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  1. Article ; Online: Recent advances in our understanding of recurrent primary glomerulonephritis after kidney transplantation.

    Cosio, Fernando G / Cattran, Daniel C

    Kidney international

    2017  Volume 91, Issue 2, Page(s) 304–314

    Abstract: Recurrent glomerulonephritis (GN) is an important cause of kidney allograft failure, particularly in younger recipients. Approximately 15% of death-censored graft failures are due to recurrent GN, but this incidence is likely an underestimation of the ... ...

    Abstract Recurrent glomerulonephritis (GN) is an important cause of kidney allograft failure, particularly in younger recipients. Approximately 15% of death-censored graft failures are due to recurrent GN, but this incidence is likely an underestimation of the magnitude of the problem. Overall, 18% to 22% of kidney allografts are lost due to GN, either recurrent or presumed de novo. The impact of recurrent GN on allograft survival was recognized from the earliest times in kidney transplantation. However, progress in this area has been slow, and our understanding of GN recurrence remains limited, in large part due to incomplete understanding of the pathogenesis of these diseases. This review focuses on recent advances in our general understanding of the pathophysiology of primary GN, the risk of recurrence in the allograft, and the consequences for kidney graft survival. We focus specifically on the most common forms of primary GN, including focal segmental glomerulosclerosis, membranous nephropathy, membranoproliferative glomerulonephritis, and IgA nephropathy. New understanding of the pathogenesis of these diseases has had direct clinical implications for transplantation, allowing better identification of candidates at high risk of recurrence and earlier diagnoses, and it is expected to lead to significance improvements in the therapy and perhaps even prevention of GN recurrence. More than ever, it is essential to fully characterize GN before transplantation as this information will direct our management posttransplantation. Further, the relative rarity of recurrent GN dictates the need for multicenter studies in order to evaluate, test, and validate recent advances and therapies.
    MeSH term(s) Allografts ; Early Diagnosis ; Glomerulonephritis/diagnosis ; Glomerulonephritis/mortality ; Glomerulonephritis/surgery ; Graft Survival ; Humans ; Kidney Transplantation/adverse effects ; Kidney Transplantation/mortality ; Predictive Value of Tests ; Recurrence ; Risk Factors ; Time Factors ; Treatment Failure
    Language English
    Publishing date 2017-02
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 120573-0
    ISSN 1523-1755 ; 0085-2538
    ISSN (online) 1523-1755
    ISSN 0085-2538
    DOI 10.1016/j.kint.2016.08.030
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Pregnancy, Contraception, and Menopause in Advanced Chronic Kidney Disease and Kidney Transplant.

    Dines, Virginia A / Garovic, Vesna D / Parashuram, Santosh / Cosio, Fernando G / Kattah, Andrea G

    Women's health reports (New Rochelle, N.Y.)

    2021  Volume 2, Issue 1, Page(s) 488–496

    Abstract: Background: ...

    Abstract Background:
    Language English
    Publishing date 2021-10-25
    Publishing country United States
    Document type Journal Article
    ISSN 2688-4844
    ISSN (online) 2688-4844
    DOI 10.1089/whr.2021.0053
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Competing Risk Analysis in Renal Allograft Survival: A New Perspective to an Old Problem.

    El Ters, Mireille / Smith, Byron H / Cosio, Fernando G / Kremers, Walter K

    Transplantation

    2020  Volume 105, Issue 3, Page(s) 668–676

    Abstract: Background: Graft survival after kidney transplant (KTX) is often estimated by the Kaplan-Meier (KM) method censoring for competing endpoints, primarily death. This method overestimates the incidence of graft loss.: Methods: In 3157 adult KTX ... ...

    Abstract Background: Graft survival after kidney transplant (KTX) is often estimated by the Kaplan-Meier (KM) method censoring for competing endpoints, primarily death. This method overestimates the incidence of graft loss.
    Methods: In 3157 adult KTX recipients followed for a mean of 79.2 months, we compared kidney and patient survival probabilities by KM versus competing risk analysis (CRA). These methods are extended to comparing different regression methods.
    Results: Compared with CRA, the probabilities of death and graft loss (censored for the other outcome) were substantially higher by KM. These differences increased with increasing follow-up time. Importantly, differences in graft losses were magnified in subgroups with greater probabilities of death. Among recipients with diabetes, the probabilities of graft loss at 20 years were 57% by KM and 32% by CRA, while for non-diabetes mellitus corresponding values were 44% and 35%. Similar results are noted when comparing older versus younger recipients. Finally, we find that the Fine-Gray method assumptions are violated when using age and gender as covariates and that the alternative method of Aalen-Johansen may be more appropriate.
    Conclusions: CRA provides more accurate estimates of long-term graft survival and death, particularly in subgroups of recipients with higher rates of the competing event. Overestimation of risk by KM leads to both quantitative and qualitative misinterpretations of long-term KTX outcomes. When using regression analyses, care should be taken to check assumptions to guide the choice of appropriate method.
    MeSH term(s) Female ; Follow-Up Studies ; Graft Rejection/mortality ; Graft Survival ; Humans ; Kidney Transplantation/mortality ; Male ; Middle Aged ; Retrospective Studies ; Risk Assessment/methods ; Risk Factors ; Survival Rate/trends ; Time Factors ; Transplantation, Homologous ; United States/epidemiology
    Language English
    Publishing date 2020-07-02
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 208424-7
    ISSN 1534-6080 ; 0041-1337
    ISSN (online) 1534-6080
    ISSN 0041-1337
    DOI 10.1097/TP.0000000000003285
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: The impact of urinary tract infections in renal transplant recipients.

    Lorenz, Elizabeth C / Cosio, Fernando G

    Kidney international

    2010  Volume 78, Issue 8, Page(s) 719–721

    Abstract: Urinary tract infections (UTIs), including cystitis and pyelonephritis, are the most common infections after kidney transplantation. On examining the role of surveillance and treatment of asymptomatic bacteriuria posttransplant, Fiorante and colleagues ... ...

    Abstract Urinary tract infections (UTIs), including cystitis and pyelonephritis, are the most common infections after kidney transplantation. On examining the role of surveillance and treatment of asymptomatic bacteriuria posttransplant, Fiorante and colleagues found that up to 50% of recipients had bacteriuria. Despite routine treatment, recurrent UTIs remained common. Many risk factors contribute to the high incidence of UTIs, which can undermine graft function and survival. Given that many UTIs are asymptomatic, screening protocols may be beneficial.
    MeSH term(s) Humans ; Incidence ; Kidney Transplantation/adverse effects ; Opportunistic Infections/etiology ; Risk Factors ; Urinary Tract Infections/etiology
    Language English
    Publishing date 2010-10
    Publishing country United States
    Document type Comment ; Journal Article
    ZDB-ID 120573-0
    ISSN 1523-1755 ; 0085-2538
    ISSN (online) 1523-1755
    ISSN 0085-2538
    DOI 10.1038/ki.2010.219
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Recurrent Proliferative Glomerulonephritis With Monoclonal Immunoglobulin Deposits in Kidney Allografts Treated With Anti-CD20 Antibodies.

    Buxeda, Anna / Said, Samar M / Nasr, Samih H / Leung, Nelson / El Ters, Mireille / Cosio, Fernando G

    Transplantation

    2019  Volume 103, Issue 7, Page(s) 1477–1485

    Abstract: Background: Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) is a distinct form of glomerulonephritis that often recurs after kidney transplantation causing severe graft injury and often failure.: Methods: We describe ...

    Abstract Background: Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) is a distinct form of glomerulonephritis that often recurs after kidney transplantation causing severe graft injury and often failure.
    Methods: We describe post transplant outcomes and response to therapy in 20 recipients with PGNMID. Evidence of PGNMID recurrence or lack thereof was determined by protocol and clinical biopsies.
    Results: Histologic recurrence (deposition of monoclonal immunoglobulin) occurred in 18 of 20 recipients (90%), a median of 7 (1 to 65) months post transplant. At diagnosis, recurrence was generally associated with mild or no clinical manifestations and often with mild glomerular morphologic changes by light microcopy. Four of the 18 patients with recurrence did not progress and were not treated. Another 4 patients with recurrences were treated with cyclophosphamide with or without plasmapheresis, and 2 of these grafts were lost from glomerulonephritis. Nine patients with recurrences were treated with anti-CD20 antibodies (rituximab) alone, resulting in improvements in estimated glomerular filtration rate (31.5 ± 16 versus 38.8 ± 13.3 mL/min/1.73 m, P = 0.011) and proteinuria (1280 [117 to 3752] versus 168 [83 to 1613] mg/24 h, P = 0.012) although complete clinical remission was rare. One graft in this later group was lost from recurrence 141 months post transplant. Posttreatment biopsies demonstrated stable or improved glomerular histology in most cases. However, PGNMID did not resolve in any case. Four patients received rituximab 4 months pretransplant to prevent recurrence. However, 3 had mild recurrences.
    Conclusions: Rituximab treatment of early PGNMID recurrence is effective, resulting in reasonable, long-term graft survival. Whether pretransplant rituximab modifies the course of recurrence requires additional studies.
    MeSH term(s) Adult ; Aged ; Antibodies, Monoclonal/analysis ; Drug Administration Schedule ; Female ; Glomerulonephritis/diagnosis ; Glomerulonephritis/drug therapy ; Glomerulonephritis/immunology ; Glomerulonephritis/surgery ; Graft Survival/drug effects ; Humans ; Immunosuppressive Agents/administration & dosage ; Immunosuppressive Agents/adverse effects ; Kidney/drug effects ; Kidney/immunology ; Kidney/pathology ; Kidney/surgery ; Kidney Transplantation/adverse effects ; Male ; Middle Aged ; Recurrence ; Retreatment ; Risk Factors ; Rituximab/administration & dosage ; Rituximab/adverse effects ; Time Factors
    Chemical Substances Antibodies, Monoclonal ; Immunosuppressive Agents ; Rituximab (4F4X42SYQ6)
    Language English
    Publishing date 2019-02-12
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 208424-7
    ISSN 1534-6080 ; 0041-1337
    ISSN (online) 1534-6080
    ISSN 0041-1337
    DOI 10.1097/TP.0000000000002577
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Significance and management of proteinuria in kidney transplant recipients.

    Amer, Hatem / Cosio, Fernando G

    Journal of the American Society of Nephrology : JASN

    2009  Volume 20, Issue 12, Page(s) 2490–2492

    Abstract: Proteinuria is common after kidney transplantation and typically urine protein levels are below 500 mg/d. However, even these low levels are associated with reduced graft survival. Most allografts with proteinuria >1500 mg/d have new glomerular pathology. ...

    Abstract Proteinuria is common after kidney transplantation and typically urine protein levels are below 500 mg/d. However, even these low levels are associated with reduced graft survival. Most allografts with proteinuria >1500 mg/d have new glomerular pathology. In contrast, lower levels of proteinuria are generally associated with nonglomerular, nonspecific histologic changes. The relationship between proteinuria and graft survival is independent of other variables, including graft function and graft histology. Thus, proteinuria allows stratification of risk in patients with or without glomerular pathology. Proteinuria should be monitored periodically posttransplant and investigation of the cause should be pursued vigorously.
    MeSH term(s) Calcineurin Inhibitors ; Graft Survival ; Humans ; Immunosuppressive Agents/adverse effects ; Kidney Failure, Chronic/complications ; Kidney Failure, Chronic/surgery ; Kidney Transplantation/adverse effects ; Prognosis ; Proteinuria/etiology ; Proteinuria/therapy ; Sirolimus/adverse effects
    Chemical Substances Calcineurin Inhibitors ; Immunosuppressive Agents ; Sirolimus (W36ZG6FT64)
    Language English
    Publishing date 2009-12
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1085942-1
    ISSN 1533-3450 ; 1046-6673
    ISSN (online) 1533-3450
    ISSN 1046-6673
    DOI 10.1681/ASN.2008091005
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  7. Article ; Online: Impact of Pregnancy on GFR Decline and Kidney Histology in Kidney Transplant Recipients.

    Kattah, Andrea G / Albadri, Sam / Alexander, Mariam P / Smith, Byron / Parashuram, Santosh / Mai, Marin L / Khamash, Hasan A / Cosio, Fernando G / Garovic, Vesna D

    Kidney international reports

    2021  Volume 7, Issue 1, Page(s) 28–35

    Abstract: Introduction: Women with advanced kidney disease are advised to wait until after transplant to pursue pregnancy, but the impact of pregnancy on estimated glomerular filtration rate (eGFR) decline and kidney histology is unclear.: Methods: We ... ...

    Abstract Introduction: Women with advanced kidney disease are advised to wait until after transplant to pursue pregnancy, but the impact of pregnancy on estimated glomerular filtration rate (eGFR) decline and kidney histology is unclear.
    Methods: We identified a cohort of women aged 18 to 44 years at transplant from 1996 to 2014 at our 3-site program (
    Results: There were 37 women with one or more pregnancies lasting longer than 20 weeks gestation post-transplant. Comparing women with and without pregnancy post-transplant, there was a significant increase in the rate of eGFR decline after pregnancy (-2.4 ml/min per 1.73 m
    Conclusion: Pregnancy affects the rate of eGFR decline in the allograft. Postpregnancy biopsy findings revealed an increase in vascular injury, which could be a potential mechanism. We did not find a significant increase in risk of graft failure or reduction in eGFR by 50% owing to pregnancy.
    Language English
    Publishing date 2021-10-30
    Publishing country United States
    Document type Journal Article
    ISSN 2468-0249
    ISSN (online) 2468-0249
    DOI 10.1016/j.ekir.2021.10.010
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  8. Article ; Online: Through a glass darkly: seeking clarity in preventing late kidney transplant failure.

    Stegall, Mark D / Gaston, Robert S / Cosio, Fernando G / Matas, Arthur

    Journal of the American Society of Nephrology : JASN

    2014  Volume 26, Issue 1, Page(s) 20–29

    Abstract: A common lament is that long-term kidney transplant outcomes remain the same despite improvements in early graft survival. To be fair, progress has been made-in both our understanding of chronic injury and modestly, graft survival. However, we are still ... ...

    Abstract A common lament is that long-term kidney transplant outcomes remain the same despite improvements in early graft survival. To be fair, progress has been made-in both our understanding of chronic injury and modestly, graft survival. However, we are still a long way from actually solving this important and difficult problem. In this review, we outline recent data supporting the existence of several causes of renal allograft loss, the incidences of which peak at different time points after transplantation. On the basis of this broadened concept of chronic renal allograft injury, we examine the challenges of clinical trial design in long-term studies, including the use of surrogate end points and biomarkers. Finally, we suggest a path forward that, ultimately, may improve long-term renal allograft survival.
    MeSH term(s) Biomarkers ; Biopsy ; Clinical Trials as Topic ; Gene Expression Profiling ; Graft Rejection/prevention & control ; Graft Survival ; Humans ; Immunosuppression ; Immunosuppressive Agents/therapeutic use ; Inflammation ; Isoantibodies/chemistry ; Kidney Diseases/prevention & control ; Kidney Failure, Chronic/therapy ; Kidney Transplantation ; Recurrence ; Treatment Outcome
    Chemical Substances Biomarkers ; Immunosuppressive Agents ; Isoantibodies
    Language English
    Publishing date 2014-08-05
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1085942-1
    ISSN 1533-3450 ; 1046-6673
    ISSN (online) 1533-3450
    ISSN 1046-6673
    DOI 10.1681/ASN.2014040378
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  9. Article ; Online: Karyomegalic interstitial nephritis in a renal allograft.

    Ravindran, Aishwarya / Cortese, Cherise / Larsen, Chris P / Wadei, Hani M / Gandhi, Manish J / Cosio, Fernando G / Sethi, Sanjeev

    American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons

    2018  Volume 19, Issue 1, Page(s) 285–290

    Abstract: Karyomegalic interstitial nephritis (KIN) is a rare renal interstitial disease entity characterized by large tubular nuclei, accompanied by interstitial inflammation, tubular atrophy, and interstitial fibrosis. Approximately 50 cases of KIN have been ... ...

    Abstract Karyomegalic interstitial nephritis (KIN) is a rare renal interstitial disease entity characterized by large tubular nuclei, accompanied by interstitial inflammation, tubular atrophy, and interstitial fibrosis. Approximately 50 cases of KIN have been described in the native kidney. In this case study, we describe the first case of KIN in a kidney allograft. A 41-year-old man presented with declining kidney function and a serum creatinine of 2.7 mg/dL. The native kidney biopsy showed large pleomorphic nuclei in the proximal and distal tubular epithelial cells, which was associated with interstitial inflammation, and extensive interstitial fibrosis and tubular atrophy. Immunohistochemistry for cytomegalovirus, adenovirus, and simian virus 40 were negative. A diagnosis of KIN was rendered. The patient received a living-related kidney transplant from his sister. At 4-, 12-, and 24-months posttransplant, protocol allograft biopsies showed KIN with large pleomorphic nuclei in the proximal and distal tubules with mild interstitial inflammation, minimal tubular atrophy, and interstitial fibrosis. At 24.7 months of follow-up, the patient has stable renal function with a serum creatinine of 1.6 mg/dL. The KIN may represent recurrent KIN or donor-associated KIN. Recognition of this rare disease entity is important as it can be mistaken for a viral infection.
    MeSH term(s) Adult ; Biopsy ; Creatinine/blood ; Diabetes Mellitus, Type 2/complications ; Fibrosis ; Glomerular Filtration Rate ; Graft Survival ; Humans ; Hyperlipidemias/complications ; Hypertension/complications ; Hypothyroidism/complications ; Inflammation ; Kidney/pathology ; Kidney/surgery ; Kidney Failure, Chronic/complications ; Kidney Failure, Chronic/surgery ; Kidney Function Tests ; Kidney Transplantation ; Kidney Tubules/pathology ; Male ; Nephritis, Interstitial/complications ; Nephritis, Interstitial/pathology ; Prevalence ; Time Factors
    Chemical Substances Creatinine (AYI8EX34EU)
    Language English
    Publishing date 2018-08-20
    Publishing country United States
    Document type Case Reports
    ZDB-ID 2060594-8
    ISSN 1600-6143 ; 1600-6135
    ISSN (online) 1600-6143
    ISSN 1600-6135
    DOI 10.1111/ajt.15035
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: De novo donor-specific antibody following BK nephropathy: The incidence and association with antibody-mediated rejection.

    Cheungpasitporn, Wisit / Kremers, Walter K / Lorenz, Elizabeth / Amer, Hatem / Cosio, Fernando G / Stegall, Mark D / Gandhi, Manish J / Schinstock, Carrie A

    Clinical transplantation

    2018  Volume 32, Issue 3, Page(s) e13194

    Abstract: Background and objectives: The risk of de novo donor-specific antibody (dnDSA) development following BK viremia (BKV) or nephropathy (BKN) after kidney transplant remains unclear. We aimed to evaluate the relationships among dnDSA, BKV (BK blood PCR > ... ...

    Abstract Background and objectives: The risk of de novo donor-specific antibody (dnDSA) development following BK viremia (BKV) or nephropathy (BKN) after kidney transplant remains unclear. We aimed to evaluate the relationships among dnDSA, BKV (BK blood PCR > 15 000 copies), BKN, antibody-mediated rejection (AMR), and allograft loss.
    Patients and methods: We performed a retrospective cohort study of 904 solitary kidney transplant recipients transplanted between 10/2007 and 5/2014. Cox proportional hazards regression with time-dependent covariates were used to assess the relationships among BKN, isolated BKV, dnDSA, and the subsequent risk of AMR and allograft loss.
    Results: In multivariate analysis, we observed that BKN, but not BKV was a risk factor for dnDSA (HR, 3.18, P = .008). Of the patients with BK nephropathy, 14.0% (6/43) developed dnDSA, which occurred within 14 months of BK diagnosis. DnDSA in this setting remains a risk factor for subsequent AMR (HR 4.75, P = .0001) and allograft loss (HR 2.63, P = .018).
    Conclusions: BKN is an independent risk factor for development of dnDSA. Improved understanding of the characteristics of patients with BKN who are at highest risk for development of dnDSA would be valuable to customize immunosuppression reduction in this population.
    MeSH term(s) BK Virus/isolation & purification ; Female ; Follow-Up Studies ; Glomerular Filtration Rate ; Graft Rejection/epidemiology ; Graft Rejection/etiology ; Graft Rejection/pathology ; Graft Survival ; Humans ; Incidence ; Isoantibodies/adverse effects ; Kidney Diseases/virology ; Kidney Function Tests ; Kidney Transplantation/adverse effects ; Male ; Middle Aged ; Minnesota/epidemiology ; Polyomavirus Infections/complications ; Polyomavirus Infections/virology ; Prognosis ; Retrospective Studies ; Risk Factors ; Tissue Donors ; Tumor Virus Infections/complications ; Tumor Virus Infections/virology
    Chemical Substances Isoantibodies
    Language English
    Publishing date 2018-02-11
    Publishing country Denmark
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 639001-8
    ISSN 1399-0012 ; 0902-0063
    ISSN (online) 1399-0012
    ISSN 0902-0063
    DOI 10.1111/ctr.13194
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