The following are true of renal calculi in pregnancy, except:
Answer A
The incidence of urolithiasis in pregnancy is similar to that in non-pregnant women because a greater concentration of inhibitors of stone formation such as citrate, magnesium and glycosaminoglycans counter the effects of hypercalcaemia, hypercalciuria and urinary stasis. Pregnant women with symptoms suggestive of acute ureteric colic are best investigated initially by ultrasound particularly in the first trimester where radiation risks (teratogenesis, carcinogenesis and mutagenesis) are greatest. However, it may be difficult to differentiate acute ureteric obstruction from the physiological hydronephrosis that is often seen on the right side in pregnancy. Transvaginal ultrasound can be helpful to assess the distal ureter. MRI is advised as a second line investigation when results are equivocal and is able to define the level of urinary obstruction, visualise stones as a filling defect and can assess non-urological organ systems. Low-dose non-contrast CT KUB (foetal exposure 0.05 Gy versus 2.5 Gy) is increasing in popularity with a high sensitivity and specificity but still is last-line as exposure to ionising radiation can be associated with teratogenic risks and development of childhood malignancies. Conservative management is the preferred treatment option for pregnant women with ureteric stones as the majority will pass spontaneously. This may be the result of ureteral dilatation secondary to the effects of elevated levels of circulating progesterone. Where expectant management fails or intervention is indicated on the grounds of infection or in the presence of a solitary kidney, urinary diversion with a percutaneous nephrostomy or ureteric stent should be considered next. This usually leads to the rapid relief of symptoms but may necessitate frequent (up to six weekly) nephrostomy or stent changes because hypercalciuria leads to rapid encrustation. Ureteroscopy has been shown to be effective and safe in pregnancy with complication rates similar to those observed in non-pregnant women. On the other hand, pregnancy is considered an absolute contraindication to extracorporeal shockwave lithotripsy (ESWL) following studies on mice that demonstrated foetal damage and death in the later stages of pregnancy.
The following are recognised inhibitors of stone formation in the metastable zone except:
Answer E
Stone formation depends on the concentration of precipitating substances in urine and reflects a complex relationship between factors that can be categorised into either promoters of crystallisation or inhibitors of crystal formation and aggregation (figure below).
Urine is ordinarily supersaturated with calcium oxalate and may be supersaturated with other compounds such as calcium phosphate and sodium and ammonium urate. However, supersaturation is variable and in the metastable zone crystal aggregation will not occur unless induced by epitaxy (one salt inducing the precipitation of another salt) or heterogenous nucleation caused by the influence of foreign particles; for example, bacteria acting as niduses for stone formation.
Crystals of one salt have been shown to induce the precipitation of crystals of other salts by a process referred to as epitaxy. For example, calcium phosphate or calcium carbonate crystals may stimulate precipitation of calcium oxalate crystals and thereby promote stone formation. It is believed that the presence of endogenous compounds such as magnesium, zinc, fluoride and citrate act as inhibitors of stone crystallisation and are the reason that stones do not generally form in urine despite its supersaturation.
Tamm-Horsfall protein, also known as uromodulin, is produced by the thick ascending limb of the loop of Henle. Its role in urolithiasis remains uncertain but it may act as both a promoter and inhibitor of stone formation. Uropontin and nephrocalcin are also glycoproteins that are thought to have an effect on kidney stone formation.
Relationship between urinary saturation and promoters and inhibitors of stone formation.
Urease producing organisms include all of the following, except:
Answer B
Urease is an enzyme that is produced by many Gram-negative, Gram-positive and Mycoplasma bacteria. Proteus species, Klebsiella species and Pseudomonas aeruginosa are examples of Gramnegative urease producing bacteria. However, Escherichia coli and Enterococci do not usually produce urease. Helicobacter pylori is present in the upper gastrointestinal tracts of more than 50% of the population and while associated with peptic ulcer disease is of no recognised importance with respect to the urinary tract. Ureaplasma urealyticum is a mycoplasma bacterium of low pathogenicity that comprises part of the normal genital flora of many men and women. Gram-positive Staphylococcus aureus and Staphylococcus epidermidis can produce urease.
Urease catalyses the conversion of urea to ammonia which is subsequently hydrolysed to ammonium ions and hydroxyl ions:
It is hydroxyl (OH−) ions that are responsible for the alkalinisation of urine which is of fundamental significance to the pathophysiology of struvite stone formation. The presence of ammonia in alkaline urine (pH > 7.2) leads to the precipitation of magnesium ammonium phosphate (struvite) crystals which can lead to staghorn stone formation. Specific therapeutic measures for struvite stones therefore include urinary acidification, use of short-term and long-term antibiotics, and the use of urease inhibitors such as acetohydroxamic acid. Percutaneous chemolysis may be combined with ESWL for selective patients with staghorn stones who are not fit for percutaneous nephrolithotomy (figure below).
Plain abdominal radiograph demonstrating a left staghorn calculus. The opacities in the right upper quadrant are gallstones.
The following represent unfavourable characteristics for successful extracorporeal shockwave lithotripsy to a lower pole stone except:
The success of ESWL depends on factors that relate to the stone characteristics, the renal anatomy, the patient anatomy and the type of lithotriptor. Stone factors include the stone size, hardness, and location within the kidney. Success rates for lower pole stones are less than for stones located in the renal pelvis or other calyces. For example, in the Lower Pole I study only 21% of patients with stones larger than 10 mm located in a lower pole calyx were stone free after lithotripsy [5]. Adverse anatomic features include an infundibulopelvic angle <90 degrees and a narrow (<5 mm) or long (>30 mm) calyceal infundibulum. The role for adjunctive measures to improve the outcome of ESWL for lower pole stones such as PDI (percussion, diuresis and inversion) is yet to be established.
The effectiveness of lithotripsy is also dependent on the hardness of the stone. For example, calcium oxalate monohydrate, dicalcium phosphate dihydrate (brushite) and cystine stones are relatively resistant to shockwaves although they are not contraindications to ESWL. Uric acid stones are radiolucent and must therefore be localised using ultrasound rather than fluoroscopy but are soft and may fragment well with lithotripsy.
Obesity reduces the effectiveness of ESWL and skin to stone difference has been shown to be an independent predictor of success. Modern lithotriptors are less effective than the Dornier HM3 lithotriptor but are safer, better tolerated and do not require general anaesthesia. A recent meta-analysis has shown that reducing the shockwave frequency from 120 to 60–90 per minute improves stone clearance.
The following dietary advice should be given to a first time calcium oxalate stone former with normal serum calcium and a normal 24-hour urine collection except:
Answer C
All stone formers independent of their risk of developing further stones should follow general preventative measures to modify their risk. Patients should be encouraged to maintain a fluid intake of 2.5–3.0 L/day which should be increased as necessary to ensure a diuresis of 2.0–2.5 L/day. Most fluids can be consumed although some carbonated drinks, such as cola, contain phosphoric acid which may increase the risk of stone formation. Lemon juice increases urinary citrate and so reduces the risk of calcium oxalate stones. Although orange juice also increases urinary citrate, it raises oxalate levels and so is not recommended.
Patients should be advised to eat a healthy and balanced diet. However, foods rich in oxalate (for example, chocolate, nuts, rhubarb, tea) should be limited or avoided particularly in those patients with hyperoxaluria. Excessive dietary animal protein may cause hypocitraturia, hyperuricosuria, hyperoxaluria and acidic urine thereby encouraging stone formation. High salt intake increases the risk of urolithiasis by causing increased tubular calcium excretion and hypocitraturia. Therefore, not more than 3–5 g sodium should be consumed per day.
Patients often ask about dietary calcium and whether hard water (containing a high mineral content typically including calcium carbonate) in their locality caused their kidney stone. The data regarding water hardness are controversial but suggest that any increased lithogenic salt excretion may be neutralised by a greater excretion of stone inhibitors such as citrate and magnesium. On the other hand, there is good evidence that restricting dietary calcium actually increases the risk of stone formation through the reciprocal absorption of oxalate in the gut. A randomised study that compared the 5-year risk of stone recurrence in patients with a normal calcium, low salt and low protein diet to a low-calcium diet found a relative risk of 0.49 (95% CI 0.24-0.98, p-0.04). At least 1000 mg calcium should be consumed each day although calcium supplementation is generally not recommended except in some cases of enteric hyperoxaluria.
Calcium oxalate stones can be predominately calcium oxalate monohydrate or calcium oxalate dihydrate. Patients who have calcium oxalate monohydrate stones are often found to have hyperoxaluria in their metabolic workup, whereas those with calcium oxalate dehydrate stones are more likely to have hypercalciuria.