Small Kidney Research Articles

Mannose antagonizes GSDME-mediated pyroptosis through AMPK activated by metabolite GlcNAc-6P

Pyroptosis is a type of regulated cell death executed by gasdermin family members. However, how gasdermin-mediated pyroptosis is negatively regulated remains unclear. Here, we demonstrate that mannose, a hexose, inhibits GSDME-mediated pyroptosis by activating AMP-activated protein kinase (AMPK). Mechanistically, mannose metabolism in the hexosamine biosynthetic pathway increases levels of the metabolite N-acetylglucosamine-6-phosphate (GlcNAc-6P), which binds AMPK to facilitate AMPK phosphorylation by LKB1. Activated AMPK then phosphorylates GSDME at Thr6, which leads to blockade of caspase-3-induced GSDME cleavage, thereby repressing pyroptosis. The regulatory role of AMPK-mediated GSDME phosphorylation was further confirmed in AMPK knockout and GSDMET6E or GSDMET6A knock-in mice. In mouse primary cancer models, mannose administration suppressed pyroptosis in small intestine and kidney to alleviate cisplatin- or oxaliplatin-induced tissue toxicity without impairing antitumor effects. The protective effect of mannose was also verified in a small group of patients with gastrointestinal cancer who received normal chemotherapy. Our study reveals a novel mechanism whereby mannose antagonizes GSDME-mediated pyroptosis through GlcNAc-6P-mediated activation of AMPK, and suggests the utility of mannose supplementation in alleviating chemotherapy-induced side effects in clinic applications.

Does Urologist-level Utilization of Active Surveillance for Low-risk Prostate Cancer Correspond with Utilization of Active Surveillance for Small Renal Masses?

Active surveillance (AS) for prostate cancer (CaP) or small renal masses (SRMs) helps in limiting the overtreatment of indolent malignancies. Implementation of AS for these conditions varies substantially across individual urologists. We examined the Michigan Urological Surgery Improvement Collaborative (MUSIC) registry to assess for correlation of AS between patients with low-risk CaP and patients with SRM managed by individual urologists. We identified 27 urologists who treated at least ten patients with National Comprehensive Cancer Network low-risk CaP and ten patients with SRMs between 2017 and 2021. For surgeons in the lowest quartile of AS use for low-risk CaP (<74%), 21% of their patients with SRMs were managed with AS, in comparison to 74% of patients of surgeons in the highest quartile (>90%). There was a modest positive correlation between the surgeon-level risk-adjusted proportions of patients managed with AS for low-risk CaP and for SRMs (Pearson correlation coefficient 0.48). A surgeon’s tendency to use AS to manage one low-risk malignancy corresponds to their use of AS for a second low-risk condition. By identifying and correcting structural issues associated with underutilization of AS, interventions aimed at increasing AS use may have effects that influence clinical tendencies across a variety of urologic conditions. Patient summaryThe use of active surveillance (AS) for patients with low-risk prostate cancer or small kidney masses varies greatly among individual urologists. Urologists who use AS for low-risk prostate cancer were more likely to use AS for patients with small kidney masses, but there is room to improve the use of AS for both of these conditions.

Ultra Sonographic Study of Kidney Changes Following Experimental Cryogenic Partial Nephrectomy in a Rabbit Model

Background and Objective: Treatment of some limited kidney neoplasms is a partial kidney resection called a partial nephrectomy. One of the concerns in partial nephrectomy is severe and uncontrolled hemorrhage that sometimes results in kidney removal. Cryosurgery is one of the less invasive methods for the management of small kidney lesions, during which the controlled freezing of unwanted tissues will eventually lead to necrosis and gradual destruction of the lesion.The advantages of the cryosurgery method are easy implementation, no thermal ischemia damage during the operation, and no need to cut and suture the kidney parenchyma. Materials and Methods: In this experimental intervention research, the caudal pole of the left kidney of 9 adult female rabbits was subjected to cryogenic partial nephrectomy through a lateral laparotomy. Rabbits were evaluated by ultrasound on 1, 3, 7, 14, 21, and 28 days after surgery to record and observe the extent of kidney damage and healing in the Sagittal and Dorsal sections. Several parameters, such as kidney length dimensions, size of the caudal cortex, and cranial cortex of the kidney, were measured and recorded. Results: Kidney length on days 1, 21, and 28 was significantly less than day 0. On the 7th day after surgery, 2 separate areas, damaged and frozen necrotic tissue (caudal cortex) and healthy and normal kidney tissue were visible. The size of the caudal cortex from day 14 onwards was significantly less than day 0. The process of significant changes in the caudal cortex of the kidney started from day 14 of surgery and the border between dead and living tissue (Line of Demarcation) was distinguishable as a transition zone. On the 21st day after surgery, both the length of the kidney and the caudal cortex decreased significantly compared to day 0. Gradual loss of the caudal pole of the kidney (caudal cortex, the place where cryosurgery was performed directly) showed the applicability of cryosurgery in surgeries during which the tumor was removed (tumor ablation). On the 28th day after surgery, due to gradual necrosis and the loss of the caudal pole of the kidney, the kidney looked like a bitten apple, and the results of changes in the dimensions of the kidney (caudal cortex and length of the kidney) indicated necrosis of the caudal pole of the kidney, which finally led to the shrinking of the kidney. Conclusion: Ultrasonographic study of kidney injury and healing showed that cryosurgery, in addition to tumor ablation, would also have the ability to remove peripheral tissues (partial nephrectomy).

Perioperative, functional, and oncologic outcomes after ablation or partial nephrectomy for solitary renal tumors: a systematic review and meta-analysis of comparative trials.

The perioperative, functional, and oncological outcomes of patients with solitary small renal tumors (SRMs) treated with ablation (AT) or partial nephrectomy (PN) remain controversial. The aim of this study was to compare the outcomes of these two surgical techniques. In April 2023, we conducted a literature search in several widely used databases worldwide, including PubMed, Embase, and Google Scholar. Review Manager was used to compare various parameters. The study was registered with PROSPERO (CRD42022377157). Our final meta-analysis included 13 cohort studies with a total of 2,107 patients. Compared to partial nephrectomy (PN), ablation (AT) had shorter hospital stays (WMD -2.37 days, 95% CI -3.05 to -1.69; p < 0.00001), shorter operating times (WMD -57.06min, 95% CI -88.92 to -25.19; p = 0.0004), less postoperative creatinine increases (WMD -0.17 mg/dL, 95% CI -0.29 to -0.05; p = 0.006), less postoperative glomerular filtration rate decreases (WMD -9.84 mL/min/1.73 m2, 95% CI -14.25 to -5.44; p < 0.0001), less postoperative new-onset chronic kidney disease (OR 0.33, 95% CI 0.16 to 0.71; p = 0.005), and less intraoperative blood loss (WMD -285.92ml, 95% CI -428.44 to -143.40; p < 0.0001). The transfusion rate was lower in the ablation group (OR 0.17, 95% CI 0.06 to 0.51; p = 0.001). The risk of local recurrence was higher in the ablation group (OR 2.96, 95% CI 1.27 to 6.89; p = 0.01), while the risk of distant metastasis was higher in the partial nephrectomy group (OR 2.81, 95% CI 1.28 to 6.18; p = 0.01). The intraoperative and postoperative complication rates were lower in the ablation group (OR 0.23, 95% CI 0.08 to 0.62; p = 0.004 and OR 0.21, 95% CI 0.11 to 0.38; p < 0.00001, respectively). However, overall survival, postoperative dialysis rate, and tumor-specific survival were not different between the two groups. Our data suggest that ablation and partial nephrectomy are equally safe and effective in the treatment of small solitary kidney tumors and are better options for patients with poor preoperative physical condition or poor renal function.

The role of GLUT2 in glucose metabolism in multiple organs and tissues.

The glucose transporter family has an important role in the initial stage of glucose metabolism; Glucose transporters 2 (GLUTs, encoded by the solute carrier family 2, SLC2A genes) is the major glucose transporter in β-cells of pancreatic islets and hepatocytes but is also expressed in the small intestine, kidneys, and central nervous system; GLUT2 has a relatively low affinity to glucose. Under physiological conditions, GLUT2 transports glucose into cells and allows the glucose concentration to reach balance on the bilateral sides of the cellular membrane; Variation of GLUT2 is associated with various endocrine and metabolic disorders; In this study, we discussed the role of GLUT2 in participating in glucose metabolism and regulation in multiple organs and tissues and its effects on maintaining glucose homeostasis.

Dnajb11-Kidney Disease Develops from Reduced Polycystin-1 Dosage but not Unfolded Protein Response in Mice.

Heterozygous DNAJB11 mutation carriers manifest with small cystic kidneys and renal failure in adulthood. Recessive cases with prenatal cystic kidney dysplasia were recently described. Our in vitro and mouse model studies investigate the proposed disease mechanism as an overlap of autosomal-dominant polycystic kidney disease and autosomal-dominant tubulointerstitial kidney disease pathogenesis. We find that DNAJB11 loss impairs cleavage and maturation of the autosomal-dominant polycystic kidney disease protein polycystin-1 (PC1) and results in dosage-dependent cyst formation in mice. We find that Dnajb11 loss does not activate the unfolded protein response, drawing a fundamental contrast with the pathogenesis of autosomal-dominant tubulointerstitial kidney disease. We instead propose that fibrosis in DNAJB11 -kidney disease may represent an exaggerated response to polycystin-dependent cysts. Patients with heterozygous inactivating mutations in DNAJB11 manifest with cystic but not enlarged kidneys and renal failure in adulthood. Pathogenesis is proposed to resemble an overlap of autosomal-dominant polycystic kidney disease (ADPKD) and autosomal-dominant tubulointerstitial kidney disease (ADTKD), but this phenotype has never been modeled in vivo . DNAJB11 encodes an Hsp40 cochaperone in the endoplasmic reticulum: the site of maturation of the ADPKD polycystin-1 (PC1) protein and of unfolded protein response (UPR) activation in ADTKD. We hypothesized that investigation of DNAJB11 would shed light on mechanisms for both diseases. We used germline and conditional alleles to model Dnajb11 -kidney disease in mice. In complementary experiments, we generated two novel Dnajb11-/- cell lines that allow assessment of PC1 C-terminal fragment and its ratio to the immature full-length protein. Dnajb11 loss results in a profound defect in PC1 cleavage but with no effect on other cystoproteins assayed. Dnajb11-/- mice are live-born at below the expected Mendelian ratio and die at a weaning age with cystic kidneys. Conditional loss of Dnajb11 in renal tubular epithelium results in PC1 dosage-dependent kidney cysts, thus defining a shared mechanism with ADPKD. Dnajb11 mouse models show no evidence of UPR activation or cyst-independent fibrosis, which is a fundamental distinction from typical ADTKD pathogenesis. DNAJB11 -kidney disease is on the spectrum of ADPKD phenotypes with a PC1-dependent pathomechanism. The absence of UPR across multiple models suggests that alternative mechanisms, which may be cyst-dependent, explain the renal failure in the absence of kidney enlargement.

Should oral medication dose be adjusted in Alzheimer’s disease?

AbstractBackgroundLittle is known about the absorption, distribution, metabolism and excretion (ADME) of both AD and non‐AD medicines currently used in people with AD. If drug disposition processes are altered in AD, individuals with AD may be at a greater risk of additional drug‐induced adverse effects, toxicity, or lack of effectiveness. Senescence Accelerated Mouse (SAMP8) is a naturally‐occurring mouse line that displays many characteristics identified in AD patients, and it is considered as a model of sporadic AD. The current study aims to assess if ADME is affected in SAMP8 mice.MethodWe utilized a proteomics approach to assess drug transporter and metabolising enzyme expression in the small intestine, liver, and kidney in SAMP8 mice. In addition, plasma concentrations of valsartan, digoxin, quetiapine (three model drugs selected based on proteome data) following oral administration in SAMP8 mice were assessed using LC‐MS. The morphological changes of small intestine, liver and kidney was evaluated using H&amp;E staining. The intestine permeability to these drugs was studied using Ussing chamber.ResultFollowing proteomic analysis, PCA plot indicated a clear separation between SAMP8 and SAMR1 intestine, liver and kidney tissue, with global functional analysis indicated altered drug metabolism in the small intestine and liver of SAMP8 mice. The oral pharmacokinetic study revealed a significant elevation in plasma exposure (i.e. AUC) to valsartan and digoxin but reduction to quetiapine in SAMP8 mice compared to their non‐AD control mice. When interpreted together with H&amp;E staining, ex vivo drug permeation study, and proteome data, the increase AUC to valsartan and digoxin is likely due to increased intestine leakiness. For digoxin, despite P‐glycoprotein expression was significantly increased in the small intestine, it failed to compensate the leaky gut. For quetiapine, the reduction in AUC in SAMP8 was due to increased hepatic metabolism, as increased levels of metabolites of quetiapine was detected in the plasma.ConclusionConsistent with our previous observation in APP/PS1 mice, drug disposition following oral administration was also noted in a mouse model of sporadic AD (SAMP8). Clinical study to evaluate altered ADME in people with AD should be considered to achieve precise medication use in people with AD.

Coexistence of acute pancreatitis and an obstructing upper ureteral calculus: does a calculus cause pancreatitis? a case report.

A 36-year-old male patient presented with epigastric, and right loin pain with decreased urine output for 3 days. On physical examination, he had central abdominal and right flank tenderness. An abdominal ultrasound showed mild to moderate ascites, a hyperechoic pancreas, a small (26×77mm) left kidney with increased echogenicity, right renal hypertrophy with moderate hydronephrosis, and a dilated upper ureter due to a 10mm obstructing stone with a perirenal fluid collection. The diagnosis of acute pancreatitis with an obstructing right upper ureteric stone was established. Under spinal anesthesia, an emergency ureteroscopy with laser fragmentation of the stone was performed, and a JJ stent was inserted. He developed postobstructive diuresis and his renal function was improved with a rapid decline of pancreatic enzymes as well. Two theories explain the presentation of acute pancreatitis by ureteral obstruction. First, the obstructed severe hydronephrotic kidney compresses the duodenum and head of the pancreas, obstructing the distal part of the common bile duct and triggering the elevation of pancreatic duct pressure, bile reflux, trypsin activation, and pancreatic autodigestion. The second theory states that acute pancreatitis develops when urine is extravasated from an obstructed kidney into the adjacent tissues, irritating the uncinate process of the pancreas. Although mentioning ureteral obstruction as a cause of pancreatitis is scarce, the clinician should be aware that in each case of ureteral obstruction, the emergence of acute pancreatitis is a possible complication.

Examining congenital renal abnormalities in adult cadavers: an observational study

Abstract To know the percentages of incidences of various types of congenital anomalies of the renal system, an observational study was conducted at Departments of Anatomy of three medical colleges by dissection method and observation was made on dissected specimens for the presence of morphological anomalies in kidneys and the anatomical locations of kidneys and ureters. We found various types of renal anomalies like agenesis of kidney, nodular kidney and constricted (small) kidney location, ectopic kidneys bilateral polycystic kidneys. Conclusion: Various abnormalities were found in this study and so, knowledge of such anomalies of kidneys not only to anatomists but to all clinicians especially to urologists and nephrologists and radiologists.

Predicting outcomes in children with congenital anomalies of the kidney and urinary tract.

Congenital anomalies of the kidney and urinary tract (CAKUT) are the most frequent causes of childhood chronic kidney disease (CKD). Using a large CAKUT cohort, we sought to identify the predictors of CKD and to develop a prediction model that informs a risk-stratified clinical pathway. This was a retrospective cohort study including cases with multicystic dysplastic kidneys (MCDK), unilateral kidney agenesis (UKA), kidney hypoplasia (KH), and posterior urethral valves (PUV). We identified risk factors for CKD (estimated glomerular filtration rate [eGFR] <60 ml/min/1.73 m2) and tested their performance in an adjusted multivariate binary regression model. Prediction probability scores for CKD were used to separate cases likely to develop complications from those not needing specialist follow-up. We identified 452 eligible cases of CAKUT with 22% developing CKD. Strongest associations with CKD included primary diagnosis (OR 3.5, 95% CI 2.6-4.6), preterm delivery (OR 2.3, 95% CI 1.2-4.4), non-kidney anomalies (OR 1.8, 95% CI 1.1-3), first eGFR<90 (OR 8.9, 95% CI 4.4-18.1), small kidney size (OR 9, 95% CI 4.9-16.6), and additional kidney anomalies (OR 1.6, 95% CI 1.2-2.8). PUV (OR 4.7, 95% CI 1.5-15.3), first eGFR <90 (OR 4.4, 95% CI 2-9.7), and kidney length to body length ratio <7.9 (OR 4.2, 95% CI 1.9-9.2) were independent predictors of CKD. The regression model had a prediction accuracy of 80% and a prediction probability c-statistic of 0.81. Using a large combined CAKUT cohort we identified risk factors for CKD. Our prediction model provides the first steps towards a risk-stratified clinical pathway. A higher resolution version of the Graphical abstract is available as Supplementary information.

Percutaneous laser mini nephrolithotomy in the treatment of renal lithiasis: Experience within the University Hospital of Fez (about 20 cases)

Laser percutaneous mini-nephrolithotomy is a minimally invasive surgical technique, used mainly for the removal of upper renal and ureteral lithiasis The objective of our work is to test the feasibility, efficacy and safety of this technique by comparing the results with those of standard NLPC, flexible uretero-nephroscopy and extracorporeal lithotripsy. We report a retrospective study of 20 cases of laser mini-NLPC over a period from January 2022 to January 2023 in the urology department. Mini-NLPC is as safe and effective as standard NLPC for the management of small and medium-sized (10-30 mm) kidney stones, including decreasing the rate of bleeding requiring transfusion and improving the rate of eradication of multiple stones... Although its use requires a longer operating time and has a slightly higher rate of postoperative fever, some of these features such as the length of hospital stay, the dose of postoperative analgesics make it a technique of choice.

Evaluation of Chronic Kidney Disease Risk Factors after Radical Nephrectomy

Intraoperative hypotension (IOH) and loss of blood during radical nephrectomy (RN) cause postoperative clinically significant renal dysfunction, which after 12 months can cause a reduction in serum creatinine clearance of &lt;60 mL/min. We conducted a prospective study of 93 adult patients in which we investigated the risk factors for developing chronic kidney disease (CKD) after RN. Forty-six (49.5%) patients had CKD, and of them, 43 patients had acute kidney injury (AKI) 48 h after surgery. Sixty-six (73.1%) of the postoperative AKI patients had CKD upstage. With each 1 mL estimated blood loss during RN (OR 1.01, p &lt; 0.001), IOH was evaluated as the main risk factor of postoperative CKD development (OR 1.09, p &lt; 0.01). Dunn’s t-test revealed that only clinically significant AKI had a main effect (g = −1.08, p &lt; 0.0001) on renal function 1 year after RN. A higher preoperative estimated glomerular filtration rate (eGFR), OR 0.89, p = 0.02, and contralateral kidney CT volume (OR 0.97, p = 0.04) had a clinically significantly decreased risk of postoperative CKD. Risk factors of AKI with CKD upstage were a small contralateral kidney CT volume (OR 46.70), NLR &gt; 3.5 (OR 1.42), higher primary eGFR (OR 1.13) and longer IOH (OR 1.05), and for all of these, p &lt; 0.03. A half of all patients after RN are at increased risk of CKD. Longer IOH and increased blood loss during RN are significant risk factors for CKD. Clinically significant postoperative AKI is related with a developed risk for postoperative eGFR decline and the presence of CKD 12 months after RN, and can be predicted by NLR &gt; 3.5. A higher preoperative eGFR and contralateral kidney CT volume reduces the risk of postoperative CKD.

The novel occurrence of non-syndromic unilateral renal hypoplasia and unilateral aplasia in two brothers

Background: Non-syndromic unilateral renal hypoplasia is a congenital condition associated with one small kidney (hypoplastic) that generally has normal residual parenchyma but smaller calyces. We have previously reported the first case of non-syndromic unilateral renal hypoplasia transmitted in an autosomal dominant fashion from the mother. Patients and methods: The brother of the boy who was the patient in the medical literature reported to have unilateral renal hypoplasia transmitted from the mother in an autosomal dominant was seen and renal ultrasound performed. Results: The present patient, the brother was seen late during June, 2022 at about the age of eighteen years, for a routine check and was asymptomatic and otherwise healthy. However, abdominal ultrasound showed unilateral right renal aplasia. The right kidney was absent, while left kidney showed compensatory hypertrophy. Conclusion: This paper reports the novel occurrence of non-syndromic unilateral renal hypoplasia and unilateral aplasia in two brothers.

Cost-effectiveness of robotic-assisted surgery vs open surgery in the context of partial nephrectomy for small kidney tumors.

To evaluate the cost-effectiveness of robotic-assisted surgery compared to open surgery in the context of partial nephrectomy for small kidney tumor management. This is a retrospective study using data from 395 patients operated on by either robot-assisted surgery (RAPN) or by open partial nephrectomy (OPN); one hospital performed RAPN exclusively and the second hospital, OPN exclusively. Cost-effectiveness analysis was conducted from the perspective of the National Health Insurance System (NHIS) by considering the costs of the initial hospital stay and the cost of complications. Clinical outcome was defined by the avoidance of major complications during the 12months postoperatively. Major complications were absent in 82% of patients in the OPN group and 93% of patients in the RAPN group, with 11% in favor of robotic assistance (p < 0.001). The average cost per patient, including the costs of complications, were, respectively, 9637 € and 8305 € for the OPN and RAPN groups. Robotic assistance was associated with a 1332 € lower cost (p < 0.001). The incremental cost-effectiveness ratio (ICER) is estimated at -12,039 €. From the perspective of the public payer, robotic assistance was associated with a lower rate of postoperative complications and a lower average cost per patient. Robotic-assisted surgery was an efficient alternative to open surgery in partial nephrectomy. Trial registration number: NCT05089006 (October 22, 2021).

Pyridoxine and Pyridoxine-5′-β-D-Glucoside Exert Different Effects on Tissue B-6 Vitamers but Similar Effects on β-Glucosidase Activity in Rats

Pyridoxine glucoside is a partially available form of vitamin B-6 present in plant-derived foods. In this set of three studies, rats were fed diets containing different concentrations of either pyridoxine or pyridoxine glucoside in the presence or absence of a fixed concentration of pyridoxine for 2 wk. The distribution of B-6 vitamers and β-glucosidase activity in tissues was examined to determine the metabolic effects of chronic consumption of pyridoxine glucoside. Rats fed pyridoxine glucoside either with or without pyridoxine exhibited a significant increase in the amount of hepatic pyridoxine 5′-phosphate (not detected in rats fed pyridoxine alone), whereas hepatic pyridoxal 5′-phosphate was decreased with increasing dietary pyridoxine glucoside. The activity of cytosolic β-glucosidases in small intestine and kidney was affected by the dietary concentration of both pyridoxine and pyridoxine glucoside. Enzymatic activity capable of hydrolyzing pyridoxine glucoside was found in mucosal and intraluminal fractions of small intestine and in the kidney. Other tissues examined, including liver, spleen and stomach, did not hydrolyze pyridoxine glucoside in detectable quantities. These findings indicate that microbial and mucosal enzymes can participate in the intestinal hydrolysis of pyridoxine glucoside and that the kidney may contribute to postabsorptive hydrolysis. These findings further support the observations that dietary pyridoxine glucoside influences vitamin B-6 metabolism.

Angiotensin-converting enzyme: a well-known stranger. Part II

The angiotensin-converting enzyme (ACE) is constitutively expressed on the surface of endothelial, epithelial and immune system cells (macrophages, dendritic cells). The lungs are believed to be the main source of circulating ACE. However, other organs such as the small intestine, kidneys, heart, brain, epididymis, and prostate have also been found to express ACE at levels comparable to those in the lungs. ACE expression is regulated not only passively by the number of endothelial cells, but also by endothelial function. In general, the biochemical environment is the driving force behind the enzymatic activity of ACE, influencing cells capable of expressing ACE and regulatory proteins. The discovery of tissue ACE has changed our understanding of the pathophysiology of many diseases. In particular, it turned out that renal versus circulating ACE is more important in the development of arterial hypertension, diabetic nephropathy, acute and chronic kidney disease.

Pathogenesis of Hypertension in Metabolic Syndrome: The Role of Fructose and Salt.

Metabolic syndrome is manifested by visceral obesity, hypertension, glucose intolerance, hyperinsulinism, and dyslipidemia. According to the CDC, metabolic syndrome in the US has increased drastically since the 1960s leading to chronic diseases and rising healthcare costs. Hypertension is a key component of metabolic syndrome and is associated with an increase in morbidity and mortality due to stroke, cardiovascular ailments, and kidney disease. The pathogenesis of hypertension in metabolic syndrome, however, remains poorly understood. Metabolic syndrome results primarily from increased caloric intake and decreased physical activity. Epidemiologic studies show that an enhanced consumption of sugars, in the form of fructose and sucrose, correlates with the amplified prevalence of metabolic syndrome. Diets with a high fat content, in conjunction with elevated fructose and salt intake, accelerate the development of metabolic syndrome. This review article discusses the latest literature in the pathogenesis of hypertension in metabolic syndrome, with a specific emphasis on the role of fructose and its stimulatory effect on salt absorption in the small intestine and kidney tubules.

Renal Functional Response-Association With Birth Weight and Kidney Volume

Renal functional response (RFR) is the acute increase in glomerular filtration rate (GFR) after a protein load. Low RFR is a marker of single nephron hyperfiltration. Low birth weight (LBW) is associated with reduced number of nephrons, lower kidney function, and smaller kidneys in adults. In the present study, we investigate the associations among LBW, kidney volume, and RFR. We studied adults aged 41 to 52 years born with either LBW (≤2300 g) or normal birth weight (NBW; 3500-4000 g). GFR was measured using plasma clearance of iohexol. A stimulated GFR (sGFR) was measured on a separate day after a protein load of 100 g using a commercially available protein powder, and RFR was calculated as delta GFR. Kidney volume was estimated from magnetic resonance imaging (MRI) images using the ellipsoid formula. A total of 57 women and 48 men participated. The baseline mean ± SD GFR was 118 ± 17 ml/min for men and 98 ± 19 ml/min for women. The overall mean RFR was 8.2 ± 7.4 ml/min, with mean RFR of 8.3 ± 8.0 ml/min and 8.1 ± 6.9 ml/min in men and women, respectively (P= 0.5). No birth-related variables were associated with RFR. Larger kidney volume was associated with higher RFR, 1.9 ml/min per SD higher kidney volume (P= 0.009). Higher GFR per kidney volume was associated with a lower RFR,-3.3ml/min per SD (P< 0.001). Larger kidney size and lower GFR per kidney volume were associated with higher RFR. Birth weight was not shown to associate with RFR in mainly healthy middle-aged men and women.

Process control of electrospinning artificial fenestrated capillary vessels

Rapid fabrication of capillary vessels is important for tissue engineering because local perfusion and oxygen exchange within the tissue depend on the network of capillaries which have diameters ranging from 5 to 10 µm. Fenestrated capillaries are microvessels that have surface pores of 80 to 100 nm in diameter. These capillaries are essential for many organs, such as small intestines, endocrine glands, and kidneys. In this paper, we presented a wet coaxial electrospinning technique for the rapid fabrication of porous microtubes as artificial fenestrated capillaries using polycaprolactone and polyethylene oxide. We characterized the effects of process parameters on the morphological features of these microtubes by regression modeling. Our study shows that the flow rate ratio of the core/sheath solutions and the viscosity of the sheath solution play a significant role in the outside diameter, wall thickness, and hollow area of the microtubes. In addition, the formation of surface pores is dominated by the humidity during the electrospinning. At the same humidity level, the size of the surface pores is positively correlated with the viscosity of the sheath solution and the outside diameter of the microtubes. Overall, this study established the process-property relationship for wet coaxial electrospinning of artificial fenestrated capillaries.

A Matched Analysis of Active Surveillance Versus Nephrectomy for T1a Small Renal Masses

While patients with a small renal mass (SRM) on active surveillance (AS) experience excellent metastasis-free survival (MFS) and cancer-specific survival (CSS), differences in overall survival (OS) observed may be explained by selection of older/comorbid patients for AS. Few studies have evaluated AS versus primary intervention in clinically balanced groups. We identified patients aged 55–75 yr with an SRM (≤4 cm, T1a) in our institutional database (2000–2020). Patients from AS and nephrectomy subgroups were matched exactly for age, sex, Eastern Cooperative Oncology Group (ECOG) performance status, biopsy status, and histology. The primary outcomes were OS and an event-free survival (EFS) composite that included OS, CSS, MFS, progression, or systemic therapy, which we tested in Cox proportional-hazards models. We identified 377 patients (205 AS, 172 nephrectomy). The cohort was balanced after matching (n = 110; mean age 64 yr, 77% male, and 75% ECOG score 0). In each arm, 47% were biopsied (predominantly clear-cell histology). The predicted 5-yr OS was 96% for the nephrectomy group and 95% for the AS group (hazard ratio for nephrectomy vs AS [HR] 0.83, 95% confidence interval [CI] 0.13–5.32; p = 0.8), with corresponding 5-yr EFS rates of 93% and 96% (HR 1.88, 95% CI 0.35–10.15; p = 0.5). Among SRM cases well matched for age and overall health status, we observed higher 5-yr OS and EFS rates for AS than previously reported; the rates were not significantly different from those after nephrectomy. The matched characteristics of our population are similar to those for treatment arms in contemporary cohorts and the results support the safety of AS in younger, healthier patients. Patient summaryWhile it has been shown that active surveillance for small kidney tumors is safe in older and more frail patients, its safety in younger, healthier patients has not been confirmed. We compared outcomes for patients aged 55–75 yr who were managed with surgery or active surveillance, and were similar in age and overall health. The probability of death after 5 years was low overall and not significantly different between the groups, suggesting that active surveillance is safe in routine clinical practice.