CHRONIC RENAL FAILURE

Mohammed Almeziny

BsPharm R,Ph. Msc PhD

Consultant clinical Pharmacist

Kidney Functions

Excretion of waste products Homeostasis

– regulation of electrolyte– blood volume.– blood pressure..

Acid-base balanceHormone secretion

– Erythropoietin.– Activation of vitamin D.

Chronic Kidney Disease (CKD)some definitions

CKD results when a disease process damages the structural or functional integrity of the kidney.

This is clinically detected using either physical exam (hypertension), laboratory (hematuria, proteinuria, microalbuminuria) or imaging studies (CT, MRI, or renal ultrasound).

Category 24-Hrs collection (mg of protein or albumin per 24 hrs

Normal <300 mg/day proteinor <30 mg/day albumin

Microalbuminuria 30-300 mg /day albumin

Clinical proteinuria or albuminuria

> 300 mg /day protein or albumin

Spot collection(Ratio)Category Protein(mg):

Creatinine(g) Albumin(Mcg) : Creatinine (mg)

Normal <200 mg/g < 30mcg/mgMicroalbuminuria Not

applicable 30-299 mcg /mg

Clinical proteinuria or albuminuria

> 200 mg /g >300mcg/mg

Category Timed collection

Normal <20 mcg/min

Microalbuminuria 20-199mcg/min

Macroalbuminuria > 200 mcg /min

CKD –SOME DEFINITIONS cont’d

Almost all patients with a GFR = 60 ml/min/1.73m2 have CKD.

However, since GFR declines normally with age (approximately 1ml/min/1.73 m2 /year after age 20), a GFR between 60 - 90 ml/min/1.73m2 in the elderly may not be indicative of the presence of CKD.

In order for patients to be classified as having CKD there must be some objective evidence on either physical exam, laboratory or imaging studies of kidney damage.

CKD- EtiologyAny primary or secondary renal parenchymal

disease that has a progressive course e.g glomerulonephritis,

Progressive tubulointerstitial nephritis, etcUnrecognized or untreated obstructive uropathyPolycystic kidney diseaseOften the cause is unknown

CKD Etiology cont’d

CAUSE ADULTS CHILDREN

GLOMERULONEPHRITIS 3+ 4+

DIABETES 4+ RARE

HYPER TENSION (cause or consequence) 2+ RARE

POLYCYSTIC KIDNEY 2+ 1+

INTERSTITIAL NEPHRITIS 2+ 2+

OBSRUCTIVE NEPHROPATHY 1+ 3+

RENAL HYPOPLACIA RARE 2+

HEREDITARY DISORDERS RARE 1+

STAGE DESCRIPTION GFR(ml/mt)

0 With risk factors >90

I Kidney damage (with normal or GFR) >60

II Mild 60-89

III Moderate 30-59

IV Severe 15-29

V Kidney failure (includes patients on dialysis) <15

CLASSIFICATION OF CKD-NKFpresent for a period of 3 months or more

CKD - symptomsStage 1 or 2 CKD disease usually do not have any

symptoms or metabolic derangements.Anorexia, nausea, vomiting, weight lossMuscle cramps, especially at nightPruritis Fatigue, weakness, coldness Amenorrhea, decreased libidoThese symptoms are collectively referred to as theuremic syndrome.

CKD – signs

Pallor (from the anemia)Hypertension (usually, but not always !)Hypertensive target organ damage (eg retinopathy,

left ventricular hypertrophy)Peripheral type sensory neuropathy

CKD - Diagnosis

May be suspected on basis of clinical presentationMore often, diagnosed by blood tests

– Elevated serum creatinine– Elevated serum urea

May be discovered incidentally during workup for– anemia, amenorrhea or anorexia

CKD– Diagnosis (cont’d)

Serum creatinine is a marker of glomerular filtration rate– GFR ~ Creatinine Clearance, or– GFR ~ Urine creatinine excretion per 24 h

Plasma Creatinine– If the SrCr is doubled, CrCl is roughly halved

– if the SrCr is tripled, CrCl is reduced to roughly one third; etc.

CKD - Diagnosis (cont’d)

Serum creatinine is also proportional to body muscle mass:

Since creatinine is a muscle byproduct, you must “eyeball” the patient’s muscle mass when

interpreting SrCr

– eg. Young well-muscled man– Elderly wasted woman– Ideal body weight

CKD – Diagnosis (cont’d)

Associated laboratory findings - hematologic: Clinical results:– normocytic normochromic anemia– predisposition to infection– easy bleeding

CKD – Diagnosis (cont’d)

Associated laboratory findings - Ca++ & P:Hypocalcemia

– decreased renal 1-hydroxylation of 25-OH D3 to 1,25(OH)2 D3– Hyperphosphatemia– retention of dietary P, GFR

CKD - Diagnosis (cont’d)

Associated laboratory findings - Ca++ & P: Secondary hyperparathyroidism– PTH secretion stimulated by– Hypocalcemia– Hyperphosphatemia– Decreased 1,25 (OH)2 D3 concentration

CKD- Diagnosis (cont’d)

Associated laboratory findings - Ca++ & P:Results:

– PTH is postulated to be one of the “uremic toxins” – besides bone problems, excess levels of PTH

associated with– Anemia– Pruritis– Myocardial fibrosis

CKD Diagnosis (cont’d) If a patient presents with an elevated SrCr, you must

distinguish if it reflects ARF or CRF

Acute renal failure Potentially reversible

Blood values are changingpt. is unstable

Chronic renal failure- Not reversible- Blood values stable- pt. is stable

Duration of symptoms Absence of acute illness in face of very high urea and

creatinine Small kidneys on imaging Bone disease Neurological Complications Skin / nail / eye changes

FACTORS SUGGESTING CHRONICITY

UREMIA PATHOPHYSIOLOGY

LOSS OF NEPHRONS

Na+ BALANCE H2O BALANCE K+ BALANCE

H+ BALANCE

EXC. OF DRUGSEXC.OF NITROGENOUSWASTES

Ca,Mg,,P,Vit DMETABOLISM

CATABOLSIM OFPEPTIDES

ERYTHROPOIETIN

DR.V.KANNAN

· DIAGNOSIS: AETIOLOGY; EST.CHRONICITY· ASSESMENT OF SEVERITY· ASSESMENT OF NUTRITIONAL STATUS· CONSERVATIVE MANAGEMENT· PREDIALYSIS / TRANSPLANTATION EVALUATION· DIALYSIS ACCESS / HBV VACCINATION· DIALYSIS / TRANSPLANTATION

APPROACH TO THE PATIENT WITH CKD

Systemic Lupus Erythematosis (SLE)Obstructive NephropathyIschemic NephropathyPyelonephritisGlomerulonephritisHypertensive Nephrosclerosis

TREATABLE CAUSES OF CKD

AVOID AGGRAVATING RF

CONSERVATIVE Mx OF CKD

SLOW PROGRESSION OF RF TREAT. UREMIC SYMP.

· Avoid volume depletion / excess· Careful drug usage· Avoid electrolyte imbalance· Avoid pregnancies in high risk cases· Avoid urinary instrumentation & contrast studies

MEASURES TO AVOID AGGRAVATING RF

· Cardiac Failure· Drugs: NSAIDS, ACEI, AG, Contrasts, etc· Volume depletion· HTN - uncontrolled / over treatment· Obstruction· Infection- renal / extra renal· Catabolism: Infection, GI bleed, surgery, etc· Electrolyte Disturbances

REVERSIBLE FACTORS AGGRAVATING CKD

Control HTN / cardiac risk factorsDietary protein restrictionScreen & treat UTIControl hyperphosphatemia / hyperuricemiaTreat hyperlipidemiaACE inhibitorsTreatment of primary causeGlycemic control in diabetes

Measures to Slow Progression of Rf

Degree of CKD GFR Action Mild 60-90 ml/min/1.73 m 2 Steps 1,2

Moderate 30- 59 ml/min/1.73 m 2 Steps 1,2,3 Severe 15- 29 ml/min/1.73 m 2 Steps 1,2,3,4

Step 1 - slow the progression of chronic kidney disease to end stage renal disease (ESRD)

Step 2 - identify and treat co-morbid conditions (cardiovascular)Step 3 - identify and prevent complications of CKD (anemia, divalent ions, malnutrition)

Step 4 - prepare the patient mentally and physically for renal replacement therapy

Stepped-care parallels impairment of GFR

Blood Pressure

TARGETS

HYPERTENSION WITHOUT CRF <130/85

HYPERTENSION WITH CRF&

PROTEINURIA <1G/DAY <130/80

HYPERTENSION WITH CRF&

PROTEINURIA >1G/DAY <125/75

CURRENT RECOMMENDATIONS FOR HYPERTENSION CONTROL IN CKD

ACEI/ARB RECOMMENDATIONS FOR USE IN CKD

ACE INHIBITOR AS FIRST LINE THEPRAPY IN TYPE-1 & TYPE-2 DM PATIENTS WITH

MICRO/ MACROALBUMINURIA EVEN WITHOUT HTN/RF

ALL PATIENTS WITH HTN AND/OR PROTEINURIA

angiotensin receptor blockers (ARBs),

Complications ANEMIA: the kidneys secrete 90% of the

endogenous hormone erythropoietinCARDIOVASCULAR DISEASEDISORDERS OF CALCIUM AND

PHOSPHORUS HOMEOSTASIS: occur in stages 3 to 5 CKD, hyperparathyroidism

MALNUTRITION:It is recommend to evaluate for signs of malnutrition when the GFR < 60 mL/min

TREATMENT OF UREMIC SYMPTOMS

GI SYMPTOMS:• Protein Restriction• Correct Acidosis• Small Frequent meals• Antiemetics • H2 Antagonists• AL.OH Gel

ITCHING:• Protein Restriction• Phosphate Restriction• Antihistaminics• Emollients• UV Radiation• Cholestyramine• Boluso of Xylocaine• Erythropoietin

NEUROMUSCULAR:• Protein Restriction• Vitamins• Exercise• Muscle Relaxants• Tranquilizers• Quinine• Anti-depressants• Correction of Anemia

SKELETAL:• Decrease & Bind Phosp• Treat acidosis• Calcium Supplements• Clacitriol / 1 Alpha• Treat severe hyperuricemia

ANEMIA• Iron, Folate & B12• Erythropoietin• Transfusion

• Uremic symptoms, e.g. nausea, weight loss• Recent change in philosophy to “early start”, where

patient is started on dialysis before getting sick• Attempt to start dialysis when creatinine clearance is <15 ml /

min• Diabetics are started on dialysis sooner (cr cl < 20

ml/min) because they don’t tolerate uremia well

INDICATIONS FOR DIALYSIS

The Philosophy of “Early Start” Dialysis

Goals of Dialysis

1. Solute/toxin removal (blood purification)2. Removal of salt and water (ultrafiltration)

Peritoneal DialysisCatheter is inserted surgically or laparoscopically

into peritoneal cavityDialysis fluid high in glucose concentration is

instilled through catheter and allowed to dwell in the cavity

Uremic toxins diffuse from ECF into the peritoneal fluid

Ultrafiltration by osmosis (glucose in fluid)

HemodialysisBlood is removed from the body and travels to the

hemodialysis machine where it is run across a semipermeable membrane with a physiologic solution on the other side of the membrane

Uremic toxins cross into dialysate by diffusion and convection

Ultrafiltration by a hydraulic pressure placed across the dialysis membrane

Hemodialysis (cont’d)Intermittent hemodialysis

– Typically patients undergo dialysis for 3 to 4 hours daily or on alternate days depending on their catabolic state

Continuous hemodialysis– Continuous renal-replacement therapy, patients undergo

dialysis Continuously usually, it is recommended because of hemodynamic instability.

Hemodialysis (cont’d)Usually done as an intermittent procedure, eg for 4

hours 3 X a weekRequires a vascular access to allow for repeated needle

insertion and high blood flow rates– construction of an arteriovenous fistula in the fore arm– insertion of a prosthetic vascular graft in the arm, or– indwelling catheter into a major vein

Renal Transplantation

A successful kidney transplant is the only way to fully, or almost fully, correct uremia

Types of Renal Transplantation

– Cadaveric (4 to 5 years waiting time)– Living related– Living unrelated

dialysis