Renal Disease - University Of Sydney
OverviewAetiology, pathophysiology, clinical signsand symptoms of acute (ARF), chronic(CRF) & end-stage renal failure (ESRF) Renal Replacement Therapy: CAPD, APD,Haemodialysis, Transplantation,Conservative Management Medical Management of ARF, CRF, &ESRF Renal DiseaseDr Philip MassonAdvanced Trainee, Renal MedicineRoyal Prince Alfred Hospital, SydneyApril 7th 2008Basic Anatomy & Physiology Regulate volume and concentration of fluids in the bodyby producing urine by a process called glomerularfiltration Involves the removal of waste products, minerals, andwater from the blood. The kidneys maintain the volume and concentration ofurine by filtering waste products and reabsorbing usefulsubstances and water from the blood.Other main renal functions: Detoxify harmful substances (e.g., free radicals,drugs)Increase the absorption of calcium from the gutby producing calcitriol (activated form of vitaminD)Produce erythropoietin (hormone that stimulatesred blood cell production in the bone marrow)Secrete renin (hormone that regulates bloodpressure and electrolyte balance)1
The components of the kidney tubule are: Proximal Loop tubuleof HenleDescending limb of loop of HenleAscending limb of loop of Henle DistalConvoluted TubuleTubule component functions Proximal tubule: Descending – permeable to water, but completelyimpermeable to salt. Water dragged out intohypertonic interstitium (ie. concentration of urineoccurs here) Ascending – impermeable to water. Pumps salt outinto the intersitium to maintain the osmotic gradientbetween medulla and loop of henle; the so-called“counter-current exchange.”of salt (Na ) and H2O Approximately 2/3 of filtered salt and waterreabsorption occurs here ALL filtered organic solutes (primarily glucoseand amino acids) reabsorbed Distal Convoluted Tubule:Cells have numerous mitochondria to produce energyto produce ATP for active transport to occur. Much ion exchange regulated by the endocrinesystem In presence of parathyroid hormone, DCT absorbsmore calcium & excretes more phosphate In presence of Aldosterone, DCT re-absorbs more Na& more K excreted Adjusts urinary concentration of Hydrogen andAmmonium to regulate acidity of urine (and blood) Loop of Henle: Reabsorption Collecting Ducts Normallyimpermeable to waterpresence of Antidiuretic Hormone (ADH),becomes water permeable ie. Levels of ADHdetermine whether urine will be dilute orconcentrated. Increased ADH indicates dehydration Water overload – low ADH and dilute urine In2
Normal Biochemical Parameters Normal Haematological ParametersHb men:13-18g/dlwomen: 11.5-16g/dl135-145 mmol/l3.5-5.0 mmol/l2.5-6.7 mmol/l70-150 micromol/l18-28 mmol/l2.12-2.65 mmol/lInvestigations in Renal Disease NaKUreaCreatHCO3Ca Blood biochemistry & haematologyUrine dipstick Protein(abnormal when 500mg/day)(infection, glomerular inflammation) Leucocytes (white cells) BloodRenal Ultrasound Useful for assessing renal size & perfusion Largekidneys in obstruction, diabetes,amyloid Small kidneys in chronic renal disease Dilated pelvicalyceal system in obstruction3
Renal Perfusion ScanNormally, at least half of theinjected radioisotope dye isexcreted by 20 minutes.Renal Biopsy If there is obstruction, dyehold up will occur in thepelvicalyceal system andthe peak wil be prolonged &excretion delayed.Mainly used when intrinsic renal disease issuspected to provide a pathologicaldiagnosis.Useful in assessment ofperfusion of newlytransplanted kidneys.CT AngiographyAcute Renal Failure Syndrome arising from rapid fall in GlomerularFiltration Rate (GFR)GFR – a measure of the “filtration capacity” ofrenal glomeruli, expressed in ml/min (correctedfor body surface area). Normal is100ml/min/1.73m2Characterized by retention of nitrogenous waste(urea, creatinine), non-nitrogenous products ofmetabolism, disordered electrolyte & fluidhomeostasis, and acid-base disturbanceAcute Kidney Injury (AKI)Functional or structural abnormalities, ormarkers of kidney damage (includingblood, urine, tissue tests or imagingstudies) present for 3 months Diagnostic Criteria: an abrupt ( 48 hours)reduction in GFR, assuming adequate fluidresuscitation, and that obstruction hasbeen excluded 4
The RIFLE classification Incidence: 7%general hospital admissionpatients with sepsis & 50% withseptic shock 65% of ICU admissions, with a mortality of43-88% 20-25%Which patients are at risk? Mortality Dialysis-requiring acute renal failure, 50% Morbidity Recoveryof renal function depends onunderlying cause Irreversible in 5% ( 16% in the elderly)How do we recognise ARF? Urea and Creatinine increasedOligo- or anuria (little or no urine)Volume depleted, or Volume overloadedHyperkalaemia (K )Hb often normalPO4 often highCa can be high or low ElderlyPre-existing chronic renal diseaseSurgeryDiabetesVolume depletion (NBM, bowel obstruction)Ischaemic heart diseaseDrugs; NSAIDS, ACE inhibitors,Immunosuppressants, IV contrast, Vancomycin,GentamicinCauses & ClassificationPre-renalIntrinsic Renal Post-renal 5
Pre-renal Decreased renal blood flow & GFRCan be secondary to hypovolaemia, or anycause of decreased effective renal blood flow(cardiac output, vasodilatation in sepsis) orintrarenal vasomotor changes (Non-steroidalmedications, ACE inhibitors)Easily reversible by restoration of renal bloodflowKidneys remain structurally normalIs it pre-renal ARF?Pre-renal: TreatmentIs the patient volume deplete?Is cardiac function good? Is the patient septic/vasodilated? Clinical signs: BP,Heart rate, Peripheral perfusion, UrineoutputFluid resuscitation, rate depends ondegree of hypovolaemia, ongoing losses,whether oligo-anuric & cardiovascularstatus ?Inotropic support (Vasoconstrict in sepsisto increase mean arterial blood pressure)Intrinsic Renal FailureRenal parenchyma damaged throughinjury to renal vasculature, glomerularfilter, or tubulo-interstitium Commonest cause is Acute TubularNecrosis (80-90% of cases, the end ofproduct of an ischaemic or nephrotoxicinjury) Large renal vessels Renovasculardiseaseartery dissection, thrombosis Cholesterol emboli Renal vein thrombosis Renal6
Small renal vessels & glomeruli Glomerulonephritis(inflammation of the filterunits). IgA disease, Membranous, Postinfective, Henoch Schonlein, Goodpasture’sdisease Vasculitis (inflammation of the peritubular,afferent or efferent blood vessels). SLE,Wegener’s, Microscopic PolyangiitisPost renalKidneys produce urine, but there isobstruction to flow Increased back pressure results indecreased tubular function Can occur at any level in renal tract Eventually causes structural (andtherefore permanent) damageTubulointerstitium AcuteInterstitial Nephritis (in response todrugs, especially Proton Pump Inhibitors,Antibiotics) Intravenous Contrast (used for CT scans) Clogging of renal tubules with casts (inmyeloma, tumour lysis syndrome)Management of ARF Pulmonary Oedema Oligo-anuricpatients rapidly accumlate saltand water unless tightly fluid restricted Management depends on whether urineoutput is maintained “LMNOP”; Lasix, Morphine, Nitrates, Oxygen,Posture” ?Haemodialysis Hyperkalaemia If Ifurine output maintained, can treat medicallyanuric, may require haemodialysis Electrolytes and Acidosis Hyperphosphataemia Fromdecreased urinary PO4 excretionclinically because it: ImportantContributes to hypocalcaemiaEncourages secondary hyperparathyroidism Promotes soft tissue/vascular calcification Causes Itch Can cause cardiac arrhythmias 7
Hypocalcaemia (normal range 2.1 – 2.45) Commonin prolonged, or severe ARFcaused by decreased active vitamin Dsynthesis (1, 25-dihydroxyvitamin D3), butalso by increased PO4 Clinical features: Mainly Rare,but can occur in non-oliguric ATNcaused by tubular toxins (vancomycin,gentamicin) Also seen as GFR recovers, especially ifpatient becomes polyuricParaesthesia, tetany, seizures Managedby oral supplementation with alfacalcidol (rocaltrol, calcitriol) HypokalaemiaMetabolic Acidosis Unmeasuredanions from dietary andmetabolic sources accumulate and causeacidic environment Blood alkali “buffers” this, and is consumed The kidney is unable to reabsorb alkali fromthe urine or generate new alkali (byproduction and excretion of ammionium)Hypomagnesaemia Usuallyasymptomaticcause neuromuscular instability, cramps,arrhythmias CanNutrition in ARFAcute Renal Failure: SummaryPre-existing and hospital acquiredmalnutrition increases mortality andmorbidity in the critically ill When prescribing supplements, enteral &parenteral feeds, consider particularly: Potassium Phosphate VolumeRapid decline in GFRUsually associated with anuria Hyperkalaemia, Fluid overload, Acidosisare main disturbances High mortality and morbidity Pre-renal, Intrinsic & Post-renal 8
Chronic Renal FailureThe US NKF-DOQI (National KidneyFederation – Outcomes Quality Initiative)classification of chronic kidney disease;adopted internationally Divides chronic kidney disease (CKD) into5 stages according to GFR Many cases or early, asymptomatic CKDare unrecognized and therefore untreated Prevalence increases with age Most common identifiable causes arediabetes and vascular disease More common in many ethnic minorities Majority of patients with CKD stages 1-3will NOT progress to ESRF. Risk of deathfrom cardiovascular disease is higher thantheir risk of progression PathophysiologyDiabetes (19%)Glomerulonephritis (13%) Reflux nephropathy (10%) Renovascular disease (7%) Hypertension (7%) Polycystic Kidney Disease (7%) Mechanisms Decline in GFR usually progressiveSeries of interacting processes results in: Glomerulosclerosis Proteinuria Tubulointersitialfibrosis Raised Intraglomerular Pressure Asnephrons scar and ‘drop out’, remainingnephrons undergo compensatory adaptationwith increased blood flow through eachnephron attempting to normalize GFR Increased pressure increases endothelial cellinjury, with deposition of ‘pro-fibrotic’biochemical elements9
Proteinuria Maybe due to underlying glomerular lesion,or result from increased intraglomerularpressure Proteins or factors bound to filtered albumin(fatty acids, growth factors, metabolic endproducts) may lead to: Direct injury to proximal tubular cellsRecruitment on inflammatory cells (cause scarring) Tubulointerstitial Scarring Chronicischaemia implicatedDamaged glomerular capillaries Intrarenal vasoconstriction (and decreasedeffective renal blood flow) Intratubular capillary loss and increased diffusiondistance Diagnosis of CKD Why identify patients? CVrisk; modifiable – smoking reduction,cholesterol lowering, BP control Some would benefit from further treatment Complications of CKD recognised & treatedearly Those who do go on to ESRF & requiredialysis or transplantation can be preparedearlyProgression of CKD Once established, tends to progress regardless ofunderlying causeDecline in GFR tends to be linearFactors influencing progression Underlying diseaseRace (faster progression in blacks)BPLevel of lled Metabolic AcidosisAnaemiaSmokingBlood Glucose Control (if diabetic)10
Preventing Progression of CKD Calciumchannel blockers: amlodipine,nifedipine, verapamil, diltiazem Beta-blockers: atenolol, metoprolol ACE inhibitors: ramipril, enalapril, lisinopril Angiotensin II Receptor Antagonists: losartan,candesartan Others: clonidine, hydralazineBlood Pressure Treataggressively Poor BP control causes GFR to decline morerapidly and increases cardiovascular risk Which antihypertensives do we use?Targets WithoutProteinuria: 130/80Proteinuria: 120/75 Diabetics: 120/75 WithPreventing ProgressionExperimental work suggestshyperlipidaemia accelerates decline inGFR No clear evidence for use of cholesterollowering drugs (statins) in patients withCKD Ongoing multi-centre, international trial(SHARP trial) aiming to determine this Hyperphosphataemia Conceptof the Calcium-Phosphate product Calcium phosphate deposition in the renaltissue may contribute to progression of CKD Acidosis Nocurrent clinical evidence that correction ofacidosis decreases renal decline Oral Sodibic (bicarbonate, buffer) often givento decrease resistant Hyperkalaemia Drugs, toxins & infections Inpatients with CKD, remaining kidneyfunction is highly susceptible to furtherdamage from:HypovolaemiaObstruction or recurrent urinary tract infections Nephrotoxins – NSAIDS, IV Contrast 11
Dietary Protein RestrictionModels; lowering protein intakeprotects against development ofglomerulosclerosis by ?decreasedintraglomerular pressure In humans, controversial Ongoing debate regarding optimal intake ofprotein. 0.8 – 1.0g/kg protein/day.Complications of CKD AnimalComplications of advanced CKD Fluid OverloadAnaemiaBone DiseaseFluid & ElectrolytesMalnutritionComplications of advanced CKD Na delivery to DCT decreasesaldosterone induced K excretion Dietary K restriction Loop diuretics (promote urinary K losses) Drug withdrawal – ACE inhibitors Correct acidosis May need chronic dialysisand water overload Dietary salt restriction Fluid intake restriction DiureticsComplications of advanced CKD Acidosis Bone– reabsorption increased Metabolism – muscle weakness, fatigue Hyperkalaemia Nutrition – promotes catabolism by inductionof proteolysis & resistance to growth hormoneHyperkalaemia Decreased SaltComplications of advanced CKD Anaemia Redcell production tightly regulated by anumber of growth factors EPO (erythropoietin); essential for maturationof immature red cells. Produced in outer renalmedulla & deep cortex. Decreased EPO in CKD12
EPO (Erythropoietin) Priorto introduction, patients were transfusiondependent Enhanced quality of life scores Reduced Fatigue Reduced LVH Improved cognitive function Improved sexual dysfunction Improved sleep quality Preparation for EPO therapyiron replete Iron deficiency found in up to 40% patientswith advance CKD If GFR 50ml/min, supplementation likely tobe neededRenal Bone Disease Ensure Pre-dialysis give orallyIf on dialysis use parenteral ironDiminshed bone strength in patients withdiminshed GFR A function of bone turnover, density,mineralization & architecture HyperparathyroidismEnd result of prolonged stimulation of parathyroidglands in neck in response to low serum Ca Eventually results in clonal proliferation of the glandwhich requires suppression, either with artificialVitamin D analogues, or surgical resection PTH release stimulated by low Ca, low vitamin D &high PO4 13
Treatment Decreaseserum PO4 with binders (oftenCalcium containing compounds) Increase serum Ca with calcium salts, orvitamin D analogues Suppress PTH secretion directly (calcimimeticagents)Hyperphosphataemia Phosphate binders Taken few minutes before meal to bind PO4 in gutShould not be taken at same time as ironsupplementsDietary restriction Meats, milk, eggs, cerealsDifficult balance between restriction & adequateprotein intakeMalnutrition in CKD It’s common! 50% dialysis patientsPowerful predictor of survivalFactors contributing to malnutrition in renal failure Decreased Intake– Anorexia– Gastroparesis– Intraperitoneal instillation of dialysate in CAPD– Uraemia– Increased Leptin Diet RestrictionsLoss of nutrients in dialysateConcurrent illness and hospitalizationsIncreased inflammatory and catabolic cytokinesChronic blood lossAcidosisAccumulation of toxins such as aluminumEndocrine disorders- Insulin resistance- Hyperglucogonemia14
Management of ESRFAs for most of the complications of CKDRenal Replacement Therapy Conservative TreatmentIndications for Dialysis in CRF Renal Replacement Therapy Number of people receiving RRT expected todouble in next 10 yearsWill eventually reach “steady state” 3 forms: GFR 15ml/min with uraemic symptomsGFR 10ml/min whether symptomatic or notRefractory hyperkalaemia, acidosis, pulmonaryoedema, pericarditis, encephalopathyPre-emptive transplantation is treatment ofchoice. Should be considered when GFR 20ml/minTake on rates (per million population)HaemodialysisPeritoneal dialysis Transplantation Haemodialysis15
Blood is exposed to dialysate (a solutioncontaining physiological concentrations ofelectrolytes) across a semi-permeablemembrane (the dialyser)Pores in the membrane allow small moleculesand electrolytes to pass throughConcentration differences allow molecules todiffuse down gradients, thereby expelling wasteproducts, and replacing desirable molecules orionsWater can be driven through the membrane byhydrostatic force (ultrafiltration); the means bywhich we control fluid statusComplications of HaemodialysisRequirements for HaemodialysisVascular access (indwelling catheter,arterio-venous fistula or graft) Anti-coagulation Dialysis membrane Dialysate Long term survival on HDLine infections (infection risk 100-300 foldhigher in dialysis patients compared togeneral population Clotted fistulae Intradialytic Hypotension Cardiac arrhythmias Cramps 16
Peritoneal DialysisTypes of PDSemi-permeable membrane of theperitoneum used as the dialysermembrane Dependent on diffusion alongconcentration gradients across peritoneum Fluid removal (ultrafiltration) depends onpresence of a high intraperitoneal osmoticgradient as generated by glucose CAPD (Continuous Ambulatory PeritonealDialysis) 3-5exchanges per day with dwell times of 410 hours Patient connects and disconnects to PDdialysate bags Automated PD (APD) Automatedmachine performs exchanges atnight whilst patient is sleeping Performs at least 4 exchanges over 8 hours Can be programmed to leave patient dry, or todo a last fill17
Complications of PDRenal TransplantationPD peritonitisExit site infections Sclerosing encapsulating peritonitis Compatibility BloodGrouptyping Antibodies Donor:recipient characteristics Tissue Symptomsof intermittent bowel obstructionUltrafiltration Malnutrition PoorBenefits of Transplantation Cadaveric v Living donor Currentaverage wait on cadaveric waiting listin NSW is 7 years!Complications of Transplantation Surgical complicationsGraft dysfunction: “chronic allograftnephropathy,” recurrent glomerulonephritis.Acute rejectionPost-transplant infections; CMV, HSV, Shingles,EBV, BKPost transplant malignancy 50% recipients 20yrs post transplant will have had askin cancer Post-transplant lymphoproliferative disorders in 1-5%:(NHL, Myeloma, Hodgkin’s Disease) Cervical and vulval cancers Solid organ tumours Decreased cardiovascular riskNormalisation of anaemia, bone disease,electrolyte imbalance, acid-base balance,normal cellular function Lifestyle! Conservative Therapy Symptomatic controlOptimal medical therapy Diuretics Anaemiatreatmentcontrol Dietary Palliative Care K 18
Summary 5 year survival rate for elderly patients 39.8%(compared to 79.8% for younger controls)Lengthier hospital admissionsMore complications - infectionsConservative therapy may not shorten lifespanand can result in improved quality of lifemeasuresQuestions? Acute renal failureChronic renal failureAnaemiaBone disease Fluid & Electrolyte disturbances Renal ReplacementHaemodialysisPeritoneal Dialysis Transplantation Conservative Therapy SummaryMultiple medical problems requiring inputfrom multiple medical teams Often associated with social and financialdifficulties Present real multidisciplinary challengerequiring input from all allied healthprofessionals, social workers, spiritualleaders, friends, families . 19
Renal Disease Dr CPhilip Masson Advanced Trainee, Renal Medicine Royal Prince Alfred Hospital, Sydney April 7th 2008 Overview Aetiology, pathophysiology, clinical signs and symptoms of acute (ARF), chronic (CRF) & end-stage renal failure (ESRF) Renal Replacement Therapy: CAPD, APD, Haemodialysis, Transplantation, o ns er v a ti M gm
MEDICAL RENAL PHYSIOLOGY (2 credit hours) Lecture 1: Introduction to Renal Physiology Lecture 2: General Functions of the Kidney, Renal Anatomy Lecture 3: Clearance I Lecture 4: Clearance II Problem Set 1: Clearance Lecture 5: Renal Hemodynamics I Lecture 6: Renal Hemodynamics II Lecture 7: Renal Hemodynam
Anatomy of the kidney Figure 11.3 The anatomy of a human kidney. 11.2 Kidney Structure renal artery renal vein ureter a. Blood vessels renal cortex nephrons b. Angiogram of kidney renal cortex renal medulla renal pelvis c. Gross anaomy, photograph d. Gross anatomy, art renal pyramid in rena
1. Prerenal (75- 80%) 2. Intrinsic renal (10-15%) 3. Postrenal (5%) Persistence of insult can convert pre renal or post renal failure to intrinsic renal failure. However, there is an increasing awareness that even moderate decrease in renal function is important in the critically ill and contributes significantly to morbidity as well as mortality.
in regional hospitals in central-western NSW, far-western NSW and on the state's north coast. The University has strong partnerships with both public and private sector health services. In 2015, the University joined with Sydney, Northern Sydney and Western Sydney Local Health Districts, the Sydney Children's Hospital Network (Westmead)
Secondary causes of hypertension Renal causes Two major types of renal diseases - renal parenchymal disease or RAS cause secondary hypertension. Renal parenchymal diseases include glomerulonephritis, polycystic kidney disease, diabetic kidney disease, and chronic pyelonephritis. Reflux ur
1. General considerations Renal failure is a risk factor for developing tuberculosis (TB). Extra -pulmonary TB is more common in patients with chronic renal disease when compared to those with normal renal function. Peritoneal disease is especially frequent in patients on chronic ambulato ry peritoneal dialysis (CAPD).
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Unit 14: Advanced Management Accounting Unit code Y/508/0537 Unit level 5 Credit value 15 Introduction The overall aim of this unit is to develop students’ understanding of management accounting. The focus of this unit is on critiquing management accounting techniques and using management accounting to evaluate company performance. Students will explore how the decisions taken through the .
