Urinary Albumin Excretion and the Risk of Graft Loss and Death in Proteinuric and Non-proteinuric Renal Transplant Recipients

Halimi, Jean‐Michel; Büchler, Matthias; Al-Najjar, Azmi; Laouad, I.; Châtelet, Valérie; Marliere, J.; Nivet, Hubert; Lebranchu, Yvon

doi:10.1111/j.1600-6143.2007.01665.x

Cited by 93 publications

(70 citation statements)

References 38 publications

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“…As previously published (11), 616 patients were followed at our institution between 1998 and 2005: both total proteinuria and UAE were measured. Most patients received our institution's immunosuppressive regimen: induction therapy with antithymocyte globulin (Thymoglobulin ® , Sangstat, Lyon, France) or interleukin-2-receptor antagonists (Simulect ® , Novartis, Rueil-Malmaison France).…”

Section: Study Populationmentioning

confidence: 99%

“…Interestingly, it was recently demonstrated that UAE was an independent powerful risk factor for graft loss and death in renal transplant recipients (11). However, it is presently unknown whether NAP has any predictive value on graft loss or death, and therefore whether UAE and NAP provide different information on patient or renal outcome.…”

mentioning

confidence: 99%

“…We recently showed that UAE is a strong risk factor for graft loss and death; both UAE and total proteinuria were measured in each 616 patients included in this study (11), which allowed us to calculate NAP values in all patients. In the present analysis, we retrospectively analyzed and compared the respective predictive value of UAE and NAP in this population.…”

mentioning

confidence: 99%

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Respective Predictive Role of Urinary Albumin Excretion and Nonalbumin Proteinuria on Graft Loss and Death in Renal Transplant Recipients

Halimi

Büchler

Al-Najjar

et al. 2007

American Journal of Transplantation

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Proteinuria is constituted by urinary albumin (UAE) and nonalbumin proteins (NAP). UAE was shown to predict ESRD and death. Whether NAP predicts graft or patient outcome is unknown in renal transplantation.We retrospectively analyzed the impact of UAE and NAP respectively on end-stage renal disease (ESRD) and death in 616 renal transplant recipients. In subjects with proteinuria <0.25 g/day, 76% of urine proteins were NAP; in those with >1 g/day, 44% of the urine proteins were NAP. Determinants of UAE and NAP were partly different: fasting glucose, body weight, donor cause of death and cyclosporine were significantly associated with NAP (but not UAE); panel reactive antibodies (PRA) and rapamycine were significantly associated with UAE (but not with NAP). NAP Massive proteinuria has been recognized as a risk factor for long-term graft loss (1,2). A recent study from our group indicated that low-grade proteinuria was a powerful independent predictor of long-term graft loss (3).Total proteinuria is made of various proportions of urine albumin (UAE) and nonalbumin proteinuria (NAP). Nonalbumin proteinuria includes several types of urinary proteins, and some of them were associated with renal damage or outcome in renal transplantation, including alpha-1 microglobulin, beta-2 macroglobulin and IgG (4). Other urinary proteins (cystatin C, transferrin, nephrin, matrix metalloproteinase-9 and tissue inhibitor of metalloproteinases-1,. . .) are biomarkers of renal damage in nontransplanted populations (5-10).Interestingly, it was recently demonstrated that UAE was an independent powerful risk factor for graft loss and death in renal transplant recipients (11). However, it is presently unknown whether NAP has any predictive value on graft loss or death, and therefore whether UAE and NAP provide different information on patient or renal outcome. The question about the respective prognostic value of UAE and NAP is not only academic: if only UAE (but not NAP) is an independent parameter associated to graft loss or death, screening for UAE may be discussed in all renal transplant recipients. Conversely, if NAP in addition to UAE also provides information on renal/patient outcome, then it would be interesting to identify the role of urinary proteins using proteomic analyses.To date, this type of analysis was not reported in the literature. We recently showed that UAE is a strong risk factor for graft loss and death; both UAE and total proteinuria were measured in each 616 patients included in this study (11), which allowed us to calculate NAP values in all patients. In the present analysis, we retrospectively analyzed and compared the respective predictive value of UAE and NAP in this population. Patients and Methods Study populationAs previously published (11), 616 patients were followed at our institution between 1998 and 2005: both total proteinuria and UAE were measured. Most patients received our institution's immunosuppressive regimen: induction therapy with antithymocyte globulin (Thymoglobulin ® , Sangstat, 2775

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Section: Study Populationmentioning

confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

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Respective Predictive Role of Urinary Albumin Excretion and Nonalbumin Proteinuria on Graft Loss and Death in Renal Transplant Recipients

Halimi

Büchler

Al-Najjar

et al. 2007

American Journal of Transplantation

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“…Importantly, hypertension was associated with significantly worse outcomes in patients with proteinuria [150] . In addition, microalbuminuria has also been found to be a powerful risk factor for increased mortality from CVD [151] . Investigation into the management of proteinuria has found that ACEinhibitors and ARBs are effective in reducing levels of proteinuria, although their overall effect on allograft function and survival are less clear [152,153] .…”

Section: Proteinuriamentioning

confidence: 99%

Cardiovascular risk factors following renal transplant

Neale

Smith

2015

WJT

118

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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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“…Previous studies in CKD populations have suggested that a decrease in microalbuminuria may lead to the suppression of renal function impairment (12,13) and cardiovascular disease (14-16) progression. In renal transplant recipients, microalbuminuria is a risk factor for graft loss and all-cause mortality (17). The effectiveness of RAS inhibitors for decreasing proteinuria following renal transplantation has been evaluated in various studies (16,(18)(19)(20).…”

Section: Discussionmentioning

confidence: 99%

Albuminuria-reducing effect of angiotensin II receptor blocker plus hydrochlorothiazide combination therapy in renal transplant recipients

Naganuma

Takemoto

Uchida

et al. 2012

Experimental and Therapeutic Medicine

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Abstract. In recent years, the combined use of angiotensin II receptor blockers (ARBs) and low-dose diuretics has become clinically possible. Moreover, the GUARD and J-CORE studies have confirmed that the addition of low-dose diuretics to renin-angiotensin system inhibitors reduces albuminuria. In this study, we investigated the clinical effects of a combination drug containing an ARB and a low-dose diuretic in renal transplant recipients. A total of 13 renal transplant recipients who were receiving the maximum dose of the ARB and presenting with microalbuminuria [urine albumin-creatinine ratio (ACR) of 30-300 mg/g-Cre] were converted to a single pill combination drug containing the same amount of the ARB and 12.5 mg of hydrochlorothiazide (HCTZ) and an intervention study of a crossover trial design was conducted. The clinical parameters were measured at baseline, 3 months after ARB/HCTZ conversion and 3 months after reverting to the ARB and the resulting data were compared. Serum creatinine (S-Cre) and uric acid (UA) levels at 3 months after conversion were significantly higher than those at baseline. The levels of the estimated glomerular filtration rate (eGFR) and ACR at 3 months were significantly lower than those at baseline. S-Cre and UA levels at 3 months after reversion were significantly lower than those at 3 months after conversion. The eGFR and levels of ACR and UA at 3 months after ARB reversion were significantly higher than those at 3 months after conversion. The results of this preliminary study suggest that the combination drug containing an ARB and low-dose diuretic was effective for reducing microalbuminuria in renal transplant recipients. In the future, larger cohort studies are needed to confirm these findings.

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Urinary Albumin Excretion and the Risk of Graft Loss and Death in Proteinuric and Non-proteinuric Renal Transplant Recipients

Cited by 93 publications

References 38 publications

Respective Predictive Role of Urinary Albumin Excretion and Nonalbumin Proteinuria on Graft Loss and Death in Renal Transplant Recipients

Respective Predictive Role of Urinary Albumin Excretion and Nonalbumin Proteinuria on Graft Loss and Death in Renal Transplant Recipients

Cardiovascular risk factors following renal transplant

Albuminuria-reducing effect of angiotensin II receptor blocker plus hydrochlorothiazide combination therapy in renal transplant recipients

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