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Clinical and Experimental Nephrology

, Volume 19, Issue 6, pp 1037–1043 | Cite as

Nephrotic range proteinuria as a strong risk factor for rapid renal function decline during pre-dialysis phase in type 2 diabetic patients with severely impaired renal function

  • Yuichiro Kitai
  • Yohei Doi
  • Keisuke Osaki
  • Sayaka Sugioka
  • Masao Koshikawa
  • Akira SugawaraEmail author
Original Article

Abstract

Background

Proteinuria is an established risk factor for progression of renal disease, including diabetic nephropathy. The predictive power of proteinuria, especially nephrotic range proteinuria, for progressive renal deterioration has been well demonstrated in diabetic patients with normal to relatively preserved renal function. However, little is known about the relationship between severity of proteinuria and renal outcome in pre-dialysis diabetic patients with severely impaired renal function.

Methods

125 incident dialysis patients with type 2 diabetes were identified. This study was aimed at retrospectively evaluating the impact of nephrotic range proteinuria (urinary protein–creatinine ratio above 3.5 g/gCr) on renal function decline during the 3 months just prior to dialysis initiation.

Results

In total, 103 patients (82.4 %) had nephrotic range proteinuria. The median rate of decline in estimated glomerular filtration rate (eGFR) in this study population was 0.98 (interquartile range 0.51–1.46) ml/min/1.73 m2 per month. Compared to patients without nephrotic range proteinuria, patients with nephrotic range proteinuria showed significantly faster renal function decline (0.46 [0.24–1.25] versus 1.07 [0.64–1.54] ml/min/1.73 m2 per month; p = 0.007). After adjusting for gender, age, systolic blood pressure, serum albumin, calcium–phosphorus product, hemoglobin A1c, and use of an angiotensin-converting enzyme inhibitor or an angiotensin II receptor blocker, patients with nephrotic range proteinuria showed a 3.89-fold (95 % CI 1.08–14.5) increased risk for rapid renal function decline defined as a decline in eGFR ≥0.5 ml/min/1.73 m2 per month.

Conclusion

Nephrotic range proteinuria is the predominant renal risk factor in type 2 diabetic patients with severely impaired renal function receiving pre-dialysis care.

Keywords

Proteinuria Type 2 diabetes Diabetic nephropathy Chronic kidney disease Renal function decline Risk factor 

Notes

Conflict of interest

The authors have declared that no conflict of interest exists.

References

  1. 1.
    Guariguata L, Whiting DR, Hambleton I, Beagley J, Linnenkamp U, Shaw JE. Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Res Clin Pract. 2014;103(2):137–49.CrossRefPubMedGoogle Scholar
  2. 2.
    KDOQI. KDOQI Clinical Practice Guideline and Clinical Practice Recommendations for anemia in chronic kidney disease: 2007 update of hemoglobin target. Am J Kidney Dis. 2007;50(3):471–530.CrossRefGoogle Scholar
  3. 3.
    Nosadini R, Velussi M, Brocco E, Bruseghin M, Abaterusso C, Saller A, et al. Course of renal function in type 2 diabetic patients with abnormalities of albumin excretion rate. Diabetes. 2000;49(3):476–84.CrossRefPubMedGoogle Scholar
  4. 4.
    Wang Y, Chen J, Chen L, Tay YC, Rangan GK, Harris DC. Induction of monocyte chemoattractant protein-1 in proximal tubule cells by urinary protein. J Am Soc Nephrol. 1997;8(10):1537–45.PubMedGoogle Scholar
  5. 5.
    Tang S, Leung JC, Abe K, Chan KW, Chan LY, Chan TM, et al. Albumin stimulates interleukin-8 expression in proximal tubular epithelial cells in vitro and in vivo. J Clin Invest. 2003;111(4):515–27.PubMedCentralCrossRefPubMedGoogle Scholar
  6. 6.
    Nangaku M, Pippin J, Couser WG. Complement membrane attack complex (C5b-9) mediates interstitial disease in experimental nephrotic syndrome. J Am Soc Nephrol. 1999;10(11):2323–31.PubMedGoogle Scholar
  7. 7.
    Perkins BA, Ficociello LH, Ostrander BE, Silva KH, Weinberg J, Warram JH, et al. Microalbuminuria and the risk for early progressive renal function decline in type 1 diabetes. J Am Soc Nephrol. 2007;18(4):1353–61.CrossRefPubMedGoogle Scholar
  8. 8.
    Breyer JA, Bain RP, Evans JK, Nahman NS, Lewis EJ, Cooper M, et al. Predictors of the progression of renal insufficiency in patients with insulin-dependent diabetes and overt diabetic nephropathy. The Collaborative Study Group. Kidney Int. 1996;50(5):1651–8.CrossRefPubMedGoogle Scholar
  9. 9.
    de Zeeuw D, Remuzzi G, Parving HH, Keane WF, Zhang Z, Shahinfar S, et al. Proteinuria, a target for renoprotection in patients with type 2 diabetic nephropathy: lessons from RENAAL. Kidney Int. 2004;65(6):2309–20.CrossRefPubMedGoogle Scholar
  10. 10.
    Rossing K, Christensen PK, Hovind P, Parving HH. Remission of nephrotic-range albuminuria reduces risk of end-stage renal disease and improves survival in type 2 diabetic patients. Diabetologia. 2005;48(11):2241–7.CrossRefPubMedGoogle Scholar
  11. 11.
    Seino Y, Nanjo K, Tajima N, Kadowaki T, Kashiwagi A, Araki E, et al. Report of the committee on the classification and diagnostic criteria of diabetes mellitus. J Diabetes Investig. 2010;1(5):212–28.PubMedCentralCrossRefPubMedGoogle Scholar
  12. 12.
    Ginsberg JM, Chang BS, Matarese RA, Garella S. Use of single voided urine samples to estimate quantitative proteinuria. N Engl J Med. 1983;309(25):1543–6.CrossRefPubMedGoogle Scholar
  13. 13.
    Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, et al. Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis. 2009;53(6):982–92.CrossRefPubMedGoogle Scholar
  14. 14.
    Molitch ME, DeFronzo RA, Franz MJ, Keane WF, Mogensen CE, Parving HH, et al. Nephropathy in diabetes. Diabetes Care. 2004;27(Suppl 1):S79–83.PubMedGoogle Scholar
  15. 15.
    Lewis EJ, Hunsicker LG, Clarke WR, Berl T, Pohl MA, Lewis JB, et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med. 2001;345(12):851–60.CrossRefPubMedGoogle Scholar
  16. 16.
    Rossing K, Christensen PK, Hovind P, Tarnow L, Rossing P, Parving HH. Progression of nephropathy in type 2 diabetic patients. Kidney Int. 2004;66(4):1596–605.CrossRefPubMedGoogle Scholar
  17. 17.
    Abbate M, Zoja C, Remuzzi G. How does proteinuria cause progressive renal damage? J Am Soc Nephrol. 2006;17(11):2974–84.CrossRefPubMedGoogle Scholar
  18. 18.
    Zoja C, Donadelli R, Colleoni S, Figliuzzi M, Bonazzola S, Morigi M, et al. Protein overload stimulates RANTES production by proximal tubular cells depending on NF-kappa B activation. Kidney Int. 1998;53(6):1608–15.CrossRefPubMedGoogle Scholar
  19. 19.
    Braun MC, Reins RY, Li TB, Hollmann TJ, Dutta R, Rick WA, et al. Renal expression of the C3a receptor and functional responses of primary human proximal tubular epithelial cells. J Immunol. 2004;173(6):4190–6.CrossRefPubMedGoogle Scholar
  20. 20.
    Mezzano S, Aros C, Droguett A, Burgos ME, Ardiles L, Flores C, et al. NF-kappaB activation and overexpression of regulated genes in human diabetic nephropathy. Nephrol Dial Transplant. 2004;19(10):2505–12.CrossRefPubMedGoogle Scholar
  21. 21.
    Keane WF, Brenner BM, de Zeeuw D, Grunfeld JP, McGill J, Mitch WE, et al. The risk of developing end-stage renal disease in patients with type 2 diabetes and nephropathy: the RENAAL study. Kidney Int. 2003;63(4):1499–507.CrossRefPubMedGoogle Scholar
  22. 22.
    Yap YS, Chuang HY, Chi WC, Lin CH, Wu YW, Chang PC, et al. Factors related to nephrotic-range proteinuria in late-stage chronic kidney disease patients with diabetes mellitus. Int Urol Nephrol. 2013;45(5):1327–37.CrossRefPubMedGoogle Scholar
  23. 23.
    Cirillo M, Stellato D, Laurenzi M, Panarelli W, Zanchetti A, De Santo NG. Pulse pressure and isolated systolic hypertension: association with microalbuminuria. The GUBBIO Study Collaborative Research Group. Kidney Int. 2000;58(3):1211–8.CrossRefPubMedGoogle Scholar
  24. 24.
    The GISEN Group (Gruppo Italiano di Studi Epidemiologici in Nefrologia). Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy. Lancet. 1997;349(9069):1857–63.CrossRefGoogle Scholar
  25. 25.
    Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving HH, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001;345(12):861–9.CrossRefPubMedGoogle Scholar
  26. 26.
    Taler SJ, Agarwal R, Bakris GL, Flynn JT, Nilsson PM, Rahman M, et al. KDOQI US commentary on the 2012 KDIGO clinical practice guideline for management of blood pressure in CKD. Am J Kidney Dis. 2013;62(2):201–13.PubMedCentralCrossRefPubMedGoogle Scholar
  27. 27.
    American Diabetes Association. Standards of medical care in diabetes—2014. Diabetes Care. 2014;37(Suppl 1):S14–80.CrossRefGoogle Scholar
  28. 28.
    Ahmed AK, Kamath NS, El Kossi M, El Nahas AM. The impact of stopping inhibitors of the renin-angiotensin system in patients with advanced chronic kidney disease. Nephrol Dial Transplant. 2010;25(12):3977–82.CrossRefPubMedGoogle Scholar
  29. 29.
    Hou FF, Zhang X, Zhang GH, Xie D, Chen PY, Zhang WR, et al. Efficacy and safety of benazepril for advanced chronic renal insufficiency. N Engl J Med. 2006;354(2):131–40.CrossRefPubMedGoogle Scholar
  30. 30.
    Hsu TW, Liu JS, Hung SC, Kuo KL, Chang YK, Chen YC, et al. Renoprotective effect of renin-angiotensin-aldosterone system blockade in patients with predialysis advanced chronic kidney disease, hypertension, and anemia. JAMA Intern Med. 2014;174(3):347–54.CrossRefPubMedGoogle Scholar
  31. 31.
    Schwartz MM, Lewis EJ, Leonard-Martin T, Lewis JB, Batlle D. Renal pathology patterns in type II diabetes mellitus: relationship with retinopathy. The Collaborative Study Group. Nephrol Dial Transplant. 1998;13(10):2547–52.CrossRefPubMedGoogle Scholar
  32. 32.
    Sharma SG, Bomback AS, Radhakrishnan J, Herlitz LC, Stokes MB, Markowitz GS, et al. The modern spectrum of renal biopsy findings in patients with diabetes. Clin J Am Soc Nephrol. 2013;8(10):1718–24.PubMedCentralCrossRefPubMedGoogle Scholar
  33. 33.
    Chen SC, Su HM, Hung CC, Chang JM, Liu WC, Tsai JC, et al. Echocardiographic parameters are independently associated with rate of renal function decline and progression to dialysis in patients with chronic kidney disease. Clin J Am Soc Nephrol. 2011;6(12):2750–8.PubMedCentralCrossRefPubMedGoogle Scholar

Copyright information

© Japanese Society of Nephrology 2015

Authors and Affiliations

  • Yuichiro Kitai
    • 1
  • Yohei Doi
    • 1
  • Keisuke Osaki
    • 1
  • Sayaka Sugioka
    • 1
  • Masao Koshikawa
    • 1
  • Akira Sugawara
    • 1
    Email author
  1. 1.Department of NephrologyOsaka Red Cross HospitalOsakaJapan

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