Normoalbuminuric Diabetic Kidney Disease- Need for Renal Biopsy? An Autopsy Study on Western Indian Population
Keywords:
Diabetic kidney disease, Normoalbuminuria, Renal biopsy
Abstract
Introduction: Persistent albuminuria and glomerular filtration rate are considered as the gold standard for the diagnosis of Diabetic Nephropathy (DN). Methods: In this autopsy study, we evaluated data from a cohort of 67 patients with Type 2 Diabetes Mellitus. We determined the histological prevalence of DN irrespective of the clinical manifestations of renal disease. Patients were stratified by proteinuria and estimated glomerular filtration rate(eGFR). The glomerular, interstitial and vascular lesions were scored as per the established histopathologic classification for DN. Results: 55 of the 67 patients had clinical as well as histological lesions consistent with DN. 12 patients had histological lesions of DN at autopsy but no clinical evidence of proteinuria, including microalbuminuria in their lifetime.4 of these patients had maintained eGFR. There was no difference in the glomerular lesions in patients with normoalbuminuria regardless of the eGFR. However,50% of the patients with low eGFR showed presence of interstitial fibrosis and tubular atrophy while no interstitial lesions were noted in patients with normoalbuminuria and maintained eGFR. Significant amount of arteriosclerosis was noted in the normoalbuminuric low eGFR patients. Haematuria was significantly associated with proteinuric low GFR patients. Conclusion: Histological evidence of DN may be seen even in the absence of clinical manifestations, suggesting that, in diabetic kidneys some amount of glomerular and tubulointerstitial damage has already occurred before the onset of proteinuria. Hence, there is a need for routine kidney biopsies in diabetic patients with normoalbuminuria. This will help in the timely diagnosis and appropriate management in the early stages of DN.References
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2.Klessens CQ, Woutman TD, Veraar KA, Zandbergen M, Valk EJ, Rotmans JI, Wolterbeek R, Bruijn JA, Bajema IM. An autopsy study suggests that diabetic nephropathy is underdiagnosed. Kidney Int.2016;90:149–156.
3. Tsalamandris C, Allen TJ, Gilbert RE, Sinha A, Panagiotopoulos S, Cooper ME, Jerums G. Progressive decline in renal function in diabetic patients with and without albuminuria. Diabetes.1994;43:649–655.
4. Chen C, Wang C, Hu C, Han Y, Zhao L, Zhu X, Xiao L, Sun L. Normoalbuminuric diabetic kidney disease. Front Med. 2017;11:310-318.
5. ThomasMC,MacisaacRJ,JerumsG,WeekesA,MoranJ,ShawJE, Atkins RC. Nonalbuminuric renal impairment in type 2 diabetic patients and in the general population (national evaluation of the frequency of renal impairment cO-existing with NIDDM [NEFRON] 11). Diabetes Care.2009;32:1497–1502.
6. American Diabetes Association. Standards of medical care in diabetes—2015 abridged for primary care providers. Clin Diabetes.2015;33:97–111.
7.Tervaert TWC, Mooyaart AL, Amann K, Cohen AH, Cook HT, Drachenberg CB Ferrario F, Fogo AB, Haas M, de Heer E, Joh K, Noël LH, Radhakrishnan J, Seshan SV, Bajema IM, Bruijn JA; Renal Pathology Society. Pathologic Classification of Diabetic Nephropathy. J. Am. Soc. Nephrol. 2010;21:556-563.
8. Comai G, Malvi D, Angeletti A, Vasuri F, Valente S, Ambrosi F, Capelli I, Ravaioli M, Pasquinelli G, D'Errico A, Fornoni A, La Manna G. Histological Evidence of Diabetic Kidney Disease Precede Clinical Diagnosis. Am J Nephrol. 2019;50:29-36.
9. Adler AI, Stevens RJ, Manley SE, Bilous RW, Cull CA, Holman RR; UKPDS GROUP. Development and progression of nephropathy in type 2 diabetes: The United Kingdom Prospective Diabetes Study (UKPDS 64). Kidney Int. 2003; 63:225–232.
10. Gesualdo L, Di Paolo S. Renal lesions in patients with type 2 diabetes: a puzzle waiting to be solved. Nephrol Dial Transplant. 2015;30:155–157.
11.Fiorentino M, Bolignano D, Tesar V, Pisano A, Biesen WV, TripepiG,D'Arrigo G, Gesualdo L; ERA-EDTA Immunonephrology Working Group. Renal biopsy in patients with diabetes: a pooled meta-analysis of 48 studies. Nephrol Dial Transplant. 2017; 32: 97–110.
12.Retnakaran R, Cull CA, Thorne KI, Adler AI, Holman RR. UKPDS Study Group. Risk factors for renal dysfunction in type 2 diabetes: U.K. Prospective Diabetes Study 74. Diabetes. 2006;55:1832–1839.
13. Kramer HJ, Nguyen QD, Curhan G, Hsu CY. Renal insufficiency in the absence of albuminuria and retinopathy among adults with type 2 diabetes mellitus. JAMA. 2003;289:3273–7.
14. Penno G, Solini A, Bonora E, Fondelli C, Orsi E, Zerbini G, Trevisan R, Vedovato M, Gruden G, Cavalot F, Cignarelli M, Laviola L, Morano S, Nicolucci A, Pugliese G; Renal InsufficiencyAnd Cardiovascular Events (RIACE) Study Group. Clinical significance of nonalbuminuric renal impairment in type 2 diabetes. J Hypertens. 2011;29:1802–1809.
15. MacIsaac RJ, Tsalamandris C, Panagiotopoulos S, Smith TJ, McNeil KJ, Jerums G. Nonalbuminuric renal insufficiency in type 2 diabetes. Diabetes Care. 2004;27:195–200.
16.Shimizu M, Furuichi K, Toyama T, Kitajima S, Hara A, Kitagawa K, Iwata Y, Sakai N, Takamura T, Yoshimura M, Yokoyama H, Kaneko S, Wada T; Kanazawa Study Group for Renal Diseases and Hypertension. Long-term outcomes of Japanese type 2 diabetic patients with biopsy-proven diabetic nephropathy.Diabetes Care. 2013;36:3655-3662.
17. Dwyer JP, Parving HH, Hunsicker LG, Ravid M, Remuzzi G, Lewis JB. Renal Dysfunction in the Presence of Normoalbuminuria in Type 2 Diabetes: results from the DEMAND Study. Cardiorenal Med. 2012;2:1–10.
18. Uzu T, Kida Y, Shirahashi N, Harada T, Yamauchi A, Nomura M,Isshiki K, Araki S, Sugimoto T, Koya D, Haneda M, Kashiwagi A, Kikkawa R. Cerebral microvascular disease predicts renal failure in type 2 diabetes. J Am Soc Nephrol. 2010;21:520–526.
19.Said SM, Nasr SH. Silent diabetic nephropathy.Kidney Int. 2016;90:24-6.
20. Sharma SG, Bomback AS, Radhakrishnan J, Herlitz LC, Stokes MB, Markowitz GS,D'Agati VD. The modern spectrum of renal biopsy findings in patients with diabetes. Clin J Am Soc Nephrol. 2013;8:1718–1724.
21. Ghani AA, Waheeb SA, Sahow AA, Hussain N. Renal biopsy in patients with type 2 diabetes mellitus: indications and nature of the lesions.
Ann Saudi Med. 2009;29:450–453.
22. Zhuo L, Zhang N, Zou G, Chen D, Li W. Clinical characteristics and outcomes of biopsyproven diabetic nephropathy. Front Med. 2017;11:386–392.
23. Mulder S, Hamidi H, Kretzler M, Ju W. An integrative systems biology approach for precision medicine in diabetic kidney disease. Diabetes ObesMetab. 2018;20:6–13.
24. Looker HC, Mauer M, Nelson RG. Role of Kidney Biopsies for Biomarker Discovery in Diabetic Kidney Disease. Adv Chronic Kidney Dis. 2018;25:192-201.
25.Alicic RZ, Rooney MT, Tuttle KR. Diabetic kidney disease challenges, progress, and possibilities. Clin J Am Soc Nephrol. 2017;12:2032‐ 2045.
Published
2020-10-25
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