The document discusses renal failure including definitions of acute renal failure (ARF), chronic renal failure (CRF), and end-stage renal disease (ESRD). It covers classifications and common causes of renal failure. Key points include that ARF can be pre-renal, renal, or post-renal in origin and has many potential causes. CRF is a slow, progressive loss of kidney function that is irreversible and can be caused by diabetes, hypertension, glomerulonephritis, and other conditions. Monitoring of renal function includes tests of serum creatinine and clearance rates.

1. R enal F ailure : acute, chronic &ESRD Saeed M.G. Al-Ghamdi, FRCPS,FACP Faculty of Medicine King Abdulaziz University Hospital

2. RF : Items for Discussion Definitions of ARF, CRF & ESRD Classification & causes of RF Statistics Presentations Investigations Treatment

3. ARF : Definition Abrupt decline of Glomerular filtration rate which is potentially reversible

4. ARF: Statistics Prevalence: In 5% of medical-surgical ward admission In 25% of non-emergent surgery In 15% of ICU admission Mortality: Oliguric ARF: 50-80% Non-Oliguric ARF: 15-40% Risk of death: 6.2 folds

5. ARF: Classification & Causes Pre-renal ARF : 40-80% Renal ARF: 20-30% Post-renal ARF : 2-10%

6. Pre-renal Causes: 1) Extra-renal fluid loss: Vomiting Continuous un-replaced NG suctioning Continuous un-replaced drainage Diarrhea , intestinal fistula Pancreatitis Intestinal obstruction Excessive Sweating & heat stroke ,burns

7. Pre-renal Causes: 2) Renal fluid loss Osmotic Diuretics: hyperglycemia, mannitol Loop and thiazide diuretics Un-replaced post-obstructive diurecis 3) Change in renal hemodynamics ACEI in bilateral Renal Artery Stenosis NSAIDS in patient with dehydration or CHF

8. Pre-renal Causes 4) Cardiac causes Due to renal hypo-perfusion In severe systolic heart failure (EF <15%) Severe valvular heart disease Arrhythmias: Complete Heart Block Cardiac temponade Right Ventricular Infarction Severe core pulmonale

9. ARF: Pre-renal Causes 5) Peripheral vasodilatation: Anti-hypertensive drugs 6) Hepato-Renal Syndrome Due to renal vaso-constrictors & third spacing In advanced irreversible liver disease Other causes of ARF should be ruled out Very low urine sodium (<10)

10. Renal Causes of ARF 1) acute tubular necrosis (ATN) Septic syndrome (with & without hypotension) Significant bleeding leading to prolonged hypotension Severe dehydration leading to prolonged hypotension Cardiogenic shock Severe PET & ET

11. Renal Causes of ARF (Cont..) 2 ) Toxic and pigment-induced ATN Aminoglycoside nephrotoxicity Amphotericin-induced nephrotoxicity Contrast-nephropathy Hemoglobinuria (severe intravascular hemolysis) Myoglobinuria (Rhabdomyolysis)

12. Renal Causes of ARF (Cont..) 3) Glomerular diseases and systemic vasculitis Rapidly progressive Glomerulonephritis (RPGN) Immune-complex nephritis: (post-infectious GN, lupus nephritis, HSP, ..Etc.) Anti-GBM disease Pauci-immune nephritis: Wegener's Granulomatosis

13. Renal Causes of ARF (Cont..) 4) acute interstitial nephritis Drug-induced (NSAIDS, beta lactam antibiotics,rifampicin, furosemide, allopurinol ..Etc.) Auto-immune (SLE, Sjogren syndrome, HES ) Infection-related (Legionella, salmonella ,..Etc.) Sarcoidosis Idiopathic

14. Renal Causes of ARF (Cont..) 5) Acute Pyelonephritis In transplant kidney In single functioning kidney 6) Acute Allograft Rejection 7) Lymphomatous Infiltration of the kidneys In HIV+ve Patients PTLD

15. ARF: Renal Causes 8) renal vasular & Ischemic disorders Vasculitis Scleroderma renal crisis Malignant HTN TTP, HUS, DIC Renal artery thrombosis Renal vein thrombosis Cholesterol Athero-embolic disease

16. ARF: Renal Causes (contin..) 9) acute cortical necrosis (ACN) In association with hypotension and DIC Abruptio placenta, placenta previa IUFD Presentation: Loin pain Anuria Gross hematuria Cortical calcification (after healing)

17. Renal Causes of ARF (Cont..) 10) acute papillary necrosis Acute Pyelonephritis in diabetic Sickle cell disease Phenacetin-induced nephropathy Pesentation: Loin pain Oligo-anuria Passage of tissues (papillae)

18. ARF : Presentation (Cont..) Features suggest renal causes of ARF History of arthritis and or arthralgia Recent drug exposure Recent surgery and or intervention Recent URTI or tonsillitis Peri-orbital and facial edema HTN and absence of signs of hypovolemia Vasculitis or livedo reticularis

19. ARF: Post-renal Causes Intra-renal (tubular) obstruction : (medical) Acute uric acid nephropathy Calcium oxalate Crystalluria: ethylene glycol poisoning or high dose vitamin C Myeloma cast nephropathy IV Methotrexate crystalluria IV acylovir and oral Indinavir crystalluria Sulfonamides crystalluria (sulfadiazine, SMZ)

20. Post-renal Causes of ARF Extra- renal ( tubular ) obstruction (surgical) Ureteral/pelvic Intrinsic: tumor, stone, clot, papilla Extrinsic: retroperitoneal and pelvic malignancies , fibrosis and ligation Bladder: stones, clots, tumor, neurogenic, BPH, Prostatic ca , post-operative Uretheral: PUV , stone …etc

21. ARF: Causes Vasculitis & thrombosis & CAED ACEI & NSAID in predisposed patients Acute GN Severe cardiac failure Surgical obstruction Interstitial nephritis Systemic vaso-dilatation Intra-tubular obstruction ATN Renal & extra-renal fluid loss Post-renal Renal Pre-Renal

22. Renal Artery Thrombosis In hyper-coagulable states Presentation: Severe loin pain Gross hematuria Complete anuria if bilateral Diagnosis by Doppler, IVP & Angiogram Treated by thrombolysis and or heparin

23. Renal Vein Thrombosis : S&S L oin pain Macro and or Microhematuria Proteinuria ARF if bilateral or single kidney Diagnosed by U/S Doppler Spiral CT Renal venography

24. RVT : Predisposing Factors Severe dehydration in neonates Severe nephrotic syndrome (S.Alb.<20 g) Hypercoagulable states Protein S or C deficiency Anti-Phospholipids antibody syndrome Homocysteinuria Malignancies

25. Cholesterol Athero-embolic Disease Predisposing factors Follows intravascular intervention May follow bellow renal vascular surgery May occur after anti-coagulation May occur spontaneously

26. CAED : Presentation 3-6 weeks after vascular instrumentation Progressive rise of S.Creatinine Livedo Reticularis Gangrenous toes and peripheral skin Thrombocytopenia Eosinophilia Hypocomplementemia Diagnosed by kidney biopsy

27. ARF : Presentation Features suggest pre-renal. Vomiting, diarrhea , NGT ..Etc. Uncontrolled DM. Diuretic use. Exposure to sun and hot weather. Postural hypotension and tachycardia. Low JVP. Dry axilla and mucous membranes.

28. ARF : Investigations Rapidly rising S.Cr. & hyperkalemia U/S kidneys & bladder Urine analysis RBCs and RBC casts suggest GN WBCs and WBC casts suggest AIN or acute pyelonephritis Brown granular casts suggest ATN

29. ARF : Investigations (Cont..) Urine Eosinophils : In AIN Urine myoglobulin : in Rhabdomyolysis Urine hemoglobin : in Hemoglobinuria Urine sodium : <10 mmol/l, suggest pre-renal Na + Excretion Fraction: <1% suggest pre-renal > 3% suggest ATN

30. ARF: Investigations Fractional excretion of sodium: U Na X P Cr FENa: ----------------- X 100 = P Na X Ucr < 1%: Pre-renal > 3%: ATN

31. ARF : Investigations (Cont..) Positive ANA & Anti-dsDNA in lupus nephritis Low C 3 & C 4 in : Lupus nephritis Pos-infectious GN MPGN Falsely positive RF in cryoglobulinemia

32. ARF : Investigations (Cont..) Positive ANCA. Wegener's Granulomatosis. Microscopic Poly-Angiitis. Poly-Arteritis Nodosa. Positive Anti-GBM in Good Pasture ’ s syn. Monoclonal band in Serum and or urine electrophoresis in patients with paraprotein.

33. ARF : Investigations (Cont..) CBC Neutrophilic Leucocytosis in infection Eosinophilia in allergic interstitial nephritis Leucopenia & Thrombocytopenia suggest SLE Prolonged PT & PTT and low fibrinogen in DIC and sepsis Prolonged uncorrectable PTT in SLE

34. ARF: Treatment First: Treatment of the underlying cause Second: Conservative treatment of established ARF Third: Dialysis if indication (s) arise

35. I) Treatment According to the Cause of ARF Pre-Renal Failure: Hydration Post-Renal Failure: Relieve obstruction Catheterization DJS Nephrostomy Dialysis if indication arises Replace urine output ( Post-Obstructive Diurecis)

36. I) Treatment According to the Cause of ARF (contin..) ATN and sepsis: IV Fluids (colloids & crystalloid) Inotropes (Dopamine, Norepinephrine) Antibiotics Furosemide In established ARF: Conservative treatment If indication for dialysis: CRRT

37. I) Treatment According to the Cause ARF (contin..) Drug-induced ATN: Discontinue the offending drug (s) Avoid nephrotoxins Conservative treatment of established ARF Recovery is the rule If indication for dialysis arises: HD, PD or CRRT

38. I) Treatment According to the Cause of ARF (contin..) Rhabdomyolysis (early with non-oliguria) Urine alkalinization with Na bicarbonate Mannitol Furosemide Rhabdomyolysis (late with oliguria) Conservative treatment of established ARF Hemodialysis if indications arise

39. II) Conservative Treatment of Established ARF Daily Fluid Intake : the previous 24 h urine output + insensible water loss Hyperkalemia: Low K + diet Calcium resonium Insulin + dextrose Inhaled Beta agonist Calcium gluconate iv (in EKG changes)

40. II) Conservative Treatment of Established ARF (contin..) Metabolic acidosis: IV Sodium bicarbonate (in severe cases) oral Na bicarbonate (in mild to moderate cases) May cause volume overload Protein intake: if catabolic, low protein diet Medications: Adjust the dose to Cr. clearance Avoid nephrotoxins

41. I) Treatment According to the Cause of ARF (contin..) Allergic Interstitial Nephritis Stop the offending drug Prednisolone 1mg/kg/d for 6 weeks Hemodialysis if indication arise Acute Pyelonephritis Hydration Amp+genta in uncomplicated Ceftazidime or ciproflox. + genta (complicated)

42. CRF: definition Chronic, slow, indolent, progressive deterioration of Glomerular filtration rate which is irreversible

43. CRF: Causes DM: 30% HTN: 26% Glomerulonephritis : 14% Other causes: 30% Chronic interstitial diseases Obstructive Uropathy ADPKD

44. CRF: Causes in Children Congenital renal hypoplasia and dysplasia. Vesico-Ureteric Reflux. Congenital cystic diseases. ARPKD. Multicystic disease. MCD (Juvenile Nephronophthasis). Obstructive diseases: PUV, etc....

45. CRF: Causes in Children Congenital glomerulonephritis Alport’s syndrome Congenital FSGS Glomerulonephritis Unresponsive GN DMS HUS Congenital HUS Post-diarrheal HUS

46. CRF: Presentation In mild to moderate disease; GFR >40 ml/min. As ymptomatic. Incidental discovery of high urea & Cr. Discovery of concomitant or causative disease, e.g... PKD, etc.... Hypertension.

47. CRF: Presentation (Cont...) In moderate to moderately severe CRF: GFR> 15 mls/min and < 40 mls/min Polyuria & polydepsia Generalized fatigue Sexual dysfunction Bruiritis Bone pain and muscle weakness

48. CRF: Diagnosis Requires three perquisites: Co-existence of disease that cause CRF Evidence of Progressive Renal Dysfunction Evidence of Extra-renal uremic organ dysfunction

49. CRF: Diagnosis Coexistence of disease that cause CRF Long standing DM (>10 years) Long standing uncontrolled HTN Remote history of hematuria or proteinuria Recurrent upper UTI Recurrent nephrolithiasis Painful conditions with chronic analgesic abuse Family history of PKD

50. CRF: Diagnosis (contin.) Evidence of Progressive Renal Dysfunction Previously documented elevated serum creatinine Radiological evidence of signs of chronicity by U/S Hyperechoic cortices Small shrunken kidneys

51. CRF: Diagnosis (Continued) Evidence of Extra-renal organ dysfunction Anemia of chronic disease (due to decrease EPO & decrease RBC survival) Renal Osteodystrophy: Decrease S. Ca ++ Increase S. PO4 -- Increase ALP & iPTH Sub-periosteal bone resumption (MCP, Phalanges, and clavicles)

52. CRF: Investigations S. Creatinine: ( > 120 mic.mol/l) S. potassium: (usually normal) S. calcium: (normal or low) S. phosphorus: (usually high) Alkaline phosphatase: (usually high) CBC: Normochromic normocytic anemia

53. CRF: Investigations (Continued) Urine analysis: Specific gravity: (1.010) RBCs: (only in patients with Chronic GN) Casts: (granular casts) Urine is bland (benign)

54. CRF: Investigations (Continued) Ultrasound kidneys: (signs of chronicity) Hyperechoic cortices Poor cortico-medullary differentiation Small sized kidneys (< 9 cm) EXCEPT Diabetic Nephropathy Malignant Hypertension Amyloidosis PKD

55. CRF: Monitoring Renal Function Serum creatinine: (70-120 mic.mol/l) Affected by muscle mass, sex & protein intake Cr.clearance = Cr U × V (urine volume) /Cr P (80-120 mls/min) Affected by: Muscle mass, sex, and protein intake Increase tubular secretion of creatinine in RF Decrease tubular secretion by cimetidine & CoTMZ

56. CRF: Monitoring Renal Function Cockroft & Gault equation: Cr Cl.= (140- age) × wt /Cr P Reliable in steady state Clearance of 125 I-isothalamate, 99 Tc-DTPA: rapid and accurate

57. Uremic Osteodystrophy: Pathogenesis Hyperphosphatemia: Due to Decrease GFR leads to decrease PO4-- excretion Hypocalcemia: due to Binding with P leads to precipitation of Ca-P byproduct Decrease calcium absorption from gut due to low level of calcitriol

58. Uremic Osteodystrophy: Pathogenesis (contin.) Low level of active Vit D (1,25-dihyroxy-cholecalciferol) Due to: unavailability of alpha hydroxylase This lead to hypocalcemia and unsuppressed Parathyroid gland High PTH: due to: Low level of calcitriol (1,25 DHCC) Hypocalcemia

59. Uremic Osteodystrophy Hyperphosphatemia Low 1,25 DHCC Hypocalcemia Hyperparathyoidism

60. CRF: Treatment Aggressive treatment of the underlying disease Aggressive control of blood sugar (DCCT 93) Optimal control of BP Discontinue all nephrotoxins Relieve Urinary Tract Obstruction Treat underlying auto-immune disease Suppress UTI in recurrent upper UTI

61. CRF: Treatment (Continued) Attenuate the hyperfiltration ACE Inhibitors and Angiotensin Receptors Antagonists (especially in DM) Low Protein Diet; 0.8g/kg BW (MDRD) Avoid all Nephrotoxins NSAIDS Aminoglycosides

62. CRF: Treatment (Continued) Treat Uremic Bone Disease Lower serum Phosphate Low Phosphate diet Calcium carbonate, or Calcium acetate, or Renagel with meal (phosphate binders) Suppress PTH & increase Ca ++ absorption Calcitriol or alfacalcidol (0.25-1.0 mic.g/day)

63. Treat. Uremic Osteodystrophy Calcitriol or Alfacalcidol Calcium Carbonate Low Phosphate Diet + +

64. CRF: Treatment (Continued) Treat anemia of CRF Iron sulfate or fumarate rh-Erythropoeitin Usually when GFR <15mls/minute Only if Hgb significantly low (<9g) After replacing Iron stores Target Hgb level (11.0-12.0g, Hct 33-36) Folic acids and multivitamins

65. CRF: Treatment (Continued) Prepare Patient for Renal Replacement Therapy (when GFR < 15 ml/minute) AVF for hemodialysis PD catheter (Tenkhoff’s catheter ) for PD Transplant workup Urological & medical assessment Radiological investigations Tissue matching (ABO, HLA & LYMPHOCYTE)

66. ESRD: definition Permanent loss of GFR to the extent where renal replacement therapy is to be instituted

67. ESRD: Statistics 330,000 patients on RRT worldwide 70% on HD 9% on PD 21% has functioning renal transplants Incidence in USA: 240 PMP Incidence in KSA: 139-215 PMP Mortality:

68. ESRD : Presentation Euremic Enchephalopathy Nausea & vomiting & hiccup Lethargy, sleepiness, drowsiness and coma Myoclonic jerks & seizures Uremic Pericarditis Chest pain Pericardial rub Pericardial effusion and temponade

69. RRT: Modalities Hemodialysis Peritoneal Dialysis Renal Transplantation Living-Related, Living-Unrelated Cadaveric CRRT CAVH, CVVH, SCUF CAVHD,CVVHD, CAVHDF, CVVHDF

70. RRT: Absolute Indications for Dialysis Fluid Overload Hyperkalemia Severe Metabolic Acidosis Uremic Pericarditis Uremic Enchephalopathy Intoxication: Methanol, ethylene glycol ASA, & Lithium

71. RRT: Relative Indications for Dialysis Uremic Neuropathy Malnutrition of CRF Correct bleeding time before surgery Cr. clearance <10 ml/minute Level of urea & creatinine ??

72. Hemodialysis: Dialyzer Arterial blood from Patient Venous blood to patient Incoming Dialysate solution out going dialysate

73. Hemodialysis: Principles Solutes are effectively removed by diffusion Water is removed by convection (UF) Both mechanisms contribute to solute removal

74. Peritoneal Dialysis: Types Continuos Ambulatory Peritoneal Dialysis (CAPD) 4 cycles of 2 liter of dialysate Intermittent Peritoneal Dialysis (IPD) Whole day or night for 2-3 times/ week Continuos Cyclic Peritoneal Dialysis (CCPD) Eight , 2 liters exchanges during night

75. Peritoneal Dialysis: Principle Diffusion: for solutes From high concentration gradient to low concentration gradient Osmosis: for water Depends on concentration of sugar in the dialysate fluid The fluid and solute removal can be enhanced by increasing the volume of dialysate and the number of exchanges

76. Peritoneal Dialysis: CAPD, IPD PD dialysate solution PD Catheter Hanger Connection set draining bag

77. PD: Advantages A more normal life-style Better residual renal function Less stringent fluid and diet restriction Stable solutes concentration (no dysequilibrium) Better hemoglobin level More economic: 2/3 of HD cost

78. PD: Complications CAPD PERITONITIS Abdominal pain Fever Turbid effluent WBC in effluent >400 Organisms: Staph. aureus and epidermedis Gram negative: Klebseilla, pseudomonas Candida

79. CAPD PERITONITIS: Treatment 3 flushes in & out Loading dose Intraperitoneal antibiotics: Cefazoline and Tobramycin Or Vancomycin & Tobramycin Maintenance dose IP antibiotics: Change antibiotics according to sensitivity

80. CAPD: Complications & Treat. Tunnel infection Pain and swelling at tunnel site Fever Treatment: Vancomycin IV Exit site infection Redness at exit site with discharge Cloxacillin or Vancomycin

81. CAPD: Complications & Treat. Catheter leak Treatment: Temporary conversion to HD Catheter dysfunction: causes Constipation: laxatives Fibrin: IP heparin Omental wrap May require replacement

82. CAPD: Complications Obesity & hypertriglyceridemia Due to excessive absorption of glucose Protein loss & hypoalbuminemia Loss with the effluent Bloody Effluent: Ruptured corpus leutium (ovulation) Endometriosis

83. CRRT: Types CAVH: UF only CVVH: UF only SCUF: slow UF CAVHD: Dialysis CVVHD: Dialysis CAVHDF: UF & Dialysis CVVHDF: UF & Dialysis

84. CRRT: Principle Ultrafiltration: The main driving force Diffusion: slow and efficient only with time Patient need replacement of fluid loss up to 18 liters/ day (in CAVH, CVVH, CAVHDF & CVVHDF)

85. CRRT: CAVH Arterial Venous UF Replacement Qb=50-100 ml/min Qf= 8-12 ml/min

86. CRRT: CAVHD Arterial Venous Dialysate out Qb=50-100 ml/min Qd=10-20 ml/min Qf= 1-3 ml/min Dialysate In

87. CRRT: CVVH Venous Venous UF Replacement Qb=50-200 ml/min Qf= 10-20 ml/min Pump

88. CRRT: CVVHD Venous Venous Dialysate out Qb=50-200 ml/min Qd=10-30 ml/min Qf= 1-5 ml/min Dialysate In Pump

89. CRRT: Indications Acute Renal failure in hemodynamically unstable patient & MOF Volume control in septic patient with no Renal failure Removal of mediators of sepsis Refractory Congestive Heart Failure ARF in acute and chronic liver disease Tumor lysis syndrome, lithium intox.?

90. RF : Natural History

91. RF: Differences Always present Usually present Not present Uremic bone disease Usually low May be normal or high Usually low May be normal or high Usually high May be normal Serum K + 1.010 Bland Sediment Sp.gr.: 1.010 Bland sediment Sp.gr.:>1.020 May be active sediment Urine analysis Polyuria or normal Polyuria Anuria, oliguria on non-oliguria Urine output Permanent no function Slow, progressive, irreversible Rapid decline Reversible GFR ESRD CRF ARF