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Chronic kidney disease 

Chronic kidney disease

Chapter:
Chronic kidney disease
Author(s):

Eberhard Ritz

, and Tilman B. Drüeke

DOI:
10.1093/med/9780199204854.003.2106_update_001

Update: Enhanced discussion of (1) increased mortality associated with very modest increase in proteinuria; (2) effect of blood pressure control on progression—new trial in African American patients with hypertensive kidney disease; (3) use of newer phosphate binders and the calcimimetic, cinacalcet; (4) timing of initiation of dialysis.

Updated on 25 May 2011. The previous version of this content can be found here.
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date: 25 April 2017

Essentials1

Definition—chronic kidney disease (CKD) is defined as kidney damage lasting for more than 3 months characterized by structural or functional abnormalities of the kidney, with or without decreased glomerular filtration rate (GFR).

Staging—CKD has been subdivided into five stages depending on the estimated GFR (eGFR), as described in Chapter 21.4, but in brief: CKD 1 is eGFR greater than 90 ml/min (per 1.73 m2) with other evidence of renal disease; CKD stage 2 is eGFR 60 to 89 ml/min, with other evidence of renal disease; CKD stage 3 is eGFR 30 to 59 ml/min CKD stage 4 is eGFR 15 to 29 ml/min and CKD stage 5 is eGFR less than 15 ml/min. CKD 3 can be divided into 3A (eGFR 45–59) and 3B (eGFR 30–44), and the suffix ‘p’ can be added to any stage to denote proteinuria (ACR >30mg/mmol, PCR >50mg/mmol).

Epidemiology—mild CKD is common, with about 10% of the population of the United States of America having CKD 1, 2, or 3 (combined), but advanced CKD is relatively rare (about 0.2% are receiving renal replacement therapy). Patients with CKD 1, 2, or 3 are at relatively low risk of progressing to require renal replacement therapy, but are at high risk of death from cardiovascular disease.

Aetiology—the causes of chronic renal failure recorded in various national registries are diabetes mellitus (22–45%), glomerulonephritis (10–23%), hypertension (5–25%), chronic pyelonephritis (0.5 to 7%), adult polycystic kidney disease (2–7%), renal vascular disease (2–7%), other recognized conditions (13–15%), and unknown causes (4–26%). However, these data are flawed for many reasons: diagnoses are often allocated as ‘best guesses’ by clinicians, there is no universal agreement on the meaning of terms such as ‘pyelonephritis’, glomerulonephritis may be diagnosed without histological proof, and hypertension is often cited when it may be no more than a consequence of whatever caused the renal failure.

Pathophysiology

Compensatory mechanisms and their consequences—as kidney function gradually fails, these generally maintain acceptable health until the GFR is about 10 to 15 ml/min, and patients will not usually die of renal failure until the GFR is less than 5 ml/min. Despite a widened range of single-nephron GFR in damaged or diseased kidneys, glomerular and tubular function remains closely integrated in all individual nephrons (the ‘intact nephron hypothesis’). However, the functional adaptations required to maintain overall homeostasis come at a price (the ‘trade-off hypothesis’), with the ‘hyperfiltration hypothesis’ most clearly articulating how these adaptive changes lead, in the long run, to glomerulosclerosis and tubulointerstitial fibrosis and progressive decrease in GFR.

Pathophysiological changes—these include impairment in: (1) concentration and/or dilution of the urine; (2) excretion and/or conservation of sodium; (3) excretion of potassium, with hyperkalaemia often the immediate life-threatening consideration in the management of patients with renal failure; (4) excretion of acid; (5) calcium/phosphate/vitamin D/bone homeostasis; (6) erythropoietin production, leading to renal anaemia; (7) excretion of many substances and metabolites that act as ‘uraemic toxins’; and (8) a wide range of endocrine functions.

The clinical presentation of CKD is discussed in Chapter 21.3 and investigation of patients with renal disease in Chapter 21.4.

Prevention of progression

Specific and general measures—in some patients, measures to conserve renal function may be specific to the cause of renal impairment, e.g. relief of obstruction, but it is probable that all patients will benefit from good blood pressure control and (when relevant) measures to reduce proteinuria, which is not only a marker but a promoter of progression of CKD.

Blood pressure and proteinuria—there is limited information on the target blood pressure to be achieved in patients with chronic kidney disease, but the consensus is that the lower the blood pressure, the better—as long as this can be achieved without unacceptable side effects. The European Society of Hypertension/European Society of Cardiology guidelines recommend a target of less than 130/80 mmHg, and even lower if there is significant proteinuria, which should be lowered as much as possible, preferably to less than 1 g/24 h (roughly equivalent to an albumin:creatinine ratio (ACR) of less than 60 mg/mmol or a protein:creatinine ratio (PCR) of less than 100 mg/mmol). Combination therapy with several antihypertensive agents (including loop diuretics) is usually required, but there is good evidence that the regimen should contain an angiotensin-converting enzyme (ACE) inhibitor and/or angiotensin receptor blocker, which have antiproteinuric effects, if these can be tolerated (hyperkalaemia being the most common reason why they cannot be used in this context).

Medical management of the consequences of CKD

Diet—only patients with oliguric endstage renal failure need to restrict their fluid intake precisely. It is sensible to recommend modest dietary sodium restriction (100 mmol/day) in most cases. Patients with a tendency to hyperkalaemia should be offered advice regarding a low-potassium diet (with particular care taken if they are given medications that induce hyperkalaemia). Chronic acidosis will benefit from treatment with alkali. Malnutrition is common in advanced CKD, can be detected by serial monitoring of body weight and serum albumin concentration, and is best treated by initiating renal replacement therapy.

Chronic kidney disease mineral and bone disorders (MBD)—these including osteitis fibrosa, osteomalacia, adynamic bone disease, and osteopenia, the impact of which extends beyond the bones to cardiovascular structure and function, with increased mortality. Pathogenesis is complex but includes phosphate retention, deficiency of active forms of vitamin D, hypocalcaemia, and the development of hyperparathyroidism. Secondary hyperparathyroidism can be prevented by giving: (1) cholecalciferol 1000 U/day if serum 25-(OH)D3 is low; (2) calcium carbonate 0.5 to 1.0 g with each meal if plasma calcium is decreased and/or plasma phosphate is increased; (3) calcium-free phosphate binder, e.g. sevelamer or lanthanum carbonate, if serum phosphate is increased and plasma calcium is normal or high; or (4) calcitriol 0.125 to 0.25 µg/day, or equivalent doses of alfacalcidol or other active vitamin D analogues, if serum intact parathyroid hormone (PTH) is consistently above target ranges and serum calcium/phosphate is normal (spontaneously or after intervention).

Advanced hyperparathyroidism can be treated by: (1) normalizing serum calcium and phosphate levels if serum intact PTH is constantly above target range; (2) reducing serum phosphate, if this is elevated, by using phosphate binders, dietary restriction, and increased dialysis; (3) reducing serum calcium if this is elevated by reducing/withdrawing calcium-containing phosphate binders and active vitamin D sterols, and by reducing dialysate calcium concentration; (4) if serum calcium and phosphate have been normalized and elevated intact PTH persists, by increasing dose or frequency of calcitriol or other active vitamin D sterols (e.g. alfacalcidol, paricalcitol, doxercalciferol), or alternatively administering the calcimimetic cinacalcet, which renders the calcium receptor more sensitive to calcium; and (5) if serum intact PTH fails to decrease and/or hypercalcaemia/hyperphosphataemia develop or persist, then consider cinacalcet or surgical parathyroidectomy.

Anaemia—this is common in chronic kidney disease and is particularly marked in patients with diabetes. Partial correction of such anaemia by use of erythropoiesis-stimulating agents (ESAs) improves patients’ physiological and clinical status, as well as quality of life. If a patient with chronic kidney disease has haemoglobin of less than 11 g/dl and symptoms that might be attributable to anaemia, then treatment to restore haemoglobin to the range 11 to 12 g/dl is warranted, but it has been convincingly shown in randomized studies that correction to a higher level (‘normal or near normal’) is associated with poorer outcomes and should be prevented. Treatment involves: (1) exclusion of other causes of anaemia; (2) optimization of iron status, which usually requires administration of intravenous iron; and (3) initiation and adjustment of dosage/frequency of administration of ESAs, with regular monitoring to achieve haemoglobin in the target range 11 to 12 g/dl.

Preparation for renal replacement therapy or conservative (palliative) management of terminal uraemia

Once endstage renal failure is inevitable, the patient must be prepared physically and psychologically for renal replacement therapy (see Chapters 21.7.1–21.7.3). In many cases it is possible to predict approximately when the endstage will be reached from consideration of the rate of renal deterioration, most easily demonstrated by plotting the reciprocal of the serum creatinine against time.

There are patients for whom dialysis is inappropriate, or who either choose not to start or to discontinue treatment. In frail patients, usually elderly and with multiple comorbidities, it is not likely that dialysis will greatly prolong life, although it can certainly lower the quality of it. The ethical and legal issues are complex and require that the patient makes the decision not to start or to discontinue treatment when fully informed and able to do so. They must be given a realistic account of what dialysis can achieve, what it cannot achieve, and at what cost—access, travel, restrictions, and complications. These conversations can be difficult and cannot be hurried, it being critically important that the patient (and their relatives/friends) does not get the entirely erroneous impression that dialysis means that ‘the doctors care and I’ll live for ever’, whereas no dialysis means that ‘the doctors don’t care and I’ll die soon’. Properly managed, death from uraemia is peaceful and free of suffering.

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