Proteinuria is accompanied by intratubular complement activation and apical membrane deposition of C3dg and C5b-9 in kidney transplant recipients

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. Complement activation split products C3c, C3dg and sC5b-9 associated C9 neoantigen were analyzed by ELISA in urine and plasma using neoepitope-specific antibodies. Urinary extracellular vesicles (uEV) were enriched by lectin- and immunoaffinity-isolation and analyzed by immunoblotting. Urine complement excretion increased significantly in KTRs with albumin/creatinine ratio ≥ 300 mg/g compared to < 30 mg/g. Urine C3dg and C9 neoantigen excretion correlated significantly to changes in albumin excretion from 3 to 12 months after transplantation. The fractional excretion of C9 neoantigen was significantly higher than for albumin indicating post-filtration generation. C9 neoantigen was detected in uEVs in six of nine of 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 SGLT2 but only weakly for AQP2. Co-isolation 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.

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Coronavirus disease 2019 in kidney transplant recipients: a systematic review and meta-analysis

Singapore Medical Journal ◽

10.11622/smedj.2021171 ◽

2021 ◽

Author(s):

QY Ho ◽

R Sultana ◽

TL Lee ◽

S Thangaraju ◽

T Kee ◽

...

Keyword(s):

Kidney Transplant ◽

Clinical Presentation ◽

Meta Analysis ◽

Kidney Injury ◽

High Dose ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Presenting Symptoms ◽

Effect Of Treatment ◽

Dose Corticosteroid

Introduction: The clinical presentation and outcomes of coronavirus disease 2019 (COVID-19) in kidney transplant recipients (KTRs) have not been well studied. Methods: We performed a meta-analysis to examine the presenting features, outcomes and the effect of treatment on outcomes of KTRs with COVID-19. Database search was performed up to 5 September 2020 through PubMed, EMBASE, Web of Science, SCOPUS, and CENTRAL. Results: Overall, 23 studies (1373 patients) were included in the review and meta-analysis. The most common presenting symptoms included fever (74.0%, 95% confidence interval [CI] 65.3–81.1), cough (63.3% 95% CI 56.5–69.6) and dyspnoea (47.5%, 95% CI 39.6–55.6). Pooled rates of mortality and critical illness were 21.1% (95% CI 15.3-28.4) and 27.7% (95% CI 21.5–34.8) respectively. Acute kidney injury occurred in 38.9% (95% CI 30.6–48.1) and dialysis was required in 12.4% (95% CI 8.3–18.0) of the cases. Discussion: KTRs with COVID-19 have a similar clinical presentation as the general population but have higher morbidity and mortality. It is uncertain whether high dose corticosteroid or hydroxychloroquine reduces the risks of mortality in KTRs with COVID-19.

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FP784LONG TERM GRAFT FUNCTION IN KIDNEY TRANSPLANT RECIPIENTS OF DECEASED DONORS WITH ACUTE KIDNEY INJURY

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfz106.fp784 ◽

2019 ◽

Vol 34 (Supplement_1) ◽

Author(s):

Reinis Lulle ◽

Gritane Klinta ◽

Asare Lasma ◽

Jushinskis Janis ◽

Malcevs Aleksandrs ◽

...

Keyword(s):

Acute Kidney Injury ◽

Kidney Transplant ◽

Graft Function ◽

Kidney Injury ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Deceased Donors

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Validation of Administrative Database Codes for Acute Kidney Injury in Kidney Transplant Recipients

Canadian Journal of Kidney Health and Disease ◽

10.1186/s40697-016-0108-7 ◽

2016 ◽

Vol 3 ◽

pp. 108 ◽

Cited By ~ 10

Author(s):

Amber O. Molnar ◽

Carl van Walraven ◽

Eric McArthur ◽

Dean Fergusson ◽

Amit X. Garg ◽

...

Keyword(s):

Acute Kidney Injury ◽

Kidney Transplant ◽

Kidney Injury ◽

Administrative Database ◽

Transplant Recipients ◽

Kidney Transplant Recipients

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A Systematic Review of COVID-19 Infection in Kidney Transplant Recipients: A Universal Effort to Preserve Patients’ Lives and Allografts

Journal of Clinical Medicine ◽

10.3390/jcm9092986 ◽

2020 ◽

Vol 9 (9) ◽

pp. 2986 ◽

Cited By ~ 2

Author(s):

Smaragdi Marinaki ◽

Stathis Tsiakas ◽

Maria Korogiannou ◽

Konstantinos Grigorakos ◽

Vassilios Papalois ◽

...

Keyword(s):

Kidney Transplant ◽

Distress Syndrome ◽

Kidney Injury ◽

Deceased Donor ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Male Predominance ◽

Transplant Patients ◽

Kidney Transplant Patients ◽

The Mean

The coronavirus disease 2019 (COVID-19) pandemic has posed a significant challenge to physicians and healthcare systems worldwide. Evidence about kidney transplant (KTx) recipients is still limited. A systematic literature review was performed. We included 63 articles published from 1 January until 7 July 2020, reporting on 420 adult KTx recipients with confirmed COVID-19. The mean age of patients was 55 ± 15 years. There was a male predominance (67%). The majority (74%) were deceased donor recipients, and 23% were recently transplanted (<1 year). Most patients (88%) had at least one comorbidity, 29% had two, and 18% three. Ninety-three percent of cases were hospitalized. Among them, 30% were admitted to the intensive care unit, 45% developed acute respiratory distress syndrome, and 44% had acute kidney injury with 23% needing renal replacement therapy. From the hospitalized patients a total of 22% died, 59% were discharged, and 19% were still in hospital at the time of publication. Immunosuppression was reduced in 27%, discontinued in 31%, and remained unchanged in 5%. Hydroxychloroquine was administered to 78% of patients, antibiotics to 73%, and antivirals to 30% while 25% received corticosteroid boluses, 28% received anti-interleukin agents, and 8% were given immunoglobulin. The main finding of our analysis was that the incidence of COVID-19 among kidney transplant patients is not particularly high, but when they do get infected, this is related to significant morbidity and mortality.

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Hospital Admission following Acute Kidney Injury in Kidney Transplant Recipients Is Associated with a Negative Impact on Graft Function after 1-Year

PLoS ONE ◽

10.1371/journal.pone.0138944 ◽

2015 ◽

Vol 10 (9) ◽

pp. e0138944 ◽

Cited By ~ 11

Author(s):

Thiago Corsi Filiponi ◽

Lúcio Roberto Requião-Moura ◽

Eduardo José Tonato ◽

Ana Cristina Carvalho de Matos ◽

Alvaro Pacheco e Silva-Filho ◽

...

Keyword(s):

Acute Kidney Injury ◽

Hospital Admission ◽

Kidney Transplant ◽

Negative Impact ◽

Graft Function ◽

Kidney Injury ◽

Transplant Recipients ◽

Kidney Transplant Recipients

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Physical Activity and Kidney Injury in Pediatric and Young Adult Kidney Transplant Recipients

The Journal of Pediatrics ◽

10.1016/j.jpeds.2016.08.079 ◽

2016 ◽

Vol 179 ◽

pp. 90-95.e2 ◽

Cited By ~ 5

Author(s):

Mattie F. Wolf ◽

Roshan P. George ◽

Barry Warshaw ◽

Elizabeth Wang ◽

Larry A. Greenbaum

Keyword(s):

Physical Activity ◽

Young Adult ◽

Kidney Transplant ◽

Kidney Injury ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Adult Kidney

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Incidence of Mortality, Acute Kidney Injury and Graft Loss in Adult Kidney Transplant Recipients with Coronavirus Disease 2019: Systematic Review and Meta-Analysis

Journal of Clinical Medicine ◽

10.3390/jcm10215162 ◽

2021 ◽

Vol 10 (21) ◽

pp. 5162

Author(s):

Jia-Jin Chen ◽

George Kuo ◽

Tao Han Lee ◽

Huang-Yu Yang ◽

Hsin Hsu Wu ◽

...

Keyword(s):

Intensive Care Unit ◽

Acute Kidney Injury ◽

Intensive Care ◽

Kidney Transplant ◽

Meta Analysis ◽

Graft Loss ◽

Kidney Injury ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Kidney Replacement Therapy

The adverse impact of Coronavirus disease 2019 (COVID-19) on kidney function has been reported since the global pandemic. The burden of COVID-19 on kidney transplant recipients, however, has not been systematically analyzed. A systematic review and meta-analysis with a random-effect model was conducted to explore the rate of mortality, intensive care unit admission, invasive mechanical ventilation, acute kidney injury, kidney replacement therapy and graft loss in the adult kidney transplant population with COVID-19. Sensitivity analysis, subgroup analysis and meta-regression were also performed. Results: we demonstrated a pooled mortality rate of 21% (95% CI: 19−23%), an intensive care unit admission rate of 26% (95% CI: 22–31%), an invasive ventilation rate among those who required intensive care unit care of 72% (95% CI: 62–81%), an acute kidney injury rate of 44% (95% CI: 39–49%), a kidney replacement therapy rate of 12% (95% CI: 9–15%), and a graft loss rate of 8% (95% CI: 5–15%) in kidney transplant recipients with COVID-19. The meta-regression indicated that advancing age is associated with higher mortality; every increase in age by 10 years was associated with an increased mortality rate of 3.7%. Regional differences in outcome were also detected. Further studies focused on treatments and risk factor identification are needed.

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