Chronic Kidney Disease

Reduction in kidney function or structural damage or both, present for more than 3 months with associated health implications

Aetiology

• Diabetes and high blood pressure are the biggest causes globally - account for almost 3/4 of cases

• Polycystic kidney disease

• Glomerular disease

• Current or previous history of Acute Kidney Injury (AKI)

• Potentially nephrotoxic drugs, e.g.: aminoglycosides, ACEi, ARBs, bisphonates, calcineurin inhibitors, diuretics, lithlium, mesalazine, NSAIDs

• Obstructive uropathy
• Calculi - along entire renal tract
• Prostate - BPH, malignancy, prostatitis, abscess
• Bladder - malignancy, chronic cystitis with bladder thickening and 'inflow obstruction'
• Malignancy - entire urethelial tract
• Strictures/stenosis - ureter or urethra, due to infections or prior injury
• Extrinsic compression - lymph nodes, colonic or gynae masses, RPF

• Multisystem diseases with renal involvement - SLE, vasculitis (GPA, MPA, EGPA), myeloma

• Family history of CKD or a hereditary kidney disease such as ADPKD, Alport syndrome, familial glomerulonephritis

• Cardiovascular disease

• Obesity with metabolic syndrome

Pathophysiology

• Transplant - anyone with a history of kidney transplantation

• Histological abnormalities detected on kidney biopsy

• Electrolyte abnormalities due to tubular disorders

• ACR (urinary albumin: creatinine ratio) greater than 3 mg/mmol

• Sediment abnomalities in the urine (haematuria/casts)

• Structural abnormalities detected by imaging

• Hereditory conditions identified on genetic testing

• AND/OR a persistent reduction in renal failure shown by a serum estimated by eGFR of less than 60 mL/min/1.73 m2

Stages of CKD

'Accelerated progression' of CKD

• Defined as a persistent decrease in eGFR by 25% or more AND a change in CKD category within 12 months

• OR can also be defined as a persistent decrease in eGFR of 15 mL/min/1.73 m2 within 12 months

Clinical presentation

• Usually asymptomatic

• Symptoms can include: pruritus, loss of appetite, nausea, oedema, muscle cramps, hypertension

Investigations

• U+Es - eGFR

• Urinalysis - proteinuria, haematuria

• Renal ultrasound can be used to investigate patients with accelerated CKD, haematuria, family history of polycystic kidney disease or evidence of obstruction

Management

• Treat the underlying condition:
• Diabetes - getting HbA1c to target
• Hypertension - target BP, use ACEi/ARBs as appropriate
• Aim for 140/90 in people with CDK
• In people with CKD and diabetes, and also in people with ACR of 70 mg/mol or more, aim for 130/80
• Autoimmune/multisystemic conditions - immunosuppression where appropriate
• Obstruction - relieve obstruction
• Nephrotoxins - stop drugs

• Prevention/management of complications as below

Complications

Cardiovascular disease

• People with advanced CKD are more likely to die prematurely than progress to ESRD - largely due to increased cardiovascular risk

• Studies show that people with CDK stage 3 or worse renal function had a 40% higher risk of developing CVD compared with people with CKD stage 1 or 2

• An inverse linear relationship has been found between GFR and stroke risk

• 25 mg/mmol increase in urinary ACR was associated with 10% increased risk of stroke

• Patients will have many of the traditional risk factors (e.g. age, male, hypertension, smoking, diabetes) as well as uraemia-related risk factors (e.g. oxidative stress, endothelial dysfunction, coagulation disorders, sympathetic activation)

• General - smoking cessation, weight loss, aerobic exercise, limiting salt intake

• Control hypertension

• Other prophylaxis - lipid-loweing therapy, consider aspirin for secondary prevention (weigh against risk of bleeding complications)

Acute kidney injury

• May initiate or accelerate CKD progression

Hypertension and dyslipidaemia

• Hypertension may contribute to the risk of accelerated CKD progression

• Secondary causes of dyslipidaemia may include renal causes such as nephrotic syndrome

• Offer atorvastatin for the primary or secondary prevention of CDK to people with CKD

• Increase the dose if a greater than 40% reduction in non-HDL cholesterol is not achieved and eGFR is 30 ml/min/1.73 m2 or more

• Agree the use of higher doses with a renal specialised if eGFR is less than 30 ml/min/1.73 m2

Renal anaemia

• Haemoglobin less than 11 g/dL

• This may present with tiredness, SOB, lethargy and palpatations

• It may be due to reduced production of erythropoeitin by the kidney, reduced RBC survival, and iron deficiency

• Less common with eGFRs > 45 (CKD 3a and above) but diabetics more at risk at lower eGFRs

• Target Hb 100-120g/L
• Lower levels of Hb are acceptable if the Hb fails to rise, despite adequate iron replacement and epoetin therapy

• Exclude other causes of anamia, B12 and folate deficiency

• Check ferritin and iron stores, aiming for ferritin > 100 and TSats > 20%

• Consider MDS/other haematological causes

• Iron therapy - oral iron, if oral iron fails to replete store or is not tolerated refer for IV injected iron (ferinject, venoder)

• If Hb ≲100-110 g/dl (despite no iron/haematinic deficiencies), consider prescribing an ESA

Renal mineral and bone disorder

• May present with bone pain, increased bone fragility, or extra skeletal calcification (e.g. in the skin or blood vessels)

• It is caused by disturbed vitamin D, calcium, PTH, and phosphate metabolism due to impaired regulation of intestinal absorption, renal tubular excretion, and vitamin D activation

• This subsequently causes abnormalities in bone turnover and mineralisation with vitamin D deficiency, raised serum phosphate, low serum calcium, and secondary or tertiary hyperparathyroidism seen in progressive CKD

• Early dietary advice
• Phopshate restriction
• Consider salt, potassium and fluid restriction

• Manage metabolic acidosis with oral sodium bicarbonate
• Can result in a salt load - may exacerabate salt and water retention, and hypertension, so may need to be offset by stricter salt restriction or the addition of a diuretic

• Alfacalcidol ('active' vitamin D)

• Phosphate binders - non-calcium based first line (lanthanum/sevelamer)

Other complications

• Peripheral neuropathy and myopathy - may present with paraethesia, sleep disturbance, and restless legs syndrome

• Malnutrition - may be seen in ESRD, due to poor dietary intake and hypoalbuminaemia

• Malignancy - people with ESRD may have an excess cancer risk, particularly affecting the renal tract and thyroid gland
• Risk factors may include exposure to immunosuppresive agents and immune dysregulation caused by chronic uraemia

• End-stage renal disease (ESRD) - people with CKD stages 405 may need renal replacement therapy (dialysis or kidney transplant)

• All-cause mortality increases with progressive CDK