Effect of renal transplantation on protein binding of drugs in serum of donor and recipient.

Blood samples were obtained periodically before and for about 3 mo after renal transplantation from a donor (mother) and a recipient (9-yr-old son with bilateral nephrectomy) for determination of serum protein binding of salicylate and sulfisoxazole. Ten days after the transplant, the recipient had an acute rejection episode which was treated successfully. The free fraction values of the drugs in serum of the recipient was considerably above normal before transplantation, decreased to normal within 2 days after transplantation, increased again several days before the rejection episode and remained elevated for about 50 days, and then returned to normal. Serum protein binding of the drugs in the serum of the donor was decreased for only a few days after transplantation and then returned to normal.

Pasteurella multocida infection of urinary tract in patient with ileal loop.

Pasteurella multocida infection in the ileal loop and in the pelvis of a hydronephrotic kidney of a patient whose other kidney had been removed at age six months was documented by the repeated isolation of this patthogen. Two episodes occurred, the first terminated after a dose of gentamicin and the other without chemotherapy. Since the patient prior to infection was in severe renal failure necessitating hemodialysis, the effect of this infection on renal function could not be ascertained. The probable source was a cat present in the household.

Renal artery stenosis and hypertension after abdominal irradiation for Hodgkin disease. Successful treatment with nephrectomy.

Hypertension secondary to stenosis of the left renal artery developed in a thirteen-year-old male six years after completion of inverted Y irradiation (3,600 rad) for abdominal Hodgkin disease. Surgical treatment with nephrectomy resulted in control of the hypertension without the use of antihypertensive agents. We review the literature for this unusual complication of abdominal irradiation, and recommend that a 99mTc-DMSA renal scan, selective renal vein sampling for renin determinations, and renal arteriography be performed on any patient in whom hypertension develops following abdominal irradiation in childhood.

Urinalysis and its clinical interpretation.

The importance of changes in urine concentration, acidification, protein, and sediment; findings at urinalysis in several common renal diseases of children.

Cell-mediated immunity to cytomegalovirus in patients receiving immunosuppressive therapy.

Employing the techniques of complement-fixation (CF), immunofluorescence (IF), and in vitro lymphocyte transformation (LTF), the humoral antibody response and cell-mediated immune (CMI) response to cytomegalovirus (CMV) were studied in the serum and peripheral blood lymphocytes in 19 normal children (controls) and 23 patients with renal disease who were receiving immunosuppressive therapy or undergoing hemodialysis. The LTF activity was determined by the whole blood microassay using two strains of CMV (AD-169 and Davis) and phytohemagglutinin (PHA). The antibody level responses to CMV in different groups of subjects were generally similar. The LTF response to PHA as evidenced by delta cpm activity was moderately depressed in immunosuppressed and hemodialyzed subjects compared to the response observed in the controls. The mean delta cpm activities in response to AD-169 and Davis strains of CMV in seropositive immunosuppressed patients were about one-fifth and one-third lower respectively than those of seropositive normal controls. These observations suggest that an impairment of CMV specific cellular immunity may be an important mechanism underlying the increased susceptibility to CMV infections in patients with chronic renal disease who receive immunosuppressive therapy.

Intrahepatic cholestasis for 15 years without cirrhosis.

Whether prolonged cholestasis is followed by hepatic cirrhosis is still controversial. We have studied two unrelated children who have had cholestasis for 15 years, but neither of whom have developed cirrhosis. Both have severe growth retardation, peculiar facies, pulmonic stenosis, transitory renal tubular acidosis, and vitamin D-resistant rickets. The patients presented in infancy with hepatomegaly and direct hyperbilirubinemia; liver biopsy at that time revealed cholestasis and paucity of bile ducts. Subsequent serial liver biopsies have continued to demonstrate cholestasis, but there has been no evidence of cirrhosis. Electron microscopy has revealed swollen and blunted microvilli of the canalicular membrane of the hepatocyte. The patients have had elevated bile acids in the serum as well as a reversed ration of tri- to dihydroxy bile acids. Treatment with cholestyramine and phenobarbital has brought about symptomatic relief from severe pruritus and excoriation and has lowered the level of serum bile acids, although they are still above the normal range. These findings suggest that cholestasis accompanied by an elevated and reversed bile acid ratio does not universally cause hepatic cirrhosis.

A useful method for predicting creatinine clearance in children.

A practical method for predicting creatinine clearance for pediatric patients from serum creatinine concentration and patient age is presented. Creatinine excretion rate (ER) can be predicted from the patient's age, in years, by the formula: ER = (0.035 X age) + 0.236. Using the predicted excretion rate and serum creatinine concentration, creatinine clearance can be predicted. There was good correlation (r = 0.90) between predicted and observed creatinine clearances in 101 subjects with various degrees of renal impairment. This method allows renal function to be rapidly estimated.

Pharmacokinetics of gentamicin during peritoneal dialysis in children.

The pharmacokinetics of gentamicin were examined on two occasions using intravenous and intraperitoneal routes in five children undergoing intermittent peritoneal dialysis for chronic renal failure. Serum, urine and dialysis fluid (DF) were assayed microbiologically for gentamicin and the data were subjected to computer analysis using equations evolved for a two-compartment model which considered the bi-directional flux of the drug. Following i.v. injection of 1 mg/kg of gentamicin, the apparent volume of distribution averaged 23% (range, 13 to 36%) of body wt (similar to normal), the mean half-life was 21 hr (range 9 to 37 hr; normal, 2 hr) and the peritoneal clearance averaged 4.0 ml/min/m2 (range, 1.2 to 7.0 ml/min/m2). During peritoneal administration of gentamicin (15 mg/liter of DF, 0.7 liters/m2 administered in each cycle over 9 to 12 cycles), serum concentrations increased towards extrapolated steady-state levels which averaged 42% (range, 25 to 68%) of DF concentrations. The mean renal clearance of gentamicin was only 1.6 ml/min/m2 while total body clearance ranged from 2.3 to 8.0 ml/min/m2 mostly occurring by a variable degree of dialysance. Peritoneal clearances and half-lives of gentamicin were similar in each patient following either treatment mode. The appreciable variability in gentamicin pharmacokinetics among adolescent patients with renal insufficiency necessitates dosage adjustments based on measurements of serum concentrations.

Histology of human tubulo-interstitial nephritis associated with antibodies to renal basement membranes.

Twenty-seven patients with diffuse "crescentic" glomerulonephritis (CSGN) were identified in 1,174 renal biopsies from nephritic patients. Patients were assigned to three groups on the basis of the immunofluorescent study of renal biopsy specimens and serologic findings. Group I included eight patients with antibodies to glomerular (anti-GBM) and tubular (anti-TBM) basement membranes; group II had eight patients with only anti-GBM antibodies; and group III had eleven patients with CSGN unassociated with antibodies to either GBM or TBM. Patients with anti-GBM/anti-TBM antibodies (group I) had severe tubulointerstitial (TI) nephritis, as characterized by the infiltration of polymorphonuclear leukocytes and macrophages along the TBM and peritubular vessels. In some patients, focal proliferation of epithelial cells of proximal convoluted tubules (PCT), gaps or extensive destruction of TBM, lesions in the walls of small peritubular vessels, and interstitial giant cells were also observed. Patients with anti-GBM antibodies (group II) had mild to moderate interstitial cellular infiltration and mild tubular changes. Five patients with CSGN not associated with antibodies to renal basement membranes (group III) had mild to moderate interstitial cellular infiltration and tubular changes. A sixth patient, with Wegener's disease had severe granulomatous TI lesions. The results of this study show that TI nephritis is most frequent and severe with anti-TBM antibodies are demonstrable and suggest that anti-TBM antibodies contribute to the development of TI lesions.

Interstitial immune complex nephritis in patients with systemic lupus erythematosus.

Interstitial immune complex nephritis in patients with systemic lupus erythematosus (SLE). Renal tissues from 45 patients with SLE nephritis, 34 patients with idiopathic membranous nephropathy (IMN) and 77 patients with minimal glomerular disease (MGD) were studied by light, immunofluorescence and electron microscopy. Interstitial nephritis characterized by focal or diffuse infiltration of inflammatory cells, tubular damage and interstitial fibrosis was observed in 66% of SLE patients. Fluorescein-conjugated antibodies to immunoglobulins or complement or both were bound to peritubular capillaries, interstitium and tubular basement membranes (TBM) in 53% of patients with a granular pattern corresponding to opaque deposits seen by light or electron microscopy or both. Antibodies reactive with thymidine or cytosine or both were bound to interstitial structures in 19% of patients tested and showed the same granular distribution. Interstitial cellular infiltration was rare and deposits of immunoglobulins and complement were rare or absent in IMN and MGD, whereas deposits of DNA products were never observed. The findings are consistent with the interpretation that in patients with SLE nephritis immune deposits, presumably containing DNA-anti-DNA complexes, localize in peritublular capillaries, TBM and interstitum, thereby producing an inflammatory reaction which contributes to development and evolution of renal diseases.

Disseminated immune deposits in lupus erythematosus.

Immunohistologic studies were performed on autopsy tissues of 2 patients with systemic lupus erythematosus. All tissues examined--the kidney, lung, spleen, liver, intestine, peritoneum, and choroid plexus--contained immune deposits. Antinuclear antibody concentration in immunoglobulin G eluted from lung and spleen tissue was higher than in serum immunoglobulin G. These findings support the assumption that in systemic lupus erythematosus the renal as well as the extrarenal lesions can be attributed to vascular deposition of immune complexes.