Advances in Anatomic Pathology:
Letters to the Editor
Farag, Youssef M.K. MD
Renal Division, Brigham and Women's Hospital, Harvard Medical School Boston, MA
To the Editor:
We all enjoyed reading the comprehensive and illustrative review article by Bonsib and Pei1 in the July 2010 issue of Advances in Anatomic Pathology. The authors discussed the tumor-related findings in the non-neoplastic kidney with an overview of their clinical implications. Two comprehensive sections on diabetic glomerulopathy and arterionephrosclerosis discussed the pathologic findings in the non-neoplastic cortex of the kidney. Although there has been a recent original investigation of the pathologic changes in the kidney of patients with metabolic syndrome,2 the authors included only the well-established evidence-based pathologic findings in the context of the non-neoplastic kidney in tumor nephrectomy specimens.
Metabolic syndrome is a cluster of metabolic disorders associated with a 2-fold increased risk of atherosclerotic cardiovascular disease (CVD) and a 5-fold increased risk of type 2 diabetes mellitus.3 Metabolic syndrome is defined by the presence of any 3 of the following 5 traits: abdominal obesity, high blood pressure, abnormalities in triglyceride and high-density lipoprotein cholesterol levels, and fasting hyperglycemia.4 Several investigators doubt whether identifying patients with metabolic syndrome would have a predictive effect on the prognosis of such patients. In contrast, the individual components of metabolic syndrome are already well-established risk factors for CVD, and the association of metabolic syndrome with chronic kidney disease (CKD) has recently been reported.5–8 As the pathologic features in the kidney in patients with metabolic syndrome have not been described in detail, we conducted a study to address this issue.
We screened the clinical records of patients who underwent nephrectomy. In each case, the tissue had been submitted from a non-neoplastic kidney parenchyma distant to the tumor for evaluation by the kidney pathology service according to the routine protocol of the department . Twelve patients met the diagnostic criteria for metabolic syndrome and we also evaluated 12 age-matched and sex-matched healthy controls, who did not meet the criteria for metabolic syndrome. Histologic sections of randomly sampled non-neoplastic kidney parenchyma, which were submitted, were processed by light microscopy and morphometric evaluation of glomerular diameter, and the total glomerular area was evaluated by using the National Institutes of Health Image J analyzer program.
In our findings, there was a significant correlation between the glomerular cross-sectional areas in the 2 groups and with body mass index (P=0.01; r=0.48). Glomerular sclerosis, as global glomerulosclerosis (22±24% vs 8±9%; P=0.04) and segmental glomerulosclerosis (12±9% vs 6.2±8%; P=0.05), was greater in patients with metabolic syndrome. Nodular glomerulosclerosis (4 vs 0; P=0.03) was significantly more frequent in patients with metabolic syndrome. Tubular atrophy (16.6±13% vs 3.7±5.6%; P=0.006), interstitial fibrosis (20±12.5% vs 5.4±4.9%; P=0.001), and moderate-to-severe arterial sclerosis (9 patients with metabolic syndrome vs 1 control; P=0.001) were more prevalent in patients with metabolic syndrome. Arteriolar hyalinosis was not detected in patients with metabolic syndrome (P=0.2). We then conducted further analysis for a composite variable that included the highly significant outcome variables in the initial analysis. The composite of tubular atrophy, interstitial fibrosis, and medial sclerosis was more prevalent in patients with metabolic syndrome compared with controls (P=0.003; odds ratio, 33; confidence interval, 2.9-374.3). These findings suggest evidence of vascular damage. In contrast, arteriolar hyalinosis, one of the initial vascular changes in diabetes, was not detected in our patients with metabolic syndrome. Therefore, the abnormalities we observed may not be explained by hyperglycemia alone.
Although our study had a relatively small sample size, we do not believe that increasing the sample size would have changed our observations. The value of our findings in detecting the early pathologic manifestations of kidney disease in patients with metabolic syndrome is to better understand the pathophysiologic mechanisms in such a patient population. Therefore, targeting certain lifestyle and medical interventions can be effective in combating metabolic syndrome before the clinical signs of kidney damage (proteinuria and low estimated glomerular filtration rate) become evident. Prospective studies with larger sample size and detailed anthropometric measurements are needed to confirm pathologic changes in the non-neoplastic kidney in tumor nephrectomy specimens. Selecting these patients who do not have CKD is challenging, as primary care physicians often fail to diagnose patients with metabolic syndrome,9 which may be explained by low awareness of CVD and CKD risk in metabolic syndrome.
Youssef M.K. Farag MD
1. Bonsib SM, Pei Y. The non-neoplastic kidney in tumor nephrectomy specimens: what can it show and what is important? Adv Anat Pathol.. 2010;17:235–250
2. Alexander MP, Patel TV, Farag YM, et al. Kidney pathological changes in metabolic syndrome: a cross-sectional study Am J Kidney Dis.. 2009;53:751–759 . [Epub Apr 1, 2009].
3. Grundy SM, Cleeman JI, Daniels SR, et al. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement Circulation.. 2005;112:2735–2752
4. . Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the national cholesterol education program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III) JAMA.. 2001;285:2486–2497
5. Kurella M, Lo JC, Chertow GM. Metabolic syndrome and the risk for chronic kidney disease among nondiabetic adults J Am Soc Nephrol.. 2005;16:2134–2140 . [PubMed].
6. Kanauchi M, Kanauchi K, Kimura K, et al. Associations of chronic kidney disease with the metabolic syndrome in non-diabetic elderly Nephrol Dial Transplant.. 2006;21:3608–3609 . [PubMed].
7. Ninomiya T, Kiyohara Y. Albuminuria and chronic kidney disease in association with the metabolic syndrome J Cardio metab Syndr.. 2007;2:104–107
8. Tanaka H, Shiohira Y, Uezu Y, et al. Metabolic syndrome and chronic kidney disease in Okinawa, Japan Kidney Int.. 2006;69:369–374
9. Ford ES. Rarer than a blue moon: the use of a diagnostic code for the metabolic syndrome in the US Diabetes Care.. 2005;28:1808–1809
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