2 Key ConceptsChronic kidney disease (CKD) is classified based on:* the cause of kidney disease, assessment of glomerular filtration rate, andextent 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 proteinuriaAnemia of CKD is primarily caused by a deficiency in the production ofendogenous erythropoietin by the kidney with iron deficiency as acontributing 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 extravascularcalcifications.
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 patientsRates 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 ESRDin 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 dysfunctionDegree of proteinuria correlates with progression of CKD.Microalbuminuria > 30mg/day: linked withvascular injury & ↑ CV mortality
12 2) Elevated BP* Systemic BP correlates with glomerularpressureElevations in both systemic BP & glomerular pressure contribute to glomerular damageThe 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 glomerulusRaises systemic BPIndependent risk factor in developing microalbumiuria in HTNIndependnt & 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 factor2)↓ # functioning nephrons3) Remaining nephrons hypertrophy to compensate whichinitially may be adaptive4) Over time →development of intraglomerular HTN may bemediated by angiotensin II (potent vasoconstrictor of bothafferent and efferent arterioles, preferentially affects theefferent arterioles).Angiotensin II may also mediate CKD progression throughnonhemodynamic effects5) 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/dOr *Spot urine dipstick > 30 mg/dLMicroalbuminuria: mg urinary albumin/day
21 Clinical Presentation: SymptomsStages 1& 2 CKD are generally asymptomaticStages 3& 4 may be associated with min. symptomsStage 5 can be associated withUremic symptoms (fatigue, weakness, shortness of breath, mentalconfusion, nausea and vomiting, bleeding, and loss of appetite), itching,cold intolerance, weight gain (from accumulation of fluid), and peripheralneuropathiesSigns:CV: Worsening HTN, edema, dyslipidemia, LVH, ECG changes, CHFMuscular: CrampingNeuropsychiatric: Depression, anxiety, impaired mental cognitionGI: GERD, GI bleeding, abdominal distensionGU: Changes in urine volume & consistency, "foaming" of urine (indicativeof 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 proteinOther 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/dNo 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 dialysisDialysis CKD pts → g/kg/dRecommendation:DM pts with CKD stages 1-4 → limit protein to0.8 g/kg/d** ↓ salt intake to < 2 g/day of sodium ( 5 gNaCl) withhypertension or proteinuria.
26 Pharmacologic Therapy: Intensive Blood Glucose Control in DM Pts:Target HbA1c < 7% to ↓proteinuria with orwithout diabetic KDIntensive insulin therapy was effective in delaying development & progression of diabetic KD in types 1 & 2 DM:Insulin 3 or more X/day to maintainpreprandial BG g/dL& postprandial BG < 180 g/dL
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 progressionTx 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 edemaSymptoms:Nocturia can present in stage 3 CKDEdema generally presents in stage 4 CKD or laterSigns:CV: Worsening HTN, edemaGU: Changes in urine volume & consistencyLab Tests:↑’d BPNa levels remain within normal rangeUrine osmolality is generally 300mOsm/L
40 Treatment:Nonpharmacologic Therapy:Pts refrain from adding salt to the dietNa restriction→(-) Na balance →Hypovolemia →↓Renal perfusion→Hastens GFR decline.Slow changes over several daysCaution 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 concentratingability is lost)Significant ↑in free H₂O po or IV intake →volume overload & hyponatremiaStage 5 CKD pts require RRT to maintain normalvolume statusFluid intake is often limited between hemodialysissessions
42 Pharmacologic Therapy: Diuretic therapy prevents volume overload in CKD who can still produce urineLoop diuretics: Mostly usedThiazides: ineffective in GFR<30ml/minMetolazone maintains itsAs CKD progresses:*Higher doses (80-1,000mg/d furosemide)*Continuous IVor *Combination diuretic therapyMay 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 CKDHyperkalemia develops when GFR<20% ofnormalCaution with use of ACIs & ARBs in stage 3 CKD orhigher
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 5Signs:ECG ChangesLab Tests:↑[K]
45 Treatment:Nonpharmacologic Therapy:Restrict dietary intake of K to mEq/dGood bowel regimen is important to minimize constipation in hemodialysis pts. to encourage GI k excretion in stage 5 CKDSevere 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 mgNaHCO₃ 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/dLin females*Risk of developing anemia ↑’s as GFR declinesCKD-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 lifeSymptoms:Cold intolerance, SOB, ↓exercise capacitySigns:CV: LVH, CHF, ECG changesNeurologic: impaired mental cognitionLab 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 foranemia* 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 between11-12g/dLThe goals for Fe supplementation therapy:*Serum Ferritin:ng/mL for Non-dialysis ptsng/mL for Hemodialysis pts*Transferrin Saturation (TSAT): >20%
57 Nonpharmacologic Therapy: Sufficient dietary intake of IronBlood transfusion is still used today for those with severe anemia or contraindicated to ESAsBlood 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 ↑BPCaution when starting ESA with very high BP (>180/110)ESA may have to be withheld if BP is refractory to antihypertensive agentsSQ route of ESA is preferred over the IV route because it is more predictable & has a sustained responseIV 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, & injectionsite reactionIV Fe Dextran use has ↓’d in CKD pts in favor of thenewer Fe gluconate & Fe sucrose due to itsassociation with anaphylactic reactions & delayedreactions i.e. arthralgias & myalgiasIV Fe requires a test dose of 25mg 30 min to be givenbefore full dose to monitor for potential anaphylacticreactions.
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 bone2) ↑’ing Ca reabsorption from the proximaltubules in kidney3) ↓’ing P reabsorption from the proximal4) Stimulation activation of vit.D by 1-alpha –hydroxylase to calcitriol (1,25-dihydroxyvit D3 ) to↑Ca absorption in GI & ↑Ca mobilization frombone
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 ofhydrxyapatite→bone dissolution2) Inhibits activity of osteoblasts & stimulatesosteoclasts3) Worsen sHPT by to↓’ing the sensitivity of PGto serum Ca levels**Excessive Al levels → Al uptake into bone inplace of Ca → weakening the bone structure
67 deposition of hydroxyapatite crystals throughout the body. ↑serum P binds to Ca in serum→deposition of hydroxyapatite crystalsthroughout the body.(Ca-P)product reflects serum solubilityCa-P>75 → crystallizat’n in eyes & jointsCa-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 symptomsSymptoms: Asymptomatic in early dz.Joint calc.→↓ range of motionConjuctival calc. → gritty sensation in eyes, redness, inflammationSigns:CV: ↑stroke index, HR, diastolic & MAPMS: Bone pain, muscle weaknessDerm: PruritisLab Tests:↑serum P, PTH levels, Ca-P product↓vit.D levels,normal-↓serum Ca levelsDiagnostic Tests:Radiography shows Ca-P deposits in joints &/or CV systemBone biopsy
70 Treatment:Monitoring Parameters: Ca, P, PTHTx 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 inaddition to P mgt.
73 Nonpharmacologic Therapy: 1st line Tx for Hyper-P: Dietary P restrictionto 800-1,000 mg/d in CKD stages ≥3Foods high in P are also high in proteinDialysis 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 persistentelevation iPTH> 800pg/mL
74 Pharmacologic Therapy: Phosphate-Binding Agents:GFR<30 → Diet. restriction will be inadequatePO4 binding agents bind dietary P in GI→ insoluble complex eliminated in feces.Administered with each mealExamples: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 accumulationAl-containing binders may be used for ashort course < 4 wks if [P]> 7mg/dL but should be replaced by other binderAl 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 calcificationsSevelamer can also ↓LDL-C & ↑HDL-CMost common S/Es: GISevelamer has much higher cost than Ca-containing PO4 bindersSevelamer: 2nd-line agents for controlling P levelsLanthanum 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 secretionEsp. useful when reducing serum P does NOT reduce PTH levelsCalcitriol : The most active form of vit.DCalcitriol effect is mediated by upregulation of vit.Dreceptors in the PG & also in the intestine→↑P & Ca GI absorption→ Hyper-P & Hyper-CaTherefore, [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 notbe activated by kidney & activated vit.D analogs mustbe used.Paricalcitol has less effect on vit.D receptors inthe GI → ↓’ing effect on intestinal Ca & Pwhile maintaining effect on PG which makes ituseful with elevated Ca-P product .
79 Doxercalciferol:*Has similar effects as calcitriol on vit.D receptoron PG & intestine[Ca], [P], Ca-P product should all be within normalrange for the CKD stage before starting it.Recommendations for vit.D analog therapydepend 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 & PBeneficial for those with ↑’d PTH& ↑’d Ca-P and can NOT use vit.DCan be used with or without vit.DReversal 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 catabolism2)↓ albumin synthesisBoth →Muscle wasting3)Worsening of cardiac dz4)Impaired glucose tolerance5)Altered growth hormone6)Altered thyroid function7)Inflammation
84 Pathophysiology:Kidneys play a role in the body’s acid-base homeostasis.Normal kidneys:*HCO3 that is freely filtered through the glomerulus isthen completely reabsorbed by renal tubules.*Hydrogen ions are generated during foodmetabolism then same rate → bodyfluids pH is maintained within a very narrow range.Impaired Kidneys:* GFR declines→ HCO3 reabsorption is maintainedbut H excretion is ↓’d →metabolic acidosis* GFR<20-30ml/min
85 Treatment:*Monitor serum electrolytesCKD metabolic acidosis is usually with ↑’d anion gap due to accumulation of PO4 & SO4& other organic anionsNonpharmacologic Therapy:Address other contributing disordersAlter 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 ≥ 3Citrate metabolized by liver→HCO3Citric acid →CO2 + H2OGoal: Serum [HCO3] of 24 mEq/LDose 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 →alterplatelet function & aggregation → bleeding*↓RBCs (in anemia)→↓plt.- vessel wall interaction*Hemodialysis & anticoagulant use duringhemodialysis ↑ risk of bleedingCKD-Bleeding includes: ecchmoses, puncturesites, mucus membranes, GI, IM,….
88 Treatment:Nonpharmacologic:Dialysis→↓uremic toxins→improves plateletfunction & ↓bleeding time*Anemia Tx & improvement in nutritional status→ ↓bleeding time
89 Pharmacologic Therapy: Cryoprecipitate:*Contains components important in plt.aggregation & clotting→↓Bleeding time in1hr (50%pts) but is costly &↑ infection risk
90 Desmopressin (DDAVP): ↑factor VIII release from endothelial tissue in vessel wallBleeding time promptly ↓’d (in 1 hr) &DA 4-8 hrsGiven IV, SQ, or intranasallyRepeated doses →Tachyphylaxis by depleting stores of factor VIIIS/Es: flushing, dizziness, headache
91 Estrogens:↓’s bleeding timeSlower OA than DDAVP but more sustained DAdepending on route of adm.*4-5 days IV therapy: OA within 6 hrs, & effectmay last up to 2 wks after D/C.PO: OA within 2 days, DA 4-5 days after D/CTransdermal patches may also be effectiveS/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 alleviateAdequate Dialysis:1st line Tx (no sig. improvement)Maintaining proper nutritional intakeControl HPTAvoid hypervitaminosisIf no relief→UV-B phototherapy
94 Pharmacologic Therapy: Topical emollients: used but not effective2) Antihistamines : 1st linee.g. Hydroxyine, Diphynhydramine po, or IV3) Cholestyramine used4) Activated charcoal : some efficacy5) Other therapies often used in combinations withother agents include oral ondansetron or naltrexone& topical capsaicin. Each reported to have efficacy inCKD-pruritus Tx.
95 8) GI Complications:Due to the effect of uremic toxins on the GI→can use H2-antagonists or proton-pumpinhibitorsConstipation 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 preferredas 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 toxicityin kidney failure.