Renal Diseases

1
Renal Diseases in Diabetic Patients Diagnosis
and Treatment
Dr Ashraf ABDELMAGED DONIA MD, DIS.C, DIU, CM
SB.
Consultant of Nephrology and Physician
Transplant National Institute of Nephrology and
Urology , Egypt. Maitre Es Science Medicale En
Nephrologie Claude Bernard University , Lyon ,
France
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Introduction

• Renal disease is a relatively common
  microvascular complication of both
  insulin-dependent and non-insulin-dependent
  diabetes mellitus.

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Introduction

• Nephropathy is the major cause of illness and
  death in diabetes
• End -stage renal disease is the major cause of
  death accounting for 59 to 66 in IDDM patients
  with nephropathy

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Renal Diseases in Diabetic Patients

• Diabetic Nephropathy
• Other Glomerular diseases in Diabetes
• Other Renal Manifestations of Diabetic
• Acute Renal Failure in Diabetes

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Introduction

• Diabetic Nephropathy is defined clinically as
  the presence of persistent proteinuria
  (gt0.5 g/24 h) in a diabetic patient with
  retinopathy, elevated blood pressure, and
  declining glomerular function in the absence of
  urinary tract infection, other renal disease, or
  heart failure.

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Epidemiology

• Overall prevalence
• Microproteinuria 30
• Macroproteinuria 35

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Epidemiology
Prevalence of nephropathy in DM
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Epidemiology
Incidence of Macroproteinuria in DM
Macroproteinuria IDDM NIDDM ( /
year) 1.2 1.5 ( 0-5) (1-2) Macroprot
einuria IDDM NIDDM ( / 25years) 25 31
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Epidemiology

• Incidence of ESRD in DM
• Cumulative incidence of ESRD in proteinuric IDDM
  patients is 50 10years after the onset of
  proteinuria compared with 3-11 10years after
  the onset of proteinuria in European NIDDM
  patients

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Cumulative incidence of clinical proteinuria by
duration of diabetes in non-insulin-dependent
subjects.
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I -Diabetic Nephropathy Clinical Picture
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Stages of Diabetic Nephropathy

• Chronology Variable duration from the diagnosis
  or From bad control of blood sugar
• Appellation Hypertrophy Hyperfunction
• Principal Characteristics
• Large size kidney
• Glomerular Hyperfiltration

Stage I
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Stage I

• Principal Anatomical Modifications
• Glomerular hypertrophy
• Normal Mesangium and GBM
• Glomerular Filtration gt160ml/min
• Urinary Albumin ExcretionNormal
• Blood Pressure Normal
• Physio-pathological modifications
• Increased intraglomerular pressure
• Increased glomerular Volume

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Stage II

• Chronology After 2 Years from onset of diabetes
  From the diagnosis
• Appellation Silent Stage
• Principal Characteristics
• Normal Urinary Albumin Excretion
• Principal Anatomical Modifications
• Thickness of GBM and mesangial inflation

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Stage II

• Principal Anatomical Modifications
• Thickness of GBM and mesangial inflation
• Glomerular Filtration Increased or Normal
• Urinary Albumin Excretion Normal
• Blood Pressure Normal
• Physio-pathological modifications
• Increased intraglomerular pressure
• Increased glomerular Volume
• Increased synthesis of basement membrane

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Stage III

• Chronology After 10-20years from diabetes
• Appellation Microabluminuric Stage
• Principal Characteristics
• Permanent abnormal excretion of urinary albumin (
  Not detected by albustix)

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Stage III

• Principal Anatomical Modifications
• Intermediate lesions between Stage II and IV
• Glomerular Filtration
• Early 160 ml/min
• Late 130 ml/min
• Urinary Albumin Excretion
• Early 20-70ug/min
• Late 70-200ug/min

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Stage III

• Blood Pressure
• Early Normal
• Late Mild increased
• Physio-pathological modifications
• Glomerular occlusion /-Glomerular
  Hyperfiltration

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Stage IV

• Chronology Many years later
• Appellation Clinical or Manifested nephropathy
• Principal Characteristics Macroproteinuria (
  Albustix ve)

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Stage IV

• Principal Anatomical Modifications
• Glomerular Occlusion
• Glomerular hypertrophy in resting glomeruli
• Increased Mesangial Matrix
• Glomerular Filtration
• Early 130-70ml/min
• Intermediate 70-30 ml/min
• Late 30-10 ml/min

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Stage IV

• Urinary Albumin Excretion gt200ug/min
• Blood Pressure Constant HTN
• Physio-pathological modifications
• Rapid increase of mesangial inflation
• Increased glomerular occlusion
• Glomerular Hyperfiltration in resting glomeruli

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Stage V

• Appellation Uremia
• Principal Characteristics ESRD
• Principal Anatomical Modifications
• Diffuse glomerular Occlusion
• Interstitial Fibrosis

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Stage V

• Glomerular Filtration 10-0 ml/min
• Urinary Albumin Excretion Decreased
• Blood PressureHigh controlled by dialysis
• Physio-pathological modifications
• Advanced renal sclerosis

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Nodular Glomerulosclerosis
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Nodular Glomerulosclerosis Trichrome S
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Diffuse and Nodular Glomerulosclerosis
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Early diffuse Glomerulosclerosis
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IFEarly Diffuse Glomerulosclerosis with IgG
Deposts
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Other Glomerular diseases in Diabetes

• Prevalence ( 8-37)
• Membranous Glomerulonephritis Most often been
  reported in association with Diabetes
• IgA Nephritis
• Mesangial GN
• Lupus Nephritis
• Amyloidosis / Cresentic GN
• Membranoproliferative GN ( Type I-II)
• Steroid-Responsive Minimal change Disease

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Other Manifestations of Diabetic

• Renal Papillary necrosis Prevalence 4,4-24
• CPSterile pyouria with microscopic hematuria,
  Sepsis , Colic , Death
• Asymptomatic in 10 of cases
• Autonomic Neuropathy of the bladder Prevalence
  1-26
• Urinary Tract Infection
• More frequent in diabetic patient
• May lead to interstitial inflammation and
  scarring

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Acute Renal failure

• Toxicity from contrast media
• Rhabidomyolysis
• Acute diabetic ketoacidosis
• Acute pyelonephritis
• Large vessels diseases
• Other glomerulonephritis Cresentic GN

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Indication of renal biopsy in diabetic patients

• Absence of retinopathy
• Macroscopic Glomerular hematuria.
• Duration of insulin-dependant diabetes lt 10y
  at onset of proteinuria
• Clinical or biological evidence of a multi
  system disorders

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Treatment General Considerations
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Blood Pressure Control

• Target Bl Pr should be lt 135/85 mmHg (Hot,
  CAPP, MDRD) , lt 125/75 mmHg ( JNCNI)
• Mono-Polytherapy
• No scientific argument to change target Bl Pr in
  the elderly diabetic except gt80years
• The majority of pts require 3-4 antihypertensive
  drugs to obtain target blood Pressure

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Antihypertensive Strategy

• First Intention
• Loop diuretic Salts and water retention
• ACE/ACER inhibitors Proteinuria . HF
• Selective BB IHD
• Second/Third Intention Same ttt
• Fourth Intention
• Ca Blockers, alpha blockers, Central

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Glycemic Control

• Predialysis Period
• IDDM Insulin therapy ( rapid- intermediate
  action )
• NIDDM
• Oral anti-diabetic therapy should be prescribed
  with caution
• Biguanide / long acting sulfamide should not be
  prescribed if serum creatinine gt 1,6mg/dl
• Glipizide drug of choice in Diabetic
  nephropathy

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Glycemic Control

• Dialysis stage
• Increased dose of insulin reflect good
  resaturation of general condition
• In peritoneal dialysis
• Intraperitoneal route should be preferred
• Introduction of rapid acting insulin in
  peritoneal pouch 30-45 min pre meal
• Introduction SC insulin if requirement exceeds
  100 u/pouch

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Dietary Control

• Pre dialysis stage ( 30 ml/min)
• Low protein diet 0,6-0,8 g/kg/day
• Dialysis stage
• Normal / Hyperproteinic diet to prevent
  multifactorial deficit leading to hypoalbuminemia
  ( 1,2-1,5 g/kg/day)
• Energetic support 35 Kcal /kg /day (
  Ideal weight)

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Cardio-Vascular Risk Factors

• Coronary Insufficiency
• Stress ECG , Echocardiography
• Myocardial Scintigraphy with thallium
  ( Dipyridomol)
• Coronography especially pretransplantation
• Cigarette Smoking Major risk
• Physical Exercise
• Early treatment of dyslipidemia

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Other Treatment

• Treatment of Anemia
• Treatment of Renal Osteodystrophy
• Vaccination HBV ( GFR lt25ml/min)
• Screening for Microalbuminuria by medical
  network Construction ( Endocrinologist ,
  Ophthalmologist and Nephrologist

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Renal Replacement Options

• 3 therapeutic options
• Hemodialysis
• Peritoneal Dialysis
• Transplantation

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Introduction

• Pancreas Tx is performed to provide a self
  regulated endogenous source of insulin and other
  islets hormones and restoring the normal
  metabolism, with the ultimate goals being
  prevention , stabilization or reversal of
  secondary degenerative complications of DM which
  develop in spite of a well conducted exogenous
  insulin therapy.
• ( Life enriching procedure)

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Types of Pancreas Transplantation
3 groups of patient can be considered for whole
organ pancreas transplantation
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Types of Pancreas Transplantation

• SIMULTANEOUS KIDNEY PLUS PANCREAS TX
• Advantage Most common type
• Only one histo-compatibility antigens
• Only one surgical procedure is required .
• The same immunosuppressive drugs is used
• No recurrence diabetic nephropathy after SKP
• Early detection of Pancreas rejection Changes
  in renal function are the first and most reliable
  indicators of rejections of both organs .
• Hyperglycemia is too late a sign of rejection

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Types of Pancreas Transplantation

• PANCREAS AFTER KIDNEY TX
• Advantage
• -Patients are already immuno-suppressed
• Disadvantage
• -Second surgical procedure
• -More HLA mis-matching .
• -Advanced diabetic complications
• -Mediocre results.

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Types of Pancreas Transplantation

• PRE-UREMIC PANCREAS ALONE TX
• Indication
• -Pre-uremic nephropathy (Cr/Cl gt50ml/min.)
• -Instable DM
• -Evolutive retinopathy or neuropathy
• Dis-advantages
• -Side effect of IS ( Ciclosporine A
  nephrotoxicity )
• -No monitoring for rejection

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Criteria For Pancreas Tx Alone In Non Uremic
IDDM

• 1-Nephropathy ( Pre uremic or non uremic)
• Albuminuria
• Mesganium lt 30 glomerular volume.
• Creatinine Clearance gt50 ml/min.
• 2-Retinopathy Pre-proliferative or proliferative
  stage
• 3-Neuropathy
• Sensory loss , Pain , Motor dysfynction.
• Sever autonomic dysfunction
• 4-Sever dysmetabolism ( hyper-labile diabetes )
• Frequent episodes of hypoglycemia and
  ketoacidosis

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Thank you for your attention
Dr Ashraf ABDELMAGED DONIA, MD,