Dm Nephropathy Case Study

  • Tang SC, Chan GC, Lai KN. Recent advances in managing and understanding diabetic nephropathy. F1000Res. 2016. 5:[Medline]. [Full Text].

  • Ekinci EI, Jerums G, Skene A, Crammer P, Power D, Cheong KY. Renal structure in normoalbuminuric and albuminuric patients with type 2 diabetes and impaired renal function. Diabetes Care. 2013 Nov. 36(11):3620-6. [Medline].

  • Hall JE, Henegar JR, Dwyer TM, Liu J, Da Silva AA, Kuo JJ. Is obesity a major cause of chronic kidney disease?. Adv Ren Replace Ther. 2004 Jan. 11(1):41-54. [Medline].

  • Yip JW, Jones SL, Wiseman MJ, Hill C, Viberti G. Glomerular hyperfiltration in the prediction of nephropathy in IDDM: a 10-year follow-up study. Diabetes. 1996 Dec. 45(12):1729-33. [Medline].

  • Odegaard JI, Chawla A. Connecting type 1 and type 2 diabetes through innate immunity. Cold Spring Harb Perspect Med. 2012 Mar. 2(3):a007724. [Medline]. [Full Text].

  • Chiarelli F, Gaspari S, Marcovecchio ML. Role of growth factors in diabetic kidney disease. Horm Metab Res. 2009 Aug. 41(8):585-93. [Medline].

  • Rask-Madsen C, King GL. Kidney complications: factors that protect the diabetic vasculature. Nat Med. 2010 Jan. 16(1):40-1. [Medline].

  • Ziyadeh FN. Mediators of diabetic renal disease: the case for tgf-Beta as the major mediator. J Am Soc Nephrol. 2004 Jan. 15 Suppl 1:S55-7. [Medline].

  • Deshpande SD, Putta S, Wang M, Lai JY, Bitzer M, Nelson RG. Transforming growth factor-ß-induced cross talk between p53 and a microRNA in the pathogenesis of diabetic nephropathy. Diabetes. 2013 Sep. 62(9):3151-62. [Medline].

  • Bherwani S, Saumya AS, Ahirwar AK, et al. The association of folic acid deficiency and diabetic nephropathy in patients with type 2 diabetes mellitus. Endocr Metab Immune Disord Drug Targets. 2016 Apr 15. [Medline].

  • de Boer IH, Rue TC, Hall YN, et al. Temporal trends in the prevalence of diabetic kidney disease in the United States. JAMA. 2011 Jun 22. 305(24):2532-9. [Medline].

  • Klessens CQ, Woutman TD, Veraar KA, et al. An autopsy study suggests that diabetic nephropathy is underdiagnosed. Kidney Int. 2016 Jul. 90 (1):149-56. [Medline].

  • Pavkov ME, Bennett PH, Knowler WC, Krakoff J, Sievers ML, Nelson RG. Effect of youth-onset type 2 diabetes mellitus on incidence of end-stage renal disease and mortality in young and middle-aged Pima Indians. JAMA. 2006 Jul 26. 296(4):421-6. [Medline].

  • Rosolowsky ET, Skupien J, Smiles AM, et al. Risk for ESRD in type 1 diabetes remains high despite renoprotection. J Am Soc Nephrol. 2011 Mar. 22(3):545-53. [Medline]. [Full Text].

  • Kostadaras A. Risk Factors for Diabetic Nephropathy. Astoria Hypertension Clinic. Available at

  • Kocasarac C, Yigit Y, Sengul E, Sakalar YB. Choroidal thickness alterations in diabetic nephropathy patients with early or no diabetic retinopathy. Int Ophthalmol. 2017 Apr 11. [Medline].

  • Iliadis F, Didangelos T, Ntemka A, et al. Glomerular filtration rate estimation in patients with type 2 diabetes: creatinine- or cystatin C-based equations?. Diabetologia. 2011 Dec. 54(12):2987-94. [Medline].

  • Park SB, Kim SS, Kim IJ, et al. Variability in glycated albumin levels predicts the progression of diabetic nephropathy. J Diabetes Complications. 2017 Feb 3. [Medline].

  • Tervaert TW, Mooyaart AL, Amann K, et al. Pathologic classification of diabetic nephropathy. J Am Soc Nephrol. 2010 Apr. 21 (4):556-63. [Medline]. [Full Text].

  • Shlipak M. Diabetic nephropathy. Clin Evid (Online). 2009 Jan 14. 2009:[Medline].

  • Burney BO, Kalaitzidis RG, Bakris GL. Novel therapies of diabetic nephropathy. Curr Opin Nephrol Hypertens. 2009 Mar. 18(2):107-11. [Medline].

  • Suckling RJ, He FJ, Macgregor GA. Altered dietary salt intake for preventing and treating diabetic kidney disease. Cochrane Database Syst Rev. 2010 Dec 8. 12:CD006763. [Medline].

  • Heerspink HJ, Holtkamp FA, Parving HH, Navis GJ, Lewis JB, Ritz E, et al. Moderation of dietary sodium potentiates the renal and cardiovascular protective effects of angiotensin receptor blockers. Kidney Int. 2012 Mar 21. [Medline].

  • Diabetes Control and Complications Research Group. Effect of intensive therapy on the development and progression of diabetic nephropathy in the Diabetes Control and Complications Trial. The Diabetes Control and Complications (DCCT) Research Group. Kidney Int. 1995 Jun. 47(6):1703-20. [Medline].

  • UK Prospective Diabetes Study 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). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998 Sep 12. 352(9131):837-53. [Medline].

  • Bergman AJ, Cote J, Yi B, Marbury T, Swan SK, Smith W. Effect of renal insufficiency on the pharmacokinetics of sitagliptin, a dipeptidyl peptidase-4 inhibitor. Diabetes Care. 2007 Jul. 30(7):1862-4. [Medline].

  • Scheen AJ. Pharmacokinetic considerations for the treatment of diabetes in patients with chronic kidney disease. Expert Opin Drug Metab Toxicol. 2013 May. 9(5):529-50. [Medline].

  • Snyder RW, Berns JS. Use of insulin and oral hypoglycemic medications in patients with diabetes mellitus and advanced kidney disease. Semin Dial. 2004 Sep-Oct. 17(5):365-70. [Medline].

  • Lamos EM, Younk LM, Davis SN. Canagliflozin , an inhibitor of sodium-glucose cotransporter 2, for the treatment of type 2 diabetes mellitus. Expert Opin Drug Metab Toxicol. 2013 Jun. 9(6):763-75. [Medline].

  • Linnebjerg H, Kothare PA, Park S, Mace K, Reddy S, Mitchell M. Effect of renal impairment on the pharmacokinetics of exenatide. Br J Clin Pharmacol. 2007 Sep. 64(3):317-27. [Medline].

  • Davidson JA, Brett J, Falahati A, Scott D. Mild renal impairment and the efficacy and safety of liraglutide. Endocr Pract. 2011 May-Jun. 17(3):345-55. [Medline].

  • Young A. Clinical studies. Adv Pharmacol. 2005. 52:289-320. [Medline].

  • Mogensen CE. The effect of blood pressure intervention on renal function in insulin-dependent diabetes. Diabete Metab. 1989. 15(5 Pt 2):343-51. [Medline].

  • Laight DW. Therapeutic inhibition of the renin angiotensin aldosterone system. Expert Opin Ther Pat. 2009 Jun. 19(6):753-9. [Medline].

  • Jennings DL, Kalus JS, Coleman CI, Manierski C, Yee J. Combination therapy with an ACE inhibitor and an angiotensin receptor blocker for diabetic nephropathy: a meta-analysis. Diabet Med. 2007 May. 24(5):486-93. [Medline].

  • Imai E, Chan JC, Ito S, et al. Effects of olmesartan on renal and cardiovascular outcomes in type 2 diabetes with overt nephropathy: a multicentre, randomised, placebo-controlled study. Diabetologia. 2011 Dec. 54(12):2978-2986. [Medline].

  • Fried LF, Emanuele N, Zhang JH, Brophy M, Conner TA, Duckworth W. Combined angiotensin inhibition for the treatment of diabetic nephropathy. N Engl J Med. 2013 Nov 14. 369(20):1892-903. [Medline].

  • Persson F, Rossing P, Reinhard H, Juhl T, Stehouwer CD, Schalkwijk C, et al. Renal effects of aliskiren compared with and in combination with irbesartan in patients with type 2 diabetes, hypertension, and albuminuria. Diabetes Care. 2009 Oct. 32(10):1873-9. [Medline]. [Full Text].

  • [Guideline] National Kidney Foundation. NKF-KDOQI Guidelines. Available at

  • Agarwal R. Vitamin D, proteinuria, diabetic nephropathy, and progression of CKD. Clin J Am Soc Nephrol. 2009 Sep. 4(9):1523-8. [Medline].

  • de Zeeuw D, Agarwal R, Amdahl M, Audhya P, Coyne D, Garimella T, et al. Selective vitamin D receptor activation with paricalcitol for reduction of albuminuria in patients with type 2 diabetes (VITAL study): a randomised controlled trial. Lancet. 2010 Nov 6. 376(9752):1543-51. [Medline].

  • Wenzel RR, Littke T, Kuranoff S, Jürgens C, Bruck H, Ritz E, et al. Avosentan reduces albumin excretion in diabetics with macroalbuminuria. J Am Soc Nephrol. 2009 Mar. 20(3):655-64. [Medline]. [Full Text].

  • Suckling RJ, He FJ, Macgregor GA. Altered dietary salt intake for preventing and treating diabetic kidney disease. Cochrane Database Syst Rev. 2010 Dec 8. 12:CD006763. [Medline].

  • Daudon M, Jungers P. Diabetes and nephrolithiasis. Curr Diab Rep. 2007 Dec. 7 (6):443-8. [Medline].

  • Daudon M, Traxer O, Conort P, Lacour B, Jungers P. Type 2 diabetes increases the risk for uric acid stones. J Am Soc Nephrol. 2006 Jul. 17 (7):2026-33. [Medline]. [Full Text].

  • Zelnick LR, Weiss NS, Kestenbaum BR, et al. Diabetes and CKD in the United States Population, 2009-2014. Clin J Am Soc Nephrol. 2017 Dec 7. 12 (12):1984-90. [Medline].

  • Cheung CY, Ma MKM, Chak WL, Tang SCW. Cancer risk in patients with diabetic nephropathy: a retrospective cohort study in Hong Kong. Medicine (Baltimore). 2017 Sep. 96 (38):e8077. [Medline]. [Full Text].

  • Fan JZ, Wang R. Non-diabetic renal diseases in patients with type 2 diabetes: a single center study. Intern Med J. 2017 Dec 5. [Medline].

  • Ueno N. Urate-Lowering Therapy Ameliorates Kidney Function in Type 2 Diabetes Patients With Hyperuricemia. J Clin Med Res. 2017 Dec. 9 (12):1007-12. [Medline]. [Full Text].

    VOL. 18 NO. 3 Summer 2000


    Case Study: A 57-Year-Old Man With Type 2 Diabetes, Hypertension, and Microalbuminuria
    R.C. is a 57-year-old man with type 2 diabetes first diagnosed 2 years ago. Other medical problems include obesity and hypothyroidism. He has a history of heavy alcohol use but quit drinking alcohol 2 years ago. He presents now for routine follow-up and is noted to have a blood pressure of 168/100 mmHg. He is asymptomatic.

    Physical exam reveals a height of 5 feet, 8 inches, weight of 243 lb, blood pressure of 160/100 mmHg, and a regular pulse of 84 beats/min. There is no retinopathy or thyromegaly. There is no clinical evidence of congestive heart failure or peripheral vascular disease.

    Laboratory evaluation reveals trace protein on urinalysis, blood urea nitrogen of 14 mg/dl, serum creatinine of 1.2 mg/dl, random serum glucose of 169 mg/dl, normal electrolytes, and normal thyroid-stimulating hormone levels. A 24-h urine collection reveals a urinary albumin excretion rate of 250 mg/day.

    1. Does this patient have renal disease?
    2. Should his blood pressure be treated?
    3. What treatment strategy should be used?
    Diabetic nephropathy is a clinical syndrome characterized by albuminuria, hypertension, and progressive renal insufficiency. Diabetic nephropathy is the most common cause of end-stage renal disease (ESRD) in Western countries, accounting for ~35% of all new ESRD cases in the United States. The life expectancy of patients with diabetic ESRD is <50% at 3 years, despite improvements in dialysis and renal transplantation.

    Early detection and treatment of albuminuria is essential in diabetes. A normal urinary albumin excretion rate (UAER) ranges from 0 to 30 mg/day. Overt albuminuria or macroalbuminuria is defined as a UAER >300 mg/day. Many studies have shown that a UAER >30 mg/day is abnormal and can be used to predict the development of overt albuminuria or diabetic nephropathy and both microvascular and macrovascular disease. As a result, the term "microalbuminuria" was coined to refer to a UAER of 30–299 mg/day.

    Many organizations, including the American Diabetes Association, recommend regular screening for microalbuminuria. Type 1 diabetic patients should be screened 5 years after diagnosis of diabetes and after puberty. People with type 2 diabetes should be screened from the time of diagnosis, since many type 2 diabetic patients have had undiagnosed disease for some time. If the initial screening is negative, then annual screenings are indicated.

    Traditional urinary dipsticks are insensitive at detecting albuminuria <300 mg/day. Spot urine samples may be assayed for microalbuminuria and creatinine and a ratio >30 �g/mg or mg/g is abnormal. Newer methods, such as Micral-Test II test strips (Boehringer Mannheim, Mannheim, Germany), permit reliable semiquantitative determination of microalbuminuria and can be used in the office for dipstick screening of diabetic patients.

    Transient elevations in urinary albumin excretion may be associated with marked hyperglycemia, acute febrile illness, exercise, hypertension, heart failure, and urinary tract infection. If the initial test is elevated, these and other potential causes of renal disease should be considered and ruled out. Because there is also marked day-to-day variability in urinary albumin excretion, a positive test should be confirmed on a subsequent occasion before designating a patient as having persistent microalbuminuria.

    Patients identified with persistent microalbuminuria should be aggressively treated both with respect to glycemic and blood pressure control. Patients are considered to be hypertensive if their blood pressure is >140/90 mmHg. The goal for the management of hypertensive diabetic patients is to keep the blood pressure <130/85 mmHg.

    The treatment of choice for hypertensive diabetic patients with or without microalbuminuria remains angiotensin-converting enzyme (ACE) inhibitors. Only captopril (Capoten) is approved for the treatment of diabetic nephropathy, but all ACE inhibitors appear to be effective. Fosinopril (Monopril) has a dual route of elimination and therefore may have an advantage over other ACE inhibitors, particularly when used for patients with renal insufficiency or failure.

    Once started, renoprotective therapy should be continued indefinitely. ACE inhibitors have been shown to prevent or slow the progression from microalbuminuria to overt nephropathy. Studies have also shown that the renoprotective effects of ACE inhibitors go beyond those expected from blood pressure reduction by itself. Additionally, the renoprotective effects apply to both normotensive and hypertensive patients with microalbuminuria. Therefore, the indication for ACE inhibition can be persistent microalbuminuria, regardless of blood pressure. Discontinuing therapy will result in a recurrence of microalbuminuria.

    In addition to aggressively managing blood pressure, attempts need to be made toward lifestyle modifications. These include meticulous control of blood glucose, seeking counseling to stop smoking, maintaining optimal body weight, following an appropriate diet, and exercising regularly.

    Clinical Pearls
    1. Screen diabetic patients for microalbuminuria.
    2. Recognize hypertension in diabetic patients with a blood pressure >140/90 mmHg.
    3. ACE inhibition is the preferred treatment of microalbuminuria and/or hypertension.
    4. Counsel diabetic patients on lifestyle modifications, including blood glucose control, weight control, smoking cessation, diet, and exercise

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