Marked Proteinuria Research Articles

Pulmonary Carcinoid Tumor Associated With Nephrotic Syndrome

A patient with carcinoid tumor of the lung associated with nephrotic syndrome was treated. Excision of the tumor resulted in remission of marked proteinuria, hypoalbuminemia, and edema. A review of the literature disclosed many neoplasms associated with the nephrotic syndrome; however, no association of the nephrotic syndrome and a carcinoid tumor of the lung has previously been reported, to our knowledge.

The effects of culture-maintained pancreatic islets on metabolic parameters, renal function, and glomerular lesions in the diabetic rat

This study was undertaken for two purposes: to determine whether cultured islets of adult donor rats could be used successfully to reverse the metabolic abnormalities of diabetes of long-term duration and to determine the effect of islet transplantation on renal function and glomerular lesions in diabetic rats. Four groups of rats were studied: (1) five age-matched normal control rats, (2) seven rats with chronic streptozotocin-induced diabetes, (3) six chronically diabetic rats transplant-improved for 3 months, and (4) five acutely diabetic rats transplant-improved for 12 months. Transplanted rats received 1500 culture-maintained adult pancreatic islets injected into the portal vein. Following successful islet transplantation, the metabolic parameters of diabetes, including hyperglycemia, glycosuria, and polyuria, returned to normal. Evaluation of renal function revealed that clearances of isotopic inulin and ϱ-aminohippuric acid were not different among the groups. However, proteinuria was significantly greater in diabetic rats than ir both normal ( p < 0.001) and transplant-improved rats ( p < 0.01). There was striking glomerular immunofluorescence for IgG and C 3 in diabetic rats and none in the other groups. Quantitative morphometric electron microscopy revealed that the glomerular mesangium was significantly greater than normal in diabetic rats and decreased in the transplant-improved rats. The data indicate that culture-maintained islets from adult donors, as previously reported for diabetes of short-term duration, have the capacity to reverse the diabetic process in chronically diabetic rats; and that although rats with chronic diabetes do not exhibit an alteration of glomerular filtration rate, they do develop marked proteinuria, glomerular immunofluorescence, and mesangial thickening, all of which improve following successful islet transplantation.

Clinicopathological correlations of persistent asymptomatic proteinuria in children.

36 patients with persistent asymptomatic proteinuria were studied over an average period of 2.9 years. All fulfilled the following criteria:persistent proteinuria, normal blood pressure, renal function and pyelogram, no previous nor family history of renal disease. Renal biopsy showed minimal change or diffuse proliferation of glomeruli. The disappearance of proteinuria correlated inversely with the degree of glomerular sclerosis. 12 of 14 children with minimal or no sclerosis lost their proteinuria. In contrast, in 8 of 11 patients with moderate sclerosis and in all 7 patients with marked sclerosis proteinuria persisted. Age over 16 years or heavy proteinuria with or without haematuria were indicative of marked glomerular sclerosis. The thickness of the glomerular basement increased with age. Impairment of renal function occurred in only 1 patient.

Anionic binding sites in the glomerular basement membrane: possible role in the pathogenesis of immune complex glomerulonephritis.

This paper details the ways in which the anionic sites of the GBM could be involved in immune complex deposition. Experiments were performed with chemically cationised proteins to test the hypotheses proposed. The most detailed investigations were concerned with the role of basic (cationic) antigen as a planted antigen, leading to in situ immune complex formation. A model was developed where it was possible to induce marked proteinuria following a single injection of small quantities of cationised human IgG or ferritin.

Some age aspects of the course of nephrotoxic nephritis in rats

Experiments on noninbred rats (aged 4 weeks and 4 months, respectively), with induced nephrotoxic glomerulonephritis showed that the course of the disease in younger rats differed from that in the older animals by its less marked proteinuria, which was selective in character, and by the smaller decrease in the concentration index of endogenous creatinine and of diuresis. Acid and ammonia formation in the young and adult rats were depressed equally. The morphological changes in the kidneys of the young rats were less severe than in the adult rats and were localized chiefly at the convoluted tubules. The level of DNA-synthesizing activity in the epithelial nuclei of the glomeruli was higher than the corresponding index for the epithelium of the convoluted tubules. The relative weight of the kidneys in young rats with nephritis showed a smaller increase than in the adult rats. The blood β-lipoprotein level in the young rats was increased eightfold. Restoration of the normal indices for the urine and blood occurred more rapidly in the young rats than in the adult animals.

1090 BRUSH BORDER ANTIGEN (BBAg) OF AUTOLOGOUS IMMUNE COMPLEX GLOMERULONEPHRITIS OF RATS (AIC) IN THE URINE OF VARIOUS SPECIES

Urine from 30 normal Sprague-Dawley (SD) rats, 20 SD rats affected with AIC having marked proteinuria (200-250 mg/day), 8 normal white New Zealand rabbits, a normal human, and from a patient with idiopathic membranous glomerulonephropathy (MGN) were examined for the presence of nephritogenic BBAg by the method of repeated immunization of five groups of normal (SD) rats with complete Freund's adjuvant (CFA) mixed with the test urine which had been dialyzed and lyophilized. Three control groups were: normal SD rats injected with normal saline only, CFA only, and CFA mixed with normal SD rat kidney cortex. Production of auto-antibodies to BBAg and the development of granular immune deposits containing rat IgG and C3 along the glomerular capillary walls in the kidneys of the immunized animal indicated the presence of BBAg in the test urine. The nephritogenic antigen was found in the urine of normal human, a patient with MGN, normal rabbit and rats with AIC. Surprisingly, it was absent in the urine of normal SD rats, a species that is highly susceptible to the development of AIC. It is hypothesized that only those species that do not have BBAg in the urine are susceptible to develop AIC or a similar glomerulonephritis.

Case Reports of the Pulmonary Artery Thrombosis and the Cerebral Artery Thrombosis in Two Nephrotic Patients

An increased coagulability of blood could be induced not only by nephrotic syndrome itself but by the therapeutic administration of corticotropine (ACTH) and cortisone. The use of modern diuretic agents and of immunosuppressive ones seemed to make the coagulation mechanism more complexed. As a result it was not so infrequent that nephrotic patients did die suddenly from the thromboembolic complications.This paper reports two cases of pulmonary artery thrombosis and cerebral artery thrombosis in nephrotic patients who died suddenly.Case 1. 25yrs. old male; There was edema in legs at the age of 23yrs. Two years had passed without any symptoms, but marked edema in legs reappeared and he developed edema on the face and discomfortness in anterior chest on exertion. He was admitted to our hospital with a diagnosis of nephrotic syndrome. Laboratory examination revealed marked proteinuria, hypoalbuminemia, hyperlipemia and the decrease in renal functions. During the hospitalization he was given diuretics, decholesterol agents, predonisolone and rinderon. However, serum total protein and cholesterol level were not changed. On the 115'th hospital day he suddenly complained discomfortness of chest and expired after three hours. Autopsy revealed extensive fresh and organized thrombosis of pulmonary arteries and focal glomerulonephritis.Case 2. 53yrs. old, female; There was edema in legs. Five months previously she had noticed abdominal extension. She was admitted to our hospital with a diagnosis of nephrotic syndrome. Predonine was administrated for one month, improving her symptoms gradually. She was discharged on the fourtieth hospital day. A few weeks after discharge abdominal extension, edema on the face developed progressively and she was readmitted to our hospital again. Laboratory examination revealed moderate proteinuria, hyperlipemia and slight decrease in renal function tests. During the hospitalization she was given predonine, imuran, decholesterol agent, diuretics and anabolic steroid, with a slight recovery of edema and proteinuria. On the 196'th hospital day she suddenly became shock state after passing the water. She gradually became stuporous. After 26 hours she expired. Autopsy revealed multiple, petechial hemorrhage with encephalomalacia in bilateral thalamus and slight membranous glomerulonephritis.

Development of a Lesion Resembling Diabetic Nephropathy in a Renal Homograft

One month following a cadaver renal transplant for obstructive uropathy, a 27-year-old man developed diabetes mellitus. Two years later, marked proteinuria and decreased renal function were detected. Eight months later, a second decline in function occurred. Light microscopy of graft biopsy specimens obtained after each decline in renal function showed increased mesangial cells and matrix, thickening of Bowman capsule, and tubular atrophy with basement membrane thickening. Vascular changes, interstitial infiltrate, and fibrosis were not prominent. Electron microscopic studies of the second biopsy specimen confirmed the light microscopic changes; subepithelial dense deposits were also detected. Immunofluorescent studies of both biopsy specimens demonstrated linear staining of glomerular and tubular basement membranes and Bowman capsule for IgG and albumin. Antikidney antibodies were not detected in the patient's serum. These observations suggest development of the diffuse form of diabetic nephropathy in a renal homograft following steroid-induced diabetes mellitus.

Benign monoclonal gammaglobulinemia and glomerulonephritis

Serum protein electrophoresis revealed a monoclonal gammopathy in three patients who presented with glomerulonephritis. Other features of myeloma were not found. Clinical manifestations of glomerulonephritis included marked proteinuria and significant hematuria. Rate of progression of renal failure was variable. Morphologically, glomerulonephritis was characterized by diffuse proliferative lesion with predominant mesangial involvement. Immunoglobulins and complement were found deposited in the mesangium. Immunoglobulins deposited in the glomeruli were found to consist exclusively of the circulating monoclonal IgG in one patient. Immunoglobulins eluted from the glomeruli of another patient consisted of immunoglobulin (IgM) which had electrophoretic mobility similar to that of the monoclonal spike in the serum. Selective deposition of monoclonal immunoglobulins in the glomeruli indicated that an active process was involved in their gtomerular localization and that the monoclonal immunoglobulins may have had a role in the pathogenesis of glomerulonephritis in these patients.

Glomerular metabolism in protein-load proteinuria.

Rats were injected with various amounts of bovine albumin (0.5, 1.0 and 1.75 g/24h), inducing thereby proteinuria ranging from 100 to 400 mg/24h. The glomerular oxygen uptake, dry weight and glucose-6-phosphate dehydrogenase (G-6-PHD) activity were measured on the 4th day of proteinuria and in a group of control animals. Oxygen uptake increased of +60%, expressed per glomerulus and of +25% when expressed per milligram dry weight and this increase was not different between the 3 groups of rats. Glomerular dry weight increased significantly in the 3 series. There was an highly significant relationship between glomerular dry weight and oxygen uptake, combining the 3 series together. G-6-PDH increased as expected from previous experiments and this increase was more marked for the more marked proteinuria. The relationship between G-6-PDH and QO2 was of borderline statistical significance (p=0.05). The glomerular hypertrophy, oxidative hyperactivity and increase in G-6-PDH activity are probably related to transcellular transport of protein.

Urinary loss of clotting factors due to hereditary membranous glomerulopathy.

Severe plasma deficiencies of clotting factors IX and XII developed in a 59-year-old woman with a nephrotic syndrome secondary to a laminated membranous glomerulopathy. Both these clotting factors were subsequently identified in the patient's urine. Chromatographic analysis of the urine revealed that the bulk of clotting activity attributed to factors IX ann XII was in early eluting gel filtration fractions containing predominately alpha-2 globulin and albumin. The unprecedented finding of two coagulation proteins in the urine is attributed to the marked proteinuria present in this case.

Patterns of some lysosomal enzymes in the plasma and of proteins in urine of workers exposed to inorganic mercury.

In a population of workers (81 subjects) exposed to inorganic mercury vapors in a chlorine alkali plant (airborne mercury concentration between 0.06 and 0.3 mg/m3) and in a group (104 subjects) of people never exposed to mercury the plasma level of β-galactosidase, β-glucuronidase, β-N-acetylglucosaminidase, and β-glucosidase was determined. The results are as follows: These results suggest the use of this procedure for detecting an undue mercury absorption in workers exposed to the metal before any clinical signs. RBC and plasma cholinesterase activities were not affected. The results of the study of urinary proteins were not useful for detecting an early impairment of the kidney function. However, in some cases we observed a marked glomerular proteinuria without any clinical explanation: this fact makes one very cautious about denying the existence of a kidney impairment in workers exposed to the metal before any clinical sign is present.

INTRAUTERINE GROWTH RETARDATION IN TOXAEMIC PREGNANCIES

Seventy-eight full term />37 weeks/ toxaemic pregnancies were observed. Classification of toxaemia: a/ Mild: diastolic pressure 81–90 Hgmm, no proteiuuria, 39 cases; b/Moderate: diastolic pressure 91–110 Hgmm, moderate proteinuria, oedema, 18 cases; c/ Severe: diastolic pressure above 110 Hgmm, or 91–110 Hgmm and marked proteinuria, oedema; 20 cases. Growth retardation was stated when ultrasonic measurements of the biparietal and abdominal diameters were below the 5th percentile in the last week of pregnancy and postpartal weight, length and head circumference values were below the 10th percentile on local growth charts. Mild to moderate toxaemia had no influence on intrauterine development. Nine babies of the 20 severely toxaemic mothers were retarded in weight, 5 in lenght and head circumference aswell. Eight of the latter nine were characterized by extremely small abdomina l diameters /10–21 mm below the mean for gestational age/. The biparietal diameter was below the 5th percentile in 4 cases of general growth retardation and in 2 cases of babies with small head circumference.

INTRAUTERINE GROWTH RETARDATION IN TOXAEMIC PREGNANCIES

Seventy-eight full term />37 weeks/ toxaemic pregnancies were observed. Classification of toxaemia: a/ Mild: diastolic pressure 81–90 Hgmm, no proteiuuria, 39 cases; b/Moderate: diastolic pressure 91–110 Hgmm, moderate proteinuria, oedema, 18 cases; c/ Severe: diastolic pressure above 110 Hgmm, or 91–110 Hgmm and marked proteinuria, oedema; 20 cases. Growth retardation was stated when ultrasonic measurements of the biparietal and abdominal diameters were below the 5th percentile in the last week of pregnancy and postpartal weight, length and head circumference values were below the 10th percentile on local growth charts. Mild to moderate toxaemia had no influence on intrauterine development. Nine babies of the 20 severely toxaemic mothers were retarded in weight, 5 in lenght and head circumference aswell. Eight of the latter nine were characterized by extremely small abdomina l diameters /10–21 mm below the mean for gestational age/. The biparietal diameter was below the 5th percentile in 4 cases of general growth retardation and in 2 cases of babies with small head circumference.

Studies on passive immunity in the foal: III. The characterization and significance of neonatal proteinuria

A marked but transient proteinuria was detected in all foals that received colostrum in the first 24 h. of life. Initially there were rising levels of urinary protein which reached a peak by 6 to 12 h., followed by sharply declining levels to 24 to 28 h. of life. Feeding high protein colostrum during and after the time of intestinal closure did not prolong the period of proteinuria. Analysis of the urinary protein by CAM electrophoresis showed that it was devoid of obvious serum components. It more closely resembled the protein composition of milk and colostrum, but contained no evidence of γ-globulin. On gel filtration it was found to consist almost exclusively of low molecular weight protein. It was concluded that the small molecular weight milk proteins were absorbed by the intestine along with the larger molecules, but were selectively excreted in the urine by virtue of their small size. The cessation of proteinuria was judged therefore to be a reflection of cessation of absorption of macromolecules by the foal's intestine.

Radioimmunoassay of maternal serum α-fetoprotein associated with pregnancy

α-Fetoprotein (AFP) associated with pregnancy was studied by radioimmunoassay. The initial appearance of demonstrable serum AFP was noted at 14 weeks of gestation. Subsequently the serum AFP level increased to reach its maximum level at approximately 35 to 38 weeks of gestation. At term it leveled off slightly. The maximum amount of serum AFP detected in the present study was 386 ng. per milliliter at 36 weeks of gestation. The serum AFP level decreased rapidly following delivery and was almost negligible by 20 days postpartum. The average half-life of AFP was 3.9 days. AFP was also detected in the serum of one patient with hydatidiform mole. AFP was found in the urine of one patient with marked albuminuria but not in normal pregnancy. It was speculated that the AFP detected in the serum of pregnant women may be, at least in part, of maternal origin. It was also suggested that the inhibition against the repressor-operator gene system which was responsible for AFP synthesis was accelerated in pregnancy due to unknown factor(s), probably of placental origin, resulting in maternal AFP production.

Adult Fanconi syndrome, amyloidosis and marked kappa-light chain proteinuria.

A 57-year-old Negro female patient is described with adult Fanconi syndrome, and marked x-light chain proteinuria over a 10-year period, without evidence of multiple myeloma. At necropsy, an unusual n

Experimental glomerulonephritis induced with the major antigen of rat kidney.

The major antigen of rat kidney (KMA) isolated in an immunochemically purified form was injected into homologous rats at 2-week intervals during 42 weeks. Circulating antibodies against KMA were constantly found in the sera of all immunized animals after 4 months of KMA treatment. Marked proteinuria accompanied by a significant increase in the serum γ-globulin level occurred only several months after the appearance of circulating antibodies. Histological examinations of the KMA-treated rat kidney revealed mild but definite glomerular lesions of the membranous, non-proliferative type. Rat &lt;i&gt;γ&lt;/i&gt;-globulin was found as a mixed, linear and granular, deposit along the basement membranes and the mesangial regions. However, rat &lt;i&gt;β&lt;/i&gt;&lt;sub&gt;1C&lt;/sub&gt;-globulin was found as an exclusively granular deposit in the same areas, but more intensively in the mesangium. The acid elution of KMA-treated rat kidney contained γ-globulin which reacted with KMA. As compared with Edgington’s nephritogenic tubular antigen RTE-α&lt;sub&gt;5&lt;/sub&gt;, KMA was found to be completely different. However, it was also localized exclusively in the proximal tubular cells. Its presence in normal rat serum and liver has been suggested as a source of autologous immunogens in the long-term development of an autoimmune complex nephritis in the rat.

Nephropathy in sucrose-fed rats. Electron and light microscopic studies.

Diffuse intercapillary glomerulosclerosis and exudative glomerulosclerosis were produced in rats fed high-sucrose diet for periods of nine to eighteen months. These lesions were observed by light and electron miscroscopy. Impairment of glucose tolerance was observed in the sucrose-fed animals and marked proteinuria developed in the course of long-term sucrose feeding. Such lesions did not develop in a control group of age-matched fed high-starch diets.

A clinicopathological study of renal amyloidosis in dogs

Forty-four cases of histologically confirmed renal amyloidosis in dogs were reviewed. The majority (77·3 per cent.) of these dogs did not have a history of typical predisposing disease. The mean age was 9·2 years. The common clinical syndrome was one of progressive renal insufficiency with marked proteinuria. The major deposits were invariably glomerular, although amyloid was also seen in the renal medula of several kidneys. Deposits were occasionally present in other organs. Electron microscopy of two renal biopsy specimens revealed mesangial and basement membrane deposits similar to those seen in human and experimentally induced amyloidosis. The clinical courses of 14 dogs (31·8 per cent.) were complicated by thrombosis, primarily involving the major pulmonary arteries.