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1. Dr. Brijesh kumar
Professor
Department of General Medicine
CHRONIC KIDNEY DISEASE
(chronic renal failure)

2. Competencies

3. Introduction
 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).
 End­
-stage renal disease or failure (ESRD)-
CKD stage 5- represents a clinical state or
condition in which there has been an irreversible
loss of endogenous renal function, of a degree
sufficient to render the patient permanently
dependent on renal replacement therapy in order
to avoid life threatening uremia.

4. The Kidney Disease Outcomes Quality Initiative
(K/DOQI) of the National Kidney Foundation (NKF)
defines chronic kidney disease (CKD)
as either kidney damage or a decreased
kidney glomerular filtration rate (GFR)
of <60 mL/min/1.73 m2
for 3 or more
months
Kidney damage is defined as either
pathologic damage or markers of damage ,
including abnormalities in blood ,urine or
imaging studies.

5. Epidemiology
 At least 6% of the adult population in the United States has
CKD at stages 1 and 2.
 An additional 4.5% of the U.S. population is estimated to
have stages 3 and 4 CKD
 The prevalence of CKD in hypertension, diabetes and
vascular disease is substantially higher, and targeted screening
for CKD should be considered in these and other high ­
risk
groups.

6. IM10.5 Describe and discuss the aetiology of CRF

8. IM10.6 Stage Chronic Kidney Disease

9. Stages of chronic kidney disease (CKD)

10. IM10.7 Describe and discuss the pathophysiology
and clinical findings of uremia

11. Pathophysiology of Chronic Kidney Disease
(1) initiating mechanisms specific to the underlying etiology
(2) 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
 Increased intrarenal activity of the renin-angiotensin axis
appears to contribute both to the initial adaptive
hyperfiltration and to the subsequent maladaptive
hypertrophy and sclerosis

15. Stages 1 and 2 CKD
 Stages 1 and 2 CKD are usually not associated with any
symptoms.
 However, there may be symptoms from the underlying renal
disease itself, such as edema in patients with nephrotic
syndrome or signs of hypertension secondary to the renal
parenchymal disease in patients with polycystic kidney
disease, some forms of glomerulonephritis, and many other
parenchymal and vascular renal diseases, even with well-
preserved GFR.

16. stages 3 and 4
 Clinical and laboratory complications of CKD become more
prominent.
 Virtually all organ systems are affected, but the most evident
complications include
1. Anaemia and associated easy fatigability; decreasing appetite
with progressive malnutrition;
2. Abnormalities in calcium, phosphorus, 1,25(OH)2D3
(calcitriol), parathyroid hormone (PTH), and fibroblast growth
factor 23 (FGF-23)= hypocalcaemia and hyperphosphatemia
3. Abnormalities in sodium, potassium, water, and acid-base
homeostasis= hyperkalaemia, oedema & metabolic acidosis

17. • Initial presentations are:
1. tiredness or breathlessness, which may, in part, be related to renal
anemia,
2. pruritus,
3. anorexia, weight loss,
4. nausea and vomiting.
• With further deterioration in renal function, patients may
suffer
1. hiccups,
2. experience unusually deep respiration related to metabolic
acidosis (Kussmaul’s respiration), and
3. develop muscular twitching, fits, drowsiness and coma.

18. Immune dysfunction
 Cellular and humoral immunity is impaired in advanced CKD
and there is increased susceptibility to infections, the
second most common cause of death in dialysis patients, after
cardiovascular disease.
Haematological dysfunction
• There is an increased bleeding tendency in advanced
CKD, which manifests as cutaneous ecchymoses and
mucosal bleeds.
• Platelet function is impaired and bleeding time prolonged

19. FLUID AND ELECTROLYTE ABNORMALITIES
 Fluid Retention
 Pulmonary Edema
 MetabolicAcidosis
 Hyperkalemia
 In both genders, there is loss of libido related to hypogonadism.
Hormonal abnormalities

20. Neurological and muscle function
 Generalized myopathy may occur due to a combination of poor
nutrition, hyperparathyroidism, vitamin D defi­
ciency and
disorders of electrolyte metabolism.
 Muscle cramps are common.
 The‘restless leg syndrome’, in which the patient’s legs are
jumpy during the night, may be troublesome.
 Both sensory and motor neuropathy can arise, presenting as
paraesthesia and foot drop, respectively, but appear late during the
course of CKD

21. IM10.8 Classify, describe and discuss
the significance of proteinuria in CKD

24.  Renal inflammation that initially damages glomerular capillaries often
spreads to the tubulointerstitium in association with heavier proteinuria.
Many clinical observations support the association of worsening
glomerular proteinuria with renal progression.
 increasingly severe proteinuria triggers a downstream inflammatory
cascade in tubular epithelial cells, producing interstitial nephritis,
fibrosis, and tubular atrophy.
 As albumin is an abundant polyanion in plasma and can bind a variety of
cytokines, chemokines, and lipid mediators, Furthermore, glomerular
injury either adds activated mediators to the proteinuric filtrate or alters
the balance of cytokine inhibitors and activators such that attainment of a
critical level of activated cytokines eventually damages downstream
tubular nephron.

25. IM10.9 Describe and discuss the pathophysiology
of anemia and hyperparathyroidism in CKD

26.  Anemia is common and is due in part to reduced erythropoietin
production. Hemoglobin can be as low as 5–7 g/dL in CKD stage
5, although it is often less severe or absent in patients with
polycystic kidney disease.
 Causes of anemia in CKD
1. Deficiency of erythropoietin
2. Toxic effects of uremia on marrow precursor cell
3. Reduced red cell survival
4. Increased blood loss due to capillary fragility and poor platelet
function
5. Reduced intake, absorption and utilization of dietary iron

27. Bone Manifestations of CKD
 The major disorders of bone disease can be classified into those
associated with
- high bone turnover with increased PTH levels (including osteitis
fibrosa cystica, the classic lesion of secondary hyperparathyroidism) and
- low bone turnover with low or normal PTH levels (adynamic
bone disease and osteomalacia).
 Patients with CKD commonly develop parathyroid gland hypertrophy
and secondary hyperparathyroidism
 In some cases, tertiary hyperparathyroidism supervenes, due to
autonomous production of PTH by the enlarged parathyroid glands; this
presents with hypercalcaemia.

28.  The pathophysiology of secondary hyperparathyroidism and the
consequent high-turnover bone disease is related to abnormal
mineral metabolism through the following events:
(1) declining GFR leads to reduced excretion of phosphate and,
thus, phosphate retention;
(2) the retained phosphate stimulates increased synthesis of PTH
and growth of parathyroid gland mass; and
(3) decreased levels of ionized calcium, resulting from diminished
calcitriol production by the failing kidney as well as phosphate
retention, also stimulate PTH production. Low calcitriol levels
contribute to hyperparathyroidism, both by leading to
hypocalcemia and also by a direct effect on PTH gene transcription.
 These changes start to occur when the GFR falls below 60
mL/min.

29. Metabolic bone disease

30. IM10.10 Describe and discuss the
association between CKD glycemia and
hypertension

31.  Glomerular hyperperfusion and renal hypertrophy occur in the first years
after the onset of DM and are associated with an increase of the GFR.
During the first 5 years of DM, thickening of the glomerular basement
membrane, glomerular hypertrophy, and mesangial volume expansion
occur as the GFR returns to normal.
 After 5–10 years of type 1 DM, 40% of individuals begin to excrete
small amounts of albumin in the urine.
 Although the appearance of microalbuminuria in type 1 DM is an
important risk factor for progression to macroalbuminuria (>300 mg/d or
> 300 g/mg creatinine), only 50% of individuals progress to
macroalbuminuria over the next 10 years.
 Microalbuminuria is a risk factor for cardiovascular disease.
 Once macroalbuminuria is present, there is a steady decline in GFR, and
50% of individuals reach ESRD in 7–10 years.
 Once macroalbuminuria develops, blood pressure rises slightly and the
pathologic changes are likely irreversible.

32.  The half-life of insulin is prolonged in CKD due to
reduced tubular metabolism of insulin but there is also
insulin resistance and reduced appetite. Because of this,
insulin requirements are unpredictable in diabetic
patients in advanced CKD.

33.  Hypertension is one of the most common complications of
CKD develops due to salt and water retention.
 It usually develops early during the course of CKD and is
associated with adverse outcomes, including the development
of ventricular hypertrophy and a more rapid loss of renal
function
 The use of exogenous erythropoiesis-stimulating agents can
increase blood pressure.

34. IM10.11 Describe and discuss the relationship
between CAD risk factors and CKD and in dialysis

35. Cardiovascular disease
 The risk of cardiovascular disease is substantially increased in
patients with CKD stage 3 or worse (GFR < 60
mL/min/1.73 m2
) and those with proteinuria or
microalbuminuria.
 Left ventricular hypertrophy may occur, secondary to
hypertension, and may account for the increased risk of
sudden death (presumed to be caused by dysrhythmias)
in this patient group.
 Pericarditis may complicate untreated or inadequately
treated ESRD and cause pericardial tamponade or constrictive
pericarditis

36.  The incremental risk of cardiovascular disease in those with
CKD compared to the age- and sex-matched general
population ranges from 10- to 200-fold, depending on the
stage of CKD.
 Between 30 and 45% of patients reaching stage 5 CKD
already have advanced cardiovascular complications.
 As a result, most patients with CKD succumb to
cardiovascular disease before ever reaching stage 5 CKD.
Thus, the focus of patient care in earlier CKD stages should
be directed to prevention of cardiovascular complications

38. Risk factor for CAD
 The increased prevalence of vascular disease in CKD patients derives from
both traditional ("classic") and nontraditional (CKD-related) risk factors.
 Traditional risk factors include hypertension, hypervolemia, dyslipidemia,
sympathetic overactivity, and hyperhomocysteinemia.
 The CKD-related risk factors comprise anemia, hyperphosphatemia,
hyperparathyroidism, sleep apnea, and generalized inflammation.
 The inflammatory state associated with a reduction in kidney function is
reflected in increased circulating acute-phase reactants, such as
inflammatory cytokines and C-reactive protein, with a corresponding fall in
the "negative acute-phase reactants," such as serum albumin and fetuin.
 The inflammatory state appears to accelerate vascular occlusive disease, and
low levels of fetuin may permit more rapid vascular calcification, especially
in the face of hyperphosphatemia.

39. • Coronary reserve, defined as the increase in coronary blood flow in
response to greater demand, is also attenuated.
• There is diminished availability of nitric oxide because of increased
concentration of asymmetric dimethyl-1-arginine and increased
scavenging by reactive oxygen species.
• In addition, hemodialysis, with its attendant episodes of hypotension
and hypovolemia, may further aggravate coronary ischemia.
• Cardiac troponin levels are frequently elevated in CKD without
evidence of acute ischemia.The elevation complicates the diagnosis
of acute myocardial infarction in this population. Serial
measurements may be needed,

40. Management
Main aims of investigations in CKD patients are:
1. to identify the underlying cause where possible, since this may
influence the treatment
2. to identify reversible factors that may worsen renal function,
such as hypertension, urinary tract obstruction, nephrotoxic
drugs, and salt and water depletion
3. to screen for complications of CKD, such as anaemia and renal
osteodystrophy
4. to screen for cardiovascular risk factors

41. Investigations

42. Treatment
 The aims of management in CKD are
1. to prevent or slow further renal damage;
2. to limit the adverse physiological effects of renal
impairment on the skeleton and on haematopoiesis;
3. to treat risk factors for cardiovascular disease; and
4. to prepare for RRT, if appropriate

43.  Antihypertensive therapy- slows the rate at which renal
function declines in CKD
 Reduction of proteinuria- Angiotensin-converting enzyme
(ACE) inhibitors and angiotensin II receptor blockers (ARBs)
reduce proteinuria and retard the progression of CKD
 Lipid-lowering therapy
 Treatment of anaemia with Recombinant human
erythropoietin
 Maintaining fluid and electrolyte balance
 Renal bone disease with active vitamin D metabolites (either
1- -hydroxyvitamin D or 1,25-dihydroxyvitamin D)
α
 Renal replacement therapy(RRT)Various options are
available, including haemodialysis, haemofiltration,
haemodiafiltration, peritoneal dialysis and renal transplantation

44. Delaying progression
of CKD
TREAT
UDERLYING
CONDITION
BLOOD
PRESSURE
CONTROL
USE OF ACE
INHIBITOR
AGGRESSIVE
GLYCEMIC
CONTROL
PROTEIN
RESTRICTION
TREATMENT OF
HYPERLIPIDEMIA
AVOIDENCE OF
NEPHROTOXIC
AGENTS

45. TREATING
PATHOLOGIC
MANIFESTATIONS
OF CKD
ANEMIA
HYPERPHOSPHATEMIA
HYPOCALCEMIA
HYPERPARATHYROIDISM
VOLUME
OVERLOAD
METABOLIC
ACIDOSIS
UREMIC
MANIFESTATION
CARDIOVASCULAR
COMPLICATIONS
ERYTHOPOETIN
DIETRY PHOSPHATE BINDERS
PHOSPHATE RESTRICTIONS
Ca SUPPLEMENTS
± CALCITROL
CALCITROL
VITAMIN-D ANALOGUE
DIURETICS
ULTRAFILTERATION
ORALALKALI
SUPPLEMENTATION
RENAL REPLACEMENT
THERAPY

46. DIET AND NUTRITION IN CKD
• Careful nutritional monitoring, Frequent nutrition
counseling and treatment of these individuals.
• Energy requirement in the range of 35 kcal/kg per day
are recommended
• Nutrition care plan should be updated on a quarterly
basis

47. Management guide lines for dietary protein
restriction in CKD
• The NKF-K/DOQI clinical practice guide lines
on hypertension and antihypertensive agents in
CKD include a recommendation based on
kidney stage of 1.4 g of protein /kg/d for
stages 1 to 2 and 0.6 – 0.8 g/kg/d for stages 3
to 4 (NKF-K/DOQI 2004)

48. • Dietary phosphorus should be restricted to 800 to 1,000
mg/day when the serum phosphorus levels are elevated
>4.6 mg/dL at Stages 3 and 4 of CKD and >5.5 mg/dL in
Stage 5
• Dietary phosphorus should be restricted to 800 to 1,000
mg/day when the plasma levels of intact PTH are
elevated above target range of the CKD
• Skim milk, other diary products , green leafy vegetables;
peas and beans; nuts; chocolate; beef liver; turkey; and
some cola drinks are PO4 rich foods to be avoided
RESTRICTION OF DIETARY PHOSPHORUS IN
PATIENTS WITH CKD

49. FAT consumptions 20 -30% of calories
Trans and saturated fatty acids <10 % of
total calorie intake
PUFA 5 – 10 % of total calories intake
ω-3 PUFA 0.6 – 1.2% of total calorie
intake(10% of the ω-3 PUFA can be
consumed as EPA and DHA)

50. DIETRY SODIUM
Less Than 2.4gm /day
1/4 tsf salt = 575 mg sodium
1/2 tsf salt = 1150 mg sodium
1 tsf salt = 2300 mg sodium
Foods rich in Sodium Canned meats, canned soups, nuts, cheese,
pickles, bakery products
DIETRY POTTASIUM
Potassium intake >4g /d for stage 1 and 2
Between 2 – 4 g/d for stage 3 and 4
2g/d for stage 5
Banana, peas, tomato, dry fruits, peanut, dairy products, ice
creams