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Cleveland Clinic Journal of Medicine Oct 2015Sickle cell disease is a common genetic disorder characterized by sickling of red blood cells under conditions of reduced oxygen tension. In turn, sickling leads to... (Review)
Review
Sickle cell disease is a common genetic disorder characterized by sickling of red blood cells under conditions of reduced oxygen tension. In turn, sickling leads to intravascular hemolysis and vaso-occlusive events with subsequent tissue ischemia-reperfusion injury affecting multiple organs, including the genitourinary system. Our review of the genitourinary manifestations of sickle cell disease focuses on sickle cell nephropathy, priapism, and other genitourinary complications such as papillary necrosis and renal medullary carcinoma.
Topics: Anemia, Sickle Cell; Female; Humans; Ischemia; Kidney Diseases; Kidney Medulla; Kidney Neoplasms; Kidney Papillary Necrosis; Male; Penis; Priapism
PubMed: 26469825
DOI: 10.3949/ccjm.82a.14029 -
Quantitative Imaging in Medicine and... Jun 2023Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease (ESRD). There are unmet needs for noninvasive diagnosis and prognosis prediction of DKD in...
Diagnostic and prognostic performance of renal compartment volume and the apparent diffusion coefficient obtained from magnetic resonance imaging in mild, moderate and severe diabetic kidney disease.
BACKGROUND
Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease (ESRD). There are unmet needs for noninvasive diagnosis and prognosis prediction of DKD in clinical practice. This study examines the diagnostic and prognostic value of magnetic resonance (MR) markers of renal compartment volume and the apparent diffusion coefficient (ADC) for mild, moderate, and severe DKD.
METHODS
This study was registered at the Chinese Clinical Trial Registry Center (registration number: ChiCTR-RRC-17012687). Sixty-seven DKD patients were prospectively randomly enrolled and underwent clinical examination and diffusion-weighted magnetic resonance imaging (DW-MRI). Patients with comorbidities that affected renal volumes or components were excluded. Ultimately, 52 DKD patients were included in the cross-sectional analysis. The ADC in the renal cortex (ADC) ADC in the renal medulla (ADC) and difference between ADC and ADC (ΔADC) were measured using a twelve-layer concentric objects (TLCO) approach. Renal compartment volumes of the parenchyma and pelvis were derived from T2-weighted MRI. Due to lost contact or ESRD diagnosed before follow-up (n=14), only 38 DKD patients remained for follow-up (median period =8.25 years) to investigate the correlations between MR markers and renal outcomes. The primary outcomes were the composite of doubling of the primary serum creatinine concentration or ESRD.
RESULTS
ADC presented superior performance in discriminating DKD with normal and declined estimated glomerular filtration rate (eGFR) over ADC, ΔADC and renal compartment volumes with an AUC of 0.904 (sensitivity of 83% and specificity of 91%) and was moderately correlated with the clinical biomarkers eGFR and proteinuria (P<0.05). The Cox survival analysis demonstrated that ADC rather than ΔADC is a predictor of renal outcomes with a hazard ratio of 3.4 (95% CI: 1.1-10.2, P<0.05) independent of baseline eGFR and proteinuria.
CONCLUSIONS
ADC is a valuable imaging marker for the diagnosis and prediction of renal function decline in DKD.
PubMed: 37284101
DOI: 10.21037/qims-23-149 -
Modern Pathology : An Official Journal... Jun 2023According to the American Joint Cancer Committee, pT3 renal pelvic carcinoma is defined as tumor invading the renal parenchyma and/or peripelvic fat and is the largest... (Review)
Review
According to the American Joint Cancer Committee, pT3 renal pelvic carcinoma is defined as tumor invading the renal parenchyma and/or peripelvic fat and is the largest pT category, with notable survival heterogeneity. Anatomical landmarks within the renal pelvis can be difficult to discern. Using glomeruli as a boundary to differentiate renal medulla invasion from renal cortex invasion, this study aimed to compare patient survival of pT3 renal pelvic urothelial carcinoma on the basis of the extent of renal parenchyma invasion and, thereafter, determine whether redefining pT2 and pT3 improves pT correlation with survival. Cases with primary renal pelvic urothelial carcinoma were identified through a review of pathology reports from nephroureterectomies completed at our institution from 2010 to 2019 (n = 145). Tumors were stratified by pT, pN, lymphovascular invasion, and invasion of the renal medulla versus invasion of the renal cortex and/or peripelvic fat. Overall survival between groups was compared using Kaplan-Meier survival models and Cox regression multivariate analysis. pT2 and pT3 tumors had similar 5-year overall survival, with multivariate analysis demonstrating an overlap between hazard ratios (HRs) for pT2 (HR, 2.20; 95% CI, 0.70-6.95) and pT3 (HR, 3.15; 95% CI, 1.63-6.09). pT3 tumors with peripelvic fat and/or renal cortex invasion had a 3.25-fold worse prognosis than pT3 tumors with renal medulla invasion alone. Furthermore, pT2 and pT3 tumors with only renal medulla invasion had similar overall survival, whereas pT3 tumors with peripelvic fat and/or renal cortex invasion had a worse prognosis (P = .00036). Reclassifying pT3 tumors with only renal medulla invasion as pT2 yielded greater separation between survival curves and HR. Thus, we recommend redefining pT2 renal pelvic carcinoma to include renal medulla invasion and restricting pT3 to peripelvic fat and/or renal cortex invasion to improve the prognostic accuracy of pT classification.
Topics: Humans; Carcinoma, Transitional Cell; Neoplasm Staging; Urinary Bladder Neoplasms; Neoplasm Invasiveness; Kidney Neoplasms; Prognosis; Retrospective Studies
PubMed: 36813117
DOI: 10.1016/j.modpat.2023.100140 -
American Journal of Physiology. Heart... Sep 2019Cholinergic receptor activation leads to premature development of hypertension and infiltration of proinflammatory CD161a/CD68 M1 macrophages into the renal medulla....
Cholinergic receptor activation leads to premature development of hypertension and infiltration of proinflammatory CD161a/CD68 M1 macrophages into the renal medulla. Renal inflammation is implicated in renal sodium retention and the development of hypertension. Renal denervation is known to decrease renal inflammation. The objective of this study was to determine the role of CD161a/CD68 macrophages and renal sympathetic nerves in cholinergic-hypertension and renal sodium retention. Bilateral renal nerve denervation (RND) and immune ablation of CD161a immune cells were performed in young prehypertensive spontaneously hypertensive rat (SHR) followed by infusion of either saline or nicotine (15 mg·kg·day) for 2 wk. Immune ablation was conducted by injection of unconjugated azide-free antibody targeting rat CD161a. Blood pressure was monitored by tail cuff plethysmography. Tissues were harvested at the end of infusion. Nicotine induced premature hypertension, renal expression of the sodium-potassium chloride cotransporter (NKCC2), increases in renal sodium retention, and infiltration of CD161a/CD68 macrophages into the renal medulla. All of these effects were abrogated by RND and ablation of CD161a immune cells. Cholinergic activation of CD161a immune cells with nicotine leads to the premature development of hypertension in SHR. The effects of renal sympathetic nerves on chemotaxis of CD161a macrophages to the renal medulla, increased renal expression of NKCC2, and renal sodium retention contribute to cholinergic hypertension. The CD161a immune cells are necessary and essential for this prohypertensive nicotine-mediated inflammatory response. This is the first study that describes a novel integrative physiological interaction between the adrenergic, cholinergic, and renal systems in the development of hypertension, describing data for the role of each in a genetic model of essential hypertension. Noteworthy findings include the prevention of nicotine-mediated hypertension following successful immune ablation of CD161a immune cells and the necessary role these cells play in the overexpression of the sodium-potassium-chloride cotransporter (NKCC2) in the renal medulla and renal sodium retention. Renal infiltration of these cells is demonstrated to be dependent on the presence of renal adrenergic innervation. These data offer a fertile ground of therapeutic potential for the treatment of hypertension as well as open the door for further investigation into the mechanism involved in inflammation-mediated renal sodium transporter expression. Taken together, these findings suggest immune therapy, renal denervation, and, possibly, other new molecular targets as having a potential role in the development and maintenance of essential hypertension.
Topics: Animals; Antibodies, Monoclonal; Blood Pressure; Disease Models, Animal; Hypertension; Inflammation Mediators; Kidney; Macrophages; Male; NK Cell Lectin-Like Receptor Subfamily B; Nicotine; Nicotinic Agonists; Phenol; Rats, Inbred SHR; Renal Artery; Renal Reabsorption; Sodium; Solute Carrier Family 12, Member 1; Sympathectomy, Chemical
PubMed: 31172810
DOI: 10.1152/ajpheart.00234.2019 -
Nefrologia 2021Kidney problems are among the most common complications in sickle cell disease (SCD). They occur early in childhood and are one of the main factors related to mortality... (Review)
Review
Kidney problems are among the most common complications in sickle cell disease (SCD). They occur early in childhood and are one of the main factors related to mortality in these patients. The main underlying pathogenic mechanisms are vaso-occlusion and haemolysis. The renal medulla has ideal conditions for the sickling of red cells due to its low partial pressure of oxygen, high osmolarity and acidic pH. Initially, sickle-cell formation in the vasa recta of the renal medulla causes hyposthenuria. This is universal and appears in early childhood. Microscopic and macroscopic haematuria also occur, in part related to renal papillary necrosis when the infarcts are extensive. Release of prostaglandins in the renal medulla due to ischaemia leads to an increase in the glomerular filtration rate (GFR). Adaptively, sodium reabsorption in the proximal tubule increases, accompanied by increased creatinine secretion. Therefore, the GFR estimated from creatinine may be overestimated. Focal segmental glomerulosclerosis is the most common glomerular disease. Albuminuria is very common and reduction has been found in 72.8% of subjects treated with ACE inhibitors or ARB. Recent evidence suggests that free haemoglobin has harmful effects on podocytes, and may be a mechanism involved in impaired kidney function in these patients. These effects need to be better studied in SCD, as they could provide a therapeutic alternative in sickle cell nephropathy.
Topics: Anemia, Sickle Cell; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Child, Preschool; Creatinine; Hemoglobins; Humans; Kidney; Oxygen; Partial Pressure; Prostaglandins; Renal Insufficiency; Sodium
PubMed: 36165106
DOI: 10.1016/j.nefroe.2021.10.001 -
American Journal of Physiology.... Nov 2019Human studies of renal hemodynamics and metabolism in obesity are insufficient. We hypothesized that renal perfusion and renal free fatty acid (FFA) uptake are higher in...
Human studies of renal hemodynamics and metabolism in obesity are insufficient. We hypothesized that renal perfusion and renal free fatty acid (FFA) uptake are higher in subjects with morbid obesity compared with lean subjects and that they both decrease after bariatric surgery. Cortical and medullary hemodynamics and metabolism were measured in 23 morbidly obese women and 15 age- and sex-matched nonobese controls by PET scanning of [O]-HO (perfusion) and 14()-[F]fluoro-6-thia-heptadecanoate (FFA uptake). Kidney volume and radiodensity were measured by computed tomography, cardiac output by MRI. Obese subjects were re-studied 6 mo after bariatric surgery. Obese subjects had higher renal volume but lower radiodensity, suggesting accumulation of water and/or lipid. Both cardiac output and estimated glomerular filtration rate (eGFR) were increased by ~25% in the obese. Total renal blood flow was higher in the obese [885 (317) (expressed as median and interquartile range) vs. 749 (300) (expressed as means and SD) ml/min of controls, = 0.049]. In both groups, regional blood perfusion was higher in the cortex than medulla; in either region, FFA uptake was ~50% higher in the obese as a consequence of higher circulating FFA levels. Following weight loss (26 ± 8 kg), total renal blood flow was reduced ( = 0.006). Renal volume, eGFR, cortical and medullary FFA uptake were decreased but not fully normalized. Obesity is associated with renal structural, hemodynamic, and metabolic changes. Six months after bariatric surgery, the hemodynamic changes are reversed and the structural changes are improved. On the contrary, renal FFA uptake remains increased, driven by high substrate availability.
Topics: Adult; Bariatric Surgery; Fatty Acids; Female; Glomerular Filtration Rate; Hemodynamics; Humans; Kidney; Kidney Cortex; Kidney Medulla; Magnetic Resonance Imaging; Middle Aged; Obesity, Morbid; Renal Circulation; Tomography, X-Ray Computed; Weight Loss
PubMed: 31550182
DOI: 10.1152/ajpendo.00135.2019 -
Proceedings of SPIE--the International... 2021Renal segmentation on contrast-enhanced computed tomography (CT) provides distinct spatial context and morphology. Current studies for renal segmentations are highly...
Renal segmentation on contrast-enhanced computed tomography (CT) provides distinct spatial context and morphology. Current studies for renal segmentations are highly dependent on manual efforts, which are time-consuming and tedious. Hence, developing an automatic framework for the segmentation of renal cortex, medulla and pelvicalyceal system is an important quantitative assessment of renal morphometry. Recent innovations in deep methods have driven performance toward levels for which clinical translation is appealing. However, the segmentation of renal structures can be challenging due to the limited field-of-view (FOV) and variability among patients. In this paper, we propose a method to automatically label the renal cortex, the medulla and pelvicalyceal system. First, we retrieved 45 clinically-acquired deidentified arterial phase CT scans (45 patients, 90 kidneys) without diagnosis codes (ICD-9) involving kidney abnormalities. Second, an interpreter performed manual segmentation to pelvis, medulla and cortex slice-by-slice on all retrieved subjects under expert supervision. Finally, we proposed a patch-based deep neural networks to automatically segment renal structures. Compared to the automatic baseline algorithm (3D U-Net) and conventional hierarchical method (3D U-Net Hierarchy), our proposed method achieves improvement of 0.7968 to 0.6749 (3D U-Net), 0.7482 (3D U-Net Hierarchy) in terms of mean Dice scores across three classes ( < 0.001, paired t-tests between our method and 3D U-Net Hierarchy). In summary, the proposed algorithm provides a precise and efficient method for labeling renal structures.
PubMed: 34531632
DOI: 10.1117/12.2581101 -
Research in Veterinary Science Apr 2020Fifty-three privately owned dogs were included in the study. Ultrasonography of the kidneys was performed ante mortem. All the dogs died or were euthanized for reasons...
Fifty-three privately owned dogs were included in the study. Ultrasonography of the kidneys was performed ante mortem. All the dogs died or were euthanized for reasons unrelated to this study. Histopathology of both kidneys was performed, and a degeneration and an inflammation score ranging from zero to two was assigned by consensus between two pathologists. A numerical score based on a three level semi-quantitative scale (0, 0.5, 1) was assigned by consensus between two of the authors to the following ultrasonographic abnormalities: cortico-medullary definition, echogenicity of the renal cortex, echogenicity of the medulla, renal shape, cysts, scars, mineralizations, subcapsular perirenal fluid accumulation, pyelectasia. The scores deriving from the consensus were summed to create a summary index called renal ultrasound score (RUS). Statistically significant differences in cortico-medullary definition, echogenicity of the renal cortex, echogenicity of the medulla, renal shape, scars and pyelectasia were evident between the degeneration score groups. There were significantly different distributions of cortico-medullary definition, renal shape and scars between the inflammatory score groups. There were statistically significant differences in the RUS between the degenerative score groups (F = 24.154, p-value<.001). Post-hoc tests revealed significant differences between all groups. There were no significant differences in the RUS between the inflammatory score groups (F = 1.312, p-value = .264). Post-hoc tests revealed no significant differences between groups. The results of the present study suggest that the number and severity of the ultrasonographic abnormalities are correlated with the severity of the kidney degeneration. On the other hand, inflammation showed poor influence on the ultrasonographic appearance of the kidneys.
Topics: Animals; Dog Diseases; Dogs; Female; Kidney; Kidney Diseases; Male; Ultrasonography
PubMed: 31931264
DOI: 10.1016/j.rvsc.2020.01.003 -
European Journal of Immunology Aug 2022Renal immune cells serve as sentinels against ascending bacteria but also promote detrimental inflammation. The kidney medulla is characterized by extreme electrolyte...
Renal immune cells serve as sentinels against ascending bacteria but also promote detrimental inflammation. The kidney medulla is characterized by extreme electrolyte concentrations. We here address how its main osmolytes, NaCl and urea, regulate tubular cell cytokine expression and monocyte chemotaxis. In the healthy human kidney, more monocytes were detected in medulla than cortex. The monocyte gradient was attenuated in patients with medullary NaCl depletion by loop diuretic therapy and in the nephrotic syndrome. Renal tubular epithelial cell gene expression responded similarly to NaCl and tonicity control mannitol, but not urea. NaCl significantly upregulated chemotactic cytokines, most markedly CCL26, CCL2, and CSF1. This induction was inhibited by the ROS scavenger n-acetylcysteine. In contrast, urea, the main medullary osmolyte in catabolism, dampened tubular epithelial CCL26 and CSF1 expression. Renal medullary chemokine and monocyte marker expression decreased in catabolic mice. NaCl-, but not urea-stimulated tubular epithelium or CCL2 and CCL26, promoted human classical monocyte migration. CCL26 improved bactericidal function. In the human kidney medulla, monocyte densities correlated with tubular CCL26 protein abundance. In summary, medullary-range NaCl, but not urea, promotes tubular cytokine expression and monocyte recruitment. This may contribute to the pyelonephritis vulnerability in catabolism but can possibly be harnessed against pathologic inflammation.
Topics: Animals; Cytokines; Epithelial Cells; Humans; Inflammation; Kidney Medulla; Mice; Monocytes; Sodium Chloride; Urea
PubMed: 35527392
DOI: 10.1002/eji.202149723 -
IScience Dec 2022Our recent study has found that gut bacteria contributes to hypertension and upregulates lysophospholipase A1 (LYPLA1) in the renal medulla of rats. This work aimed to...
Our recent study has found that gut bacteria contributes to hypertension and upregulates lysophospholipase A1 (LYPLA1) in the renal medulla of rats. This work aimed to investigate the role of LYPLA1 in the development of -induced hypertension. Compared to control, treatment increased blood pressure (BP), serum angiotensin II, sodium reabsorption, and expression of αENaC and LYPLA1 in the renal medulla of mice, and these effects were attenuated by knockdown of LYPLA1. Moreover, the intrarenal overexpression increased sodium reabsorption and BP. Further studies showed that LYPLA1 promoted the accumulation of renal glycerophosphocholine (GPC), which directly elevated the expression of αENaC and sodium reabsorption. In addition, enriched abundance of LYPLA1 in the renal medulla and urine was also observed in other hypertensive animals. Overall, our results demonstrate that LYPLA1 contributes to -induced hypertension by accumulating GPC and activating ENaC in the renal medulla.
PubMed: 36419851
DOI: 10.1016/j.isci.2022.105403