Can Donor Implantation Renal Biopsy Predict Long-Term Renal Allograft Outcome?

El-Husseini, Amr; Sabry, Alaa; Zahran, Ahmed; Shoker, Ahmed

doi:10.1159/000099944

Cited by 40 publications

(24 citation statements)

References 81 publications

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“…Patients who would benefit from a kidney transplant may have to remain on the waitlist because kidneys with mild interstitial fibrosis are being rejected for transplantation [19]. Our study conducted in native kidneys is consistent with several studies in the transplant literature showing that a mild to moderate degree of fibrosis on time-zero biopsy does not necessarily predict worse graft function in living or deceased donor kidney transplantation [20-23]. …”

Section: Discussionsupporting

confidence: 82%

Renal Interstitial Fibrosis: An Imperfect Predictor of Kidney Disease Progression in Some Patient Cohorts

Menn-Josephy

Lee²,

Nolin³

et al. 2016

Am J Nephrol

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Background: The extent of interstitial fibrosis on kidney biopsy is regarded as a prognostic indicator and guide to treatment. Patients with extensive fibrosis are assigned to supportive treatments with the expectation that they have advanced beyond the point at which immunosuppressive or other disease-modifying therapies would be of benefit. Our study highlights some of the limitations of using interstitial fibrosis to predict who will develop end-stage renal disease (ESRD). Methods: Analysis of 434 consecutive renal biopsies performed between 2001 and 2012 at a single center. We assessed the influence of various clinical factors along with fibrosis as predictors of ESRD and dialysis-free survival in various patient groups. Results: Interstitial fibrosis performed well overall as a predictor of progression to dialysis. On average, patients with >50% fibrosis progressed more rapidly than those with either 25-49 or 0-24% fibrosis with a median time to dialysis of 1.2, 6.5 and >10 years, respectively. In contrast, interstitial fibrosis was of less value as a predictor of disease progression in a subset of cases that included patients over the age of 70 and those with diabetic nephropathy on biopsy. Surprisingly, 13.9% of patients with normal renal function had 25-49% fibrosis and 5% had more than 50% fibrosis on biopsy, and 5 years after undergoing biopsy 21% of patients with >50% fibrosis still remained dialysis free. Conclusion: Renal fibrosis is an imperfect prognostic indicator for the development of ESRD and caution should be exercised in applying it too rigidly, especially in elderly or diabetic patients.

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Section: Discussionsupporting

confidence: 82%

Renal Interstitial Fibrosis: An Imperfect Predictor of Kidney Disease Progression in Some Patient Cohorts

Menn-Josephy

Lee²,

Nolin³

et al. 2016

Am J Nephrol

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“…It is obvious that higher age of a kidney is independently associated with chronic histologic damage, as was described in autopsy studies (314). From this, it is no surprise that higher kidney age is an independent predictor of tubular atrophy, interstitial fibrosis, and functional impairment after renal transplantation, which was shown in protocol biopsy studies in adult and pediatric renal allograft recipients (85,261,315,316). However, these studies not only showed an association with nonspecific chronic histologic damage, but also demonstrated an association of higher donor age with medial arteriolar hyalinosis suggestive of CNI nephrotoxicity (85,261).…”

Section: Local Renal Susceptibility Factors For Cni Nephrotoxicitymentioning

confidence: 85%

Calcineurin Inhibitor Nephrotoxicity

Naesens

Kuypers²,

Sarwal³

2009

Clinical Journal of the American Society of Nephrology

1,268

1,000

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The use of the calcineurin inhibitors cyclosporine and tacrolimus led to major advances in the field of transplantation, with excellent short-term outcome. However, the chronic nephrotoxicity of these drugs is the Achilles' heel of current immunosuppressive regimens. In this review, the authors summarize the clinical features and histologic appearance of both acute and chronic calcineurin inhibitor nephrotoxicity in renal and nonrenal transplantation, together with the pitfalls in its diagnosis. The authors also review the available literature on the physiologic and molecular mechanisms underlying acute and chronic calcineurin inhibitor nephrotoxicity, and demonstrate that its development is related to both reversible alterations and irreversible damage to all compartments of the kidneys, including glomeruli, arterioles, and tubulo-interstitium. The main question-whether nephrotoxicity is secondary to the actions of cyclosporine and tacrolimus on the calcineurin-NFAT pathway-remains largely unanswered. The authors critically review the current evidence relating systemic blood levels of cyclosporine and tacrolimus to calcineurin inhibitor nephrotoxicity, and summarize the data suggesting that local exposure to cyclosporine or tacrolimus could be more important than systemic exposure. Finally, other local susceptibility factors for calcineurin inhibitor nephrotoxicity are reviewed, including variability in P-glycoprotein and CYP3A4/5 expression or activity, older kidney age, salt depletion, the use of nonsteroidal anti-inflammatory drugs, and genetic polymorphisms in genes like TGF-␤ and ACE. Better insight into the mechanisms underlying calcineurin inhibitor nephrotoxicity might pave the way toward more targeted therapy or prevention of calcineurin inhibitor nephrotoxicity.Clin J Am Soc Nephrol 4: 481-508, 2009. doi: 10.2215/CJN.04800908 T he introduction of the calcineurin inhibitor (CNI) cyclosporine in human kidney transplantation in the late 1970s revolutionized transplantation medicine, and made transplantation a preferable therapeutic intervention for end-stage renal diseases (1,2). In 1984, the potent immunosuppressive properties of another CNI, tacrolimus, were discovered, and tacrolimus was used successfully in human liver, kidney, and heart allograft recipients (3,4). Currently, 94% of kidney transplant recipients are discharged after transplantation with a CNI-based immunosuppressive regimen (5).The immunosuppressive properties of cyclosporine and tacrolimus result from inhibition of calcineurin, a calcium-and calmodulin-dependent phosphatase (protein phosphatase 3 [PPP3C], formerly PP2B). Intracellularly, these completely different molecules bind to cyclophylin and FKBP12 for cyclosporine and tacrolimus, respectively (6 -9). The competitive binding of cyclosporine-cyclophylin and tacrolimus-FKBP12 complexes to calcineurin inhibits phosphatase activity of calcineurin. This inhibition then suppresses the transcription of IL-2 via inhibition of the dephosphorylation and impaired translocation of the nucl...

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“…28–31 Cosio et al have demonstrated graft interstitial fibrosis (7%), tubular atrophy (25%), and arterial hyalinosis (10%) in biopsies taken from living donor kidneys. 32 They reported that interstitial fibrosis correlated well with both function and eventual graft survival.…”

Section: Discussionmentioning

confidence: 99%

Live Donor Renal Anatomic Asymmetry and Posttransplant Renal Function

et al. 2015

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Background Relationship between live donor renal anatomic asymmetry and post-transplant recipient function has not been studied extensively. Methods We analyzed 96 live-kidney donors, who had anatomical asymmetry (>10% renal length and/or volume difference calculated from CT angiograms) and their matching recipients. Split function differences (SFD) were quantified with 99mTc-DMSA renography. Implantation biopsies at time-zero were semi-quantitatively scored. A comprehensive model utilizing donor renal volume adjusted to recipient weight (Vol/Wgt), SFD, and biopsy score was used to predict recipient estimated glomerular filtration rate (eGFR) at one-year. Primary analysis consisted of a logistic regression model of outcome (odds of developing eGFR>60ml/min/1.73 m2 at one-year), a linear regression model of outcome (predicting recipient eGFR at one-year, using the CKD-EPI formula), and a Monte Carlo simulation based on the linear regression model (N=10,000 iterations). Results In the study cohort, the mean Vol/Wgt and eGFR at one-year were 2.04 ml/kg and 60.4 ml/min/1.73m2, respectively. Volume and split ratios between two donor kidneys were strongly correlated (r=0.79, p-value<0.001). The biopsy scores among SFD categories (<5%, 5–10%, >10%) were not different (p=0.190). On multivariate models, only Vol/Wgt was significantly associated with higher odds of having eGFR>60ml/min/1.73 m2 (OR=8.94, 95% CI 2.47–32.25, p=0.001) and had a strong discriminatory power in predicting the risk of eGFR<60ml/min/1.73m2 at one-year (ROC curve=0.78, 95% CI 0.68–0.89). Conclusion In the presence of donor renal anatomic asymmetry, Vol/Wgt appears to be a major determinant of recipient renal function at one-year post-transplantation. Renography can be replaced with CT volume calculation in estimating split renal function.

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Can Donor Implantation Renal Biopsy Predict Long-Term Renal Allograft Outcome?

Cited by 40 publications

References 81 publications

Renal Interstitial Fibrosis: An Imperfect Predictor of Kidney Disease Progression in Some Patient Cohorts

Renal Interstitial Fibrosis: An Imperfect Predictor of Kidney Disease Progression in Some Patient Cohorts

Calcineurin Inhibitor Nephrotoxicity

Live Donor Renal Anatomic Asymmetry and Posttransplant Renal Function

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