Complications of Nephrotic syndrome

Introduction 3/100,000 (adults) Llach, 1984 Postgraduate Medicine Proteinuria >3.5g/24h Lipiduria Anasarca Minimal change disease Membranous GN FSGS

3/100,000 (adults)

Llach, 1984 Postgraduate Medicine

Proteinuria >3.5g/24h

Lipiduria

Anasarca

Minimal change disease

Membranous GN

FSGS

Introduction 1950’s- infection was commonest cause of death Now  thromboembolic events

1950’s- infection was commonest cause of death

Now  thromboembolic events

Complications nephrotic syndrome selective loss of low molecular weight protein in the urine overproduction of all hepatically synthesized proteins accumulation of the higher molecular weight species proteins smaller than 180–200 kDa show lower plasma concentrations, and above this size increased levels.

selective loss of low molecular weight protein in the urine

overproduction of all hepatically synthesized proteins

accumulation of the higher molecular weight species

proteins smaller than 180–200 kDa show lower plasma concentrations, and above this size increased levels.

Nephrotic Oedema EFP (effective filtration pressure)  ( P c − P i ) − (π c − π i ) Underfill theory Overfill theory

EFP (effective filtration pressure)  ( P c − P i ) − (π c − π i )

Underfill theory

Overfill theory

Nephrotic Oedema- Underfill (classical) theory 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

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

Nephrotic Oedema- Underfill (classical) theory Elevated plasma renin, aldosterone Rasher, Journal of Paeds, 1985 Non osmotic increase in production of ADH Increase plasma and urinary cathecholamines Usberti, KI, 1984

Elevated plasma renin, aldosterone

Rasher, Journal of Paeds, 1985

Non osmotic increase in production of ADH

Increase plasma and urinary cathecholamines

Usberti, KI, 1984

Nephrotic Oedema- Arguments against Underfill (classical) theory However, reduction in blood/plasma volume not shown in all studies Vande Walle, Lancet 1995 Renal sodium water retention found in many pt with mild reduction in serum albumin Vande Walle, Lancet 1995 Natriuresis precedes increase in plasma albumin Brown, Nephron, 1982 Koomans, Nephron, 1987 Correction of intravscular volume didn’t correct the natriuresis Remuzzi, AJKD, 1993

However, reduction in blood/plasma volume not shown in all studies

Vande Walle, Lancet 1995

Renal sodium water retention found in many pt with mild reduction in serum albumin

Vande Walle, Lancet 1995

Natriuresis precedes increase in plasma albumin

Brown, Nephron, 1982

Koomans, Nephron, 1987

Correction of intravscular volume didn’t correct the natriuresis

Remuzzi, AJKD, 1993

Nephrotic Oedema- Overfill theory Primary renal disturbance  sodium and water retention

Primary renal disturbance  sodium and water retention

Nephrotic Oedema- treatment Low salt diet? Diuretics Many are diuretic resistance Decrease delivery to tubules from reduced GFR Low serum albumin promotes distribution of drug in extravascular space IVI preferred as it prevents postdiuretic rebound sodium reabsorption Kramer, Am J Med, 1999. Bumetemide may be better as metabolised by liver Metalazone- success in few studies Spironolactone- if elevated aldosterone level

Low salt diet?

Diuretics

Many are diuretic resistance

Decrease delivery to tubules from reduced GFR

Low serum albumin promotes distribution of drug in extravascular space

IVI preferred as it prevents postdiuretic rebound sodium reabsorption

Kramer, Am J Med, 1999.

Bumetemide may be better as metabolised by liver

Metalazone- success in few studies

Spironolactone- if elevated aldosterone level

Nephrotic Oedema- treatment IV salt free albumin 100mls of 20% Can lead to circulatory overload and hypertension if diuresis is not induced Using it alone has little effect Rabelink, KI, 1994 Diuretic vs Diuretic + IV albumin No advantage in combination Akcicek, BMJ, 1995 Beneficial Fliser, KI, 1999 Suggest- EOD Diuretics+Albumin to allow re-equilibration of interstitial and plasma albumin. Up to 40L/2 weeks can be removed by this regime

IV salt free albumin

100mls of 20%

Can lead to circulatory overload and hypertension if diuresis is not induced

Using it alone has little effect

Rabelink, KI, 1994

Diuretic vs Diuretic + IV albumin

No advantage in combination

Akcicek, BMJ, 1995

Beneficial

Fliser, KI, 1999

Suggest- EOD Diuretics+Albumin to allow re-equilibration of interstitial and plasma albumin. Up to 40L/2 weeks can be removed by this regime

Nephrotic Oedema- treatment Gentle dialysis HD PD Fauchald, Acta Medica Scandinavia, 1985 ? Albumin use + UF

Gentle dialysis

HD

PD

Fauchald, Acta Medica Scandinavia, 1985

? Albumin use + UF

Infection

Infections in nephrotic patients important cause of deaths in children with NS even today: 6/10 deaths in 389 children with minimal change NS were from sepsis International Study of Kidney Disease in Children 1984 higher in children treated with cytotoxic drugs than in those treated with prednisone alone chlorambucil (6.5 per cent) cyclophosphamide (1.5 per cent) 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.

important cause of deaths in children with NS even today: 6/10 deaths in 389 children with minimal change NS were from sepsis

International Study of Kidney Disease in Children 1984

higher in children treated with cytotoxic drugs than in those treated with prednisone alone

chlorambucil (6.5 per cent)

cyclophosphamide (1.5 per cent)

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.

Primary peritonitis particular feature of children with NS older patients have been noted 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. Onset- insidious usually sudden abdominal pain diagnosis must be confirmed by direct microscopic examination of a Gram stain or an immunochemical search for bacterial antigens in ascitic fluid Blood cultures are usually positive Hypotension, shock, and even acute renal failure  DIVC

particular feature of children with NS

older patients have been noted

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.

Onset- insidious

usually sudden

abdominal pain

diagnosis must be confirmed by direct microscopic examination of a Gram stain or an immunochemical search for bacterial antigens in ascitic fluid

Blood cultures are usually positive

Hypotension, shock, and even acute renal failure  DIVC

Primary peritonitis Streptococcus pneumoniae (commonest) Up to 50% Penicillin-resistant strains of S. pneumoniae are now emerging Giebink, G. S. (2001). The prevention of pneumococcal disease in children. New England Journal of Medicine 345 , 1177–1183. β-haemolytic streptococci Haemophilus Gram-negative Gorensek et al . 1988 ).

Streptococcus pneumoniae (commonest)

Up to 50%

Penicillin-resistant strains of S. pneumoniae are now emerging

Giebink, G. S. (2001). The prevention of pneumococcal disease in children. New England Journal of Medicine 345 , 1177–1183.

β-haemolytic streptococci

Haemophilus

Gram-negative Gorensek et al . 1988 ).

Cellulitis Spontaneous/ result of venepuncture B-hemolytic strep Gm –ve Toxic, febrile, septic shock Blood C+S usu +ve

Spontaneous/ result of venepuncture

B-hemolytic strep

Gm –ve

Toxic, febrile, septic shock

Blood C+S usu +ve

Other infections Viral infections  varicella, measles esp those with steroids/cytotoxics Bacterium alkaligenes Bacteroides Aerobacter Streptococcus viridans Tuberculosis

Viral infections  varicella, measles esp those with steroids/cytotoxics

Bacterium alkaligenes

Bacteroides

Aerobacter

Streptococcus viridans

Tuberculosis

Pathogenesis of infections Physical factors Fluid collection in cavities Ruptures fragile skin Dilution of local humoral defences by oedema Immunological factors Low IgG (but need to be <2g/L) Tend to be chronic, staph, sinopulmonary site

Physical factors

Fluid collection in cavities

Ruptures fragile skin

Dilution of local humoral defences by oedema

Immunological factors

Low IgG (but need to be <2g/L)

Tend to be chronic, staph, sinopulmonary site

Alternative complement pathway spontaneous hydrolysis of C3 allows the binding of plasma protein Factor B allows Factor D to cleave Factor B into Ba and Bb. Bb- C3 convertase consists of the activated B and D factors

spontaneous hydrolysis of C3

allows the binding of plasma protein Factor B

allows Factor D to cleave Factor B into Ba and Bb.

Bb- C3 convertase

consists of the activated B and D factors

Alternative complement pathway stable after binding properdin cleave multiple C3 proteins into C3a and C3b

stable after binding properdin

cleave multiple C3 proteins into C3a and C3b

Pathogenesis of infections Factor B, Factor I Alternative pathway of complement system Approx 55kDa Lost in urine Imp in opsonization of encapsulated organisms eg strep pneumoniae Transferrin Essential for lymphocyte function Carrier for zinc Lost of Transferrin-Zinc  diminished production of Zn dependent thymic hormone thymulin Reduced lymphocyte/polymorph function

Factor B, Factor I

Alternative pathway of complement system

Approx 55kDa

Lost in urine

Imp in opsonization of encapsulated organisms eg strep pneumoniae

Transferrin

Essential for lymphocyte function

Carrier for zinc

Lost of Transferrin-Zinc  diminished production of Zn dependent thymic hormone thymulin

Reduced lymphocyte/polymorph function

Treatment Induce remission ASAP Pt with previous pneumococcal infection  prophylactic penicillin Pneumococcal vaccine  start 14 days after discontinuing high dose steroids/cytotoxics IV antibiotics- broad spectrum Varicella zoster Zoster Immune Globulin within 72h of contact IV acyclovir

Induce remission ASAP

Pt with previous pneumococcal infection  prophylactic penicillin

Pneumococcal vaccine  start 14 days after discontinuing high dose steroids/cytotoxics

IV antibiotics- broad spectrum

Varicella zoster

Zoster Immune Globulin within 72h of contact

IV acyclovir

Thromboembolic complications

Thromboembolic complications Arterial/venous circulation 10% nephrotic adults 50% nephrotic adults (subclinical) 1.8% (paeds) Higher levels of 92-macroglobulin (thrombin inhibitor) Highest risk in adult Membranous nephropathy What is the cause? Abnormalities of coagulation

Arterial/venous circulation

10% nephrotic adults

50% nephrotic adults (subclinical)

1.8% (paeds)

Higher levels of 92-macroglobulin (thrombin inhibitor)

Highest risk in adult Membranous nephropathy

What is the cause?

Abnormalities of coagulation

Commonest presentation DVT +/- PE Renal vein thrombosis Hepatic vein thrombosis Budd Chiari syndrome Intracranial venous sinus thrombosis

DVT +/- PE

Renal vein thrombosis

Hepatic vein thrombosis

Budd Chiari syndrome

Intracranial venous sinus thrombosis

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

Physical Factors Immobility Haemoconcentration from hypovolaemia Increase blood viscosity Changes in red cell deformability Increase fibrinogen  favours margination of platlets and increased platlet aggregability 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.

Immobility

Haemoconcentration from hypovolaemia

Increase blood viscosity

Changes in red cell deformability

Increase fibrinogen

 favours margination of platlets and increased platlet aggregability

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.

Alterations in zymogen (enzyme precursors) and cofactors Increase  VWF, fibrinogen, FV, X, VII Fibrinogen and FVII – independent variables predicting vascular disease Cameron, J. S. (1984). Thromboembolic complications of the nephrotic syndrome. Advances in Nephrology 13 , 75–114.

Increase  VWF, fibrinogen, FV, X, VII

Fibrinogen and FVII – independent variables predicting vascular disease

Cameron, J. S. (1984). Thromboembolic complications of the nephrotic syndrome. Advances in Nephrology 13 , 75–114.

Alterations in fibrinolytic, regulator proteins and platlet function Low antithrombin III Low plasminogens Low functional Protein S +/- C Hyperaggregability of platlets Increased TxA2 LDL enhance platlet aggre via adenylate cyclase LDL inhibits prostacyclin on endothelial cells HDL has opposite effect from LDL

Low antithrombin III

Low plasminogens

Low functional Protein S +/- C

Hyperaggregability of platlets

Increased TxA2

LDL enhance platlet aggre via adenylate cyclase

LDL inhibits prostacyclin on endothelial cells

HDL has opposite effect from LDL

Alterations in fibrinolytic, regulator proteins and platlet function LDL is enriched with lysolecithin Toxic to endothelial cells Reduce NO production Diminished platlet adhesion Hyperaggregability to ristocetin ? d/t increased vWF ?altered charge on platlets Impaired response to endothelium dependent vasodilatation

LDL is enriched with lysolecithin

Toxic to endothelial cells

Reduce NO production

Diminished platlet adhesion

Hyperaggregability to ristocetin

? d/t increased vWF

?altered charge on platlets

Impaired response to endothelium dependent vasodilatation

Summary :- Loss of antithrombin III Loss of Protein S Increase Fibrinogen Platlets hyperactive d/t increase responsiveness to ADP Llach , Postgraduate Medicine, 1984 Vigano D’Angelo, Annals of Int Med, 1987

Loss of antithrombin III

Loss of Protein S

Increase Fibrinogen

Platlets hyperactive d/t increase responsiveness to ADP

Llach , Postgraduate Medicine, 1984

Vigano D’Angelo, Annals of Int Med, 1987

Role of drugs Steroids Increases some zymogens Decrease PT, PTT Anta Warfarin effect But increase ATIII and inhibit platlet aggregation at high doses Diuretics Increases blood viscosity (d/t increase fibrinogen) 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.

Steroids

Increases some zymogens

Decrease PT, PTT

Anta Warfarin effect

But increase ATIII and inhibit platlet aggregation at high doses

Diuretics

Increases blood viscosity (d/t increase fibrinogen)

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.

Peripheral venous thrombosis and PE DVT 3-12% 25% by doppler USG PE 0-15% 9-12% via V/Q scan Mortality:- Hemodynamically stable  8.1% Cardiogenic shock  25% Need CPR  65% Recurrence: 28% (diagnosed via V/Q) Other venous thrombi Renal vein thrombosis Subclavian, axillary, jugular, iliac, portal, splenic, hepatic, mesenteric vein thrombosis Sagittal sinus thrombosis Cameron et al 1984, 1988

DVT

3-12%

25% by doppler USG

PE

0-15%

9-12% via V/Q scan

Mortality:-

Hemodynamically stable  8.1%

Cardiogenic shock  25%

Need CPR  65%

Recurrence: 28% (diagnosed via V/Q)

Other venous thrombi

Renal vein thrombosis

Subclavian, axillary, jugular, iliac, portal, splenic, hepatic, mesenteric vein thrombosis

Sagittal sinus thrombosis

Cameron et al 1984, 1988

Arterial Thrombosis Less common than venous thrombosis Occurred in almost every artery Some multiple arterial thrombi Some combined arterial and venous thrombosis Commonest  femoral artery

Less common than venous thrombosis

Occurred in almost every artery

Some multiple arterial thrombi

Some combined arterial and venous thrombosis

Commonest  femoral artery

Renal Vein Thrombosis 4-8% in membranous nephropathy Cameron et al 1988 Up to 50% via venography Llach, F. (1985). Hypercoagulability, renal vein thrombosis, and other thrombotic complications of nephrotic syndrome (Nephrology Forum). Kidney International 28 , 429–439. 13-18% 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. Men more affected 35% have PE as well Cameron et al 1988

4-8% in membranous nephropathy

Cameron et al 1988

Up to 50% via venography

Llach, F. (1985). Hypercoagulability, renal vein thrombosis, and other thrombotic complications of nephrotic syndrome (Nephrology Forum). Kidney International 28 , 429–439.

13-18%

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.

Men more affected

35% have PE as well

Cameron et al 1988

Renal Vein Thrombosis Loin pain Hematuria Renal enlargement Pain and swelling in ipsilateral testicle in male Deterioration of renal function Lower limb oedema if vena cava involved

Loin pain

Hematuria

Renal enlargement

Pain and swelling in ipsilateral testicle in male

Deterioration of renal function

Lower limb oedema if vena cava involved

Renal Vein Thrombosis- Prognosis Unknown As most are anticoagulated Impaired renal function is poor prognostic sign

Unknown

As most are anticoagulated

Impaired renal function is poor prognostic sign

Treatment/prevention of thromboembolic events Paucity of RCTs Only 1 study looking into prophylactic LMWH for TEE in NS Rostoker, Nephron, 1995 No known standard protocol for :- Duration of anticoagulation Intensity of anticoagulation Type of anticoagulation Expert opinion mainly (no evidence)

Paucity of RCTs

Only 1 study looking into prophylactic LMWH for TEE in NS

Rostoker, Nephron, 1995

No known standard protocol for :-

Duration of anticoagulation

Intensity of anticoagulation

Type of anticoagulation

Expert opinion mainly (no evidence)

Prevention Mobilize patient Avoid sepsis Treat sepsis Avoid dehydration Judicious use of diuretics Minimize haemoconcentration

Mobilize patient

Avoid sepsis

Treat sepsis

Avoid dehydration

Judicious use of diuretics

Minimize haemoconcentration

Heparin acts mainly via activation of AT III (decrease concentration in nephrotics) May need higher dose Heparin binds to α 2-macroglobulin and endothelial cell surface  may enhance platlet aggregation Warfarin  bound to albumin. Dosing problem

Heparin acts mainly via activation of AT III (decrease concentration in nephrotics)

May need higher dose

Heparin binds to α 2-macroglobulin and endothelial cell surface  may enhance platlet aggregation

Warfarin  bound to albumin.

Dosing problem

Should we anticoagulate asymptomatic DVT? Yes Heparin UF/LMWH, Warfarin INR 2-4 When to stop anticoagulation? Min 3 months 6 months When stopping, ensure no edema, serum albumin > 25g/l

Yes

Heparin UF/LMWH, Warfarin

INR 2-4

When to stop anticoagulation?

Min 3 months

6 months

When stopping, ensure no edema, serum albumin > 25g/l

Prophylactic anticoagulation in nephrotic patients? Yes esp if membranous nephropathy Bellomo and Atkins, Nephron, 1993 Sarasin and Schifferli, KI, 1994 Standard anticoagulants Low dose aspirin Dipyridamole Andrassy, 1980

Yes esp if membranous nephropathy

Bellomo and Atkins, Nephron, 1993

Sarasin and Schifferli, KI, 1994

Standard anticoagulants

Low dose aspirin

Dipyridamole

Andrassy, 1980

Lipid abnormalities

Hyperlipidaemia Commonest complication 90% of pt with nephrotic range proteinuria Contributes to atherosclerosis and progression of renal damage Samuelsson, NDT, 1997 Correlates inversely with serum albumin Independent of cause of nephrosis

Commonest complication

90% of pt with nephrotic range proteinuria

Contributes to atherosclerosis and progression of renal damage

Samuelsson, NDT, 1997

Correlates inversely with serum albumin

Independent of cause of nephrosis

Hyperlipidaemia Increase VLDL, IDL, LDL (esp smaller and denser), Tg HDL usually normal (decrease in HDL-2, increase in HDL-3) Increase in Lp(a) (strong predictor of vascular events in general pop)

Increase VLDL, IDL, LDL (esp smaller and denser), Tg

HDL usually normal (decrease in HDL-2, increase in HDL-3)

Increase in Lp(a) (strong predictor of vascular events in general pop)

Hyperlipidaemia- Pathogenesis Reduced oncotic pressure or albumin concentration  increase transcription of liver regulated proteins Infusion of IV albumin reduces cholesterol levels Appel, NEJM, 1985 Result of increase synthesis and decreased catabolism of lipoprotein Impaired conversion of VLDL to LDL Increased hepatic LDL secretion Increase Lp(a) production by liver Impaired HDL maturation Decrease receptor mediated clearance of circulating VLDL

Reduced oncotic pressure or albumin concentration  increase transcription of liver regulated proteins

Infusion of IV albumin reduces cholesterol levels

Appel, NEJM, 1985

Result of increase synthesis and decreased catabolism of lipoprotein

Impaired conversion of VLDL to LDL

Increased hepatic LDL secretion

Increase Lp(a) production by liver

Impaired HDL maturation

Decrease receptor mediated clearance of circulating VLDL

Hyperlipidaemia- Pathogenesis Increase synthesis and reduce degradation of Tg Loss of ApoC-II in urine

Increase synthesis and reduce degradation of Tg

Loss of ApoC-II in urine

Hyperlipidaemia- consequences Nephrotics 5.5 fold MI 2.8 fold coronary death Ordonez, KI, 1993 No difference from controls Wass, Lancet, 1979 Duration of hyperlipidaemia is most critical Highest risk in patients with unremitting proteinuria A/W glomerular and interstitial renal disease in animal studies. Never proven in humans

Nephrotics

5.5 fold MI

2.8 fold coronary death

Ordonez, KI, 1993

No difference from controls

Wass, Lancet, 1979

Duration of hyperlipidaemia is most critical

Highest risk in patients with unremitting proteinuria

A/W glomerular and interstitial renal disease in animal studies. Never proven in humans

Hyperlipidaemia- treatment Controversial Most extrapolated from general population Increase in premature atherosclerosis and MI in nephrotics Niaudet, Paediatric nephrology, 1992 Independent risk factor for atherosclerotic disease Radhakrishnan, AJKD, 1993 May promote progression of renal disease Falk, 2001

Controversial

Most extrapolated from general population

Increase in premature atherosclerosis and MI in nephrotics

Niaudet, Paediatric nephrology, 1992

Independent risk factor for atherosclerotic disease

Radhakrishnan, AJKD, 1993

May promote progression of renal disease

Falk, 2001

Hyperlipidaemia- treatment Reduce proteinuria Statins Nicotinic acid Bile acid resins (cholestyramine, colestipol) Lipopheresis No effect on protein excretion and serum albumin levels

Reduce proteinuria

Statins

Nicotinic acid

Bile acid resins (cholestyramine, colestipol)

Lipopheresis

No effect on protein excretion and serum albumin levels

Acute Renal Failure in Nephrotic Syndrome, Hein, NDT 2001 Rapid progression of original glomerular disease Renal vein thrombosis Allergic interstitial nephritis Diuretics Antibiotics NSAIDS Foscarnet Interferon alpha Sepsis ATN Tubular obstruction from proteinuria (protein cast)

Rapid progression of original glomerular disease

Renal vein thrombosis

Allergic interstitial nephritis

Diuretics

Antibiotics

NSAIDS

Foscarnet

Interferon alpha

Sepsis

ATN

Tubular obstruction from proteinuria (protein cast)

Acute Renal Failure in Nephrotic Syndrome- Pathology 85%- MCD 60%  ATN findings 40%  interstitial oedema ARF group also have more arteriolosclerosis (intimal hyperplasia amd hyalinosis)

85%- MCD

60%  ATN findings

40%  interstitial oedema

ARF group also have more arteriolosclerosis (intimal hyperplasia amd hyalinosis)

Acute Renal Failure in Nephrotic Syndrome Elderly Hypertensive Severe proteinuria Very low albumin 2/3  male Most have severe oedema Time between onset of NS and ARF is 4 weeks Recovery usually over 7 weeks Smith, AJKD, 1992 Children and young adults  progression can be early with fast occurrence and resolution Protracted ARF needing dialysis less commonly occur in children

Elderly

Hypertensive

Severe proteinuria

Very low albumin

2/3  male

Most have severe oedema

Time between onset of NS and ARF is 4 weeks

Recovery usually over 7 weeks

Smith, AJKD, 1992

Children and young adults  progression can be early with fast occurrence and resolution

Protracted ARF needing dialysis less commonly occur in children

Others Loss of metal binding proteins Serum iron/ transferrin Caeruloplasmin Zinc Loss of vitamins and hormones Vit D binding protein Thyroid binding globulin Cortisol binding protein Erythropoietin

Loss of metal binding proteins

Serum iron/ transferrin

Caeruloplasmin

Zinc

Loss of vitamins and hormones

Vit D binding protein

Thyroid binding globulin

Cortisol binding protein

Erythropoietin