The definition of chronic kidney disease (CKD) is based on the presence of kidney damage (ie albuminuria) or decreased kidney function (ie glomerular filtration rate (GFR) <60 ml/minute per 1•73 m²) for three months or more, irrespective of clinical diagnosis.

When symptoms are severe they can be treated only by dialysis and transplantation (end-stage renal disease). Kidney failure is defined as a GFR of less than 15 ml/minute per 1•73 m², or the need for treatment with dialysis or transplantation.
Progression of CKD is defined as a decline in estimated glomerular filtration rate (eGFR) of > 5 ml/minute/1.73 m² within one year, or >10 ml/minute/1.73 m² within five yearsUntil recently, the emphasis has been on patients needing dialysis or transplantation. It is now realised that less severe CKD is quite common, and monitoring in primary care will enable the minority of patients who go on to develop a more severe form to be detected at any earlier stageThis is important because the earlier the intervention, the greater the impact.

Epidemiology
• A large primary care study (practice population 162,113) suggests an age standardised prevalence of stage 3-5 chronic kidney disease (CKD) of 8.5% (10.6% in females and 5.8% in males).[

Aetiology
In developed countries, CKD is often associated with old age, diabetes, hypertension, obesity and cardiovascular disease (CVD).
• Arteriopathic renal disease.
• Hypertension.
• Glomerulonephritis.
• Diabetes.
• Infective, obstructive and reflux nephropathies.
• Family history of stage 5 CKD or hereditary kidney disease – eg, polycystic kidneys.
• Hypercalcaemia.
• Multisystem diseases with potential kidney involvement – eg systemic lupus erythematosus (SLE).
• Neoplasms.
• Myeloma.

Risk factors
Factors other than the underlying disease process that may cause progressive renal injury include the following:
• Acute insults from nephrotoxins or decreased perfusion.
• Proteinuria.
• Increased renal ammonia formation with interstitial injury.
• Hyperlipidaemia.
• Hyperphosphataemia with calcium phosphate deposition.

Classification of chronic kidney disease

Kidney function should be assessed by eGFR and CKD is classified on this basis:
• Stage 1: normal; eGFR >90 ml/minute/1.73 m2 with other evidence of chronic kidney damage (see below).
• Stage 2: mild impairment; eGFR 60-89 ml/minute/1.73 m2 with other evidence of chronic kidney damage.
• Stage 3a: moderate impairment; eGFR 45-59 ml/minute/1.73 m2.
• Stage 3b: moderate impairment; eGFR 30-44 ml/minute/1.73 m2.
• Stage 4: severe impairment; eGFR 15-29 ml/minute/1.73 m2.
• Stage 5: established renal failure (ERF); eGFR less than 15 ml/minute/1.73 m2 or on dialysis.
Use the suffix (p) to denote the presence of proteinuria when staging CKD.

NB: patients with a GFR of >60 ml/minute/1.73 m2 without evidence of chronic kidney damage should NOT be considered to have CKD and do not necessarily need further investigation.

The other evidence of chronic kidney damage may be one of the following:
• Persistent microalbuminuria.
• Persistent proteinuria.
• Persistent haematuria (after exclusion of other causes – eg, urological disease).
• Structural abnormalities of the kidneys, demonstrated on ultrasound scanning or other radiological tests – eg, polycystic kidney disease, reflux nephropathy.
• Biopsy-proven chronic glomerulonephritis.

Presentation
Symptoms
• it usually presents with nonspecific symptoms caused by renal failure, complications – eg, anaemia in chronic renal failure (CRF), and the underlying disease.
• It may be discovered by chance following a routine blood or urine test.
• Specific symptoms usually develop only in severe renal failure, and include anorexia, nausea, vomiting, fatigue, weakness, pruritus, lethargy, peripheral oedema, dyspnoea, insomnia, muscle cramps, pulmonary oedema, nocturia, polyuria and headache.
• Sexual dysfunction is common.
• Hiccups, pericarditis, coma and seizures are only seen in very severe renal failure.

Signs
• The physical examination is often not very helpful but may reveal findings characteristic of the underlying cause (eg SLE, severe arteriosclerosis, hypertension) or complications of CRF (eg, anaemia, bleeding diathesis, pericarditis).
• Signs of CKD include increased skin pigmentation or excoriation, pallor, hypertension, postural hypotension, peripheral oedema, left ventricular hypertrophy, peripheral vascular disease, pleural effusions, peripheral neuropathy and restless legs syndrome.

Screening
Patients who are at increased risk of developing CKD should be offered screening tests to detect CKD, which should include assessment of the eGFR as well asurinalysis. Offer people testing for CKD if they have any of the following risk factors:
• Diabetes.
• Hypertension.
• CVD (ischaemic heart disease, chronic heart failure,peripheral vascular disease and cerebrovascular disease).
• Structural renal tract disease, renal calculi or prostatic hypertrophy.
• Multisystem diseases with potential kidney involvement – for example, SLE.
• Family history of stage 5 CKD or hereditary kidney disease.
• Opportunistic detection of haematuria or proteinuria.

Differential diagnosis
• Acute kidney injury (acute renal failure):
• Making the distinction between AKI and CRF can be very difficult. A history of chronic symptoms of fatigue, weight loss, anorexia, nocturia, and pruritus all suggest CKD.
• The history and examination will provide clues, but renal ultrasound will provide the most important information. Renal abnormalities on ultrasound, such as small kidneys in chronic glomerulonephritis or large cystic kidneys in adult polycystic kidney disease, will almost always be present in patients with CKD.
• Acute on chronic renal failure: may have features indicating CKD but also features suggesting a cause of an acute deterioration of renal function – eg, infection.
Investigations
Investigations are focused on assessment of renal function and therefore stage of CKD, identification of the underlying cause and assessment of complications of CKD.

• Assessment of renal function:
• Serum urea is a poor marker of renal function, because it varies significantly with hydration and diet, is not produced constantly and is reabsorbed by the kidney.
• Serum creatinine also has significant limitations. The level can remain within the normal range despite the loss of over 50% of renal function.
• A gold-standard measurement is an isotopic GFR, but this is expensive and not widely available.
• For most purposes in primary care, the best assessment or screening tool is the eGFR. – Most laboratories now provide an eGFR when requesting serum creatinine.

• Biochemistry:
• Plasma glucose: to detect undiagnosed diabetes or assess control of diabetes.
• Serum sodium: usually normal, but may be low.
• Serum potassium: raised.
• Serum bicarbonate: low.
• Serum albumin: hypoalbuminaemia in patients who are nephrotic and/or malnourished (low levels at the start of dialysis are associated with a poor prognosis).
• Serum calcium: may be normal, low or high.
• Serum phosphate: usually high.
• Serum alkaline phosphatase: raised when bone disease develops.
• Serum parathyroid hormone: rises progressively with declining renal function.
• Serum cholesterol and triglycerides: dyslipidaemia is common.

• Haematology:
• Normochromic normocytic anaemia; haemoglobin falls with progressive renal failure.
• White cells and platelets are usually normal.

• Serology:
• Autoantibodies, particularly antinuclear antibodies, classical antineutrophil cytoplasmic antibodies (c-ANCA), protoplasmic-staining antineutrophil cytoplasmic antibodies (p-ANCA), antiglomerular basement membrane (anti-GBM) antibodies (very suggestive of underlying Goodpasture’s syndrome) and serum complement.
• Hepatitis serology: ensure not infected and vaccinate against hepatitis B.
• HIV serology: performed before dialysis or transplantation.

• Urine:
• Urinalysis: dipstick proteinuria may suggest glomerular or tubulointerstitial disease. Urine sediment with red blood cells and red blood cell casts suggests proliferative glomerulonephritis.
• Pyuria and/or white cell casts suggest interstitial nephritis (especially if eosinophils are present in the urine) or urinary tract infection (UTI).
• Spot urine collection for total protein:creatinine ratio allows reliable estimation of total 24-hour urinary protein excretion. The degree of proteinuria correlates with the rate of progression of the underlying kidney disease and is the most reliable prognostic factor in CKD.
• 24-hour urine collection for total protein and creatinine clearance. To detect and identify proteinuria, use urine albumin:creatinine ratio (ACR) in preference, as it has greater sensitivity than protein:creatinine ratio (PCR) for low levels of proteinuria. For quantification and monitoring of proteinuria, PCR can be used as an alternative. ACR is the recommended method for people with diabetes.
• Patients in whom initial urinalysis reveals microscopic haematuria should have a urine culture performed to exclude a UTI. If a UTI is excluded, two further tests should be performed to confirm the presence of persistent microscopic haematuria.[6]
• Patients over 40 years of age with persistent non-visible/microscopic haematuria in the absence of significant proteinuria or a reduced GFR should be referred to a urology department for further investigation.
• Serum and urine protein electrophoresis: to screen for a monoclonal protein possibly representing multiple myeloma.

• ECG and echocardiography: to detect left ventricular hypertrophy and ischaemia, and to assess cardiac function.

• Imaging of the renal tract:
• Plain abdominal X-ray: may show radio-opaque stones or nephrocalcinosis.
• Intravenous (IV) pyelogram: not often used because of potential for contrast nephropathy.

• Renal ultrasound:
• Small echogenic kidneys are seen in advanced renal failure.
• Kidneys are usually initially large and then become normal in size in advanced diabetic nephropathy.
• Structural abnormalities may be seen – eg, polycystic kidneys.
• It is also used to screen for hydronephrosis caused by urinary tract obstruction, or involvement of the retroperitoneum with fibrosis, tumour or diffuse adenopathy.
• Retrograde pyelogram: may be indicated if there is clinical suspicion of obstruction despite a negative ultrasound study finding.
• Renal radionuclide scan:
• Useful to screen for renal artery stenosis when performed with captopril administration but is unreliable for GFR of less than 30 ml/minute.
• Also quantifies differential renal contribution to total GFR.
• CT scan: to define renal masses and cysts, seen on ultrasound, better; this is the most sensitive test for identifying renal stones.
• MRI:
• For patients who require a CT scan but who cannot receive IV contrast.
• Like CT scan and renal venography, it is reliable in the diagnosis of renal vein thrombosis.
• Magnetic resonance angiography is also useful for diagnosis of renal artery stenosis, although renal arteriography remains the investigation of choice.
• Micturating cystourethrogram: for diagnosis of vesicoureteric reflux.
• Renal biopsy.

Criteria for referral to specialist services
Take into account the individual’s wishes and comorbidities when considering referral.
• People with CKD in the following groups should normally be referred for specialist assessment:
• Stage 4 and 5 CKD (with or without diabetes).
• Higher levels of proteinuria (ACR ?70 mg/mmol) unless known to be due to diabetes and already appropriately treated.
• Proteinuria (ACR ?30 mg/mmol) together with haematuria.
• Rapidly declining eGFR (>5 ml/minute/1.73 m2 in one year, or >10 ml/minute/1.73 m2 within five years).
• Hypertension that remains poorly controlled despite the use of at least four antihypertensive drugs at therapeutic doses.
• People with, or suspected of having, rare or genetic causes of CKD.
• Suspected renal artery stenosis.
• People with CKD and renal outflow obstruction should normally be referred to urological services, unless urgent medical intervention is required.
• Consider discussing management issues with a specialist in cases where it may not be necessary for the person with CKD to be seen by the specialist.
• Once a referral has been made and a plan jointly agreed, consider routine follow-up at the person’s GP surgery rather than in a specialist clinic and specify criteria for future referral or re-referral.

Dr G Mohan.

Management continued in the next post…