The risk of cardiovascular disease associated with proteinuria in renal transplant patients

Fernández‐Fresnedo, Gema; Escallada, R; Rodrigo, Emilio; Al, de Francisco; Jg, Cotorruelo; S, Sanz de Castro; Ja, Zubimendi; Jc, Ruiz; Arias, Manuel

doi:10.1097/00007890-200204270-00028

Cited by 108 publications

(66 citation statements)

References 10 publications

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“…In renal transplantation, the presence of proteinuria at 12 mo is associated with a twofold risk of CV death [147] . Furthermore, persistent proteinuria is pre dictive of subsequent IHD and PVOD [148] . Even lowgrade proteinuria detected at early time points after renal transplantation is associated with inferior graft and patient outcomes [149] .…”

Section: Proteinuriamentioning

confidence: 99%

Cardiovascular risk factors following renal transplant

Neale

Smith

2015

WJT

119

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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. Nontraditional 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. Core tip: Cardiovascular disease (CVD) is the leading cause of death and disability in patients following a renal transplant. Identification of risk factors for CVD and strategies for their improvement are required in order to prevent graft failure in this complex patient

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Section: Proteinuriamentioning

confidence: 99%

Cardiovascular risk factors following renal transplant

Neale

Smith

2015

WJT

119

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“…It is also associated with higher risk for mortality and cardiovascular disease events (6,7). Accordingly, the 2009 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline on the care of the kidney transplant recipient (8) suggested measuring urine protein excretion at least once within the first month after transplantation, then every 3 months during the first year, then annually thereafter.…”

Section: Introductionmentioning

confidence: 99%

Posttransplantation Proteinuria

Shamseddin

Knoll²

2011

Clinical Journal of the American Society of Nephrology

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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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“…Histologic studies showed slight glomerulopathy in the kidney grafts; electron microscopic examination indicated effacement of the foot processes of the podocytes even though the creatinine level was stable. 7 Similar to clinical situations in which proteinuria leads to a higher risk of death and cardiovascular disease events and is considered to be a predictor of graft loss, [8][9][10][11] in the xenogeneic model it is associated with post-transplant hypoproteinemia, resulting in severe ascites, pleural effusion, and increased susceptibility to infection. Thus, studies to determine the mechanism responsible for this phenomenon and the development of preventive strategies are crucial to the success of future xeno-transplantation studies.…”

mentioning

confidence: 99%

Rituximab Treatment Prevents the Early Development of Proteinuria following Pig-to-Baboon Xeno-Kidney Transplantation

Tasaki

Shimizu

Hanekamp

et al. 2014

Journal of the American Society of Nephrology

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We previously reported life-supporting a1,3-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 . 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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The risk of cardiovascular disease associated with proteinuria in renal transplant patients

Cited by 108 publications

References 10 publications

Cardiovascular risk factors following renal transplant

Cardiovascular risk factors following renal transplant

Posttransplantation Proteinuria

Rituximab Treatment Prevents the Early Development of Proteinuria following Pig-to-Baboon Xeno-Kidney Transplantation

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