Kalcifilaksja – Rokowania, prognozy i postęp choroby

Kalcifilaksja
Rokowania, prognozy i postęp choroby

Kalcifilaksja, znana również jako wapniejąca arteriolopatia mocznicowa, charakteryzuje się wysoką śmiertelnością, z jednorocznymi wskaźnikami sięgającymi 45-80%. Szczególnie niekorzystne rokowanie obserwuje się u pacjentów poddawanych hemodializie, u których śmiertelność jest niemal trzykrotnie wyższa niż u dializowanych bez kalcifilaksji. Kluczowymi czynnikami wpływającymi na przeżycie są obecność owrzodzeń skóry, funkcja nerek (wskaźnik 12-miesięcznego przeżycia: 100% u pacjentów z prawidłową funkcją nerek, 29% po przeszczepie nerki, 57% na hemodializie) oraz poziom albumin w surowicy. Zgon najczęściej następuje w wyniku sepsy związanej z infekcją zmian skórnych, która dotyka zwłaszcza pacjentów z owrzodzeniami, a śmiertelność z powodu sepsy sięga 60-80%.

Prognoza w kalcifilaksji (kalcyfilaksji)

Kalcifilaksja (znana również jako kalcyfilaksja lub wapniejąca arteriolopatia mocznicowa) charakteryzuje się niekorzystnym rokowaniem z wysokim wskaźnikiem śmiertelności. Jednoroczne wskaźniki śmiertelności wahają się między 45% a 80%, a odpowiedź na terapię jest często niewystarczająca.¹²³ Badania wykazały, że śmiertelność u pacjentów poddawanych przewlekłej hemodializie z kalcifilaksją była prawie 3-krotnie wyższa niż u pacjentów dializowanych bez tej choroby, według danych z United States Renal Data System.⁴

Czynniki wpływające na śmiertelność

Śmiertelność w kalcifilaksji zależy od wielu czynników, a wśród najważniejszych można wymienić:

Stan owrzodzenia zmian skórnych – pacjenci z owrzodzonymi zmianami są szczególnie narażeni na rozwój infekcji, co stanowi główną przyczynę zgonów.⁵⁶
Funkcja nerek – pacjenci z prawidłową funkcją nerek mają zdecydowanie lepsze rokowanie (wskaźnik 12-miesięcznego przeżycia 100%) w porównaniu do pacjentów z przewlekłą niewydolnością nerek, zwłaszcza po przeszczepie nerki (wskaźnik przeżycia 29%) czy będących na hemodializie (wskaźnik przeżycia 57%).⁷
Hipoalbuminemia – obniżony poziom albumin w surowicy jest istotnym czynnikiem ryzyka śmiertelności.⁸

Czas przeżycia i przebieg choroby

Przebieg kalcifilaksji jest często ciężki i prowadzi do znaczącego obniżenia jakości życia. Pacjenci cierpią z powodu nieznośnego bólu, który często nie reaguje na konwencjonalne leki przeciwbólowe.⁹ Badania wykazały, że:

40,4% zgonów spowodowanych kalcifilaksją występuje w pierwszym roku po diagnozie
56,2% zgonów następuje w ciągu 5 lat od rozpoznania
Główną okolicznością zgonu jest opieka paliatywna u pacjentów z kalcifilaksją¹⁰

Pozytywne czynniki prognostyczne

Mimo ogólnie złego rokowania, pewne czynniki mogą wpływać na lepsze wyniki leczenia i dłuższe przeżycie pacjentów z kalcifilaksją:

Całkowite wygojenie zmian – odnotowano w 37,1% przypadków¹¹
Wyższy wskaźnik masy ciała (BMI) – związany z lepszym rokowaniem w analizie jednowymiarowej
Wyższy poziom albumin w momencie pojawienia się zmian
Zaprzestanie leczenia antagonistami witaminy K (VKA) – istotny czynnik poprawiający przeżycie w analizie jednowymiarowej¹²

Interwencje wpływające na rokowanie

W analizie wielowymiarowej zidentyfikowano czynniki niezależnie związane z przeżyciem pacjentów z kalcifilaksją:

Chirurgiczne oczyszczenie ran – korzystnie wpływa na przeżycie
Antybiotykoterapia – poprawia rokowanie
Paratyroidektomia – zwiększa ryzyko zgonu¹³

Kalcifilaksja a zaburzenia mineralnej gospodarki kostnej

Warto zauważyć, że choć kalcifilaksja tradycyjnie uważana jest za przejaw ciężko zaburzonego metabolizmu wapniowo-fosforanowego u pacjentów dializowanych, to nie jest to jedyny czynnik ryzyka jej rozwoju. Mimo wysokiej częstości zaburzeń mineralnych i kostnych u pacjentów dializowanych, kalcifilaksja pozostaje chorobą rzadką. Ponadto istnieją liczne doniesienia opisujące pacjentów dializowanych, u których rozwinęła się kalcifilaksja pomimo braku znaczących nieprawidłowości laboratoryjnych w zakresie gospodarki mineralnej.¹⁴

Grupy ryzyka pod względem rokowania

Na podstawie dostępnych danych można wyróżnić grupy pacjentów o szczególnie niekorzystnym rokowaniu:

Pacjenci po przeszczepie nerki – najniższy wskaźnik przeżycia (29% po 12 miesiącach)
Pacjenci hemodializowani – pośredni wskaźnik przeżycia (57% po 12 miesiącach)
Pacjenci z owrzodzonymi zmianami skórnymi – wysokie ryzyko infekcji i sepsy
Pacjenci z hipoalbuminemią – znacząco wyższe ryzyko zgonu¹⁵¹⁶

Godne uwagi jest, że pacjenci z kalcifilaksją i prawidłową funkcją nerek (tzw. nieuremiczna kalcifilaksja) mają zdecydowanie lepsze rokowanie – w badaniach wykazano 100% przeżycie w 12-miesięcznej obserwacji.¹⁷¹⁸

Przyczyny zgonów

Najczęstszą przyczyną zgonu w kalcifilaksji jest sepsa związana z infekcją zmian skórnych. Śmiertelność z powodu sepsy w kalcifilaksji sięga 60-80%.¹⁹ Pacjenci z owrzodzonymi zmianami są szczególnie narażeni na rozwój infekcji prowadzących do sepsy.²⁰

Podsumowując, kalcifilaksja pozostaje chorobą o bardzo poważnym rokowaniu, zwłaszcza u pacjentów z przewlekłą chorobą nerek. Jednak wczesne rozpoznanie, odpowiednie leczenie z chirurgicznym oczyszczeniem ran i antybiotykoterapią, a także ścisła kontrola czynników ryzyka mogą przyczynić się do poprawy rokowania w tej rzadkiej i wyniszczającej chorobie.

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Materiały źródłowe

#1 Calciphylaxis – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK519020/
Calciphylaxis has a poor prognosis with 1-year mortality rates between 45% and 80%, and the response to therapy is also poor. […] Patients with ulcerated lesions are particularly prone to developing an infection, which is the leading cause of death. […] The outlook for most patients with calciphylaxis is poor. Most patients have a poor quality of life and suffer from excruciating pain, which is often not responsive to conventional analgesics.
#2 Calciphylaxis: Risk Factors, Diagnosis, and Treatment
https://pmc.ncbi.nlm.nih.gov/articles/PMC4696752/
Calciphylaxis is a rare and highly morbid condition that has continued to challenge the medical community since its early descriptions. Calciphylaxis predominantly affects chronic kidney failure patients treated by dialysis. However, calciphylaxis is not limited to patients treated by dialysis and also occurs in patients with normal kidney function and in those with earlier stages of chronic kidney disease (referred to as non-uremic calciphylaxis). Both uremic and non-uremic calciphylaxis are associated with significant morbidity and mortality. The one-year mortality in calciphylaxis patients is reported at 45-80% with ulcerated lesions associated with higher mortality compared to non-ulcerated lesions and sepsis being the leading cause of death. Mortality rates in chronic hemodialysis patients with calciphylaxis were almost 3 times higher than for chronic hemodialysis patients without calciphylaxis in the United States Renal Data System. Some studies also report that the incidence of calciphylaxis is increasing in dialysis population; however, whether this is truly an increase in incidence or enhanced awareness remains unclear.
#3 Calciphylaxis epidemiology, risk factors, treatment and survival among French chronic kidney disease patients: a case-control study | BMC Nephrology | Full Text
https://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-020-01722-y
Calcific uremic arteriolopathy (CUA), also called calciphylaxis, is a rare but devastating disease involving patients with end stage renal disease (ESRD). CUA causes painful skin lesions that evolve to ulcerative lesions at risk of superinfection and sepsis, with a poor prognosis. One year survival rates vary between 45 to 55%. CUA management lacks strong recommendations and therefore is heterogeneous. […] 40.4% of deaths due to calciphylaxis occurred during the first year after diagnosis and 56.2% after 5 years. Mortality of dialysis cases was significantly higher than paired hemodialysis controls. […] The main circumstance of death was in palliative care for CUA patients. […] Complete healing of CUA lesions occurred in 37.1%. […] Higher BMI, higher serum albumin at onset of lesions and VKA discontinuation were associated with better survival in univariate analysis only. […] By multivariate analysis, factors independently associated with survival were surgical debridement and antibiotherapy, whereas parathyroidectomy increased the risk of death.
#4 Calciphylaxis: Risk Factors, Diagnosis, and Treatment
https://pmc.ncbi.nlm.nih.gov/articles/PMC4696752/
Calciphylaxis is a rare and highly morbid condition that has continued to challenge the medical community since its early descriptions. Calciphylaxis predominantly affects chronic kidney failure patients treated by dialysis. However, calciphylaxis is not limited to patients treated by dialysis and also occurs in patients with normal kidney function and in those with earlier stages of chronic kidney disease (referred to as non-uremic calciphylaxis). Both uremic and non-uremic calciphylaxis are associated with significant morbidity and mortality. The one-year mortality in calciphylaxis patients is reported at 45-80% with ulcerated lesions associated with higher mortality compared to non-ulcerated lesions and sepsis being the leading cause of death. Mortality rates in chronic hemodialysis patients with calciphylaxis were almost 3 times higher than for chronic hemodialysis patients without calciphylaxis in the United States Renal Data System. Some studies also report that the incidence of calciphylaxis is increasing in dialysis population; however, whether this is truly an increase in incidence or enhanced awareness remains unclear.
#5 Calciphylaxis – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK519020/
Calciphylaxis has a poor prognosis with 1-year mortality rates between 45% and 80%, and the response to therapy is also poor. […] Patients with ulcerated lesions are particularly prone to developing an infection, which is the leading cause of death. […] The outlook for most patients with calciphylaxis is poor. Most patients have a poor quality of life and suffer from excruciating pain, which is often not responsive to conventional analgesics.
#6 Calciphylaxis: Risk Factors, Diagnosis, and Treatment
https://pmc.ncbi.nlm.nih.gov/articles/PMC4696752/
Calciphylaxis is a rare and highly morbid condition that has continued to challenge the medical community since its early descriptions. Calciphylaxis predominantly affects chronic kidney failure patients treated by dialysis. However, calciphylaxis is not limited to patients treated by dialysis and also occurs in patients with normal kidney function and in those with earlier stages of chronic kidney disease (referred to as non-uremic calciphylaxis). Both uremic and non-uremic calciphylaxis are associated with significant morbidity and mortality. The one-year mortality in calciphylaxis patients is reported at 45-80% with ulcerated lesions associated with higher mortality compared to non-ulcerated lesions and sepsis being the leading cause of death. Mortality rates in chronic hemodialysis patients with calciphylaxis were almost 3 times higher than for chronic hemodialysis patients without calciphylaxis in the United States Renal Data System. Some studies also report that the incidence of calciphylaxis is increasing in dialysis population; however, whether this is truly an increase in incidence or enhanced awareness remains unclear.
#7 Calciphylaxis: Beyond CKD-MBD | NefrologÃa
https://www.revistanefrologia.com/en-relaccionados-calciphylaxis-beyond-ckd-mbd-articulo-S201325141730158X
Calcific uraemic arteriolopathy (CUA), also called calciphylaxis, is a rare but potentially fatal vascular disorder that almost exclusively affects patients with chronic renal failure. […] The objective of this study was to analyse various risk factors for developing CUA and its subsequent clinical course according to the treatment received. […] Patient survival at 12 months was 29% in transplant patients, 57% in haemodialysis patients and 100% in normal renal function patients (log-rank 6.88, p=0.032). […] Chronic renal failure (p=0.03) and hypoalbuminaemia (p=0.02) were the main risk factor for CUA mortality. […] Although the incidence of CUA remains low, CUA mortality is very high, Special attention to its occurrence in kidney transplant patients and non-renal CUA forms is required.
#8 Calciphylaxis: Beyond CKD-MBD | NefrologÃa
https://www.revistanefrologia.com/en-relaccionados-calciphylaxis-beyond-ckd-mbd-articulo-S201325141730158X
Calcific uraemic arteriolopathy (CUA), also called calciphylaxis, is a rare but potentially fatal vascular disorder that almost exclusively affects patients with chronic renal failure. […] The objective of this study was to analyse various risk factors for developing CUA and its subsequent clinical course according to the treatment received. […] Patient survival at 12 months was 29% in transplant patients, 57% in haemodialysis patients and 100% in normal renal function patients (log-rank 6.88, p=0.032). […] Chronic renal failure (p=0.03) and hypoalbuminaemia (p=0.02) were the main risk factor for CUA mortality. […] Although the incidence of CUA remains low, CUA mortality is very high, Special attention to its occurrence in kidney transplant patients and non-renal CUA forms is required.
#9 Calciphylaxis – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK519020/
Calciphylaxis has a poor prognosis with 1-year mortality rates between 45% and 80%, and the response to therapy is also poor. […] Patients with ulcerated lesions are particularly prone to developing an infection, which is the leading cause of death. […] The outlook for most patients with calciphylaxis is poor. Most patients have a poor quality of life and suffer from excruciating pain, which is often not responsive to conventional analgesics.
#10 Calciphylaxis epidemiology, risk factors, treatment and survival among French chronic kidney disease patients: a case-control study | BMC Nephrology | Full Text
https://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-020-01722-y
Calcific uremic arteriolopathy (CUA), also called calciphylaxis, is a rare but devastating disease involving patients with end stage renal disease (ESRD). CUA causes painful skin lesions that evolve to ulcerative lesions at risk of superinfection and sepsis, with a poor prognosis. One year survival rates vary between 45 to 55%. CUA management lacks strong recommendations and therefore is heterogeneous. […] 40.4% of deaths due to calciphylaxis occurred during the first year after diagnosis and 56.2% after 5 years. Mortality of dialysis cases was significantly higher than paired hemodialysis controls. […] The main circumstance of death was in palliative care for CUA patients. […] Complete healing of CUA lesions occurred in 37.1%. […] Higher BMI, higher serum albumin at onset of lesions and VKA discontinuation were associated with better survival in univariate analysis only. […] By multivariate analysis, factors independently associated with survival were surgical debridement and antibiotherapy, whereas parathyroidectomy increased the risk of death.
#11 Calciphylaxis epidemiology, risk factors, treatment and survival among French chronic kidney disease patients: a case-control study | BMC Nephrology | Full Text
https://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-020-01722-y
Calcific uremic arteriolopathy (CUA), also called calciphylaxis, is a rare but devastating disease involving patients with end stage renal disease (ESRD). CUA causes painful skin lesions that evolve to ulcerative lesions at risk of superinfection and sepsis, with a poor prognosis. One year survival rates vary between 45 to 55%. CUA management lacks strong recommendations and therefore is heterogeneous. […] 40.4% of deaths due to calciphylaxis occurred during the first year after diagnosis and 56.2% after 5 years. Mortality of dialysis cases was significantly higher than paired hemodialysis controls. […] The main circumstance of death was in palliative care for CUA patients. […] Complete healing of CUA lesions occurred in 37.1%. […] Higher BMI, higher serum albumin at onset of lesions and VKA discontinuation were associated with better survival in univariate analysis only. […] By multivariate analysis, factors independently associated with survival were surgical debridement and antibiotherapy, whereas parathyroidectomy increased the risk of death.
#12 Calciphylaxis epidemiology, risk factors, treatment and survival among French chronic kidney disease patients: a case-control study | BMC Nephrology | Full Text
https://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-020-01722-y
Calcific uremic arteriolopathy (CUA), also called calciphylaxis, is a rare but devastating disease involving patients with end stage renal disease (ESRD). CUA causes painful skin lesions that evolve to ulcerative lesions at risk of superinfection and sepsis, with a poor prognosis. One year survival rates vary between 45 to 55%. CUA management lacks strong recommendations and therefore is heterogeneous. […] 40.4% of deaths due to calciphylaxis occurred during the first year after diagnosis and 56.2% after 5 years. Mortality of dialysis cases was significantly higher than paired hemodialysis controls. […] The main circumstance of death was in palliative care for CUA patients. […] Complete healing of CUA lesions occurred in 37.1%. […] Higher BMI, higher serum albumin at onset of lesions and VKA discontinuation were associated with better survival in univariate analysis only. […] By multivariate analysis, factors independently associated with survival were surgical debridement and antibiotherapy, whereas parathyroidectomy increased the risk of death.
#13 Calciphylaxis epidemiology, risk factors, treatment and survival among French chronic kidney disease patients: a case-control study | BMC Nephrology | Full Text
https://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-020-01722-y
Calcific uremic arteriolopathy (CUA), also called calciphylaxis, is a rare but devastating disease involving patients with end stage renal disease (ESRD). CUA causes painful skin lesions that evolve to ulcerative lesions at risk of superinfection and sepsis, with a poor prognosis. One year survival rates vary between 45 to 55%. CUA management lacks strong recommendations and therefore is heterogeneous. […] 40.4% of deaths due to calciphylaxis occurred during the first year after diagnosis and 56.2% after 5 years. Mortality of dialysis cases was significantly higher than paired hemodialysis controls. […] The main circumstance of death was in palliative care for CUA patients. […] Complete healing of CUA lesions occurred in 37.1%. […] Higher BMI, higher serum albumin at onset of lesions and VKA discontinuation were associated with better survival in univariate analysis only. […] By multivariate analysis, factors independently associated with survival were surgical debridement and antibiotherapy, whereas parathyroidectomy increased the risk of death.
#14 Calciphylaxis: Risk Factors, Diagnosis, and Treatment
https://pmc.ncbi.nlm.nih.gov/articles/PMC4696752/
Calciphylaxis has been traditionally considered as a manifestation of severely dysregulated calcium-phosphorous metabolism in dialysis patients due to the high prevalence of mineral bone abnormalities, the frequent use of pro-calcification treatments (such as calcium salts and vitamin D), and the original description of parathyroid hormone, and vitamin D as sensitizing agents in Selye’s model. However, it is important to take into account that despite the high prevalence of mineral bone abnormalities in dialysis patients, calciphylaxis is a rare disease and a number of reports in the literature describe dialysis patients who developed calciphylaxis despite the absence of significant mineral bone laboratory abnormalities. […] In our opinion, although the role of dysregulated calcium-phosphorous metabolism as a risk factor for calciphylaxis cannot be overlooked and requires further investigation in larger observation studies, it is not the sole risk factor for calciphylaxis.
#15 Calciphylaxis: Beyond CKD-MBD | NefrologÃa
https://www.revistanefrologia.com/en-relaccionados-calciphylaxis-beyond-ckd-mbd-articulo-S201325141730158X
Calcific uraemic arteriolopathy (CUA), also called calciphylaxis, is a rare but potentially fatal vascular disorder that almost exclusively affects patients with chronic renal failure. […] The objective of this study was to analyse various risk factors for developing CUA and its subsequent clinical course according to the treatment received. […] Patient survival at 12 months was 29% in transplant patients, 57% in haemodialysis patients and 100% in normal renal function patients (log-rank 6.88, p=0.032). […] Chronic renal failure (p=0.03) and hypoalbuminaemia (p=0.02) were the main risk factor for CUA mortality. […] Although the incidence of CUA remains low, CUA mortality is very high, Special attention to its occurrence in kidney transplant patients and non-renal CUA forms is required.
#16 Calciphylaxis: Beyond CKD-MBD | NefrologÃa
https://www.revistanefrologia.com/en-relaccionados-calciphylaxis-beyond-ckd-mbd-articulo-S201325141730158X
The prognosis of this disease is very poor, as it shows a mortality rate of up to 60-80%, with calciphylaxis-related sepsis as the most common cause of death. […] In addition, it is important to note that patients with normal renal function have an excellent prognosis with regard to calciphylaxis (none of them died due to this reason), compared with patients with CKD (especially renal transplant patients), who have a very high probability of dying within a few months (p=0.032).
#17 Calciphylaxis: Beyond CKD-MBD | NefrologÃa
https://www.revistanefrologia.com/en-relaccionados-calciphylaxis-beyond-ckd-mbd-articulo-S201325141730158X
Calcific uraemic arteriolopathy (CUA), also called calciphylaxis, is a rare but potentially fatal vascular disorder that almost exclusively affects patients with chronic renal failure. […] The objective of this study was to analyse various risk factors for developing CUA and its subsequent clinical course according to the treatment received. […] Patient survival at 12 months was 29% in transplant patients, 57% in haemodialysis patients and 100% in normal renal function patients (log-rank 6.88, p=0.032). […] Chronic renal failure (p=0.03) and hypoalbuminaemia (p=0.02) were the main risk factor for CUA mortality. […] Although the incidence of CUA remains low, CUA mortality is very high, Special attention to its occurrence in kidney transplant patients and non-renal CUA forms is required.
#18 Calciphylaxis: Beyond CKD-MBD | NefrologÃa
https://www.revistanefrologia.com/en-relaccionados-calciphylaxis-beyond-ckd-mbd-articulo-S201325141730158X
The prognosis of this disease is very poor, as it shows a mortality rate of up to 60-80%, with calciphylaxis-related sepsis as the most common cause of death. […] In addition, it is important to note that patients with normal renal function have an excellent prognosis with regard to calciphylaxis (none of them died due to this reason), compared with patients with CKD (especially renal transplant patients), who have a very high probability of dying within a few months (p=0.032).
#19 Calciphylaxis: Beyond CKD-MBD | NefrologÃa
https://www.revistanefrologia.com/en-relaccionados-calciphylaxis-beyond-ckd-mbd-articulo-S201325141730158X
The prognosis of this disease is very poor, as it shows a mortality rate of up to 60-80%, with calciphylaxis-related sepsis as the most common cause of death. […] In addition, it is important to note that patients with normal renal function have an excellent prognosis with regard to calciphylaxis (none of them died due to this reason), compared with patients with CKD (especially renal transplant patients), who have a very high probability of dying within a few months (p=0.032).
#20 Calciphylaxis – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK519020/
Calciphylaxis has a poor prognosis with 1-year mortality rates between 45% and 80%, and the response to therapy is also poor. […] Patients with ulcerated lesions are particularly prone to developing an infection, which is the leading cause of death. […] The outlook for most patients with calciphylaxis is poor. Most patients have a poor quality of life and suffer from excruciating pain, which is often not responsive to conventional analgesics.