Kidney stone pathophysiology: Difference between revisions

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{{Kidney stone}}
{{Kidney stone}}


{{CMG}}; {{AE}}  
{{CMG}}; {{AE}} {{ADS}}
==Overview==
==Overview==
It is understood that nephrolithiasis is the result of combination of different mechanism responsible for different types of stones. Calcium stones are the most common type of kidney stones.  Approximately 80% of all calcium stones are [[calcium oxalate]] stones. The pathophysiology of calcium stones is complex and involves dietary concerns, [[hypercalciuria]], [[hypocitaturia]], [[hyperoxaluria]][[hyperuricosuria|, hyperuricosuria]] and biomineralization. The underlying pathophysiological mechanisms responsible for uric acid stones are low urine volume[[Hyperuricosuria|, hyperuricosuria]] and high acidic urine. [[Cystinuria]] is a rare hereditary gene disorder which causes impaired renal reabsorption of cationic amino acids and cystine. It is caused by mutations in either of the two subunits (rBAT(SLC3A2) and b0,+AT(SLC7A9)) forming cystine stones. Struvite stones are usually seen in patients which have infection with [[urease]] +ve organisms. Urine pH is usually alkaline (>7.2).  Nephrolithiasis can be passed on to following generations due to rare causes of hypercalciuria such as hereditary [[distal renal tubular acidosis]], [[dent disease]], [[Bartter syndrome]] types III and IV, autosomal dominant hypocalcemic hypercalciuria and familial [[hypomagnesemia]]. Nephrolithiasis associated with [[Hyperparathyroidism]], [[Gout]], [[Hypocitaturia]], [[Sarcoidosis]], chronic [[urinary tract infections]] and [[Obesity]].On gross pathology, the characteristic findings of nephrolithiasis include location = 80% unilateral, usually in calyces, pelvis or bladder. The size=variable, 2-3 mm usually. All stones contain an organic matrix of mucoprotein. The shape of struvite stone is staghorn shaped. On microscopic histopathological analysis, the characteristic findings of nephrolithiasis include different shapes of stones/crystals are  such as cystine= hexagonal, struvite= coffin lid shape, calcium oxalate= pyramid shape to dumbbell shape and [[uric acid]]= rectangular/rhomboidal. Oxalate crystals are highlighted by polarized light. Also, foreign body giant cells and macrophages are seen with the stones.


==Pathophysiology==
==Pathophysiology==


===Pathogenesis===
===Pathogenesis===
*It is understood that nephrolithiasis is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].
*It is understood that nephrolithiasis is the result of combination of different mechanism responsible for different types of stones:
*[Pathogen name] is usually transmitted via the [transmission route] route to the human host.
 
*Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
====== Calcium stones ======
*[Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
* Calcium stones are the most common type of kidney stones.<ref name="pmid1962646">{{cite journal |vauthors=Pak CY |title=Etiology and treatment of urolithiasis |journal=Am. J. Kidney Dis. |volume=18 |issue=6 |pages=624–37 |date=December 1991 |pmid=1962646 |doi= |url=}}</ref>
*The progression to [disease name] usually involves the [molecular pathway].
* Approximately 80% of all calcium stones are [[calcium oxalate]] stones.<ref name="pmid2585627">{{cite journal |vauthors=Mandel NS, Mandel GS |title=Urinary tract stone disease in the United States veteran population. II. Geographical analysis of variations in composition |journal=J. Urol. |volume=142 |issue=6 |pages=1516–21 |date=December 1989 |pmid=2585627 |doi= |url=}}</ref><ref name="pmid12649987">{{cite journal |vauthors=Hochreiter W, Knoll T, Hess B |title=[Pathophysiology, diagnosis and conservative therapy of non-calcium kidney calculi] |language=German |journal=Ther Umsch |volume=60 |issue=2 |pages=89–97 |date=February 2003 |pmid=12649987 |doi=10.1024/0040-5930.60.2.89 |url=}}</ref>
*The pathophysiology of [disease/malignancy] depends on the histological subtype.
* The pathophysiology of calcium stones is complex and involves:<ref name="pmid9337641">{{cite journal |vauthors=Messa P, Marangella M, Paganin L, Codardini M, Cruciatti A, Turrin D, Filiberto Z, Mioni G |title=Different dietary calcium intake and relative supersaturation of calcium oxalate in the urine of patients forming renal stones |journal=Clin. Sci. |volume=93 |issue=3 |pages=257–63 |date=September 1997 |pmid=9337641 |doi= |url=}}</ref>
** Dietary concerns<ref name="pmid93376412">{{cite journal |vauthors=Messa P, Marangella M, Paganin L, Codardini M, Cruciatti A, Turrin D, Filiberto Z, Mioni G |title=Different dietary calcium intake and relative supersaturation of calcium oxalate in the urine of patients forming renal stones |journal=Clin. Sci. |volume=93 |issue=3 |pages=257–63 |date=September 1997 |pmid=9337641 |doi= |url=}}</ref><ref name="pmid23392537">{{cite journal |vauthors=Trinchieri A |title=Diet and renal stone formation |journal=Minerva Med. |volume=104 |issue=1 |pages=41–54 |date=February 2013 |pmid=23392537 |doi= |url=}}</ref><ref name="pmid26150027">{{cite journal |vauthors=Prezioso D, Strazzullo P, Lotti T, Bianchi G, Borghi L, Caione P, Carini M, Caudarella R, Ferraro M, Gambaro G, Gelosa M, Guttilla A, Illiano E, Martino M, Meschi T, Messa P, Miano R, Napodano G, Nouvenne A, Rendina D, Rocco F, Rosa M, Sanseverino R, Salerno A, Spatafora S, Tasca A, Ticinesi A, Travaglini F, Trinchieri A, Vespasiani G, Zattoni F |title=Dietary treatment of urinary risk factors for renal stone formation. A review of CLU Working Group |journal=Arch Ital Urol Androl |volume=87 |issue=2 |pages=105–20 |date=July 2015 |pmid=26150027 |doi=10.4081/aiua.2015.2.105 |url=}}</ref>
** [[Hypercalciuria]]
** [[Hypocitaturia]]
** [[Hyperoxaluria]]
** [[Hyperuricosuria]]
** Biomineralization<ref name="pmid11786090">{{cite journal |vauthors=Umekawa T, Chegini N, Khan SR |title=Oxalate ions and calcium oxalate crystals stimulate MCP-1 expression by renal epithelial cells |journal=Kidney Int. |volume=61 |issue=1 |pages=105–12 |date=January 2002 |pmid=11786090 |doi=10.1046/j.1523-1755.2002.00106.x |url=}}</ref>
 
====== Uric acid stones ======
* The underlying pathophysiological mechanisms responsible for uric acid stones are:
** Low urine volume
** [[Hyperuricosuria]]
** High acidic urine.
 
====== Cystine stones ======
* [[Cystinuria]] is a rare hereditary gene disorder which causes impaired renal rabsorption of cationic amino acids and cystine.
* The cationic amino acids commonly involved are called as COLA amino acids that stands for:
** C= [[cystine]]
** O=[[ornithine]]
** L=[[lysine]]
** A=[[arginine]]  
* It is caused by mutations in either of the two subunits (rBAT(SLC3A2) and b0,+AT(SLC7A9)) forming the apical transporter for cationic amino acids system b0,+; thus excretion of the dibasic COLA amino acids is increased.<ref name="pmid25685869">{{cite journal |vauthors=Pereira DJ, Schoolwerth AC, Pais VM |title=Cystinuria: current concepts and future directions |journal=Clin. Nephrol. |volume=83 |issue=3 |pages=138–46 |date=March 2015 |pmid=25685869 |doi= |url=}}</ref>
 
====== Struvite/Ammonium magnesium sulfate stones ======
* These are usually seen in patients which have infection with [[urease]] +ve organisms.<ref name="pmid12135839">{{cite journal |vauthors=Bichler KH, Eipper E, Naber K, Braun V, Zimmermann R, Lahme S |title=Urinary infection stones |journal=Int. J. Antimicrob. Agents |volume=19 |issue=6 |pages=488–98 |date=June 2002 |pmid=12135839 |doi= |url=}}</ref><ref name="pmid24818849">{{cite journal |vauthors=Flannigan R, Choy WH, Chew B, Lange D |title=Renal struvite stones--pathogenesis, microbiology, and management strategies |journal=Nat Rev Urol |volume=11 |issue=6 |pages=333–41 |date=June 2014 |pmid=24818849 |doi=10.1038/nrurol.2014.99 |url=}}</ref>
* Urine pH is usually alkaline (>7.2)
 
The following table summarizes major mechanism of stone formation: <ref name="Moe2006">{{cite journal|last1=Moe|first1=Orson W|title=Kidney stones: pathophysiology and medical management|journal=The Lancet|volume=367|issue=9507|year=2006|pages=333–344|issn=01406736|doi=10.1016/S0140-6736(06)68071-9}}</ref><ref name="FreitagHruska1983">{{cite journal|last1=Freitag|first1=Jeffrey|last2=Hruska|first2=Keith|title=Pathophysiology of Nephrolithiasis|year=1983|pages=523–553|doi=10.1007/978-1-4613-3524-5_16}}</ref><ref name="pmid22460990">{{cite journal |vauthors=Gambaro G, Fabris A, Abaterusso C, Cosaro A, Ceol M, Mezzabotta F, Torregrossa R, Tiralongo E, Del Prete D, D'Angelo A, Anglani F |title=Pathogenesis of nephrolithiasis: recent insight from cell biology and renal pathology |journal=Clin Cases Miner Bone Metab |volume=5 |issue=2 |pages=107–9 |date=May 2008 |pmid=22460990 |doi= |url=}}</ref><ref name="Sakhaee2009">{{cite journal|last1=Sakhaee|first1=Khashayar|title=Recent advances in the pathophysiology of nephrolithiasis|journal=Kidney International|volume=75|issue=6|year=2009|pages=585–595|issn=00852538|doi=10.1038/ki.2008.626}}</ref>
{| class="wikitable"
! colspan="2" style="background:#4479BA; color: #FFFFFF;" align="center" |Type of stone/Mechanism
! style="background:#4479BA; color: #FFFFFF;" align="center" |Cause
! style="background:#4479BA; color: #FFFFFF;" align="center" |Pathophysiology
! style="background:#4479BA; color: #FFFFFF;" align="center" |Stone composition
! style="background:#4479BA; color: #FFFFFF;" align="center" |Labs
|-
| style="background:#4479BA; color: #FFFFFF;" align="center" |All stones
|Low urine volume
(raises production of solutes)
|Reduced intake or increased loss of water
|Renal water conservation
|All stones
|
* Urine volume <1 L per day
* Osmolarity >600 mOsm/kg
|-
| rowspan="16" style="background:#4479BA; color: #FFFFFF;" align="center" |Calcium stones
| rowspan="6" |[[Hypercalciuria]]
(raises saturation of calcium salts)
|Absorptive [[hypercalciuria]]
|Increased absorption in gut
| rowspan="6" |[[Calcium oxalate]] or [[phosphate]]
|Urine calcium concentrations >6 mmol/L (240 mg) per day
|-
|[[Hyperparathyroidism]]
|Increased absorption in gut and bone release
|High concentrations of [[parathyroid hormone]]
|-
|Immobilization
|[[Bone resorption]]
|High concentrations of [[vitamin D]]
|-
|Excess of [[sodium]] in the diet
|Sodium-induced physiological renal calcium leak. Possible component of gut hyperabsorption
|Urine sodium concentrations >200 mmol/L per day
|-
|Excess of [[protein]] or acid in diet
|Protein-induced bone loss and renal leak.
|
* Urine [[ammonium]] iron concentrations high
* Urine [[sulfate]] concentrations high
* [[Urine pH]] low
* Urine [[citrate]] concentrations <1·7 mmol/L per day
|-
|Range of monogenic disorders
|Bone loss, gut hyperabsorption, and renal leak in various combinations
|
|-
| rowspan="2" |[[Hypocitraturia]]
(raises levels of ionised calcium and reduces inhibitor activity against calcium salts)
|[[Renal tubular acidosis]] (distal type)
|Renal defense of [[acid-base balance]]
|[[Calcium phosphate]]
|
* Urine [[citrate]] concentrations <1·7 mmol/L per day
* Urine pH high
|-
|High acid load (absence of detectable acidemia)
|Physiological [[hypocitraturia]]
|[[Calcium oxalate]] or phosphate
|
* Urine [[citrate]] concentrations <1·7 mmol/L per day
* Urine pH low
|-
| rowspan="3" |[[Hyperoxaluria]]
(raises saturation of [[calcium oxalate]])
|Excess of [[oxalate]] in diet
|Increased delivery of luminal oxalate
| rowspan="8" |[[Calcium oxalate]]
|Urine oxalate concentrations >70·7 mmol/L per day
|-
|Bowel pathology
|Reduced formation of luminal calcium and calcium-oxalate complex
|
|-
|Increased production of endogenous oxalate
|[[Primary hyperoxaluria]] (type 1 and type 2)
|
|-
| rowspan="5" |[[Hyperuricosuria]]
(sodium urate precipitation causes crystallization of calcium salts)
|High [[purine]] intake
| rowspan="4" |Raised production and urinary excretion of sodium and urate
|
* Urine uric acid concentrations >600 mg per day
* Hyperuricaemia
|-
|[[Myeloproliferative disease|Myeloproliferative diseases]]
|
|-
|Enzymatic defects
|Urine [[uric acid]] concentrations >600 mg per day
|-
|[[Uricosuric]] drugs
|Hypouricaemia
|-
|Genetic primary renal leak
|Increased excretion of [[uric acid]]
|
|-
| style="background:#4479BA; color: #FFFFFF;" align="center" |Uric acid stones
|Low urine pH or [[hyperuricosuria]]
|
* High acid load
* [[Metabolic syndrome]]
|Titrates [[urate]] to poorly soluble uric acid
|[[Uric acid]]
|Urine pH <5·5
|-
| style="background:#4479BA; color: #FFFFFF;" align="center" |Cystine stones
|[[Cystinuria]]
|Congenital mutations of dibasic aminoacid transporter subunits rBAT and b0+AT
|Renal leak of basic aminoacids
|[[Cystine]]
|Urine concentrations of [[cystine]] high (>150 μmol/mmol creatinine)
|-
| style="background:#4479BA; color: #FFFFFF;" align="center" |Infection stones
|[[Urinary tract infection]]
|Urea-splitting organisms
|Production of [[ammonium]] and [[bicarbonate]] from [[urea]]
|
* Magnesium [[ammonium phosphate]]
* Carbonate apatite
|
* Urine pH high
* [[Pyuria]]
* Culture +ve for [[urease]]
|}


==Genetics==
==Genetics==
*[Disease name] is transmitted in [mode of genetic transmission] pattern.
*Nephrolithiasis can be passed on to following generations due to rare causes of hypercalciuria:
*Genes involved in the pathogenesis of [disease name] include [gene1], [gene2], and [gene3].
**Hereditary [[distal renal tubular acidosis]]
*The development of [disease name] is the result of multiple genetic mutations.
**[[Dent disease]]
**[[Bartter syndrome]] types III and IV
**Autosomal dominant hypocalcemic hypercalciuria
**Familial [[hypomagnesemia]]


==Associated Conditions==
==Associated Conditions==
Line 35: Line 195:


==Gross Pathology==
==Gross Pathology==
*On gross pathology,the characteristic findings of nephrolithiasis are:
*On gross pathology, the characteristic findings of nephrolithiasis are:
** Location = 80% unilateral, usually in calyces, pelvis or bladder
** Location = 80% unilateral, usually in calyces, pelvis or bladder
** Size=variable, 2 - 3 mm usually
** Size=variable, 2-3 mm usually
** All stones contain an organic matrix of mucoprotein
** All stones contain an organic matrix of mucoprotein
**Shape=
** Shape:
***Struvite stone= staghorn calculus
***Struvite stone= staghorn calculus


<gallery widths="250px">
<gallery widths="300px">


File:Càlcul ronyó.0552.jpg| Nephrolithiasis, Source: wikimedia commons<ref>By Amadalvarez - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=46706235</ref>
File:Càlcul ronyó.0552.jpg| Nephrolithiasis, Source: Wikimedia commons<ref>By Amadalvarez - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=46706235</ref>


File:Nephrolith 01.jpg|Staghorn shape of struvite stones, Source : wikimedia commons<ref>By H. Zell [GFDL (http://www.gnu.org/copyleft/fdl.html) or CC BY-SA 3.0 (https://creativecommons.org/licenses/by-sa/3.0)], from Wikimedia Commons </ref>
File:Nephrolith 01.jpg|Staghorn shape of struvite stones, Source: Wikimedia commons<ref>By H. Zell [GFDL (http://www.gnu.org/copyleft/fdl.html) or CC BY-SA 3.0 (https://creativecommons.org/licenses/by-sa/3.0)], from Wikimedia Commons </ref>


File:Kidney stones ( renal calculi ), Бубрежни камења 15.jpg| Reanl calculi, different shapes and sizes, Source : wikimedia commons<ref>By Jakupica - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=45324355</ref>
File:Kidney stones ( renal calculi ), Бубрежни камења 15.jpg| Renal calculi, different shapes and sizes, Source: Wikimedia commons<ref>By Jakupica - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=45324355</ref>
 
File:Kidney stone 5mm.png|Kidney stone with a maximum dimension of 5mm, Source: Wikimedia commons<ref>By RJHall - Own work, Public Domain, https://commons.wikimedia.org/w/index.php?curid=4070842</ref>


</gallery>
</gallery>


==Microscopic Pathology==
==Microscopic Pathology==
*On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of nephrolithiasis
*On microscopic histopathological analysis, the characteristic findings of nephrolithiasis are:
**Shapes of different stones/crystals are different:
***Cysteine= hexagonal
***Struvite= coffin lid shape
***Calcium oxalate= pyramid shape
***Calcium oxalate= dumbbell shape
***Uric acid= rectangular/rhomboidal
**Oxalate crystals are highlighted by polarized light
**Foreign body giant cells and macrophages are seen with the stones
 
<gallery widths="300px">
 
File:PMC4525130 cnr-4-137-g001.png|Type of stones. Light microscopy of urine crystals. (A) Hexagonal cystine crystal (200X); (B) coffin-lid shaped struvite crystals (200X); (C) pyramid-shaped calcium oxalate dehydrate crystals (200X); (D) dumbbell-shaped calcium oxalate monohydrate crystal (400X); (E) rectangular uric acid crystals (400X); and (F) rhomboidal uric acid crystals (400X).<ref name="pmid26251832">{{cite journal |vauthors=Han H, Segal AM, Seifter JL, Dwyer JT |title=Nutritional Management of Kidney Stones (Nephrolithiasis) |journal=Clin Nutr Res |volume=4 |issue=3 |pages=137–52 |date=July 2015 |pmid=26251832 |pmc=4525130 |doi=10.7762/cnr.2015.4.3.137 |url=}}</ref>
 
File:Oxalato.4.w.jpg|Deposits of oxalate with variable size and form; they occupy mainly distal tubules. The asterisks indicate proximal tubules, which usually do not contain these crystals, H&E seen with polarized light, X200<ref>http://kidneypathology.com/Imagenes/Diabetes/Oxalato.4.w.jpg</ref>
 
File:Ac.Urico.w.jpg| Medullary interstitial urate crystal deposits in chronic nephropathy by urates as seen after Masson's trichome stain X400<ref>http://www.kidneypathology.com/English_version/Diabetes_and_others.html</ref>
 
File:Surface of a kidney stone with tetragonal crystals of Weddellite (calcium oxalate dihydrate). REM 21.jpg|Calcium oxalate dihydrate crystals under Scanning Electron Micrograph (SEM) taken at 30 KV. Source: Wikimedia commons<ref>By Kempf EK - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=18036112</ref>
 
File:DDC-SEM of kidney stone - 2.jpg|Density-dependent color scanning electron micrograph of kidney stone, Source: Wikimedia commons<ref>By Sergio Bertazzo - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=45316797</ref>
 
</gallery>


==References==
==References==

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Amandeep Singh M.D.[2]

Overview

It is understood that nephrolithiasis is the result of combination of different mechanism responsible for different types of stones. Calcium stones are the most common type of kidney stones. Approximately 80% of all calcium stones are calcium oxalate stones. The pathophysiology of calcium stones is complex and involves dietary concerns, hypercalciuria, hypocitaturia, hyperoxaluria, hyperuricosuria and biomineralization. The underlying pathophysiological mechanisms responsible for uric acid stones are low urine volume, hyperuricosuria and high acidic urine. Cystinuria is a rare hereditary gene disorder which causes impaired renal reabsorption of cationic amino acids and cystine. It is caused by mutations in either of the two subunits (rBAT(SLC3A2) and b0,+AT(SLC7A9)) forming cystine stones. Struvite stones are usually seen in patients which have infection with urease +ve organisms. Urine pH is usually alkaline (>7.2). Nephrolithiasis can be passed on to following generations due to rare causes of hypercalciuria such as hereditary distal renal tubular acidosis, dent disease, Bartter syndrome types III and IV, autosomal dominant hypocalcemic hypercalciuria and familial hypomagnesemia. Nephrolithiasis associated with Hyperparathyroidism, Gout, Hypocitaturia, Sarcoidosis, chronic urinary tract infections and Obesity.On gross pathology, the characteristic findings of nephrolithiasis include location = 80% unilateral, usually in calyces, pelvis or bladder. The size=variable, 2-3 mm usually. All stones contain an organic matrix of mucoprotein. The shape of struvite stone is staghorn shaped. On microscopic histopathological analysis, the characteristic findings of nephrolithiasis include different shapes of stones/crystals are such as cystine= hexagonal, struvite= coffin lid shape, calcium oxalate= pyramid shape to dumbbell shape and uric acid= rectangular/rhomboidal. Oxalate crystals are highlighted by polarized light. Also, foreign body giant cells and macrophages are seen with the stones.

Pathophysiology

Pathogenesis

  • It is understood that nephrolithiasis is the result of combination of different mechanism responsible for different types of stones:
Calcium stones
Uric acid stones
  • The underlying pathophysiological mechanisms responsible for uric acid stones are:
Cystine stones
  • Cystinuria is a rare hereditary gene disorder which causes impaired renal rabsorption of cationic amino acids and cystine.
  • The cationic amino acids commonly involved are called as COLA amino acids that stands for:
  • It is caused by mutations in either of the two subunits (rBAT(SLC3A2) and b0,+AT(SLC7A9)) forming the apical transporter for cationic amino acids system b0,+; thus excretion of the dibasic COLA amino acids is increased.[9]
Struvite/Ammonium magnesium sulfate stones
  • These are usually seen in patients which have infection with urease +ve organisms.[10][11]
  • Urine pH is usually alkaline (>7.2)

The following table summarizes major mechanism of stone formation: [12][13][14][15]

Type of stone/Mechanism Cause Pathophysiology Stone composition Labs
All stones Low urine volume

(raises production of solutes)

Reduced intake or increased loss of water Renal water conservation All stones
  • Urine volume <1 L per day
  • Osmolarity >600 mOsm/kg
Calcium stones Hypercalciuria

(raises saturation of calcium salts)

Absorptive hypercalciuria Increased absorption in gut Calcium oxalate or phosphate Urine calcium concentrations >6 mmol/L (240 mg) per day
Hyperparathyroidism Increased absorption in gut and bone release High concentrations of parathyroid hormone
Immobilization Bone resorption High concentrations of vitamin D
Excess of sodium in the diet Sodium-induced physiological renal calcium leak. Possible component of gut hyperabsorption Urine sodium concentrations >200 mmol/L per day
Excess of protein or acid in diet Protein-induced bone loss and renal leak.
Range of monogenic disorders Bone loss, gut hyperabsorption, and renal leak in various combinations
Hypocitraturia

(raises levels of ionised calcium and reduces inhibitor activity against calcium salts)

Renal tubular acidosis (distal type) Renal defense of acid-base balance Calcium phosphate
  • Urine citrate concentrations <1·7 mmol/L per day
  • Urine pH high
High acid load (absence of detectable acidemia) Physiological hypocitraturia Calcium oxalate or phosphate
  • Urine citrate concentrations <1·7 mmol/L per day
  • Urine pH low
Hyperoxaluria

(raises saturation of calcium oxalate)

Excess of oxalate in diet Increased delivery of luminal oxalate Calcium oxalate Urine oxalate concentrations >70·7 mmol/L per day
Bowel pathology Reduced formation of luminal calcium and calcium-oxalate complex
Increased production of endogenous oxalate Primary hyperoxaluria (type 1 and type 2)
Hyperuricosuria

(sodium urate precipitation causes crystallization of calcium salts)

High purine intake Raised production and urinary excretion of sodium and urate
  • Urine uric acid concentrations >600 mg per day
  • Hyperuricaemia
Myeloproliferative diseases
Enzymatic defects Urine uric acid concentrations >600 mg per day
Uricosuric drugs Hypouricaemia
Genetic primary renal leak Increased excretion of uric acid
Uric acid stones Low urine pH or hyperuricosuria Titrates urate to poorly soluble uric acid Uric acid Urine pH <5·5
Cystine stones Cystinuria Congenital mutations of dibasic aminoacid transporter subunits rBAT and b0+AT Renal leak of basic aminoacids Cystine Urine concentrations of cystine high (>150 μmol/mmol creatinine)
Infection stones Urinary tract infection Urea-splitting organisms Production of ammonium and bicarbonate from urea

Genetics

Associated Conditions

Gross Pathology

  • On gross pathology, the characteristic findings of nephrolithiasis are:
    • Location = 80% unilateral, usually in calyces, pelvis or bladder
    • Size=variable, 2-3 mm usually
    • All stones contain an organic matrix of mucoprotein
    • Shape:
      • Struvite stone= staghorn calculus
  • Nephrolithiasis, Source: Wikimedia commons[16]

    Nephrolithiasis, Source: Wikimedia commons[16]

  • Staghorn shape of struvite stones, Source: Wikimedia commons[17]

    Staghorn shape of struvite stones, Source: Wikimedia commons[17]

  • Renal calculi, different shapes and sizes, Source: Wikimedia commons[18]

    Renal calculi, different shapes and sizes, Source: Wikimedia commons[18]

  • Kidney stone with a maximum dimension of 5mm, Source: Wikimedia commons[19]

    Kidney stone with a maximum dimension of 5mm, Source: Wikimedia commons[19]

Microscopic Pathology

  • On microscopic histopathological analysis, the characteristic findings of nephrolithiasis are:
    • Shapes of different stones/crystals are different:
      • Cysteine= hexagonal
      • Struvite= coffin lid shape
      • Calcium oxalate= pyramid shape
      • Calcium oxalate= dumbbell shape
      • Uric acid= rectangular/rhomboidal
    • Oxalate crystals are highlighted by polarized light
    • Foreign body giant cells and macrophages are seen with the stones
  • Type of stones. Light microscopy of urine crystals. (A) Hexagonal cystine crystal (200X); (B) coffin-lid shaped struvite crystals (200X); (C) pyramid-shaped calcium oxalate dehydrate crystals (200X); (D) dumbbell-shaped calcium oxalate monohydrate crystal (400X); (E) rectangular uric acid crystals (400X); and (F) rhomboidal uric acid crystals (400X).[20]

    Type of stones. Light microscopy of urine crystals. (A) Hexagonal cystine crystal (200X); (B) coffin-lid shaped struvite crystals (200X); (C) pyramid-shaped calcium oxalate dehydrate crystals (200X); (D) dumbbell-shaped calcium oxalate monohydrate crystal (400X); (E) rectangular uric acid crystals (400X); and (F) rhomboidal uric acid crystals (400X).[20]

  • Deposits of oxalate with variable size and form; they occupy mainly distal tubules. The asterisks indicate proximal tubules, which usually do not contain these crystals, H&E seen with polarized light, X200[21]

    Deposits of oxalate with variable size and form; they occupy mainly distal tubules. The asterisks indicate proximal tubules, which usually do not contain these crystals, H&E seen with polarized light, X200[21]

  • Medullary interstitial urate crystal deposits in chronic nephropathy by urates as seen after Masson's trichome stain X400[22]

    Medullary interstitial urate crystal deposits in chronic nephropathy by urates as seen after Masson's trichome stain X400[22]

  • Calcium oxalate dihydrate crystals under Scanning Electron Micrograph (SEM) taken at 30 KV. Source: Wikimedia commons[23]

    Calcium oxalate dihydrate crystals under Scanning Electron Micrograph (SEM) taken at 30 KV. Source: Wikimedia commons[23]

  • Density-dependent color scanning electron micrograph of kidney stone, Source: Wikimedia commons[24]

    Density-dependent color scanning electron micrograph of kidney stone, Source: Wikimedia commons[24]

References

  1. ↑ Pak CY (December 1991). "Etiology and treatment of urolithiasis". Am. J. Kidney Dis. 18 (6): 624–37. PMID 1962646.
  2. ↑ Mandel NS, Mandel GS (December 1989). "Urinary tract stone disease in the United States veteran population. II. Geographical analysis of variations in composition". J. Urol. 142 (6): 1516–21. PMID 2585627.
  3. ↑ Hochreiter W, Knoll T, Hess B (February 2003). "[Pathophysiology, diagnosis and conservative therapy of non-calcium kidney calculi]". Ther Umsch (in German). 60 (2): 89–97. doi:10.1024/0040-5930.60.2.89. PMID 12649987.
  4. ↑ Messa P, Marangella M, Paganin L, Codardini M, Cruciatti A, Turrin D, Filiberto Z, Mioni G (September 1997). "Different dietary calcium intake and relative supersaturation of calcium oxalate in the urine of patients forming renal stones". Clin. Sci. 93 (3): 257–63. PMID 9337641.
  5. ↑ Messa P, Marangella M, Paganin L, Codardini M, Cruciatti A, Turrin D, Filiberto Z, Mioni G (September 1997). "Different dietary calcium intake and relative supersaturation of calcium oxalate in the urine of patients forming renal stones". Clin. Sci. 93 (3): 257–63. PMID 9337641.
  6. ↑ Trinchieri A (February 2013). "Diet and renal stone formation". Minerva Med. 104 (1): 41–54. PMID 23392537.
  7. ↑ Prezioso D, Strazzullo P, Lotti T, Bianchi G, Borghi L, Caione P, Carini M, Caudarella R, Ferraro M, Gambaro G, Gelosa M, Guttilla A, Illiano E, Martino M, Meschi T, Messa P, Miano R, Napodano G, Nouvenne A, Rendina D, Rocco F, Rosa M, Sanseverino R, Salerno A, Spatafora S, Tasca A, Ticinesi A, Travaglini F, Trinchieri A, Vespasiani G, Zattoni F (July 2015). "Dietary treatment of urinary risk factors for renal stone formation. A review of CLU Working Group". Arch Ital Urol Androl. 87 (2): 105–20. doi:10.4081/aiua.2015.2.105. PMID 26150027.
  8. ↑ Umekawa T, Chegini N, Khan SR (January 2002). "Oxalate ions and calcium oxalate crystals stimulate MCP-1 expression by renal epithelial cells". Kidney Int. 61 (1): 105–12. doi:10.1046/j.1523-1755.2002.00106.x. PMID 11786090.
  9. ↑ Pereira DJ, Schoolwerth AC, Pais VM (March 2015). "Cystinuria: current concepts and future directions". Clin. Nephrol. 83 (3): 138–46. PMID 25685869.
  10. ↑ Bichler KH, Eipper E, Naber K, Braun V, Zimmermann R, Lahme S (June 2002). "Urinary infection stones". Int. J. Antimicrob. Agents. 19 (6): 488–98. PMID 12135839.
  11. ↑ Flannigan R, Choy WH, Chew B, Lange D (June 2014). "Renal struvite stones--pathogenesis, microbiology, and management strategies". Nat Rev Urol. 11 (6): 333–41. doi:10.1038/nrurol.2014.99. PMID 24818849.
  12. ↑ Moe, Orson W (2006). "Kidney stones: pathophysiology and medical management". The Lancet. 367 (9507): 333–344. doi:10.1016/S0140-6736(06)68071-9. ISSN 0140-6736.
  13. ↑ Freitag, Jeffrey; Hruska, Keith (1983). "Pathophysiology of Nephrolithiasis": 523–553. doi:10.1007/978-1-4613-3524-5_16.
  14. ↑ Gambaro G, Fabris A, Abaterusso C, Cosaro A, Ceol M, Mezzabotta F, Torregrossa R, Tiralongo E, Del Prete D, D'Angelo A, Anglani F (May 2008). "Pathogenesis of nephrolithiasis: recent insight from cell biology and renal pathology". Clin Cases Miner Bone Metab. 5 (2): 107–9. PMID 22460990.
  15. ↑ Sakhaee, Khashayar (2009). "Recent advances in the pathophysiology of nephrolithiasis". Kidney International. 75 (6): 585–595. doi:10.1038/ki.2008.626. ISSN 0085-2538.
  16. ↑ By Amadalvarez - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=46706235
  17. ↑ By H. Zell [GFDL (http://www.gnu.org/copyleft/fdl.html) or CC BY-SA 3.0 (https://creativecommons.org/licenses/by-sa/3.0)], from Wikimedia Commons
  18. ↑ By Jakupica - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=45324355
  19. ↑ By RJHall - Own work, Public Domain, https://commons.wikimedia.org/w/index.php?curid=4070842
  20. ↑ Han H, Segal AM, Seifter JL, Dwyer JT (July 2015). "Nutritional Management of Kidney Stones (Nephrolithiasis)". Clin Nutr Res. 4 (3): 137–52. doi:10.7762/cnr.2015.4.3.137. PMC 4525130. PMID 26251832.
  21. ↑ http://kidneypathology.com/Imagenes/Diabetes/Oxalato.4.w.jpg
  22. ↑ http://www.kidneypathology.com/English_version/Diabetes_and_others.html
  23. ↑ By Kempf EK - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=18036112
  24. ↑ By Sergio Bertazzo - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=45316797

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