Endocrinology Book

Diabetes Mellitus

  • Diabetic Nephropathy

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Diabetic Nephropathy

Aka: Diabetic Nephropathy, Nephropathy of Diabetes Mellitus, Diabetic Kidney Disease, ACE Inhibitors and ARBs in Diabetic Nephropathy
  1. See Also
    1. Diabetes Mellitus
    2. Prevention of Kidney Disease Progression
    3. Coronary Artery Disease Prevention in Diabetes
    4. Acute Kidney Injury
    5. Intravenous Contrast Related Acute Renal Failure
    6. Drug Dosing in Chronic Kidney Disease
    7. Nephrotoxic Drugs
    8. Renal Osteodystrophy
    9. Risk Score for Prediction of Contrast-Induced Nephropathy After Percutaneous Coronary Intervention
    10. Hypertension in Diabetes Mellitus
    11. Hyperlipidemia in Diabetes Mellitus
    12. Antiplatelet Management in Diabetes Mellitus
  2. Epidemiology
    1. Urine Microalbuminuria and Macroalbuminuria
      1. Prevalence in Diabetes Mellitus: 35%
    2. Stage 2-3 Chronic Kidney Disease in Diabetes Mellitus
      1. Stage 2-3 CKD Prevalence: 29% of those with Diabetes (2010)
    3. Stage 4-5 Chronic Kidney Disease (ESRD) in Diabetes Mellitus
      1. Diabetes Mellitus accounts for 44% of all new cases of ESRD in United States (2008)
      2. Prevalence: Over 200,000 cases of ESRD in Diabetes Mellitus in United States (2008)
      3. Incidence: Approximately 48,000 new cases of Diabetes related ESRD annually in United States (2008)
  3. Risk Factors: Microlbuminuria
    1. Hypertension
    2. Higher average Serum Glucose
    3. Hyperlipidemia
    4. Tobacco abuse
    5. Type II Diabetes Mellitus
      1. Even more than Type I Diabetes Mellitus
    6. Ethnic groups with higher risk of developing Microalbuminuria
      1. Native american
      2. Asian
      3. Hispanic
      4. Black
  4. Precaution
    1. Worsening Renal Function may present with sudden improvement in glycemic control or Hypoglycemia
  5. Pathophysiology: Nephropathy progression
    1. Step 1: Incipient Nephropathy phase
      1. Microalbuminuria (low levels of albumin) present
      2. Urine Albumin levels gradually rise during this phase
    2. Step 2: Overt Nephropathy phase
      1. Urine Albumin >300 mg/24 hours
      2. Hyperfiltration transiently occurs
        1. Glomerular filtration (Creatinine Clearance) rises
    3. Step 3: Renal Insufficiency
      1. Glomerular filtration (Creatinine Clearance) falls
      2. Ultimately Renal Failure ensues
  6. Protocol: Monitoring
    1. Initiating monitoring
      1. Type I Diabetes Mellitus: 5 years after diagnosis
      2. Type II Diabetes Mellitus: Start at time of diagnosis
    2. Labs
      1. Spot Urine Albumin to Creatinine Ratio (random Urine Microalbumin)
        1. Obtain every 6-12 months
      2. Serum Creatinine with estimated GFR
        1. Obtain every 6-12 months
  7. Labs: Urine Microalbumin
    1. See Urine Microalbumin (Urine Albumin to Creatinine Ratio) for diagnostic criteria
    2. Nephropathy diagnosis needs 2 of 3 samples positive
    3. Spot Urine Albumin to Creatinine Ratio (first morning void preferred)
      1. Microalbuminuria: 30-300 mcg/mg Creatinine
      2. Macroalbuminuria: >300 mcg/mg Creatinine
  8. Imaging: Renal Ultrasound
    1. Evaluation for reversible causes of Kidney disease
    2. Indications
      1. New onset Chronic Kidney Disease
      2. New onset Microalbuminuria or Macroalbuminuria
  9. Diagnostics: Biopsy
    1. Indications: Unclear diagnosis (see precautions below)
    2. Findings suggestive of classic Diabetic Nephropathy
      1. Light microscopy
        1. Glomerular sclerosis
        2. Nodular mesangial expansion and proliferation (Kimmelstiel-Wilson Nodules)
      2. Electron microscopy
        1. Glomerular basement membrane thickening
  10. Management: General
    1. See Chronic Kidney Disease
    2. See Prevention of Kidney Disease Progression
    3. Avoid Nephrotoxins (e.g. NSAIDs)
    4. Most important modifiable factors (see below)
      1. Diabetes Mellitus glycemic control
      2. Hypertension Control
    5. Other modifiable factors
      1. Hyperlipidemia
  11. Management: Diabetes Mellitus
    1. Tight glycemic control is critical to reduce risk of progression in Diabetic Nephropathy
      1. Keep Hemoglobin A1C <7%
      2. Better glycemic control reduces nephropathy risk
      3. Microalbuminuria risk with Hemoglobin A1C > 8.1%
      4. Precaution: ACCORD Study found higher overall mortality with intensive glycemic control in Type II Diabetes
        1. Gerstein (2008) N Engl J Med 358(24): 2545-59 [PubMed]
    2. References
      1. Krolewski (1995) N Engl J Med 332(19):1251-5 [PubMed]
      2. (2011) Diabetes Care 34(Suppl 1): S4-S10 [PubMed]
  12. Management: Hypertension
    1. Hypertension goals
      1. Keep Blood Pressure under 130/80
      2. Isolated Systolic Hypertension goals
        1. Keep Systolic Blood Pressure under 140
      3. Avoid overaggressive Blood Pressure lowering to systolic Blood Pressure below 120 mmHg
        1. Associated with more adverse events (e.g. Hypotension, Bradycardia, Azotemia)
        2. Cushman (2010) N Engl J Med 362(17): 1575-85 [PubMed]
    2. First-line Antihypertensives: ACE Inhibitors and ARBs
      1. ACE Inhibitors and ARBs are preferred first-line agents for Hypertension and Proteinuria
        1. Best evidence is for Macroalbuminuria, in which case these agents are indicated even without Hypertension
        2. However evidence does not support ACE Inhibitor use for Microalbuminuria without Hypertension
          1. Microalbuminuria alone is not a good marker for renal disease
          2. (2012) Prescr Lett 19(4): 24
        3. Do not use ACE Inhibitors in combination with Angiotensin Receptor Blockers
          1. Higher rate of progression to ESRD
          2. Mann (2008) Lancet 372(9638): 547-53 [PubMed]
        4. Recent trials suggest ACE Inhibitors and ARBs are equivalent in renal outcomes
          1. Mann (2008) Lancet 372(9638): 547-53 [PubMed]
          2. Lewis (2001) N Engl J Med 345:851-60 [PubMed]
        5. All-cause mortality is reduced with ACE Inhibitors, but not with Angiotensin Receptor Blockers
          1. Strippoli (2004) BMJ 329(7470): 828 [PubMed]
        6. Indications to stop ACE Inhibitors or Angiotensin Receptor Blockers
          1. Serum Creatinine rises 30% or more above baseline in first 2 months of starting medication or
          2. Hyperkalemia persists with Serum Potassium >5.6 mEq/L
      2. Agents
        1. ACE Inhibitors (preferred - see above)
        2. Angiotensin Receptor Blockers (ARB)
    3. Second-line Antihypertensives
      1. Thiazide Diuretics (especially in combination with ACE Inhibitors or ARB agents above)
        1. Hydrochlorothiazide
        2. Chlorthalidone
        3. Bakris (2008) Kidney Int 73(11); 1303-9 [PubMed]
      2. Calcium Channel Blockers
        1. Renal protection
          1. Calcium Channel Blockers in general appear to be effective in maintaining Renal Function
          2. Segura (2005) JASN 16(3):S64-6 [PubMed]
        2. Proteinuria
          1. Non-Dihydropyridine Calcium Channel Blockers (e.g. Verapamil, Diltiazem)
            1. Reduce Proteinuria (less than ACE Inhibitor)
          2. Dihydropyridine Calcium Channel Blockers (mixed results)
            1. Amlodipine appears to also reduce Microalbuminuria
              1. Bakris (2008) Kidney Int 73(11); 1303-9 [PubMed]
            2. Nifedipine may increase Proteinuria
  13. Management: Dietary changes (incomplete evidence)
    1. Dietary modification: CR-LIPE
      1. Better than protein restriction in retarding CRI
      2. Components
        1. 50% carbohydrate restricted (CR)
        2. Low Iron available (LI)
        3. Polyphenol enriched (PE)
      3. References
        1. Facchini (2003) Diabetes 52:1204-9 [PubMed]
    2. Protein restriction
      1. Efficacy
        1. Decreases Microalbuminuria
        2. Decreases progression to Macroalbuminuria
      2. Protocol
        1. Near Normal GFR: <0.8g/kg/day Protein
        2. Falling GFR: <0.6g/kg/day Protein
  14. Management: Referral to Nephrology Indications
    1. Serum Creatinine over 2.0 mg/dl
    2. Glomerular Filtration Rate (GFR) less than 70 ml/min
  15. Precautions: Findings that suggest cause other than typical Diabetic Nephropathy
    1. See Proteinuria Causes
    2. Albuminuria absent despite stage 3-5 CKD
    3. Diabetic Retinopathy absent despite Diabetic Nephropathy
    4. Active urinary sediment (red cells or casts accompany Proteinuria)
    5. Low GFR estimated at the time of initial diagnosis
    6. GFR reduced >30% within 3 months of starting ACE Inhibitor or Angiotensin Receptor Blocker (ARB)
    7. GFR decreases rapidly (4 ml/min/year)
    8. Proteinuria increases rapidly (or Nephrotic Syndrome)
    9. Refractory Hypertension
    10. (2007) Am J Kidney Dis 49(suppl 2): S12-S154 [PubMed]
  16. Prognosis
    1. Dialysis usually needed when GFR reaches 10 ml/min
    2. Onset of Proteinuria after diagnosis of Diabetes Mellitus
      1. Microalbuminuria develops in 2.0% of patients with diabetes per year
      2. Macroalbuminuria develops in 2.8% of diabetic patients with Microalbuminuria per year
      3. Increased Serum Creatinine develops in 2.3% of diabetic patients with Macroalbuminuria per year
      4. Adler (2003) Kidney Int 63(1): 225-32 [PubMed]
    3. GFR decline after onset Microalbuminuria
      1. No ACE Inhibitor: 10 ml/min/year
      2. ACE Inhibitor: 4-6 ml/min/year
      3. Blood Pressure <130/80: 1-4 ml/min/year
  17. Complications
    1. Microalbuminuria (and Macroalbuminuria) are associated with an increased cardiovascular mortality and overall mortality
  18. References
    1. Molitch (1997) Am J Med 102:392-8 [PubMed]
    2. Cooper (1998) Lancet 352:213-9 [PubMed]
    3. Thorp (2005) Am Fam Physician 72:96-99 [PubMed]
    4. Roett (2012) Am Fam Physician 85(9): 883-9 [PubMed]

Diabetic Nephropathy (C0011881)

Definition (MEDLINEPLUS)

If you have diabetes, your blood glucose, or blood sugar, levels are too high. Over time, this can damage your kidneys. Your kidneys clean your blood. If they are damaged, waste and fluids build up in your blood instead of leaving your body.

Kidney damage from diabetes is called diabetic nephropathy. It begins long before you have symptoms. An early sign of it is small amounts of protein in your urine. A urine test can detect it. A blood test can also help determine how well your kidneys are working.

If the damage continues, your kidneys could fail. In fact, diabetes is the most common cause of kidney failure in the United States. People with kidney failure need either dialysis or a kidney transplant.

You can slow down kidney damage or keep it from getting worse. Controlling your blood sugar and blood pressure, taking your medicines and not eating too much protein can help.

NIH: National Institute of Diabetes and Digestive and Kidney Diseases

Definition (NCI) Progressive kidney disorder caused by vascular damage to the glomerular capillaries, in patients with diabetes mellitus. It is usually manifested with nephritic syndrome and glomerulosclerosis.
Definition (MSH) KIDNEY injuries associated with diabetes mellitus and affecting KIDNEY GLOMERULUS; ARTERIOLES; KIDNEY TUBULES; and the interstitium. Clinical signs include persistent PROTEINURIA, from microalbuminuria progressing to ALBUMINURIA of greater than 300 mg/24 h, leading to reduced GLOMERULAR FILTRATION RATE and END-STAGE RENAL DISEASE.
Definition (CSP) kidney disease and resultant kidney function impairment due to the long standing effects of diabetes on the microvasculature (glomerulus) of the kidney; features include increased urine protein and declining kidney function.
Concepts Disease or Syndrome (T047)
MSH D003928
ICD9 250.4
SnomedCT 127013003, 267470000, 21858001, 190338009, 60009009
LNC LA10570-2
English Diabetic Nephropathies, Nephropathies, Diabetic, Diabetes with renal manifestations, DIABETIC NEPHROPATHY, Nephropathy, Diabetic, Renal disorder associated with diabetes mellitus, diabetic nephropathy, diabetic nephropathy (diagnosis), Diabetic nephropathy NOS, Diabetic Nephropathies [Disease/Finding], Nephropathy;diabetic, diabetic nephropathies, nephropathy diabetic, diabetic renal disease, diabetes with renal manifestations (diagnosis), diabetes with renal manifestations, Diabetic Kidney Problems, Diabetes + nephropathy, Diabetes with renal manifestations (disorder), Nephropathy - diabetic, Diabetic nephropathies, -- Diabetic Kidney Disease, Diabetic nephropathy, Diabetic renal disease, Diabetic renal disease (disorder), diabetes; nephropathy (manifestation), nephropathy; diabetes (manifestation), Diabetic Nephropathy, Diabetic Kidney Diseases, Diabetic Kidney Disease, Kidney Disease, Diabetic, Kidney Diseases, Diabetic
Spanish trastorno renal asociado con diabetes mellitus, Nefropatía diabética NEOM, Enfermedad renal diabética, Diabetes con manifestaciones renales, diabetes con manifestaciones renales (trastorno), diabetes con manifestaciones renales, enfermedad renal diabética, nefropatía diabética (trastorno), nefropatía diabética, Nefropatía diabética, Nefropatías Diabéticas
Dutch diabetische nierziekte, diabetische nefropathie NAO, diabetes met renale manifestaties, diabetes; nefropathie, nefropathie; diabetes, diabetische nefropathie, Diabetische nefropathie, Nefropathie, diabetische, Diabetische nefropathieën, Nefropathieën, diabetische
French Diabète avec manifestations rénales, Néphropathie diabétique SAI, Néphropathie diabétique, Néphropathies diabétiques, Maladie rénale diabétique
German diabetische Nierenerkrankung, Diabetes mit renalen Manifestationen, diabetische Nephropathie NNB, diabetische Nephropathie, Diabetische Nephropathien
Italian Nefropatia diabetica NAS, Diabete con manifestazioni renali, Nefropatia diabetica, Nefropatie diabetiche
Portuguese Nefropatia diabética NE, Doença renal diabética, Diabetes com manifestações renais, Glomeruloesclerose Diabética, Nefropatia diabética, Nefropatias Diabéticas
Japanese 糖尿病性腎症NOS, 腎症状をともなう糖尿病, トウニョウビョウセイジンショウNOS, ジンショウジョウヲトモナウトウニョウビョウ, トウニョウビョウセイジンショウ, 糖尿病性ネフロパシー, 糖尿病性腎障害, 糖尿病ネフロパシー, 糖尿病腎症, 糖尿病性腎症
Swedish Diabetiska njursjukdomar
Czech diabetické nefropatie, Diabetická nefropatie, Diabetes mellitus s postižením ledvin, Diabetická nefropatie NOS, diabetické onemocnění ledvin, diabetická nefropatie
Finnish Diabeettiset nefropatiat
Russian GLOMERULOSKLEROZ DIABETICHESKII, GLOMERULOSKLEROZ INTERKAPILLIARNYI, DIABETICHESKIE NEFROPATII, ГЛОМЕРУЛОСКЛЕРОЗ ДИАБЕТИЧЕСКИЙ, ГЛОМЕРУЛОСКЛЕРОЗ ИНТЕРКАПИЛЛЯРНЫЙ, ДИАБЕТИЧЕСКИЕ НЕФРОПАТИИ
Croatian DIJABETIČNE NEFROPATIJE
Polish Nefropatie cukrzycowe, Nefropatia cukrzycowa, Cukrzycowa choroba nerek, Cukrzycowe choroby nerek
Hungarian diabeteses vesebetegség, Diabetes veseérintettséggel, diabeteses nephropathia k.m.n., diabeteses nephropathia
Norwegian Diabetisk nefropati, Nyresykdommer ved diabetes
Sources
Derived from the NIH UMLS (Unified Medical Language System)


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