Histopathological analysis of the non - tumour parenchyma following radical nephrectomy: can it predict renal functional outcome?

Birendra, Rana; John, Nirmal Thampi; Duhli, Neelaveni; Devasia, Antony; Kekre, Nitin S; Manojkumar, Ramani

doi:10.1590/s1677-5538.ibju.2016.0417

Cited by 5 publications

(5 citation statements)

References 10 publications

(16 reference statements)

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“…A study of 73 patients followed for a mean of 1 year did not find glomerulosclerosis, arteriosclerosis, or interstitial fibrosis to predict eGFR decline. 6 Conversely, a study of 156 patients followed a mean of 4 years found that arteriosclerosis, glomerulosclerosis, and interstitial fibrosis predicted a rise in serum creatinine. 3 Another study in 49 patients found that for each 10% increase of glomerulosclerosis, there was a 9% decrease in eGFR at 6 months postoperative follow-up.…”

Section: Discussionmentioning

confidence: 99%

“…Prior kidney structure-outcome associations in patients undergoing nephrectomy have used small samples (49-222 patients) with short follow-up and had limited and only descriptive characterization of the structural pathology. [2][3][4][5][6][7] Adjustment for baseline kidney function has been lacking or inadequate. Many of these studies also included patients who had a partial nephrectomy.…”

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confidence: 99%

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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%

mentioning

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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“…13,14 Recently, we reported that both nephron hypertrophy and nephrosclerosis, including IF/TA, predicted progressive CKD, and that IF/TA alone predicted noncancer mortality in patients after radical nephrectomy. 14 However, this study and other past studies in patients who underwent nephrectomy [15][16][17][18][19][20][21] have only characterized IF/TA as a percentage of cortical involvement (%IF/TA), without consideration of its pattern of distribution within the cortex.…”

mentioning

confidence: 90%

A Higher Foci Density of Interstitial Fibrosis and Tubular Atrophy Predicts Progressive CKD after a Radical Nephrectomy for Tumor

Archila

Denic

Mullan

et al. 2021

JASN

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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 tumor in 2000 to 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 chronic kidney disease (CKD) was defined as dialysis, kidney transplantation, or 40% decline from the postnephrectomy estimated glomerular filtration rate (eGFR). Cox models assessed risk of CKD or noncancer mortality with morphometric measures of tubulointerstitial injury after adjustment for 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.

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“…In our work, we were able to take the influence of any (neo-)adjuvant and potentially nephrotoxic therapy into account for the evaluation of postoperative renal function. This had been a difficulty other colleagues encountered in earlier studies [ 6 – 8 , 18 , 19 ]. Thus, in the context of a putative kidney tumor, the presence of proteinuria should prompt a thorough nephrological investigation for glomerular disease.…”

Section: Discussionmentioning

confidence: 96%

“…The same held true for vascular nephropathy, which was also associated with reduced eGFR at surgery. Hypertension and diabetes are the principal causes for such changes, and predictors of eGFR decrease [4,18,[23][24][25][26]. Consequently, describing these lesions in the pathology report, regardless of their cause, should be mandatory as they could be a hurdle for the use of a potentially nephrotoxic adjuvant chemo-or targeted therapy.…”

Section: Discussionmentioning

confidence: 99%

More than ancillary records: clinical implications of renal pathology examination in tumor nephrectomy specimens

et al. 2021

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Background Nephrectomy is the management of choice for the treatment of renal tumors. Surgical pathologists primarily focus on tumor diagnosis and investigations relating to prognosis or therapy. Pathological changes in non-neoplastic tissue may, however, be relevant for further management and should be thoroughly assessed. Methods Here, we examined the non-neoplastic renal parenchyma in 206 tumor nephrectomy specimens for the presence of glomerular, tubulo-interstitial, or vascular lesions, and correlated them with clinical parameters and outcome of renal function. Results We analyzed 188 malignant and 18 benign or pseudo-tumorous lesions. The most common tumor type was clear cell renal cell carcinoma (CCRCC, n = 106) followed by papillary or urothelial carcinomas (n = 25). Renal pathology examination revealed the presence of kidney disease in 39 cases (18.9%). Glomerulonephritis was found in 15 cases (7.3%), and the most frequent was IgA nephropathy (n = 6; 2.9%). Vasculitis was found in two cases (0.9%). In 15 cases we found tubulo-interstitial nephritis, and in 9 severe diabetic or hypertensive nephropathy. Partial nephrectomy was not linked to better eGFR at follow-up. Age, vascular nephropathy, glomerular scarring and interstitial fibrosis were the leading independent negative factors influencing eGFR at time of surgery, whereas proteinuria was associated with reduced eGFR at 1 year. Conclusion Our large study population indicates a high incidence of renal diseases potentially relevant for the postoperative management of patients with renal neoplasia. Consistent and systematic reporting of non-neoplastic renal pathology in tumor nephrectomy specimens should therefore be mandatory.

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Histopathological analysis of the non - tumour parenchyma following radical nephrectomy: can it predict renal functional outcome?

Cited by 5 publications

References 10 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

A Higher Foci Density of Interstitial Fibrosis and Tubular Atrophy Predicts Progressive CKD after a Radical Nephrectomy for Tumor

More than ancillary records: clinical implications of renal pathology examination in tumor nephrectomy specimens

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