Glomerulopathies. 1

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Glomerulopathies. 1

  1. 1.  Glomerulitis is the exact term of inflammation of glomeruli but as there is usualy affection of the adjacent tubules and interstitial tissue, so the term Glomerulonephritis It can refer to a process that is inflammatory or non- inflammatory, so the term Glomerulopathy
  2. 2. Nephritic Glomerulopathies Nephrotic Glomerulopathies= Active Urinary Sediment = Bland Urinary Sediment• RBCs (dysmorphic) • Proteinuria• RBCs casts • Hyaline casts• +/- Proteinuria (usually non nephrotic) • Lipiduria (oval fat bodies)
  3. 3. Nephritic Glomerulopathies Nephrotic Glomerulopathies= Active Urinary Sediment = Bland Urinary Sediment• RBCs (dysmorphic) • Proteinuria• RBCs casts • Hyaline casts• +/- Proteinuria (usually non nephrotic) • Lipiduria (oval fat bodies)Parts affected of Glomeruli: Parts affected of Glomeruli: 1. Mesangial cells 1. Podocyte (Epithelial Cells) 2. Endothelial Cells 2. GBM 3. GBM
  4. 4.  Situated retroperitoneally on either side of the vertebral column, at the level of T12-L3, where they underlie the costovertebral angles posteriorly. The right kidney is about 1.5 cm lower than the left, and both move up and down about 3cm during respiration.
  5. 5. 1 renal papilla, 15 interlobular vein,2 renal column, 16 renal sinus,3 capsule, 17 arcuate vein,4 renal pyramid, 18 medulla,5 calyx, 19 vasa recta,6 ureter, 20 loop of Henle,7 renal pelvis, 21 collecting duct,8 renal vein, 22 arcuate vein,9 renal artery, 23 arcuate artery,10 interlobar artery, 24 proximal convoluted11 arcuate artery, tubule,12 interlobular artery, 25 glomerulus,13 interlobar vein, 26 Bowman’s capsule,14 cortex, 27 distal convoluted tubule
  6. 6. 1 renal papilla,2 renal column,3 capsule,4 renal pyramid,5 calyx,6 ureter,7 renal pelvis,8 renal vein,9 renal artery, 15 interlobular vein, 21 collecting duct, 26 Bowman’s10 interlobar artery, 16 renal sinus, 22 arcuate vein, capsule,11 arcuate artery, 17 arcuate vein, 23 arcuate artery, 27 distal convoluted12 interlobular artery, 18 medulla, 24 proximal convoluted tubule13 interlobar vein, 19 vasa recta, tubule,14 cortex, 20 loop of Henle, 25 glomerulus,
  7. 7. 1 renal papilla, 15 interlobular vein,2 renal column, 16 renal sinus,3 capsule, 17 arcuate vein, 144 renal pyramid, 18 medulla,5 calyx, 19 vasa recta,6 ureter, 20 loop of Henle,7 renal pelvis, 21 collecting duct,8 renal vein, 22 arcuate vein, 159 renal artery, 23 arcuate artery,10 interlobar artery, 24 proximal convoluted11 arcuate artery, tubule,12 interlobular artery, 25 glomerulus,13 interlobar vein, 26 Bowman’s capsule,14 cortex, 27 distal convoluted tubule
  8. 8. Arteries (down) Veins (up)Abdominal aorta Vena cavaRenal artery Renal veinSegmental arteries -Lobar arteries -Interlobar artery Interlobar veinArcuate arteries Arcuate veinInterlobular artery Interlobular veinAfferent arterioles Efferent arteriolesGlomerulus Glomerulus
  9. 9. Kidney glomeruli. Coloured scanning electron micrograph (SEM)The core of a glomerulus is a tightly coiled balls of capillaries. The cast was made by injecting resin into the blood vessels. The surrounding tissues were then chemically digested.
  10. 10. `` 1. 1- Glom. Cap. 2. 2- Bowman`s capsule 3. 3- Afferent a. 4. 4- Efferent a. 5. 5- PCT 6. 6- DCT 7. 7- Collecting tubule 8. 8- Juxtaglomerular app Affarent a. is wider than the efferent a.
  11. 11. 4 nm 40 nmAlbumin 3.5 nmRBC 6-8 um
  12. 12. Subepithelial spaceSubendothelial space
  13. 13. Sub-epithelial and sub-endothelial spaces The subepithelial space (between GBM and epithelial cells) is relatively immunologically privileged, compared to the subendothelial space (between vascular endothelium and GBM). Immune deposits in subepithelial region of the glomerulus tend to result in proteinuria without much in the way of active inflammation. Whereas those in the subendothelial space (as may be seen in postinfectious GN and mesangiocapillary GN) tend to result in ‘nephritic syndrome’, with haematuria and urinary casts.
  14. 14. A - Renal corpuscleB - Proximal tubuleC - Distal convoluted tubuleD - Juxtaglomerular apparatus1. Basement membrane (Basal lamina)2. Bowmans capsule - parietal layer3. Bowmans capsule - visceral layer3a. Pedicels (podocytes)3b. Podocyte or sometimes calledBowmans cells4. Bowmans space (urinary space)5a. Mesangium - Intraglomerular cell5b. Mesangium - Extraglomerular cell6. Granular cells (Juxtaglomerular cells)7. Macula densa8. Myocytes (smooth muscle)9. Afferent arteriole10. Glomerulus Capillaries11. Efferent arteriole
  15. 15. Nephritic Glomerulopathies Nephrotic Glomerulopathies= Active Urinary Sediment = Bland Urinary Sediment• RBCs (dysmorphic) • Proteinuria• RBCs casts • Hyaline casts• +/- Proteinuria (usually non nephrotic) • Lipiduria (oval fat bodies)Parts affected of Glomeruli: Parts affected of Glomeruli: 1. Mesangial cells 1. Podocyte (Epithelial Cells) 2. Endothelial Cells 2. GBM 3. GBM
  16. 16. Nephritic Glomerulopathies Nephrotic Glomerulopathies= Active Urinary Sediment = Bland Urinary Sediment• RBCs (dysmorphic) • Proteinuria• RBCs casts • Hyaline casts• +/- Proteinuria (usually non nephrotic) • Lipiduria (oval fat bodies)Parts affected of Glomeruli: Parts affected of Glomeruli: 1. Mesangial cells 1. Podocyte (Epithelial Cells) 2. Endothelial Cells 2. GBM 3. GBM
  17. 17.  Primary: Pathology limited to kidney Secondary: kidney involvement as manifestation of systemic disease Focal: < 50% of glomeruli involved Diffuse: > 50% of glomeruli involved Global: Involvement of the whole glomerulus Segmental: Involvement of part of the glomerulus Proliferative: increased no of glomerular cells ( resident and infiltrative) Cresentic GN: Cresent shaped collection of cells in Bowman`s capsule associated e` RPGN Sclerosis: scarred area -acellular - presumed irreversible
  18. 18. Normal Proliferative
  19. 19. Non Inflammatory NatureBland urine sediment NephroticEpithelial Cells + GBMCirculating Factor or in Situ ICInflammatory NatureActive urine sediment NephriticEndothelial + Mesangial+GBMCirculating IC + Others Both 1+2 Nephrotic & Nephritic2 + Cresent Formation Rapidly Progressive
  20. 20. Non Inflammatory NatureBland urine sediment NephroticEpithelial Cells + GBMCirculating Factor or in Situ ICInflammatory NatureActive urine sediment NephriticEndothelial + Mesangial+GBMCirculating IC + Others Both 1+2 Nephrotic & Nephritic2 + Cresent Formation Rapidly Progressive
  21. 21. 1. Proteinuria: • Adult: > 3.5 gm/ day • Children: > 40 mg/m2/hour (N: < 4mg/m2/h).2. Hypoalbuminemia3. Bland urine sediment4. Hyperlipedemia5. Edema
  22. 22. Primary causes: Minimal Change Disease Focal Segmental glomerulosclerosis Membranous NephropathySecondary causes: Diabetes Mellitus Amyloidosis Drugs: gold, lithium, penicillamin, NSAIDs
  23. 23.  The dipstick  The dipstick results Dipstick Protein Conc. results have the Negative the following have < 150 mg / day following approximate Trace 150 mg /day approximate correlations with +1 correlations protein mg /day 300 with protein + 2 concentration: 1000 mg /day concentration: +3 3000-4000 mg /day +4 > 5000 mg /day
  24. 24. MCD Normal
  25. 25.  Prednisolone: 60 mg/m2/daily given early in the morning for 6 weeks followed by 40 mg/m2 every other morning for an additional 6 weeks. Or slower taper of 60 mg/m2 every other morning for 4 weeks, tapering further by 10 mg/m2 every 4 weeks for an additional 20 weeks. 95% will experience complete remission. 60-75% will develop relapse. Relapse treated with another steroid coarse but with slower tapering. Frequent relapse and steroid resistant: cyclosporin, tacrolimus or MMF.
  26. 26.  Prednisolone: single morning dose of 1 mg/kg/day, maximum of 80 mg, is continued for a minimum of 8 weeks. For those patients not in remission at 8 weeks, daily prednisone may be continued for another 2 months until remission is attained. A gradual taper is then recommended on an every-other- day schedule until the patient is tapered off over many months.
  27. 27. MINIMAL CHANGE DISEASE
  28. 28. NORMAL PODOCYTES
  29. 29. Effacement or fusion of podocytes
  30. 30. Minimal Change Disease (MCD) Fused podocytes Normal glomerulus Minimal changes of glomeruli
  31. 31. ??? An 8-year-old boy complains of nausea and vomiting and fatigue. On examination, he is oedematous and his blood pressure is 160/100 mmHg. Blood urea and serum creatinine levels are normal. Urine microscopy shows oval fat bodies. 24-hour urine protein is 2g. The doctor plans to start a course of corticosteroids, which he says will cure the condition.
  32. 32. ??? An 8-year-old boy complains of nausea and vomiting and fatigue. On examination, he is oedematous and his blood pressure is 160/100 mmHg. Blood urea and serum creatinine levels are normal. Urine microscopy shows oval fat bodies. 24-hour urine protein is 2g. The doctor plans to start a course of corticosteroids, which he says will cure the condition.
  33. 33. ??? A 6-year-old boy presents with oedema of his face and ascites. The 24-hour urinary protein is 4.0 g, while the serum albumin concentration is 25 g/l. Hypertriglyceridaemia is present.
  34. 34. ??? A 6-year-old boy presents with oedema of his face and ascites. The 24-hour urinary protein is 4.0 g, while the serum albumin concentration is 25 g/l. Hypertriglyceridaemia is present.
  35. 35. ??? A 28-year-old woman presents with painless lymphadenopathy in her neck region. She has had fevers and night sweats intermittently over the past few weeks, weight loss and generalised malaise. She has abandoned her Friday nights out after work due to abdominal pain after drinking alcohol. On examination there is neck lymphadenopathy, abdominal fullness (which may be ascites) and peripheral oedema. Routine initial bloods reveal a decreased serum albumin concentration, and a 24-h urine collection reveals a protein excretion of 4.5 g over a 24-h period (< 0.2 g/24 h). Initial renal biopsy shows no significant abnormality.
  36. 36. ??? A 28-year-old woman presents with painless lymphadenopathy in her neck region. She has had fevers and night sweats intermittently over the past few weeks, weight loss and generalised malaise. She has abandoned her Friday nights out after work due to abdominal pain after drinking alcohol. On examination there is neck lymphadenopathy, abdominal fullness (which may be ascites) and peripheral oedema. Routine initial bloods reveal a decreased serum albumin concentration, and a 24-h urine collection reveals a protein excretion of 4.5 g over a 24-h period (< 0.2 g/24 h). Initial renal biopsy shows no significant abnormality.
  37. 37. ??? A 28-year-old woman presents with painless lymphadenopathy in her neck region. She has had fevers and night sweats intermittently over the past few weeks, weight loss and generalised malaise. She has abandoned her Friday nights out after work due to abdominal pain after drinking alcohol. On examination there is neck lymphadenopathy, abdominal fullness (which may be ascites) and peripheral oedema. Routine initial bloods reveal a decreased serum albumin concentration, and a 24-h urine collection reveals a protein excretion of 4.5 g over a 24-h period (< 0.2 g/24 h). Initial renal biopsy shows no significant abnormality.
  38. 38. Light microscopy (LM): only focally (in some glomeruli – especially juxtamedullar ones) asegmentally (only in some segments of glomeruli) presence and sclerotisation of glomerularloops, caused by accumulation of acellular matrix with adhesions to Bowman´s.capsule(hyalinosis).
  39. 39. Normal Glomerulus Prehilar FSGS
  40. 40. FSGS – basic histological typesPerihilar FSGS: most common Tip lesion FSGS: more often Collapsing FSGS: rare variant, corticosensitive ? often secondary (HIV)
  41. 41.  It has become the most common diagnosed primary glomerular disease reported in most published kidney biopsy series. 30-40% in adult, 10% in children It is the fourth most common cause of ESRD, following diabetes, hypertension, and glomerulonephritis not otherwise specified. Among children it is the second leading cause of ESRD, following congenital kidney anomalies.
  42. 42. FSGS: Clinical Full blown picture of NS  HTN is more common (young adult with HTN)  RFT is impaired in 60% at presentation Spontaneous remission is rare. Poor response to steroid (20-30%).
  43. 43. Secondary FSGS Secondary FSGS  Drugs  Heroin1. HIV  Analgesics2. Heroin  Viruses  HIV3. Sickle cell  Hepatitis B  Parvovirus4. Obesity  Hemodynamic factors - With5. Reflux nephropathy reduced renal mass  Solitary kidney  Renal allograft  Renal dysplasia  Renal agenesis  Vesicoureteric reflux
  44. 44. Secondary FSGS Secondary FSGS  Hemodynamic causes - Without reduced renal mass1. HIV  Massive obesity  Sickle cell nephropathy2. Heroin  Congenital cyanotic heart disease3. Sickle cell  Malignancies  Lymphomas4. Obesity  Other malignancies  Scarring - Postinflammatory in5. Reflux nephropathy postinfectious glomerulonephritis  Miscellaneous6. Lymphomas  Hypertensive nephrosclerosis  Alport syndrome  Sarcoidosis  Radiation nephritis
  45. 45. Patogenesis of primary FSGS Permeability factor: Increased glomerular permeability and injury to podocytes.
  46. 46. FSGS: Pathology LM:  focal segmental glomerular sclerosis (hyalinosis) is seen, especially in juxtamedullary glomeruli.  In HIV: Collapsed appearance of glomeruli. IF: IgM and C3 in these sclerotic areas. EM: Effacement of foot processes + segmental sclerosis (not immune complexes). No immune deposits. Histopathology may be normal and confused for MCD.
  47. 47. FOCAL SEGMENTAL GLOMERULOSCLEROSIS
  48. 48. FOCAL SEGMENTAL GLOMERULOSCLEROSIS
  49. 49. FOCAL SEGMENTAL GLOMERULOSCLEROSIS (IF)
  50. 50. FSGS: recurrence after Tx Recurrence may occur in up to 70% of patients. It may occur immediately after transplant, or it may take months or years to recur. Prevention: Plasmapheresis or immunoadsorption pre and post-transplant.
  51. 51. Q 1 The pathogenesis of focal glomerulosclerosis (FSGS) is unknown. Increased glomerular permeability and injury to podocytes have been postulated as possible aetiological factors.
  52. 52. Q 1 The pathogenesis of focal glomerulosclerosis (FSGS) is unknown. Increased glomerular permeability and injury to podocytes have been postulated as possible aetiological factors.
  53. 53. Q 2 A 32-year-old Afro–Caribbean man with a 5-year history of HIV infection presents with swollen ankles. He has been treated with highly active antiretroviral therapy (HAART) for 2 years, with partial response. His plasma creatinine concentration is 358 umol/l, albumin is 12 g/dl, CD4 count is 35/u l and 24-hour urine protein excretion rate is 6.8 g. Renal ultrasound shows echogenic kidneys 13.5 cm in length. What would a renal biopsy show?  Focal necrotising crescentic nephritis  Kimmelstiel–Wilson lesions  Membranous nephropathy  Microcystic tubular dilatation and collapsing FSGS  Minimal-change disease
  54. 54. Q 2 A 32-year-old Afro–Caribbean man with a 5-year history of HIV infection presents with swollen ankles. He has been treated with highly active antiretroviral therapy (HAART) for 2 years, with partial response. His plasma creatinine concentration is 358 mmol/l, albumin is 12 g/dl, CD4 count is 35/u l and 24-hour urine protein excretion rate is 6.8 g. Renal ultrasound shows echogenic kidneys 13.5 cm in length. What would a renal biopsy show?  Focal necrotising crescentic nephritis  Kimmelstiel–Wilson lesions  Membranous nephropathy  Microcystic tubular dilatation and collapsing FSGS  Minimal-change disease
  55. 55. Q 3 A 38-year-old man presents with fever, increased symptoms of asthma, and hypertension. His GP has also noticed that a sample of faeces was positive for blood. On examination he looks pale, his BP Is 155/92 mmHg and he has a palpable purpuric rash. Auscultation of the chest reveals signs consistent with asthma.
  56. 56. Q 3  Which of the following are the most likely findings on renal biopsy?  Glomerulosclerosis  Focal segmental glomerulonephritis  Minimal change disease  Membranous glomerulonephritis  Large vessel vasculitis
  57. 57. Q 3  Which of the following are the most likely findings on renal biopsy?  Glomerulosclerosis  Focal segmental glomerulonephritis  Minimal change disease  Membranous glomerulonephritis  Large vessel vasculitis
  58. 58. FSGS: Facts  Focal segmental glomerulonephritis may occur as a primary disease, but it is also seen in  Systemic lupus erythematosus,  Subacute infective endocarditis  Shunt nephritis (infected atrioventricular shunts)  Henoch–Schönlein purpura  IgA nephropathy.  Vasculitis
  59. 59.  Normal Glomerulus  thin GBM (equivalent to tubular basement membrane)  mesangium limited to stalk of capillary tuft (double arrows)  Membranous Nephropathy  thick GBM (in relation to tubular basement membrane)  mesangial expansion (asterisks)images from www.uptodate.com
  60. 60.  Immunofluorescence  diffuse granular IgG deposits along GBM  Silver Stain  spike pattern in GBM highlights deposits between new GBMimages from www.uptodate.com
  61. 61.  Normal EM  thin, homogenous GBM  epithelial cell with foot processes  fenestrated endothelial cell (arrow) Membranous EM  thick GMB, with deposits (D)  effacement of foot processes
  62. 62. MN: Facts MN is a leading cause of idiopathic nephrotic syndrome in adults (30–40%) and a rare cause in children (< 5%). Peak incidence is between 30 and 50 years of age and Male:female ratio is 2:1. 1/3 of MN is secondary to  HBV  SLE  Drugs: gold, penicillamin, NSAIDs and captopril.  Malignancy: Solid Tumour (adenocarcinoma of GI and squamous cell ca of lung)
  63. 63. Membranous Nephropathy Rule of Thirds 1/3 1/3 1/3Spontaneous Subnephrotic ESRD Remission Proteinuria
  64. 64. MN:Histopathology Light microscopy the glomerular basement membrane is uniformly thickened. IF granular deposits of immunoglobulins and complements are distributed along the basement membrane. EM reveals subepithelial deposits with spike and dome pattern-later incorporating into GBM, thickening of basement membrane and loss of foot process of podocytes.
  65. 65. MEMBRANOUS GLOMERULONEPHRITIS
  66. 66. Lai KN. Kidney Int 2007; 71: 841–843
  67. 67. MEMBRANOUS GLOMERULONEPHRITIS
  68. 68. MEMBRANOUS GLOMERULONEPHRITIS (IF)
  69. 69. MEMBRANOUS GLOMERULONEPHRITIS (EM)
  70. 70. MN: Renal Vein Thrombosis RVT occurs in 35% of NS patients.  The most common is MN 20-60% The important risk factor: S. Albumin ≤ 25 gm/l May be unilateral or bilateral Clinical: flank pain + hematuria (gross or microscopic) + enlarged kidney size + marked ↑ of LDH. If bilateral  AKI will occur. Diagnosis: IVC gram with selective renal venography, CT, MR. doppler US may reveal false +ve and -ve result. Therapy: Anticoagulant (Heparin and Warfarin), Thrombolytic tharapy and rarely surgical removal
  71. 71. Q 1 Membranous glomerulopathy is associated with:  Idiopathic nephrotic syndrome in children  Adenocarcinoma of the stomach  Elevated anti-nuclear antibody levels  Selective proteinuria  A progressive course ending in end-stage renal disease (ESRD)
  72. 72. Q 1 Membranous glomerulopathy is associated with:  Idiopathic nephrotic syndrome in children  Adenocarcinoma of the stomach  Elevated anti-nuclear antibody levels  Selective proteinuria  A progressive course ending in end-stage renal disease (ESRD)
  73. 73. Q 2 A 65-year-old man with a known history of lung cancer presents with anorexia, malaise and drowsiness. A CT scan shows metastatic lesions in the liver. Laboratory test results are as follows: Hb, 7.8 g/dl; WCC, 11.5 x 109/l; Ferritin, 5.0 nmol/l; Urea, 27 mmol/l; Creatinine, 377 µmol/l; 24 hour urine protein, 3.8g. A renal biopsy shows focal subepithelial deposition of IgG and C3.A probable diagnosis is: Focal segmental glomerulosclerosis Nodular glomerulosclerosis Microcytic hypochromic anaemia Minimal change glomerulonephropathy Membranous glomerulonephropathy
  74. 74. Q 2 A 65-year-old man with a known history of lung cancer presents with anorexia, malaise and drowsiness. A CT scan shows metastatic lesions in the liver. Laboratory test results are as follows: Hb, 7.8 g/dl; WCC, 11.5 x 109/l; Ferritin, 5.0 nmol/l; Urea, 27 mmol/l; Creatinine, 377 µmol/l; 24 hour urine protein, 3.8g. A renal biopsy shows focal subepithelial deposition of IgG and C3.A probable diagnosis is: Focal segmental glomerulosclerosis Nodular glomerulosclerosis Microcytic hypochromic anaemia Minimal change glomerulonephropathy Membranous glomerulonephropathy
  75. 75. Q 3 A 47-year-old man attends the outpatient clinic complaining of swelling in the ankles and lethargy. On examination, his blood pressure is 160/90 and he is found to have pitting oedema in both legs. Laboratory investigations reveal: Hb 11.5 g/dl, Urea 35 mmol/l, Creatinine 275 µmol/l , Hepatitis B antigen Positive ,Anti-nuclear antibodies NegativeWhat is the probable diagnosis? Membranous glomerulonephritis Hepatitis B infection Acute interstitial nephritis Renal tubular acidosis Systemic lupus erythematosus
  76. 76. Q 3 A 47-year-old man attends the outpatient clinic complaining of swelling in the ankles and lethargy. On examination, his blood pressure is 160/90 and he is found to have pitting oedema in both legs. Laboratory investigations reveal: Hb 11.5 g/dl, Urea 35 mmol/l, Creatinine 275 µmol/l , Hepatitis B antigen Positive ,Anti-nuclear antibodies NegativeWhat is the probable diagnosis? Membranous glomerulonephritis Hepatitis B infection Acute interstitial nephritis Renal tubular acidosis Systemic lupus erythematosus
  77. 77. Q 4 A 32-year-old woman presents with bilateral flank pain. Her GP had diagnosed a urinary tract infection 2 weeks earlier on the basis of proteinuria, but she returned with further pain, tiredness and general malaise. He noted a raised serum creatinine of 285  mol/l at this time. Repeat urinalysis revealed blood and protein, but no bacterial growth and no active urinary sediment. Her only past medical history is that she discontinued the oral contraceptive pill after a DVT.
  78. 78. Q 4 A 32-year-old woman presents with bilateral flank pain. Her GP had diagnosed a urinary tract infection 2 weeks earlier on the basis of proteinuria, but she returned with further pain, tiredness and general malaise. He noted a raised serum creatinine of 285  mol/l at this time. Repeat urinalysis revealed blood and protein, but no bacterial growth and no active urinary sediment. Her only past medical history is that she discontinued the oral contraceptive pill after a DVT.What diagnosis fits best with this clinical picture? Nephrotic syndrome Nephritic syndrome Inadequately treated UTI with associated renal failure Ciprofloxacin-associated nephritis Bilateral renal vein thrombosis
  79. 79. Q 4 A 32-year-old woman presents with bilateral flank pain. Her GP had diagnosed a urinary tract infection 2 weeks earlier on the basis of proteinuria, but she returned with further pain, tiredness and general malaise. He noted a raised serum creatinine of 285  mol/l at this time. Repeat urinalysis revealed blood and protein, but no bacterial growth and no active urinary sediment. Her only past medical history is that she discontinued the oral contraceptive pill after a DVT.What diagnosis fits best with this clinical picture? Nephrotic syndrome Nephritic syndrome Inadequately treated UTI with associated renal failure Ciprofloxacin-associated nephritis Bilateral renal vein thrombosis
  80. 80. Diabetes Diagnostic criteria of DN Most common cause of NS In diabetic patient (>10 DM-1, in adult. may be at diagnosis in DM-2) development of: Most common cause of  Persistent proteinuria ESRD worldwide. >300mg/24h  In presence of HTN, P. retinopathy, RF and absense of other causes
  81. 81. Pathology Pathogenesis Wide spread thickening of the GBM  Advanced glycosylation end products accounts for thickening of GBM & Diffuse glomerulosclerosis (increase in increased mesangial matrix (seen in mesangial matrix & mild proliferation of all patients) mesangial cells) Nodular glomerulosclerosis ( hyaline  Hemodynamic effects associated with mass within mesangial core- glomerular hypertrophy leads to Kimmelsteil-Wilson disease) glomerulosclerosis Hyalinization of arteriolar walls. IF may demonstrate immunoglobulins and complement in the glomeruli. EM regularly shows marked thickening of the GBM and increased mesangial matrix material.
  82. 82.  Nodular glomerulosclerosis (Kimmelstiel-Wilson lesion) of diabetes mellitus. Nodules of pink hyaline material form in regions of glomerular capillary loops in the glomerulus. This is due to a marked increase in mesangial matrix from damage as a result of non-enzymatic glycosylation of proteins.
  83. 83. <30mg/day30-300mg/day >300mg/d
  84. 84.  Amyloidosis is due to the systemic extracellular deposition of:  Antiparallel, β-pleated sheet  Nonbranching  8- to 12-nm fibrils  Stain positive with Congo red (Apple green birefringence with polarized light). Amyloidosis is frequently confirmed by biopsy of the abdominal fat, kidney, or, in the case of AL amyloidosis bone marrow
  85. 85.  Primary (AL) amyloidosis:  AL amyloidosis: a single population (or clone) of plasma cells grows excessively and produces abnormal proteins which are deposited as amyloid fibrils in tissues and organs.  AL amyloidosis can occur spontaneously, however, it is often associated with other blood disorders, such as multiple myeloma and Waldenströms macroglobulinemia  kidneys are affected in 50% of patients.  Patients are typically older than 50 years.  Common renal manifestations include proteinuria, nephrotic syndrome (25% of patients), and renal failure.
  86. 86.  Primary (AL) amyloidosis:  Immunofluorescence generally demonstrates λ light chains in the glomeruli (75% of patients).  For patients with cardiac involvement, the prognosis is poor, with a median survival of less than 2 years.  Treatment with prednisone and melphalan can be beneficial in some patients. In selected cases, high dose melphalan followed by bone marrow transplantation has led to resolution of the disease.
  87. 87.  Secondary (AA) amyloidosis  Most common in patients with rheumatoid arthritis, inflammatory bowel disease, chronic infection, or familial Mediterranean fever and in subcutaneous drug users (heroin).  Treatment of AA amyloidosis is directed at the underlying inflammatory process. Colchicine is helpful in patients with familial Mediterranean fever.
  88. 88. Amyloid deposits in the lip and tongue are present in this patient. Note the "scalloped"appearance of the tongue in which indentations are present on both sides (arrows). This occurs because the enlarged tongue chronically presses against the upper teeth.
  89. 89. Pale deposits of amyloid are present in the cortex, most prominently at the upper center. (arrow)
  90. 90. The amorphous pink depositis of amyloid may be found in and around arteries, in interstitium, or in glomeruli, as seen here with H&E stain.
  91. 91. Amyloid deposits are seen in glomeruli at the left and in arteries at the right
  92. 92. Glomerulus from renal biopsy stained with congo red and examined by polarization microscopy. The characteristic "apple-green" birefringence of amyloid is apparent
  93. 93. Glomerulus from renal biopsy stained with congo red and examined by polarization microscopy. The characteristic "apple-green" birefringence of amyloid is apparent
  94. 94.  Overwhelming infection  Loss of opsonising factors in the urine w` is imp against encapsulated bacteria such as Pneumococcus and Hemophilus influenza.  Hypogammaglobulinemia Thromboembolism  Children: sagittal sinus thrombosis, pulmonary artery thrombosis, or inferior vena caval thrombosis  Adults: deep vein or renal vein thrombosis.  The hypercoagulable state results from:  Increased clotting factor synthesis (fibrinogen, II, V, VII, IX, X, XIII)  Urinary losses of anticoagulants (antithrombin III)  Platelet abnormalities (thrombocytosis, increased aggregability)  Hyperlipidemia Cardiovascular complications related to hyperlipidemia. Acute kidney injury: secondary to decreased renal perfusion and edema of the renal interstitium.
  95. 95. Infection Clinical features Common organisms Antibiotics, duration Abdominal pain, tenderness, Cefotaxime or ceftriaxone for distension; diarrhea, vomiting; ascitic S. pneumoniae, S. pyogenes,Peritonitis fluid >100 leukocytes/mm3; >50% E. coli 7-10 days; ampicillin and an aminoglycoside for 7-10 days neutrophils Fever, cough, tachypnea, intercostal S. pneumoniae, H. influenzae, Oral: amoxicillin, co-Pneumonia recessions, crepitations S. aureus amoxiclav, erythromycin Parenteral: ampicillin and aminoglycoside; or cefotaxime/ceftriaxone for 7- 10 days Cutaneous erythema, induration, Staphylococci, Group A Cloxacillin and ceftriaxone forCellulitis tenderness streptococci, H. influenzae 7-10 days co-amoxiclavFungal Skin, mucosa: fluconazole for Pulmonary infiltrates, persistent Candida, Aspergillus spp.infections 10 days Fever unresponsive to antibiotics, Systemic: amphotericin for 14- sputum/urine showing septate hyphae 21 days
  96. 96.  Vaccines:  23-valent pneumococcal vaccine: for all adults and all children older than 2 years.  Influenza vaccine: yearly  Childhood vaccines : Children should receive all  Live virus vaccines (measles-mumps-rubella, varicella) may postponed until they are in remission off of immunosuppressive medications.  The administration of live virus vaccine may be associated with a relapse  Varicella-zoster IgG titer: should be checked in all patients (Varicella infections in individuals who are immune compromised, may be fatal).  If the patient does not have a protective titer against varicella, vaccine should be given if possible.  If the patient cannot receive vaccine because of continued immunosuppression, varicella- zoster immune globulin (VZIG) should be administered.  If a patient who is immunosuppressed develops zoster, he or she should receive immediate treatment with intravenous acyclovir.
  97. 97.  Reduction of thromboembolic complications:  Protecting the intravascular volume of a critically ill patient in relapse.  Central venous catheters should be avoided whenever possible.  If a patient experiences a thromboembolic event, treatment should include heparin or low molecular weight heparin, followed by warfarin for 6 months. Therapy for chronic hyperlipidemia. Hypertension is best treated initially with an ACE inhibitor and/or an ARB, which should help reduce the risk of cardiovascular complications later.

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