Chronic kidney disease (CKD)

T. khutchua
 CKD
Chronic kidney disease (CKD) encompasses a
spectrum of different pathophysiologic processes
associated with abnormal kidney func­tion and a
progressive decline in glomerular filtration rate (GFR) .
 CKD
CKD
is staged by the GFR
 There are 5 stages of CKD
 end-stage renal disease represents a stage of CKD where the
accumulation of toxins, fluid, and electrolytes results in the
uremic syndrome
 Uremic syndrome leads to death unless the toxins are
removed by renal replacement therapy, using dialysis or
kidney transplantation
GFR
 EPIDEMIOLOGY

 6% of the adult population in the United States has CKD at stages 1 and 2

 4.5% of population is estimated to have stages 3 and 4 CKD

 The most frequent cause of CKD in North America and Europe is diabetic
nephropathy (type 2)
 ETIOLOGY
 Genetically determined abnormalities in kidney
development or integrity

 Immune complex deposition and inflammation in certain

types of glomerulonephritis

 Toxin exposure in certain diseases of the renal tubules

and interstitium
LEADING CATEGORIES OF ETIOLOGIES OF CKD

. Diabetic nephropathy
. Glomerulonephritis
. Hypertension-associated CKD
. Autosomal dominant polycystic kidney disease
. Other cystic and tubulointerstitial nephropathy
 PATHOPHYSIOLOGY

 initiating mechanisms specific to the underlying etiol­ogy

 A set of progressive mechanisms, involving hyperfiltration
and hypertrophy of the remaining viable nephrons, that
are a common consequence following long-term reduction
of renal mass
 RISK FACTORS
 childhood obesity
 hypertension
 diabetes mellitus
 autoimmune disease
 advanιed age
 African ancestry
 Hereditable and a family history of kidney disease
 a previous episode of acute kidney injury
 The presence of proteinuria, abnormal urinary sediment
 structural abnormalities of the urinary tract
 Invironmental trigger (e.g., viral pathogen)
 UREMIA

 Serum urea and creatinine concentrations are used to mea­sure

the excretory capacity of the kidneys
 Accumulation of these two molecules themselves does not
account for the many symptoms and signs that characterize the
uremic syndrome in advanced renal failure
 Uremic synrome

A host of metabolic and endocrine functions normally performed by the kidneys is

also impaired or suppressed, and this results in
 Anemia,
 Malnutrition
 Abnormal metabolism of carbohydrates, fats, and proteins
 Plasma levels of many hormones, including PTH, FGF 23, insulin, glucagon, steroid
hormones including vitamin D and sex hormones, and prolactin, change with CKD
as a result of reduced excretion, decreased degradation, or abnormal regulation.
 Uremia leads to disturbances in the function of virtually every organ
system
 Chronic dialysis can reduce the incidence and severity of these
disturbances
 Optimal dialysis therapy is not completely effective as renal
replacement therapy
CLINICAL AND LABORATORY MANIFESTATIONS
 Fluid, electrolyte, and acid-base disorders
 Bone Manifestations of CKD (Ca and Phosph)
 Cardiovascular abnormalities
 Hematologic abnormalities
 Neuromuscular abnormalities
 Dermatologic abnormalities
 Gastrointestinal and Nutritional abnormalities
 Endocrine-metabolic disturbances
FLUID, ELECTROLYTE, AND ACID-BASE DISORDERS
 Sodium and Water Homeostasis
. sodium and water is modestly increased
. extracellular fluid volume (ECFV) expansion
 Potassium Homeostasis is predominantly mediated by

. aldosterone-dependent secretion in the distal nephron

. Augmented potassium excretion in the GI tract
 Metabolic Acidosis
. The pH is <7.36
 DISORDERS OF CALCIUM AND PHOSPHATE META BOLlSM
 Treatment
 Dieta ry salt restriction
 The use of loop diuretics
 Water restriction is indicated only if there is a problem with hyponatremia
 dietary restriction of potassium
 avoidance of both
- potassium supplements (includ­ing occult sources, such as dietary salt substitutes)
- potassium­ retaining medications (especially angiotensin-converting enzyme [ACE]
inhibitors or angiotensin receptor blockers [A RBs])
 potassium­ binding resins, such as ca lcium resonium or sod ium polystyrene, can
promote potassium loss through the GI tract
 Intractable hyperkalemia is an indication of dialysis in a CKD patient.
 Bone Manifestations of CKD
 High bone turnover with increased PTH levels (including osteitis fibrosa cystica, the
classic lesion of secondary hyperparathyroidism)
* Bone histology show abnormal osteoid, bone and bone marrow fibrosisthe formation of
bone cysts, sometimes with hemorrhagic elements so that they appear brown in
color, hence the term brown tumor
* Clinical manifestations of severe hyperparathyroidism include bone pain and
fragility, brown tumors, compression syndromes, and erythropoietin resistance
in part related to the bone marrow fibrosis
 low bone turnover with low or normal PTH levels (adynamic bone disease and
osteomalacia)
* Occasionally the cal­cium will precipitate in the soft tissues into large concretions
termed "tumoral calcinosis"
 Hyperparathyroidism

 Declining GFR leads to reduced excretion of phosphate and, thus,

phosphate retention;
 The retained phosphate stimulates increased synthesis of both FGF-23
by osteocytes and PTH and stimulates growth of parathyroid gland
mass;
 Decreased levels of ionized calcium, resulting from suppression of
calcitriol production by FGF-23 and by the failing kidney, as well as
phosphate retention, also stimulate PTH production

These changes start to occur when the GFR falls below 60 mLlmin.
 Calciphylaxis
cal­cific uremic arteriolopathy
 vascular occlusion in association
with extensive vascular and soft
tissue calcification
 advances to patches of ischemic
necrosis, especially on the legs,
thighs, abdomen, and breasts
 Warfarin treatment is considered a
risk factor for calciphylaxis, and if
a patient develops this syndrome,
this medication should be replaced
with alternative forms of
anticoagulation.
 Treatment

 Low-phosphate diet
 Use of phosphate-binding agents
 Calcitriol exerts a direct suppressive effect on PTH secretion and
also indirectly suppresses PTH secretion by raising the concentra­tion
of ionized calcium
 Calcimimetic agents that enhance the sensitivity of the parathyroid
cell to the suppressive effect of calcium (e.g. cinacalcet)
 CARDIOVASCULAR ABNORMALITIES

 Ischemic Vascular Disease

 Left ventricular hypertrophy
 Hypertension
 Heart Failure

Cardiac troponin levels are frequently elevated in

CKD without evidence of acute ischemia
 treatment


Salt restriction should be the first line of therapy
 Volume management
 The choice of antihypertensive agent is similar to that in
the general population
 ACE inhibitors and ARBs appear to slow the rate of decline
of kidney function, may also develop hyperkalemia
 Lifestyle changes, including regular exercise
 HEMATOLOGIC ABNORMALlTIES
 Anemia – relative deficiency of erythropoietin (EPO)
diminished red blood cell survival
iron, folate or vitamin B12 deficiency
exogenous erythropoietic-stimulating agents (ESA)rezistent

 Abnormal Hemostasis
Patients may have a prolonged bleeding time,
decreased activity of platelet factor III,
abnormal platelet aggregation and adhesiveness,

impaired pro­thrombin consumption

 Treatment

 Exogenous erythropoietic-stimulating agents (ESA)

 Abnormal bleeding time and coagulopathy in patients with
renal fail­ure may be reversed temporarily with
desmopressin (DDAVP),
IV conjugated estrogens
blood transfusions
 Optimal dialysis will usually correct a prolonged bleeding
time.
 NEUROMUSCULAR ABNORMALlTIES

Central nervous system (CNS), peripheral, and

autonomic neuropathy as well as abnormalities
in muscle structure and function are all well
recognized complications of CKD
 DERMATOLOGiIC ABNORMALlTIES

 Pruritus is quite common and one of the most vexing manifestations

 More pigmentation, from the deposition of retained pigmented metabolites, or
urochromes
 Nephrogenic fibrosing dermopathy consists of progressive subcutaneous induration,
especially on the arms and legs

Current recommendations are that patients with CKD stage 3 (GFR 30-59 mL/min)
should minimize exposure to gadolinium, and those with CKD stages 4-5 (GFR <30 mL/min)
should avoid the use of gadolinium agents unless it is medically necessary.
 GASTROINTESTINAL AND NUTRITIONAL
ABNORMALlTIES
 Uremic fetor, a urine-like odor on the breath, derives
from the break­-down of urea to ammonia in saliva and is
often associated with an unpleasant metallic taste
(dysgeusia)
 Gastritis, peptic disease
 mucosaI ulcerations at any level of the GI tract
 abdominaI pain, nausea, vomiting, and GI bleeding
 ENDOCRINE-METABOLlC DISTURBANCES

 mild glucose intolerance

 plasma levels of insulin are slightly to moderately elevated
 Hypoglycemic agents require dose reduction in renal failure.
metformin, are contraindicated when the GFR is less than half
of normal
 In women estrogen levels are low, and menstrual abnormalities,
infertility, and inability to carry pregnancies
EVALUATlON AND MANAGEMENT OF PATIENTS

 History and Physical Examination

 Laboratory Investigation

 Imaging Studies: bilaterally small kidneys supports the diagnosis of

CKD of long-standing duration

 Kidney Biopsy
In the patient with bilaterally small kidneys, renal biopsy
is not advised
 Treatment CKD
 Optimized glucose control in diabetes mellitus
 Immunosuppressive agents for glomerulonephritis
 Emerging specific therapies to retard cystogenesis in polycystic kidney
disease
 Prevent uncontrol led hypertension, urinarytract infection, new obstructive
uropathy, exposure to nephrotoxic agents (such as NSAIDs or radiographic
dyel, and reactivation or flare of the original disease (lupus or va sculitis)
 SLOWING THE PROGRESSION OF CKD - Reducing Intraglomerular
Hypertension and Proteinuria
 PREPARATION FOR RENAL REPLACEMENT THERAPY
Thanks you