4. Simpo 2 Progressing ADPKD Dr. HK, dr. ato.pdf

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1. The Importance of Early
Diagnose of Rapidly Progressing
ADPKD
NasrumMachmud
MORNING 2025

2. •ADPKD→mostcommonhereditarykidneydiseaseandoneofleadingcausekidneyfailure
•MutationsPKD1andPKD2genescodingforpolycystin-1(PC1)andpolycystin-2(PC2)
•Characterized→developmentandexpansionofmultiplecysts
•Progressiveloss→end-stagekidneydisease(sixthdecadeoflife)
•Cystgrowthandexpansion→complications(acuteandchronicpain,grosshematuria,cyst
infection,andnephrolithiasis)
•Extrarenalmanifestations(hepaticandpancreaticcysts,intracranialaneurysms,abdominal
hernias,andcardiacvalvularlesions)
“Therapeutics and Clinical Risk Management,2019”
AUTOSOMALDOMINANTPOLYCYSTICKIDNEYDISEASE

3. •Fourthleadingcauseofend-stagerenal
•
•70%progresstoend-stagerenaldisease(ESRD)ata
medianageof58years
•Renalparenchymadestroyed→compensatorynefron
hyperfiltrationinsurvivingglomerulimaintains→nephrons
destroyed→renalfunctiondecline(afterthefourth
decade)
•LateifonlyseeGFRtoevaluateADPKD
“Rastagiet al. Autosomal Dominant Polycystic Kidney Disease : Updated Perspective,Therapeuticsand Clinical Risk Management 2019:15 1041-1052”
“So that if we can detect the progressiveness of ADPKD as
early as possible and proper treatment we can prevent ESRD”
ADPKD: Why we must concern ?

4. PREVALENCE
❑GenMutationPKD1:PKD2=85%:15%
❑Prevalence:2.4-9.0per10.000populations
❑Arecentstudyofgenomicsequencinginlargepopulationsyieldedaminimalestimateof
1per1000populations
❑About7in10ADPKDpatients→kidneyfailure
❑MenhavehigherratesofprogressiontokidneyfailureintheUSthanwomen
CJASN,2021

5. ADPKD Burden
Cloutier et al, Cloutier et al. BMC Health Services Research (2020) 20:126
Distribution of total excess costs associated with ADPKD
in the US in 2018
Direct healthcare costs

6. ✓Mutationinoneofthepolycystingenealleles→dilation
ofthetubules(throughincreasedcellproliferation,fluid
secretion,andseparationfromtheparentaltubule)→
cystformation
✓Cystformationandgrowthresultfromderegulationof
multiplecellularpathwayslikeproliferation,apoptosis,
metabolicprocesses,cellpolarity,andimmunedefense
✓Basedonrecentknowledgeofmolecularmechanisms
underlyingPKDpathogenicity,newtherapeutic
approaches are being examined for
treatmentofthisdisease
Rastogi et al, Autosomal dominant polycystic kidney disease: updated perspectives , Therapeutics and Clinical Risk Management2019:15 1041–1052
Pathophysiology and genetics of ADPKD
Mutations in the PKD1 and PKD2 genes
coding for polycystin-1 (PC1) 85 %
polycystin-2 (PC2) 15 % of ADPKD cases

7. KIDNEY MANIFESTATIONS ADPKD
Pain →could be an acute pattern as nephrolithiasis, urinary tract infection, cyst infection, or hemorrhage
oRadicular pain
oLocated in the low back, abdomen, chest, and legs
oMay be referred pain in some patients
Cyst complications
oCyst infection →fever, leukocytosis, flank pain
Rupture of an infected cyst →extravasation into the retroperitoneal space with symptoms of
peritonitis
Cystic hemorrhage
oGross hematuria and passage of clots, sharp localized abdominal pain, perirenalhematoma
CLINICAL KIDNEY JOURNAL, 2018

8. RENAL AND EXTRARENAL
MANIFESTATIONS IN
ADPKD
CLINICAL KIDNEY JOURNAL, 2018

9. ADPKD Symptom Checklist
ADPKD symptomscan include:
if your patient develop some of the signs and symptoms or if your patient have family member
with ADPKD your patient may be atrisk for ADPKD.
PKD FOUNDATION OF CANADA FOR RESEARCH IN POLYCYSTIC KIDNEY DISEASE
https://d3n8a8pro7vhmx.cloudfront.net/endpkd/pages/660/attachments/original/1586233556/PKD_Symptom_Checklist.pdf
1. ADPKD Screening
DIAGNOSIS

10. YeshwanterRadhakrishnan, Parikshit Duriseti, Fouad T. Chebib, 2022, Management of autosomal dominant polycystic kidney disease in the era of disease-
modifying treatment options Kidney Res Clin Pract2022; 41(4): 422-431
2. ADPKD Confirmation
ADPKD diagnostic criteria for both ultrasound and CT/MRI in the
presence or absence of family history

11. ADPKD Risk for Rapid Progression Checklist
If your patient have ADPKD and, check all that apply to see if they are at risk for rapid progression:
If you checked one or more of the above, your patient may be at risk for rapidly progressing ADPKD
https://www.jynarque.com/downloadable-resources/adpkd-risk-factors-checklist.pdf
3. Rapid Progression Screening

12. Prognostic tools to assess ADPKD Progressivity
1. Riccardo Magistroniet al,AReview of the Imaging Techniques for Measuring Kidney and Cyst Volume in Establishing Autosomal Dominant Polycystic Kidney Disease
Progression, Am J Nephrol 2018;48:67–78; 2. Cornec-Le Gall E, et al. The PROPKD score: a new algorithm to predict renal survival in autosomal dominant polycystic kidney
disease.J Am Soc Nephrol.2016;27(3):942-951. 3. Gansevoort RT, et al. Nephrol Dial Transplant. 2016;31:337-348
4. Rapid Progression Confirmation

13. Mayo Class (Using CT or MRI)
1. Order an MRI or CT: Request length (L), width (W), and depth (D) dimensions for both kidneys
Riccardo Magistroniet al,AReview of the Imaging Techniques for Measuring Kidney and Cyst Volume in Establishing Autosomal Dominant Polycystic Kidney Disease Progression,
Am J Nephrol 2018;48:67–78

15. Mayo Class (Using CT or MRI)
2. Calculate htTKV: Use the TKV and height to calculate htTKV
Riccardo Magistroniet al,AReview of the Imaging Techniques for Measuring Kidney and Cyst Volume in Establishing Autosomal Dominant Polycystic Kidney Disease Progression,
Am J Nephrol 2018;48:67–78

16. Mayo Class (Using CT or MRI)
3. Determine ADPKD Imaging Classification: Plot hyTKVby age on the graph below
Riccardo Magistroniet al,AReview of the Imaging Techniques for Measuring Kidney and Cyst Volume in Establishing Autosomal Dominant Polycystic Kidney Disease Progression,
Am J Nephrol 2018;48:67–78

17. PROPKD Score
Limitations:
•PROPKD score may not
be helpful identifying
rapid progressionin
patients <35 yearsold
unless they are already
hypertensive and have
experienced urologic
complications.
•PROPKD score requires
genetic testing.
Cornec-Le Gall E, et al. The PROPKD score: a new algorithm to predict renal survival in autosomal dominant polycystic kidney disease.J Am Soc Nephrol.2016;27(3):942-951.

18. ERA EDTA ALGORITHM

19. Ultrasound Kidney Length (US-KL)
Limitations:
•In data analysis, KL was not normalized for height, which is an important variable.
•US-measured KL is less accurate with larger kidneys.
•US measurements are operator-dependent and lack precision and accuracy for detecting short-
term changes in kidney volume and increase the risk of misclassifying ADPKD progression.
•Young patients with lengths < 16.5 cm may still have rapidly progressing disease.
•Atypical patients with slow progression may have lengths > 16.5 cm.
1.BhutaniH, et al. A comparison of ultrasound and magnetic resonance imaging shows that kidney length predicts chronic kidney disease inautosomal dominant polycystic
kidney disease. Kidney Int. 2015;88:146-151.
2.Gansevoort RT, et al. Nephrol Dial Transplant. 2016;31:337-348.

20. ROC curve predicting CKD stage 3a comparing MR and US
based length along with MR and US based htTKV.
AUC ROC values for htTKVand Kidney Length (KL) predicting CKD
Stage 3 (GFR < 60 ml/min) within 8 years in CRISP
US: Ultrasound
AUC: Area Under Curve
MR: Magnetic Resonance
AUROC: Areas under the receiver operator
characteristic)
Ultrasound shows same accuracy compared MRI
Bhutani et al, Kidney Int. 2015 July ; 88(1): 146–151

21. Why Early Diagnosis is Critical?
•TimelyIntervention:Identifyingthediseaseearlyallowsfortheimplementationoftherapeutic
strategiesaimedatslowingdisease
•MonitoringandManagementofComplications:helppreservekidneyfunction
•RiskStratification:Earlyidentification→stratifypatientsbasedontheirriskofprogressionto
end-stagerenaldisease(ESRD
•ImprovedOutcomes:identifyinghigh-riskpatientsandinitiatingappropriatemanagementcan
leadtobetterlong-termoutcomes
Yen PW, Chen YA, Wang W, Mao FS, Chao CT, Chiang CK, Lin SH, TarngDC, Chiu YW, Wu MJ, Chen YC, Kao JT, Wu MS, Lin CL, Huang JW, Hung KY. The screening, diagnosis, and management of patients with autosomal
dominant polycystic kidney disease: A national consensus statement from Taiwan. Nephrology (Carlton). 2024 May;29(5):245-258. doi: 10.1111/nep.14287. Epub2024 Mar 10. PMID: 38462235.
Earlydiagnosisofautosomaldominantpolycystickidneydisease(ADPKD)iscriticalforseveralreasons:

22. Basic Optimized ADPKD
Management

24. SUMMARY
✓ADPKDcancausesignificantburdenonpatientsduetoitscomplexsymptomatology,hereditarynature,and
gradualdiseaseprogression
✓Asamajorgeneticdisorderandoneofthemostcommonglobalcauseforrenalreplacementtherapy,
improvementsinthediagnosisandmanagementofthediseasemanifestationsarerequired.
✓Substantialandexcitingadvanceshavebeenmaderegardingthediagnosis,prognosis,andmanagementof
ADPKD.
✓Normalizationofbloodpressure,anappropriatediet,sufficientfluidintake,avoidanceofsmokingand
nephrotoxicagentsweresuggestedtoslowdiseaseprogressionofADPKD.

25. THANK YOU