diabetic nephropathy & lupus nephritis

08/04/23 Dr (Brig) YD Singh

Diabetic NephropathyDiabetic Nephropathy

&&

Lupus NephritisLupus Nephritis

Dr (Brig) YD Singh, MD, FIACM, DIT

Professor (Internal Medicine)SKN Medical College & Gen Hospital

Pune 411 041

Diabetic Nephropathy: Introduction

• The abnormal glycaemic milieu of diabetes– Related to microvascular complications

• Causal relationship with hyperglycaemia is not linear

– 30% develop clinically overt nephropathy.– Most patients with diabetes escape renal failure

• Although some histological damage occurs in their kidneys

• Their renal function remains essentially normal

– Hyperglycaemia appears necessary• But not sufficient to cause Kidney damage & failure



• Diabetic nephropathy is the most common cause of ESRD world wide– Accounting for over 40% of dialysis patients

• The 5-year mortality rate for a dialysis patient is 93%




Number of patients initiating Renal Replacement Therapy (RRT)Number of patients initiating Renal Replacement Therapy (RRT)for ESRD related to DM, 1984-2001 in USAfor ESRD related to DM, 1984-2001 in USA

Diabetic Nephropathy: Historic Note

• Rolo (1798) Reported• Presence of protein in urine of DM pts

• Bright (1836) Described• Seriousness of protein in urine of DM pts

• Kimmelstiel, Wilson (1936 ) • Described Nodular glomerular lesions in DM


Diabetic Nephropathy: Definition

• DN is microvascular complication of DM

• Characterized by: – Presence of Albuminuria – Elevated blood pressure – Declining glomerular function


Diabetic Nephropathy: Epidemiology

Type 1 Diabetic

• 25 - 40% will develop nephropathy

• 80 - 90% with micro-albuminuria – progress to overt DN in 5 - 10 years

• Nearly 100% with gross proteinuria – Will progress to ESRD in 7 - 10 yrs


Diabetic Nephropathy: Epidemiology

Type 2 Diabetic• 50% have micro-albuminuria

– at the time of presentation (secondary to HTN)

• 10-20% with microalbuminuria – Will progress to overt nephropathy


Diabetic Nephropathy: Risk Factors


• Age, Race, Ethnicity

• History of microalbuminuria

• Hypertension

• Poor glycaemic control

• Smoking

• Family history of nephropathy– Genetic abnormalities of ACE gene

Diabetic Nephropathy: Stages• Stage I – Hyperfiltration

– Increased blood flow in the kidney, – Early renal hypertrophy

• Stage II - Glomerular lesions – Without clinically evident disease

• Stage III - Incipient nephropathy with microalbuminuria – Alb/Cr ratio 0.03 - 0.3 or – Albumin 20-200 mcg/min on timed specimen


Diabetic Nephropathy: Stages

• Stage IV - Overt diabetic nephropathy– With proteinuria >500 mg/24 hr– Creatinine clearance <70 ml/min

• Stage V – End stage renal disease (ESRD)– Creatinine clearance <15 ml/min– Creatinine = 6mg/dl


Diabetic Nephropathy: Stages


020406080

100120140160180

0 5 10 15 20 25 30

Duration of Diabetes

GF

R

III III

IV

V

Incipient Nephropathy

Type 1 Diabetes

• 2 out of 3 urine tests + for microalbuminuria – Screening should start 5 yrs after initial Δ

• Presence of proliferative Diab Retinopathy

• 80-90% of patients with microalbuminuria– Will progress to Diab Neuropathy


Incipient Nephropathy

Type 2 Diabetes• 2 out of 3 urine tests + for microalbuminuria

– Start screening at the time of diabetes Δ

• Presence of diabetic retinopathy– 20-30% may have diabetic nephropathy but not

diabetic retinopathy

• 25% may have a diagnosis of nephropathy other than diabetic nephropathy


Overt Diabetic Nephropathy

• Gold Standard is biopsy

• Diagnosis can be made – By clinical history and – Exclusion of other renal disease

• Workup includes– Renal ultrasound

• For size, shape, abnormalities

– 24 hour urine for total protein and • Creatinine clearance


Diabetic Nephropathy: Morphological Changes


• Glomerular & tubular hypertrophy• Thickening of GBM & TBM

A .Normal capillary wall thickness

A .Normal capillary wall thickness

B. Severe capillary wall thickening

B. Severe capillary wall thickening

AA BB



Mesangial expansion is the morphological lesion that closely related to the evolution of the GFR



Nodular lesion in Type 1 DM Nodular lesion in Type 1 DM (Kimmelstiel Wilson Lesion)



• Glomerular & tubular hypertrophy

• Thickening of GBM & TBM

• Mesangial expansion

• Nodular & Diffuse glomerulosclerosis

• Arteriosclerosis and hyalinosis of a.a & e.a

• Tubulointerstitial fibrosis

Diabetic Nephropathy: Treatment

• Lifestyle changes– Lose weight– Stop smoking– Low salt diet for BP control– Low protein diet?

• Glycaemic Control – Benefit in both Type 1 and Type 2 patients– Recommended: HbA1C <6.5 - 7.0 %


Diabetic Nephropathy : HbA1C


06

7

8

9

0 3 6 9 12 15

HbA 1

c (%

)

Years from randomisation

Conventional

Intensive

6.2% upper limit of normal range

UK Prospective Diabetes StudyUK Prospective Diabetes Study


• Blood Pressure control– Current recommendations for BP

<130/80-85 – If nephropathy BP <125/75

• Several randomized controlled trials– Indicate improved blood pressure control

• Decreases rate of progression of renal disease • In both type 1 & type 2 patients



• ACE inhibitors & ARBs use– Decrease microalbuminurea– Improve diabetic nephropathy

• Mechanism of action– ACE-inhibitors limit angiotensin II production

• By blocking angiotensin converting enzyme

• ARB-agents block angiotensin II receptors


Diabetic Nephropathy:Protein Restriction


• 0.8 g/kg/day in– Overt nephropathy

• 0.6 g/kg/day in– Diabetics with

falling GFR

Diabetic Nephropathy: Management Summary (1)

• Annual screening for microalbuminuria

• ACEI, ARBs Regardless of BP level

• BP control <135/80 - <125/75 (2-3 drugs)

• Intensive glycemic control (HB A1c <7%)

• Smoking cessation

• Prevent radiocontrast nephropathy

• Restrict dietary protein (0.8-0.6 g/kg/d)

• Control dyslipidemia (LDL- C <100 mg/dl)


Diabetic Nephropathy: Management Summary (2)

• At GFR 25 ml/m– Vascular access be established

• At GFR 15-20 ml/m– RRT should start

• In all patients of Type 1 DM – Renal / Pancreas Transplant to be considered


Thank U


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