KIDNEY DISEASE

A Brief Discussion
 APPROACH TO RENAL DISEASE

Renal disease presents in one of two ways:

 Discovered incidentally during a routine medical
evaluation
or
 With evidence of renal dysfunction

CMDT 2009
SYMPYOMS OF RENAL DYSFUNCTION

 Hypertension
 Edema

 Nausea

 Hematuria

CMDT 2009
 EVALUATION

1. An estimation of disease duration

2. A careful urine analysis
3. An assessment of the glomerular filtration rate (GFR)

CMDT 2009
 DISEASE DURATION

 Renal disease may be acute or chronic.

 Acute renal failure is worsening of renal function over
hours to days, resulting in the retention of nitrogenous
wastes (such as urea nitrogen) and creatinine in the
blood.
 Retention of these substances is called azotemia.

 Chronic kidney disease results from an abnormal loss of

renal function over months to years.

CMDT 2009
 DIFFERENCIATION

 Oliguria is unusual in chronic kidney disease

 Anemia (from low renal erythropoietin production) is
rare in the initial period of acute renal failure
 Small kidneys are most consistent with chronic kidney
disease
 normal to large-size kidneys can be seen with both
chronic and acute disease

CMDT 2009
 CHRONIC KIDNEY DISEASE

 Progressive azotemia over months to years.

 Symptoms and signs of uremia when nearing end-stage
disease.
 Hypertension in the majority.

 Isosthenuria and broad casts in urinary sediment are

common.
 Bilateral small kidneys on ultrasound are diagnostic.

CMDT 2009
 CHRONIC KIDNEY DISEASE
 A Growing Problem

CKD is a growing problem in the United States. Between

1990 and 2000, the number of people with kidney failure
requiring dialysis or transplantation virtually doubled to
380,000. If this trend continues, the number of people
with kidney failure will approach 700,000 by 2010. The
annual cost of treating kidney failure in the United States
has already topped $20 billion.

Chronic Kidney Disease: A Family Affair

STATISTICAL DATA OF KIDNEY PATIENTS
IN BANGLADESH
 The number of kidney patients in Bangladesh is on the
rise and during the last 10 years the number doubled to
reach 20 million, local media reported. (10 million in
1997)

 According to the Kidney Foundation in Dhaka, about 1

million new patients are being added to the total number
annually & every year about forty thousand people suffer
from renal failure .

The Daily Ittefaq

MAJOR CAUSES OF CHRONIC KIDNEY
DISEASE
Glomerulopathies
  Primary glomerular
diseases:
 Focaland segmental
glomerulosclerosis
 Membranoproliferative
glomerulonephritis
 IgA nephropathy
 Membranous nephropathy    membranoproliferative
Secondary glomerular diseases:

 Diabetic nephropathy
 Amyloidosis
 Postinfectious
glomerulonephritis
 HIV-associated nephropathy
 Collagen-vascular diseases
 Sickle cell nephropathy
 HIV-associated
glomerulonephritis
CMDT 2009
MAJOR CAUSES OF CHRONIC KIDNEY
DISEASE
 Tubulointerstitial nephritis
 Drug
hypersensitivity
 Heavy metals
 Analgesic nephropathy
 Reflux/chronic pyelonephritis
 Idiopathic
 Hereditary diseases
 Polycystic kidney disease
 Medullary cystic disease
 Alport syndrome
 Obstructive nephropathies
 Prostatic disease
 Nephrolithiasis
 Retroperitoneal fibrosis/tumor
 Congenital
 Vascular diseases 
 Hypertensive nephrosclerosis
 Renal artery stenosis
CMDT 2009
 STAGES OF CHRONIC KIDNEY
DISEASE
Stage Description GFR (mL/min/1.73 m2) Action

1 Kidney > 90 Diagnosis and treatment. Treatment of

damage with comorbid conditions. Slowing of
normal or GFR progression. Cardiovascular disease risk
reduction
2 Kidney 60–89 Estimating progression
damage with
mildly GFR
3 Moderately 30–59 Evaluating and treating complications
GFR
4 Severely GFR 15–29 Preparation for kidney replacement therapy

5 Kidney failure < 15 (or dialysis) Replacement (if uremia is present)

CMDT 2009
 FATE OF CHRONIC KIDNEY DISEASE
(CKD)
 Chronic kidney disease is rarely reversible and leads to a
progressive decline in renal function.
 This occurs even after an inciting event has been
removed.
 Reduction in renal mass leads to hypertrophy of the
remaining nephrons with hyperfiltration.
 The GFR in these nephrons is transiently at supranormal
levels.
 These adaptations place a burden on the remaining
nephrons and lead to progressive glomerular sclerosis
and interstitial fibrosis.

CMDT 2009
 CLINICAL FINDINGS
Organ System Symptoms Signs
General Fatigue, weakness Sallow-appearing, chronically ill

Skin Pruritus, easy bruisability Pallor, ecchymoses, excoriations,

edema, xerosis
ENT Metallic taste in mouth, epistaxis Urinous breath
Eye Pale conjunctiva
Pulmonary Shortness of breath Rales, pleural effusion
Cardiovascular Dyspnea on exertion, retrosternal pain on Hypertension, cardiomegaly,
inspiration (pericarditis) friction rub
Gastrointestinal Anorexia, nausea, vomiting, hiccups

Genitourinary Nocturia, impotence Isosthenuria

Neuromuscular Restless legs, numbness and cramps in legs

Neurologic Generalized irritability and inability to Stupor, asterixis, myoclonus,

concentrate, decreased libido peripheral neuropathy

CMDT 2009
 PHYSICAL EXAMINATION
 Patient appears chronically ill
 Hypertension

 Skin may be yellow

 Signs of easy bruisability

 Uremic frost

 Uremic fetor

 Decreased concentration to confusion

 Stupor

 Coma

CMDT 2009
 LABORATORY FINDINGS
 The diagnosis of renal failure is made by documenting
elevations of the BUN and serum creatinine
concentrations.
Further evaluation is needed to differentiate between
acute and chronic renal failure
 Anemia, metabolic acidosis, hyperphosphatemia,
hypocalcemia, and hyperkalemia can occur with both
acute and chronic renal failure
 The urinary sediment can show broad waxy casts as a
result of dilated, hypertrophic nephrons

CMDT 2009
 REVERSIBLE CAUSES OF RENAL
FAILURE
Reversible Factors Diagnostic Clues
Infection Urine culture and sensitivity tests
Obstruction Bladder catheterization, then renal
ultrasound
Extracellular fluid volume Orthostatic blood pressure and pulse: blood
depletion pressure and pulse upon sitting up from a
supine position
Hypokalemia, hypercalcemia, Serum electrolytes, calcium, phosphate,
and hyperuricemia (usually >15 uric acid
mg/dL)

Nephrotoxic agents Drug history

Hypertension Blood pressure, chest x-ray
Congestive heart failure Physical examination, chest x-ray
CMDT 2009
 COMPLICATIONS
 Hyperkalemia
 Acid–Base Disorders
 Cardiovascular Complications
 Hypertension
 Pericarditis
 Congestive heart failure
 Hematologic Complications
 Anemia
 Coagulopathy
 Neurologic Complications
 Disorders of Mineral Metabolism
 Endocrine Disorders

CMDT 2009
 TREATMENT
 Dietary Management
 Protein restriction
 Salt and water restriction
 Potassium restriction
 Phosphorus restriction
 Magnesium restriction

 Dialysis
 Hemodialysis
 Peritoneal dialysis
 Kidney Transplantation

CMDT 2009
 THE PRIMARY CAUSE OF ANEMIA
IN PATIENTS WITH CKD
 Inadequate production of erythropoietin by the
failing kidney
 Blood loss from repeated laboratory testing or
GI bleeding
 Blood loss or RBC destruction from the dialysis
machine itself
 Severe hyperparathyroidism
 Heightened state of inflammation and associated
elevations in inflammatory cytokines
 Aluminum toxicity.
 CAUSE OF ANAEMIA IN CRF
Anemia in Chronic Renal Failure Caused by Decreased
Erythropoietin Secretion
 Patients with severe chronic renal failure almost always
develop anemia.
 The most important cause of this is decreased renal
secretion of erythropoietin, which stimulates the bone
marrow to produce red blood cells.
 If the kidneys are seriously damaged, they are unable to
form adequate quantities of erythropoietin, which leads to
diminished red bloodcell production and consequent
anemia.

Textbook of Medical Physiology; Guyton and Hall 11th edition

 CAUSE OF ANAEMIA IN CRF
Artificial kidneys or Dialysis
 Most artificial kidneys can clear urea from the plasma at
a rate of 100 to 225 ml/min so it can function about
twice as rapidly as two normal kidneys together
 Yet the artificial kidney is used for only 4 to 6 hours per
day, three times a week
 But it is important to keep in mind that the artificial
kidney cannot replace some of the other functions of the
kidneys, such as secretion of erythropoietin, which is
necessary for red blood cell production.

Textbook of Medical Physiology; Guyton and Hall 11th edition

 FACTS OF DEVELOPING IRON
DEFICIENCY ANEMIA IN CHRONIC
KIDNEY DISEASE

 Inadequate production of the erythropoetin by the

diseased kidney
 Blood loss due to blood retention in the dialyzer &
frequent blood sampling
 Lower intake of protein because of declining renal
function
 Malabsorption syndrome
 PHYSIOLOGICIAL ROLE OF
ERYTHROPOIETIN
The total mass of red blood cells in the circulatory system
is regulated within narrow limits, so that
i. An adequate number of red cells is always available to
provide sufficient transport of oxygen from the lungs to
the tissues, yet
ii. The cells do not become so numerous that they impede
blood flow.What we know about this control mechanism
is diagrammed

Textbook of Medical Physiology; Guyton and Hall 11th edition

PHYSIOLOGICAL FUNCTION OF
ERYTHROPOIETIN

Textbook of Medical Physiology; Guyton and Hall 11th edition

 ROLE OF THE KIDNEYS IN
FORMATION OF ERYTHROPOIETIN
 In the normal person, about 90 per cent of all
erythropoietin is formed in the kidneys; the remainder is
formed mainly in the liver.
 One likely possibility is that the renal tubular epithelial
cells secrete the erythropoietin, because anemic blood is
unable to deliver enough oxygen from the peritubular
capillaries to the highly oxygen-consuming tubular cells,
thus stimulating erythropoietin production.
 Both norepinephrine and epinephrine and several of the
prostaglandins stimulate erythropoietin production

Textbook of Medical Physiology; Guyton and Hall 11th edition

LOW LEVEL OF ERYTHROPOIETIN IN
CRD
 When both kidneys are removed from a person or when the
kidneys are destroyed by renal disease, the person invariably
becomes very anemic because the 10 per cent of the normal
erythropoietin formed in other tissues (mainly in the liver) is
sufficient to cause only one third to one half the red blood
cell formation needed by the body.

Textbook of Medical Physiology; Guyton and Hall 11th edition

ERYTHROPOISIS
 REGULATION OF ERYTHROCYTE
PRODUCTION
 The kidneys secrete erythropoietin, which stimulates the
production of red blood cells.
 The kidneys normally account for almost all the
erythropoietin secreted into the circulation.
 In people with severe kidney disease or who have had
their kidneys removed and have been placed on
hemodialysis, severe anemia develops as a result of
decreased erythropoietin production.

Textbook of Medical Physiology; Guyton and Hall 11th edition

FORMATION OF HEMOGLOBIN

Textbook of Medical Physiology; Guyton and Hall 11th edition

 FORMATION OF HB IN RBC
 Synthesis of hemoglobin begins in the proerythroblasts
and continues even into the reticulocyte stage of the red
blood cells.
 when reticulocytes leave the bone marrow and pass into
the blood stream, they continue to form minute
quantities of hemoglobin for another day or so until they
become mature erythrocytes

Textbook of Medical Physiology; Guyton and Hall 11th edition

ROLE OF IRON IN PRODUCTION OF
RBC

 In the absence of erythropoietin, few red blood cells are

formed by the bone marrow.
 when large quantities of erythropoietin are formed
available, and if there is plenty of iron and other
required nutrients available, the rate of red blood cell
production can rise to perhaps 10 or more times normal.

Textbook of Medical Physiology; Guyton and Hall 11th edition

 IRON DEFICIENCY IN CKD
 Many CKD patient have Iron deplation in Bonemarrow
despite normal serum indices
 Reasons for Iron Deficiency
 Decreased oral intake
 Decreased intestinal absorption
 GI bleeding
 Phosphate binders

 30% of CKD patient can attain HCT of 35% with IV iron

alone.

Silverberg DS kidney int 55(suppl 69) S-79, S-85,1999

CKD PATIENTS WITH HB<11.2 ARE 3 TIMES
MORE LIKELY TO PROGRESS THAN THOSE
WITH HB > 13.8

Keane WF et al. Kidney int. 63(40): 1499-1507, 2003

MORBIDITY OF ANAEMIA IN PATIENTS
WITH CKD

 Anaemia is a significant risk factor for CVD disease and

progressive renal insufficiency
 Therapy of anaemia may improve renal outcome

 Therapy of anaemia in CKD patients may improve

outcomes in the ESRD period
TREATMENT OF ANEMIA IN CKD

 Traditional therapy, which is based on either oral

administration of Iron or blood transfusion or both
 The efficacy of orally administered high-dose Iron was
limited by the high incidence of side effects and thus
non-compliance
 Blood transfusion remain the last resort because of
patient choice and the risk of infection and transfusion
reaction
 Intravenous iron preparation
 TREATMENT OF ANEMIA IN CKD
Where there is a clinical need for a rapid iron supply
 Chronic Kidney Disease (CKD):
 Pre-Dialysis
 Hemodialysis
 Peritoneal Dialysis patients
 For replenishing iron in patients
• receiving erythropoietin (stimulates RBC production)
• undergoing chronic hemodialysis (filtering the blood in order to
remove waste products)
 Anemia of renal failure treated with erythropoetin

 So, Therapy of anaemia requirs iron and EPO

 ASSESSING IRON STATUS
Absolute Iron Deficiency Functional Iron Deficiency

TSAT <20% TSAT >20%

Ferritin <100 ng/mL   Ferritin ≥100 ng/mL

 The current K/DOQI Anemia of Chronic Kidney Disease

guideline recommends an anemia workup for patients
with chronic renal failure when:
• HCT is <33% and/or Hb <11 g/dL in premenopausal
women and patients before puberty
• HCT is <37% and/or Hb <12 g/dL in adult males and
postmenopausal females
WHY I.V. IRON SHOULD BE USED IN CKD?
• As Iron losses are high, especially in hemodialysis patients
.One study shows that an average monthly blood loss of 167
to 226 ml & a monthly iron loss of 57 to 78 mg .
• Oral iron usually cannot maintain adequate iron stores,
especially in hemodialysis patients receiving erythropoietin
• Erythropoietin stimulates erythropoiesis to greater than
normal levels, often leading to functional iron deficiency
• Prevention of functional and absolute iron deficiency by
regular use of I.V. iron improves erythropoiesis
 IV IRON ALONE IN CKD

11.05

10.67

9.76
9.68

Silverberg DS, et al.Clinical Nephrology 55(3): 212-219, 2001

 EFFICACY OF IV IRON THERAPY
OVER ORAL IRON THERAPY IN CKD
 Quickly replenishes depleted iron stores
 Raises serum ferritin
 Corrects iron-deficient erythropoiesis
 Raises transferrin saturation (TSAT) and Hb reticulocyte
content (CHr)
 Increases Hb, or decreases epoetin dose
for same Hb
 Maintains iron-sufficient erythropoiesis
 Replenishing iron stores assures adequate iron supply in
patients prone to blood loss
(eg, hemodialysis-related)
 More efficacious than oral iron without increased mortality
& morbidity when used in accordance with clinical
practice guidelines.
 Advantages of Iron Sucrose

Parameters Iron Sucrose Iron Iron

Dextran Gluconate
Release of Iron Rapid Slow Rapid
Preservative None None Yes
Test Dose Required No Yes No
‘Black Box’ Warning No Yes No
…for faster & safer recovery from IDA

introduces
MECHANISM OF ACTION
DOSAGE AND ADMINISTRATION
 Adults and the Elderly: 5-10 ml Feroven (100-200 mg
Iron) once to three times a week depending on the
hemoglobin level.
 Children: There is limited data on children under study
conditions. If there is a clinical need, it is recommended
not to exceed 0.15 ml Feroven (3 mg Iron) per kg body
weight once to three times per week depending on the
hemoglobin level.
DOSAGE AND ADMINISTRATION

 Intravenous Injection: Feroven can also be

administered undiluted by slow IV injection at the
(normal) recommended rate of 1 ml Feroven (20 mg
Iron) per minute [5 ml Feroven (100 mg Iron) in 2 to 5
minutes]. A maximum of 10 ml Feroven (200 mg Iron)
can be injected per injection.
DOSAGE AND ADMINISTRATION

 To avoid hypotensive episodes Feroven should

preferably be administered by drip infusion in a dilution
of 1 ml Feroven (20 mg Iron) in max. 20 ml 0.9% w/v
Sodium Chloride in a infusion rate of 100 mg Iron in at
least 15 minutes; 200 mg Iron in at least 30 minutes.
Dilution must take place immediately prior to infusion.