WRITTEN REPORT ON

CHRONIC KIDNEY DISEASE

Prepared By: Riel, Karylle Wencee C.

BSPH-3A, A.Y. 2024-2025

December 03, 2024

CHRONIC KIDNEY DISEASE

− Abnormalities in kidney structure or function, present for 3 months or longer, with implications for health
− Structural Abnormalities:
o Albuminuria >30mg/day
o Presence of hematuria or red cell casts in urine sediment
o Electrolyte and other abnormalities due to tubular disorders
o Abnormalities detected by histology
o Structural abnormalities detected by imaging, or history of kidney transplant
− Classified by cause of kidney disease,
glomerular filtration rate (GFR) category, and
albuminuria level based on new
recommendations from the Kidney Disease:
Improving Global Outcomes (KDIGO)
guidelines, referred to as CGA staging
(cause, GFR, albuminuria)

− CKD stage 5, previously referred to as end-stage renal disease (ESRD), occurs when the GFR falls below
15mL/min/1.73m2 (<0.14 mL/s/m2) or in patients receiving renal replacement therapy (RRT). ESRD refers
specifically to patients who receive chronic dialysis
− Prognosis depends on cause of kidney disease, GFR at time of diagnosis, degree of albuminuria, and presence
of other comorbid conditions

PATHOPHYSIOLOGY

SUSCEPTIBILITY FACTORS INITIATION FACTORS PROGRESSION FACTORS

● Increase the risk for kidney ● Directly result in kidney damage ● Hasten the decline in kidney
disease but do not directly and are modifiable by drug function after initiation of kidney
cause kidney damage therapy damage
● Includes diabetes mellitus, ● Includes glycemia in diabetics,
● Includes advanced age, reduced hypertension, glomerulonephritis, hypertension, proteinuria,
kidney mass and low birth polycystic kidney disease, hyperlipidemia, obesity, and
weight, racial or ethnic minority, Wegener granulomatosis, smoking
family history, low income or vascular disease, and human
education, systemic immunodeficiency virus (HIV) ● Most progressive nephropathies
inflammation, and dyslipidemia nephropathy share a final common pathway to
irreversible renal parenchymal
damage and ESRD. Key pathway
elements include loss of nephron
mass, glomerular capillary
hypertension, and proteinuria
CLINICAL PRESENTATION

Stage 1 or 2 CKD
− usually do not have symptoms or metabolic derangements seen with stages 3 to 5, such as anemia,
secondary hyperparathyroidism, cardiovascular disease (CVD), malnutrition, and fluid and electrolyte
abnormalities that are common as kidney function deteriorates
Uremic symptoms (fatigue, weakness, shortness of breathy, mental confusion, nausea, vomiting, bleeding,
and anorexia)
− generally absent in stages 1 and 2, minimal during stages 3 and 4, and common in patients with stage 5 CKD
who may also experience itching, cold intolerance, weight gain, and peripheral neuropathies
− Signs and symptoms of uremia are foundational to the decision to implement RRT

TREATMENT

General Approach
Goal of Treatment: delay the progression of CKD, minimizing the 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 • Progression of CKD can be limited by optimal control of hyperglycemia
Hypertension with CKD and hypertension

• Adequate blood pressure (BP) control can reduce the rate of decline in
GFR and albuminuria in patients without diabetes.

• KDIGO guidelines recommend a 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 > 30 mg/24 h or equivalent, the target blood

pressure is 130/80 mm Hg or less and initiate first-line therapy with an
angiotensin converting 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.
 • Second-line Antiproteinuric Drugs
o Nondihydropyridine calcium channel blockers are generally
used when ACEIs or ARBs are contraindicated or not tolerated

• ACEI clearance is reduced in CKD; therefore, treatment should begin with

the lowest possible dose followed by gradual titration:
o to achieve target BP
o to minimize proteinuria
No individual ACEI is superior to another

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
− 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.
• Oral therapy
− limited by poor absorption and nonadherence with therapy
primarily due to adverse effects

• IV Iron Preparations
− have different pharmacokinetic profiles, which do not correlate with
pharmacodynamic effect
− Adverse effects of IV iron include:
o allergic reactions
o hypotension
o dizziness
o dyspnea
o headaches
 o lower back pain
o arthralgia
o syncope
o 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
• ESAs are well tolerated
o Hypertension is the most common adverse event

Evaluation of Anemia • Iron indices (transferrin saturation [TSat]; ferritin) should be evaluated
Therapeutic Outcomes 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 • Disorders of mineral and Bone Metabolism (CKD-MBD)

Bone Disorder − common in the CKD population
− include abnormalities in:
o parathyroid hormone (PTH)
o calcium, phosphorus
o the calcium-phosphorus product
o vitamin D
o bone turnover, as well as soft tissue calcifications
• Calcium-phosphorus Balance
− mediated through a complex interplay of hormones and their
effects on bone, the gastrointestinal (GI) tract, kidneys, and the
parathyroid gland.
− As kidney disease progresses, renal activation of vitamin D is
impaired, which reduces gut absorption of calcium.
− Low blood calcium concentration stimulates secretion of PTH.
− As renal function declines, serum calcium balance can be
maintained only at the expense of increased bone resorption,
ultimately resulting in Renal Osteodystrophy (ROD)
• Secondary Hyperparathyroidism
− associated with increased morbidity and mortality and sudden
death in hemodialysis patients
TREATMENT

1. Hyperphosphatemia and CKD-MBD

− Nonpharmacologic approaches:
• Dietary phosphorus restriction
• Dialysis
• parathyroidectomy
− The KDOQI guidelines provide desired ranges of calcium, phosphorus, calcium phosphorus product, and
intact PTH based on the stage of CKD

2. 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.
➢ may necessitate a combination of calcium- and non–calcium-containing products (eg,
sevelamer HCL and lanthanum carbonate)
• Adverse Effects of all phosphate binders are generally limited to GI effects:
 o constipation
o diarrhea
o nausea
o vomiting
o 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
o aluminum binders have been associated with CNS toxicity and the worsening of anemia
o magnesium binders may lead to hypermagnesemia and hyperkalemia
3. 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
− upregulates vitamin D receptors
− The dose depends on the stage of CKD

• Newer Vitamin D Analogues:

o Paricalcitol – may be associated with less hyperphosphatemia.
o Doxercalciferol – may be associated with less hypercalcemia
− Vitamin D therapy, regardless of agent, is associated with decreased mortality
4. Calcimimetics
• Cinacalcet
− reduces PTH secretion by increasing the sensitivity of the calcium sensing 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