Number Of Glomeruli Research Articles

Down syndrome and mild kidney dysfunction.

Few studies have evaluated kidney function in children with Down syndrome (DS) in detail. This study investigated kidney function in pediatric DS patients without complications that affect kidney function. Creatinine (Cr)- and cystatin C (cysC)-based estimated glomerular filtration rate (eGFR) were measured in a cohort of Japanese DS patients. The kidney function in these children with DS was approximately 80% that of the healthy Japanese children, suggesting that children with DS have smaller kidneys or a lower number of glomeruli than children without DS.

Conditional ablation of the prorenin receptor in nephron progenitor cells results in developmental programming of hypertension.

Nephron induction during kidney development is driven by reciprocal interactions between progenitor cells (NPCs) of the cap mesenchyme (CM) and the ureteric bud (UB). The prorenin receptor (PRR) is a receptor for renin and prorenin, and an accessory subunit of the vacuolar proton pump V‐ATPase. Previously, we demonstrated that conditional ablation of the PRR in Six2+ NPCs in mice (Six2 PRR −/−) causes early neonatal death. Here, we identified genes that are regulated by PRR in Six2+ NPCs FACS‐isolated from Six2 PRR −/− and control kidneys on embryonic day E15.5 using whole‐genome expression analysis. Seven genes with expression in CM cells previously shown to direct kidney development, including Notch1, β‐catenin, Lef1, Lhx1, Jag1, and p53, were downregulated. The functional groups within the downregulated gene set included genes involved in embryonic and cellular development, renal regeneration, cellular assembly and organization, cell morphology, death and survival. Double‐transgenic Six2 PRR −/−/BatGal + mice, a reporter strain for β‐catenin transcriptional activity, showed decreased β‐catenin activity in the UB in vivo. Reduced PRR gene dosage in heterozygous Six2 PRR +/− mice was associated with decreased glomerular number, segmental thickening of the glomerular basement membrane with focal podocyte foot process effacement, development of hypertension and increased soluble PRR (sPRR) levels in the urine at 2 months of age. Together, these data demonstrate that NPC PRR performs essential functions during nephrogenesis via control of hierarchy of genes that regulate critical cellular processes. Both reduced nephron endowment and augmented urine sPRR likely contribute to programming of hypertension in Six2 PRR +/− mice.

Combined Fluoroscopy and Ultrasound-Guided Transjugular Kidney Biopsy in Cirrhotic Patients

PurposeTo evaluate the safety and diagnostic yield of combined fluoroscopy and ultrasound-guided transjugular kidney biopsy (TJKB) in cirrhotic patients with suspected renal parenchymal disease. Materials and MethodsA retrospective review was made of 27 patients (21 men; overall mean age 44.7 y) who underwent TJKB from June 2013 to June 2016; 21 patients had coagulopathy and/or thrombocytopenia, 4 underwent simultaneous TJKB with transjugular liver biopsy, and 1 patient each had severe obesity and gross ascites. All procedures were performed with the use of fluoroscopy and simultaneous transabdominal ultrasound guidance. The data were analyzed for number of passes taken, number of glomeruli in the tissue cores, adequacy of tissue core for histopathologic diagnosis, and incidence and severity of complications. ResultsThe average number of passes per case was 3.6 (range 2–6). The total length of tissue cores ranged from 0.4 cm to 2.5 cm. The mean numbers of glomeruli per procedure on light microscopy were 6.7 (range 0–17). Diagnostic biopsy specimens were obtained in 23 out of 27 patients (85%). Eleven patients had minor complications. One patient had major complication in the form of hemoglobin drop of 2.1 mg/dL which required embolization and blood transfusion. ConclusionsCombined use of fluoroscopy and ultrasound guidance for TJKB yielded adequate tissue samples with fewer passes and a low rate of complications in high-risk patients with cirrhosis.

Rac1 in podocytes promotes glomerular repair and limits the formation of sclerosis

Rac1, a Rho family member, is ubiquitously expressed and participates in various biological processes. Rac1 expression is induced early in podocyte injury, but its role in repair is unclear. To investigate the role of Rac1 expression in podocytes under pathological conditions, we used podocyte-specific Rac1 conditional knock-out (cKO) mice administered adriamycin (ADR), which causes nephrosis and glomerulosclerosis. Larger areas of detached podocytes, more adhesion of the GBM to Bowman’s capsule, and a higher ratio of sclerotic glomeruli were observed in Rac1 cKO mice than in control mice, whereas no differences were observed in glomerular podocyte numbers in both groups after ADR treatment. The mammalian target of rapamycin (mTOR) pathway, which regulates the cell size, was more strongly suppressed in the podocytes of Rac1 cKO mice than in those of control mice under pathological conditions. In accordance with this result, the volumes of podocytes in Rac1 cKO mice were significantly reduced compared with those of control mice. Experiments using in vitro ADR-administered Rac1 knockdown podocytes also supported that a reduction in Rac1 suppressed mTOR activity in injured podocytes. Taken together, these data indicate that Rac1-associated mTOR activation in podocytes plays an important role in preventing the kidneys from developing glomerulosclerosis.

Percutaneous Renal Biopsy: Comparison of Blind and Real-time Ultrasound Guided Technique

Percutaneous renal biopsy is performed for diagnosis and prediction of prognosis of renal diseases. Adequacy of tissue and clinically significant bleeding are the main issues of the procedure. We aimed to compare these issues in renal biopsy by blind and real time ultrasound guided technique. It was a cross sectional, randomized study conducted between June 2016 to December 2016. In blind technique, marking for biopsy was done by ultrasound. Two attempts were performed for all and more if tissue was inadequate. Patients kept in bed rest for 24 hours, observed for post procedure hematuria and ultrasound done at 6 hours and 24 hours to diagnose perinephric hematoma. Total 75 biopsies (blind = 37 and Ultrasound -guided = 38) were evaluated. Blind and Ultrasound-guided technique had significant difference of number of attempt (mean±SD) 2.4±0.6 and 2.1±0.3 (p<0.01) respectively with no difference of number of glomeruli in light microscopy. Bleeding complications were macroscopic hematuria (11(30%)vs15(40%)) and perinephric hematoma ( 5(13.5%)vs3(7.9%)) in blind and Ultrasound-guided technique respectively with no significant difference. Those patients who developed perinephric hematoma was observed in all at 6 hours. Ultrasound-guided technique of percutaneous renal biopsy is superior with fewer attempts and equivalent in adequacy of tissue and bleeding complication than blind technique.

Mannitol reduces nephron loss after warm renal ischemia in a porcine model

BackgroundMannitol has been employed to ameliorate renal warm ischemia damage during partial nephrectomy, however, there is limited scientific evidence to support the use of mannitol during partial nephrectomy. The objective of the present study was to investigate the glomerular number after renal warm ischemia, with and without the use of mannitol in a Pig Model.MethodsTwenty-four male pigs were assigned into three groups. Eight animals were allocated to the sham group that was subjected to laparoscopic dissection of the left renal hilum, without renal ischemia. Eight animals were allocated to the ischemia group that had the left renal hilum clamped for 30 min through laparoscopic access. Eight animals received mannitol (250 mg/kg) before the occlusion of renal hilum for 30 min. The kidneys were collected after the euthanasia of the pigs 21 days post surgery. The right kidney was utilized as a self-control for each animal. Serum creatinine, urea levels, the weight and volume of the kidneys were measured. Glomerular volumetric density, volume-weighted glomerular volume, and cortical volume were quantified through stereological methods and employed to determine the number of nephrons per kidney. Student’s t test and ANOVA were used for statistical analysis.ResultsIn the ischemia group, the left kidney recorded a reduction of 24.6% (290, 000 glomeruli) in the number of glomeruli in comparison to the right kidney. Kidneys subjected to ischemia also displayed decreased weight and volume in comparison to the sham and mannitol groups. No difference was observed between the left and right kidneys from the sham and mannitol groups. Further, no distinction in serum creatinine and urea among the groups was observed.ConclusionThe use of mannitol significantly reduces nephron loss during warm ischemia in pigs.

Структурные перестройки позвоночно-двигательного сегмента при длительных динамических нагрузках

Purpose: to study structural rearrangements of intervertebral discs and adjacent structures of the spine of rats and the possibility of their preservation under conditions of prolonged dynamic loads in the experiment. Material & Methods : study was performed in an experiment with 90 male rats of the Wistar line, using a training run in a linear treadmill for 20 and 90 days. On the histotopographic sections, after injection into the aortic arch of the animal mascara-gelatin mass, the number of capillary glomeruli in the subchondral parts of the vertebral bodies was counted. Using standard histology methods, structural changes in metaphyseal cartilages, apophyses of vertebral bodies and intervertebral discs of the lumbar spine. Result: The running regimes are defined that cause damage to various structures of the spine and, on the contrary, increase their reliability. Conclusion : it is established that with age the number of blood vessels in the bodies of the vertebrae and capillary glomeruli in their subchondral regions gradually decreases, which is accompanied by a tightening of the intervertebral disk and contiguous structures. Different in intensity and duration of physical activity cause a corresponding change in the number of blood vessels in the vertebrae and, as a consequence, the level of their blood supply.

Does a Ureteral Obstruction Affect the Contralateral Kidney Morphology? A Stereological Analysis in a Rodent Model

Objective: To investigate, in a rodent model, the influence of an obstructed kidney/ureter on the contralateral organ morphology. Methods: Thirty-six rats were randomly assigned into the following groups: untreated ureteral obstruction group (UO-U, n = 10), submitted to a ligature of the ureter at day 0; UO group (at day 0) followed by nephrectomy after 24 h (UO-N, n = 8); nephrectomy group (N, n = 9), submitted to nephrectomy at day 0; and sham group (S, n = 9), submitted to simulated surgery at day 0. All these procedures were performed on the left kidney/ureter. All animals were euthanized 30 days after surgery, and the right kidneys were collected for stereological analysis. Data were compared using a one-way analysis of variance with Bonferroni’s post test, considering p < 0.05 as significant. Results: The kidney volume, weight, and cortical volume were augmented in groups UO-N and N, compared to group S. Kidneys from the UO-U group showed only a moderate augmentation in kidney weight, with a reduction in the cortical-medullar ratio, compared to the kidneys in group S. No differences in the glomerular volumetric density, volume-weighted glomerular volume, and number of glomeruli were observed among the right kidneys of the studied groups. Conclusion: An obstructed kidney/ureter is more prejudicial to the contralateral kidney morphology than an absent kidney.

In Situ Tissue Regeneration of Renal Tissue Induced by Collagen Hydrogel Injection.

Host stem/progenitor cells can be mobilized and recruited to a target location using biomaterials, and these cells may be used for in situ tissue regeneration. The objective of this study was to investigate whether host biologic resources could be used to regenerate renal tissue in situ. Collagen hydrogel was injected into the kidneys of normal mice, and rat kidneys that had sustained ischemia/reperfusion injury. After injection, the kidneys of both animal models were examined up to 4 weeks for host tissue response. The infiltrating host cells present within the injection regions expressed renal stem/progenitor cell markers, PAX‐2, CD24, and CD133, as well as mesenchymal stem cell marker, CD44. The regenerated renal structures were identified by immunohistochemistry for renal cell specific markers, including synaptopodin and CD31 for glomeruli and cytokeratin and neprilysin for tubules. Quantitatively, the number of glomeruli found in the injected regions was significantly higher when compared to normal regions of renal cortex. This phenomenon occurred in normal and ischemic injured kidneys. Furthermore, the renal function after ischemia/reperfusion injury was recovered after collagen hydrogel injection. These results demonstrate that introduction of biomaterials into the kidney is able to facilitate the regeneration of glomerular and tubular structures in normal and injured kidneys. Such an approach has the potential to become a simple and effective treatment for patients with renal failure. Stem Cells Translational Medicine 2018;7:241–250

Tempol, a superoxide dismutase-mimetic drug, prevents chronic ischemic renal injury in two-kidney, one-clip hypertensive rats

ABSTRACTTempol, a superoxide dismutase-mimetic drug, has been shown to attenuate radical-induced damage, exerting beneficial effects in the animal models of oxidative stress and hypertension. This study evaluated the effect of Tempol on renal structural and functional alterations in two-Kidney, one-Clip hypertensive rats. In this study, young male Wistar rats had the left kidney clipped (2K1C), and sham-operated animals (Sham) were used as controls. Animals received Tempol (1mmol/L in drinking water) or vehicle for 5 weeks. Systolic blood pressure was evaluated once a week. At the end of the experimental protocol, the animals were placed in metabolic cages to collect urine (24h) and then anesthetized with thiopental (70mg/kg i.p.) to collect blood by puncturing the descending aorta for biochemical analysis, and the clipped kidney for morphological and immunohistochemical analyses. The vasodilator effect of Tempol was evaluated in mesenteric arterial bed (MAB) isolated from adult Wistar rats. The chronic treatment with Tempol prevented the development of hypertension and the increased plasma levels of urea, creatinine, and 8-isoprostane in 2K1C animals. Tempol also improved both glomeruli number and kidney volume to normal levels in the 2K1C+Tempol group. In addition, the treatment prevented the increased collagen deposition and immunostaining for renin, caspase-3, and 8-isoprostane in the stenotic kidney of 2K1C animals. Moreover, Tempol induced a dose-dependent vasodilator response in MAB from Wistar rats. These results suggest that Tempol protects the stenotic kidney against chronic ischemic renal injury and prevents renal dysfunction in the 2K1C model, probably through its antioxidant, vasodilator and antihypertensive actions.

Prematurity disrupts glomeruli development, whereas prematurity and hyperglycemia lead to altered nephron maturation and increased oxidative stress in newborn baboons.

BackgroundPremature birth occurs when nephrogenesis is incomplete and has been linked to increased renal pathologies in the adult. Metabolic factors complicating preterm birth may have additional consequences for kidney development. Here, we evaluated the effects of prematurity and hyperglycemia on nephrogenesis in premature baboons when compared to term animals.MethodsBaboons were delivered prematurely (67% gestation; n=9) or at term (n=7) and survived 2–4 weeks. Preterm animals were classified by glucose control during the first five days of life (DOL): normoglycemic (PtN; serum glucose 50–100mg/dL, n=6) and hyperglycemic (PtH; serum glucose 150–250mg/dL, n=3). Kidneys were assessed histologically for glomeruli relative area, maturity, size, and overall morphology. Kidney lysates were evaluated for oxidative damage with 4-hydroxynonenal (4-HNE) antibody.ResultsHistological examination revealed decreased glomeruli relative area (p<0.05), fewer glomerular generations (p<0.01), and increased renal corpuscle area (p<0.001) in preterm compared to term animals. Numbers of apoptotic glomeruli were similar between groups. PtH kidneys exhibited reduced nephrogenic zone width (p<0.0001), increased numbers of mature glomeruli (p<0.05), and increased 4-HNE staining compared to PtN kidneys.ConclusionPrematurity interrupts normal kidney development, independent of glomerular cell apoptosis. When prematurity is complicated by hyperglycemia; kidney development shifts towards accelerated maturation and increased oxidative stress.

Pattern of glomerular disease and clinicopathological correlation: A single-center study from Eastern Nepal.

The pattern of glomerular disease varies worldwide. In the absence of kidney disease/kidney biopsy registry in Nepal, the exact etiology of different forms of glomerular disease is primarily unknown in our country. We analyzed 175 cases of renal biopsies performed from September 2014 to August 2016 in Internal Medicine Ward at B.P. Koirala Institute of Health Sciences. The most common indication for renal biopsy was nephrotic syndrome (34.9%), followed by systemic lupus erythematosus (SLE) with suspected renal involvement (22.3%). Majority of patients were in the 30-60 years' bracket (57.2%), with the mean age of the patients being 35.37 years. The average number of glomeruli per core was 13, with inadequate sampling in 5.1%. Immunoglobulin A (IgA) nephropathy (17%) was found to be the most common primary glomerular disease, followed by membranous nephropathy (14.6%) and focal segmental glomerulosclerosis (14.6%). The most common secondary glomerular disease was lupus nephritis (LN). Complications associated with renal biopsy were pain at biopsy site in 18% of cases, hematuria in 6%, and perinephric hematoma in 4% cases. Although the most common primary glomerular disease was IgA nephropathy, significantly higher population of SLE with LN among Nepalese in comparison with other developing countries warrants further evaluation. As an initial attempt toward documentation of glomerular diseases in the national context, this study should serve as a stepping stone toward the eventual establishment of a full-fledged national registry of glomerular diseases in Nepal.

Stereological study of developing glomerular forms during human fetal kidney development.

Human fetal kidney development is a complex and stepwise process. The number, shape, size and distribution of glomeruli provide important information on kidney organization. The aim of this study was to quantify glomerular developing forms during human fetal kidney development using stereological methods. Kidney tissue specimens of 40 human fetuses with gestational ages ranging from 9 to 40weeks were analyzed. Specimens were divided into eight groups based on gestational age, each corresponding to 1 lunar month. Stereological methods were used at the light microscopy level to estimate volume, surface and numerical density of the glomerular developing forms. During gestation, nephrogenesis continually advanced, and the number of nephrons increased. Volume, surface and numerical densities of vesicular forms and S-shaped bodies decreased gradually in parallel with gradual increases in estimated stereological parameters for vascularized glomeruli. Volume density and surface density of vascularized glomeruli increased gradually during fetal kidney development, and numerical density increased until the seventh lunar month. A relative decrease in vascularized glomeruli per unit volume of cortex occurred during the last 3 lunar months. Nephrogenesis began to taper off by 32weeks and was completed by 36weeks of gestation. The last sample in which we observed vesicles was from a fetus aged 32weeks, and the last sample with S-shaped bodies was from a fetus aged 36weeks. The present study is one of few quantitative studies conducted on human kidney development. Knowledge of normal human kidney morphogenesis during development could be important for future medical practice. Events occurring during fetal life may have significant consequences later in life.

Toxopathological effects of camphor on some organs of female rats

Objective: The histological change of the effects camphor on some organs of female rats.In Iraq camphor in the form of tablets was added to wash dead bodies, and thus putting washers in great risk, especially female washers. Though, literature concerning its histological toxicity has not been documented. It has long been used in dead bodies washed, in our study we used camphor to kndewledge to effect high dose from camphor on histological change in some organs.Methods: The rats were divided into 3 groups (n = 6), the first group (A) was a control group treated with D.W., the second and third groups (B and C), treated with 50 mg camphor/kg and 75 mg camphor/kg. At the end of one month of treatment, animals were anesthetized, liver ,kidney, spleen and ovary were removed for serial sections and histological staining.Results: Showed vaculation in hepatocytes, and infiltration of inflammatory cells loss of most of the architecture and loss of cell boundaries in liver of group (B), while in group (C) there was congestion in area of Portia, detachment of some hepatocytes and inflammatory cells. Kidney of group B showed edematous glomerulus, glomerular lobulation, and increase number of nuclei. Also, there was swollen glomerulus, increase number of uclei and congestion of blood cells in kidney of group C. Spleen of groups B and C revealed non active lymphoid tissue and degenerated lymphocytes cells, congestion in lymphoid tissue and depletion of white pulp mainly neutrophils and macrophage. Also the results showed congestion in follicles (B) and hemorrhage (C), detachment in oocytes in treatment groups compared with control group.Conclusions: The oral administration of varying concentration of camphor solution to the animal rat has a cytotoxic effect on organs such as ,the liver, kidney, spleen and ovary.

The relationship between low-birth weight and nephrotic syndrome in children

Introduction: The body weight of an infant is one of the most important factors that influences its survival, growth and development. Many clinical studies have shown a higher risk of an aggravated course of renal disease in children born with low- birth weight (LBW), due to reduction in glomerular number and development. However, there are limited clinical studies about this relationship. Objectives: This study was conducted to evaluate the relationship between LBW and risk of idiopathic nephrotic syndrome (INS) in children. Patients and Methods: In this case–control study, we evaluated nephrotic syndrome patients who were referred to Imam Raza hospital. Seventy patients with nephrotic syndrome as case group and 140 healthy children under age 16 with normal birth weight as control group were enrolled in the study. Data including age, sex, and birth weight were collected from patient’s records. Results: This study revealed that the risk of nephrotic syndrome in patients with LBW is two times higher than those with normal birth weight. However, there was no statistically significant difference (χ2 = 1.58, P = 0.12) Conclusion: Although the result of this study cannot show a statistically significant relationship between INS and LBW, the risk of nephrotic syndrome was twice in the case group.

Evaluation of Frozen and Paraffin Sections Using the Maryland Aggregate Pathology Index Score in Donor Kidney Biopsy Specimens of a Brazilian Cohort

The Maryland aggregate pathology index (MAPI) score is an important tool developed to help pathologists in evaluating potential organs for transplantation. It is based on analysis of five variables (present or absent): arteriolar hyalinosis (4 points), periglomerular fibrosis (2 points), arterial wall-lumen ratio superior to 0.5 (2 points), global glomerulosclerosis in more than 15% of glomeruli (2 points), and interstitial scar (3 points). Kidneys with a MAPI score >7 points are considered inadequate for donation. This study aimed to evaluate pathology agreement between frozen sections (FS) and paraffin sections (PS) using the MAPI score in a cohort of 262 biopsy specimens obtained at the General Hospital of Fortaleza, Brazil. We performed a retrospective review of pathological reports of FS (signed out by an on-call pathologist) and their corresponding PS (authorized by a specialist in renal pathology). Agreement was calculated using the Kappa test. Kappa values ranging from 0.29 to 0.51 were obtained when MAPI parameters were separately evaluated. When the score was used, the coefficient was 0.59. Fourteen of 262 kidneys were classified as inadequate for donation using PS and 8 cases were diagnosed using FS. There were no differences between wedge-shaped and filiform samples, apart from the mean number of glomeruli. Discordant cases had no statistical difference from concordant ones when clinical and macroscopic pathological parameters were analyzed. The MAPI score can be useful to minimize disagreements between FS and PS, but more effort should be made to standardize criteria and enable pathologists to recognize chronic lesions in FS samples.

Cutting-edge microangio-CT: new dimensions in vascular imaging and kidney morphometry.

In the last decades, the contrast-enhanced micro-computed tomography (micro-CT) imaging of a whole animal kidney became increasingly important. The visualization was mainly limited to middle-sized vessels. Since modern desktop micro-CT scanners provide the necessary detail resolution, we developed an approach for rapid visualization and consistent assessment of kidney vasculature and glomeruli number. This method is based on μAngiofil, a new polymerizing contrast agent with homogenous X-ray absorption, which provides continuous filling of the complete vasculature and enables correlative imaging approaches. For rapid and reliable kidney morphometry, the microangio-CT (µaCT) data sets from glial cell line-derived neurotrophic factor (GDNF)+/- mice and their wild-type littermates were used. The results were obtained much faster compared with the current gold standard, histology-based stereology, and without processing artifacts. The histology-based morphometry was done afterward on the same kidneys. Both approaches revealed that the GDNF+/- male mice had about 40% fewer glomeruli. Furthermore, our approach allows for the definition of sites of interest for further histological investigation, i.e., correlative morphology. The polymerized μAngiofil stays in perfused vessels and is autofluorescent, which is what greatly facilitates the matching of histological sections with µaCT data. The presented approach is a time-efficient, reliable, qualitative, and quantitative methodology. Besides glomerular morphometry, the µaCT data can be used for qualitative and quantitative analysis of the kidney vasculature and correlative morphology.

Effects of bisphenol A treatment during pregnancy on kidney development in mice: a stereological and histopathological study.

Bisphenol A (BPA) is a chemical found in plastics that resembles oestrogen in organisms. Developmental exposure to endocrine-disrupting chemicals, such as BPA, increases the susceptibility to type 2 diabetes (T2DM) and cardiovascular diseases. Animal studies have reported a nephron deficit in offspring exposed to maternal diabetes. The aim of this study was to investigate the prenatal BPA exposure effects on nephrogenesis in a mouse model that was predisposed to T2DM. This study quantitatively evaluated the renal structural changes using stereology and histomorphometry methods. The OF1 pregnant mice were treated with a vehicle or BPA (10 or 100 μg/kg/day) during days 9-16 of gestation (early nephrogenesis). The 30-day-old offspring were sacrificed, and tissue samples were collected and prepared for histopathological and stereology studies. Glomerular abnormalities and reduced glomerular formation were observed in the BPA offspring. The kidneys of the BPA10 and BPA100 female offspring had a significantly lower glomerular number and density than those of the CONTROL female offspring. The glomerular histomorphometry revealed a significant difference between the female and male CONTROL offspring for the analysed glomerular parameters that disappeared in the BPA10 and BPA100 offspring. In addition, the kidney histopathological examination showed typical male cuboidal epithelial cells of the Bowman capsule in the female BPA offspring. Exposure to environmentally relevant doses of BPA during embryonic development altered nephrogenesis. These structural changes could be associated with an increased risk of developing cardiometabolic diseases later in life.

Measuring rat kidney glomerular number and size in vivo with MRI.

number is highly variable in humans and is thought to play an important role in renal health. Chronic kidney disease (CKD) is the result of too few nephrons to maintain homeostasis. Currently, nephron number can only be determined invasively or as a terminal assessment. Due to a lack of tools to measure and track nephron number in the living, the early stages of CKD often go unrecognized, preventing early intervention that might halt the progression of CKD. In this work, we present a technique to directly measure glomerular number ( Nglom) and volume in vivo in the rat kidney ( n = 8) using MRI enhanced with the novel contrast agent cationized ferritin (CFE-MRI). Adult male rats were administered intravenous cationized ferritin (CF) and imaged in vivo with MRI. Glomerular number was measured and each glomerulus was spatially mapped in 3D in the image. Mean apparent glomerular volume (a Vglom) and intrarenal distribution of the individual glomerular volume (IGV), were also measured. These metrics were compared between images of the same kidneys scanned in vivo and ex vivo with CFE-MRI. In vivo Nglom and a Vglom correlated to ex vivo metrics within the same kidneys and were within 10% of Nglom and a Vglom previously validated by stereologic methods. This is the first report of direct in vivo measurements of Nglom and a Vglom, introducing an opportunity to investigate mechanisms of renal disease progression and therapeutic response over time.

Re-expression of Sall1 in podocytes protects against adriamycin-induced nephrosis

The highly conserved spalt (sal) gene family members encode proteins characterized by multiple double zinc finger motifs of the C2H2 type. Humans and mice each have four known Sal-like genes (SALL1–4 in humans and Sall1–4 in mice). Sall1 is known to have a crucial role in kidney development. To explore the significance of Sall1 in differentiated podocytes, we investigated podocyte-specific Sall1-deficient mice (Sall1 KOp°d°/p°d°) using a podocin-Cre/loxP system and siRNA Sall1 knockdown (Sall1 KD) podocytes. Under physiological conditions, Sall1 KOp°d°/p°d° mice exhibited no proteinuria during their lifetime, but foot-process effacement was detected in some of the podocytes. To elucidate the role of Sall1 in injured podocytes, we used an adriamycin (ADR)-induced model of nephrosis and glomerulosclerosis. Surprisingly, the expression of Sall1 was elevated in control mice on day 14 after ADR injection. On day 28 after ADR injection, Sall1 KOp°d°/p°d° mice exhibited significantly higher levels of proteinuria and higher numbers of sclerotic glomeruli. Differentiated Sall1 KD podocytes showed a loss of synaptopodin, suppressed stress fiber formation, and, ultimately, impaired directed cell migration. In addition, the loss of Sall1 increased the number of apoptotic podocytes following ADR treatment. These results indicated that Sall1 has a protective role in podocytes; thus, we investigated the endoplasmic reticulum stress marker GRP78. GRP78 expression was higher in ADR-treated Sall1 KOp°d°/p°d° mice than in control mice. Sall1 appeared to influence the expression of GRP78 in injured podocytes. These results suggest that Sall1 is associated with actin reorganization, endoplasmic reticulum stress, and apoptosis in injured podocytes. These protective aspects of Sall1 re-expression in injured podocytes may have the potential to reduce apoptosis and possibly glomerulosclerosis.