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I have never yet examined the body of a patient dying with dropsy attended by albuminous urine, in whom some obvious derangement was not discovered in the kidneys.
RICHARD BRIGHT 1827
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Chronic kidney failure
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In the diagnostic model the problem of chronic kidney failure (CKF) as a masquerade has been highlighted. The reason for this is that the dysfunction associated with progressive chronic kidney disease (CKD) can be difficult to diagnose as there may be no or minimal symptoms. The underlying cause needs to be identified. In fact the patient may present with a subtle terminal illness. It is important that all general practitioners are aware of the seriousness of the problem and keep it in mind when the patient presents with apparent minor problems such as fatigue or weakness. Sometimes the kidneys can develop acute failure, which may recover or progress to chronicity.
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If CKD is detected early and managed appropriately then the otherwise inevitable deterioration in kidney function can be reduced by as much as 50% and may even be reversible.1
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Key facts and checkpoints
10% of people attending general practice1 have CKD but most do not know it.
At least 95 people per million of the population are treated for end-stage kidney disease/kidney failure (ESKF) each year.
Two-thirds of these are under 60 years of age.
Important causes are glomerulonephritis (25%), diabetes mellitus (35%), polycystic kidney disease (8%), reflux nephropathy (8%) and hypertension (13%) (see TABLE 31.1).2
The commonest cause of ESKF in Australia is diabetes mellitus.
The commonest cause of nephritis leading to kidney failure in Australia is IgA nephropathy.
In children the incidence of chronic kidney failure is quite low (1 to 2 per million of the population).2
Warmer climates, poorer living conditions and certain genetic predispositions are associated with a higher prevalence of kidney failure.
Kidney failure should be considered in the diagnosis of patients with unexplained anaemia, unexplained poor health and unusually high analgesic intake.2
CKD is an important risk factor for cardiovascular disease.
Uraemic symptoms are non-specific and usually are not recognised until the creatinine clearance is less than 20% of normal.
CKF is characterised by the accumulation of uraemic toxins and a deficiency of kidney hormones that cause dysfunction of organs other than kidneys.
This interaction can cause phosphate retention, secondary hyperparathyroidism and bone disorders such as osteomalacia.
Age is an issue—we lose 1% of renal function per year
It is possible to identify stages of kidney failure (see TABLE 31.2).
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Acute kidney failure (AKF, a forerunner of CKF) is defined as a sudden (days to weeks) decrease in kidney function (azotaemia) with or without oliguria. It results in dysfunctional fluid and electrolyte balance and nitrogenous waste excretion with a sudden increase in blood urea and creatinine levels.
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AKF is usually classified into:
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prerenal (e.g. acute circulatory failure → kidney hypoperfusion)
postrenal (e.g. obstruction)
kidney (intrinsic) (e.g. acute glomerulonephritis)
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Early diagnosis with hospital admission is important and this is achieved by being aware of the patient at risk and the early detection of hypovolaemia, hypertension or hypotension, oliguria or urine abnormalities.
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Treatment options include renal dialysis, blood filtration and fluid and electrolyte restriction.
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DxT malaise (extreme) + a/n/v + confusion (± oliguria) ➜ AKF
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Chronic kidney disease and failure
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Chronic kidney disease (CKD) is diagnosed as:1
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an estimated or measured glomerular filtration rate (GFR)1 <60 mL/min/1.73m2 that is present for ≥3 months with or without evidence of kidney damage
evidence of kidney damage with or without decreased GFR that is present for ≥3 months as evidenced by the following, irrespective of the underlying cause:
– albuminuria
– haematuria after exclusion of urological causes
– structural abnormalities (e.g. on kidney imaging tests)
– pathological abnormalities (e.g. renal biopsy)
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Chronic kidney (or renal) failure (CKF) is defined as a severe reduction in nephron mass over an extended period of time, resulting in uraemia. It can present surreptitiously and be a real master of disguise in clinical practice. Asymptomatic CKF may be discovered on routine health screening, as a chance finding in hospitalised or hypertensive patients, or during follow-up of patients with known kidney disease.4 Symptoms only manifest when stage 4 is reached.
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Important clinical associations5
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The possibility of CKF should be monitored in patients with:
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diabetes mellitus
hypertension
established cardiovascular disease
severe gout
a history of urinary tract abnormality (e.g. vesicoureteric reflux, bladder outflow obstruction) or kidney failure
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The possibility of CKF should be considered and investigated in patients presenting with:
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unexplained poor health
hypertension
anaemia
pruritus
hyperparathyroidism
pericarditis
urinary tract symptoms or signs: proteinuria, haematuria, oedema, nocturia, loin pain, prostatic obstruction
neurological disturbances: confusion, coma, peripheral neuropathy, seizures
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Patients with CKF may present with features of acute kidney failure with the intervention of complicating factors such as:
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drug toxicity
infection
fluid imbalance
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Urgent treatment of the following conditions, which can lead to rapid kidney failure, is essential:
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progressive nephritis
systemic lupus erythematosus
vasculitides (see CHAPTER 32), for example, polyarteritis nodosa, Wegener granulomatosis
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Risk factors for chronic kidney disease5
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The clinical approach
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A hallmark of early-stage CKF is a non-specific history and examination, and the diagnosis is very difficult in the absence of a known past history of kidney disease. Inquire about drugs, UTIs, LUTs, systemic disease and family history. The diagnosis can be established only by kidney function tests. Symptoms from CKF are rare unless the creatinine clearance is less than 20% of normal and only become common when less than 10% of normal.
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In patients with chronic kidney disease, symptomatic uraemia may be precipitated by prerenal factors, such as fluid loss from vomiting or diarrhoea, infection, antibiotic therapy especially tetracyclines, or increasing hypertension.
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The symptoms and signs of CKF are summarised in FIGURE 31.1.
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The common early presenting symptoms are generally non-specific and referable to the GIT, presumably due to the formation of ammonia in the upper GIT. However, anaemia is the main cause of symptoms.
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Such symptoms, which indicate uraemia, include:
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malaise
anorexia, nausea, vomiting
tiredness/lethargy
nocturia
restless legs (esp. if eGFR <15)
pruritus
dyspnoea
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If a patient presents with these symptoms and has a sallow ‘lemon’ tinge appearance due to a combination of anaemia and brownish pigmentation, then CKF should be highly suspected.
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DxT fatigue + a/n/v + sallow skin ➜ CKF
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Physical examination6
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General inspection of the patient with CKF will usually reveal a sallow complexion with yellow-brown pigmentation in the skin, which is often dry and pruritic. The patient’s mental state should be noted. The respiratory and pulse rates are usually rapid because of anaemia and metabolic acidosis. Other findings may include bruising, uraemic fetor, reduced mental status, pericarditis and peripheral neuropathy. The abdomen should be carefully palpated, especially in the kidney areas. A rectal examination is indicated to detect prostatomegaly or other rectal or pelvic pathology. Ophthalmoscopic examination may show hypertensive or diabetic retinopathy. Urinalysis should test glucose, blood and protein. This involves a dipstick testing on the first morning specimen. Proteinuria should be confirmed with a 24-hour urine protein estimation or (preferably) an albumin creatinine ratio (ACR). Two out of these three positive results are required.
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Urine dipstick (poor sensitivity and specificity)1
24-hour urine protein
Albumin creatinine ratio
Microculture of urine
ESR and FBE (? anaemia)
Kidney function tests (most appropriate for the GP):
Plasma electrolytes:
Consider:
– magnesium, urate, glucose
– lipids
– prescribed drug level
– cardiac studies
– protein electrophoresis (? myeloma)
– ANA for lupus
– ANCA for vasculitis
Determination of underlying cause:
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The traditional test in identifying and monitoring CKD is the serum creatinine level.7 The normal range is about 40–120 μmol/L (0.04–0.12 mmol/L) but the laboratory will indicate their appropriate reference level. However, serum creatinine is an unreliable and insensitive marker of CKD. To improve detection and management guidelines laboratories now report on estimated glomerular filtration rate (eGFR) using the CKP-EPI (chronic kidney disease epidemiology collaboration) formula with every request for serum creatinine concentration, which is required to calculate to GFR.8
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Although common in older people, an eGFR <60 is associated with increased risks of adverse clinical outcomes, especially renal and cardiovascular.
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Guiding rule
eGFR = 140 − age
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Drug prescribing in CKD3,9
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Drugs that can damage the kidneys include:
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classic nephrotoxic drugs, e.g. gentamicin, vancomycin
NSAIDs, COX-2 inhibitors
ACE inhibitors and AIIR blockers (ARBs)
aminoglycosides
cephalosporins (various)
tetracyclines
lithium
colchicine
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Beware of the ‘triple whammy’
NSAIDs/COX-2 inhibitors
ACE inhibitors
diuretics
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These three agents individually or in combination are implicated in over 50% of cases of iatrogenic acute kidney failure.10
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Diuretics should be used with care.
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Drugs causing hyperkalaemia
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NSAIDs/COX-2
ACE inhibitors
ARBs
Aldactone
Moduretic
Trimethoprim
Digoxin
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Increased risk of adverse reaction
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Do not use statins and gemfibrozil together.
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Beta lactams: interstitial nephritis
LMW heparin: bleeding
Aspirin/NSAID: GIT bleeding
Omeprazole and related agents: interstitial nephritis
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Dangerous drug accumulation is presented in TABLE 31.3.
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The basic object is to slow progression of disease. The patient should be referred to an appropriate specialist as early as possible. The underlying disease and any abnormalities causing progressive kidney damage must be corrected where possible. The management of CKF is based on the team approach involving specialists and paramedical personnel, including a dietitian. Attention to lifestyle, especially nutrition and fluid control, is fundamental. The patient is usually faced with years of ongoing care so that an empathic support team based around the patient’s GP is very important to the patient, who will require considerable psychosocial support. The common problem of depression necessitates surveillance.
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Optimum treatment includes:
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regular review
good blood pressure control (the most effective way to slow progression)
keeping plasma phosphate levels in normal range
maintaining effective fluid and electrolyte balance
prompt treatment of intercurrent illness
judicious use of drugs
avoiding treatment errors, especially with drugs
– avoid potassium-sparing diuretics
– avoid nephrotoxic medications
– other drugs that may cause problems include digoxin, tetracyclines, gentamicin, NSAIDs, nitrofurantoin and ACE inhibitors (ACEIs)
rapid treatment of complications, especially salt and water depletion and acute urinary tract infection
diet: low protein, sodium and potassium
avoid toxins: nicotine, alcohol, caffeine
treating anaemia with human recombinant erythropoietin and iron (iron infusions)
attention to an advanced care plan
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Targets: goals of management1,5
The following are optimal targets for patients with chronic kidney disease:
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The main goal is to treat blood pressure, achieve resolution of proteinuria and reduce CVD risk. Recommend an advanced care plan.
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Blood pressure control
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No added salt diet (with care)
Drug control: none of the antihypertensive agents is specifically contraindicated but those eliminated mainly by the kidney (e.g. ACE inhibitors, atenolol, sotalol) should be given in lower dosage. ACE inhibitors should not be used in the presence of kidney artery stenosis; loop diuretics (e.g. frusemide) are effective in larger doses.2 The first-line agents are ACEIs or ARBs, which should not be used together. They should be ceased if the creatinine levels exceed 30% above baseline or if the serum K exceeds 6 mmol/L (despite dose reduction).4 The non-dihydropyridine calcium channel blockers are next choice. Beta blockers can be used. Diuretics have a vital role in the patient with diastolic heart failure (see CHAPTER 88).9 Control the blood pressure to the lowest tolerable level since a lower level is associated with a slower decline in GFR.
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Exclude chronic infection and iron deficiency.
Give iron for iron deficiency and also erythropoietin especially for Hb <100 g/L initiated in a renal unit.
Avoid transfusions where possible.
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Hyperphosphataemia control
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Hyperkalaemia treatment
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(A concern if >6.5 mmol/L.)
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Dialysis is indicated when all other methods fail. About two-thirds of patients receive haemodialysis and about 22% are on continuous ambulatory peritoneal dialysis and automated overnight peritoneal dialysis (nocturnal dialysis).
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The preferred access is via an AV fistula usually between the radial artery and a cephalic vein.
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Transplantation is the treatment of choice for kidney failure except where contraindicated, such as with active malignancy or tuberculosis and perhaps the elderly. However, a critical shortage of donors remains a problem. Rejection and infection are problems, occurring especially in the first 6 months. As a rule, never stop the immunosuppressants. With time there is a high rate of malignancy especially of skin, lymphoma × 5–10 and solid organs × 2–3 (except breast and prostate).