Title

Arteriolar hyalinosis in nephrectomy patients predicts chronic kidney disease independent of clinical and other biopsy pathology.

Authors

Praveen Gowtham Varma Dasaraju¹ MBBS; Bhawna Randhi¹ MBBS; Austin Reynolds^1,2 BS; Aleksandar Denic¹ MD, PhD; Aidan F. Mullan³ MA; Muhammad Sohaib Asghar¹ MBBS; Laura Barisoni⁴ MD; Maxwell L. Smith⁵ MD; Mariam Priya Alexander⁶ MD; Andrew D. Rule^1,7 MD.

¹Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA.

²University of Minnesota, Rochester, Minnesota, USA.

³Division of Clinical Trials and Biostatistics, Mayo Clinic, Rochester, Minnesota, USA.

⁴Department of Pathology and Medicine, Duke University, Durham, North Carolina, USA.

⁵Department of Laboratory Medicine and Pathology, Mayo Clinic, Scottsdale, Arizona, USA.

⁶Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.

⁷Division of Epidemiology, Mayo Clinic, Rochester, Minnesota, USA.

Introduction

Many chronic changes on kidney biopsy are predictive of end-stage renal disease (ESRD). Arteriolar hyalinosis (AH) is an understudied and under-reported chronic change in kidney biopsies. Radical nephrectomy patients are a unique opportunity to thoroughly evaluate AH on large sections in a patient population not selected on the presence or absence of kidney disease. The primary goal of this study was to determine the risk of progressive CKD with AH in post-nephrectomy patients.

Methods

200 patients underwent radical nephrectomy between 2000-2019 and were followed with an annual eGFR test. A nested matched case-control study identified 50 CKD patients (40% decline in eGFR from post-nephrectomy baseline) matched to non-CKD controls (n=150) on sex, age, and follow-up time. Parenchymal tissue away from the tumor was cut into 3µm sections, stained with periodic-acid-Schiff (PAS), and scanned into high-resolution images using an Aperio XT system scanner. Each AH lesion was identified using Aperio Image Scope software by manual annotations. Clinical and other biopsy data were extracted from the patient’s medical records. The association of AH with CKD was assessed with and without adjustment for clinical characteristics.

Results

A total of 200 patients with a median age of 66.0 [62-74] years were included. There was no difference among the 50 CKD cases and 150 controls with respect to clinical factors except the CKD cases had higher baseline 24hr proteinuria. Complete AH and total AH (normalized per cortex) were found associated with CKD irrespective of %IFTA, %GSG, NSG volume, and clinical characteristics (OR: 1.54 [1.08-2.18]). Complete AH (normalized per area cortex) correlated with measures of nephrosclerosis (% artery luminal stenosis, % GSG, and IF/TA density but not with measures of nephron size (glomerular volume and tubular cross-sectional area).

Conclusion

Assessment of AH on the non-tumor kidney tissue of patients who undergo radical nephrectomy may be useful for predicting which of these patients will develop progressive CKD where they are at increased risk of needing dialysis or kidney transplant. These findings are consistent with the independent prognostic significance of AH on kidney biopsies in other patient populations such as diagnostic biopsies ordered by nephrologists.

References

Acknowledgements: Supported by NIH Grants: R25-DK101405, U54-DK100227, R01-DK90358

References:

Zamami R, Kohagura K, Miyagi T, Kinjyo T, Shiota K, Ohya Y. Modification of the impact of hypertension on proteinuria by renal arteriolar hyalinosis in nonnephrotic chronic kidney disease. J Hypertens. 2016 Nov;34(11):2274-2279.

Denic, A., et al.Clinical and Pathology Findings Associate Consistently with Larger Glomerular Volume. J Am Soc Nephrol. 2018 Jul;29(7):1960-1969.