Presentation on theme: "Chronic Kidney Disease (CKD). Key Concepts 1.Chronic kidney disease (CKD) is classified based on: * the cause of kidney disease, assessment of glomerular."— Presentation transcript:
Chronic Kidney Disease (CKD)
Key Concepts 1.Chronic kidney disease (CKD) is classified based on: * the cause of kidney disease, assessment of glomerular filtration rate, and extent of proteinuria. 2.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 4. 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. 5. 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.
6.Guidelines provide information to assist healthcare providers in clinical decisions and the design of appropriate therapy to manage CKD progression and the associated complications. 7.Patient education plays a critical role in the appropriate management of patients with CKD and related complications. 8.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. 9.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.
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).
The prognosis of CKD can vary and depends on: (a)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: 1)Altered sodium and water balance, 2)Hyperkalemia, 3)Metabolic acidosis, 4) Anemia, 5) CKD-related mineral and bone disorder (CKD-MBD), 6) Cardiovascular disease (CVD).
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.
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: 2 nd leading cause of ESRD *Glomerulonephritis: 3 rd leading cause of ESRD
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.
Progression Factors: 1)Proteinuria: Marker of glomerular & tubular dysfunction Degree of proteinuria correlates with progression of CKD. Microalbuminuria > 30mg/day: linked with vascular injury & ↑ CV mortality
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
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)
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
Proposed mechanisms for progression of renal disease
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.
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.
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
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
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)
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
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.
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
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.
Pharmacologic Therapy: 1)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
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
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↓)
4) Hyperlipidemia: ** Goals of Tx of dyslipidemia are to: 1 st to ↓ atherosclerotic CVD risk 2 nd 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
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
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
Complications of CKD: 1.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
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
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
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
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
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
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]
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
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.
2) Temporary measures that could shift K intracellularly within min. to stabilize the cell membrane from the effects of excessive serum [K], include: a.Reg. Insulin (5-10 U IV)+ Dextrose (5-50%IV) b.Nebulized albuterol mg c.NaHCO₃ is used for shifting only if severe metabolic acidosis (pH<7.2)
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
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
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)
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
Treatment: Anemia Tx →↓morbidity ↑Exercise capacity & tolerance Slow the progression of CKD *GFR 2mg/dL →Evaluate for anemia * Abnormalities found during anemia work up (esp. iron deficiency)should be corrected before starting erythrpoeitin stimulating agents(ESAs).
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%
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 3 rd line therapy for CKD-anemia
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
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.
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.
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
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 tubules in kidney 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
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.
Metabolic acidosis :(a complicat’n of CKD) 1)↓’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
↑ 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%
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
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.
Nonpharmacologic Therapy: 1 st 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
Pharmacologic Therapy: 1)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
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 7mg/dL but should be replaced by other binder Al intoxication cause neurological & hematological toxicities
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: 2 nd -line agents for controlling P levels Lanthanum has similar pharmacological effect as Sevelamer but S/Es include nausea, peripheral edema, & myalgia
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.
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.
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
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
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
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
Treatment: *Monitor serum electrolytes CKD metabolic acidosis is usually with ↑’d anion gap due to accumulation of PO 4 & SO 4 & other organic anions Nonpharmacologic Therapy: Address other contributing disorders Alter HCO3 levels in the dialysate in dialysis pts. Pharmacologic therapy is required
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
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,….
Treatment: Nonpharmacologic: Dialysis→↓uremic toxins→improves platelet function & ↓bleeding time *Anemia Tx & improvement in nutritional status → ↓bleeding time
Pharmacologic Therapy: Cryoprecipitate: *Contains components important in plt. aggregation & clotting→↓Bleeding time in 1hr (50%pts) but is costly &↑ infection risk
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
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
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
Treatment: Nonpharmacologic Therapy: CKD-pruritus difficult to alleviate Adequate Dialysis:1 st line Tx (no sig. improvement) Maintaining proper nutritional intake Control HPT Avoid hypervitaminosis If no relief→UV-B phototherapy
Pharmacologic Therapy: 1)Topical emollients: used but not effective 2) Antihistamines : 1 st 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.
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
9) Musculoskeletal Complaints: Due to hyperuricemia in renal impairment. Allopurinol :↓’s UA production is preferred as a prophylactic agent.
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.