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Uro Flash 2018 › Uro Flash Vol-4, No-1, 2018

Global Guidelines and Stone Inhibition

Stone disease: An introduction

Worldwide kidney stone is a common problem and its prevalence has increased over the past 20 years. The National Health and Nutrition Examination Survey (NHANES 2007-2010) report that the prevalence of kidney stones among American adults is 8.8%: 10.6% among men and 7.1% among women, and it is anticipated that there will be an increase in kidney stones in the future due to global warming, lifestyle changes, diet and obesity.1Xu H, Zisman AL, Coe FL, Worcester EM. Kidney stones: an update on current pharmacological management and future directions. Expert Opin Pharmacother. 2013 Mar;14(4):435–47.  In the Middle East, the lifetime risk of kidney stone appears to be even higher. The awareness of renal stone disease in children is high and recurrence rates of 50% after 10 years and 75% after 20 years have been reported.2XHeilberg IP, Schor N. Renal Stone Disease: Causes, Evaluation and Medical Treatment. Arq Bras Endocrinol Metabol. 2006 Aug;50(4):823–31.

 

 

Kidney stones are characterised by sudden onset of lumbar pain that may be accompanied by nausea and vomiting, gross or microscopic haematuria. The location of the pain depends on the location of stone in the urinary tract.2XHeilberg IP, Schor N. Renal Stone Disease: Causes, Evaluation and Medical Treatment. Arq Bras Endocrinol Metabol. 2006 Aug;50(4):823–31.  Apart from being costly due to both medical treatment and time lost from work, kidney stones are also associated with increased rates of chronic kidney disease, hypertension and myocardial infarction. The recurrence rate of kidney stones is high. After an initial stone, there is a 50% chance of forming a second stone within 7 years if left untreated. Since most patients with stone disease have identifiable risk factors, it is advisable to evaluate the underlying causes of stone formation.1Xu H, Zisman AL, Coe FL, Worcester EM. Kidney stones: an update on current pharmacological management and future directions. Expert Opin Pharmacother. 2013 Mar;14(4):435–47.

Roughly 80% of kidney stones contain calcium, and majority of them are composed mainly of calcium oxalate. Most of calcium oxalate stones contain some calcium phosphate, while 5% have hydroxyapatite or brushite as their main constituent and 10% contain some uric acid. Pure uric acid, cystine and infection stones are less common. Although composition of each stone correlates with supersaturation values in the urine, calculi are seldom found without an admixture of many salts and not every passed stone can be retrieved for chemical analysis.2XHeilberg IP, Schor N. Renal Stone Disease: Causes, Evaluation and Medical Treatment. Arq Bras Endocrinol Metabol. 2006 Aug;50(4):823–31.

Pathophysiology

Calcium stone formation involves different phases of increasing accumulation of calcium oxalate and calcium phosphate– nucleation, crystal growth, crystal aggregation and crystal retention.3Basavaraj DR, Biyani CS, Browning AJ, Cartledge JJ. The Role of Urinary Kidney Stone Inhibitors and Promoters in the Pathogenesis of Calcium Containing Renal Stones. EAU-EBU Update Series. 2007;5(3):126-136.

Nucleation

Nucleation is the process by which free ions in solution associate into microscopic particles. Crystallisation can occur in solution micro-environments, such as may be present in certain points in the nephron, as well as on surfaces, such as those of cells and on extracellular matrix. There is considerable dispute about the importance of free solution crystallisation vs. crystallisation at other sites, in renal tubules or on bladder walls, on normal or damaged cells, on areas denuded of cells by certain forms of injury, or at interstitial sites.3Basavaraj DR, Biyani CS, Browning AJ, Cartledge JJ. The Role of Urinary Kidney Stone Inhibitors and Promoters in the Pathogenesis of Calcium Containing Renal Stones. EAU-EBU Update Series. 2007;5(3):126-136.

Crystal growth

Crystal growth is the next major step of stone formation after nucleation. Reduction in the potential energy of the atoms or molecules when they form bonds to each other is the driving force for crystallisation. In a supersaturated liquid, several atoms or molecules start forming clusters; the bulk free energy of the cluster is less than that of the liquid.3Basavaraj DR, Biyani CS, Browning AJ, Cartledge JJ. The Role of Urinary Kidney Stone Inhibitors and Promoters in the Pathogenesis of Calcium Containing Renal Stones. EAU-EBU Update Series. 2007;5(3):126-136. The total free energy of the cluster is increased by the surface energy (surface tension). Molecular size and shape of the molecule, the physical properties of the material, supersaturation levels, pH, and defects that may form in the crystal’s structure determine the crystal growth. Crystal growth is one of the prerequisites for particle formation. Using the powerful atomic-force microscope (AFM), laboratory researchers are discovering complex growth mechanisms and three-dimensional structures of solution-based crystals.3Basavaraj DR, Biyani CS, Browning AJ, Cartledge JJ. The Role of Urinary Kidney Stone Inhibitors and Promoters in the Pathogenesis of Calcium Containing Renal Stones. EAU-EBU Update Series. 2007;5(3):126-136.

Crystal aggregation (crystal agglomeration)

In crystal aggregation, crystals in the solution stick together and form larger particles. Aggregation of particles in solution is determined by a balance of forces, some with aggregating effects and some with disaggregating effects. A small interparticle distance increases attractive force and favours particle aggregation. In addition, Tamm-Horsfall glycoprotein and other molecule may act as glue and increase viscous binding.3Basavaraj DR, Biyani CS, Browning AJ, Cartledge JJ. The Role of Urinary Kidney Stone Inhibitors and Promoters in the Pathogenesis of Calcium Containing Renal Stones. EAU-EBU Update Series. 2007;5(3):126-136.

Furthermore, aggregate may be stabilised by solid bridges formed by crystalline material connecting two particles. The main force that inhibits aggregation is the repulsive electrostatic surface charge, known as Zeta potential. In various steps of stone formation, crystal aggregation is a more important factor than nucleation and growth because aggregation occurs within seconds.3Basavaraj DR, Biyani CS, Browning AJ, Cartledge JJ. The Role of Urinary Kidney Stone Inhibitors and Promoters in the Pathogenesis of Calcium Containing Renal Stones. EAU-EBU Update Series. 2007;5(3):126-136.

Crystal retention

Urolithiasis requires formation of crystals followed by their retention and accumulation in the kidney. Crystal retention can be caused by the association of crystals with the epithelial cells lining the renal tubules. Crystal formation predominantly depends on the composition of the tubular fluid, while crystal retention might depend on the composition of the renal tubular epithelial cell surface. A non-adherent surface of the distal tubules, collecting ducts, ureters, bladder, and the urethra may provide a natural defence mechanism against crystal retention, and may become defective when the anti-adherence properties are compromised. In a cell culture model, Verhulst et al., observed upregulated cell surface expression of hyaluronic acid, osteopontin, and their receptor CD44, as well as the formation of a hyaluronic acid-dependent cell coat, and suggested that it may play a crucial role in the process of crystal retention.3Basavaraj DR, Biyani CS, Browning AJ, Cartledge JJ. The Role of Urinary Kidney Stone Inhibitors and Promoters in the Pathogenesis of Calcium Containing Renal Stones. EAU-EBU Update Series. 2007;5(3):126-136.

Risk factors

Professional chefs and taxi drivers who often try to minimise their fluid intake to avoid too many ‘toilet stops’ are at higher risk of getting stone disease. Apart from environmental and lifestyle factors diet-related factors are also known to increase stone risk. Diet-related factors that are known to increase stone risk are listed in Table 1.4Johri N, Cooper B, Robertson W. An update and practical guide to renal stone management. Nephron Clin Pract. 2010;116(3):c159–71.

Tea or coffee (particularly instant coffee) without milk has been shown to increase oxalate excretion, although this effect is probably offset by their diuretic action. Dietary calcium has a biphasic risk curve: Stone risk is greater in those on a high or low calcium diet. The link between vitamin D intake and renal stones is less clear: While excessive active (1,25-OH) vitamin D supplementation, increases the risk of stone formation, there is no evidence that correction of native (25-OH) vitamin D deficiency has the same effect; moreover, correction, especially if there is secondary hyperparathyroidism, is likely to be a health benefit. Excess of vitamin C could also increase the risk of calcium oxalate stone formation, but in practice this is rarely encountered. High dietary intake of potassium or magnesium is inversely related to stone formation because potassium promotes urinary citrate excretion, and both citrate and magnesium inhibit crystal formation. However, the impact of low urinary magnesium on stone risk is at best modest.4Johri N, Cooper B, Robertson W. An update and practical guide to renal stone management. Nephron Clin Pract. 2010;116(3):c159–71.

Sites of stone growth

Randall’s plaques

Supersaturation of calcium phosphate may exist in the loop of Henle even though urine is not generally supersaturated with it. This may lead to precipitation of calcium phosphate in interstitial sites in the inner medulla. These deposits often become extensive enough to be visible macroscopically in the form of Randall’s Plaques. Some studies have demonstrated stones that appear to have been attached directly to the Randall’s plaque which has eroded through the overlying uroepithelium at the surface of a renal papilla. Although Randall’s plaques appear to be a risk factor for stone formation, it is still unclear whether they are necessary in every stone that is formed, since intratubular crystals and prominent crystalluria are features of stone disease.5Ratkalkar VN, and Kleinman JG. Mechanisms of Stone Formation. Clin Rev Bone Miner Metab. 2011 Dec; 9(3-4):187–197.

Calcium oxalate receptors in collecting duct epithelium

Crystalluria is commonly observed in hyperoxaluric pati-ents, as well as in patients with the usual sort of calcium oxalate nephrolithiasis where intratubular crystals of calcium
oxalate have also been demonstrated.5Ratkalkar VN, and Kleinman JG. Mechanisms of Stone Formation. Clin Rev Bone Miner Metab. 2011 Dec; 9(3-4):187–197.

Cells internalise the crystals, where they may undergo dissolution or transcytosis through the epithelial layer. This process may have consequences for cell function; initiating mitogenesis, activation of arachidonic acid and other signaling pathways. The interaction of stone crystals of various types with primary cultures of inner medullary collecting duct cells demonstrates saturability and inhibition to some degree of one crystal type by others. Thus, it seems like there are some receptor-like features of cells to which stone crystals adhere.5Ratkalkar VN, and Kleinman JG. Mechanisms of Stone Formation. Clin Rev Bone Miner Metab. 2011 Dec; 9(3-4):187–197.

Loss of cell polarity increases adherence of calcium oxalate crystals. This suggests that the basolateral membranes of tubule cells have components to which the crystals can attach. Enrichment of cell membranes with phosphatidylserine also leads to enhanced calcium oxalate adherence. Also, proteins and glycosaminoglycan expressed at the cell surface have also been implicated as attachment sites for calcium oxalate. These include hyaluronan, nucleolin, annexin II, and osteopontin. It is likely that a number of different structure or molecular components are responsible for crystal attachment, and these may include phosphatidylserine component of the lipid bilayer, the acidic side chains of proteins (carboxyl groups of amino acids or sialic acid-containing glycosidic side chains). AFM has been used to measure the force of attraction of carboxyl and amidinium groups to the surface of crystals.5Ratkalkar VN, and Kleinman JG. Mechanisms of Stone Formation. Clin Rev Bone Miner Metab. 2011 Dec; 9(3-4):187–197.

Clinical feature of stone disease

Stone passage

Stones that are nonobstructing produce no symptoms or signs apart from haematuria. Stone passage produces renal colic that usually begins as a mild discomfort and progresses to a plateau of extreme severity over 30–60 minutes. In case of obstruction in the uretero-pelvic junction, pain localises to the flank, and as the stone moves down the ureter, the pain moves downward and anterior. Stones at the uretero-vesicular junction often cause dysuria and urinary frequency mistaken for infection. Colic is free of body position or motion and is described as a boring or burning sensation associated with nausea and vomiting.6Coe FL, Evan A, and Worcester E. Kidney stone disease. J Clin Invest. 2005 Oct 1; 115(10): 2598–2608.

Urological management of stones

Sound waves are used to break the stone into small pieces that can more easily pass into the bladder. Extracorporeal shock wave lithotripsy (ESWL) is widely used and valuable for small stones. Modern instruments permit local stone disruption with high-powered lasers by facilitating passage of endoscopes up the ureter into the kidney pelvis. Percutaneous stone removal via instruments introduced into the kidney through a small flank incision permits disruption and removal of even very large stones.6Coe FL, Evan A, and Worcester E. Kidney stone disease. J Clin Invest. 2005 Oct 1; 115(10): 2598–2608.

Renal function reduction in stone
forming people

The National Health and Nutrition Examination Survey III data set states that subjects with a BMI greater than or equal to 27 who had kidney stones had lower estimated glomerular filtration rates than non-stone formers (non-SFs) matched for age, sex, race, and BMI. SFs also have higher blood pressures than non-SFs. Urinary tract obstruction, sequelae of urological interventions, and the processes that cause stone formation may all injure renal tissue, reduce renal function and raise blood pressure.6Coe FL, Evan A, and Worcester E. Kidney stone disease. J Clin Invest. 2005 Oct 1; 115(10): 2598–2608.

Stone inhibitors

Stone inhibitors are defined as molecules that increase the supersaturation required to initiate nucleation, decrease crystal growth rate and aggregation, and inhibit secondary nucleation. Inhibitors of calcium stone formation act by preventing crystal growth and aggregation by coating the surface of growing calcium crystals or by complexing with calcium and oxalate.3Basavaraj DR, Biyani CS, Browning AJ, Cartledge JJ. The Role of Urinary Kidney Stone Inhibitors and Promoters in the Pathogenesis of Calcium Containing Renal Stones. EAU-EBU Update Series. 2007;5(3):126-136.

Citrate

Citrate, a tricarboxylic acid, circulates in the blood and is derived from endogenous oxidative metabolism. It is complexed to calcium, magnesium and sodium at physiological pH of 7.4. Citrate has been widely studied for its stone inhibiting action in urine and it has been found to be particularly effective against the calcium oxalate and phosphate stones. Citrate appears to alter both calcium oxalate monohydrate and calcium phosphate crystallisation. It reduces the concentration of calcium oxalate by complexing with calcium and this is possibly due to direct effects on the crystal surface rather than to an alteration of the availability of free calcium.3Basavaraj DR, Biyani CS, Browning AJ, Cartledge JJ. The Role of Urinary Kidney Stone Inhibitors and Promoters in the Pathogenesis of Calcium Containing Renal Stones. EAU-EBU Update Series. 2007;5(3):126-136.

Pyrophosphates

Pyrophosphate at low concentration of 16 μM, inhibits calcium oxalate monohydrate (COM) crystal growth by 50%. The urinary pyrophosphate levels are (20–40 mM) enough to inhibit calcium oxalate and calcium phosphate crystallisation. Pyrophosphate and diphosphate inhibits the precipitation of calcium phosphate, while diphosphates inhibit the growth of apatite crystals.3Basavaraj DR, Biyani CS, Browning AJ, Cartledge JJ. The Role of Urinary Kidney Stone Inhibitors and Promoters in the Pathogenesis of Calcium Containing Renal Stones. EAU-EBU Update Series. 2007;5(3):126-136.

Pyrophosphate reduces the absorption of calcium in the intestine and this action is probably mediated by formation of 1,25 (OH)2 – vitamin D. A study by Sharma et al., reported low 24-hour urinary excretion of pyrophosphate in SFs (50.67-2.16 mmol/24 h) as compared to normal subjects (71.46-5.46 mmol/24 h)
(p < 0.01). Oral administration of orthophosphate has shown little benefit in prevention of stone recurrence. Scientific evidence that support preventive role of orthophosphate is also lacking.3Basavaraj DR, Biyani CS, Browning AJ, Cartledge JJ. The Role of Urinary Kidney Stone Inhibitors and Promoters in the Pathogenesis of Calcium Containing Renal Stones. EAU-EBU Update Series. 2007;5(3):126-136.

Magnesium

Magnesium is the fourth most abundant mineral in the body and is largely found in bones and only 1% of total body magnesium circulates in blood. Dietary magnesium is absorbed in the small intestines and excreted through the kidney. Magnesium
(2 mmol/L) in a supersaturated calcium oxalate solution reduced particle number by 50%. Oral intake of magnesium will decrease the oxalate absorption and urinary excretion, in a manner similar to calcium by binding to oxalate in the gut. In subjects with magnesium deficiency, magnesium supplementation increases the excretion of citrate in urine. However, there is little evidence to recommend magnesium therapy in patients with urolithiasis.3Basavaraj DR, Biyani CS, Browning AJ, Cartledge JJ. The Role of Urinary Kidney Stone Inhibitors and Promoters in the Pathogenesis of Calcium Containing Renal Stones. EAU-EBU Update Series. 2007;5(3):126-136.

Osteopontin

Osteopontin (OPN) also called uropontin is a negatively-charged aspartic acid rich protein that is intimately involved in the regulation of both physiological and pathological mineralisation. OPN is synthesised within the kidney and present in the human urine at levels in excess of 100 nM. The bone derived and kidney derived forms of this protein appear to be very similar to amino acid sequence. OPN inhibits growth of calcium oxalate crystals in a supersaturated solution and it is involved in various biologic processes like inflammation, leucocyte recruitment, wound healing and cell survival.3Basavaraj DR, Biyani CS, Browning AJ, Cartledge JJ. The Role of Urinary Kidney Stone Inhibitors and Promoters in the Pathogenesis of Calcium Containing Renal Stones. EAU-EBU Update Series. 2007;5(3):126-136.

In vitro studies have suggested that OPN may inhibit the nucleation, growth and aggregation of calcium oxalate crystals. Also, it inhibits the crystal adhesion to cultured epithelial cells. Although clinical studies report inconclusive data regarding the relationship between OPN and renal stone disease, a few investigators have reported decreased concentrations of OPN in urine from SFs compared to normal individuals.3Basavaraj DR, Biyani CS, Browning AJ, Cartledge JJ. The Role of Urinary Kidney Stone Inhibitors and Promoters in the Pathogenesis of Calcium Containing Renal Stones. EAU-EBU Update Series. 2007;5(3):126-136.

Inter-alpha-trypsin inhibitor family of proteins

Inter-α-inhibitor (IαI) is a glycoprotein that belongs to the Kunitz-type protein superfamily, a group of proteins possessing a common structural element (kunin) and the ability to inhibit serine proteases. It is composed of 2 heavy chains HC1 and HC2 and one light chain, also known as bikunin. Bikunin circulates free in plasma and is excreted in urine where it degrades further to fragments HI14 and HI8. It is expressed mainly in the proximal tubules and the thin descending segment near the loop of Henle and may contribute to the regulation of crystal adhesion and retention within tubules during kidney stone formation. The potent inhibition of calcium oxalate crystal growth by these proteins, along with the known presence of bikunin and its fragments in urine, suggest the possible existence of a relationship between IαI and calcium oxalate stone formation.3Basavaraj DR, Biyani CS, Browning AJ, Cartledge JJ. The Role of Urinary Kidney Stone Inhibitors and Promoters in the Pathogenesis of Calcium Containing Renal Stones. EAU-EBU Update Series. 2007;5(3):126-136.

Urinary prothrombin fragment 1

Prothrombin, a blood clotting factor, is made of three fragments –thrombin, fragment 1 and fragment 2. Fragment 1 that is excreted in urine and is named urinary prothrombin fragment (UPTF1) and is a potent inhibitor of calcium oxalate stone formation in vitro. Presence of UPTF1 in the organic matrix calcium oxalate crystals provides evidence that links the role of blood coagulation proteins with urolithiasis. UPTF1 is an important inhibitor of calcium oxalate crystal aggregation and adherence of crystals to renal cells.3Basavaraj DR, Biyani CS, Browning AJ, Cartledge JJ. The Role of Urinary Kidney Stone Inhibitors and Promoters in the Pathogenesis of Calcium Containing Renal Stones. EAU-EBU Update Series. 2007;5(3):126-136.

Tamm-Horsfall protein

Tamm-Horsfall protein (THP) is an 80-kDa glycoprotein synthesised exclusively in the thick ascending limb of the loop of Henle’s loop (TAL). The protein was isolated from the human urine nearly 50 years ago by Tamm and Horsfall. Most authors believe that it is an effective inhibitor of COM crystal aggregation in solutions with high pH, low ionic strength and low concentration of divalent ions and THP.3Basavaraj DR, Biyani CS, Browning AJ, Cartledge JJ. The Role of Urinary Kidney Stone Inhibitors and Promoters in the Pathogenesis of Calcium Containing Renal Stones. EAU-EBU Update Series. 2007;5(3):126-136.

Glycosaminoglycans

Glycosaminoglycans (GAGs) is one of the macromolecules present in the stone matrix. Main GAGs found in stone matrix were identified as heparan sulphate and hyaluronic acid and are thought to play an important role in calcium oxalate crystallization. In vitro studies have shown that GAGs act as inhibitors of calcium oxalate crystal growth and crystal aggregation.3Basavaraj DR, Biyani CS, Browning AJ, Cartledge JJ. The Role of Urinary Kidney Stone Inhibitors and Promoters in the Pathogenesis of Calcium Containing Renal Stones. EAU-EBU Update Series. 2007;5(3):126-136.

Renal lithostathine

Lithostathine is a protein of pancreatic secretion that inhibits calcium carbonate crystal growth. This protein is localised to the cells of the proximal tubules and thick ascending limbs of the loop of Henle. Because of its structural and functional similarities with pancreatic lithostathine, it was called renal lithostathine (RL). RL appears to control growth of calcium carbonate crystals.3Basavaraj DR, Biyani CS, Browning AJ, Cartledge JJ. The Role of Urinary Kidney Stone Inhibitors and Promoters in the Pathogenesis of Calcium Containing Renal Stones. EAU-EBU Update Series. 2007;5(3):126-136.

Other macromolecules

Human urinary trefoil factor (THF1) belongs to the trefoil factor family proteins that may act as a potent inhibitor of calcium oxalate crystal growth. Calgranulin, an S100 protein, is present in the kidney and human urine and can inhibit growth of calcium oxalate crystals, which is the major component of kidney stones. The inhibitory properties of calgranulin may be due to its ability to bind to the crystal surface.3Basavaraj DR, Biyani CS, Browning AJ, Cartledge JJ. The Role of Urinary Kidney Stone Inhibitors and Promoters in the Pathogenesis of Calcium Containing Renal Stones. EAU-EBU Update Series. 2007;5(3):126-136.

Recommendations for stone inhibition

American Urological Association (AUA) Guidelines

The purpose of AUA 2014 guidelines is to provide a clinical framework for the prevention, diagnosis, and follow-up of adult patients with kidney stones. Out of the many guideline statements few are described below.7Pearle MS, Goldfarb DS, Assimos DG, et al. Medical management of kidney stones: AUA guideline. J Urol. 2014 Aug;192(2):316–24.

Evaluation

Diet therapies

  • Clinicians should recommend to all SFs a fluid intake that will achieve a urine volume of at least 2.5 liters daily.
  • Clinicians should counsel patients with calcium stones and relatively high urinary calcium to limit sodium intake and consume 1,000-1,200 mg per day of dietary calcium.
  • Clinicians should counsel patients with cystine stones to limit sodium and protein intake.
  • Clinicians should counsel patients with uric acid stones or calcium stones and relatively high urinary uric acid to limit intake of non-dairy animal protein.

Pharmacologic therapies

  • Clinicians should offer thiazide diuretics to patients with high or relatively high urine calcium and recurrent calcium stones.
  • Clinicians should offer potassium citrate therapy to patients with recurrent calcium stones and low or relatively low urinary citrate.
  • Clinicians should offer allopurinol to patients with recurrent calcium oxalate stones who have hyperuricosuria and normal urinary calcium.
  • Clinicians should offer potassium citrate to patients with uric acid and cystine stones to raise urinary pH to an
    optimal level.

Follow-up

  • Clinicians should obtain a single 24-hour urine specimen for stone risk factors within six months of the initiation of treatment to assess response to dietary and/or medical therapy.
  • After the initial follow-up, clinicians should obtain a single 24-hour urine specimen annually or with greater frequency, depending on stone activity, to assess patient adherence and metabolic response.
  • Clinicians should obtain a repeat stone analysis, when available, especially in patients not responding to treatment.
  • Clinicians should monitor patients with struvite stones for reinfection with urease-producing organisms and utilise strategies to prevent such occurrences.

The European Association of Urology (EAU) Guidelines

The European Association of Urology (EAU) guidelines help urologists assess evidence-based management of stones/calculi and incorporate recommendations into clinical practice. Few recommendations of the guidelines are mentioned below.8Türk C, Knoll T, Petrik A, et al. EAU Guidelines on Urolithiasis. 2016. Available from: https://uroweb.org/wp-content/uploads/EAU-Guidelines-Urolithiasis-2016-1.pdf. [Accessed on 4th November 2017].

Recommendations

  • Offer α-blockers as MET as one of the treatment options.
  • With fever or solitary kidney, and when diagnosis is doubtful, immediate imaging is indicated.
  • Prescribe potassium citrate.
  • Advice patients to follow a diet reduced in fat and oxalate.8
  • Perform a contrast study if stone removal is planned and the anatomy of the renal collecting system needs to be assessed.
  • Use enhanced CT in complex cases because it enables 3D reconstruction of the collecting system, as well as measurement of stone density and skin-to-stone distance. intravenous urogram may also be used.
  • In pregnant women, use MRI as a second-line imaging modality.
  • In pregnant women, use low-dose CT as a last-line option.
  • Urgently decompress the collecting system in case of sepsis with obstructing stones, using percutaneous drainage or ureteral stenting.
  • Delay definitive treatment of the stone until sepsis is resolved.
  • Offer perioperative antibiotic prophylaxis to all patients undergoing endourological treatment.

Conclusion

Stone formation is a complex process involving crystal nucleation, aggregation and/or secondary nucleation, fixation within the kidney, and more aggregation and secondary nucleation. Deficiency of inhibitors in the urine is almost certain to predispose to stone disease. Citrate, pyrophosphate, and perhaps magnesium are the main inhibitors for calcium phosphate and calcium oxalate precipitation.

References

  1. Xu H, Zisman AL, Coe FL, Worcester EM. Kidney stones: an update on current pharmacological management and future directions. Expert Opin Pharmacother. 2013 Mar;14(4):435–47.
  2. Heilberg IP, Schor N. Renal Stone Disease: Causes, Evaluation and Medical Treatment. Arq Bras Endocrinol Metabol. 2006 Aug;50(4):823–31.
  3. Basavaraj DR, Biyani CS, Browning AJ, Cartledge JJ. The Role of Urinary Kidney Stone Inhibitors and Promoters in the Pathogenesis of Calcium Containing Renal Stones. EAU-EBU Update Series.2007;5(3):126-136.
  4. Johri N, Cooper B, Robertson W. An update and practical guide to renal stone management. Nephron Clin Pract. 2010;116(3):c159–71.
  5. Ratkalkar VN, and Kleinman JG. Mechanisms of Stone Formation. Clin Rev Bone Miner Metab. 2011 Dec; 9(3-4):187–197.
  6. Coe FL, Evan A, and Worcester E. Kidney stone disease. J Clin Invest. 2005 Oct 1; 115(10): 2598–2608.
  7. Pearle MS, Goldfarb DS, Assimos DG, et al. Medical management of kidney stones: AUA guideline. J Urol. 2014 Aug;192(2):316–24.
  8. Türk C, Knoll T, Petrik A, et al. EAU Guidelines on Urolithiasis. 2016. Available from: https://uroweb.org/wp-content/uploads/EAU-Guidelines-Urolithiasis-2016-1.pdf. [Accessed on 4 November 2017].
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