Activity of cathepsin B and collagenase in urine and excretion of fibronectin and TGF-beta 1 in urine of patients with membranous glomerulonephritis

In 30% cases nephrotic syndrome is due to membranous glomerulonephritis (MG). Fifty percent of patients reveal end stage renal disease in 15 years follow-up. The another 50% gain persistent remission. The pathogenesis of disease is not known. Protein accumulation in glomeruli leads to progressive loss of kidney structure and function in MG. Also the role of tissue proteolytic systems and growth factors in this process is not known. We aimed to estimate urine cathepsin B, collagenase activity and urine excretion of TGF-beta 1 and fibronectin in MG. MG patients revealed increased urine cathepsin B activity (10.58 +/- 8.73 pmol AMC/mg creatinine/min. vs. control 7.11 +/- 2.05 pmol AMC/mg creatinine/min. [p < 0.05]), urine collagenase activity (8.59 +/- 4.26 pmol AMC/mg creatinine/min. vs. control 3.84 +/- 2.09 pmol AMC/mg creatinine/min. [p > 0.02]) and increased urine excretion of fibronectin (214 +/- 335 ng/mg creatinine vs. control 12.7 +/- 6.7 ng/mg creatinine [p < 0.05]) and increased urine excretion of TGF-beta 1 (283.55 +/- 248.13 pg/ml vs. control 36.11 +/- 48.01 pg/ml [p < 0.05]). The results indicates on glomerular overproduction of TGF-beta 1 and urinary leak of proteolytic enzymes which may exacerbate glomerular proteolytic activity in MG. This may lead to glomerular protein accumulation and progressive loss of kidney function and structure in MG. Increased urine fibronectin excretion in MG patients seems to confirm the hypothesis.     

Can fingernail creatinine concentrations be used to predict duration of azotemia?

Clinical use of fingernail creatinine estimation to predict duration of azotemia is yet to be validated. We studied the fingernail creatinine concentrations in 48 subjects: seven controls, nine with acute renal failure, five with rapidly progressive glomerulonephritis, 12 with chronic renal failure and 15 with end-stage renal failure on maintenance hemodialysis. The creatinine concentration in aqueous eluates of powdered nail clippings was determined by the alkaline picrate reaction. The mean fingernail creatinine concentration was significantly higher in patients with chronic renal failure (93.7 +/- 83.7 micrograms/g) and end-stage renal disease on maintenance hemodialysis (118.4 +/- 46.8 micrograms/g) as compared to those with acute renal failure (36.6 +/- 23.7 micrograms/g) and rapidly progressive glomerulonephritis (35.8 +/- 20.6 micrograms/g). The creatinine concentrations did not differ significantly between normal subjects (27.2 +/- 28.7 micrograms/g) and those with acute renal failure and rapidly progressive glomerulonephritis. However because of large variability in the values of fingernail creatinine concentrations within each group, the test lacked specificity. Therefore, this investigation is an unreliable indicator of duration of azotemia in individual patients and is not likely to be of much clinical use.     

Diagnosis of thoracic outlet syndrome in the emergency department

Gadodiamide at a dose of 0.1 mmol/kg was administered intravenously to 10 renal transplanted patients with stable, impaired, or slowly deteriorating renal function (serum creatinine 194-362 mumol/l). The patients were referred for contrast medium enhanced magnetic resonance imaging to rule out possible graft circulation abnormalities. The excretion of gadodiamide in urine was prolonged as compared with healthy controls. After 120 h 92% of the injected dose was excreted in urine and only 0.4% in faeces. The plasma clearance of gadodiamide was 28.6 +/- (SD) 5.5 ml/min (n = 10), and the renal clearance (0-72 h) was 26.3 ml/min. The renal clearance of 125I-iothalamate for the same time period was 27.9 +/- 5.3 ml/min. Thus, gadodiamide is eliminated by glomerular filtration also in renal transplant patients with moderately to severe impaired renal function, and gadodiamide clearance may serve as an alternative marker for the determination of the glomerular filtration rate. Serum values of creatinine and beta(2)-microglobulin and creatinine clearance were unchanged by gadodiamide and neither was the urinary enzyme excretion significantly changed. These results suggest that the renal tolerance to gadodiamide is good also in renal transplant patients with impaired renal function.     

Effect of administration and subsequent cessation of buserelin on cancellous bone of female rats

OBJECTIVE: Low-dose dopamine has been used in critically ill patients to minimize renal dysfunction without sufficient data to support its use. The aim of this study was to determine whether low-dose dopamine improves renal function, and whether dobutamine, a nondopaminergic inotrope, improves renal function. DESIGN: Prospective, randomized, double-blind trial. PATIENTS: Twenty-three patients at risk for renal dysfunction were entered into the study. Five patients were later withdrawn. Study data for the remaining 18 patients were: mean age 55 yrs; mean Acute Physiology and Chronic Health Evaluation (APACHE) II score of 18; mean weight 71 kg). The following conditions were present: mechanical ventilation (n = 17 [inverse-ratio ventilation, n = 6]); inotrope administration (n = 11); sepsis (n = 13); and adult respiratory distress syndrome or multiple organ failure syndrome (n = 9). INTERVENTIONS: The study patients were administered dopamine (200 micrograms/min), dobutamine (175 micrograms/min), and placebo (5% dextrose) over 5 hrs each in a randomized order. Ventilator settings, fluid management, and preexisting inotropic support were not altered during the study. MEASUREMENTS AND MAIN RESULTS: Systemic hemodynamic values and indices of renal function (4-hr urine volume, fractional excretion of sodium, and creatinine clearance) were measured during the last 4 hrs of each infusion. Dopamine produced a diuresis (145 +/- 148 mL/hr) compared with placebo (90 +/- 44 mL/hr; p < .01) without a change in creatinine clearance. Conversely, dobutamine caused a significant increase in creatinine clearance (97 +/- 54 mL/min) compared with placebo (79 +/- 38 mL/min; p < .01), without an increase in urine output. CONCLUSIONS: In stable critically ill patients, dopamine acted primarily as a diuretic and did not improve creatinine clearance. Dobutamine improved creatinine clearance without a significant change in urine output.     

Evaluation of highly damaged renal function following extracorporeal circulation--usefulness of alpha 1-microglobulin index

The patients with highly damaged renal functions following extracorporeal circulation (ECC) were reviewed. Markers such as serum and urine creatinine (SCr, UCr), blood urea nitrogen (BUN), alpha 1-microglobulin in urine (as a marker of renal tubular function, abbreviated as U alpha 1-m), microalbumin in urine (as a marker of renal glomerular function, abbreviated as UA1b) were measured in each cases. Twenty patients were selected with the maximum value of U alpha 1-mover 60 micrograms/dl during or after ECC. The patients were classified into three groups according to preoperative value of alpha 1-m index (alpha 1-m index (I) = U alpha 1-m/UCr x 100 mg/g Cr), and Albumin index (Albumin index (I) = UA1b/UCr x 100 mg/g Cr). Group I (n = 13); alpha 1-m I > 10 and, Alb I > or = 50 (abnormal value of tubular and glomerular function), Group II (n = 3); alpha 1-m I < or = 10, Alb I > or = 50 (abnormal value of glomerular function), Group III (n = 4); alpha 1-m I < or = 10, Alb I < 50 (normal value of tubular and glomerular function). Six patients in Group I required postoperative hemodialysis (HD) and one patient in Group II. No one required HD in Group III. These facts suggest that preoperative damage of tubular and glomerular functions may become prolonged or irreversible damages may occur after operation. HD is required frequently in patients with alpha 1-m I level over 500 mg/g Cr, especially continuous HD may be needed in patient with alpha 1-m I level over 1000 mg/g Cr.     

Association of crescentic glomerulonephritis with membranous glomerulonephropathy: a report of three cases

Association of membranous glomerulonephropathy with crescentic glomerulonephritis is apparently extremely rare. We report three patients who had this combination. One patient had biopsy-proven membranous glomerulonephropathy thirteen months prior to sudden and rapid decline in renal function necessitating hemodialysis. A repeat renal biopsy showed a superimposed crescentic nephritis and antiglomerular (GBM) antibodies were demonstrable in the serum. A second patient had proteinuria of unknown duration and then developed renal failure. Renal biopsy showed crescentic nephritis with a fine granular glomerular immunofluorescence for IgG typical of membranous glomerulonephropathy. Anti-GBM antibodies were present in this patient's serum. The third patient presented with acute renal failure of moderate severity. A renal biopsy revealed crescentic nephritis, granular deposits of immunoglobulins, and epimembranous electron-dense deposits typical of membranous glomerulonephropathy. Although his creatinine clearance improved spontaneously, nephrotic syndrome has persisted and a repeat renal biopsy showed a progression of the membranous glomerulonephropathy with the disappearance of the crescentic lesions. The reason for this peculiar association of membranous glomerulonephropathy and crescentic glomerulonephritis is unclear. It is possible that deposition of immune-complexes along glomerular basement membrane may render the glomerulus more susceptible to additional injury from a variety of other agents. Alternatively, depostis formed in one disease could initiate release of normal or altered basement membrane material and lead to formation of anti-GBM antibodies and subsequent development.     

The significance of focal glomerular sclerosis in children who have nephrotic syndrome

This study was undertaken to learn the significance of focal glomerular sclerosis in children who have nephrotic syndrome. Tissue obtained by percutaneous renal biopsy 10-15 years previously was re-examined. Initially, two of the 29 biopsy specimens contained focal segmental hyalinosis or sclerosis and five of the 29 had focal glomerular obsolescence. The paraffin blocks were serially sectioned and examined. Following this procedure, seven of the 29 biopsies had focal segmented hyalinosis and 16 of the 29 had focal glomerular obsolescence. The percentages of focal segmental hyalinosis and focal glomerular obsolescence were recorded. Only those patients whose focal segmental hyalinosis exceeded 2% progressed to renal failure. Age-matched autopsy material from patients dying without renal dysfunction was used as a control. Focal glomerular sclerosis was seen in 75.8% of the control specimens, although few glomeruli within each specimen were involved. Focal glomerular sclerosis may be found normally; it may be found in nephrotic children who do not develop renal failure. The quantification of sclerotic lesions may be of prognostic significance in childhood nephrosis.     

Clinicopathological significance of intratubular giant macrophages in progressive glomerulonephritis

Very large macrophages, which we have termed "giant macrophages" (G-M phi), have been found in renal tubules, some containing cytoplasmic vacuoles. To elucidate their pathophysiological roles, we examined renal biopsy tissues from various primary glomerulonephritis (GN) and tubulointerstitial nephritis (TIN) using immunohistochemistry with monoclonal antibodies against M phi and other cell surface markers. Giant macrophages were absent or rare in TIN, minimal change nephrotic syndrome, and minor glomerular abnormalities, but G-M phi was plentiful in progressive glomerulonephrides such as IgA nephropathy with crescents, membranoproliferative GN, focal segmental glomerulosclerosis, and especially in crescentic GN. These G-M phi were usually seen in the lumen of renal tubules, but occasionally were found in the Bowman's spaces and glomerular tufts, and similar cells were also found in urine. Moreover, they frequently made contact with tubular epithelial cells expressing intercellular adhesion molecule-1, and the tubular epithelial cells in such lesions often had degenerative changes. Giant M phi may damage tubular epithelial cells from the luminal side. Phenotypically, G-M phi showed activated (CD71+) and mature (25F9+) characteristics along with features of M phi (CD68+), and the cytoplasm contained a great deal of lipids. The numbers of G-M phi in renal tissues closely correlated with the degree of hematuria (rho = 0.5, P < 0.001), serum creatinine value (r = 0.63, P < 0.001) in GN patients (N = 96) and with proteinuria in IgA nephropathy patients (r = 0.89, P < 0.001, N = 27). These data suggest that G-M phi are M phi that were activated and matured in certain active inflammatory sites, which flowed into tubules and then into urine. Thus, the existence of G-M phi in biopsy tissue or urine reflect the activity of GN and may have a predictive value for the progression of GN.     

Renal handling of Zn-alpha2-glycoprotein as compared with that of albumin and the retinol-binding protein

An unusual electrophoretic pattern of the urine from a patient with malignant lymphoma was observed. One of the major proteins, identified Zn-alpha2-glycoprotein (Zn-alpha2), was isolated from the urine and partly characterized. The Stokes radius was found to be 3.24 nm and the molecular weight, determined by sodium dodecyl sulfate polyacrylamide electrophoresis, 42,000. The plasma level in healthy individuals was 39 +/- 7 (SD) mg/liter. In 12 of 25 healthy individuals, Zn-alpha2 was measurable in the urine and was found to be 1.0 +/- 1.1 mg/liter. In 23 patients with chronic glomerulonephritis (CGN), in 9 with proximal tubular dysfunction (PTD), in 23 with various renal diseases (VRD), and in 10 with malignant lymphoma, the plasma level and the urinary excretion were compared with those of albumin (mol wt 67,000) and of the retinol-binding protein (RBP, mol wt 21,000). A close correlation was found between the urine-to-plasma (U/P) ratios of Zn-alpha2 and albumin in the patients with CGN, whereas in the PTD patients the U/P ratios of Zn-alpha2 and RBP were correlated. No significant renal arteriovenous difference in Zn-alpha2 could be demonstrated. The Zn-alpha2 excretion was increased also in two patients with malignant lymphoma and proteinuria of a tubular pattern. The plasma Zn-alpha2 varied inversely with the glomerular filtration rate in the patients with renal disease, but was normal in those with malignant lymphoma. The results are consistent with the assumption of a sieving coefficient of Zn-alpha2, substantially exceeding that of albumin, but notably lower than that of smaller low-molecular-weight proteins. An increased excretion of Zn-alpha2 may be due to increased glomerular permeability as well as to defective proximal tubular reabsorption.     

Mechanism of increased renal clearnace of amylase/creatinine in acute pancreatitis

We investigated three possible causes of the increased ratio of amylase/creatinine clearance observed in acute pancreatitis. The presence of rapidly cleared isoamylase was excluded by studies of serum and urine, which demonstrated no anomalous isoamylases. In pancreatitis, the ratios (+/-1 S.E.M.) of both pancreatic isoamylase (9.2+/-0.6 per cent) and salivary isoamylase (8.6+/-1.6 per cent) were significantly (P less than 0.01) elevated over respective control values (2.4+/-0.2 and 1.8+/-0.2 per cent). Increased glomerular permeability to amylase was excluded by the demonstration of normal renal clearance of dextrans. We tested tubular reabsorption of protein by measuring the renal clearance of beta2-microglobulin, which is relatively freely filtered at the glomerulus and then avidly reabsorbed by the normal tubule. During acute pancreatitis the ratio of the renal clearance of beta2-microglobulin to that of creatinine was 1.22+/-0.52 per cent, an 80-fold increase over normal (0.015+/-0.002 per cent), with a rapid return toward normal during convalescence. Presumably, this reversible renal tubular defect also reduces amylase reabsorption and accounts for the elevated renal clearance of amylase/creatinine observed in acute pancreatitis.     

Relationship between appearance of urinary red blood cell/white blood cell casts and the onset of renal relapse in systemic lupus erythematosus

The purpose of the study was to determine the extent to which urinary sediment findings (changes in red blood cells [RBCs], white blood cells [WBCs], and the appearance of RBC and WBC casts) predict the onset of renal relapse (defined as a specific increase in proteinuria and/or serum creatinine level) in patients with systemic lupus erythematosus (SLE). Seventeen SLE patients with biopsy-proven diffuse proliferative glomerulonephritis at initial presentation were followed prospectively for 1,129 patient-months under a study protocol. Semiquantitative urinalyses were performed at 2-month intervals during periods with little or no SLE activity and, more frequently, during periods with increased SLE activity. Each urinalysis was accompanied by a clinical evaluation and a panel of screening tests relevant to the evaluation of SLE activity. During this study, 877 semiquantitative urinalyses were performed and 43 renal relapses were observed in 14 patients. No relapse occurred in three patients. Of the renal relapses, 30 were defined as proteinuria relapses (mean baseline proteinuria increased from 0.8 +/- 0.1 g/24 hr to 2.7 +/- 0.3 g/24 hr; P < 0.001) and 13 were defined as serum creatinine relapses (mean baseline serum creatinine increased from 2.7 +/- 0.4 mg/dL to 3.8 +/- 0.5 mg/dL; P < 0.001). Red blood cell and/or WBC casts (cellular casts) were observed before or at the onset of 35 of the 43 renal relapses (sensitivity, 81%). The mean and median intervals between the appearance of cellular casts and the onset of renal relapse was 10 +/- 2 weeks and 8 weeks, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Anatomy and embryology of the lateral sellar compartment (cavernous sinus) medial wall

The protease inhibitor cystatin C is a non-glycosylated low molecular weight protein (Mr=13359) which is produced by all nucleated cells at a constant rate, freely filtered by the renal glomeruli, and catabolized in the tubuli. The aim of the study was to elucidate the applicability of serum cystatin C as a marker of glomerular filtration rate (GFR) in patients with various kidney diseases with a wide range of renal function and in dialysis patients. Seventy-six patients with various kidney diseases (aged 20 to 79 years) and 61 dialysis patients (aged 21 to 82 years) were included. Serum cystatin C was measured by automated particle-enhanced immunoturbidimetry, serum and urine creatinine by an enzymatic method, and GFR by 99mTc-DTPA-clearance using a single plasma sample method. Serum cystatin C in patients with various kidney diseases was 1.90+/-0.98 mg/L (mean+/-SD) and in dialysis patients 7.14+/-1.91 mg/L. In the non-dialysis patients a linear relationship was found between 99mTc-DTPA-clearance and 1/serum cystatin C (r=0.91, p-value<0.0001), 1/serum creatinine (r=0.89, p-value<0.0001), and creatinine-clearance (r=0.88, p-value<0.0001). Comparison of the non-parametric ROC plots for serum cystatin C (area under the curve (AUC)=0.9665; SE=0.0169), serum creatinine (AUC=0.9554; SE=0.0205), and creatinine-clearance (AUC=0.9731; SE=0.0160) revealed no significant differences (p-values: 0.50, 0.78, and 0.49). In conclusion, cystatin C may be a likewise good marker of the GFR as serum creatinine and creatinine-clearance, cystatin C having the advantage being independent of gender and muscle mass.     

Fenoldopam improves renal hemodynamics impaired by positive end-expiratory pressure

BACKGROUND: Mechanical ventilation with positive end-expiratory pressure (PEEP) can impair renal hemodynamics. Fenoldopam, a dopamine receptor agonist, has been shown, in animal experiments, to improve renal perfusion. The purpose of the current study was to examine the effects of this agent on altered renal hemodynamics secondary to positive pressure ventilation. METHODS: Twelve patients requiring mechanical ventilation of their lungs and PEEP for the treatment of hypoxemia after multiple trauma or visceral surgery were studied. Hemodynamic variables, renal vascular resistance, urine flow, creatinine, inulin and PAH clearance, and excretion of sodium and potassium (NaE and KE) were measured before and after introduction of a level of PEEP high enough to decrease urine flow rate by 25% or more, and after administration of intravenous fenoldopam. RESULTS: No hemodynamic effect resulted from 0.1 microgram.kg-1.min-1, but 0.2 micrograms.kg-1.min-1 fenoldopam decreased both diastolic and mean arterial blood pressure from 66 +/- 37 (mean +/- SEM) to 57 +/- 21 mmHg, and from 83 +/- 3 to 74 +/- 4 mmHg, respectively. Renal vascular resistance was reduced from 54 +/- 12 to 19 +/- 5 dynes.s.cm-5 at 0.2 micrograms.kg-1.min-1. Fenoldopam produced a dose-related increase in renal blood flow and PAH clearance. With 0.2 micrograms.kg-1.min-1 fenoldopam, urine flow increased from 81 +/- 25 to 116 +/- 29 ml/h, NaE from 28 +/- 7 to 85 +/- 70 microM/min, and KE from 65 +/- 12 to 109 +/- 16 microM/min. CONCLUSIONS: The results of the current study indicate that intravenous fenoldopam at a dose of 0.2 micrograms.kg-1.min-1 improves renal hemodynamics and increases Na and K excretion in patients requiring mechanical ventilation of their lungs and PEEP. These effects are probably caused by an increased kidney perfusion secondary to renal artery vasodilation.     

Renal hemodynamics during norepinephrine and low-dose dopamine infusions in man

OBJECTIVE: To characterize the effects of pressor doses of norepinephrine and low-dose dopamine (3 micrograms/kg/min) on renal hemodynamics in man, as well as to determine the clinical relevance of combining dopamine with norepinephrine. DESIGN: Prospective, single-blind, randomized study. SETTING: Clinical research unit of a tertiary care hospital. SUBJECTS. Six healthy male volunteers ranging in age between 20 and 28 yrs. INTERVENTIONS: The subjects were assigned randomly to four treatments (1 wk apart) in which renal hemodynamics and electrolyte excretion were assessed. Treatments consisted of 180-min infusions of the following: a) 0.9% sodium chloride (control); b) pressor doses of norepinephrine; c) dopamine at 3 micrograms/kg/min; and d) pressor doses of norepinephrine and dopamine at 3 micrograms/kg/min. Pressor doses of norepinephrine was defined as doses required to increase mean arterial pressure (MAP) by 20 mm Hg. MEASUREMENTS AND MAIN RESULTS: Glomerular filtration rate and renal blood flow were derived from inulin and para-aminohippurate clearances, respectively. Urine output and urine solute excretion were also determined. The mean norepinephrine dose required to increase MAP by 22 +/- 2 mm Hg was 118 +/- 30 ng/kg/min (range 76 to 164). After the addition of dopamine, similar doses of norepinephrine resulted in an MAP increase of 15 +/- 4 mm Hg. Glomerular filtration rate and urine output were comparable under all conditions. The infusion of norepinephrine decreased renal blood flow from 1241 +/- 208 to 922 +/- 143 mL/min/1.73 m2 (p = .03). The addition of dopamine returned renal blood flow to baseline values. The clearance of urine sodium increased significantly with the infusion of dopamine alone (p = .03). All subjects completed the four treatment periods. Adverse events, manifested mostly as palpitations and flushing, were rare and self-limiting. CONCLUSIONS: The addition of dopamine (3 micrograms/kg/min) to pressor doses of norepinephrine normalized renal blood flow in healthy volunteers. These hemodynamic changes were not reflected in urine output and glomerular filtration rate; hence, these monitoring parameters may be unreliable indicators of renal function in the setting of vasopressor therapy. In addition, systemic effects were observed with dopamine (3 micrograms/kg/min), as indicated by a decrease in MAP.     

Symmetrical cyanosis circumscripta e lipomate

In order to assess the Se status in individuals living in the Veneto region, a series of related measurements was performed. These included plasma selenium by PIXE and glutathione-peroxidase (GSH-Px) activities in plasma, red blood cells and platelets. Individuals were either normals or people suffering from various liver diseases. Moreover, an oral supplement of sodium selenite was given to 13 patients suffering from stable chronic renal failure (CRF) in parallel to 26 normals: data on plasma GSH-Px and on serum creatinine and creatinine clearance were collected either before or after supplementation. Results were in support of a relatively low selenium status: mean +/- SD plasma Se values of normals (0.82 +/- 0.17mumol/L, n = 82) were comparable to data observed in European regions where Se deficiency was already known. Even lower values were observed in those with liver diseases. Among enzyme activities, the distribution of the data of platelet GSH-Px was in further support of low Se status in the evaluated individuals. After Se supplementation, both normals and CRF patients showed a significant increase in the creatinine clearance, reflecting an improvement of the glomerular filtration rate. We suggest that more extensive surveys of the Se status should be carried out in Italy; moreover, Se supplementation may be advisable in individuals affected with moderate impairment of renal function.     

Glomerular morphology in nephrotic heroin addicts

Renal biopsies of 23 heroin addicts who presented with the nephrotic syndrome were examined by light and electron microscopy. The majority of patients (14) showed focal segmental glomerular sclerosis on light microscopy, four patients showed "minimal change", and two were classified as "focal global sclerosis." In one case focal mesangial proliferation was the outstanding feature; one patient had diabetic glomerulosclerosis; and one had mesangiocapillary glomerulonephritis and dysproteinemia. Visceral epithelial swelling and proliferation were present in 14 patients on light on light microscopy. Electron microscopy showed distinct podocyte changes consisting of loss of foot processes, vacuolization, and cytoplasmic degeneration; focal separation of podocytes from basement membranes was found in 11 of 18 cases. In some instances a few electron-dense deposits were present in the mesangium. Membranous nephropathy was not encountered, although it occurs in 30 to 40% of unselected adult nephrotic individuals. Of 15 patients followed for 2 months to 5 years, one died of heroin overdose, eight went into renal failure, two improved, and four continued to have proteinuria. It is concluded that nephrotic syndrome of heroin addicts is most often associated with focal segmental glomerular sclerosis and occasionally with minimal change disease or focal global sclerosis. Conceivably these three conditions represent different phases of one disease process, although different reactions to heroin or its various vehicles and contaminants cannot be excluded. The morphologic resemblance to experimental aminonucleoside and N,N'-diacetylbenzidine-induced nephrosis suggests a possible toxic origin.     

Objectives to direct the training of emergency medicine residents on off-service rotations: surgery, Part 3

Immunoglobulin A nephropathy (IgAN) frequently recurs in patients after renal transplantation (RT) on a conventional regimen of immunosuppressive therapy, but little is known about the influence of cyclosporine (Cs) on such a recurrence. We studied 84 patients retrospectively who underwent RT for renal failure attributable to IgAN (n = 71) or Henoch-Sch?nlein purpura nephropathy (HSPN) (n = 13) in two transplantation units, between January 1985 and June 1991 and were treated with Cs. Four patients died 3 months to 8 years after RT. Graft survival was 88% at 1 year, 75.2% at 5 years, and 63% at 8 years. Fifty patients underwent at least one graft biopsy, but studies with immunofluorescence were performed on only 28 (23 IgAN and 5 HSPN). After a mean follow-up of 68.1 +/- 37.2 months, mesangial IgA deposits recurred in 13 of the 28 patients (12 IgAN and 1 HSP) (prevalence, 46.4%). Among the 13 patients with recurrence of IgA deposits, all but 4 had urinary abnormalities. Light microscopy showed mesangial deposits and focal and segmental glomerular changes in 9 cases. Four patients lost their graft function 69 to 119 months after RT, and 2 had severe graft dysfunction. The rates of graft failure and mean serum creatinine at 1, 5, and 8 years were similar in the 13 patients with recurrence and the 15 patients without proven recurrence. In conclusion, Cs did not reduce the incidence or severity of IgAN recurrence. The latter was the cause of graft loss or dysfunction in 46.1 % of the patients with recurrent IgA deposits. Recurrent glomerulonephritis did not influence the 8-year graft survival in patients with IgAN or HSPN, but it may be an important cause of graft loss as evidenced by more extended follow-up.     

In vivo determination of very-low-density lipoprotein-apolipoprotein B100 secretion rates in humans with a low dose of l-[1-13C]valine and isotope ratio mass spectrometry

Beta2-Microglobulin (beta2-m) is a polypeptide that is freely filtered and then mostly reabsorbed and degraded in the proximal renal tubule. Beta2-m is a marker of glomerular filtration (GFR) in renal failure, whereas urinary beta2-m is a marker of proximal renal tubular dysfunction. Preeclampsia (PE) (ie, de novo hypertension in pregnancy with accompanying renal, cerebral, or liver disease or thrombocytopenia) often has renal involvement characterized by proteinuria, decreasing glomerular filtration, or renal tubular dysfunction. The aim of this study was to determine whether serum beta2-m concentration or urinary beta2-m excretion were greater in women with PE than in women with gestational hypertension (GH) (ie, isolated de novo hypertension in the second half of pregnancy) and normal pregnant women. Seventy-five pregnant women (35 with PE, 22 with GH, and 18 normotensives) were studied prospectively. Serum creatinine and beta2-m concentrations, 24-hour proteinuria, and fractional excretion (FE) of beta2-m were measured. Preeclamptics had similar serum creatinine but higher serum beta2-m (3.26+/-0.99 mg/L) than gestational hypertensives (2.44+/-0.77 mg/L; P = 0.016), and both groups had higher serum beta2-m than controls (1.62+/-0.54 mg/L; P = 0.001). FE of beta2-m was similar amongst groups (PE: 0.27%; interquartile range [IQR]: 0.20-0.86; GH: 0.21%; IQR: 0.11-0.40; controls: 0.26%, IQR: 0.12-0.69). PE is characterized by higher serum beta2-m but similar serum creatinine to GH. Because FE beta2-m is similar in these groups, this implies reduced filtering of beta2-m in PE rather than altered tubular handling of beta2-m. Further studies are now necessary to assess whether measurement of serum beta2-m is helpful in the clinical management of the hypertensive disorders of pregnancy.     

Relationship between prorenin, IGF-I, IGF-binding proteins and retinopathy in diabetic patients

Plasma prorenin and renin, serum insulin-like growth factor I (IGF-I) and IGF-binding protein (IGFBP-2 and IGFBP-3) concentrations were measured in 22 randomly selected male and female patients with insulin-dependent diabetes mellitus (IDDM) or non-IDDM (NIDDM). Plasma prorenin concentration was significantly elevated in patients with proliferative retinopathy (1869.5 +/- 785.0 mUL-1, mean +/- SEM) compared to patients with nonproliferative retinopathy (325.5 +/- 73.2 mUL-1, P < 0.003) and those without retinopathy (318.6 +/- 47.3 mUL-1, P < 0.007). Similarly, serum insulin-like growth factor-I (IGF-I) concentration in patients with proliferative retinopathy (126.3 +/- 21.5 micrograms L-1) was significantly higher than in patients with nonproliferative retinopathy (126.3 +/- 14.85 micrograms L-1, P < 0.004) and without retinopathy (135.2 +/- 37.26, P < 0.05). There was moderately strong positive correlation between plasma prorenin and serum IGF-I concentrations (r = 0.56, P < 0.01). Plasma prorenin concentration was uninfluenced by change in renal function (creatinine clearance, serum creatinine or BUN), but IGF-I levels were inversely related to creatinine clearance (r = 0.67, P < 0.002). There was no demonstrable relationship between IGF-binding proteins and prorenin or renin concentrations. In view of some overlap between plasma prorenin and serum IGF-I concentrations in diabetic patients with proliferative and nonproliferative retinopathy, measurement of both markers may be more useful in predicting the development of proliferative retinopathy in patients with diabetes mellitus than either measurement alone.