Patterns of Kidney Function Decline in Autosomal Dominant Polycystic Kidney Disease: A Post Hoc Analysis From the HALT-PKD Trials

Steinman, Theodore I.; Wei, Jesse; Czarnecki, Peter G.; Pedrosa, Iván; Braun, William E.; Nurko, Samuel; Remer, Erick M.; Chapman, Arlene B.; Martín, Diego R.; Rahbari-Oskoui, Frederic; Mittal, Pardeep; Torres, Vicente E.; Hogan, Marie C.; El-Zoghby, Ziad M.; Harris, Peter C.; Glockner, James F.; King, Bernard F.; Perrone, Ronald D.; Halin, Neil J.; Miskulin, Dana C.; Schrier, Robert W.; Brosnahan, Godela; Gitomer, Berenice; Kelleher, Cass; Masoumi, Amirali; Patel, Nayana; Winklhofer, Franz T.; Yu, Alan; Wang, Connie; Wetzel, Louis H.; Moore, Charity G.; Bost, James E.; Bae, Kyongtae T.; Abebe, Kaleab Z.; Miller, John P.; Thompson, Paul A.; Briggs, Josephine P.; Flessner, Michael F.; Meyers, Catherine M.; Star, Robert A.; Shayman, James A.; Henrich, William L.; Greene, Tom; Leonard, Mary B.; McCullough, P. R.; Moe, Sharon M.; Rocco, Michael V.; Wendler, David

doi:10.1053/j.ajkd.2017.10.023

Cited by 34 publications

(36 citation statements)

References 42 publications

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“…The rate of GFR decline in ADPKD has often been considered to have a "hockey stick" trajectory of conserved function followed by a period of rapid decline of 3-5 mL/ min/1.73 m 2 /y (22)(23)(24). This is partially reflected in recent analysis of the CRISP and HALT PKD populations (25,26). While mild groups had extended preserved function, steeper curvilinear slopes were associated with increasingly severe MICs, with close to a linear decline for MIC-1E.…”

Section: Introductionmentioning

confidence: 99%

The value of genotypic and imaging information to predict functional and structural outcomes in ADPKD

Lavu

Vaughan²,

Senum

et al. 2020

JCI Insight

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BACKGROUND. A treatment option for autosomal dominant polycystic kidney disease (ADPKD) has highlighted the need to identify rapidly progressive patients. Kidney size/age and genotype have predictive power for renal outcomes, but their relative and additive value, plus associated trajectories of disease progression, are not well defined. METHODS. The value of genotypic and/or kidney imaging data (Mayo Imaging Class; MIC) to predict the time to functional (end-stage kidney disease [ESKD] or decline in estimated glomerular filtration rate [eGFR]) or structural (increase in height-adjusted total kidney volume [htTKV]) outcomes were evaluated in a Mayo Clinic PKD1/PKD2 population, and eGFR and htTKV trajectories from 20-65 years of age were modeled and independently validated in similarly defined CRISP and HALT PKD patients. RESULTS. Both genotypic and imaging groups strongly predicted ESKD and eGFR endpoints, with genotype improving the imaging predictions and vice versa; a multivariate model had strong discriminatory power (C-index = 0.845). However, imaging but not genotypic groups predicted htTKV growth, although more severe genotypic and imaging groups had larger kidneys at a young age. The trajectory of eGFR decline was linear from baseline in the most severe genotypic and imaging groups, but it was curvilinear in milder groups. Imaging class trajectories differentiated htTKV growth rates; severe classes had rapid early growth and large kidneys, but growth later slowed. CONCLUSION. The value of imaging, genotypic, and combined data to identify rapidly progressive patients was demonstrated, and reference values for clinical trials were provided. Our data indicate that differences in kidney growth rates before adulthood significantly define patients with severe disease.

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Section: Introductionmentioning

confidence: 99%

The value of genotypic and imaging information to predict functional and structural outcomes in ADPKD

Lavu

Vaughan²,

Senum

et al. 2020

JCI Insight

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“…This variability in risk for ESKD is likely due to the interaction of genic factors[ 3 ] with environmental variables[ 4 ] that alter the expressivity of the clinical phenotype[ 5 , 6 ]. Routine tests performed during the initial clinical evaluation of affected patients, such as estimated glomerular filtration rate (eGFR), lack sensitivity as prognostic markers in early disease[ 7 ], and other clinical information (such as family history of early-onset of ESKD) do not have precision[ 8 ]. The uncertainty in predicting renal prognosis causes tremendous anxiety to patients and their families[ 9 ].…”

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confidence: 99%

Is serum copeptin a modifiable biomarker in autosomal dominant polycystic kidney disease?

Tasneem

Mannix

Wong

et al. 2018

WJN

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The availability of disease-modifying drugs for the management of autosomal dominant polycystic kidney disease (ADPKD) has accelerated the need to accurately predict renal prognosis and/or treatment response in this condition. Arginine vasopressin (AVP) is a critical determinant of postnatal kidney cyst growth in ADPKD. Copeptin (the C-terminal glycoprotein of the precursor AVP peptide) is an accurate surrogate marker of AVP release that is stable and easily measured by immunoassay. Cohort studies show that serum copeptin is correlated with disease severity in ADPKD, and predicts future renal events [decline in renal function and increase in total kidney volume (TKV)]. However, serum copeptin is strongly correlated with creatinine, and its additional value as a prognostic biomarker over estimated glomerular filtration rate and TKV is not certain. It has also been suggested that copeptin could be a predictive biomarker to select ADPKD patients who are most likely to benefit from AVP-modifying therapies, but prospective data to validate this assumption are required. In this regard, long-term randomised clinical trials evaluating the effect of prescribed water intake on renal cyst growth may contribute to addressing this hypothesis. In conclusion, although serum copeptin is aligned with the basic pathogenesis of ADPKD, further rigorous studies are needed to define if it will contribute to enabling the delivery of personalised care in ADPKD.

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“…Spontaneous periods of stability or increase in estimated glomerular filtration rate occur in a significant proportion of patients with ADPKD. 13 Mechanical cyst reduction strategies, such as cyst aspiration and sclerosis with ethanol or laparoscopic cyst decortication, have been used for decades in an effort to relieve the pain associated with large cysts and/or large kidneys, with success rates for pain relief varying from 25% to 100% and follow-up ranging from 12 months to more than 10 years. [14][15][16][17] Similarly, among the 41 patients in the present study who reported symptoms due to mass effect of the large kidneys, w70% experienced improvement in their symptoms.…”

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“…Spontaneous periods of stability or increase in estimated glomerular filtration rate occur in a significant proportion of patients with ADPKD. 13 …”

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Quest for the Cure: Testing the Old and New to Prevent Progression of Autosomal Dominant Polycystic Kidney Disease

Brosnahan

2019

Kidney Medicine

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Patterns of Kidney Function Decline in Autosomal Dominant Polycystic Kidney Disease: A Post Hoc Analysis From the HALT-PKD Trials

Abstract: Although many individuals with ADPKD have a linear decline in eGFR, prolonged intervals of stable GFRs occur in a substantial fraction. Lower body mass index was associated with more stable kidney function in early ADPKD.

Cited by 34 publications

References 42 publications

The value of genotypic and imaging information to predict functional and structural outcomes in ADPKD

The value of genotypic and imaging information to predict functional and structural outcomes in ADPKD

Is serum copeptin a modifiable biomarker in autosomal dominant polycystic kidney disease?

Quest for the Cure: Testing the Old and New to Prevent Progression of Autosomal Dominant Polycystic Kidney Disease

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