Kidney growth progression patterns in autosomal dominant polycystic kidney disease.

BACKGROUND: Prognosis for autosomal dominant polycystic kidney disease (ADPKD), the main inherited cause of kidney failure, relies on estimating cystic growth using linear formulas derived from height-adjusted total kidney volume (Ht-TKV). However, nonlinear renal growth patterns may occur in typical ADPKD. AIMS: To determine kidney outcomes of subjects diagnosed with typical ADPKD exhibiting nonlinear, and unpredictable cystic growth during follow-up. METHODS: Retrospective cohort study. We categorized TKV changes in individuals with typical ADPKD according to observed kidney growth trajectories. Ht-TKV was calculated from consecutive CT or MRI using the ellipsoid method. We compared estimated glomerular filtration rate (eGFR) trajectories with linear mixed models. RESULTS: We included 83 individuals with ADPKD (67% women; age 47 ± 12 years; follow-up 5.2 years [IQR 2.8-9.0]). Three kidney growth patterns were observed: slow progression (24%, <3%/year linear increase), fast progression (39%, ≥3%/year linear increase), and atypical progression (37%, nonlinear growth). Adjusted ht-TKV change in mL/m/year was +1.4 (IQR -4.5 to +10.0), +40.3 (+16.9 to +89.3), and +32.8 (+15.9 to +85.9) for slow, fast, and atypical progressors, respectively (p < 0.001). Atypical progressors exhibited a significantly greater decline in eGFR in mL/min/m²/year (-7.9, 95% CI -6.5, -3.9) compared to slow (-0.5, 95% CI -3.1 to +0.5) and fast progressors (-3.4, 95% CI -7.9, -2.0; between-group p < 0.001). Atypical progressors had a higher proportion of acute complications, including hemorrhages, infections, and urolithiasis (84%), compared to slow (20%) and fast progressors (31%) (p < 0.001). CONCLUSION: In typical ADPKD, nonlinear, abrupt, and unpredictable cyst growth occurs frequently, leading to a higher risk of acute complications and kidney function decline.

Increased Body Fat and Organic Acid Anions Production Are Associated with Larger Kidney Size in ADPKD.

Background and Objectives: A high body mass index (BMI) is associated with the progression of autosomal dominant polycystic kidney disease (ADPKD). However, body fat (BF), which is another adiposity marker, has not yet been studied. Excessive weight may promote elevation in the endogenous synthesis of organic acid (OA) anions. Accordingly, we aimed to investigate the possible association of the aforementioned markers with kidney volume and renal function in patients with ADPKD. Materials and Methods: We conducted a retrospective cohort study of adult ADPKD outpatients involving clinical, serum, and urinary laboratorial data and body composition assessments retrieved from their medical records. BF was estimated by skinfold thickness (mm) on the non-dominant arm and was considered as normal or high for each sex. Total kidney volume (TKV) and height-adjusted volume (htTKV) were measured by magnetic resonance imaging. The annual estimated glomerular filtration rate (eGFR) slope was analyzed during a median follow-up time of 6 (5.0-7.0) years to calculate rapid progression (decline in renal function ≥2.5 mL/min/year over 5 years). Results: A total of 104 patients were included (41.9 ± 11.9 years old, 38.5% men), with 62.5% of the patients classified as high BF. The High BF group presented higher levels of OA, glycosylated hemoglobin (HbA1c), C-reactive protein (CRP), 24 h urinary sodium (UNa), and htTKV, and lower eGFR than those with a normal BF. In the multivariate linear regression, the associated variables with TKV were high BF, OA and BMI (std. ß 0.47, p < 0.05; std. ß 0.36, p = 0.001; std. ß 0.25, p = 0.01, respectively). In the binary logistic regression, when adjusted for potential confounders, UNa was the only parameter associated with an increased risk of eGFR decline ≥2.5 mL/min/year (OR 1.02, 95% CI 1.01-1.03, p = 0.02). Conclusions: Increased body fat and endogenous production of organic acid anions are associated with larger kidney size in ADPKD but not with a decline in renal function.

Low agreement between kidney volume and kidney length z-scores.

BACKGROUND: Pediatric nephrologists use kidney length and kidney volume z-scores to longitudinally assess normal nephron endowment. However, most radiologists only report kidney length. Agreement between kidney length and kidney volume z-scores in children has been understudied. This study aims to assess agreement between kidney length and kidney volume z-scores in children. METHODS: This novel cross-sectional cohort study prospectively followed prematurely born babies from a large specialized prematurity follow-up center. A healthy control group matched the cases by age and sex and was recruited from schools. Children were assessed for kidney length and kidney volumes at age 5 by three independent ultrasonographers. All measurements were performed in triplicate. Detailed anthropometry, blood pressure, and kidney function were also obtained. Age-independent z-scores were calculated for all parameters according to Scholbach and Weitzel and compared using descriptive statistics. RESULTS: We studied 89 premature patients (median 32 weeks gestational age) and 33 healthy controls (median 38 weeks gestational age). There were 732 determinations of kidney length, width, and thickness. The mean z-score of the right kidney length was 0.65 ± 0.08 (SEM) compared with 0.88 ± 0.08 of the left kidney length (p = 0.0003, two-sided paired t test). The squared correlation coefficient for kidney volume to kidney length was 0.32 (p < 0.0001). Bland and Altman analysis revealed considerable bias with - 1.36 ± 0.76 standard deviations and 95% limits of agreement from - 2.83 to - 0.16. CONCLUSION: Reporting only kidney length results in significant overestimation of age-independent z-scores. Based on our findings, consideration to measuring all kidney dimensions may be more appropriate.

Association of Vitamin D Levels With Kidney Volume in Autosomal Dominant Polycystic Kidney Disease (ADPKD).

Vitamin D possesses renoprotective effects beyond mineral metabolism, potentially reducing arterial blood pressure and inflammation and vitamin D enzymes (CYP24A1 and CYP27B1) as well as vitamin D receptor (VDR) contribute to its homeostasis. In the present study, we aimed to determine vitamin D association with kidney volume, blood pressure parameters and inflammatory markers in ADPKD. This cross-sectional study, conducted from August 2011 through May 2016, evaluated 25(OH)D, 1,25(OH)2D and other hormonal/biochemical serum and urinary parameters, inflammatory markers and monocyte expression of VDR, CYP24A1, CYP27B1 in 74 ADPKD patients. The height-adjusted total kidney volume (htTKV) was determined by MRI and blood pressure (BP) measured through 24-h ambulatory BP monitoring (ABPM).Vitamin D insufficiency was present in 62% of patients and CYP24A1 was overexpressed in this group, raising a hypothesis of 25(OH)D increased catabolism. Serum 25(OH)D levels and VDR expression were negatively correlated with htTKV as was VDR with IL-6, IL-10, CRP, and NFκB. A multiple linear regression analysis with htTKV as dependent variable, including hypertension, CRP, eGFR, age, time since diagnosis, VDR, and 25(OH)D adjusted for season of the year showed that only the first three parameters were independent predictors of the former. There has been no association of serum 25(OH)D and VDR expression with ABPM parameters. Present findings suggested that low levels of serum 25(OH)D and VDR expression are associated with a higher kidney volume in ADPKD patients, but do not represent independent risk factors for htTKV.

Cyst infection in hospital-admitted autosomal dominant polycystic kidney disease patients is predominantly multifocal and associated with kidney and liver volume

Positron-emission tomography/computed tomography (PET/CT) has improved cyst infection (CI) management in autosomal dominant polycystic kidney disease (ADPKD). The determinants of kidney and/or liver involvement, however, remain uncertain. In this study, we evaluated clinical and imaging factors associated with CI in kidney (KCI) and liver (LCI) in ADPKD. A retrospective cohort study was performed in hospital-admitted ADPKD patients with suspected CI. Clinical, imaging and surgical data were analyzed. Features of infected cysts were evaluated by PET/CT. Total kidney (TKV) and liver (TLV) volumes were measured by CT-derived multiplanar reconstruction. CI was detected in 18 patients who experienced 24 episodes during an interval of 30 months (LCI in 12, KCI in 10 and concomitant infection in 2). Sensitivities of CT, magnetic resonance imaging and PET/CT were 25.0, 71.4, and 95.0%. Dysuria (P<0.05), positive urine culture (P<0.01), and previous hematuria (P<0.05) were associated with KCI. Weight loss (P<0.01) and increased C-reactive protein levels (P<0.05) were associated with LCI. PET/CT revealed that three or more infected cysts were present in 70% of the episodes. TKV was higher in kidney-affected than in LCI patients (AUC=0.91, P<0.05), with a cut-off of 2502 mL (72.7% sensitivity, 100.0% specificity). TLV was higher in liver-affected than in KCI patients (AUC=0.89, P<0.01) with a cut-off of 2815 mL (80.0% sensitivity, 87.5% specificity). A greater need for invasive procedures was observed in LCI (P<0.01), and the overall mortality was 20.8%. This study supports PET/CT as the most sensitive imaging method for diagnosis of cyst infection, confirms the multifocal nature of most hospital-admitted episodes, and reveals an association of kidney and liver volumes with this complication.