The spatially resolved transcriptome signatures of glomeruli in chronic kidney disease.

Here, we used digital spatial profiling (DSP) to describe the glomerular transcriptomic signatures that may characterize the complex molecular mechanisms underlying progressive kidney disease in Alport syndrome, focal segmental glomerulosclerosis, and membranous nephropathy. Our results revealed significant transcriptional heterogeneity among diseased glomeruli, and this analysis showed that histologically similar glomeruli manifested different transcriptional profiles. Using glomerular pathology scores to establish an axis of progression, we identified molecular pathways with progressively decreased expression in response to increasing pathology scores, including signal recognition particle-dependent cotranslational protein targeting to membrane and selenocysteine synthesis pathways. We also identified a distinct signature of upregulated and downregulated genes common to all the diseases investigated when compared with nondiseased tissue from nephrectomies. These analyses using DSP at the single-glomerulus level could help to increase insight into the pathophysiology of kidney disease and possibly the identification of biomarkers of disease progression in glomerulopathies.

C3aR-initiated signaling is a critical mechanism of podocyte injury in membranous nephropathy.

The deposition of antipodocyte autoantibodies in the glomerular subepithelial space induces primary membranous nephropathy (MN), the leading cause of nephrotic syndrome worldwide. Taking advantage of the glomerulus-on-a-chip system, we modeled human primary MN induced by anti-PLA2R antibodies. Here we show that exposure of primary human podocytes expressing PLA2R to MN serum results in IgG deposition and complement activation on their surface, leading to loss of the chip permselectivity to albumin. C3a receptor (C3aR) antagonists as well as C3AR gene silencing in podocytes reduced oxidative stress induced by MN serum and prevented albumin leakage. In contrast, inhibition of the formation of the membrane-attack-complex (MAC), previously thought to play a major role in MN pathogenesis, did not affect permselectivity to albumin. In addition, treatment with a C3aR antagonist effectively prevented proteinuria in a mouse model of MN, substantiating the chip findings. In conclusion, using a combination of pathophysiologically relevant in vitro and in vivo models, we established that C3a/C3aR signaling plays a critical role in complement-mediated MN pathogenesis, indicating an alternative therapeutic target for MN.

Identification and Characterization of the Wilms Tumor Cancer Stem Cell.

A nephrogenic progenitor cell (NP) with cancer stem cell characteristics driving Wilms tumor (WT) using spatial transcriptomics, bulk and single cell RNA sequencing, and complementary in vitro and transplantation experiments is identified and characterized. NP from WT samples with NP from the developing human kidney is compared. Cells expressing SIX2 and CITED1 fulfill cancer stem cell criteria by reliably recapitulating WT in transplantation studies. It is shown that self-renewal versus differentiation in SIX2+CITED1+ cells is regulated by the interplay between integrins ITGß1 and ITGß4. The spatial transcriptomic analysis defines gene expression maps of SIX2+CITED1+ cells in WT samples and identifies the interactive gene networks involved in WT development. These studies define SIX2+CITED1+ cells as the nephrogenic-like cancer stem cells of WT and points to the renal developmental transcriptome changes as a possible driver in regulating WT formation and progression.

Continued use of scrotal ultrasounds for the workup of undescended testes: Confirmation bias and inaccuracies.

AIM: Scrotal ultrasounds are utilised in some primary care settings for suspected cryptorchidism, despite inaccuracies. We aim to identify the correlation between ultrasound and primary care provider (PCP) findings of undescended testicles (UDTs) as a potential source of confirmation bias. METHODS: Males referred for suspected UDT by PCPs who underwent scrotal ultrasound and paediatric urologist examination from 2014 to 2019 were included. Correlation between PCP and ultrasound findings and diagnostic accuracy were evaluated. Logistic regression was utilised to determine associations between patient factors and UDT misdiagnosis. RESULTS: Out of 145 testes, ultrasound corroborated PCPs' UDT diagnoses 87.6% of the time, 49.6% of which were confirmed as UDT by paediatric urologists. Ultrasound had a false positivity rate of 81.0% and specificity of 19.0%. Ultrasound versus paediatric urologist findings regarding testicle location were significantly different (P < 0.0001). Patients aged ≥8 years old had 5.2 times greater odds of being misdiagnosed with UDT than patients <8 years old (95% confidence interval: 1.6-16.7; P < 0.002) by PCP and ultrasound. CONCLUSION: Scrotal ultrasound highly corroborated PCPs' UDT diagnoses. Older patients were more likely to be misdiagnosed with UDT by PCP and ultrasound. As ultrasounds rarely refute PCP examinations for suspected UDTs and are highly inaccurate, confirmation bias may explain the use of ultrasound in the workup of UDT.

Utility of renal scintigraphy in diagnosis of multicystic dysplastic kidney.

PURPOSE: To compare the prevalence of vesicoureteral reflux (VUR), febrile urinary tract infection (fUTI), and chronic kidney disease (CKD) among patients with multicystic dysplastic kidney (MCDK) diagnosed by renal scintigraphy (RS) versus follow-up renal ultrasound (RUS) alone. METHODS: This was a retrospective review of patients seen at a tertiary care center from 2010 to 2020 with MCDK diagnosed by RS or follow-up RUS. Differences in the prevalence of VUR, fUTI, and CKD by cohort were assessed using logistic regression analysis, Pearson X2 , and Fisher's Exact tests. Temporal trends in diagnostic methods used (RUS versus RUS + RS) were evaluated using the Cochran-Armitage trend test. RESULTS: One-hundred seventy-two patients were included: 50% (n = 86) underwent RUS + RS and 50% (n = 86) underwent RUS alone to diagnose MCDK. Prevalence of VUR, fUTI, and CKD did not significantly vary between groups. Among patients who had a VCUG, 4.4% had contralateral VUR (1.7% RUS + RS group; 7.4% RUS group; p = 0.19) and 14.5% had at least one fUTI (16.3% RUS + RS group; 12.8% RUS group; p = 0.52). Females were significantly more likely to have at least one fUTI (p = 0.04). Four patients (2.3%) developed CKD, all in the RUS + RS cohort (p = 0.12). Diagnosis of MCDK by RUS versus RUS + RS did not significantly vary over time (p = 0.17). CONCLUSION: Patients with unilateral MCDK confirmed by RS versus RUS alone do not significantly vary in the prevalence of VUR, fUTI, or CKD. Renal scintigraphy studies may not be necessary in unilateral MCDK diagnosis but continue to be used.

Effect of disease progression on the podocyte cell cycle in Alport Syndrome.

Progression of glomerulosclerosis is associated with loss of podocytes with subsequent glomerular tuft instability. It is thought that a diminished number of podocytes may be able to preserve tuft stability through cell hypertrophy associated with cell cycle reentry. At the same time, reentry into the cell cycle risks podocyte detachment if podocytes cross the G1/S checkpoint and undergo abortive cytokinesis. In order to study cell cycle dynamics during chronic kidney disease (CKD) development, we used a FUCCI model (fluorescence ubiquitination-based cell cycle indicator) of mice with X-linked Alport Syndrome. This model exhibits progressive CKD and expresses fluorescent reporters of cell cycle stage exclusively in podocytes. With the development of CKD, an increasing fraction of podocytes in vivo were found to be in G1 or later cell cycle stages. Podocytes in G1 and G2 were hypertrophic. Heterozygous female mice, with milder manifestations of CKD, showed G1 fraction numbers intermediate between wild-type and male Alport mice. Proteomic analysis of podocytes in different cell cycle phases showed differences in cytoskeleton reorganization and metabolic processes between G0 and G1 in disease. Additionally, in vitro experiments confirmed that damaged podocytes reentered the cell cycle comparable to podocytes in vivo. Importantly, we confirmed the upregulation of PDlim2, a highly expressed protein in podocytes in G1, in a patient with Alport Syndrome, confirming our proteomics data in the human setting. Thus, our data showed that in the Alport model of progressive CKD, podocyte cell cycle distribution is altered, suggesting that cell cycle manipulation approaches may have a role in the treatment of various progressive glomerular diseases characterized by podocytopenia.

Author Correction: A glomerulus-on-a-chip to recapitulate the human glomerular filtration barrier.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A glomerulus-on-a-chip to recapitulate the human glomerular filtration barrier.

In this work we model the glomerular filtration barrier, the structure responsible for filtering the blood and preventing the loss of proteins, using human podocytes and glomerular endothelial cells seeded into microfluidic chips. In long-term cultures, cells maintain their morphology, form capillary-like structures and express slit diaphragm proteins. This system recapitulates functions and structure of the glomerulus, including permselectivity. When exposed to sera from patients with anti-podocyte autoantibodies, the chips show albuminuria proportional to patients' proteinuria, phenomenon not observed with sera from healthy controls or individuals with primary podocyte defects. We also show its applicability for renal disease modeling and drug testing. A total of 2000 independent chips were analyzed, supporting high reproducibility and validation of the system for high-throughput screening of therapeutic compounds. The study of the patho-physiology of the glomerulus and identification of therapeutic targets are also feasible using this chip.

Direct Isolation and Characterization of Human Nephron Progenitors.

Mature nephrons originate from a small population of uninduced nephrogenic progenitor cells (NPs) within the cap mesenchyme. These cells are characterized by the coexpression of SIX2 and CITED1. Many studies on mouse models as well as on human pluripotent stem cells have advanced our knowledge of NPs, but very little is known about this population in humans, since it is exhausted before birth and strategies for its direct isolation are still limited. Here we report an efficient protocol for direct isolation of human NPs without genetic manipulation or stepwise induction procedures. With the use of RNA-labeling probes, we isolated SIX2+ CITED1+ cells from human fetal kidney for the first time. We confirmed their nephrogenic state by gene profiling and evaluated their nephrogenic capabilities in giving rise to mature renal cells. We also evaluated the ability to culture these cells without complete loss of SIX2 and CITED1 expression over time. In addition to defining the gene profile of human NPs, this in vitro system facilitates studies of human renal development and provides a novel tool for renal regeneration and bioengineering purposes. Stem Cells Translational Medicine 2017;6:419-433.

A step towards clinical application of acellular matrix: A clue from macrophage polarization.

The outcome of tissue engineered organ transplants depends on the capacity of the biomaterial to promote a pro-healing response once implanted in vivo. Multiple studies, including ours, have demonstrated the possibility of using the extracellular matrix (ECM) of animal organs as platform for tissue engineering and more recently, discarded human organs have also been proposed as scaffold source. In contrast to artificial biomaterials, natural ECM has the advantage of undergoing continuous remodeling which allows adaptation to diverse conditions. It is known that natural matrices present diverse immune properties when compared to artificial biomaterials. However, how these properties compare between diseased and healthy ECM and artificial scaffolds has not yet been defined. To answer this question, we used decellularized renal ECM derived from WT mice and from mice affected by Alport Syndrome at different time-points of disease progression as a model of renal failure with extensive fibrosis. We characterized the morphology and composition of these ECMs and compared their in vitro effects on macrophage activation with that of synthetic scaffolds commonly used in the clinic (collagen type I and poly-L-(lactic) acid, PLLA). We showed that ECM derived from Alport kidneys differed in fibrous protein deposition and cytokine content when compared to ECM derived from WT kidneys. Yet, both WT and Alport renal ECM induced macrophage differentiation mainly towards a reparative (M2) phenotype, while artificial biomaterials towards an inflammatory (M1) phenotype. Anti-inflammatory properties of natural ECMs were lost when homogenized, hence three-dimensional structure of ECM seems crucial for generating an anti-inflammatory response. Together, these data support the notion that natural ECM, even if derived from diseased kidneys promote a M2 protolerogenic macrophage polarization, thus providing novel insights on the applicability of ECM obtained from discarded organs as ideal scaffold for tissue engineering.

Testicular Adrenal Rest Tumors in Boys and Young Adults with Congenital Adrenal Hyperplasia.

PURPOSE: Testicular adrenal rest tumors are a well-known complication in males who have congenital adrenal hyperplasia with potential infertility in adulthood. We assessed the prevalence of testicular adrenal rest tumors in infants to young men presenting to a congenital adrenal hyperplasia Comprehensive Care Center. MATERIALS AND METHODS: A total of 35 males with congenital adrenal hyperplasia due to 21-hydroxylase deficiency underwent scrotal ultrasonography, including 7 younger than 5 years, 9 who were 5 to 12 years old and 19 who were older than 12 years. Three and 35 patients had classic and nonclassic congenital adrenal hyperplasia, respectively. Bone age x-ray or advanced bone age x-ray history, glucocorticoid dose, fludrocortisone dose, and serum 17-hydroxyprogesterone, testosterone and androstenedione levels within 3 months of ultrasound were also recorded. RESULTS: Testicular adrenal rest tumors were detected in 5 of 35 patients (14%), including 1 of 9 (11%) who were 5 to 12 years old and 4 of 19 (21%) who were older than 12 years. The tumors were not detected in any patients younger than 5 years, including 1 infant with poor hormonal control. The youngest patient with positive findings was 6.6 years old. All patients with positive findings had bilateral disease and only 1 had suspicious physical findings. The glucocorticoid dose and 17-hydroxyprogesterone did not differ between patients with vs without a testicular adrenal rest tumor. Those with a tumor were more likely to have advanced bone age x-ray results (100% vs 42%, p = 0.04) and higher fludrocortisone dose (p <0.01). All males with nonclassic congenital adrenal hyperplasia had negative tumor findings. CONCLUSIONS: Testicular adrenal rest tumors were present in young males with classic congenital adrenal hyperplasia but not in infants or toddlers. These tumors were associated with higher fludrocortisone requirements and a history of advanced bone age x-ray results. However, the tumors did not develop in all poorly controlled males. Longitudinal studies are needed to understand the individual predisposition to testicular adrenal rest tumors and the age at which to begin screening patients with congenital adrenal hyperplasia.

Decellularized Renal Matrix and Regenerative Medicine of the Kidney: A Different Point of View.

Over the past years, extracellular matrix (ECM) obtained from whole organ decellularization has been investigated as a platform for organ engineering. The ECM is composed of fibrous and nonfibrous molecules providing structural and biochemical support to the surrounding cells. Multiple decellularization techniques, including ours, have been optimized to maintain the composition, microstructure, and biomechanical properties of the native renal ECM that are difficult to obtain during the generation of synthetic substrates. There are evidences suggesting that in vivo implanted renal ECM has the capacity to induce formation of vasculature-like structures, but long-term in vivo transplantation and filtration activity by these tissue-engineered constructs have not been investigated or reported. Therefore, even if the process of renal decellularization is possible, the repopulation of the renal matrix with functional renal cell types is still very challenging. This review aims to summarize the current reports on kidney tissue engineering with the use of decellularized matrices and addresses the challenges in creating functional kidney units. Finally, this review discusses how future studies investigating cell-matrix interaction may aid the generation of a functional renal unit that would be transplantable into patients one day.

Renal Extracellular Matrix Scaffolds From Discarded Kidneys Maintain Glomerular Morphometry and Vascular Resilience and Retains Critical Growth Factors.

BACKGROUND: Extracellular matrix (ECM) scaffolds, obtained through detergent-based decellularization of native kidneys, represent the most promising platform for investigations aiming at manufacturing kidneys for transplant purposes. We previously showed that decellularization of the human kidney yields renal ECM scaffolds (hrECMs) that maintain their basic molecular components, are cytocompatible, stimulate angiogenesis, and show an intact innate vasculature. However, evidence that the decellularization preserves glomerular morphometric characteristics, physiological parameters (pressures and resistances of the vasculature bed), and biological properties of the renal ECM, including retention of important growth factors (GFs), is still missing. METHODS: To address these issues, we studied the morphometry and resilience of hrECMs' native vasculature with resin casting at electronic microscopy and pulse-wave measurements, respectively. Moreover, we determined the fate of 40 critical GFs post decellularization with a glass chip-based multiplex enzyme-linked immunosorbent assay array and in vitro immunofluorescence. RESULTS: Our method preserves the 3-dimensional conformation of the native glomerulus. Resin casting and pulse-wave measurements, showed that hrECMs preserves the microvascular morphology and morphometry, and physiological function. Moreover, GFs including vascular endothelial growth factor and its receptors are retained within the matrices. CONCLUSIONS: Our results indicate that discarded human kidneys are a suitable source of renal scaffolds because they maintain a well-preserved structure and function of the vasculature, as well as GFs that are fundamental to achieve a satisfying recellularization of the scaffold in vivo due to their angiogenic properties.

Penile urethra replacement with autologous cell-seeded tubularized collagen matrices.

Acellular collagen matrices have been used as an onlay material for urethral reconstruction. However, cell-seeded matrices have been recommended for tubularized urethral repairs. In this study we investigated whether long segmental penile urethral replacement using autologous cell-seeded tubularized collagen-based matrix is feasible. Autologous bladder epithelial and smooth muscle cells from nine male rabbits were grown and seeded onto preconfigured tubular matrices constructed from decellularized bladder matrices obtained from lamina propria. The entire anterior penile urethra was resected in 15 rabbits. Urethroplasties were performed with tubularized matrices seeded with cells in nine animals, and with matrices without cells in six. Serial urethrograms were performed at 1, 3 and 6 months. Retrieved urethral tissues were analysed using histo- and immunohistochemistry, western blot analyses and organ bath studies. The urethrograms showed that animals implanted with cell-seeded matrices maintained a wide urethral calibre without strictures. In contrast, the urethras with unseeded scaffolds collapsed and developed strictures. Histologically, a transitional cell layer surrounded by muscle was observed in the cell-seeded constructs. The epithelial and smooth muscle phenotypes were confirmed with AE1/AE3 and α-actin antibodies. Organ bath studies of the neourethras confirmed both physiological contractility and the presence of neurotransmitters. Tubularized collagen matrices seeded with autologous cells can be used successfully for long segmental penile urethra replacement, while implantation of tubularized collagen matrices without cells leads to poor tissue development and stricture formation. The cell-seeded collagen matrices are able to form new tissue, which is histologically similar to native urethra.

Autologous cell seeded biodegradable scaffold for augmentation cystoplasty: phase II study in children and adolescents with spina bifida.

PURPOSE: Augmentation cystoplasty using gastrointestinal segments in children/adolescents with medically refractory neurogenic bladder is associated with significant complications. We evaluated an autologous cell seeded biodegradable scaffold (Tengion®) for bladder augmentation as an alternative to traditional enterocystoplasty in this population. MATERIALS AND METHODS: A phase II prospective study was performed in children with neurogenic bladder due to spina bifida requiring enterocystoplasty for detrusor pressure 40 cm H2O or greater despite maximum antimuscarinic medication. Following open bladder biopsy, urothelial and smooth muscle cells were grown ex vivo and seeded onto a biodegradable scaffold to form a regenerative augment as the foundation for bladder tissue regeneration. Bladder neck sling was the only concomitant surgical procedure permitted. Bladders were cycled postoperatively to promote regeneration. Primary and secondary outcomes at 12 months included change in bladder compliance, bladder capacity and safety. Long-term assessment was done with similar outcomes at 36 months. RESULTS: Compliance improved in 4 patients at 12 months and in 5 patients at 36 months, although the difference was not clinically or statistically significant. There was no clinical or statistical improvement in bladder capacity at 12 or 36 months in any patient. Adverse events occurred in all patients, and most were easily treated. Two patients had low cell growth following bladder biopsy, of whom 1 withdrew from the study and 1 underwent a second biopsy. Serious adverse events of bowel obstruction and/or bladder rupture occurred in 4 patients. CONCLUSIONS: Our autologous cell seeded biodegradable scaffold did not improve bladder compliance or capacity, and our serious adverse events surpassed an acceptable safety standard.

A novel source of cultured podocytes.

Amniotic fluid is in continuity with multiple developing organ systems, including the kidney. Committed, but still stem-like cells from these organs may thus appear in amniotic fluid. We report having established for the first time a stem-like cell population derived from human amniotic fluid and possessing characteristics of podocyte precursors. Using a method of triple positive selection we obtained a population of cells (hAKPC-P) that can be propagated in vitro for many passages without immortalization or genetic manipulation. Under specific culture conditions, these cells can be differentiated to mature podocytes. In this work we compared these cells with conditionally immortalized podocytes, the current gold standard for in vitro studies. After in vitro differentiation, both cell lines have similar expression of the major podocyte proteins, such as nephrin and type IV collagen, that are characteristic of mature functional podocytes. In addition, differentiated hAKPC-P respond to angiotensin II and the podocyte toxin, puromycin aminonucleoside, in a way typical of podocytes. In contrast to immortalized cells, hAKPC-P have a more nearly normal cell cycle regulation and a pronounced developmental pattern of specific protein expression, suggesting their suitability for studies of podocyte development for the first time in vitro. These novel progenitor cells appear to have several distinct advantages for studies of podocyte cell biology and potentially for translational therapies.

Anorectal malformation and associated end-stage renal disease: management from newborn to adult life.

BACKGROUND/OBJECTIVE: Renal failure remains one of the most significant causes of morbidity in patients with anorectal malformations (ARM). In the modern era, an increasing number of children born with ARM and genito-urinary (GU) anomalies reach adulthood and require continued multidisciplinary care for the rest of their life. The aim of this study is to present our institutional experience in the management of pediatric chronic renal failure related to severe GU anomalies and anorectal malformations. METHODS AND RESULTS: Three hundred twenty-one patients with ARM have been followed at our institution since 1987. Six patients developed end-stage renal disease (ESRD) and received a kidney transplant at different ages. One patient is currently followed for mild, progressive chronic renal failure. These seven cases are reported along with a broad discussion concerning etiology of renal failure, neonatal surgical management, pediatric dialysis, urologic issues, and kidney transplantation. CONCLUSION: Complex GU anomalies associated with ARM require a long-term approach by specialized pediatric and adult clinicians to optimize the care of this selected population of patients.

Injection of amniotic fluid stem cells delays progression of renal fibrosis.

Injection of amniotic fluid stem cells ameliorates the acute phase of acute tubular necrosis in animals by promoting proliferation of injured tubular cells and decreasing apoptosis, but whether these stem cells could be of benefit in CKD is unknown. Here, we used a mouse model of Alport syndrome, Col4a5(-/-) mice, to determine whether amniotic fluid stem cells could modify the course of progressive renal fibrosis. Intracardiac administration of amniotic fluid stem cells before the onset of proteinuria delayed interstitial fibrosis and progression of glomerular sclerosis, prolonged animal survival, and ameliorated the decline in kidney function. Treated animals exhibited decreased recruitment and activation of M1-type macrophages and a higher proportion of M2-type macrophages, which promote tissue remodeling. Amniotic fluid stem cells did not differentiate into podocyte-like cells and did not stimulate production of the collagen IVa5 needed for normal formation and function of the glomerular basement membrane. Instead, the mechanism of renal protection was probably the paracrine/endocrine modulation of both profibrotic cytokine expression and recruitment of macrophages to the interstitial space. Furthermore, injected mice retained a normal number of podocytes and had better integrity of the glomerular basement membrane compared with untreated Col4a5(-/-) mice. Inhibition of the renin-angiotensin system by amniotic fluid stem cells may contribute to these beneficial effects. In conclusion, treatment with amniotic fluid stem cells may be beneficial in kidney diseases characterized by progressive renal fibrosis.

Cryptorchidism and testicular germ cell tumors: comprehensive meta-analysis reveals that association between these conditions diminished over time and is modified by clinical characteristics.

INTRODUCTION: Risk of testicular germ cell tumors (TGCT) is consistently associated with a history of cryptorchidism (CO) in epidemiologic studies. Factors modifying the association may provide insights regarding etiology of TGCT and suggest a basis for individualized care of CO. To identify modifiers of the CO-TGCT association, we conducted a comprehensive, quantitative evaluation of epidemiologic data. MATERIALS AND METHODS: Human studies cited in PubMed or ISI Web of Science indices through December 2011 and selected unpublished epidemiologic data were reviewed to identify 35 articles and one unpublished dataset with high-quality data on the CO-TGCT association. Association data were extracted as point and 95% confidence interval estimates of odds ratio (OR) or standardized incidence ratio (SIR), or as tabulated data. Values were recorded for each study population, and for subgroups defined by features of study design, CO and TGCT. Extracted data were used to estimate summary risk ratios (sRR) and evaluate heterogeneity of the CO-TGCT association between subgroups. RESULTS: The overall meta-analysis showed that history of CO is associated with four-fold increased TGCT risk [RR = 4.1(95% CI = 3.6-4.7)]. Subgroup analyses identified five determinants of stronger association: bilateral CO, unilateral CO ipsilateral to TGCT, delayed CO treatment, TGCT diagnosed before 1970, and seminoma histology. CONCLUSIONS: Modifying factors may provide insight into TGCT etiology and suggest improved approaches to managing CO. Based on available data, CO patients and their parents or caregivers should be made aware of elevated TGCT risk following orchidopexy, regardless of age at repair, unilateral vs. bilateral non-descent, or position of undescended testes.

Stem cells as a therapeutic approach to chronic kidney diseases.

Much attention recently has been focused on stem cell technology as a possible alternative modality of treatment of a variety of diseases. Chronic kidney disease is a serious health problem and most chronic kidney diseases share in common the presence of interstitial and glomerular fibrosis, regardless of the underlying cause. To date there are no specific therapies aimed at treating fibrosis in the kidney. In a novel effort to address the underlying pathology in kidney disease, researchers are demonstrating that stem cell therapy can attenuate fibrosis in chronic kidney disease in animal models. This review will focus on the recent developments in stem cell research and their possible implications to treat chronic kidney disease.