**7.2. Diet**

Dietary modification can help reduce the risk of stone formation in cystinuria. Patients are advised to follow a low sodium and relatively low animal protein diet. A low sodium diet is effective as dibasic amino acid reabsorption in the proximal tubule is partially sodium-dependent; a low sodium intake encourages reabsorption of cystine and sodium, thereby minimising excess urinary cystine excretion [4]. A low animal protein, or ideally vegan diet, is advised as this leads to a more alkaline urine being produced and also reduces the intake of the amino acid methionine, which is the precursor to cysteine [16]. Recipe books have been written especially for cystinuric patients that provide ideas regarding foods with high fluid content and low animal protein [17].

#### **7.3. Urinary alkalinisation**

Cystine solubility is increased in alkaline pH; a target urinary pH of 7.0–7.5 is recommended in cystinuria patients [16]. This can be achieved either by supplementation with potassium citrate or sodium bicarbonate, or through following a vegan diet. Potassium citrate is the preferred medication, but its use is limited in patients with chronic renal impairment due to the risk of hyperkalemia. It is important for the urine to remain within the target pH range, as over-alkalinisation can paradoxically increase the risk of calcium stone formation. Patients can use urine dipsticks to regularly check their urine pH [16].

#### **7.4. Cystine-binding thiol drugs**

Thiol-containing medications (penicillamine, tiopronin and captopril) can play a role in cystinuria treatment. These drugs bind to cystine in the urine, reducing the disulphide bond which forms cystine and producing two molecules of cysteine which are more soluble [4].

The use of penicillamine and tiopronin may be limited by their side-effect profile. Captopril, an angiotensin converting enzyme inhibitor, may be used as an alternative, although there is not strong evidence for its use in cystinuria [16]. Therapeutic success (reduction in stone events) is only likely to be achieved if conservative measures such as increased fluid intake are also followed simultaneously. Clinical trials using a new thiol binding drug called bucillamine are underway and will be completed by March 2018 [18].

#### **7.5. Surgical therapies**

Although stone prevention is the aim of cystinuria management, in cases where medical therapy has failed minimally-invasive surgical intervention can be required to break up and remove stones. This may be through lithotripsy (or extracorporeal shock wave lithotripsy), ureteroscopy or percutaneous nephrolithotomy [16]. These techniques are similar to those used for other types of renal stones. However, extracorporeal shock wave lithotripsy may be less successful in cystinuria patients due to the recognised increased resistance of cystine stones to fragmentation by shock wave lithotripsy [4]. Cystinuria is a recognised form of staghorn calculus which may require open surgical intervention and even nephrectomy in some cases.
