Submit manuscript...
Open Access Journal of
eISSN: 2576-4578

Translational Medicine & Research

Correspondence:

Received: January 01, 1970 | Published: ,

Citation: DOI:

Download PDF

Abstract

Nephrolithiasis or urinary stone disease is a common problem across the world. Ample of research is going on in expedition for extenuating this disease condition. The procedure of preparing stones in the kidney, bladder or urethra is called as Nephrolithiasis. Stones form twice as often in men as women. The characteristic of stones that impede the renal pelvis is unbearable, blinking pain that goes from the flank to the groin or to the genital area and inner thigh. Control diet, use of prescribed medicines, and proper nutrient use can assist in thwart the development of kidney stones. Obe¬sity surge the threat of kidney stones. However, diminish in weight could deterrence of kidney stones if taken with a high ani¬mal protein intake. A vigilant medical and dietary history, stone analysis, serologic tests, and urine analysis comprise the preliminary screening in patients who have been identified with stones. Computed tomography and multi detector computed tomography played vital role in exploration of choice for the characterization of urinary stone disease. The appearance of dual–energy CT has further armoured the pre–eminence of this modality over other imaging techniques in the management of nephrolithiasis. This review is an effort to revitalize the previous data available for nephrolithiasis, basically work on its diagnosis and healing and endow with comprehensive and up–to–date information on area under discussion. This article also put light on synthetic drugs and medicines accessible for the mitigation of nephrolithiasis in the internationally and also discuss a part mentioning risk factors and management of nephrolithiasis.

Keywords: computed topography, cystine, hematuria, metabolic evaluation, medical exclusive therapy, pathophysiology

Introduction

Nephrolithiasis is one of the main ailment of the urinary tract and is a chief source of morbidity. Stone formation is one of the painful urologic disorders that happen in approximately 15% of the global population and its re–occurrence rate in males is 74–86% and 45–62% in female. Kidney stones are linked with chronic kidney disease. Preventing reappearance is precisely to the type of stone like calcium oxalate, calcium phosphate, cystine, magnesium ammonium phosphate and uric acid stones.1,2

Renal stone formation and the biggest chemical stone composition depend on age and gender. The majority stones are formed in older age people. However, clinical interpretations have mentioned not only an altering frequency and composition of urinary calculi but also a swing in gender and age–related incidences. Con­tributing risk factors for kidney stones are obesity, insulin resistance and gastrointestinal pathology, living in warmer climates, and certain dietary patterns and medications.3–6

The escalating frequency of nephrolithiasis is associated with rising utilization of imaging for diagnosis, treatment planning, and post treatment follow–up. Imaging in nephrolithiasis has rise over the years due to technologic advancement and an improved understanding of the disease process. Since its beginning in the 1990s, unenhanced computed tomogra­phy has become the gold standard for the characterization of urinary stone disease.7–9

Classification of nephrolithiasis

Hypercalciuria

  1. Absorptive hypercalciuria
  2. Renal hypercalciuria
  3. Resorptive hypercalciuria

Hyperuricosuric calcium nephrolithiasis

Hypocitraturic calcium nephrolithiasis

  1. Chronic diarrheal syndrome
  2. Distal RTA
  3. Thiazide–induced

Hyperoxaluric calcium nephrolithiasis

  1. Primary hyperoxaluria
  2. Dietary hyperoxaluria
  3. Enteric hyperoxaluria

Gouty diathesis

Cystinuria

Infection stones

Figure 1 & 2

Figure 1 Therapeutic indication as per size (1 to 2 cm) of kidney stones.

Figure 2 Therapeutic indication as per size (around 10 cm) of kidney stones.

Kidney stone formation theories in the form of flow chart

Flowchart 1–5

Flowchart 1 Blocked lymphatic theory >10,11.

Flowchart 2 Vascular theory 12.

Flowchart 3 Free particle theory 13,14.

Flowchart 4 Fixed particle theory 15.

Flowchart 5 Randall’s plaque hypothesis 16,18.

Stone formation as per anatomic site

There are quite a few diverse theories according to that stone formation happened in the kidney:

  1. Deposition of calcium on the basement membrane of collecting tubules and on the surface of papillae.
  2. Deposition of linear precipitates of calcium within the renal lym­phatics to produce obstruction and breakdown of the membrane separating the lymphatics from the collect­ing tubules.
  3. Intratubular deposits of amorphous necrotic calcific cellular debris or organized mi–crocalculi (Table 1).

Type

Adults (%)

Children (%)

Uric Acid

10 to 16

1 to 3

Cystine

6 to 9

1

Calcium Phosphate

6 to 15

22 to 28

Magnesium Ammonium Phosphate

1 to 3

8 to 12

Calcium Oxalate

54 to 60

43 to 58

Table 1 Proportion of percentage of kidney stones as per age factor.

Stone formation theories

Crystallization and stone formation in urine engage a vastly complex process, the true nature of which is still scantily understood. The immense efforts devoted to the research of this condition have furnished so far only accessory information and do not seem to have penetrated the core of the problem.

Nucleation theory

Stone formation is initiated by the presence of a crystal or foreign body in urine supersaturated with a crystallizing salt that favours growth of a crystal lattice.

Randall’s plaque theory

Randall in 1937 mentioned two kinds of calcific foci in the renal pyramids. Type I lesions were tiny calcified plaques located in the interstitial tissue below the surface epithelium of the renal papillae which progressively became exposed to the urine by the erosion of the epithelium overlying the plaque. Type II lesions contained of calcific masses found in the terminal parts of the ducts of Bellini.19

Vascular theory

Vasa recta and other capillaries in the renal papillary region, due to their repeated bifurcations are prone to quick changes from laminar to turbulent flow of blood, which is similar to as seen with the bifurcated arteries. Owing to this repeated blood flow changes as well as their hyperosmolar and hypoxic milieu, they are exposed to afflictions and injuries and as is case with arteries, these blood flow changes and vulnerable tissue structures result in the formation of atherosclerotic plaques in the vasculature of the renal papilla followed by calcification.11

Blocked lymphatic theory

The theory describes that renal lymphatic system drains the renal pelvis and prevents accretion and aggregation of precipitating salts in the kidney. But in case of destruction of these renal lymphatics, salt precipitates tend to grow into big concretions during their passage through the lymph vessels and get thwarted at the fornices of the calyces just outside the collecting system where the concretions eventually grind down the surrounding membrane ultimately causing urine percolation and then grow into big renal stones by being in constant contact with the salts and other organic substances in the urine.12

Diagnostic characterization

Symptoms & signs at presentation

Symptoms related to stones at specific sites:

  1. Caliceal stones
  2. Renal pelvic stones
  3. Proximal ureteral stones
  4. Distal uretheral stones

Associated non renal symptoms

Variability of symptoms

Finding on physical examination

Radiographic findings

  1. Intravenous urography
  2. Tomography
  3. Retrograde urography
  4. Ultrasonography
  5. CT scanning

Surgical treatment for renal stones:

  1. Hypothermia in urologic surgery
  2. Intraoperative X rays

Open surgical procedures:

  1. Nephrectomy and partial nephrectomy
  2. Pyelolithotomy
  3. Extended Pyelolithotomy
  4. Pyelonephrolithotomy
  5. Coagulum Pyelolithotomy
  6. Anatropic Nephrolithotomy
  7. Radial nephrotomy

Flowchart 6

Flowchart 6 Metabolic evaluation 20,21.

Role of individual weight on kidney stone

Obesity plays a vital role in kidney stones more than dietary factors. The related changes in body compo­sition pretence biophysical challenges linked with troubled thermogenesis and dehydration. The part of body water diminishes due to hydrophobicity of body fat with escalating obesity, by which dehydration surge. Addition to that, the dwindle in surface area to body volume make difficult heat exchange and metabolic rate. Obesity is a proinflam­matory state related to electrolyte imbalances and transformed urine chemistry. Fatty persons with kidney stones are exposed to hyperuricemia, gout, hypoci­traturia, hyperuricosuria, and uric acid stones. A current retrospective investigation found that patients with diabetes and kid­ney stones emit more oxalate and have lower urine pH, which is partially an outcome of elevated sulfate excretion and fewer acid emitted as ammonium ions.22–24

Role of fructose intake

Escalated fructose intake surges urinary calcium excretion in persons with magnesium deficiency, and fructose is the barely dietary carbohydrate known to raise uric acid lev­els. Augmented dietary fructose has been related with up to a 40 percent high risk of kidney stones. However, sugar–sweetened beverages and orange juice also play important role to gout.25,26

Kidney stone and alkaline urine

Eating a diet high in fruits and vegetables produces alkalinizing urine. For impediment of calcium oxalate, cystine, and uric acid stones, urine should be alkalinized. Western diets are characteristically high in acid–producing foods, such as grains, dairy products, legumes, and meat. So more problems associated with kidney stones in those countries.27,28

Low urine pH and kidney stone

Sodium chloride sinks urine pH but it can snowball the blood pressure, insulin excretion, and urine calcium excretion. For deterrence of calcium phosphate and struvite stones, urine should be acidified. Cranberry juice or betaine can dwindle the urine pH without the undesirable effects related to with foods with acidic environment.29

Treatment of nephrolithiasis

  1. Non–steroidal anti–inflammatory drugs (NSAIDs) and opioids are used to relieve pain associated with nephrolithiasis.30
  2. Medical expulsive therapy is used to allow spontaneous expulsion of moderately sized distal ureteral calculi from the urinary tract. Offer α–blockers as MET as one of the treatment options, in particular for (distal) ureteral stones>5mm.31
  3. Allopurinol is prescribed for the treatment of calcium oxalate and uric acid stones.32
  4. Thiazide and related diuretics are indicated in renal stone disease associated with idiopathic hypercalciuria.33
  5. Acetohydroxamic acid is prescribed in case of struvite stones that are usually formed due to or are associated with the UTI caused by urease producing organisms.34
  6. D–penicillamine is used in case of cystine stones for treating cystinuria.35
  7. Alpha mercaptopropionylglycine (or tiopronin) is a better tolerated alternative to D–penicillamine, but its efficacy and availability is very less as compared to D–penicillamine.36
  8. Potassium citrate basically raises urinary citrate levels. Citrate complexes urinary calcium to a soluble form, thus inhibiting calcium phosphate and calcium oxalate crystal aggregation.37
  9. Chemolytic dissolution therapy is a dissolution technique that aims at the dissolution and removal of urinary stones via pH alteration, chelation and disulphide rearrangement.38
  10. Sodium cellulose phosphate is known to bind to intestinal calcium and thus inhibit absorption of calcium leading to reduction in the elevated calcium excretion thus reducing calcium stone formation.39<
  11. Acetohydroxamic acid is prescribed in case of struvite stones that are usually formed due to or are associated with the UTI caused by urease producing organisms.40
  12. Chemolytic dissolution therapy can be used as an adjunct to extracorporeal shock wave lithotripsy and Percutaneous nephrolithotomy, or can also be used to completely avoid surgery (Table 2–4).41

Type of Formulations/Medicines

Examples

Potassium Sparing Diuretics

Triamterene

Antibiotics

Sulfonamides, Amoxicillin, Ceftriaxone

Carbonic Anhydrase Inhibitors

Acetazolamide, Topiramate

Uric Acid Production Decrement

Allopurinol

Sulfonyl Ureas

For type 2 diabetes mellitus

Potassium Channel Blockers

Amiodarone, Sotalol

Table 2 Medicines used to plummet kidney stone formation.

Management Type

Suggestive Approach or Therapies

Pain management

Codeine, Acetaminophen, Hydrocone

Fluids

Oral intake of water, Intravenous saline if patient is unconscious

Antispasmodics

Doxazosin, Tamsulosin, Nifedipine,

Table 3 Management of kidney stones in adults.

Clinical Indications

Treatment

Common

Stone less than 1 cm in kidney

Shock wave lithotripsy

Stone less than 1 cm in kidney in women

Ureteroscopy with lithotripsy (semi rigid)

Stone less than 1 cm in proximal ureter, stones less than 1.5 cm in kidney

Ureteroscopy with lithotripsy (flexible)

stones greater than 1.5 cm in kidney or proximal ureter

Percutaneous nephrolithotomy

Uncommon

Large stone in middle or distal ureter

Open or laparoscopic ureterolithotomy

Larges tones in horseshoe kidney

Open or laparoscopic ureterolithotomy

Full staghorn calculi

Anatrophic nephrolithotomy

Table 4 Treatment of Various clinical indications of Nephrolithiasis.

Conclusion

Nephrolithiasis is a frequent disease with an escalating occurrence and pervasiveness worldwide. Lifestyle and dietary choices concerned in the complex of the metabolic syndrome are imperative factors contributing to such developments. Keeping a close watch on one’s body weight, maintaining healthy routine and healthy diet that includes vegetables, fruits, fibres and adequate amount of fluids is forever a good call not only when it comes to preventing nephrolithiasis but any ailment condition, because these are the indices that when compromised might lead to one or the other health impairments. Metabolic evaluation is a significant component of management for patients with nephrolithiasis. Although empiric drug therapy may give effectual prophylaxis against stone recurrence, treatment based on metabolic evaluation allows classification of patients into simple diagnostic groups to which an uncomplicated treatment algorithm can be applied in a cost–effective manner. In addition, characterization is beneficial because of the supplementary medical information it gives. Multidetector CT currently plays an imperative management role in patients with urolithiasis, from the initial diagnosis in patients with acute flank pain to treatment planning and posttreat­ment follow–up.

Acknowledgements

None.

Conflict of interest

The author declares no conflict of interest.

References

  1. Soundararajan P, Mahesh R, Ramesh T, et al. Effect of Aerva Lanata on calcium oxalate urolithiasis in rats. Indian J Exp Biol. 2006;44(12):981–986.
  2. Singh RG, Behura SK, Kumar R. Litholytic Property of Kulattha (Dolichous Biflorus) vs Potassium Citrate in Renal Calculus Disease: a comparative study. J Assoc Physicians India. 2010;58:286–289.
  3. Daudon M, Dore JC, Jungers P, et al. Changes in stone composition according to age and gender of patients: a multivariate epidemiological approach. Urol Res. 2004;32(3):241–247.
  4. Strope SA, Wolf Jr JS, Hollenbeck BK. Changes in gender distribution of urinary stone disease. Urology. 2010;75(3):543.e.1–546.e1.
  5. Scales Jr CD, Curtis LH, Norris RD. Changing gender prevalence of stone disease. J Urol. 2007;177(3):979–982.
  6. Rule AD, Bergstralh EJ, Melton LJ III, et al. Kidney stones and the risk for chronic kidney disease. Clin J Am Soc Nephrol. 2009;4(4):804–811.
  7. Smith RC, Rosenfield AT, Choe KA, et al. Acute flank pain: comparison of non–contrast–enhanced CT and intravenous urography. Radiology. 1995;194(3):789–794.
  8. Smith RC, Verga M, McCarthy S, et al. Diagnosis of acute flank pain: value of unenhanced helical CT. AJR Am J Roentgenol. 1996;166(1):97–101.
  9. Saw KC, McAteer JA, Monga AG, et al. Helical CT of urinary cal­culi: effect of stone composition, stone size, and scan collimation. AJR Am J Roentgenol. 2000;175(2):329–332.
  10. Carr RJ. A new theory on the formation of renal calculi. Br J Urol. 1954;26(2):105–117.
  11. King JS Jr. Currents in renal stone research. Clin Chem. 1971;17(10):971–982.
  12. Stoller ML, Meng MV, Abrahams HM, et al. The primary stone event: a new hypothesis involving a vascular etiology. J Urol. 2004;171(5):1920–1924.
  13. Evan AP. Physiopathology and etiology of stone formation in the kidney and the urinary tract. Pediatr Nephrol. 2010;25(5):831–841.
  14. Robertson WG. The scientific basis of urinary stone formation. In: Mundy AR, et al. editors. The scientific basis of urology. 3rd ed. USA: CRC Press; 2010. p. 162–181.
  15. Knoll T. Epidemiology, pathogenesis, and pathophysiology of urolithiasis. Eur Urol Suppl. 2010;9(12):802–806.
  16. Evan AP, Coe FL, Lingeman JE, et al. Mechanism of formation of human calcium oxalate renal stones on Randall’s plaque. Anat Rec (Hoboken). 2007;290(10):1315–1323.
  17. Randall A. The origin and growth of renal calculi. Ann Surg. 1937;105(6):1009–1027.
  18. Matlaga BR, Coe FL, Evan AP, et al. The role of Randall’s plaques in the pathogenesis of calcium stones. The Journal of Urology. 2007;177(1):31–38.
  19. Green W, Ratan H. Molecular mechanisms of urolithiasis. Urology. 2013;81(4):701–704.
  20. Borghi L, Meschi T, Guerra A, et al. Randomized prospective study of a nonthiazide diuretic, indapamide, in preventing calcium stone recurrences. J Cardiovasc Pharmacol. 1993;22(Suppl 6):S78–S86.
  21. Nicar MJ, Peterson R, Pak CY. Use of potassium citrate as potassium supplement during thiazide therapy of calcium nephrolithiasis. J Urol. 1984;131(3):430–433.
  22. Batmanghelidj F, Kohlstadt I. Water: a driving force in the musculoskel­etal system. In: Scientific Evidence for Musculoskeletal, Bariatric and Sports Nutrition. USA: CRC Press; 2006. p. 127–135.
  23. Livingston EH, Kohlstadt I. Simplified resting metabolic rate–predicting formulas for normal–sized and obese individuals. Obes Res. 2005;13(7):1255–1262.
  24. Ekeruo WO, Tan YH, Young MD, et al. Metabolic risk factors and the impact of medical therapy on the management of nephrolithiasis in obese patients. J Urol. 2004;172(1):159–163.
  25. Breslau NA, Brinkley L, Hill KD, et al. Relationship of animal protein–rich diet to kidney stone formation and calcium metabolism. J Clin Endocrinol Metab. 1988;66(1):140–146.
  26. Taylor EN, Curhan GC. Fructose consumption and the risk of kidney stones. Kidney Int. 2008;73(2):207–212.
  27. Trinchieri A, Esposito N, Castelnuovo C. Dissolution of radiolucent renal stones by oral alkalinization with potassium citrate/potassium bicarbon­ate. Arch Ital Urol Androl. 2009;81(3):188–191.
  28. Sakhaee K, Nicar M, Hill K, et al. Contrasting effects of potassium citrate and sodium citrate therapies on urinary chemistries and crystal­lization of stone–forming salts. Kidney Int. 1983;24(3):348–352.
  29. Pizzarelli F, Peacock M. Effect of chronic administration of ammonium sulfate on phosphatic stone recurrence. Nephron. 1987;46(3):247–252.
  30. Micali S, Grande M, Sighinolfi MC, et al. Reviews in endourology: medical therapy of urolithiasis. Journal of Endourology. 2006;20(11):841–847.
  31. Romics I. The role of alpha–adrenoreceptors in the treatment of urological diseases. Neurochem Int. 2007;51(5):328–331.
  32. Grosser T, Smyth E, FitzGerald GA. Anti‒inflammatory, antipyretic and analgesic agents; pharmacotherapy of gout. In: Brunton LL, editor. Goodman and Gilman's the pharmacological basis of therapeutics. 12th ed. New York: McGraw Hill; 2011. p. 959–1004.
  33. Finkielstein VA, Goldfarb DS. Strategies for preventing calcium oxalate stones. CMAJ. 2006;174(10):1407–1409.
  34. Saklayen MG. Medical management of nephrolithiasis. Med Clin North Am. 1997;81(3):785–799.
  35. Reynolds TM. Chemical pathology clinical investigation and management of nephrolithiasis. J Clin Pathol. 2005;58:134–140.
  36. Spernat D, Kourambas J. Urolithiasis– medical therapies. BJU Int. 2011;108(Suppl 2):9–13.
  37. Heilberg IP, SchorN. Renal stone disease: causes, evaluation and medical treatment. Arq Bras Endocrinol Metabol. 2006;50(4):823–831.
  38. Korets R, Graversen JA, Gupta M. Dissolution of stones by oral and irrigative therapy. In: Talati JJ, Tiselius HG, Albala DM, Ye Z, editors. Urolithiasis: basic science and clinical practice. London: Springer–Verlag; 2012. p. 533–537.
  39. Bandi G, Nakada SY, Penniston KL. Practical approach to metabolic evaluation and treatment of the recurrent stone patient. WMJ. 2008;107(2):91–100.
  40. Manjula K, Pazhanichami K, Rajendran K, et al. Herbal Remedy for Urinary Stones. In: Rana MK, editor. Vegetables and human health. India: Scientific Publisher; 2015. p. 454–668.
  41. Heimbach D, Bӓumler D, Schoeneich G, et al. Percutaneous chemolysis– an important tool in the treatment of urolithiasis. Int Urol Nephrol. 1998;30(6):655–664.
Creative Commons Attribution License

© . This is an open access article distributed under the terms of the, which permits unrestricted use, distribution, and build upon your work non-commercially.