Diabetic Nephropathy

By Amna Abdul Sattar

Introduction

• Diabetic nephropathy, also known as diabetic kidney disease, is the

chronic loss of kidney function occurring in those with diabetes
mellitus.
• Diabetic nephropathy is the leading causes of chronic kidney disease
(CKD) and end-stage renal disease (ESRD) globally
• Diabetic nephropathy is a major cause of morbidity and mortality in
type 1 and type 2 diabetes.
• It is the leading cause of end-stage renal failure in developed
countries, accounting for 20% to 50% of patients starting renal
replacement therapy.
Prevalence

• About 30% of patients with type 1 diabetes develop diabetic nephropathy 20 years
after diagnosis.
• In Caucasian populations with type 2 diabetes, the nephropathy risk is similar to type
1 diabetes but may be worsened by obesity.
• Some ethnic groups face a higher risk due to genetic factors. Interestingly, some
patients with poorly controlled, long-standing diabetes do not develop nephropathy,
indicating a lack of genetic predisposition.
• Better glycemic control and blood pressure management are reducing overt
nephropathy cases, but the rising global incidence of type 2 diabetes is increasing the
number of people with diabetes and end-stage renal failure.
Prevalence

A Caucasian family Obesity

Pathophysiology

• The pathophysiology of diabetic nephropathy is not fully understood.

• Hyperglycemia is believed to cause renal damage through activation
of the renin-angiotensin system and direct toxic effects, leading to
inflammation and fibrosis.
• Early changes include glomerular basement membrane thickening
and mesangial matrix accumulation, coinciding with microalbuminuria
onset.
• Progression involves nodular deposits and worsening
glomerulosclerosis with heavy proteinuria, ultimately leading to
glomerular loss and renal function decline.
Pathophysiology
Histopathology

• Basement
membrane
thickening
• Mesangial
expansion
• Kimmelstiel
wilson nodule
Diagnosis and screening

• Microalbuminuria is the presence of small amounts of albumin in

urine, undetectable by a standard dipstick.
• Overt nephropathy is defined by macroalbuminuria (urinary
albumin > 300 mg/24 hrs, detectable by dipstick).
• Microalbuminuria is a strong predictor of nephropathy progression
in type 1 diabetes and a useful marker for increased
macrovascular disease risk in type 2 diabetes, though less reliable
for nephropathy prediction in older patients due to other diseases.
 Microalbuminuria

Diabetic nephropathy progression: In the first few years of type 1 diabetes, hyperfiltration occurs and
normalizes by about 10 years. In about 30% of patients, proteinuria develops around 10 years and
reaches nephrotic levels by 14 years. Renal function continues to decline, reaching end-stage around
16 years.
Management objectives

• Aggressive reduction of blood pressure

• Aggressive reduction of cardiovascular
risk factors
• Optimisation of glycaemic control
Management

• Blockade of the renin-angiotensin system with ACE inhibitors or ARBs is

recommended as first-line therapy for nephropathy.
• Adding a diuretic or salt restriction enhances the treatment’s effects. This
approach reduces hyperfiltration and protein leakage, though it increases
the risk of hyperkalemia and may worsen renal function in some cases.
• Monitoring electrolytes and renal function is crucial.
• If renin-angiotensin system blockade isn’t feasible, standard treatments
like calcium channel blockers and diuretics are alternatives.
• Reduction in albuminuria by half with ACE inhibitors or ARBs significantly
lowers the risk of end-stage renal disease.
 Renal replacement therapy

• Renal replacement therapy is often required at a higher eGFR than

in other causes of renal failure, due to fluid overload or
symptomatic uraemia.
 Renal transplantation

• Renal transplantation significantly

improves life, with slow recurrence
of diabetic nephropathy in the new
kidney.
• Pancreatic transplantation alongside
renal transplantation can achieve
insulin independence and reverse
microvascular disease, but organ
availability is limited.
Thank You