Luisa Ricaurte Archila1, Aleksandar Denic1, Aidan F Mullan2, Ramya Narasimhan1, Marija Bogojevic1, R Houston Thompson3, Bradley C Leibovich3, S Jeson Sangaralingham4, Maxwell L Smith5, Mariam P Alexander6, Andrew D Rule7,8. 1. Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota. 2. Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota. 3. Department of Urology, Mayo Clinic, Rochester, Minnesota. 4. Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota. 5. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota. 6. Department of Laboratory Medicine and Pathology, Mayo Clinic, Scottsdale, Arizona. 7. Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota rule.andrew@mayo.edu. 8. Division of Epidemiology, Mayo Clinic, Rochester, Minnesota.
Abstract
BACKGROUND: Chronic tubulointerstitial injury on kidney biopsy is usually quantified by the percentage of cortex with interstitial fibrosis/tubular atrophy (IF/TA). Whether other patterns of IF/TA or inflammation in the tubulointerstitium have prognostic importance beyond percentage IF/TA is unclear. METHODS: We obtained, stained, and digitally scanned full cortical thickness wedge sections of renal parenchyma from patients who underwent a radical nephrectomy for a tumor over 2000-2015, and morphometrically analyzed the tubulointerstitium of the cortex for percentage IF/TA, IF/TA density (foci per mm2 cortex), percentage subcapsular IF/TA, striped IF/TA, percentage inflammation (both within and outside IF/TA regions), and percentage subcapsular inflammation. Patients were followed with visits every 6-12 months. Progressive CKD was defined as dialysis, kidney transplantation, or 40% decline from the postnephrectomy eGFR. Cox models assessed the risk of CKD or noncancer mortality with morphometric measures of tubulointerstitial injury after adjustment for the percentage IF/TA and clinical characteristics. RESULTS: Among 936 patients (mean age, 64 years; postnephrectomy baseline eGFR, 48 ml/min per 1.73m2), 117 progressive CKD events and 183 noncancer deaths occurred over a median 6.4 years. Higher IF/TA density predicted both progressive CKD and noncancer mortality after adjustment for percentage IF/TA and predicted progressive CKD after further adjustment for clinical characteristics. Independent of percentage IF/TA, age, and sex, higher IF/TA density correlated with lower eGFR, smaller nonsclerosed glomeruli, more global glomerulosclerosis, and smaller total cortical volume. CONCLUSIONS: Higher density of IF/TA foci (a more scattered pattern with more and smaller foci) predicts higher risk of progressive CKD after radical nephrectomy compared with the same percentage of IF/TA but with fewer and larger foci.
BACKGROUND: Chronic tubulointerstitial injury on kidney biopsy is usually quantified by the percentage of cortex with interstitial fibrosis/tubular atrophy (IF/TA). Whether other patterns of IF/TA or inflammation in the tubulointerstitium have prognostic importance beyond percentage IF/TA is unclear. METHODS: We obtained, stained, and digitally scanned full cortical thickness wedge sections of renal parenchyma from patients who underwent a radical nephrectomy for a tumor over 2000-2015, and morphometrically analyzed the tubulointerstitium of the cortex for percentage IF/TA, IF/TA density (foci per mm2 cortex), percentage subcapsular IF/TA, striped IF/TA, percentage inflammation (both within and outside IF/TA regions), and percentage subcapsular inflammation. Patients were followed with visits every 6-12 months. Progressive CKD was defined as dialysis, kidney transplantation, or 40% decline from the postnephrectomy eGFR. Cox models assessed the risk of CKD or noncancer mortality with morphometric measures of tubulointerstitial injury after adjustment for the percentage IF/TA and clinical characteristics. RESULTS: Among 936 patients (mean age, 64 years; postnephrectomy baseline eGFR, 48 ml/min per 1.73m2), 117 progressive CKD events and 183 noncancer deaths occurred over a median 6.4 years. Higher IF/TA density predicted both progressive CKD and noncancer mortality after adjustment for percentage IF/TA and predicted progressive CKD after further adjustment for clinical characteristics. Independent of percentage IF/TA, age, and sex, higher IF/TA density correlated with lower eGFR, smaller nonsclerosed glomeruli, more global glomerulosclerosis, and smaller total cortical volume. CONCLUSIONS: Higher density of IF/TA foci (a more scattered pattern with more and smaller foci) predicts higher risk of progressive CKD after radical nephrectomy compared with the same percentage of IF/TA but with fewer and larger foci.
Authors: Aleksandar Denic; John C Lieske; Harini A Chakkera; Emilio D Poggio; Mariam P Alexander; Prince Singh; Walter K Kremers; Lilach O Lerman; Andrew D Rule Journal: J Am Soc Nephrol Date: 2016-07-08 Impact factor: 10.121
Authors: Aleksandar Denic; Mariam P Alexander; Vidhu Kaushik; Lilach O Lerman; John C Lieske; Mark D Stegall; Joseph J Larson; Walter K Kremers; Terri J Vrtiska; Harini A Chakkera; Emilio D Poggio; Andrew D Rule Journal: Am J Kidney Dis Date: 2016-02-06 Impact factor: 8.860
Authors: Anand Srivastava; Ragnar Palsson; Arnaud D Kaze; Margaret E Chen; Polly Palacios; Venkata Sabbisetti; Rebecca A Betensky; Theodore I Steinman; Ravi I Thadhani; Gearoid M McMahon; Isaac E Stillman; Helmut G Rennke; Sushrut S Waikar Journal: J Am Soc Nephrol Date: 2018-06-04 Impact factor: 10.121
Authors: Alastair J Rankin; David Kipgen; Colin C Geddes; Jonathan G Fox; Gordon Milne; Bruce Mackinnon; Emily P McQuarrie Journal: Clin Kidney J Date: 2018-10-10
Authors: Aleksandar Denic; Marija Bogojevic; Aidan F Mullan; Moldovan Sabov; Muhammad S Asghar; Sanjeev Sethi; Maxwell L Smith; Fernando C Fervenza; Richard J Glassock; Musab S Hommos; Andrew D Rule Journal: J Am Soc Nephrol Date: 2022-08-03 Impact factor: 14.978