Renal Failure and Renal Failure and Cardiovascular DiseaseCardiovascular Disease

Rey TuandoRey Tuando

Renal Dialysis UnitRenal Dialysis Unit

IntroductionIntroduction■ Refresh our knowledgeRefresh our knowledge■ Know more about the Kidney and RFKnow more about the Kidney and RF■ Major Cardiovascular Changes in RFMajor Cardiovascular Changes in RF■ Review of StatisticsReview of Statistics■ Nursing implicationsNursing implications

■ Prevelance statistics about Kidney failure: The following statistics relate to the prevalence of Kidney failure:

• 56,598 people with end-stage renal disease were waiting for kidney transplants in the US (United Network for Organ Sharing, 2003, NIDDK)

• 2,444 people with end-stage renal disease were waiting for kidney and pancreas transplants in the US (United Network for Organ Sharing, 2003, NIDDK)

Incidence statistics about Kidney failure: The following statistics relate to the incidence of Kidney failure:

•Kidney failure rates were approximately 5 times higher for the indigenous population in Australia 2000-02 (Australia’s Health 2004, AIHW)

•93,327 people commenced treatment for end-stage renal disease annually in the US 2001 (United States Renal Data System, 2003, NIDDK)

Death statistics for Kidney failure: The following are statistics from various sources about deaths and Kidney failure:

•76,584 people undergoing end-stage renal treatment died each year in the US 2001 (United States Renal Data System, 2003, NIDDK)

•26.1% of deaths from kidney failure were also associated with coronary heart disease in Australia (Australia’s Health 2004, AIHW)

•28.6% of deaths from kidney failure were also associated with heart failure in Australia (Australia’s Health 2004, AIHW)

•1,006 women died from renal failure in Australia 2002 (AIHW National Morbidity Database, Australia’s Health 2004, AIHW)

•919 men died from renal failure in Australia 2002 (AIHW National Morbidity Database, Australia’s Health 2004, AIHW)

•1.3% of all male deaths was due to renal failure in Australia 2002 (AIHW National Morbidity Database, Australia’s Health 2004, AIHW)

•1.6% of all female deaths was due to renal failure in Australia 2002 (AIHW National Morbidity Database, Australia’s Health 2004, AIHW)

•15% of deaths from diabetes also had renal failure as an associated cause of death in Australia, 2002 (Australia’s Health 2004, AIHW)

Topics of DiscussionTopics of Discussion■ Kidney and the Nephron. How is urine Kidney and the Nephron. How is urine

formedformed■ RF: Classification and Major Causes RF: Classification and Major Causes ■ Effect on the CV SystemEffect on the CV System■ Approach to TreatmentApproach to Treatment■ Dialysis and TransplantationDialysis and Transplantation

The Kidney The Kidney

■ Bean shaped; behind peritoneum; 12T-3L vertebra; Bean shaped; behind peritoneum; 12T-3L vertebra; right one a little lower; 10-15cm length; 120-170gm; right one a little lower; 10-15cm length; 120-170gm; 11x6x3cm size;<1% of body weight11x6x3cm size;<1% of body weight

■ Blood supply Blood supply ■ 1-1.2M nephrons:1-1.2M nephrons: 1. Bowman’s capsule1. Bowman’s capsule

2. Proximal Convoluted Tubule2. Proximal Convoluted Tubule 3. Loop Of Henle3. Loop Of Henle 4. Distal Convoluted Tubule4. Distal Convoluted Tubule 5. Collecting Ducts 5. Collecting Ducts

■ Cortex (outer) (pad of fat) (filtering and reabsorption Cortex (outer) (pad of fat) (filtering and reabsorption components)components)

■ Medulla (inner) (concentrating/diluting, collecting Medulla (inner) (concentrating/diluting, collecting duct)duct)

Kidney FunctionsKidney Functions

■ ExcretoryExcretory■ RegulatoryRegulatory■ MetabolicMetabolic

Mechanism of Renal Excretory Mechanism of Renal Excretory FunctionFunction

■ Renal Blood/plasma flow 20% of CORenal Blood/plasma flow 20% of CO■ Glomerular Ultrafiltration=protein-free ultrafiltrate Glomerular Ultrafiltration=protein-free ultrafiltrate ■ Urine Volume = 1.5L/day (roughly 1ml/min)Urine Volume = 1.5L/day (roughly 1ml/min)■ small residuum=2 opposing processes:small residuum=2 opposing processes: Ultrafiltration (UF) of Ultrafiltration (UF) of >>180L (125ml/min)180L (125ml/min) Reclamation of 99% of ultrafiltrateReclamation of 99% of ultrafiltrate■ Filtration Filtration <<10,000 molecular weight10,000 molecular weight

Rate of Ultrafiltration (GFR)Rate of Ultrafiltration (GFR)

■ Glomerular Capillary Hydrosatic Pressure + Bowman’sGlomerular Capillary Hydrosatic Pressure + Bowman’s space Oncotic Pressure = Glomerular Capillary space Oncotic Pressure = Glomerular Capillary

Oncotic Pressure + Bowman’s Space Hydrostatic Oncotic Pressure + Bowman’s Space Hydrostatic PressurePressure

■ Rate of Plasma FlowRate of Plasma Flow■ Permeability and Total Surface AreaPermeability and Total Surface Area■ Decrease in GFR:Decrease in GFR: Glomerular Hydrostatic Pres. Glomerular Hydrostatic Pres. Tubule Hydrostatic Pres. Tubule Hydrostatic Pres. Renal Blood/Plasma Flow Renal Blood/Plasma Flow

Plasma Oncotic Pres. Plasma Oncotic Pres. Permeability/Filtering Surface Area Permeability/Filtering Surface Area

■ Barrier to Protein filtration:Barrier to Protein filtration:

1.Glomerular Capillary Basement Membrane and Slitlike1.Glomerular Capillary Basement Membrane and Slitlike diaphragmsdiaphragms 2. Eletrostatic Factors2. Eletrostatic Factors

■ The Juxtaglomerular ApparatusThe Juxtaglomerular Apparatus

a specialised structure: Tubular componenta specialised structure: Tubular component Vascular componentVascular component Interstitial componentInterstitial component

■ Erythropoietin productionErythropoietin production■ Acid Base BalanceAcid Base Balance

Types of Renal FailureTypes of Renal FailureI. Acute RFI. Acute RF ARF: ARF: i.e. Bi. Arterial Occlusion Bi. Acute Renal Vein Thrombosisi.e. Bi. Arterial Occlusion Bi. Acute Renal Vein Thrombosis

ATN Acute Uric Acid NephropathyATN Acute Uric Acid Nephropathy

Hypovolaemia CV Collapse Hypovolaemia CV Collapse

RPRF: RPRF: i.e. Idiopathic Rapidly Progressing GNi.e. Idiopathic Rapidly Progressing GN

Goodpasture’s SyndGoodpasture’s Synd

Acute Bacterial Endocarditis or Visceral SepsisAcute Bacterial Endocarditis or Visceral Sepsis

Microscopic Polyarteritis NodosaMicroscopic Polyarteritis Nodosa

Wegener’s GranulomatosisWegener’s Granulomatosis II. ChronicII. Chronic Several forms of GNSeveral forms of GN

HTNHTN

DMDM

Physiology of Ischaemic ARFPhysiology of Ischaemic ARFINEFFECTIVE CIRCULATORY VOLUME-HYPOPERFUSIONINEFFECTIVE CIRCULATORY VOLUME-HYPOPERFUSION

Activation of Central BaroreceptorsActivation of Central Baroreceptors

Angiotensin II (+) Norepinephrine (+) Vasopressin (+) Endothelin (+)Angiotensin II (+) Norepinephrine (+) Vasopressin (+) Endothelin (+)

Preferrential ConstrictionPreferrential ConstrictionEfferent Arteriole (-)Efferent Arteriole (-) Prostaglandin Synthesis (-) Renal Vasoconstriction Tubuloglomerular Prostaglandin Synthesis (-) Renal Vasoconstriction Tubuloglomerular Mesangial Cell Contraction FeedbackMesangial Cell Contraction FeedbackAutoregulation (-)Autoregulation (-)

Nitric Oxide (-) Nitric Oxide (-) Epithelial Cell Ischaemic Injury Impaired NaClEpithelial Cell Ischaemic Injury Impaired NaCl (proximal tubule-pars recta Reabsorption(proximal tubule-pars recta Reabsorption medullary thick ascending limb)medullary thick ascending limb) Tubule ObstructionTubule Obstruction

Reduced Glomerular Filtration Pressure Tubular BackleakReduced Glomerular Filtration Pressure Tubular Backleakand Surface Area of Filtration Markersand Surface Area of Filtration Markers

REDUCED GLOMERULAR FILTRATION RATEREDUCED GLOMERULAR FILTRATION RATE

Effect on Heart and CirculationEffect on Heart and Circulation■ HypertensionHypertension Volume Dependent (50%) Volume Dependent (50%)

Non-Volume Dependent (34% , 16%)Non-Volume Dependent (34% , 16%)■ HyperlipidaemiaHyperlipidaemia Hypertriglyceridaemia (1/3)Hypertriglyceridaemia (1/3)

Abno Serum apolipoprotein Abno Serum apolipoprotein concentrationsconcentrations

Lipid peroxidationLipid peroxidation HypercholesterolaemiaHypercholesterolaemia■ Ischaemic Cardiac DiseaseIschaemic Cardiac Disease

■ Left Ventricular Dysfunction and HypertrophyLeft Ventricular Dysfunction and Hypertrophy Heart Failure versus Fluid OverloadHeart Failure versus Fluid Overload

■ Pericardial Disease ( Pericarditis 3-4% of death)Pericardial Disease ( Pericarditis 3-4% of death) Uraemic PericarditisUraemic Pericarditis

Dialysis-associated Pericarditis (bact or viral Dialysis-associated Pericarditis (bact or viral infection, hypercatabolism, volume overload, infection, hypercatabolism, volume overload, HyperPTism, hyperuricaemia, malnutrition)HyperPTism, hyperuricaemia, malnutrition) Constrictive PericarditisConstrictive Pericarditis Purulent PericarditisPurulent Pericarditis

■ Endocarditis (from access site infection)Endocarditis (from access site infection)

■ ArrhythmiasArrhythmias

Risk Factors for Atherogenesis in ESRD/F:Risk Factors for Atherogenesis in ESRD/F:■ HypertensionHypertension■ Cigarette SmokingCigarette Smoking■ DMDM■ Insulin ResistanceInsulin Resistance■ Lipid DisordersLipid Disorders■ Vascular CalcificationVascular Calcification■ ? Elevated plasma urate and oxalate? Elevated plasma urate and oxalate■ ? Free oxygen radicals? Free oxygen radicals■ ? Polyamines? Polyamines

Risks of Dialysis Therapy in Patients with Risks of Dialysis Therapy in Patients with PericarditisPericarditis

■ BleedingBleeding■ ArrhythmiaArrhythmia■ Hypotension and Cardiac TamponadeHypotension and Cardiac Tamponade■ DehydrationDehydration■ Hypokalaemia and HypophosphataemiaHypokalaemia and Hypophosphataemia■ Metabolic AlkalosisMetabolic Alkalosis

Factors leading to Left Ventricular Factors leading to Left Ventricular Dysfunction and/or Hypertrophy in Dysfunction and/or Hypertrophy in

Dialysis PatientsDialysis Patients

■ HypertensionHypertension■ Fluid OverloadFluid Overload■ AnaemiaAnaemia■ Ischaemic Heart DiseaseIschaemic Heart Disease■ Arteriovenous FistulaArteriovenous Fistula■ Myocardial CalcificationMyocardial Calcification■ Systemic Disease ( e.g., amyloidosis, polyarteritis, Systemic Disease ( e.g., amyloidosis, polyarteritis,

scleroderma)scleroderma)■ UraemiaUraemia

BASELINE

+ 4L WATER

BASELINE

+ 4L WATER

BASELINE

+ 4L SALINE

BASELINE

+ 4L SALINE

Saline Overload is more important than Water OverloadSaline Overload is more important than Water Overload

CRP – thought to be an “idle” marker but is a nasty CRP – thought to be an “idle” marker but is a nasty protagonistprotagonist

■ Present in damaged endothelium/vessel wallPresent in damaged endothelium/vessel wall■ Attraction of monocytes via MCP-1 to vessel wallAttraction of monocytes via MCP-1 to vessel wall■ Attraction/adherence/migration of monocytesAttraction/adherence/migration of monocytes■ Opsonizes LDL and facilitates LDL uptake by Opsonizes LDL and facilitates LDL uptake by

macrophagesmacrophages– Foam cell / atheroma propagationFoam cell / atheroma propagation

■ Activates C’ via classical pathwayActivates C’ via classical pathway– Promotes local inflammationPromotes local inflammation

■ Suppresses NO synthesisSuppresses NO synthesis– Endothelial dysfunction (vasoreaction)Endothelial dysfunction (vasoreaction)

UraemiaUraemiaCharacterized by:Characterized by:■ A chronic state of oxidant stress and A chronic state of oxidant stress and

disordered free radical chemistrydisordered free radical chemistry■ A chronic state of activated A chronic state of activated

inflammationinflammation■ Endothelial dysfunction and a highly Endothelial dysfunction and a highly

proatherogenic stateproatherogenic state■ Excessive morbidity and mortality Excessive morbidity and mortality

attributable to occlusive vascular attributable to occlusive vascular diseasedisease

DialysisDialysis

■ HaemodialysisHaemodialysis■ Peritoneal DialysisPeritoneal Dialysis■ Plasmapheresis (TPE)Plasmapheresis (TPE)■ TransplantationTransplantation