History

Fact Explanation
Passage of foamy urine Due to abnormal, excessive urinary protein excretion which is found in diabetic nephropathy.[2,3]
Ankle swelling Due to hypoalbuminimia, if nephrotic syndrome is present.[2]
History of diabetic retinopathy Patient with diabetic retinopathy must investigate for diabetic nephropathy as it is found that these two conditions go in hand in hand.[1,2,3]
History of hypertension Co-existent hypertension with diabetes is a main risk factors for the development of diabetic nephropathy.[1,2,3]
Family history of diabetic nephropathy Since there is a genetic predisposition, positive family history is a risk factor for the development of diabetic nephropathy.[1,2]
Nationality of the patient Diabetic nephropathy is more prevalent among African Americans, Asians, and Native Americans than Caucasians.[1]
References
  1. GROSS L. Jorge, DE AZVEDO Mirela J., SILVEIRO Sandra P., CANANI et al. Diabetic Nephropathy: Diagnosis, Prevention, and Treatment. Diabetes Care.[online] January 2005 vol. 28 no. 1 164-176. [viewed 23.04.2014] Available from: doi: 10.2337/diacare.28.1.164 http://care.diabetesjournals.org/content/28/1/164.long
  2. EVANS C. Timothy, CAPBELL Peter. Diabetic Nephropathy. Clinical Diabetes.[online] 2000, vol.18 (1). [viewed 28.04.2014] Available from: http://journal.diabetes.org/clinicaldiabetes/v18n12000/Pg7.htm
  3. WATKINS P J. ABC of diabetes. clinical presentation: why is diabetes so often missed?.Br Med J (Clin Res Ed).[online] Jun 12, 1982; 284(6331): 1771–1772. [viewed 28.04.2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1498652/

Examination

Fact Explanation
Ankle oedema Due to hypoalbuminemia if there is nephrotic syndrome.[1,2]
Elevated blood pressure Usually there is associated hypertension in patients with diabetic nephropathy.[1,2]
Signs of peripheral vascular disease - absent or low volume peripheral pulses, carotid bruits Patients may have peripheral vascular disease as a cor-morbid disease.[1,2]
Signs suggestive of peripheral neuropathy - absent or diminished sensations, reflexes With long term poorly controlled diabetes, these patients are more likely to develop other complications of diabetes such as peripheral neuropathy. [1,2]
Non healing foot ulcers Long term poor glycemic control can give rise to non healing foot ulcers due to associated peripheral sensory neuropathy, peripheral vascular disease and defective healing process in diabetes. [1,2]
Ophthalmoscope examination - changes of diabetic retinopathy Diabetic nephropathy and retinopathy are related to each other, so in a patient with diabetic nephropathy retina should be examined for the changes of diabetic retinopathy.[1,2]
References
  1. WATKINS P J. ABC of diabetes. clinical presentation: why is diabetes so often missed?.Br Med J (Clin Res Ed).[online] Jun 12, 1982; 284(6331): 1771–1772. [viewed 28.04.2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1498652/
  2. ORIT PINHAS-HAMIEL, PhIL Zeitler. Clinical presentation and treatment of type 2 diabetes in children. Pediatric Diabetes.[online] Dec 2007 Vol 8,Suppl 9,16–27. [viewed 23.04.2014] Available from: DOI: 10.1111/j.1399-5448.2007.00330.x http://onlinelibrary.wiley.com/doi/10.1111/j.1399-5448.2007.00330.x/abstract;jsessionid=6F92CB6C55CFBD8272E68E52718B333E.f04t04

Differential Diagnoses

Fact Explanation
Urinary tract infection Increased passage of protein in urine can occur in a urinary tract infection also which is commonly found in diabetic patients. So it should be excluded.[1,2]
Lupus nephritis Consider in females with skin rashes, joint pain as it may indicate systemic lupus erythematosus.[1,3]
Kidney disease associated with HIV, hepatitis C, or hepatitis B Suspect in patients with risk factors such as IV drug users, health care workers.[1]
Kidney disease of any other etiology other than diabetes If there is a family history of kidney disease consider polycystic kidney disease or other genetic diseases. Suspect other causes of glomerulonephritis if there is history of proteinuria or hypertension during childhood or pregnancy.[1]
References
  1. GROSS L. Jorge, DE AZVEDO Mirela J., SILVEIRO Sandra P., CANANI et al. Diabetic Nephropathy: Diagnosis, Prevention, and Treatment. Diabetes Care.[online] January 2005 vol. 28 no. 1 164-176. [viewed 23.04.2014] Available from: doi: 10.2337/diacare.28.1.164 http://care.diabetesjournals.org/content/28/1/164.long
  2. GUIDO SCHMIEMANN, MPH, Eberhardt Kniehl, Eva Hummers-Pradie. The Diagnosis of Urinary tract infections. Dtsch Arztebl Int.[online] May 2010;107(21):361-367. [viewed 28.04.2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2883276/
  3. CHI CHIU MOK. Understanding Lupus Nephritis: Diagnosis, Management and Treatment options. Int J Womens Health.[online] 2012;4: 213-222. [viewed 23.04.2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3367406/

Investigations - for Diagnosis

Fact Explanation
24 hour urinary protein excretion Diabetic nephropathy defined by the presence of proteinuria >0.5 g/24 hours.[1]
Albumin level in a spot urine sample Expression can be either urinary albumin concentration (mg/l) or urinary albumin - creatinine ratio (mg/g or mg/mmol). The cutoff value of 17 mg/l in a random urine specimen had a sensitivity of 100% and a specificity of 80% for the diagnosis of microalbuminuria in diabetic nephropathy.[1]
Glomerular Filtration Rate (GFR) GFR should be done to assess the renal function.[1]
Renal Biopsy Diabetes causes unique changes in kidney structure but renal biopsy is only recommended in special situations. Patients with type 1 diabetes who present with proteinuria in association with short diabetes duration and/or rapid decline of renal function, especially in the absence of diabetic retinopathy and In type 2 diabetic patients with unexplained hematuria.[1]
References
  1. GROSS L. Jorge, DE AZVEDO Mirela J., SILVEIRO Sandra P., CANANI et al. Diabetic Nephropathy: Diagnosis, Prevention, and Treatment. Diabetes Care.[online] January 2005 vol. 28 no. 1 164-176. [viewed 23.04.2014] Available from: doi: 10.2337/diacare.28.1.164 http://care.diabetesjournals.org/content/28/1/164.long

Investigations - Followup

Fact Explanation
Glomerular Filtration Rate (GFR) GFR is the best indicator of kidney function and should be measured/estimated in patients with diabetic nephropathy to assess the renal function.[1]
Urine albumin level Should be checked monthly during the first 2–3 months after starting treatment with ACE inhibitors or ARBs. [1]
Serum creatinine Should be checked monthly during the first 2–3 months after starting treatment with ACE inhibitors or ARBs.[1]
Serum pattasium Should be checked monthly during the first 2–3 months after starting treatment with ACE inhibitors or ARBs.[1]
24-hours ambulatory blood pressure monitoring To assess the blood pressure treatment in patients with treatment-resistant hypertension, when suspecting white coat hypertension, or to identify drug-induced or autonomic neuropathy–related hypotensive episodes. [1]
Glycosylated hemoglobin leavel (HbA1c) To assess the glycemic control.[1]
References
  1. GROSS L. Jorge, DE AZVEDO Mirela J., SILVEIRO Sandra P., CANANI et al. Diabetic Nephropathy: Diagnosis, Prevention, and Treatment. Diabetes Care.[online] January 2005 vol. 28 no. 1 164-176. [viewed 23.04.2014] Available from: doi: 10.2337/diacare.28.1.164 http://care.diabetesjournals.org/content/28/1/164.long

Investigations - Screening/Staging

Fact Explanation
Microalbuminuria In patients with type 2 diabetes it should be done at the time of diagnosis of diabetes and yearly thereafter and in type 1 diabetics it should be done annually, starting 5 years after diagnosis in type 1 diabetes or earlier in the presence of puberty or poor glycemic control.[1,2]
Semiquantitative dipstick measurements of albuminuria such as Micral Test II In situations where specific urinary albumin excretion measurements are not available this test can be used.[1]
Serum creatinine Should be measured at least annually to estimate glomerular filtration rate (GFR) in all with diabetes regardless of the results of urine albumin excretion.[2]
References
  1. GROSS L. Jorge, DE AZVEDO Mirela J., SILVEIRO Sandra P., CANANI et al. Diabetic Nephropathy: Diagnosis, Prevention, and Treatment. Diabetes Care.[online] January 2005 vol. 28 no. 1 164-176. [viewed 23.04.2014] Available from: doi: 10.2337/diacare.28.1.164 http://care.diabetesjournals.org/content/28/1/164.long
  2. American Diabetes Association (2006) Standards of medical care in diabetes - 2006. Diabetes Care.[online] 2006. 29(Suppl 1), 54-542. [viewed 23.04.2014] Available from: http://care.diabetesjournals.org/content/29/suppl_1/s4.full

Management - General Measures

Fact Explanation
Patient and family education Patient and the family members should educate about the disease process, available treatment options, importance of compliance and family support to the patient to adhere to the health life style changes.[1]
Diet Diet should contain moderate amount of protein and little fat. Chicken is preferred than red meat as there is higher proportion of polyunsaturated fat and lower amount of saturated fat in chicken compared to red meat.[1,2]
Anemia management Anemia found in patients with diabetic nephropatht is due to erythropoietin deficiency. And also it is a risk factor for progression of nephropathy and retinopathy. Therefore erythropoietin treatment should start when Hb levels are <11 g/dl. The target Hb level is 12–13 g/dl. Note: There is a risk of hypertension with erythropoietin treatment.[1]
Low dose aspirin (100 mg/day) To prevent the cardiovascular events in adults with diabetes. Aspirin therapy do not deteriorate renal functions.[1]
Smoking cessation It is important to slower the disease progression.[1]
Excercise Light - moderate exercise programme should be implemented at least 3 - 5 days per week.[1]
References
  1. GROSS L. Jorge, DE AZVEDO Mirela J., SILVEIRO Sandra P., CANANI et al. Diabetic Nephropathy: Diagnosis, Prevention, and Treatment. Diabetes Care.[online] January 2005 vol. 28 no. 1 164-176. [viewed 23.04.2014] Available from: doi: 10.2337/diacare.28.1.164 http://care.diabetesjournals.org/content/28/1/164.long
  2. American Diabetes Association (2006) Standards of medical care in diabetes - 2006. Diabetes Care.[online] 2006. 29(Suppl 1), 54-542. [viewed 23.04.2014] Available from: http://care.diabetesjournals.org/content/29/suppl_1/s4.full

Management - Specific Treatments

Fact Explanation
Tight glycemic control The effect of tight control of blood glucose levels on the progression from micro- to macroalbuminuria and on the deterioration rate of renal function in macroalbuminuric patients is still controversial. Oral hypoglycemics: Since there is a increased risk of lactic acidosis metformin should not be used when serum creatinine is >1.5 mg/dl in men and >1.4 mg/dl in women. Sulfonylureas, eliminated via renal excretion should not be used in patients with decreased renal function. Repaglinide and nateglinide are preferred as both have a short half life and are excreted independently of renal function, and have a safety profile in patients with renal impairment. Insulin: Not only type 1 diabetics most type 2 diabetic patients with diabetic nephropathy will require insulin therapy.[1]
Management of hypertension Antihypertensive therapy improves albuminuria, irrespective of the drug used. The blood pressure goal is 125/75 mmHg in patients with proteinuria >1.0 g/24 hours and increased serum creatinine. Usually to achieve the target 3-4 antihypertensive agents are necessary. The combination of ACE inhibitors and ARBs has a synergistic effect in blood pressure and urinary albumin excretion reduction in patients with diabetic nephropathy. [1,4]
ACE (Angiotensin Converting Enzyme) inhibitors/ ARBs (Angiotensin Receptor Blockers) Effect of these drugs may be related to decreased intraglomerular pressure and passage of proteins into the proximal tubule which inturn decrease urinary albumin excretion and the rate of progression from microalbuminuria to more advanced stages of diabetic nephropathy. The use of either ACE inhibitors or ARBs is recommended as a first-line therapy for diabetic patients with microalbuminuria, even if they are normotensive. Note: The use of these drugs in patients with critical renal-artery stenosis could reduce transcapillary filtration pressure, leading to acute or chronic renal insufficiency. Also should not be used in pregnancy. [1,2,3,4]
Treat dyslipidemia All diabetic patients should be on statins. The goal for LDL cholesterol is <100 mg/dl for diabetic patients in general and <70 mg/dl for diabetic patients with cardiovascular disease. The effect of lipid reduction by antilipemic agents on progression of diabetic nephropathy is still unknown.[1,4]
Evaluate for associated other complications of diabetes Patients should be assessed for diabetic retinopathy, neuropathy, cardiovascular complications including peripheral vascular disease.[1]
Prevention - normoalbuminuric diabetic patients Optimize the treatment of the risk factors such as hypertension, hyperglycemia and dyslipidemia. Consider stopping smoking.[1,2]
Newer drugs Newer drugs such as ALT-711( a cross-link breaker of the advanced glycation end products), ruboxistaurin (a protein kinase C β inhibitor), Sulodexide (a glycosaminoglycan) and Pimagedine (a second-generation inhibitor of advanced glycation end products) also have the potential to improve the disease progression in diabetic nephropathy.[1]
End Stage Kidney Disease management Patients should be given renal replacement therapy either kidney transplantation or regular dialysis.[2,4]
References
  1. GROSS L. Jorge, DE AZVEDO Mirela J., SILVEIRO Sandra P., CANANI et al. Diabetic Nephropathy: Diagnosis, Prevention, and Treatment. Diabetes Care.[online] January 2005 vol. 28 no. 1 164-176. [viewed 23.04.2014] Available from: doi: 10.2337/diacare.28.1.164 http://care.diabetesjournals.org/content/28/1/164.long
  2. American Diabetes Association (2006) Standards of medical care in diabetes - 2006. Diabetes Care.[online] 2006. 29(Suppl 1), 54-542. [viewed 23.04.2014] Available from: http://care.diabetesjournals.org/content/29/suppl_1/s4.full
  3. BARNETT A.H, BAIN S.C., BOUTER P. et al.Angiotensin-receptor blockade versus converting-enzyme inhibition in type 2 diabetes and nephropathy. New England Journal of Medicine.[online] 2004. 351(19), 1952-1961. [viewed 23.04.2014] Available from:http://www.nejm.org/doi/full/10.1056/NEJMoa042274
  4. CRAIG KJ, Donovan K, Munnery M, Owens DR,et al. Identification and management of diabetic nephropathy in the diabetes clinic. Diabetes Care.[online] 2003,vol.26:1806–1811. [viewed 23.04.2014] Available from: http://care.diabetesjournals.org/content/26/6/1806.long