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Ahmed Fathi Elkeraie,1 Saeed Al-Ghamdi,2 Ali K Abu-Alfa,3 Torki Alotaibi,4 Ali Jasim AlSaedi,5 Abdulkareem AlSuwaida,6 Mustafa Arici,7 Tevfik Ecder,8 Mohammad Ghnaimat,9 Mohamed Hany Hafez,10 Mohamed H Hassan,11 Tarik Sqalli12 1Department of Internal Medicine and Nephrology, Alexandria University, Alexandria, Egypt; 2Department of Medicine, College of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; 3Department of Internal Medicine, Division of Nephrology and Hypertension, American University of Beirut, Beirut, Lebanon; 4Transplant Nephrology, Hamed Al-Essa Organ Transplant Center, Sabah Health Region, Kuwait City, Kuwait; 5Department of Nephrology, College of Medicine, University of Baghdad, Nephrology and Transplantation Center, Medical City Complex, Baghdad, Iraq; 6Department of Medicine, King Saud University, Riyadh, Saudi Arabia; 7Department of Nephrology, Faculty of Medicine, Hacettepe University, Altındağ, Ankara, Turkey; 8Department of Medicine, Istinye University; Division of Nephrology, Topkapı, Istanbul, Turkey; 9Department of Nephrology, Specialty Hospital, Jaber Ibn Hayyan St. Shmeisani, Amman, Jordan; 10Department of Nephrology and Medicine, Cairo University, Cairo, Egypt; 11Department of Medicine, Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates; 12Department of Nephrology, Moroccan Society of Nephrology, Casablanca, MoroccoCorrespondence: Ahmed Fathi Elkeraie, Department of Internal Medicine and Nephrology Alexandria University, Alexandria, Egypt, Email drahmed@hotmail.comAbstract: Chronic kidney disease (CKD) is a major public health concern in the Middle East and Africa (MEA) region and a leading cause of death in patients with type 2 diabetes mellitus (T2DM) and hypertension. Early initiation of sodium-glucose cotransporter - 2 inhibitors (SGLT-2i) and proper sequencing with renin-angiotensin-aldosterone system inhibitors (RAASi) in these patients may result in better clinical outcomes due to their cardioprotective properties and complementary mechanisms of action. In this review, we present guideline-based consensus recommendations by experts from the MEA region, as practical algorithms for screening, early detection, nephrology referral, and treatment pathways for CKD management in patients with hypertension and diabetes mellitus. This study will help physicians take timely and appropriate actions to provide better care to patients with CKD or those at high risk of CKD.Keywords: chronic kidney disease, nephrology referral, screening, sodium-glucose cotransporter-2 inhibitors

Peritoneal dialysis-associated peritonitis from such resistant organisms as vancomycin-resistant enterococci increasingly is occurring and is challenging to treat. We describe 2 cases of vancomycin-resistant entercoccus peritonitis successfully treated with intraperitoneal daptomycin. Both patients were on automated peritoneal dialysis therapy with culture-positive vancomycin-resistant Enterococcus faecium peritonitis and were treated with 10 to 14 days of intraperitoneal daptomycin given every 4 hours through manual peritoneal dialysate exchanges. Despite the known degradation in dextrose solutions, intraperitoneal daptomycin was effective in clearing both infections. Neither patient experienced a relapse or repeated peritonitis. Additional studies of dosing and pharmacokinetics of intraperitoneal daptomycin in the treatment of patients with vancomycin-resistant enterococcus peritonitis are needed. Copyright © 2009 National Kidney Foundation, Inc. [ABSTRACT FROM AUTHOR]

Purpose of Review: Disasters, natural and man-made, are rising in frequency and pose significant challenges to the provision of renal care worldwide. Patients with kidney disease, particularly those on dialysis, are extremely vulnerable during disasters. This timely review summarizes the potential roles international renal disaster preparedness working groups have in addressing these challenges., Recent Findings: The vulnerability of kidney patients has galvanized the evolution of global response mechanisms and the contemporary efforts of various organizations. In this review, the importance of preparedness, networking, and collaborations at all levels are highlighted, citing recent crises. It will also note key areas for improvement, including an enhanced engagement with global health organizations. Finally, it is imperative to urge the international community to recognize that individuals with kidney disease are often among the first patient groups to suffer in disaster zones. These messages are intended to persuade global stakeholders that kidney patients, including pediatric ones, should be prioritized as requiring immediate support during disasters., Summary: The unique and life-threatening challenges faced by individuals with kidney disease in natural disaster- or war-torn areas demand special consideration in humanitarian efforts and international crisis response strategies. International organizations can play a major role in this regard., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Lanthanum carbonate (LC) is a phosphate binder used in end-stage renal disease (ESRD) with few adverse effects due to poor systemic absorption. Gastrointestinal deposition is likely due to alterations in epithelial permeability from inflammation in ESRD. It is challenging to detect in cases with minimal deposition and may be missed on endoscopy and biopsy. A 36-year-old with ESRD who was evaluated for gastrectomy was found to have LC deposition histologically. Years later, the excised portion had similar findings. This case allows for evaluation of LC gastropathy in a resection specimen, providing the opportunity to showcase its unique pathology features.

The highest financial and symptom burdens and the lowest health-related quality-of-life scores are seen in people with kidney failure. A total of 11 countries in the International Society of Nephrology (ISN) Middle East region responded to the ISN-Global Kidney Health Atlas. The prevalence of chronic kidney disease (CKD) in the region ranged from 4.9% in Yemen to 12.2% in Lebanon, whereas prevalence of kidney failure treated with dialysis or transplantation ranged from 152 per million population (pmp) in the United Arab Emirates to 869 pmp in Kuwait. Overall, the incidence of kidney transplantation was highest in Saudi Arabia (20.2 pmp) and was lowest in Oman (2.2 pmp). Chronic hemodialysis (HD) and peritoneal dialysis (PD) services were available in all countries, whereas kidney transplantation was available in most countries of the region. Public government funding that makes acute dialysis, chronic HD, chronic PD, and kidney transplantation medications free at the point of delivery was available in 54.5%, 72.7%, 54.5%, and 54.5% of countries, respectively. Conservative kidney management was available in 45% of countries. Only Oman had a CKD registry; 7 countries (64%) had dialysis registries, and 8 (73%) had kidney transplantation registries. The ISN Middle East region has a high burden of kidney disease and multiple challenges to overcome. Prevention and detection of kidney disease can be improved by the design of tailored guidelines, allocation of additional resources, improvement of early detection at all levels of care, and implementation of sustainable health information systems., (© 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Objective: To describe the clinical, endoscopic, histologic, and treatment outcomes of Helicobacter heilmannii (H. heilmannii) associated gastritis in children in the New England region of the United States., Methods: Retrospective study of children (1-18 years) with H. heilmannii identified on gastric mucosal biopsies from two pediatric centers over a 21-year period, January 2000-December 2021. Cases were identified by querying pathology databases at each institution. Demographic and clinical data were obtained from the medical record. Endoscopic and histologic findings were extracted from endoscopy and pathology reports, respectively., Results: Thirty-eight children were diagnosed with H. heilmannii-associated gastritis during the study period. The mean age at diagnosis was 10.1 ± 5.3 years, and 25/38 (66%) cases were male. Abdominal pain (32%) and nausea with or without vomiting (26%) were the most common symptoms. Thirty-two children (84%) had endoscopic findings including gastric nodularity (55%) and erythema (26%). All children had histologic signs of chronic gastritis, including those with normal endoscopic exams. Antibiotic regimens used for treating Helicobacter pylori were frequently prescribed. Of the 17 children who underwent a follow-up endoscopy (range 2-68 months), 15 (88%) did not have H. heilmannii identified on gastric biopsies., Conclusion: H. heilmannii was an infrequent but potential cause of epigastric abdominal pain and nausea in our cohort of New England children. While morphologically distinct from H. pylori, the bacteria can result in similar endoscopic and histologic findings of nodularity and chronic gastritis, respectively. The rate of eradication, as assessed by histology following treatment with H. pylori therapies, was below the 90% recommended goal for antimicrobial therapies., (© 2023 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Purpose: Biobanking helps source tissue and blood for studying cancer genomics. Access to biorepository resources in low- and middle-income countries is lacking. Memorial Sloan Kettering Cancer Center (MSK) and the American University of Beirut (AUB) established a joint tissue biorepository at AUB in Beirut, Lebanon. The undertaking encountered key challenges that were unanticipated., Materials and Methods: Patients age 18 years or older were eligible for enrollment at AUB. After consent, biospecimens were obtained at the time of routine diagnostic and/or therapeutic interventions. Both normal and abnormal tissue and solid and/or liquid specimens were collected from varied body sites. Early on, declining consent was frequently observed, and this was highlighted for investigation to understand potential participants reasoning., Results: Of 850 patients approached, 704 (70.8%) elected to consent and 293 (29.5%) declined participation. The number of declined consents led to an amendment permitting the documentation of reasons for same. Of 100 potential participants who declined to consent and to whom outreach was undertaken, 63% indicated lack of research awareness and 27% deferral to their primary physician or family member. A financial gain for AUB was cited as concern by 5%, cultural boundaries in 4%, and 1% expressed concern about confidentiality. Of the patients who elected to consent, 682 biospecimens were procured., Conclusion: The AUB-MSK biospecimen repository has provided a unique resource for interrogation. Patient participation rate was high, and analyses of those who elected not to consent (29%) provide important insights into educational need and the local and cultural awareness and norms.

Background: The Food and Drug Administration (FDA)-approved submucosal injection of lifting agents such as ORISE ® has become a widespread, routine and standard practice in endoscopic mucosal resection and endoscopic submucosal dissection of gastrointestinal lesions. Lifting agent granulomas result from transformation of injected material into a mass-forming amorphous hyaline-like material eliciting a strong foreign body giant cell reaction. This report of three cases shows how lifting agent granulomas can act as potential clinical and gross mimickers of invasive adenocarcinoma., Cases Description: Three cases were identified in a six-month span based on the histological presence of a lifting agent granuloma in a colonic/colorectal resection specimen with associated clinical, imaging and gross concern for invasive malignancy. Each case resulted in an escalation of clinical and surgical management due to the suspicion of an unresectable neoplastic process that was at least partially involved by an exuberant granulomatous reaction due to the utilization of a lifting agent. Colonic transmural involvement and sub-serosal vascular infiltration by the granulomas are described., Conclusions: Lifting agent granulomas have become a routine endoscopic technique to help achieve full resection of flat/sessile colorectal polyps and early-stage cancers. This report confirms that these granulomas exhibit colonic transmural involvement. Sub-serosal blood vessel involvement is reported for the first time. It is important to recognize the unique characteristics of these new synthetic lifting agents. Their propensity to develop a mass-forming granulomatous reaction has the potential to mimic invasive adenocarcinoma clinically, radiologically and pathologically. This can significantly impact patient care and management both clinically and surgically., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://acr.amegroups.com/article/view/10.21037/acr-22-59/coif). The authors have no conflicts of interest to declare., (2023 AME Case Reports. All rights reserved.)

Type 2 diabetes (T2D) is a global health problem accompanied by an elevated risk of complications, the most common being cardiac and renal diseases. In Lebanon, the prevalence of T2D is estimated at 8-13%. Local medical practice generally suffers from clinical inertia, with gaps in the yearly assessment of clinical manifestations and suboptimal screening for major complications. The joint statement presented here, endorsed by five Lebanese scientific medical societies, aims at providing physicians in Lebanon with a tool for early, effective, and comprehensive care of patients with T2D. Findings from major randomized clinical trials of antidiabetic medications with cardio-renal benefits are presented, together with recommendations from international medical societies. Optimal care should be multidisciplinary and should include a multifactorial risk assessment, lifestyle modifications, and a regular evaluation of risks, including the risks for cardiovascular (CV) and renal complications. With international guidelines supporting a shift in T2D management from glucose-lowering agents to disease-modifying drugs, the present statement recommends treatment initiation with metformin, followed by the addition of sodium-glucose cotransporter 2 inhibitors or glucagon-like peptide-1 receptor agonists due to their CV and renal protection properties, whenever possible. In addition to the selection of the most appropriate pharmacological therapy, efforts should be made to provide continuous education to patients about their disease, with the aim to achieve a patient-centered approach and to foster self-management and adherence to the medical plan. Increasing the level of patient engagement is expected to be associated with favorable health outcomes. Finally, this statement recommends setting an achievable individualized management plan and conducting regular follow-ups to monitor the patients' glycemic status and assess their risks every 3-6 months., (© 2022. The Author(s).)

Kidney failure is the permanent impairment of kidney function associated with increased morbidity, hospitalization, and requirement for kidney replacement therapy. A total of 11 countries in the Middle East region (84.6%) responded to the survey. The prevalence of chronic kidney disease in the region ranged from 5.2% to 10.6%, whereas prevalence of treated kidney failure ranged from 152 to 826 per million population. Overall, the incidence of kidney transplantation was highest in Iran (30.9 per million population) and lowest in Oman and the United Arab Emirates (2.2 and 3.0 per million population, respectively). Long-term hemodialysis services were available in all countries, long-term peritoneal dialysis services were available in 9 (69.2%) countries, and transplantation services were available in most countries of the region. Public funding covered the costs of nondialysis chronic kidney disease care in two-thirds of countries, and kidney replacement therapy in nearly all countries. More than half of the countries had dialysis registries; however, national noncommunicable disease strategies were lacking in most countries. The Middle East is a region with high burden of kidney disease and needs cost-effective measures through effective health care funding to be available to improve kidney care in the region. Furthermore, well-designed and sustainable health information systems are needed in the region to address current gaps in kidney care in the region., (© 2021 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Collagenofibrotic glomerulopathy (CG) is a rare disease characterized by the deposition of collagen type 3 fibrils in the glomeruli. Patients may have proteinuria, hematuria, and/or renal dysfunction. CG is considered a progressive disease with variable rates of progression. The definitive diagnosis is made by electron microscopy with the presence of characteristic subendothelial and mesangial curved, comma-like, banded collagen type 3 fibers of 40-65 nm periodicity. We are reporting the first case of CG in a kidney transplant recipient with kidney disease of unknown cause., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Competing Interests: The author has nothing to disclose.

Achievement of equity in health requires development of a health system in which everyone has a fair opportunity to attain their full health potential. The current, large country-level variation in the reported incidence and prevalence of treated end-stage kidney disease indicates the existence of system-level inequities. Equitable implementation of kidney replacement therapy (KRT) programs must address issues of availability, affordability, and acceptability. The major structural factors that impact equity in KRT in different countries are the organization of health systems, overall health care spending, funding and delivery models, and nature of KRT prioritization (transplantation, hemodialysis or peritoneal dialysis, and conservative care). Implementation of KRT programs has the potential to exacerbate inequity unless equity is deliberately addressed. In this review, we summarize discussions on equitable provision of KRT in low- and middle-income countries and suggest areas for future research., (© 2020 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Secular increases in the burden of kidney failure is a major challenge for health systems worldwide, especially in low- and middle-income countries (LMICs) due to growing demand for expensive kidney replacement therapies. In LMICs with limited resources, the priority of providing kidney replacement therapies must be weighed against the prevention and treatment of chronic kidney disease, other kidney disorders such as acute kidney injury, and other noncommunicable diseases, as well as other urgent public health needs. Kidney failure is potentially preventable-not just through primary prevention of risk factors for kidney disease such as hypertension and diabetes, but also by timely management of established chronic kidney disease. Among people with established or incipient kidney failure, there are 3 key treatment strategies-conservative care, kidney transplantation, and dialysis-each of which has its own benefits. Joining up preventive care for people with or at risk for milder forms of chronic kidney disease with all 3 therapies for kidney failure (and developing synergistic links between the different treatment options) is termed "integrated kidney care" and has potential benefits for patients, families, and providers. In addition, because integrated kidney care implicitly considers resource use, it should facilitate a more sustainable approach to managing kidney failure than providing one or more of its components separately. There is currently no agreed framework that LMIC governments can use to establish and/or scale up programs to prevent and treat kidney failure or join up these programs to provide integrated kidney care. This review presents a suggested framework for establishing integrated kidney care programs, focusing on the anticipated needs of policy makers in LMICs., (© 2020 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Cinacalcet is an effective and safe alternative to parathyroidectomy in end stage renal disease (ESRD) patients with secondary hyperparathyroidism. Hypocalcemia is a known complication of treatment that is usually readily reversible upon discontinuation of the drug. It rarely manifests severely and symptomatically requiring hospital admission. We present the case of a 55 year old man with severe, symptomatic and prolonged hypocalcemia that occurred 2 weeks after starting cinacalcet. Cinacalcet induced a state of pharmacological parathyroidectomy with subsequent hungry bone syndrome. Serum calcium returned to normal range after 4 weeks of stopping the drug while receiving high doses of elemental calcium and vitamin D receptor activation therapy (VDRA).

Objective: To compare and contrast three databases, that is, The International Centre for Nephrogenic Systemic Fibrosis Registry (ICNSFR), the Food and Drug Administration Adverse Event Reporting System (FAERS) and a legal data set, through pharmacovigilance and to evaluate international nephrogenic systemic fibrosis (NSF) safety efforts., Methods: The Research on Adverse Drug events And Reports methodology was used for assessment-the FAERS (through June 2009), ICNSFR and the legal data set (January 2002 to December 2010). Safety information was obtained from the European Medicines Agency, the Danish Medicine Agency and the Food and Drug Administration., Results: The FAERS encompassed the largest number (n = 1395) of NSF reports. The ICNSFR contained the most complete (n = 335, 100%) histopathological data. A total of 382 individual biopsy-proven, product-specific NSF cases were analysed from the legal data set. 76.2% (291/382) identified exposure to gadodiamide, of which 67.7% (197/291) were unconfounded. Additionally, 40.1% (153/382) of cases involved gadopentetate dimeglumine, of which 48.4% (74/153) were unconfounded, while gadoversetamide was identified in 7.3% (28/382) of which 28.6% (8/28) were unconfounded. Some cases involved gadobenate dimeglumine or gadoteridol, 5.8% (22/382), all of which were confounded. The mean number of exposures to gadolinium-based contrast agents (GBCAs) was gadodiamide (3), gadopentetate dimeglumine (5) and gadoversetamide (2). Of the 279 unconfounded cases, all involved a linear-structured GBCA. 205 (73.5%) were a non-ionic GBCA while 74 (26.5%) were an ionic GBCA., Conclusion: Clinical and legal databases exhibit unique characteristics that prove complementary in safety evaluations. Use of the legal data set allowed the identification of the most commonly implicated GBCA., Advances in Knowledge: This article is the first to demonstrate explicitly the utility of a legal data set to pharmacovigilance research.

Background: Nephrogenic systemic fibrosis is a fibrosing disorder associated with exposure to gadolinium-based contrast agents in people with severely compromised renal function., Objective: The purpose of this study was to determine the reported number of cases of nephrogenic systemic fibrosis in children using three distinct publicly available data sources., Materials and Methods: We conducted systematic searches of the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS), the International Center for Nephrogenic Systemic Fibrosis Research (ICNSFR) registry and published literature from January 1997 through September 2012. We contacted authors of individual published cases to obtain follow-up data. Data sets were cross-referenced to eliminate duplicate reporting., Results: We identified 23 children with nephrogenic systemic fibrosis. Seventeen had documented exposure to gadolinium-based contrast agents. Six children had been reported in both the FAERS and the literature, four in the FAERS and the ICNSFR registry and five in all three data sources., Conclusion: Nephrogenic systemic fibrosis has been rarely reported in children. Although rules related to confidentiality limit the ability to reconcile reports, active pharmaco-vigilance using RADAR (Research on Adverse Drug events And Reports) methodology helped in establishing the number of individual pediatric cases within the three major data sources.

Lichen planus (LP) affects mucocutaneous surfaces and is characterized by intraepithelial and lamina propria lymphocytosis and squamous cell apoptosis (Civatte bodies). Lichen planus esophagitis (LPE) is underrecognized; concurrent cutaneous disease is present in some patients, but LPE alone is more common. We diagnose patients with characteristic pathologic findings of LPE and known correlation with skin disease or immunofluorescence (IF) results as LPE but use descriptive terminology ("lichenoid esophagitis pattern" [LEP]) when confirmation is unavailable. We reviewed clinicopathologic features of patients diagnosed at our institution with LPE or LEP. There were 88 specimens with LPE or LEP from 65 patients. Most patients were female. Seventeen patients had LPE confirmed by IF. Five patients had both esophageal (1 with IF) and skin LP. Strictures were a prominent presenting feature in LPE patients, with disease distribution more frequent in the upper and lower esophagus. Dysphagia was a common reason for endoscopy in LEP patients. Rheumatologic diseases are more common in patients with LPE compared with LEP. Viral hepatitides and human immunodeficiency virus (HIV) infections are associated with LEP. We defined polypharmacy as patients taking >3 medications; this finding was present in both LPE and LEP cohorts; however, this is a prominent feature in those with established LPE. Progression to dysplasia was noted in both cohorts. About 5% of LPE patients have tandem skin manifestations. LPE is more likely than LEP to arise in women, result in stricture formation, and be associated with rheumatologic disorders and polypharmacy, whereas LEP is associated with viral hepatitis and HIV. Both can progress to neoplasia. As the risk of stricture formation is high in patients with LPE, it is worth performing pertinent IF studies to confirm LPE, although knowledge of the clinical association of LEP with viral hepatitis, HIV, and use of multiple medications is of value in daily practice.

Increasing evidence nowadays is showing that obesity by itself, independent of other comorbidities like diabetes and hypertension, is associated with renal functional changes and structural damage. Intentional weight loss demonstrates beneficial reduction in proteinuria and albuminuria in patients with mild to moderate chronic kidney disease, particularly those whose renal damage is likely induced by obesity. The safety of some weight loss interventions, particularly the use of high-protein diets and/or medications, is questionable in this population due to the lack of well-designed randomized controlled studies reporting on their efficacy or harm. Bariatric surgery showed the most promising results with regards to ameliorating glomerular hyperfiltration and albuminuria albeit with a modest risk of increased perioperative complications with advanced stages of chronic kidney disease (CKD).

Aims: Microcarcinoids refer to microscopic nests of monotonous cells with endocrine and squamoid features. Their peculiar morphology can appear infiltrative with a desmoplastic-like background, raising concerns for an infiltrating adenocarcinoma. To further characterise microcarcinoids, we undertook a prospective clinicopathological study., Methods: 11 specimens originating from five men and six women (average age=58.9 years) were prospectively collected from December 2004 to December 2011., Results: Microcarcinoids were most commonly identified in high-risk adenomas (size ≥10 mm (n=10), villous components (n=8) and/or high-grade dysplasia (n=4)). All polyps had mucosal prolapse and four displayed background fibrosis reminiscent of desmoplasia. The microcarcinoid component was most often multifocal (n=7) within the individual polyp and extended over an average length of 3.9 mm. The individual microcarcinoid cells were cuboidal with abundant eosinophilic cytoplasm. All cases had monotonous nuclei which lacked pleomorphism, hyperchromasia and mitotic activity. All available microcarcinoids were β-catenin and synaptophysin reactive and non-reactive for chromogranin and p53 with a negligible Ki-67 proliferation index (<2%). In addition, the microcarcinoids were variably reactive for p63 and/or CK 5/6, thereby demonstrating focal squamoid features. Two of the study cases were submitted with a concern for invasive carcinoma. Clinical information was available in 10 patients with up to 24 months of follow-up: all patients are alive and well and no subsequent malignancy has been reported., Conclusions: Awareness of this unique morphology is important to avoid overdiagnosing microcarcinoids as invasive adenocarcinoma. Moreover, this immunohistochemical panel can be helpful in discriminating microcarcinoids from its malignant mimic in challenging cases.

The strong association between nephrogenic systemic fibrosis (NSF) and exposure to gadolinium-based contrast agents (GBCAs) has greatly affected the care of patients with kidney disease. NSF has been reported in patients with ESRD, CKD, and acute kidney injury (AKI). The majority of cases have occurred in patients with ESRD, but about 20% have been reported in patients with AKI or CKD stages 4 and 5. There is also a risk difference among GBCAs, with the Food and Drug Administration contraindicating 3 linear agents in patients at risk. Given the significant morbidity and mortality of NSF, it is imperative to identify individuals at risk. Although there are no data to support a role for hemodialysis (HD) in reducing the risk for NSF after administration of GBCAs, immediate HD is still recommended within 2 hours. Patients maintained on peritoneal dialysis seem to be at high risk and immediate HD is also recommended. However, this is not the current recommendation for CKD stages 4 and 5, especially with suspected lower risk of noncontraindicated agents. Individualized assessment is important and especially in those patients close to dialysis initiation. Instituting policies is important to address the imaging needs of patients with CKD and AKI while ensuring a balance between benefits and risks., (Copyright © 2011 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Nephrogenic systemic fibrosis (NSF) is a rare fibrosing disorder described among patients with renal disease. Currently, no standard therapy exists, although therapeutic modalities have included plasmapheresis, extracorporeal photopheresis, sodium thiosulphate, imatinib and renal transplantation. We describe a patient with NSF who was physically debilitated and underwent renal transplantation. After transplantation, the patient's lesions improved clinically, and the patient was ambulatory. Despite developing worsening renal function, her lesions remained unchanged. We conclude that renal transplantation improves symptoms of NSF, and believe that in patients with NSF, careful consideration should be made for early renal transplantation.

Native kidney biopsy is still performed primarily with hospital inpatient observation period. Experience with outpatient Computed Tomographic (CT)-guided renal biopsy at Yale New Haven Medical Center was studied to assess efficacy and safety. A total of 146 outpatient native kidney biopsies were identified between 1995 and 2001. Records were reviewed for demographics, clinical, and laboratory data and details of the procedure. Time of admission to the outpatient unit, duration of procedure and post-biopsy observation period were recorded. Complications such as bleeding, infection, admission to the hospital, transfusion, or intervention for continued bleeding were noted. Mean age was 43.9 ± 14.9 years and mean serum creatinine was 1.8 ± 1.4 mg/dl. Renal size averaged 11.4 cm. Post-procedure observation time of 4 - 6 h appeared to be adequate. Diagnostic tissue was successfully sampled in 98.6% of cases. Procedure was well tolerated with no hemodynamically significant changes. Hematocrit and hemoglobin concentration changes averaged 3.6 ± 2.5% and 1.0 ± 0.9 mg/dl, respectively (p < 0.001). There were no instances of death or need for intervention. Transfusion was required in 1 patient while 6 patients had detectable bleeding and were hospitalized for observation. Outpatient CT-guided kidney biopsy provides adequate tissue and appears to be safe with very low complication rates.

Tumor lysis syndrome (TLS) describes a constellation of biochemical and clinical abnormalities resulting from rapid and massive tumor cell death. TLS is frequently associated with hyperuricemia, hyperkalemia, hyperphosphatemia, and secondary hypocalcemia that may lead to serious clinical complications, including acute kidney injury and cardiac arrest. Identification of tumor- and patient-specific risk factors for TLS and early recognition of laboratory and clinical TLS based on established criteria are essential for preventing TLS and forestalling acute kidney injury. Early collaboration between oncologists and nephrologists will help improve assessment of patients' kidney function and risk factors, paving the way for timely and efficacious interventions., (Copyright 2010 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

This article addresses two questions about gadolinium-based contrast agents (GBCAs) and nephrogenic systemic fibrosis (NSF): "Why did it happen" and "What have we learned"? It reviews the events leading to the discovery of an association between NSF and GBCAs. Various factors are elucidated that contributed to the delay between the time when GBCA came into widespread clinical use and a link was made with NSF, including use in renal-compromised patients, high-dose magnetic resonance angiography (MRA), lack of documentation and adequate databases, policy and regulatory changes, and an absence of scientific evidence. The authors conclude that the overriding cause was lack of awareness. J. Magn. Reson. Imaging 2009;30:1236-1239. (c) 2009 Wiley-Liss, Inc.

Gadolinium-containing magnetic resonance imaging (MRI) contrast agents such as Omniscan are associated with nephrogenic systemic fibrosis (NSF). To determine if Omniscan can affect the differentiation of monocytes into fibroblast-like cells called fibrocytes that are found in the fibrotic lesions of NSF, peripheral blood mononuclear cells (PBMCs) from NSF patients, hemodialysis patients without NSF, and healthy, renally sufficient controls were exposed to Omniscan in a standardized in vitro fibrocyte differentiation protocol. When added to PBMCs, the gadolinium-containing MRI contrast agent Omniscan generally had little effect on fibrocyte differentiation. However, 10(-8) to 10(-3) mg/mL Omniscan reduced the ability of the fibrocyte differentiation inhibitor serum amyloid P (SAP) to decrease fibrocyte differentiation in PBMCs from 15 of 17 healthy controls and one of three NSF patients. Omniscan reduced the ability of SAP to decrease fibrocyte differentiation from purified monocytes, indicating that the Omniscan effect does not require the presence of other cells (such as T cells) in the PBMCs. Omniscan also reduced the ability of a different fibrocyte differentiation inhibitor, interleukin-12, to decrease fibrocyte differentiation. These data suggest that Omniscan interferes with the regulatory action of signals that inhibit the differentiation of monocytes to fibrocytes. J. Magn. Reson. Imaging 2009;30:1284-1288. (c) 2009 Wiley-Liss, Inc.

Systemic amyloidosis which is characterized by extracellular deposition of monoclonal immunoglobulin light chains in various organs may be difficult to diagnose at an early stage, especially when the Congo red stain is negative. We describe herein a case of Congo red negative primary amyloidosis associated with Hashimoto thyroiditis. The patient presented with multiple organ involvement suggestive of amyloidosis including heart failure, renal failure, and macroglossia. Serum and urine immunofixation studies were positive for monoclonal chains. Even though a biopsy taken from the enlarged tongue of the patient was negative when stained with Congo red, electron microscopy showed ultrastructural features of amyloid deposition. In conclusion, we are reporting a rare case of primary amyloidosis with a negative Congo red stain associated with Hashimoto thyroiditis.

Objective: Anemia of chronic kidney disease (CKD) decreases patients' health-related quality of life (HRQoL). The objective of this subanalysis was to determine the effect of every-other-week (Q2W) darbepoetin alfa on hemoglobin (Hb) levels and HRQoL measures in subjects with CKD who are naïve to erythropoiesis-stimulating agents (ESAs)., Methods: STAAR was a 52-week, multicenter, single-arm study. Subject inclusion criteria included: > or = 18 years of age and creatinine clearance < or = 70 mL/min or estimated glomerular filtration rate < or = 60 mL/min/1.73 m(2) but not receiving dialysis. Subjects included in this subanalysis were previously naïve to ESAs, had Hb < 11 g/dL, were initiated on subcutaneous Q2W darbepoetin alfa to achieve a Hb level not to exceed 12 g/dL, and had responses to at least one question on the KDQOL-CRI forms administered at baseline, week 12, and week 52., Results: Of 911 ESA-naïve subjects enrolled in the study, 277 (30.4%) were included in this subanalysis. The majority of subanalysis subjects were Caucasian (63.2%) and/or women (54.5%). Mean Hb concentrations and all KDQOL-CRI scores improved significantly between baseline and week 12 (p < 0.0001), and were maintained until week 52. Darbepoetin alfa was well tolerated., Conclusions: Darbepoetin alfa initiated Q2W achieved and maintained Hb targets, and significantly improved and maintained HRQoL in study subjects with CKD. Limitations of the study must be considered when extrapolating these results to assess the benefits of treatment on HRQoL in the general CKD population.

Invasive colorectal carcinomas (CRCs) with invasion confined to the lamina propria (LP) [intramucosal carcinoma (IMC)] lack access to lymphatics and therefore have no potential for metastases and local intervention (usually polypectomy) should be adequate treatment. For this reason, they are classified as "Tis" in the TNM system. It is believed that carcinomas invading the submucosa with unfavorable histology (tumors at/near the margin, and/or vascular invasion, and/or poor differentiation) require additional intervention after polypectomy, whereas those with favorable histology can be safely treated endoscopically. However, there are few data on poorly differentiated (PD) carcinomas showing invasion confined to the LP. Polypectomy is theoretically curative but in practice this has not been well demonstrated. Thus, the clinicopathologic features of 15 cases of PD CRCs with invasion limited to the LP on initial biopsies were studied to determine the best course of management for this rare subset of carcinomas. A computer search and histologic review of cases seen at Johns Hopkins Hospital was performed. Fifteen cases of PD CRC with invasion limited to the LP were identified. The clinicopathologic features of these tumors were reviewed. All 15 cases showed PD IMC with single cells infiltrating only the LP. Patients were 38 to 79 years (median, 62) of age with a male predominance (M:F=4:1). Three cases had signet ring cell differentiation, 1 had focal small cell features, and another had focal squamous differentiation. Fourteen of the cases were associated with background adenomas or adenomalike lesions including: 7 involving tubulovillous or villous adenomas, 6 involving tubular adenomas, 1 involving dysplasia associated with chronic inflammatory bowel disease. Nine of the lesions had surrounding high-grade dysplasia. One case showed no background dysplasia or adenoma. One patient was lost to follow-up and the remaining 14 were followed for 1 to 96 months (mean, 21.3 mo; median, 13 mo). Seven patients had no residual disease on follow-up colonoscopy, and no resection was performed. The remaining 7 patients were treated with partial colectomy (6) or low anterior resection (1), and of these, 5 had no infiltrating carcinoma and negative lymph nodes. One patient had a separate large colorectal (T3) carcinoma with 8/10 positive regional lymph nodes; the IMC seen on biopsy was presumably a metastasis as it was unassociated with an in situ component. Finally, the resected rectum from which an IMC had been previously detected had no residual invasive carcinoma, but the anal skin was involved by Paget disease. Thus, of the 15 cases of PD CRCs limited to the LP, 1 was a metastasis from a separate CRC and another had associated Paget disease of the anal skin. As such, even in the setting of PD carcinomas, no metastatic disease was seen arising from any of the cases that were confirmed as early primary lesions. These preliminary findings suggest that patients with isolated intramucosal PD CRCs may be managed endoscopically.

Aim: In patients with end-stage renal disease (ESRD), hyperphosphataemia and an elevated calcium-phosphorus (Ca-P) product contribute to morbidity and mortality. Suggested target goals for serum phosphorus concentration and calcium-phosphorus product have recently been lowered. As a result, long-term comparative studies of the efficacy of phosphate binders are critical. This study compares the long-term efficacy of sevelamer hydrochloride to calcium-containing binders (CCB)., Methods: A retrospective chart review was conducted in 30 patients receiving sevelamer hydrochloride for >1 years and 25 patients receiving CCB., Results: Patients on sevelamer hydrochloride had lower serum bicarbonate concentration than those on CCB, 18.6 +/- 2.7 versus 20.3 +/- 1.8 mmol/L (P = 0.0017). Serum phosphorus concentration was higher in patients on sevelamer hydrochloride compared to CCB 2.10 +/- 0.87 versus 1.74 +/- 0.28 mmol/L (P = 0.0013), as was the Ca-P product 4.97 +/- 0.94 mmol2L2 (62.1 +/- 11.8 mg2/dL2) versus 3.97 +/- 1.18 mmol2/L2 (49.7 +/- 14.7 mg2/dL2), P = 0.0009). Only 36% of patients on sevelamer hydrochloride compared with 68% on CCB (P = 0.015) met the serum phosphorus goal of < or =1.78 mmol/L., Conclusion: Patients on sevelamer hydrochloride for >1 years compared to those on CCB had a lower serum bicarbonate concentration, a higher serum phosphorus concentration and a higher Ca-P product. Clinicians should balance the increase in calcium load with CCB versus the cost and effectiveness of sevelamer hydrochloride in choosing a phosphate binder for ESRD patients.

Mucosal nerve sheath tumors have been well described in the gastrointestinal tract and other mucosal sites. In a series of mucosal biopsies, we have encountered a distinct subset of mucosal peripheral nerve sheath tumors characterized by small epithelioid cells and a benign clinical course. Such epithelioid nerve sheath tumors have been observed as a component of a larger study of colorectal "schwannomas," but herein we describe them in detail. A series of 7 of these lesions detected on mucosal biopsies (6 colonic, 1 bladder) was received by a single large institution in consultation material. The histologic and clinicopathologic features of the cases were reviewed. The mean age at presentation was 58.6 years with a slight female predominance (4 females, 3 males). Five of the colonic lesions were from the left colon and one from the right colon. The bladder biopsy was from the bladder neck. All of the colonic lesions were discovered as small (0.2-1.0 cm) polyps during the time of colonoscopy (3 at the time of routine screening, 2 for the workup of occult blood in the stool). The bladder neck mass was seen on bladder ultrasound after the patient presented with vaginal bleeding. None of the patients had a known history of neurofibromatosis. Histologically, the lesions showed an infiltrative growth pattern and were composed of spindled to predominantly epithelioid cells arranged in nests and whorls. The epicenters of the lesions were located in the lamina propria and extended to the superficial submucosa. The proliferating cells had uniform round to oval nuclei with frequent intranuclear pseudoinclusions and eosinophilic fibrillary cytoplasm. No mitoses were seen. All lesions expressed diffuse S-100 protein, and 3 of 5 lesions stained showed CD34 labeling in supporting cells. All were negative for CD117. All 5 lesions tested were negative for calretenin, while SM31 showed no intralesional neuraxons. One lesion was stained for epithelial membrane antigen and was negative. One lesion was associated with superficial mucosal erosion, and 1 had an inflammatory infiltrate predominantly composed of eosinophils. On follow-up of 5 patients, none has had any symptoms or recurrence of disease. Mucosal epithelioid nerve sheath tumors are a rare entity characterized by prominent epithelioid round to oval cells with an infiltrative growth pattern. These lesions are often discovered incidentally and have a benign clinical course.

Sertraline has shown promise in the treatment of dialysis-associated hypotension (DAH) in a limited number of end-stage renal disease patients. We undertook a study to evaluate the effect of adding sertraline to other therapies for patients with documented DAH. We also measured the effect of sertraline on intradialytic haemodynamics. We used the ultrasound dilution technique (HD01 monitor) to measure cardiac output (CO), central blood volume (CBV) and peripheral vascular resistance (PVR) in these patients. The study was performed in two phases. Phase 1 was a control, while the second phase consisted of treatment with sertraline (50 mg/day). Cardiac output and central blood volume were measured 30 min following the initiation of dialysis and 30 min prior to the termination of dialysis. Blood pressure (BP) was monitored during haemodynamic measurements and throughout dialysis. Eighteen patients with documented DAH completed the study. Cardiac output, CBV and PVR were no different in the sertraline phase as compared with the control phase. The declines in systolic BP, diastolic BP and mean arterial pressures from pre-haemodialysis (HD) to lowest intradialytic and pre-HD to post-HD were not significantly different for the sertraline phase versus the control phase. In conclusion, it appears that sertraline has no additive effect on intradialytic haemodynamics to improve blood pressure in patients with DAH who are under therapy (with sodium modelling, cool dialysate and midodrine).

Background/aims: Vascular access thrombosis is one of the most morbid problems encountered by hemodialysis patients. Surveillance protocols utilizing venous pressure (Vp) and vascular access blood flow (VABF) measurements have been employed to preserve vascular access. We undertook a study to evaluate combined dynamic Vp and VABF measurements in the identification of vascular access impairment. We also assessed the effect of preventive repair on thrombosis rates in impaired vascular accesses identified by surveillance., Methods: Eighty-six chronic hemodialysis patients with a functioning vascular access were enrolled into the surveillance protocol. All vascular accesses with greater than 50% of monthly Vp readings >120 mm Hg or VABF <500 ml/min in arteriovenous fistulas (AVFs) and VABF <650 ml/min in arteriovenous grafts (AVGs), or a decrease in VABF >25% compared to the highest previously measured value, were considered positive. Stenosis >50% on fistulography or a thrombotic event were defined as a 'vascular access impairment episode' while a stenosis <50% or the absence of a thrombotic event was defined as 'no vascular access impairment episode'. Thrombosis rates and intervention rates were calculated per access year at risk., Results: The sensitivity and specificity of the combined surveillance protocol for AVFs were 73.3 and 91%, respectively. In AVGs, they were 68.8 and 87.5%, respectively. The rate of thrombotic events was lower in patients who underwent early repair. The addition of dynamic Vp did not reduce the thrombosis rate any further than surveillance based on VABF alone., Conclusion: Combined monitoring for surveillance of AVFs improved sensitivity but had little benefit in AVGs over VABF monitoring alone. Raising VABF cutoff levels might increase and improve identification of vascular access risk for thrombosis, but at the expense of lower specificity., (Copyright 2003 S. Karger AG, Basel)

Background: Renal disease in patients infected with HIV has evolved to include several lesions, including HIV-associated nephropathy (HIV-AN), which can promote progressive loss of renal function. Although angiotensin-converting enzyme inhibitors and corticosteroids are beneficial in selected patients, the effect of highly active antiretroviral therapy (HAART) on renal function is currently being explored., Methods: We undertook a retrospective study to determine the types of renal lesions present in patients infected with HIV with renal insufficiency and/or proteinuria during the era of HAART availability and the effect of HAART on renal outcomes in these patients. Patients with HIV infection referred to the renal clinic from July 1996 through December 2000 were evaluated. Patient characteristics and data were collected including CD4 count, viral load, serum creatinine, blood pressure, proteinuria, renal ultrasound, and biopsy results, and treatment with HAART. Study endpoints were doubling of serum creatinine, initiation of dialysis, or death., Results: Twenty-three patients met study criteria, 13 received HAART, and 10 did not. Baseline characteristics were similar except for renal function parameters, viral loads, and CD4 counts. A variety of lesions were noted on 12 renal biopsies. A clinical diagnosis of HIV-AN was made in the other 11 patients. Only 2 patients receiving HAART before renal evaluation were noted to have HIV-AN. In the HAART group, none of the patients, including those with HIV-AN, developed a doubling of serum creatinine. In the non-HAART group, all patients manifested a doubling of serum creatinine, 2 patients died, and 8 patients required dialysis., Conclusions: A variety of renal lesions are noted in patients infected with HIV during the HAART era. Patients who received HAART maintained stable renal function, whereas patients who did not required dialysis therapy or died with advanced renal failure. It seems that HAART may improve renal outcomes in patients with HIV and renal disease.

Cool dialysate and midodrine have been used successfully to treat intradialytic hypotension (IDH) in the end-stage renal disease population. However, the exact mechanisms by which these interventions improve hemodynamic stability are not well known. We undertook a study to evaluate the effect of these modalities on intradialytic hemodynamics in patients with documented dialysis-associated hypotension. We used the ultrasound dilution technique to measure cardiac output (CO), central blood volume (CBV), and peripheral vascular resistance (PVR) in these patients. The study was performed in two phases. Phase 1 consisted of control (1A) and cool dialysate (1B) studies, whereas phase 2 consisted of control (2A) and midodrine (2B) studies. CO, CBV, and PVR were measured 30 minutes after the initiation of hemodialysis (HD) and 30 minutes before the termination of HD using the HD01 monitor. Blood pressure was measured pre-HD and post-HD. Fourteen patients with documented IDH completed the study. CO and CBV were significantly more preserved in the cool dialysate and midodrine phases compared with control phases. PVR increased in all phases of the study. Declines in mean arterial pressures from pre-HD to post-HD were less with cool dialysate versus control and midodrine versus control. Ultrafiltration volumes were not significantly different between phases. Cool dialysate and midodrine appear to improve intradialytic hemodynamics in patients with dialysis-associated hypotension, mainly through the preservation of CBV and CO, rather than significantly elevating PVR., (Copyright 2002 by the National Kidney Foundation, Inc.)

Treatment of intradialytic hypotension (IDH) in the end-stage renal disease population has been a difficult task for nephrologists caring for these patients. The presence of multiple pathogenic factors contributes to hemodynamic instability and explains why therapies that modulate only a specific aspect of the problem are only partially effective. Cool dialysate (34.5 degrees C to 35.5 degrees C) and midodrine may provide hemodynamic stability through an increase in peripheral vascular resistance, whereas high dialysate calcium concentration (HDCa; 3.5 mEq/L) improves intradialytic blood pressure through preservation of cardiac output. Theoretically, the combination of these two types of therapies might further reduce the frequency and severity of hypotension during hemodialysis (HD). We undertook a study to evaluate the effect of HDCa added to midodrine and/or cool dialysate in the treatment of patients with severe IDH. Twenty-eight patients met the entry criteria, and 23 patients completed the prospective crossover study. Five patients dropped out of the study secondary to hypercalcemia. The addition of HDCa significantly improved post-HD mean arterial pressure (MAP; 95.6 +/- 12.7 versus 90.8 +/- 12.5 mm Hg; P = 0.002). The decreases in MAP from pre-HD to lowest intradialytic (16.3 +/- 8.2 versus 20.6 +/- 10.0 mm Hg; P = 0.009) and pre-HD to post-HD (2.0 +/- 8.5 versus 8.15 +/- 10.8 mm Hg; P = 0.002) were significantly reduced with HDCa compared with low dialysate calcium. However, there were no significant improvements in symptoms of or interventions for IDH. Thus, it appears that the addition of HDCa to midodrine and/or cool dialysate further improves blood pressure in patients with IDH. However, this therapy did not reduce symptoms or interventions required for IDH. In addition, hypercalcemia complicated this therapy in 22% of the patients.