Yong-ran Zhu

Factors influencing weight gain after renal transplantation.

Weight gain following renal transplantation occurs frequently but has not been investigated quantitatively. A retrospective chart review of 115 adult renal transplant recipients was used to describe patterns of weight gain during the first 5 years after transplantation. Only 23 subjects (21%) were overweight before their transplant. Sixty-six subjects (57%) experienced a weight gain of greater than or equal to 10%, and 49 subjects (43%) were overweight according to Metropolitan relative weight criteria at 1 year after transplantation. There was an inverse correlation between advancing age and weight gain, with the youngest patients (18–29 years) having a 13.3% weight gain and the oldest patients (age greater than 50 years) having the lowest gain of 8.3% at 1 year (P =0.047). Black recipients experienced a greater weight gain than whites during the first posttransplant year (14.6% vs. 9.0%; P =0.043), and maintained or increased this difference over the 5-year period. Men and women experienced comparable weight gain during the first year (9.5% vs. 12.1%), but women continued to gain weight throughout the 5-year study (21.0% total weight gain). The men remained stable after the first year (10.8% total weight gain). Recipients who experienced at least a 10% weight gain also increased their serum cholesterol (mean 261 vs. 219) and triglyceride (mean 277 vs. 159) levels significantly, whereas those without weight gain did not. Weight gain did not correlate with cumulative steroid dose, donor source (living-related versus cadaver), rejection history, pre-existing obesity, the number of months on dialysis before transplantation, or posttransplant renal function. Posttransplant weight gain is related mainly to demographic factors, not to treatment factors associated with the transplant. The average weight gain during the first year after renal transplantation is approximately 10%. This increased weight, coupled with changes in lipid metabolism, may be significant in terms of altering risk from cardiovascular morbidity.

A prospective randomized comparison of quadruple versus triple therapy for first cadaver transplants with immediate function.

In January 1988, we initiated a prospective, randomized comparison of prophylactic antilymphoblast globulin (ALG; quadruple therapy) versus no prophylactic ALG (triple therapy) in the setting of immediate graft function (defined by a brisk diuresis and a 20% decline in serum creatinine within 24 hr). Recipients were stratified according to presence of diabetes and age greater or less than 50 years. Recipients on quadruple therapy (n=61) received 7 days of prophylactic Minnesota ALG (5 mg/kg on day 1,10 mg/kg on day 2, 20 mg/kg on days 3–7). CsA, 10 mg/kg/day, began on day 6. AZA began at 2.5 mg/kg/day and was adjusted according to white blood cell count. Recipients on triple therapy (n=60) began immediate CsA, 10 mg/kg/day orally and AZA, 5 mg/kg/day, tapering to 2.5 mg/kg/day by day 8. Both groups received identical prednisone tapers beginning at 1 mg/kg/day, decreasing to 0.5 mg/kg/day by 2 weeks and to 0.15 mg/kg/day by 6 months. Demographic characteristics between groups were not different with respect to diabetes, age, sex, race, per cent panel-reactive antibodies (PRA), or HLA matching. Follow-up ranged from 2 to 4.5 years. Patient survival was 93% for the quadruple therapy group and 90% for triple therapy. Actuarial graft survival was 79% in the quadruple group and 72% in the triple group (P =0.18). Graft loss due to rejection occurred in 6/61 receiving ALG versus 7/60 in the immediate CsA group. Three of 4 high PRA recipients in the immediate CsA group lost their grafts within 30 days compared with none in the ALG group. The mean time to graft loss was significantly longer for the quadruple therapy group (17 ± 8 months) compared with the triple therapy group (4 ± 5 months), P =0.006. The total number of rejection episodes was similar for both groups (29/61 vs. 31/60), as was the number who were rejection free (51% vs. 47%). The use of OKT3 was also similar between groups (28% vs. 30%). The quadruple therapy group had a higher incidence of CMV infection: 20% vs. 7% (P <0.05), but no grafts or patients were lost as a result. Serum Cr was not different at 1 and 12 months (1.5 and 1.6 vs. 1.6 and 1.7, respectively), nor were Cr clearances (63 and 68 vs. 60 and 63). Conclusion. Early initiation of oral CsA in the setting of immediate graft function is not associated with significant nephrotoxicity. In first cadaver transplants, prophylactic ALG (for 7 days) does not reduce the incidence of rejection or lessen the use of OKT3. It does lengthen the time to graft loss and may protect high PRA recipients from early graft loss. Ultimately, patient survival, graft survival, and graft function are not significantly different as a result of these two induction protocols.

Renal Transplantation With Final Allocation Based on the Virtual Crossmatch

Solid phase immunoassays (SPI) are now routinely used to detect HLA antibodies. However, the flow cytometric crossmatch (FCXM) remains the established method for assessing final donor–recipient compatibility. Since 2005 we have followed a protocol whereby the final allocation decision for renal transplantation is based on SPI (not the FCXM). Here we report long‐term graft outcomes for 508 consecutive kidney transplants using this protocol. All recipients were negative for donor‐specific antibody by SPI. Primary outcomes are graft survival and incidence of acute rejection within 1 year (AR <1 year) for FCXM+ (n = 54) and FCXM− (n = 454) recipients. Median follow‐up is 7.1 years. FCXM+ recipients were significantly different from FCXM− recipients for the following risk factors: living donor (24% vs. 39%, p = 0.03), duration of dialysis (31.0 months vs. 13.5 months, p = 0.008), retransplants (17% vs. 7.3%, p = 0.04), % sensitized (63% vs. 19%, p = 0.001), and PRA >80% (20% vs. 4.8%, p = 0.001). Despite these differences, 5‐year actual graft survival rates are 87% and 84%, respectively. AR <1 year occurred in 13% FCXM+ and 12% FCXM− recipients. Crossmatch status was not associated with graft outcomes in any univariate or multivariate model. Renal transplantation can be performed successfully, using SPI as the definitive test for donor–recipient compatibility.

Delayed gastroduodenal emptying is an important mechanism for control of intestinal transit in short-gut syndrome

PURPOSE To understand the relative importance of changes in ileal smooth muscle contractility versus alteration of intestinal flow rate as control mechanisms for regulating intestinal transit in a surgical model of short-gut syndrome. METHODS A model of short-gut syndrome was created by performing a 70% proximal small-bowel resection in dogs. Ten control and 6 animals with short-gut syndrome were instrumented with strain gauge transducers, steel collection cannulas, and a Silastic intraluminal infusion catheter in the midileum. Motor activity was analyzed by computer programs that determine frequency, amplitude, and propagation behavior of postprandial contractions. Perfusions of 14C-polyethylene glycol and bolus injection of 3H-polyethylene glycol were used to determine intestinal flow and transit rates. Total gastroduodenal emptying was determined using a 14C-polyethylene glycol-labelled meal. RESULTS Postprandial contraction frequency was decreased in animals with short-gut syndrome, but other significant changes in amplitude, mean area, and propagation behavior of postprandial ileal contractions were not seen. Gastroduodenal emptying and mean intestinal flow rates were markedly slower in animals with short-gut syndrome, as were intestinal transit rates. CONCLUSIONS In this model of short-gut syndrome, the major adaptive change is decreased intestinal flow rate, related to delayed gastroduodenal emptying. The spatial organization of ileal contractions does not change substantially aside from a change in frequency which can be accounted for by transection of the intestinal wall.