Kidney Structural Features from Living Donors Predict Graft Failure in the Recipient

Issa, Naim; Lopez, Camden L.; Denic, Aleksandar; Taler, Sandra J.; Larson, Joseph J.; Kremers, Walter K.; Ricaurte, Luisa; Merzkani, Massini; Alexander, Mariam P.; Chakkera, Harini A.; Stegall, Mark D.; Augustine, Joshua J.; Rule, Andrew D.

doi:10.1681/asn.2019090964

Cited by 31 publications

(44 citation statements)

References 31 publications

(41 reference statements)

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“…26 Recipients of kidneys from living donors who have higher percentage IF/TA and larger cross-sectional tubular area are at a higher risk for graft failure. 27 Studies in patients with specific kidney diseases have also found measures of nephrosclerosis and nephron size to be predictive of progressive CKD. [28][29][30][31] This study demonstrates that in a population that does not have a specific kidney disease that would typically warrant a kidney biopsy (other than diabetic nephropathy and hypertensive nephrosclerosis), underlying larger nephron size and nephrosclerosis are predictors of progressive CKD.…”

Section: Discussionmentioning

confidence: 99%

Larger Nephron Size and Nephrosclerosis Predict Progressive CKD and Mortality after Radical Nephrectomy for Tumor and Independent of Kidney Function

Denic

Elsherbiny

Mullan

et al. 2020

JASN

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BackgroundNephron hypertrophy and nephrosclerosis may be important determinants of CKD and mortality. However, studies of outcomes associated with these microstructural features have been limited to small tissue specimens from patients selected for either good kidney health or known kidney disease.MethodsTo determine whether microstructural features are predictive of progressive CKD and mortality outcomes, we studied patients who underwent a radical nephrectomy for a tumor. Large wedge sections of renal parenchyma distal to the tumor were stained and scanned into high-resolution images; we annotated the cortex and all glomeruli to calculate glomerular volume, cortex volume per glomerulus, and percentage of globally sclerotic glomeruli. Morphometric measurements also included percentages of artery luminal stenosis and interstitial fibrosis/tubular atrophy (IF/TA) of the cortex. At follow-up visits every 6–12 months, we determined which patients experienced progressive CKD (defined as dialysis, kidney transplantation, or a 40% decline from postnephrectomy eGFR). Cox models for these outcomes were adjusted for age, sex, body mass index, hypertension, diabetes, smoking, eGFR, and proteinuria.ResultsAmong 936 patients (mean age, 64 years; postnephrectomy baseline eGFR, 48 ml/min per 1.73 m2), 117 progressive CKD events, 183 noncancer deaths, and 116 cancer deaths occurred during a median follow-up of 6.4 years. Larger glomerular volume, larger cortex per glomerulus, and higher percentage of globally sclerotic glomeruli or IF/TA predicted progressive CKD. Higher percentage IF/TA also predicted noncancer mortality. Microstructural features did not predict cancer mortality or recurrence.ConclusionsAfter a radical nephrectomy, larger nephrons and nephrosclerosis predicted progressive CKD, and IF/TA predicted noncancer mortality. Morphometric analysis of renal parenchyma can predict noncancer clinical events in patients long after their radical nephrectomy.

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Section: Discussionmentioning

confidence: 99%

Larger Nephron Size and Nephrosclerosis Predict Progressive CKD and Mortality after Radical Nephrectomy for Tumor and Independent of Kidney Function

Denic

Elsherbiny

Mullan

et al. 2020

JASN

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“…This is a prospective cohort study of living kidney donors (aged !18 years) at the Mayo Clinic sites in Minnesota and Arizona from May 1, 1999, through December 31, 2018, in the Aging Kidney Anatomy Study. 18,19 Our inclusion criteria required a time-zero biopsy during the transplant surgery with 2 or more mm 2 of nondistorted cortex with at least 4 glomeruli. To study long-term kidney function outcomes, we targeted donors with 5 or more years of followup for participation.…”

Section: Study Design and Study Samplementioning

confidence: 99%

“…[14][15][16][17] They also modestly predict a lower postdonation glomerular filtration rate (GFR), albuminuria, and hypertension early after donation 18 and the death-censored risk for graft failure in the kidney recipient. 19 Long-term follow-up is needed to more fully comprehend the clinical importance of baseline microstructural features in the kidney at the time of donation. Thus, we performed a cohort study from the living donors in the Aging Kidney Anatomy study to determine whether nephron size, nephron number per kidney, or nephrosclerosis at the time of donation predict a long-term risk for developing low GFR, self-reported proteinuria, or hypertension.…”

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confidence: 99%

Kidney Microstructural Features at the Time of Donation Predict Long-term Risk of Chronic Kidney Disease in Living Kidney Donors

Merzkani

Denic

Narasimhan

et al. 2021

Mayo Clinic Proceedings

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Objective: To determine whether microstructural features on a kidney biopsy specimen obtained during kidney transplant surgery predict long-term risk of chronic kidney disease in the donor. Patients and Methods: We studied kidney donors from May 1, 1999, through December 31, 2018, with a follow-up survey for the results of recent blood pressure and kidney function tests (estimated glomerular filtration rate [eGFR] and proteinuria). If not recently available, blood pressure and eGFRs were requested from a local clinic. Microstructural features on kidney biopsy at the time of donation were assessed as predictors of hypertension and kidney function after adjusting for years of follow-up, baseline age, sex, and clinical predictors. Results: There were 807 donors surveyed a mean 10.5 years after donation. An eGFR less than 45 mL/ min/1.73 m 2 in 6.4% (43/673) of donors was predicted by larger glomerular volume per standard deviation (odds ratio [OR], 1.48; 95% CI, 1.08 to 2.04) and nephron number below the age-specific 5th percentile (OR, 3.38; 95% CI, 1.31 to 8.72). An eGFR less than 60 mL/min/1.73 m 2 in 42.5% (286/ 673) of donors was not predicted by any microstructural feature. Residual eGFR (postdonation/predonation eGFR) was predicted by nephron number below the age-specific 5th percentile (difference, À6.07%; 95% CI, À10.24% to À1.89%). Self-reported proteinuria in 5.1% (40/786) of donors was predicted by larger glomerular volume (OR, 1.42; 95% CI, 1.08 to 1.86). Incident hypertension in 18.8% (119/633) of donors was not predicted by any microstructural features. Conclusion: Low nephron number for age and larger glomeruli are important microstructural predictors for long-term risk of chronic kidney disease after living kidney donation.

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“…Kidney graft outcomes can be divided in short-term outcomes, such as early failure or one-year graft function, and long-term outcomes, such as (death-censored) graft failure and graft function decline [ 4 ]. Death-censored graft failure, as return to dialysis or re-transplantation, is seen in 10–12.5% of kidney transplant recipients at 5–6.2 years after transplantation [ 5 , 6 ]. Overall graft failure, including death with a functioning graft, is seen at a rate of 5% each year of follow-up, of which 40–60% is attributed to death with a functioning graft [ 7 , 8 , 9 , 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Aorto-Iliac Artery Calcification and Graft Outcomes in Kidney Transplant Recipients

Benjamens

Alghamdi

Rijkse

et al. 2021

JCM

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While the association of vascular calcification with inferior patient outcomes in kidney transplant recipients is well-established, the association with graft outcomes has received less attention. With this dual-centre cohort study, we aimed to determine the clinical impact of recipient pre-transplant aorto-iliac calcification, measured on non-contrast enhanced computed tomography (CT)-imaging within three years prior to transplantation (2005–2018). We included 547 patients (61.4% male, age 60 (interquartile range 51–68) years), with a median follow-up of 3.1 (1.4–5.2) years after transplantation. The aorto-iliac calcification score (CaScore) was inversely associated with one-year estimated-glomerular filtration rate (eGFR) in univariate linear regression analysis (standard β −3.3 (95% CI −5.1 to −1.5, p < 0.0001), but not after adjustment for potential confounders, including donor and recipient age (p = 0.077). In multivariable Cox regression analyses, a high CaScore was associated with overall graft failure (p = 0.004) and death with a functioning graft (p = 0.002), but not with death-censored graft failure and graft function decline. This study demonstrated that pre-transplant aorto-iliac calcification is associated with one-year eGFR in univariate, but not in multivariable linear regression analyses. Moreover, this study underlines that transplantation in patients with a high CaScore does not result in earlier transplant function decline or worse death censored graft survival, although ongoing efforts for the prevention of death with a functioning graft remain essential.

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Kidney Structural Features from Living Donors Predict Graft Failure in the Recipient

Cited by 31 publications

References 31 publications

Larger Nephron Size and Nephrosclerosis Predict Progressive CKD and Mortality after Radical Nephrectomy for Tumor and Independent of Kidney Function

Larger Nephron Size and Nephrosclerosis Predict Progressive CKD and Mortality after Radical Nephrectomy for Tumor and Independent of Kidney Function

Kidney Microstructural Features at the Time of Donation Predict Long-term Risk of Chronic Kidney Disease in Living Kidney Donors

Aorto-Iliac Artery Calcification and Graft Outcomes in Kidney Transplant Recipients

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