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Category: Volume 06 Issue 06 June 2018
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Title: Correlation between Spot Urine Protein-Creatinine Ratio and 24-Hour Urine Protein Estimation in Type 2 Diabetes Mellitus Patients Attending A Tertiary Care Centre in Alappuzha

Authors: Sharath Thomas Roy, Dr Udayamma K P

 DOI:  https://dx.doi.org/10.18535/jmscr/v6i6.69

Abstract

About 20% of cases of chronic renal failure is due to diabetic nephropathy and is the most common cause of end stage renal disease (ESRD) in many countries. Proteinuria is an independent risk factor for renal diseases and a predictor of ESRD.  For the diagnosis and management of chronic renal disease, accurate identification and quantification of proteinuria is very important. An increased proteinuria has both diagnostic and prognostic values in detection and confirmation of renal diseases and to assess response to therapy. Increased proteinuria is associated with an increased risk of progressive renal failure. The gold standard for the quantitative evaluation of proteinuria is the measurement of protein excretion in a 24hr urine sample. 24hr urine sample collection is an inconvenient method especially in outpatient setting. An alternate convenient method for evaluation of proteinuria is measurement of protein to creatinine ratio in a spot urine sample. There are a number of studies that show urine spot protein to creatinine ratio (urinary PCR) can replace 24hr urine protein estimation in the screening and evaluation of diabetic nephropathy.

Objectives

1) To determine the correlation of spot urine protein creatinine ratio (PCR) with 24 hr urine protein estimation in patients with type 2 diabetes mellitus.

2) To study the association of biochemical and clinical parameters like serum creatinine, eGFR , glycated hemoglobin,  duration of diabetes, presence of diabetic retinopathy with urine PCR in patients with type 2 diabetes mellitus.

Methodology: The design of study is cross sectional study and the study population included Type II Diabetes Mellitus patients attending Medicine OPD, of either sex, in Govt. TDMC, Alappuzha for a period of 12 months from December 2015 to December 2016.The sample size is 73. 24hour urine protein and urine protein creatinine ratio was done in the study population.The patients were also evaluated for associated clinical and biochemical parameters. The data collected was analyzed using a standard statistical package-SPSS version 16.

Results: Seventy three patients with type 2 diabetes mellitus and proteinuria were studied. Maximum number of patients were noted in the age group 41-50 years. Males were more than females in the ratio of 2.04:1.  The mean duration of diabetes was 9.24 +/- 6.1 yrs.  Majority of patients had a duration of diabetes between 5 -10 yrs (52.05%).Ten patients (13.7%) did not   have diabetic retinopathy. Twenty five patients (34.25%) had nephrotic range proteinuria. There was good correlation between urine PCR and 24 hr urine protein at different levels of GFR. The correlation in different levels of GFR  were : (0-15 ) group : r = 0.784 , p = <0.001 ,  (15-30) group : r = 0.756 , p = <0.001,  (30-60) group : r = 0.725 , p = <0.001 , >60 group : r = 0.99 , p = <0.001. Maximum correlation between urine PCR and 24 hr urine protein was seen in the GFR >60 group. There was good correlation between urine PCR and 24 hr urine protein at different ranges of proteinuria. The correlation in different levels of proteinuria were: <300 mg ( r= 0.93, P<0.001), 300-3500 mg (r= 0.632, P<0.001) and ≥3500 mg (r=0.783, P <0.001).Maximum correlation between urine PCR and 24 hr urine was seen in the proteinuria group  <300 mg. No statistically significant correlation was found between HBA1C levels and degree of proteinuria. There was good correlation between degree of diabetic retinopathy and proteinuria. No significant correlation was found between duration of diabetes and urine PCR.

Conclusion: Spot urine protein creatinine ratio can replace 24 hr urine protein estimation in the screening and evaluation of diabetic nephropathy.

References

  1. Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract 2010; 87: 4–14.
  2. Akmal M. Hemodialysis in diabetic patients. Am J Kidney Dis 2001; 38 (4 Suppl 1): S195–S199.
  3. Price CP, Newall RG, Boyd JC. Use of protein:creatinine ratio measurements on random urine samples for prediction of significant proteinuria: a systematic review. Clin Chem.2005;51(9):1577–86.
  4. Methven S, MacGregor MS, Traynor JP, O’Reilly DJ, Deighan CI. Assessing proteinuria in chronic kidney disease: protein-creatinine ratio versus albumin–creatinine ratio. Nephrol Dial Transplant. 2010;25(9):2991–6.
  5. Stevens LA, Levey AS. Current status and future perspectives for CKD testing. American Journal of Kidney Diseases. 2009;53(3):S17–S26.
  6. Ahmed AM. History of diabetes mellitus. Saudi Med J Apr;23 (4):373-378.
  7. Alebiosu CO, Kadiri S, Akang EEU. Clinicopathological study of Diabetic Nephropathy based on Renal Biopsy. Diabetes Intemational. 2002;12:66-69.
  8. Kimmestiel P, Wilson C. Intercapillary lesions in the glomeruli of the kidney. Am J Path. 1936;1 2:83-97.
  9. Mora-Fernández C, Domínguez-Pimentel V, de Fuentes MM, et al. (2014). "Diabetic kidney disease: from physiology to therapeutics".  Physiol. 592(18): 3997–4012. 
  10. Ding Y, Choi ME (January 2015).  "Autophagy in diabetic nephropathy". J Endocrinol. 
  11. Lizicarova D, Krahulec B, Hirnerova E, Gaspar L, Celecova Z (2014). "Risk factors in diabetic nephropathy progression at present". Bratisl Lek Listy. 115(8): 517–21.
  12. Pálsson R, Patel UD (2014).  "Cardiovascular complications of diabetic kidney disease". Adv Chronic Kidney Dis. 21(3): 273–80.
  13. Mongessen CE. Renal function changes in diabetes. Diabetes. 1976;15 (Suppl 2):872-879.
  14. American Diabetes Association. Diabetic Nephropathy (Position Statement). Diabetes Care. 2002;25(Suppl 1 ):S85-S89.
  15. Remmuzi G, Schiepatti A, Ruggenenti P. Nephropathy in patients with type-2 diabetes. NEJM. 2002;346:1145-1151.
  16. Ritz E, Orth SR. Nephropathy in patients with type-2 diabetes mellitus. NEJM 1999;341:1127-1133.
  17. Caramori ML, Fioretto P, Mauer M:The need for early predictors of diabetic nephropathy risk: is albumin excretion rate sufficient? Diabetes 2000, 49:1399-1408.
  18. Perkins BA, Ficociello LH, Silva KH, Finkelstein DM, Warram JH, Krolewski AS:Regression of microalbuminuria in type 1 diabetes. N Engl J Med 2003, 348:2285-2293.
  19. Dinneen SF, Gerstein HC:The association of microalbuminuria and mortality in non-insulin-dependent diabetes mellitus. A systematic overview of the literature. Arch Intern Med 1997, 157:1413-1418.
  20. Stehouwer CD, Gall MA, Twisk JW, Knudsen E, Emeis JJ, Parving HH:Increased urinary albumin excretion, endothelial dysfunction, and chronic low-grade inflammation in type 2 diabetes: progressive, interrelated, and independently associated with risk of death. Diabetes 2002, 51:1157-1165.
  21. Viberti GC, Bilous RW, Mackintosh D, Keen H:Monitoring glomerular function in diabetic nephropathy. A prospective study. Am J Med 1983, 74:256-264.
  22. Gall MA, Nielsen FS, Smidt UM, Parving HH:The course of kidney function in type 2 (non-insulin-dependent) diabetic patients with diabetic nephropathy. Diabetologia 1993, 36:1071-1078.
  23. Friedman R, Gross JL:Evolution of glomerular filtration rate in proteinuric NIDDM patients. Diabetes Care 1991, 14:355-359.
  24. Nosadini R, Velussi M, Brocco E, Bruseghin M, Abaterusso C, Saller A, Dalla Vestra M, Carraro A, Bortoloso E, Sambataro M, Barzon I, Frigato F, Muollo B, Chiesura-Corona M, Pacini G, Baggio B, Piarulli F, Sfriso A, Fioretto P:Course of renal function in type 2 diabetic patients with abnormalities of albumin excretion rate. Diabetes 2000, 49:476-484.
  25. Krolewski AS, Warram JH, Christlieb AR, Busick EJ, Kahn CR:The changing natural history of nephropathy in type I diabetes. Am J Med 1985, 78:785-794. 
  26. Krolewski AS:Genetics of diabetic nephropathy: evidence for major and minor gene effects. Kidney Int 1999, 55:1582-1596.
  27. Krolewski AS, Ng DP, Canani LH, Warram JH:Genetics of diabetic nephropathy: how far are we from finding susceptibility genes? Adv Nephrol Necker Hosp 2001, 31:295-315.
  28. Quinn M, Angelico MC, Warram JH, Krolewski AS:Familial factors determine the development of diabetic nephropathy in patients with IDDM. Diabetologia 1996, 39:940-945.
  29. Pettitt DJ, Saad MF, Bennett PH, Nelson RG, Knowler WC:Familial predisposition to renal disease in two generations of Pima Indians with type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia 1990, 33:438-443. 
  30. Freedman BI, Tuttle AB, Spray BJ:Familial predisposition to nephropathy in African-Americans with non-insulin-dependent diabetes mellitus. Am J Kidney Dis 1995, 25:710-713. 
  31. Clustering of long-term complications in families with diabetes in the diabetes control and complications trial. The Diabetes Control and Complications Trial Research Group Diabetes1997, 46:1829-1839. 
  32. Canani LH, Gerchman F, Gross JL:Familial clustering of diabetic nephropathy in Brazilian type 2 diabetic patients. Diabetes 1999, 48:909-913.
  33. Ritz E, Orth SR. Nephropathy in patients with type-2 diabetes mellitus. NEJM 1999;341:1127-1133.
  34. Krowleski AS. Genetics of diabetic nephropathy: evidence for major and minor gene effects. Kidney Int. 1999;55:1582-1596.
  35. Pettitt DJ, Saad MF, Bennett PH, et al. Familial predisposition to renal disease in two generations of Pima Indians with type-2 (noninsulin-dependent)diabetes mellitus. 1990; 33:438-443.
  36. Gall M-A, Hougaard P, Borch-Johnsen K, et al. Risk factors for development of incipient and overt diabetic nephropathy in patients with noninsulin- dependent diabetes mellitus: prospective observa-tional study. BMJ.1997; 314:783-788.
  37. Ravid M, Neumann L, Lishner M. Plasma lipids and the progression of nephropathy in diabetes mellitus type-2: effect of ACE inhibitors. Kidney Int.1995; 47:907-910.
  38. Hovind P, Rossing P, Tarnow L, et al. Progression of diabetic nephropathy. Kidney Int. 2001; 59:702-709.
  39. Cooper ME. Pathogenesis, prevention, and treatment of diabetic nephropathy. Lancet. 1998; 352:213-219.
  40. Predictors of the development of microalbuminuria in patients with Type 1 diabetes mellitus: a seven-year prospective study. The Microalbuminuria Collabo-rative Study Group Diabet Med1999, 16:918-925. 
  41. Ravid M, Brosh D, Ravid-Safran D, Levy Z, Rachmani R:Main risk factors for nephropathy in type 2 diabetes mellitus are plasma cholesterol levels, mean blood pressure, and hyperglycemia. Arch Intern Med 1998, 158:998-1004.
  42. The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression at long-term complications in insulin-dependent diabetes mellitus. NEJM 1993:329:977-986.
  43. United Kingdom Prospective Diabetes Study (UKPDS) Group. Intensive blood glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type-2 diabetes (UKPDS 33). 1998; 352:837-853 [Erratum. Lancet. 1999; 354:602].
  44. Mulec H, Blohme G, Grandi B, et al. The effect of metabolic control on rate of decline in renal function in insulin-dependent diabetes mellitus with overt diabetic nephropathy. Nephrol Dial Tronspoant. 1998;13:651-655.
  45. Park JY, Kim HK, Chung YE, Kim SW, Hong SK, Lee KU:Incidence and determinants of microalbuminuria in Koreans with type 2 diabetes. Diabetes Care 1998, 21:530-534.
  46. Arauz-Pacheco C, Parrott MA, Raskin P. The treatment of hypertension in adult patients with diabetes. Diabetes Care. 2002;25:134-147.
  47. American Diabetes Association. Treatment of hypertension in adults with diabetes. Diabetes Care. 2003;26(Suppl 1 ):S80-S82.
  48. Ruggenenti P, Remuzzi G:Nephropathy of type-2 diabetes mellitus. J Am Soc Nephrol 1998, 9:2157-2169.
  49. Loon NR. Diabetic kidney disease: preventing dialysis and transplantation Clinical Diabetes. 2003;21:55-62.
  50. Jeffers BW, Estacio RO, Raynolds MV, et al. Angiotensin-converting enzyme gene polymorphism in noninsulin-dependent diabetes mellitus and its relationship with diabetic nephropathy. Kidney Int.1997; 52:473-477.
  51. Biesenbach G, Zazgornik J. Influence of smoking on the survival rate of diabetic patients requiring hemodialysis. Diabetes Care. 1996;19:635-638.
  52. Klein R, Klein BEK, Moss SE, et al. The 10-year incidence of renal insufficiency in people with type-I diabetes. Diabetes Care. 1999; 22:743-751.
  53. Chaturvedi N, Fuller JH, Taskinen MR:Differing associations of lipid and lipoprotein disturbances with the macrovascular and microvascular complications of type 1 diabetes. Diabetes Care 2001, 24:2071-2077. 
  54. Loon NR. Diabetic kidney disease: preventing dialysis and transplantation. Clinical Diabetes. 2003;21:55-62.
  55. Jeffers BW, Estacio RO, Raynolds MV, et al. Angiotensin-converting enzyme gene polymorphism in noninsulin-dependent diabetes mellitus and its relationship with diabetic nephropathy. Kidney Int.1997; 52:473-477.
  56. Kuramoto N, Lizuka T, Ito H, et al. Effect of ACE gene on diabetic nephropathy in NIDDM patients with insulin resistance. Am J Kidney Dis.1999; 33:276-28 1.
  57. Kunz R, Bork JP, Fritsche L, et al. Association between the angiotensin converting enzyme insertion/deletion polymorphism and diabetic nephropathy. A methodologic appraisal and systematic review. J Am Soc Nephrol. 1998; 9:1653-1663.
  58. Shah VO, Scavini M, Nikolic J, et al. Z-2 microsatellite allele is linked to increased expression of the aldose reductase gene in diabetic nephropathy. J Clin Endocrinol Metab. 1998;83:2886.
  59. Pugh JA, Stern MP, Haffner SM, et al. Excess incidence of treatment of end-stage renal disease in Mexican Americans. Am J Epidemiol. 1998;127:135-144.
  60. Brancati FL, Whittle JC, Whelton PK, et al. The excess incidence of diabetic end-stage renal disease among blacks. A population-based study of potential explanatory factors JAMA 1992;268:3079-3084.
  61. Fioretto P, Caramori ML, Mauer M:The kidney in diabetes: dynamic pathways of injury and repair. The Camillo Golgi Lecture. Diabetologia 2007, 51:1347-1355.
  62. Pezzolesi MG, Poznik GD, Mychaleckyj JC, Paterson AD, Barati MT, Klein JB, Ng DP, Placha G, Canani LH, Bochenski J, Waggott D, Merchant ML, Krolewski B, Mirea L, Wanic K, Katavetin P, Kure M, Wolkow P, Dunn JS, Smiles A, Walker WH, Boright AP, Bull SB, Doria A, Rogus JJ, Rich SS, Warram JH, Krolewski AS:Genome-wide Association Scan for Diabetic Nephropathy Susceptibility Genes in Type 1 Diabetes Mellitus. Diabetes 
  63. Brosius FC 3rd:New insights into the mechanisms of fibrosis and sclerosis in diabetic nephropathy. Rev Endocr Metab Disord 2008, 9:245-254.
  64. Dronavalli S, Duka I, Bakris GL:The pathogenesis of diabetic nephropathy. Nat Clin Pract Endocrinol Metab 2008, 4:444-452. 
  65. Nosadini R, Velussi M, Brocco E, Bruseghin M, Abaterusso C, Saller A, Dalla Vestra M, Carraro A, Bortoloso E, Sambataro M, Barzon I, Frigato F, Muollo B, Chiesura-Corona M, Pacini G, Baggio B, Piarulli F, Sfriso A, Fioretto P:Course of renal function in type 2 diabetic patients with abnormalities of albumin excretion rate. Diabetes 2000, 49:476-484.
  66. Thomas MC,. Lai KN, Tang SCW. Pathogenesis and Progression of Proteinuria: Diabetes and the Kidney. Contrib 2011; 170: 48–56.
  67. Singh A, Satchell SC, Neal CR, McKenzie EA, Tooke JE, Mathieson PW. Glomerular endothelial glycocalyx constitutes a barrier to protein permeability. J Am Soc Neph‐ 2007; 18(11):2885-93.
  68. Pan CY, Ho LT, Soegondo S, Prodjosudjadi W, Suwanwalaikorn S, Lim SC, Chan TM, Chow KW, Thoenes M, Choi DS; DEMAND Study Investigators. Prevalence of albuminuria and cardiovascular risk profile in a referred cohort of patients with type 2 diabetes: an Asian perspective. Diabetes Technol Ther. 2008; 10(5):397-403.
  69. Dalla Vestra M, Saller A, Bortoloso E, Mauer M, Fioretto P. Structural involvement in type 1 and type 2 diabetic nephropathy. Diabetes Metab. 2000; 26 Suppl 4:8-14.
  70. Sharma K, Eltayeb BO, McGowan TA, Dunn SR, Alzahabi B, Rohde R, Ziyadeh FN, Lewis EJ:Captopril-induced reduction of serum levels of transforming growth factor-beta1 correlates with long-term renoprotection in insulin-dependent diabetic patients. Am J Kidney Dis1999, 34:818-823.
  71. Welsh GI, Hale LJ, Eremina V, et al. Insulin signaling to the glomerular podocyte is critical for normal kidney function. Cell Metab 2010; 12(4):329.
  72. Fornoni A .Proteinuria, the podocyte, and insulin resistance diabetes mellitus Type 2 and proteinuria. N Engl J Med 2010;363 (21):2068.

Corresponding Author

Sharath Thomas Roy

Junior Resident, Department of General Medicine

Govt. T D Medical College, Alappuzha, Kerala