Long-term follow up of renal function and histology after renal allograft transplantation in early childhood

Abstract Survival rates, renal function, and histopathology were evaluated in 49 prospectively followed patients transplanted under 5 years of age at our center. Most patients (84%) suffered from congenital nephrosis of the Finnish type. Triple immunosuppression with cyclosporin administered in three daily doses to pre-school children was used. Patient survival 7 years after transplantation was 98 % and graft survival 88 %. All graft losses were due to post-transplantation nephrosis. The proportion of pathological findings in the follow-up biopsies did not change substantially with time. Five years after transplantation, 47 % showed a normal histology and after 7 years this rose to 67 %. Mean glomerular filtration rate (GFR) was 68 and 55 ml min per 1.73 m² 5 years and 7 years, respectively, after transplantation. The decline in GFR with time was significant. We conclude that good long-term results can be achieved with individually tailored triple immunosuppression in the youngest age group, even with cadaveric donors.     

Calcineurin activity in tacrolimus-treated renal transplant patients early after and 5 years after transplantation

The pharmacodynamic (PD) action of tacrolimus (FK) within the T-cell is inhibition of calcineurin phosphatase (CaN). Determination of CaN activity provides us with an important PD marker. Eleven renal transplant patients treated with FK were investigated on day 14 following transplantation and 5 years later. Blood samples drawn before as well as 1, 2, 3, and 4 hours after oral intake of FK were analyzed for CaN activity and blood FK concentrations. Twenty healthy subjects had one blood sample drawn for CaN activity, which was measured as the release of (32)P from a phosphorylated peptide. Radioactivity of (32)P was quantitated by liquid scintillation counting with the results converted to units of CaN utilizing a calibration curve. On day 14, we observed significant inhibition of CaN activity at T:1, 2, and 3 compared with the predose level (P = .002; P = .015; P = .015). Furthermore, all measured CaN activities were significantly different from those observed in healthy nonmedicated subjects. In contrast, at 5 years posttransplant only the CaN activity at T:2 was significantly inhibited compared with the predose level (P = .02). Additionally, all CaN activities at this time were not significantly different from CaN activities in the healthy subjects. We were not able to demonstrate individual CaN activity profiles in the patients. The lack of CaN inhibition at 5 years after transplantation despite relevant drug concentrations, probably reflected the lower drug dose used long after transplantation. This result raises the question of whether CaN inhibition is necessary to hold graft function and whether FK possess CaN-independent mechanisms of action.     

Growth after renal transplantation in infancy or early childhood

Forty-one children <5 years of age at kidney transplantation (TX) were investigated for growth, bone age, and renal function up to 7 years (n=26) after TX. All children received triple immunosuppression, including alternate-day corticosteroid treatment. Catch-up growth was seen in 81% of 30 children without growth hormone (GH) treatment. Children <2 years of age without GH had a mean height standard deviation score (hSDS) of –1.1±0.8 at TX and –1.1±0.5 at 7 years; children between 2 and 5 years improved their hSDS from –1.9±0.9 to –0.4±0.8 (P<0.0001). The hSDS at TX correlated inversely with the ΔhSDS from TX to 7 years (r=–0.80, P=0.0002). Glomerular filtrations rate (GFR) at 5 years post TX correlated with the subsequent growth rate from 5 to 7 years TX (r=0.58, P=0.01). Catch-up growth was seen in all 11 children receiving GH. Their mean hSDS improved from –2.5±0.9 to –1.1±0.9 (P<0.0001). In the majority of children receiving a kidney graft in early life, triple immunosuppression with alternate-day steroids can ensure catch-up growth. In children <5 years of age at TX, growth is predicted better by the degree of stunting than by age. Received: 9 September 2001 / Revised: 2 January 2002 / Accepted: 4 January 2002     

Course of renal allograft histopathology after transplantation in early childhood

BACKGROUND: We report a long-term prospective follow-up of renal allograft histology in children <5 years of age at transplantation (Tx). METHODS: Fifty-one kidney allograft recipients were prospectively followed for renal allograft histology and function up to 7 years after Tx. Twenty patients were recipients of kidneys from living related donors, and 31 were cadaveric kidney recipients. All patients received triple immunosuppression. Biopsies were analyzed according to the Banff classification and scored semiquantitatively. The "chronic allograft damage index" (CADI) was calculated. RESULTS: Five of seven grafts were lost because of nephrosis in patients with congenital nephrotic syndrome of the Finnish type. Most of the biopsies (52-69%) were considered normal (Banff classification), and the proportion with chronic allograft nephropathy did not increase with time. The median CADI score was 2.5 (scale: 0-36) at 1.5 years and 3.5 at 7 years. Recipients with an acute rejection episode had higher CADI scores than recipients without acute rejection episode. Patients with a high CADI score at 3 years had inferior graft function at 5 years. Recipients <2 years of age had CADI scores and numbers of acute rejection episode similar to recipients between 2 and 5 years of age. However, in contrast to the older recipients, the younger recipients did not improve their absolute glomerular filtration rate with time. CONCLUSIONS: The long-term histopathological findings were mostly mild and stable with time. Acute rejection episode had an impact on these changes and CADI predicted later graft function. Nonimmunological risk factors seem to be more important in the youngest recipients.     

Left ventricular function in children and adults after renal transplantation in childhood

Background

Renal transplantation improves left ventricular (LV) function, but cardiovascular mortality remains elevated. The aim of this cross-sectional study was to determine whether subclinical abnormalities of LV longitudinal function also persist in patients who underwent renal transplant in childhood.

Methods

Conventional and speckle tracking echocardiography was performed in 68 renal transplant recipients (34 children and 34 adults, median 9.8?years (range 2.0–28.4?years) after first transplantation and 68 age- and sex-matched healthy controls.

Results

Mean age at first transplantation was 8.8?±?4.8?years. Forty-three percent had a pre-emptive transplant. Of the remaining, 70% received haemodialysis and 30% peritoneal dialysis on average for 6.9?months. Thirty-one percent of paediatric and 35% of adult patients had hypertension. LV mass index was increased in adult patients (92?±?24 vs 75?±?11?g/m², P P?Conclusions Patients who underwent renal transplantation in childhood have abnormal LV diastolic function and impaired exercise capacity, despite preserved LV longitudinal systolic deformation.     

Long-term outcome after renal transplantation in childhood

The purpose of this article is to review:

Flow cytometric crossmatching in renal transplantation - outcome after five years

Abstract  The association of a positive flow cytometric crossmatch between recipient IgG directed against donor T lymphocytes and poor out come is well described in renal transplantation. Until now, no long-term follow-up on such patients has been available. A total of 117 renal transplant patients were followed up for a period of 5 years. Of these, 21 were known to have donor T cell-directed IgG and 5 had B lympho cyte-directed IgG. Both groups of patients with these antibodies had a significantly poorer outcome at 5 years than did the group of patients without IgG ( P < 0.0001 Han del Maenzel test). Patients with antibody detected preoperatively were tested again, either at the time of graft failure or at 5 years posttrans plantation. The sera were tested against stored donor cells and the intensity of surface IgG compared with the preoperative levels. In those recipients who lost their grafts, the levels increased in 60 % of cases but those that retained their grafts also had an increase in levels of do nor-directed antibody in 50 % of cases. The changing levels of anti body therefore appeared to have little relevance to outcome. However, when IgG isotypes were considered, for those who experienced graft failure and also had a γ₃ isotype, a rise in IgG was demonstrated in all cases. Conversely, successful grafts with γ₃ had a decline in levels between preoperative and 5–year sam ples in three of the four cases ( p not significant).     

Decline in native renal function early after bladder-drained pancreas transplantation alone

BACKGROUND: Pancreas transplant alone (PTA) has become accepted therapy for select nonuremic patients with type 1 diabetes mellitus. However, PTA may lead to significant complications including a decline in native renal function. This study examines trends in native renal function during the first posttransplant year in PTA recipients with a spectrum of pretransplant glomerular filtration rates (GFR). METHODS: Renal function was studied in 23 recipients of bladder-drained PTA who underwent transplantation from April 1998 through September 2001. GFR was measured by corrected iothalamate clearance at the time of transplant evaluation and 1 year posttransplant and also calculated using the Cockcroft-Gault method at the transplant evaluation; at the day of transplantation; and at 1, 6, and 12 months posttransplant. RESULTS: Iothalamate clearance decreased in the first year in 96% of patients (22 of 23). The mean measured GFR decreased from 84 +/- 33 mL/min/1.73 m2 pretransplant to 52 +/- 26 mL/min/1.73 m2 at 1 year (P <0.001). Calculated creatinine clearance declined in the majority of patients at both 1 and 12 months after PTA, but some patients, including a few with low GFR, maintained stable renal function. Calculated GFR generally correlated well with measured GFR in most patients, with a few notable exceptions. One patient (baseline GFR, 42 mL/min/1.73 m2) developed renal failure in the first year after transplant and required kidney transplantation. CONCLUSIONS: Bladder-drained PTA results in a decline in native renal function in the majority of patients regardless of the pretransplant GFR. These data suggest the need for strategies to prevent or minimize the decline in renal function after PTA.     

Immediate and early renal function after living donor transplantation.

BACKGROUND: In order to assess the immediate renal function after living donor transplantation, renal function was compared in eight renal allograft recipients and their living related kidney donors during the first 24 h after transplantation. METHODS: Substantial and comparable intraoperative volume loading with Ringer's acetate and mannitol was performed together with the administration of frusemide. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were estimated by the clearances of inulin and p-aminohippurane, respectively. Tubular reabsorptive function and injury were estimated from the clearance of lithium, the fractional excretion of sodium and the urinary excretion of N-acetyl-beta-glucosaminidase. RESULTS: One hour after completion of surgery, GFR (54 +/- 7 ml/min) and ERPF (294 +/- 35 ml/min) were only 30% lower in the grafts than in the remaining donor kidneys, increasing to similar levels within 3 h. Only minor tubular dysfunction and injury were revealed in the grafted kidneys, and these tended to normalize within 24 h. CONCLUSIONS: By the present transplantation procedure comprising short ischaemia time and substantial volume expansion combined with mannitol and frusemide administration, kidneys from living donors regain nearly normal function within a few hours after transplantation.     

Results of early active rehabilitation 5-7 years after surgical treatment for lumbar disc herniation

A prospective and randomized study was conducted of 52 patients who were treated by two home training programs after surgical treatment of lumbar disc herniation. Twenty-six patients followed an early active treatment program, and 26 patients followed a less active training program (control group). Forty-nine patients (82%) answered a questionnaire 5-7 years postoperatively. The reoperation rate was two of 49 patients. None of these patients had followed the early active treatment program. Patients with signs of depression before surgery were not significantly less satisfied with the outcome than patients with no signs of depression before surgery.     

Impact of selected factors on early graft function in patients after renal transplantation

Transplantation is the best treatment for end-stage renal diseases. For transplantologists, it is most important to know the factors that worsen graft survival prognosis. The aim of the study was to investigate factors predictive of graft loss and shortened graft survival. We retrospectively reviewed 442 renal transplant patients between 1990 and 1995 in two Szczecin units, all of whom received a triple-drug immunosuppressive regimen. One hundred thirty patients showed graft disorders such as delayed graft function or primary nonfunction. The occurrence of these disorders was examined as a function of donor and recipient age and sex, cause of ESRD, HLA compatibility, ABO and Rh compatibility, cold ischemia time, warm ischemia time, antileukocyte antibody level (PRA), and period of dialysis therapy before transplantation. The study showed that a high maximal PRA level, incompatibility for ABO group, and a longer warm ischemia time increase the probability of early graft function disorders.     

Association of hyperglycemia on allograft function in the early period after renal transplantation

Hyperglycemia is common following renal transplantation. This study was conducted to evaluate the relationship of perioperative serum glucose levels and acute rejection in 100 nondiabetic patients who underwent renal transplantation. Blood glucose was measured immediately following surgery and every 6 hours during the first 48 hours posttransplant as well as for 1 month to evaluate occurrence of acute rejection episodes (ARE). The rate of ARE was 33%. The mean blood glucose level immediately after surgery in patients with versus without ARE was 249.67 +/- 61.78 and 184.82 +/- 73.35 mg/dL, respectively (P=.000). There was no significant correlation between ARE and donor or recipient age or sex, delayed graft function, type of donor, or treatment. This study suggested a correlation between immediate blood glucose and ARE. In this regard, blood glucose monitoring and control during operation and immediate postoperatively may reduce the acute rejection rate.     

Arterial function after successful renal transplantation

BACKGROUND: Renal transplantation is increasingly the preferred method of renal replacement therapy. Cardiovascular disease is the major barrier to long-term survival for transplant recipients. The aim of this study was to determine whether the increased arterial stiffness of patients with chronic renal failure is improved after successful renal transplantation. METHODS: The study involved a group of 36 patients, aged 27 to 68 years (mean +/- SD, 46 +/- 11 years) who had cardiovascular risk assessment and measurements of carotid artery intima-media thickness (IMT), arterial pulse wave velocity [aorto-femoral (PWV a-f) and femoral-dorsalis pedis (PWV f-d)], systemic arterial compliance (SAC), and arterial wave reflection (augmentation index, AI(x)) performed before and 12 months after successful renal transplantation. B-mode ultrasound measurements were used to determine mean carotid IMT and applanation tonometry techniques to determine SAC, AI(x), PWV (a-f), PWV (f-d), and central pressures. On each occasion the following were also measured: fasting lipids, homocysteine (tHcy), red cell folate, cobalamin, and fibrinogen levels. RESULTS: One year after transplantation, mean serum creatinine was 143 +/- 47 micromol/L, and creatinine clearance 60 +/- 16 mL/min/1.74m(2) (range 25 to 104 mL/min/1.74m(2)). Total and low-density lipoprotein (LDL) cholesterol were significantly reduced. tHcy was decreased by 38% and normalized in 45%. Systolic and diastolic blood pressure and mean arterial pressure were all improved. From baseline to 12 months' post-transplantation, there was no significant change in carotid IMT (mean IMT 0.76 +/- 0.11 vs. 0.75 +/- 0.14 mm, P= 0.28) or SAC (0.45 +/- 0.23 vs. 0.46 +/- 0.22 units, P= 0.95), but PWV [PWV (a-f) 9.6 +/- 2.6 vs. 8.8 +/- 2.2 m/sec, P= 0.007; PWV (f-d) 10.7 +/- 1.8 vs. 8.4 +/- 1.7 m/sec, P < 0.001] and AI(x) (24.3 +/- 13.4 vs. 15.9 +/- 11.4%, P= 0.003) improved. After adjusting for the differences in blood pressure, the changes in PWV (a-f) were no longer significant, but the differences in PWV (f-d) persisted. The change in AI(x) remained significant after adjusting for differences in heart rate, and the fall in AI(x) was greater in patients on immunosuppression with tacrolimus compared with those on cyclosporine. CONCLUSION: One year after successful renal transplantation, improvement in cardiovascular risk factors was associated with improvement in indices of arterial stiffness.     

Comparison of early renal function parameters for the prediction of 5-year graft survival after kidney transplantation.

BACKGROUND: Early graft function (EGF) has an enduring effect on the subsequent course after kidney transplantation. This study compares quantitative parameters of EGF for the prediction of graft survival. METHODS: We involved 300 consecutive transplant recipients from deceased donors from 1989 to 2005. Urine output during 24 h post-transplant (UO), and serum creatinine after 1 week (Cr7) were taken for explanatory variables. We generated Kaplan-Meier (K-M) estimates of graft survival, by quintiles of the explanatory variable. Cox regression was applied to control for various recipient factors. RESULTS: K-M survival estimates indicate a threshold effect of UO and Cr7, which can dissect the risk of graft failure. The thresholds referring to the 2nd quintile correspond to a UO >630 ml and a Cr7 <2.5 mg/dl and were associated with a proportional hazard ratio of 0.52 (95% CI 0.33-0.84) and 0.34 (95% CI 0.18-0.65), respectively. Combining both of the parameters predicted a 5-year graft survival probability >90%, according to a hazard ratio of 0.21 (95% CI 0.09-0.46). Requirement of dialysis post-transplant lost its discriminatory power and was not a significant explanatory variable in the multivariate analysis. CONCLUSION: Routine parameters for monitoring of EGF display a threshold effect allowing accurate prediction of 5-year graft survival at the earliest point in time. The quantitative threshold levels for an optimum discriminatory power require validation in a larger, preferably multicentre database.     

Peritoneal dialysis favorably influences early graft function after renal transplantation compared to hemodialysis

BACKGROUND: Delayed graft function (DGF) and acute renal failure (ARF) after renal transplantation negatively influence short- and long-term graft outcome. Peritoneal dialysis as pretransplantation dialysis modality was reported to influence favorably the recovery of renal function immediately after kidney transplantation. It has been hypothesized that fluid status was the factor explaining this better outcome. This hypothesis was tested in this study by multivariate analysis, also including other factors related to DGF and ARF. METHODS: The records of peritoneal dialysis (PD; n=40) and hemodialysis (HD; n=79) patients receiving a first cadaveric kidney transplantation at the University Hospital Gent were analyzed. RESULTS: DGF and ARF were observed in 33 (27 HD and 6 PD, P=0.03) and 14 (14 HD and 0 PD, P=0.01) patients, respectively. The number of days needed to reach a serum creatinine 50% below that before transplantation (T1/2(SCr)), was correlated with cold ischemia time (CIT) (P<0.001) and body weight gain (BWG) (P<0.01) and was inversely correlated with urinary output in the first 24 hr (P<0.001), fluid load (P<0.001), and central venous pressure (P<0.001). A multivariate model with CIT (P<0.001), PD as pretransplantation dialysis mode (P=0.01), urinary output in the first 24 hr (P=0.001), BWG (P=0.05), and fluid load (P=0.01) resulted in an R2 of 0.32 (P<0.001). Using Cox regression analysis, the relative risk for a prolonged T1/2(SCr) increased with 4%/hr CIT (P=0.01) and with 1%/kg BWG (P=0.02). Fluid load decreased the relative risk with 5%/liter (P<0.001) and PD as pretransplantation modality favorably modified the relative risk by a factor of 1.6 (P=0.01). CONCLUSION: PD as pretransplantation dialysis modality can reduce the incidence and the severity of delayed recovery of renal function after renal transplantation. This protective effect was independent from CIT, and fluid status, two other major influencing factors.