Nephron hypertrophy and nephrosclerosis may be important determinants of chronic kidney disease (CKD) progression and death after radical nephrectomy (RN), according to new study findings.

Using a precise approach, pathologists detailed microstructural features of kidney parenchyma (a large wedge not involved with tumor) obtained from 936 patients without a specific kidney disease (mean age 64 years; 92% White). Mean estimated glomerular filtration rate (eGFR) at 4 months after RN was 48 mL/min/1.73 m2. Over a median follow-up of 6.4 years, 117 patients had CKD progression (dialysis, kidney transplantation, or a 40% decline in eGFR), 183 died from noncancer causes, and 116 died from cancer.

Larger glomerular size and more severe nephrosclerosis significantly predicted later CKD progression, Andrew D. Rule, MD, of Mayo Clinic in Rochester, Minnesota, and colleagues reported in the Journal of the American Society of Nephrology. Each doubling of nonsclerotic glomerular volume, cortex volume per glomerulus, and nonfibrotic cortex per glomerulus was associated with a 2.2-, 2.0, and 1.8-fold higher risk for CKD progression, respectively, in a fully adjusted model. Interstitial fibrosis/tubular atrophy (IF/TA) of the cortex and globally sclerotic glomeruli (GSG) also increased CKD progression risk by 1.2- and 1.3-fold, respectively, per doubling (all P <.001).

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In addition, the risk of noncancer mortality significantly increased by 13% (P =.005) for levels of IF/TA exceeding approximately 5%, which may reflect systemic end organ damage, according to the investigators. Microstructural features did not predict cancer mortality or recurrence.

The investigators adjusted all results for eGFR, proteinuria, hypertension, type 2 diabetes, body mass index, smoking, sex, and age. Their study findings are particularly relevant for patients with renal tumors undergoing RN.  

“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,” Dr Rule’s team stated. 

Individuals with these microstructural features warrant close monitoring to treat CKD risk factors and screen for CKD progression, according to the authors. For example, larger glomerular size might prompt targeted antihypertensive treatment. To prevent kidney failure, partial nephrectomy (PN) may be preferable to RN. Refinements in pathologic assessment also are needed, such as the use of artificial intelligence to measure nephron size.

Compared with previous research, strengths of this study include the large sample size, longer follow-up, less distorted histology by excluding small PN specimens, focus on the nonsurgical decline in eGFR after nephrectomy, accurate and quantitative morphologic measures of nephrosclerosis, assessment of nephron size as a predictor, and more thorough adjustment for CKD risk factors and kidney function, including proteinuria.


Denic A, Elsherbiny H, Mullan AF, et al. Larger nephron size and nephrosclerosis predict progressive CKD and mortality after radical nephrectomy for tumor and independent of kidney function. J Am Soc Nephrol. Published online September 16, 2020. doi:10.1681/ASN.2020040449