Chapter 31: Chronic kidney failure

Chronic kidney failure

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.

Acute kidney failure

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.

AKF is usually classified into:

• prerenal (e.g. acute circulatory failure → kidney hypoperfusion)

• postrenal (e.g. obstruction)

• kidney (intrinsic) (e.g. acute glomerulonephritis)

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.

Treatment options include renal dialysis, blood filtration and fluid and electrolyte restriction.

Chronic kidney disease and failure

Chronic kidney disease (CKD) is diagnosed as:¹

• 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

  • or

• 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)

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.

Important clinical associations⁵

The possibility of CKF should be monitored in patients with:

• diabetes mellitus

• hypertension

• established cardiovascular disease

• severe gout

• a history of urinary tract abnormality (e.g. vesicoureteric reflux, bladder outflow obstruction) or kidney failure

The possibility of CKF should be considered and investigated in patients presenting with:

• 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

Patients with CKF may present with features of acute kidney failure with the intervention of complicating factors such as:

• drug toxicity

• infection

• fluid imbalance

Urgent treatment of the following conditions, which can lead to rapid kidney failure, is essential:

• progressive nephritis

• systemic lupus erythematosus

• vasculitides (see CHAPTER 32), for example, polyarteritis nodosa, Wegener granulomatosis

The clinical approach

History

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.

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.

Symptoms and signs

The symptoms and signs of CKF are summarised in FIGURE 31.1.

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.

Such symptoms, which indicate uraemia, include:

• malaise

• anorexia, nausea, vomiting

• tiredness/lethargy

• nocturia

• restless legs (esp. if eGFR <15)

• pruritus

• dyspnoea

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.

Physical examination⁶

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.

ACR guidelines

• Normoalbuminuria

•  Men:    <2.5 mg/mmol

•  Women:   <3.5 mg/mmol

• Microalbuminuria

•  Men:    2.5–25 mg/mmol

•  Women:   3.5–35 mg/mmol

• Macroalbuminuria (if persistent, indicates moderate to severe CKF)

•  Men:    >25 mg/mmol

•  Women:   >35 mg/mmol

Investigations

• 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 urea

  • – plasma creatinine

  • – creatinine clearance (more precise)

  • – eGFR (the new standard)

• Plasma electrolytes:

  • – sodium, potassium, chloride, bicarbonate

  • – calcium and phosphate

• Consider:

  • – magnesium, urate, glucose

  • – lipids

  • – prescribed drug level

  • – cardiac studies

  • – protein electrophoresis (? myeloma)

  • – ANA for lupus

  • – ANCA for vasculitis

• Determination of underlying cause:

  • – imaging of urinary tract—ultrasound

  • – immunological tests

  • – kidney biopsy

• Biochemical changes—elevation of:

  • – potassium

  • – phosphate

  • – creatinine and urea

  • – urinary protein

  • – hydrogen ions → acidosis; anion group

• Consider renal biopsy

Monitoring CKD

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

Although common in older people, an eGFR <60 is associated with increased risks of adverse clinical outcomes, especially renal and cardiovascular.

Drug prescribing in CKD^3,9

Drugs that can damage the kidneys include:

• classic nephrotoxic drugs, e.g. gentamicin, vancomycin

• NSAIDs, COX-2 inhibitors

• ACE inhibitors and AIIR blockers (ARBs)

• aminoglycosides

• cephalosporins (various)

• tetracyclines

• lithium

• colchicine

These three agents individually or in combination are implicated in over 50% of cases of iatrogenic acute kidney failure.¹⁰

Diuretics should be used with care.

Drugs causing hyperkalaemia

• NSAIDs/COX-2

• ACE inhibitors

• ARBs

• Aldactone

• Moduretic

• Trimethoprim

• Digoxin

Increased risk of adverse reaction

• Allopurinol:

  • – vasculitis

  • – liver dysfunction

• Statins:

  • – liver dysfunction

  • – myopathy

  • – rhabdomyolysis

• Gemfibrozil: rhabdomyolysis

Do not use statins and gemfibrozil together.

• Beta lactams: interstitial nephritis

• LMW heparin: bleeding

• Aspirin/NSAID: GIT bleeding

• Omeprazole and related agents: interstitial nephritis

Dangerous drug accumulation is presented in TABLE 31.3.

Management

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.

Optimum treatment includes:

• 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

The main goal is to treat blood pressure, achieve resolution of proteinuria and reduce CVD risk. Recommend an advanced care plan.

Blood pressure control

• 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.

Anaemia

• 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.

Hyperphosphataemia control

• Balanced nutrition to reduce dietary phosphate

• Protein restriction

• Calcium carbonate tablets (to bind phosphate)

Hyperkalaemia treatment

(A concern if >6.5 mmol/L.)

• Low potassium diet

• Cease ACEI/ARB/spironolactone (if applicable)

• Nebulised salbutamol

• IV insulin and dextrose

• IV calcium gluconate

• Oral resonium A

• Then dialysis

Dialysis

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).

The preferred access is via an AV fistula usually between the radial artery and a cephalic vein.

Transplantation

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).

The incidence of CKF in children is about two per million of the total population per year. The commonest causes include chronic glomerulonephritis, obstructive nephropathy and reflux nephropathy. Identification of structural kidney abnormalities by obstetric ultrasound and early investigation of urinary tract infections may decrease the incidence of CKF. Dialysis and transplantation are normally considered for children over 2 years of age with end-stage CKF. For children under 2 years there are complex ethical, psychological and technical problems.⁷ Nevertheless the prognosis for such treatment is poor.

Chronic kidney failure in elderly

An eGFR <60 is common but still predictive of significant increased risk of adverse clinical outcomes. Do not regard as physiological. Individualise management.

• (Glomerular) haematuria

• eGFR <30 (stage 4 or 5 CKD)

• Rapidly declining kidney function

• Significant proteinuria >1 g/24 hours or ACR >30

• Glomerular haematuria with macroalbuminuria

• Kidney impairment + hypertension (poor control)

• Diabetes with kidney impairment: eGFR <60 or albuminuria/proteinuria

Any person with rapidly declining eGFR and/or signs of acute nephritis (oliguria, haematuria, oedema and acute hypertension) should be regarded as a medical emergency.

Hand-out sheets from Murtagh’s Patient Education 7th edition:

• Kidney disease

Kidney Health Australia, <www.kidney.org.au>

Renal Drug Reference Guide, <www.renaldrugreference.com.au>

ATSIP, <www.naccho.org.au>

Australian absolute cardiovascular disease risk calculator, <www.cvdcheck.org.au>

NICE guidelines, chronic kidney disease, <www.nice.org.uk>