Donald Potter

Deliberate donor-specific blood transfusions prior to living related renal transplantation. A new approach.

In order to select MLC incompatible one-haplotype related donor-recipient pairs that would achieve better graft survival and in an effort to alter the recipient immune response, 45 patients received three fresh blood transfusions from their prospective kidney donors. Recipient sensitization was evaluated by cross-match testing weekly sera obtained during and after the blood transfusions against donor T- and B-lymphocytes at 5 C (cold) and 37 C (warm). Thirteen (29%) of the 45 potential related recipients developed a positive warm T-cell cross-match or a persistent warm B-cell cross-match to their blood donor and related transplantation was not performed. Thirty-two (71%) patients had an appropriate negative cross-match to their blood donor. Thirty of these patients subsequently received kidneys from their blood donor. Ninety-seven per cent of the kidneys are functioning from one to 25 months with a single graft failure due to a patient discontinuing immunosuppressive medication. In addition to the excellent graft survival there was an unusually low incidence of rejection episodes in the recipients of kidneys from their blood donor so that the posttransplant course paralleled that of HLA-identical siblings. This approach may have future application with two-haplotype mismatched donor-recipient pairs, both related and unrelated.

Relation of calorie deficiency to growth failure in children on hemodialysis and the growth response to calorie supplementation.

Abstract To determine if a relation existed between calorie intake and growth of children on hemodialysis, linear growth rate was observed for periods of three to nine months in children on dialysis and compared to 50th-percentile growth rates taken from tables for normal children having the same age or comparable secondary sexual development. Five children (six observations) with calorie intakes of less than 67 per cent of Recommended Dietary Allowances (RDA) grew at an average rate of 34 per cent of normal (range, 0 to 59). Ten children (11 observations) with calorie intakes of greater than 67 per cent of RDA grew at an average rate of 117 per cent normal (range, 87 to 150). Therefore, in this patient population, only calorie intakes of approximately 70 per cent of RDA or more were compatible with normal growth.

Continuous ambulatory peritoneal dialysis in children: comparison with hemodialysis.

The clinical and biochemical effects of continuous ambulatory peritoneal dialysis in 20 children and of hemodialysis in 16 children were compared over a 2 1/2-year period. Statistically significant differences between the treatment groups included higher hematocrit, higher serum carbon dioxide and cholesterol levels, large intake of calories and protein, and lower systolic blood pressure and rates of transfusion in the patients receiving continuous ambulatory peritoneal dialysis. These patients had more complications than the patients receiving hemodialysis, but hospitalization rates in the two groups were similar. The cost of continuous ambulatory peritoneal dialysis was +19,600 per patient-year; the cost of hemodialysis was +54,300 per patient-year; the cost of hemodialysis was +54,300 per patient-year. There were four treatment failures with continuous ambulatory peritoneal dialysis and one with hemodialysis. Patients treated with both forms of dialysis preferred continuous ambulatory peritoneal dialysis. We conclude that continuous ambulatory peritoneal dialysis is an important alternative to hemodialysis in children.

A seven-year experience with donor-specific blood transfusions. Results and considerations for maximum efficacy.

Two hundred thirty-nine transplants have been performed following donor-specific blood transfusions (DSTs) since 1978. Graft and patient survival in 1-and O-haplotype-matched transplants with DST pretreatment is comparable to HLA-identical results through 4 years. Graft survival in 174 consecutive nondiabetic, non-HLA-identical DST recipients shows that the transfusion effect persists for at least 4 years, with graft survival of 88\pm3% at that time, compared with 83\pm4% in the concurrent HLA-identical group. Graft function, as determined by serum creatinine, was the same in both groups. Graft and patient survival in 20 O-haplotype matched pairs with DST pretreatment is 100% at 2 years. Low-dose Imuran coverage during DST administration (n=91) was compared with a concurrent group with no Imuran (n=93). Imuran had its maximum effect in patients undergoing their first transplant and with a pre-DST PRA less than 10% (12% vs. 21% sensitization rate in the no-Imuran group). Imuran did not appear to confer any beneficial effect in primary transplants with high PRAs and in patients undergoing a second or third transplant. The majority of patients formally excluded from transplantation because of a post-DST positive B-warm crossmatch can now be successfully transplanted with the use of flow cytometry analysis to rule out previously undetectable low levels of anti-T-lymphocyte antibodies. Of 62 patients with a positive B-warm crossmatch alone since 1982, 73% had a subsequent negative fluorescence-activated cell sorter (FACS) crossmatch permitting transplantation. Preliminary results of a DST and cyclosporine treatment study are described. In conclusion, a long-term immunologic effect of DST has been confirmed and the indications and considerations for optimum use of the DST protocol have been more clearly defined.

Hyperparathyroid bone disease in children undergoing long-term hemodialysis; treatment with vitamin D

Or 17 children who had been in a hemodialysis program for more than six months, three had hyperparathyroid bone disease before entering the program and five developed it after two to 17 months of dialysis. The incidence of bone disease was related to the duration of azotemia and not to the duration of dialysis, to the dialysate concentration of calcium, or to the predialysis serum concentrations of urea nitrogen, calcium, and phosphorus. Six children with bone disease were treated with vitamin D in average daily doses ranging from 32,000 to 57,000 IU for periods of five to 13 months. In three the bone lesions healed, in two they were improved, and in one there was progression until a renal transplant was performed. Hypercalcemia was slight; conjunctival calcification was the only form of metastatic calcification observed. The calcium content in the skin of the children was less than that in adults who had had dialysis for comparable periods of time.

Role of Twenty-Four-Hour Ambulatory Blood Pressure Monitoring in Children on Dialysis

BACKGROUND AND OBJECTIVES Pre- or postdialysis BP recordings are imprecise, can be biased, and have poor test-retest reliability in children on dialysis. We aimed to examine the possible differences between pre- and postdialysis BP levels and 24-hour ambulatory BP monitoring (ABPM) in diagnosis of hypertension (HTN). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Twenty-four children on dialysis had 24-hour ABPM in the interdialytic period, and values were compared with average pre- and postdialysis systolic BP (SBP) and diastolic BP (DBP) recordings that week. Each patient had an echocardiogram to determine presence of left ventricular hypertrophy (LVH). RESULTS By ABPM, 8% of patients had white coat HTN and 12% had masked HTN. There was no significant difference in diagnosis of systolic HTN based on ABPM daytime SBP mean or load and postdialysis SBP. However, only 15% of patients had diastolic HTN based on postdialysis measures, whereas 46% of patients had significantly elevated daytime DBP loads and 71% had high nighttime DBP loads on ABPM. Forty-eight percent of patients were SBP nondippers. Children with LVH had higher daytime and nighttime SBP loads, significantly higher daytime and nighttime DBP loads, and lesser degree of nocturnal dipping of SBP compared with those who did not. CONCLUSION ABPM is more informative than pre- and postdialysis BPs and improves the predictability of BP as a risk factor for target organ damage. Diagnosis and treatment monitoring of HTN among pediatric dialysis patients is enhanced with addition of ABPM.

Renal homotransplantation in children

Abstract From 1964 through 1971, sixty-three transplantations were performed in fifty-four children under the age of eighteen at the University of California Medical Center, San Francisco. Thirty-two of the children received their first renal graft from a related donor and twenty-one from a cadaver donor. In the living related donor group, survival of first grafts was 90 per cent at one year, and in the cadaver donor group it was 67 per cent at one year. Ten patients died during the eight year period. Linear growth of children who had reached their adult height prior to transplantation was favorably influenced by changing the prednisone schedule from daily doses to doses every other day. By performing retransplantation if graft failure occurred, 80 per cent of the fifty-four patients now have functioning grafts up to eight years postoperatively. These results show that children with end stage renal disease are favorable candidates for renal transplantation.

Treatment of high-renin hypertension with propranolol in children after renal transplantation**

Ten children with hypertension poorly controlled with other drugs and high peripheral plasma renin activity after renal transplantation were treated with propranolol. The mean systolic pressure decreased from 139 to 127 mm Hg (p less than 0.05) and the mean diastolic pressure from 98 to 83 mm Hg (p less than 0.01). Eight children had an antihypertensive response; two did not respond. The maximum dose of propranolol in responders varied from 1.0 to 6.2 mg/kg/day and duration of treatment until response varied from four to 49 days. PRA, repeated in seven responders, decreased in all (p less than 0.01). There was no correlation between changes in PRA and blood pressure. Propranolol was well tolerated and was a valuable antihypertensive drug in these children.

Character of Function and Size in Kidney During Normal Growth of Rats

Extract: During normal growth in male rats (3 weeks to 3 months of age) weighing from 50–400 g, kidney weight and glomerular filtration rate (GFR) increased at slower rates than did body weight; in contrast, the rate of increase in kidney weight and glomerular filtration rate were the same, and the ratio of GFR:g kidney weight was constant after 4–5 weeks of age. The ratio of maximal glucose reabsorption (TmG) to GFR increased only slightly with growth. Na-K-dependent ATPase activity/mg light microsomal protein from kidney cortex and QO2 did not change during growth. Kidney growth up to 200 g body weight at 16 weeks of age was due more to an increase in cell number; beyond then it was due more to an increase in cell size. The pattern of function-structure relation during growth differed from that observed in kidney hypertrophy secondary to uninephrectomy. It was not specifically determined from cell number or size but from some property proportional to total protein mass or to the product of cell number and cell mass.Speculation: Tubular functions of the nephron during growth increase in proportion to each other and in proportion to total renal mass. This pattern of increase differs in several respects from that which occurs following uninephrectomy. The inference is that growth response differs in fundamental biological character from the hypertrophy response.

Are blood transfusions beneficial in the cyclosporine era

In patients treated with conventional immunosuppression (azathioprine and prednisone) after renal transplantation, there is a beneficial effect of pre-transplant blood transfusions on graft survival; in patients treated with cyclosporine, this effect may be lost. In 66 children who received living-related donor transplants after donor-specific transfusions (DST) and were treated with azathioprine-prednisone in our center, 1- and 5-year graft survival rates were 99% and 77% respectively. These rates were similar to those reported for children who did not receive DST but were treated with cyclosporine in other centers. There were 634 adult and pediatric recipients of cadaver transplants in our center who were treated with cyclosporine and prednisone (non-sequential therapy,n=89) or antilymphoblast globulin, azathioprine preduisone, and cyclosporin (sequential therapy,n=545). When all patients were considered, graft survival rates were higher in transfused than in non-transfused patients at 3–5 years, but in the sequential therapy group, there were no differences in graft survival rates between transfused and non-transfused patients. The results suggest that transfusions do not improve cadaver graft survival in patients receiving optimal cyclosporine therapy and that equally good related donor graft survival can be achieved with DST and conventional immunosuppression or no DST and cyclosporine.