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Clinical choroidal thrombosis, hypertension, and diabetes mellitus: an electron microscopic study.

Changes in the choroidal artery were examined at autopsy in 16 Japanese patients with hypertension and insulin-dependent diabetes mellitus. These changes could be divided into 1) arteriosclerotic ones consisting of intimal thickening due to migration of smooth muscle cells, 2) hyaline deposits in the subendothelium, 3) extensive degeneration (moth-eaten atrophy and necrosis) of medial smooth muscle cells, and 4) changes resulting from fibrinoplatelet thrombi and their organization (recanalization and obstruction). The intimal thickening and medial damage correlated with aging, were accelerated by hypertension, and were remarkable in arterioles less than 60 micron in diameter. Diabetes mellitus apparently did not enhance these vascular changes. Thrombotic occlusion or narrowing of the choroidal artery was frequently observed in the arterioles of patients with hypertension and diabetes mellitus who had chronic azotemia or renal insufficiency. Subendothelial hyaline deposits were increased in patients with diabetes. The narrowing or obstructive changes in the choroidal artery were extensive in the intraocular blood vessels. These changes may be secondary and induce damage to other intraocular blood vessels and tissues, including the retina.

Aged↗

Outcomes of primary valve ablation versus urinary tract diversion in patients with posterior urethral valves.

OBJECTIVES: Although valve ablation is the treatment of choice for patients with posterior urethral valves, debate continues as to the role of urinary diversion. We sought to retrospectively compare the clinical and radiologic outcomes between valve ablation and urinary diversion for patients with posterior urethral valves. METHODS: We retrospectively reviewed the records of 50 consecutive patients with posterior urethral valves since January 1995. On the basis of the initial renal function and radiologic findings, patients were divided into three groups: group 1, normal renal function and radiologically normal upper tracts; group 2, normal renal function with hydronephrosis and/or reflux; and group 3, azotemia with hydronephrosis or reflux. RESULTS: All 22 patients in group 1 were treated with valve ablation. After a mean follow-up of 32 months, these children had normal renal function and no evidence of upper tract deterioration. All 13 patients in group 2 were also treated with valve ablation. The radiologic abnormalities (hydronephrosis, reflux) resolved in 50% of cases, with an average follow-up of 28 months. Of the 15 patients in group 3, 7 underwent valve ablation and 8 underwent urinary diversion. Urinary diversion was performed in patients with renal deterioration and severe hydronephrosis and/or high-grade reflux. Renal function returned to normal in all patients who underwent valve ablation except one; renal function returned to normal in only 3 of 8 patients who underwent urinary diversion. Radiologically, the severity of the hydronephrosis and reflux was downgraded in patients who underwent valve ablation but not in the diverted group. CONCLUSIONS: Valve ablation is the mainstay of treatment for patients with posterior urethral valves. Prenatal and postnatal factors, such as renal dysplasia and urinary tract infection, respectively, rather than the posterior valve treatment dictate the long-term renal and radiologic outcomes.

Adolescent↗

An open-label study of abarelix in men with symptomatic prostate cancer at risk of treatment with LHRH agonists.

OBJECTIVES: To evaluate the ability of abarelix, a gonadotropin-releasing hormone antagonist, to provide an alternative treatment to bilateral orchiectomy in men with advanced prostate cancer symptoms and to evaluate its safety, clinical and biochemical efficacy, and effects on prostate-specific antigen and serum hormone levels. METHODS: For 168 days, 81 patients from 17 centers received monthly intramuscular injections of open-label abarelix 100 mg (at least one dose). Patients were evaluated for the avoidance of bilateral orchiectomy, efficacy, disease response, percentage of change in prostate-specific antigen level, change in the intensity of pain, neurologic compromise, and other efficacy variables. Safety was evaluated through reports of adverse events and abnormal laboratory values. RESULTS: No patients required bilateral orchiectomy, but 2 patients were withdrawn from the study because of treatment-related events and were considered as failures to avoid orchiectomy. Treatment produced an 88% (38 of 43) objective response rate on day 85. Sixty-five (90%) of 72 patients experienced improvement in the pain score and/or analgesic use, urinary obstruction, urinary catheter removal, hydronephrosis, and/or azotemia. No patient with impending neurologic compromise at study entry developed spinal cord compression. The median reduction from the baseline prostate-specific antigen value was 75% on day 15 and greater than 95% from day 57 onward. Abarelix was well tolerated, and adverse events were the sequelae of advanced prostate cancer, comorbid medical disorders, or medical castration. CONCLUSIONS: These results suggest that abarelix provides a safe and effective medical alternative to surgical castration in symptomatic patients with advanced prostate cancer without the risk of the clinical flare associated with luteinizing hormone-releasing hormone agonists.

Adenocarcinoma↗

Protease inhibitor-induced urolithiasis.

OBJECTIVES: To describe protease inhibitor-induced urinary stone disease in patients with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) who are taking indinavir sulfate (Crixivan), a protease inhibitor, for the treatment of AIDS. METHODS: Patients with HIV/AIDS and symptomatic renal colic temporally related to the initiation of indinavir sulfate therapy were prospectively identified. Seven patients (mean age 42 years; all men) with HIV and renal colic who were taking indinavir were identified. Retrospective chart reviews and patient interviews were performed. RESULTS: Indinavir therapy averaged 5.7 months prior to presentation with renal colic. All patients had microscopic hematuria. One patient presented with acute azotemia from bilateral urinary obstruction. Six patients had no history of urinary stones prior to initiating indinavir. The median number of symptomatic urinary stone episodes after initiating indinavir was two stones per patient. All patients had moderate- to high-grade urinary obstruction from radiolucent calculi. Abdominal computed tomography (CT) demonstrated hydronephrosis without urinary calcifications. Three patients spontaneously passed stones and 4 required intervention. Yellow debris and/or brown matrix-like material was seen endoscopically. Stone analysis revealed pure protease inhibitor. Six patients (86%) eventually discontinued protease inhibitor therapy. CONCLUSIONS: Protease inhibitor-induced urinary stones are radiolucent and can cause high-grade ureteral obstruction. Protease inhibitor-induced urinary stones were not identified on unenhanced abdominal CT scans. The radiolucent gelatinous nature of such stones makes lithotripsy a poor choice of treatment. Ureteral stenting may allow spontaneous stone passage if symptomatic obstruction occurs. Urologists may encounter a greater number of patients with symptomatic protease inhibitor-induced urinary calculi as these medications become more popular.

Adult↗

The use of dynamic magnetic resonance imaging to evaluate orthotopic continent urinary diversion.

OBJECTIVES: The purpose of this study was to evaluate a dynamic magnetic resonance (MR) examination in patients after radical cystoprostatectomy with a neobladder. METHODS: All 12 subjects were studied with the injection of gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) and showed normal renal enhancement patterns and upper urinary tracts, except 1 patient who had mild right hydronephrosis. All neobladders were also visualized with gadolinium and 9 of 11 patients were able to void on command. There was close agreement in all cases with the MR findings and other imaging studies. RESULTS: A static and dynamic Gd-DTPA contrast medium MR did image the entire urinary system, similar to a computed tomographic scan or intravenous urogram. Renal function data, similar to a renal radioisotope scan, was obtained from the Gd-DTPA scans. A dynamic voiding study provided visualization of the lower genitourinary tract similar to a conventional voiding cystourethrogram. CONCLUSIONS: We conclude that this single MR technique may provide information similar to that obtained from multiple standard imaging studies in the postoperative assessment of the radical cystectomy patient with a neobladder. It may be especially helpful in the presence of azotemia or contrast allergy.

Adult↗

Cisplatin as second-line therapy in ovarian carcinoma treated initially with single-agent paclitaxel: a Gynecologic Oncology Group study.

OBJECTIVES: The platinum compounds are the most active agents in the treatment of ovarian carcinoma. Phase II trials demonstrated the activity of paclitaxel in patients with disease clinically resistant to platinum-based front-line therapy, and phase III studies confirmed that a combination of paclitaxel plus a platinum was superior to cyclophosphamide plus a platinum. This study evaluated the activity of platinum in patients with bulky advanced disease treated with single-agent paclitaxel as front-line therapy on a Gynecologic Oncology Group protocol. Those patients who had persistent (stable) or progressive disease while receiving paclitaxel, or a recurrence of disease within 6 months of completing six cycles of paclitaxel therapy, received single-agent cisplatin. METHODS: Thirty-nine eligible patients with ovarian carcinoma persistent, progressive, or recurrent after initial treatment with paclitaxel 200 mg/m(2) over 24 h every 3 weeks received cisplatin 100 mg/m(2) every 3 weeks until disease progression or unacceptable toxicity. RESULTS: Among 37 patients evaluable for response, 8 complete (22%) and 13 partial (35%) responses resulted. Twelve (32%) patients exhibited stable disease, while 4 (11%) had increasing disease. Median progression-free survival was 11.0 months. Median survival was 15.0 months. All but two patients were clinically resistant to paclitaxel (progression during or within 6 months after completion of paclitaxel). Grade 2 or worse adverse effects among 39 patients evaluable for toxicity included neutropenia (23), thrombocytopenia (3), anemia (10), nausea and vomiting (23), azotemia (7), neurotoxicity (9), fever (2), and tinnitus (1). CONCLUSION: These data provide evidence that cisplatin is active as second-line therapy in patients clinically resistant to paclitaxel. The overall response rate is high (57%) with excellent progression-free and overall survival in the second-line setting.

Adult↗

Radiation nephropathy is treatable with an angiotensin converting enzyme inhibitor or an angiotensin II type-1 (AT1) receptor antagonist.

BACKGROUND AND PURPOSE: Previous studies showed that progression of established radiation nephropathy could be delayed by continuous treatment with high doses of captopril, an angiotensin-converting-enzyme (ACE) inhibitor. The current studies were designed to determine whether a lower dose or a shorter treatment with captopril would be effective and whether an angiotensin II type-1 (AT1) receptor antagonist (AII blocker) would be effective. MATERIALS AND METHODS: In the captopril studies, rats were given renal irradiation at doses sufficient to produce radiation nephropathy. Six months after irradiation, animals were stratified by azotemia and assigned to no treatment, continuous high- or low-dose captopril, or 6 weeks of high-dose captopril. Captopril was given in drinking water at 62.5 mg/l (low dose) or 500 mg/l (high dose). The AII blocker study had a similar design, except that the nephropathy was the result of total body irradiation and bone marrow transplantation and the treatments were no treatment or continuous treatment with an AII blocker, L-158,809 (20 mg/l in drinking water). Animals were followed for 1 year with periodic studies of renal function. RESULTS: Survival and renal function were significantly enhanced by all treatments. Continuous captopril treatment was more effective than the 6-week course of treatment, but there was no difference in effectiveness between the high and low doses of captopril. In continuous therapy, captopril and the AII blocker had roughly equivalent efficacy. CONCLUSIONS: Both the ACE inhibitor and the AII blocker were effective treatments for established radiation nephropathy. The best results with the ACE inhibitor required continuous therapy, but could be achieved with a low dose of the drug.

Angiotensin Receptor Antagonists↗

Bright basal ganglia in T1-weighted magnetic resonance images are frequent in patients with portal vein thrombosis without liver cirrhosis and not suggestive of hepatic encephalopathy.

BACKGROUND/AIMS: Deposition of paramagnetic substances in basal ganglia, resulting in increased signals in T1-weighted magnetic resonance images (bright basal ganglia), is frequently seen in liver cirrhosis. The present study describes the prevalence of bright basal ganglia and its clinical significance in patients with long-standing portal vein thrombosis in the absence of liver cirrhosis. METHODS: Six patients with angiographically proven complete portal vein thrombosis and cavernomatous transformation without signs of acute or chronic liver disease were studied by magnetic resonance imaging of the brain, neuropsychiatric evaluation, psychometric tests, electroencephalography, and determination of arterial ammonia levels and of serum manganese concentrations from peripheral venous blood. RESULTS: Five out of six patients demonstrated increased signal intensity in the basal ganglia. Overt portal-systemic encephalopathy was not noted prior to or at the time of evaluation. Normal EEG results were recorded in all patients. Only one of the six patients had pathological results in at least two out of four psychometric tests. This latter patient had had a large right-sided brain infarction. Arterial ammonia concentrations were normal in four of the six patients; one patient with increased ammonia levels had concomitant renal insufficiency with azotemia. The other four patients had no relevant concomitant diseases. Serum manganese levels were non-significantly increased compared with a control group (p=0.06), but they were significantly correlated to basal ganglia signal intensity (R=0.88; p=0.02). CONCLUSIONS: Our results demonstrate that bright basal ganglia primarily represent shunt-induced alterations. They are not directly associated with disturbed liver function nor with portal-systemic encephalopathy.

Adult↗

[Massive bilateral adrenal hemorrhage after conservative tumor surgery in the isthmus of a horseshoe kidney].

OBJECTIVE: To present a fatal case of massive bilateral suprarrenal haemorrhage (MBSH) after partial nephrectomy. CLINICAL CASE: An 82 year old male treated with oral anticoagulants was diagnosed by means of CT scan and arteriography of having an avascular tumor located at the isthmus of a horseshoe kidney. A tumorectomy with safety surgical margins was performed; It was diagnosed of having a renal adenocarcinoma, which was almost completely necrotic. During the postoperative period, the patient presented abdominal pain, nausea, fever, hypotension and severe respiratory distress. Biochemical studies showed mild hyponatremia and azotemia, accompanied by anemia, leucocytosis and thrombocytosis. An abdominal CT scan demonstrated a MBSH, which produced the patients death soon afterwards. DISCUSSION: Tumoral pathology of horseshoe kidneys presents important topographic and anatomopathologic differences with respect to non-fused kidneys. MBSH is a rare complication of many stress processes especially if an anticoagulant treatment coexists. The treatment has to be initiated as soon as we suspect MBSH, which should be confirmed by hormonal determinations and/or the presence of hyperdense suprarenal lesions at the CT scan.

Adenocarcinoma↗

Radiation nephropathy.

The pronounced radiosensitivity of renal tissue limits the total radiotherapeutic dose that can be applied safely to treatment volumes that include the kidneys. The incidence of clinical radiation nephropathy has increased with the use of total-body irradiation (TBI) in preparation for bone marrow transplantation and as a consequence of radionuclide therapies. The clinical presentation is azotemia, hypertension, and, disproportionately, severe anemia seen several months to years after irradiation that, if untreated, leads to renal failure. Structural features include mesangiolysis, sclerosis, tubular atrophy, and tubulointerstitial scarring. Similar changes are seen in a variety of experimental animal models. The classic view of radiation nephropathy being inevitable, progressive, and untreatable because of DNA damage-mediated cell loss at division has been replaced by a new paradigm in which radiation-induced injury involves not only direct cell kill but also involves complex and dynamic interactions between glomerular, tubular, and interstitial cells. These serve both as autocrine and as paracrine, if not endocrine, targets of biologic mediators that mediate nephron injury and repair. The renin angiotensin system (RAS) clearly is involved; multiple experimental studies have shown that antagonism of the RAS is beneficial, even when not initiated until weeks after irradiation. Recent findings suggest a similar benefit in clinical radiation nephropathy.

Animals↗

Clinical characteristics of atherosclerotic renovascular disease.

In addition to its role in secondary hypertension, ischemic renal disease is becoming recognized as a significant cause of renal insufficiency. The prevalence and natural history of this disease remain unknown due to difficulty in identification of the process. There are several scenarios that may help alert the clinician to the presence of atherosclerotic renovascular disease. In hypertensive patients, poorly controlled blood pressure on several medications or rapid acceleration of hypertension can suggest renovascular disease. In addition, high-grade retinopathy or abdominal bruits seem to be associated with this condition: bruits have the highest positive predictive value of the clinical signs. Renal artery stenosis also may be related to rapidly progressive renal failure. The classic association is renal failure after use of angiotensin-converting enzyme inhibitors; however, acute renal failure induced through any sudden therapeutic decrease in blood pressure may imply the presence of renal artery stenosis. Unexplained azotemia in the elderly patient also has been associated with renovascular disease. It is possible that the majority of patients with renal artery stenosis are those with a clinically silent process. Advanced age, peripheral atherosclerotic vascular disease, and coronary artery disease may all have a high association with stenosis of one or both renal arteries. It is nevertheless unknown whether a radiographically detected lesion implies current or future clinical complications.(ABSTRACT TRUNCATED AT 250 WORDS)

Arteriosclerosis↗

Defining the role of renal angiography in the diagnosis of renal artery disease.

The current goal of angiography in the diagnosis of renal artery disease is poorly defined, probably because of the diversity of patients presenting for management. The current application of angiography is better understood when put into perspective with the patient population that we are trying to screen. There are two distinct patient populations with renovascular disease: those with uncontrolled hypertension and those with azotemia or risk of progression to end-stage renal disease. The role of angiography in these two patient populations is quite different. In patients with hypertensive renovascular disease, angiography should be applied rather late and should be preceded by other noninvasive testing to screen patients from those with essential hypertension, since the prevalence of this disease is low and the cost implications of applying angiography primarily are immense. The two promising tests in this setting are captropril renography and duplex ultrasound scanning. In contradistinction, patients with azotemic renovascular disease, suffering from bilateral renal artery stenoses, or suffering from stenosis of the renal artery in a solitary kidney may be better studied by early application of renal angiography, especially those at risk of progression and for whom intervention is indicated.

Angiography↗

Advantages of donor-specific blood transfusion in the rat via the portal vein for renal transplantation.

It is well known that blood transfusion can promote immune unresponsiveness to a renal allograft in both animals and humans. The present study examined the differences between either portal venous (PV) or intravenous (IV) donor-specific transfusion (DST) alone on the survival of rat renal allografts without other immunosuppression. Seven days before LEW (RT1(1)) renal transplantation, recipient WKA rats (RT1u) were inoculated with graded doses (1.0 to 0.0001 mL) of LEW whole blood through either the portal vein or the tail vein. A dose of 0.001 mL whole blood PV resulted in significantly greater prolongation of renal allograft survival than occurred with IV preimmunization (38.5 +/- 10.6 days v 12.5 +/- 2.7 days). Although recipient survival was not significantly different for the two routes for a lower dose (0.1 mL) of whole blood preimmunization 7 days before transplantation, azotemia and rejection were prevented when the PV route, but not the IV route, was used. However, when 0.1 mL of whole blood was administered 5 days before transplantation, survival was prolonged only in animals preimmunized by the PV route (54.7 +/- 14.0 days v 14.3 +/- 4.0 days). In the stronger reciprocal combination of WKA to LEW, there was an advantage of PV with 0.1 mL whole blood, but not with 1 mL. These results indicate that the beneficial effects of DST on renal allograft survival can be obtained when a smaller volume of blood is given via the PV rather than the IV route and a shorter interval elapses between preimmunization and transplantation.

Animals↗

Long-term follow-up of non-systemic lupus erythematosus glomerulonephritis in patients with hereditary angioedema: report of four cases.

Hereditary angioedema (HAE) is characterized by a deficiency in C1 inhibitor protein (C1 INH) and by clinical symptoms of episodic swelling of subcutaneous or mucosal tissue. It has rarely been reported in association with non-systemic lupus erythematosus (SLE) glomerulonephritis (GN). A recent report of two cases indicates the prognosis to be poor, with both patients progressing to chronic renal failure 8 and 20 years after diagnosis. This report describes the 5-year follow-up of a previously unreported case of an 8-year-old boy with HAE and non-SLE membranoproliferative glomerulonephritis (MPGN). The patient developed macroscopic hematuria, azotemia, and a vasculitic rash. Treatment included prednisone and cyclophosphamide, resulting in clinical improvement. The present report also summarizes the long-term follow-up of three previously reported cases of HAE and non-SLE GN, 25, 16, and 10 years after their initial presentation. Patients monitored for 25 and 16 years had MPGN and normal renal function and received no therapy. The third patient, monitored for 10 years, had segmental MPGN. This patient presented with urinary abnormalities and, after treatment with prednisone, had improvement in her hematuria. None of these four patients developed chronic renal failure. These observations indicate a variable outcome in patients with HAE and non-SLE GN.

Aged↗

Nephronophthisis with massive proteinuria.

A 23-year-old male whose uncle died of nephronophthisis, and whose pathology is also discussed, presented with 5 g of protein in a 24-hour urine collection. Nephrogenic diabetes insipidus and salt wasting were present in addition to azotemia. Characterization of the proteinuria, including elevated alpha globulins by electrophoresis and markedly elevated urinary beta-microglobulins by radioimmunoassay (49.55 mg/L) indicated predominantly tubular proteinuria. A percutaneous renal biopsy showed normal glomeruli, interstitial inflammation and fibrosis, and tubular atrophy. Electron microscopy revealed notable alterations of the tubular basement membrane.

Adult↗

Henoch-Schönlein nephritis: prognostic features and the challenge of therapy.

Henoch-Schönlein purpura is an intriguing entity of uncertain etiology associated with circulating IaA immune complexes, enhanced spontaneous immunoglobulin production, and an apparent imbalance in T cell regulatory functions. The associated glomerulonephritis is highly variable in nature and may profoundly influence clinical outcome. Prognostic features are reviewed in an effort to identify high-risk patients. Age, non-renal manifestations, non-selectivity of proteinuria, and evidence of preceding streptococcal infection are relatively weak predictors of end-stage renal disease. The presenting clinical and histologic expressions of nephritis are more useful prognosticators, but neither are completely reliable. Patients with greater than 50% crescents, and those with nephrotic syndrome complicated by various combinations of hypertension, azotemia, oliguria, and/or hypoproteinemia, are at increased risk of renal failure and might benefit from therapeutic interventions. Experience with various modalities is reviewed. Faced with uncontrolled clinical data, it is unclear whether immunosuppressive agents or plasmapheresis offer a therapeutic advantage over oral corticosteroids alone.

Adolescent↗

Membranoproliferative glomerulonephritis type I in children: correlation of clinical features with pathologic subtypes.

Renal biopsies from 33 patients with membranoproliferative glomerulonephritis (MPGN) type I were reviewed to identify pathologic subtypes of this disease and assess their correlation to clinical features. The patients were divided into two groups: group A included 16 patients in chronic or end-stage renal failure and group B 17 patients with no evidence of renal insufficiency. At presentation, a nephrotic or nephritic syndrome and azotemia were equally common in both groups. The incidence of hypertension was significantly increased in group A (P less than 0.05), while recurrent gross hematuria was more common in group B. Nephrotic syndrome was more common during the course of illness in group A. Three subtypes of MPGN type I were recognized, based on whether duplication of glomerular capillary basement membranes was focal segmental (FS; 9 cases), diffuse global (DG; 18 cases), or mixed segmental and global (6 cases). Eight of nine patients showing FS MPGN type I were in group B (p less than 0.05). In contrast, 11 of 18 patients with DG MPGN type I and 4 of 6 with a segmental and global pattern were in group A (P = not significant). Therefore, FS MPGN is a good predictor of a favorable clinical outcome, whereas the other two subtypes are not. This was confirmed by a 100% actuarial kidney survival for the nine patients with FS MPGN and a 50% kidney survival of 7.5 years for patients with the other two subtypes.

Adolescent↗

Successful management of thrombocytopenia, microangiopathic anemia, and acute renal failure by plasmapheresis.

We report on the outcome of six consecutive adult patients who presented with microangiopathic anemia and thrombocytopenia. Clinical parameters on admission included platelet counts less than 45,000/mm3, microangiopathic red blood cell morphology, mental status abnormalities, and in three, rapidly progressive azotemia requiring dialysis. All patients underwent plasma exchange therapy as part of their treatments. Patients with renal failure underwent plasma exchange with a hollow fiber plasma separator, while those without renal failure were treated with a cytocentrifuge. All received fresh frozen plasma as replacement solution and were treated with glucocorticoids as well. For all six patients, plasmapheresis and conventional drug therapy resulted in remission that has lasted for 16 +/- 5 months (range 8 to 24 months). Early cessation of plasmapheresis in two patients resulted in rapid relapse. Patients who required dialysis now have a mean creatinine of 2.0 +/- 0.9 mg/dL (range 1.2 to 3.5). With similar volumes of exchange, and the same number of treatments, less fresh frozen plasma was used in the three patients treated with the hollow fiber separator than in patients treated with the cytocentrifuge (6.3 +/- 3.7 v 14.8 +/- 4.3 U/exchange, P less than 0.05). We conclude that plasmapheresis is a useful therapeutic modality for the treatment of thrombocytopenia and microangiopathic hemolytic anemia. In addition the use of a hollow fiber plasma separator for plasmapheresis is safe and efficient, particularly when concurrent dialysis is required.

Acute Kidney Injury↗