cohort of 151 patients ≥65 years old with biopsy-proven IgA nephropathy diagnosed between 1990 and 2015. The main outcome was a composite end point of kidney replacement therapy or death before kidney replacement therapy. RESULTS We found a significant increase in the diagnosis of IgA nephropathy over time from six patients in 1990-1995 to 62 in 2011-2015 (P value for trend =0.03). After asymptomatic urinary abnormalities (84 patients; 55%), AKI was the most common form of presentation (61 patients; 40%). Within the latter, 53 (86%) patients presented with hematuria-related AKI (gross hematuria and tubular necrosis associated with erythrocyte casts as the most important lesions in kidney biopsy), and eight patients presented with crescentic IgA nephropathy. Six (4%) patients presented with nephrotic syndrome. Among hematuria-related AKI, 18 (34%) patients were receiving oral anticoagulants, and this proportion rose to 42% among the 34 patients older than 72 years old who presented with hematuria-related AKI. For the whole cohort, survival rates without the composite end point were 74%, 48%, and 26% at 1, 2, and 5 years, respectively. Age, serum creatinine at presentation, and the degree of interstitial fibrosis in kidney biopsy were risk factors significantly associated with the outcome, whereas treatment with renin-angiotensin-aldosterone blockers was associated with a lower risk. Immunosuppressive treatments were not significantly associated with the outcome. CONCLUSIONS The diagnosis of IgA nephropathy among older adults in Spain has progressively increased in recent years, and anticoagulant therapy may be partially responsible for this trend. Prognosis was poor. PODCAST This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2019_07_16_CJASNPodcast_19_08_.mp3.
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Affiliation(s)
- Angel M Sevillano
- Department of Nephrology, Hospital Universitario 12 de Octubre, Madrid, Spain.,Department of Medicine, Complutense University, Madrid, Spain
| | - Monserrat Diaz
- Department of Nephrology, Fundación Puigvert, Barcelona, Spain
| | - Fernando Caravaca-Fontán
- Department of Nephrology, Hospital Universitario 12 de Octubre, Madrid, Spain.,Department of Medicine, Complutense University, Madrid, Spain
| | - Clara Barrios
- Department of Nephrology, Hospital del Mar, Barcelona, Spain
| | - Carmen Bernis
- Department of Nephrology, Hospital Universitario de La Princesa, Madrid, Spain
| | - Jimena Cabrera
- Programa de prevención y tratamiento de las glomerulopatias (PPTG) de Uruguay, Sociedad Uruguaya de Nefrologia Centro de Nefrología, Hospital de Clinicas Montevideo, Montevideo, Uruguay
| | - Jesus Calviño
- Department of Nephrology, Hospital de Lucus Augusti, Lugo, Spain
| | - Lorena Castillo
- Department of Nephrology, Hospital Universitario Joan XXIII, Tarragona, Spain
| | - Carmen Cobelo
- Department of Nephrology, Hospital de Lucus Augusti, Lugo, Spain
| | | | - Mario Espinosa
- Department of Nephrology, Hospital Universitario Reina Sofia, Cordoba, Spain
| | - Gema Fernandez-Juarez
- Department of Nephrology, Hospital Universitario Fundación Alcorcón, Alcorcon, Spain
| | | | | | - Patricia Garcia
- Department of Nephrology, Hospital Virgen de la Victoria, Malaga, Spain
| | - Marian Goicoechea
- Department of Nephrology, Hospital Universitario Gregorio Marañón, Madrid, Spain
| | - Fayna Gonzalez-Cabrera
- Department of Nephrology, Hospital Universitario de Gran Canaria Dr. Negrin, Gran Canaria, Spain
| | - Diomaris A Guzmán
- Department of Nephrology, Hospital Regional Universitario de Málaga, Malaga, Spain
| | - Manuel Heras
- Department of Nephrology, Hospital General de Segovia, Segovia, Spain
| | | | - Alberto Martinez
- Department of Nephrology, Hospital Universitario Joan XXIII, Tarragona, Spain
| | - Teresa Olea
- Department of Nephrology, Hospital Universitario La Paz, Madrid, Spain
| | - Jessy Korina Peña
- Department of Nephrology, Hospital Principe de Asturias, Alcala de Henares, Spain
| | - Luis F Quintana
- Department of Nephrology, Hospital Clinic de Barcelona, Barcelona, Spain
| | - Cristina Rabasco
- Department of Nephrology, Hospital Universitario Reina Sofia, Cordoba, Spain
| | - Katia López Revuelta
- Department of Nephrology, Hospital Universitario Fundación Alcorcón, Alcorcon, Spain
| | - Lida Rodas
- Department of Nephrology, Hospital Clinic de Barcelona, Barcelona, Spain
| | | | - Eva Rodriguez
- Department of Nephrology, Hospital del Mar, Barcelona, Spain
| | - Luz San Miguel
- Department of Nephrology, Fundación Puigvert, Barcelona, Spain
| | | | - Amir Shabaka
- Department of Nephrology, Hospital Clínico de Madrid, Madrid, Spain
| | - Milagros Sierra
- Department of Nephrology, Hospital San Pedro, Logrono, Spain
| | - Alfonso Valera
- Department of Nephrology, Hospital Virgen de la Victoria, Malaga, Spain
| | - Mercedes Velo
- Department of Nephrology, Hospital Clínico de Madrid, Madrid, Spain
| | - Eduardo Verde
- Department of Nephrology, Hospital Universitario Gregorio Marañón, Madrid, Spain
| | - Jose Ballarin
- Department of Nephrology, Fundación Puigvert, Barcelona, Spain
| | - Oscar Noboa
- Nephrology Center, Hospital de Clínicas, Department of Medicine, Republic University, Montevideo, Uruguay; and
| | - Juan Antonio Moreno
- Department of Cell Biology, Physiology, and Immunology, Maimonides Biomedical Research Institute of Cordoba, University of Cordoba, Cordoba, Spain
| | - Eduardo Gutiérrez
- Department of Nephrology, Hospital Universitario 12 de Octubre, Madrid, Spain
| | - Manuel Praga
- Department of Nephrology, Hospital Universitario 12 de Octubre, Madrid, Spain; .,Department of Medicine, Complutense University, Madrid, Spain
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Yasukawa M, Kitagawa S, Togashi R, Asakawa S, Nagura M, Arai S, Yamazaki O, Tamura Y, Kondo F, Ohashi R, Uchida S, Shibata S, Fujigaki Y. A Patient with MPO-ANCA-positive IgA Nephropathy Diagnosed with the Clinical Onset of Macrohematuria. Intern Med 2019; 58:2051-2056. [PMID: 30918194 PMCID: PMC6702016 DOI: 10.2169/internalmedicine.2475-18] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
A 21-year-old woman presented with renal dysfunction during macrohematuria. A kidney biopsy revealed IgA nephropathy with a small percentage of crescent formation and macrohematuria-associated tubular injury. Macrohematuria-associated acute kidney injury could explain her renal dysfunction. However, she was seropositive for myeloperoxidase (MPO)-anti-neutrophil cytoplasmic antibody (ANCA) and showed fibrin deposition around one arteriole. Corticosteroids and mycophenolate mofetil were administered as for ANCA vasculitis, and the serum creatinine, abnormal urinalysis and MPO-ANCA titer all gradually ameliorated. The presence of extra-glomerular vasculitis, which was probably induced by ANCA, suggested that MPO-ANCA was an exacerbating factor for her prolonged renal dysfunction. This condition has so far only rarely been addressed in ANCA-positive IgA nephropathy.
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Affiliation(s)
- Minoru Yasukawa
- Department of Internal Medicine, Teikyo University School of Medicine, Japan
| | - Sachiko Kitagawa
- Department of Internal Medicine, Teikyo University School of Medicine, Japan
| | - Ryo Togashi
- Department of Internal Medicine, Teikyo University School of Medicine, Japan
| | - Shinichiro Asakawa
- Department of Internal Medicine, Teikyo University School of Medicine, Japan
| | - Michito Nagura
- Department of Internal Medicine, Teikyo University School of Medicine, Japan
| | - Shigeyuki Arai
- Department of Internal Medicine, Teikyo University School of Medicine, Japan
| | - Osamu Yamazaki
- Department of Internal Medicine, Teikyo University School of Medicine, Japan
| | - Yoshifuru Tamura
- Department of Internal Medicine, Teikyo University School of Medicine, Japan
| | - Fukuo Kondo
- Department of Pathology, Teikyo University Hospital, Japan
| | - Ryuji Ohashi
- Department of Diagnostic Pathology, Nippon Medical School Musashikosugi Hospital, Japan
| | - Shunya Uchida
- Department of Internal Medicine, Teikyo University School of Medicine, Japan
| | - Shigeru Shibata
- Department of Internal Medicine, Teikyo University School of Medicine, Japan
| | - Yoshihide Fujigaki
- Department of Internal Medicine, Teikyo University School of Medicine, Japan
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Glomerular Hematuria: Cause or Consequence of Renal Inflammation? Int J Mol Sci 2019; 20:ijms20092205. [PMID: 31060307 PMCID: PMC6539976 DOI: 10.3390/ijms20092205] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2019] [Revised: 04/21/2019] [Accepted: 04/28/2019] [Indexed: 12/12/2022] Open
Abstract
Glomerular hematuria is a cardinal symptom of renal disease. Glomerular hematuria may be classified as microhematuria or macrohematuria according to the number of red blood cells in urine. Recent evidence suggests a pathological role of persistent glomerular microhematuria in the progression of renal disease. Moreover, gross hematuria, or macrohematuria, promotes acute kidney injury (AKI), with subsequent impairment of renal function in a high proportion of patients. In this pathological context, hemoglobin, heme, or iron released from red blood cells in the urinary space may cause direct tubular cell injury, oxidative stress, pro-inflammatory cytokine production, and further monocyte/macrophage recruitment. The aim of this manuscript is to review the role of glomerular hematuria in kidney injury, the role of inflammation as cause and consequence of glomerular hematuria, and to discuss novel therapies to combat hematuria.
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Li X, Cheung CY. Dabigatran causing severe acute kidney injury in a patient with liver cirrhosis. CEN Case Rep 2019; 8:125-127. [PMID: 30659506 DOI: 10.1007/s13730-019-00378-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2018] [Accepted: 01/08/2019] [Indexed: 01/09/2023] Open
Abstract
Anticoagulant-related nephropathy (ARN), a significant but frequently undiagnosed problem in patients receiving anticoagulation, is found to be associated with increased renal morbidity and all-cause mortality. While ARN is mainly associated with warfarin use, recent case reports suggest that it may also occur in patients taking direct oral anticoagulants (DOAC). We report a patient who had a history of alcoholic liver cirrhosis and paroxysmal atrial fibrillation, and received dabigatran 110 mg twice daily for 1 year. He presented with gross hematuria and severe acute kidney injury with an international normalized ratio of 4.09. Dabigatran was stopped and he was put on temporary hemodialysis support. His renal function gradually improved when the hematuria subsided. Renal biopsy later confirmed the presence of red blood cell casts inside the renal tubules with features of IgA nephropathy. Finally, his renal function returned back to baseline level. As DOAC has been increasingly used nowadays for the treatment of various thromboembolic diatheses, regular monitoring of renal function is warranted, especially in patients with underlying glomerular diseases and coagulopathy such as chronic liver diseases.
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Affiliation(s)
- Xin Li
- Department of Microbiology, Queen Mary Hospital, Hong Kong, SAR, China
| | - Chi Yuen Cheung
- Renal Unit, Department of Medicine, Queen Elizabeth Hospital, 30 Gascoigne Road, Kowloon, Hong Kong, SAR, China.
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Praga M, Caravaca F, Yuste C, Cavero T, Hernández E, Morales E, Mérida E, Moreno JA, Sevillano A, Gutiérrez E. IgA nephropathy: What patients are at risk of progression to end-stage renal disease and how should they be treated? Nefrologia 2018; 38:347-352. [PMID: 29636281 DOI: 10.1016/j.nefro.2018.01.001] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2017] [Revised: 01/04/2018] [Accepted: 01/15/2018] [Indexed: 11/25/2022] Open
Affiliation(s)
- Manuel Praga
- Servicio de Nefrología, Hospital Universitario 12 de Octubre, Instituto de Investigación Sanitaria, Hospital 12 de Octubre (imas12), Madrid, España; Departamento de Medicina, Universidad Complutense, Madrid, España.
| | - Fernando Caravaca
- Servicio de Nefrología, Hospital Universitario 12 de Octubre, Instituto de Investigación Sanitaria, Hospital 12 de Octubre (imas12), Madrid, España
| | - Claudia Yuste
- Servicio de Nefrología, Hospital Universitario 12 de Octubre, Instituto de Investigación Sanitaria, Hospital 12 de Octubre (imas12), Madrid, España
| | - Teresa Cavero
- Servicio de Nefrología, Hospital Universitario 12 de Octubre, Instituto de Investigación Sanitaria, Hospital 12 de Octubre (imas12), Madrid, España
| | - Eduardo Hernández
- Servicio de Nefrología, Hospital Universitario 12 de Octubre, Instituto de Investigación Sanitaria, Hospital 12 de Octubre (imas12), Madrid, España
| | - Enrique Morales
- Servicio de Nefrología, Hospital Universitario 12 de Octubre, Instituto de Investigación Sanitaria, Hospital 12 de Octubre (imas12), Madrid, España
| | - Eva Mérida
- Servicio de Nefrología, Hospital Universitario 12 de Octubre, Instituto de Investigación Sanitaria, Hospital 12 de Octubre (imas12), Madrid, España
| | - Juan Antonio Moreno
- Renal, Vascular and Diabetes Research Laboratory, Fundación Instituto de Investigaciones Sanitarias-Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Madrid, España
| | - Angel Sevillano
- Servicio de Nefrología, Hospital Universitario 12 de Octubre, Instituto de Investigación Sanitaria, Hospital 12 de Octubre (imas12), Madrid, España
| | - Eduardo Gutiérrez
- Servicio de Nefrología, Hospital Universitario 12 de Octubre, Instituto de Investigación Sanitaria, Hospital 12 de Octubre (imas12), Madrid, España
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High-normal albuminuria and incident chronic kidney disease in a male nondiabetic population. Clin Exp Nephrol 2017; 22:835-842. [PMID: 29280046 DOI: 10.1007/s10157-017-1522-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2017] [Accepted: 12/11/2017] [Indexed: 10/18/2022]
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30
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Duan ZY, Cai GY, Li JJ, Bu R, Chen XM. Urinary Erythrocyte-Derived miRNAs: Emerging Role in IgA Nephropathy. Kidney Blood Press Res 2017; 42:738-748. [DOI: 10.1159/000481970] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2015] [Accepted: 07/17/2017] [Indexed: 11/19/2022] Open
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Golbin L, Vigneau C, Touchard G, Thervet E, Halimi JM, Sawadogo T, Lagoutte N, Siohan P, Zagdoun E, Hertig A, Rioux-Leclercq N, Frouget T. Warfarin-related nephropathy induced by three different vitamin K antagonists: analysis of 13 biopsy-proven cases. Clin Kidney J 2017; 10:381-388. [PMID: 28616216 PMCID: PMC5466118 DOI: 10.1093/ckj/sfw133] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2016] [Accepted: 11/22/2016] [Indexed: 12/04/2022] Open
Abstract
Background: Acute kidney injury (AKI) with renal tubular obstruction by red blood cell casts (RBCC) has been described in patients treated with warfarin and is known as warfarin-related nephropathy (WRN). Methods: To determine whether other vitamin K antagonists (VKA) cause WRN, we retrospectively collected and analyzed the clinical and histological data of 13 patients treated with different VKA (seven with fluindione, four with warfarin and two with acenocoumarol) in seven French hospitals. Results: They all developed gross hematuria following overanticoagulation complicated by severe AKI (median serum creatinine concentration = 693 μmol/L). Histological analysis of the kidney biopsies highlighted the presence of intratubular RBCC and acute tubular necrosis in all patients and of an underlying kidney disease in 12 patients. WRN was suspected in patients treated with warfarin; however, the initial diagnosis was incorrect in six of the nine patients treated with other VKA. Nine patients progressed to chronic kidney disease, one fully recovered renal function, two died and one still needs dialysis. Conclusions: This is the first report of AKI caused by fluindione. In agreement with the recent publication on AKI in two patients treated with dabigatran, we suggest that the term ‘anticoagulant-related nephropathy’ is more appropriate than WRN. Gross hematuria in patients with an underlying kidney disease and treated with VKA requires rapid control of the international normalized ratio and renal function monitoring.
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Affiliation(s)
- Léonard Golbin
- CHU Pontchaillou, Department of Nephrology, Rennes, France
| | - Cécile Vigneau
- CHU Pontchaillou, Department of Nephrology, Rennes, France
| | - Guy Touchard
- CHU Miletrie, Department of Nephrology, Poitiers, France
| | - Eric Thervet
- CHU Europeen Georges Pompidou, Assistance Publique-Hopitaux de Paris, Department of Nephrology, Paris, France
| | | | | | | | - Pascale Siohan
- Hopital Cornouaille, Department of Nephrology, Quimper, France
| | - Elie Zagdoun
- Hopital Memorial, Department of Nephrology, Saint-Lô, France
| | - Alexandre Hertig
- CHU Tenon, Assistance Publique-Hopitaux de Paris, Department of Nephrology, Paris, France
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Kalaitzidis RG, Duni A, Liapis G, Balafa O, Xiromeriti S, Rapsomanikis PK, Elisaf MS. Anticoagulant-related nephropathy: a case report and review of the literature of an increasingly recognized entity. Int Urol Nephrol 2017; 49:1401-1407. [DOI: 10.1007/s11255-017-1527-9] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2016] [Accepted: 01/25/2017] [Indexed: 02/01/2023]
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Watanabe H, Goto S, Kondo D, Takata T, Yamazaki H, Hosojima M, Yamamoto S, Kaneko Y, Aoyagi R, Narita I. Comparison of methods of steroid administration combined with tonsillectomy for IgA nephropathy patients. Clin Exp Nephrol 2016; 21:257-265. [PMID: 27216016 DOI: 10.1007/s10157-016-1282-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2015] [Accepted: 04/27/2016] [Indexed: 10/21/2022]
Abstract
BACKGROUND IgA nephropathy (IgAN) is a chronic glomerular disease that causes end-stage renal disease in 20-40 % of patients within 20 years. The efficacy of tonsillectomy combined with steroid pulse (SP) administration (TSP) for clinical remission of IgAN has been reported. Particularly in Japan, TSP has been performed widely. However, the optimum method for steroid administration in TSP has not been established. METHODS We retrospectively compared clinical remission in IgAN patients treated with tonsillectomy combined with two different steroid administration methods: (1) three courses of SP therapy and oral prednisolone administered on alternate days (group 3A; n = 25); and (2) one course of SP therapy and oral prednisolone administered on consecutive days (group 1C; n = 22). RESULTS There was no significant difference in the clinical remission rates between the two groups at 12 (48.0 vs. 40.9 %, P = 0.77) and 24 months after starting treatment (68.0 vs. 72.7 %, P = 0.76) and at the final observation (76.0 vs. 81.8 %, P = 0.73). The mean period from starting treatment to remission of hematuria in group 3A was significantly shorter than that in group 1C (5.7 ± 4.4 vs. 9.9 ± 5.9 months, P = 0.03). Dyslipidemic patients treated for the first time with statin after the SP therapy were more present in group 3A at 24 months (P = 0.02). CONCLUSIONS In IgAN patients, treatment of group 3A may be effective for inducing rapid remission of hematuria. Further studies are needed to establish an appropriate protocol for TSP.
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Affiliation(s)
- Hirofumi Watanabe
- Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuoku, Niigata, Niigata, 951-8510, Japan
| | - Shin Goto
- Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuoku, Niigata, Niigata, 951-8510, Japan.
| | - Daisuke Kondo
- Department of Nephrology and Rheumatology, Niigata City General Hospital, Niigata, Japan
| | - Takuma Takata
- Department of Nephrology, Nagaoka Chuo General Hospital, Nagaoka, Japan
| | - Hajime Yamazaki
- Department of Internal Medicine, Nagaoka Red Cross Hospital, Nagaoka, Japan
| | - Michihiro Hosojima
- Department of Clinical Nutrition Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Suguru Yamamoto
- Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuoku, Niigata, Niigata, 951-8510, Japan
| | - Yoshikatsu Kaneko
- Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuoku, Niigata, Niigata, 951-8510, Japan
| | - Ryuji Aoyagi
- Department of Nephrology, Tachikawa General Hospital, Nagaoka, Japan
| | - Ichiei Narita
- Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuoku, Niigata, Niigata, 951-8510, Japan
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Zhang L, Li J, Yang S, Huang N, Zhou Q, Yang Q, Yu X. Clinicopathological features and risk factors analysis of IgA nephropathy associated with acute kidney injury. Ren Fail 2016; 38:799-805. [PMID: 27050722 DOI: 10.3109/0886022x.2016.1163153] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
OBJECTIVE The aim of this work is to investigate the distinctive clinicopathological characteristics of AKI in Chinese IgAN population and possible risk factors for AKI. METHODS We performed a retrospective analysis of 1512 patients with biopsy-proven primary IgAN in the period 2006 through 2011 in The First Affiliated Hospital of Sun Yat-sen University. AKI was defined as 2012 KDIGO (Kidney Diseases: Improving Global Outcomes) criteria, and the patients were divided into AKI group (n = 145) and non-AKI group (n = 1367). RESULTS The prevalence of AKI of the IgAN patients in our center was 9.59% (145/1512). Most AKI patients were older age, male, with higher percentage of smoke, hypertension, hyperlipidemia and preexisting impaired kidney function (Scr > 133 μmol/L), and higher serum creatinine, proteinuria, uric acid, whilst less onset of macroscopic hematuria as well as lower serum albumin and hemoglobin (p < 0.05). The pathological features were much more severe in AKI group as well. Acute tubulointerstitial nephritis was found as the most predominant pathological change of intrinsic AKI in our IgAN population instead of macroscopic hematuria associated acute tubular injury/necrosis. In multivariate logistic regression analysis, we found that older age, male gender, malignant hypertension, proteinuria, cellular crescent, fibrocellular crescent, glomerular sclerosis ≥ 50% were possible risk factors for AKI. CONCLUSIONS AKI is commonly seen among IgAN population. The clinicopathological features are much more severe in IgAN patients with AKI. Useful clinicopathological predictors are recognized to improve the identification of IgAN patients who are at high risk for AKI.
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Affiliation(s)
- Ling Zhang
- a Department of Nephrology , The First Affiliated Hospital, Sun Yat-sen University, Key Laboratory of Nephrology, Ministry of Health , Guangzhou , PR China
| | - Jianbo Li
- a Department of Nephrology , The First Affiliated Hospital, Sun Yat-sen University, Key Laboratory of Nephrology, Ministry of Health , Guangzhou , PR China
| | - Shicong Yang
- b Department of Pathology , The First Affiliated Hospital, Sun Yat-sen University , Guangzhou , PR China
| | - Naya Huang
- a Department of Nephrology , The First Affiliated Hospital, Sun Yat-sen University, Key Laboratory of Nephrology, Ministry of Health , Guangzhou , PR China
| | - Qian Zhou
- c Epidemiology Research Unit, Translational Medicine Research Center, The First Affiliated Hospital, Sun Yat-sen University , Guangzhou , PR China
| | - Qiongqiong Yang
- a Department of Nephrology , The First Affiliated Hospital, Sun Yat-sen University, Key Laboratory of Nephrology, Ministry of Health , Guangzhou , PR China
| | - Xueqing Yu
- a Department of Nephrology , The First Affiliated Hospital, Sun Yat-sen University, Key Laboratory of Nephrology, Ministry of Health , Guangzhou , PR China
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35
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Moreno JA, Yuste C, Gutiérrez E, Sevillano ÁM, Rubio-Navarro A, Amaro-Villalobos JM, Praga M, Egido J. Haematuria as a risk factor for chronic kidney disease progression in glomerular diseases: A review. Pediatr Nephrol 2016; 31:523-33. [PMID: 25980470 DOI: 10.1007/s00467-015-3119-1] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2015] [Revised: 04/15/2015] [Accepted: 04/20/2015] [Indexed: 12/18/2022]
Abstract
Haematuria has long been considered to be a benign condition associated with glomerular diseases. However, new evidences suggest that haematuria has a pathogenic role in promoting kidney disease progression. An increased risk for end-stage renal disease has been reported in adolescents and young adults with persistent microscopic haematuria. A persistent impairment of renal function has been also reported following macroscopic haematuria-associated acute kidney injury in immunoglobulin A nephropathy. Haematuria-induced renal damage has been related to oxidant, cytotoxic and inflammatory effects induced by haemoglobin or haem released from red blood cells. The pathophysiological origin of haematuria may be due to a more fragile and easily ruptured glomerular filtration barrier, as reported in several glomerular diseases. In this review we describe a number of the key issues associated with the epidemiology and pathogenesis of haematuria-associated diseases, provide an update of recent knowledge on the role of haematuria on renal function outcome and discuss specific therapeutic approaches in this setting. KEY SUMMARY POINTS: 1. Glomerular haematuria is a common observation in a number of renal diseases that may lead to persistent renal injury. 2. Haematuria in children differs from that in adults in specific aspects, particularly in the frequency of glomerular diseases and renal disease outcome. 3. Regular follow-up of renal function in children with isolated microhaematuria may be recommended.
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Affiliation(s)
- Juan Antonio Moreno
- Renal, Vascular and Diabetes Research Laboratory, IIS-Fundación Jiménez Díaz, Autonoma University, Av. Reyes Católicos 2, 28040, Madrid, Spain.
| | - Claudia Yuste
- Department of Nephrology, Gregorio Marañon Hospital, 28007, Madrid, Spain
| | - Eduardo Gutiérrez
- Department of Nephrology, 12 de Octubre Hospital, 28041, Madrid, Spain
| | - Ángel M Sevillano
- Department of Nephrology, 12 de Octubre Hospital, 28041, Madrid, Spain
| | - Alfonso Rubio-Navarro
- Renal, Vascular and Diabetes Research Laboratory, IIS-Fundación Jiménez Díaz, Autonoma University, Av. Reyes Católicos 2, 28040, Madrid, Spain
| | - Juan Manuel Amaro-Villalobos
- Renal, Vascular and Diabetes Research Laboratory, IIS-Fundación Jiménez Díaz, Autonoma University, Av. Reyes Católicos 2, 28040, Madrid, Spain
| | - Manuel Praga
- Department of Nephrology, 12 de Octubre Hospital, 28041, Madrid, Spain
| | - Jesús Egido
- Renal, Vascular and Diabetes Research Laboratory, IIS-Fundación Jiménez Díaz, Autonoma University, Av. Reyes Católicos 2, 28040, Madrid, Spain.,Spanish Biomedical Research Network in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid, Spain
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Yuste C, Rivera F, Moreno JA, López-Gómez JM. Haematuria on the Spanish Registry of Glomerulonephritis. Sci Rep 2016; 6:19732. [PMID: 26818712 PMCID: PMC4730139 DOI: 10.1038/srep19732] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2015] [Accepted: 12/15/2015] [Indexed: 12/24/2022] Open
Abstract
Recent studies suggest a pathogenic role for glomerular haematuria among renal function. However, there is no data on the prevalence of haematuria from a large renal biopsy registry. We analysed the prevalence of gross (GH) and microscopic (mH) haematuria in 19,895 patients that underwent native renal biopsies from the Spanish Registry of Glomerulonephritis. Haematuria's overall incidence was 63% (GH 8.6% and mH 55.1%), being more frequent in males (64.7% vs. 62.4%). GH was more prevalent in patients <18 years (21.3% vs. 7.7%). The commonest clinical presentation associated with GH was acute kidney injury (31.5%) and IgA Nephropathy (IgAN) (33.6%) was the most frequent histological finding. GH patients showed a significantly (p < 0.05) lower eGFR and proteinuria levels as compared with patients with mH and without haematuria. Moreover, mH was more prevalent in adults (56.3%). Nephrotic syndrome was the commonest clinical presentation in mH patients (32.2%) and IgAN (18.5%) the most frequent histological finding. In conclusion, haematuria, is a frequent urinalysis finding in patients underwent native renal biopsy. The most frequent histological finding in both GH and mH is IgAN. Whereas, GH is more frequent in young males with acute kidney injury, mH is commoner among adults with nephrotic syndrome.
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Affiliation(s)
| | | | - Juan Antonio Moreno
- Renal,Vascular and Diabetes Research Lab. IIS-Fundación Jiménez Díaz. Autonóma University, Madrid, Spain
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Rojas-Rivera J, Fernández-Juárez G, Praga M. Rapidly progressive IgA nephropathy: a form of vasculitis or a complement-mediated disease? Clin Kidney J 2015; 8:477-81. [PMID: 26413269 PMCID: PMC4581398 DOI: 10.1093/ckj/sfv095] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2015] [Accepted: 09/02/2015] [Indexed: 01/07/2023] Open
Abstract
A rapidly progressive and crescentic IgA nephropathy (IgAN) is uncommon, but it has a high risk of progression to end-stage renal disease and variable response to immunosuppression. The importance of a positive anti-neutrophil cytoplasmic antibody (ANCA) serology in this group of patients is not fully understood but may have prognostic significance. On the other hand, there is growing evidence of the role of complement in the pathogenesis of IgAN, especially in cases of crescentic IgAN. Therapies directed against the complement system are a potential and rational therapeutic approach. In this issue, two clinical studies of crescentic IgAN are presented. The first work, is a retrospective case-control study describing clinical presentation, histological findings and response to treatment of crescentic IgAN/positive ANCA patients, comparing them with IgAN/negative ANCA patients and ANCA vasculitis patients. The second is a case report showing the effect of eculizumab, a humanized monoclonal antibody that is a terminal cascade complement inhibitor, as salvage therapy for crescentic IgAN resistant to conventional immunosuppression. Both studies broaden our approach to patients with aggressive forms of IgAN.
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Affiliation(s)
- Jorge Rojas-Rivera
- Spanish Study Group of Glomerular Disease (GLOSEN) , Hospital Universitario Fundación Jiménez Díaz , Madrid , Spain
| | - Gema Fernández-Juárez
- Spanish Study Group of Glomerular Disease (GLOSEN) , Hospital Fundación Alcorcón , Madrid , Spain
| | - Manuel Praga
- Spanish Study Group of Glomerular Disease (GLOSEN) , Hospital Universitario 12 de Octubre , Madrid , Spain
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38
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Yuste C, Rubio-Navarro A, Barraca D, Aragoncillo I, Vega A, Abad S, Santos A, Macias N, Mahillo I, Gutiérrez E, Praga M, Egido J, López-Gómez JM, Moreno JA. Haematuria increases progression of advanced proteinuric kidney disease. PLoS One 2015; 10:e0128575. [PMID: 26016848 PMCID: PMC4446357 DOI: 10.1371/journal.pone.0128575] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2015] [Accepted: 04/28/2015] [Indexed: 02/04/2023] Open
Abstract
Background Haematuria has been traditionally considered as a benign hallmark of some glomerular diseases; however new studies show that haematuria may decrease renal function. Objective To determine the influence of haematuria on the rate of chronic kidney disease (CKD) progression in 71 proteinuric patients with advanced CKD (baseline eGFR <30 mL/min) during 12 months of follow-up. Results The mean rate of decline in eGFR was higher in patients with both haematuria and proteinuria (haemoproteinuria, HP, n=31) than in patients with proteinuria alone (P patients, n=40) (-3.8±8.9 vs 0.9±9.5 mL/min/1.73m2/year, p<0.05, respectively). The deleterious effect of haematuria on rate of decline in eGFR was observed in patients <65 years (-6.8±9.9 (HP) vs. 0.1±11.7 (P) mL/min/1.73m2/year, p<0.05), but not in patients >65 years (-1.2±6.8 (HP) vs. 1.5±7.7 (P) mL/min/1.73m2/year). Furthermore, the harmful effect of haematuria on eGFR slope was found patients with proteinuria >0.5 g/24 h (-5.8±6.4 (HP) vs. -1.37± 7.9 (P) mL/min/1.73m2/year, p<0.05), whereas no significant differences were found in patients with proteinuria < 0.5 g/24 h (-0.62±7.4 (HP) vs. 3.4±11.1 (P) mL/min/1.73m2/year). Multivariate analysis reported that presence of haematuria was significantly and independently associated with eGFR deterioration after adjusting for traditional risk factors, including age, serum phosphate, mean proteinuria and mean serum PTH (β=-4.316, p=0.025). Conclusions The presence of haematuria is closely associated with a faster decrease in renal function in advanced proteinuric CKD patients, especially in younger CKD patients with high proteinuria levels; therefore this high risk subgroup of patients would benefit of intensive medical surveillance and treatment.
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Affiliation(s)
- Claudia Yuste
- Renal Unit. Gregorio Marañón Hospital, Madrid, Spain
| | - Alfonso Rubio-Navarro
- Renal, Vascular and Diabetes Research Lab. IIS-Fundación Jiménez Díaz, Autonoma University, Madrid, Spain
| | | | | | - Almudena Vega
- Renal Unit. Gregorio Marañón Hospital, Madrid, Spain
| | - Soraya Abad
- Renal Unit. Gregorio Marañón Hospital, Madrid, Spain
| | - Alba Santos
- Renal Unit. Gregorio Marañón Hospital, Madrid, Spain
| | | | - Ignacio Mahillo
- Department of Epidemiology. IIS-Fundación Jiménez Díaz, Madrid, Spain
| | | | - Manuel Praga
- Department of Nephrology. Doce de Octubre Hospital, Madrid, Spain
| | - Jesús Egido
- Renal, Vascular and Diabetes Research Lab. IIS-Fundación Jiménez Díaz, Autonoma University, Madrid, Spain
- Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Madrid, Spain
- Fundación Renal Iñigo Alvarez de Toledo-Instituto Reina Sofía de Investigaciones Nefrológicas (FRIAT-IRSIN), Madrid, Spain
| | | | - Juan Antonio Moreno
- Renal, Vascular and Diabetes Research Lab. IIS-Fundación Jiménez Díaz, Autonoma University, Madrid, Spain
- * E-mail:
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Yuste C, Gutierrez E, Sevillano AM, Rubio-Navarro A, Amaro-Villalobos JM, Ortiz A, Egido J, Praga M, Moreno JA. Pathogenesis of glomerular haematuria. World J Nephrol 2015; 4:185-95. [PMID: 25949932 PMCID: PMC4419128 DOI: 10.5527/wjn.v4.i2.185] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2014] [Revised: 12/19/2014] [Accepted: 12/29/2014] [Indexed: 02/06/2023] Open
Abstract
Haematuria was known as a benign hallmark of some glomerular diseases, but over the last decade, new evidences pointed its negative implications on kidney disease progression. Cytotoxic effects of oxidative stress induced by hemoglobin, heme, or iron released from red blood cells may account for the tubular injury observed in human biopsy specimens. However, the precise mechanisms responsible for haematuria remain unclear. The presence of red blood cells (RBCs) with irregular contours and shape in the urine indicates RBCs egression from the glomerular capillary into the urinary space. Therefore glomerular haematuria may be a marker of glomerular filtration barrier dysfunction or damage. In this review we describe some key issues regarding epidemiology and pathogenesis of haematuric diseases as well as their renal morphological findings.
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Le W, Liang S, Chen H, Wang S, Zhang W, Wang X, Wang J, Zeng CH, Liu ZH. Long-term outcome of IgA nephropathy patients with recurrent macroscopic hematuria. Am J Nephrol 2014; 40:43-50. [PMID: 24994520 DOI: 10.1159/000364954] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2014] [Accepted: 05/29/2014] [Indexed: 11/19/2022]
Abstract
BACKGROUND/AIMS The long-term renal outcomes of patients with IgA nephropathy (IgAN) who present with recurrent macroscopic hematuria (RMH) have not been described in previous studies. METHODS Patients with biopsy-proven primary IgAN in Jinling Hospital were divided into three groups according to different patterns of macroscopic hematuria (MH): RMH, isolated MH (IMH), and those without a history of MH (NMH). RESULTS A total of 1,155 patients were enrolled in the study (158 in the RMH group, 256 in the IMH group, and 741 in the NMH group). At biopsy, patients with RMH were younger, had lower median proteinuria, a lower incidence of hypertension, and a higher estimated glomerular filtration rate than those in the NMH group. Pathologically, patients with RMH had a lower level of mesangial hypercellularity and segmental glomerulosclerosis as well as less tubular atrophy than those with NMH. The demographic and clinical features of patients with IMH fell between patients with RMH and those with NMH. During a median follow-up of 7.9 years, the 5-, 10- and 20-year cumulative renal survival after biopsy, as calculated by K-M methods, were 98, 91, and 91% in the RMH group, 95, 89, and 64% in the IMH group, and 95, 79, and 57% in the NMH group. The renal survival in patients with RMH was significantly better than patients with NMH or IMH. CONCLUSIONS The long-term prognosis of patients who present with RMH is significantly better than patients with NMH or IMH.
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Affiliation(s)
- WeiBo Le
- National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China
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Han SS, Ahn SY, Ryu J, Baek SH, Chin HJ, Na KY, Chae DW, Kim S. Proteinuria and hematuria are associated with acute kidney injury and mortality in critically ill patients: a retrospective observational study. BMC Nephrol 2014; 15:93. [PMID: 24942179 PMCID: PMC4072664 DOI: 10.1186/1471-2369-15-93] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2013] [Accepted: 05/23/2014] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Proteinuria and hematuria are both important health issues; however, the nature of the association between these findings and acute kidney injury (AKI) or mortality remains unresolved in critically ill patients. METHODS Proteinuria and hematuria were measured by a dipstick test and scored using a scale ranging from a negative result to 3+ in 1883 patients admitted to the intensive care unit. AKI was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. The odds ratios (ORs) for AKI and 3-year mortality were calculated after adjustment for multiple covariates according to the degree of proteinuria or hematuria. For evaluating the synergistic effect on mortality among proteinuria, hematuria, and AKI, the relative excess risk due to interaction (RERI) was used. RESULTS Proteinuria and hematuria increased the ORs for AKI: the ORs of proteinuria were 1.66 (+/-), 1.86 (1+), 2.18 (2+), and 4.74 (3+) compared with non-proteinuria; the ORs of hematuria were 1.31 (+/-), 1.58 (1+), 2.63 (2+), and 2.52 (3+) compared with non-hematuria. The correlations between the mortality risk and proteinuria or hematuria were all significant and graded (Ptrend<0.001). There was a relative excess risk of mortality when both AKI and proteinuria or hematuria were considered together: the synergy indexes were 1.30 and 1.23 for proteinuria and hematuria, respectively. CONCLUSIONS Proteinuria and hematuria are associated with the risks of AKI and mortality in critically ill patients. Additionally, these findings had a synergistic effect with AKI on mortality.
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Affiliation(s)
- Seung Seok Han
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Shin Young Ahn
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Korea
| | - Jiwon Ryu
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon-si, Gangwon-do, Korea
| | - Seon Ha Baek
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Korea
| | - Ho Jun Chin
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Korea
| | - Ki Young Na
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Korea
| | - Dong-Wan Chae
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Korea
| | - Sejoong Kim
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Korea
- Department of Biomedical Engineering, University of Michigan, Ann Arbor, USA
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CD16+CD56+ cells are a potential culprit for hematuria in IgA nephropathy. Clin Exp Nephrol 2014; 19:216-24. [PMID: 24798970 DOI: 10.1007/s10157-014-0968-z] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2013] [Accepted: 03/20/2014] [Indexed: 10/25/2022]
Abstract
BACKGROUND Hematuria is the first manifestation of urinary abnormality in immunoglobulin A nephropathy (IgAN). Hematuria has recently been reported as a risk factor for deterioration of renal function; however, its cause remains unknown. METHODS We analyzed the surface marker of peripheral blood mononuclear cells before and immediately after tonsillectomy in IgAN patients and controls (chronic tonsillitis or tonsillar hypertrophy) by flow cytometry and investigated the association with hematuria. To prove our hypothesis that NK cells induce hematuria, we administered IL-12, activator of NK cells, to HIGA mice. In addition, we transferred cultured NK cells to nude rats and transferred the CD16(+)CD56(+) cells, including NK cells, that are derived from the peripheral blood of IgAN patients immediately after tonsillectomy to nude rats to assess the hematuria level and renal histology of the recipients. We also performed cytotoxicity assays against glomerular endothelial cells by NK cells. RESULTS We found that IgAN patients who showed rapid deterioration of hematuria after tonsillectomy also displayed a significant increase in CD16(+)CD56(+) cells in the peripheral blood immediately after tonsillectomy. Exogenous administration of IL-12 to HIGA mice induced hematuria. Adoptive transfer of either cells of an NK cell line, or of CD16(+)CD56(+) cells derived from IgAN patients, into nude rats induced hematuria in the recipients. In vitro analysis showed that NK cells exert cytotoxic activity toward human glomerular endothelial cells in a dose-dependent manner. CONCLUSIONS CD16(+)CD56(+) cells seem to be responsible for hematuria in IgAN.
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Kim S, Chang W. Atypical triad of IgA nephropathy: reversible acute kidney injury, gross hematuria, and severe bilateral flank pain. CEN Case Rep 2013; 3:145-147. [PMID: 28509188 DOI: 10.1007/s13730-013-0106-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2011] [Accepted: 11/06/2013] [Indexed: 10/25/2022] Open
Abstract
Reversible acute kidney injury very rarely complicates the course of immunoglobulin A (IgA) nephropathy. We report an atypical case of reversible acute kidney injury, gross hematuria, and severe bilateral flank pain as the presenting triad of IgA nephropathy. Renal biopsy revealed mesangial IgA deposition without glomerular crescents. The patient's renal dysfunction, mediated by red cell tubular obstruction, interstitial nephritis, and tubular necrosis, resolved without intervention. We conclude that IgA nephropathy should be considered in the differential diagnosis for transient acute kidney injury with gross hematuria, and should be appropriately treated based on known prognostic factors.
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Affiliation(s)
- Susan Kim
- Department of Internal Medicine, St. Mary's Medical Center, 450 Stanyan Street, San Francisco, CA, 94117, USA.
| | - Warren Chang
- Department of Internal Medicine, St. Mary's Medical Center, 450 Stanyan Street, San Francisco, CA, 94117, USA.,Division of Nephrology, St. Mary's Medical Center, San Francisco, CA, 94117, USA
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IgA Nephropathy Factors that Predict and Accelerate Progression to End-Stage Renal Disease. Cell Biochem Biophys 2013; 68:443-7. [DOI: 10.1007/s12013-013-9741-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Beck L, Bomback AS, Choi MJ, Holzman LB, Langford C, Mariani LH, Somers MJ, Trachtman H, Waldman M. KDOQI US commentary on the 2012 KDIGO clinical practice guideline for glomerulonephritis. Am J Kidney Dis 2013; 62:403-41. [PMID: 23871408 DOI: 10.1053/j.ajkd.2013.06.002] [Citation(s) in RCA: 158] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2013] [Accepted: 06/04/2013] [Indexed: 01/28/2023]
Abstract
Glomerulonephritis (GN) is an important cause of morbidity and mortality in patients of all ages throughout the world. Because these disorders are relatively rare, it is difficult to perform randomized clinical trials to define optimal treatment for many of the specific glomerulopathies. In the absence of high-grade evidence to guide the care of glomerular diseases, in June 2012, KDIGO (Kidney Disease: Improving Global Outcomes) published an international clinical guideline for GN. The Work Group report represents an important review of the literature in this area and offers valid and useful guidelines for the most common situations that arise in the management of patients with glomerular disease. This commentary, developed by a panel of clinical experts convened by the National Kidney Foundation, attempts to put the GN guideline into the context of the US health care system. Overall, we support the vast majority of the recommendations and highlight select areas in which epidemiological factors and medical practice patterns in this country justify modifications and adjustments in order to achieve favorable outcomes. There remain large gaps in our knowledge of the best approaches to treat glomerular disease and we strongly endorse an expanded clinical research effort to improve the health and long-term outcomes of children and adults with GN.
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Affiliation(s)
- Laurence Beck
- Boston University School of Medicine, Boston, MA, USA
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Han SS, Kim M, Lee SM, Lee JP, Kim S, Joo KW, Lim CS, Kim YS, Kim DK. Cadmium exposure induces hematuria in Korean adults. ENVIRONMENTAL RESEARCH 2013; 124:23-7. [PMID: 23642677 DOI: 10.1016/j.envres.2013.04.001] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/27/2012] [Revised: 03/15/2013] [Accepted: 04/09/2013] [Indexed: 05/15/2023]
Abstract
INTRODUCTION Toxic heavy metals have adverse effects on human health. However, the risk of hematuria caused by heavy metal exposure has not been evaluated. METHODS Data from 4701 Korean adults were obtained in the Korean National Health and Nutritional Examination Survey (2008-2010). Blood levels of the toxic heavy metals cadmium, lead, and mercury were measured. Hematuria was defined as a result of ≥+1 on a urine dipstick test. The odds ratios (ORs) for hematuria were measured according to the blood heavy metal levels after adjusting for multiple variables. RESULTS Individuals with blood cadmium levels in the 3rd and 4th quartiles had a greater OR for hematuria than those in the 1st quartile group: 3rd quartile, 1.35 (1.019-1.777; P=0.037); 4th quartile, 1.52 (1.140-2.017; P=0.004). When blood cadmium was considered as a log-transformed continuous variable, the correlation between blood cadmium and hematuria was significant: OR, 1.97 (1.224-3.160; Ptrend=0.005). In contrast, no significant correlations between hematuria and blood lead or mercury were found in the multivariate analyses. DISCUSSION The present study shows that high cadmium exposure is associated with a risk of hematuria.
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Affiliation(s)
- Seung Seok Han
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul 110-744, Republic of Korea
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Persistent asymptomatic isolated hematuria in children: clinical and histopathological features and prognosis. World J Pediatr 2013; 9:163-8. [PMID: 23677832 DOI: 10.1007/s12519-013-0415-3] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2012] [Accepted: 04/23/2013] [Indexed: 12/22/2022]
Abstract
BACKGROUND This study involving 351 children who had undergone kidney biopsy secondary to persistent asymptomatic isolated hematuria was undertaken to assess histological diagnosis of the disease and its natural history and prognosis. METHODS The patients were divided into two groups: 215 patients with asymptomatic isolated microhematuria (AIMH; proteinuria <0.1 g/day) and 136 patients with persistent asymptomatic microhematuria, recurrent macrohematuria and/or proteinuria (AMHP; proteinuria 0.1-0.25 g/day). After kidney biopsy, the patients were monitored for 2-10 years. RESULTS Normal biopsies or minor abnormalities were more frequent in AIMH patients than those in AMHP patients, who exhibited IgA nephropathy more frequently. During the 2- to 10-year follow-up period, adverse renal events (i.e., development of proteinuria, hypertension, or impaired renal function) were observed in 13/215 (6.0%) patients with AIMH and 31/136 (22.8%) patients with AMHP (χ(2)=15.521, P<0.001). CONCLUSIONS Normal biopsies or minor abnormalities were more frequently observed in AIMH patients, whereas IgA nephropathy and adverse renal events were more frequent in AMHP. Microscopic hematuria, especially when accompanied by macroscopic hematuria and proteinuria, may represent an important risk factor for the development of chronic kidney disease.
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Soo Han J, Dug Lim S, Hyeok Choi W, Chul Hong S, Hee Park J, Park E, Jin Hong M, Lee CI, Hwan Park J, Ho Lee J, Oh Song J, Il Jo Y. Association of acute tubular necrosis with gross hematuria in cirrhosis-related immunoglobulin A nephropathy. Kidney Res Clin Pract 2013; 32:43-6. [PMID: 26889437 PMCID: PMC4716105 DOI: 10.1016/j.krcp.2012.12.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2012] [Revised: 07/13/2012] [Accepted: 07/31/2012] [Indexed: 12/01/2022] Open
Abstract
Immunoglobulin A (IgA) nephropathy associated with cirrhosis is the most common form of secondary IgA nephropathy (IgAN). Cirrhosis-related IgAN is usually clinically silent with a rare occurrence of gross hematuria, unlike in cases of idiopathic IgAN. Especially, acute tubular necrosis (ATN) associated with gross hematuria is very rare in cirrhosis-related IgAN, although acute renal failure is a frequently reported complication in advanced cirrhosis. Herein, we report an unusual case of ATN requiring renal replacement therapy, associated with gross hematuria in a patient with nonalcoholic, hepatitis B virus-associated cirrhosis. Results of a histopathological analysis revealed obstruction of the lumen of renal tubules by red blood cell casts, a marked tubular necrosis, and IgA deposition in the mesangium. The patient's renal function and gross hematuria were clearly improved after lamivudine treatment.
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Affiliation(s)
- Jang Soo Han
- Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
| | - So Dug Lim
- Department of Pathology, Konkuk University School of Medicine, Seoul, Korea
| | - Won Hyeok Choi
- Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
| | - Sung Chul Hong
- Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
| | - Jung Hee Park
- Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
| | - Eugene Park
- Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
| | - Mi Jin Hong
- Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
| | - Cho I Lee
- Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
| | - Jung Hwan Park
- Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
| | - Jong Ho Lee
- Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
| | - Jong Oh Song
- Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
| | - Young Il Jo
- Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
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Eitner F, Floege J. In search of a better understanding of IgA nephropathy-associated hematuria. Kidney Int 2013; 82:513-5. [PMID: 22892858 DOI: 10.1038/ki.2012.160] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Although microscopic or episodic macroscopic hematuria is the key clinical manifestation of IgA nephropathy (IgAN), still very little is known about its pathogenesis. Cox et al. studied IgAN patients during episodes of macroscopic hematuria and identified an upregulated expression of the chemokine receptor CX3CR1 in their circulating leukocytes. On the basis of a series of additional experimental approaches, they suggest that CX3CR1 and its ligand fractalkine may contribute to the onset of macroscopic hematuria in IgAN.
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Lim AKH, Campbell DA. Haematuria and acute kidney injury in elderly patients admitted to hospital with supratherapeutic warfarin anticoagulation. Int Urol Nephrol 2013; 45:561-70. [PMID: 23292508 DOI: 10.1007/s11255-012-0364-0] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2012] [Accepted: 12/12/2012] [Indexed: 01/06/2023]
Abstract
BACKGROUND AND OBJECTIVES Warfarin-related nephropathy is reported to occur with an INR >3.0 as a result of glomerular bleeding. There is a lack of prospective studies examining the effect of supratherapeutic warfarin anticoagulation on haematuria and acute kidney injury (AKI). Older patients may be susceptible due to greater warfarin use, prevalence of kidney disease and comorbidities. The objective of this study was to determine the incidence and nature of haematuria and AKI in older patients on warfarin and to determine any association with high INR levels. DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS This was a prospective, observational study of 150 elderly patients receiving warfarin anticoagulation who were acutely hospitalised in a tertiary hospital. AKI was assessed using RIFLE criteria. Urinalysis was performed to quantify haematuria, characterise erythrocyte morphology and measure the albumin-creatinine ratio. Positive cases received follow-up at 4-6 weeks to determine resolution. RESULTS An INR >3.0 was found in 54 % of patients. Pre-admission antibiotic use increased the risk of excessive anticoagulation. The incidence of isolated AKI, isolated haematuria and both was 18.7, 13.3 and 12 %, respectively. Factors associated with a higher risk of haematuria were an INR >4.0, non-urinary infection, catheterisation and albuminuria. Most cases of AKI were mild, and there was no demonstrable correlation between the admission INR and AKI. Admission with heart failure was significantly associated with an increased risk of persistent kidney impairment at follow-up. CONCLUSIONS Supratherapeutic warfarin anticoagulation was associated with an increased risk of haematuria, but not with AKI. The majority of cases of haematuria were transient.
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Affiliation(s)
- Andy K H Lim
- Department of General Medicine, Monash Medical Centre, 246 Clayton Road, Clayton, VIC 3168, Australia.
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