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Beaudrey T, Bedo D, Weschler C, Caillard S, Florens N. From Risk Assessment to Management: Cardiovascular Complications in Pre- and Post-Kidney Transplant Recipients: A Narrative Review. Diagnostics (Basel) 2025; 15:802. [PMID: 40218153 PMCID: PMC11988545 DOI: 10.3390/diagnostics15070802] [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: 02/14/2025] [Revised: 03/17/2025] [Accepted: 03/21/2025] [Indexed: 04/14/2025] Open
Abstract
Kidney transplantation remains the best treatment for chronic kidney failure, offering better outcomes and quality of life compared with dialysis. Cardiovascular disease (CVD) is a major cause of morbidity and mortality in kidney transplant recipients and is associated with decreased patient survival and worse graft outcomes. Post-transplant CVD results from a complex interaction between traditional cardiovascular risk factors, such as hypertension and diabetes, and risk factors specific to kidney transplant recipients including chronic kidney disease, immunosuppressive drugs, or vascular access. An accurate assessment of cardiovascular risk is now needed to optimize the management of cardiovascular comorbidities through the detection of risk factors and the screening of hidden pretransplant coronary artery disease. Promising new strategies are emerging, such as GLP-1 receptor agonists and SGLT2 inhibitors, with a high potential to mitigate cardiovascular complications, although further research is needed to determine their role in kidney transplant recipients. Despite this progress, a significant gap remains in understanding the optimal management of post-transplant CVD, especially coronary artery disease, stroke, and peripheral artery disease. Addressing these challenges is essential to improve the short- and long-term outcomes in kidney transplant recipients. This narrative review aims to provide a comprehensive overview of cardiovascular risk assessment and post-transplant CVD management.
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Affiliation(s)
- Thomas Beaudrey
- Nephrology Department, Hôpitaux Universitaires de Strasbourg, 67000 Strasbourg, France; (T.B.); (D.B.); (C.W.); (S.C.)
- Inserm UMR_S 1109 Immuno-Rhumatology Laboratory, Translational Medicine Federation of Strasbourg (FMTS), FHU Target, Faculté de Médecine, Université de Strasbourg, 67000 Strasbourg, France
| | - Dimitri Bedo
- Nephrology Department, Hôpitaux Universitaires de Strasbourg, 67000 Strasbourg, France; (T.B.); (D.B.); (C.W.); (S.C.)
- Inserm UMR_S 1109 Immuno-Rhumatology Laboratory, Translational Medicine Federation of Strasbourg (FMTS), FHU Target, Faculté de Médecine, Université de Strasbourg, 67000 Strasbourg, France
| | - Célia Weschler
- Nephrology Department, Hôpitaux Universitaires de Strasbourg, 67000 Strasbourg, France; (T.B.); (D.B.); (C.W.); (S.C.)
| | - Sophie Caillard
- Nephrology Department, Hôpitaux Universitaires de Strasbourg, 67000 Strasbourg, France; (T.B.); (D.B.); (C.W.); (S.C.)
- Inserm UMR_S 1109 Immuno-Rhumatology Laboratory, Translational Medicine Federation of Strasbourg (FMTS), FHU Target, Faculté de Médecine, Université de Strasbourg, 67000 Strasbourg, France
| | - Nans Florens
- Nephrology Department, Hôpitaux Universitaires de Strasbourg, 67000 Strasbourg, France; (T.B.); (D.B.); (C.W.); (S.C.)
- Inserm UMR_S 1109 Immuno-Rhumatology Laboratory, Translational Medicine Federation of Strasbourg (FMTS), FHU Target, Faculté de Médecine, Université de Strasbourg, 67000 Strasbourg, France
- INI-CRCT (Cardiovascular and Renal Trialists), F-CRIN Network, 67000 Strasbourg, France
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2
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Paccagnella C, Andreola S, Gambaro A, Gambaro G, Caletti C. Immunosuppressive Therapy-Related Cardiovascular Risk Factors in Renal Transplantation: A Narrative Review. Cardiorenal Med 2025; 15:209-228. [PMID: 39956105 DOI: 10.1159/000542378] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2024] [Accepted: 10/24/2024] [Indexed: 02/18/2025] Open
Abstract
BACKGROUND Kidney transplantation is the best treatment for patients with chronic renal failure, capable of improving life expectancy and the risk of death from all causes, which, however, remains higher than in the general population. The leading cause of death in transplant patients is cardiovascular events, burdened by a significant impact brought about by anti-rejection therapy. Experimental and clinical studies to date show that in kidney transplant recipients, traditional cardiovascular risk factors (hypertension, diabetes, dyslipidemia, obesity, tobacco, etc.) may be exacerbated or worsened by the dysmetabolic effects of immunosuppressive drugs, which may also result in additional risk factors such as proteinuria, anemia, and arterial stiffness. The aim of this review was to provide an in-depth evaluation of the effect of immunosuppressive treatments on cardiovascular risk factors. SUMMARY We have investigated and described the main cardiovascular risk factors related to immunosuppressive drugs. We searched for relevant scientific articles in medicine, transplant, cardiologic, and nephrological journals in major medical science libraries. KEY MESSAGES Immunosuppressive drugs allow graft survival and successful bunking of the transplant; however, they are not without significant side effects and should always be prescribed weighing the risk/benefit ratio and the individual patient's therapeutic needs.
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Affiliation(s)
- Chiara Paccagnella
- Nephrology Postgraduate School, Division of Nephrology and Dialysis, Department of Medicine, University of Verona, Verona, Italy
| | - Stefano Andreola
- Division of Nephrology and Dialysis, Department of Medicine, University of Verona, Verona, Italy
| | - Alessia Gambaro
- Division of Cardiology, Department of Medicine, University of Verona, Verona, Italy
| | - Giovanni Gambaro
- Division of Nephrology and Dialysis, Department of Medicine, University of Verona, Verona, Italy
| | - Chiara Caletti
- Division of Nephrology and Dialysis, Department of Medicine, University of Verona, Verona, Italy
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3
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Kanbay M, Copur S, Mizrak B, Mallamaci F, Zoccali C. Mineralocorticoid receptor antagonists in kidney transplantation. Eur J Clin Invest 2024; 54:e14206. [PMID: 38578116 DOI: 10.1111/eci.14206] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Revised: 03/16/2024] [Accepted: 03/19/2024] [Indexed: 04/06/2024]
Abstract
BACKGROUND The fundamental role of the renin-angiotensin-aldosterone system in the pathophysiology of chronic kidney disease, congestive heart failure, hypertension and proteinuria is well established in pre-clinical and clinical studies. Mineralocorticoid receptor antagonists are among the primary options for renin-angiotensin-aldosterone system blockage, along with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. METHODS In this narrative review, we aim to evaluate the efficiency and safety of mineralocorticoid receptor antagonists in kidney transplant recipients, including the potential underlying pathophysiology. RESULTS The efficiency and safety of mineralocorticoid receptor antagonists in managing chronic kidney disease and proteinuria, either non-nephrotic or nephrotic range, have been demonstrated among nontransplanted patients, though studies investigating the role of mineralocorticoid receptor antagonists among kidney transplant recipients are scarce. Nevertheless, promising results have been reported in pre-clinical and clinical studies among kidney transplant recipients regarding the role of mineralocorticoid receptor antagonists in terms of ischaemia-reperfusion injury, proteinuria, or calcineurin inhibitor-mediated nephrotoxicity without considerable adverse events such as hypotension, hyperkalaemia or worsening renal functions. CONCLUSION Even though initial results regarding the role of mineralocorticoid receptor antagonist therapy for kidney transplant recipients are promising, there is clear need for large-scale randomized clinical trials with long-term follow-up data.
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Affiliation(s)
- Mehmet Kanbay
- Division of Nephrology, Department of Internal Medicine, Koc University School of Medicine, Istanbul, Turkey
| | - Sidar Copur
- Department of Internal Medicine, Koc University School of Medicine, Istanbul, Turkey
| | - Berk Mizrak
- Department of Internal Medicine, Koc University School of Medicine, Istanbul, Turkey
| | - Francesca Mallamaci
- Nephrology, Dialysis and Transplantation Unit Azienda Ospedaliera "Bianchi-Melacrino-Morelli" & CNR-IFC, Institute of Clinical Physiology, Research Unit of Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension of Reggio Calabria, Reggio Calabria, Italy
| | - Carmine Zoccali
- Renal Research Institute, New York, New York, USA
- Associazione Ipertensione Nefrologia Trapianto Renal (IPNET), Reggio Calabria, Italy
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4
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Larsson P, Englund B, Ekberg J, Felldin M, Broecker V, Mjörnstedt L, Baid-Agrawal S. Difficult-to-Treat Rejections in Kidney Transplant Recipients: Our Experience with Everolimus-Based Quadruple Maintenance Therapy. J Clin Med 2023; 12:6667. [PMID: 37892805 PMCID: PMC10607360 DOI: 10.3390/jcm12206667] [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: 10/04/2023] [Revised: 10/15/2023] [Accepted: 10/18/2023] [Indexed: 10/29/2023] Open
Abstract
All chronic and treatment-resistant acute rejections are "difficult-to-treat" and lead to progressive loss of graft function in kidney transplant recipients (KTR), as no effective treatment exists for such rejections to date. We review our experience with a novel strategy to treat such rejections by adding everolimus as a "rescue" to conventional triple maintenance therapy with prednisolone, mycophenolate mofetil and calcineurin inhibitor. We retrospectively analysed data in 28 KTR who received everolimus-based quadruple therapy at our institution for biopsy-proven chronic active T cell-mediated or antibody-mediated rejection (n = 19) or treatment-resistant acute rejections (n = 9) between 2011-2017. The primary outcome was 5-year death-censored graft survival. Main secondary outcomes were response to treatment defined by stable or improved graft function, 5-year patient survival and discontinuation rate of treatment. The Kaplan-Meier estimate for 5-year death-censored graft survival was 79% in all patients, 90% for patients with chronic active T cell-mediated rejections, 78% for chronic active antibody-mediated rejection and 67% for acute rejections. Response to treatment was achieved in 43% and 5-year patient survival was 94%. Treatment was stopped in 12 (43%) patients due to adverse events. Everolimus-based maintenance quadruple therapy, despite high rate of everolimus discontinuation due to adverse events, may be a valid approach in a subset of kidney transplant recipients with such difficult-to-treat rejections, which otherwise would lead to a high rate of graft loss.
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Affiliation(s)
- Pierre Larsson
- Transplantation Center, Sahlgrenska University Hospital, University of Gothenburg, 41345 Gothenburg, Sweden; (P.L.); (J.E.)
- Department of Pathology, Sahlgrenska University Hospital, 41345 Gothenburg, Sweden
| | - Bodil Englund
- Department of Nephrology, Danderyd Hospital, Karolinska Institute, 18288 Stockholm, Sweden
| | - Jana Ekberg
- Transplantation Center, Sahlgrenska University Hospital, University of Gothenburg, 41345 Gothenburg, Sweden; (P.L.); (J.E.)
| | - Marie Felldin
- Transplantation Center, Sahlgrenska University Hospital, University of Gothenburg, 41345 Gothenburg, Sweden; (P.L.); (J.E.)
| | - Verena Broecker
- Department of Pathology, Sahlgrenska University Hospital, 41345 Gothenburg, Sweden
| | - Lars Mjörnstedt
- Transplantation Center, Sahlgrenska University Hospital, University of Gothenburg, 41345 Gothenburg, Sweden; (P.L.); (J.E.)
| | - Seema Baid-Agrawal
- Transplantation Center, Sahlgrenska University Hospital, University of Gothenburg, 41345 Gothenburg, Sweden; (P.L.); (J.E.)
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5
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Antiproteinuric effect of paricalcitol in kidney transplant recipients with severe proteinuria: a prospective cohort study. J Nephrol 2022; 35:1943-1945. [PMID: 35900720 DOI: 10.1007/s40620-022-01399-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Accepted: 07/06/2022] [Indexed: 10/16/2022]
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Isaksson GL, Nielsen MB, Hinrichs GR, Krogstrup NV, Zachar R, Stubmark H, Svenningsen P, Madsen K, Bistrup C, Jespersen B, Birn H, Palarasah Y, Jensen BL. Proteinuria is accompanied by intratubular complement activation and apical membrane deposition of C3dg and C5b-9 in kidney transplant recipients. Am J Physiol Renal Physiol 2021; 322:F150-F163. [PMID: 34927448 PMCID: PMC8791842 DOI: 10.1152/ajprenal.00300.2021] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
Proteinuria predicts accelerated decline in kidney function in kidney transplant recipients (KTRs). We hypothesized that aberrant filtration of complement factors causes intraluminal activation, apical membrane attack on tubular cells, and progressive injury. Biobanked samples from two previous studies in albuminuric KTRs were used. The complement-activation split products C3c, C3dg, and soluble C5b-9-associated C9 neoantigen were analyzed by ELISA in urine and plasma using neoepitope-specific antibodies. Urinary extracellular vesicles (uEVs) were enriched by lectin and immunoaffinity isolation and analyzed by immunoblot analysis. Urine complement excretion increased significantly in KTRs with an albumin-to-creatinine ratio of ≥300 mg/g compared with <30 mg/g. Urine C3dg and C9 neoantigen excretion correlated significantly to changes in albumin excretion from 3 to 12 mo after transplantation. Fractional excretion of C9 neoantigen was significantly higher than for albumin, indicating postfiltration generation. C9 neoantigen was detected in uEVs in six of the nine albuminuric KTRs but was absent in non-albuminuric controls (n = 8). In C9 neoantigen-positive KTRs, lectin affinity enrichment of uEVs from the proximal tubules yielded signal for iC3b, C3dg, C9 neoantigen, and Na+-glucose transporter 2 but only weakly for aquaporin 2. Coisolation of podocyte markers and Tamm–Horsfall protein was minimal. Our findings show that albuminuria is associated with aberrant filtration and intratubular activation of complement with deposition of C3 activation split products and C5b-9-associated C9 neoantigen on uEVs from the proximal tubular apical membrane. Intratubular complement activation may contribute to progressive kidney injury in proteinuric kidney grafts. NEW & NOTEWORTHY The present study proposes a mechanistic coupling between proteinuria and aberrant filtration of complement precursors, intratubular complement activation, and apical membrane attack in kidney transplant recipients. C3dg and C5b-9-associated C9 neoantigen associate with proximal tubular apical membranes as demonstrated in urine extracellular vesicles. The discovery suggests intratubular complement as a mediator between proteinuria and progressive kidney damage. Inhibitors of soluble and/or luminal complement activation with access to the tubular lumen may be beneficial.
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Affiliation(s)
- Gustaf Lissel Isaksson
- Dept. of Molecular Medicine - Cardiovascular and Renal Research, University of Southern Denmark, Odense, Denmark.,Dept. of Nephrology, Odense University Hospital, Odense, Denmark
| | - Marie Bodilsen Nielsen
- Dept. of Renal Medicine, Aarhus University Hospital, Aarhus, Denmark.,Dept of Biomedicine, Aarhus University, Aarhus, Denmark
| | - Gitte Rye Hinrichs
- Dept. of Molecular Medicine - Cardiovascular and Renal Research, University of Southern Denmark, Odense, Denmark.,Dept. of Nephrology, Odense University Hospital, Odense, Denmark
| | | | - Rikke Zachar
- Dept. of Molecular Medicine - Cardiovascular and Renal Research, University of Southern Denmark, Odense, Denmark
| | - Heidi Stubmark
- Dept. of Molecular Medicine - Cardiovascular and Renal Research, University of Southern Denmark, Odense, Denmark
| | - Per Svenningsen
- Dept. of Molecular Medicine - Cardiovascular and Renal Research, University of Southern Denmark, Odense, Denmark
| | - Kirsten Madsen
- Dept. of Molecular Medicine - Cardiovascular and Renal Research, University of Southern Denmark, Odense, Denmark.,Dept. of Pathology, Odense University Hospital, Odense, Denmark
| | - Claus Bistrup
- Dept. of Nephrology, Odense University Hospital, Odense, Denmark.,Dept. of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Bente Jespersen
- Dept. of Renal Medicine, Aarhus University Hospital, Aarhus, Denmark.,Dept. of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | | | - Henrik Birn
- Dept. of Renal Medicine, Aarhus University Hospital, Aarhus, Denmark.,Dept of Biomedicine, Aarhus University, Aarhus, Denmark
| | - Yaseelan Palarasah
- Dept. of Molecular Medicine - Cancer and Inflammation Research, University of Southern Denmark, Odense, Denmark
| | - Boye L Jensen
- Dept. of Molecular Medicine - Cardiovascular and Renal Research, University of Southern Denmark, Odense, Denmark
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7
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Kuper T, Famure O, Greenfield J, Li Y, Ibrahim S, Narang T, Ashwin M, Joseph Kim S. Time-Varying Proteinuria and the Risk of Cardiovascular Disease and Graft Failure in Kidney Transplant Recipients. Prog Transplant 2021; 31:288-297. [PMID: 34839728 DOI: 10.1177/15269248211046011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Introduction: Proteinuria is recognized as an independent risk factor for cardiovascular disease in kidney transplant recipients, but previous studies have not considered the impact of changes in urine protein over time. Research Question and Design: We used time-dependent, multivariable Cox proportional hazards models in this observational cohort study of adult kidney transplant recipients to evaluate whether proteinuria measured by dipstick on random spot urine samples starting from 1-month post-transplant was associated with the risk of major adverse cardiac events and graft loss. Results: A total of 144 major adverse cardiac events, defined as acute myocardial infarction, cerebrovascular accident, revascularization, or all-cause mortality, were observed in 1106 patients over 5728.7 person-years. Any level of proteinuria greater or equal to trace resulted in a two-fold increase in the risk of major adverse cardiac events (hazard ratio 2.00 [95% confidence interval 1.41, 2.84]). This relationship was not found to be dose-dependent (hazard ratios of 2.98, 1.76, 1.63, and 1.54 for trace, 1+, 2+, and 3+ urine protein, respectively). There was an increased risk of graft failure with greater urine protein concentration (hazard ratios 2.22, 2.85, 6.41, and 19.71 for trace, 1+, 2+, and 3+, respectively). Conclusion: Urine protein is associated with major adverse cardiac events and graft loss in kidney transplant recipients. The role of interventions to reduce proteinuria on decreasing the risk of adverse cardiovascular and graft outcomes in kidney transplant recipients requires further study.
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Affiliation(s)
- Tanya Kuper
- Toronto General Hospital, 7989University Health Network, Toronto, Ontario, Canada
| | - Olusegun Famure
- Toronto General Hospital, 7989University Health Network, Toronto, Ontario, Canada
| | - Jamie Greenfield
- Toronto General Hospital, 7989University Health Network, Toronto, Ontario, Canada
| | - Yanhong Li
- Toronto General Hospital, 7989University Health Network, Toronto, Ontario, Canada
| | - Syed Ibrahim
- Toronto General Hospital, 7989University Health Network, Toronto, Ontario, Canada
| | - Tanya Narang
- Toronto General Hospital, 7989University Health Network, Toronto, Ontario, Canada
| | - Monika Ashwin
- Toronto General Hospital, 7989University Health Network, Toronto, Ontario, Canada
| | - S Joseph Kim
- Toronto General Hospital, 7989University Health Network, Toronto, Ontario, Canada.,University of Toronto, Toronto, Ontario, Canada.,St Michael's Hospital, Toronto, Ontario, Canada.,University of Toronto, Toronto, Ontario, Canada
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8
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Parajuli S, Swanson KJ, Alstott J, Aziz F, Garg N, Zhong W, Djamali A, Mandelbrot D. Transplant kidney biopsy for proteinuria with stable creatinine: Findings and outcomes. Clin Transplant 2021; 35:e14436. [PMID: 34291509 DOI: 10.1111/ctr.14436] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2021] [Revised: 07/08/2021] [Accepted: 07/19/2021] [Indexed: 11/27/2022]
Abstract
INTRODUCTION Little is known aboutbiopsy findings and outcomes when kidney transplant recipients (KTRs) undergo biopsy for isolated proteinuria with stable serum creatinine (SCr). METHODS We analyzed all KTRs who underwent biopsy for isolated proteinuria with stable SCr between January 2016 and June 2020. Patients were divided into three groups based on the biopsy findings: Active Rejection (AR), Glomerulonephritis (GN), and Other. RESULTS A total of 130 KTRs fulfilled our selection criteria; 38 (29%) in the AR group, 26 (20%) in the GN group, and 66 (51%) in the Other group. Most baseline characteristics were similar between the groups. In multivariate analysis, higher HLA mismatch (HR per mismatch: 1.30; 95% CI:1.06-1.59; P = .01) and male gender (HR: .45; 95% CI .23-.89; P = .02) were associated with AR. There was no significant correlation between the degree of proteinuria and rejection (r = .05, P = .58) or GN (r = .07, P = .53). Graft survival was also similar between the groups. Likely due to the early diagnosis without a significant rise in SCr, outcomes were similar among all three groups. CONCLUSION Routine monitoring for proteinuria followed by a biopsy and appropriate management may help to identify early acute graft injury and prevent graft failure.
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Affiliation(s)
- Sandesh Parajuli
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA
| | - Kurtis J Swanson
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA
| | - James Alstott
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA
| | - Fahad Aziz
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA
| | - Neetika Garg
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA
| | - Weixiong Zhong
- Department of Pathology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA
| | - Arjang Djamali
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA
| | - Didier Mandelbrot
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA
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Jang HR, Kim M, Hong S, Lee K, Park MY, Yang KE, Lee CJ, Jeon J, Lee KW, Lee JE, Park JB, Kim K, Kwon GY, Kim YG, Kim DJ, Huh W. Early postoperative urinary MCP-1 as a potential biomarker predicting acute rejection in living donor kidney transplantation: a prospective cohort study. Sci Rep 2021; 11:18832. [PMID: 34552150 PMCID: PMC8458304 DOI: 10.1038/s41598-021-98135-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2021] [Accepted: 09/01/2021] [Indexed: 11/16/2022] Open
Abstract
We investigated the clinical relevance of urinary cytokines/chemokines reflecting intrarenal immunologic micromilieu as prognostic markers and the optimal measurement timing after living donor kidney transplantation (LDKT). This prospective cohort study included 77 LDKT patients who were followed for ≥ 5 years. Patients were divided into control (n = 42) or acute rejection (AR, n = 35) group. Early AR was defined as AR occurring within 3 months. Serum and urine cytokines/chemokines were measured serially as follows: intraoperative, 8/24/72 h, 1 week, 3 months, and 1 year after LDKT. Intrarenal total leukocytes, T cells, and B cells were analyzed with immunohistochemistry followed by tissueFAXS. Urinary MCP-1 and fractalkine were also analyzed in a validation cohort. Urinary MCP-1 after one week was higher in the AR group. Urinary MCP-1, fractalkine, TNF-α, RANTES, and IL-6 after one week were significantly higher in the early AR group. Intrarenal total leukocytes and T cells were elevated in the AR group compared with the control group. Urinary fractalkine, MCP-1, and IL-10 showed positive correlation with intrarenal leukocyte infiltration. Post-KT 1 week urinary MCP-1 showed predictive value in the validation cohort. One-week post-KT urinary MCP-1 may be used as a noninvasive diagnostic marker for predicting AR after LDKT.
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Affiliation(s)
- Hye Ryoun Jang
- Division of Nephrology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro, Gangnam-Gu, Seoul, 06351, Republic of Korea
| | - Minjung Kim
- Division of Nephrology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro, Gangnam-Gu, Seoul, 06351, Republic of Korea
| | - Sungjun Hong
- Department of Digital Health, Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University, Seoul, Republic of Korea
| | - Kyungho Lee
- Division of Nephrology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro, Gangnam-Gu, Seoul, 06351, Republic of Korea
| | - Mee Yeon Park
- Division of Nephrology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro, Gangnam-Gu, Seoul, 06351, Republic of Korea
| | - Kyeong Eun Yang
- Research Center for Materials Analysis, Korea Basic Science Institute, Daejeon, Republic of Korea
| | - Cheol-Jung Lee
- Research Center for Materials Analysis, Korea Basic Science Institute, Daejeon, Republic of Korea
| | - Junseok Jeon
- Division of Nephrology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro, Gangnam-Gu, Seoul, 06351, Republic of Korea
| | - Kyo Won Lee
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jung Eun Lee
- Division of Nephrology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro, Gangnam-Gu, Seoul, 06351, Republic of Korea
| | - Jae Berm Park
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Kyunga Kim
- Statistics and Data Center, Samsung Medical Center, Seoul, Republic of Korea
| | - Ghee Young Kwon
- Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Yoon Goo Kim
- Division of Nephrology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro, Gangnam-Gu, Seoul, 06351, Republic of Korea
| | - Dae Joong Kim
- Division of Nephrology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro, Gangnam-Gu, Seoul, 06351, Republic of Korea
| | - Wooseong Huh
- Division of Nephrology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro, Gangnam-Gu, Seoul, 06351, Republic of Korea.
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10
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Mrevlje M, Oblak M, Mlinšek G, Lindič J, Jadranka-Buturović-Ponikvar, Arnol M. First and second morning spot urine protein measurements for the assessment of proteinuria: a diagnostic accuracy study in kidney transplant recipients. BMC Nephrol 2021; 22:192. [PMID: 34022831 PMCID: PMC8141254 DOI: 10.1186/s12882-021-02406-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2021] [Accepted: 05/11/2021] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND Quantification of proteinuria in kidney transplant recipients is important for diagnostic and prognostic purposes. Apart from correlation tests, there have been few evaluations of spot urine protein measurements in kidney transplantation. METHODS In this cross-sectional study involving 151 transplanted patients, we investigated measures of agreement (bias and accuracy) between the estimated protein excretion rate (ePER), determined from the protein-to-creatinine ratio in the first and second morning urine, and 24-h proteinuria and studied their performance at different levels of proteinuria. Measures of agreement were reanalyzed in relation to allograft histology in 76 patients with kidney biopsies performed for cause before enrolment in the study. RESULTS For ePER in the first morning urine, percent bias ranged from 1 to 28% and accuracy (within 30% of 24-h collection) ranged from 56 to 73%. For the second morning urine, percent bias ranged from 2 to 11%, and accuracy ranged from 71 to 78%. The accuracy of ePER (within 30%) in first and second morning urine progressively increased from 56 and 71% for low-grade proteinuria (150-299 mg/day) to 60 and 74% for moderate proteinuria (300-999 mg/day), and to 73 and 78% for high-grade proteinuria (≥1000 mg/day). Measures of agreement were similar across histologic phenotypes of allograft injury. CONCLUSIONS The ability of ePER to accurately predict 24-h proteinuria in kidney transplant recipients is modest. However, accuracy improves with an increase in proteinuria. Given the similar accuracy of ePER measurements in first and second morning urine, second morning urine can be used to monitor protein excretion.
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Affiliation(s)
- Maja Mrevlje
- Department of Nephrology, Centre for Kidney Transplantation, University Medical Centre Ljubljana, Zaloska 7, 1000, Ljubljana, Slovenia
- Department of internal medicine, General Hospital Izola, Izola, Slovenia
| | - Manca Oblak
- Department of Nephrology, Centre for Kidney Transplantation, University Medical Centre Ljubljana, Zaloska 7, 1000, Ljubljana, Slovenia
| | - Gregor Mlinšek
- Department of Nephrology, Centre for Kidney Transplantation, University Medical Centre Ljubljana, Zaloska 7, 1000, Ljubljana, Slovenia
| | - Jelka Lindič
- Department of Nephrology, Centre for Kidney Transplantation, University Medical Centre Ljubljana, Zaloska 7, 1000, Ljubljana, Slovenia
| | - Jadranka-Buturović-Ponikvar
- Department of Nephrology, Centre for Kidney Transplantation, University Medical Centre Ljubljana, Zaloska 7, 1000, Ljubljana, Slovenia
- Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Miha Arnol
- Department of Nephrology, Centre for Kidney Transplantation, University Medical Centre Ljubljana, Zaloska 7, 1000, Ljubljana, Slovenia.
- Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
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11
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Rashid M, Nagaraja V, Shoaib A, Curzen N, Ludman PF, Kapadia SR, Palmer N, Elgendy IY, Kalra A, Vachharajani TJ, Anderson HV, Kwok CS, Mohamed M, Banning AP, Mamas MA. Outcomes Following Percutaneous Coronary Intervention in Renal Transplant Recipients: A Binational Collaborative Analysis. Mayo Clin Proc 2021; 96:363-376. [PMID: 33358453 DOI: 10.1016/j.mayocp.2020.04.045] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2020] [Accepted: 04/21/2020] [Indexed: 01/10/2023]
Abstract
OBJECTIVE To investigate the clinical and procedural characteristics in patients with a history of renal transplant (RT) and compare the outcomes with patients without RT in 2 national cohorts of patients undergoing percutaneous coronary intervention (PCI). PATIENTS AND METHODS Data from the National Inpatient Sample (NIS) and British Cardiovascular Intervention Society (BCIS) were used to compare the clinical and procedural characteristics and outcomes of patients undergoing PCI who had RT with those who did not have RT. The primary outcome of interest was in-hospital mortality. RESULTS Of the PCI procedures performed in 2004-2014 (NIS) and 2007-2014 (BCIS), 12,529 of 6,601,526 (0.2%) and 1521 of 512,356 (0.3%), respectively, were undertaken in patients with a history of RT. Patients with RT were younger and had a higher prevalence of congestive cardiac failure, hypertension, and diabetes but similar use of drug-eluting stents, intracoronary imaging, and pressure wire studies compared with patients who did not have RT. In the adjusted analysis, patients with RT had increased odds of in-hospital mortality (NIS: odds ratio [OR], 1.90; 95% CI, 1.41-2.57; BCIS: OR, 1.60; 95% CI, 1.05-2.46) compared with patients who did not have RT but no difference in vascular or bleeding events. Meta-analysis of the 2 data sets suggested an increase in in-hospital mortality (OR, 1.79; 95% CI, 1.40-2.29) but no difference in vascular (OR, 1.24; 95% CI, 0.77-2.00) or bleeding (OR, 1.21; 95% CI, 0.86-1.68) events. CONCLUSION This large collaborative analysis of 2 national databases revealed that patients with RT undergoing PCI are younger, have more comorbidities, and have increased mortality risk compared with the general population undergoing PCI.
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Affiliation(s)
- Muhammad Rashid
- Keele Cardiovascular Research Group, Centre for Prognosis Research, Institute of Primary Care and Health Sciences, Keele University, Keele, UK, and Academic Department of Cardiology, Royal Stoke Hospital, University Hospitals of North Midlands, Stoke-on-Trent, UK
| | - Vinayak Nagaraja
- Department of Cardiovascular Medicine, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, OH
| | - Ahmad Shoaib
- Keele Cardiovascular Research Group, Centre for Prognosis Research, Institute of Primary Care and Health Sciences, Keele University, Keele, UK, and Academic Department of Cardiology, Royal Stoke Hospital, University Hospitals of North Midlands, Stoke-on-Trent, UK
| | - Nick Curzen
- Department of Cardiology, University Hospital Southampton, and University of Southampton, Southampton, UK
| | - Peter F Ludman
- Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, UK
| | - Samir R Kapadia
- Department of Cardiovascular Medicine, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, OH
| | - Nick Palmer
- Department of Cardiology, Liverpool Heart and Chest Hospital, Liverpool, UK
| | - Islam Y Elgendy
- Division of Cardiology, Massachusetts General Hospital and Harvard Medical School, Boston
| | - Ankur Kalra
- Department of Cardiovascular Medicine, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, OH
| | - Tushar J Vachharajani
- Department of Cardiovascular Medicine, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, OH
| | - H Vernon Anderson
- Department of Internal Medicine, Division of Cardiology, McGovern Medical School, University of Texas Health Science Center, Houston
| | - Chun Shing Kwok
- Keele Cardiovascular Research Group, Centre for Prognosis Research, Institute of Primary Care and Health Sciences, Keele University, Keele, UK, and Academic Department of Cardiology, Royal Stoke Hospital, University Hospitals of North Midlands, Stoke-on-Trent, UK
| | - Mohamed Mohamed
- Keele Cardiovascular Research Group, Centre for Prognosis Research, Institute of Primary Care and Health Sciences, Keele University, Keele, UK, and Academic Department of Cardiology, Royal Stoke Hospital, University Hospitals of North Midlands, Stoke-on-Trent, UK
| | - Adrian P Banning
- Oxford Heart Centre, Oxford University Hospitals, NHS Trust, Oxford, UK
| | - Mamas A Mamas
- Keele Cardiovascular Research Group, Centre for Prognosis Research, Institute of Primary Care and Health Sciences, Keele University, Keele, UK, and Academic Department of Cardiology, Royal Stoke Hospital, University Hospitals of North Midlands, Stoke-on-Trent, UK; Department of Cardiology, Thomas Jefferson University Hospital, Philadelphia, PA.
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12
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Asleh R, Alnsasra H, Lerman A, Briasoulis A, Pereira NL, Edwards BS, Toya T, Stulak JM, Clavell AL, Daly RC, Kushwaha SS. Effects of mTOR inhibitor-related proteinuria on progression of cardiac allograft vasculopathy and outcomes among heart transplant recipients. Am J Transplant 2021; 21:626-635. [PMID: 32558174 DOI: 10.1111/ajt.16155] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2020] [Revised: 05/19/2020] [Accepted: 06/13/2020] [Indexed: 01/25/2023]
Abstract
We have previously described the use of sirolimus (SRL) as primary immunosuppression following heart transplantation (HT). The advantages of this approach include attenuation of cardiac allograft vasculopathy (CAV), improvement in glomerular filtration rate (GFR), and reduced malignancy. However, in some patients SRL may cause significant proteinuria. We sought to investigate the prognostic value of proteinuria after conversion to SRL. CAV progression and adverse clinical events were studied. CAV progression was assessed by measuring the Δ change in plaque volume (PV) and plaque index (PI) per year using coronary intravascular ultrasound. Proteinuria was defined as Δ urine protein ≥300 mg/24 h at 1 year after conversion to SRL. Overall, 137 patients were analyzed (26% with proteinuria). Patients with proteinuria had significantly lower GFR (P = .005) but similar GFR during follow-up. Delta PV (P < .001) and Δ PI (P = .001) were significantly higher among patients with proteinuria after adjustment for baseline characteristics. Multivariate Cox regression analysis showed higher all-cause mortality (hazard ratio 3.8; P = .01) with proteinuria but similar risk of CAV-related events (P = .61). Our results indicate that proteinuria is a marker of baseline renal dysfunction, and that HT recipients who develop proteinuria after conversion to SRL have less attenuation of CAV progression and higher mortality risk.
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Affiliation(s)
- Rabea Asleh
- Department of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota, USA.,Department of Cardiology, Hadassah University Medical Center, Jerusalem, Israel
| | - Hilmi Alnsasra
- Department of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota, USA
| | - Amir Lerman
- Department of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota, USA
| | - Alexandros Briasoulis
- Division of Cardiovascular Diseases, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA
| | - Naveen L Pereira
- Department of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota, USA
| | - Brooks S Edwards
- Department of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota, USA
| | - Takumi Toya
- Department of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota, USA
| | - John M Stulak
- Department of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota, USA
| | - Alfredo L Clavell
- Department of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota, USA
| | - Richard C Daly
- Department of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota, USA
| | - Sudhir S Kushwaha
- Department of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota, USA
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13
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Thongprayoon C, Hansrivijit P, Leeaphorn N, Acharya P, Torres-Ortiz A, Kaewput W, Kovvuru K, Kanduri SR, Bathini T, Cheungpasitporn W. Recent Advances and Clinical Outcomes of Kidney Transplantation. J Clin Med 2020; 9:1193. [PMID: 32331309 PMCID: PMC7230851 DOI: 10.3390/jcm9041193] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2020] [Accepted: 04/20/2020] [Indexed: 02/07/2023] Open
Abstract
Recent advances in surgical, immunosuppressive and monitoring protocols have led to the significant improvement of overall one-year kidney allograft outcomes. Nonetheless, there has not been a significant change in long-term kidney allograft outcomes. In fact, chronic and acute antibody-mediated rejection (ABMR) and non-immunological complications following kidney transplantation, including multiple incidences of primary kidney disease, as well as complications such as cardiovascular diseases, infections, and malignancy are the major factors that have contributed to the failure of kidney allografts. The use of molecular techniques to enhance histological diagnostics and noninvasive surveillance are what the latest studies in the field of clinical kidney transplant seem to mainly focus upon. Increasingly innovative approaches are being used to discover immunosuppressive methods to overcome critical sensitization, prevent the development of anti-human leukocyte antigen (HLA) antibodies, treat chronic active ABMR, and reduce non-immunological complications following kidney transplantation, such as the recurrence of primary kidney disease and other complications, such as cardiovascular diseases, infections, and malignancy. In the present era of utilizing electronic health records (EHRs), it is strongly believed that big data and artificial intelligence will reshape the research done on kidney transplantation in the near future. In addition, the utilization of telemedicine is increasing, providing benefits such as reaching out to kidney transplant patients in remote areas and helping to make scarce healthcare resources more accessible for kidney transplantation. In this article, we discuss the recent research developments in kidney transplants that may affect long-term allografts, as well as the survival of the patient. The latest developments in living kidney donation are also explored.
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Affiliation(s)
- Charat Thongprayoon
- Division of Nephrology, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA;
| | - Panupong Hansrivijit
- Department of Internal Medicine, University of Pittsburgh Medical Center Pinnacle, Harrisburg, PA 17105, USA;
| | - Napat Leeaphorn
- Department of Nephrology, Department of Medicine, Saint Luke’s Health System, Kansas City, MO 64111, USA;
| | - Prakrati Acharya
- Division of Nephrology, Department of Medicine, Texas Tech University Health Sciences Center, El Paso, TX 79905, USA;
| | - Aldo Torres-Ortiz
- Department of Medicine, Ochsner Medical Center, New Orleans, LA 70121, USA;
| | - Wisit Kaewput
- Department of Military and Community Medicine, Phramongkutklao College of Medicine, Bangkok 10400, Thailand;
| | - Karthik Kovvuru
- Division of Nephrology, Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA; (K.K.); (S.R.K.)
| | - Swetha R. Kanduri
- Division of Nephrology, Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA; (K.K.); (S.R.K.)
| | - Tarun Bathini
- Department of Internal Medicine, University of Arizona, Tucson, AZ 85724, USA;
| | - Wisit Cheungpasitporn
- Division of Nephrology, Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA; (K.K.); (S.R.K.)
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14
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Molcho M, Rozen-Zvi B, Shteinmats T, Ben Dor N, Vahav I, Nesher E, Rahamimov R. Temporal changes of proteinuria after kidney transplantation: association with cardiovascular morbidity and mortality. J Nephrol 2020; 33:1059-1066. [PMID: 31953621 DOI: 10.1007/s40620-020-00703-6] [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: 10/25/2019] [Accepted: 01/06/2020] [Indexed: 12/17/2022]
Abstract
BACKGROUND Proteinuria is common in kidney transplant recipients and has been established as a risk factor for graft-loss and mortality. In the general population, proteinuria has also been tied to a higher risk of cardiovascular disease. There is limited data exploring the association between changes in proteinuria over time and cardiovascular disease in kidney transplant recipients. METHODS In this retrospective cohort study we evaluated proteinuria as a time-varying covariate using urine dipstick protein values at 6 month intervals post-transplant. The primary outcome was the occurrence a major cardiovascular event (MACE). Univariate and multivariate time varying Cox model was used. RESULTS 579 patients were included in the final cohort. 120 episodes of MACE were documented in 98 patients. Time varying proteinuria was associated with MACE by univariate and multivariate analysis (HR 2.63, 95% CI 1.76-3.93, p < 0.001) and (HR 2.33, 95% CI 1.53-3.54, p < 0.001). Reduction of proteinuria to normal was associated with reduced risk of MACE compared with active proteinuria (HR 0.44, 95% CI 0.28-0.69, p < 0.001) and (HR 0.47, 95% CI 0.3-0.76, p = 0.002) for univariate and multivariate analyses. Exposure to proteinuria for more than 1 year was significantly associated with an increased risk of MACE for univariate and multivariate analysis (HR 2.33, 95% CI 1.48-3.68, p < 0.001) and (HR 2.18, 95% CI 1.37-3.45, p = 0.002) respectively, in comparison to exposure of less than 1 year. CONCLUSION These findings may suggest that we should consider applying clinical interventions that are known to reduce cardiovascular morbidity in these patients.
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Affiliation(s)
- Maya Molcho
- Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Benaya Rozen-Zvi
- Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.,Department of Nephrology and Hypertension, Rabin Medical Center, Beilinson campus. 39, Jabutinsky St., Petah-Tikva, Israel
| | - Tali Shteinmats
- Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.,Department of Nephrology and Hypertension, Rabin Medical Center, Beilinson campus. 39, Jabutinsky St., Petah-Tikva, Israel
| | - Naomi Ben Dor
- Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.,Department of Nephrology and Hypertension, Rabin Medical Center, Beilinson campus. 39, Jabutinsky St., Petah-Tikva, Israel
| | - Itay Vahav
- Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Eviatar Nesher
- Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.,Department of Transplantation, Rabin Medical Center, Beilinson campus, Petah-Tikva, Israel
| | - Ruth Rahamimov
- Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel. .,Department of Nephrology and Hypertension, Rabin Medical Center, Beilinson campus. 39, Jabutinsky St., Petah-Tikva, Israel. .,Department of Transplantation, Rabin Medical Center, Beilinson campus, Petah-Tikva, Israel.
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15
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Medina S, De Las Heras-Gómez I, Casas-Pina T, Bultel-Poncé V, Galano JM, Durand T, Martínez-Hernández P, Ferreres F, Jimeno L, Llorente S, Gil-Izquierdo Á. Urinary oxylipin signature as biomarkers to monitor the allograft function during the first six months post-renal transplantation. Free Radic Biol Med 2020; 146:340-349. [PMID: 31734358 DOI: 10.1016/j.freeradbiomed.2019.11.010] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2019] [Revised: 10/30/2019] [Accepted: 11/07/2019] [Indexed: 12/13/2022]
Abstract
Oxylipins such as isoprostanes (IsoPs), prostaglandins (PGs) and thromboxanes (TXs) are lipid mediators derived from the oxidation of polyunsaturated fatty acids, which regulate the magnitude of oxidative stress and inflammation processes and play an important role in pathophysiological processes in the kidney. A total of 36 oxylipins were analyzed by UHPLC-QqQ-MS/MS in the urine of 41 renal recipients from cadaveric donors of the Nephrology Unit of the University Hospital Virgen de la Arrixaca during the first six months after renal transplantation, in order to investigate several candidate oxylipins as more accurate and predictive biomarkers in renal transplantation than classical biological variables. A decrease in nine PGs, mostly from the AA-D pathway (p < 0.05) and one IsoP: 15-keto-15-F2t-IsoP (p < 0.001) was observed. Moreover, two PGs (2,3-dinor-11β-PGF2α and 17-trans-PGF3α) increased between five days and six months after renal transplantation (p < 0.05). In addition, when kidney function improved, a positive correlation between oxylipin levels and the excretion of urine proteins was observed. These results suggest that oxylipins could be useful markers for monitoring renal function in the post-renal transplantation period. These findings could be of utility not only for the development of strategies for long-term preservation of graft function, but also for innovative and alternative therapies -using oxylipins as predictive markers-to avoid organ rejection.
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Affiliation(s)
- Sonia Medina
- Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS (CSIC), P.O. Box 164, 30100, Campus University Espinardo, Murcia, Spain.
| | - Ignacio De Las Heras-Gómez
- Clinical Analysis Service, University Hospital Virgen de la Arrixaca, Murcia, Ctra. Madrid-Cartagena, S/n, 30120, El Palmar, Spain
| | - Teresa Casas-Pina
- Clinical Analysis Service, University Hospital Virgen de la Arrixaca, Murcia, Ctra. Madrid-Cartagena, S/n, 30120, El Palmar, Spain
| | - Valérie Bultel-Poncé
- Institut des Biomolécules Max Mousseron (IBMM), UMR 5247 - CNRS, University of Montpellier - ENSCM, Faculty of Pharmacy, Montpellier, France
| | - Jean-Marie Galano
- Institut des Biomolécules Max Mousseron (IBMM), UMR 5247 - CNRS, University of Montpellier - ENSCM, Faculty of Pharmacy, Montpellier, France
| | - Thierry Durand
- Institut des Biomolécules Max Mousseron (IBMM), UMR 5247 - CNRS, University of Montpellier - ENSCM, Faculty of Pharmacy, Montpellier, France
| | - Pedro Martínez-Hernández
- Clinical Analysis Service, University Hospital Virgen de la Arrixaca, Murcia, Ctra. Madrid-Cartagena, S/n, 30120, El Palmar, Spain
| | - Federico Ferreres
- Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS (CSIC), P.O. Box 164, 30100, Campus University Espinardo, Murcia, Spain
| | - Luisa Jimeno
- Nephrology Service, University Hospital Virgen de la Arrixaca, Murcia, Ctra. Madrid-Cartagena, S/n, 30120, El Palmar, Spain
| | - Santiago Llorente
- Nephrology Service, University Hospital Virgen de la Arrixaca, Murcia, Ctra. Madrid-Cartagena, S/n, 30120, El Palmar, Spain
| | - Ángel Gil-Izquierdo
- Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS (CSIC), P.O. Box 164, 30100, Campus University Espinardo, Murcia, Spain.
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16
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Göknar N, Saygılı S, Canpolat N, Özlük Y, Kılıçaslan I, Sever L, Çalışkan S. A rare cause of proteinuria after kidney transplantation: Answers. Pediatr Nephrol 2019; 34:2333-2335. [PMID: 31041519 DOI: 10.1007/s00467-019-04263-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2019] [Revised: 04/05/2019] [Accepted: 04/08/2019] [Indexed: 11/30/2022]
Affiliation(s)
- Nilüfer Göknar
- Faculty of Medicine, Department of Pediatric Nephrology, Goztepe Education and Research Hospital, Istanbul Medeniyet University, Istanbul, Turkey.
| | - Seha Saygılı
- Cerrahpaşa Faculty of Medicine, Department of Pediatric Nephrology, Istanbul University-Cerrahpaşa, Istanbul, Turkey
| | - Nur Canpolat
- Cerrahpaşa Faculty of Medicine, Department of Pediatric Nephrology, Istanbul University-Cerrahpaşa, Istanbul, Turkey
| | - Yasemin Özlük
- Istanbul Faculty of Medicine, Department of Pathology, Istanbul University, Istanbul, Turkey
| | - Işın Kılıçaslan
- Istanbul Faculty of Medicine, Department of Pathology, Istanbul University, Istanbul, Turkey
| | - Lale Sever
- Cerrahpaşa Faculty of Medicine, Department of Pediatric Nephrology, Istanbul University-Cerrahpaşa, Istanbul, Turkey
| | - Salim Çalışkan
- Cerrahpaşa Faculty of Medicine, Department of Pediatric Nephrology, Istanbul University-Cerrahpaşa, Istanbul, Turkey
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17
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Nomura S, Ariyoshi Y, Watanabe H, Pomposelli T, Takeuchi K, Garcia G, Tasaki M, Ayares D, Sykes M, Sachs D, Johnson R, Yamada K. Transgenic expression of human CD47 reduces phagocytosis of porcine endothelial cells and podocytes by baboon and human macrophages. Xenotransplantation 2019; 27:e12549. [PMID: 31495971 DOI: 10.1111/xen.12549] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2019] [Revised: 06/12/2019] [Accepted: 07/24/2019] [Indexed: 12/16/2022]
Abstract
BACKGROUND Our initial studies utilizing a galactosyl-α1-3-galactosyltransferase gene knockout (GalTKO) pig-to-baboon renal transplant model demonstrated that the early development of nephrotic syndrome has been a significant obstacle to the long-term survival of baboon recipients. We have recently documented that sphingomyelin phosphodiesterase-3 (SMPDL3b) and CD80 expressed on podocytes in porcine kidney grafts contribute to this complication. We have hypothesized that one regulator of immune function is CD47 and that incompatibilities in CD47 between pig and baboon could potentially affect macrophage function, increasing the susceptibility of the kidney grafts to immunologically induced injury. METHODS In order to address this hypothesis in vitro, we isolated and cultured porcine podocytes and ECs from GalTKO alone, human CD47 (hCD47)/hCD55 expressing transgenic (Tg) GalTKO swine, and GalTKO hCD46/hCD55 Tg swine along with baboon or human macrophages. RESULTS We found that baboon macrophages phagocytosed porcine ECs in a similar manner to human macrophages, and this response was significantly reduced when porcine ECs and podocytes expressed hCD47/hCD55 but not hCD46/hCD55 without hCD47. Furthermore, masking hCD47 by anti-hCD47 antibody on hCD47/hCD55Tg ECs restored phagocytosis. These results are consistent with the hypothesis that CD47 incompatibility plays an important role in promoting macrophage phagocytosis of endogenous cells from the transplanted kidney. CONCLUSIONS The similar levels of phagocytosis of porcine cells by baboon and human macrophages suggest that the expression of hCD47Tg on glomerular cells in donor porcine kidneys may prove to be a key strategy for preventing proteinuria following kidney xenotransplantation in a pig-to-human as well as a pig-to-baboon model.
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Affiliation(s)
- Shunichiro Nomura
- Columbia Center for Translational Immunology (CCTI)/Surgery, Columbia University Medical Center, New York, NY, USA
| | - Yuichi Ariyoshi
- Columbia Center for Translational Immunology (CCTI)/Surgery, Columbia University Medical Center, New York, NY, USA
| | - Hironosuke Watanabe
- Columbia Center for Translational Immunology (CCTI)/Surgery, Columbia University Medical Center, New York, NY, USA
| | - Thomas Pomposelli
- Columbia Center for Translational Immunology (CCTI)/Surgery, Columbia University Medical Center, New York, NY, USA
| | - Kazuhiro Takeuchi
- Columbia Center for Translational Immunology (CCTI)/Surgery, Columbia University Medical Center, New York, NY, USA
| | - Gabriela Garcia
- Department of Medicine, University of Colorado Hospital- Renal Clinic/Nephrology, Aurora, CO, USA
| | - Masayuki Tasaki
- Department of Urology, Graduate School of Medicine, Niigata University, Niigata, Japan
| | | | - Megan Sykes
- Columbia Center for Translational Immunology (CCTI)/Surgery, Columbia University Medical Center, New York, NY, USA
| | - David Sachs
- Columbia Center for Translational Immunology (CCTI)/Surgery, Columbia University Medical Center, New York, NY, USA
| | - Richard Johnson
- Department of Medicine, University of Colorado Hospital- Renal Clinic/Nephrology, Aurora, CO, USA
| | - Kazuhiko Yamada
- Columbia Center for Translational Immunology (CCTI)/Surgery, Columbia University Medical Center, New York, NY, USA
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18
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Pile T, Raftery M, Thuraisingham R, Kirwan CJ, Harwood S, Yaqoob MM. Treating Posttransplant Anemia With Erythropoietin Improves Quality of Life but Does Not Affect Progression of Chronic Kidney Disease. EXP CLIN TRANSPLANT 2019; 18:27-33. [PMID: 31180297 DOI: 10.6002/ect.2018.0283] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
OBJECTIVES Posttransplant anemia affects 30% to 45% of kidney transplant recipients and is associated with increased morbidity. However, there is lack of evidence about safe hemoglobin levels after erythropoietin treatment. Studies are needed to better understand the potential benefits and risks, as well as to define safe target hemoglobin ranges in these patients. MATERIALS AND METHODS In this single-center exploratory, open-label randomized controlled trial, kidney trans-plant recipients with anemia 3 months posttransplant were either treated with epoetin beta to a hemoglobin target level of 11.5 to 13.5 g/dL (n = 28) or given no treatment (n = 27). Treatment effects on graft function and health quality of life were assessed. RESULTS After 2 years, hemoglobin concentrations were significantly higher in the epoetin beta treatment group than in the no treatment group (12.3 ± 0.18 vs 9.99 ± 0.22 g/dL; P < .0001). Estimated glomerular filtration rate, calculated by Modified Diet in Renal Disease 7, declined by 1.7 mL/min (interquartile range, -6 to 4.24) in the epoetin treatment group and by 4.16 mL/min (interquartile range, -12.42 to 2.78) in the no treatment group (P = .32). Rate of progression, determined by estimated glomerular filtration rate slope, was not significantly different between groups (-0.09 ± 0.1 vs -0.12 ± 0.15 mL/min for treated vs not treated; P = .78). Moreover, we observed no significant differences in proteinuria and blood pressure. Treated patients had greater improvements in the vitality and mental health domains of the Medical Outcomes Short Form Health Survey quality of life scores. CONCLUSIONS Treatment of anemia in kidney transplant recipients to a hemoglobin level of 11.5 to 13.5 g/dL with erythropoietin improves some quality of life scores. The treatment was safe and not associated with adverse outcomes. There were no changes in rate of decline of graft function.
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Affiliation(s)
- Taryn Pile
- From the Translational Medicine and Therapeutics, William Harvey Research Institute, Queen Mary University of London, London, United Kingdom
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Devine PA, Courtney AE, Maxwell AP. Cardiovascular risk in renal transplant recipients. J Nephrol 2019; 32:389-399. [PMID: 30406606 PMCID: PMC6482292 DOI: 10.1007/s40620-018-0549-4] [Citation(s) in RCA: 72] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2018] [Accepted: 10/30/2018] [Indexed: 02/07/2023]
Abstract
Successful kidney transplantation offers patients with end-stage renal disease the greatest likelihood of survival. However, cardiovascular disease poses a major threat to both graft and patient survival in this cohort. Transplant recipients are unique in their accumulation of a wide range of traditional and non-traditional cardiovascular risk factors. Hypertension, diabetes, dyslipidaemia and obesity are highly prevalent in patients with end-stage renal disease. These risk factors persist following transplantation and are often exacerbated by the drugs used for immunosuppression in organ transplantation. Additional transplant-specific factors such as poor graft function and proteinuria are also associated with increased cardiovascular risk. However, these transplant-related factors remain unaccounted for in current cardiovascular risk prediction models, making it challenging to identify transplant recipients with highest risk. With few interventional trials in this area specific to transplant recipients, strategies to reduce cardiovascular risk are largely extrapolated from other populations. Aggressive management of traditional cardiovascular risk factors remains the cornerstone of prevention, though there is also a potential role for selecting immunosuppression regimens to minimise additional cardiovascular injury.
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Affiliation(s)
- Paul A Devine
- Regional Nephrology and Transplant Unit, Belfast City Hospital Northern Ireland, Belfast, BT9 7AB, UK.
- Centre for Public Health, Queen's University Belfast, Belfast, UK.
| | - Aisling E Courtney
- Regional Nephrology and Transplant Unit, Belfast City Hospital Northern Ireland, Belfast, BT9 7AB, UK
| | - Alexander P Maxwell
- Regional Nephrology and Transplant Unit, Belfast City Hospital Northern Ireland, Belfast, BT9 7AB, UK
- Centre for Public Health, Queen's University Belfast, Belfast, UK
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Lim LM, Kung LF, Kuo MC, Kuo HT. The Risk Factors of mTORi-Associated Posttransplant Proteinuria. Transplant Proc 2018; 50:2535-2538. [PMID: 30316393 DOI: 10.1016/j.transproceed.2018.03.090] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2018] [Accepted: 03/02/2018] [Indexed: 11/16/2022]
Abstract
Treatment with mammalian target of rapamycin inhibitors (mTORi) has been associated with an increased incidence of proteinuria after kidney transplantation as compared to other immunosuppressive agents. Proteinuria after mTORi use may occur in different clinical conditions and the precise mechanism remains unclear. The objective of this study was to investigate the related risk factors for proteinuria after mTORi treatment in kidney transplant recipients. This retrospective observational study population consisted of kidney transplant recipients followed up in a medical center in Southern Taiwan from January 1999 to April 2016. The baseline characteristics and transplantation-related profiles were collected at the time of enrollment. We examined risk factors for mTORi-associated proteinuria using a multivariate logistic regression analysis. P < .05 was considered as statistically significant. Hyperlipidemia and obesity at the initiation of mTORi treatment were strong predictors for proteinuria. Earlier identification of these risk factors may assist physicians in deciding the best candidate for mTORi conversion in order to optimize transplantation outcomes.
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Affiliation(s)
- L M Lim
- Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - L-F Kung
- Department of Nursing, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - M-C Kuo
- Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Faculty of Renal Care, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - H-T Kuo
- Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Faculty of Renal Care, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
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21
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Nephrotic Range Proteinuria in Renal Transplantation: Clinical and Histologic Correlates in a 10-year Retrospective Study. Transplant Proc 2017; 49:792-794. [DOI: 10.1016/j.transproceed.2017.01.066] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
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Habicht A, Stangl M. [Care of the adult kidney transplant recipient]. MMW Fortschr Med 2016; 158:64-72. [PMID: 27844359 DOI: 10.1007/s15006-016-9013-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/06/2023]
Affiliation(s)
- Antje Habicht
- Transplantationszentrum der Universität München, Campus Großhadern, Marchioninistr. 15, D-81377, München, Deutschland.
| | - Martin Stangl
- Transplantationszentrum der Universität München, Campus Großhadern, Marchioninistr. 15, D-81377, München, Deutschland
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Brakemeier S, Kannenkeril D, Dürr M, Braun T, Bachmann F, Schmidt D, Wiesener M, Budde K. Experience with belatacept rescue therapy in kidney transplant recipients. Transpl Int 2016; 29:1184-1195. [PMID: 27514317 DOI: 10.1111/tri.12822] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2015] [Revised: 01/16/2016] [Accepted: 07/27/2016] [Indexed: 12/18/2022]
Abstract
In kidney transplant recipients with chronic graft dysfunction, long-term immunosuppression with calcineurin inhibitors (CNIs) or mTOR inhibitors (mTORi) can be challenging due to adverse effects, such as nephrotoxicity and proteinuria. Seventy-nine kidney transplant recipients treated with CNI-based or mTORi-based maintenance immunosuppression who had CNI-induced nephrotoxicity or severe adverse events were switched to belatacept. Mean time from transplantation to belatacept conversion was 69.0 months. Mean estimated glomerular filtration rate (eGFR) ± standard deviation at baseline was 26.1 ± 15.0 ml/min/1.73 m2 , increasing to 34.0 ± 15.2 ml/min/1.73 m2 at 12 months postconversion (P < 0.0005). Renal function improvements were also seen in patients with low eGFR (<25 ml/min/1.73 m2 ) or high proteinuria (>500 mg/l) at conversion. The Kaplan-Meier estimates for patient and graft survival at 12 months were 95.0% and 85.6%, respectively. The discontinuation rate due to adverse events was 7.9%. One case of post-transplant lymphoproliferative disorder occurred at 17 months postconversion. For comparison, a historical control group of 41 patients converted to mTORi-based immunosuppression because of biopsy-confirmed CNI-induced toxicity was examined; eGFR increased from 27.6 ± 7.2 ml/min/1.73 m2 at baseline to 31.1 ± 11.9 ml/min/1.73 m2 at 12 months (P = 0.018). Belatacept-based immunosuppression may be an alternative regimen for kidney transplant recipients with CNI- or mTORi-induced toxicity.
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Affiliation(s)
- Susanne Brakemeier
- Division of Nephrology, Department of Internal Medicine, Charité Campus Mitte, Berlin, Germany.
| | - Dennis Kannenkeril
- Department of Nephrology and Hypertension, University Erlangen-Nürnberg, Erlangen, Germany
| | - Michael Dürr
- Division of Nephrology, Department of Internal Medicine, Charité Campus Mitte, Berlin, Germany
| | - Tobias Braun
- Department of Nephrology and Hypertension, University Erlangen-Nürnberg, Erlangen, Germany
| | - Friederike Bachmann
- Division of Nephrology, Department of Internal Medicine, Charité Campus Mitte, Berlin, Germany
| | - Danilo Schmidt
- Division of Nephrology, Department of Internal Medicine, Charité Campus Mitte, Berlin, Germany
| | - Michael Wiesener
- Department of Nephrology and Hypertension, University Erlangen-Nürnberg, Erlangen, Germany
| | - Klemens Budde
- Division of Nephrology, Department of Internal Medicine, Charité Campus Mitte, Berlin, Germany
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McKenna GJ. Is It Time to Use De Novo mTOR Inhibitors Posttransplant? CURRENT TRANSPLANTATION REPORTS 2016. [DOI: 10.1007/s40472-016-0111-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
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Monfá E, Rodrigo E, Belmar L, Sango C, Moussa F, Ruiz San Millán JC, Piñera C, Fernández-Fresnedo G, Arias M. A high sodium intake reduces antiproteinuric response to renin-angiotensin-aldosterone system blockade in kidney transplant recipients. Nefrologia 2016; 36:545-551. [PMID: 27431273 DOI: 10.1016/j.nefro.2016.01.018] [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: 11/16/2015] [Revised: 01/05/2016] [Accepted: 01/28/2016] [Indexed: 01/13/2023] Open
Abstract
BACKGROUND Post-transplant proteinuria is associated with lower graft and patient survival. Renin-angiotensin-aldosterone system blockers are used to reduce proteinuria and improve renal outcome. Although it is known that a high salt intake blunts the antiproteinuric effect of ACEI and ARB drugs in non-transplant patients, this effect has not been studied in kidney transplant recipients. OBJECTIVE To analyse the relationship between sodium intake and the antiproteinuric effect of ACEI/ARB drugs in kidney transplant recipients. METHODS We selected 103 kidney transplant recipients receiving ACEI/ARB drugs for more than 6 months due to proteinuria>1 g/day. Proteinuria was analysed at baseline and at 6 months after starting ACEI/ARB treatment. Salt intake was estimated by urinary sodium to creatinine ratio (uNa/Cr). RESULTS Proteinuria fell to less than 1g/day in 46 patients (44.7%). High uNa/Cr was associated with a smaller proteinuria decrease (r=-0.251, P=.011). The percentage proteinuria reduction was significantly lower in patients in the highest uNa/Cr tertile [63.9% (IQR 47.1%), 60.1% (IQR 55.4%), 38.9% (IQR 85.5%), P=.047]. High uNa/Cr independently relates (OR 2.406 per 100 mEq/g, 95% CI: 1.008-5.745, P=.048) to an antiproteinuric response <50% after renin-angiotensin-aldosterone system blockade. CONCLUSIONS A high salt intake results in a smaller proteinuria decrease in kidney transplant recipients with proteinuria treated with ACEI/ARB drugs.
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Affiliation(s)
- Elena Monfá
- Servicio de Nefrología, Hospital Universitario Marqués de Valdecilla, Santander (Cantabria), España
| | - Emilio Rodrigo
- Servicio de Nefrología, Hospital Universitario Marqués de Valdecilla, Santander (Cantabria), España.
| | - Lara Belmar
- Servicio de Nefrología, Hospital Universitario Marqués de Valdecilla, Santander (Cantabria), España
| | - Cristina Sango
- Servicio de Nefrología, Hospital Universitario Marqués de Valdecilla, Santander (Cantabria), España
| | - Fozi Moussa
- Servicio de Nefrología, Hospital Universitario Marqués de Valdecilla, Santander (Cantabria), España
| | | | - Celestino Piñera
- Servicio de Nefrología, Hospital Universitario Marqués de Valdecilla, Santander (Cantabria), España
| | - Gema Fernández-Fresnedo
- Servicio de Nefrología, Hospital Universitario Marqués de Valdecilla, Santander (Cantabria), España
| | - Manuel Arias
- Servicio de Nefrología, Hospital Universitario Marqués de Valdecilla, Santander (Cantabria), España
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de Vries LV, Dobrowolski LC, van den Bosch JJ, Riphagen IJ, Krediet CP, Bemelman FJ, Bakker SJ, Navis G. Effects of Dietary Sodium Restriction in Kidney Transplant Recipients Treated With Renin-Angiotensin-Aldosterone System Blockade: A Randomized Clinical Trial. Am J Kidney Dis 2016; 67:936-44. [DOI: 10.1053/j.ajkd.2015.11.026] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2015] [Accepted: 11/30/2015] [Indexed: 01/13/2023]
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Summaria F, Giannico MB, Talarico GP, Patrizi R. Percutaneous coronary interventions and antiplatelet therapy in renal transplant recipients. Ther Adv Cardiovasc Dis 2016; 10:86-97. [PMID: 26680559 PMCID: PMC5933627 DOI: 10.1177/1753944715622120] [Citation(s) in RCA: 3] [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] [Indexed: 11/17/2022] Open
Abstract
Cardiovascular disease is the leading cause of mortality and morbidity following renal transplantation (RT), accounting for 40-50% of all deaths. After renal transplantation, an adverse cardiovascular event occurs in nearly 40% of patients; given the dialysis vintage and the average wait time, the likelihood of receiving coronary revascularization is very high. There is a significant gap in the literature in terms of the outcomes of prophylactic coronary revascularization in renal transplantation candidates. Current guidelines on myocardial revascularization stipulate that renal transplant patients with significant coronary artery disease (CAD) should not be excluded from the potential benefit of revascularization. Compared with percutaneous coronary intervention (PCI), however, coronary artery bypass grafting is associated with higher early and 30-day mortality. About one-third of renal transplant patients with CAD have to be treated invasively and so PCI is currently the most popular mode of revascularization in these fragile and compromised patients. A newer generation drug-eluting stent (DES) should be preferred over a bare metal stent (BMS) because of its lower risk of restenosis and improved safety concerns (stent thrombosis) compared with first generation DES and BMS. Among DES, despite no significant differences being reported in terms of efficacy, the newer everolimus and zotarolimus eluting stents should be preferred given the possibility of discontinuing, if necessary, dual antiplatelet therapy before 12 months. Since there is a lack of randomized controlled trials, the current guidelines are inadequate to provide a specifically tailored antiplatelet therapeutic approach for renal transplant patients. At present, clopidogrel is the most used agent, confirming its central role in the therapeutic management of renal transplant patients undergoing PCI. While progress in malignancy-related mortality seems a more distant target, a slow but steady reduction in cardiovascular deaths, improving pharmacological and interventional therapy, is nowadays an achievable medium-term target in renal transplant patients.
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Affiliation(s)
- Francesco Summaria
- Cath-Lab/Department of Cardiology-Policlinico Casilino, Via Casilina, 1049, Rome 00199, Italy
| | | | | | - Roberto Patrizi
- Cath-Lab/Department of Cardiology-Policlinico Casilino, Rome, Italy
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28
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Neale J, Smith AC. Cardiovascular risk factors following renal transplant. World J Transplant 2015; 5:183-95. [PMID: 26722646 PMCID: PMC4689929 DOI: 10.5500/wjt.v5.i4.183] [Citation(s) in RCA: 100] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2015] [Revised: 08/19/2015] [Accepted: 09/25/2015] [Indexed: 02/05/2023] Open
Abstract
Kidney transplantation is the gold-standard treatment for many patients with end-stage renal disease. Renal transplant recipients (RTRs) remain at an increased risk of fatal and non-fatal cardiovascular (CV) events compared to the general population, although rates are lower than those patients on maintenance haemodialysis. Death with a functioning graft is most commonly due to cardiovascular disease (CVD) and therefore this remains an important therapeutic target to prevent graft failure. Conventional CV risk factors such as diabetes, hypertension and renal dysfunction remain a major influence on CVD in RTRs. However it is now recognised that the morbidity and mortality from CVD are not entirely accounted for by these traditional risk-factors. Immunosuppression medications exert a deleterious effect on many of these well-recognised contributors to CVD and are known to exacerbate the probability of developing diabetes, graft dysfunction and hypertension which can all lead on to CVD. Non-traditional CV risk factors such as inflammation and anaemia have been strongly linked to increased CV events in RTRs and should be considered alongside those which are classified as conventional. This review summarises what is known about risk-factors for CVD in RTRs and how, through identification of those which are modifiable, outcomes can be improved. The overall CV risk in RTRs is likely to be multifactorial and a complex interaction between the multiple traditional and non-traditional factors; further studies are required to determine how these may be modified to enhance survival and quality of life in this unique population.
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29
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Mazanowska O, Zabińska M, Kościelska-Kasprzak K, Kamińska D, Krajewska M, Banasik M, Madziarska K, Zmonarski SC, Chudoba P, Biecek P, Boratyńska M, Klinger M. Increased plasma matrix metalloproteinase-2 (MMP-2), tissue inhibitor of proteinase-1 (TIMP-1), TIMP-2, and urine MMP-2 concentrations correlate with proteinuria in renal transplant recipients. Transplant Proc 2015; 46:2636-9. [PMID: 25380883 DOI: 10.1016/j.transproceed.2014.08.034] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
BACKGROUND The most frequent cause of kidney allograft loss is chronic allograft injury, often with proteinuria as the clinical feature. Occurrence of proteinuria late after kidney transplantation is associated with worse graft function and patient survival. AIM The aim of the study was to assess plasma and urine matrix metalloproteinases (MMP-2 and MMP-9) and tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) in proteinuric renal transplant recipients (RTRs). The factors were determined by enzyme-linked immunosorbent assay in 150 RTRs (51 women and 99 men), aged 49.2 ± 11.5 years, at mean 73.4 ± 41.2 months after kidney transplantation (range: 12 to 240 months). RESULTS Proteinuric RTRs compared with non-proteinuric RTRs had higher median plasma MMP-2 (P = .012), TIMP-1 (P = .0003), and TIMP-2 (P = .0021) concentrations, as well as higher urine MMP-2 (P < .0001) excretion. The presence of proteinuria had no impact on plasma MMP-9 and urine MMP-9, TIMP-1, and TIMP-2. Proteinuria and estimated daily proteinuria (uPr:uCr) correlated positively with plasma MMP-2 (rs = 0.226, P = .0054 and rs = 0.241, P = .003), TIMP-1 (rs = 0.305, P = .00015 and rs = 0.323, P = .000055), TIMP-2 (rs = 0.273, P = .0007 and rs = 0.269, P = .001) and urine MMP-2 (rs = 0.464, P < .0001 and rs = 0.487, P < .0001), respectively. Proteinuric RTRs had impaired graft function with higher median serum creatinine concentrations (1.91 [1.60-2.43] mg/dL versus 1.41 [1.20-1.65] mg/dL, P < .00001) and lower estimated glomerular filtration rate (36 [28-45] mL/min/1.73 m(2) versus 53 [43-61] mL/min/1.73 m(2), P < .00001) than RTRs without proteinuria. CONCLUSIONS Our research revealed that in RTRs, proteinuria was significantly associated with increased concentrations of enzymes involved in extracellular matrix (ECM) degradation: plasma MMP-2, TIMP-1, TIMP-2, and urine MMP-2. Findings strongly emphasize increased plasma TIMPs in proteinuric RTRs that inhibit degradation of ECM by MMPs and favor excessive deposition of ECM proteins.
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Affiliation(s)
- O Mazanowska
- Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wroclaw, Poland.
| | - M Zabińska
- Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wroclaw, Poland
| | - K Kościelska-Kasprzak
- Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wroclaw, Poland
| | - D Kamińska
- Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wroclaw, Poland
| | - M Krajewska
- Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wroclaw, Poland
| | - M Banasik
- Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wroclaw, Poland
| | - K Madziarska
- Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wroclaw, Poland
| | - S C Zmonarski
- Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wroclaw, Poland
| | - P Chudoba
- Department of Vascular, General and Transplant Surgery, Wroclaw Medical University, Wroclaw, Poland
| | - P Biecek
- Interdisciplinary Centre for Mathematical and Computational Modelling University of Warsaw, Warsaw, Poland
| | - M Boratyńska
- Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wroclaw, Poland
| | - M Klinger
- Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wroclaw, Poland
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Jeon HJ, Kim CT, An JN, Lee H, Kim H, Park SK, Joo KW, Lim CS, Jung IM, Ahn C, Kim YS, Kim YH, Lee JP. Time-varying maximal proteinuria correlates with adverse cardiovascular events and graft failure in kidney transplant recipients. Nephrology (Carlton) 2015; 20:945-51. [DOI: 10.1111/nep.12529] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/31/2015] [Indexed: 01/23/2023]
Affiliation(s)
- Hee Jung Jeon
- Department of Internal Medicine; Seoul National University College of Medicine; Seoul Korea
- Department of Internal Medicine; Kangdong Sacred Heart Hospital; Seoul Korea
| | - Clara Tammy Kim
- Graduate School of Public Health; Seoul National University; Seoul Korea
| | - Jung Nam An
- Department of Internal Medicine; Seoul National University Boramae Medical Center; Seoul Korea
| | - Hajeong Lee
- Department of Internal Medicine; Seoul National University College of Medicine; Seoul Korea
| | - Hyosang Kim
- Department of Internal Medicine; Asan Medical Center and University of Ulsan College of Medicine; Seoul Korea
| | - Su-Kil Park
- Department of Internal Medicine; Asan Medical Center and University of Ulsan College of Medicine; Seoul Korea
| | - Kwon Wook Joo
- Department of Internal Medicine; Seoul National University College of Medicine; Seoul Korea
| | - Chun Soo Lim
- Department of Internal Medicine; Seoul National University Boramae Medical Center; Seoul Korea
| | - In Mok Jung
- Department of Surgery; Seoul National University Boramae Medical Center; Seoul Korea
| | - Curie Ahn
- Department of Internal Medicine; Seoul National University College of Medicine; Seoul Korea
| | - Yon Su Kim
- Department of Internal Medicine; Seoul National University College of Medicine; Seoul Korea
| | - Young Hoon Kim
- Department of Surgery; Asan Medical Center and University of Ulsan College of Medicine; Seoul Korea
| | - Jung Pyo Lee
- Department of Internal Medicine; Seoul National University Boramae Medical Center; Seoul Korea
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Talreja H, Akbari A, White CA, Ramsay TO, Hiremath S, Knoll G. Predicting Kidney Transplantation Outcomes Using Proteinuria Ascertained From Spot Urine Samples Versus Timed Urine Collections. Am J Kidney Dis 2014; 64:962-8. [DOI: 10.1053/j.ajkd.2014.07.027] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2014] [Accepted: 07/28/2014] [Indexed: 11/11/2022]
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Wisanuyotin S, Jiravuttipong A, Puapairoj A. De novo lupus nephritis in a renal transplanted child: a case report. Transplant Proc 2014; 46:648-50. [PMID: 24656036 DOI: 10.1016/j.transproceed.2013.12.023] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2013] [Accepted: 12/10/2013] [Indexed: 10/25/2022]
Abstract
De novo lupus nephritis (LN) is a rare complication in renal transplantation recipients. We present the clinical manifestations of de novo LN in a 12-year-old boy who received a cadaveric renal transplant. The cause of end-stage renal disease was prune belly syndrome with renal dysplasia. His immunosuppressive drugs included tacrolimus, mycophenolate sodium, and prednisolone. After 3 years of treatment, he developed nephrotic syndrome (NS) without other symptoms of systemic lupus erythematosus (SLE). The renal pathology of the transplanted kidney showed suspicious acute cellular rejection and LN World Health Organization class IV-G (A/C). Antinuclear antibody was positive, but anti-dsDNA and anti-Smith were negative. The serum complements were initially normal. Pulse methylprednisolone was given and the dosages of all immunosuppressive drugs increased; notwithstanding, his edema and hypoalbuminemia worsened. Repeated biopsy of the transplanted kidney was done. A full-house pattern was documented under immunofluorescent examination which confirmed LN WHO class IV-G (A/C) without evidence of rejection. He then developed macrophage-associated hemophagocytic syndrome and cytomegalovirus pneumonia. He ultimately developed pulmonary hemorrhage and died owing to severe pneumonia. De novo LN should be considered in renal transplant recipients with new onset of NS despite there not being any other clinical manifestations of SLE.
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Affiliation(s)
- S Wisanuyotin
- Department of Pediatrics, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
| | - A Jiravuttipong
- Department of Pediatrics, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - A Puapairoj
- Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
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Akbari A, Fergusson D, Kokolo MB, Ramsay T, Beck A, Ducharme R, Ruzicka M, Grant-Orser A, White CA, Knoll GA. Spot urine protein measurements in kidney transplantation: a systematic review of diagnostic accuracy. Nephrol Dial Transplant 2014; 29:919-26. [DOI: 10.1093/ndt/gft520] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open
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Tasaki M, Shimizu A, Hanekamp I, Torabi R, Villani V, Yamada K. Rituximab treatment prevents the early development of proteinuria following pig-to-baboon xeno-kidney transplantation. J Am Soc Nephrol 2014; 25:737-44. [PMID: 24459229 DOI: 10.1681/asn.2013040363] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
We previously reported life-supporting α1,3-galactosyltransferase knockout (GalTKO) thymokidney xenograft survival of >2 months in baboons. However, despite otherwise normal renal function, recipients developed proteinuria with morphologic changes (podocyte effacement), a condition that presents a major obstacle to long-term studies in this model. A recent clinical study showed that rituximab therapy after allogeneic transplant prevented proteinuria possibly associated with loss of sphingomyelin phosphodiesterase acid-like 3b (SMPDL-3b). Here, we demonstrate that rituximab prevents the disruption of pig podocytes in an SMPDL-3b-dependent manner in vitro and the early development of proteinuria after xenogeneic kidney transplantation in baboons. Immunofluorescence showed SMPDL-3b expression in pig glomerular epithelium; immunoprecipitation demonstrated rituximab binding to SMPDL-3b in glomeruli. Culture of isolated pig podocytes with naive baboon sera, which has preformed antipig natural antibodies, reduced SMPDL-3b expression, disrupted podocyte morphology, and decreased podocyte proliferation, whereas pretreatment with rituximab prevented these effects. Six baboons received rituximab before transplantation to deplete B cells and again in the peri-transplant period; 18 baboons treated only before transplantation served as historical controls. The onset of post-transplant proteinuria was significantly delayed in a B cell-independent manner in the animals that received peri-transplant rituximab treatment. Although further optimization of this protocol is required, these data provide intriguing clues to the mechanisms of post-transplant proteinuria in xenogeneic kidney transplantation and a potential strategy for its prevention.
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Affiliation(s)
- Masayuki Tasaki
- Transplantation Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
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Jóźwiak L, Książek A. Painful Crural Ulcerations and Proteinuria as Complications After Several Years of Therapy With mTOR Inhibitors in the Renal Allograft Recipient: A Case Report. Transplant Proc 2013; 45:3418-20. [DOI: 10.1016/j.transproceed.2013.06.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2013] [Accepted: 06/28/2013] [Indexed: 10/26/2022]
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Sprangers B, Kuypers DR. Recurrence of glomerulonephritis after renal transplantation. Transplant Rev (Orlando) 2013; 27:126-34. [PMID: 23954034 DOI: 10.1016/j.trre.2013.07.004] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2013] [Revised: 07/09/2013] [Accepted: 07/09/2013] [Indexed: 02/07/2023]
Abstract
Recurrence of glomerulonephritis following renal transplantation is considered an important cause of allograft failure. The incidence of recurrence of glomerulonephritis varies widely depending on the definition of recurrence (pathologic recurrence or clinicopathologic recurrence) and the original glomerular disease. Moreover the impact of recurrence of glomerular disease on allograft outcome varies widely between different forms of glomerulonephritis. Whereas IgA nephritis recurs in up to one third of transplanted patients, this is not associated with adverse effects on graft survival. In contrast, recurrent focal segmental glomerulosclerosis and membranoproliferative glomerulopathy have an unfavorable prognosis. Overall, long-term graft survival in patients transplanted for glomerulonephritis is comparable to survival in patients with other causes of ESRD. In recent years, several mechanisms for recurrent disease after transplantation (e.g. PLA2R antibodies in membranous nephropathy and suPAR in FSGS) have been identified, and these findings have helped to elucidate the pathogenesis of glomerular diseases. Although renal transplantation is the treatment of choice for end-stage renal disease as a consequence of glomerulonephritis, further studies are required to develop optimal strategies to prevent, diagnose and treat recurrent glomerular diseases.
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Affiliation(s)
- Ben Sprangers
- Department of Nephrology, University Hospitals Leuven, Leuven, Belgium
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Oblak M, Kandus A, Mlinšek G, Buturović-Ponikvar J, Arnol M. Increase in Proteinuria After Acute Kidney Graft Rejection is Associated With Decreased Graft Function and Survival. Transplant Proc 2013; 45:1453-7. [DOI: 10.1016/j.transproceed.2013.02.106] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2012] [Revised: 02/08/2013] [Accepted: 02/27/2013] [Indexed: 01/21/2023]
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Rodrigo E, Ruiz JC, Fernández-Fresnedo G, Fernández MD, Piñera C, Palomar R, Monfá E, Gómez-Alamillo C, Arias M. Cystatin C and albuminuria as predictors of long-term allograft outcomes in kidney transplant recipients. Clin Transplant 2013; 27:E177-83. [PMID: 23373671 DOI: 10.1111/ctr.12082] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/26/2012] [Indexed: 12/18/2022]
Abstract
Although cystatin C (Cys) and albuminuria (Alb) are predictors of end-stage renal disease in the general population, there are limited data about the performance of these markers alone or combined with respect to the prediction of the kidney transplant outcome. We assessed the ability of one-yr creatinine (Cr), MDRD equation, Cys, Hoek equation, Alb, the logarithm of albuminuria (LogAlb), and two products of these variables for predicting death-censored graft loss (DCGL) in 127 kidney transplant recipients. Mean follow-up time was 5.6 ± 1.7 yr. During this time, 18 patients developed DCGL. The area under the receiver operating characteristic curve for DCGL ranged from 71.1% to 85.4%, with Cys*LogAlb being the best predictor. Cys-based variables and variables combining LogAlb and renal function estimates have better discrimination ability than Cr-based variables alone. After multivariate analysis, quartiles of all one-yr variables (except of Cr and MDRD) were independent predictors for DCGL. Predictors combining Alb and a Cr- or Cys-based estimate of renal function performed better than those markers alone to predict DCGL. Cys-based predictors performed better than Cr-based predictors. Using a double-marker in kidney transplantation, it is possible to identify the highest risk group in which to prioritize specialty care.
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Affiliation(s)
- Emilio Rodrigo
- Nephrology Service, University Hospital "Marqués de Valdecilla", University of Cantabria, Fundación Marqués de Valdecilla-IFIMAV, Santander, Spain.
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Wiseman AC, McCague K, Kim Y, Geissler F, Cooper M. The effect of everolimus versus mycophenolate upon proteinuria following kidney transplant and relationship to graft outcomes. Am J Transplant 2013; 13:442-9. [PMID: 23205690 DOI: 10.1111/j.1600-6143.2012.04334.x] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2012] [Revised: 09/06/2012] [Accepted: 10/10/2012] [Indexed: 01/25/2023]
Abstract
Although mTOR inhibitor use has been associated with proteinuria in kidney transplant recipients, dose dependency and impact on allograft function are unknown. In a post hoc analysis, we compared rates of proteinuria 3 months posttransplant among everolimus (EVR) and mycophenolate (MPA) treatment arms and used a time-dependent model to correlate the risk of proteinuria to EVR trough levels up to 24 months posttransplant. eGFR and graft loss was compared by proteinuria status at 3 months. Of 833 randomized patients, 24%, 36% and 19% of lower exposure EVR (1.5 mg/day), higher exposure EVR (3.0 mg/day) and MPA-treated patients had proteinuria ≥ 300 mg/g Cr at 3 months, respectively. EVR 1.5 was not associated with an increase in risk of proteinuria (HR 1.20; p = 0.19) unlike EVR 3.0 (HR 1.84; p < 0.001) versus MPA. EVR trough levels >8 ng/mL were significantly associated with proteinuria compared to 3-8 ng/mL (HR 1.86; p < 0.001). Those patients with proteinuria at 3 months and those who developed proteinuria thereafter had lower eGFR and higher graft loss at 24 months, regardless of treatment arm. We identify a dose-dependent effect of EVR with the risk of proteinuria; however, its independent impact upon eGFR and graft survival at 2 years was not evident.
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Galichon P, Xu-Dubois YC, Finianos S, Hertig A, Rondeau E. Clinical and histological predictors of long-term kidney graft survival. Nephrol Dial Transplant 2013; 28:1362-70. [DOI: 10.1093/ndt/gfs606] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
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Dongping G, Yang L, Xiaobei S, Junxiang X, Yuan Y, Hui C. Long-term Factors Influencing Survial After Kidney Transplantation. Transplant Proc 2013; 45:129-33. [DOI: 10.1016/j.transproceed.2012.08.014] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2012] [Accepted: 08/29/2012] [Indexed: 11/25/2022]
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Early association of low-grade albuminuria and allograft dysfunction predicts renal transplant outcomes. Transplantation 2012; 93:297-303. [PMID: 22228419 DOI: 10.1097/tp.0b013e31823ec0a7] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Data on the combined associations of albuminuria and estimated glomerular filtration rate (eGFR) with renal transplant outcomes are limited. Our objective was to explore how renal transplant outcomes could be predicted by a combined variable of early low-grade albuminuria and allograft dysfunction. METHODS We studied a cohort of adult deceased-donor kidney transplant recipients who were subdivided into four groups according to median albuminuria (100 mg/day, interquartile range, 0-470 mg/day) and median eGFR (60 mL/min/1.73 m(2); interquartile range, 30-73 mL/min/1.73 m(2)) at third month posttransplantation as follows: group I (albuminuria <100 and eGFR >60, n=238); group II (albuminuria ≥100 and eGFR >60, n=151); group III (albuminuria <100 and eGFR ≤60; n=167); and group IV (albuminuria ≥100 and eGFR ≤60, n=228). RESULTS Death-censored graft survival was significantly lower in group IV compared with the rest (P<0.0001). Multivariate Cox regression analysis using fixed and time-dependent covariates showed that the combination of low-grade albuminuria and lower eGFR was associated with graft failure (hazard ratio, 2.2, 95% confidence interval, 1.3-3.7; P=0.003). Likewise, but to a lesser extent, the risk of mortality was increased for group IV (hazard ratio, 1.7, 95% confidence interval, 1.01-2.8; P=0.042). CONCLUSIONS Early association of low-grade albuminuria and allograft dysfunction represents an important risk factor of graft failure and mortality. This additive effect should be considered to identify individuals at risk for adverse kidney transplantation outcomes.
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Prognostic significance and diagnosis of proteinuria in renal transplantation. Transplant Rev (Orlando) 2012; 26:30-5. [DOI: 10.1016/j.trre.2011.07.008] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2011] [Accepted: 07/28/2011] [Indexed: 12/20/2022]
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Ruiz JC, Sánchez-Fructuoso A, Zárraga S. Management of proteinuria in clinical practice after kidney transplantation. Transplant Rev (Orlando) 2012; 26:36-43. [DOI: 10.1016/j.trre.2011.07.007] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2011] [Accepted: 07/28/2011] [Indexed: 01/06/2023]
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Shamseddin MK, Knoll GA. Posttransplantation proteinuria: an approach to diagnosis and management. Clin J Am Soc Nephrol 2011; 6:1786-93. [PMID: 21734095 DOI: 10.2215/cjn.01310211] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
Proteinuria is a common problem encountered in the treatment of renal transplant recipients, occurring in up to 45% of patients. Proteinuria from native kidneys falls rapidly after renal transplantation, and persistent or worsening proteinuria is usually indicative of allograft pathology. Biopsy studies of transplant patients with proteinuria have confirmed that transplant-specific diagnoses (transplant glomerulopathy, interstitial fibrosis and tubular atrophy, and acute rejection) are more commonly found than other proteinuric conditions, such as glomerulonephritis. As in the nontransplant setting, proteinuria is associated with worse clinical outcomes, including an increased risk for death, cardiovascular events, and graft loss. Blockade of the renin-angiotensin-aldosterone system with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers will reduce proteinuria, but the long-term effect of these medications on patient and graft survival remains unknown.
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Affiliation(s)
- M Khaled Shamseddin
- Division of Nephrology, Faculty of Medicine, University of Ottawa Hospital, Ottawa, Ontario, Canada
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Kasiske BL. Proteinuria and other urinary biomarkers in kidney transplantation: why are we still waiting for Godot? Am J Kidney Dis 2011; 57:654-6. [PMID: 21496726 DOI: 10.1053/j.ajkd.2011.01.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2011] [Accepted: 01/07/2011] [Indexed: 11/11/2022]
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Thymoglobulin induction and sirolimus versus tacrolimus in kidney transplant recipients receiving mycophenolate mofetil and steroids. Transplantation 2010; 89:1511-7. [PMID: 20386144 DOI: 10.1097/tp.0b013e3181db09e4] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
BACKGROUND To define the role of mammalian target of rapamycin inhibitors in kidney transplantation, we compared efficacy and safety of two immunosuppressive regimens-a calcineurin inhibitor-free regimen with depletive induction versus a calcineurin inhibitor-based regimen. METHODS De novo renal allograft recipients were randomized before transplantation to receive sirolimus (SRL; n=71, group A) or tacrolimus (n=70, group B). All patients received mycophenolate mofetil and corticosteroids. In group A, patients received rabbit antithymocyte globulin induction. In group B, antithymocyte globulin therapy could be given in case of delayed graft function. The estimated glomerular filtration rate (GFR) (Nankivell's formula) at month 12 was the primary endpoint. RESULTS GFR showed no significant difference at month 12, with 56.1 in group A versus 58.4 mL/min/1.73 m in group B. In functioning grafts, renal function was significantly better in the SRL group, with higher GFR values at months 1, 2, 3, 6, and 9 (P<0.05). At month 12, patient survival and incidence of biopsy-proven rejection were not different between groups (95.8% vs. 97.1%, and 16.9% vs. 12.9%, respectively). However, proportion of graft loss was higher with SRL at months 6 and 12 (11.3% vs. 0.0%, P=0.004; 14.1% vs. 4.3%, P=0.044, respectively). Adverse events and premature withdrawals were more frequent with SRL (P<0.001 and P<0.05, respectively), whereas cytomegalovirus infections were more frequent with tacrolimus (P<0.001). CONCLUSION Patients treated with induction plus SRL, mycophenolate mofetil, and corticosteroids may obtain good renal function but have a higher risk of adverse events, drug withdrawal, and graft loss.
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