Immediate post-transplant nephrosis in a patient with congenital nephrotic syndrome.

A 19-month-old girl with congenital nephrotic syndrome of the Finnish type underwent a living-related renal transplant; 24 h after transplantation she became massively nephrotic. She did not respond to steroids, plasmapheresis, and high-dose cyclosporine. A month later, a renal biopsy showed only glomerular foot process effacement. She was treated with high-dose methylprednisolone pulses and oral cyclophosphamide. She rapidly went into complete remission with no further relapses. Graft function has been stable 2 years after transplantation.

Simultaneous postinfectious glomerulonephritis and thrombotic microangiopathy: a renal biopsy study.

The simultaneous occurrence of postinfectious glomerulonephritis and thrombotic microangiopathy is described in renal biopsy specimens from three patients. Each presented with diverse manifestations: two patients had hypertension and acute renal failure, and in the third, it was unclear whether an atypical postinfectious glomerulonephritis or an atypical thrombotic microangiopathy was present. All biopsy specimens disclosed a combination of irregular granular complement and immunoglobulin deposits in mesangial regions and capillary walls along with fibrin in a linear pattern in capillary walls by immunofluorescence. Light microscopy showed diffuse hypercellularity in some glomeruli, endothelial cell swelling, luminal thrombi and mesangiolysis in others, and both types of changes in a third group. Ultrastructurally, subepithelial hump-shaped deposits coexisted with widened and lucent subendothelial spaces. Possible pathogenic mechanisms for the synchronous lesions include endothelial injury, perhaps triggered by infection and immunologic tissue damage.

Hematuria in children.

A work-up of a child with suspected hematuria should be undertaken once the primary physician has determined that there actually are red blood cells in the urine and that the hematuria is persistent. Evaluation of a child with persistent microscopic hematuria is facilitated with the determination of whether the blood originates from the glomeruli or whether it comes from elsewhere in the urinary tract. Clues to a glomerular origin include the presence of other manifestations of glomerular disease such as significant proteinuria, RBC casts, and dysmorphic erythrocytes in the urinary sediment, hypertension, and renal insufficiency. Clues to the blood originating from the lower urinary tract include blood clots in the urine, normal erythrocyte morphology, and a pertinent history pointing to the lower tract such as that of trauma, urolithiasis, urological or vascular abnormality, or symptoms of bladder inflammation. The initial evaluation should include a detailed patient history and family history as well as a careful physical examination looking for clues to the presence of a familial, hereditary, or chronic kidney disease. A logical, stepwise initial work-up should follow with the goal of ruling out life-threatening and treatable diseases. If there are no indications for immediate further intervention and the cause of the hematuria remains unclear after the initial work-up has been completed, the parents and patient should be reassured that there are no life-threatening conditions and that although the etiology of the blood in the urine is yet unknown, there is time to follow the patient and plan for additional studies if and when they are indicated. The family's concerns (ie, "Is this cancer?," "Will my child require dialysis and transplantation?") should be addressed frankly, and the physician should mention those diagnoses that may lead to renal failure, but have not been absolutely ruled out yet before a kidney biopsy has been performed, such as Alport's syndrome and IgA nephropathy. The child with isolated microhematuria should be evaluated regularly with urinalyses looking for persistence of the hematuria and appearance of proteinuria, blood pressure measurements, and renal function tests. If the microhematuria persists for 6 to 12 months, a kidney biopsy should be considered.(ABSTRACT TRUNCATED AT 400 WORDS)

Five years experience with recombinant human growth hormone treatment of children with chronic renal failure.

11 males, aged 2.5-16.3 years (6.8 +/- 4.1) with growth retardation (Standard Deviation Score--SDS > -2.00) consequent to chronic renal failure (CRF) received recombinant human growth hormone (rhGH) for 18 to 60 mo (40.9 +/- 15.4). Growth velocity (GV) increased from 5.4 +/- 2.2 for the year prior to rhGH to 8.9 +/- 1.6 (p = 0.00001), 7.4 +/- 1.7 (p < 0.03), 7.6 +/- 1.6 (p < 0.006), 6.5 +/- 1.0 (p < 0.05) and 7.5 +/- 1.3 (p = NS) cm/yr following 12, 24, 36, 48 and 60 mo respectively of treatment. The mean SDS for height decreased from -3.21 at baseline to -0.85 at 60 mo (p = 0.0004); 7 of 8 pts treated for > 36 mo had a SDS more positive than -2.00; 3 reached the 50th percentile on the growth curve. In 2 patients the dosage was doubled to achieve the increase in GV; in one patient it took 5 yrs to reach a SDS more positive than -2.00. A significant increase in weight gain and mid-arm muscle circumference over baseline values were indicative of the anabolic effect of rhGH. The mean increase in bone age was similar to the increase in chronologic age; the delta bone age-delta height age was not significant indicating no loss of growth potential following rhGH. Although 3 patients required the initiation of dialysis following rhGH treatment, the mean calculated creatinine clearance did not decrease significantly. No significant adverse effects were noted. These data indicate that long-term rhGH treatment is effective in improving the GV of children with CRF and facilitating catch-up growth without loss of growth potential.

Use of recombinant human growth hormone in children with chronic renal insufficiency: an update.

Growth retardation is common in children with chronic renal insufficiency (CRI). Now that dialysis and renal transplantation (TX) have become life sustaining, permanent stunted growth and adult short stature often occurs. Thus, efforts to enhance growth using recombinant human growth hormone (rhGH) have been undertaken in three groups of patients: chronic renal failure (CRF) prior to dialysis; end-stage renal disease (ESRD) on some form of dialysis; and following TX (post-TX) in whom growth retardation persists. Our initial study was in CRF. Eleven males, ages 2.5-16.3 years, with height standard deviation scores (SDS) of > 2.0 below the mean, have been treated with rhGH for 18-48 months. rhGH was started in a dose of 0.125 mg/kg three times a week in the first 8 patients and subsequently changed to daily dosing (0.053 mg/kg/day) within the first 24 months. To date, overall, growth velocity (GV) increased from 5.4 +/- 2.2 to 8.9 +/- 1.6, 7.5 +/- 1.8, 7.5 +/- 1.6 and 6.9 +/- 0.9 cm/year in those completing 12 (n = 11), 24 (n = 9), 36 (n = 7), and 48 (n = 3) months. The mean height SDS increased from > 3.0 to < 1.5 below the mean with 1 patient reaching the 50th centile. Dialysis was initiated in 2 patients, a frequency not different from that expected over time in children with this degree of CRF. In the others, calculated creatinine clearance did not change, and no significant adverse effects were noted as a consequence of the rhGH treatment. Thus, rhGH increases GV and facilitates catch-up growth in CRF.(ABSTRACT TRUNCATED AT 250 WORDS)

Extended recombinant human growth hormone treatment after renal transplantation in children.

Recombinant human growth hormone (rhGH) was administered to 13 pediatric renal allograft recipients, ages 7.6 to 17.7 yr, who were 14 to 92 months posttransplant and growth retarded as manifested by either a standard deviation (SD) more negative than -2.00 or a height velocity index of less than 25%. The rhGH was given either daily or thrice weekly (0.375 mg/kg/wk) for a period of 12 to 36 months. Growth velocity increased from 2.7 +/- 2.1 SD for the 12-month period before the initiation of treatment of 6.3 +/- 2.9 SD (P less than 0.00005) and 5.2 +/- 2.9 SD (P less than 0.02) after 12 and 24 months of treatment, respectively. Although individual recipients had improvement in their SD scores, the mean values did not increase despite the increased growth velocity. Except for a 0.5-yr increase over 24 months in two recipients, the bone age did not increase at a rate greater than the increase in chronologic age. Four rejection episodes occurred in two recipients during rhGH treatment--an incidence not greater than that which occurred during a comparable time interval before the initiation of treatment. The calculated creatinine clearance declined from 66 +/- 26 SD mL/min/1.73 m2 at the initiation of treatment to 55 +/- 30 SD mL/min/1.73 m2 at 24 months and 52 +/- 28 SD mL/min/1.73 m2 (P = not significant).(ABSTRACT TRUNCATED AT 250 WORDS)

Recombinant human growth hormone treatment of children with chronic renal failure: long-term (1- to 3-year) outcome.

Treatment of nine boys, aged 2.8-16.3 years, with growth retardation consequent to chronic renal failure (CRF), with recombinant human growth hormone (rhGH) for 12-36 months demonstrated a significant improvement in growth velocity at each 12-month interval compared with that achieved the year prior to treatment. Despite the acceleration in growth velocity the bone age did not increase more than the increase in chronological age during the period of treatment. The mean calculated creatinine clearance did not decrease significantly during the 36 months of treatment; however, two patients required institution of dialysis at 18 and 30 months following the initiation of rhGH treatment. There was no exacerbation of the glucose intolerance of uremia following rhGH treatment. Currently, six of seven patients who have been treated for more than 24 months have achieved sufficient acceleration of growth velocity to attain a standard deviation score that was more positive than -2.00, and are above the 5th per centile for chronological age on the growth curve. These data indicate that rhGH treatment of growth-retarded children with CRF results in accelerated growth velocity during the 2nd and 3rd years of treatment, and demonstrate the potential for such children to achieve normal stature for chronological age despite the continued presence of renal failure.

Recombinant human growth hormone treatment of children following renal transplantation.

Nine growth-retarded renal allograft recipients received either thrice weekly or daily subcutaneous recombinant human growth hormone (rhGH) for 6-30 months. The annualized growth velocity for the initial year of rhGH treatment was significantly greater than that of the preceding year (2.5 +/- 2.1 vs 5.7 +/- 2.7; P less than 0.0001). There was no advancement in bone age greater than the increase in chronological age, no significant increase in the mean fasting serum glucose or insulin levels, nor significant decrease in the calculated creatinine clearance following rhGH treatment. However, two patients experienced rejection episodes following rhGH treatment indicating the potential adverse consequences of the treatment on allograft function. This will require further delineation in prospective controlled studies. The serum insulin-like growth factor-1 levels significantly increased at 6 months (P less than 0.009) and 12 months (P less than 0.002) following rhGH treatment compared with baseline values. These preliminary data indicate that rhGH treatment may be effective in improving the growth velocity of growth-retarded renal allograft recipients.

Natural autoantibodies in the serum of healthy women--a five-year follow-up.

Autoantibodies are often found among healthy individuals. The significance of these findings, regarding the potential development of overt autoimmune disease and the severity of such an eventuality, is as yet unclear. In order to elucidate these issues 506 healthy women were screened and 60 women of child-bearing age were found to posses high titres of various anti-nuclear antibodies. After a 5-year follow-up, 57 of these 60 women were found to have autoantibodies to a variety of autoantigens. Seven of the women had some symptoms that could be associated with the presence of the antibodies (i.e. arthritis, multiple abortions, Raynaud's phenomenon), however, none exhibited overt clinical signs of an autoimmune disease. Our study may point to the fact that in normal subjects (women aged 22-44 years) high titres of natural autoantibodies are not necessarily indicative of a high risk of developing an overt autoimmune condition, at least for a follow-up period of 5 years.

Familial studies on the occurrence of natural autoantibodies.

Natural autoantibodies are often incidentally found in healthy individuals who are not first-degree relatives of known patients with autoimmune diseases. In an attempt to examine whether there exists a familial tendency in the production of such natural autoantibodies, 134 healthy members of 32 families were examined for antibodies against ss-DNA, ds-DNA, poly (I), poly (G), cardiolipin, histones, Sm, RNP, SS-A (Ro) and SS-B (La), using an enzyme-linked immunosorbent assay. Only 16 of the 134 subjects (11.9%) were found to possess autoantibodies in their sera in a titer exceeding the mean by 3 SD, and none of the 'positive' subjects were related. We conclude that in contrast to the familial occurrence of the autoantibodies of first-degree relatives of patients with autoimmune disease, there is no familial tendency in the occurrence of natural autoantibodies.

Survival of a premature neonate with obstructive anuria due to Candida: the role of early sonographic diagnosis and antimycotic treatment.

A low birth weight premature neonate with systemic candidiasis developed complete renal obstruction by fungus balls, diagnosed by ultrasonography. The neonate was treated with temporary urinary diversion, amphotericin B, 5-fluorocytosine and survived. This case emphasizes the need for a high index of suspicion of renal obstruction by fungus balls in neonates with systemic candidiasis when renal function deteriorates. In such cases early urinary diversion can be life-saving.