Papilledema and retinopathy lead to diagnosis of IgA nephropathy: a case report.

This case features a young healthy male who was diagnosed with immunoglobulin A (IgA) nephropathy after presenting with blurry vision that was caused by hypertensive retinopathy and papilledema. In this report, we examine the relationship between hypertension and increased intracranial pressure (ICP), along with the ocular signs of IgA nephropathy that may present in the setting of kidney disease.

Immunoglobulin A (IgA) nephropathy is an immune-mediated inflammatory condition that affects the kidneys and is characterized by deposits of IgA antibodies across the body. Nephropathy in general is defined as the deterioration of kidney function. Hypertension is a common complication because of the resultant kidney damage. IgA can also deposit widely across the body, including within the eyes, and may lead to various inflammatory manifestations affecting the front and back of the eyes. We present a case of a 38-year-old male with 2 weeks of worsening vision and headaches. His blood pressure was extremely high (206/116 mmHg) and he was found to have acute kidney injury. Examination of his eye revealed hypertensive retinopathy but also significant swelling of both of his optic discs, concerning for increased intracranial pressure (ICP), which is unusual in a young, otherwise healthy male. The investigation for the cause of increased ICP led to the diagnosis of IgA nephropathy. Treatment of his increased ICP and blood pressure resulted in improvement of his vision. It is important to consider increased ICP as a cause of optic disc swelling in patients with very high blood pressures. Prompt evaluation and management of elevated ICP is important to preserve vision, prevent brain complications and diagnose the underlying disease process. Especially important is the communication and coordination across medical specialties to ensure safe treatment given the multisystem organ involvement. In this article, we also review the eye findings associated with IgA nephropathy, as well as other immune-mediated complications of this rare disease.

Glomerular inflammation correlates with endothelial injury and with IL-6 and IL-1ß secretion in the peripheral blood.

BACKGROUND: Transplant glomerulitis is an active form of glomerular injury associated with suboptimal graft outcome, inadequate histologic reproducibility, and poorly understood pathogenesis. Using a modified pathologic schema where glomerular inflammation is defined by the presence of five or more leukocytes per glomerulus, we sought to assess the reproducibility of transplant glomerulitis and to prospectively investigate the pathogenesis of glomerular inflammation. METHODS: Our cohort includes 59 kidney transplant recipients who underwent 60 "for cause" allograft biopsies. In addition to light microscopy, the majority of the biopsies were assessed using immunohistochemistry, immunofluorescence, and electron microscopy studies. Biopsies were classified as noninflamed (n=21), inflamed (borderline changes or above) without glomerulitis (n=21), and transplant glomerulitis (n=18). Peripheral blood was collected on the day of biopsy and cytokines secreted by peripheral blood mononuclear cells (PBMCs) were measured ex vivo. RESULTS: Our modified schema had higher inter-observer agreement for detecting glomerulitis than that of the current Banff schema. Biopsies with glomerulitis showed ultrastructural signs of glomerular capillary wall remodeling. In contrast to other anatomic compartments, intraglomerular leukocytes in glomerulitis group consisted largely of monocytes. Patients with glomerulitis had high levels of IL-6 and IL-1ß secreted by PBMCs. Furthermore, the percentage of inflamed glomeruli and the number of intraglomerular monocytes showed independent association with IL-6 and IL-1ß levels, which tended to correlate with subsequent estimated glomerular filtration rate decline. CONCLUSIONS: Inter-observer reproducibility of transplant glomerulitis can be improved by using more stringent histologic criteria. Glomerular inflammation correlates with endothelial injury, monocyte influx, and IL-6 and IL-ß secretion by circulating immune cells.

Temporary targeted renal blood flow interruption using a reverse thermosensitive polymer to facilitate bloodless partial nephrectomy: a swine survival study.

UNLABELLED: What's known on the subject? and What does the study add? Lumagel™ is a reverse thermosensitive polymer (RTP) that has previously been described in the literature as providing temporary vascular occlusion to allow for bloodless partial nephrectomy (PN) while maintaining blood flow to the untargeted portion of the kidney. At body temperature, Lumagel™ has the consistency of a viscous gel but upon cooling rapidly converts to a liquid state and does not reconstitute thereafter. This property has allowed for it to be used in situations requiring temporary vascular occlusion. Previous experience with similar RTPs in coronary arteries proved successful, with no detectable adverse events. We have previously described our technique for temporary vascular occlusion of the main renal artery, as well as segmental and sub-segmental renal branches, to allow for bloodless PN in either an open or minimally invasive approach. These experiments were performed in the acute setting. This study is a two-armed survival trial to assess whether this RTP is as safe as hilar clamping for bloodless PN. Surviving animals showed normal growth after using the RTP, absence of toxicity, no organ dysfunction, and no pathological changes attributable to the RTP. We conclude that Lumagel™ is as safe as conventional PN with hilar clamping, while adding the advantage of uninterrupted perfusion during renal resection. OBJECTIVE: To examine whether randomly selected regions of the kidney could undergo temporary flow interruption with a reverse thermosensitive polymer (RTP), Lumagel™ (Pluromed, Inc., Woburn, MA, USA), followed by partial nephrectomy (PN), without adding risks beyond those encountered in the same procedure with the use of hilar clamping. MATERIALS AND METHODS: A two-armed (RTP vs hilar clamp), 6-week swine survival study was performed. Four swine underwent PN using hilar clamps, while six underwent PN with flow interruption using the RTP. The RTP, administered angiographically, was used for intraluminal occlusion of segmental or subsegmental arteries and was compared with main renal artery clamping with hilar clamps. The resection site was randomized for each swine. Laboratory studies were performed preoperatively, and at weeks 1, 3 and 6. Before killing the swine, repeat angiography was performed with emphasis on the site of previous flow interruption. Gross and microscopic examination of kidney, liver, lung, heart, skeletal muscle was later performed, and the vessel that had supported the previous plug was examined. RESULTS: All animals survived. No abnormal chemistry or haematology results were encountered over the 6 weeks. There were no surgical complications in either group. Using angiography we found 100% patency of vessels that had been occluded with the polymer 6 weeks previously for PN. The only gross or microscopic abnormalities were related to the renal resection and scar formation, and were similar in the two groups. CONCLUSION: Targeted flow interruption with the RTP added no additional risk to PN while allowing bloodless resection and uninterrupted flow to untargeted renal tissue.

MicroRNA-21 promotes fibrosis of the kidney by silencing metabolic pathways.

Scarring of the kidney is a major public health concern, directly promoting loss of kidney function. To understand the role of microRNA (miRNA) in the progression of kidney scarring in response to injury, we investigated changes in miRNA expression in two kidney fibrosis models and identified 24 commonly up-regulated miRNAs. Among them, miR-21 was highly elevated in both animal models and in human transplanted kidneys with nephropathy. Deletion of miR-21 in mice resulted in no overt abnormality. However, miR-21(-/-) mice suffered far less interstitial fibrosis in response to kidney injury, a phenotype duplicated in wild-type mice treated with anti-miR-21 oligonucleotides. Global derepression of miR-21 target mRNAs was readily detectable in miR-21(-/-) kidneys after injury. Analysis of gene expression profiles up-regulated in the absence of miR-21 identified groups of genes involved in metabolic pathways, including the lipid metabolism pathway regulated by peroxisome proliferator-activated receptor-α (Pparα), a direct miR-21 target. Overexpression of Pparα prevented ureteral obstruction-induced injury and fibrosis. Pparα deficiency abrogated the antifibrotic effect of anti-miR-21 oligonucleotides. miR-21 also regulated the redox metabolic pathway. The mitochondrial inhibitor of reactive oxygen species generation Mpv17l was repressed by miR-21, correlating closely with enhanced oxidative kidney damage. These studies demonstrate that miR-21 contributes to fibrogenesis and epithelial injury in the kidney in two mouse models and is a candidate target for antifibrotic therapies.

Feasibility of bloodless liver resection using Lumagel, a reverse thermoplastic polymer, to produce temporary, targeted hepatic blood flow interruption.

BACKGROUND: Lumagel, a reverse thermosensitive polymer (RTP), provides targeted flow interruption to the kidney by reversibly plugging segmental branches of the renal artery, allowing blood-free partial nephrectomy. Extending this technology to the liver requires the development of techniques for temporary occlusion of the hepatic artery and selected portal vein branches. METHODS: A three-phased, 15 swine study was performed to determine feasibility, techniques and survival implications of using Lumagel for occlusion of inflow vessels to targeted portions of the liver. Lumagel was delivered using angiographic techniques to sites determined by pre-operative 3-D vascular reconstructions of arterial and venous branches. During resection, the targeted liver mass was resected without vascular clamping. Three survival swine were sacrificed at 3 weeks; the remainder at 6 weeks for pathological studies. RESULTS: Six animals (100%) survived, with normal growth, blood tests and no adverse events. Three left lateral lobe resections encountered no bleeding during resection; one right median resection bled; two control animals bled significantly. Pre-terminal angiography and autopsy showed no local pathology and no remote organ damage. CONCLUSIONS: Targeted flow interruption to the left lateral lobe of the swine liver is feasible and allows resection without bleeding, toxicity or pathological sequelae. Targeting the remaining liver will require more elaborate plug deposition owing to the extensive collateral venous network.

Targeted endovascular temporary vessel occlusion with a reverse thermosensitive polymer for near-bloodless partial nephrectomy: comparison to standard surgical clamping techniques.

PURPOSE: To determine whether reversible blood flow interruption to a randomly chosen target region of the kidney may be achieved with the injection of a reverse thermoplastic polymer through an angiographic catheter, thereby facilitating partial nephrectomy without compromising blood flow to the remaining kidney or adding risks beyond those encountered by the use of hilar clamping. METHODS: Fifteen pigs underwent partial nephrectomy after blood flow interruption by vascular cross-clamping or injection of polymer (Lumagel™) into a segmental artery. Five animals were euthanized after surgery (three open and two laparoscopic resection, cross-clamping n = 2), and 10 (open resection, cross-clamping n = 4) were euthanized after 6 weeks' survival. Blood specimens were obtained periodically, and angiogram and necropsy were performed at 6 weeks. RESULTS: Selective renal ischemia was achieved in all cases. Surgical resection time averaged 9 and 24.5 min in the open and laparoscopic groups, respectively. Estimated blood loss was negligible with the exception of one case where an accessory renal artery was originally overlooked. Reversal of the polymer to a liquid state was consistent angiographically and visually in all cases. Time to complete flow return averaged 7.4 and 2 min for polymer and clamping, respectively. Angiography at 6 weeks revealed no evidence of vascular injury. Laboratory data and necropsies revealed no differences between animals undergoing vascular clamping or polymer injection. CONCLUSION: Lumagel was as effective as vascular clamping in producing a near bloodless operative field for partial nephrectomy while maintaining flow to the uninvolved portion of the affected kidney.

Unusual presentation of B-cell lymphoma as a cutaneous abscess.

Cutaneous abscesses can result from many conditions and are primarily managed with incision, drainage and antibiotics, without the need for extensive diagnostic workup. We herein report a case of a B-cell lymphoma manifesting as an abscess on the back of a 67-year-old female. Standard therapies failed to improve her condition, and, by the time of tissue diagnosis, a greater than palm-sized necrotic ulcer eroding through skin and fat, and into the psoas muscle had developed. Primary or secondary cutaneous B-cell lymphomas almost never lead to tissue necrosis but should be entertained in cases of abscesses or ulcers with unusual presentation.

Resource utilization among kidney transplant recipients.

BACKGROUND: Hospitalization consumes a significant portion of the end-stage renal disease (ESRD) program, which includes kidney transplant recipients. Identification of kidney transplant recipients at risk of increased resource utilization could lead to appropriate interventions to attenuate the complications related to kidney transplant, which may reduce resource utilization. METHODS: This retrospective cohort study of kidney transplant recipients was performed to identify risk factors for hospital utilization. The study population consisted of patients who received kidney transplant at our center between October 1990 and September 1999 and were followed in the outpatient clinic. RESULTS: Of the 220 patients, 171 (78%) were hospitalized during a median follow-up of 36 months. The number of hospitalizations, hospital days, and outpatient visits per patient-year at risk were 1.1, 6.3, and 21.6, respectively. Infection episodes were the leading cause of hospitalization. In a multivariate regression analysis, cytomegalovirus (CMV)-positive status of donor (RR 1.58; 95% CI 1.15, 2.18) and a higher number of hospital days during the transplant hospitalization (RR 1.10 per 7 days increase; 95% CI 1.03, 1.19) were associated with a higher risk of hospitalization, while higher serum albumin (RR 0.84 per 0.5 g/dL increase; 95% CI 0.73, 0.97), higher hematocrit (RR 0.95 per 1% increase; 95% CI 0.92, 0.98), higher glomerular filtration rate (GFR) (RR 0.91 per 10 mL/min/1.73 m2; 95% CI 0.85, 0.99), and an increased interval since transplant (RR 0.84 per 6 months increase; 95% CI 0.75, 0.93) were associated with a lower risk of hospitalization. CMV-positive status of the donor (RR 1.11; 95% CI 1.00, 1.21) and presence of cardiovascular disease (RR 1.12; 95% CI 1.00, 1.24) were associated with a higher risk of outpatient visits, while Caucasian race (RR 0.82; 95% CI 0.73, 0.94), higher serum albumin (RR 0.88 per 0.5 g/dL increase; 95% CI 0.84, 0.93), higher hematocrit (RR 0.96 per 1% increase; 95% CI 0.95, 0.97), and an increased interval since transplant (RR 0.79 per 6 months increase; 95% CI 0.76, 0.83) were associated with a lower risk of outpatient visits. CONCLUSION: Identification of risk factors associated with increase resource utilization among kidney transplant recipients could aid in the development of targeted interventions to improve clinical and economic outcomes.