Nephrotic Syndrome

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Dr Chow Yok Wai
Hospital Kuala Lumpur

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Nephrotic Syndrome

  1. 1. Complications of Nephrotic syndrome
  2. 2. Introduction <ul><li>3/100,000 (adults) </li></ul><ul><ul><ul><ul><ul><li>Llach, 1984 Postgraduate Medicine </li></ul></ul></ul></ul></ul><ul><li>Proteinuria >3.5g/24h </li></ul><ul><li>Lipiduria </li></ul><ul><li>Anasarca </li></ul><ul><li>Minimal change disease </li></ul><ul><li>Membranous GN </li></ul><ul><li>FSGS </li></ul>
  3. 3. Introduction <ul><li>1950’s- infection was commonest cause of death </li></ul><ul><li>Now  thromboembolic events </li></ul>
  4. 4. Complications nephrotic syndrome <ul><li>selective loss of low molecular weight protein in the urine </li></ul><ul><li>overproduction of all hepatically synthesized proteins </li></ul><ul><li>accumulation of the higher molecular weight species </li></ul><ul><li>proteins smaller than 180–200 kDa show lower plasma concentrations, and above this size increased levels. </li></ul>
  5. 6. Nephrotic Oedema <ul><li>EFP (effective filtration pressure)  ( P c − P i ) − (π c − π i ) </li></ul><ul><li>Underfill theory </li></ul><ul><li>Overfill theory </li></ul>
  6. 7. Nephrotic Oedema- Underfill (classical) theory <ul><li>Albuminuria not compensated by increased hepatic synthesis  reduction in COP  decrease in plasma volume  stimulate RAAS, sympathetic nervous system and supress atrial natriuretic peptide (ANP)  renal sodium and water retention </li></ul>
  7. 8. Nephrotic Oedema- Underfill (classical) theory <ul><li>Elevated plasma renin, aldosterone </li></ul><ul><ul><ul><ul><li>Rasher, Journal of Paeds, 1985 </li></ul></ul></ul></ul><ul><li>Non osmotic increase in production of ADH </li></ul><ul><li>Increase plasma and urinary cathecholamines </li></ul><ul><ul><ul><ul><li>Usberti, KI, 1984 </li></ul></ul></ul></ul>
  8. 9. Nephrotic Oedema- Arguments against Underfill (classical) theory <ul><li>However, reduction in blood/plasma volume not shown in all studies </li></ul><ul><ul><ul><ul><li>Vande Walle, Lancet 1995 </li></ul></ul></ul></ul><ul><li>Renal sodium water retention found in many pt with mild reduction in serum albumin </li></ul><ul><ul><ul><ul><li>Vande Walle, Lancet 1995 </li></ul></ul></ul></ul><ul><li>Natriuresis precedes increase in plasma albumin </li></ul><ul><ul><ul><ul><li>Brown, Nephron, 1982 </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Koomans, Nephron, 1987 </li></ul></ul></ul></ul><ul><li>Correction of intravscular volume didn’t correct the natriuresis </li></ul><ul><ul><ul><ul><li>Remuzzi, AJKD, 1993 </li></ul></ul></ul></ul>
  9. 10. Nephrotic Oedema- Overfill theory <ul><li>Primary renal disturbance  sodium and water retention </li></ul>
  10. 11. Nephrotic Oedema- treatment <ul><li>Low salt diet? </li></ul><ul><li>Diuretics </li></ul><ul><ul><li>Many are diuretic resistance </li></ul></ul><ul><ul><ul><li>Decrease delivery to tubules from reduced GFR </li></ul></ul></ul><ul><ul><ul><li>Low serum albumin promotes distribution of drug in extravascular space </li></ul></ul></ul><ul><ul><ul><li>IVI preferred as it prevents postdiuretic rebound sodium reabsorption </li></ul></ul></ul><ul><ul><ul><ul><ul><li>Kramer, Am J Med, 1999. </li></ul></ul></ul></ul></ul><ul><ul><ul><li>Bumetemide may be better as metabolised by liver </li></ul></ul></ul><ul><ul><ul><li>Metalazone- success in few studies </li></ul></ul></ul><ul><ul><ul><li>Spironolactone- if elevated aldosterone level </li></ul></ul></ul>
  11. 12. Nephrotic Oedema- treatment <ul><li>IV salt free albumin </li></ul><ul><ul><li>100mls of 20% </li></ul></ul><ul><ul><li>Can lead to circulatory overload and hypertension if diuresis is not induced </li></ul></ul><ul><ul><li>Using it alone has little effect </li></ul></ul><ul><ul><ul><ul><ul><li>Rabelink, KI, 1994 </li></ul></ul></ul></ul></ul><ul><li>Diuretic vs Diuretic + IV albumin </li></ul><ul><ul><li>No advantage in combination </li></ul></ul><ul><ul><ul><ul><ul><li>Akcicek, BMJ, 1995 </li></ul></ul></ul></ul></ul><ul><ul><li>Beneficial </li></ul></ul><ul><ul><ul><ul><ul><li>Fliser, KI, 1999 </li></ul></ul></ul></ul></ul><ul><li>Suggest- EOD Diuretics+Albumin to allow re-equilibration of interstitial and plasma albumin. Up to 40L/2 weeks can be removed by this regime </li></ul>
  12. 13. Nephrotic Oedema- treatment <ul><li>Gentle dialysis </li></ul><ul><ul><ul><li>HD </li></ul></ul></ul><ul><ul><ul><li>PD </li></ul></ul></ul><ul><ul><ul><ul><li>Fauchald, Acta Medica Scandinavia, 1985 </li></ul></ul></ul></ul><ul><ul><li>? Albumin use + UF </li></ul></ul>
  13. 14. Infection
  14. 15. Infections in nephrotic patients <ul><li>important cause of deaths in children with NS even today: 6/10 deaths in 389 children with minimal change NS were from sepsis </li></ul><ul><ul><ul><li>International Study of Kidney Disease in Children 1984 </li></ul></ul></ul><ul><li>higher in children treated with cytotoxic drugs than in those treated with prednisone alone </li></ul><ul><ul><li>chlorambucil (6.5 per cent) </li></ul></ul><ul><ul><li>cyclophosphamide (1.5 per cent) </li></ul></ul><ul><ul><ul><ul><li>Latta, K., vom Schnakenburg, C., and Ehrich, J. H. H. (2001). A meta-analysis of cytotoxic treatment for frequently relapsing nephrotic syndrome in children. Pediatric Nephrology 16 , 271–282. </li></ul></ul></ul></ul>
  15. 16. Primary peritonitis <ul><li>particular feature of children with NS </li></ul><ul><li>older patients have been noted </li></ul><ul><ul><ul><ul><ul><li>Chuang, T. F. et al . (1999). Spontaneous bacterial peritonitis as the presenting feature in an adult with nephrotic syndrome. Nephrology, Dialysis, Transplantation 14 , 181–182. </li></ul></ul></ul></ul></ul><ul><li>Onset- insidious </li></ul><ul><li>usually sudden </li></ul><ul><li>abdominal pain </li></ul><ul><li>diagnosis must be confirmed by direct microscopic examination of a Gram stain or an immunochemical search for bacterial antigens in ascitic fluid </li></ul><ul><li>Blood cultures are usually positive </li></ul><ul><li>Hypotension, shock, and even acute renal failure  DIVC </li></ul>
  16. 17. Primary peritonitis <ul><li>Streptococcus pneumoniae (commonest) </li></ul><ul><ul><li>Up to 50% </li></ul></ul><ul><ul><li>Penicillin-resistant strains of S. pneumoniae are now emerging </li></ul></ul><ul><ul><ul><li>Giebink, G. S. (2001). The prevention of pneumococcal disease in children. New England Journal of Medicine 345 , 1177–1183. </li></ul></ul></ul><ul><li>β-haemolytic streptococci </li></ul><ul><li>Haemophilus </li></ul><ul><li>Gram-negative Gorensek et al . 1988 ). </li></ul>
  17. 18. Cellulitis <ul><li>Spontaneous/ result of venepuncture </li></ul><ul><li>B-hemolytic strep </li></ul><ul><li>Gm –ve </li></ul><ul><li>Toxic, febrile, septic shock </li></ul><ul><li>Blood C+S usu +ve </li></ul>
  18. 19. Other infections <ul><li>Viral infections  varicella, measles esp those with steroids/cytotoxics </li></ul><ul><li>Bacterium alkaligenes </li></ul><ul><li>Bacteroides </li></ul><ul><li>Aerobacter </li></ul><ul><li>Streptococcus viridans </li></ul><ul><li>Tuberculosis </li></ul>
  19. 20. Pathogenesis of infections <ul><li>Physical factors </li></ul><ul><ul><li>Fluid collection in cavities </li></ul></ul><ul><ul><li>Ruptures fragile skin </li></ul></ul><ul><ul><li>Dilution of local humoral defences by oedema </li></ul></ul><ul><li>Immunological factors </li></ul><ul><ul><li>Low IgG (but need to be <2g/L) </li></ul></ul><ul><ul><ul><li>Tend to be chronic, staph, sinopulmonary site </li></ul></ul></ul>
  20. 21. Alternative complement pathway <ul><li>spontaneous hydrolysis of C3 </li></ul><ul><li>allows the binding of plasma protein Factor B </li></ul><ul><li>allows Factor D to cleave Factor B into Ba and Bb. </li></ul><ul><li>Bb- C3 convertase </li></ul><ul><li>consists of the activated B and D factors </li></ul>
  21. 22. Alternative complement pathway <ul><li>stable after binding properdin </li></ul><ul><li>cleave multiple C3 proteins into C3a and C3b </li></ul>
  22. 23. Pathogenesis of infections <ul><ul><li>Factor B, Factor I </li></ul></ul><ul><ul><ul><li>Alternative pathway of complement system </li></ul></ul></ul><ul><ul><ul><li>Approx 55kDa </li></ul></ul></ul><ul><ul><ul><li>Lost in urine </li></ul></ul></ul><ul><ul><ul><li>Imp in opsonization of encapsulated organisms eg strep pneumoniae </li></ul></ul></ul><ul><ul><li>Transferrin </li></ul></ul><ul><ul><ul><li>Essential for lymphocyte function </li></ul></ul></ul><ul><ul><ul><li>Carrier for zinc </li></ul></ul></ul><ul><ul><ul><li>Lost of Transferrin-Zinc  diminished production of Zn dependent thymic hormone thymulin </li></ul></ul></ul><ul><ul><li>Reduced lymphocyte/polymorph function </li></ul></ul>
  23. 24. Treatment <ul><li>Induce remission ASAP </li></ul><ul><li>Pt with previous pneumococcal infection  prophylactic penicillin </li></ul><ul><li>Pneumococcal vaccine  start 14 days after discontinuing high dose steroids/cytotoxics </li></ul><ul><li>IV antibiotics- broad spectrum </li></ul><ul><li>Varicella zoster </li></ul><ul><ul><li>Zoster Immune Globulin within 72h of contact </li></ul></ul><ul><ul><li>IV acyclovir </li></ul></ul>
  24. 25. Thromboembolic complications
  25. 26. Thromboembolic complications <ul><li>Arterial/venous circulation </li></ul><ul><ul><li>10% nephrotic adults </li></ul></ul><ul><ul><li>50% nephrotic adults (subclinical) </li></ul></ul><ul><ul><li>1.8% (paeds) </li></ul></ul><ul><ul><ul><li>Higher levels of 92-macroglobulin (thrombin inhibitor) </li></ul></ul></ul><ul><ul><li>Highest risk in adult Membranous nephropathy </li></ul></ul><ul><li>What is the cause? </li></ul><ul><ul><li>Abnormalities of coagulation </li></ul></ul>
  26. 27. Commonest presentation <ul><li>DVT +/- PE </li></ul><ul><li>Renal vein thrombosis </li></ul><ul><li>Hepatic vein thrombosis </li></ul><ul><li>Budd Chiari syndrome </li></ul><ul><li>Intracranial venous sinus thrombosis </li></ul>
  27. 28. Concentrations of proteins important in coagulation in the nephrotic syndrome in relation to molecular weight Reduced 54,000 α 1 -Antitrypsin Raised–normal 65,000 Protein C Normal–reduced 68,000 Antithrombin III Normal–reduced 70,000 α 2 -Antiplasmin Normal–reduced 75,000 Protein S Normal–reduced 81,000 Plasminogen Raised 840,000 α 1 -Macroglobulin Regulator proteins Normal–reduced 55,400 Factor IX Normal–reduced 56,000 Factor X Normal–reduced 72,000 Factor II (prothrombin) Normal–reduced 79,000 Factor XII Normal–reduced 160,000 Factor XI Raised–normal 200,000 Factor VII Raised 330,000 Factor I (fibrinogen) Raised 350,000 Factor V Raised 840,000 Von Willebrand factor Zymogens and cofactors Concentration in nephrotic plasma MW (Da) Protein
  28. 29. Physical Factors <ul><li>Immobility </li></ul><ul><li>Haemoconcentration from hypovolaemia </li></ul><ul><li>Increase blood viscosity </li></ul><ul><ul><li>Changes in red cell deformability </li></ul></ul><ul><ul><li>Increase fibrinogen </li></ul></ul><ul><ul><ul><li> favours margination of platlets and increased platlet aggregability </li></ul></ul></ul><ul><ul><ul><ul><li>Zwaginga, J. J. et al . (1994). Thrombus formation and platelet vessel wall interaction in the nephrotic syndrome under flow conditions. Journal of Clinical Investigation 93 , 204–211. </li></ul></ul></ul></ul>
  29. 30. Alterations in zymogen (enzyme precursors) and cofactors <ul><li>Increase  VWF, fibrinogen, FV, X, VII </li></ul><ul><li>Fibrinogen and FVII – independent variables predicting vascular disease </li></ul><ul><ul><ul><ul><li>Cameron, J. S. (1984). Thromboembolic complications of the nephrotic syndrome. Advances in Nephrology 13 , 75–114. </li></ul></ul></ul></ul>
  30. 31. Alterations in fibrinolytic, regulator proteins and platlet function <ul><li>Low antithrombin III </li></ul><ul><li>Low plasminogens </li></ul><ul><li>Low functional Protein S +/- C </li></ul><ul><li>Hyperaggregability of platlets </li></ul><ul><li>Increased TxA2 </li></ul><ul><li>LDL enhance platlet aggre via adenylate cyclase </li></ul><ul><li>LDL inhibits prostacyclin on endothelial cells </li></ul><ul><li>HDL has opposite effect from LDL </li></ul>
  31. 32. Alterations in fibrinolytic, regulator proteins and platlet function <ul><li>LDL is enriched with lysolecithin </li></ul><ul><ul><li>Toxic to endothelial cells </li></ul></ul><ul><ul><ul><li>Reduce NO production </li></ul></ul></ul><ul><ul><ul><ul><li>Diminished platlet adhesion </li></ul></ul></ul></ul><ul><li>Hyperaggregability to ristocetin </li></ul><ul><ul><li>? d/t increased vWF </li></ul></ul><ul><ul><li>?altered charge on platlets </li></ul></ul><ul><li>Impaired response to endothelium dependent vasodilatation </li></ul>
  32. 33. Summary :- <ul><li>Loss of antithrombin III </li></ul><ul><li>Loss of Protein S </li></ul><ul><li>Increase Fibrinogen </li></ul><ul><li>Platlets hyperactive d/t increase responsiveness to ADP </li></ul><ul><ul><ul><ul><ul><li>Llach , Postgraduate Medicine, 1984 </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Vigano D’Angelo, Annals of Int Med, 1987 </li></ul></ul></ul></ul></ul>
  33. 34. Role of drugs <ul><li>Steroids </li></ul><ul><ul><li>Increases some zymogens </li></ul></ul><ul><ul><li>Decrease PT, PTT </li></ul></ul><ul><ul><li>Anta Warfarin effect </li></ul></ul><ul><ul><li>But increase ATIII and inhibit platlet aggregation at high doses </li></ul></ul><ul><li>Diuretics </li></ul><ul><ul><li>Increases blood viscosity (d/t increase fibrinogen) </li></ul></ul><ul><ul><ul><ul><li>Lilova, M. I., Velkovski, I. G., and Topalov, I. B. (2000). Thromboembolic complications in children with nephrotic syndrome in Bulgaria. Pediatric Nephrology 15 , 74–78. </li></ul></ul></ul></ul>
  34. 35. Peripheral venous thrombosis and PE <ul><li>DVT </li></ul><ul><ul><li>3-12% </li></ul></ul><ul><ul><li>25% by doppler USG </li></ul></ul><ul><li>PE </li></ul><ul><ul><li>0-15% </li></ul></ul><ul><ul><li>9-12% via V/Q scan </li></ul></ul><ul><ul><li>Mortality:- </li></ul></ul><ul><ul><ul><li>Hemodynamically stable  8.1% </li></ul></ul></ul><ul><ul><ul><li>Cardiogenic shock  25% </li></ul></ul></ul><ul><ul><ul><li>Need CPR  65% </li></ul></ul></ul><ul><ul><li>Recurrence: 28% (diagnosed via V/Q) </li></ul></ul><ul><li>Other venous thrombi </li></ul><ul><ul><li>Renal vein thrombosis </li></ul></ul><ul><ul><li>Subclavian, axillary, jugular, iliac, portal, splenic, hepatic, mesenteric vein thrombosis </li></ul></ul><ul><ul><li>Sagittal sinus thrombosis </li></ul></ul><ul><ul><ul><ul><li>Cameron et al 1984, 1988 </li></ul></ul></ul></ul>
  35. 36. Arterial Thrombosis <ul><li>Less common than venous thrombosis </li></ul><ul><li>Occurred in almost every artery </li></ul><ul><li>Some multiple arterial thrombi </li></ul><ul><li>Some combined arterial and venous thrombosis </li></ul><ul><li>Commonest  femoral artery </li></ul>
  36. 37. Renal Vein Thrombosis <ul><li>4-8% in membranous nephropathy </li></ul><ul><ul><ul><ul><li>Cameron et al 1988 </li></ul></ul></ul></ul><ul><li>Up to 50% via venography </li></ul><ul><ul><ul><ul><li>Llach, F. (1985). Hypercoagulability, renal vein thrombosis, and other thrombotic complications of nephrotic syndrome (Nephrology Forum). Kidney International 28 , 429–439. </li></ul></ul></ul></ul><ul><li>13-18% </li></ul><ul><ul><ul><ul><li>Rostoker, G. et al . (1992). Asymptomatic renal-vein thrombosis in adult nephrotic syndrome. Ultrasonography and urinary fibrin–fibrinogen degradation products: a prospective study. European Journal of Medicine 1 , 19–22. </li></ul></ul></ul></ul><ul><li>Men more affected </li></ul><ul><li>35% have PE as well </li></ul><ul><ul><ul><ul><li>Cameron et al 1988 </li></ul></ul></ul></ul>
  37. 38. Renal Vein Thrombosis <ul><li>Loin pain </li></ul><ul><li>Hematuria </li></ul><ul><li>Renal enlargement </li></ul><ul><li>Pain and swelling in ipsilateral testicle in male </li></ul><ul><li>Deterioration of renal function </li></ul><ul><li>Lower limb oedema if vena cava involved </li></ul>
  38. 39. Renal Vein Thrombosis- Prognosis <ul><li>Unknown </li></ul><ul><ul><li>As most are anticoagulated </li></ul></ul><ul><li>Impaired renal function is poor prognostic sign </li></ul>
  39. 40. Treatment/prevention of thromboembolic events <ul><li>Paucity of RCTs </li></ul><ul><li>Only 1 study looking into prophylactic LMWH for TEE in NS </li></ul><ul><ul><ul><ul><ul><li>Rostoker, Nephron, 1995 </li></ul></ul></ul></ul></ul><ul><li>No known standard protocol for :- </li></ul><ul><ul><li>Duration of anticoagulation </li></ul></ul><ul><ul><li>Intensity of anticoagulation </li></ul></ul><ul><ul><li>Type of anticoagulation </li></ul></ul><ul><li>Expert opinion mainly (no evidence) </li></ul>
  40. 41. Prevention <ul><li>Mobilize patient </li></ul><ul><li>Avoid sepsis </li></ul><ul><li>Treat sepsis </li></ul><ul><li>Avoid dehydration </li></ul><ul><li>Judicious use of diuretics </li></ul><ul><li>Minimize haemoconcentration </li></ul>
  41. 42. <ul><li>Heparin acts mainly via activation of AT III (decrease concentration in nephrotics) </li></ul><ul><ul><li>May need higher dose </li></ul></ul><ul><li>Heparin binds to α 2-macroglobulin and endothelial cell surface  may enhance platlet aggregation </li></ul><ul><li>Warfarin  bound to albumin. </li></ul><ul><ul><li>Dosing problem </li></ul></ul>
  42. 43. Should we anticoagulate asymptomatic DVT? <ul><li>Yes </li></ul><ul><li>Heparin UF/LMWH, Warfarin </li></ul><ul><li>INR 2-4 </li></ul><ul><li>When to stop anticoagulation? </li></ul><ul><ul><li>Min 3 months </li></ul></ul><ul><ul><li>6 months </li></ul></ul><ul><ul><li>When stopping, ensure no edema, serum albumin > 25g/l </li></ul></ul>
  43. 44. Prophylactic anticoagulation in nephrotic patients? <ul><li>Yes esp if membranous nephropathy </li></ul><ul><ul><ul><ul><li>Bellomo and Atkins, Nephron, 1993 </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Sarasin and Schifferli, KI, 1994 </li></ul></ul></ul></ul><ul><li>Standard anticoagulants </li></ul><ul><li>Low dose aspirin </li></ul><ul><li>Dipyridamole </li></ul><ul><ul><ul><ul><li>Andrassy, 1980 </li></ul></ul></ul></ul>
  44. 45. Lipid abnormalities
  45. 46. Hyperlipidaemia <ul><li>Commonest complication </li></ul><ul><li>90% of pt with nephrotic range proteinuria </li></ul><ul><li>Contributes to atherosclerosis and progression of renal damage </li></ul><ul><ul><ul><ul><li>Samuelsson, NDT, 1997 </li></ul></ul></ul></ul><ul><li>Correlates inversely with serum albumin </li></ul><ul><li>Independent of cause of nephrosis </li></ul>
  46. 47. Hyperlipidaemia <ul><li>Increase VLDL, IDL, LDL (esp smaller and denser), Tg </li></ul><ul><li>HDL usually normal (decrease in HDL-2, increase in HDL-3) </li></ul><ul><li>Increase in Lp(a) (strong predictor of vascular events in general pop) </li></ul>
  47. 48. Hyperlipidaemia- Pathogenesis <ul><li>Reduced oncotic pressure or albumin concentration  increase transcription of liver regulated proteins </li></ul><ul><li>Infusion of IV albumin reduces cholesterol levels </li></ul><ul><ul><ul><ul><li>Appel, NEJM, 1985 </li></ul></ul></ul></ul><ul><li>Result of increase synthesis and decreased catabolism of lipoprotein </li></ul><ul><li>Impaired conversion of VLDL to LDL </li></ul><ul><li>Increased hepatic LDL secretion </li></ul><ul><li>Increase Lp(a) production by liver </li></ul><ul><li>Impaired HDL maturation </li></ul><ul><li>Decrease receptor mediated clearance of circulating VLDL </li></ul>
  48. 49. Hyperlipidaemia- Pathogenesis <ul><li>Increase synthesis and reduce degradation of Tg </li></ul><ul><li>Loss of ApoC-II in urine </li></ul>
  49. 50. Hyperlipidaemia- consequences <ul><li>Nephrotics </li></ul><ul><ul><li>5.5 fold MI </li></ul></ul><ul><ul><li>2.8 fold coronary death </li></ul></ul><ul><ul><ul><ul><ul><li>Ordonez, KI, 1993 </li></ul></ul></ul></ul></ul><ul><ul><li>No difference from controls </li></ul></ul><ul><ul><ul><ul><ul><li>Wass, Lancet, 1979 </li></ul></ul></ul></ul></ul><ul><li>Duration of hyperlipidaemia is most critical </li></ul><ul><li>Highest risk in patients with unremitting proteinuria </li></ul><ul><li>A/W glomerular and interstitial renal disease in animal studies. Never proven in humans </li></ul>
  50. 51. Hyperlipidaemia- treatment <ul><li>Controversial </li></ul><ul><li>Most extrapolated from general population </li></ul><ul><li>Increase in premature atherosclerosis and MI in nephrotics </li></ul><ul><ul><ul><ul><li>Niaudet, Paediatric nephrology, 1992 </li></ul></ul></ul></ul><ul><li>Independent risk factor for atherosclerotic disease </li></ul><ul><ul><ul><ul><li>Radhakrishnan, AJKD, 1993 </li></ul></ul></ul></ul><ul><li>May promote progression of renal disease </li></ul><ul><ul><ul><ul><li>Falk, 2001 </li></ul></ul></ul></ul>
  51. 52. Hyperlipidaemia- treatment <ul><li>Reduce proteinuria </li></ul><ul><li>Statins </li></ul><ul><li>Nicotinic acid </li></ul><ul><li>Bile acid resins (cholestyramine, colestipol) </li></ul><ul><li>Lipopheresis </li></ul><ul><ul><li>No effect on protein excretion and serum albumin levels </li></ul></ul>
  52. 53. Acute Renal Failure in Nephrotic Syndrome, Hein, NDT 2001 <ul><li>Rapid progression of original glomerular disease </li></ul><ul><li>Renal vein thrombosis </li></ul><ul><li>Allergic interstitial nephritis </li></ul><ul><ul><li>Diuretics </li></ul></ul><ul><ul><li>Antibiotics </li></ul></ul><ul><ul><li>NSAIDS </li></ul></ul><ul><ul><li>Foscarnet </li></ul></ul><ul><ul><li>Interferon alpha </li></ul></ul><ul><li>Sepsis </li></ul><ul><li>ATN </li></ul><ul><li>Tubular obstruction from proteinuria (protein cast) </li></ul>
  53. 54. Acute Renal Failure in Nephrotic Syndrome- Pathology <ul><li>85%- MCD </li></ul><ul><li>60%  ATN findings </li></ul><ul><li>40%  interstitial oedema </li></ul><ul><li>ARF group also have more arteriolosclerosis (intimal hyperplasia amd hyalinosis) </li></ul>
  54. 55. Acute Renal Failure in Nephrotic Syndrome <ul><li>Elderly </li></ul><ul><li>Hypertensive </li></ul><ul><li>Severe proteinuria </li></ul><ul><li>Very low albumin </li></ul><ul><li>2/3  male </li></ul><ul><li>Most have severe oedema </li></ul><ul><li>Time between onset of NS and ARF is 4 weeks </li></ul><ul><li>Recovery usually over 7 weeks </li></ul><ul><ul><ul><ul><li>Smith, AJKD, 1992 </li></ul></ul></ul></ul><ul><li>Children and young adults  progression can be early with fast occurrence and resolution </li></ul><ul><li>Protracted ARF needing dialysis less commonly occur in children </li></ul>
  55. 56. Others <ul><li>Loss of metal binding proteins </li></ul><ul><ul><li>Serum iron/ transferrin </li></ul></ul><ul><ul><li>Caeruloplasmin </li></ul></ul><ul><ul><li>Zinc </li></ul></ul><ul><li>Loss of vitamins and hormones </li></ul><ul><ul><li>Vit D binding protein </li></ul></ul><ul><ul><li>Thyroid binding globulin </li></ul></ul><ul><ul><li>Cortisol binding protein </li></ul></ul><ul><ul><li>Erythropoietin </li></ul></ul>

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