Renal Failure: acute, chronic &ESRD

Saeed M.G. Al-Ghamdi,FRCPS,FACP

Faculty of Medicine King Abdulaziz University

Hospital

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

ARF: Definition

Abrupt decline of Glomerular filtration rate which is potentially reversible

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

ARF: Classification & Causes

Pre-renal ARF: 40-80% Renal ARF: 20-30% Post-renal ARF: 2-10%

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

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

Pre-renal Causes4) 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

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)

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

Renal Causes of ARF (Cont..)

2) Toxic and pigment-induced ATN Aminoglycoside nephrotoxicity Amphotericin-induced nephrotoxicity Contrast-nephropathy Hemoglobinuria (severe intravascular

hemolysis) Myoglobinuria (Rhabdomyolysis)

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

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

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

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

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)

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)

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

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)

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

ARF: Causes

Pre-Renal Renal Post-renal

Renal & extra-renal fluid loss

ATN Intra-tubular obstruction

Systemic vaso-dilatation

Interstitial nephritis

Surgical obstruction

Severe cardiac failure

Acute GN

ACEI & NSAID in

predisposed patients

Vasculitis & thrombosis & CAED

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

Renal Vein Thrombosis: S&S

Loin pain Macro and or Microhematuria Proteinuria ARF if bilateral or single kidney Diagnosed by

U/S Doppler Spiral CT Renal venography

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

Cholesterol Athero-embolic Disease

Predisposing factors Follows intravascular intervention May follow bellow renal vascular

surgery May occur after anti-coagulation May occur spontaneously

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

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.

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

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

ARF: Investigations Fractional excretion of sodium:

UNa X PCr FENa: ----------------- X 100 =

PNa X Ucr

< 1%: Pre-renal > 3%: ATN

ARF: Investigations (Cont..) Positive ANA & Anti-dsDNA in lupus

nephritis Low C3 & C4 in :

Lupus nephritis Pos-infectious GN MPGN

Falsely positive RF in cryoglobulinemia

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.

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

ARF: Treatment

First: Treatment of the underlying cause

Second: Conservative treatment of established ARF

Third: Dialysis if indication (s) arise

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)

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

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

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

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)

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

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)

CRF:definition

Chronic, slow, indolent, progressive deterioration of Glomerular filtration rate which is irreversible

CRF: Causes DM: 30% HTN: 26% Glomerulonephritis : 14% Other causes: 30%

Chronic interstitial diseases Obstructive Uropathy ADPKD

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....

CRF: Causes in Children Congenital glomerulonephritis

Alport’s syndrome Congenital FSGS

Glomerulonephritis Unresponsive GN DMS

HUS Congenital HUS Post-diarrheal HUS

CRF: PresentationIn mild to moderate disease; GFR >40

ml/min. Asymptomatic. Incidental discovery of high urea &

Cr. Discovery of concomitant or

causative disease, e.g... PKD, etc.... Hypertension.

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

CRF: Diagnosis

Requires three perquisites: Co-existence of disease that cause

CRF Evidence of Progressive Renal

Dysfunction Evidence of Extra-renal uremic

organ dysfunction

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

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

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)

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

CRF: Investigations (Continued)

Urine analysis: Specific gravity: (1.010) RBCs: (only in patients with Chronic

GN) Casts: (granular casts)

Urine is bland (benign)

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

CRF: Monitoring Renal Function Serum creatinine: (70-120 mic.mol/l)

Affected by muscle mass, sex & protein intake

Cr.clearance = CrU × V(urine volume)/CrP

(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

CRF: Monitoring Renal Function Cockroft & Gault equation: Cr Cl.= (140- age) × wt /Cr P

Reliable in steady state

Clearance of 125 I-isothalamate, 99Tc-DTPA: rapid and accurate

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

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

Uremic OsteodystrophyHyperphosphatemia Low 1,25 DHCC

Hypocalcemia

Hyperparathyoidism

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

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

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)

Treat. Uremic Osteodystrophy

Calcitriol orAlfacalcidol

Calcium Carbonate

Low PhosphateDiet

+ +

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

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)

ESRD:definition

Permanent loss of GFR to the extent where renal replacement therapy is to be instituted

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:

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

RRT: Modalities Hemodialysis Peritoneal Dialysis Renal Transplantation

Living-Related, Living-Unrelated Cadaveric

CRRT CAVH, CVVH, SCUF CAVHD,CVVHD, CAVHDF, CVVHDF

RRT: Absolute Indications for Dialysis Fluid Overload Hyperkalemia Severe Metabolic Acidosis Uremic Pericarditis Uremic Enchephalopathy Intoxication: Methanol, ethylene

glycol ASA, & Lithium

RRT: Relative Indications for Dialysis Uremic Neuropathy Malnutrition of CRF Correct bleeding time before

surgery Cr. clearance <10 ml/minute Level of urea & creatinine ??

Arterial blood fromPatient

Venous blood to patient

IncomingDialysate solution

Hemodialysis: Dialyzer

Hemodialysis: Principles Solutes are effectively removed by

diffusion Water is removed by convection

(UF) Both mechanisms contribute to

solute removal

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

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

Peritoneal Dialysis: CAPD, IPD

PD dialysate solution

PD Catheter

Hanger

Connectionset

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

PD: Complications CAPD PERITONITIS

Abdominal pain Fever Turbid effluent WBC in effluent >400 Organisms:

Staph. aureus and epidermedis Gram negative: Klebseilla, pseudomonas Candida

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

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

CAPD: Complications & Treat. Catheter leak

Treatment: Temporary conversion to HD

Catheter dysfunction: causes Constipation: laxatives Fibrin: IP heparin Omental wrap May require replacement

CAPD: Complications Obesity & hypertriglyceridemia

Due to excessive absorption of glucose

Protein loss & hypoalbuminemia Loss with the effluent

Bloody Effluent: Ruptured corpus leutium (ovulation) Endometriosis

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

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)

CRRT: CAVH

ArterialVenous

UF

Replacement

Qb=50-100 ml/minQf= 8-12 ml/min

CRRT: CAVHD

Arterial Venous

Dialysate out

Qb=50-100 ml/minQd=10-20 ml/minQf= 1-3 ml/min

Dialysate In

CRRT: CVVH

Venous Venous

UF

Replacement

Qb=50-200 ml/minQf= 10-20 ml/min

Pump

CRRT: CVVHD

Venous Venous

Dialysate out

Qb=50-200 ml/minQd=10-30 ml/min Qf= 1-5 ml/min

Dialysate In Pump

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.?

RF: Natural History

RF: Differences

ARF CRF ESRDGFR Rapid decline

Reversible Slow,progressive,irreversible

Permanent no function

Urine output Anuria, oliguria on non-oliguria

Polyuria Polyuria or normal

Urine analysis

Sp.gr.:>1.020May be active sediment

Sp.gr.: 1.010Bland sediment

1.010Bland Sediment

Serum K+ Usually high May be normal

Usually lowMay be normal or high

Usually lowMay be normal or high

Uremic bone disease

Not present Usually present Always present