Acute renal failureARF

Definition

ARF is a clinical syndrome characterized byan abrupt decline in GFR and theaccumulation of nitrogenous waste (BUN & creatinine). The decrease in GFR occursrelatively rapidly, over the course of days toweeks. (By contrast, CRF develops overmonths or years.)

Epidemiology of acute renal failure

• Common clinical syndrome• broad aetiological profile• 5 % of hospital admissions, 30 % of

admissions to ICU.

Etiology

• prerenal (about 75 %),• intrinsic or parenchymal renal disease (25

%),• postrenal (5 %)

Clinical approach to the diagnosis

• Is it ARF or acute-on-chronic renal failure?• Is there renal tract obstruction?• Is there reduction in effective ECF volume?• Has there been a major vascular occlusion?• Is there parenchymal renal disease other

than ATN?

Is the renal failure really acute?Differential diagnosis

Acute renal failure• normal or enlarged

kidneys• no/mild anemia (BUT

HUS)• Ca & P normal

Chronic renal failure• smaller kidneys• severe anemia without

serious symptomes• nocturia, pruritus, long

lasting HT, neuropathy

• Ca⇓, P⇑, • abnormal biochemical

values / patient withoutserious symptomes

• Urine volume– oliguria < 400 ml/day– anuria < 50 ml/day

• Serum chemistry– BUN (back-diffusion

depends on urine flowrate)

– creatinine

Treatment of ARF

Prerenal ARF

• Glomerular perfusion ⇓• GFR ⇓

• absence of any structural abnormality of the renal parenchyma

• rapidly and completely reversed• RBF sufficient to sustain the viability of

renal tubular cells (⇔ ATN)

Acute tubular necrosis (ATN)

• Renal parenchymal injury caused by ischemia or exposure to nephrotoxins, which particularly injure the tubular epithelium.– Ischemic– nephrotoxins

• endogenous (e.g. myoglobin, light chains)• exogenous (e.g. drugs, heavy metals)

Causes of acute interstitialnephritis (AIN)

1. Drug-related AIN2. Infection-related AIN3. Systemic diseases

lupus erythematosusSarcoidosisSjögren’s syndrome

4. Malignancy5. Idiopathic AIN

CHRONIC RENAL FAILURE

Diabetes: The Most Common Cause of ESRD

Primary Diagnosis for Patients Who Start Dialysis

United States Renal Data System. USRDS 2000 Annual Data Report. June 2000.

Diabetes50%

Hypertension27%

Glomerulonephritis

13%

Other10%

Patients (n)Projection95% CI

1984 1988 1992 1996 2000 2004 20080

100

200

300

400

500

600

700

r2 = 99.8%243,524

281,355520,240

No. of Dialysis Patients

(thousands)

CHRONIC RENAL FAILURE

• The progression of chronickidney disease

• Uremia – clinical abnormalities• Renal anemia and renalosteodystrophy

• Renal replacement therapy

Risk Factors for Renal Disease Progression

Proteinuria > 1.5 g/24 hrHypertensionType of underlying renal diseaseAfrican-American raceMale sexObesityDiabetes mellitusHyperlipidemiaSmokingHigh protein dietPhosphate retentionMetabolic acidosis

The epidemiology of CKD

USA: 11 % of the population, around 20 million people haveCKD

Treatment of Renal DiseaseProgression

• Goals:– stop or slow the rate of GFR

decline– prevent additional kidney damage

cused by superimposed events– maintain nutritional status and

prevent complications of the uremicsyndrome.

Slowing the progresion of chronic kidneydisease

Tight blood pressure control (BP≤ 130/80 mm Hg) using:low sodium dietACE inhibitorsangiotensin receptor antagonistsdiureticscalcium channel blockers +…

Dietary protein restriction (0.8-1 g/kg bodyweight)

Glycemic controlDecreasing proteinuria

CHRONIC RENAL FAILURE

• The progression of chronickidney disease

• Uremia – clinical abnormalities• Renal anemia and renalosteodystrophy

• Renal replacement therapy

Uremic toxins

• Low molecular mass solutes: 10-3000 Da– urea, creatinine

• Middle molecules: 3000-15000 Da– PTH, ß2-microglobulin

• Large solutes: more than 15000 Da– myoglobin

Major Clinical Abnormalities in Uremia I.

Water and electrolyte abnormalities:volume expansionhyperkalaemiametabolic acidosishyperphosphatemia and hypercalaemia

Cardiovascular abnormalities:hypertensioncongestive heart failurecardiomiopathypericarditisaccelerated atherosclerosisarrhythmias

Major Clinical Abnormalities in Uremia II.

Gastrointestinal abnormalities:anorexia, nausea, and vomitinguremic fetorstomatitis, gastritispeptic ulcergastrointinal bleeding

Hematologic and immunologic abnormalities:anemiableedingphagocyte inhibitionlymphocytopeniaincreased susceptibily to infection andneoplasia

Major Clinical Abnormalities in Uremia III.

Neurological abnormalities:malaiseheadacheirritability and sleep disordersmuscle crampstremorseizuresstupor and comaperipheral neuropathyrestless legsmotor weakness

Major Clinical Abnormalities in Uremia IV.Endocrine and metabolic abnormalities:

hypertriglyceridemiaprotein malnutritionimpaired growthinfertility, sexual dysfunction, andamenorrhearenal osteodystrophysecondary hyperparathyreoidism

Dermatologic abnormalities:pallorhyperpigmentationpruritus

CHRONIC RENAL FAILURE

• The progression of chronickidney disease

• Uremia – clinical abnormalities• Renal anemia and renalosteodystrophy

• Renal replacement therapy

Renal Anemia• Anemia develops early during renal failure

and is one of the major causes of malaiseand fatigue.

• It is normocytic and normochromic but maybe complicated by– iron deficiency due to gastrointestinal bleeding

(microcytic)– folate deficiency due to dietary restriction

(macrocytic)– fibrosis of the bone marrow due to

hyperparathyroidism.

Correction of Anemia

• Improves cardiac function, centralnervous system symptoms, appetiteand sexual function.

• Erythropoietin administration shouldbe started in the predialysis period.

• Target hemoglobin: 110-120 g/l.• Sufficient iron and folate stores

should be maintained!

Renal Osteodystrophy

• Includes all sceletal disorders ofpatients with renal failure:– osteitis fibrosa– osteomalacia– mixed and adynamic bone lesions– dialysis related amyloidosis

CHRONIC RENAL FAILURE

• The progression of chronickidney disease

• Uremia – clinical abnormalities• Renal anemia and renalosteodystrophy

• Renal replacement therapy

Renal Replacement Therapy

• Hemodialysis• Peritoneal dialysis• Kidney transplantation

Absolute Indications for Initiation of Dialysis

Ø PericarditisØ Advanced or progressive uraemic encephalopathy

or neuropathyØ Pulmonary edema and fluid overload unresponsive

to diuretic measuresØ Hypertension poorly responsive to treatmentØ Hyperkalaemia attributed to ESRD unresponsive to

conservative treatmentØ Bleeding diathesis with clinical bleeding attributed to

uraemiaØ Persistent nausea

Hakim, Advances Nephrol 23: 295-309, 1994

Relative Relative Indications for Indications for Initiation of DialysisInitiation of Dialysis

Ø General

Anorexia, fatigue, weaknessGFR < 20 ml/min in diabetics or

GFR = 10-15 ml/min (other etiologies)

Hakim, Advances Nephrol 1994; 23: 295-309

Ø Neurological

Peripheral neuropathy (often burning dysesthesia)Restless leg syndrome

Ø Cardiovascular

Peripheral edema unresponsive to diuretics

Ø Gastrointestinal

Anorexia progressing to nausea and vomitingGastritis, duodenitis, constipationAscites without liver disease

RelativeRelative Indications for Indications for Initiation of Dialysis (continued)Initiation of Dialysis (continued)

Hakim, Advances Nephrol 1994; 23: 295-309

Ø Hematological

Anaemia with poor response to erythropoeitinInfectionsIncreased bleeding tendency due to platelet dysfunction

Ø Dermatological

Persistent and severe itching

BloodInflow

DialysateOutflow

DialysateInflow

BloodOutflow

Countercurrent flow of blood (within capillaries) and dialysate(outside of capillaries).

Solute Transferacross the Capillary Walls

Principles of dialysers

Blood PumpAnticoagulation

Blood tothe Patient

Blood fromthe Patient

Dialyser

Fresh Dialysate

UsedDialysate

Flow Scheme Hemodialysis

Standard Arteriovenous (AV) Fistulaat the Wrist

modified from Man, Zingraff, Jungers, Long-Term Hemodialysis, 1995

Patient access

Twin Catheters Placed in the Internal Jugular Vein

modified from Man, Zingraff, Jungers, Long-Term Hemodialysis, 1995

Patient access

Haemodialysis

Standard Standard TherapyTherapy::IntermittentIntermittent HDHD

ca. 3x4ca. 3x4--5 h / 5 h / weekweek

Peritoneal Dialysis

„„NaturalNatural““Semipermeable Semipermeable

Membrane :Membrane :

PeritoneumPeritoneumThe transport of substances

via Peritoneum occurs in both directions: i.e. Wastesubstances from the bloodinto the solution and buffer

substances in the otherdirection.

Principles of Peritoneal Dialysis

• Small solute movement occurs by diffusionbased on the concentration gradient (urea, creatinine, potasssium).

• Large solute removal occurs by convection: the solute movement is related to fluid removal.

• The volume of ultrafiltration depends onthe concentration of glucose solution (thelength of dwell and the peritonealmembrane characteristics).

C C ontinuousontinuous

A A mbulatorymbulatory

P P eritonealeritoneal

D D ialysisialysis

the patient can walk aroundwhile it's happening

constant dialysis24 hours a day

peritoneal membraneworks as a filter

What is CAPD ? What is CAPD ?

Summary –Renal Replacement Therapies

Peritoneal dialysis• Most frequent home dialysis modality, lower

efficiency but continuous treatment• Risk of infectious complications

Kidney Transplantation• Best outcome• Risk for infections, tumours, bone fractures• Not all patients are eligible for transplantation

Hemodialysis• Most frequent modality, highly efficient but

intermittent• Risk of intradialytic complications• Mainly centre treatment