The incidence of kidney stone disease is rising, with a lifetime risk of 10–15% (Khan et al, 2016). In 2019-2020 there were approximately 90 000 hospital admissions in England with kidney stone disease (NHS Digital, 2020) equating to substantial economic burden in excess of £324 million (Geraghty et al, 2020). Kidney stone disease encompasses stones, commonly referred to as calculi, located within the urinary tract, which includes the kidneys, ureters, bladder and the urethra (Kaisary et al, 2016). Urolithiasis refers to formation of stones anywhere in the urinary tract, nephrolithiasis is stones in the kidneys and ureterolithiasis stones located in the ureters (Khan et al, 2016).
Risk of stone formation is multifaceted, including intrinsic factors such as ethnicity and gender, with a 3:1 ratio of men to women (National Institute for Health and Care Excellence (NICE), 2019) and genetical dispositions paired with extrinsic factors such as climate, lifestyle, dietary and water intake (Alelign and Petros, 2018). Aune et al's (2018) meta-analysis concluded there is a 21% increase in risk of stones per 5 units increase in body mass index (BMI). Poore et al (2020) reiterated the association between obesity and stone formation, suggesting the constituents involved in stone formation such as calcium, oxalate, and urate levels were much higher in obese subjects; furthermore, there are bidirectional associations with stone formation and comorbidities commonly attached to obesity such as hypertension and diabetes.
Stone formation
Stones form in the presence of increased urinary supersaturation, which occurs when the urine solvent contains more solutes than it can hold in solution (Khan et al, 2016). Supersaturation results in an imbalance of stone-forming constituents, subsequently forming crystalline particles as a precursor to stone formation. Other formation factors include crystal nucleation, aggregation of ion particles, cell surface molecules that favour or inhibit crystal adhesion and stagnancy of substrate (urine) (Kaisary et al, 2016; Reynard et al, 2019).
There are several types of stone, grouped according to their biochemical composition. Calcium-based stones account for 60-80% and include calcium oxalate and calcium phosphate stones, usually a mixture of both (British Association of Urological Surgeons (BAUS), 2021a). Formation predominately stems from elevated calcium in the urine, known as hypercalciuria (Kumar and Clark, 2017), of which there are three types: absorptive, which refers to increased intestinal absorption of dietary calcium; renal, where there is impaired renal reabsorption equating to increased urinary levels; and resorptive, referring to an excessive skeletal resorption of calcium (Kaisary et al 2016).
Struvite stones, often the composition of staghorn calculi, account for 10-15% and are made of calcium, magnesium and ammonium phosphate (BAUS, 2022). Struvite stone formation occurs in the presence of infection, associated with bacteria that produce the enzyme urease; urease hydrolyses urinary urea producing ammonia (Flannigan et al, 2014; Alelign and Petros, 2018). As ammonia production increases urine pH becomes higher (more alkaline), the alkalisation of urine paired with increased ammonium ion availability promotes crystallisation (Kumar and Clark, 2017).
Uric acid stones account for up to 10% in the UK (BAUS, 2022), the primary causative factors are low urinary pH, low urine volume and increased uric acid production. Uric acid is the end breakdown product of purine metabolism, some causes of hyperuricosuria include increased cellular breakdown, protein catabolism and inherited metabolic disorders (Sakhaee, 2014; Kaisary et al, 2016). Other types of stone are rare and include formation from underlying inherited enzyme deficiencies, genetic defects, for example cystinuria, and some medications result in an increased risk of crystal growth (BAUS, 2022).
Symptoms
A substantial proportion of urolithiasis can be asymptomatic; stone movement within the ureters often is the predisposing factor to acute symptoms (BAUS, 2022). Severe colicky loin to groin pain known as renal colic is the classic presentation of urolithiasis (NICE, 2020; BAUS, 2022). Renal colic is caused by a combination of physiological factors including ureteral muscle spasms, increased proximal peristalsis, stone-induced localised inflammatory changes, renal oedema and generalised irritation (Reynard et al, 2019). The mainstay analgesic recommendation is non-steroidal anti-inflammatories (NSAIDs) (NICE, 2019; BAUS, 2022). A Cochrane review by Afshar et al (2015) concluded that NSAIDs were significantly more effective in reducing pain, by 50% within the first hour compared with alternative non-opioid medications and placebo. Pathan et al (2018) supported this, concluding NSAIDs reduced the requirement for rescue medication and had lowered rates of side-effects compared with opioids.
Haematuria, the presence of blood in the urine—which can be established by performing urine analysis—is also a positive predictor for urolithiasis (NHS website, 2019; NICE, 2020; Skolarikos et al, 2022). Urine analysis is a quick, easy, cost-efficient screening tool used in the work-up of many clinical presentations including suspected renal colic, with relatively high sensitivity, approximately 84% (Minotti et al, 2020). However, absence of haematuria does not exclude renal colic as a differential diagnosis as an estimated 10–20% of patients with urolithiasis can present without microscopic haematuria (Mefford et al, 2017). Attention should also be paid to the presence or absence of leukocytes, nitrates and to the urinary pH. Pyuria, the presence of white blood cells in urine, is a fairly common response to irritation caused by a stone, however it may be indicative of a more serious infective urolithiasis complication (Dorfman et al, 2016).
Investigations
Alongside urine analysis initial investigations of suspected urolithiasis should include full blood count (FBC), C-reactive protein (CRP), serum creatinine and electrolytes and calcium. A clotting screen as a baseline if percutaneous intervention is likely and blood cultures if the patient is pyrexial or displaying signs of infection are also recommended (Wright et al, 2014; Tsiotras et al, 2018). Timely thorough assessment is vital to acknowledge and respond to any systematic stone complications. Complications of urolithiasis increase risk of morbidity and mortality ten-fold (Kum et al, 2016). Advanced clinical practitioners (ACPs) are optimally placed to conduct such an assessment, by practising in accordance with the four pillars of advanced practice (Health Education England (HEE), 2017). ACPs' high level of critical thinking and rational clinical-decision making can improve timely recognition and management. Furthermore, evidence has provided overwhelmingly positive conclusions that ACPs provide equivalent quality of care to medical colleagues, enhance patient satisfaction, improve departmental efficiency and cost-efficiency and provide a service that supplements and complements care delivery (Li et al, 2013; Martínez-González et al, 2014; Royal College of Nursing, 2018).
Complications
The main complications of renal and ureteric stones are obstruction of urinary flow, potentially leading to hydronephrosis and infection, which occur in an estimated 8.5% of acute presentations (Skolarikos et al, 2022). Ureteral obstruction in the form of calculi prevent homeostatic urinary flow, in turn increasing intratubular pressures leading to intense renal vasoconstriction and a rapid fall in renal blood flow alongside a decline in the glomerular filtration rate; if prolonged fibrosis, cellular toxicity and nephron damage ensue (Keddis and Rule, 2013; Reynard et al, 2019). Obstructing urolithiasis is one of the main causes of post-renal acute kidney injury (AKI) characterised by a decline in renal excretory function resulting in failure to maintain fluid, electrolyte, and acid–base homeostasis (NICE, 2021).
AKI is associated with significant mortality as high as 20-30% (NICE, 2021) paired with extensive and potentially debilitating long-term consequences for the patient, care providers and the economy (Caskey and Dreyer, 2018). Early recognition and treatment are paramount in preventing deaths and reducing complications (NICE, 2021). Local guidelines suggest management strategies are guided by consideration of four domains (University Hospitals of Derby and Burton NHS Foundation Trust, 2019):
- Perfusion considers volume status, strict fluid balance and the appropriate administration of intravenous fluids and conjuncts such as vasodepressors
- Underlying cause and the management of cause, and medication optimisation of nephrotoxic drugs
- Monitoring
- Prevent and treat complications.
Considering medicine optimisation in specific relation to the topic, NSAIDs have been discussed as the gold standard analgesia for renal colic but NSAIDs are also nephrotoxic. The Medicines and Healthcare products Regulatory Agency (MHRA) issued a safety alert recommending NSAIDs should be avoided in patients at risk of renal impairment, a known risk with urolithiasis (MHRA, 2014). Hence prescribing NSAIDs in the acute phase of renal colic should be done with a high degree of caution and careful balance of risk and benefit until an accurate assessment of a patient's renal function is obtained.
Prolonged obstruction consequently can result in an inability to filter metabolic waste products, causing retention of nitrogenous wastes, which act as a reservoir for bacterial culture. Urinary stasis enables bacteria to adhere to the urothelium, mediating the production of pro-inflammatory cytokines that induce cellular and humoral cascades (Wagenlehner et al, 2013). This complex amplified pro-inflammatory and anti-inflammatory response induces widespread dysregulation of innate homeostatic systems and ultimately multi-organ failure (Kumar and Clark, 2017). Management of sepsis or anuria in an obstructed kidney is a urological emergency. Initial care should mirror that of any acutely unwell patient: a comprehensive airway, breathing, circulation, disability, exposure assessment, appropriate fluid resuscitation, timely antibiotic administration and source control (Reynard et al, 2019). Given the potential devastating impacts of sepsis, the Surviving Sepsis Campaign was introduced providing international recommendations including the ‘Sepsis 6’ bundle, which is used in the authors' local area (UK Sepsis Trust, 2019). This care bundle has six components, three baseline measurements and three treatment interventions, which when instigated within the first hour of suspected sepsis have been demonstrated to reduce relative risk of mortality by up to 46% (NHS England, 2014).
Urgent decompression is required in the means of placement of an indwelling ureteral stent or percutaneous placement of nephrostomy tube (PCN) (Tsiotras et al, 2018; Skolarikos et al, 2022). Borofsky et al (2013) stressed the need for urgent decompression, which directly increases the chance of survival. In their trial, the mortality rate was 8.82% compared with 19.2% in the absence of decompression. The choice of mode of drainage is predominantly guided by logistical factors (to prevent any delays), patient stability, surgeon preference and patient choice (Tsiotras et al, 2018; Reynard et al, 2019). However, there is some evidence that mode of decompression can potentially impact on long-term quality of life: Shoshany et al (2019) suggested PCN was favourable for symptom relief and overall quality of life compared with stenting, where higher proportions of patients suffered persistent symptoms and reduced quality of life.
Imaging
Imaging to provide accurate diagnosis is essential (NICE, 2019) being recommended to occur within 14 hours of presentation (Tsiotras et al, 2018). ACPs are often the static workforce member in an ever-changing medical workforce, the resulting awareness of local hospital policy, treatment pathways and processes can enhance efficiency of patient journeys (Li et al, 2013) enabling targets such as the above to be achieved.
In the acute phase computed tomography (CT) of the kidneys, ureter and bladder (KUB) is the gold standard imaging modality given high sensitivity and specificity of 95-97% (Tsiotras et al, 2018; NICE, 2019). However, there is a radiation risk with CTKUB, so in specific cohorts—for example, pregnant females and known stone formers who have had multiple CTKUBs—an ultrasound (US) of KUB is the recommended alternative (NICE, 2019). A multicentre trial by Smith-Bindman et al (2014) supported use of USKUB as a non-invasive, cost-effective technique, achieving accurate diagnosis in most cases without the need for radiation.
Treatment options
Treatment decisions are based on several general aspects such as stone composition, stone size, anatomical location and patient symptoms (NICE, 2019; Skolarikos et al, 2022). In the clinically stable patient, with stones less than 5 mm in size, watchful waiting is recommended (NICE, 2019) as stones of 4 mm or less have an estimated 95% chance of spontaneous passage within 40 days (Skolarikos et al, 2022).
Medical expulsive therapy (MET) in the form of alpha-blockers such as tamsulosin remains controversial and widely debated. NICE (2019) guidelines recommend consideration of alpha-blockers in stones less than 10 mm, whereas in direct contrast the BAUS suggests patients should not be routinely commenced on MET (Tsiotras et al, 2018). Based on their trial, Pickard et al (2015) advocated not administering alpha-blockers, finding the percentage of subjects not requiring further intervention was mirrored in the treatment and placebo group, 80% and 81%, overall concluding alpha-blockers are not effective at decreasing the need for further treatment, likelihood of spontaneous passage or analgesia requirement. This was a large, blinded, multicentre randomised controlled trial, which are considered the gold standard in health care, implying the conclusions drawn are highly reliable and generalisable (Denscombe, 2021). However, on the contrary, the use of alpha-blockers was supported in a large Cochrane systematic review—at the top of the quantitative research hierarchy according to Bowling (2014). In their Cochrane review, Campschroer et al (2018) found results were supportive of alpha-blockers with reduced episodes of pain, significantly higher stone-free rates and stone expulsion reduced by 2.91 days in the alpha-blocker group. However, they did also conclude that patients using alpha-blockers were more likely to experience adverse effects. There is clear controversy regarding the evidence on the use of alpha-blockers, so it is vital to acknowledge that recommendations are only based on the evidence available, and although it can be informative evidence-based medicine does not replace a clinician's expertise or individualised holistic judgment (Fernandez et al, 2015).
Definitive surgical management is the gold standard for symptomatic stones greater than 5 mm (Tsiotras et al, 2018; NICE, 2019). Extracorporeal shock wave lithotripsy (ESWL), ureteroscopy and percutaneous nephrolithotomy (PCNL) are the mainstay treatment modalities for renal stones. Treatment choice is multifactorial including clinician factors, patient factors such as body habitus and medical comorbidities alongside stone factors including size and anatomical location (Khan et al, 2016).
ESWL involves the non-invasive delivery of high-energy acoustic waves that fragment a kidney stone into smaller particles that will pass spontaneously (Kaisary et al, 2016). ESWL is non-invasive, has a low risk of complications, and does not require anaesthesia equating to reduced hospital stay and cost effectiveness (McClinton et al, 2020). However, efficacy of stone clearance in larger stones and lower-pole stones appears relatively low and it may require repeated treatments to match the effectiveness of its counterparts; residual fragments increase risk of stone re-formation (Khan et al, 2016). Broadly speaking, ESWL is a favourable option in stones less than 10 mm in size located in the upper pole, middle pole and renal pelvis (Tsiotras et al, 2018; NICE, 2019; Skolarikos et al, 2022).
Ureteroscopy involves the passage of a small telescope through the urethra and bladder, up the ureter to the location of the stone, allowing delivery of instruments, such as laser fibres and baskets (BAUS, 2021a). Ureteroscopy requires anaesthesia to minimise pain and the visceral response to ureteral and renal dilation (Khan et al, 2016). As technologies have progressed, with availability of high-definition rigid and flexible ureteroscopies, ureteroscopy is suitable for nearly all size stones and in any anatomical location given the majority of areas in the urinary tract can be readily accessed (Khan et al, 2016; Skolarikos et al, 2022). Benefits include it is minimally invasive with high accuracy of stone assessment and low complication rates of approximately 3.5%, which are mostly minor (Wright et al, 2014). Furthermore, it has minimal contraindications and it is suitable for specific high-risk cohorts such as those who are on anticoagulation therapy and those who are pregnant (Skolarikos et al, 2022). A Cochrane review by Aboumarzouk et al (2012) concluded ureteroscopy was favourable in terms of stone-free rates and rate of need for re-treatment when directly compared with ESWL; although further finding higher complication rates and longer hospital stays.
PCNL is considered the treatment of choice for large and staghorn calculi, it involves the direct passage of an endoscope percutaneously through skin, muscle and perirenal fat, and into the kidney, making it the most invasive of the three procedures (Khan et al, 2016; Skolarikos et al, 2022). PCNL has high rates of stone clearance, attaining stone-free rates of up to 95% and can be successful in treating even the most challenging staghorn calculi (Ganpule et al, 2016). PCNL is, however, associated with higher risk of complications, including infection, bleeding and damage to surrounding structures, with rates reported of approximately 10% (Skolarikos et al, 2022).
Preventive strategies
Following the initial management, long-term preventive strategies are paramount given a 10-year recurrence rate of 50% (Kumar and Clark, 2017). Providing health promotion is part of all health professionals' duty of care, working collaboratively to improve the health of the population (HEE, 2017; Nursing and Midwifery Council, 2018). Health promotion is essential to reduce health inequalities and sustain the NHS for future generations (Public Health England et al, 2016). ACPs can use their dual approach gained from their diverse and experienced clinical backgrounds to make every contact count.
All stone formers, independent of their individual risk, should be given fluid intake, diet and lifestyle advice (NICE, 2019; Skolarikos et al, 2022). The relationship between low fluid intake and increased stone formation has been repeatedly demonstrated, hence drinking adequate amounts of fluid can independently reduce the likelihood of stone recurrence by 30-40% (BAUS, 2021b). NICE (2019) recommends adults should drink 2.5 to 3 litres of water a day. A common-sense approach to diet should be taken, that is, a mixed, balanced diet with contributions from all food groups, without any excesses, alongside caution in the use of salt (BAUS, 2021b; Skolarikos et al, 2022). NICE (2019) suggests adults have a daily salt intake of no more than 6 g; Sorensen et al (2012) found that a higher dietary sodium intake increased the risk of nephrolithiasis by 11% to 61%. More specific dietary advice can be tailored dependent on the chemical composition of the stone (Skolarikos et al, 2022).
Individual risk, including potential underlying genetical dispositions and causative medical conditions, should be investigated and treated where possible (Kaisary et al, 2016). Targeted medical therapy can be an effective preventive method following biochemical analysis of a stone—the drug should halt stone formation with minimal side effects to achieve good compliance (Skolarikos et al, 2022). Most ACPs are non-medical prescribers, enabling holistic autonomous care. Non-medical prescribers are accountable to ensure that before any prescribing decision is reached they have assessed the patient, considered the options and reached a shared decision to maintain safe, effective, patient-centred prescribing (Royal Pharmaceutical Society, 2021).
Medication suitability is dependent on underlying metabolic abnormalities and stone composition (Skolarikos et al, 2022). Considering calcium-based stones are most prevalent, thiazide diuretics or potassium citrate can be considered (NICE, 2019). Thiazides stimulate calcium reabsorption in the distal renal tubule and decrease extracellular fluid volume, increasing proximal renal tubular calcium reabsorption (Skolarikos et al, 2022). Potassium citrate binds with urinary calcium, thereby reducing the supersaturation of urine, and binds calcium oxalate crystals further preventing crystal growth (Krieger et al, 2015). In their meta-analysis Phillips et al (2015) concluded that potassium citrate significantly reduced stone size and prevented new stone formation by up to 75%.
Conclusion
The incidence of urolithiasis is on the increase, subsequently it is frequently encountered in the acute urological setting. The textbook symptoms are renal colic and haematuria in the acute presentation; a detailed synthesis of history of presenting complaint and clinical examination should occur to rule out potential differential diagnoses. ACPs are in the ideal position to use their knowledge and rational clinical-decision making to ensure timely recognition, prompt investigation and initial management. Once a diagnosis is confirmed, treatment decisions are based on several aspects such as stone composition, stone size, anatomical location and patient symptoms, employing conservative, medical and surgical management strategies.
KEY POINTS
- Kidney stone disease is a term that encompasses the presence of stones (calculi) anywhere within the urinary tract—kidneys, ureter and bladder
- The prevalence of kidney stone disease is increasing
- There are different types of stones, named in relation to their biochemical composition
- The main complication of stones are obstruction of urinary flow potentially causing hydronephrosis, infection, and acute kidney injury
CPD reflective questions
- What are considered risk factors for developing ‘kidney stones’ (urolithiasis)?
- If your patient was diagnosed with a 4 mm stone, but otherwise asymptomatic, what lifestyle advice would you offer?
- Kidney stones can lead to more serious complications. Reflecting on this point, what analgesia would you offer if required?