Upper Urinary Tract Emergencies

Ragada El-Damanawi and Andrew Fry¹ / Ben Pullar and Samih Al-Hayek²^,³

Definition and staging

Acute kidney injury (AKI) is defined as a rapid decline in glomerular filtration rate that occurs over hours to days. It results in the accumulation of nitrogenous waste products including urea and creatinine, plus reduced urine output.

The 2012 KDIGO (Kidney Disease Improving Global Outcomes) definition is one of the most recognised (Box 2.1) and classifies AKI into three stages based on severity (Table 2.1).

Box 2.1 KDIGO AKI definition.

AKI is defined as any of the following (not graded):

•Increase in serum creatinine by ≥0.3mg/dL (≥26.5µmol/L) within 48 hours.

•Increase in serum creatinine to ≥1.5 × baseline, which is known or presumed to have occurred within the prior 7 days

•Urine volume <0.5ml/kg/h for 6 hours.

Epidemiology

It is now recognised that even a modest acute reduction in kidney function is associated with an increased risk of in-hospital mortality. There is also an increased risk of developing chronic kidney disease (CKD) and cardiovascular disease in the longer term. About 5-10% of general hospital admissions and 50% of all Intensive therapy unit (ITU) admissions have AKI. In those with AKI requiring renal replacement therapy, the overall mortality remains high at >50%.

Causes and classification

The causes of AKI can be classified into pre-renal, intrinsic renal and post-renal.

Pre-renal AKI

Pre-renal AKI is caused by renal hypoperfusion. It is related to loss of blood volume and/or blood pressure (BP). There is no injury to the renal parenchyma, and restoration of renal blood flow restores glomerular filtration, reversing AKI (Figure 2.1).

Table 2.1 Stages of AKI.

Stage	Serum creatinine	Urine output
1	1.5–1.9 × baseline OR ≥0.3mg/dL (≥26.5µmol/L) increase	<0.5ml/kg/h for 6–12h
2	2.0–2.9 × baseline	<0.5ml/kg/h for ≥12h
3	3.0 × baseline OR Increase in serum creatinine to ≥4.0mg/dL (≥353.6µmol/L) OR Initiation of renal replacement therapy OR Decrease in eGFR to <35ml/min per 1.73m² (in those <18 years old)	<0.3ml/kg/h for ≥24h OR Anuria for ≥12h

Figure 2.1 Causes of pre-renal acute kidney injury.

Intrinsic AKI

Intrinsic renal AKI refers to conditions that affect the glomeruli, tubules, interstitium or the vasculature of the kidneys. The commonest causes include sepsis, nephrotoxins (Box 2.2) and ischaemia (Figure 2.2).

Acute tubular necrosis

Just under half (about 45%) of all cases of AKI are due to acute tubular necrosis (ATN). The two major causes of ATN are ischaemia and nephrotoxins. ATN represents the endpoint of pre-renal AKI. In ATN, a prolonged insult leads to parenchymal damage, and the resulting AKI does not promptly resolve on restoration of glomerular filtration.

Contrast-induced AKI (CI-AKI)

This is defined as AKI within 72 hours of receiving iodinated contrast. It occurs in 1–2% of adults with normal renal function who receive contrast and it usually resolves within 5 days, although some individuals are at increased risk (Table 2.2). There are two main mechanisms: 1) the contrast is vasoactive causing significant afferent arteriolar vasoconstriction and therefore a reduction in blood flow to the glomerulus; 2) it is directly toxic to the tubules.

Box 2.2 Nephrotoxic medications listed by mechanism of nephrotoxicity.

1.Pre-renal (low BP or volume depletion) Antihypertensives, diuretics

2.Renal vasoconstriction NSAIDs, ACEIs, ARBs, radio-contrast agents, cyclosporin, tacrolimus

3.Glomerulonephritis D-penicillamine, hydralazine, propylthiouracil

4.Acute tubular necrosis Amphotericin, aminoglycosides, tenofovir, cidofovir, cisplatin, heavy metals

5.Acute interstitial nephritis Antibiotics (penicillin, rifampicin, cephalosporin, ciprofloxacin),NSAIDs, proton pump inhibitors, diuretics

6.Obstruction Crystal formation: aciclovir, methotrexate, ethylene glycol

Urinary retention: anticholinergics, tricyclic antidepressants

Figure 2.2 Intrinsic renal causes of acute kidney injury.

In high-risk patients it should be considered whether a contrast-enhanced scan is necessary or alternative imaging would be sufficient. Table 2.3 outlines other measures to prevent CI-AKI. The use of magnetic resonance imaging (MRI) with gadolinium contrast should also be avoided in those with a low estimated glomerular filtration rate (eGFR) (<30ml/min) due to its association with nephrogenic systemic fibrosis (NSF) – a rare condition where there is severe fibrosis of the skin and deeper structures (with significant morbidity and mortality).

Table 2.4 outlines the distinguishing features of pre-renal and intrinsic renal AKI (including established acute tubular necrosis [ATN] as intrinsic). If in doubt, or if AKI persists, a renal biopsy is often diagnostic and helpful in excluding other treatable causes.

Table 2.2 Risk factors for CI-AKI.

CKD with eGFR <60ml/min

Age >75 years

Diabetes

Heart failure

Hypovolaemia

Concurrent nephrotoxins: NSAIDs, aminoglycosides

Contrast: large volumes and intra-arterial administration

CI-AKI: contrast-induced acute kidney injury; CKD: chronic kidney disease; eGFR: estimated glomerular filtration rate; NSAID: non-steroidal anti-inflammatory drug.

Table 2.3 Measures to prevent CI-AKI.

Consider alternative imaging

Stop nephrotoxins (NSAIDs, ACEI, ARB)

Pre-hydration with normal saline

Reduce volume of contrast

Low or iso-osmolar contrast

Measure renal function 24–48h post-contrast

ACEI: angiotensin converting enzyme inhibitor; ARB: angiotensin receptor II blocker; CI-AKI: contrast-induced acute kidney injury; NSAID: non-steroidal anti-inflammatory drug.

Table 2.4 Distinguishing features of pre-renal and intrinsic renal AKI.

	Pre-renal AKI	Intrinsic renal AKI
BP	Hypotension common	Normal or elevated
Volume status (jugular venous pressure, postural BP)	Evidence of hypovolaemia	Normal
Urine dipstick	Unremarkable	Blood and protein (more in glomerulonephritis than ATN and acute interstitial nephritis)
Urine microscopy	Unremarkable	Red cell casts pathognomonic of acute glomerulonephritis
Response to effective fluid challenge	Improvement in urine output	No effect

Post-renal AKI

Post-renal AKI is caused by obstruction of the urinary tract and may be categorised as either supra-vesical or infra-vesical, depending upon the level of obstruction in relation to the bladder (Figure 2.3).

Figure 2.3 Post-renal causes of acute kidney injury.

Presentation

Table 2.5 outlines the main clinical presentation of AKI. It is most frequently encountered in the setting of another acute illness.

A careful history is often key to determining the underlying cause of AKI. Ask about recent illnesses, changes in medication (including over-the-counter drugs), previous renal history (is this new AKI or known CKD?).

Table 2.5 Clinical features of AKI.

Non-specifically unwell

Reduced urine output

Disordered volume status:

Fluid overloaded

Dehydration

Hyperkalaemia: cardiac arrest or arrhythmias

Uraemia:

Skin: dry skin, pruritis, uraemic frosting (last sign)

GI: nausea, anorexia, weight loss

Nervous system: involuntary movement (restless legs), peripheral and autonomic neuropathy, psychological disturbances, encephalopathy

Haematological: anaemia, bleeding

Sexual dysfunction and reduced fertility

GI: gastrointestinal.

Investigation

A simple urine dipstick is very important. Pre-renal and post-renal causes generally produce an unremarkable urine dipstick result. An ‘active’ urine dip (blood and protein) could indicate an intrinsic cause such as a glomerulonephritis.

Look for and treat life-threatening complications first such as abnormalities identified on electrocardiography (ECG) or hyperkalaemia identified on urea and electrolytes (U&E) and then consider other blood tests (Table 2.6). Imaging in the form of a basic urinary tract ultrasound scan can help to rule out obstruction. Finally, once pre- and post-renal causes have been excluded, a renal biopsy is helpful in differentiating the varying causes of intrinsic renal disease, especially in the presence of an ‘active’ urine dip. It is vital to determine the underlying cause of AKI as this directs the treatment and offers the best chance of reversal.

Table 2.6 Key investigations in AKI.

Urine dip

Evidence of infection, or intrinsic renal disease

Blood tests

FBC:

•Anaemia: haemolysis or active bleed

•WCC: raised in sepsis

•ESR: raised in SLE, myeloma

U&E:

•Increased plasma urea: creatinine ratio more likely pre-renal cause

•Increased plasma creatinine: urea ratio makes obstruction and intrinsic disease more likely

•Hyperkalaemia: associated with life-threatening arrhythmias

LFT:

•Abnormal in hepatorenal syndrome

Calcium:

•Hypercalcaemia is seen with malignancy and myeloma

Creatine kinase:

•Rhabdomyolysis: consider in patients with a history of burns, crush injuries or lying for a prolonged time

Immunology screen:

•ANA: positive in autoimmune disease

•ANCA: small vessel vasculitis:

•Cytoplasmic ANCA – PR3 antigen – granulomatosis with polyangiitis

•Perinuclear ANCA – MPO antigen – microscopic polyangiitis and Churg Strauss syndrome*

•Anti-GBM: Goodpasture’s disease** – an important cause of pulmonary–renal syndrome

•Myeloma screen: serum free light chains, protein and urine electrophoresis

Imaging:

•Ultrasound renal tract (urgent)

•Exclude obstruction

•Ensure presence of 2 kidneys and assess size: small scarred kidneys suggest CKD

Renal biopsy:

•Mainly to identify intrinsic renal disease

*Churg Strauss syndrome, also known as eosinophilic granulomatosis with polyangiitis, is a disorder characterised by inflammation of the small to medium sized blood vessels (vasculitis). Its features include adult-onset asthma, peripheral blood eosinophilia and vasculitis affecting the lungs, heart, kidney, nerves and skin.
**Goodpasture’s disease is an autoimmune condition where antiglomerular basement membrane (anti-GBM) antibodies attack the basement membrane structure within the kidneys and alveoli causing an acute glomerulonephritis and lung haemorrhage. It makes up an important cause of pulmonary–renal syndrome.

ANA: antinucleic acid; ANCA: antineutrophil cytoplasmic antibody; CKD: chronic kidney disease; ESR: erythrocyte sedimentation rate; FBC: full blood count; LFT: liver function test; SLE: systemic lupus erythematosus; U&E: urea and electrolytes; WCC: white cell count.

Management

In pre-renal AKI it is important to achieve and maintain haemodynamic stability. Fluid resuscitation is key and dependent on accurate clinical assessment of fluid balance. Crystalloids should be given, except in the case of bleeding, where blood and blood products are indicated (Table 2.7).

The management of AKI can be divided into general supportive measures (Table 2.8) and renal replacement therapy. The indications for renal replacement therapy are outlined in Table 2.9. In particular, obstruction should always be excluded, especially in oligouric and anuric patients with no other obvious cause (e.g. no overt haemodynamic disturbance).

Table 2.7 Fluid resuscitation in pre-renal AKI.

Assess fluid balance:

•Pulse: tachycardia

•BP: hypertension or hypotension

•Jugular venous pressure

•Evidence of pulmonary oedema

•Urine output

Management:

•Give 500ml crystalloid fluid bolus (reduce to 250ml in those with cardiac failure or >75 years old)

•Reassess fluid balance

•If required give further 500ml of crystalloid (250ml in those with cardiac failure or >75 years old)

•Continue maintenance fluids until euvolaemic

•If the patient remains oligoanuric despite adequate filling, defined as having volume unresponsive AKI, they require input from a nephrologist

BP: blood pressure.

Table 2.8 General supportive management.

Investigate and treat the underlying cause

Achieve normal haemodynamic status – fluids, vasopressor or inotropic support

Adjust dose and frequency of medications appropriately for level of renal function – renal drug handbook or pharmacist may help

Avoid nephrotoxins – ACEI, NSAID, aminoglycosides (Box 2.2)

Avoid hyperglycaemia

Nutritional support

ACEI: angiotensin converting enzyme inhibitor; NSAID: non-steroidal anti-inflammatory drug.

Table 2.9 Indications for renal replacement therapy.

Resistant hyperkalaemia

Acid–base disturbances – metabolic acidosis

Volume overload/pulmonary oedema refractory to diuretics

Severe uraemia causing encephalopathy, pericarditis, coagulopathy

The indications for referral to a nephrologist are outlined in Table 2.10. If the cause of AKI is clear, e.g. obstruction or dehydration, and responds to management with rapid improvement, nephrology input is generally not required. Patients who are haemodynamically unstable, or those with multi-organ failure are better managed in an intensive care setting.

It is important to acknowledge that renal replacement therapy may not be appropriate for all patients with the indications above, for example, patients with metastatic cancer with a poor prognosis.

Table 2.10 Indications for referral to a nephrologist.

Patients meeting the criteria for renal replacement therapy

Diagnosis requires specialist input, e.g. vasculitis, GN or TIN

Cause of AKI unclear

Inadequate response to initial treatment

Renal transplant patient

Stage 3 AKI

Pre-existing advanced CKD (CKD 4 and 5)

AKI: acute kidney injury; CKD: chronic kidney disease; GN: glomerulonephritis; TIN: tubulointerstitial nephritis.

Hyperkalaemia

Hyperkalaemia can result in life-threatening arrhythmias and cardiac arrest. It is therefore important to monitor the patient for ECG changes (Figure 2.4) and treat hyperkalaemia promptly (Table 2.11).