Management of Chronic Kidney Disease

General Principles

  • CKD is divided into five stages based on the estimated GFR (Figure 13-1). To be classified as stage 1 or stage 2, there must be an accompanying structural or functional defect (e.g., proteinuria, hematuria) because the GFR is normal or near normal in these stages.
    Figure 13-1 Stages of chronic kidney disease.
    Descriptive text is not available for this image

    CKD, chronic kidney disease; GFR, glomerular filtration rate.

    (Reprinted from Summary of recommendation statements. Kidney Int Suppl (2011). 2013;3(suppl):5-14 with permission from Elsevier.)

  • Patients are usually asymptomatic until significant renal function is lost (late stage 4 and stage 5). However, complications including hypertension, anemia, and mineral bone disorders (renal osteodystrophy and secondary hyperparathyroidism) often develop during stage 3 and thus must be investigated and addressed before patients become symptomatic.
  • The decline in GFR may be followed by plotting the reciprocal of Cr versus time, revealing a linear decrement. This can be useful in end-stage planning and in predicting when renal replacement therapy will be needed. A steeper than anticipated decline in GFR suggests a superimposed renal insult.
  • In the setting of CKD, initiation of dialysis based solely on a target GFR has not shown a mortality benefit.1 Dialysis should be started before the worsening of the patient’s metabolic or nutritional status.

Risk Factors

  • Decreased renal perfusion can lead to a decline in GFR. This can occur with true volume depletion or diminished effective circulating volume (e.g., congestive heart failure, hepatic cirrhosis). NSAIDs can be particularly deleterious in this setting because they block the renal autoregulatory mechanisms to preserve GFR. ACE inhibitors or ARBs also produce a reversible decrement in GFR through alterations in hemodynamics.
  • Uncontrolled hypertension leads to hyperfiltration, which may lead to worsening proteinuria and further damage to the glomeruli.
  • Albuminuria has also been identified as a risk factor for progression of renal disease. A prognostic scale has been developed incorporating both the GFR and degree of albuminuria to predict the likelihood to renal failure (see Figure 13-1).
  • Nephrotoxic agents, such as iodinated contrast agents and aminoglycosides, should be avoided when possible. Careful attention to drug dosing is mandatory, frequently guided by the estimated GFR or CKD stage. Drug levels should be monitored where appropriate.
  • Patients undergoing coronary angiography are at particular risk for worsening CKD. Contrast nephropathy and atheroembolic disease are potential complications of coronary angiography, and the risks and benefits of the procedure must be weighed with the patient before proceeding.
  • UTI or obstruction should be considered in all patients with an unexplained drop in renal function.
  • Worsening renal artery stenosis may also lead to a more rapid decline in GFR as well as sudden worsening in previously controlled hypertension.
  • Renal vein thrombosis may occur as a complication of the nephrotic syndrome and can exacerbate CKD. Hematuria and flank pain may be present.


Treatment of CKD is focused on avoidance of risk factors (listed above), dietary modification, blood pressure control, adequate treatment of the associated conditions, and ultimately, preparation for renal replacement therapy.

  • Dietary restrictions
    • Sodium restriction to <3 g/d is usually adequate for most CKD patients. Restriction to <2 g/d should be used if heart failure or refractory hypertension is present. A 24-hour urine sodium level of 100 mEq roughly correlates with a 2.4 g/d diet.
    • Fluid restriction is generally not required in CKD patients and, if excessive, may lead to volume depletion and hypernatremia. Restriction is appropriate in patients with dilutional hyponatremia.
    • Potassium should be restricted to 60 mEq/d in individuals with hyperkalemia. Tomato-based products, bananas, potatoes, and citrus drinks are high in potassium and should be avoided in these patients.
    • Dietary phosphate restriction should be to 800–1000 mg/d. Dairy products, dark colas, and nuts should be avoided in hyperphosphatemia. Oral binders (calcium carbonate or acetate, lanthanum carbonate, sevelamer carbonate) can be taken with meals if dietary restrictions are unable to control phosphate levels.
  • Hypertension
    • Uncontrolled hypertension accelerates the rate of decline of renal function. Blood pressure control to <140/90 mm Hg is recommended for patients with CKD.2
    • ACE inhibitors or ARBs should be used preferentially in the CKD population. They lower intraglomerular pressure and possess renoprotective properties beyond their antihypertensive effect, particularly in proteinuric states. Because of their effects on intrarenal hemodynamics, a 30% rise in serum Cr should be anticipated and tolerated; a further rise should prompt a search for possible renal artery stenosis. The Cr and serum potassium should be checked approximately 1–2 weeks after a dose adjustment. Combined therapy with ACE inhibitors and ARBs is not recommended because of an increased risk of hyperkalemia and AKI without statistical benefit in mortality or long-term renal protection.3
    • Diuretics are also beneficial in achieving euvolemia in hypertensive CKD patients. Thiazide diuretics become less effective as the GFR falls below 30 mL/min, whereas loop diuretics retain their efficacy, although higher doses may be required for the desired effect.
  • Anemia
    • A normocytic anemia is common in CKD and should be evaluated once the GFR falls below 60 mL/min/1.73 m (stage 3).
    • Alternate causes for an anemia should be entertained in the appropriate setting and iron stores assessed. If the transferrin saturation is <30% and there is no evidence of iron overload (ferritin <1000 ng/mL), consideration should be given to iron repletion with 1 g of an IV preparation of iron dextran (1000 mg once with test dose of 25 mg), ferric gluconate (125 mg, 8 doses), or iron sucrose (100 mg, 10 doses).
    • Erythropoiesis-stimulating agents (ESAs), such as epoetin and darbepoetin, can effectively reduce but do not prevent the need for RBC transfusions. ESA therapy increases the risk of stroke and thrombotic and cardiovascular events and worsens outcomes in patients with cancer. These agents should not be started in CKD unless the hemoglobin is <10 g/dL, other causes of anemia such as iron deficiency are addressed, and reduction in transfusions is a goal. The minimum dose that maintains the hemoglobin above the need for transfusion and below 11 g/dL should be used. Correction of iron deficiency frequently decreases the ESA dose requirement and may defer the need for ESA. Targeting the hemoglobin to higher levels has been associated with increased cardiovascular mortality, and this risk may be related to the higher doses of ESA.4
  • Bone mineral disorders
    • CKD bone mineral disorders increase in prevalence as the GFR declines through stage 3 and more advanced disease. They include disorders of bone turnover and secondary hyperparathyroidism.
    • Osteitis fibrosa cystica is commonly associated with secondary hyperparathyroidism and increased bone turnover, resulting in bone pain and increased fracture risk. Adynamic bone disease is a low-turnover state with suppressed parathyroid hormone (PTH) levels. Osteomalacia can involve deposition of aluminum into bone and is less commonly seen today with the decreased use of aluminum-based phosphate binders.
    • In CKD, starting in stage 3, vitamin D deficiency, low calcium, and elevated phosphate can all contribute to secondary hyperparathyroidism. The general goal of therapy is to suppress PTH toward normal while maintaining normal serum calcium and phosphate. This can be addressed in three steps: repletion of vitamin D stores (25-OH vitamin D), control of dietary phosphate with binders, and administration of active vitamin D (1,25-dihydroxyvitamin D or an analogue).
      • Deficient stores (25-OH vitamin D <30 ng/mL) should be corrected with oral ergocalciferol 50,000-IU capsule weekly or every other week or cholecalciferol 2000–4000 IU daily. The duration of treatment depends on severity of the deficiency, with levels <5 ng/dL warranting at least 12 weeks of treatment. Once at goal, maintenance therapy can rely on either monthly ergocalciferol 50,000 IU or daily cholecalciferol 1000–2000 IU.
      • Phosphate control can be difficult as GFR declines, even with appropriate dietary restriction. Phosphate binders inhibit gastrointestinal absorption. Calcium-based binders are effective when given with meals as calcium carbonate (200 mg of elemental calcium per 500-mg tablet) or calcium acetate (169 mg of elemental calcium per 667-mg tablet). In general, the total daily elemental calcium administered should be <1500 mg. Lanthanum carbonate and sevelamer carbonate are non–calcium-based alternatives.
      • Active vitamin D (1,25-dihydroxyvitamin D) and its synthetic analogues are potent suppressors of PTH and can be administered if serum PTH remains elevated. Options include daily calcitriol (0.25–1 μg), paricalcitol (1–5 μg), or doxercalciferol (1–5 μg). Calcium levels need to be monitored regularly and doses adjusted to avoid hypercalcemia.
      • Cinacalcet is a calcimimetic that acts on the parathyroid gland to suppress PTH release. It should be used only in dialysis patients and usually in conjunction with active vitamin D because it may induce significant hypocalcemia and is relatively ineffective as monotherapy.
  • Metabolic acidosis. As renal function deteriorates, the kidney is unable to appropriately excrete sufficient acid, resulting in metabolic acidosis (mixed high and normal anion gap). To compensate, alkaline buffer is released from the skeleton but can ultimately worsen bone mineral disease.
    • Treatment with sodium bicarbonate 650–1300 mg thrice daily can help maintain the serum bicarbonate level at 22 mEq/L. Such therapy, however, can increase the sodium load and contribute to edema or hypertension.
    • Citrate, another alkaline source, should not be used in the CKD or ESRD population because it can dramatically enhance gastrointestinal absorption of aluminum and lead to aluminum toxicity or osteomalacia.
  • Hyperlipidemia. Therapy with statins combined with ezetimibe has shown improved cardiovascular outcomes with fewer major atherosclerotic events in patients with moderate to severe CKD and in the dialysis population, although the benefit in patients on dialysis was less.5 Use of lipid-lowering therapy is appropriate in patients with atherosclerotic disease at all stages of CKD.
  • Preparation for renal replacement therapy
    • Patients should be counseled at an early stage to determine preferences for renal replacement therapies, including hemodialysis, peritoneal dialysis (PD), and eligibility for renal transplantation.
    • In stage 4 CKD, preparation for the creation of a permanent vascular access for hemodialysis should be initiated by protecting the nondominant forearm from IV catheters and blood draws. Timely referral for vein mapping and to an access surgeon can facilitate the creation and maturation of an arteriovenous (AV) access.


  1. Cooper BA, Branley P, Bulfone L, et al. A randomized, controlled trial of early versus late initiation of dialysis. N Engl J Med. 2010;363:609-619.  [PMID:20581422]
  2. James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311:507-520.  [PMID:24352797]
  3. Fried LF, Emanuele N, Zhang JH, et al. Combined angiotensin inhibition for the treatment of diabetic nephropathy. N Engl J Med. 2013;369:1892-1903.  [PMID:24206457]
  4. Solomon SD, Uno H, Lewis EF, et al. Erythropoietic response and outcomes in kidney disease and type 2 diabetes. N Engl J Med. 2010;363:1146-1155.  [PMID:20843249]
  5. Baigent C, Landray MJ, Reith C, et al. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial. Lancet. 2011;377:2181-2192.  [PMID:21663949]


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