Unobstructed Kidneys Research Articles

Contralateral renal change in a unilateral ureteral obstruction rat model using intravoxel incoherent motion diffusion-weighted imaging

Objectives Most functional magnetic resonance research has primarily examined alterations in the affected kidney, often neglecting the contralateral kidney. Our study aims to investigate whether imaging parameters accurately depict changes in both the renal cortex and medulla in a unilateral ureteral obstruction rat model, thereby showcasing the utility of intravoxel incoherent motion (IVIM) in evaluating contralateral renal changes. Methods Six rats underwent MR scans and were subsequently sacrificed for baseline histological examination. Following the induction of left ureteral obstruction, 48 rats were scanned, and the histopathological examinations were conducted on days 3, 7, 10, 14, 21, 28, 35, and 42. The apparent diffusion coefficient (ADC), pure molecular diffusion (D), pseudodiffusion (D*), and perfusion fraction (f) values were measured using IVIM. Results On the 10th day of obstruction, both cortical and medullary ADC values differed significantly between the UUO10 group and the sham group (p < 0.01). The cortical D values showed statistically significant differences between UUO3 group and sham group (p < 0.01) but not among UUO groups at other time point. Additionally, the cortical and medullary f values were statistically significant between the UUO21 group and the sham group (p < 0.01). Especially, the cortical f values exhibited significant differences between the UUO21 group and the UUO groups with shorter obstruction time (at time point of 3, 7, 10, 14 day) (p < 0.01). Conclusions Significant hemodynamic alterations were observed in the contralateral kidney following renal obstruction. IVIM accurately captures changes in the unobstructed kidney. Particularly, the cortical f value exhibits the highest potential for assessing contralateral renal modifications.

Exploring the potential of the novel imidazole-4,5-dicarboxyamide chemical exchange saturation transfer scaffold for pH and perfusion imaging.

Here, we describe and assess the potential of 14 newly synthesized imidazole-4,5-dicarboxyamides (I45DCs) for pH and perfusion imaging. A number of these aromatic compounds possess large labile proton chemical shifts (up to 7.7ppm from water) because of their intramolecular hydrogen bonds and a second labile proton to allow for chemical exchange saturation transfer (CEST) signal ratio-based pH measurements. We have found that the contrast produced is strong for a wide range of substitutions and that the inflection points in the CEST signal ratio versus pH plots used to generate concentration-independent pH maps can be adjusted based on these subsitutions to tune the pH range that can be measured. These I45DC CEST agents have advantages over the triiodobenzenes currently employed for tumor and kidney pH mapping, both preclinically and in initial human studies. Finally, as CEST MRI combined with exogenous contrast has the potential to detect functional changes in the kidneys, we evaluated our highest performing anionic compound (I45DC-diGlu) on a unilateral urinary obstruction mouse model and observed lower contrast uptake in the obstructed kidney compared with the unobstructed kidney and that the unobstructed kidney displayed a pH of ~6.5 while the obstructed kidney had elevated pH and an increased range in pH values. Based on this, we conclude that the I45DCs have excellent imaging properties and hold promise for a variety of medical imaging applications, particularly renal imaging.

Noninvasive assessment of renal dynamics and pH in a unilateral ureter obstruction model using DCE MR-CEST urography.

To assess the potential of DCE MR CEST urography for assessing renal function in mice with unilateral ureter obstruction (UUO) by simultaneous pH and renal uptake/clearance measurements following injection of iopamidol. The right ureter of nine mice was obstructed via suture ligation. The animals were imaged at day 1, 2, and 3 post-obstruction on an 11.7T MRI scanner. Ninety-six sets of saturated CEST images at 4.3 and 5.5ppm were collected. Renal pH values were obtained by calculating the signal ratio for these two frequencies and using a pH calibration curve. Renal time activity curves were measured as a percentage change in the post-injection CEST signal at 4.3ppm relative to the average pre-injection signal. For the healthy mice, the time activity curves of both kidneys were nearly identical and displayed rapid excretion of contrast. For the UUO mice, the dynamic CEST curves for the obstructed kidneys displayed prolonged time to peak (TTP) values and delayed contrast excretion compared with the contralateral (CL) kidneys. Renal pH maps of the healthy animals showed similar acidic values for both kidneys (pH6.65 ± 0.04 vs 6.67 ± 0.02), whereas in the obstructed kidneys there was a significant increase in pH values compared with the CL kidneys (pH6.67 ± 0.08 vs 6.79 ± 0.11 in CL and UUO kidneys, respectively). Our findings indicate that DCE-MR-CEST urography can detect changes in renal uptake/excretion and pH homeostasis and distinguish between obstructed and unobstructed kidney as early as 1 day after UUO.

Twist-related protein 1 induces epithelial-mesenchymal transition and renal fibrosis through the upregulation of complement 3.

We have demonstrated that complement 3 (C3) is upregulated and induces epithelial-mesenchymal transition (EMT) phenomenon and renal fibrosis in unilateral ureteral obstruction (UUO) kidney. We investigated roles of twist-related protein 1 (TWIST1) in EMT phenomenon and renal fibrosis through C3 upregulation in a mouse UUO model with gene silencer pyrrole-imidazole (PI) polyamides targeting TWIST1. We designed and synthesized PI polyamides targeting TWIST1 binding site on mouse pre-pro C3 promoter. Increased expression C3 mRNA with interferon-γ was significantly inhibited with PI polyamide in nephrotubular epithelial cells. Immunofluorescence showed suppression of E-cadherin and enhancement of α-smooth muscle actin (α-SMA) stainings as EMT phenomena in UUO kidney. TWIST1 and C3 expression was significantly increased in UUO kidney versus contralateral unobstructed kidney (CUK). Expression of transforming growth factor-β1 (TGF-β1), α-SMA and renin mRNAs was increased in UUO kidney versus CUK. Systemic administration of TWIST1 PI polyamide significantly suppressed increased C3 expression in UUO kidney versus CUK. PI polyamide administration also suppressed the increased expression of TGF-β1, α-SMA and renin mRNAs and histologically improved renal fibrosis in UUO kidney. These findings indicate that TWIST1 induces EMT phenomenon and renal fibrosis by TGF-β1 upregulation of C3 in mouse UUO model and that TWIST1 PI polyamide may be a novel medicine for renal fibrosis.

The cell membrane repair protein MG53 modulates transcription factor NF-κB signaling to control kidney fibrosis

Kidney fibrosis is associated with the progression of acute kidney injury to chronic kidney disease. MG53, a cell membrane repair protein, has been shown to protect against injury to kidney epithelial cells and acute kidney injury. Here, we evaluated the role of MG53 in modulation of kidney fibrosis in aging mice and in mice with unilateral ureteral obstruction (UUO) a known model of progressive kidney fibrosis. Mice with ablation of MG53 developed more interstitial fibrosis with age than MG53-intact mice of the same age. Similarly, in the absence of MG53, kidney fibrosis was exaggerated compared to mice with intact MG53 in the obstructed kidney compared to the contralateral unobstructed kidney or the kidneys of sham operated mice. The ureteral obstructed kidneys from MG53 deficient mice also showed significantly more inflammation than ureteral obstructed kidneys from MG53 intact mice. Invitro experiments demonstrated that MG53 could enter the nuclei of proximal tubular epithelial cells and directly interact with the p65 component of transcription factor NF-κB, providing a possible explanation of enhanced inflammation in the absence of MG53. To test this, enhanced MG53 expression through engineered cells or direct recombinant protein delivery was given to mice subject to UUO. This reduced NF-κB activation and inflammation and attenuated kidney fibrosis. Thus, MG53 may have a therapeutic role in treating chronic kidney inflammation and thereby provide protection against fibrosis that leads to the chronic kidney disease phenotype.

Restricted diffusion MRI as a functional biomarker for the assessment of acute calcular upper urinary tract obstruction: initial experience

BackgroundAcute renal obstruction due to stone is a prevalent scenario. The diffusion-weighted magnetic resonance imaging (DWI) of the kidneys provides a noninvasive information on renal function. Our objective is to prospectively assess the potential role of DWI to predict the signal changes of a kidney with acute calcular obstruction.ResultsChi-square and Fissure exact tests were used to assess the association of diffusion signal changes among patients and control groups. Cohen's Kappa test was run to determine the degree of agreement between the two radiologists. An independent sample t-test was performed to assess the significant difference among ADC values between the two groups. Restricted signals of the obstructed kidneys showed a statistically significant difference when compared with contralateral unobstructed kidney and control group with p value (0.001) and (0.01), respectively. Furthermore, there is a moderate agreement between the two radiologists K = 0.7, p = 0. 001. There is no statistically significant difference in ADC values when comparing the obstructed kidney and the contralateral unobstructed kidney of the patient group or with the control group p value (0.06) and (0.05), respectively.ConclusionRestricted signals of the obstructed kidney by DWI may be a helpful tool in diagnosing acute unilateral renal obstruction and can affect its management; however, it needs further validation by more studies.

Influence of Early Bladder Imaging in Experimental Rabbits on the Quantitative Determination of Glomerular Filtration Rate by the Gates Method.

Objective To investigate the influence of early bladder imaging (EBI) in experimental rabbits on the quantitative calculation of glomerular filtration rate (GFR) by the Gates method. Methods We retrospectively analyzed the data of dynamic renal scintigraphy (DRS) in experimental rabbits. We calculated renal uptake during minutes 1-2 and 2-3 by correcting bladder radioactivity and computed the split GFR by renal uptake. Then, the EBI and GFR between 1-2 min and 2-3 min were compared, respectively. Results The EBI proportion (57.3%) at 2-3 min of DRS was higher than that (8.5%) at 1-2 min (P < 0.05). The correlations between the 1-2 min and 2-3 min uptake rates of unobstructed kidneys after correction (r = 0.952‐0.979) were higher than those before correction (r = 0.859‐0.936). However, the correlation between the two in obstructed kidneys was not improved (rbefore = 0.967 versus rafter = 0.968). For unobstructed kidneys, the difference in GFR based on 2-3 min uptake between before and after correction was significant (P < 0.05), but not in obstructed kidneys (P > 0.05). For GFR based on 1-2 min uptake, the difference between before and after correction was not significant in obstructed or unobstructed kidneys (P > 0.05). Before correction, the GFR of unobstructed kidneys of 10.5% of the rabbits in the protein load test was lower than that in the baseline status, but not so after correction. Conclusion The 2-3 min EBI on DRS has a significant influence on the GFR calculated by the Gates method in experimental rabbits. Controlling water intake or calculating the GFR by 1-2 min renal uptake helps to avoid the influence of EBI on GFR.

Huoxue Jiedu Huayu Recipe Ameliorates Mesangial Cell Pyroptosis in Contralateral Kidney of UUO Rats.

Objectives To observe the effects of the Huoxue Jiedu Huayu Recipe (HJHR) on pyroptosis of glomerular mesangial cells in the contralateral unobstructed kidney (CK) of unilateral ureteral obstruction (UUO) rats. Methods Sprague-Dawley rats were randomly divided into 4 groups: sham group, UUO group (10 days of left ureter ligation), UUO treated with eplerenone (EPL) (UUO + EPL) group, and UUO treated with HJHR (UUO + HJHR) group. The CKs of all rats were collected for studies. Results Cell pyroptosis and macrophage infiltration was found in contralateral glomeruli, and nucleotide-binding oligomerization domain-like pyrin domain containing protein 3 (NLRP3) and interleukin (IL)-1β expression was upregulated in the CK of UUO rats. All of these changes were inhibited by HJHR and eplerenone. To determine how aldosterone (Aldo) activated the mineralocorticoid receptor (MR) and then induced mesangial cell pyroptosis with NLRP3-caspase-1-IL-1β pathway, human mesangial cells (HMCs) were treated with HJHR and eplerenone, which were examined to detect the expression of NLRP3 inflammasome-associated proteins following treatment with Aldo. Conclusion These results suggest that HJHR and eplerenone suppressed HMC pyroptosis via the MR/NLRP3 pathway.

Potential Role of the Resident Mesenchymal Stem-Like Cells in Renal Fibrogenesis after Ureteral Obstruction.

The mechanisms of renal fibrogenesis after ureteral obstruction remain unclear. We tried to primarily expand mesenchymal stem cells from renal tissues and then investigated their role in fibrogenesis after ureteral obstruction. Unilateral ureteral obstruction was induced by ligating the left ureteral duct of adult C57BL/6 mice. We collected the kidneys for experiments at 2, 7, and 14 days after operation. Histological analysis showed obviously fibrotic changes in the left kidney at 7 days and further increased at 14 days after ureteral obstruction. To expand mesenchymal stem cells, we minced the renal tissues into small explants (about 1 mm3) and cultured onto 10 cm dishes. Interestingly, the outgrowth of cells was observed significantly earlier from the explants of the obstructed left kidney than that of the unobstructed right kidney. These expanded cells showed the potency of adipogenic, osteogenic, and chondrogenic differentiations and positively expressed with CD44 and partly expressed with CD90, CD105, and CD106, but negatively expressed with CD34, CD45, and FSP1, suggesting the phenotype of mesenchymal stem-like cells (MSLCs). The mouse fibrosis RT2 profiler PCR array showed that many genes were changed over 2-fold in the MSLCs expanded from both kidneys at 2, 7, and 14 days after operation. Interestingly, profibrotic genes were prevalently enhanced in the left kidney with ureteral obstruction. Histological analysis also showed obviously infiltration of inflammatory cells in the left kidney at 14 days after operation. Our data indicate the potential role of resident MSLCs in renal fibrogenesis after ureteral obstruction, but further experiments are required to understand the relevant mechanisms.

Ileocalicostomy Ureteral Substitution for Complex Ureteropelvic Junction Stricture: Technique and Initial Experience

ObjectiveTo present our novel surgical technique, ileocalicostomy ureteral substitution, for the management of long upper ureteral strictures in patients without a dilated extra-renal pelvis. Materials and MethodsTwo patients were identified with long, complex proximal ureteral strictures who were treated with our novel surgical technique by a single surgeon at a single institution. Perioperative data for these two patients are presented along with a detailed description of the surgical technique. ResultsIleocalicostomy ureteral substitution was successfully performed in two cases. The total operative time for these cases was 436 minutes and 246 minutes, with estimated blood loss of 300 mL and 200 mL. Length of stay for the two patients was 8 days and 6 days, respectively. There were no major (Clavien-Dindo Classification ≥ grade 3) complications. Both patients are entirely free of urinary tubes with unobstructed kidneys since reconstruction. ConclusionIleocalicostomy ureteral substitution is a feasible reconstructive option for select patients. To our knowledge this report is the initial experience in the literature presented.

Evaluation of renal metabolic response to partial ureteral obstruction with hyperpolarized 13 C MRI.

Hyperpolarized 13 C magnetic resonance imaging (MRI) may be used to non-invasively image the transport and chemical conversion of 13 C-labeled compounds in vivo. In this study, we utilize hyperpolarized 13 C MRI to evaluate metabolic markers in the kidneys longitudinally in a mouse model of partial unilateral ureteral obstruction (pUUO). Partial obstruction was surgically induced in the left ureter of nine adult mice, leaving the right ureter as a control. 1 H and hyperpolarized [1-13 C]pyruvate MRI of the kidneys was performed 2days prior to surgery (baseline) and at 3, 7 and 14days post-surgery. Images were evaluated for changes in renal pelvis volume, pyruvate, lactate and the lactate to pyruvate ratio. After 14days, mice were sacrificed and immunohistological staining of both kidneys for collagen fibrosis (picrosirius red) and macrophage infiltration (F4/80) was performed. Statistical analysis was performed using a linear mixed effects model. Significant kidney × time interaction effects were observed for both lactate and pyruvate, indicating that these markers changed differently between time points for the obstructed and unobstructed kidneys. Both kidneys showed an increase in the lactate to pyruvate ratio after obstruction, suggesting a shift towards glycolytic metabolism. These changes were accompanied by marked hydronephrosis, fibrosis and macrophage infiltration in the obstructed kidney, but not in the unobstructed kidney. Our results show that pUUO is associated with increased pyruvate to lactate metabolism in both kidneys, with injury and inflammation specific to the obstructed kidney. The work also demonstrates the feasibility of the use of hyperpolarized 13 C MRI to study metabolism in renal disease.

Immunomodulatory Molecule IRAK-M Balances Macrophage Polarization and Determines Macrophage Responses during Renal Fibrosis.

Activation of various innate immune receptors results in IL-1 receptor-associated kinase (IRAK)-1/IRAK-4-mediated signaling and secretion of proinflammatory cytokines such as IL-12, IL-6, or TNF-α, all of which are implicated in tissue injury and elevated during tissue remodeling processes. IRAK-M, also known as IRAK-3, is an inhibitor of proinflammatory cytokine and chemokine expression in intrarenal macrophages. Innate immune activation contributes to both acute kidney injury and tissue remodeling that is associated with chronic kidney disease (CKD). Our study assessed the contribution of macrophages in CKD and the role of IRAK-M in modulating disease progression. To evaluate the effect of IRAK-M in chronic renal injury in vivo, a mouse model of unilateral ureteral obstruction (UUO) was employed. The expression of IRAK-M increased within 2 d after UUO in obstructed compared with unobstructed kidneys. Mice deficient in IRAK-M were protected from fibrosis and displayed a diminished number of alternatively activated macrophages. Compared to wild-type mice, IRAK-M-deficient mice showed reduced tubular injury, leukocyte infiltration, and inflammation following renal injury as determined by light microscopy, immunohistochemistry, and intrarenal mRNA expression of proinflammatory and profibrotic mediators. Taken together, these results strongly support a role for IRAK-M in renal injury and identify IRAK-M as a possible modulator in driving an alternatively activated profibrotic macrophage phenotype in UUO-induced CKD.

Influence of bladder fullness on the detection of urinary tract obstruction by dynamic renal scintigraphy.

ObjectiveTo investigate the influence of bladder fullness on the diagnosis of urinary tract obstruction during dynamic renal scintigraphy with a diuretic stimulator.Materials and methodsWe studied 82 kidneys in 82 patients submitted to dynamic renal scintigraphy with a diuretic stimulator. We compared the proportional elimination of the radiopharmaceutical 99mTc-DTPA from the kidneys before and after bladder emptying in post-diuretic images, classifying each image as representing an obstructed, indeterminate, or unobstructed kidney.ResultsThe overall elimination of 99mTc-DTPA from the kidneys was 10.4% greater after bladder emptying than before. When the analysis was performed with a full bladder, we classified 40 kidneys as obstructed, 16 as indeterminate, and 26 as unobstructed. When the 40 kidneys classified as obstructed were analyzed after voiding, 11 were reclassified as indeterminate and 3 were reclassified as unobstructed. Of the 16 kidneys classified as indeterminate on the full-bladder images, 13 were reclassified as unobstructed after voiding.ConclusionIn dynamic renal scintigraphy with a diuretic stimulator, it is important to obtain images after voiding, in order to perform a reliable analysis of the proportional excretion of 99mTc-DTPA from the kidneys, avoiding possible false-positive results for urinary tract obstruction.

Quantitative means for differentiating renal obstruction by analysing renography by compartmental modelling of renal fluid flow rate.

The aim of this study was to investigate the accuracy of using a newly developed index, the ratio of urine outflow to renal pelvis volume U/V2 (1/s), in evaluating renal obstruction and determining the severity of obstruction. A total of 42 patients' renograms (80 kidneys) were studied. Compartmental modelling was used to model the behaviour of tracers flowing through the kidney. The derived model led to the formation of the normalized urine flow rate U/V2. An analysis was carried to test the accuracy of the developed index by comparing the developed model and the clinical evaluation of renograms. The Support Vector Machine algorithm was implemented to predict the renal obstruction status. From the comparison performed between the index and the clinical evaluation from certified experts, it was shown that a higher value of index U/V2 indicated a normal kidney, whereas a lower value indicated an obstructed kidney. The classifier developed could provide a 100% accurate diagnosis of differentiated unobstructed kidneys (42/42) and obstructed kidney (18/18). For further classification of obstructed kidneys, the system grouped the samples into slightly obstructed cases with an accuracy of 100% (9/9) and heavily obstructed cases with an accuracy of 89% (8/9). The use of the single parameter U/V2 could produce the diagnosis of renal obstruction with a high level of accuracy. This method has the potential to be used as a benchmark to distinguish the severity level of the renal obstruction.

Upregulation of Interleukin-33 in obstructive renal injury

Interstitial fibrosis and loss of parenchymal tubular cells are the common outcomes of progressive renal diseases. Pro-inflammatory cytokines have been known contributing to the damage of tubular cells and fibrosis responses after renal injury. Interleukin (IL)-33 is a tissue-derived nucleus alarmin that drives inflammatory responses. The regulation and function of IL-33 in renal injury, however, is not well understood. To investigate the involvement of cytokines in the pathogenesis of renal injury and fibrosis, we performed the mouse renal injury model induced by unilateral urinary obstruction (UUO) and analyze the differentially upregulated genes between the obstructed and the contralateral unobstructed kidneys using RNA sequencing (RNAseq). Our RNAseq data identified IL33 and its receptor ST2 were upregulated in the UUO kidney. Quantitative analysis confirmed that transcripts of IL33 and ST2 were upregulated in the obstructed kidneys. Immunofluorescent staining revealed that IL-33 was upregulated in Vimentin- and alpha-SMA-positive interstitial cells. By using genetically knockout mice, deletion of IL33 reduced UUO-induced renal fibrosis. Moreover, in combination with BrdU labeling technique, we observed that the numbers of proliferating tubular epithelial cells were increased in the UUO kidneys from IL33-or ST2-deficient mice compared to wild type mice. Collectively, our study demonstrated the upregulation of IL-33/ST2 signaling in the obstructed kidney may promote tubular cell injury and interstitial fibrosis. IL-33 may serve as a biomarker to detect renal injury and that IL-33/ST2 signaling may represent a novel target for treating renal diseases.

Noninvasive Monitoring and Evaluation of the Renal Structure and Function in a Mouse Model of Unilateral Ureteral Occlusion Using Microcomputed Tomography.

Mouse unilateral ureteral occlusion (UUO) is widely used as a model of renal experimental obstructive nephropathy with interstitial fibrosis. Microcomputed tomography (micro-CT) imaging has the potential to produce quantitative images. The aim of this study was to establish standard images of micro-CT for renal anatomic and functional evaluations in a mouse model of UUO. UUO was induced in adult male mice BALB/c. In total, 27 mice were used in this study. Three mice per group (a total of 6 groups) were examined with contrast-enhanced micro-CT prior to UUO (day 0) and on days 1, 3, 5, 7, 10, and 14 after UUO. In order to determine the histopathologic correlations at each point in time, contrast-enhanced micro-CT imaging was performed in the 18 remaining mice. All animals were sacrificed, and both kidneys were harvested after the final micro-CT examination. UUO resulted in hydronephrosis and changes in the renal parenchyma. The predominant alteration was substantial changes in the hemodynamics of the renal vascular system after ureteral obstruction for 24 hours or longer, which may be resulting from increased action of vasoconstrictors versus vasodilators. The renal parenchyma was significantly reduced after 1 week, and the features of the histologic changes supported the findings of the micro-CT images. In the contralateral unobstructed kidneys, the images showed a normal structure and function and the pathohistology revealed a normal histoarchitecture. Micro-CT is a useful tool for providing noninvasive monitoring and evaluating the renal structure and function.

Unilateral ureteral obstruction attenuates intrarenal angiotensin II generation induced by podocyte injury.

The renal tissue renin-angiotensin system is activated in chronic kidney diseases. We previously demonstrated that intrarenal ANG II is synthesized primarily from liver-derived angiotensinogen filtered through the glomerulus and that podocyte injury increases the passage of angiotensinogen into the tubular lumen and generation of ANG II. In the present study, we tested the effect of cessation of glomerular filtration by ureteral obstruction on renal ANG II generation in kidneys with podocyte injury under two experimental conditions. Ureteral obstruction is known to activate the renin-angiotensin system in nonproteinuric kidneys. Transgenic mice expressing hCD25 in podocyte (NEP25) were injected with 1.25 or 10 ng/g body wt of LMB2, a hCD25-targeted immunotoxin, subjected to unilateral ureteral ligation on the following day, and euthanized 7 and 4 days later, respectively. In both experiments, compared with the kidney in untreated wild-type mice, renal angiotensinogen protein, as assessed by immunostaining and Western blot analysis, was increased in the contralateral unobstructed kidney. However, it was markedly decreased in the obstructed kidney. Whereas intrarenal ANG II content was increased in the contralateral kidney compared with the untreated kidney (248 ± 83 vs. 106 ± 21 and 298 ± 185 vs. 64.8 ± 20 fmol/g kidney, respectively), this increase was suppressed in the obstructed kidney (161 ± 75 and 113 ± 34 fmol/g kidney, respectively), a pattern opposite to what we expected in obstructed kidneys without podocyte injury. Thus, our study indicates that the major source of increased renal ANG II in podocyte injury is filtered angiotensinogen.

Diffusion-weighted MRI does not reflect kidney fibrosis in a rat model of fibrosis.

To assess the apparent diffusion coefficient (ADC) derived from diffusion-weighted (DW) magnetic resonance imaging (MRI) as a specific marker of renal fibrosis in rats with unilateral ureteral obstruction (UUO). Thirteen rats were analyzed in group 1 (n = 4), group 2 (n = 3), and group 3 (n = 6) and measured using a clinical 3.0T MR scanner. Groups 1 and 2 were used to establish the final imaging protocols for group 3. DW imaging with four b-values (0, 50, 300, 800 s/mm(2) ) was conducted before UUO, at days 3 and 5 after UUO, after release of the obstruction, and after sacrifice. Renal cortical ADCs were correlated with histological and ultrastructural analyses. ADC values of group 3 are shown as mean ± standard deviation of [10(-3) mm(2) /s]. On day 5, in vivo cortical ADC of obstructed fibrotic kidneys was significantly reduced compared to unobstructed kidneys (1.4 ± 0.086 vs. 1.535 ± 0.087, P = 0.0018). Postmortem ADC dropped by 50% and was significantly increased in obstructed vs. unobstructed kidneys (0.711 ± 0.094 vs. 0.566 ± 0.049, P = 0.0046). Histopathology of obstructed kidneys showed tubular dilation, tubular cell atrophy, and expansion of the interstitial space. Postmortem ADC correlated tightly with tubular lumen area (r = 0.9, P < 0.001), fibronectin (r = 0.8, P = 0.003), collagen type I (r = 0.73, P = 0.007), and interstitial expansion (r = 0.69, P = 0.013). Compared to the in vivo measurements, postmortem renal ADCs were considerably reduced and, unlike in vivo, fibrotic kidneys exhibited consistently higher ADC compared to healthy kidney parenchyma. Our data suggest that in vivo ADC is unlikely to be a direct measure of renal fibrosis.

Functional Multiparametric Magnetic Resonance Imaging of the Kidneys Using Blood Oxygen Level Dependent and Diffusion-Weighted Sequences

Little data are available on noninvasive magnetic resonance imaging based assessment of renal function during upper urinary tract obstruction. We determined whether functional multiparametric kidney magnetic resonance imaging could monitor the treatment response in cases of acute unilateral upper urinary tract obstruction. Between January 2008 and January 2010, 18 patients with acute unilateral upper urinary tract obstruction due to calculi were prospectively enrolled to undergo kidney magnetic resonance imaging with conventional, blood oxygen level dependent and diffusion-weighted sequences upon emergency hospital admission and after release of obstruction. We assessed functional imaging parameters of obstructed and contralateral unobstructed kidneys derived from blood oxygen level dependent (apparent spin relaxation rate) and diffusion-weighted (total apparent diffusion coefficient, pure diffusion coefficient and perfusion fraction) sequences during acute upper urinary tract obstruction and after its release. During acute obstruction the apparent spin relaxation rate and perfusion fraction were lower in the cortex (p=0.020 and 0.031) and medulla (p=0.012 and 0.190, respectively) of obstructed kidneys compared to contralateral unobstructed kidneys. After obstruction release the apparent spin relaxation rate and perfusion fraction increased in the cortex (p=0.016 and 0.004) and medulla (p=0.071 and 0.044, respectively) of formerly obstructed kidneys to values similar to those in contralateral kidneys. Total apparent diffusion coefficient and pure diffusion coefficient values did not significantly differ between obstructed and contralateral unobstructed kidneys during or after obstruction. In our patients with acute unilateral upper urinary tract obstruction due to calculi functional kidney magnetic resonance imaging using blood oxygen level dependent and diffusion-weighted sequences enabled us to monitor pathophysiological changes in obstructed kidneys during obstruction and after its release.

Intravascular large B-cell lymphoma diagnosed at renal biopsy.

A 77-year-old woman was referred with renal impairment—serum creatinine 230 mmol/L (2.61 mg/dL) and proteinuria 2.14 g/day. The past medical history included hypertension, sicca symptoms and osteoarthritis. Her medications included amlodipine 5 mg od, omeprazole 20 mg od and prednisolone 10 mg od. Systematic enquiry revealed lethargy and 6 kg weight loss over 6 months. Examination was unremarkable. Laboratory investigations revealed normocytic normochromic anaemia with reactive thrombocytosis. Serum lactate dehydrogenase was elevated. Bone biochemistry, liver function tests, serum protein electrophoresis, immunoglobulins, anti-nuclear antibodies, anti-neutrophil cytoplasmic antibodies and complements were all negative or normal. Ultrasound showed normal-sized unobstructed kidneys of normal echogenicity.