Is it Diabetic Nephropathy? (When to Biopsy?)

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Is It Diabetic Nephropathy?(When to Biopsy?) : 

Is It Diabetic Nephropathy?(When to Biopsy?) Mohammed Abdel Gawad Nephrology Specialist Kidney & Urology Center (KUC)- Alexandria drgawad@gmail.com

IMPORTANT MESSAGE : 

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 : 

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 : 

Is it Diabetic Nephropathy?You have to answer the following What is the type of DM? Is there an evidence of Diabetic retinopathy? Proteinuria: Is the evolution of proteinuria is typical (micro then macro)? Is the range of proteinuria coincides with DN stage? What is the rate of proteinuria progression? Hematuria: Is it microscopic or macroscopic? Rising Cr and decreasing GFR: Is it related to proteinuria? What is the rate of renal impairment progression? Hypertension: refractory or not? What is the drug history? Is there any ppt factor for AKI?

Diabetic Nephropathy & Diabetic Retinopathy Type 1 DM : 

Diabetic Nephropathy & Diabetic Retinopathy Type 1 DM Mogensen CE. Diabetes. 1997;56(Suppl 2):104-111.

Diabetic Nephropathy & Diabetic Retinopathy Type 1 DM : 

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 : 

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. ** Wolf G, Müller N, Mandecka A, Müller UA. Clin Nephrol. 2007;68:81-86. * GIUSEPPE REMUZZI et al. N Engl J Med, Vol. 346, No. 15· April 11, 2002 * In type 2 DM the prevalence of nondiabetic renal disease could vary from 12 to 38% *** *** Huang F et al. Clin ephrol 2007, 67: 293-297. When to suspect other cause? 1- Short duration of DM 2- Atypical presentation (atypical proteinuria or hematuria, rapid rising Cr ….. etc) or other ppt factors (discussed later) When to Suspect other cause?

Is Fluorescein Angiography Safe in Diabetics with Renal Impairment? : 

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? : 

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 : 

Is it Diabetic Nephropathy?You have to answer the following What is the type of DM? Is there an evidence of Diabetic retinopathy? Proteinuria: Is the evolution of proteinuria is typical (micro then macro)? Is the range of proteinuria coincides with DN stage? What is the rate of proteinuria progression? Hematuria: Is it microscopic or macroscopic? Rising Cr and decreasing GFR: Is it related to proteinuria? What is the rate of renal impairment progression? Hypertension: refractory or not? What is the drug history? Is there any ppt factor for AKI?

Diabetic Nephropathy & Proteinuria : 

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 AlbuminuriaIschemic Nephropathy – Type 2 DM : 

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 DN without AlbuminuriaIschemic Nephropathy – Type 2 DM

DN without AlbuminuriaIschemic Nephropathy – Type 2 DM : 

DN without AlbuminuriaIschemic Nephropathy – Type 2 DM Renal ultrasound reveals small kidneys. High serum Cr, low GFR. Without albuminuria Jamine P. Dwyer et al. DEMAND study. Cardiorenal Med, 2012;2:1-10

Slide 14: 

Jamine P. Dwyer et al. DEMAND study. Cardiorenal Med, 2012;2:1-10

DN without Albuminuria - Type 1 DM : 

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 : 

Is it Diabetic Nephropathy?You have to answer the following What is the type of DM? Is there an evidence of Diabetic retinopathy? Proteinuria: Is the evolution of proteinuria is typical (micro then macro)? Is the range of proteinuria coincides with DN stage? What is the rate of proteinuria progression? Hematuria: Is it microscopic or macroscopic? Rising Cr and decreasing GFR: Is it related to proteinuria? What is the rate of renal impairment progression? Hypertension: refractory or not? What is the drug history? Is there any ppt factor for AKI?

Diabetic Nephropathy & HematuriaIs it Micro or Macroscopic? : 

Diabetic Nephropathy & HematuriaIs it Micro or Macroscopic? * 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 : 

Is it Diabetic Nephropathy?You have to answer the following What is the type of DM? Is there an evidence of Diabetic retinopathy? Proteinuria: Is the evolution of proteinuria is typical (micro then macro)? Is the range of proteinuria coincides with DN stage? What is the rate of proteinuria progression? Hematuria: Is it microscopic or macroscopic? Rising Cr and decreasing GFR: Is it related to proteinuria? What is the rate of renal impairment progression? Hypertension: refractory or not? What is the drug history? Is there any ppt factor for AKI?

Diabetic Nephropathy & Renal Impairment : 

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 : 

Is it Diabetic Nephropathy?You have to answer the following What is the type of DM? Is there an evidence of Diabetic retinopathy? Proteinuria: Is the evolution of proteinuria is typical (micro then macro)? Is the range of proteinuria coincides with DN stage? What is the rate of proteinuria progression? Hematuria: Is it microscopic or macroscopic? Rising Cr and decreasing GFR: Is it related to proteinuria? What is the rate of renal impairment progression? Hypertension: refractory or not? What is the drug history? Is there any ppt factor for AKI?

Diabetic Nephropathy & Refractory HTN : 

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 : 

Is it Diabetic Nephropathy?You have to answer the following What is the type of DM? Is there an evidence of Diabetic retinopathy? Proteinuria: Is the evolution of proteinuria is typical (micro then macro)? Is the range of proteinuria coincides with DN stage? What is the rate of proteinuria progression? Hematuria: Is it microscopic or macroscopic? Rising Cr and decreasing GFR: Is it related to proteinuria? What is the rate of renal impairment progression? Hypertension: refractory or not? What is the drug history? Is there any ppt factor for AKI?

Diabetic Nephropathy & Drugs : 

Diabetic Nephropathy & Drugs ACEi & ARBs > 30% reduction in GFR within 2-3 months after initiation Suspect renovascular disease

Diabetic Nephropathy & Drugs : 

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 : 

Is it Diabetic Nephropathy?You have to answer the following What is the type of DM? Is there an evidence of Diabetic retinopathy? Proteinuria: Is the evolution of proteinuria is typical (micro then macro)? Is the range of proteinuria coincides with DN stage? What is the rate of proteinuria progression? Hematuria: Is it microscopic or macroscopic? Rising Cr and decreasing GFR: Is it related to proteinuria? What is the rate of renal impairment progression? Hypertension: refractory or not? What is the drug history? Is there any ppt factor for AKI?

ppt factors for AKI in DiabeticsThey are the same as any high risk population : 

ppt factors for AKI in DiabeticsThey are the same as any high risk population Dehydration (fluid loss, hyperglycemia, decrease fluid intake). UTI. Drugs. Cardiac problem. Septicemia. Surgery.

USS & Renal Biopsy : 

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 : 

USS & Renal Biopsy

Pathology : 

Pathology Pathology - Diffuse Pathology - Nodular

Pathology - Nodular : 

Pathology - Nodular

Pathology - Nodular : 

Pathology - Nodular Kimmelstiel Wilson nodule pathognomonic for diabetes but are reported in only 10% to 50% of biopsy specimens in both type 1 and type 2 diabetes. Nodules are also seen in MPGN, amyloidosis and light-chain deposition disease, so IF is important to exclude others causes.

Pathology - Nodular : 

Pathology - Nodular

Pathology - Diffuse : 

Pathology - Diffuse

Pathology – Diffuse & Nodular : 

Pathology – Diffuse & Nodular

Pathology - Diffuse : 

Pathology - Diffuse The diffuse glomerular lesion * is MORE FREQUENT than the nodular lesion, with an incidence of: more than 90% for patients with type 1 diabetes longer than 10 years in duration incidence of 25% to 50% in patients with type 2 diabetes. In contrast to nodular lesions, which are of little functional significance, the degree of diffuse glomerulosclerosis correlates with the clinical manifestations of worsening renal function. Accumulation of mesangial. * Fioretto P et al. Diabetologia. 1996;39:1569-1576.

To Conclude : 

To Conclude

To Conclude : 

To Conclude

To ConcludeWhen to suspect other Cause(s) of Renal Disease rather than DN? (Is it DN?) : 

To ConcludeWhen to suspect other Cause(s) of Renal Disease rather than DN? (Is it DN?) !!!!!!!

To ConcludeWhen to suspect other Cause(s) of Renal Disease rather than DN? (Is it DN?) – Step 1 : 

To ConcludeWhen to suspect other Cause(s) of Renal Disease rather than DN? (Is it DN?) – Step 1

To ConcludeWhen to suspect other Cause(s) of Renal Disease rather than DN? (Is it DN?) – Step 2 : 

To ConcludeWhen to suspect other Cause(s) of Renal Disease rather than DN? (Is it DN?) – Step 2 Red and green colored indications are not listed in KDOQI Guidelines for Diabetes & CKD

Case 1 : 

Case 1 Case 1 Is it DN?

Slide 42: 

Clinical Diabetes. April 2001 vol. 19 no. 2 74 Case 2 Is it DN? Would you biopsy?

Slide 43: 

Case 2 cont Clinical Diabetes. April 2001 vol. 19 no. 2 74

Slide 44: 

Case 3 Is it DN? Would you biopsy?

Slide 45: 

Case 3 Cont

Slide 46: 

Case 4 Is it DN? Would you biopsy?

Slide 47: 

Case 4 Cont

Take Home Message : 

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

www.kidneyadvances.com : 

www.kidneyadvances.com

www.nephrotube.blogspot.comhfacebook group: NephroTube : 

www.nephrotube.blogspot.comhfacebook group: NephroTube Mohammed Abdel Gawad

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