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Is It Diabetic Nephropathy? (When to Biopsy?)
Mohammed Abdel Gawad Nephrology Specialist
Kidney & Urology Center (KUC)- Alexandria
IMPORTANT MESSAGE
• Renal diseases in diabetic patients are NOT ALWAYS due to diabetic nephropathy and
even it may not be due to DM.
Hematuria Proteinuria Rising creatinine Others
Renal & Urological Problems that may be presented in Diabetics
Papillary necrosis
- Ischemic nephropathy due to
microvascular disease - Renal artery stenosis
Diabetic glomerulopathy (diabetic nephropathy)
Autonomic neuropathy of the bladder
UTI Any other glomerular disease
not related to DM
- Drug induced - Other ppt factors for AKI
When to suspect other cause rather than DN?
Is it DN?
When to biopsy?
Is it Diabetic Nephropathy? You have to answer the following
1. What is the type of DM? 2. Is there an evidence of Diabetic retinopathy? 3. Proteinuria:
a. Is the evolution of proteinuria is typical (micro then macro)? b. Is the range of proteinuria coincides with DN stage? c. What is the rate of proteinuria progression?
4. Hematuria: Is it microscopic or macroscopic? 5. Rising Cr and decreasing GFR:
a. Is it related to proteinuria? b. What is the rate of renal impairment progression?
6. Hypertension: refractory or not? 7. What is the drug history? 8. Is there any ppt factor for AKI?
Diabetic Nephropathy & Diabetic Retinopathy Type 1 DM
Mogensen CE. Diabetes. 1997;56(Suppl 2):104-111.
Diabetic Nephropathy & Diabetic Retinopathy Type 1 DM
Pre (1 &2)
Incipient (3) (microalbuminuria
& HTN)
Overt (4) (proteinuria,
nephrotic syndrome and decreasing GFR)
ESRD (5)
At 5 years from onset of DM type 1, nephropathy coincides with
retinopathy
So if nephropathy is evident in absence of retinopathy in Type 1 DM
Search for other cause of nephropathy rather that DM ±
Renal Biopsy (especially if there is S&S of
other systemic disease)
Diabetic retinopathy is present in virtually all patients with type 1 diabetes and
nephropathy *
* Girach A, Vignati L. Diabetic microvascular complications. J Diabetes Complications. 2006;20:228-237.
5y 15y 25y
Diabetic Nephropathy & Diabetic Retinopathy Type 2 DM
± Renal Biopsy
Only 50% to 60% of proteinuric patients with type 2 diabetes suffer from retinopathy. **
Consequently, the absence of retinopathy does not exclude
the diagnosis of DN in patients with type 2 diabetes.
*
In type 2 DM the prevalence of nondiabetic renal disease could
vary from 12 to 38% ***
When to suspect other cause****? 1- Younger patients with DM 2- Short duration of DM 3- Atypical presentation (atypical proteinuria or hematuria, rapid rising Cr ….. etc) or other ppt factors (discussed later)
When to suspect other
cause?
* GIUSEPPE REMUZZI et al. N Engl J Med, Vol. 346, No. 15· April 11, 2002
*** Huang F et al. Clin ephrol 2007, 67: 293-297.
**** Pham TT et al. Am J Nephrol. 2007;27:322-328.
** Wolf G, Müller N, Mandecka A, Müller UA. Clin Nephrol. 2007;68:81-86.
Is Fluorescein Angiography Safe in Diabetics with Renal Impairment?
DIABETES CARE, VOLUME 32, NUMBER 3, MARCH 2009
Is Fluorescein Angiography Safe in Diabetics with Renal Impairment?
M.J. ALEMZADEH-ANSARI ET AL. Nefrologia 2011;31(5):612-3
Is it Diabetic Nephropathy? You have to answer the following
1. What is the type of DM? 2. Is there an evidence of Diabetic retinopathy? 3. Proteinuria:
a. Is the evolution of proteinuria is typical (micro then macro)? b. Is the range of proteinuria coincides with DN stage? c. What is the rate of proteinuria progression?
4. Hematuria: Is it microscopic or macroscopic? 5. Rising Cr and decreasing GFR:
a. Is it related to proteinuria? b. What is the rate of renal impairment progression?
6. Hypertension: refractory or not? 7. What is the drug history? 8. Is there any ppt factor for AKI?
Diabetic Nephropathy & Proteinuria
Pre (1 &2)
Incipient (3) (microalbuminuria
& HTN)
Overt (4) (proteinuria,
nephrotic syndrome and decreasing GFR)
ESRD (5)
If evolution of proteinuria is atypical: development of overt proteinuria without
previous microalbuminuria.
Search for other cause of nephropathy rather that DM ± Renal Biopsy
(especially if there is S&S of other systemic disease)
If the onset of proteinuria has
been sudden and rapid
10-15 years
Overt proteinuria in diabetes type 1
for <10 years
Rate of proteinuria progression is slow
5y 15y 25y
DN without Albuminuria Ischemic Nephropathy – Type 2 DM
• Renal ultrasound reveals small kidneys.
• Raised Serum Cr after administration of ACE-i
• Without albuminuria
Jamine P. Dwyer et al. DEMAND study. Cardiorenal Med, 2012;2:1-10
HYPERperfusion/ Hyperfiltration
↑
Intraglomerular Pressure
Hyperglycemia
Proteinuria
Angiotensin II
HYPOperfusion/ Ischemia
↓
Intraglomerular Pressure
Atherosclerosis
J Am Soc Nephrol. 2003;14:3217-3232
Jamine P. Dwyer et al. DEMAND study. Cardiorenal Med, 2012;2:1-10
• MARK E. MOLITCH. Diabetes Care 33:1536–1543, 2010 •Also same results are reported in:
•Caramori ML et al. Diabetes 52:1036-1040, 2003.
•Lane PH et al. Diabetes 41:581-586, 1992
•MacIsaac RJ et al. Diabetes Care 27:195-200,2004
DN without Albuminuria - Type 1 DM
Is it Diabetic Nephropathy? You have to answer the following
1. What is the type of DM? 2. Is there an evidence of Diabetic retinopathy? 3. Proteinuria:
a. Is the evolution of proteinuria is typical (micro then macro)? b. Is the range of proteinuria coincides with DN stage? c. What is the rate of proteinuria progression?
4. Hematuria: Is it microscopic or macroscopic? 5. Rising Cr and decreasing GFR:
a. Is it related to proteinuria? b. What is the rate of renal impairment progression?
6. Hypertension: refractory or not? 7. What is the drug history? 8. Is there any ppt factor for AKI?
Diabetic Nephropathy & Hematuria Is it Micro or Macroscopic?
Hematuira in diabetic patient
Microscopic hematuria is seen in 66% of patients with
DN *
Macroscopic hematuria
±
active nephritic urinary sediment (acanthocytes and red cell casts)
Search for other cause of nephropathy rather that DM ± Renal Biopsy
(especially if there is S&S of other systemic disease)
* Akimoto T, Ito C, Saito O, et al. Nephron Clin Pract. 2008; 109:c119-c126.
** Lopes de Faria et al. Clin Nephrol. 1988;30(3):117
Red blood cell casts have also been described in patients with diabetic
nephropathy **
Is it Diabetic Nephropathy? You have to answer the following
1. What is the type of DM? 2. Is there an evidence of Diabetic retinopathy? 3. Proteinuria:
a. Is the evolution of proteinuria is typical (micro then macro)? b. Is the range of proteinuria coincides with DN stage? c. What is the rate of proteinuria progression?
4. Hematuria: Is it microscopic or macroscopic? 5. Rising Cr and decreasing GFR:
a. Is it related to proteinuria? b. What is the rate of renal impairment progression?
6. Hypertension: refractory or not? 7. What is the drug history? 8. Is there any ppt factor for AKI?
Diabetic Nephropathy & Renal Impairment
Pre (1 &2)
Incipient (3) (microalbuminuria
& HTN)
Overt (4) (proteinuria,
nephrotic syndrome and decreasing GFR)
ESRD (5)
Search for other cause
If renal impairment is rapid
Significant proteinuria without/with non coinciding renal impairment
first, of course, renovascular disease must be excluded
other cause of nephropathy rather that DM ± Renal Biopsy
(especially if there is S&S of other systemic disease)
Rate of renal impairment
progression is slow
5y 15y 25y
Is it Diabetic Nephropathy? You have to answer the following
1. What is the type of DM? 2. Is there an evidence of Diabetic retinopathy? 3. Proteinuria:
a. Is the evolution of proteinuria is typical (micro then macro)? b. Is the range of proteinuria coincides with DN stage? c. What is the rate of proteinuria progression?
4. Hematuria: Is it microscopic or macroscopic? 5. Rising Cr and decreasing GFR:
a. Is it related to proteinuria? b. What is the rate of renal impairment progression?
6. Hypertension: refractory or not? 7. What is the drug history? 8. Is there any ppt factor for AKI?
Diabetic Nephropathy & Refractory HTN
Refractory hypertension (and fluid retention) in diabetic patients is highly
suggestive for renovascular disease
Is it Diabetic Nephropathy? You have to answer the following
1. What is the type of DM? 2. Is there an evidence of Diabetic retinopathy? 3. Proteinuria:
a. Is the evolution of proteinuria is typical (micro then macro)? b. Is the range of proteinuria coincides with DN stage? c. What is the rate of proteinuria progression?
4. Hematuria: Is it microscopic or macroscopic? 5. Rising Cr and decreasing GFR:
a. Is it related to proteinuria? b. What is the rate of renal impairment progression?
6. Hypertension: refractory or not? 7. What is the drug history? 8. Is there any ppt factor for AKI?
Diabetic Nephropathy & Drugs
ACEi & ARBs
> 30% reduction in GFR within 2-3 months after
initiation
Suspect renovascular disease
Diabetic Nephropathy & Drugs
Contrast NSAIDs
Diabetics kidneys are at high risk to be affected by nephrotoxic drugs
Any other nephrotoxic drug
Is it Diabetic Nephropathy? You have to answer the following
1. What is the type of DM? 2. Is there an evidence of Diabetic retinopathy? 3. Proteinuria:
a. Is the evolution of proteinuria is typical (micro then macro)? b. Is the range of proteinuria coincides with DN stage? c. What is the rate of proteinuria progression?
4. Hematuria: Is it microscopic or macroscopic? 5. Rising Cr and decreasing GFR:
a. Is it related to proteinuria? b. What is the rate of renal impairment progression?
6. Hypertension: refractory or not? 7. What is the drug history? 8. Is there any ppt factor for AKI?
ppt factors for AKI in Diabetics They are the same as any high risk population
1. Dehydration (fluid loss, hyperglycemia, decrease fluid intake).
2. UTI.
3. Drugs.
4. Cardiac problem.
5. Septicemia.
6. Surgery.
USS & Renal Biopsy
• If renal ultrasound reveals small kidneys it is prudent not to perform biopsy.
• Overall, renal biopsy is indicated only in a small minority of diabetic patients.
USS & Renal Biopsy
Pathology Pathology - Diffuse Pathology - Nodular
Kimmelstiel Wilson nodules
Pathognomonic for diabetes
But reported in only 10% to 50% of biopsy specimens in both type 1
and type 2 diabetes.
- MORE FREQUENT than the nodular lesion - Correlates with the clinical manifestations
of worsening renal function
Pathology
DN Other
Pathology
DN + Other Pathology
LM/IF/EM whenever possible, especially if there is high suspicion of other pathology
To Conclude
Diabetes & Kidney Scenarios
Diabetic with recent discovered
renal problem
Due to DN Not due to DN
Diabetic with known old DN &
recent renal problem
Due to DN Not due to DN
To Conclude
To Conclude When to suspect other Cause(s) of Renal
Disease rather than DN? (Is it DN?)
!!!!!!!
To Conclude When to suspect other Cause(s) of Renal
Disease rather than DN? (Is it DN?) – Step 1
Step 1:
Renal US
Evidence of chronic changes
No need for biopsy
No evidence of chronic changes
Go to Step 2
To Conclude When to suspect other Cause(s) of Renal Disease
rather than DN? (Is it DN?) – Step 2 Suspect other cause rather that DN if:
Diabetic retinopathy - Absent in Type 1 - Absent in type 2 +
1- Short duration of DM 2- Atypical presentation or other ppt factors
Proteinuria & Nephrotic syndrome (Don’t forget DN without
albuminuria)
- Development of overt proteinuria without previous microalbuminuria - Overt proteinuria in diabetes type 1 for <10 years - If the onset of proteinuria has been sudden and rapid - Resistant Nephrotic Syndrome
Hematuria Macroscopic hematuria & active urinary sediment (Don’t forget casts are described in DN also)
Rising Cr and decreasing GFR - If renal impairment is rapid - If significant proteinuria without renal impairment
Hypertension Refractory HTN
Drug history - ACEi & ARBs: > 30% reduction in GFR within 2-3 months after initiation - NSAIDs & Contrast - Others
ppt factor for AKI Dehydration, UTI, Drugs, Cardiac problem, Septicemia, Surgery.
Systemic disease S&S of other systemic disease
Red and green colored indications are not listed in KDOQI Guidelines for Diabetes & CKD
Case 1
Case 1
Is it DN?
Clinical Diabetes. April 2001 vol. 19 no. 2 74
Case 2
Is it DN? Would you biopsy?
Case 2 cont
Clinical Diabetes. April 2001 vol. 19 no. 2 74
Case 3
Is it DN? Would you biopsy?
Case 3 Cont
Case 4
Is it DN? Would you biopsy?
Case 4 Cont
Take Home Message
• Renal diseases in diabetic patients are NOT ALWAYS due to diabetic nephropathy and
even it may not be due to DM.
Hematuria Proteinuria Rising creatinine Others
www.kidneyadvances.com
www.kidneyadvances.com
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facebook group: NephroTube
Mohammed Abdel Gawad