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Pilot project programs offer early-stage and other investigators support to pursue emerging research areas, explore new methodologies, gain experience as principal investigators, and collect pilot data needed to pursue larger extramural research funding, such as from the National Institutes of Health. Pilot project programs may be particularly important to early-stage investigators from underrepresented backgrounds, who must overcome unique challenges to launching careers in community-based participatory research. This paper describes the structure, function, and impact of the Native Center for Alcohol Research and Education (NCARE) Pilot Project Core. Methods: During four calls for applications from 2018 to 2021, research investigators interested in conducting alcohol use disorder research in partnership with Tribal communities were recruited, with a focus on early-stage and American Indian and Alaska Native investigators. Eligible investigators were required to submit letters of intent prior to preparing full applications, which underwent a rigorous review process. Results: Eight pilot projects were awarded. Of the eight pilot project investigators, seven were early-stage scholars, seven were female, and four identified as American Indian or Alaska Native. The funded projects included two primary areas of research, epidemiological studies and intervention projects. Once funded, the Pilot Project Core assisted pilot project investigators with securing approvals for their research studies, responding to methodological and analysis questions, and mentoring and monitoring their progress. At the time of writing this paper, three pilot project investigators have completed their pilot projects, three investigators are currently collecting data, and one is in the analysis phase. One pilot project investigator did not complete their project due to COVID-19 restrictions early in the pandemic. The pilot project investigators submitted 36 grant proposals for independent external funding and received 25 grants after funding of their pilot project; four were directly related to pilot project grants. Additionally, four peer-reviewed manuscripts resulting from Pilot Project Core support were published. Conclusions: Despite challenges related to the COVID-19 pandemic the pilot project funding through NCARE provided eight pilot grants, half of which identified as AI/AN and most of which led directly to multiple grants and papers. The NCARE pilot program provides a model for other similar programs seeking to support early-stage investigators who identify as AI/AN or other groups underrepresented in science. Keywords: Pilot projects; training programs; substance use disorders; American Indian and Alaska Native communities, BACKGROUND Recently, the National Institutes of Health (NIH) has introduced a variety of initiatives focused on increasing the diversity of the scientific workforce (National Institutes of Health, 2022). These efforts [...]

In vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) are 2 major assisted reproductive techniques (ARTs) used widely to treat infertility. Recently, spermatogonia! transplantation emerged as a new ART to restore fertility to young patients with cancer after cancer therapy. To examine the influence of germ cell manipulation on behavior of offspring, we produced [F.sub.1] offspring by a combination of two ARTs, spermatogonial transplantation and ICSI. When these animals were compared with [F.sub.1] offspring produced by ICSI using fresh wild-type sperm, not only spermatogonial transplantation- ICSI mice but also ICSI-only control mice exhibited behavioral abnormalities, which persisted in the [F.sub.2] generation. Furthermore, although these [F.sub.1] offspring appeared normal, [F.sub.2] offspring produced by IVF using [F.sub.1] sperm and wild- type oocytes showed various types of congenital abnormalities, including anophthalmia, hydrocephalus, and missing limbs. Therefore, ARTs can induce morphological and functional defects in mice, some of which become evident only after germline transmission., Introduction Since its first report in 1978, in vitro fertilization (IVF) has been used in assisted reproductive techniques (ARTs) in humans (1). IVF is often used when a woman's fallopian [...]

Background After the major changes with regard to acute and chronic ABMR in the Banff classification initiated in 2013, there has been an improvement in diagnosing antibody-mediated rejection (ABMR) in adult studies but no data have been published in the paediatric population. Methods We assessed 56 paediatric kidney transplant biopsies due to kidney dysfunction in patients with donor-specific antibodies (DSA) in a retrospective single-centre study between January 2006 and March 2012. The results were compared with 2003/2007 Banff classification noting the subsequent 2017 and 2019 modifications do not change the 2013 Banff classification with regard to acute antibody-mediated rejection (apart from the addition of gene transcripts/classifiers that do not affect our analysis). Results Following the 2013 Banff classification, there were seven cases (12.5%) diagnosed with ABMR that would have been misclassified when applying the 2003/2007 classification. Evaluating the histological features of all ABMR-related cases, we report the importance of v- (intimal arteritis) and t- (tubulitis) lesions: absence of v- and t- lesions in the biopsy is related to significantly higher kidney allograft survival (OR 7.3, 95%CI 1.1-48.8, p = 0.03 and OR 5.3, 95%CI 1.2-25.5, p = 0.04 respectively). Moreover, absence of t- lesions was associated with significantly fewer rejection episodes the year after the initial biopsy (OR 5.1, 95%CI 1.4-19.8, p = 0.01). Conclusions Our study supports that the updated 2013 Banff classification shows superior clinicopathological correlation in identifying ABMR in paediatric kidney transplant recipients. Our results can be extrapolated to the recently updated 2019 Banff classification., Author(s): Evgenia Preka [sup.1] [sup.2] , Thivya Sekar [sup.3] , Sergio C Lopez Garcia [sup.1] , Olivia Shaw [sup.4] , Nicos Kessaris [sup.5] , Nizam Mamode [sup.5] , Jelena Stojanovic [...]

Since our previous results suggest that lactoferrin (LF) might have roles in the reproductive process and that its levels might change in the female tract as a response to various factors, the aim of this investigation was to assess whether LF levels in cervical secretions correlate with reproductive parameters from in vitro fertilization (IVF) patients. Cervical fluid samples were obtained from 34 women under 40 years old enrolled for assisted reproduction techniques, and LF concentration was measured. The mean total protein concentration in all cervical fluid samples was 842.8 6 116.9 lg/mL. The mean concentration of LF was 0.73 6 0.06 ng LF/lg of total proteins. We observed that higher LF levels in cervical fluid correlated with lower IVF rates when all patients were analyzed; this negative correlation was also sustained when only patients [greater than or equal to]35 years were studied. The mean LF concentration in cervical fluid was significantly lower among patients with normal IVF rates than in those with values 50% or less. Using a LF cutoff value of 0.83 ng/lg of total proteins, the study revealed a significant association between the LF levels below 0.83 ng/lg of total proteins and IVF rates above 50%. LF levels in cervical mucus could potentially be used as a marker of fertilization outcome. Key words: lactoferrin, in vitro fertilization, outcome, cervical fluid. Puisque les resultats obtenus precedemment par les auteurs suggerent que la LF pourrait jouer un role dans le processus de reproduction et que ses niveaux pourraient changer dans les voies genitales feminines en reponse a divers facteurs, l'objectif de cette etude consistait a evaluer si les niveaux de LF des secretions cervicales sont correles avec les parametres reproducteurs de patientes ayant subi une fecondation in vitro (FIV). Des echantillons de liquide cervical ont ete obtenus de 34 femmes de moins de 40 ans inscrites a un protocole de procreation assistee et la concentration de LF a ete mesuree. La concentration moyenne de proteines totales dans tous les echantillons de liquide cervical etait de 842,8 6 116,9 lg/mL. La concentration moyenne de LF etait de 0,73 60,06 ng LF/lg de proteines totales. Les auteurs ont observe que des niveaux plus eleves de LF dans le liquide cervical etaient correles avec des taux de FIV plus faibles lorsque les donnees de toutes les patientes etaient analysees; cette correlation negative etait egalement maintenue lorsque seules les patientes de 35 ans et moins etaient etudiees. La concentration moyenne de LF du liquide cervical etait significativement plus faible chez les patients presentant des taux de FIV normaux que chez celles dont les taux etaient de 50 % et moins. En utilisant une valeur seuil de LF de 0,83 ng LF/lg de proteines totales, cette etude a revele une association significative entre les niveaux de LF inferieurs a 0,83 ng LF/lg de proteines totales et des taux de FIV superieurs a 50 %. Les niveaux de LF dans le mucus cervical pourraient potentiellement etre utilises comme marqueur du resultat de la fecondation. [Traduit par la Redaction] Mots-cles : lactoferrine, fecondation in vitro, resultat, liquide cervical., Introduction Evidence from many studies has indicated that lactoferrin (LF) is present in the female reproductive tract secretions (Shaw et al. 2007; Zumoffen et al. 2013). It is known that [...]

Immunoglobulin A nephropathy (IgAN) is the most frequently occurring primary glomerulonephritis in Caucasian and Asian populations. Nonetheless, therapeutic recommendations are based on weak evidence, large controlled trials are scarce and, in particular, the additional value of immunosuppression beyond comprehensive supportive measures is not well-established. The use of immunosuppressants is supported by experimental insights into IgAN pathogenesis that suggest an autoimmune component in disease development. The so-called 'multi-hit' theory comprises multiple steps, starting with defective glycosylation of IgA subclass IgA1 that results in overproduction of galactose-deficient IgA1 (Gd-IgA1), occurrence of anti-Gd-IgA1 autoantibodies, and mesangial deposition of nephritogenic immune complexes. This eventually results in an increased mesangial cell proliferation, inflammatory responses, and complement activation. Recent genome-wide association studies have identified several susceptibility genes, many of which support the 'multi-hit' concept. In light of these discoveries, it is astonishing that the vast majority of adult IgAN patients obviously do not need and/or benefit from immunosuppressive therapies in the first place. In fact, a number of supportive measures are highly effective in reducing the risk for disease progression in many patients. These measures need to be optimized before immunosuppression should be considered at all. In this review we focus on the underlying pathogenetic cornerstones and the central question of whether systemic inflammation in adult IgAN patients should be treated. Treatment options in children with IgAN are also discussed., Author(s): Thomas Rauen [sup.1] , Jürgen Floege [sup.1] Author Affiliations: (1) Division of Nephrology and Clinical Immunology, RWTH Aachen University, 0000 0001 0728 696X, grid.1957.a, , Pauwelsstr. 30, 52057, Aachen, [...]

Background Severe multilayering (ML) of the peritubular capillary basement membranes in kidney allografts is considered to be an ultrastructural hallmark of chronic antibody-mediated rejection (CAMR). We describe here the unexpected findings in a young male adolescent with underlying focal segmental glomerulosclerosis who underwent a living-related donor transplant procedure, a case which brought into question the specificity of ML. Methods The patient received a kidney from his mother, whose donor screening was unremarkable. He developed nephrotic-range proteinuria shortly after the procedure. Biopsies performed within the first 6 months after transplantation demonstrated ML (5-6 layers). Results Since there were no other criteria for CAMR, electron microscopic analysis of the baseline biopsy was performed, which in retrospect also demonstrated ML. The donor is still asymptomatic after 7 years of follow-up, with normal renal function and no proteinuria. Conclusions We discuss the phenomenon of ML in renal disease and together with the findings in our case would like to draw attention to the fact that ML in the setting of renal transplantation is not specific to CAMR, as it can exist in several kidney diseases and even in asymptomatic donors., Author(s): Diana Maria Lopategui [sup.1] [sup.2] , Evelyne Lerut [sup.3] , Maarten Naesens [sup.4] [sup.5] , Rita Van Damme-Lombaerts [sup.2] , Elena Levtchenko [sup.2] , Noël Knops [sup.2] Author Affiliations: [...]

Histopathology is still an indispensable tool for the diagnosis of kidney transplant dysfunction in adult and pediatric patients. This review presents consolidated knowledge, recent developments and future prospects on the biopsy procedure, the diagnostic work-up, classification schemes, the histopathology of rejection, including antibody-mediated forms, ABO-incompatible transplants, protocol biopsies, recurrent and de novo disease, post-transplant lymphoproliferative disorder, infectious complications and drug-induced toxicity. It is acknowledged that frequently the correct diagnosis can only be reached in consensus with clinical, serological, immunogenetical, bacteriological and virological findings. This review shall enhance the understanding of the pediatric nephrologist for the thought processes of nephropathologists with the aim to facilitate teamwork between these specialist groups for the benefit of the patient., Author(s): Jan U. Becker [sup.1] Author Affiliations: (1) 0000 0000 8852 305Xgrid.411097.aInstitute of Pathology, University Hospital of Cologne, Kerpener Straße 62, 50937, Cologne, Germany Introduction The renal biopsy remains an [...]

Retransplantation accounts for approximately 15 % of the annual transplants performed in the USA, and in the recent International Collaborative Transplant Study report on pediatric patients 15.2 % of the 9209 patients included in the report were retransplant recipients. Although the significant advances in clinical management and newer immunosuppressive agents have had a significant impact on improving short-term allograft function, it is apparent that long-term allograft function remains suboptimal. Therefore, it is likely that the majority of pediatric renal allograft recipients will require one or more retransplants during their lifetime. Unfortunately, a second or subsequent graft in pediatric recipients has inferior long-term graft survival rates compared to initial grafts, with decreasing rates with each subsequent graft. Multiple issues influence the outcome of retransplantation, with the most significant being the cause of the prior transplant failure. Non-adherence-associated graft loss poses unresolved ethical issues that may impact access to retransplantation. Graft nephrectomy prior to retransplantation may benefit selected patients, but the impact of an in situ failed graft on the development of panel-reactive antibodies remains to be definitively determined. It is important that these and other factors discussed in this review be taken into consideration during the counseling of families on the optimal approach for their child who requires a retransplant., Author(s): Rebecca C. Graves[sup.1] , Richard N. Fine[sup.2] [sup.3] Author Affiliations: (1) Pediatric Residency Program, Los Angeles County + University of Southern California (LAC+USC) Medical Center, Los Angeles, CAUSA (2) [...]

ABO-compatible as well as ABO-incompatible kidney transplantation are well established in the pediatric population. There are particularities in the histopathological evaluation of pediatric kidney transplant biopsies as for example the recurrence of certain diseases different from the adult population. Furthermore, the challenging transition of pediatric renal transplant recipients to adulthood is associated with an increased rate of non-adherence triggered rejection episodes. With modern immunosuppressive drugs, T-cell-mediated rejection of renal allografts is well controlled. In contrast, antibody-mediated rejection (AMR) is increasingly recognized as one of the major reasons for allograft loss. However, the 2001 diagnostic Banff criteria for antibody-mediated rejection require further refinement, as the morphological spectrum of AMR expands while effective therapeutic strategies are lacking. For example, endarteritis, which traditionally has been attributed to T-cell-mediated rejection, has recently been shown to be part of the AMR spectrum in some cases. Many findings in transplant renal biopsies are not specific for a certain disease but need consideration of differential diagnoses. To use the term 'chronic allograft nephropathy' as a diagnostic entity is no longer appropriate. Therefore, the precise identification of specific diseases is paramount in the assessment of transplant renal biopsies in order to enable tailored therapeutic management. Keywords Kidney transplantation * Acute rejection * Chronic rejection * Donor-specific antibodies * Endarteritis * Allograft loss * Banff classification, Introduction Since 1995, the 5-year kidney graft survival has not substantially increased and currently, estimated graft survival probabilities are reported to be approx. 84 and 78 % for the first [...]

Invasive pneumococcal disease (IPD), such as meningitis, sepsis, and empyema, substantially contributes to illness and death in children (1,2). After increasing numbers of cases caused by penicillin (PEN)-resistant Streptococcus pneumoniae [...]

An effective treatment for children with refractory nephrotic syndrome (NS), especially in those with cyclosporine (CsA)-resistant or CsA-intolerant NS, has yet to be established. Recently, the efficacy of multidrug therapy consisting of tacrolimus (Tac), mycophenolate mofetil (MMF) in combination with prednisolone (PDN) in adult patients with refractory NS has been reported. We successfully treated 14 consecutive children with refractory CsA-resistant or CsA-intolerant NS using combination therapy consisting of relatively low-dose Tac, mizoribine (MZR), which has a mechanism of action very similar to that of MMF, and PDN. There were no serious clinical toxicities. Of the 14 children, 9 with a mean age of 13.0 years had steroid-dependent NS (SDNS) and 5 with a mean age of 9.6 years had steroid-resistant NS (SRNS). All SDNS patients had minimal change disease (MCD), 4 with SRNS had focal segmental glomerulosclerosis (FSGS), and the remaining child had MCD on renal biopsy. All patients were in a prospective cohort, but were evaluated retrospectively. The mean follow-up from the initiation of multidrug therapy was 18.4 months in SDNS and 18.6 months in SRNS patients. At the last observation point, the calculated relapse rate and minimum dose of PDN required for maintenance of clinical remission after the start of multidrug therapy were significantly decreased compared with those prior to this therapy, while on CsA, in SDNS patients (0.4 [+ or -] 0.5 times/year vs 2.9 [+ or -] 1.5 times/year, P=0.0077, and 0.3 [+ or -] 0.2 mg/kg on alternate days vs 0.5 [+ or -] 0.2 mg/kg on alternate days, P=0.0184 respectively). All SDNS and two SRNS patients (40%) achieved complete remission, allowing further decreases in the minimal doses of PDN required for maintenance of clinical remission in most our patients. However, one patient with FSGS remained refractory to multidrug therapy and subsequently developed end-stage renal disease. These clinical observations, although preliminary and involving a small number of patients, suggest that multidrug therapy consisting of relatively low-dose Tac, MZR, and PDN might be effective and safe for treating children with refractory CsA-resistant or CsA-intolerant NS. However, further studies involving larger numbers of patients are needed. Keywords Cyclosporine-intolerant * Cyclosporine-resistant * Mizoribine * Multidrug therapy * Refractory nephrotic syndrome * Tacrolimus, Introduction Since cyclosporine A (CsA) is reportedly effective for pediatric patients with refractory nephrotic syndrome (NS), of both the steroid-dependent relapsing (SDNS) and steroid-resistant (SRNS) type, CsA may now serve [...]

We describe the clinical aspects of pandemic (H1N1) 2009 virus infection in children who developed spontaneous pneumomediastinum (1) or plastic bronchitis (2). In Mexico, 18 persons, including 5 children, had [...]

Fabry disease is an X-linked lysosomal storage disorder caused by mutations of the GLA gene and deficiency in α-galactosidase A activity. Glycosphingolipids accumulation causes renal injury that manifests early during childhood as tubular dysfunction and later in adulthood as proteinuria and renal insufficiency. Nephrotic syndrome as the first evidence of Fabry-related kidney damage is rare. We report the case of a teenager with known Fabry disease and normal renal function who developed acute nephrotic syndrome. He was found to have typical glycosphingolipids accumulation with no other findings suggestive of alternative causes of nephrotic syndrome on kidney biopsy. After treatment with enzyme replacement therapy and oral steroids, he went into complete remission from nephrotic syndrome, a response that is atypical for Fabry disease patients who develop heavy proteinuria as a result of longstanding disease and chronic renal injury. The nephrotic syndrome in this patient appears to have developed secondary to minimal change disease. We recommend considering immunotherapy in addition to enzyme replacement therapy in those patients with confirmed Fabry disease and acute nephrotic syndrome with clinical and microscopic findings suggestive of minimal change disease. Keywords Fabry disease * Nephrotic syndrome * Proteinuria * Prednisone * Enzyme replacement therapy * Minimal change disease, Introduction Fabry disease (Anderson-Fabry disease, OMIM 301500) is an X-linked lysosomal storage disorder caused by a deficiency in α-galactosidase A. Children usually develop pain, hypohydrosis, postprandial diarrhea, abdominal pain, nausea, [...]

The explosion of new discoveries in the field of immunology has provided new insights into mechanisms that promote an immune response directed against a transplanted organ. Central to the allograft response are T lymphocytes. This review summarizes the current literature on allorecognition, costimulation, memory T cells, T cell migration, and their role in both acute and chronic graft destruction. An in depth understanding of the cellular mechanisms that result in both acute and chronic allograft rejection will provide new strategies and targeted therapeutics capable of inducing long-lasting, allograft-specific tolerance., Author(s): Elizabeth Ingulli [sup.1] [sup.2] Author Affiliations: (1) grid.266100.3, 0000000121074242, Department of Pediatrics, University of California, , San Diego, CA, USA (2) grid.266100.3, 0000000121074242, University of California, San Diego, , [...]

The explosion of new discoveries in the field of immunology has provided new insights into mechanisms that promote an immune response directed against a transplanted organ. Central to the allograft response are T lymphocytes. This review summarizes the current literature on allorecognition, costimulation, memory T cells, T cell migration, and their role in both acute and chronic graft destruction. An in depth understanding of the cellular mechanisms that result in both acute and chronic allograft rejection will provide new strategies and targeted therapeutics capable of inducing long-lasting, allograft-specific tolerance. Keywords Allograft * Children * Rejection * Tlymphocytes * Transplantation, Introduction Transplantation of solid organs has emerged as a viable therapeutic modality for the treatment of a variety of ailments, such as end stage renal disease. Acute allograft rejection is [...]

Egg activation, which is the first step in the initiation of embryo development, involves both completion of meiosis and progression into mitotic cycles. In mammals, the fertilizing sperm delivers the activating signal, which consists of oscillations in free cytosolic [Ca.sup.2+] concentration ([[[Ca.sup.2+]].sub.i]). Intracytoplasmic sperm injection (ICSI) is a technique that in vitro fertilization clinics use to treat a myriad of male factor infertility cases. Importantly, some patients who repeatedly fail ICSI also fail to induce egg activation and are, therefore, sterile. Here, we have found that sperm from patients who repeatedly failed ICSI were unable to induce [[[Ca.sup.2+]].sub.i] oscillations in mouse eggs. We have also shown that PLC, zeta 1 (PLCZ1), the sperm protein thought to induce [[[Ca.sup.2+]].sub.i] oscillations, was localized to the equatorial region of wild-type sperm heads but was undetectable in sperm from patients who had failed ICSI. The absence of PLCZ1 in these patients was further confirmed by Western blot, although genomic sequencing failed to reveal conclusive PLCZ1 mutations. Using mouse eggs, we reproduced the failure of sperm from these patients to induce egg activation and rescued it by injection of mouse Plcz1 mRNA. Together, our results indicate that the inability of human sperm to initiate [[[Ca.sup.2+]].sub.i] oscillations leads to failure of egg activation and sterility and that abnormal PLCZ1 expression underlies this functional defect., Introduction After the luteinizing hormone surge, fully grown mammalian oocytes resume meiosis and undergo maturation, advancing to the second meiotic metaphase (MII), where exit from meiosis is halted. Following ovulation, [...]

Lung transplantation is now a viable therapeutic option in the care of patients with advanced pulmonary parenchymal or pulmonary vascular disease. Lung transplantation, however, with chronic posttransplant immunosuppression, creates a [...]

Abstract Mutations in the NPHS2 gene, which encodes podocin, are associated with steroid-resistant nephrotic syndrome in childhood. Renal histology frequently presents focal segmental glomerulosclerosis (FSGS). Post-transplant recurrence of proteinuria in [...]

Abstract Updated guidelines on the diagnosis of acute allograft rejection including criteria for biopsy specimen adequacy were published in 1999. We sought to determine the adequacy of specimens in paediatric [...]

Abstract Background: End-stage renal disease (ESRD) is associated with moderately severe hyperhomocysteinemia that is incompletely normalized by oral folic acid therapy and vitamin [B.sub.12]. Method: We administered 1 mg hydroxocobalamin [...]

Lankat-Buttgereit, Brigittte, and Robert Tampe. The Transporter Associated With Antigen Processing: Function and Implications in Human Diseases. Physiol Rev 82: 187-204, 2002; 10.1152/physrev.00025.2001.--The adaptive immune systems have evolved to protect [...]

To the Editor: In the late 1990s, triple-reassortant influenza A viruses containing genes from avian, human, and swine influenza viruses emerged and became enzootic in swine herds in North America [...]

Byline: A. Köksal, I. Kalkan, S. Torun, M. Yüksel, R. Ökten, E. Kayacetin Sir, Herein, we report the first case of lymphoma causing isolated splenic vein thrombosis (SVT) and splenic [...]

Author(s): Michelle R. Denburg[sup.1] , Lea F. Surrey[sup.1] , Bruce R. Pawel[sup.1] , Bernard S. Kaplan[sup.1] Author Affiliations: (1) The Children's Hospital of Philadelphia, Perelman School of Medicine at the [...]

* Context.--Nodular, intercapillary glomerulosclerotic lesions resembling Kimmelstiel-Wilson nodules commonly observed in diabetic nephropathy can also be seen in patients without any clinical history or evidence of diabetes. Objectives.--To discuss the pathobiology of lesions reminiscent of diabetes nephropathy, including light-chain deposition disease, amyloidosis, immunotactoid nephropathy, the membranoproliferative form of glomerulonephritis, and idiopathic nodular glomerulosclerosis, and how to differentiate them from diabetic nephropathy. Data Sources.--Published literature and authors' personal experience. Conclusions.--The well-formed, intercapillary, nodular mesangial lesions, along with thickened glomerular basement membranes and tubular basement membranes, and hyaline arteriolosclerosis are virtually pathognomic of diabetic nephropathy. However, the pathologist must exclude lesions reminiscent of diabetic nephropathy by performing special stains on histologic sections, immunofluorescence, and electron microscopic studies. (Arch Pathol Lab Med. 2013;137:351-359; doi: 10.5858/arpa.2012-0243-RA), Diabetic nephropathy is a long-term, insidious complication of diabetes mellitus. It is characterized clinically by the onset of microalbuminuria, progressing to overt nephrotic-range proteinuria, and a steady decline in the [...]

Byline: M. Shamsi, K. Kumar, R. Dada Genetic factors contribute upto 15%-30% cases of male infertility. Formation of spermatozoa occurs in a sequential manner with mitotic, meiotic, and postmeiotic differentiation [...]

Context.--Most renal diseases with organized deposits are relatively uncommon conditions, and proper pathologic characterization determines the specific diagnosis. Different entities with specific clinical correlates have been recognized, and their correct diagnosis has an impact on patient management, treatment options, and determination of prognosis. Objective.--The diagnosis of these conditions depends on careful evaluation of the findings by light microscopy together with immunofluorescence and electron microscopy. The objective of this manuscript is to delineate an algorithmic approach helpful in the pathologic assessment of these conditions at the light microscopic level. In some diseases, the immunomorphologic parameters short of electron microscopy provide solid information to suggest or make a definitive diagnosis. Nevertheless, electron microscopy plays a crucial role, because the criteria to separate these entities often are heavily influenced by the electron microscopic findings. Accepted diagnostic criteria for each of these conditions are discussed. Design.--Information used for this manuscript is gathered from published data and the authors' experience. Results.--The most common of these conditions is amyloidosis, which may account for as many as 5% to 8% of all renal biopsies in some renal pathology practices. Fibrillary, immunotactoid, and cryoglobulinemic glomerulopathies together represent, at most, 1% of all renal biopsies performed for medical renal diseases. Diabetic fibrillosis also is uncommon. Glomerulopathies associated with fibronectin deposits and collagenofibrotic glomerulopathy are extremely rare. Conclusions.--A systematic, algorithmic approach to the evaluation of the renal biopsies from patients with these disorders is very helpful to rule out certain conditions in the early stages of the evaluation of the biopsies. However, it is not uncommon for the final definitive diagnosis to be reached only after electron microscopic evaluation. (Arch Pathol Lab Med. 2010;134:512-531), Evaluation of renal diseases with organized deposits requires a careful integration of information emanating from a number of sources (Figure 1). Clinical history and pertinent laboratory data may provide useful [...]