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Is It Diabetic Nephropathy? (When to Biopsy?)

Mohammed Abdel Gawad Nephrology Specialist

Kidney & Urology Center (KUC)- Alexandria

drgawad@gmail.com

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

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Mohammed Abdel Gawad