Hypertension is common in autosomal dominant polycystic kidney disease (ADPKD) and is associated with increased total kidney volume, activation of the renin-angiotensin-aldosterone system, and ...progression of kidney disease.
In this double-blind, placebo-controlled trial, we randomly assigned 558 hypertensive participants with ADPKD (15 to 49 years of age, with an estimated glomerular filtration rate GFR >60 ml per minute per 1.73 m(2) of body-surface area) to either a standard blood-pressure target (120/70 to 130/80 mm Hg) or a low blood-pressure target (95/60 to 110/75 mm Hg) and to either an angiotensin-converting-enzyme inhibitor (lisinopril) plus an angiotensin-receptor blocker (telmisartan) or lisinopril plus placebo. The primary outcome was the annual percentage change in the total kidney volume.
The annual percentage increase in total kidney volume was significantly lower in the low-blood-pressure group than in the standard-blood-pressure group (5.6% vs. 6.6%, P=0.006), without significant differences between the lisinopril-telmisartan group and the lisinopril-placebo group. The rate of change in estimated GFR was similar in the two medication groups, with a negative slope difference in the short term in the low-blood-pressure group as compared with the standard-blood-pressure group (P<0.001) and a marginally positive slope difference in the long term (P=0.05). The left-ventricular-mass index decreased more in the low-blood-pressure group than in the standard-blood-pressure group (-1.17 vs. -0.57 g per square meter per year, P<0.001); urinary albumin excretion was reduced by 3.77% with the low-pressure target and increased by 2.43% with the standard target (P<0.001). Dizziness and light-headedness were more common in the low-blood-pressure group than in the standard-blood-pressure group (80.7% vs. 69.4%, P=0.002).
In early ADPKD, the combination of lisinopril and telmisartan did not significantly alter the rate of increase in total kidney volume. As compared with standard blood-pressure control, rigorous blood-pressure control was associated with a slower increase in total kidney volume, no overall change in the estimated GFR, a greater decline in the left-ventricular-mass index, and greater reduction in urinary albumin excretion. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; HALT-PKD Study A ClinicalTrials.gov number, NCT00283686.).
To evaluate the utility of hepatocyte-phase gadoxetate disodium-enhanced magnetic resonance (MR) imaging in staging hepatic fibrosis and to compare it with diffusion-weighted imaging.
This ...retrospective study had institutional review board approval, and the requirement for informed consent was waived. Gadoxetate disodium-enhanced and diffusion-weighted MR images obtained in 114 consecutive patients (70 men, 44 women; age range, 37-91 years) were evaluated. Liver-to-muscle signal intensity (SI) ratio on hepatocyte-phase images (SI(post)), contrast enhancement index calculated as SI(post) /SI(pre), where SI(pre) is liver-to-muscle SI ratio on nonenhanced images, and apparent diffusion coefficient (ADC) of the liver were measured. Necroinflammatory activity grades and hepatic fibrosis stages were histopathologically determined in 99 patients. Multiple regressions of SI(post), contrast enhancement index, ADC, serum albumin concentration, serum total bilirubin level, prothrombin time, and Child-Pugh score were examined to determine correlation with hepatic necroinflammatory activity grades and fibrosis stages.
Among the MR, hematologic, and clinical parameters, contrast enhancement index was most strongly correlated with fibrosis stage (r = -0.79, P < .001). Multiple regression analysis showed that the contrast enhancement index, ADC, and prothrombin time were significantly correlated (r(2) = 0.66, P < .05) with fibrosis stage and that the contrast enhancement index and serum total bilirubin level were weakly correlated (r(2) = 0.24, P < .05) with the necroinflammatory activity grade.
Gadoxetate disodium-enhanced MR imaging is more reliable for staging hepatic fibrosis than are diffusion-weighted MR imaging, hematologic, and clinical parameters.
The objective of our study was to compare diffusion kurtosis imaging (DKI) with conventional diffusion-weighted imaging (DWI) for assessing the response to treatment in hypervascular hepatocellular ...carcinoma (HCC).
Sixty-two consecutive patients with treated or untreated hypervascular HCC underwent MRI of the liver including DKI (b values of 0, 100, 500, 1000, 1500, and 2000 s/mm(2)). The mean kurtosis (MK) and apparent diffusion coefficient (ADC) values of the hepatic parenchyma and of the HCCs were computed. The detectability of viable HCC based on MK and ADC values was compared. We also assessed the correlation between Child-Pugh grades and MK or ADC values.
For a total of 112 HCC nodules (viable, n = 63; nonviable, n = 49), the MK value was significantly higher for the viable group (mean ± SD, 0.81 ± 0.11) than for the non-viable group (0.57 ± 0.11) (p < 0.001). The mean ADC value was significantly lower for the viable group (1.44 ± 0.42 × 10(-3) mm(2)/s) than for the nonviable group (1.94 ± 0.52 × 10(-3) mm(2)/s) (p < 0.001). The sensitivity, specificity, and AUC of the ROC curve for the assessment of HCC viability were greater (p < 0.001) using MK (85.7%, 98.0%, and 0.95, respectively; cutoff value = 0.710) than using ADC (79.6%, 68.3%, and 0.77, respectively; cutoff value = 1.535 × 10(-3) mm(2)/s). Although the ADC of hepatic parenchyma was lower in patients with Child-Pugh grade B or C disease than in those with grade A disease (p = 0.02), no significant difference in MK (p = 0.45) was found among the Child-Pugh grades.
DKI can be a new option for the assessment of posttherapeutic response in HCC.
Background
Cystogenesis in polycystic kidney disease (PKD) is likely accelerated by various renal insults, including crystal deposition, that activate renal tubule obstruction and dilation. We ...developed a capsule-based device that can be applied to cystic kidneys to restrict tubular lumen dilatation and cyst expansion.
Methods
Kidney capsule devices were designed from computed tomography images of wild-type and Cy/+ rats. Capsule devices were surgically implanted on kidneys in six surgical sessions over a period of 14 months in 7 wild-type rats of 6.5–8 weeks (3 sham operations, 2 right, 2 left) and 6 Cy/+ rats of 6.5 weeks (2 sham, 3 left, 1 bilateral). After surgery, the rats were followed for 5.4–12.4 weeks’ growth and sacrificed to retrieve the kidneys. During the follow-up, serum creatinine was measured and retrieved kidneys were weighed. Histological analysis including cystic area measurement and immunohistochemistry was performed.
Results
Morphometric capsule devices were configured and developed by an image processing technique and produced using a 3D printer. Encapsulated Cy/+ kidneys (
n
= 5; mean weight 3.64 g) were consistently smaller in size (by 21–36%;
p
< 0.001) than unencapsulated Cy/+ kidneys (
n
= 7; mean weight 5.52 g). Encapsulated Cy/+ kidneys (mean %cyst area: 29.4%) showed smaller histological cystic area (by 28–58%;
p
< 0.001) than unencapsulated Cy/+ kidneys (mean %cyst area 48.6%). Cell proliferation and macrophages were also markedly reduced in encapsulated Cy/+ kidneys, compared to unencapsulated Cy/+ kidneys.
Conclusions
We report a pilot feasibility study for the application of a novel morphometric 3D capsule device to the Cy/+ rat model showing restricted kidney volume expansion on polycystic kidney disease progression.
The continuing advances in computed tomographic (CT) technology in the past decades have provided ongoing opportunities to improve CT image quality and clinical practice and discover new clinical CT ...imaging applications. New CT technology, however, has introduced new challenges in clinical radiology practice. One of the challenges is with intravenous contrast medium administration and scan timing. In this article, contrast medium pharmacokinetics and patient, contrast medium, and CT scanning factors associated with contrast enhancement and scan timing are presented and discussed. Published data from clinical studies of contrast medium and physiology are reviewed and interpreted. Computer simulation data are analyzed to provide an in-depth analysis of various factors associated with contrast enhancement and scan timing. On the basis of basic principles and analysis of the factors, clinical considerations and modifications to protocol design that are necessary to optimize contrast enhancement for common clinical CT applications are proposed.
The association of overweight/obesity with disease progression in patients with autosomal dominant polycystic kidney disease (ADPKD) remains untested. We hypothesized that overweight/obesity ...associates with faster progression in early-stage ADPKD. Overall, 441 nondiabetic participants with ADPKD and an eGFR>60 ml/min per 1.73 m
who participated in the Halt Progression of Polycystic Kidney Disease Study A were categorized on the basis of body mass index (BMI; calculated using nonkidney and nonliver weight) as normal weight (18.5-24.9 kg/m
; reference;
=192), overweight (25.0-29.9 kg/m
;
=168), or obese (≥30 kg/m
;
=81). We evaluated the longitudinal (5-year) association of overweight/obesity with change in total kidney volume (TKV) by magnetic resonance imaging using linear regression and multinomial logistic regression models. Among participants, mean±SD age was 37±8 years, annual percent change in TKV was 7.4%±5.1%, and BMI was 26.3±4.9 kg/m
The annual percent change in TKV increased with increasing BMI category (normal weight: 6.1%±4.7%, overweight: 7.9%±4.8%, obese: 9.4%±6.2%;
<0.001). In the fully adjusted model, higher BMI associated with greater annual percent change in TKV (
=0.79; 95% confidence interval 95% CI, 0.18 to 1.39, per 5-unit increase in BMI). Overweight and obesity associated with increased odds of annual percent change in TKV ≥7% compared with <5% (overweight: odds ratio, 2.02; 95% CI, 1.15 to 3.56; obese: odds ratio, 3.76; 95% CI, 1.81 to 7.80). Obesity also independently associated with greater eGFR decline (slope) versus normal weight (fully adjusted
=-0.08; 95% CI, -0.15 to -0.02). In conclusion, overweight and, particularly, obesity are strongly and independently associated with rate of progression in early-stage ADPKD.
Obesity increases the risk of adverse outcomes during acute critical illnesses such as burns, severe trauma, and acute pancreatitis. Although individuals with more body fat and higher serum cytokines ...and lipase are more likely to experience problems, the roles that these characteristics play are not clear. We used severe acute pancreatitis as a representative disease to investigate the effects of obesity on local organ function and systemic processes. In obese humans, we found that an increase in the volume of intrapancreatic adipocytes was associated with more extensive pancreatic necrosis during acute pancreatitis and that acute pancreatitis was associated with multisystem organ failure in obese individuals. In vitro studies of pancreatic acinar cells showed that unsaturated fatty acids were proinflammatory, releasing intracellular calcium, inhibiting mitochondrial complexes I and V, and causing necrosis. Saturated fatty acids had no such effects. Inhibition of lipolysis in obese (ob/ob) mice with induced pancreatitis prevented a rise in serum unsaturated fatty acids and prevented renal injury, lung injury, systemic inflammation, hypocalcemia, reduced pancreatic necrosis, and mortality. Thus, therapeutic approaches that target unsaturated fatty acid-mediated lipotoxicity may reduce adverse outcomes in obese patients with critical illnesses such as severe acute pancreatitis.
Autosomal dominant polycystic kidney disease (ADPKD) often results in ESRD but with a highly variable course. Mutations to PKD1 or PKD2 cause ADPKD; both loci have high levels of allelic ...heterogeneity. We evaluated genotype-phenotype correlations in 1119 patients (945 families) from the HALT Progression of PKD Study and the Consortium of Radiologic Imaging Study of PKD Study. The population was defined as: 77.7% PKD1, 14.7% PKD2, and 7.6% with no mutation detected (NMD). Phenotypic end points were sex, eGFR, height-adjusted total kidney volume (htTKV), and liver cyst volume. Analysis of the eGFR and htTKV measures showed that the PKD1 group had more severe disease than the PKD2 group, whereas the NMD group had a PKD2-like phenotype. In both the PKD1 and PKD2 populations, men had more severe renal disease, but women had larger liver cyst volumes. Compared with nontruncating PKD1 mutations, truncating PKD1 mutations associated with lower eGFR, but the mutation groups were not differentiated by htTKV. PKD1 nontruncating mutations were evaluated for conservation and chemical change and subdivided into strong (mutation strength group 2 MSG2) and weak (MSG3) mutation groups. Analysis of eGFR and htTKV measures showed that patients with MSG3 but not MSG2 mutations had significantly milder disease than patients with truncating cases (MSG1), an association especially evident in extreme decile populations. Overall, we have quantified the contribution of genic and PKD1 allelic effects and sex to the ADPKD phenotype. Intrafamilial correlation analysis showed that other factors shared by families influence htTKV, with these additional genetic/environmental factors significantly affecting the ADPKD phenotype.
Many clinical applications of thoracic computed tomography (CT) require contrast medium to enhance and delineate vascular, mediastinal, hilar, and cardiac structures, and differentiate normal and ...pathologic vascular or tumoral conditions. Multidetector row computed tomography (MDCT) is superior to single-detector row CT (SDCT) because MDCT permits more efficient and flexible use of intravenous contrast medium to achieve enhancement. However, to fully reap the benefits of MDCT contrast enhancement, the technical challenges associated with optimizing enhancement and scan timing in MDCT need to be solved. This article reviews the basic principles of CT contrast enhancement and discusses common clinical considerations and the protocol design modifications that are necessary to achieve optimal contrast enhancement in thoracic MDCT.
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