Autosomalna dominująca wielotorbielowatość nerek – Rokowania, prognozy i postęp choroby

Autosomalna dominująca wielotorbielowatość nerek
Rokowania, prognozy i postęp choroby

Autosomalna dominująca wielotorbielowatość nerek (ADPKD) cechuje się zmiennym przebiegiem klinicznym, z około 35-45% pacjentów rozwijających niewydolność nerek do 60. roku życia, a 50-75% wymagających leczenia nerkozastępczego do 75. roku życia. Rokowanie jest silnie zależne od mutacji genetycznych, gdzie mutacje w genie PKD1, zwłaszcza mutacje skracające, wiążą się z gorszym przebiegiem niż mutacje w PKD2. Mediana wieku rozpoczęcia leczenia nerkozastępczego jest podobna dla obu genotypów (około 51-52 lat). Do oceny ryzyka progresji stosuje się modele prognostyczne, takie jak Klasyfikacja Obrazowania Mayo (MIC) oparta na skorygowanej względem wzrostu objętości nerek (ht-TKV) oraz skala PROPKD, łącząca dane genetyczne i kliniczne, choć ich zastosowanie w codziennej praktyce jest ograniczone ze względu na koszty i dostępność specjalistycznych badań.

Prognoza autosomalnej dominującej wielotorbielowatości nerek

Czynniki prognostyczne oparte na mutacjach genetycznych
Modele prognostyczne w ADPKD
Biomarkery prognostyczne
Objętość nerek jako biomarker prognostyczny
Czynniki modyfikowalne wpływające na prognozę
Powikłania wpływające na prognozę

Przewidywanie progresji ADPKD u dzieci
Podsumowanie prognozy w ADPKD

Kolejne rozdziały

Prognoza autosomalnej dominującej wielotorbielowatości nerek

Autosomalna dominująca wielotorbielowatość nerek (ADPKD) charakteryzuje się wysoce zmienną prognozą. Rokowanie pacjentów z ADPKD jest zróżnicowane – u niektórych niewydolność nerek rozwija się wkrótce po rozpoznaniu choroby, podczas gdy inni mogą przeżyć resztę życia z relatywnie dobrze funkcjonującymi nerkami¹. Średnio około połowa pacjentów z ADPKD wymaga leczenia nerkozastępczego przed ukończeniem 60. roku życia². Badania wykazują, że u 35-45% pacjentów z ADPKD niewydolność nerek rozwija się do 60. roku życia, a do 75. roku życia 50-75% pacjentów wymaga terapii nerkozastępczej (dializy lub przeszczepienia)³.

Czynniki prognostyczne oparte na mutacjach genetycznych

Istotny wpływ na prognozę ADPKD mają czynniki genetyczne. Pacjenci z mutacjami genu PKD1, szczególnie z mutacjami skracającymi (truncating), wykazują gorsze rokowanie w porównaniu do pacjentów z mutacjami PKD2⁴⁵. Obserwuje się znaczącą różnicę w proporcji pacjentów, którzy wymagają leczenia nerkozastępczego w zależności od genotypu (32,3% dla PKD1 vs 20,8% dla PKD2)⁶.

Szczegółowa analiza typów mutacji wykazała, że rokowanie nerkowe różni się w zależności od rodzaju mutacji zarówno w genach PKD1, jak i PKD2. Pacjenci z mutacjami splicingowymi PKD1, mutacjami przesunięcia ramki odczytu (frameshift) PKD1 oraz mutacjami splicingowymi PKD2 mają szczególnie złe rokowanie⁷⁸. Co interesujące, mimo obecności mutacji skracających, rokowanie nerkowe było względnie korzystne u pacjentów z mutacjami nonsensownymi⁹¹⁰.

Należy zauważyć, że rokowanie nerkowe u pacjentów z mutacjami PKD2 nie zawsze jest korzystne, jak wcześniej sądzono. Badania wykazały, że trzech z pięciu pacjentów z mutacją PKD2 wymagało leczenia nerkozastępczego przed 58. rokiem życia¹¹¹². Porównanie pacjentów, którzy osiągnęli stadium wymagające leczenia nerkozastępczego, nie wykazało różnicy w wieku osiągnięcia tego stadium między pacjentami z mutacjami PKD1 i PKD2 (mediana 52 lata vs 51 lat)¹³.

Modele prognostyczne w ADPKD

Obecnie stosowanych jest kilka modeli prognostycznych do przewidywania progresji ADPKD. Najlepszym predyktorem progresji choroby jest model prognostyczny oparty na skorygowanej względem wieku objętości nerek (ht-TKV), czyli Klasyfikacja Obrazowania Mayo (Mayo Imaging Classification, MIC), która kategoryzuje pacjentów z ADPKD do klas od 1A do 1E, przy czym wyższe klasy wiążą się ze znacznie większym ryzykiem progresji do schyłkowej niewydolności nerek¹⁴.

Innym powszechnie stosowanym modelem prognostycznym jest skala PROPKD (Predicting Renal Outcome in Polycystic Kidney Disease), która łączy informacje o mutacji genetycznej i klinicznych czynnikach ryzyka, kategoryzując pacjentów z ADPKD jako osoby o niskim, pośrednim lub wysokim ryzyku progresji do schyłkowej niewydolności nerek¹⁵.

Chociaż MIC i PROPKD są obecnie najczęściej stosowanymi modelami prognostycznymi w badaniach klinicznych ADPKD, wszystkie te predykcyjne skale mają ograniczenia związane z dostępnością, wysokimi kosztami i koniecznością posiadania specjalistycznej wiedzy do uzyskania takich parametrów, przez co nie są przydatne w codziennej praktyce klinicznej¹⁶.

Biomarkery prognostyczne

W związku z ograniczeniami istniejących modeli prognostycznych, intensywnie poszukuje się biomarkerów, które mogłyby przewidywać szybką progresję choroby u pacjentów z ADPKD. Wśród różnych badanych cząsteczek, najbardziej obiecującymi biomarkerami do przewidywania progresji ADPKD są¹⁷:

kopeptyna
apelina
angiotensynogen
czynnik wzrostu fibroblastów 23 (FGF23)
suPAR (rozpuszczalny receptor urokinazowego aktywatora plazminogenu)
wodorowęglany w surowicy
sFRP4 (secreted frizzled-related protein 4)
KIM1 (kidney injury molecule-1)
MCP1 (monocyte chemoattractant protein-1)
2MG (β2-mikroglobulina)
CD14
fetuina A
osteopontyna

¹⁸

Badania wykazały, że stosunek albuminy do kreatyniny w moczu, stosunek MCP-1 do kreatyniny w moczu oraz kopeptyna w surowicy wykazują najsilniejsze związki ze wskaźnikiem spadku eGFR i są niezależnymi predyktorami szybko postępującej choroby¹⁹. Te biomarkery mogą poprawić stratyfikację ryzyka u pacjentów z ADPKD, nawet w podgrupach, w których prognozowanie jest najbardziej wymagające i istotne²⁰.

Dodatkowo parametry takie jak osmolalność moczu i stosunek mocznika w moczu do osocza (U/P urea) są wiarygodnymi zastępczymi biomarkerami maksymalnej zdolności zagęszczania moczu i wydają się mieć użyteczność kliniczną jako predyktory szybkiej progresji ADPKD²¹.

Objętość nerek jako biomarker prognostyczny

Całkowita objętość nerek (TKV), szczególnie skorygowana względem wzrostu (ht-TKV), została uznana za wczesny biomarker oceny ciężkości choroby u pacjentów z ADPKD²². Pomiary objętości torbieli i nerek przewidują ryzyko progresji do przewlekłej choroby nerek i schyłkowej niewydolności nerek, często przed zmianami w rutynowych badaniach laboratoryjnych²³.

Amerykańska Agencja ds. Żywności i Leków (FDA) wydała decyzję kwalifikacyjną w formie projektu wytycznych dla całkowitej objętości nerek (TKV) jako biomarkera prognostycznego do wyboru pacjentów do badań klinicznych nowych terapii ADPKD²⁴. TKV jest miarą wpływu ADPKD na wielkość nerek i uważa się, że przewiduje przyszły spadek funkcji nerek. Wytyczne te zawierają zalecenia kwalifikacyjne dotyczące stosowania TKV, mierzonego na początku badania, jako biomarkera wzbogacenia prognostycznego do wyboru pacjentów z ADPKD o wysokim ryzyku progresywnego spadku funkcji nerek (definiowanego jako potwierdzony 30% spadek szacowanej filtracji kłębuszkowej pacjenta (eGFR))²⁵.

Czynniki modyfikowalne wpływające na prognozę

Ostatnio wyższy wskaźnik masy ciała (BMI ≥25kg/m2) i zespół metaboliczny zostały uznane za dodatkowe modyfikowalne czynniki ryzyka szybkiej progresji ADPKD²⁶. Lepsze kontrolowanie czynników ryzyka sercowo-naczyniowego wydaje się być związane z mniejszym obciążeniem chorobami układu krążenia, co w dłuższej perspektywie może prowadzić do lepszego rokowania²⁷.

Obecnie jedyną terapią zatwierdzoną przez FDA w leczeniu ADPKD jest tolwaptan²⁸. Identyfikacja pacjentów z wyższym ryzykiem przyspieszonej progresji choroby we wczesnym stadium ma kluczowe znaczenie dla wyboru pacjentów, którzy skorzystają z wczesnego wprowadzenia terapii²⁹.

Powikłania wpływające na prognozę

Oprócz niewydolności nerek, ADPKD może powodować szereg innych potencjalnie poważnych problemów, takich jak zawały serca i udary spowodowane wysokim ciśnieniem krwi, lub krwawienie do mózgu (krwotok podpajęczynówkowy) spowodowane tętniakiem w ścianie naczynia krwionośnego w mózgu (tętniak mózgu)³⁰.

Ból jest częstym objawem u osób z ADPKD, doświadczanym przez ponad 60% chorych przed ukończeniem 40. roku życia³¹. Inicjatywa SONG-PKD (Standardized Outcomes in Nephrology-PKD) zidentyfikowała ból jako jeden z czterech podstawowych wyników w PKD, zdefiniowanych jako wyniki o krytycznym znaczeniu dla wszystkich kluczowych interesariuszy³². Pomimo uznania go za krytycznie ważny wynik, ból jest często niedostatecznie rozpoznawany i źle leczony³³.

ADPKD nie zwiększa ryzyka raka nerki, ale jeśli pacjenci z ADPKD rozwiną raka nerki, istnieje większe prawdopodobieństwo, że będzie on obustronny. Rak nerki rzadko powoduje śmierć. Pacjenci zwykle umierają z powodu chorób serca (czasami zastawkowych), rozsianego zakażenia lub pękniętego tętniaka mózgu³⁴.

Przewidywanie progresji ADPKD u dzieci

Dzieci z bardzo wczesnym początkiem ADPKD (ADPKDVEO) mają wyższe ryzyko wczesnej utraty funkcji nerek³⁵. Badanie kliniczno-kontrolne zdefiniowało bardzo wczesny początek (VEO) jako rozpoznanie przed 18. miesiącem życia, przy czym większość pacjentów została zdiagnozowana w latach 90. XX wieku³⁶.

Aktualnie trwa badanie kliniczne u dzieci, jednak brakuje ważnych modeli predykcyjnych do identyfikacji dzieci, które mogą cierpieć z powodu niewydolności nerek³⁷. W przypadku dzieci wiedza na temat prognozy jest jeszcze bardziej ograniczona i potrzebne są znacznie dłuższe badania, aby osiągnąć ten sam cel³⁸. Jednak zanim tolwaptan lub inne leki będą mogły być stosowane u dzieci z ADPKD, pilnie potrzebne są ważne modele predykcyjne do wyboru odpowiednich populacji pacjentów, a długoterminowe bezpieczeństwo i trwały efekt muszą zostać zweryfikowane³⁹.

Podsumowanie prognozy w ADPKD

Szczegółowa ocena typów mutacji może być przydatna w przewidywaniu rokowania nerkowego u pacjentów z ADPKD⁴⁰⁴¹. Współczynnik przeżycia nerek zależy od genów przyczynowych (PKD1, PKD2) oraz różnic między mutacjami skracającymi a nieskracającymi⁴².

Średnio współczynnik filtracji kłębuszkowej (GFR) spada o około 5 ml/min/rok po czwartej dekadzie życia⁴³. Po wystąpieniu schyłkowej niewydolności nerek progresja choroby jest względnie stała i można ją monitorować za pomocą współczynnika filtracji kłębuszkowej (GFR)⁴⁴.

Wśród różnych badanych biomarkerów, najobiecniejsze dla przewidywania progresji ADPKD są kopeptyna, apelina, angiotensynogen, FGF23, suPAR, wodorowęglany w surowicy, sFRP4, KIM1, MCP1, 2MG, CD14, fetuina A, osteopontyna, a także bezobjawowa ropomocz, osmolalność moczu i stosunek mocznika w moczu do osocza⁴⁵.

Postęp w zrozumieniu genetycznych podstaw ADPKD, ilościowego określenia objawów choroby u dzieci, eksploracji ADPKD o bardzo wczesnym początku, a także farmakologicznego opóźnienia progresji choroby u dorosłych, przyczynia się do lepszego zrozumienia tej choroby i potencjalnie lepszych wyników leczenia⁴⁶.

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Materiały źródłowe

#1
https://www.nhs.uk/conditions/autosomal-dominant-polycystic-kidney-disease-adpkd/
Autosomal dominant polycystic kidney disease (ADPKD) is an inherited condition that causes small fluid-filled sacs called cysts to develop in the kidneys. […] Kidney function may gradually deteriorate until so much is lost that kidney failure occurs. […] The outlook for ADPKD is highly variable. Some people experience kidney failure soon after the condition is diagnosed, whereas others may live the rest of their life with their kidneys working relatively well. […] On average, around half of people with ADPKD require treatment for kidney failure by the time they’re 60. […] As well as kidney failure, ADPKD can also cause a number of other potentially serious problems, such as heart attacks and strokes caused by high blood pressure, or bleeding on the brain (subarachnoid haemorrhage) caused by a bulge in the wall of a blood vessel in the brain (brain aneurysm).
#2
https://www.nhs.uk/conditions/autosomal-dominant-polycystic-kidney-disease-adpkd/
Autosomal dominant polycystic kidney disease (ADPKD) is an inherited condition that causes small fluid-filled sacs called cysts to develop in the kidneys. […] Kidney function may gradually deteriorate until so much is lost that kidney failure occurs. […] The outlook for ADPKD is highly variable. Some people experience kidney failure soon after the condition is diagnosed, whereas others may live the rest of their life with their kidneys working relatively well. […] On average, around half of people with ADPKD require treatment for kidney failure by the time they’re 60. […] As well as kidney failure, ADPKD can also cause a number of other potentially serious problems, such as heart attacks and strokes caused by high blood pressure, or bleeding on the brain (subarachnoid haemorrhage) caused by a bulge in the wall of a blood vessel in the brain (brain aneurysm).
#3 Autosomal Dominant Polycystic Kidney Disease (ADPKD) – Genitourinary Disorders – Merck Manual Professional Edition
https://www.merckmanuals.com/professional/genitourinary-disorders/cystic-kidney-disease/autosomal-dominant-polycystic-kidney-disease-adpkd
Renal failure develops in 35 to 45% of patients with autosomal dominant polycystic kidney disease (ADPKD) by age 60. By age 75, 50 to 75% of patients require renal replacement therapy (dialysis or transplantation). On average, glomerular filtration rate (GFR) declines by about 5 mL/minute/year after the fourth decade of life. Predictors of more rapid progression to renal failure include the following: […] Cyst and kidney volume measurements predict risk of progression to chronic kidney disease and end-stage kidney disease, often before changes in routine laboratory studies. For example, cyst size and kidney size predict 8-year risk of chronic kidney disease more accurately than age, degree of proteinuria, or serum blood urea nitrogen (BUN) or creatinine. Kidney size is the most important predictor for progression, particularly total kidney volume and end-stage kidney disease, often before changes in routine laboratory studies. […] ADPKD does not increase risk of renal cancer, but if patients with ADPKD develop renal cancer, it is more likely to be bilateral. Renal cancer rarely causes death. Patients usually die of heart disease (sometimes valvular), disseminated infection, or ruptured cerebral aneurysm.
#4 Prediction of Renal Prognosis in Patients with Autosomal Dominant Polycystic Kidney Disease Using PKD1/PKD2 Mutations
https://pmc.ncbi.nlm.nih.gov/articles/PMC7019244/
Autosomal dominant polycystic kidney disease (ADPKD) patients with PKD1 mutations, particularly those with truncating mutations, show poor prognosis. […] Renal prognosis was poor for those with PKD1 splicing, PKD1 frameshift, and PKD2 splicing mutations. […] Despite the truncating mutation, the renal prognosis was relatively favorable for patients with nonsense mutations. […] Three out of five patients with PKD2 mutation required renal replacement therapy before 58 years of age. […] In conclusion, we showed that renal prognosis differs according to mutation types in both PKD1 and PKD2, and that it was favorable for those with nonsense mutations among patients with PKD1 truncating mutations. […] It was also confirmed that renal prognosis was not always favorable in patients with PKD2 mutations.
#5 Prediction of Renal Prognosis in Patients with Autosomal Dominant Polycystic Kidney Disease Using PKD1/PKD2 Mutations
https://pmc.ncbi.nlm.nih.gov/articles/PMC7019244/
A detailed assessment of mutation types may be useful for predicting the renal prognosis of patients with ADPKD. […] The kidney survival rate depends on the causal genes (PKD1, PKD2) and differences between truncating or non-truncating mutations. […] Patients with PKD1 mutations, particularly those with truncating mutations, show poor prognosis. […] In this study, we observed a significant difference between PKD1 and PKD2 mutations in terms of the proportion of patients who progressed to RRT within each genotype (32.3% in PKD1; 20.8% in PKD2), suggesting that renal prognosis is poorer in patients with mutations in PKD1 than in those with PKD2 mutations. […] In the present study, both Cox analyses and KaplanMeier curves showed that renal prognosis was poorer in patients with truncating mutations than in those with non-truncating mutations in PKD1.
#6 Prediction of Renal Prognosis in Patients with Autosomal Dominant Polycystic Kidney Disease Using PKD1/PKD2 Mutations
https://pmc.ncbi.nlm.nih.gov/articles/PMC7019244/
A detailed assessment of mutation types may be useful for predicting the renal prognosis of patients with ADPKD. […] The kidney survival rate depends on the causal genes (PKD1, PKD2) and differences between truncating or non-truncating mutations. […] Patients with PKD1 mutations, particularly those with truncating mutations, show poor prognosis. […] In this study, we observed a significant difference between PKD1 and PKD2 mutations in terms of the proportion of patients who progressed to RRT within each genotype (32.3% in PKD1; 20.8% in PKD2), suggesting that renal prognosis is poorer in patients with mutations in PKD1 than in those with PKD2 mutations. […] In the present study, both Cox analyses and KaplanMeier curves showed that renal prognosis was poorer in patients with truncating mutations than in those with non-truncating mutations in PKD1.
#7 Prediction of Renal Prognosis in Patients with Autosomal Dominant Polycystic Kidney Disease Using PKD1/PKD2 Mutations
https://pmc.ncbi.nlm.nih.gov/articles/PMC7019244/
When we evaluated renal prognosis by mutation types, it was poor in patients with PKD1 splicing, PKD1 frameshift, and PKD2 splicing mutations; however, unexpectedly, it was relatively favorable in patients with PKD1 nonsense and PKD2 nonsense mutations. […] Our study is the first report that compares renal prognosis by mutation types among PKD1 truncating mutations and highlights that renal prognosis is poorer in patients with splicing and frameshift mutations than in patients with nonsense mutations. […] In this study, a comparison of only patients who progressed to RRT revealed no difference in the age of reaching RRT between patients with mutations in PKD1 and those with mutations in PKD2 (median 52 years versus 51 years). […] These observations suggested that the renal prognosis of patients with PKD2 mutations was not always favorable compared to that of patients with PKD1 mutations. […] In conclusion, we showed that a detailed assessment of mutation types might be useful for determining the renal prognosis of patients with ADPKD.
#8 Prediction of Renal Prognosis in Patients with Autosomal Dominant Polycystic Kidney Disease Using PKD1/PKD2 Mutations
https://www.mdpi.com/2077-0383/9/1/146
Autosomal dominant polycystic kidney disease (ADPKD) patients with PKD1 mutations, particularly those with truncating mutations, show poor prognosis. […] Renal prognosis was poor for those with PKD1 splicing, PKD1 frameshift, and PKD2 splicing mutations. […] Despite the truncating mutation, the renal prognosis was relatively favorable for patients with nonsense mutations. […] Three out of five patients with PKD2 mutation required renal replacement therapy before 58 years of age. […] In conclusion, we showed that renal prognosis differs according to mutation types in both PKD1 and PKD2, and that it was favorable for those with nonsense mutations among patients with PKD1 truncating mutations. […] It was also confirmed that renal prognosis was not always favorable in patients with PKD2 mutations. […] A detailed assessment of mutation types may be useful for predicting the renal prognosis of patients with ADPKD.
#9 Prediction of Renal Prognosis in Patients with Autosomal Dominant Polycystic Kidney Disease Using PKD1/PKD2 Mutations
https://pmc.ncbi.nlm.nih.gov/articles/PMC7019244/
When we evaluated renal prognosis by mutation types, it was poor in patients with PKD1 splicing, PKD1 frameshift, and PKD2 splicing mutations; however, unexpectedly, it was relatively favorable in patients with PKD1 nonsense and PKD2 nonsense mutations. […] Our study is the first report that compares renal prognosis by mutation types among PKD1 truncating mutations and highlights that renal prognosis is poorer in patients with splicing and frameshift mutations than in patients with nonsense mutations. […] In this study, a comparison of only patients who progressed to RRT revealed no difference in the age of reaching RRT between patients with mutations in PKD1 and those with mutations in PKD2 (median 52 years versus 51 years). […] These observations suggested that the renal prognosis of patients with PKD2 mutations was not always favorable compared to that of patients with PKD1 mutations. […] In conclusion, we showed that a detailed assessment of mutation types might be useful for determining the renal prognosis of patients with ADPKD.
#10 Prediction of Renal Prognosis in Patients with Autosomal Dominant Polycystic Kidney Disease Using PKD1/PKD2 Mutations
https://www.mdpi.com/2077-0383/9/1/146
Autosomal dominant polycystic kidney disease (ADPKD) patients with PKD1 mutations, particularly those with truncating mutations, show poor prognosis. […] Renal prognosis was poor for those with PKD1 splicing, PKD1 frameshift, and PKD2 splicing mutations. […] Despite the truncating mutation, the renal prognosis was relatively favorable for patients with nonsense mutations. […] Three out of five patients with PKD2 mutation required renal replacement therapy before 58 years of age. […] In conclusion, we showed that renal prognosis differs according to mutation types in both PKD1 and PKD2, and that it was favorable for those with nonsense mutations among patients with PKD1 truncating mutations. […] It was also confirmed that renal prognosis was not always favorable in patients with PKD2 mutations. […] A detailed assessment of mutation types may be useful for predicting the renal prognosis of patients with ADPKD.
#11 Prediction of Renal Prognosis in Patients with Autosomal Dominant Polycystic Kidney Disease Using PKD1/PKD2 Mutations
https://pmc.ncbi.nlm.nih.gov/articles/PMC7019244/
Autosomal dominant polycystic kidney disease (ADPKD) patients with PKD1 mutations, particularly those with truncating mutations, show poor prognosis. […] Renal prognosis was poor for those with PKD1 splicing, PKD1 frameshift, and PKD2 splicing mutations. […] Despite the truncating mutation, the renal prognosis was relatively favorable for patients with nonsense mutations. […] Three out of five patients with PKD2 mutation required renal replacement therapy before 58 years of age. […] In conclusion, we showed that renal prognosis differs according to mutation types in both PKD1 and PKD2, and that it was favorable for those with nonsense mutations among patients with PKD1 truncating mutations. […] It was also confirmed that renal prognosis was not always favorable in patients with PKD2 mutations.
#12 Prediction of Renal Prognosis in Patients with Autosomal Dominant Polycystic Kidney Disease Using PKD1/PKD2 Mutations
https://www.mdpi.com/2077-0383/9/1/146
Autosomal dominant polycystic kidney disease (ADPKD) patients with PKD1 mutations, particularly those with truncating mutations, show poor prognosis. […] Renal prognosis was poor for those with PKD1 splicing, PKD1 frameshift, and PKD2 splicing mutations. […] Despite the truncating mutation, the renal prognosis was relatively favorable for patients with nonsense mutations. […] Three out of five patients with PKD2 mutation required renal replacement therapy before 58 years of age. […] In conclusion, we showed that renal prognosis differs according to mutation types in both PKD1 and PKD2, and that it was favorable for those with nonsense mutations among patients with PKD1 truncating mutations. […] It was also confirmed that renal prognosis was not always favorable in patients with PKD2 mutations. […] A detailed assessment of mutation types may be useful for predicting the renal prognosis of patients with ADPKD.
#13 Prediction of Renal Prognosis in Patients with Autosomal Dominant Polycystic Kidney Disease Using PKD1/PKD2 Mutations
https://pmc.ncbi.nlm.nih.gov/articles/PMC7019244/
When we evaluated renal prognosis by mutation types, it was poor in patients with PKD1 splicing, PKD1 frameshift, and PKD2 splicing mutations; however, unexpectedly, it was relatively favorable in patients with PKD1 nonsense and PKD2 nonsense mutations. […] Our study is the first report that compares renal prognosis by mutation types among PKD1 truncating mutations and highlights that renal prognosis is poorer in patients with splicing and frameshift mutations than in patients with nonsense mutations. […] In this study, a comparison of only patients who progressed to RRT revealed no difference in the age of reaching RRT between patients with mutations in PKD1 and those with mutations in PKD2 (median 52 years versus 51 years). […] These observations suggested that the renal prognosis of patients with PKD2 mutations was not always favorable compared to that of patients with PKD1 mutations. […] In conclusion, we showed that a detailed assessment of mutation types might be useful for determining the renal prognosis of patients with ADPKD.
#14 Predicting autosomal dominant polycystic kidney disease progression: review of promising Serum and urine biomarkers
https://pmc.ncbi.nlm.nih.gov/articles/PMC10667601/
More recently, higher baseline body mass index (25kg/m2) and metabolic syndrome have been recognized as additional modifiable risk factors for a rapid ADPKD progression. […] After ESRD onset, disease progression is relatively constant and may be monitored by glomerular filtration rate (GFR). […] The best predictor of disease progression currently is a prognostic model based on age-adjusted htTKV, the Mayo Imaging Classification (MIC), which categorizes ADPKD patients into classes 1A through 1E with higher classes at a substantially greater risk of progression to ESRD. […] Another widely used prognostic model for predicting progression to ESRD in patients with ADPKD is the Predicting Renal Outcome in Polycystic Kidney Disease (PROPKD) score which combines underlying genetic mutation and clinical risk factors to categorize ADPKD patients as low, intermediate or high risk of progression to ESRD.
#15 Predicting autosomal dominant polycystic kidney disease progression: review of promising Serum and urine biomarkers
https://pmc.ncbi.nlm.nih.gov/articles/PMC10667601/
More recently, higher baseline body mass index (25kg/m2) and metabolic syndrome have been recognized as additional modifiable risk factors for a rapid ADPKD progression. […] After ESRD onset, disease progression is relatively constant and may be monitored by glomerular filtration rate (GFR). […] The best predictor of disease progression currently is a prognostic model based on age-adjusted htTKV, the Mayo Imaging Classification (MIC), which categorizes ADPKD patients into classes 1A through 1E with higher classes at a substantially greater risk of progression to ESRD. […] Another widely used prognostic model for predicting progression to ESRD in patients with ADPKD is the Predicting Renal Outcome in Polycystic Kidney Disease (PROPKD) score which combines underlying genetic mutation and clinical risk factors to categorize ADPKD patients as low, intermediate or high risk of progression to ESRD.
#16 Predicting autosomal dominant polycystic kidney disease progression: review of promising Serum and urine biomarkers
https://pmc.ncbi.nlm.nih.gov/articles/PMC10667601/
Although MIC, ADPKD-OM and PROPKD are nowadays the most commonly used prognostic models in ADPKD clinical trials, all of these predictive scores remain limited by availability, high price and expertise mandatory for obtaining such parameters and therefore are not useful in everyday clinical practice. […] Currently, the only Food and Drug Administration-approved ADPKD therapy is tolvaptan. […] Identifying patients with a higher risk of an accelerated disease progression in an early disease stage is of the uppermost importance for selecting patients who will benefit from an early introduction of therapy. […] For these reasons, growing number of studies are investigating multiple serum and urinary molecules, particularly those involved in underlying pathophysiology, as alternative biomarkers for predicting fast disease progression in ADPKD patients.
#17 Predicting autosomal dominant polycystic kidney disease progression: review of promising Serum and urine biomarkers
https://pmc.ncbi.nlm.nih.gov/articles/PMC10667601/
Both urinary osmolality and U/P urea are reliable surrogate biomarkers for maximal urine-concentrating capacity and, based on the analyzed findings, seem to have a clinical utility as predictors of a rapid ADPKD progression. […] Considering all the presented data, it is reasonable to conclude that uAGT is a valid early biomarker of ADPKD progression that reflects underlying pathophysiology. […] Fibroblast growth factor 23 (FGF23) is a potential prognostic biomarker for accelerated disease progression and early-onset undesirable clinical outcomes in ADPKD. […] The studies incorporated in this review demonstrate the multifaceted character of the pursuit of identifying the most reliable prognostic marker for ADPKD. […] Among various molecules under investigation, the most promising ones for predicting ADPKD progression are copeptin, apelin, angiotensinogen, FGF23, suPAR, serum bicarbonate, sFRP4, KIM1, MCP1, 2MG, CD14, fetuin A, osteopontin, along with asymptomatic pyuria, urine osmolality and urine to plasma urea ratio.
#18 Predicting autosomal dominant polycystic kidney disease progression: review of promising Serum and urine biomarkers
https://pmc.ncbi.nlm.nih.gov/articles/PMC10667601/
Both urinary osmolality and U/P urea are reliable surrogate biomarkers for maximal urine-concentrating capacity and, based on the analyzed findings, seem to have a clinical utility as predictors of a rapid ADPKD progression. […] Considering all the presented data, it is reasonable to conclude that uAGT is a valid early biomarker of ADPKD progression that reflects underlying pathophysiology. […] Fibroblast growth factor 23 (FGF23) is a potential prognostic biomarker for accelerated disease progression and early-onset undesirable clinical outcomes in ADPKD. […] The studies incorporated in this review demonstrate the multifaceted character of the pursuit of identifying the most reliable prognostic marker for ADPKD. […] Among various molecules under investigation, the most promising ones for predicting ADPKD progression are copeptin, apelin, angiotensinogen, FGF23, suPAR, serum bicarbonate, sFRP4, KIM1, MCP1, 2MG, CD14, fetuin A, osteopontin, along with asymptomatic pyuria, urine osmolality and urine to plasma urea ratio.
#19
https://journals.lww.com/cjasn/fulltext/9900/predicting_kidney_outcomes_in_autosomal_dominant.564.aspx
Urinary albumin/creatinine, MCP-1/creatinine, and serum copeptin exhibited the strongest associations with eGFR slope. […] In the primary cohort, 303 of 596 patients (50.8%) exhibited rapidly progressive disease. Urinary albumin/creatinine, MCP-1/creatinine, and serum copeptin were independent predictors of rapidly progressive disease. […] The combined kidney end point was reached in 28 of 140 (20.0%) patients with early disease. In this subgroup, albumin/creatinine and MCP-1/creatinine were independent predictors of the end point. […] Urinary albumin/creatinine, MCP-1/creatinine, and serum copeptin were most consistently associated with kidney outcomes beyond established risk factors.
#20
https://journals.lww.com/cjasn/fulltext/9900/predicting_kidney_outcomes_in_autosomal_dominant.564.aspx
Risk prognostication in autosomal dominant polycystic kidney disease can be improved by combining clinical, genetic, and volumetric data. […] Various biomarkers have been explored in autosomal dominant polycystic kidney disease, but it is unclear which biomarkers are most suitable to integrate into risk stratification tools. […] Urinary albumin/creatinine, monocyte chemotactic protein-1/creatinine, and serum copeptin are independently associated with kidney outcomes, even in early disease and MIC 1C. […] Risk stratification tools for autosomal dominant polycystic kidney disease (ADPKD) predict kidney outcomes on a group level but lack precision in patients. […] Our findings suggest that incorporating these biomarkers into ADPKD risk stratification tools will improve risk prediction, even in subgroups where prognostication is most challenging and relevant.
#21 Predicting autosomal dominant polycystic kidney disease progression: review of promising Serum and urine biomarkers
https://pmc.ncbi.nlm.nih.gov/articles/PMC10667601/
Both urinary osmolality and U/P urea are reliable surrogate biomarkers for maximal urine-concentrating capacity and, based on the analyzed findings, seem to have a clinical utility as predictors of a rapid ADPKD progression. […] Considering all the presented data, it is reasonable to conclude that uAGT is a valid early biomarker of ADPKD progression that reflects underlying pathophysiology. […] Fibroblast growth factor 23 (FGF23) is a potential prognostic biomarker for accelerated disease progression and early-onset undesirable clinical outcomes in ADPKD. […] The studies incorporated in this review demonstrate the multifaceted character of the pursuit of identifying the most reliable prognostic marker for ADPKD. […] Among various molecules under investigation, the most promising ones for predicting ADPKD progression are copeptin, apelin, angiotensinogen, FGF23, suPAR, serum bicarbonate, sFRP4, KIM1, MCP1, 2MG, CD14, fetuin A, osteopontin, along with asymptomatic pyuria, urine osmolality and urine to plasma urea ratio.
#22 Predicting autosomal dominant polycystic kidney disease progression: review of promising Serum and urine biomarkers
https://pmc.ncbi.nlm.nih.gov/articles/PMC10667601/
Autosomal dominant polycystic kidney disease (ADPKD) is one of the leading causes of end-stage renal disease. […] Considering emerging new targeted therapies for ADPKD, it has become crucial to disclose easily measurable and widely available biomarkers for identifying patients with future rapid disease progression. […] The rate of the ADPKD progress varies significantly between patients. […] Conventional kidney function measures, such as glomerular filtration rate (GFR), are not suitable for monitoring disease progression in ADPKD, particularly in its early stages. […] Height-adjusted total kidney volume (ht-TKV) has been accepted as an early biomarker for assessing disease severity in ADPKD patients. […] The aim of the current review is to provide an overview of all of the published evidence on potentially clinically valuable serum and urine biomarkers that could be used for predicting disease progression or response to therapy in patients with ADPKD.
#23 Autosomal Dominant Polycystic Kidney Disease (ADPKD) – Genitourinary Disorders – Merck Manual Professional Edition
https://www.merckmanuals.com/professional/genitourinary-disorders/cystic-kidney-disease/autosomal-dominant-polycystic-kidney-disease-adpkd
Renal failure develops in 35 to 45% of patients with autosomal dominant polycystic kidney disease (ADPKD) by age 60. By age 75, 50 to 75% of patients require renal replacement therapy (dialysis or transplantation). On average, glomerular filtration rate (GFR) declines by about 5 mL/minute/year after the fourth decade of life. Predictors of more rapid progression to renal failure include the following: […] Cyst and kidney volume measurements predict risk of progression to chronic kidney disease and end-stage kidney disease, often before changes in routine laboratory studies. For example, cyst size and kidney size predict 8-year risk of chronic kidney disease more accurately than age, degree of proteinuria, or serum blood urea nitrogen (BUN) or creatinine. Kidney size is the most important predictor for progression, particularly total kidney volume and end-stage kidney disease, often before changes in routine laboratory studies. […] ADPKD does not increase risk of renal cancer, but if patients with ADPKD develop renal cancer, it is more likely to be bilateral. Renal cancer rarely causes death. Patients usually die of heart disease (sometimes valvular), disseminated infection, or ruptured cerebral aneurysm.
#24 Critical Path Institute’s Polycystic Kidney Disease Outcomes Consortium Secures FDA Qualification for Enrichment Biomarker in Autosomal Dominant Polycystic Kidney Disease (ADPKD)
https://c-path.org/critical-path-institutes-polycystic-kidney-disease-outcomes-consortium-secures-fda-qualification-for-enrichment-biomarker-in-autosomal-dominant-polycystic-kidney-disease-adpkd/
The Critical Path Institute (C-Path) announced today that the U.S. Food and Drug Administration (FDA) has issued a qualification decision in the form of a draft guidance to C-Pathâs Polycystic Kidney Disease Outcomes Consortium (PKDOC) for total kidney volume (TKV) as a prognostic biomarker to select patients for clinical trials of new therapies for Autosomal Dominant Polycystic Kidney Disease (ADPKD). […] TKV is a measurement of the impact of ADPKD on the size of the kidneys and is considered to be predictive of a future decline in kidney function. This draft guidance provides qualification recommendations for the use of TKV, measured at baseline, as a prognostic enrichment biomarker to select patients with ADPKD at high risk for a progressive decline in renal function (defined as a confirmed 30% decline in the patientâs estimated glomerular filtration rate (eGFR)). […] The impact of this biomarker qualification will be to enhance the recruitment and performance of clinical trials in ADPKD, and hopefully bring new therapies to patients in a shorter period of time.
#25 Critical Path Institute’s Polycystic Kidney Disease Outcomes Consortium Secures FDA Qualification for Enrichment Biomarker in Autosomal Dominant Polycystic Kidney Disease (ADPKD)
https://c-path.org/critical-path-institutes-polycystic-kidney-disease-outcomes-consortium-secures-fda-qualification-for-enrichment-biomarker-in-autosomal-dominant-polycystic-kidney-disease-adpkd/
The Critical Path Institute (C-Path) announced today that the U.S. Food and Drug Administration (FDA) has issued a qualification decision in the form of a draft guidance to C-Pathâs Polycystic Kidney Disease Outcomes Consortium (PKDOC) for total kidney volume (TKV) as a prognostic biomarker to select patients for clinical trials of new therapies for Autosomal Dominant Polycystic Kidney Disease (ADPKD). […] TKV is a measurement of the impact of ADPKD on the size of the kidneys and is considered to be predictive of a future decline in kidney function. This draft guidance provides qualification recommendations for the use of TKV, measured at baseline, as a prognostic enrichment biomarker to select patients with ADPKD at high risk for a progressive decline in renal function (defined as a confirmed 30% decline in the patientâs estimated glomerular filtration rate (eGFR)). […] The impact of this biomarker qualification will be to enhance the recruitment and performance of clinical trials in ADPKD, and hopefully bring new therapies to patients in a shorter period of time.
#26 Predicting autosomal dominant polycystic kidney disease progression: review of promising Serum and urine biomarkers
https://pmc.ncbi.nlm.nih.gov/articles/PMC10667601/
More recently, higher baseline body mass index (25kg/m2) and metabolic syndrome have been recognized as additional modifiable risk factors for a rapid ADPKD progression. […] After ESRD onset, disease progression is relatively constant and may be monitored by glomerular filtration rate (GFR). […] The best predictor of disease progression currently is a prognostic model based on age-adjusted htTKV, the Mayo Imaging Classification (MIC), which categorizes ADPKD patients into classes 1A through 1E with higher classes at a substantially greater risk of progression to ESRD. […] Another widely used prognostic model for predicting progression to ESRD in patients with ADPKD is the Predicting Renal Outcome in Polycystic Kidney Disease (PROPKD) score which combines underlying genetic mutation and clinical risk factors to categorize ADPKD patients as low, intermediate or high risk of progression to ESRD.
#27 Cardiovascular risk factors and the impact on prognosis in patients with chronic kidney disease secondary to autosomal dominant polycystic kidney disease | BMC Nephrology | Full Text
https://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-021-02313-1
Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent hereditary renal disease. There is an increased rate of cardiovascular disease (CVD) in ADPKD. […] ADPKD patients show intermediate control rates of CVD. A better control of CVD risk seems to be related with a lower load of CVD compared to other groups, which may lead in the long term to a better prognosis. […] Better control of cardiovascular risk factors appears to be associated with a lower burden of CVD, which may lead in the long term to a better prognosis. However, we are still far from achieving the optimal goals for the control of cardiovascular risk factors in patients with ADPKD. Further investigation is needed to deepen our knowledge about the course of CVD in ADPKD and to determine the usefulness of specific therapeutic measures to improve cardiovascular prognosis in ADPKD.
#28 Predicting autosomal dominant polycystic kidney disease progression: review of promising Serum and urine biomarkers
https://pmc.ncbi.nlm.nih.gov/articles/PMC10667601/
Although MIC, ADPKD-OM and PROPKD are nowadays the most commonly used prognostic models in ADPKD clinical trials, all of these predictive scores remain limited by availability, high price and expertise mandatory for obtaining such parameters and therefore are not useful in everyday clinical practice. […] Currently, the only Food and Drug Administration-approved ADPKD therapy is tolvaptan. […] Identifying patients with a higher risk of an accelerated disease progression in an early disease stage is of the uppermost importance for selecting patients who will benefit from an early introduction of therapy. […] For these reasons, growing number of studies are investigating multiple serum and urinary molecules, particularly those involved in underlying pathophysiology, as alternative biomarkers for predicting fast disease progression in ADPKD patients.
#29 Predicting autosomal dominant polycystic kidney disease progression: review of promising Serum and urine biomarkers
https://pmc.ncbi.nlm.nih.gov/articles/PMC10667601/
Although MIC, ADPKD-OM and PROPKD are nowadays the most commonly used prognostic models in ADPKD clinical trials, all of these predictive scores remain limited by availability, high price and expertise mandatory for obtaining such parameters and therefore are not useful in everyday clinical practice. […] Currently, the only Food and Drug Administration-approved ADPKD therapy is tolvaptan. […] Identifying patients with a higher risk of an accelerated disease progression in an early disease stage is of the uppermost importance for selecting patients who will benefit from an early introduction of therapy. […] For these reasons, growing number of studies are investigating multiple serum and urinary molecules, particularly those involved in underlying pathophysiology, as alternative biomarkers for predicting fast disease progression in ADPKD patients.
#30
https://www.nhs.uk/conditions/autosomal-dominant-polycystic-kidney-disease-adpkd/
Autosomal dominant polycystic kidney disease (ADPKD) is an inherited condition that causes small fluid-filled sacs called cysts to develop in the kidneys. […] Kidney function may gradually deteriorate until so much is lost that kidney failure occurs. […] The outlook for ADPKD is highly variable. Some people experience kidney failure soon after the condition is diagnosed, whereas others may live the rest of their life with their kidneys working relatively well. […] On average, around half of people with ADPKD require treatment for kidney failure by the time they’re 60. […] As well as kidney failure, ADPKD can also cause a number of other potentially serious problems, such as heart attacks and strokes caused by high blood pressure, or bleeding on the brain (subarachnoid haemorrhage) caused by a bulge in the wall of a blood vessel in the brain (brain aneurysm).
#31 Patient-reported outcome measures for pain in autosomal dominant polycystic kidney disease: A systematic review | PLOS One
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252479
Pain is a common symptom in people with autosomal dominant polycystic kidney disease (ADPKD), but it is assessed and reported inconsistently in research, and the validity of the measures remain uncertain. […] Pain is a debilitating symptom that is experienced by more than 60% of people with autosomal dominant polycystic kidney disease (ADPKD) by the age of 40 years old. […] The Standardized Outcomes in Nephrology-PKD (SONG-PKD) initiative identified pain as one of the four core outcomes in PKD, defined as outcomes of critical importance to all key stakeholders, including patients/caregivers, health professionals, policy makers/funders from recently completed consensus workshop. […] Despite being identified as a critically important outcome, pain is often under recognized and poorly managed.
#32 Patient-reported outcome measures for pain in autosomal dominant polycystic kidney disease: A systematic review | PLOS One
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252479
Pain is a common symptom in people with autosomal dominant polycystic kidney disease (ADPKD), but it is assessed and reported inconsistently in research, and the validity of the measures remain uncertain. […] Pain is a debilitating symptom that is experienced by more than 60% of people with autosomal dominant polycystic kidney disease (ADPKD) by the age of 40 years old. […] The Standardized Outcomes in Nephrology-PKD (SONG-PKD) initiative identified pain as one of the four core outcomes in PKD, defined as outcomes of critical importance to all key stakeholders, including patients/caregivers, health professionals, policy makers/funders from recently completed consensus workshop. […] Despite being identified as a critically important outcome, pain is often under recognized and poorly managed.
#33 Patient-reported outcome measures for pain in autosomal dominant polycystic kidney disease: A systematic review | PLOS One
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252479
Pain is a common symptom in people with autosomal dominant polycystic kidney disease (ADPKD), but it is assessed and reported inconsistently in research, and the validity of the measures remain uncertain. […] Pain is a debilitating symptom that is experienced by more than 60% of people with autosomal dominant polycystic kidney disease (ADPKD) by the age of 40 years old. […] The Standardized Outcomes in Nephrology-PKD (SONG-PKD) initiative identified pain as one of the four core outcomes in PKD, defined as outcomes of critical importance to all key stakeholders, including patients/caregivers, health professionals, policy makers/funders from recently completed consensus workshop. […] Despite being identified as a critically important outcome, pain is often under recognized and poorly managed.
#34 Autosomal Dominant Polycystic Kidney Disease (ADPKD) – Genitourinary Disorders – Merck Manual Professional Edition
https://www.merckmanuals.com/professional/genitourinary-disorders/cystic-kidney-disease/autosomal-dominant-polycystic-kidney-disease-adpkd
Renal failure develops in 35 to 45% of patients with autosomal dominant polycystic kidney disease (ADPKD) by age 60. By age 75, 50 to 75% of patients require renal replacement therapy (dialysis or transplantation). On average, glomerular filtration rate (GFR) declines by about 5 mL/minute/year after the fourth decade of life. Predictors of more rapid progression to renal failure include the following: […] Cyst and kidney volume measurements predict risk of progression to chronic kidney disease and end-stage kidney disease, often before changes in routine laboratory studies. For example, cyst size and kidney size predict 8-year risk of chronic kidney disease more accurately than age, degree of proteinuria, or serum blood urea nitrogen (BUN) or creatinine. Kidney size is the most important predictor for progression, particularly total kidney volume and end-stage kidney disease, often before changes in routine laboratory studies. […] ADPKD does not increase risk of renal cancer, but if patients with ADPKD develop renal cancer, it is more likely to be bilateral. Renal cancer rarely causes death. Patients usually die of heart disease (sometimes valvular), disseminated infection, or ruptured cerebral aneurysm.
#35
https://link.springer.com/article/10.1007/s00467-021-04974-4
Significant progress has been made in understanding the genetic basis of autosomal dominant polycystic kidney disease (ADPKD), quantifying disease manifestations in children, exploring very-early onset ADPKD as well as pharmacological delay of disease progression in adults. […] A clinical trial in children is currently ongoing; however, valid prediction models to identify children likely to suffer kidney failure are lacking. […] Children with ADPKDVEO have a higher risk of early loss of kidney function. […] This case-control study defined VEO as diagnosis before the age of 18 months, with most patients being diagnosed in the 1990s. […] Genetic research has been helpful in understanding some of the large clinical variability of ADPKD. […] The lack of early prognostic markers to inform long-term decision making in adults remains a dilemma for both physicians and patients.
#36
https://link.springer.com/article/10.1007/s00467-021-04974-4
Significant progress has been made in understanding the genetic basis of autosomal dominant polycystic kidney disease (ADPKD), quantifying disease manifestations in children, exploring very-early onset ADPKD as well as pharmacological delay of disease progression in adults. […] A clinical trial in children is currently ongoing; however, valid prediction models to identify children likely to suffer kidney failure are lacking. […] Children with ADPKDVEO have a higher risk of early loss of kidney function. […] This case-control study defined VEO as diagnosis before the age of 18 months, with most patients being diagnosed in the 1990s. […] Genetic research has been helpful in understanding some of the large clinical variability of ADPKD. […] The lack of early prognostic markers to inform long-term decision making in adults remains a dilemma for both physicians and patients.
#37
https://link.springer.com/article/10.1007/s00467-021-04974-4
Significant progress has been made in understanding the genetic basis of autosomal dominant polycystic kidney disease (ADPKD), quantifying disease manifestations in children, exploring very-early onset ADPKD as well as pharmacological delay of disease progression in adults. […] A clinical trial in children is currently ongoing; however, valid prediction models to identify children likely to suffer kidney failure are lacking. […] Children with ADPKDVEO have a higher risk of early loss of kidney function. […] This case-control study defined VEO as diagnosis before the age of 18 months, with most patients being diagnosed in the 1990s. […] Genetic research has been helpful in understanding some of the large clinical variability of ADPKD. […] The lack of early prognostic markers to inform long-term decision making in adults remains a dilemma for both physicians and patients.
#38
https://link.springer.com/article/10.1007/s00467-021-04974-4
In children, such knowledge is even more limited and much longer-term studies are needed to achieve the same goal. […] However, before tolvaptan or other drugs can be used in children with ADPKD, valid prediction models are urgently needed to select appropriate patient populations and the long-term safety and sustained effect need to be verified.
#39
https://link.springer.com/article/10.1007/s00467-021-04974-4
In children, such knowledge is even more limited and much longer-term studies are needed to achieve the same goal. […] However, before tolvaptan or other drugs can be used in children with ADPKD, valid prediction models are urgently needed to select appropriate patient populations and the long-term safety and sustained effect need to be verified.
#40 Prediction of Renal Prognosis in Patients with Autosomal Dominant Polycystic Kidney Disease Using PKD1/PKD2 Mutations
https://pmc.ncbi.nlm.nih.gov/articles/PMC7019244/
Autosomal dominant polycystic kidney disease (ADPKD) patients with PKD1 mutations, particularly those with truncating mutations, show poor prognosis. […] Renal prognosis was poor for those with PKD1 splicing, PKD1 frameshift, and PKD2 splicing mutations. […] Despite the truncating mutation, the renal prognosis was relatively favorable for patients with nonsense mutations. […] Three out of five patients with PKD2 mutation required renal replacement therapy before 58 years of age. […] In conclusion, we showed that renal prognosis differs according to mutation types in both PKD1 and PKD2, and that it was favorable for those with nonsense mutations among patients with PKD1 truncating mutations. […] It was also confirmed that renal prognosis was not always favorable in patients with PKD2 mutations.
#41 Prediction of Renal Prognosis in Patients with Autosomal Dominant Polycystic Kidney Disease Using PKD1/PKD2 Mutations
https://www.mdpi.com/2077-0383/9/1/146
Autosomal dominant polycystic kidney disease (ADPKD) patients with PKD1 mutations, particularly those with truncating mutations, show poor prognosis. […] Renal prognosis was poor for those with PKD1 splicing, PKD1 frameshift, and PKD2 splicing mutations. […] Despite the truncating mutation, the renal prognosis was relatively favorable for patients with nonsense mutations. […] Three out of five patients with PKD2 mutation required renal replacement therapy before 58 years of age. […] In conclusion, we showed that renal prognosis differs according to mutation types in both PKD1 and PKD2, and that it was favorable for those with nonsense mutations among patients with PKD1 truncating mutations. […] It was also confirmed that renal prognosis was not always favorable in patients with PKD2 mutations. […] A detailed assessment of mutation types may be useful for predicting the renal prognosis of patients with ADPKD.
#42 Prediction of Renal Prognosis in Patients with Autosomal Dominant Polycystic Kidney Disease Using PKD1/PKD2 Mutations
https://pmc.ncbi.nlm.nih.gov/articles/PMC7019244/
A detailed assessment of mutation types may be useful for predicting the renal prognosis of patients with ADPKD. […] The kidney survival rate depends on the causal genes (PKD1, PKD2) and differences between truncating or non-truncating mutations. […] Patients with PKD1 mutations, particularly those with truncating mutations, show poor prognosis. […] In this study, we observed a significant difference between PKD1 and PKD2 mutations in terms of the proportion of patients who progressed to RRT within each genotype (32.3% in PKD1; 20.8% in PKD2), suggesting that renal prognosis is poorer in patients with mutations in PKD1 than in those with PKD2 mutations. […] In the present study, both Cox analyses and KaplanMeier curves showed that renal prognosis was poorer in patients with truncating mutations than in those with non-truncating mutations in PKD1.
#43 Autosomal Dominant Polycystic Kidney Disease (ADPKD) – Genitourinary Disorders – Merck Manual Professional Edition
https://www.merckmanuals.com/professional/genitourinary-disorders/cystic-kidney-disease/autosomal-dominant-polycystic-kidney-disease-adpkd
Renal failure develops in 35 to 45% of patients with autosomal dominant polycystic kidney disease (ADPKD) by age 60. By age 75, 50 to 75% of patients require renal replacement therapy (dialysis or transplantation). On average, glomerular filtration rate (GFR) declines by about 5 mL/minute/year after the fourth decade of life. Predictors of more rapid progression to renal failure include the following: […] Cyst and kidney volume measurements predict risk of progression to chronic kidney disease and end-stage kidney disease, often before changes in routine laboratory studies. For example, cyst size and kidney size predict 8-year risk of chronic kidney disease more accurately than age, degree of proteinuria, or serum blood urea nitrogen (BUN) or creatinine. Kidney size is the most important predictor for progression, particularly total kidney volume and end-stage kidney disease, often before changes in routine laboratory studies. […] ADPKD does not increase risk of renal cancer, but if patients with ADPKD develop renal cancer, it is more likely to be bilateral. Renal cancer rarely causes death. Patients usually die of heart disease (sometimes valvular), disseminated infection, or ruptured cerebral aneurysm.
#44 Predicting autosomal dominant polycystic kidney disease progression: review of promising Serum and urine biomarkers
https://pmc.ncbi.nlm.nih.gov/articles/PMC10667601/
More recently, higher baseline body mass index (25kg/m2) and metabolic syndrome have been recognized as additional modifiable risk factors for a rapid ADPKD progression. […] After ESRD onset, disease progression is relatively constant and may be monitored by glomerular filtration rate (GFR). […] The best predictor of disease progression currently is a prognostic model based on age-adjusted htTKV, the Mayo Imaging Classification (MIC), which categorizes ADPKD patients into classes 1A through 1E with higher classes at a substantially greater risk of progression to ESRD. […] Another widely used prognostic model for predicting progression to ESRD in patients with ADPKD is the Predicting Renal Outcome in Polycystic Kidney Disease (PROPKD) score which combines underlying genetic mutation and clinical risk factors to categorize ADPKD patients as low, intermediate or high risk of progression to ESRD.
#45 Predicting autosomal dominant polycystic kidney disease progression: review of promising Serum and urine biomarkers
https://pmc.ncbi.nlm.nih.gov/articles/PMC10667601/
Both urinary osmolality and U/P urea are reliable surrogate biomarkers for maximal urine-concentrating capacity and, based on the analyzed findings, seem to have a clinical utility as predictors of a rapid ADPKD progression. […] Considering all the presented data, it is reasonable to conclude that uAGT is a valid early biomarker of ADPKD progression that reflects underlying pathophysiology. […] Fibroblast growth factor 23 (FGF23) is a potential prognostic biomarker for accelerated disease progression and early-onset undesirable clinical outcomes in ADPKD. […] The studies incorporated in this review demonstrate the multifaceted character of the pursuit of identifying the most reliable prognostic marker for ADPKD. […] Among various molecules under investigation, the most promising ones for predicting ADPKD progression are copeptin, apelin, angiotensinogen, FGF23, suPAR, serum bicarbonate, sFRP4, KIM1, MCP1, 2MG, CD14, fetuin A, osteopontin, along with asymptomatic pyuria, urine osmolality and urine to plasma urea ratio.
#46
https://link.springer.com/article/10.1007/s00467-021-04974-4
Significant progress has been made in understanding the genetic basis of autosomal dominant polycystic kidney disease (ADPKD), quantifying disease manifestations in children, exploring very-early onset ADPKD as well as pharmacological delay of disease progression in adults. […] A clinical trial in children is currently ongoing; however, valid prediction models to identify children likely to suffer kidney failure are lacking. […] Children with ADPKDVEO have a higher risk of early loss of kidney function. […] This case-control study defined VEO as diagnosis before the age of 18 months, with most patients being diagnosed in the 1990s. […] Genetic research has been helpful in understanding some of the large clinical variability of ADPKD. […] The lack of early prognostic markers to inform long-term decision making in adults remains a dilemma for both physicians and patients.