Overview of the management of diabetic kidney disease

Credits
- Section Writer: Dr. Om J Lakhani
- Section Editor: Dr. Om J Lakhani

Connected Notes:

Video lecture

Q. What is the more appropriate term – Diabetic nephropathy or diabetic kidney disease?
- Diabetic kidney disease is more appropriate since Diabetic nephropathy is a histopathological diagnosis
Q. What are the major clinical manifestations of diabetic kidney disease?
- Albuminuria
- Progressive decline in renal function
Q. Which are the stages of albuminuria?
- Hyperfiltration- mainly in type 1 diabetes
- Moderately increased albuminuria – previously called Microalbuminuria- 30 -300 mg/day
- Severely increased albuminuria- previously called macroalbuminuria - >300 mg/day
Q. Can non-albuminuric diabetic patients also have a decline in GFR?
- Yes
- This is more common in type 1 patients
Q. Does hematuria occur in diabetic nephropathy?
- Yes
- It can occur in diabetic nephropathy
- It is mainly microscopic hematuria
- Sometimes it is because of other renal disorder associated
- Sometimes red cell casts are also seen
**Epidemiology **
Q. How common is microalbumiuria in type 1 diabetics ?
- 20-30% of type 1 diabetics with the duration of disease > 15 years have Microalbuminuria
- 50% of these progress to progressive renal disease
- Intensive glycemic control and use of ACEI /ARB have reduced the incidence of progressive renal disease and ESRD
Q. In the intensive treatment arm of DCCT, how many developed overt nephropathy?
- Only 2% developed creatinine of >2 mg/dl over follow up of 30 years with intensive glycemic control
Q. Can macroalbumuniria and microalbuminuria regress ?
- Yes, regression has been shown in DCCT trial with intensive glycemic control
#Clinicalpearl
- Alternate cause of renal disorder must be considered in patients who develop new-onset over nephropathy more than 20 years after the beginning of the disease
Q. Do Type 2 diabetics have less renal disease than type 1 diabetics?
- Yes
- But maybe a function of the lesser duration of the disease
- However, current data suggest that renal risk is equivalent
**Pathology **
Q. Which are the significant structural changes in diabetic kidney disease?
- Mesangial expansion
- Glomerular sclerosis
- Glomerular basement membrane thickening
Q. What is Kimmelsteil- Wilson syndrome ?
- Nodular intercapillary glomerulosclerosis
Q. What is the renal pathology society classification of diabetic nephropathy
- Class I- basement membrane thickening only
- Class II- Mesangial expansion
- Class III- at least one nodular glomerulosclerosis and <50% global glomerulosclerosis
- Class IV- >50% of global glomerulosclerosis
Q. How much thickening of the basement membrane is considered significant?
- Greater than 430 nm in males above nine years
- GReater than 395 mm in females
Q. What are other causes of nodular glomerulosclerosis?
- Amyloidosis
- Hypertension and metabolic syndrome without Diabetes
- Chronic hypoxic condition like cyanotic heart disease
**Pathogenesis **
Q. What is the cause of glomerulosclerosis in a patient with diabetic nephropathy?
- intraglomerular hypertension is the reason for glomerulosclerosis in a patient with diabetic nephropathy
Q. What causes mesangial expansion?
- Probably by hyperglycemia and increase AGE
Q. Which biomarker has been linked with possible pathogenesis in diabetic nephropathy?
- Prorenin
- Increased level is seen in diabetic nephropathy
- May increase MAPK pathway expression
Q. Which Cytokine is associated with diabetic nephropathy?
- TGF beta
**RISK FACTORS **
Q. What is the relation between glomerular hyperfiltration and risk of progression?
- People with type 1 diabetes diagnosed < 5 years – some of them have glomerular hyperfiltration with GFR 25-50 above normal
- This subgroup seems to have an increased risk of progression
Q. Why do people with Diabetes have intraglomerular hypertension?
- Intraglomerular hypertension is associated with increase glomerulosclerosis and progressive decline in renal function
- Diabetes impaired renal autoregulation → ideally systemic hypertension should cause renal vasoconstriction, which is absent in these cases → hence it causes intraglomerular hypertension
Q. Enlist the risk factors associated with diabetic nephropathy?
- Genetic susceptibility
- Race
- Glycemic control
- Oral contraceptive pills use
- Obesity
- Hypertension
- Age and duration of Diabetes
- Initial glomerular hyperfiltration in type 1
Q. What is the correlation between diabetic retinopathy and nephropathy ?
- In type 1 diabetes, most patients with diabetic nephropathy have retinopathy
- Retinopathy often precedes nephropathy
- However, patients with retinopathy do not necessarily have nephropathy
- In type 2 diabetics- those who have Proteinuria + Retinopathy are more likely to have diabetic nephropathy, while those not having them are more likely to have other causes of nephropathy
- Those who have Klimmesteil-Wilson syndrome features (nodules) are more likely to have associated retinopathy
- Those having mesangiosclerosisis are less likely to have associated retinopathy
- According to 2007 K/DOQI guidelines
  - Consider Diabetes as etiology of CKD – if retinopathy present + albuminuria
  - If above are absent- consider other etiology for CKD
**Nondiabetic renal disease **
Q. Does any diabetic treatment have a relation with some other cause of nephropathy?
- Porcine insulin may cause an immunological response which can lead to membranous nephropathy
Q. When should other causes of renal failure be considered in diabetic patients?
- Acute /subacute renal dysfunction
- Proteinuria onset is <5 years after the onset of type 1 diabetes
- Other systemic signs and symptoms
- Nephropathy without retinopathy in type 1 and without retinopathy and proteinuria in type 2
- Reduction in GFR by >30 % within 2-3 months of starting ACEI/ARB
- Presence of active urine sediment
Q. Which are the common nondiabetic cause of CKD in diabetic patients?
- IgA nephropathy
- Membranous nephropathy
- Minimal change disease
- FSGS

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