Kamica nerkowa
Patofizjologia i mechanizm

Kamica nerkowa jest złożonym procesem patologicznym, w którym kluczową rolę odgrywa przesycenie moczu substancjami kamieniotwórczymi, takimi jak wapń, szczawian, fosforany i kwas moczowy. Przesycenie to, wyrażane wskaźnikiem przekraczającym 1, prowadzi do nukleacji (homogennej lub heterogennej), wzrostu i agregacji kryształów, które zatrzymują się w nerkach, tworząc złogi. Istotne mechanizmy patogenetyczne obejmują także rolę płytek Randalla (fosforan wapnia w tkance śródmiąższowej brodawek nerkowych) jako podłoża do powstawania kamieni szczawianowo-wapniowych. Czynniki promujące kamicę to m.in. hiperkalciuria, hiperoksaluria, hiperurykozuria, niskie pH moczu (≤5,5) lub zasadowe (≥6,7) oraz niska objętość moczu, natomiast inhibitory, takie jak cytrynian (wydalanie obniżone u 20-60% pacjentów), magnez, pirofosforany i glikoproteiny, hamują nukleację, wzrost i agregację kryształów. W patogenezie kamicy istotne są także procesy zapalne i immunologiczne, w tym aktywacja makrofagów (fenotypy M1 i M2) oraz rola mikrobioty jelitowej i moczowej, wpływającej na metabolizm szczawianów i pH moczu.

  1. Mechanizm powstawania kamicy nerkowej (Pathogenesis of Kidney Stones)
    1. Przesycenie moczu (Supersaturation)
    2. Nukleacja kryształów (Crystal Nucleation)
    3. Wzrost i agregacja kryształów
    4. Zatrzymanie i retencja kryształów w nerkach
  2. Rola płytki Randalla w powstawaniu kamicy nerkowej
  3. Rola inhibitorów i promotorów w powstawaniu kamicy nerkowej
    1. Inhibitory kamicy nerkowej
    2. Promotory kamicy nerkowej
  4. Rola procesów zapalnych i odpowiedzi immunologicznej
    1. Mechanizmy zapalne
    2. Rola makrofagów
  5. Rola mikrobioty w patogenezie kamicy nerkowej
    1. Mikrobiota jelitowa
    2. Mikrobiota układu moczowego
  6. Patogeneza różnych typów kamieni nerkowych
    1. Kamienie wapniowe
    2. Kamienie z kwasu moczowego
    3. Kamienie struwitowe (infekcyjne)
    4. Kamienie cystynowe
  7. Czynniki genetyczne i środowiskowe w patogenezie kamicy nerkowej
    1. Czynniki genetyczne
    2. Czynniki środowiskowe
  8. Mechanizm powstawania kamicy nerkowej – podsumowanie
    1. Kolejne rozdziały

Mechanizm powstawania kamicy nerkowej (Pathogenesis of Kidney Stones)

Kamica nerkowa to złożony i wieloczynnikowy proces patologiczny, który prowadzi do tworzenia się złogów mineralnych w układzie moczowym. Mechanizm powstawania kamieni nerkowych obejmuje kilka kluczowych etapów, które w konsekwencji prowadzą do powstania klinicznie znaczących złogów. Główną siłą napędową w tym procesie jest przesycenie moczu substancjami kamieniotwórczymi, co prowadzi do nukleacji, wzrostu i agregacji kryształów oraz ich zatrzymania w nerkach.12

Przesycenie moczu (Supersaturation)

Podstawowym warunkiem do formowania się kamieni jest przesycenie moczu substancjami kamieniotwórczymi, takimi jak wapń, szczawian, fosforany i kwas moczowy. Przesycenie występuje, gdy stężenie tych substancji w moczu przekracza ich rozpuszczalność, co prowadzi do termodynamicznej niestabilności roztworu.12 Wskaźnik przesycenia jest wyrażany jako stosunek stężenia danej substancji w moczu do jej rozpuszczalności. Gdy wartość tego wskaźnika przekracza 1, kryształy mogą się formować i rosnąć, natomiast przy wartościach poniżej 1 kryształy ulegają rozpuszczeniu.1

Badania wykazały, że mocz (a prawdopodobnie również płyn cewkowy) osób z kamicą nerkową jest często bardziej przesycony substancjami kamieniotwórczymi niż mocz zdrowych osób, co sprzyja nukleacji i wzrostowi kryształów.12 Przesycenie może być konsekwencją:

  • Zwiększonego wydalania substancji tworzących kamienie1
  • Zmniejszonej objętości moczu (najczęściej z powodu niskiego spożycia płynów)12
  • Zmiany pH moczu12
  • Kombinacji powyższych czynników1

Nukleacja kryształów (Crystal Nucleation)

Nukleacja jest procesem, w którym rozpuszczone jony lub cząsteczki agregują, tworząc początkowe mikroskopijne ośrodki krystalizacji w przesyconym moczu.12 Wyróżnia się dwa główne typy nukleacji:

  • Nukleacja homogenna – zachodzi gdy jony wapnia i szczawianu tworzą małe kryształy, które następnie rosną, tworząc czyste kamienie szczawianowo-wapniowe.1
  • Nukleacja heterogenna – występuje gdy jony wapnia i fosforanu początkowo tworzą małe kryształy fosforanu wapnia, które następnie stanowią podłoże do osadzania się szczawianu wapnia, prowadząc do powstania mieszanego kamienia szczawianowo-fosforanowego.1

Proces nukleacji może być ułatwiony przez obecność innych kryształów, komórek lub struktur wewnątrznerkowych, które służą jako miejsca zarodkowania.1 Zaobserwowano, że płytki Randalla (ang. Randall’s plaques) – złogi fosforanu wapnia znajdujące się w tkance śródmiąższowej brodawek nerkowych – odgrywają kluczową rolę jako podłoże do powstawania kamieni szczawianowo-wapniowych.12

Wzrost i agregacja kryształów

Po utworzeniu się jąder krystalizacji, kryształy mogą rosnąć poprzez dodawanie nowych cząsteczek do sieci krystalicznej oraz łączyć się ze sobą, tworząc większe agregaty.1 Wzrost kryształów może zachodzić na drodze:

  • Wzrostu pojedynczych kryształów – stopniowe dodawanie jonów do istniejących kryształów1
  • Agregacji – łączenie się mniejszych kryształów w większe struktury12
  • Wtórnej nukleacji – tworzenie się nowych kryształów na powierzchni istniejących12

Badania sugerują, że wzrost kryształów do rozmiarów umożliwiających ich zatrzymanie w nerkach wyłącznie na podstawie wielkości nie może nastąpić bez agregacji lub przyłączenia się do określonych struktur wewnątrznerkowych.1 Agregacja jest uważana za główny mechanizm wzrostu kryształów.1

Zatrzymanie i retencja kryształów w nerkach

Zatrzymanie kryształów w nerkach jest kluczowym etapem tworzenia się kamieni nerkowych. Proces ten może zachodzić na kilka sposobów:12

  1. Model wolnych cząstek (free particle model) – jądra kryształów tworzą się poprzez nukleację homogenną w świetle nefronu w warunkach zmiany fazy (wzrastające przesycenie) rozpuszczonych soli obecnych w ultrafiltratcie.1
  2. Model ustalonych cząstek (fixed particle model) – jądra kryształów tworzą się w świetle nefronu, a następnie przylegają do powierzchni szczytowej nabłonka cewkowego, co umożliwia ich dalszy wzrost.1
  3. Model płytek Randalla – kryształy moczu przyłączają się do odsłoniętych złogów śródmiąższowych fosforanu wapnia (płytek Randalla) po utracie normalnej pokrywy urotelialnej brodawki nerkowej.1

Interakcja kryształów z komórkami nabłonka nerkowego odgrywa istotną rolę w patogenezie kamieni nerkowych. Gdy kryształy przylegają do powierzchni komórek, mogą powodować uszkodzenia i stan zapalny.1 Badania wykazały, że uszkodzenie komórkowe może zwiększać zatrzymywanie cząstek na powierzchniach brodawek nerkowych.1

Rola płytki Randalla w powstawaniu kamicy nerkowej

Płytki Randalla (Randall’s plaques) są mikroskopowymi złogami fosforanu wapnia zlokalizowanymi w tkance śródmiąższowej brodawek nerkowych.1 Stanowią one podłoże dla powstawania kamieni szczawianowo-wapniowych, szczególnie u pacjentów z idiopatyczną kamicą szczawianowo-wapniową.1

Mechanizm powstawania kamieni w oparciu o płytki Randalla obejmuje następujące etapy:12

  1. Fosforan wapnia wytrąca się w błonie podstawnej cienkich ramion pętli Henlego
  2. Złogi erodują do tkanki śródmiąższowej
  3. Gromadzą się w przestrzeni podnabłonkowej brodawki nerkowej
  4. Złogi podnabłonkowe (płytki Randalla) ostatecznie erodują przez nabłonek brodawki nerkowej
  5. Macierz kamieni, fosforan wapnia i szczawian wapnia stopniowo osadzają się na odsłoniętym podłożu, tworząc kamień nerkowy

Badania histopatologiczne wykazały, że około 75% kamieni szczawianowo-wapniowych tworzy się w miejscach przylegania do płytek Randalla i dotyczy to wszystkich pacjentów z idiopatyczną kamicą szczawianowo-wapniową.12 Powierzchnia brodawki nerkowej pokryta płytkami Randalla koreluje bezpośrednio z poziomem wapnia w moczu oraz odwrotnie proporcjonalnie z objętością moczu i jego pH.1

Rola inhibitorów i promotorów w powstawaniu kamicy nerkowej

W moczu znajdują się zarówno substancje promujące tworzenie się kamieni (promotory), jak i substancje hamujące ten proces (inhibitory). Zaburzenie równowagi między tymi substancjami może prowadzić do powstawania kamieni nerkowych.12

Inhibitory kamicy nerkowej

Inhibitory są naturalnymi substancjami ochronnymi, które zapobiegają tworzeniu się kamieni poprzez:1

  • Hamowanie nukleacji kryształów
  • Hamowanie wzrostu kryształów
  • Hamowanie agregacji kryształów
  • Tworzenie kompleksów z jonami promującymi powstawanie kamieni

Najważniejsze inhibitory kamicy nerkowej to:12

  • Cytrynian – endogenny inhibitor tworzenia się kamieni wapniowych, działa poprzez wiązanie wapnia i tworzenie rozpuszczalnych kompleksów, zmniejszając stężenie wolnych jonów wapnia w moczu. Hipocytraturię (niskie wydalanie cytrynianu) stwierdza się u 20-60% pacjentów z kamicą wapniową.12
  • Magnez – tworzy rozpuszczalne kompleksy ze szczawianami, zmniejszając dostępność szczawianów do tworzenia nierozpuszczalnych kompleksów z wapniem.1
  • Pirofosforany – hamują nukleację i wzrost kryształów fosforanu wapnia.1
  • Glikoproteiny – białka takie jak nefrocalcina czy białko Tamma-Horsfalla hamują agregację i wzrost kryształów.1
  • Całkowita objętość moczu – większa objętość moczu zmniejsza stężenie substancji kamieniotwórczych.1

Promotory kamicy nerkowej

Promotory to substancje, które ułatwiają tworzenie się kamieni poprzez różne mechanizmy:1

  • Hiperkalciuria – najczęściej występująca nieprawidłowość u pacjentów z kamicą wapniową, zwiększa przesycenie moczu solami wapnia. Mechanizmy patofizjologiczne hiperkalciurii są liczne i mogą obejmować zwiększone wchłanianie wapnia w jelitach, zmniejszoną reabsorpcję wapnia w nerkach i zwiększoną mobilizację wapnia z kości.1
  • Hiperoksaluria – wykrywana u 10-50% pacjentów z kamicą wapniową, zwiększa przesycenie szczawianem wapnia.1
  • Hiperurykozuria – jako izolowana nieprawidłowość występuje u 10% pacjentów z kamicą wapniową. Wysokie stężenie kwasu moczowego w moczu może prowadzić do wytrącania się moczanu sodu, który z kolei może stanowić podłoże do krystalizacji soli wapnia.1
  • Niewłaściwe pH moczu – zarówno mocz silnie kwaśny (pH ≤ 5,5), jak i silnie zasadowy (pH ≥ 6,7) predysponuje pacjentów do tworzenia kamieni wapniowych. Kamienie z kwasu moczowego tworzą się głównie w kwaśnym pH, podczas gdy kamienie fosforanowo-wapniowe i struwity tworzą się w zasadowym pH.12
  • Niska objętość moczu – prowadzi do zwiększonego stężenia substancji kamieniotwórczych w moczu.1

Rola procesów zapalnych i odpowiedzi immunologicznej

Coraz więcej dowodów wskazuje na istotną rolę procesów zapalnych i odpowiedzi immunologicznej w patogenezie kamicy nerkowej.1

Mechanizmy zapalne

Interakcja między kryształami a komórkami nabłonka cewek nerkowych (RTECs) może prowadzić do produkcji białek prozapalnych, takich jak TNF-alfa i IL-1β, poprzez aktywację makrofagów.1 Nadprodukcja reaktywnych form tlenu (ROS) może działać jednocześnie jako przyczyna i konsekwencja stanu zapalnego w błędnym kole, w którym uszkodzenie cewek spowodowane obecnością kryształów promuje stan zapalny, który z kolei sprzyja tworzeniu się kryształów.1

Rola makrofagów

Makrofagi od dawna są kojarzone z kryształami śródmiąższowymi w brodawkach nerkowych u ludzi. W procesie powstawania kamieni nerkowych uczestniczą fenotypy makrofagów prozapalnych (M1) i przeciwzapalnych (M2).1 Makrofagi M2 mogą fagocytować kryształy szczawianu wapnia, zmniejszając rozwój kamieni. Mechanizmy sygnalizacyjne, które promują polaryzację makrofagów podobnych do M2 w kierunku nefrocalcynozy ze szczawianu wapnia, obejmują szlaki NLRP3, PPARg-miR-23-Irf1/Pknox1, miR-93-TLR4/IRF1 i miR-185-5p/CSF1.1

Rola mikrobioty w patogenezie kamicy nerkowej

W ostatnich latach wykazano, że mikrobiota jelitowa i moczowa odgrywa rolę w utrzymywaniu homeostazy oraz w procesach patologicznych prowadzących do kamicy nerkowej.12

Mikrobiota jelitowa

Szczawian jest wydalany z moczem po wchłonięciu w jelicie. Brak bakterii komensalnych o aktywności rozkładającej szczawian został powiązany z tworzeniem się kamieni.1 Obserwacje wykazały, że ogólny skład mikrobiologiczny u pacjentów z kamicą nerkową znacznie różni się od składu u zdrowych osób kontrolnych, co dodatkowo potwierdza, że mikrobiota jelitowa jest ważnym czynnikiem przyczyniającym się do powstawania kamieni.1

Mikrobiota układu moczowego

Niektóre bakterie mają wpływ na promowanie tworzenia się kamieni. Szczególnie bakterie ureazododatnie, takie jak Proteus mirabilis, mogą wytwarzać enzym ureazę, który przekształca mocznik w amoniak i dwutlenek węgla, co prowadzi do alkalizacji moczu i sprzyja tworzeniu się kamieni struwitu (fosforanu magnezowo-amonowego).12

Coraz więcej dowodów wskazuje na to, że mikroorganizmy należące do mikrobiomu człowieka, w tym mikroorganizmy nerek i dróg moczowych, prawdopodobnie mają głęboki wpływ na zdrowie urologiczne, zarówno pozytywny, jak i negatywny, ze względu na ich produkty metaboliczne i inne czynniki.1

Patogeneza różnych typów kamieni nerkowych

Mechanizmy patogenetyczne różnią się w zależności od typu kamienia nerkowego.1

Kamienie wapniowe

Kamienie wapniowe stanowią około 75% wszystkich kamieni nerkowych. Głównie składają się ze szczawianu wapnia (50%), fosforanu wapnia (5%) lub obu tych związków (45%).12 Patofizjologia kamieni wapniowych jest złożona i obejmuje:1

  • Niską objętość moczu
  • Hiperkalciurię
  • Hiperurykozurię
  • Hipocytraturię
  • Hiperoksalurię
  • Nieprawidłowości pH moczu

Istnieje ścisła korelacja między powstawaniem kamieni szczawianowo-wapniowych a dietą. Wyższe spożycie sodu prowadzi do zwiększonej natriurezy i wydalania wapnia z moczem. Podobnie, wyższe spożycie szczawianów może prowadzić do zwiększonej oksalurii. Dodatkowo, wyższe spożycie białka zwierzęcego/aminokwasów siarkowych prowadzi do bardziej kwaśnego moczu, sprzyjającego tworzeniu się kamieni.1

Kamienie z kwasu moczowego

Kamienie z kwasu moczowego stanowią 7-10% wszystkich kamieni nerkowych.1 Przyczyny etiologiczne powstawania kamieni z kwasu moczowego są genetyczne, nabyte lub ich kombinacją.1 Podstawowe mechanizmy patofizjologiczne odpowiedzialne za kamicę moczanową to:1

  1. Niska objętość moczu
  2. Hiperurykozuria
  3. Zbyt kwaśne pH moczu

Najczęstszym czynnikiem ryzyka kamicy moczanowej jest utrzymujące się kwaśne pH moczu, w tym brak normalnej poposiłkowej fali zasadowej.1

Kamienie struwitowe (infekcyjne)

Kamienie struwitowe są uważane za kamienie infekcyjne, ponieważ są tworzone specjalnie przez organizmy wytwarzające ureazę, z których najczęstszym jest Proteus mirabilis.1 Najważniejszymi czynnikami tworzenia kamieni infekcyjnych są wysoce zasadowe pH moczu w obecności organizmów wytwarzających ureazę oraz przesycone środowisko moczowe w odniesieniu do jonów magnezu, amonu i fosforanu.1

Ponieważ bakterie wytwarzające ureazę pozostają w kamieniu i w moczu, ureaza, którą wytwarzają, nadal rozszczepia mocznik, co prowadzi do utrzymującego się zasadowego pH moczu.1

Kamienie cystynowe

Kamica cystynowa stanowi tylko niewielką część kamieni nerkowych u dorosłych, ale jest bardziej rozpowszechniona wśród dzieci i młodzieży z kamieniami.1 Kamienie cystynowe powstają u pacjentów z homozygotycznym recesywnym genem transportu cystyny, co prowadzi do nadmiernego wydalania cystyny z moczem.1

Rozpuszczalność i wytrącanie cystyny zależy w dużej mierze od stężenia cystyny w moczu i pH, ponieważ nie ma znanych inhibitorów produkcji cystyny.1

Czynniki genetyczne i środowiskowe w patogenezie kamicy nerkowej

Kamica nerkowa jest chorobą wielogenową i wieloczynnikową o ogólnoświatowym rozmieszczeniu, a jej częstość występowania i chorobowość stale rosną.1

Czynniki genetyczne

Istnieją ważne czynniki genetyczne leżące u podstaw kamicy nerkowej. Szacowana dziedziczność tej choroby wynosi około 45%, co sugeruje, że czynniki genetyczne silnie wpływają na tę chorobę.1 U pacjentów z nawracającymi kamieniami odnotowano wyższy odsetek kamieni nerkowych wśród krewnych pierwszego stopnia i członków rodziny.1

Niektóre rzadkie przyczyny hiperkalciurii, takie jak dziedziczna dystalna kwasica cewkowa nerkowa, choroba Denta, zespół Bartera typu III i IV, autosomalnie dominująca hipokalcemiczna hiperkalciuria i rodzinna hipomagnezemia, mogą być dziedziczone.1

Czynniki środowiskowe

Czynniki środowiskowe mogą być jednymi z najważniejszych czynników w powstawaniu kamieni.1 Do modyfikowalnych czynników ryzyka kamicy nerkowej należą:12

  • Wskaźnik masy ciała (BMI) – otyłość z BMI 30 lub więcej, szczególnie w młodej populacji, jest silnie związana ze zwiększoną częstością występowania kamicy nerkowej. Otyłość może pośredniczyć w występowaniu kamicy nerkowej poprzez zmianę pH moczu i wydalanych składników, z efektem różnicującym w zależności od płci.1
  • Spożycie płynów – niskie spożycie płynów prowadzi do zmniejszonej objętości moczu i zwiększonego stężenia substancji kamieniotwórczych. Istnieją dowody na to, że wysokie spożycie płynów może zmniejszyć ryzyko kamicy o 40% do 50%.1
  • Spożycie wapnia – wbrew powszechnym przekonaniom, normalne spożycie wapnia może zmniejszyć ryzyko powstawania kamieni poprzez wiązanie szczawianów w przewodzie pokarmowym, zmniejszając w ten sposób wchłanianie szczawianów i ryzyko hiperoksalurii.1
  • Spożycie napojów słodzonych cukrem – dieta bogata we fruktozę jest związana ze zwiększoną częstością występowania kamicy nerkowej.1
  • Dieta – wysokie spożycie sodu prowadzi do wyższej natriurezy i wydalania wapnia z moczem. Podobnie, wyższe spożycie szczawianów może prowadzić do zwiększonej oksalurii. Wyższe spożycie białka zwierzęcego/aminokwasów siarkowych prowadzi do bardziej kwaśnego moczu, sprzyjającego tworzeniu się kamieni.12

Mechanizm powstawania kamicy nerkowej – podsumowanie

Powstawanie kamieni nerkowych jest złożonym procesem obejmującym nukleację składników kamienia, ich wzrost lub agregację do rozmiaru, który może oddziaływać z wewnętrznymi strukturami nerek, ich zatrzymanie w nerkach lub w układzie zbiorczym nerek oraz dalszą agregację i/lub wtórną nukleację, prowadzącą do powstania kamienia klinicznego.1

Kryształy tworzą się w płynie cewkowym nerkowym lub w płynie śródmiąższowym nerkowym, który jest przesycony tymi składnikami, co z kolei może być konsekwencją zwiększonego wydalania cząsteczek tworzących kamienie, zmniejszonej objętości moczu, zmiany pH moczu lub kombinacji tych czynników.1

Podstawowe mechanizmy patogenetyczne, które prowadzą do powstawania kamieni nerkowych, obejmują:

  1. Przesycenie moczu substancjami kamieniotwórczymi
  2. Nukleację kryształów
  3. Wzrost i agregację kryształów
  4. Zatrzymanie kryształów w nerkach
  5. Dalszą akrecję substancji krystalicznych i matrycy organicznej, prowadzącą do powstania kamienia klinicznego

Na te procesy wpływają zarówno czynniki promujące (promotory), jak i hamujące (inhibitory) tworzenie się kamieni. Zaburzenie równowagi między tymi czynnikami może prowadzić do powstawania kamieni nerkowych.1

Pomimo obecnego zrozumienia fizycznej chemii powstawania kamieni, nie zidentyfikowano pojedynczej nieprawidłowości, która wyróżniałaby osoby z kamicą od osób zdrowych, a wiele osób z kamicą nie ma identyfikowalnej nieprawidłowości, która wyjaśniałaby skłonność ich moczu (lub płynu cewkowego) do nukleacji składników kamienia przy niższych poziomach przesycenia, do wspomagania przyspieszonego wzrostu powstałych kryształów lub do umożliwiania kryształom przylegania do siebie (agregacji) lub do jakiejś struktury wewnątrznerkowej.1

Kolejne rozdziały

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  1. 09.04.2026
  2. www.leksykon.com.pl

Materiały źródłowe

  • #1 Mechanisms of Stone Formation
    https://pmc.ncbi.nlm.nih.gov/articles/PMC3252394/
    The mechanism of stone formation include nucleation of stone constituent crystals, their growth or aggregation to a size that can interact with some intrarenal structure, their retention within the kidney or renal collecting system and further aggregation and/or secondary nucleation to form the clinical stone. This sequence is depicted in Figure 1. The crystals form either in renal tubular fluid or in the renal interstitial fluid that is supersaturated with respect to these constituents, which in turn may be a consequence of increased excretion of stone constituent molecules, reduced urine volume, an alteration in urine pH, or a combination of these factors. […] The urine and, presumably, the tubular fluid of stone formers is often more highly supersaturated than that of normal healthy adults, which favors nucleation and growth of crystals.
  • #1 Kidney Stones 2012: Pathogenesis, Diagnosis, and Management
    https://pmc.ncbi.nlm.nih.gov/articles/PMC3387413/
    The pathogenetic mechanisms of kidney stone formation are complex and involve both metabolic and environmental risk factors. […] The pathophysiological mechanisms for calcium kidney stone formation are complex and diverse and include low urine volume, hypercalciuria, hyperuricosuria, hypocitraturia, hyperoxaluria, and abnormalities in urine pH. […] Hypercalciuria is the most prevalent abnormality in calcium kidney stone formers. […] The pathophysiological mechanisms for hypercalciuria are numerous and may involve increased intestinal calcium absorption, decreased renal calcium reabsorption, and enhanced calcium mobilization from bone. […] Hyperuricosuria as an isolated abnormality is detected in 10% of calcium stone formers. […] Citrate is an endogenous inhibitor of calcium stone formation, and low urine citrate excretion (hypocitraturia) is encountered in 20-60% of calcium nephrolithiasis.
  • #1 Mechanisms of Stone Formation
    https://pmc.ncbi.nlm.nih.gov/articles/PMC3252394/
    Supersaturation is expressed as the ratio of urinary calcium oxalate or calcium phosphate concentration to its solubility, which is the driving force in stone formation. Supersaturation is generally higher in patients with recurrent kidney stones than in those without, and the type of stone that is formed correlates with urinary supersaturation. […] At supersaturation levels above 1, crystals can nucleate and grow, promoting stone formation, while they dissolve at levels below 1. […] It has been proposed that the growth of these microscopic crystals to the extent that they can be retained in the kidney on the basis of size alone cannot occur without aggregation or attachment to specific intrarenal structures. […] These deposits have been proposed to act as a nidus for development of the most usual variety of calcium oxalate stones.
  • #1 Kidney stones: Mechanism of formation, pathogenesis and possible treatments
    https://www.pulsus.com/scholarly-articles/kidney-stones-mechanism-of-formation-pathogenesis-and-possible-treatments-4896.html
    With a very high recurrence rate in both males and females, kidney stones also called as urolithiasis (nephrolithiasis) are affecting a remarkably significant population around the globe. As kidney stones formation largely depends on urines oxalate content rather than the calcium concentration of the urine, kidney stones are predominantly made up of oxalate and also there are multiple steps involved in the pathogenesis of calcium oxalate including nucleation, crystal growth, crystal aggregation and crystal retention. […] The prime cause of nephrolithiasis is the super saturation of urine with calcium and oxalate that leads to pathological mineralization in the kidneys. […] The mechanism involved in the process of stone formation include nucleation of crystals fractions, growth or gathering of these crystals to a size so that they can interact with some intra-renal structure(s), confinement of these crystals inside the kidney or renal collecting system succeeded by further aggregation and/ or secondary nucleation ultimately forming the clinical stone.
  • #1 Calcium Kidney Stones: Pathogenesis, Evaluation, and Treatment Options
    https://www.uspharmacist.com/article/calcium-kidney-stones-pathogenesis-evaluation-and-treatment-options
    Calcium stones form when urine is supersaturated with the constituent ions that comprise the stone. Hence, supersaturation with calcium and oxalate ions will promote the formation of calcium oxalate stones. Supersaturation of urine with calcium and phosphate ions will promote the formation of calcium phosphate stones. Supersaturation occurs when the product of the ionic activity of calcium [Ca2+]a and oxalate [Oxalate2-]a exceeds the solubility product for calcium oxalate (SP1); or the product of the ionic activity of calcium [Ca2+]a and phosphate [HPO42-]a exceeds the solubility product for calcium phosphate (SP2). […] […] Homogeneous nucleation occurs when calcium and oxalate ions complex to form small crystals that then grow to larger pure calcium oxalate stones. Heterogeneous nucleation occurs when calcium and phosphate ions complex to initially form small crystals of calcium phosphate. These small crystals form the substrate upon which calcium oxalate subsequently deposits. This results in a mixed calcium oxalate-calcium phosphate stone. Various factors contribute, including the concentrations of individual free (unbound) ions such as calcium and oxalate, the pH, and the presence or absence of other substances that can either accelerate or retard the formation of calcium stones. For example, citrate is a known inhibitor of calcium crystallization, because citrate forms soluble complexes with calcium, which then lowers the ionic activity of free calcium ions in the urine and decreases stone formation. […]
  • #1 Urolithiasis unveiled: pathophysiology, stone dynamics, types, and inhibitory mechanisms: a review | African Journal of Urology | Full Text
    https://afju.springeropen.com/articles/10.1186/s12301-024-00436-z
    The process of crystallization occurs when urine becomes oversaturated, leading to the formation of solid crystals. […] The phenomenon of nucleation is a crucial aspect of crystal formation from a supersaturated solution. It involves the aggregation of solute molecules or ions to form a stable nucleus, which then serves as a basis for subsequent crystal growth. […] After nuclei formation, crystals grow by adding new molecules to the crystal lattice. […] Over time, crystals can aggregate to form larger particles, which may lead to the formation of stones. […] The interaction between crystals and renal epithelial cells is a critical factor in the pathogenesis of kidney stones. When crystals adhere to the cell surface, they can cause injury and inflammation.
  • #1
    https://link.springer.com/article/10.1007/s00467-009-1116-y
    All stones share similar presenting symptoms, and urine supersaturation with respect to the mineral phase of the stone is essential for stone formation. […] Three general pathways for kidney stone formation are seen: (1) stones fixed to the surface of a renal papilla at sites of interstitial apatite plaque (termed Randalls plaque), as seen in idiopathic calcium oxalate stone formers; (2) stones attached to plugs protruding from the openings of ducts of Bellini, as seen in hyperoxaluria and distal tubular acidosis; and (3) stones forming in free solution in the renal collection system, as in cystinuria. […] The presence of hydroxyapatite crystals in either the interstitial or tubule compartment (and sometimes both) of the renal medulla in stone formers is the rule and has implications for the initial steps of stone formation and the potential for renal injury.
  • #1 Pathophysiology of Kidney stones | PPT
    https://www.slideshare.net/slideshow/pathophysiology-of-kidney-stones/231838705
    Kidney stones, also known as renal calculi, form in the kidneys from mineral deposits in urine and can be classified by their location and composition. Common types include calcium, uric acid, struvite, and cystine stones. Kidney stones form via a three step process – supersaturation of urine leading to nucleation of crystals that then aggregate into solid masses. […] For a stone to form, 3 processes occur 1. Supersaturation 2. Nucleation 3. Aggregation. […] Supersaturation Cations and anions are charged soluble molecules such as calcium and oxalate. However, at a specific concentration and pH, the equilibrium state of these molecules reach a critical point called supersaturation. Beyond this point, these molecules cannot remain dissolved and will become insoluble and precipitate. […] A nucleation represents a focus where crystals start precipitating.
  • #1 How Are Kidney Stones Formed? | St Pete Urology
    https://stpeteurology.com/how-kidney-stones-formed/
    Kidney stones typically form from soluble salts found in urine. […] When the urine concentration of these soluble salts is very high, solid crystals may be formed. […] Therefore, urine must become supersaturated for the balance between stone-promoters and inhibitors to be broken and allow larger stones to form. […] Kidney stone formation begins by the process of nucleation, an association of free ions into microscopic particles. […] Once tiny crystals are formed, they can undergo secondary nucleation or aggregation, the processes through which the crystals formed in solution form into bigger multi-component particles. […] […] Larger crystals then can grow into giant single crystals which can be retained in the kidney by further aggregation and attachment to specific intra-renal structures.
  • #1 Mechanisms of Stone Formation
    https://pmc.ncbi.nlm.nih.gov/articles/PMC3252394/
    Control of crystal formation by inhibitors has been proposed to play a role in the normal defense against the development of stones, and abnormalities of these inhibitors may permit stone formation and growth. […] Stone formation is a complex process involving crystal nucleation, aggregation and/or secondary nucleation, fixation within the kidney, and more aggregation and secondary nucleation.
  • #1 Mechanism of stone formation.
    https://www.periodicos.capes.gov.br/index.php/acervo/buscador.html?task=detalhes&id=W138720061
    The process of nucleation results in a reduction of excess free energy to a more thermodynamically stable environment. […] Aggregation appears to be the major mechanism for crystal growth. […] A final factor that is important in the effective growth of renal calculi is the retention of microcrystals in the urinary tract, possibly correlated with prior injury.
  • #1
    https://link.springer.com/article/10.1007/s00467-009-1116-y
    Kidney stone development is thought to require the formation of crystals in the tubular fluid, followed by crystal retention and accumulation in the kidney. […] The first hypothesis, termed the free particle model, states that crystal nuclei form by homogeneous nucleation in the lumen of the nephron under conditions of a phase change (increasing supersaturation) in the dissolved salts present in the ultrafiltrate. […] The second hypothesis, termed the fixed particle model, also requires crystal nuclei to form in the lumen of the nephron, and then adhere to the apical surface of the tubular epithelium. […] Once the crystalcell attachment step has occurred, the crystal nuclei would be fixed in position and exposed to the potentially supersaturated ultrafiltrate that would facilitate further growth of these crystals.
  • #1
    https://link.springer.com/article/10.1007/s00467-009-1116-y
    A third pathway suggests that crystals in the urine can become attached to a site of exposed crystalline deposits of interstitial calcium phosphate (termed Randalls plaque), following the loss of the normal urothelial covering of a renal papilla. […] Randall was convinced that interstitial plaque was a perquisite for stone formation and growth. […] The majority (approximately 75%) of CaOx stones are formed attached to sites of Randalls plaque and represents all ICSF patients. […] In all other types of kidney stone formers that we have studied, plugs were formed along the inner medullary collecting ducts and ducts of Bellini, which can serve as attachment sites for developing stones. […] These stones found attached to plugs extending from ducts of Bellini have never been found to be CaOx stones but, instead, have been apatite stones. […] Our recent studies using a combination of intraoperative endoscopic mapping and papillary biopsies have clearly shown distinct patterns of histopathologic characteristics for each type of kidney stone former that predicts the mechanism of stone formation.
  • #1
    http://isfcppharmaspire.com/article_html.php?did=15076&issueno=0
    Kidney stones (calculi) comprise mineral concretions which can form in both renal calyces and pelvis and can be free floating or associated with the renal papillae. […] The major component of most stones is calcium oxalate, and many of them develop on a foundation of calcium phosphate known as Randalls plaques, which are located on the renal papillary surface. The mechanism of stone formation is a complicated process that involves multiple physicochemical phenomena such as supersaturation, nucleation, growth, aggregation, and retention of urinary stone ingredients inside tubular cells. Cellular damage is also thought to enhance particle retention on renal papillary surfaces. […] There is a great demand for recurrence prevention, which necessitates a deeper knowledge of the processes involved in the development of stones to design more effective medications. […] As a result, furthering our knowledge of the biology of kidney stone development is a research focus for treating urolithiasis with novel medications.
  • #1 The role of Randall plaques on kidney stone formation – Chung – Translational Andrology and Urology
    https://tau.amegroups.org/article/view/4081/html
    Randalls plaque is microscopically a plaque of calcium deposited in the interstitial tissue of the renal papilla. These plaques are thought to serve as a nidus for urinary stone formation. […] Randalls plaque plays an important role and is prerequisite of kidney stone formation in idiopathic calcium oxalate stone formers. […] The presence of papillary plaques is associated with calcium nephrolithiasis and may contribute to the pathogenesis of calcium urinary stones. […] The urine molecules, osteopontin and Tamm Horsfall protein, and crystals in urine, driven by supersaturations, react with the exposed plaque to form a ribbon of alternating matrix and crystal layers by repeated coating and crystallization. Eventually crystallization escapes from matrix modulation and crystals extend outward into the space of urine and begin to form a calcium oxalate stone proper. […] Although Randalls plaque can be found in other stone formers, its role on kidney stone formation might not be important as its role in idiopathic calcium oxalate stone formers.
  • #1 The role of Randall plaques on kidney stone formation – Chung – Translational Andrology and Urology
    https://tau.amegroups.org/article/view/4081/5591
    Randalls plaque is microscopically a plaque of calcium deposited in the interstitial tissue of the renal papilla. These plaques are thought to serve as a nidus for urinary stone formation. […] Randalls plaque plays an important role and is prerequisite of kidney stone formation in idiopathic calcium oxalate stone formers. […] The presence of papillary plaques is associated with calcium nephrolithiasis and may contribute to the pathogenesis of calcium urinary stones. […] The original formation of Randalls plaques in the basement membrane of the thin loops of Henle resembles the ectopic calcification process. […] For calcium oxalate stones formation and growth in idiopathic calcium oxalate stone formers, Randalls plaques play an important role and are prerequisite. […] The majority (approximately 75%) of calcium oxalate stones is formed attached to sites of Randalls plaque and represents all idiopathic calcium oxalate stone formers. […] Although Randalls plaque can be found in other stone formers, its role on kidney stone formation might not be important as its role in idiopathic calcium oxalate stone formers.
  • #1
    https://www.jci.org/articles/view/26662
    Stones form on interstitial apatite plaque. CaOx stones form on the surfaces of the renal papillae over collections of interstitial suburothelial CaP particles named Randall plaque. The number of CaOx stones formed, adjusted for duration of stone formation, varies directly with plaque surface coverage, as would be expected if plaque were a surface that promotes CaOx overgrowth. […] The driving force for CaOx overgrowth on plaque is urine CaOx SS. But the forces that create the plaque are not so clear. The fraction of papillary surface covered by plaque in idiopathic CaOx SFs correlates directly with urine calcium level and inversely with urine volume and pH. […] High fluid intake may be beneficial not only to prevent CaOx overgrowth, but also to reduce plaque formation itself. […] The vast majority of CaOx SFs suffer from no systemic disease and as such are described as idiopathic CaOx SFs. Some have primary hyperparathyroidism or other disorders of calcium metabolism, and others present with hyperoxaluria because of bowel disease (enteric hyperoxaluria) and genetic disorders of oxalate metabolism (primary hyperoxaluria [PH]). We discuss these groups separately below.
  • #1 Kidney stones: Mechanism of formation, pathogenesis and possible treatments
    https://www.pulsus.com/scholarly-articles/kidney-stones-mechanism-of-formation-pathogenesis-and-possible-treatments-4896.html
    The urine and presumably, the tubular fluid of stone formers are often more highly supersaturated than that of normal healthy adults, which favors nucleation and growth of crystals. […] Long-term accretion of additional elements, crystalline as well as organic matrix produces the clinical stone. […] The reciprocal actions between genetic susceptibility and environmental factors in different proportions promote both hypercalciuria and hyperoxaluria. […] The above mentioned processes in humans are influenced by several factors known as promoters and inhibitors that either support or prevent the process of stone formation thus affecting a persons ability to promote or prevent stone formation. Stone formation is facilitated by promoters while inhibitors prevent it. […] The uneven proportion of inhibitors and promoters are responsible to the complex process of stone formation in kidneys or urolithiasis.
  • #1 How Are Kidney Stones Formed? | St Pete Urology
    https://stpeteurology.com/how-kidney-stones-formed/
    Kidney stones are hard mineral or salt deposits formed in the kidney when urine is concentrated. Originating as microscopic crystals or particles that develop over time into pebble-sized calculi or larger deposits as minerals crystallize and fuse together, kidney stones can affect any section of the urinary tract (the kidney, bladder, ureters and urethra). […] However, if the minerals and other wastes fail to dissolve completely in urine, microscopic particles may develop which may grow into larger stones. […] Formation of urine crystals is a common occurrence even in those who never form stones. The natural existence of substances promoting crystal development in all urine means that everyone can have urine crystals. […] Nevertheless, urine also has natural inhibitors of crystal formation such as magnesium, citrate, phytate, pyrophosphate, proteins, total urine volume and other byproducts of normal metabolism.
  • #1 The Management of Urolithiasis
    https://www.uspharmacist.com/article/the-management-of-urolithiasis
    In contrast, promoters are substances that facilitate stone formation by various means. These include cell-membrane lipids (e.g., phospholipids, cholesterol, glycolipids), calcitriol hormone enhancement via parathyroid-hormone stimulation, oxalate, cystine, calcium, sodium, and low urine volume. Among patients with recurrent stone formation, urinary oxalate excretion was found to be higher, whereas citrate excretion was lower. It has been suggested that an imbalance between urinary stone inhibitors and promoters is, in general, the cause of stone formation.
  • #1 Kidney Stones 2012: Pathogenesis, Diagnosis, and Management
    https://pmc.ncbi.nlm.nih.gov/articles/PMC3387413/
    Hyperoxaluria is detected in 10-50% of calcium stone formers. […] Both highly acidic urine (pH 5.5) and highly alkaline urine (pH 6.7) predispose patients to calcium kidney stone formation. […] One suggested mechanism for the formation of calcium stones is increased urinary supersaturation of stone-forming salts, which leads to homogeneous nucleation in the lumen of the nephron, followed by crystal growth and consequent obstruction in the distal nephron. […] A higher percentage of kidney stones has been reported in first-degree relatives and family members with kidney stones. […] The etiological causes of UA stone formation are genetic, acquired, or a combination of both. […] The underlying pathophysiological mechanisms responsible for UA nephrolithiasis are: 1) low urine volume; 2) hyperuricosuria; and 3) unduly acidic urine.
  • #1 Pathophysiology and Main Molecular Mechanisms of Urinary Stone Formation and Recurrence
    https://www.mdpi.com/1422-0067/25/5/3075
    Macrophages have long been known to be associated with interstitial crystals in human kidney papillae. Pro-inflammatory (also termed M1) and anti-inflammatory (termed M2) phenotypes of macrophages are involved in the process of kidney stone formation. M2 macrophages can phagocytose CaOx crystals reducing stone development. The signaling mechanisms that promote M2-like macrophage polarization toward CaOx nephrocalcinosis include the NLRP3, PPARg-miR-23-Irf1/Pknox1, miR-93-TLR4/IRF1, and miR-185-5p/CSF1 pathways. […] The importance of inflammation is also suggested by the evidence of a deep correlation between renal tubular epithelial cells (RTECs) and crystals. Such an interaction is crucial and mediates the production of proinflammatory proteins, such as TNF-alpha and IL-1b, through the activation of macrophages. The overproduction of reactive oxygen species (ROS) might work contemporaneously as a cause and a consequence of inflammation in a vicious cycle where tubular injury due to crystal presence promotes inflammation which promotes crystal formation.
  • #1 Pathophysiology and Main Molecular Mechanisms of Urinary Stone Formation and Recurrence
    https://www.mdpi.com/1422-0067/25/5/3075
    Calcium deposition in the kidneys can either lead to nephrocalcinosis when it happens in renal parenchyma, or to the formation of calcium kidney stones when it happens in renal tubules. Various pieces of evidence, including human renal tissue biopsies and intra-operative endourologic imaging, have led to the development of several mechanisms aimed at elucidating the initiation and progression of the stone formation process in the urinary tract. Among the most considered mechanisms in this context is the overgrowth on interstitial CaP plaques (Randall’s plaque), and every mechanism probably contributes to this process. […] In recent years, the microbiome has been shown to be involved in maintaining homeostasis and the pathological processes of diseases. Emerging evidence indicates the active participation of the gut/microbiome in the pathogenesis of nephrolithiasis. Oxalate is excreted via the urine after absorption in the intestine. The lack of commensal bacteria with oxalate-degrading activity has been shown to be associated with stone formation. Observations have shown that the overall microbial composition in patients with kidney stones is considerably different from that in healthy controls, which further supports the intestinal microbiota as an important contributor to stone formation.
  • #1 Kidney stone disease – Wikipedia
    https://en.wikipedia.org/wiki/Kidney_stone_disease
    Supersaturation of the urine with respect to a calculogenic compound is pH-dependent. […] Randall’s plaques, which are calcium phosphate deposits that form in the papillary interstitium, are thought to be the nidus required for stone development. […] Some bacteria have roles in promoting stone formation. Specifically, urease-positive bacteria, such as Proteus mirabilis, can produce the enzyme urease, which converts urea to ammonia and carbon dioxide. […] Normal urine contains chelating agents, such as citrate, that inhibit the nucleation, growth, and aggregation of calcium-containing crystals. […] Hypocitraturia or low urinary-citrate excretion can be a contributing cause of kidney stones in up to 2/3 of cases.
  • #1 Recent advances on the mechanisms of kidney stone formation (Review)
    https://www.spandidos-publications.com/10.3892/ijmm.2021.4982
    Theoretically, AR may be a new potential target and can be evaluated for novel therapeutics for the suppression of kidney stone formation. […] Emerging evidence has indicated that microorganisms belonging to the human microbiome, including microorganisms of the kidney and urinary tract, are likely to have a profound effect on urological health, both positive and negative, due to their metabolic output and other contributions. […] Given the critical role of immune-response in CaOx crystal formation and development, the immunotherapy approach has been proposed to prevent stone recurrences in certain individuals through the modulation of the immune response, in order to degrade CaOx crystals and thus prevent stones from developing. […] Future comprehensive studies are mandatory to further elucidate the mechanisms of the microbiome and immune response in kidney stone formation, in order to develop novel prophylactic and therapeutic approaches.
  • #1 Mechanisms of Stone Formation
    https://pmc.ncbi.nlm.nih.gov/articles/PMC3252394/
    Long-term accretion of additional elements, crystalline as well as organic matrix, produces the clinical stone. […] The mechanisms responsible for the greater degree of supersaturation of stone chemical constituents in stone-forming individuals may differ depending on the type of stone; however, excessively low urine volume is often present. […] However, despite current understanding of the physical chemistry of stone formation, no single abnormality has served to distinguish stone formers from normal individuals, and many stone formers have no identifiable abnormality that explains the propensity of their urine (or tubular fluid) to nucleate stone constituents at lower levels of supersaturation, to support accelerated growth of the crystals formed, or to permit crystals to adhere to each other (aggregate) or to some intrarenal structure.
  • #1 Pathophysiology and Main Molecular Mechanisms of Urinary Stone Formation and Recurrence
    https://www.mdpi.com/1422-0067/25/5/3075
    Body mass index (BMI), fluid intake, calcium intake, and sugar sweetened drink consumption are considered modifiable risk factors for nephrolithiasis. Indeed, a diet high in fructose and obesity with a BMI of 30 or above, especially in a young population, are strongly associated with an increased incidence of nephrolithiasis. Obesity can mediate the occurrence of nephrolithiasis by changing the urinary pH and excreted components, with an effect that is differential based on gender. […] Calcium-containing stones are mainly composed of CaOX (50%), CaP (5%), or both (45%). A strict correlation between CaOX stone formation and diet has been described. Higher sodium intake leads to higher natriuresis and urinary excretion of calcium. Similarly, higher oxalate intake might lead to increased oxaluria. Additionally, higher animal protein/sulphated amino acid intake leads to more acidic urine favoring stone formation. The differential effect of modifiable risk factors on stone formation has been partially explained by epigenetic modulation.
  • #1 Medical Student Curriculum: Kidney Stones – American Urological Association
    https://www.auanet.org/meetings-and-education/for-medical-students/medical-students-curriculum/kidney-stones
    Uric acid is a product of purine metabolism and forms 7-10 percent of all urinary calculi. […] The most common risk factor for uric acid lithiasis is persistently acidic urine including the lack of a normal postprandial alkaline tide. […] Struvite stones are considered an infectious stone because they are formed specifically by urease producing organisms, the most common being Proteus mirabilis. […] As the bacteria that produce urease remain within the stone and in the urine, the urease they produce continues to cleave urea resulting in persistently alkaline urine. […] Most calcium stones will have a nidus or core of calcium phosphate which originally came from Randalls plaques. […] Calcium phosphate stones typically form in an alkaline pH of 7.2 or higher, which is a good reason to avoid prolonged overtreatment with urinary alkalinizing agents.
  • #1 Kidney Stones 2012: Pathogenesis, Diagnosis, and Management
    https://pmc.ncbi.nlm.nih.gov/articles/PMC3387413/
    Cystine nephrolithiasis comprises only a small fraction of kidney stones in adults but is more prevalent among children and adolescents with stones. […] The most important factors for the formation of infectious stones are highly alkaline urine pH in the presence of urease-producing organisms and supersaturated urinary environment with respect to magnesium, ammonium, and phosphate ions.
  • #1 Medical Student Curriculum: Kidney Stones – American Urological Association
    https://www.auanet.org/meetings-and-education/for-medical-students/medical-students-curriculum/kidney-stones
    Cystine stones are produced in patients with a homozygous recessive gene for cystine transport resulting in excessive urinary cystine levels. […] Cystine solubility and precipitation depends greatly on urinary cystine concentration and pH as there are no known inhibitors of cystine production. […] All stones may produce obstruction and pain. […] Thus, obstruction from urinary stones threatens GFR, reduces renal blood flow and, if the obstruction is not relieved, renal ischemia which leads eventually to irreversible renal impairment. […] The classic presentation of a renal stone is acute, colicky flank pain radiating to the groin or scrotum, often associated with nausea and vomiting. […] Importantly, the absence of hematuria with acute flank pain does not preclude renal or ureteral calculi as there may be complete obstruction with absence of urine emanating from the obstructed side.
  • #1
    https://link.springer.com/article/10.1007/s12551-014-0144-4
    Kidney stone disease is a polygenic and multifactorial disorder with a worldwide distribution, and its incidence and prevalence are increasing. […] However, none of the proposed mechanisms specifically consider the role(s) of the trace elements and, consequently, the contribution of trace constituents to the pathogenesis of kidney stones remains unclear and under debate. […] The findings of some studies seem to support a role for some major and trace elements in the initiation of stone crystallization, including as a nucleus or nidus for the formation of the stone or simply as a contaminant of the stone structure. […] Thus, the analysis of kidney stones is an important component of investigations on nephrolithiasis in order to understand the role of trace constituents in the formation of kidney stones and to formulate future strategies for the treatment and prevention of stone formation and its recurrence. […] We also highlight the role of major and trace elements in the pathogenesis of kidney stones.
  • #1 EAU Guidelines on Urolithiasis – Uroweb
    https://uroweb.org/guidelines/urolithiasis/chapter/guidelines
    Urolithiasis can compromise renal function because of the renal stone (obstruction, infection), renal tissue damage due to the primary condition causing stone formation (some genetic diseases, nephrocalcinosis, enteric hyperoxaluria, etc.), or urological treatments for the condition. […] Certain risk factors have been shown to be associated with such a risk in stone formers. […] There are important genetic factors underlying kidney stone disease (KSD). Indeed, KSD has an estimated heritability of ~45% suggesting that genetic factors strongly influence this disease. […] Genetic testing should be performed in combination with other metabolic testing (blood and 24 hour urine tests), and the patient should always have pre-genetic test counselling. […] Urinary stones can be classified according to size, location, X-ray characteristics, aetiology of formation, composition, and risk of recurrence. […] The most appropriate imaging modality will be determined by the clinical situation, which will differ depending on if a ureteral or a renal stone is suspected.
  • #1 Kidney stone pathophysiology – wikidoc
    https://www.wikidoc.org/index.php/Kidney_stone_pathophysiology
    It is understood that nephrolithiasis is the result of combination of different mechanism responsible for different types of 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. […] Struvite stones are usually seen in patients which have infection with urease +ve organisms. […] 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.
  • #1
    https://journals.lww.com/nutritiontodayonline/fulltext/2013/07001/pathogenesis_and_cost_effectiveness_of_preventing.7.aspx
    Environmental factors may be among the most significant factors in stone formation. […] Obesity and diabetes are associated with an increased risk for uric acid and calcium oxalate stone formation. […] Although there is not a current strategy of primary prevention of nephrolithiasis, there are known strategies to reduce the risk of formation and recurrence of stones. […] Increased fluid intake is the best reported strategy. […] Other strategies include modifying the diet to limit intake of salt and animal protein along with a normal calcium intake or an overall healthful diet such as the Dietary Approaches to Stop Hypertension diet. […] Low salt intake reduced urinary calcium excretion, which can reduce the risk of stone formation. […] Nephrolithiasis is a common problem that results in considerable cost and morbidity. […] Focusing on prevention strategies in high-risk populations can significantly increase cost effectiveness.
  • #1
    https://journals.lww.com/nutritiontodayonline/fulltext/2013/07001/pathogenesis_and_cost_effectiveness_of_preventing.7.aspx
    Nephrolithiasis is a common problem that results in considerable cost and morbidity. […] There is evidence that high volume intake can reduce the risk of stone disease by 40% to 50%. […] Nephrolithiasis has considerable morbidity with significant pain in the acute phase, resulting in loss of work and potential surgery as well as long-term complications including pyelonephritis and chronic kidney disease. […] Calcium comprises the most common component of stones, occurring in nearly 75% of cases. […] For the most part, kidney stones form as a result of super saturation of crystals, resulting in the precipitation of crystals out of solution. […] Factors that contribute to stone formation are first and foremost low urine volume, which can contribute to all types of stone formation. […] Inhibitors in urine can help prevent stone formation even with higher concentration of solutes.
  • #2 Kidney stones: Mechanism of formation, pathogenesis and possible treatments
    https://www.pulsus.com/scholarly-articles/kidney-stones-mechanism-of-formation-pathogenesis-and-possible-treatments-4896.html
    With a very high recurrence rate in both males and females, kidney stones also called as urolithiasis (nephrolithiasis) are affecting a remarkably significant population around the globe. As kidney stones formation largely depends on urines oxalate content rather than the calcium concentration of the urine, kidney stones are predominantly made up of oxalate and also there are multiple steps involved in the pathogenesis of calcium oxalate including nucleation, crystal growth, crystal aggregation and crystal retention. […] The prime cause of nephrolithiasis is the super saturation of urine with calcium and oxalate that leads to pathological mineralization in the kidneys. […] The mechanism involved in the process of stone formation include nucleation of crystals fractions, growth or gathering of these crystals to a size so that they can interact with some intra-renal structure(s), confinement of these crystals inside the kidney or renal collecting system succeeded by further aggregation and/ or secondary nucleation ultimately forming the clinical stone.
  • #2 Kidney Stone Disease: Overview » Kidney Stone Disease » Department of Urology » College of Medicine » University of Florida
    https://urology.ufl.edu/patient-care/stone-disease/
    Because most urinary crystals contain calcium, it is not surprising that 65-70% of kidney stones are calcium based. The commonly accepted calcium stone distributions are calcium oxalate (35-70%, either in monohydrate or dihydrate form), calcium phosphate (5-20%, either in apatite or brushite form), or a mixture of both (10-30%). Pure uric acid stones account for ~10% of all stones, while struvite stones (aka infection stones), composed of magnesium ammonium phosphate crystals, account for about 15%. Cystinuria, a genetic disorder, is a rare (2%) but significant cause of nephrolithiasis. […] Crystals can be found within the urine of almost all humans. These crystals are thought to be a normal body response to get rid of excess dietary mineral and to conserve water. Instead of being harmlessly excreted, stone formers urinary crystals nucleate (grow) and aggregate (stick) within the kidney, resulting in a cascade of events that lead to stone formation. The exact biological mechanisms remain unclear, but one way to prevent urinary crystals is to decrease the amount of acid, calcium, and oxalate in the urine OR to increase the amount of citrate and magnesium.
  • #2 Kidney stones: Mechanism of formation, pathogenesis and possible treatments
    https://www.pulsus.com/scholarly-articles/kidney-stones-mechanism-of-formation-pathogenesis-and-possible-treatments-4896.html
    The urine and presumably, the tubular fluid of stone formers are often more highly supersaturated than that of normal healthy adults, which favors nucleation and growth of crystals. […] Long-term accretion of additional elements, crystalline as well as organic matrix produces the clinical stone. […] The reciprocal actions between genetic susceptibility and environmental factors in different proportions promote both hypercalciuria and hyperoxaluria. […] The above mentioned processes in humans are influenced by several factors known as promoters and inhibitors that either support or prevent the process of stone formation thus affecting a persons ability to promote or prevent stone formation. Stone formation is facilitated by promoters while inhibitors prevent it. […] The uneven proportion of inhibitors and promoters are responsible to the complex process of stone formation in kidneys or urolithiasis.
  • #2 Mechanisms of Stone Formation
    https://pmc.ncbi.nlm.nih.gov/articles/PMC3252394/
    Long-term accretion of additional elements, crystalline as well as organic matrix, produces the clinical stone. […] The mechanisms responsible for the greater degree of supersaturation of stone chemical constituents in stone-forming individuals may differ depending on the type of stone; however, excessively low urine volume is often present. […] However, despite current understanding of the physical chemistry of stone formation, no single abnormality has served to distinguish stone formers from normal individuals, and many stone formers have no identifiable abnormality that explains the propensity of their urine (or tubular fluid) to nucleate stone constituents at lower levels of supersaturation, to support accelerated growth of the crystals formed, or to permit crystals to adhere to each other (aggregate) or to some intrarenal structure.
  • #2 Kidney Stones 2012: Pathogenesis, Diagnosis, and Management
    https://pmc.ncbi.nlm.nih.gov/articles/PMC3387413/
    Hyperoxaluria is detected in 10-50% of calcium stone formers. […] Both highly acidic urine (pH 5.5) and highly alkaline urine (pH 6.7) predispose patients to calcium kidney stone formation. […] One suggested mechanism for the formation of calcium stones is increased urinary supersaturation of stone-forming salts, which leads to homogeneous nucleation in the lumen of the nephron, followed by crystal growth and consequent obstruction in the distal nephron. […] A higher percentage of kidney stones has been reported in first-degree relatives and family members with kidney stones. […] The etiological causes of UA stone formation are genetic, acquired, or a combination of both. […] The underlying pathophysiological mechanisms responsible for UA nephrolithiasis are: 1) low urine volume; 2) hyperuricosuria; and 3) unduly acidic urine.
  • #2 How Are Kidney Stones Formed? | St Pete Urology
    https://stpeteurology.com/how-kidney-stones-formed/
    Kidney stones typically form from soluble salts found in urine. […] When the urine concentration of these soluble salts is very high, solid crystals may be formed. […] Therefore, urine must become supersaturated for the balance between stone-promoters and inhibitors to be broken and allow larger stones to form. […] Kidney stone formation begins by the process of nucleation, an association of free ions into microscopic particles. […] Once tiny crystals are formed, they can undergo secondary nucleation or aggregation, the processes through which the crystals formed in solution form into bigger multi-component particles. […] […] Larger crystals then can grow into giant single crystals which can be retained in the kidney by further aggregation and attachment to specific intra-renal structures.
  • #2 The role of Randall plaques on kidney stone formation – Chung – Translational Andrology and Urology
    https://tau.amegroups.org/article/view/4081/html
    Randalls plaque is microscopically a plaque of calcium deposited in the interstitial tissue of the renal papilla. These plaques are thought to serve as a nidus for urinary stone formation. […] Randalls plaque plays an important role and is prerequisite of kidney stone formation in idiopathic calcium oxalate stone formers. […] The presence of papillary plaques is associated with calcium nephrolithiasis and may contribute to the pathogenesis of calcium urinary stones. […] The urine molecules, osteopontin and Tamm Horsfall protein, and crystals in urine, driven by supersaturations, react with the exposed plaque to form a ribbon of alternating matrix and crystal layers by repeated coating and crystallization. Eventually crystallization escapes from matrix modulation and crystals extend outward into the space of urine and begin to form a calcium oxalate stone proper. […] Although Randalls plaque can be found in other stone formers, its role on kidney stone formation might not be important as its role in idiopathic calcium oxalate stone formers.
  • #2 Pathophysiology of Kidney stones | PPT
    https://www.slideshare.net/slideshow/pathophysiology-of-kidney-stones/231838705
    Aggregation is the process where precipitating crystals accumulate on each others and form a bigger crystal in a geometrical and organized fashion. […] Kidney stones form when dietary minerals in urine become concentrated enough to crystallize. They are typically classified by location and chemical composition, with calcium salts and uric acid being most common. Stones form through supersaturation when urine is too concentrated for minerals to remain in solution. […] Renal calculi, also known as kidney stones, form when minerals in urine crystallize and deposit on the inner surfaces of the kidneys. The most common types are calcium-containing stones, uric acid stones, struvite-carbonate stones, and cystine stones.
  • #2
    https://link.springer.com/article/10.1007/s00467-009-1116-y
    A third pathway suggests that crystals in the urine can become attached to a site of exposed crystalline deposits of interstitial calcium phosphate (termed Randalls plaque), following the loss of the normal urothelial covering of a renal papilla. […] Randall was convinced that interstitial plaque was a perquisite for stone formation and growth. […] The majority (approximately 75%) of CaOx stones are formed attached to sites of Randalls plaque and represents all ICSF patients. […] In all other types of kidney stone formers that we have studied, plugs were formed along the inner medullary collecting ducts and ducts of Bellini, which can serve as attachment sites for developing stones. […] These stones found attached to plugs extending from ducts of Bellini have never been found to be CaOx stones but, instead, have been apatite stones. […] Our recent studies using a combination of intraoperative endoscopic mapping and papillary biopsies have clearly shown distinct patterns of histopathologic characteristics for each type of kidney stone former that predicts the mechanism of stone formation.
  • #2 Recent advances on the mechanisms of kidney stone formation (Review)
    https://www.spandidos-publications.com/10.3892/ijmm.2021.4982
    A number of receptors or receptor-like features have been reported to play critical roles in crystal-cell interaction, which is recognized as the most important process for crystal retention in kidney. […] The present review provides an update on the mechanisms of kidney stone formation, in order to improve the understanding of kidney stones for urologists, nephrologists and primary care givers. […] RPs, first proposed by Alexander Randall in 1937, are regions of subepithelial mineralized tissue at the papillary tip, surrounding the openings of the ducts of Bellini containing CaP. […] An increasing number of studies have suggested that RPs are the origin of renal stones. […] These studies provide novel insight into the pathogenesis of RP-mediated kidney stone disease, while further studies are urgently anticipated to explore the mechanisms of RP formation, as well as additional roles of RP in the context of stone formation.
  • #2 The role of Randall plaques on kidney stone formation – Chung – Translational Andrology and Urology
    https://tau.amegroups.org/article/view/4081/5591
    Randalls plaque is microscopically a plaque of calcium deposited in the interstitial tissue of the renal papilla. These plaques are thought to serve as a nidus for urinary stone formation. […] Randalls plaque plays an important role and is prerequisite of kidney stone formation in idiopathic calcium oxalate stone formers. […] The presence of papillary plaques is associated with calcium nephrolithiasis and may contribute to the pathogenesis of calcium urinary stones. […] The original formation of Randalls plaques in the basement membrane of the thin loops of Henle resembles the ectopic calcification process. […] For calcium oxalate stones formation and growth in idiopathic calcium oxalate stone formers, Randalls plaques play an important role and are prerequisite. […] The majority (approximately 75%) of calcium oxalate stones is formed attached to sites of Randalls plaque and represents all idiopathic calcium oxalate stone formers. […] Although Randalls plaque can be found in other stone formers, its role on kidney stone formation might not be important as its role in idiopathic calcium oxalate stone formers.
  • #2 How Are Kidney Stones Formed? | St Pete Urology
    https://stpeteurology.com/how-kidney-stones-formed/
    Kidney stones are hard mineral or salt deposits formed in the kidney when urine is concentrated. Originating as microscopic crystals or particles that develop over time into pebble-sized calculi or larger deposits as minerals crystallize and fuse together, kidney stones can affect any section of the urinary tract (the kidney, bladder, ureters and urethra). […] However, if the minerals and other wastes fail to dissolve completely in urine, microscopic particles may develop which may grow into larger stones. […] Formation of urine crystals is a common occurrence even in those who never form stones. The natural existence of substances promoting crystal development in all urine means that everyone can have urine crystals. […] Nevertheless, urine also has natural inhibitors of crystal formation such as magnesium, citrate, phytate, pyrophosphate, proteins, total urine volume and other byproducts of normal metabolism.
  • #2 Kidney stone disease – Wikipedia
    https://en.wikipedia.org/wiki/Kidney_stone_disease
    Supersaturation of the urine with respect to a calculogenic compound is pH-dependent. […] Randall’s plaques, which are calcium phosphate deposits that form in the papillary interstitium, are thought to be the nidus required for stone development. […] Some bacteria have roles in promoting stone formation. Specifically, urease-positive bacteria, such as Proteus mirabilis, can produce the enzyme urease, which converts urea to ammonia and carbon dioxide. […] Normal urine contains chelating agents, such as citrate, that inhibit the nucleation, growth, and aggregation of calcium-containing crystals. […] Hypocitraturia or low urinary-citrate excretion can be a contributing cause of kidney stones in up to 2/3 of cases.
  • #2 Calcium Kidney Stones: Pathogenesis, Evaluation, and Treatment Options
    https://www.uspharmacist.com/article/calcium-kidney-stones-pathogenesis-evaluation-and-treatment-options
    Calcium stones form when urine is supersaturated with the constituent ions that comprise the stone. Hence, supersaturation with calcium and oxalate ions will promote the formation of calcium oxalate stones. Supersaturation of urine with calcium and phosphate ions will promote the formation of calcium phosphate stones. Supersaturation occurs when the product of the ionic activity of calcium [Ca2+]a and oxalate [Oxalate2-]a exceeds the solubility product for calcium oxalate (SP1); or the product of the ionic activity of calcium [Ca2+]a and phosphate [HPO42-]a exceeds the solubility product for calcium phosphate (SP2). […] […] Homogeneous nucleation occurs when calcium and oxalate ions complex to form small crystals that then grow to larger pure calcium oxalate stones. Heterogeneous nucleation occurs when calcium and phosphate ions complex to initially form small crystals of calcium phosphate. These small crystals form the substrate upon which calcium oxalate subsequently deposits. This results in a mixed calcium oxalate-calcium phosphate stone. Various factors contribute, including the concentrations of individual free (unbound) ions such as calcium and oxalate, the pH, and the presence or absence of other substances that can either accelerate or retard the formation of calcium stones. For example, citrate is a known inhibitor of calcium crystallization, because citrate forms soluble complexes with calcium, which then lowers the ionic activity of free calcium ions in the urine and decreases stone formation. […]
  • #2 Kidney stones Information | Mount Sinai – New York
    https://www.mountsinai.org/health-library/report/kidney-stones
    The key process in the development of kidney stones is supersaturation. […] These substances can become extremely concentrated if there is not enough urine, or if unusually high amounts of crystal-forming salts are present. […] When the chemical concentration levels reach the point at which they no longer dissolve in urine, these substances form crystals. […] Not having enough of these protective substances can cause stones. […] Changes in the acid balance of the urine can affect stone formation. […] Uric acid and cystine stones mainly form in acidic urine. […] Calcium phosphate and struvite stones increase in alkaline urine. […] Research suggests that nearly all stones result from problems in the breakdown and absorption of calcium and oxalate. […] Hypercalciuria is a condition in which there is too much calcium in the urine.
  • #2 Recent advances on the mechanisms of kidney stone formation (Review)
    https://www.spandidos-publications.com/10.3892/ijmm.2021.4982
    Theoretically, AR may be a new potential target and can be evaluated for novel therapeutics for the suppression of kidney stone formation. […] Emerging evidence has indicated that microorganisms belonging to the human microbiome, including microorganisms of the kidney and urinary tract, are likely to have a profound effect on urological health, both positive and negative, due to their metabolic output and other contributions. […] Given the critical role of immune-response in CaOx crystal formation and development, the immunotherapy approach has been proposed to prevent stone recurrences in certain individuals through the modulation of the immune response, in order to degrade CaOx crystals and thus prevent stones from developing. […] Future comprehensive studies are mandatory to further elucidate the mechanisms of the microbiome and immune response in kidney stone formation, in order to develop novel prophylactic and therapeutic approaches.
  • #2 Medical Student Curriculum: Kidney Stones – American Urological Association
    https://www.auanet.org/meetings-and-education/for-medical-students/medical-students-curriculum/kidney-stones
    Uric acid is a product of purine metabolism and forms 7-10 percent of all urinary calculi. […] The most common risk factor for uric acid lithiasis is persistently acidic urine including the lack of a normal postprandial alkaline tide. […] Struvite stones are considered an infectious stone because they are formed specifically by urease producing organisms, the most common being Proteus mirabilis. […] As the bacteria that produce urease remain within the stone and in the urine, the urease they produce continues to cleave urea resulting in persistently alkaline urine. […] Most calcium stones will have a nidus or core of calcium phosphate which originally came from Randalls plaques. […] Calcium phosphate stones typically form in an alkaline pH of 7.2 or higher, which is a good reason to avoid prolonged overtreatment with urinary alkalinizing agents.
  • #2
    https://journals.lww.com/nutritiontodayonline/fulltext/2013/07001/pathogenesis_and_cost_effectiveness_of_preventing.7.aspx
    Environmental factors may be among the most significant factors in stone formation. […] Obesity and diabetes are associated with an increased risk for uric acid and calcium oxalate stone formation. […] Although there is not a current strategy of primary prevention of nephrolithiasis, there are known strategies to reduce the risk of formation and recurrence of stones. […] Increased fluid intake is the best reported strategy. […] Other strategies include modifying the diet to limit intake of salt and animal protein along with a normal calcium intake or an overall healthful diet such as the Dietary Approaches to Stop Hypertension diet. […] Low salt intake reduced urinary calcium excretion, which can reduce the risk of stone formation. […] Nephrolithiasis is a common problem that results in considerable cost and morbidity. […] Focusing on prevention strategies in high-risk populations can significantly increase cost effectiveness.

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Proteus mirabilis hiperkalciuria szczawian kamień struwitu agregacja kryształów kamień cystynowy makrofagi kamień szczawianowo-wapniowy nukleacja kryształów przesycenie moczu kamień z kwasu moczowego hiperurykozuria kamień struwitowy pH moczu fosforan magnezowo-amonowy płytka Randalla choroba Denta hipocytratura kamica nerkowa cytrynian mikrobiota jelitowa hiperoksaluria kamień wapniowy białko Tamma-Horsfalla zespół Bartera