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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

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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.

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References

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed Central  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  17. Abbate M, Zoja C, Remuzzi G. How does proteinuria cause progressive renal damage? J Am Soc Nephrol. 2006;17(11):2974–84.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed Central  PubMed  Google Scholar 

  27. American Diabetes Association. Standards of medical care in diabetes—2014. Diabetes Care. 2014;37(Suppl 1):S14–80.

    Article  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed Central  PubMed  Google Scholar 

  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.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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The authors have declared that no conflict of interest exists.

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Correspondence to Akira Sugawara.

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Kitai, Y., Doi, Y., Osaki, K. et al. 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. Clin Exp Nephrol 19, 1037–1043 (2015). https://doi.org/10.1007/s10157-015-1094-2

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  • DOI: https://doi.org/10.1007/s10157-015-1094-2

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