Skip to main content

Advertisement

SpringerLink
Log in

Factors related to nephrotic-range proteinuria in late-stage chronic kidney disease patients with diabetes mellitus

  • Nephrology - Original Paper
  • Published:
International Urology and Nephrology Aims and scope Submit manuscript

Abstract

Purpose

Diabetic nephropathy and proteinuria are important risk factors for both end-stage renal disease and cardiovascular events. The present study aimed to identify the factors associated with nephrotic-range proteinuria in patients with advanced diabetic nephropathy.

Methods

This cross-sectional study enrolled 386 diabetic patients with chronic kidney disease (CKD) stages 3–5, from our outpatient Department of Nephrology. Urinary protein-to-creatinine ratio was recorded. Additionally, other laboratory parameters, body mass index, blood pressure, comorbidities, and medications were also reviewed.

Results

The mean age of the patients was 65.1 ± 11.6 years. Among patients with CKD stage 3 and 4, the odds ratio (OR) for nephrotic-range proteinuria in relation with systolic blood pressure significantly increased starting from 121 mmHg (OR 7.04 and 11.79 for systolic blood pressure of 121–140 and ≥141 mmHg, respectively, in comparison with systolic blood pressure below 121 mmHg). In addition, serum phosphorus ≥4.7 mg/dl was associated with significantly higher risk (OR 15.45) for severe proteinuria, compared with a phosphorus level ≤2.6 mg/dl. Finally, hypertriglyceridemia ≥241 mg/dl was also associated with higher OR for severe proteinuria, compared with a triglyceride level ≤200 mg/dl. Similar associations were found in patients with CKD stage 5.

Conclusions

Higher systolic blood pressure, serum phosphorus, and triglyceride levels are associated with nephrotic-range proteinuria in patients with diabetic nephropathy and CKD stage 3–5. Further studies should clarify whether a reduction in serum phosphorus would lead to a decrease in proteinuria in these patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. American Diabetes Association (2003) Standards of medical care for patients with diabetes mellitus. Diabetes Care 26:33–50

    Article  Google Scholar 

  2. Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving HH, Remuzzi G, Snapinn SM, Zhang Z, Shahinfar S, RENAAL Study Investigators (2001) Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 345:861–869

    Article  PubMed  CAS  Google Scholar 

  3. Culleton BF, Larson MG, Parfrey PS, Kannel WB, Levy D (2000) Proteinuria as a risk factor for cardiovascular disease and mortality in older people: a prospective study. Am J Med 109:1–8

    Article  PubMed  CAS  Google Scholar 

  4. Taal MW, Brenner BM (2006) Predicting initiation and progression of chronic kidney disease: developing renal risk scores. Kidney Int 70:1694–1705

    Article  PubMed  CAS  Google Scholar 

  5. Evans M, Fryzek JP, Elinder CG, Cohen SS, McLaughlin JK, Nyrén O, Fored CM (2005) The natural history of chronic renal failure: results from an unselected, population-based, inception cohort in Sweden. Am J Kidney Dis 46:863–870

    Article  PubMed  Google Scholar 

  6. Hallan SI, Ritz E, Lydersen S, Romundstad S, Kvenild K, Orth SR (2009) Combining GFR and albuminuria to classify CKD improves prediction of ESRD. J Am Soc Nephrol 20:1069–1077. doi:10.1681/ASN.2008070730

    Article  PubMed  CAS  Google Scholar 

  7. Ramirez SP, McClellan W, Port FK, Hsu SI (2002) Risk factors for proteinuria in a large, multiracial, southeast Asian population. J Am Soc Nephrol 13(7):1907–1917

    Article  PubMed  Google Scholar 

  8. Retnakaran R, Cull CA, Thorne KI, Adler AI, Holman RR, UKPDS Study Group (2006) Risk factors for renal dysfunction in type 2 diabetes: U.K. Prospective Diabetes Study 74. Diabetes Care 55:1832–1839

    Article  CAS  Google Scholar 

  9. Yokoyama H, Sone H, Oishi M, Kawai K, Fukumoto Y, Kobayashi M, Japan Diabetes Clinical Data Management Study Group (2009) Prevalence of albuminuria and renal insufficiency and associated clinical factors in type 2 diabetes: the Japan Diabetes Clinical Data Management study (JDDM15). Nephrol Dial Transplant 24:1212–1219. doi:10.1093/ndt/gfn603

    Article  PubMed  CAS  Google Scholar 

  10. Jia W, Gao X, Pang C, Hou X, Bao Y, Liu W, Wang W, Zuo Y, Gu H, Xiang K (2009) Prevalence and risk factors of albuminuria and chronic kidney disease in Chinese population with type 2 diabetes and impaired glucose regulation: Shanghai diabetic complications study (SHDCS). Nephrol Dial Transplant 24:3724–3731. doi:10.1093/ndt/gfp349

    Article  PubMed  CAS  Google Scholar 

  11. Leoncini G, Viazzi F, Rosei EA, Ambrosioni E, Costa FV, Leonetti G, Pessina AC, Trimarco B, Volpe M, Deferrari G, Pontremoli R (2010) Chronic kidney disease in hypertension under specialist care the I-DEMAND study. J Hypertens 28:156–162

    Article  PubMed  CAS  Google Scholar 

  12. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D (1999) A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 130:461–470

    Article  PubMed  CAS  Google Scholar 

  13. Foundation NK (2002) Clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 39:1–266

    Google Scholar 

  14. Foundation NK (2003) K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis 42:1–201

    Google Scholar 

  15. Yuyun MF, Adler AI, Wareham NJ (2005) What is the evidence that microalbuminuria is a predictor of cardiovascular disease events? Curr Opin Nephrol Hypertens 14:271–276

    Article  PubMed  CAS  Google Scholar 

  16. Fuller JH, Stevens LK, Wang SL (2001) Risk factors for cardiovascular mortality and morbidity: the WHO Multinational Study of Vascular Disease in Diabetes. Diabetologia 44:54–64

    Article  Google Scholar 

  17. Dinneen SF, Gerstein HC (1997) The association of microalbuminuria and mortality in non-insulin-dependent diabetes mellitus: a systematic overview of the literature. Arch Intern Med 157:1413–1418

    Article  PubMed  CAS  Google Scholar 

  18. Sexton DJ, Kinsella SM, Eustace JA (2012) Serum phosphate varies with degree of proteinuria in nephrotic syndrome and is associated with elevated pulse wave velocity. J Nephrol. doi:10.5301/jn.5000186

    PubMed  Google Scholar 

  19. Yap YS, Chi WC, Lin CH, Wu YW, Liu YC (2012) Hyperphosphatemia is associated with overt proteinuria in non-diabetic patients with late-stage chronic kidney disease: a cross-sectional study. Int Urol Nephrol. doi:10.1007/s11255-11012-10163-11257

    PubMed  Google Scholar 

  20. Pijls LT, de Vries H, Donker AJ, van Eijk JT (1999) The effect of protein restriction on albuminuria in patients with type 2 diabetes mellitus: a randomized trial. Nephrol Dial Transplant 14:1445–1453

    Article  PubMed  CAS  Google Scholar 

  21. Kojima F, Uchida K, Ogawa T, Tanaka Y, Nitta K (2008) Plasma levels of fibroblast growth factor-23 and mineral metabolism in diabetic and non-diabetic patients on chronic hemodialysis. Int Urol Nephrol 40:1067–1074

    Article  PubMed  CAS  Google Scholar 

  22. Titan SM, Zatz R, Graciolli FG, dos Reis LM, Barros RT, Jorgetti V, Moysés RM (2011) FGF-23 as a predictor of renal outcome in diabetic nephropathy. Clin J Am Soc Nephrol 6:241–247

    Article  PubMed  CAS  Google Scholar 

  23. Yilmaz MI, Sonmez A, Saglam M, Yaman H, Kilic S, Demirkaya E, Eyileten T, Caglar K, Oguz Y, Vural A, Yenicesu M, Zoccali C (2010) FGF-23 and vascular dysfunction in patients with stage 3 and 4 chronic kidney disease. Kidney Int 78:679–685

    Article  PubMed  CAS  Google Scholar 

  24. Ix JH, Shlipak MG, Wassel CL, Whooley MA (2010) Fibroblast growth factor-23 and early decrements in kidney function: the Heart and Soul Study. Nephrol Dial Transplant 25:993–997

    Article  PubMed  CAS  Google Scholar 

  25. Dhingra R, Sullivan LM, Fox CS, Wang TJ, D’Agostino RB Sr, Gaziano JM, Vasan RS (2007) Relations of serum phosphorus and calcium levels to the incidence of cardiovascular disease in the community. Arch Intern Med 167:879–885

    Article  PubMed  CAS  Google Scholar 

  26. Taskapan H (2012) Is 24,25(OH)D level really high in dialysis patients with high FGF23 levels? Int Urol Nephrol 44:1135–1144

    Article  PubMed  CAS  Google Scholar 

  27. Sekiguchi S, Suzuki A, Asano S, Nishiwaki-Yasuda K, Shibata M, Nagao S, Yamamoto N, Matsuyama M, Sato Y, Yan K, Yaoita E, Itoh M (2011) Phosphate overload induces podocyte injury via type III Na-dependent phosphate transporter. Am J Physiol Renal Physiol 300:848–856

    Article  Google Scholar 

  28. Fox ER, Benjamin EJ, Sarpong DF, Nagarajarao H, Taylor JK, Steffes MW, Salahudeen AK, Flessner MF, Akylbekova EL, Fox CS, Garrison RJ, Taylor HA Jr (2010) The relation of C-reactive protein to chronic kidney disease in African Americans: the Jackson Heart Study. BMC Nephrol 11:1. doi:10.1186/1471-2369-11-1

    Article  PubMed  Google Scholar 

  29. Voormolen N, Noordzij M, Grootendorst DC, Beetz I, Sijpkens YW, van Manen JG, Boeschoten EW, Huisman RM, Krediet RT, Dekker FW, PREPARE Study Group (2007) High plasma phosphate as a risk factor for decline in renal function and mortality in pre-dialysis patients. Nephrol Dial Transplant 22:2909–2916. doi:10.1093/ndt/gfm286

    Article  PubMed  CAS  Google Scholar 

  30. Isakova T, Gutiérrez OM, Patel NM, Andress DL, Wolf M, Levin A (2011) Vitamin D deficiency, inflammation, and albuminuria in chronic kidney disease: complex interactions. J Ren Nutr 21:295–302

    Article  PubMed  CAS  Google Scholar 

  31. Portale AA, Halloran BP, Morris RC Jr (1989) Physiologic regulation of the serum concentration of 1,25-dihydroxyvitamin D by phosphorus in normal men. J Clin Invest 83:1494–1499

    Article  PubMed  CAS  Google Scholar 

  32. Cirillo M, Stellato D, Laurenzi M, Panarelli W, Zanchetti A, De Santo NG (2000) Pulse pressure and isolated systolic hypertension association with microalbuminuria. Kidney Int 58:1211–1218

    Article  PubMed  CAS  Google Scholar 

  33. Agarwal R, Andersen MJ (2005) Correlates of systolic hypertension in patients with chronic kidney disease. Hypertension 46:514–520. doi:10.1161/01.HYP.0000178102.85718.66

    Article  PubMed  CAS  Google Scholar 

  34. Magri CJ, Calleja N, Buhagiar G, Fava S, Vassallo J (2012) Factors associated with diabetic nephropathy in subjects with proliferative retinopathy. Int Urol Nephrol 44:197–206. doi:10.1007/s11255-011-9958-1

    Article  PubMed  CAS  Google Scholar 

  35. Rossing K, Christensen PK, Hovind P, Parving HH (2005) Remission of nephrotic-range albuminuria reduces risk of end-stage renal disease and improves survival in type 2 diabetic patients. Diabetologia 48:2241–2247

    Article  PubMed  CAS  Google Scholar 

  36. Viswanathan V, Tilak P, Kumpatla S (2012) Risk factors associated with the development of overt nephropathy in type 2 diabetes patients: a 12 years observational study. Indian J Med Res 136:46–53

    PubMed  CAS  Google Scholar 

  37. Cusick M, Chew EY, Hoogwerf B, Agrón E, Wu L, Lindley A, Ferris FL III, Early Treatment Diabetic Retinopathy Study Research Group (2004) Risk factors for renal replacement therapy in the Early Treatment Diabetic Retinopathy Study (ETDRS), Early Treatment Diabetic Retinopathy Study report no. 26. Kidney Int 66:1173–1179

    Article  PubMed  Google Scholar 

  38. Coonrod BA, Ellis D, Becker DJ, Bunker CH, Kelsey SF, Lloyd CE, Drash AL, Kuller LH, Orchard TJ (1993) Predictors of microalbuminuria in individuals with IDDM: Pittsburgh Epidemiology of Diabetes Complications Study. Diabetes Care 16:1376–1383

    Article  PubMed  CAS  Google Scholar 

  39. Leehey DJ, Kramer HJ, Daoud TM, Chatha MP, Isreb MA (2005) Progression of kidney disease in type 2 diabetes—beyond blood pressure control: an observational study. BMC Nephrol 6:8. doi:10.1186/1471-2369-6-8

    Article  PubMed  Google Scholar 

  40. Shankar A, Klein R, Moss SE, Klein BE, Wong TY (2004) The relationship between albuminuria and hypercholesterolemia. J Nephrol 17:658–665

    PubMed  Google Scholar 

  41. Nakhjavani M, Esteghamati A, Khalilzadeh O, Asgarani F, Mansournia N, Abbasi M (2010) Association of macroalbuminuria with oxidized LDL and TGF-beta in type 2 diabetic patients: a case–control study. Int Urol Nephrol 42:487–492. doi:10.1007/s11255-009-9643-9

    Article  PubMed  CAS  Google Scholar 

  42. Prakash J, Sen D, Usha, Kumar NS (2001) Non-diabetic renal disease in patients with type 2 diabetes mellitus. J Assoc Physicians India 49:415–420

    PubMed  CAS  Google Scholar 

Download references

Conflict of interest

The authors report no conflicts of interest.

Author information

Authors and Affiliations

  1. Division of Nephrology, Department of Internal Medicine, Yuan’s General Hospital, No. 162, Chenggong 1st Rd., LingYa District, Kaohsiung, 802, Taiwan, ROC

    Yit-Sheung Yap, Wen-Che Chi, Cheng-Hao Lin & Yi-Chun Liu

  2. Department of Environmental and Occupational Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, ROC

    Hung-Yi Chuang

  3. Department of Public Health, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC

    Hung-Yi Chuang

  4. Division of Nephrology, Chronic Kidney Disease Education Center, Yuan’s General Hospital, Kaohsiung, Taiwan, ROC

    Yi-Wen Wu & Pai-Chun Chang

Authors
  1. Yit-Sheung Yap
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hung-Yi Chuang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wen-Che Chi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Cheng-Hao Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yi-Wen Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Pai-Chun Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yi-Chun Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yi-Chun Liu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yap, YS., Chuang, HY., Chi, WC. et al. Factors related to nephrotic-range proteinuria in late-stage chronic kidney disease patients with diabetes mellitus. Int Urol Nephrol 45, 1327–1337 (2013). https://doi.org/10.1007/s11255-013-0378-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11255-013-0378-2

Keywords

Search

Navigation