Biomedical subjects
V E Torres
Publications and source records attributed to V E Torres.
Intracranial cysts in autosomal dominant polycystic kidney disease.
Autosomal dominant polycystic kidney disease (ADPKD) is a systemic disorder well known for its association with intracranial aneurysms. A series of patients with ADPKD who were screened for the presence of an intracranial aneurysm were reviewed and found to include an unexpectedly high number with intracranial arachnoid cysts. Among 247 patients with ADPKD who underwent magnetic resonance imaging (180 cases) or high-resolution contrast-enhanced computerized tomography (67 cases), there were 151 women and 96 men with a mean age of 44 years. Intracranial arachnoid cysts were found in 20 patients (8.1%) with ADPKD compared to two (0.8%) in a control group without ADPKD matched for age, sex, and method of imaging (p < 0.0001). Multiple intracranial arachnoid cysts were found in two patients. Polycystic liver disease was present in 17 (85.0%) of the 20 patients with intracranial arachnoid cysts compared to 119 (52.4%) of the 227 patients without (p < 0.004). Pineal cysts were found in two patients (0.8%) and choroid plexus cysts were found in three patients (1.2%) but this was not different from the control population. None of the intracranial cysts was symptomatic and none was treated surgically. Intracranial arachnoid cysts are a relatively frequent incidental finding in patients with ADPKD, providing further support for the systemic nature of this disease. In the authors' experience with approximately 1500 patients with ADPKD, no complication has been encountered from an intracranial arachnoid cyst, suggesting that asymptomatic intracranial arachnoid cysts in patients with ADPKD require no treatment.
Extrapulmonary lymphangioleiomyomatosis and lymphangiomatous cysts in tuberous sclerosis complex.
OBJECTIVE: To describe the clinical manifestations, imaging findings, and histologic features of extrapulmonary lymphangioleiomyomatosis (LAM) in the tuberous sclerosis complex (TSC). DESIGN: We retrospectively reviewed institutional medical records since 1940 to identify patients with TSC and extrapulmonary LAM. MATERIAL AND METHODS: Of 403 patients with TSC, 3 had pulmonary and extrapulmonary LAM and retroperitoneal lymphangiomatous cysts. The clinical, imaging, and histologic features of these three patients were summarized, including analysis of biopsy specimens by conventional histology, immunohistology, radiolabeled ligand-binding assays, and tissue culture. RESULTS: The three young women had characteristic dermatologic findings of TSC and pulmonary LAM. Two patients were of normal intelligence, and one had a recent history of contraceptive use. All three patients had intra-abdominal lymphangiomatous cysts, uterine LAM, and renal angiomyolipomas. Renal and uterine biopsy specimens demonstrated positive immunostaining for melanoma-related antigens and expression of estrogen and progesterone receptors by ligand-binding assay and immunohistology. Cells cultured from LAM tissue of one of the patients exhibited a mitogenic response to estradiol. CONCLUSION: Clinically significant extrapulmonary LAM is a rare manifestation of TSC and may occur in women with this disease who also have pulmonary LAM. The clinical features of these patients confirm the importance of sex steroids in the development of these lesions. Immunohistochemical findings suggest that LAM and angiomyolipomas have a neuroectodermal origin. The development of lymphangiomatous cysts in these patients is probably due to smooth muscle proliferation in lymph vessels, which can result in lymphatic obstruction.
Effect of sodium chloride, enalapril, and losartan on the development of polycystic kidney disease in Han:SPRD rats.
We found that the administration of an angiotensin I-converting enzyme inhibitor and sodium chloride loading lessen the development of renal cystic disease induced by 2-amino-4-5-diphenylthiazole in rats. To determine whether similar effects could be observed in an autosomal dominant model of polycystic kidney disease, heterozygous cystic (Cy/+) and homozygous normal (+/+) Han:SPRD rats were divided into experimental groups at 3 weeks of age. The first study included four groups receiving enalapril (50 mg/L), losartan (400 mg/L), hydralazine (80 mg/L), or no drug in their drinking water. The second study included four groups fed a sodium-deficient diet or the same diet supplemented with 0.25%, 0.6%, or 3.3% sodium chloride. The Cy/+ rats receiving enalapril had lower kidney weights and histologic scores than those in the control group, and lower kidney weights, plasma creatinines, and histologic scores than those in the hydralazine group. The Cy/+ rats receiving losartan had lower plasma creatinines and histologic scores than those in the control and hydralazine treatment groups. A sodium-deficient diet markedly blunted the growth of the animals and the development of cystic disease. Increases in the sodium content of the diet in the other three groups were accompanied by higher relative kidney weights and histology scores, while the levels of plasma creatinine were not significantly different. Regression of the cystic disease was observed between 3 and 4 months of age. These results indicate that the development of autosomal dominant polycystic kidney disease in the rat can be modulated by pharmacologic and nutritional factors.(ABSTRACT TRUNCATED AT 250 WORDS)
Renal ammonia in autosomal dominant polycystic kidney disease.
Recent studies have suggested that defective medullary trapping of ammonia underlies the acidosis associated with renal failure and sets in motion maladaptive compensatory mechanisms that contribute to the progression of renal disease. Since a renal concentrating defect is an early functional abnormality in autosomal dominant polycystic kidney disease (ADPKD), defective medullary trapping and urinary excretion of ammonia may also occur early and have important pathophysiological consequences. The urinary pH and excretions of ammonia, titratable acid, and bicarbonate, were measured during a 24-hour baseline period and following the administration of ammonium chloride (100 mg/kg body wt) in ADPKD patients with normal glomerular filtration rate and in age- and gender-matched healthy control subjects. The distal nephron hydrogen ion secretory capacity was assessed during a bicarbonate infusion. Ammonia, sodium, pH, C3dg, and C5b-9 were measured in cyst fluid samples. The excretion rates of ammonia during the 24-hour baseline period and following the administration of ammonium chloride were significantly lower, and the relationship of ammonia excretion to urinary pH was significantly shifted downward in ADPKD. No difference in the increment of urinary pCO2 (delta pCO2) or the peripheral blood-urine pCO2 gradient (U-B pCO2) between ADPKD patients and control subjects was detected during a sodium bicarbonate infusion. Calculated concentrations of free-base ammonia in cyst fluid samples exceeded those calculated from reported concentrations of ammonia in renal venous blood of normal subjects. C3dg and C5b-9 were detected in some cyst fluids. The urinary excretion of ammonia is reduced in ADPKD patients with normal glomerular filtration rate.(ABSTRACT TRUNCATED AT 250 WORDS)
Renal cell carcinoma in autosomal dominant polycystic kidney disease.
To provide information on the clinical presentation, diagnosis, pathology, and biologic behavior of renal cell carcinoma in patients with autosomal dominant polycystic kidney disease (ADPKD), three cases seen at this institution between 1955 and 1992, as well as the cases reported in the literature, were reviewed in detail. No male predominance was observed (12 men, 13 women) in the 25 patients who met the inclusion criteria. The age of presentation was earlier than that seen in the general population (45 versus 61 yr). Fever, night sweats, and weight loss were prominent at presentation. Fever is a more common presenting symptom of renal cell carcinoma in ADPKD (32%) than in the general population (7%). Twenty percent of the patients had metastatic disease at presentation. Even with computed tomography and magnetic resonance, the diagnosis was difficult and often delayed, and the accumulation of 111In-labeled white blood cells can wrongly suggest a cyst infection. Renal cell carcinoma in ADPKD is more often concurrently bilateral (12 versus 1 to 5%), multicentric (28 versus 6%), and sarcomatoid in type (33 versus 1 to 5%) than in the general population. Because previous studies have failed to demonstrate a higher prevalence of renal cell carcinoma in ADPKD, this information suggests either a malignant potential restricted to a small subset of patients with this disease or an alteration in the biologic behavior of renal cell carcinoma when it develops in the setting of ADPKD.
Hepatic venous outflow obstruction in autosomal dominant polycystic kidney disease.
To discuss the clinical presentation, diagnosis, and treatment of hepatic venous outflow obstruction as a complication of polycystic liver disease, four cases diagnosed and treated at our institution have been reviewed and the information from six previously published case reports has been summarized. Eight of the 10 patients were women. All presented with severe ascites. Nine had polycystic kidneys. Three had moderate-to-advanced renal insufficiency, four were on hemodialysis, and one had a renal allograft. Possible predisposing factors were identified in seven patients; the most common was recent abdominal surgery, which, in three cases, was a bilateral nephrectomy. All patients had extrinsic compression of the hepatic veins and the inferior vena cava by hepatic cysts, and four had proven superimposed thrombosis of the inferior vena cava and/or hepatic veins. In the patients seen in this institution, magnetic resonance imaging was helpful in determining the level of obstruction in the inferior vena cava and the patency of the hepatic and portal veins. The outcome was worse in the patients with thrombosis; one recovered after a portocaval shunt, and the remaining three patients died. On the other hand, five of the six patients without thrombosis recovered after alcohol sclerosis of a large dominant cyst (one patient) or after hepatic resection and cyst fenestration (four patients). Hepatic venous outflow obstruction probably has been underrecognized as a cause of portal hypertension, ascites, and liver dysfunction in polycystic liver disease. The diagnosis can be reliably established with current imaging techniques, especially magnetic resonance imaging.(ABSTRACT TRUNCATED AT 250 WORDS)
Renal cystic disease and ammoniagenesis in Han:SPRD rats.
Cyst formation in conditions associated with increased renal ammoniagenesis (hypokalemia, distal renal tubular acidosis, renal mass reduction) and experimental links between increased ammoniagenesis and interstitial inflammation have suggested a role for ammonia in the pathogenesis of polycystic kidney disease (PKD). To explore this hypothesis, Han:SPRD rats, a PKD model that affects male more severely than female animals, have been used. Heterozygous cystic (Cy/+) and homozygous normal (+/+) male and female offspring of Cy/+ rats were divided at 3 wk of age into control groups drinking water and experimental groups drinking 300 mM NH4Cl, 300 mM KHCO3, 200 mM KHCO3, 200 mM KCl, 200 mM NaHCO3, or 200 mM NaCl. At 2 months of age, the rats were kept fasting from 8:00 p.m. to 8:00 a.m. in metabolic cages and urine samples were collected under mineral oil. The rats were then weighed and anesthetized for the collection of blood and kidneys. The administration of 300 mM NH4Cl, and to a lesser extent that of 200 mM NaCl, was accompanied by an increase in the urinary excretion of ammonia and aggravation of the renal cystic disease. On the other hand, the administration of 300 mM KHCO3, 200 mM KHCO3, or 200 mM NaHCO3 lowered the urinary excretion of ammonia and markedly reduced the severity of the cystic disease and interstitial inflammation. The administration of 300 mM KHCO3, and to a lesser extent that of 200 mM KHCO3, resulted in the precipitation of calcium phosphate in the medullary collecting ducts.(ABSTRACT TRUNCATED AT 250 WORDS)
The kidney in the tuberous sclerosis complex.
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Renal stone disease in autosomal dominant polycystic kidney disease.
Nephrolithiasis is an important manifestation of autosomal dominant polycystic kidney disease (ADPKD), which occurs in approximately 20% of patients. It should always enter the differential diagnosis of flank pain in patients with ADPKD. The diagnosis is hindered by the distorted anatomy of the polycystic kidneys and the frequent occurrence of parenchymal and cyst wall calcifications, and requires demonstration of the relationship to the collecting system by intravenous urography and/or computed tomography. Computed tomography is the most sensitive imaging technique for detection of stones or calcifications, whereas intravenous urography is the most sensitive for visualization of the intrarenal collecting system. Precaliceal tubular ectasia can be detected in 15% of patients with ADPKD and nephrolithiasis, but this association may not be specific to ADPKD. The composition of the stones is most frequently uric acid and/or calcium oxalate. Metabolic factors are important in their pathogenesis. Distal acidification defects may be important in a few patients, while an abnormal transport of ammonium, low urine pH, and hypocitruria are the most common abnormalities. The treatment of nephrolithiasis in patients with ADPKD is not different from that in patients without ADPKD. Extracorporeal shock wave lithotripsy and percutaneous nephrostolithotomy in patients with early disease and normal renal function are not contraindicated.
Renal tumors.
Renal tumors including renal cortical adenoma, renal cell carcinoma (hypernephroma), oncocytoma, angiomyolipoma (hamartoma), medullary fibroma, juxtaglomerular cell tumor, nephroblastoma (Wilms' tumor), mesoblastic nephroma, renal blastema, sarcoma, and secondary metastatic lesions are discussed. The syndromes of tuberous sclerosis, von Hippel-Lindau disease, and acquired renal cystic disease are reviewed. Renal cell carcinoma accounts for 85% of clinically relevant renal tumors. Development of renal cell carcinoma appears to be associated with loss of tumor suppressor genes on the short arm of chromosome 3. Over the past year, there were no major advances in the imaging of renal tumors. Ultrasound and computed tomography remain the standards, whereas magnetic resonance imaging, although having a high sensitivity for detection of renal masses, is used primarily for staging the inferior vena cava. The only effective therapy for localized renal cell carcinoma remains surgical resection. There are objective responses seen with immune modulation therapy (interferon-alpha, interleukin-2), but cures are infrequent.
Value of magnetic resonance angiography for the detection of intracranial aneurysms in autosomal dominant polycystic kidney disease.
The association of intracranial aneurysms with autosomal dominant polycystic kidney disease (ADPKD), the 30-day mortality rate exceeding 50% for aneurysmal rupture, the effectiveness of surgical repair of unruptured aneurysms with a low surgical risk, and the development of noninvasive imaging techniques for their detection have led physicians to consider the value of screening patients with ADPKD for unruptured intracranial aneurysms. The sensitivity and specificity of high-resolution computed tomography and magnetic resonance imaging for the diagnosis of small intracranial aneurysms have been disappointing. To determine the value of magnetic resonance angiography (MRA), 85 patients with ADPKD without symptoms related to an intracranial aneurysm and 2 patients with ADPKD presenting with a subarachnoid hemorrhage or a suspected aneurysmal leak were studied. MRA was performed with the Multisequence Vascular Package (GE Medical Systems) with use of three-dimensional time-of-flight and three-dimensional phase-contrast techniques, and postprocessing maximum intensity projection images were generated to eliminate the problem of overlapping vessels. Asymptomatic intracranial aneurysms were detected in 6 (22%) of 27 patients with and 3 (5%) of 56 patients without a family history of intracranial aneurysm or subarachnoid hemorrhage (P = 0.02, information missing in 2 patients) and in the 2 patients who presented with a symptomatic aneurysm. A stepwise logistic regression analysis indicated that a family history of intracranial aneurysm or subarachnoid hemorrhage was independently associated with the presence of intracranial aneurysms. All of the aneurysms were < or = 6.5 mm in diameter.(ABSTRACT TRUNCATED AT 250 WORDS)
Measurement of normal renal artery blood flow: cine phase-contrast MR imaging vs clearance of p-aminohippurate.
OBJECTIVE: The purpose of this study was to compare cine phase-contrast MR imaging with renal clearance of p-aminohippurate for measuring normal renal blood flow. A reliable technique for evaluation of renal hemodynamics would be useful for studying renal vascular diseases and the effects of treatment. Measurements of renal blood flow based on renal clearance of p-aminohippurate are limited in that the kidneys are not studied separately, temporal resolution is poor, and normal renal function is required. SUBJECTS AND METHODS: Bilateral oblique sagittal cine phase-contrast MR images were obtained simultaneously in 10 healthy adult volunteers, with the imaging planes oriented perpendicular to the left and right renal arteries in order to measure through-plane flow. Velocity encoding was 150 cm/sec (seven of 10 volunteers) and 100 cm/sec (eight of 10 volunteers). Axial cine phase-contrast images of the abdominal aorta above and below the origins of the renal arteries were obtained in six volunteers. In these cases, renal blood flow was determined by measuring the difference between suprarenal and infrarenal aortic flow. For all volunteers, renal clearance of p-aminohippurate was determined immediately after MR measurements. RESULTS: Renal blood flow measurements determined by using cine phase-contrast MR imaging were in close agreement with those determined by using clearance of p-aminohippurate. At a velocity encoding of 150 cm/sec, the mean difference was 69 ml/min (95% confidence interval, -31 to 169 ml/min). At a velocity encoding of 100 cm/sec, the mean difference was 39 ml/min (95% confidence interval, -100 to 177 ml/min). Aortic flow measurements using cine phase-contrast MR imaging appeared to be less reliable for determining renal blood flow than measurements in the individual renal arteries, with a mean difference of -75 ml/min (95% confidence interval, -381 to 231 ml/min) compared with renal blood flow determined by using clearance of p-aminohippurate. CONCLUSION: We conclude that cine phase-contrast MR imaging is a promising technique for noninvasive measurement of renal blood flow. Measurements agreed closely with those obtained by using clearance of p-aminohippurate. In addition, the MR technique is faster, can be used to measure unilateral or bilateral renal blood flow, and does not depend on renal function.
Screening for unruptured intracranial aneurysms in autosomal dominant polycystic kidney disease.
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Lupus anticoagulant in systemic lupus erythematosus: a clinical and renal pathological study.
Circulating lupus anticoagulant (LA) is associated with thrombosis in large and small vessels. To determine how often the presence of LA is associated with thrombosis within the renal microcirculation, 33 patients with systemic lupus erythematosus (SLE), renal dysfunction, and LA were identified over a 25-year period (LA group) and 32 patients with renal SLE but with normal gross coagulation screen were matched for age, sex, and biopsy timing (C group). Prevalences of serositis, neuropsychiatric illness, leukopenia, thrombocytopenia, hemolysis, anti-DS-DNA elevation, and complement reduction were similar. Arthritis was less and biologic false-positive (BFP) syphilis serology more common in LA. More LA patients had thrombotic events (LA 39% v C 13%; P = 0.014); bleeding episodes, including postbiopsy, were similar. At biopsy, hypertension (LA 55%, C 41%), serum creatinine (mean +/- SD: LA 186 +/- 168 mumol/L [2.1 +/- 1.9 mg/dL] v C 150 +/- 168 mumol/L [1.7 +/- 1.9 mg/dL]) and proteinuria (LA 2.6 +/- 3.1 g/24 h v C 3.1 +/- 2.7) were similar. Lesions by World Health Organization (WHO) class, activity, and chronicity indices, as well as immunofluorescence (IF) and electron microscopy (EM) findings, were not significantly different. Occlusive glomerular, arteriolar, and arterial fibrin thrombi, along with varying degrees of renal thrombotic microangiopathy, were seen in five of 33 patients with LA, but zero of 32 C patients (P = 0.053); three of these five patients died soon after biopsy. Overall, mortality was not different between LA and C. We conclude that the majority of patients with SLE, renal dysfunction, and LA exhibit renal morphologic findings indistinguishable from patients without LA. However, a significant minority of LA patients have thrombotic microangiopathy in their biopsy, which is accompanied by a worse prognosis.
Synthesis of renin by tubulocystic epithelium in autosomal-dominant polycystic kidney disease.
Evidence suggests an important role for the renin-angiotensin system in the pathogenesis of autosomal-dominant polycystic kidney disease (ADPKD). Therefore, we studied the presence of immunoreactive renin in renal biopsies and measured the concentrations of renin in cyst fluids. Normal kidneys and kidneys with renal artery stenosis were used for comparison. In ADPKD, immunoreactive renin was present in juxtaglomerular apparatus, associated arterioles, and in some cells within the connective tissue surrounding the cysts. Vascular immunoreactive renin was less prominent than in renal artery stenosis. Increased amounts of tubular immunoreactive renin were noted in polycystic kidneys, as compared to normal kidneys and kidneys with renal artery stenosis. Cyst fluids contained renin detected by Western analysis and enzymatic activity; concentrations were greater in gradient cysts than in nongradient cysts. Seventy-four percent of the renin in gradient cysts was active as compared to 23% in nongradient cysts and 15% in plasma. To determine whether cyst epithelial cells are capable of synthesizing renin, these cells were isolated in tissue culture. Enzymatic assay of extracts from these cells revealed the presence of renin-like enzymatic activity (1.3 +/- 0.8 ng AI/mg protein/hr). The synthesis of renin by tubulocystic epithelium was confirmed by [35S]-methionine radiolabeling of cyst-derived cells, followed by immunoprecipitation and SDS-PAGE and by detection of renin mRNA by the polymerase chain reaction. These results indicate that the tubulocystic epithelium has the potential to synthesize renin. Elevated levels of active renin in renal cysts may be linked to the pathogenesis of hypertension in ADPKD. The occurrence of renin in the lining epithelium of cyst walls raises the possibility that abnormal expression of the renin-angiotensin system may, by a paracrine or autocrine mechanism, regulate epithelial hyperplasia in growing renal cysts.
Cyst decompression surgery for autosomal dominant polycystic kidney disease.
A prospective study was undertaken to evaluate the efficacy of surgical cyst decompression for retarding the progression of renal failure and for the management of chronic pain associated with autosomal dominant polycystic kidney disease (ADPKD). Thirty patients with ADPKD and pain (14 patients), renal insufficiency (4 patients), or both (12 patients) underwent unilateral (19 patients) or bilateral (11 patients) cyst reduction surgery. The patients were monitored for 21 +/- 2 months postoperatively. The probability of being painfree was 80% at 1 yr and 62% at 2 yr. Preoperative and 1-to 3-month postoperative serum creatinine levels and GFR (clearance of insulin or (125I) iothalamate) were not significantly different (2.2 +/- 0.3 versus 2.2 +/- 0.3 mg/dL and 49 +/- 8 versus 54 +/- 9 mL/min/1.73 m2, respectively). One-year serum creatinine levels remained unchanged in patients with normal preoperative renal function (1.0 +/- 0.07 versus 1.0 +/- 0.05 mg/dL), whereas those with preoperative progressive renal insufficiency had no difference in the mean slope of reciprocal serum creatinine plots preceding and after surgery (-0.008 +/- 0.001 versus -0.009 +/- 0.002 dL/mg/month). In patients who underwent unilateral surgery, split function isotope scans showed no change in function of the operated kidney when compared with the nonoperated kidney. Surgical cyst decompression provides effective relief of chronic pain without compromising renal function. However, the data in this article do not support the use of this procedure to slow progression of renal insufficiency in ADPKD.
Saccular intracranial aneurysms in autosomal dominant polycystic kidney disease.
The literature on the association of intracranial aneurysms in autosomal dominant polycystic kidney disease (ADPKD) consists mainly of case reports and small series of patients. To provide a more-detailed description of this association and its frequency, the records of all ADPKD patients with saccular intracranial aneurysms, all ADPKD autopsy cases including brain examination, and sex- and age-matched autopsy cases without ADPKD seen at the Mayo Clinic between 1950 and 1989 and of all Rochester residents with a diagnosis of subarachnoid hemorrhage or ADPKD between 1945 and 1984 were reviewed. The presentation of the 41 patients (22 men and 19 women; mean age, 46.4 yr) with this association was subarachnoid hemorrhage in 33, transient ischemic attacks in 2, incidental angiographic or autopsy finding in 5, and discovery during angiographic screening in 1. Thirty-one, seven, and three patients harbored one, two, and three aneurysms, respectively, arising from the middle cerebral artery (N = 23), anterior communicating artery (N = 16), internal carotid artery (N = 11), and vertebral or basilar artery (N = 4). A family history of intracranial aneurysm, subarachnoid hemorrhage, or intracranial hemorrhage at an early age was present in 22% of the patients. Small aneurysms (less than 5 mm) were less likely to have ruptured or caused symptoms (P less than 0.04). There was a trend for hypertension to be associated with the severity of the subarachnoid hemorrhage. Aneurysmal rupture occurred before age 50 in 64% of patients. Of the 89 ADPKD autopsy cases with brain examination, 22.5% had intracranial aneurysms.(ABSTRACT TRUNCATED AT 250 WORDS)