Intact Kidney Research Articles

Rapid identification of antibiotic residues in bovine kidney using coated blade spray-mass spectrometry.

The use of certain antibiotics in food-producing animals is allowed in Europe following Regulation (EU) 2017/625. However, use could result in antibiotic residues in foodstuffs of animal origin. Maximum residue limits (MRLs) are in place to protect consumers. For monitoring purposes, animal matrices are tested to verify their compliance with these MRLs. Initially, matrices of (slaughtered) food animals are screened, often using a microbiological assay. Faster screening tests for antibiotics would be an advantage for control laboratories. Therefore, the present study describes, for the first time, the use of coated blade spray (CBS) followed by direct mass spectrometry (MS) analysis for the screening of tetracyclines, sulfonamides, quinolones, and macrolides residues from the renal area of intact bovine kidneys. An optimized workflow using two different desorption/ionization solutions per blade allowed screening of target compounds within 1min per sample. The proof-of-principle of the CBS-MS method is validated according to (EU) 2021/808, presenting CCβ screening values of 0.1 × MRL for 43 analytes, 0.5 × MRL for 4 analytes, and 2.5µgkg-1 for the prohibited substance dapsone, respectively. The developed method was successfully applied to seven official control samples of bovine kidneys. One of these samples was found to be positive using the CBS-MS method, which was confirmed as a true positive by LC-MSMS analysis. The developed method demonstrates that CBS devices can directly extract and analyze kidney samples for food safety testing.

Actin cytoskeleton and associated myosin motors within the renal epithelium.

This review highlights the complexity of renal epithelial cell membrane architectures and organelles through careful review of ultrastructural and physiological studies published over the past several decades. We also showcase the vital roles played by the actin cytoskeleton and actin-associated myosin motor proteins in regulating cell type-specific physiological functions within the cells of the renal epithelium. The purpose of this review is to provide a fresh conceptual framework to explain the structure-function relationships that exist between the actin cytoskeleton, organelle structure, and cargo transport within the mammalian kidney. With recent advances in technologies to visualize the actin cytoskeleton and associated proteins within intact kidneys, it has become increasingly imperative to reimagine the functional roles of these proteins in situ to provide a rationale for their unique, cell type-specific functions that are necessary to establish and maintain complex physiological processes.

Sparsentan improves glomerular hemodynamics, cell functions, and tissue repair in a mouse model of FSGS.

Dual endothelin-1 (ET-1) and angiotensin II (AngII) receptor antagonism with sparsentan has strong antiproteinuric actions via multiple potential mechanisms that are more pronounced, or additive, compared with current standard of care using angiotensin receptor blockers (ARBs). Considering the many actions of ET-1 and AngII on multiple cell types, this study aimed to determine glomeruloprotective mechanisms of sparsentan compared to the ARB losartan by direct visualization of its effects in the intact kidney in focal segmental glomerulosclerosis (FSGS) using intravital multiphoton microscopy. In both healthy and FSGS models, sparsentan treatment increased afferent/efferent arteriole diameters; increased or preserved blood flow and single-nephron glomerular filtration rate; attenuated acute ET-1 and AngII-induced increases in podocyte calcium; reduced proteinuria; preserved podocyte number; increased both endothelial and renin lineage cells and clones in vasculature, glomeruli, and tubules; restored glomerular endothelial glycocalyx; and attenuated mitochondrial stress and immune cell homing. These effects were either not observed or of smaller magnitude with losartan. The pleiotropic nephroprotective effects of sparsentan included improved hemodynamics, podocyte and endothelial cell functions, and tissue repair. Compared with losartan, sparsentan was more effective in the sustained preservation of kidney structure and function, which underscores the importance of the ET-1 component in FSGS pathogenesis and therapy.

Mapping the blood vasculature in an intact human kidney using hierarchical phase-contrast tomography.

The architecture of the kidney vasculature is essential for its function. Although structural profiling of the intact rodent kidney vasculature has been performed, it is challenging to map vascular architecture of larger human organs. We hypothesised that hierarchical phase-contrast tomography (HiP-CT) would enable quantitative analysis of the entire human kidney vasculature. Combining label-free HiP-CT imaging of an intact kidney from a 63-year-old male with topology network analysis, we quantitated vasculature architecture in the human kidney down to the scale of arterioles. Although human and rat kidney vascular topologies are comparable, vascular radius decreases at a significantly faster rate in humans as vessels branch from artery towards the cortex. At branching points of large vessels, radii are theoretically optimised to minimise flow resistance, an observation not found for smaller arterioles. Structural differences in the vasculature were found in different spatial zones of the kidney reflecting their unique functional roles. Overall, this represents the first time the entire arterial vasculature of a human kidney has been mapped providing essential inputs for computational models of kidney vascular flow and synthetic vascular architectures, with implications for understanding how the structure of individual blood vessels collectively scales to facilitate organ function.

Effect of Curcumin Plus Piperine on Redox Imbalance, Fecal Calprotectin and Cytokine Levels in Inflammatory Bowel Disease Patients: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Patients with Crohn's disease (CD) or ulcerative colitis (UC) who were at least 18 years old and had intact liver and kidney function participated in this randomized, double-blind trial (trial registration: ensaiosclinicos.gov.br as RBR-89q4ydz). For 12 weeks, participants were randomly assigned to one of three groups: placebo, curcumin (1000 mg/day), or curcumin plus piperine (1000 mg + 10 mg/day). In order to examine oxidative stress indicators, CalF, and pro-inflammatory cytokines, blood and fecal samples were obtained, both prior to and following the intervention time. After adjusting for age, sex, and type of IBD, the curcumin plus piperine group had substantially higher serum levels of superoxide dismutase (SOD) than the placebo group (4346.9 ± 879.0 vs. 3614.5 ± 731.5; p = 0.041). There were no discernible variations between the groups in CalF, inflammatory markers, or other indicators of oxidative stress. In patients with inflammatory bowel disease (IBD), our study indicates that a 12-week curcumin plus piperine treatment effectively increases enzymatic antioxidant defense, especially SOD. These results demonstrate the potential therapeutic benefits of managing redox imbalance in individuals with IBD.

Aluminum and ABC transporter activity

Aluminum is the third most common element on Earth´s crust and despite its wide use in our workaday life it has been associated with several health risks after overexposure. In the present study the impact of aluminum salts upon ABC transporter activity was studied in the P-GP-expressing human blood-brain barrier cell line hCMEC/D3, in MDCKII cells overexpressing BCRP and MRP2, respectively, and in freshly isolated, functionally intact kidney tubules from Atlantic killifish (Fundulus heteroclitus), which express the analog ABC transporters, P-gp, Bcrp and Mrp2. In contrast to previous findings with heavy metals salts (cadmium(II) chloride or mercury(II) chloride), which have a strong inhibitory effect on ABC transporter activity, or zinc(II) chloride and sodium arsenite, which have a stimulatory effect upon ABC transport function, the results indicate no modulatory effect of aluminum salts on the efflux activity of the human ABC transporters P-GP, BCRP and MRP2 nor on the analog transporters P-gp, Bcrp and Mrp2.

Nephron-Sparing Surgery for Upper Urinary Tract Urothelial Carcinoma

Radical nephroureterectomy (RNU) remains the gold standard for the surgical management of upper tract urothelial carcinoma (UTUC) from the ureterovesical junction to the renal pelvis. However, the removal of the ipsilateral intact kidney causes morbidity due to renal functional deterioration after RNU. Recently, the indications for nephron-sparing surgery (NSS) in UTUC have been expanded to preserve the intact kidney. Minimally invasive surgical approaches, including endourological, laparoscopic, and robotic-assisted techniques for segmental resection of the distal ureter with ureteral reimplantation have shown favorable oncological and clinical outcomes (for both noninvasive and invasive ureteral tumors). The established guidelines for UTUC have limited indications for NSS. Because of low tumor burden, stage Ta/T1 UTUC is considered the best indication for NSS. NSS requires close follow-up and managing the risk of recurrence in the preserved ipsilateral ureter and/or renal pelvis. To overcome these limitations, adjuvant administration of various immuno-chemotherapeutic agents is being explored to overcome the resistance to therapeutic cell death and evasion of immune destruction from current therapies with better prognostic outcomes. The aim is to reduce urothelial cancer recurrence improving the effectiveness of NSS and to achieve comparable outcomes to RNU in UTUC. In this review article, we have comprehensively discussed the different types of NSS in UTUC, the indications for NSS in the international guidelines, and oncological outcomes of each of the NSS techniques.

Renal tubular estrogen ß receptors are expressed at high levels in small vessel vasculitis and are primarily localized in the distal tubule.

This study investigated the possible roles of renal estrogen receptors (ER) in glomerulonephritis associated with small vessel vasculitis. The relationships of ERs were investigated in antineutrophilic cytoplasmic antibody (ANCA)-associated glomerulonephritis and immunoglobulin A (IgA) nephropathy groups, which are small vessel vasculitis subtypes with two different glomerulonephritis development pathophysiologies. The design of this study was prepared as a retrospective cohort study. The study included 42 patients with ANCA-associated vasculitis and 18 with IgA nephropathy in the small vessel vasculitis group. For the control group, intact renal tissues of 28 patients who underwent nephrectomy due to renal cell carcinoma were used. Renal biopsy samples of the groups were stained with ER beta (ß) and ER alpha (α). Tubular ER ß expression score (TERßES) median values were found to be significantly higher in ANCA- associated vasculitis (B = 0.724, OR [95%CI]: 2.064 [1.141-3.731], p = .016) and IgA nephropathy (B = 0.898, OR [95%CI]: 2.454 [1.307-4.609], p = .005) than in intact kidney tissue. It was determined that tubular ERß was most frequently localized in the distal tubule at 57.9% and the second most common in the proximal tubule at 20.4%. The expression of tubular ERß is increased in glomerulonephritis due to small vessel vasculitis. Tubular ERßs are most commonly localized in the distal tubule. Further studies are needed to understand the physiological and pathophysiological effects of altered renal ER levels in small vessel vasculitis.

Ascorbate protects human kidney organoids from damage induced by cell-free hemoglobin.

Sepsis-associated acute kidney injury is associated with high morbidity and mortality in critically ill patients. Cell-free hemoglobin (CFH) is released into the circulation of patients with severe sepsis and the levels of CFH are independently associated with mortality. CFH treatment increased cytotoxicity in the human tubular epithelial cell line HK-2. To better model the intact kidney, we cultured human kidney organoids derived from induced pluripotent stem cells. We treated human kidney organoids grown using both three-dimensional and transwell protocols with CFH for 48 h. We found evidence for increased tubular toxicity, oxidative stress, mitochondrial fragmentation, endothelial cell injury and injury-associated transcripts compared to those of the untreated control group. To evaluate the protective effect of clinically available small molecules, we co-treated CFH-injured organoids with ascorbate (vitamin C) or acetaminophen for 48 h. We found significantly decreased toxicity, preservation of endothelial cells and reduced mitochondrial fragmentation in the group receiving ascorbate following CFH treatment. This study provides direct evidence that ascorbate or ascorbic acid protects human kidney cells from CFH-induced damage such as that in sepsis-associated acute kidney injury.

Renal tubular and glomerular estrogen receptor ß levels are lower in lupus nephritis than in familial Mediterranean fever-associated renal amyloidosis.

Estrogen has been thought to play an essential role in the disease pathogenesis of systemic lupus erythematosus, which is 9-10 times more prevalent in the female population. It has been shown that irregular estrogen/estrogen receptor signaling pathways may contribute to the pathophysiology of various renal diseases. In this study, we compared renal estrogen receptors between lupus nephritis, familial Mediterranean fever-associated renal amyloidosis, ANCA-associated nephritis, and intact kidney to investigate their role in the pathophysiology of renal diseases. This study was designed as a retrospective cohort study. Thirty systemic lupus erythematosus patients with lupus nephritis, 12 familial Mediterranean fever amyloidosis and 10 ANCA-associated glomerulonephrites, and 14 individuals with normal renal histology were included in the study. Tubular estrogen receptor ß expression score was found to be significantly higher in the familial Mediterranean fever [5 (1-8)] group than in the lupus nephritis [0 (0-1)] (B = 1.385, OR = 3.996, CI %95 = 1.805-8.846, p = .001) and ANCA [4 (1-6.5)] (B = -1.431, OR = 0.239, CI 95% = 0.093-0.614, p = .003) groups. A significant correlation was found between serum creatinine values and tubular estrogen receptor ß expression score (OR = 0.565, CI 95% = 0.622-1.402, p < .0001). In ANCA-associated glomerulonephritis, a significant relationship was found between fibro cellular crescents in renal biopsy and glomerular estrogen receptor ß expression score (OR = 0.247, CI 95% = 0.11-0.999, p = .045) and tubular estrogen receptor ß expression score (OR = 0.282, CI 95% = -0.180-2.812, p = .026). This study showed that tubular estrogen receptor ß expression score was elevated in familial Mediterranean fever amyloidosis and correlated with serum creatinine levels and renal crescents.

Sample preparation and analysis protocols for the elucidation of structure and chemical distribution in kidney stones

Examining intact kidney stones both qualitatively and quantitatively can be difficult due to their size and fragility. Many modern analysis methods often lead to the destruction of the stone's structure during sample preparation. Preserving the structural integrity is crucial for accurately determining the chemical distribution of the components of kidney stones, which, in turn, improves our understanding of the disease's etiology. Infrared microspectroscopy and imaging play a vital role in revealing the stone's microstructure and component distribution. Consequently, this research focuses on investigating the impact of different sample preparation techniques on kidney stone analysis using infrared microspectroscopy. Specifically, it explores how polishing the surface of cross-sectioned stones influences the results. The polishing was performed utilizing abrasive discs and lapping films. A polishing device was also designed for the optimization of sample preparation. Additionally, this work involved a comparison of reflection infrared imaging with Attenuated Total Internal Reflection (ATR) infrared microspectroscopic imaging for the analysis of the microstructure of urinary stones.

Primary Extra Renal Papillary Renal Cell Carcinoma Masquerading as A Metastatic Carcinoma: A Unique Case with Dual Malignancies

A 50-year-old male presented with abdominal pain, pain during defaecation, constipation, bleeding per rectum for 2 months. Colonoscopy showed an ulcero-proliferative growth, that is 2.5 cm from anal verge. Further PET-CT confirmed the growth in the lower rectum with mesorectal fat stranding and an irregular, lobulated, encapsulated solid-cystic mass in right perinephric fat, separated from the kidney (suggestive of metastasis), with intact bilateral kidneys. Biopsy of the rectum revealed an adenocarcinoma and biopsy of right perinephric mass revealed a papillary neoplasm. Following which abdominoperineal resection with perinephric mass excision was performed, due to encapsulation of mass. Histopathological evaluation and further immunohistochemistry performed was positive for vimentin, AMACR, CD10 and negative for other markers to rule out metastasis of either. This led to the diagnosis of synchronous primaries i.e., Extra-renal papillary renal cell carcinoma and adenocarcinoma of rectum.

Elucidating Immune Monitoring of Tissue-Resident Macrophages by Intravital Microscopy.

Intravital microscopy is an invaluable tool to study in real time the dynamic behavior of leukocytes in vivo. We describe herein a simple protocol for time-lapse imaging of tissue-resident macrophages in intact kidney, liver, and spleen in live mice. This method can be used in any commercially available inverted confocal microscope, doesn't require expensive lasers or optics, exhibits minimal organ perturbation, photo bleaching, or phototoxicity, and, hence, it enables the study of tissue-resident macrophages in situ and in vivo under steady state and inflammation.

Decreased renal expression of PAQR5 is associated with the absence of a nephroprotective effect of progesterone in a rat UUO model

Fibrosis is a severe complication of chronic kidney disease (CKD). Progesterone, like other sex hormones, plays an important role in renal physiology, but its role in CKD is poorly understood. We investigated progesterone effect on renal fibrosis progression in the rat model of unilateral ureteral obstruction (UUO). Female rats were exposed to UUO, ovariectomy and progesterone administration after UUO with ovariectomy. Expression of key fibrosis markers, proinflammatory cytokines, levels of membrane-bound (PAQR5) and nuclear (PGR) progesterone receptors, and matrix metalloproteinase (MMP) activity were analyzed in the obstructed and intact rat kidney. In all groups exposed to UUO, decreased PAQR5 expression was observed in the obstructed kidney while in the contralateral kidney, it remained unaffected. We found increased mRNA levels for profibrotic COL1A1, FN1, MMP2, TIMP1, TIMP2, proinflammatory IL1α, IL1β, and IL18, as well as elevated α-SMA and MMP9 proteins, collagen deposition, and MMP2 activity in all UUO kidneys. Progesterone had slight or no effect on the change in these markers. Thus, we demonstrate for the first time diminished sensitivity of the kidney to progesterone associated with renal fibrosis due to a severe decrease in PAQR5 expression that was accompanied by the lack of nephroprotection in a rat UUO model.

Onconephrology: Renal cancer

Renal cancer (RC) ranks eighth among the most prevalent oncopathologies, making it one of the most widespread types of cancer. Over the last decade, there has been an average annual increase in morbidity of 2 percent. RC is a collective term that encompasses parenchymal tumors and pelvis tumors with distinct histologic characteristics.&#x0D; Renal cancer can appear in intact kidneys and cause additional damage except for the actual tumor process, or in patients with previously affected kidneys.&#x0D; The main treatment option for renal cell carcinoma (RCC) is surgery, which can be performed through various approaches, including open-access surgery, laparoscopic surgery, and robotic-assisted surgery. These surgical techniques enable the performance of radical nephrectomy, partial nephrectomy, and cytoreductive nephrectomy. The selection of the surgical method and the extent of the intervention fall within the expertise of oncourologists.&#x0D; Anti-angiogenic drugs, including tyrosine kinase inhibitors, humanized monoclonal antibodies, and immune checkpoint inhibitors, as well as mTOR inhibitors, are commonly utilized in the treatment of advanced-stage RCC (II-IV) or its relapse. However, it is important to note that these drugs possess considerable nephrotoxicity. Therefore, kidney status plays a crucial role in determining the appropriate treatment options, the dosage of antitumor drugs, and the potential nephrotoxicity associated with them, thereby becoming the main limiting factor affecting the quality and duration of life for RCC patients.&#x0D; The present review focuses on the analysis of recent data concerning the issues mentioned above, primarily in relation to RCC, and provides recommendations for the investigation and treatment of this specific category of patients.

Assessment of the effect of copaiba oil (copaifera sp.) on the kidneys of rats with hepatic dysfunction

Copaiba oil reveals therapeutic properties and has actions such as anti-inflammatory, healing, antiseptic, antitumor, antibacterial, germicidal, expectorant, diuretic and analgesic. Given the anti-inflammatory properties of copaiba oil, the present study aims to evaluate the action of the oil on possible nephrotoxic effects of rats with liver dysfunction caused by the drug thioacetamide. Wistar rats were randomly divided into four groups, consisting of the control group (C), copaiba oil group (O), thioacetamide group (TAA) and thioacetamide + copaiba oil group (TAA + O). The animals received treatment via gavage for eight weeks and were fed standard rodent chow. The kidney fragments were histologically prepared using the historresin technique and HE staining and, later, the images were photographed and processed in an image analyzer for histological characterization of the kidney tissue. The histological results showed an intact kidney tissue with a homogeneous pattern between the groups. Typical cortical and medullary layers and very distinct renal tubules with their well stained and healthy cells. The renal corpuscles showed regular contours, well-distributed anastomosed capillaries and typical macula densa. Histopathological analysis of the kidneys did not reveal alterations or any type of lesion in important structures such as renal tubules and renal corpuscles, and no lymphocytic infiltrate was observed in the renal interstitium. In contrast, the liver tissue from the parallel histological study developed cirrhosis in the group treated with thioacetamide, however, this drug did not compromise the renal histological pattern of the present study. It is concluded that the kidney tissue did not show morphological changes when submitted to thioacetamide, supposedly due to the exposure time, the dose used or that the thioacetamide has been metabolized into less toxic compounds to the kidneys to the detriment of hepatic damage. However, the parallel study of liver tissue and the present study ensure the use of copaiba oil for therapeutic purposes.

A Rare Case of Urethral Tuberculosis

Urethral tuberculosis is a rare disease since the advent of highly effective anti-tuberculosis drugs. The article describes an extremely rare clinical observation of a 34-year-old patient with the transition of tuberculous inflammation from the subcutaneous tissue to the wall of the urethra with intact kidneys. Since the first blood discharge from the urethra, the diagnostic process took 3.5 years, all these years, multiple examinations for tuberculosis were carried out and the results were negative, while the disease progressed. The diagnosis was differentiated between acute purulent anterior subcutaneous paraproctitis and festering pararectal cyst. There were repeated openings of the perineal abscess, no bacterial growth was observed, histological tests revealed chronic purulent inflammation. In view of the persistent recurrent course of perineal abscess, tuberculosis was repeatedly suspected. Acid-resistant mycobacteria were found in the discharge from the fistula by fluorescent microscopy: 10-99 in the sample. Tuberculous mycobacteria were not found in the urine by polymerase chain reaction. The patient was diagnosed with A18.4. Tuberculosis of subcutaneous fat (perineum). Mycobacterium tuberculosis (+). The course of disease was complicated by perineal fistula. With the anti-tuberculosis treatment, the fistulous opening healed within a month.

S-07-2: DISCOVERY OF NEUROENDOTHELIAL CELLS AND THEIR ROLE IN HYPERTENSION AND AGING

Objective: Vascular endothelial cells (ECs) play important roles in the physiological maintenance of organ blood flow and in the development of renal and cardiovascular diseases. Tissue-specific EC dysfunction can contribute to several different diseases including hypertension. Recent transcriptomic studies identified many EC subtypes in multiple organs including the brain and the kidneys, however, their functions are incompletely understood. The present study aimed to explore physiological functional significance and cardiovascular disease and hypertension relevance of a newly discovered minority subtype of scattered ECs expressing neuronal nitric oxide synthase (Nos1). Design and method: A comprehensive research toolbox was applied in this study including transgenic mouse models (Nos1-GFP, GCaMP6, mTORgof/lof), intravital multiphoton imaging of calcium dynamics of Nos1+ endothelial cells in the brain and the kidney, genetic cell fate tracking, two-kidney one-clip (2K1C) model of renovascular (Goldblatt) hypertension (RVHT), whole mount organ imaging for 3D vascular density measurements, and single-cell transcriptomic analysis. Results: Our studies identified and characterized, for the first time, a new endothelial cell type expressing both endothelial and neuron-like functional and gene transcriptomic signatures, therefore we named them neuroendothelial cells (NECs). NECs exhibit a well-defined arteriovenous zonal localization exclusively to small resistance arterioles. NECs are found only in the three organs that exhibit the best blood flow autoregulation capacity, with the highest density in the brain&gt;kidney&gt;heart (NEC/EC (%) 8.42+/-0.79, 3.21+/−0.33, 1.73+/−0.07, respectively). NEC density is reduced with aging in the brain and the kidney (NEC/EC (%) 4.675, and 1.850, respectively, p &lt; 0.01, 2.5 years old compared to 2-month-old). The number of NECs increased significantly in the hypo-perfused, hypoxic clipped (CK) kidney, but reduced in the hyperperfused non-clipped (NCK) kidney in RVHT. Intravital multiphoton microscopy (MPM) of intact brain and kidney arterioles in vivo revealed regular, autonomous NEC calcium transients with blood pressure-dependent frequency alterations. Newly established NEC gain-of-function mouse models exhibited increased endothelium-dependent vasodilation and diminished agonist-induced vascular contractility in brain and kidney resistance arterioles compared to controls. In addition, preliminary single-cell RNA sequencing and transcriptomic analyses showed that, in contrast to other ECs, NECs highly express several traditional (e.g., Nos1, Klotho) and novel (e.g., Aard) tissue trophic factors that are known to play important roles in angiogenesis, aging, vascular (dys)function, and chronic vascular diseases. Conclusions: These new vascular anatomy and hemodynamic findings strongly suggest sensory, blood flow and/or baroreceptor functions of NECs as well as a role in the autoregulation of organ blood flow and hypertension pathogenesis.

Brain-specific biomarkers in urine as a non-invasive approach to monitor neuronal and glial damage.

This study evaluates the quantitative measurability of glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) and total tau (t-tau) in urine of patients with acute cerebral damage. Serum and urine samples were prospectively collected from patients with an acute ischemic stroke or intracerebral hemorrhage (target group) and compared to healthy subjects (control group); samples were measured using ultrasensitive single-molecule arrays (Simoa®). Glomerular barrier function was assessed based on albumin-creatinine ratio (ACR); biomarker-creatinine ratios were calculated for correction of urine dilution. Ninety-three urine-serum pairs in the target group and 10 urine-serum pairs in the control group were measured. The mean absolute concentration ± standard deviation in urine of the target and control groups were 184.7± 362.4pg/ml and 27.3± 24.1pg/ml for GFAP (r= 0.3 [Wilcoxon effect size], p= 0.007), 17.5± 38.6pg/ml and 0.9± 0.3pg/ml for NfL (r= 0.4, p< 0.005), 320.2± 443.3pg/ml and 109.6± 116.8pg/ml for UCH-L1 (r= 0.26, p= 0.014), and 219.5± 255.8pg/ml and 21.1± 27.1pg/ml for t-tau (r= 0.37, p< 0.005), respectively, whereas biomarker-creatinine ratio was significantly different only for NfL (r= 0.29, p= 0.015) and t-tau (r= 0.32, p< 0.01). In patients with intact glomerular barrier (ACR<30 mg/g), only NfL in urine was significantly different between the target and control group and showed a significant correlation with the respective serum concentrations (r= 0.58 [Pearson's correlation-coefficient], p< 0.005). All four investigated biomarkers could be measured in urine, with NfL and t-tau showing the strongest effect size after correction for urine dilution. NfL revealed the most accurate relation between serum and urine concentrations in patients with intact kidney function.

Translating Organoids into Artificial Kidneys.

Purpose of Review Kidney disease affects more than 13% of the world population, and current treatment options are limited to dialysis and organ transplantation. The generation of kidney organoids from human-induced pluripotent stem (hiPS) cells could be harnessed to engineer artificial organs and help overcome the challenges associated with the limited supply of transplantable kidneys. The purpose of this article is to review the progress in kidney organoid generation and transplantation and highlight some existing challenges in the field. We also examined possible improvements that could help realize the potential of organoids as artificial organs or alternatives for kidney transplantation therapy.Recent FindingsOrganoids are useful for understanding the mechanisms of kidney development, and they provide robust platforms for drug screening, disease modeling, and generation of tissues for organ replacement therapies. Efforts to design organoids rely on the ability of cells to self-assemble and pattern themselves into recognizable tissues. While existing protocols for generating organoids result in multicellular structures reminiscent of the developing kidney, many do not yet fully recapitulate the complex cellular composition, structure, and functions of the intact kidney. Recent advances toward achieving these goals include identifying cell culture conditions that produce organoids with improved vasculature and cell maturation and functional states. Still, additional improvements are needed to enhance tissue patterning, specialization, and function, and avoid tumorigenicity after transplantation.SummaryThis report focuses on kidney organoid studies, advancements and limitations, and future directions for improvements towards transplantation.