kidney disease

Chronic Kidney disease

Chronic Kidney disease

Chronic kidney disease (CKD) is defined as abnormalities in kidney structure or function, present for 3 months or longer, 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 and other abnormalities due to tubular disorders, abnormalities detected by histology, structural abnormalities detected by imaging, or history of kidney transplant.

CKD is 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 15 mL/min/1.73 m2 (0.14 mL/s/m2) or in patients receiving renal replacement therapy (RRT). In this post, 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. 


Susceptibility factors increase the risk for kidney disease but do not directly cause kidney damage. They include advanced age, reduced kidney mass and low birth weight, racial or ethnic minority, family history, low income or education, systemic inflammation, and dyslipidemia.

Initiation factors directly result in kidney damage and are modifiable by drug therapy. They include diabetes mellitus, hypertension, glomerulonephritis, polycystic kidney disease, Wegener granulomatosis, vascular diseases, and human immunodeficiency virus (HIV) nephropathy.

Progression factors hasten the decline in kidney function after initiation of kidney damage. They include glycemia in diabetics, hypertension, proteinuria, hyperlipidemia, obesity, and smoking.

Most progressive nephropathies 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

CKD development and progression are insidious. Patients with 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 more common as kidney function deteriorates.

Uremic symptoms (fatigue, weakness, shortness of breath, mental confusion, nausea, vomiting, bleeding, and anorexia) are 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.


Non-pharmacological 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.
  • Dietary phosphorus restriction, dialysis, and parathyroidectomy are nonpharmacologic approaches to management of hyperphosphatemia and CKD-MBD. The KDOQI guidelines provide desired ranges of calcium, phosphorus, calciumphosphorus product, and intact PTH based on the stage of CKD.

Diabetes and Hypertension With CKD

Progression of CKD can be limited by optimal control of hyperglycemia and hypertension. Adequate blood pressure (BP) control can reduce the rate of decline in GFR and albuminuria inpatients without diabetes. KDIGO guidelines recommend a target blood pressure of 140/90 mmHg 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, the target blood pressure is130/80 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 isneeded. 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; therefore, treatment should begin with the lowest possible dose followed by gradual titration to achieve target BP and, secondarily, 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 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 non-adherence 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 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.

ESAs are well tolerated. Hypertension is the most common adverse event.

CKD-Related Mineral and Bone Disorder

Disorders of mineral and bone metabolism (CKD-MBD) are common in the CKD population and include abnormalities in parathyroid hormone (PTH), calcium, phosphorus, the calcium-phosphorus product, vitamin D, and bone turnover, as well as soft tissue calcifications.

Calcium-phosphorus balance is 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 is associated with increased morbidity and mortality and sudden death in hemodialysis patients.

Dietary phosphorus restriction, dialysis, and parathyroidectomy are nonpharmacologic approaches to management of hyperphosphatemia and CKD-MBD. The KDOQI guidelines provide desired ranges of calcium, phosphorus, calciumphosphorus product, and intact PTH based on the stage of CKD.


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. This 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, 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

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.


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.


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.



Leave a Reply

%d bloggers like this: