Antigenic streptococcal components in acute glomerulonephritis.

Fluorescein-labeled immunoglobulin G fractions from serums of patients with acute glomerulonephritis and from many normal serums stained the glomerular basement membrane and mesangium of renal tissue from patients with early acute glomerulonephritis; these serums did not stain the corresponding tissues from patients with any other kidney disease. Previous absorption of the serum fraction with frozen and thawed nephritogenic beta hemolytic streptococci abolished all staining. Other bacteria studied did not abolish the staining. Only the plasma membrane of the streptococcus absorbed the immunoglobulin G fraction; such absorption eliminated staining. Fluorescein-labeled antiserums against streptococcal plasma membrane had staining properties similar to patients' serums.

Ultrasonic guidance for renal biopsy.

B-mode ultrasonic guidance was used to perform 76 percutaneous renal biopsies. Renal tissue was obtained from 73 (96.1%) subjects with adequate tissue for interpretation or diagnosis in 72 instances. Major bleeding complications occurred in four (5.3%) patients. Ultrasound has proved to be a safe and effective means of guiding physicians performing renal biopsies. In addition, it has many advantages over other techniques.

Renal-hepatic-pancreatic dysplasia: a syndrome reconsidered.

Five infants, three dying neonatally and two later in the first year of life, had renal, hepatic, and pancreatic dysplasia, a combination of abnormalities first described by Ivemark et al [1959]. The renal malformation consisted of cystic dysplasia, with abnormally differentiated ducts, deficient nephron differentiation, and glomerular cysts. The hepatic abnormality consisted of enlarged portal areas containing numerous elongated biliary "profiles," with a tendency to perilobular fibrosis. Serial liver biopsies in one child with cholestasis from birth showed a progression from bile duct paucity at 1 1/2 wk to typical biliary "dysgenesis" at 7 mo. Four of the five children had intrahepatic ductal dilatation, diagnosed ante mortem in the two older children as Caroli disease. The pancreatic abnormality consisted of fibrosis and cysts, with a diminution of parenchymal tissue. The clinical and functional reflection of these abnormalities in the two children surviving the newborn period included renal insufficiency, chronic jaundice, and insulin-dependent diabetes mellitus. Similar renal, hepatic, and pancreatic abnormalities occur in other syndromes, including trisomy 9, Meckel syndrome, Jeune, Saldino-Noonan, and Elejalde types of chondrodysplasia, and glutaric aciduria II. After exclusion of identifiable syndromes, the remaining cases of renal-hepatic-pancreatic dysplasia do not necessarily constitute a homogeneous group.

Effects of amino acid additives during hemodialysis of children.

The intradialytic losses into the dialysate of free amino acids (AA) and alpha-amino nitrogen were determined during the dialysis of three children. Variations in plasma AA were determined pre- and postdialysis. The effect of these losses with the addition of an Abbott General Amino Acid Mixture to the dialysate in concentrations of 8.5, 17, and 34 mg/100 ml was studied. The major determinant of AA losses was the plasma concentration of the AA before beginning the dialysis treatment. Dialysance of individual AA varied inversely with their molecular weights. A zero flux of alpha-amino nitrogen occurred at a derived concentration of 22 mg/100 ml of the AA additive in the dialysate. Plasma concentrations of nonessential amino acids were little affected by the dialysate additive. In contrast, total essential amino acid nitrogen which fell during baseline dialyses showed significant improvement when the AA solution was added to the dialysate. This study suggests that the addition of AA to the dialysate bath may be effective in decreasing AA nitrogen losses during dialysis.

Urinary lactate dehydrogenase isoenzyme analysis in adult population.

This investigation was a systemic study on an adult population of urinary lactate dehydrogenase (LDH) isoenzyme analysis for the distinction between upper and lower urinary tract infections. The study included 160 urine samples from patients and healthy individuals. On the basis of clinical symptoms, urinary bacterial colony counts, renal function tests and radiologic findings, the adults were divided into pyelonephritis group, cystitis group, pelvic lesion group, and control group. This technique correctly identified 23 of 26 patients with pyelonephritis by the presence of elevated LDH-V (over 10 percent) and all of 12 patients with cystitis by the presence of elevated LDH-I (over 60 relative units) but low LDH-V (below 10 percent or lower than LDH-I). In the pelvic group, the results of eight patients were consistent with cystitis and four with pyelonephritis. Our study confirms the sensitivity and specificity of the LDH isoenzyme technique for the differential diagnosis of urinary tract infection on adult patients and is consistent with previous studies on pediatric patients. However, one should be cautious to interpret the results of LDH isoenzymogram before extra-urinary tract lesions are excluded.

Diagnosis and imaging of the fetal and neonatal abdominal mass: an integrated approach.

Almost all of the renal causes of NAM and adrenal neuroblastoma, the most common nonrenal cause, can be categorized as cystic or solid by sonography. Evaluation with CT is usually the most appropriate next step for assessment of solid renal tumors lacking clinical features of RVT. Renal scintigraphy and diuretic renal scintigraphy offer valuable information about relative individual kidney GFR and excretory function, whether normal, partially, or completely obstructed. Many dilated urinary tracts, especially those diagnosed in utero, are found to resolve spontaneously when serial studies are performed. The informed pediatrician should play a major role in the selection of diagnostic procedures and determination of management strategy. Only he or she has the detailed clinical knowledge of the patient that can give appropriate direction to the consultants. A tentative algorithm for imaging studies in the evaluation of NAM is presented in Figure 1 and emphasizes the functionally more informative radionuclide studies 15,25,26 over the traditional radiocontrast studies.

Pathogenesis of the anemia of chronic renal failure: the role of erythropoietin.

In summary, the anemia of CRF results from several interactive processes, chief among these inadequate Ep production relative to the degree of anemia. The anemia of renal failure can be regarded as an endocrine deficiency state, which is corrected by the specific replacement therapy. The advances of molecular biology have provided a biosynthetic Ep, a potent tool for correction and prevention of the anemia of renal failure. However, new problems often arise as new treatments become available. The rapid improvement in hematocrit and the resultant lowering in plasma volume may affect dialysis clearances in hemodialysis patients. Since the well-being and appetite of the patients improves as the hematocrit rises, newer methods to increase the weekly dialysis clearances will be needed to prevent the complication of underdialysis in these patients.

Nephrotic syndrome and multiple tubular defects in children: an early sign of focal segmental glomerulosclerosis.

The nephrotic syndrome is rarely associated with renal tubular defects, and the combination has been reported only in association with advanced renal insufficiency. We report here five children with nephrotic syndrome and multiple tubular defects which evolved when glomular filtration rate ranged between 56 and 90 ml/minute/1.73 m2. The tubular defects were first noted at 3, 4, 4, 7, and 22 months after the onset of the nephrotic syndrome, and renal glycosuria was the first sign in all five children. Glycosuria was intermittent in three patients, constant in two, and ceased with loss of kidney function. Four patients had hyperaminoaciduria and renal tubular acidosis (two of four tested had distal renal tubular acidosis). Three patients had decreased tubular reabsorption of phosphorus and defective maximum concentrating capacity. All five had focal segmental glomerulosclerosis proven by renal biopsy. Over a follow-up period of seven years, all of the children have developed advanced renal insufficiency, four of the five have required dialysis or transplantation within 21 to 72 months after onset, and one has stabilized renal function at 35 ml/minute/1.73 m2. The one patient receiving a kidney transplant has had recurrence of focal segmental glomerulosclerosis in the transplanted kidney and became nephrotic with three subsequent transplants. Our experience suggests that the nephrotic syndrome associated with tubular defects in children forms a subgroup of focal segmental glomerulosclerosis, with rapid progression to renal insufficiency and the potential for recurrence of the lesion in the transplanted kidney.

Transient urodynamic dysfunction of infancy: relationship to urinary tract infections and vesicoureteral reflux.

PURPOSE: Urinary tract infections and vesicoureteral reflux are more common in male than female infants. Since these problems can result from voiding dysfunction, we obtained a detailed history of voiding patterns and urodynamic testing in infants with urinary tract infections in the first year of life. MATERIALS AND METHODS: We evaluated 39 male and 22 female infants, including 40 with primary vesicoureteral reflux and 21 with no reflux or obstruction. RESULTS: Voiding abnormalities were noted in 97% of the male and 77% of the female infants, including high voiding detrusor pressure of greater than 40 cm. water in 92% of the male and 66% of the female infants, residual urine greater than 2 ml./kg. in 13% of the male and 23% of the female infants, and detrusor hyperreflexia with filling pressure greater than 40 cm. water in a third of the male infants. Voiding detrusor pressure was significantly higher in male than female infants and in male infants with grade IV to V reflux than those with lower grades of reflux or no reflux. Followup urodynamic testing in 15 infants with high voiding detrusor pressure revealed resolution of detrusor hyperreflexia and improvement in post-void residual in all and decreased voiding detrusor pressure in 14. CONCLUSIONS: We coined the term transient urodynamic dysfunction of infancy to describe this constellation of abnormalities, which predisposes infants to urinary tract infections and vesicoureteral reflux but improves spontaneously. The higher incidence of urinary tract infections and reflux in male infants may be related to higher intravesical pressures.

Experimental focal segmental glomerulosclerosis: correlation with protein excretion, glomerular filtration rate, and renal plasma flow.

A rat model of focal segmental glomerulosclerosis (FSGS) produced by repeated injections of aminonucleoside (AMN) of puromycin was used to evaluate the relative roles of hemodynamic alterations and AMN-induced glomerular visceral epithelial cell injury in the development of FSGS. Twenty rats received three intraperitoneal injections of AMN on days 1, 21, and 28 and developed significant proteinuria. On day 50, 14 rats (group 1) underwent selective left renal perfusion with AMN and six rats (group 2) received left renal perfusion with saline. At sacrifice on day 70 or 110, group 2 rats had similar values in left and right kidneys for glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and the amount of FSGS (13.1 +/- 5.6% in left and 12.9 +/- 7.8% in right). In contrast, group 1 rats manifested a significantly higher amount of FSGS in right kidneys as compared to left kidneys (3.1 +/- 1.3% in left and 6.3 +/- 2.0% in right, as well as significantly diminished GFR and ERPF in left as compared to right kidneys. A higher degree of FSGS was seen in kidneys with a higher GFR and ERPF. A positive correlation was observed between the mean 24-h protein excretion of the rats and the percentage of FSGS in left and right kidneys (r = 0.66, p less than 0.01).

Relation of serum erythropoietin levels to renal excretory function: evidence for lowered set point for erythropoietin production in chronic renal failure.

The relationship of serum erythropoietin (Ep) levels to hematocrit and glomerular (GFR) filtration rate was evaluated in patients with chronic renal disease. The Ep level was measured by radioimmunoassay in 119 blood samples from 48 patients obtained over a period of up to 5 years. Hematocrit values correlated significantly with the GFR, but serum Ep levels did not change with a decline in the GFR. Significant anemia was noted only when the GFR fell below 20 ml/min/1.73 m2. Episodes of spontaneous acute hypoxic stress were observed in six patients with chronic renal failure. Serum Ep levels obtained during these episodes (mean +/- SEM: 273 +/- 76 mU/ml) were tenfold higher than Ep levels during stable steady-state chronic renal failure (26 +/- 6 mU/ml), even though Ep levels were inappropriately low for the degree of anemia in the stable state. Our findings suggest that the tissue oxygenation-Ep-hematocrit feedback mechanism operates at a lower set point in patients with chronic renal failure in comparison with normal subjects.

Splenic hypofunction in the nephrotic syndrome of childhood.

The reticuloendothelial system, including the spleen, subserves important immunologic functions. Loss of splenic function results in an increased incidence of severe bacterial infections and is accompanied by thrombocytosis. Several nephrotic children were noted to have remarkably high platelet counts and predisposition to bacterial infection with encapsulated organisms. We, therefore, investigated the splenic function of nine children with primary nephrotic syndrome and measured the phagocytic function of the spleen by sequestration of Technetium-99-labelled heat-treated autologous RBC, administered intravenously. Four children had decreased splenic function. Repeat studies performed in two of these children after remission of the nephrotic syndrome gave normal results. There were six episodes of bacterial infection (3 peritonitis, 1 septic arthritis, 1 cellulitis, and 1 Escherichia coli urinary tract infection) among the four patients with decreased splenic function. There were no episodes of bacterial infection among the five nephrotic children with normal splenic function. Nephrotic patients with decreased splenic function had significantly increased platelet counts (921,000 +/- 196,000; mean +/- SEM) compared to those with normal function (435,000 +/- 46,000; P less than 0.001). Our findings suggest the possibility that some nephrotic children may have decreased splenic function in association with increased susceptibility to bacterial infections.

Intraperitoneal production of erythropoietin with continuous ambulatory peritoneal dialysis.

Higher hematocrit and serum erythropoietin (EPO) levels have previously been shown in end-stage renal disease patients treated with continuous ambulatory peritoneal dialysis (CAPD) compared with hemodialysis. We investigated whether EPO was produced intraperitoneally in CAPD patients. EPO concentration was 3.5 +/- 0.3 mU/ml by radioimmunoassay in 26 samples of peritoneal dialysis effluent obtained from 15 CAPD patients. EPO was not detectable in the fresh unused dialysate. No correlation was observed between EPO levels in the serum and dialysis effluent. Peritoneal macrophages were isolated from the dialysis effluent of 9 CAPD patients after an overnight dwell. The culture supernatant obtained after 24 h of in vitro culture of a million cells yielded EPO of 3.5 +/- 0.3 mU/ml. Our study demonstrated that peritoneal macrophages from CAPD patients produce EPO on in vitro stimulation, and EPO is present in the dialysis effluent of CAPD patients.

Inhibition of sodium intestinal transport and mucosal (Na+-K+)-ATPase in experimental Fanconi syndrome.

The administration of 1.5 or 9.0 mmoles/kg ip of maleate to rats induced, in addition to renal alterations similar to those occurring in the Fanconi syndrome, a decline in the intestinal mucosa (Na+-K+)-ATPase with a simultaneous decrease in sodium intestinal transport and an increase in potassium absorption. Further differences in the behavior of the two electrolytes were observed when the concentration of sodium in the perfusates was altered. No changes occurred in amino acid or glucose transport in experimental animals.

Hypertension secondary to renin-secreting juxtaglomerular cell tumor: case report and review of 38 cases.

A 15-year-old girl with severe high renin hypertension caused by a juxtaglomerular cell tumor (JCT) was successfully treated with the calcium channel blocker nifedipine until surgical removal effected a permanent cure. This case was incorporated into a review of the 37 cases previously published. Comparison of the children and adolescents with the adult population showed that the features of JCT were similar in the two groups except for the average duration of symptoms prior to diagnosis (pediatric group 2.6 years vs. 6.0 years for the adult group). Analysis of all 38 cases demonstrated the following: 1. Teenagers constituted the largest single population with JCT (39%) and approximately two-thirds of the entire population were female. 2. Many patients failed to show persistent hypokalemia despite high plasma renin activity and secondary hyperaldosteronism. 3. Renal angiography was initially negative in more than half the cases. 4. Renal vein renin failed to show lateralization to the affected kidney in 52% of the cases. 5. Computerized tomography demonstrated a renal mass in all of the cases in which it was performed, even when other imaging studies were negative. 6. Calcium channel blockers may evolve as the preferred treatment for the high renin hypertension of JCT.

Rapid onset of co-trimoxazole induced interstitial nephritis.

An infant developed anuric renal failure within 18 hours of starting therapy with Co-trimoxazole for otitis media. There was no prior exposure to Co-trimoxazole, sulfonamides or trimethoprim. A renal biopsy revealed acute interstitial nephritis with eosinophilic infiltration (AIN). The lymphocyte blast transformation test revealed increased proliferation of the patient's lymphocytes on exposure to Co-trimoxazole (Bactrim). Both parents have clinically demonstrated hypersensitivity to sulfonamides. The extremely short latent period between ingestion of the offending drug and the onset of AIN in the absence of prior exposure to the drug has been reported previously. It suggests that drug induced AIN may develop more rapidly in patients with a strong genetic hypersensitivity to the drug.

Serum immunoreactive erythropoietin levels in patients with polycystic kidney disease as compared with other hemodialysis patients.

Serum erythropoietin levels were randomly collected and measured by a sensitive radioimmunoassay in a hemodialysis population. For analysis, the patients were divided into two groups: those with polycystic kidney disease and those with other kidney diseases. In 12 polycystic kidney disease patients, serum erythropoietin was 22.6 +/- 2.4 mU/ml, hematocrit 29.7 +/- 1.0%, and absolute reticulocyte count 17.0 +/- 4.1 X 10(4)/microliters. In 24 other kidney disease patients, serum erythropoietin was 12.4 +/- 0.7 mU/ml, hematocrit 21.2 +/- 0.8%, and reticulocyte count 7.5 +/- 1.5 X 10(4)/microliters. Serum erythropoietin was 18.5 +/- 0.7 mU/ml in normal controls. Polycystic kidney disease patients manifested higher hematocrit, reticulocyte counts, and serum erythropoietin levels when compared to other kidney disease patients (p less than 0.01). The data suggest (1) an inappropriately low serum erythropoietin level for the severity of anemia in uremic hemodialysis patients and (2) that greater availability of erythropoietin results in more effective erythropoiesis, even in the uremic environment.