Antiphospholipid antibodies and renal transplant: A systematic review and meta-analysis

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Abstract

Objective

To evaluate the effect of antiphospholipid antibodies (aPL) on renal allograft outcome after kidney transplantation.

Methods

A systematic search of EMBASE and PubMed databases from inception to July 2018 was run according to PRISMA guidelines; Peto's odds ratio (OR) for rare events was used for the meta-analysis.

Results

Our inclusion/exclusion criteria were met by 22 cohort studies having different outcomes: allograft thrombosis (n = 9) and thromboprophylaxis (n = 3), allograft loss from any cause (n = 9), allograft malfunction (n = 3), duration (n = 2), glomerular filtration rate at 1 year (n = 3) and allograft rejection (n = 5). The pooled prevalence of allograft thrombosis and of thrombotic microangiopathy was greater in aPL+ve than negative recipients (10.4% vs 1.7%, p < 0.0001 and 10.2% vs 0%, p = 0.005, respectively). The pooled prevalence of allograft thrombosis was 75% in patients not taking anticoagulation whereas none of the anticoagulated recipients developed thrombosis (p < 0.0001). The pooled prevalence of allograft loss was greater in aPL+ve recipients (28% vs 18% respectively, p < 0.0001); the pooled prevalence of aPL was greater in allograft loss recipients compared to those who did not lose it (51% vs 33%, p < 0.0001). The pooled prevalence of allograft malfunction and rejection was similar in aPL−ve and aPL+ve recipients (32.2% vs 40.3% and 14.9% vs 14.4%, respectively) but graft duration was shorter in aPL+ve than aPL−ve recipients (p = 0.001) and glomerular filtration rate at 1 year was lower in aPL + ve than aPL−ve recipients (p < 0.0001).

Conclusion

APL relate strongly to allograft thrombosis, loss and duration but not to allograft malfunction and rejection. Oral antivitamin K anticoagulants effectively prevent allograft thrombosis in aPL recipients. The debate on the role of aPL in renal transplant is limited by the expression of data as percentage of recipients positive for aPL rather than aPL titres in many studies.

Introduction

The presence and persistence of antiphospholipid antibodies (aPL) detected via immune or clotting assays in association with vascular occlusions in either arterial or venous districts characterises the antiphospholipid syndrome (APS): in isolation it is defined primary APS, in association to other autoimmune disease including systemic lupus erythematosus it is defined as secondary [1]. While renal artery stenosis and thrombosis, renal infarction, renal vein thrombosis and chronic nephropathy are recognised features of kidney involvement in the APS [2], the role of aPL in kidney transplantation is less clear given the varying types of studies performed, the different aPL measured and the different endpoints employed [3]. We performed this systematic review to evaluate the outcome of renal allograft post kidney transplantation in recipients positive for aPL pre and/or post allograft; in particular the systematic review will try to answer two major questions: whether aPL influence the outcome of the renal allograft and whether anticoagulation affects allograft survival.

Section snippets

Search strategy and selection criteria

A systematic review according to the PRISMA guidelines [4] was carried out by searching the electronic databases MEDLINE and EMBASE from January 1985 to March 2018; for the search strategy, we used the terms [‘renal ‘OR ‘kidney transplant ’] and [‘anticardiolipin’ OR ‘anti-beta 2-glycoprotein-I’ OR ‘antiphospholipid syndrome,’ OR ‘lupus anticoagulant’ OR ‘lupus inhibitor’]. The same terms were used screen two data bases for grey literature, Open Grey and OAIster. The first search yielded 392

Number and quality of the studies

After completion of the screening and exclusion process (Fig. 1) we identified 22 cohort studies exploring the relationship between aPL and renal transplant [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31] (Table 1). A score of ≥7 on the NOQAS arbitrarily defined a good study and only two studies had low score at 4; the inter-rater reliability agreement of the two investigators (MM and PRJA) for NOQAS was

Allograft thrombosis

The diagnosis of allograft thrombosis was consistently biopsy proven [11], [14], [15], [23], [25], [26], [27], [28], [29], [30], [31] and occasionally supported by renal ultrasound or radionuclide scanning before biopsy [18].

Non allograft thrombosis

Two specific studies defined non allograft thrombosis as de novo coronary artery disease, cerebrovascular disease, peripheral vascular disease post renal allograft transplant [17], [22].

Allograft loss from all causes

The definition of allograft loss varied amongst studies: one study defined it as

Allograft thrombosis

Nine articles evaluated the relationship between different aPL and allograft thrombosis. They comprised 2106 aPL−ve and 1019 aPL+ve recipients for the effect size of this outcome [11,14,15,23,26,28–31]; the pooled prevalence of allograft thrombosis was significantly greater in aPL+ve than negative recipients (10.4% vs 1.7%) with wide heterogeneity (I2 = 89.5%, p < 0.0001) (Fig. 2(A)). Subgroup analysis after removal of three studies dealing with primary APS [10,13,30] still yielded a

Discussion

To gather a meaningful picture of the relation between aPL and renal allograft the studies included in the systematic review were grouped according to outcomes that for their nature dealt with the loss of the grafted kidney however defined: thrombosis, allograft loss proper, allograft rejection, allograft malfunction and duration with some information on vascular occlusion other than graft thrombosis.

Amongst the outcomes, the meta-analysis shows that aPL strongly associated with allograft

Conclusion

There is a strong link between aPL and different renal allograft outcomes including intra and extra-renal thrombosis, allograft loss proper and allograft duration but not with allograft rejection. AVK anticoagulants are effective in preventing allograft thrombosis though this could be offset by an increased risk of bleeding in the perioperative period. The limited numbers of papers reporting data on LA and the expression of data as percentage of recipients positive for aPL rather than aPL

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    Conflict of interest: None of the authors have any conflict of interest to declare.

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