Diabetic nephropathy in details

1. Diabetic kidney diseas
e ( Diabetic nephropat
hy )
Dr. Khalid Abdalaziz

2. Introduction :
• Diabetic kidney disease (DKD) is the lead
ing cause of end-stage kidney disease (E
SKD) in developed countries
• It is considered a microvascular complic
ation and occurs in both diabetes mellitu
s type 1 (T1DM) and diabetes mellitus typ
e 2 (T2DM).
• The disorder presents with persistent alb
uminuria and a progressive decline in the
glomerular filtration rate.

3. • early treatment can delay or prevent the progr
ession of the disorder.
• Optimizing glycemia and reasonable blood pre
ssure control are pivotal in halting the progressi
on of DKD.

4. • In type 1 diabetes microalbuminuria usually oc
curs 5-15 years after the diagnosis of diabetes
mellitus.While patients with type 2 diabetes me
llitus may present with albuminuria at the time
the diabetes is detected
• The peak incidence of frank albuminuria is 17
years after diagnosis of type 1 diabetes
•
• Diabetic nephropathy develops in approximat
ely 40% of patients with type 1 diabetes and in
5% to 40% of patients with type 2 diabetes

5. • The majority of patients with diabetic nephropath
y have type 2 diabetes, however this is due to hig
her prevalence of type 2, rather than higher incide
nce of nephropathy (as incidence is in
• fact higher in type 1 DM)
• Patients who have no proteinuria after 25 years
of diabetes have only a very small risk of develo
ping DN
• The greater risk of death from associated CV dis
ease

6. Pathophysiology
Hyperglycemia leads to the production of
reactive oxygen species and activation of
pathways, including :
 protein kinase C
 polyol
 hexosamine (TGF - B)
 advanced glycation end products (AGE).

7.  Endothelin1 production
 Podocytes dysfunction
 RAS activations

8.  increase in cytokines and chemokines,
including IL-6, MCP-1, TGF-beta , and
VEGF , causing inflammation fibrosis and
increased vascular permeability

9.  The resulting systemic and
intraglomerular hypertension results in
proteinuria
 Proteinuria causes epithelial-
mesenchymal cell transformation leading
to fibroblasts and chronic tubular injury.

13. Diabetic glomerulopathy. Changes in glomerular histology
in diabetic glomerulopathy (A) Normal glomerulus. (B) Di
ffuse mesangial expansion with mesangial cell proliferatio
n. (C) Prominent mesangial expansion with early nodularit
y and mesangiolysis. (D) Accumulation of mesangial matri
x forming Kimmelstiel-Wilson nodules. (E) Dilation of cap
illaries forming microaneurysms, with subintimal hyaline (
plasmatic insudation). (F) Obsolescent glomerulus

23. Risk factors
 DM, poor glycemic control
 uncontrolled hypertension
 A family history of hypertension and
cardiovascular events in first-degree
relatives
 Obesity
 smoking
 hyperlipidemia
 Male

25. Clinical presentation
 patients are often asymptomatic and are
diagnosed during screening with levels
of AER 30 to 300 mg/g
 fatigue
 foamy urine (urine protein greater than
3.5 g per day)
 pedal edema due to hypoalbuminemia
 nephrotic syndrome.

26. They may also have associated :
• peripheral vascular disease,
• hypertension
• coronary artery disease
• diabetic retinopathy.
• 30% have high BP at diagnosis of T2DM ,,
• 70% have high BP at diagnosis of DN.

28. Diagnosis
 Diabetic nephropathy is diagnosed by
persistent albuminuria on two or more
occasions, separated at least by three
months on early morning urine samples.
 Moderately increased albuminuria is
when the urine albumin excretion rate is
between 30 to 300 mg over 24 hours and
is a marker of early DN

29.  Persistent albuminuria is greater than
300 mg over 24 hours or greater than
200 micrograms per minute.
 It is critical to exclude a urinary tract
infection as the cause of albuminuria by
a urinalysis.

32. investigation and assessment
 Urinalysis : quantify proteinuria
 S.Cr , eGFR, U&E, serum albumin, HbA1C,
lipid profile.
 Consider serum and urine protein
electrophoresis in older patients.
 Check visual acuity, fundoscopy, and arrange
ophthalmology review, if not already under
follow up

33.  Check BP.
 Examine for other evidence of vascular
disease (bruits, peripheral
pulses, etc.).
 Assess for peripheral neuropathy.
 ECG
 Consider USS kidneys(kidneys are often
normal-sized in DN)

34. Screening
 all patients should be screened annually
 albumin:creatinine ratio (ACR) in early
morning specimen
 ACR > 2.5 = microalbuminuria

37. Primary prevention
 Improve glycaemic control: Aim HbA1C
<7%
 Target BP <130/80mmHg
 Stop smoking
 Encourage weight loss
 exercise

38. Management

51.  Many nephrologists will aim
<125/75mmHg if proteinuria >1g/24h.
 Add further therapy in a stepwise
manner, selecting drugs according to the
comorbidity of the individual patient.

52.  Diuretics may enhance the anti-
proteinuric effects of RAS
inhibition.Furthermore, volume overload
is often an important driver of high BP in
DN with renal impairment.
 Thiazides may be suitable initially, but
loop diuretics are preferred as GFR
deteriorates (<40mL/min)

53.  B-blockers if arrhythmias, CCF, coronary
artery disease.
 Evidence favours non-dihydropyridine
calcium channel blockers (e.g. diltiazem)
over dihydropyridine (e.g. amlodipine )

54. Management of proteinuria
 Proteinuria is itself an important
treatment target.
 Aim <0.5g/24h (uACR <30mg/mmol or
uPCR < 50mg/mmol), as BP allows.
 ACE-I or ARBs should be used in
normotensive patients with proteinuria
(micro- or macroalbuminuria)

67. Novel treatments for DN
 Pyridoxamine :reduces mesangial
expansion, decreases albuminuria
 Pirfenidone :reduces mesangial
expansion and collagen gene expression,
improve GFR but not albuminuria
 Ruboxistaurin :Is a selective protein
kinase C inhibitor that reduces
albuminuria

68.  Avosentan : Is an ET-1 receptor
antagonist that reduces urinary albumin
excretion ( SE : CCF , volume overload )
 Doxycycline :may also have anti-fibrotic
properties and has been shown to reduce
proteinuria.

69.  Sulodexide : A glycosaminoglycan,
inhibits TGF- B production and causes
dose-dependent reductions in
albuminuria (persistent after
discontinuation)

70. Other diabetes-related urinary tract
disorders
 Papillary Necrosis
 Renovascular disease
 Neurogenic bladder
 UTI
 Contrast induced AKI