1. Chronic Kidney Disease (CKD)

2. Key Concepts
Chronic kidney disease (CKD) is classified based on:
* the cause of kidney disease, assessment of glomerular filtration rate, and
extent of proteinuria.
Frequent complications of advanced CKD include altered sodium and water balance, hyperkalemia, metabolic acidosis, anemia, CKD-related mineral and bone disorder (CKD-MBD), and cardiovascular disease.
3. Key mechanisms responsible for the progression of CKD: Reduction of kidney mass, development of glomerular hypertension, and intratubular proteinuria
Anemia of CKD is primarily caused by a deficiency in the production of
endogenous erythropoietin by the kidney with iron deficiency as a
contributing factor.
CKD-MBD includes abnormalities in parathyroid hormone (PTH), calcium,
phosphorus, the calcium–phosphorus product, vitamin D, bone turnover,
and soft-tissue calcifications and contributes to extravascular
calcifications.

3. Guidelines provide information to assist healthcare providers in clinical decisions and the design of appropriate therapy to manage CKD progression and the associated complications.
Patient education plays a critical role in the appropriate management of patients with CKD and related complications.
ACEIs and ARBs are key pharmacologic treatments of CKD because of their effects on renal hemodynamics and reduction ofBP, which help to limit kidney disease progression.
Management of anemia includes administration of erythropoietic-stimulating agents (ESAs) (epoetin alfa, darbepoetin alfa) and regular iron supplementation (oral or IV administration) to maintain hemoglobin and prevent the need for blood transfusions. There is evidence indicating a higher risk of cardiovascular events when hemoglobin is targeted to greater than 11 g/dL.
10. Management of CKD-MBD includes dietary phosphorus restriction, phosphate-binding agents, vitamin D supplementation, and calcimimetic therapy.

4. CKD Definition:
**Abnormalities in kidney structure or function for ≥ 3 months, with implications for health.
Structural abnormalities include:
*Albuminuria of more than 30 mg/day,
*Presence of hematuria or red cell casts in urine sediment,
*Electrolyte & other abnormalities due to tubular disorders,
*Abnormalities detected by histology,
*Structural abnormalities detected by imaging,
Or *history of kidney transplantation.
** An abnormality in kidney function is usually indicated by a ↓ (GFR).

6. The prognosis of CKD can vary and depends on:
Cause of kidney disease;
(b) GFR at time of diagnosis;
(c) Degree of albuminuria;
(d) Presence of other comorbid conditions.
*Frequent Complications of Advanced CKD:
Altered sodium and water balance,
Hyperkalemia,
Metabolic acidosis,
Anemia,
CKD-related mineral and bone disorder (CKD-MBD),
Cardiovascular disease (CVD).

7. Epidemiology:
13% of the U.S. population.
CKD is more likely in:
* Those over 60 years of age
* Diabetics
* Hypertension patients
* CVD patients
Rates of ESRD are > in African Americans (3.4 X greater) and Native Americans (0.5 X greater) compared with whites and 1.5 times > in Hispanics than in non-Hispanics.

8. Etiology of CKD:
1. Susceptibility Factors:
Most of these susceptibility factors are not amenable to pharmacologic or lifestyle, interventions, but are useful for identifying individuals at high risk of CKD.
2. Initiation Factors:
Conditions that directly result in kidney damage & are modifiable by pharmacologic therapy.
*Diabetes mellitus: leading cause of CKD & of ESRD
in the USA
*Hypertension: 2nd leading cause of ESRD
*Glomerulonephritis: 3rd leading cause of ESRD

9. 3. Progression Factors:
Result in faster decline in kidney function & cause worsening of CKD.
* May be modified by pharmacologic therapy or lifestyle modifications to slow the progression of CKD.

11. Progression Factors:
Proteinuria:
Marker of glomerular & tubular dysfunction
Degree of proteinuria correlates with progression of CKD.
Microalbuminuria > 30mg/day: linked with
vascular injury & ↑ CV mortality

12. 2) Elevated BP
* Systemic BP correlates with glomerular
pressure
Elevations in both systemic BP & glomerular pressure contribute to glomerular damage
The rate of GFR decline is related to elevated systolic BP

13. 3) Elevated Blood Glucose:
The reaction between glucose & protein in blood produces advanced glycation end products (AGEs), which are metabolized in the proximal tubules.
Hyperglycemia→↑ AGEs synthesis in diabetics
(suspected to cause Diabetic kidney disease)

14. 4) Tobacco Smoking:
Induces thickening & hyperplasia of glomerulus
Raises systemic BP
Independent risk factor in developing microalbumiuria in HTN
Independnt & dose-dependent risk factor in developing CKD & microalbuminuria, & progression to ESKD.
Risk is more pronounced in men than in women

15. Proposed mechanisms for progression of renal disease

16. Pathophysiology of CKD:
1) Initial kidney damage from initiation factor
2)↓ # functioning nephrons
3) Remaining nephrons hypertrophy to compensate which
initially may be adaptive
4) Over time →development of intraglomerular HTN may be
mediated by angiotensin II (potent vasoconstrictor of both
afferent and efferent arterioles, preferentially affects the
efferent arterioles).
Angiotensin II may also mediate CKD progression through
nonhemodynamic effects
5) High intraglomerular capillary pressure impairs the size-
selective function of the glomerular permeability barrier →
↑urinary excretion of albumin and proteinuria.

17. Pathophysiology of CKD (cont
Pathophysiology of CKD (cont.): 6) Proteinuria alone may → progressive loss of nephrons by direct cellular damage. (Filtered proteins i.e., albumin, transferrin, complement factors, IGs, cytokines, & angiotensin II in the renal tubule → ↑production of inflammatory & vasoactive cytokines (i.e. endothelin and monocyte chemoattractant protein-1 (MCP-1) → tubular cell toxicity. 7) Proteinuria may also →activation of complement components on the apical membrane of proximal tubules which may be the key mechanism of damage in the progressive proteinuric nephropathies. 8) These events ultimately → a) scarring of the interstitium, b) progressive loss of structural nephron units, c) reduction in GFR.

18. Assessment:
Screening for CKD should be done in all pts. with↑’d risk for developing CKD.
Assessment for CKD should include:
*SCr measurement
*Urinalysis
*BP
*Serum electrolytes
&/or *Imaging studies

19. Proteinuria is the 1⁰ marker for structural kidney damage even with normal GFR.
Clinically significant proteinuria is defined as:
* urinary protein execret’n > 300mg/d
Or *Spot urine dipstick > 30 mg/dL
Microalbuminuria: mg urinary albumin/day

21. Clinical Presentation:
Symptoms
Stages 1& 2 CKD are generally asymptomatic
Stages 3& 4 may be associated with min. symptoms
Stage 5 can be associated with
Uremic symptoms (fatigue, weakness, shortness of breath, mental
confusion, nausea and vomiting, bleeding, and loss of appetite), itching,
cold intolerance, weight gain (from accumulation of fluid), and peripheral
neuropathies
Signs:
CV: Worsening HTN, edema, dyslipidemia, LVH, ECG changes, CHF
Muscular: Cramping
Neuropsychiatric: Depression, anxiety, impaired mental cognition
GI: GERD, GI bleeding, abdominal distension
GU: Changes in urine volume & consistency, "foaming" of urine (indicative
of proteinuria)

22. Laboratory tests All Stages 1-5 CKD: ↑BUN, SCr, ↓GFR Advanced Stages:
Decreased:
bicarbonate (metabolic acidosis), RBCs/Hb/Hct (anemia), iron indices (iron deficiency), vitamin D levels, albumin (malnutrition), glucose (may result from decreased degradation of insulin with impaired kidney function or poor oral intake), and calcium (in early stages).
Increased:
potassium, phosphorus, magnesium, PTH, HTN, glucose (uncontrolled diabetes is a cause of CKD), LDL and TG, and calcium (in ESRD).
Other: may be hemoccult-positive if GI bleeding occurs (uremia)
Urine may be positive for protein
Other diagnostic tests:
Structural abnormalities of kidney may be present on diagnotic test

23. Treatment:
The 1⁰ goal : To slow & prevent the progression of CKD.
Therefore, it requires early identificat’n of risk for CKD to initiate interventions early in the course of the dz.

24. Nonpharmacologic Therapy:
Nutritional Management:
↓dietary protein intake → slows the progression of kidney dz.
Recommendation:
GFR< 25 ml/min→ ↓ protein to 0.6g/kg/d
No adequate dietary energy intake → ↑ protein to 0.75 g/kg/d

25. Malnutrition: common in CKD & may be due to: *↓’d appetite
* hypercatabolism
* nutrients losses through dialysis
Dialysis CKD pts → g/kg/d
Recommendation:
DM pts with CKD stages 1-4 → limit protein to
0.8 g/kg/d
** ↓ salt intake to < 2 g/day of sodium ( 5 gNaCl) with
hypertension or proteinuria.

26. Pharmacologic Therapy:
Intensive Blood Glucose Control in DM Pts:
Target HbA1c < 7% to ↓proteinuria with or
without diabetic KD
Intensive insulin therapy was effective in delaying development & progression of diabetic KD in types 1 & 2 DM:
Insulin 3 or more X/day to maintain
preprandial BG g/dL
& postprandial BG < 180 g/dL

29. 2) Optimal BP Control:
Recommendation:
** Goal BP < 130/80 mmHg in CKD
<125/75 mmHg in proteinuria
All antihypertensives have similar effects on BP
** ≥ 3 agents are required to achieve the
BP < 130/80

32. 3) Reduction of Proteinuria:
*ACEIs & ARBs ↓ glomerular capillary pressure
& volume due to their effects on Angiotensin II → ↓proteinuria (independent of their ↓ BP)
** ACEIs & ARBs: Antihypertensives of choice for all CKD pts unless contraindicated due to their ability to ↓ proteinuria more than any other antihypertensives (up to 35-40%)
Nonhydropyridine CCBs also↓proteinuria
(related to their effects on BP↓)

34. 4) Hyperlipidemia: ** Goals of Tx of dyslipidemia are to: 1st to ↓ atherosclerotic CVD risk 2nd to ↓ proteinuria & decline in kidney function in CKD pts.( prteinuria is associated with ↑d TC, LDL-C, TG) **Statins & Fibric acid derivatives (NOT combined due to ↑d rhabdomyolysis ): Statins are First-line therapy unless contraindicated. ** Hyperlipidemia Tx can ↓ proteinuria & CKD progression. **Most statins are affected by enzyme inhibitors EXCEPT Pravastatin & Fluvastatin

36. 5) Smoking Cessation & Exercise:
5) Smoking Cessation & Exercise: *Smoking cessation is encouraged to slow progression of CKD & to ↓ risk of CVD. *Smoking cessation does not reverse kidney dysfunction in former smokers. *Exercise is recommended for CKD least 30 minutes 5X/week

37. 6)Anemia:
*Anemia→↓O₂ delivery to renal tubules→
release of inflamm. & vasoactive cytokines →
CDK progression.
Anemia Tx in CKD pts→ ↓CV effects of anemia & slow CKD progression
Tx will be discussed later

38. Complications of CKD:
Impaired Na & Water Homeostasis:
Pathophysiology:
Na & H₂O balance can be maintained by the FENa & wide range of urine osmolality despite the wide variations in intake with normal kidney function.
As # of functioning nephrons ↓→Remaining nephrons ↑FENa → osmotic diuresis→Impairs the kidneys’ ability to concentrate or dilute the urine →nocturia in stage 3.
As # of functioning nephrons continues to ↓→ Na load overwhelms the remaining nephrons→↓total Na execretion→Na overload→Fluid retention → ↑Intravascular volume ↑systemic BP.
Volume overload can→Pulmonary edema

39. Clinical Presentation & Diagnosis of Impaired Na & H₂O Homeostasis:
General:
Alterations in Na & H₂O balance in CKD manifests as ↑’d edema
Symptoms:
Nocturia can present in stage 3 CKD
Edema generally presents in stage 4 CKD or later
Signs:
CV: Worsening HTN, edema
GU: Changes in urine volume & consistency
Lab Tests:
↑’d BP
Na levels remain within normal range
Urine osmolality is generally 300mOsm/L

40. Treatment:
Nonpharmacologic Therapy:
Pts refrain from adding salt to the diet
Na restriction→(-) Na balance →Hypovolemia →↓Renal perfusion→Hastens GFR decline.
Slow changes over several days
Caution in using Saline-containing solutions in CKD pts to avoid volume overload

41. Fluid restriction unnecessary as long as Na intake is controlled
The intact thirst mechanism maintains total body H₂O & plasma osmolality near normal
(fixed 2L/d as urine concentrating
ability is lost)
Significant ↑in free H₂O po or IV intake →
volume overload & hyponatremia
Stage 5 CKD pts require RRT to maintain normal
volume status
Fluid intake is often limited between hemodialysis
sessions

42. Pharmacologic Therapy:
Diuretic therapy prevents volume overload in CKD who can still produce urine
Loop diuretics: Mostly used
Thiazides: ineffective in GFR<30ml/min
Metolazone maintains its
As CKD progresses:
*Higher doses (80-1,000mg/d furosemide)
*Continuous IV
or *Combination diuretic therapy
May be used to ↑ Na & H₂O excretion
**AVOID DEHYDRATION

43. 2. Impaired Potassium Homeostasis:
Pathophysiology:
The ↓ in functioning nephrons→
↑K distal tubular secretion & ↑K GI elim. due to aldosterone stimulation → maintains serum[K]
within normal in stages 1-4 of CKD
Hyperkalemia develops when GFR<20% of
normal
Caution with use of ACIs & ARBs in stage 3 CKD or
higher

44. Clinical Presentation & Diagnosis of Hyperkalemia:
General:
Generally asymptomatic in CKD until [K]>5.5mEq/L when cardiac abnormalities present.
Symptoms:
Symptoms generally appear in CKD stages 4 or 5
Signs:
ECG Changes
Lab Tests:
↑[K]

45. Treatment:
Nonpharmacologic Therapy:
Restrict dietary intake of K to mEq/d
Good bowel regimen is important to minimize constipation in hemodialysis pts. to encourage GI k excretion in stage 5 CKD
Severe hyperkalemia is most effectively managed by hemodialysis

46. Pharmacologic Therapy:
Until Dialysis is started, other therapies should include:
1) * Ca gluconate or Ca chloride 1g IV to reverse hyperkalemia-induced life threatening arrhythmias.

47. 2) Temporary measures that could shift K intracellularly within min. to stabilize the cell membrane from the effects of excessive serum [K], include:
Reg. Insulin (5-10 U IV)+ Dextrose (5-50%IV)
Nebulized albuterol mg
NaHCO₃ is used for shifting only if severe metabolic acidosis (pH<7.2)

48. 3) Sodium Polystyrene Sulfonate (SPS) 15-30g po or rectally: Na-K exchange resin promotes K excretion from GI with OA of 2 hrs & max. effect may take up to 6 hrs (limiting its effect in severe hyperkalemia). 4) Loop diuretics may ↓[K] in normal-mild kidney function but NOT in CKD stage 5

49. 3) Anemia:
Epidemiology & Etiology:
*Defined as Hgb< 13.5 g/dL in males & < 12g/dL
in females
*Risk of developing anemia ↑’s as GFR declines
CKD-anemia→↓O₂ delivery & utilization &
LVH→ ↑ CV risk & mortality in CKD

50. Pathophysiology:
The 1⁰ cause of anemia in CKD is ↓in EPO production as # functioning nephrons ↓
→normochromic normocytic anemia
*Uremia may also contribute in developing anemia by ↓’ing life span of RBC from 120 days → 60 days in stage 5 CKD.
Other contributing factors include Fe deficiency anemia (from malnutrition , RBC production by EPO-Stimulating Agent) & blood loss (from lab testing & hemodialysis)

51. Clinical Presentation of Anemia in CKD:
General:
Fatigue & ↓Quality of life
Symptoms:
Cold intolerance, SOB, ↓exercise capacity
Signs:
CV: LVH, CHF, ECG changes
Neurologic: impaired mental cognition
Lab Test:
↓RBCs, Hgb, Hct
↓ [Fe], Serum Ferritin, & TSAT
↓[EPO] relative to degree of hypoxia present

52. Treatment:
Anemia Tx →↓morbidity
↑Exercise capacity & tolerance Slow the progression of CKD
*GFR<60 mL/min or SCr>2mg/dL →Evaluate for
anemia
* Abnormalities found during anemia work up (esp. iron deficiency)should be corrected before starting erythrpoeitin stimulating agents(ESAs).

53. Generally, Tx of CKD-anemia requires A combination of ESA & Fe supplements
The goal of Tx : to maintain Hgb between
11-12g/dL
The goals for Fe supplementation therapy:
*Serum Ferritin:
ng/mL for Non-dialysis pts
ng/mL for Hemodialysis pts
*Transferrin Saturation (TSAT): >20%

57. Nonpharmacologic Therapy:
Sufficient dietary intake of Iron
Blood transfusion is still used today for those with severe anemia or contraindicated to ESAs
Blood transfusion is considered a 3rd line therapy for CKD-anemia

58. Pharmacologic Therapy:
All ESAs are equivalent in their efficacy & have similar adverse-effect profile but have different half-lives .
The most common ADR to ESAs is ↑BP
Caution when starting ESA with very high BP (>180/110)
ESA may have to be withheld if BP is refractory to antihypertensive agents
SQ route of ESA is preferred over the IV route because it is more predictable & has a sustained response
IV ESAs are often used in pts receiving hemodialysis or have an established IV access

59. FDA recommended a black box warning to be added to the product information for all ESAs indicating the maximum target Hgb should be between 10 & 12 g/dL for pts receiving ESAs since 2 clinical trials showed that targeting Hgb > 13 g/dL resulted in more CV complications or death.

60. IV iron preparations are equally effective in increasing iron stores
The most common S/Es of IV Fe preparations:
hypotension, flushing, nausea, & injection
site reaction
IV Fe Dextran use has ↓’d in CKD pts in favor of the
newer Fe gluconate & Fe sucrose due to its
association with anaphylactic reactions & delayed
reactions i.e. arthralgias & myalgias
IV Fe requires a test dose of 25mg 30 min to be given
before full dose to monitor for potential anaphylactic
reactions.

63. 4) Secondary Hyperparathyroidism & Bone & Mineral Metabolism Disorders: Pathophysiology: *Evaluation begins when GFR<60ml/min *CKD→↓P excret’n→ ↑P → ↓Ca *↓’d vit.D activation by kidney →↓Ca GI absorption *In response to ↓Ca & ↑P→ Parathyroid gland releases PTH

64. The actions of PTH include:
1)↑’ing Ca resorption from bone
2) ↑’ing Ca reabsorption from the proximal
tubules in kidney
3) ↓’ing P reabsorption from the proximal
4) Stimulation activation of vit.D by 1-alpha –
hydroxylase to calcitriol (1,25-dihydroxyvit D3 ) to
↑Ca absorption in GI & ↑Ca mobilization from
bone

65. 5) Calcitriol ↓ PTH by (-) feedback
5) Calcitriol ↓ PTH by (-) feedback *These measures are sufficient to correct earlier CKD stages. 6) GFR<40ml/min→ P excret’n continues to↓ & Calcitriol production↓→sig.↑↑↑ PTH→ secondary hyperparathyroidism (sHPT) → Parathyroid gland hyperplasia→↓sensitivity of Parathyroid gland to serum[Ca] & Calcitriol feedback→promoting further sHPT 7) The most dramatic consequence of sHPT is alterations in bone turnover & BMMD.

66. Metabolic acidosis :(a complicat’n of CKD)
↓’s bone formation by altering solubility of
hydrxyapatite→bone dissolution
2) Inhibits activity of osteoblasts & stimulates
osteoclasts
3) Worsen sHPT by to↓’ing the sensitivity of PG
to serum Ca levels
**Excessive Al levels → Al uptake into bone in
place of Ca → weakening the bone structure

67. deposition of hydroxyapatite crystals throughout the body.
↑serum P binds to Ca in serum→
deposition of hydroxyapatite crystals
throughout the body.
(Ca-P)product reflects serum solubility
Ca-P>75 → crystallizat’n in eyes & joints
Ca-P>55 → crystallizat’n in soft tissues
(coronary art., heart, lungs,
vascular tissue)
* This ↑mortality rate by 40%

69. Clinical Presentation & Diagnosis of sHPT & ROD:
General: May not be associated with symptoms
Symptoms: Asymptomatic in early dz.
Joint calc.→↓ range of motion
Conjuctival calc. → gritty sensation in eyes, redness, inflammation
Signs:
CV: ↑stroke index, HR, diastolic & MAP
MS: Bone pain, muscle weakness
Derm: Pruritis
Lab Tests:
↑serum P, PTH levels, Ca-P product
↓vit.D levels,
normal-↓serum Ca levels
Diagnostic Tests:
Radiography shows Ca-P deposits in joints &/or CV system
Bone biopsy

70. Treatment:
Monitoring Parameters: Ca, P, PTH
Tx of Renal osteodystrophy (ROD) in CKD depends on corrected serum levels of Ca, P, Ca-P & intact PTH levels (iPTH)
The target varies with each CKD stage (see table)
The 1⁰ target for Tx : to control serum P levels
(may be difficult to control in advanced stages)
Mgt. of sHPT often requires supplemental Tx in
addition to P mgt.

73. Nonpharmacologic Therapy:
1st line Tx for Hyper-P: Dietary P restriction
to 800-1,000 mg/d in CKD stages ≥3
Foods high in P are also high in protein
Dialysis may remove some P but not enough to control Hyper-P.
Restriction of Al exposure ( avoid Al-containing antacids & may use purification techniques of dialysate solutions)
Parathyroidectomy:
Last resort for sHPT considered with persistent
elevation iPTH> 800pg/mL

74. Pharmacologic Therapy:
Phosphate-Binding Agents:
GFR<30 → Diet. restriction will be inadequate
PO4 binding agents bind dietary P in GI
→ insoluble complex eliminated in feces.
Administered with each meal
Examples:
Ca carbonate or Ca acetate (more potent)
Ca citrate NOT recommended coz Al absorption
*Help in correcting metabolic acidosis
* Should NOT provide > 1,500 mg elemental Ca/d &
Total elemental Ca intake should NOT > 2,000 mg/d (including meds
& dietary intake

75. Al-containing & Mg-containing PO4 binders are NOT recommended for chronic use in CKD to avoid accumulation
Al-containing binders may be used for ashort course < 4 wks if [P]> 7mg/dL but should be replaced by other binder
Al intoxication cause neurological & hematological toxicities

76. Other PO4 Binders that do Not contain Ca, Al, or Mg:
Sevelamer & Lanthanum.
Esp. useful for Hyper-P with ↑[Ca] or with calcifications
Sevelamer can also ↓LDL-C & ↑HDL-C
Most common S/Es: GI
Sevelamer has much higher cost than Ca-containing PO4 binders
Sevelamer: 2nd-line agents for controlling P levels
Lanthanum has similar pharmacological effect as Sevelamer but S/Es include nausea, peripheral edema, & myalgia

77. Vitamin D:
Mimic activity of calcitriol act directly on the PG to
↓PTH secretion
Esp. useful when reducing serum P does NOT reduce PTH levels
Calcitriol : The most active form of vit.D
Calcitriol effect is mediated by upregulation of vit.D
receptors in the PG & also in the intestine
→↑P & Ca GI absorption
→ Hyper-P & Hyper-Ca
Therefore, [Ca], [P], Ca-P product should all be within normal range for the CKD stage before starting Calcitriol.

78. Ergocalciferol vit.D supplement: Effective in
↓’ing PTH in Stage 3 CKD but in stages 4 &5 can not
be activated by kidney & activated vit.D analogs must
be used.
Paricalcitol has less effect on vit.D receptors in
the GI → ↓’ing effect on intestinal Ca & P
while maintaining effect on PG which makes it
useful with elevated Ca-P product .

79. Doxercalciferol:
*Has similar effects as calcitriol on vit.D receptor
on PG & intestine
[Ca], [P], Ca-P product should all be within normal
range for the CKD stage before starting it.
Recommendations for vit.D analog therapy
depend on the CKD stage.(see table)
*Monitor vit.D therapy carefully because oversuppression of PTH→Adynamic bone dz

82. Calcimimetics:
Cinacalcet: a calcimimetic that ↑’s the sensitivity of receptors on PG to serum Ca levels to ↓PTH secretion.
It can also slightly ↓serum levels of Ca & P
Beneficial for those with ↑’d PTH
& ↑’d Ca-P and can NOT use vit.D
Can be used with or without vit.D
Reversal of Metabolic Acidosis can improve bone dz

83. 5) Metabolic Acidosis:
In ~ 80% of pts with GFR < 20-30ml/min.
Consequences of Metabolic Acidosis:
1)↑ protein catabolism
2)↓ albumin synthesis
Both →Muscle wasting
3)Worsening of cardiac dz
4)Impaired glucose tolerance
5)Altered growth hormone
6)Altered thyroid function
7)Inflammation

84. Pathophysiology:
Kidneys play a role in the body’s acid-base homeostasis.
Normal kidneys:
*HCO3 that is freely filtered through the glomerulus is
then completely reabsorbed by renal tubules.
*Hydrogen ions are generated during food
metabolism then same rate → body
fluids pH is maintained within a very narrow range.
Impaired Kidneys:
* GFR declines→ HCO3 reabsorption is maintained
but H excretion is ↓’d →metabolic acidosis
* GFR<20-30ml/min

85. Treatment:
*Monitor serum electrolytes
CKD metabolic acidosis is usually with ↑’d anion gap due to accumulation of PO4 & SO4
& other organic anions
Nonpharmacologic Therapy:
Address other contributing disorders
Alter HCO3 levels in the dialysate in dialysis pts.
Pharmacologic therapy is required

86. Pharmacologic Therapy:
Na HCO3, or Na or K Citrate /Citric acids preps. may be needed in CKD stage ≥ 3
Citrate metabolized by liver→HCO3
Citric acid →CO2 + H2O
Goal: Serum [HCO3] of 24 mEq/L
Dose determination (discussed later in A/B lecture)
Should be corrected slowly to prevent metabolic alkalosis, volume overload, & other complications

87. 6) Uremic Bleeding:
Pathophysiology:
*Uremia alters a # of mechanisms →alter
platelet function & aggregation → bleeding
*↓RBCs (in anemia)→↓plt.- vessel wall interaction
*Hemodialysis & anticoagulant use during
hemodialysis ↑ risk of bleeding
CKD-Bleeding includes: ecchmoses, puncture
sites, mucus membranes, GI, IM,….

88. Treatment:
Nonpharmacologic:
Dialysis→↓uremic toxins→improves platelet
function & ↓bleeding time
*Anemia Tx & improvement in nutritional status
→ ↓bleeding time

89. Pharmacologic Therapy:
Cryoprecipitate:
*Contains components important in plt.
aggregation & clotting→↓Bleeding time in
1hr (50%pts) but is costly &↑ infection risk

90. Desmopressin (DDAVP):
↑factor VIII release from endothelial tissue in vessel wall
Bleeding time promptly ↓’d (in 1 hr) &
DA 4-8 hrs
Given IV, SQ, or intranasally
Repeated doses →Tachyphylaxis by depleting stores of factor VIII
S/Es: flushing, dizziness, headache

91. Estrogens:
↓’s bleeding time
Slower OA than DDAVP but more sustained DA
depending on route of adm.
*4-5 days IV therapy: OA within 6 hrs, & effect
may last up to 2 wks after D/C.
PO: OA within 2 days, DA 4-5 days after D/C
Transdermal patches may also be effective
S/Es: hot flashes, fluid retention, HTN

92. 7) Pruritus: Pathophysiology:. Unknown cause
7) Pruritus: Pathophysiology: *Unknown cause *Several Proposed Mechanisms: *Vit. A accumulation in skin & serum in CKD pts. *↑Histamine linked to mast cell prolifer’n in HD * HPT *Accumulation of divalent ions (Mg, Al) *Inadequate dialysis *Dry skin *Peripheral neuropathy *Uremic toxins

93. Treatment:
Nonpharmacologic Therapy:
CKD-pruritus difficult to alleviate
Adequate Dialysis:1st line Tx (no sig. improvement)
Maintaining proper nutritional intake
Control HPT
Avoid hypervitaminosis
If no relief→UV-B phototherapy

94. Pharmacologic Therapy:
Topical emollients: used but not effective
2) Antihistamines : 1st line
e.g. Hydroxyine, Diphynhydramine po, or IV
3) Cholestyramine used
4) Activated charcoal : some efficacy
5) Other therapies often used in combinations with
other agents include oral ondansetron or naltrexone
& topical capsaicin. Each reported to have efficacy in
CKD-pruritus Tx.

95. 8) GI Complications:
Due to the effect of uremic toxins on the GI→
can use H2-antagonists or proton-pump
inhibitors
Constipation is common in advanced CKD & may be due to:
*Diet & fluid restriction
*Al or Ca (PO4-binding agents)
*Fe supplements
*Treatment:
Long-term use of stimulants is permitted in CKD

96. 9) Musculoskeletal Complaints:
Due to hyperuricemia in renal impairment.
Allopurinol :↓’s UA production is preferred
as a prophylactic agent.

97. Vitamin Replacement:
Water-soluble vitamins removed by HD contribute to malnutrition& vit-deficiency syndromes & require replacement.
These vits. Include: ascorbic acid, thiamine, biotin, folic acid, riboflavin, pyridoxine.
HD pts. should receive a multivitamin B complex & vitamin C supplement.
Should NOT take fat-soluble vitamins
(vits A,E, or K) which can accumulate & cause toxicity
in kidney failure.