Limited Performance of Estimated Total Kidney Volume for Follow-up of ADPKD.

INTRODUCTION: Total kidney volume (TKV) is a qualified biomarker for disease progression in autosomal dominant polycystic kidney disease (ADPKD). Recent studies suggest that TKV estimated using ellipsoid formula correlates well with TKV measured by manual planimetry (gold standard). We investigated whether the ellipsoid formula could replace manual planimetry for follow-up of ADPKD patients. METHODS: Abdominal magnetic resonance images of patients with ADPKD performed between January 1, 2013, and June 31, 2019, in Saint-Luc Hospital, Brussels, were used. Two radiologists independently performed manual TKV (mTKV) measures and kidney axial measures necessary for estimating TKV (eTKV) using ellipsoid equation. Repeatability and reproducibility of axial measures, mTKV and eTKV, and agreement between mTKV and eTKV were assessed (Bland-Altman). Intraclass correlation coefficient (ICC) was used to assess agreement on Mayo Clinic Imaging Classification (MCIC) scores. RESULTS: 140 patients were included with mean age 45±13 years, estimated glomerular filtration rate (eGFR) 71±31 ml/min per 1.73 m2, and mTKV 1697±1538 ml. Repeatability and reproducibility were superior for mTKV versus eTKV (repeatability coefficient 2.4% vs. 14% in senior reader, and reproducibility coefficient 6.7% vs. 15%). Intertechnique reproducibility coefficient (95% confidence interval [CI]) was 19% (17%, 21%) in senior reader. Intertechnique agreement on derived MCIC scores was very good (ICC = 0.924 [0.884, 0.949]). CONCLUSION: TKV estimated using ellipsoid equation demonstrates poor repeatability and reproducibility compared with that of mTKV. Intertechnique agreement is also limited, even when measurements are performed by an experienced radiologist. Estimated TKV, however, accurately determines MCIC score.

Urinary biomarkers at early ADPKD disease stage.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by a decline in renal function at late disease stage when the majority of functional renal parenchyma is replaced by cystic tissue. Thus, kidney function, assessed by estimated glomerular filtration rate (eGFR) does not well represent disease burden in early disease. Here, we investigated various urinary markers for tubular injury and their association with disease burden in ADPKD patients at early disease course. METHODS: ADPKD patients between 18 and 40 years with an eGFR greater or equal to 70 ml per min per 1.73m2 were eligible for this cross-sectional study. Urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL), Kidney Injury Molecule-1 (KIM-1), and Uromodulin (UMOD) were investigated by Enzyme-Linked Immunosorbent Assay. Clara Cell Protein 16 (CC16) was investigated by Latex Immuno Assay. Cryoscopy was performed to assess urine osmolality and Urinary Albumin-to-Creatinine Ratio (UACR) was calculated. The association and the predictive properties of the markers on eGFR and height adjusted total kidney volume (htTKV) was evaluated using multiple regression analysis, incorporating different control variables for adjustment. Internal bootstrapping validated the obtained results. RESULTS: In 139 ADPKD patients (age 31 ±7 years, mean eGFR of 93 ± 19 ml per min per 1.73 m2) the total kidney volume was negatively correlated with eGFR and UMOD and positive associated with age, UACR, KIM-1 and urine osmolality after adjustment for possible confounders. Urine osmolality and htTKV were also associated with eGFR, whereas no association of CC16, NGAL and UMOD with eGFR or htTKV was found. CONCLUSION: UACR and urinary KIM-1 are independently associated with kidney size but not with renal function in our study population. Urine osmolality was associated with eGFR and kidney volume following adjustment for multiple confounders. Despite statistical significance, the clinical value of our results is not yet conceivable. Further studies are needed to evaluate the property of the aforementioned biomarkers to assess disease state at early ADPKD stage.

Development and validation of a polycystic liver disease complaint-specific assessment (POLCA).

BACKGROUND & AIMS: Polycystic liver disease (PCLD) may lead to extensive hepatomegaly and invalidating complaints. Therapeutic decisions, including somatostatin-analogues (SAs) and (non)-transplant surgery are besides the existence of hepatomegaly, also guided by the severity of complaints. We developed and validated a self-report instrument to capture the presence and severity of disease specific complaints for PCLD. METHODS: The study population consisted of 129 patients. Items for the PCLD-complaint-specific assessment (POLCA) were developed based on the chart review of symptomatic PCLD patients (n=68) and literature, and discussed during expert-consensus-meetings. 61 patients who needed therapy were asked to complete the POLCA and the short form health survey version 2 (SF36V2) at baseline and after 6 months of SA-treatment. CT-scans were used to calculate liver volumes (LV). Factor analysis was conducted to identify subscales and remove suboptimal items. Reliability was assessed by Cronbach's alpha. Convergent, criterion validity and responsiveness were tested using prespecified hypotheses. RESULTS: In the validation group (n=61), 47 received lanreotide (LAN) and 14 were offered LAN as bridge to liver transplantation (LTx). Factor analysis identified four subscales, which correlated with the physical component summary (PCS). Baseline POLCA scores were significantly higher in LTx-listed patients. In contrast to SF36V2, POLCA-paired observations in 47 patients demonstrated that 2 subscales were lowered significantly and 2 borderline. LV reduction of ⩾ 120 ml resulted in a numerical, more pronounced relative decrease of all scores. CONCLUSIONS: In contrast to SF36V2, the POLCA shows good validity and responsiveness to measure complaint severity in PCLD.

Autosomal dominant polycystic kidney disease is associated with central and nephrogenic defects in osmoregulation.

Autosomal dominant polycystic kidney disease (ADPKD) is associated with a urine-concentrating defect attributed to renal cystic changes. As PKD genes are expressed in the brain, altered central release of arginine vasopressin could also play a role. In order to help determine this we measured central and nephrogenic components of osmoregulation in 10 adults and 10 children with ADPKD, all with normal renal function, and compared them to 20 age- and gender-matched controls. Overnight water deprivation caused a lower rise in urine osmolality in the patients with ADPKD than controls, reflecting an impaired release of vasopressin and a peripheral defect in the patients. The reactivity of plasma vasopressin to water deprivation, as found in controls, was blunted in the patients with the latter showing lower urine osmolality for the same range of plasma vasopressin. The maximal urine osmolality correlated negatively with total kidney volume. Defective osmoregulation was confirmed in the children with ADPKD but was unrelated to number of renal cysts or kidney size. Thus, patients with ADPKD have an early defect in osmoregulation, with a blunted release of arginine vasopressin. This reflects expression of polycystins in hypothalamic nuclei that synthesize vasopressin, and this should be considered when evaluating treatments targeting the vasopressin pathway in ADPKD.