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

Abstract

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.

Antifibrotic Agents for the Management of CKD: A Review

“…Kidney biopsies are invasive, but glomerulosclerosis or interstitial fibrosis has been found to predict progressive CKD after unilateral nephrectomy, and in native kidneys and kidney graft biopsies (6)(7)(8). While molecular imaging of fibrosis proteins is still preclinical (9)(10)(11)(12)(13), whole kidney fibrosis may be assessed by non-invasive tools such as urine biomarkers and magnetic resonance imaging (MRI).…”

M2 Macrophages Serve as Critical Executor of Innate Immunity in Chronic Allograft Rejection

“…Tissue fibrosis is a dangerous condition and pathological manifestations characterized by an excessive accumulation of ECM in response to acute/chronic injuries. In addition, interstitial fibrosis and tubular atrophy (IF/TA) of kidney cortex is best known as its paramount importance in development of poorer renal function and outcome in chronic kidney disease (CKD) and kidney transplantation ( 41 , 42 ). In spite of the fact that emphasizing the predominated effects of adaptive antibody-mediated rejection (AMR) in loss of implants, innate-immune-dominated fibrotic rejection triggered by macrophages should not be neglected ( 43 ).…”

Critical timing of ACEi initiation prevents compensatory glomerular hypertrophy in the remaining single kidney

“…Uni-Nx (3/6 nephrectomy) in rats also induces autonomous development of proteinuria, glomerulosclerosis, and ESKD, but only after a period of apparent stability manifest by increased protein excretion reflecting ongoing hyperfiltration and compensatory glomerular and kidney enlargement. In uni-nephrectomized humans larger nephron size is associated with worse long-term outcomes 4 . This raises the question of whether single kidney states should be viewed as metastable and at risk of reduced kidney lifespan absent hypertrophic stress prevention.…”