AKI AND CKD THERAPY

ARMENIA
2021
KIDNEY FUNCTIONS

 EXCRET METABOLIC WASTE AND TOXIN

 WATER AND ELECTROLYTE BALANCE
 BP CONTROL
 HEMATOPEUTICS
 ACTIVATION OF VIT D → CALCIUM REABSORBTION
 HORMON PRODUCTION
PATHOPHYSIOLOGY OF AKI
CRITERIA
 FENa = (UNa × SCr × 100)/(UCr × SNa)
 where UNa = urine sodium,
 SCr = serum creatinine,
 UCr = urine creatinine, and
 SNa = serum sodium
PREVENTION

 Goals of Prevention:
 to screen and identify patients at risk;
 monitor high-risk patients;
 implement prevention strategies when
appropriate.
Nonpharmacologic Therapies
 Hydration
 prevent contrast-induced nephropathy (CIN):
 isotonic crystalloids over colloids and parenteral over oral
administration in high-risk individuals, including those with
chronic kidney disease (CKD), diabetes, volume depletion,
concurrent nephrotoxic drug therapy, or hemodynamic
instability
 KDIGO guidelines:
A common sodium bicarbonate regimen is 154 mEq/L (154
mmol/L) infused at 3 mL/kg/h for 1 hour before the procedure
and at 1 mL/kg/h for 6 hours after the procedure. One
frequently cited normal saline regimen is 1 mL/kg/h for 12
hours pre- and postprocedure.
Pharmacologic Therapies

 Ascorbic acid (3 g orally pre- and 2 g orally

twice daily for two doses postprocedure)
 N-acetylcysteine (600–1200 mg orally every
12 hours for 2–3 days [first two doses
precontrast]) are antioxidant options for
prevention of CIN
Current KDIGO guidelines

 moderate control of blood glucose to levels of 110 to 149

mg/dL (6.1–8.3 mmol/L) → insulin
 prevent intensive care unit–acquired AKI.
 limiting use of loop diuretics
 avoiding use for sole purpose of preventing or treating
AKI.
 Current evidence and KDIGO guidelines do not support use
of low-dose dopamine, erythropoietin, or fenoldopam for
prevention or treatment of AKI.
TREATMENT OF ACUTE KIDNEY INJURY

 Goals of Treatment:
 Short-term goals:
 minimizing the degree of insult to the kidney,
 reducing extrarenal complications,
 expediting recovery of renal function.
 Restoration of renal function to pre-AKI
baseline is the ultimate goal.
Nonpharmacologic Therapies
 Supportive care goals include maintenance of adequate
cardiac output and blood pressure to optimize tissue
perfusion while restoring renal function
 Discontinue medications associated with diminished
renal blood flow.
 Avoid use of nephrotoxins.
 In severe AKI → renal replacement therapy (RRT),
 hemodialysis

 peritoneal dialysis,
 maintainsfluid and electrolyte balance while removing
waste products.
Nonpharmacologic Therapies (Cont.)

 Intermittent hemodialysis (IHD) is the most frequently used for 3 to 4 hours.

(Disadvantages in hypotensive patients and hypotension due to rapid removal
of large amounts of fluid)
 Several continuous RRT (CRRT) variants have been developed including:
 continuous hemofiltration,
 continuous hemodialysis
 combination.
 CRRT gradually removes solute, resulting in better tolerability by critically ill
patients. Disadvantages include limited availability of equipment, need for
intensive nursing care, and the need to individualize IV replacement, dialysate
fluids, and drug therapy adjustments
 Pharmacologic Therapies

 Mannitol 20% is typically started at a dose of 12.5 to 25 g IV over 3 to 5 minutes.

 Disadvantages
 IV administration,
 hyperosmolality risk,
 need for monitoring urine output and serum electrolytes and osmolality
 mannitol can contribute to AKI.
 Loop diuretics effectively reduce fluid overload but can worsen AKI.
 furosemide, bumetanide, torsemide, and ethacrynic acid) → similar efficacy.
 Continuous infusions of loop diuretics → overcome diuretic resistance and to have fewer
adverse effects than intermittent boluses.
 Initial IV loading dose (equivalent to furosemide 40–80 mg) should be administered before
starting a continuous infusion (equivalent to furosemide 10–20 mg/h).
RENAL REPLACEMENT THERAPY
Modern criteria[11] for the initiation of RRT
in ICU include

 Oliguria (urine output <200 ml/12 h)

 Anuria (urine output: 0–50 ml/12 h)
 [Blood urea] > 35 mmol/L (>98 mg/dL)
 [Serum creatinine] > 400 mmol/L (>4.5 mg/dL)
 Uncompensated metabolic acidosis (pH < 7.1)
Modern criteria[11] for the initiation of
RRT in ICU include (Continued)
 [Serum K+] > 6.5 mmol/L or rapidly rising values
 [Serum Na+] < 110 and >160 mmol/L
 Pulmonary edema unresponsive to diuretics
 Temperature >40°C
 Uremic complications (encephalopathy / myopathy /
neuropathy / pericarditis)
 Overdose with a dialyzable toxin (e.g. lithium)
Don’t do RRT to

 Cardiac failure
 Patientsrequiring a large amount of fluid,
parenteral nutrition or blood products, but at risk
of developing pulmonary edema or ARDS
DIURETIC
RESISTANCE
ELECTROLYTE MANAGEMENT AND
NUTRITION INTERVENTIONS
 Serum electrolytes should be monitored daily.
 Hyperkalemia in AKI.
 Hypernatremia
 fluid retention
 Need to calculation of daily sodium intake, including sodium contained in commonly
administered antibiotic and antifungal agents. •
 Phosphorus and magnesium should be monitored, especially in patients with significant
tissue destruction due to increased amounts of released phosphorus; neither is efficiently
removed by dialysis.
 Nutritional management of critically ill patients with AKI is complex due to multiple
mechanisms for metabolic derangements. Nutritional requirements are altered by stress,
inflammation, and injury that lead to hypermetabolic and hypercatabolic states.
M
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DRUG-DOSING CONSIDERATIONS

 Drugtherapy optimization in AKI is a

challenge. Confounding variables
include residual drug clearance, fluid
accumulation, and use of RRTs.
Volume distribution and drug dosing

 Volume of distribution for water-soluble drugs is significantly increased due to

edema.
 Use of dosing guidelines for CKD does not reflect the clearance and volume of
distribution in critically ill patients with AKI.
 Patients with AKI may have a higher residual nonrenal clearance than those
with CKD with similar creatinine clearances; this complicates drug therapy
individualization, especially with RRTs.
 The mode of CRRT determines rate of drug removal, further complicating
individualization of drug therapy.
 Rates of ultrafiltration, blood flow, and dialysate flow influence drug
clearance during CRRT.
Q&A
CHRONIC KIDNEY DISEASE

 abnormalities in kidney structure or function, present for 3

months or longer, with implications for health.
 Structural abnormalities:
 albuminuria of more than 30 mg/day,
 presence of hematuria or red cell casts in urine sediment,
 electrolyte and other abnormalities due to tubular disorders,
 abnormalities detected by histology,
 structural abnormalities detected by imaging,
 or history of kidney transplant
CLASSIFICATION
CLINICAL PRESENTATION

 stage 1 or 2 CKD
 do not have symptoms or metabolic derangements
 stages 3 to 5 CKD,
 anemia,
 secondary hyperparathyroidism,
 cardiovascular disease (CVD),
 malnutrition, and
 fluid and electrolyte abnormalities
 Uremic symptoms (fatigue, weakness, shortness of breath, mental confusion,
nausea, vomiting, bleeding, and anorexia (Stage 5) → decision to implement
RRT.
Goal of Treatment:

 to delay the progression of CKD,

 minimizingthe development or severity of
complications.
NONPHARMACOLOGIC THERAPY

 Restrict protein to 0.8 g/kg/day if GFR is less than

30 mL/min/1.73 m2 .
 Encourage smoking cessation to slow progression
of CKD and reduce the risk of CVD.
 Encourage exercise at least 30 minutes five times
per week and achievement of a body mass index
(BMI) of 20 to 25 kg/m2
PHARMACOLOGIC THERAPY
 Diabetes and Hypertension With CKD
 Progression of CKD can be limited by optimal control of
hyperglycemia and hypertension.
 Adequate blood pressure (BP) → reduce the rate of decline in GFR
and albuminuria in patients without diabetes.
 KDIGO → target blood pressure of 140/90 mm Hg or less if urine
albumin excretion or equivalent is less than 30 mg/24 h.
 If urine albumin excretion is greater than 30 mg/24 h or
equivalent, → BP ≤130/80 mm Hg
PHARMACOLOGIC THERAPY
 Angiotensinconverting enzyme inhibitor (ACEI) or an angiotensin II
receptor blocker (ARB).
 Add a thiazide diuretic in combination with an ARB if additional
reduction in proteinuria is needed.
 Nondihydropyridine calcium channel blockers are generally used as
second-line antiproteinuric drugs when ACEIs or ARBs are
contraindicated or not tolerated.
 ACEI clearance is reduced in CKD; → treatment should begin with
the lowest possible dose followed by gradual titration to achieve
target BP and,
Anemia of CKD

 KDIGO definition of anemia: Hemoglobin (Hb) less than 13 g/dL (130 g/L; 8.07
mmol/L) for adult males and less than 12 g/dL (120 g/L; 7.45 mmol/L) for
adult females.
 Initiate erythropoietic-stimulating agent (ESA) therapy in all CKD patients
with Hb is between 9 and 10 g/dL (90 and 100 g/L; 5.59 and 6.21 mmol/L).
 Target Hb is controversial. • Iron deficiency is the primary cause of resistance
to treatment of anemia with ESAs. Iron supplementation is required by most
CKD patients to replete iron stores depleted by ongoing blood loss and
increased iron demands. • Parenteral iron therapy improves response to ESA
therapy and reduces the dose required to achieve and maintain target
indices. In contrast, oral therapy is limited by poor absorption and
nonadherence with therapy primarily due to adverse effects (Fig. 74–4).
Anemia of CKD
 IV iron preparations have different pharmacokinetic profiles, which do not correlate with
pharmacodynamic effect.
 Adverse effects of IV iron include allergic reactions, hypotension, dizziness, dyspnea,
headaches, lower back pain, arthralgia, syncope, and arthritis. Some of these reactions can be
minimized by decreasing the dose or rate of infusion.
 Sodium ferric gluconate, iron sucrose, and ferumoxytol have a better safety record than iron
dextran products.
 Subcutaneous (SC) administration of epoetin alfa is preferred because IV access is not
required, and the SC dose that maintains target indices is 15% to 30% lower than the IV
dose.
 Darbepoetin alfa has a longer half-life than epoetin alfa and prolonged biologic activity.
 Doses are administered less frequently, starting at once a week when administered IV or SC.
 Erythropoiesis-stimulating agents (ESAs) are well tolerated. Hypertension is the most
common adverse event.
Evaluation of Anemia Therapeutic
Outcomes
 Iron indices (transferrin saturation [TSat]; ferritin) should be
evaluated before initiating an ESA. Iron status should be
reassessed every month during initial ESA treatment and every
3 months for those on a stable ESA regimen.
 Hemoglobin should be monitored at least monthly, although
more frequent monitoring (eg, every 1–2 weeks) is warranted
after initiation of an ESA or after a dose change until
hemoglobin is stable.
 Patients should be monitored for potential complications, such
as hypertension, which should be treated before starting an ESA
CKD-Related Mineral and Bone Disorder

 Disorders of mineral and bone metabolism (CKD-MBD) are common in

the CKD
 abnormalities in parathyroid hormone (PTH),
 calcium,
 phosphorus,
 calcium-phosphorus product
 vitamin D,
 bone turnover,
 soft tissue calcifications.
PHOSPHATE-BINDING AGENTS
 Phosphate-binding agents decrease phosphorus absorption from the gut and are first-line
agents for controlling both serum phosphorus and calcium concentrations
 KDOQI guidelines recommend that elemental calcium from calcium-containing binders
should not exceed 1500 mg/day, and the total daily intake from all sources should not
exceed 2000 mg.
 Adverse effects of all phosphate binders are generally limited to GI effects, including
constipation, diarrhea, nausea, vomiting, and abdominal pain.
 Risk of hypercalcemia may necessitate restriction of calcium-containing binder use
and/or reduction in dietary intake.
 Aluminum and magnesium binders are not recommended for regular use in CKD because
aluminum binders have been associated with CNS toxicity and the worsening of anemia,
whereas magnesium binders may lead to hypermagnesemia and hyperkalemia.
VITAMIN D THERAPY

 Reasonable control of calcium and phosphorus must be achieved

before initiation and during continued vitamin D therapy.
 Calcitriol, 1,25-dihydroxyvitamin D3 , directly suppresses PTH
synthesis and secretion and upregulates vitamin D receptors. The
dose depends on the stage of CKD (Table 74–4).
 The newer vitamin D analogues paricalcitol and doxercalciferol
may be associated with less hypercalcemia and, for paricalcitol,
hyperphosphatemia. Vitamin D therapy, regardless of agent, is
associated with decreased mortality
CALCIMIMETICS

 Cinacalcet reduces PTH secretion by increasing the

sensitivity of the calciumsensing receptor. The most
common adverse events include nausea and vomiting.
 The most effective way to use cinacalcet with other
therapies has not been decided. The starting dose is 30
mg daily, which can be titrated to the desired PTH and
calcium concentrations every 2 to 4 weeks to a maximum
of 180 mg daily
Hyperlipidemia

 The prevalence of hyperlipidemia increases as renal function

declines.
 National guidelines differ on how aggressively dyslipidemia
should be managed in patients with CKD. KDIGO guidelines
recommend treatment with a statin (eg, atorvastatin 20 mg,
fluvastatin 80 mg, rosuvastatin 10 mg, simvastatin 20 mg) in
adults aged 50 and older with stage 1 to 5 CKD not on dialysis.
 In patients with ESRD, lipid profile should be reassessed at
least annually and 2 to 3 months after changing treatment.
 For more information on dyslipidemias, see Chap. 8.
Q&A