Living-related-donor kidney transplantation outcome in recipients with primary focal-segmental glomerulosclerosis

We studied the outcome of renal transplantation in 30 patients with primary focal-segmental glomerulosclerosis (FSGS) and in 30 controls in whom renal failure was secondary to nonglomerular renal diseases. All patients received living-related-donor kidneys, and the majority had one-haplotype HLA matching. Within the follow-up period, the mean serum creatinine values were significantly higher in FSGS recipients as compared with the control group (p = 0.02). However, the frequency of acute rejection episodes and the mean blood pressure values were not significantly different between the two groups. There was a tendency of a higher incidence of proteinuria among FSGS recipients in comparison with the controls. Moreover, nephrotic-range proteinuria occurred only in 3 recipients of the FSGS group. Recurrence of FSGS was morphologically documented in 2 recipients 7 and 18 months, respectively, after transplantation. It is concluded that FSGS as the primary disease has a negligible impact on the living-related-donor kidney transplantation in the Egyptian population. Therefore, this disease should not discourage transplantation for this group of patients.     

The kidney allocation system does not appropriately stratify risk of pediatric donor kidneys: Implications for pediatric recipients

Kidney Allocation System (KAS) was enacted in 2014 to improve graft utility, while facilitating transplantation of highly‐sensitized patients and preserving pediatric access to high‐quality kidneys. Central to this system is the Kidney Donor Profile Index (KDPI), a metric intended to predict transplant outcomes based on donor characteristics but derived using only adult donors. We posited that KAS had inadvertently altered the profile and quantity of kidneys made available to pediatric recipients. This question arose from our observation that most pediatric donors carry a KDPI over 35 and have therefore been rendered relatively inaccessible to pediatric recipients under KAS. Here we explore early trends in pediatric transplantation following KAS, including: (i) use of pediatric donors, (ii) use of Public Health System (PHS) high infectious risk donors, (iii) wait time, and (iv) living donor transplantation. We note some concerning preliminary changes following KAS implementation, including the allocation of fewer deceased donor pediatric kidneys to children and stagnation in pediatric wait times. Moreover, the poor predictive power of the KDPI for adult donors appears to be even worse when applied to pediatric donors. These early trends warrant further observation and consideration of changes in pediatric kidney allocation if they persist.     

Transplantation of pediatric donor kidneys to adult recipients. Is there a critical donor age?

Cadaver kidneys remain a scarce resource, yet single pediatric donor kidneys are underutilized at some centers. Between 1967 and 1984, 133 single pediatric and 318 adult donor cadaver transplants were performed. Patient and graft survival, renal function, and complications in adult recipients grouped by donor age were compared. Recipient age for all groups was similar (34-36 years). Life table analysis revealed no difference in graft survival in recipients of kidneys from donors aged 2, 3, 4, 5-10, and 11-15 when compared with adult donors. Graft survival in these groups improved over time with current 1-year survival over 75%. Recipients from donors less than 24 months of age demonstrated significantly poorer results, with no kidney surviving greater than 2 months. Serum creatinine of grafts functioning greater than 6 months was similar in all groups. It is concluded that single pediatric kidneys from donors greater than 2 years of age can be successfully transplanted to adults with good long-term results.     

Transplantation of pediatric cadaveric kidneys into adult or pediatric recipients

In Japan, nationwide cadaveric organ sharing for kidney transplantation by the Japan Organ Transplant Network (JOTN) has operated since April 1995. This study retrospectively analyzed the long-term results of single pediatric donor kidneys transplanted into adult or pediatric recipients at a single center. From March 1983 to December 2002, 281 cadaveric renal allografts were transplanted at our center, including, 17 recipients of cadaveric kidneys from donors aged less than 16 years. We divided these 17 recipients into two groups: 10 adult recipients (group 1; G1) and seven pediatric recipients (group 2; G2). HLA-AB, -DR mismatches were 1.3 +/- 1.3, 0.7 +/- 0.5 in G1 and 2.6 +/- 1.3, 1.4 +/- 0.8 in G2, respectively (P < .05 for both). The end of the observation of this study was March 2003. Among G1, two recipients died with functioning grafts and one died after graft loss. Among G2, no recipients died. Patient survival rates at 1 and 5 years were 90% and 80% in G1 and 100% and 100% in G2, respectively. At the end of the observation in this study, five recipients among G1 and six recipients among G2 had functioning grafts. Graft survival rates at 1 and 5 years were 90% and 80% in G1 and 85.7% and 85.7% in G2, respectively. Our results demonstrate that transplantation of pediatric cadaveric kidneys into pediatric recipients was excellent compared to adult recipients in terms of survival. Priority to pediatric patients should be given especially in cases of pediatric donors.     

Living donor kidney transplantation in pediatric recipients

Currently, kidney transplantation is the treatment of choice in children with end stage renal disease, showing higher survivals than dialysis and proper weight-height, social and psychological-intellectual development. The indications for transplantation have been extended with time, so that today the indication for kidney transplantation is set for end stage renal disease with symptoms that cannot be eliminated by conservative treatment. In the pediatric age, mainly in children under two years, living donor kidney transplantation is specially indicated because it has longer survival than cadaver donor kidneys. Complications may appear: rejection, high blood pressure, infections, neoplasias, adverse events related to immunosuppressive drugs, and primary renal disease recurrences, besides surgical complications. Five-year results have improved over the last 5 decades, being mortality lower than 5%. Graft survival may reach 90% for living donor kidneys and 17% for cadaver donor. Factors related to graft survival include age (worse in receptors under 2 yr.), pretransplant dialysis, acute rejection, and race (better in caucasians).     

Transplantation of single pediatric kidneys into adult recipients

AIM: To evaluate the outcome of single pediatric kidneys transplanted into adult recipients. METHODS: A retrospective single-center review was performed of transplants from donors less than 5 years of age. Outcomes were compared with recipients of grafts from donors 18 to 45 years transplanted during the same time period. RESULTS: Thirty single renal transplants from pediatric donors and 117 transplants from adult donors between 18 and 45 years of age were performed during the study period. The mean age of the pediatric donors was 2.9 +/- 0.8 years versus 31.5 +/- 8.9 years for adult donors (P < .001). The mean age of the recipients of pediatric donors was 41.9 +/- 13 years versus 48 +/- 12.6 years for recipients of adult grafts (P = .020). The mean recipient weight of pediatric donors was 55.9 +/- 7.8 kg versus 78.0 +/- 17.7 kg for recipients of adult donors (P < .001). Sixty-six percent of pediatric donor recipients were of female gender compared to only 36% of adult donor recipients (P = .005). Death-censored actuarial graft survivals at 1 and 4 years for recipients of pediatric donor grafts were 90% and 85% compared to 93% and 85% for recipients of adult donor grafts (P = NS). The mean calculated creatinine clearances of adult donor graft recipients at 1 and 4 years posttransplantation were 70.8 +/- 26.5 and 73.7 +/- 27.2 mL/min, respectively, compared to 50.3 +/- 20.1 and 56.3 +/- 21.4 mL/min for pediatric donor grafts (P < .01 at 1 and 4 years). CONCLUSION: The use of single pediatric donor kidneys provides an excellent opportunity to safely expand the donor pool.     

Anti-vimentin antibody detection in recipients of heart-beating and non-heart beating donor kidneys

Alternative donor sources include non-heart-beating donors (NHBDs). There donors have been exposed to significant ischemia, so that it is common to utilize machine perfusion to either improve the organs or at least assess their viability. Both prolonged warm ischemia and machine perfusion can potentially damage the vascular endothelium, thereby exposing vimentin to antigenic recognition. The aim of this study was to determine whether anti-vimentin antibodies could be detected in the blood of renal transplant recipients at specific time points after transplant and whether they could be related to the donor source. Fifty-one recipients of NHBD kidneys were compared to 52 recipients of heart-beating donor (HBD) kidneys. All recipients had similar anti-vimentin levels pretransplant. However, at 1 month those kidneys from Maastricht category II NHB donors showed significantly higher levels. At 6 months both Maastricht category II and category III NHB donor recipients displayed significantly higher levels than recipients of HBD kidneys.     

Transplantation of single and paired pediatric kidneys into adult recipients

Background:The transplantation of kidneys from cadaveric donors ≤ 5 years of age into adult recipients is controversial. The large disparity between donor renal mass and recipient body mass is feared to be problematic. Controversy also exists whether to transplant kidneys from these young donors individually or as a pair into a single recipient.Study Design:We retrospectively reviewed our experience from January 1991 to January 1995 with 22 adulrenal transplantations using kidneys from cadaveric donors ≤ 5 years of age. Ten patients received single allografts. Twelve received organs paired en bloc. Fiftytwo adult recipients from cadaveric donors aged 18–55 years served as controls. All patients received cyclosporine-based immunosuppression. Recipient characteristics did not differ significantly between the groups.Results:Actuarial patient and graft survival rates were similar for the two groups. The incidence of urinary complications was higher in the recipients of pediatric kidneys than in the adult-donor group (18.2% versus 3.8%, respectively, p = not significant). No grafts were lost from urinary complications. Renal function, as determined by the calculated creatinine clearance, was significantly greater in the pediatric group (76.1 ± 4.0 versus 61.4 ± 23.2 mL/min, p = 0.035) by 6 months after transplantation. Recipients of paired pediatric kidneys initially had better renal function (63.9 ± 21.4 mL/min) than those receiving single pediatric kidneys (38.2 ± 11.6 mL/min) (p = 0.004), but by 6 months, no significant difference existed. At 2 years, renal function in the pediatric-donor group remained significantly better than in the adult-donor group. Hematocrit levels as a measure of erythropoiesis were similar for single pediatric, paired pediatric, and adult-donor recipients.Conclusions:Kidneys from cadaveric donors ≤ 5 years of age are suitable for transplantation into adults. Pediatric kidneys provide excellent renal function despite an initially tremendous disparity between renal mass and recipient body mass. Rapid true renal growth probably occurs. No appreciable advantage is achieved by using two pediatric kidneys for a single recipient.     

Survival in recipients of marginal cadaveric donor kidneys compared with other recipients and wait-listed transplant candidates

An increasing number of cadaveric kidney transplants are now performed with organs from donors who would have been deemed unsuitable in earlier times. Although good allograft outcomes have been obtained with these marginal donor transplants, it is unclear whether recipients of marginal kidney transplants achieve a reduction in long-term mortality as do recipients of "ideal" kidneys. Patients with end-stage renal disease registered on the cadaveric renal transplant waiting list between January 1, 1992, and June 30, 1997, were studied for mortality risks according to three outcomes: wait-listed on dialysis treatment with no transplant (WLD); transplantation with marginal donor kidney (MDK); and "ideal" or optimal donor kidney transplantation (IDK). Thirty-four percent of wait-list registrants had received a cadaveric kidney transplant by June 30, 1998. Of these, 18% received a marginal kidney that had one or more of the following pretransplant factors: donor age >55 yr, non-heartbeating donor, cold ischemia time >36 h, and donor hypertension or diabetes mellitus of > 10 yr duration. Five-year graft and patient survival was 53% and 74% for MDK recipients compared with 67% (P< 0.001) and 80% (P< 0.001) for IDK recipients. Adjusted annual death rate and estimated remaining life time was 6.3%, 4.7%, and 3.3% and 15.3 yr, 20.4 yr, and 28.7 yr for WLD, MDK, and IDK groups, respectively. The average increase in life expectancy for MDK recipients compared with the WLD cohort was 5 yr, although this benefit varied from 3 to 10 yr depending on the recipient's characteristics. It is concluded that transplantation of a marginal kidney is associated with a significant survival benefit when compared with maintenance dialysis.     

Glomerular size and global glomerulosclerosis in normal Caucasian donor kidneys: effects of aging and gender

BACKGROUND: To assess the effects of aging and gender on glomerular size and global glomerulosclerosis (GS) and evaluate the relationship between glomerular size and GS in normal Caucasian donor kidneys. METHODS: All baseline graft biopsies between 1990 and 1998 were reviewed and sections with tissues containing at least 15 glomeruli were selected for morphometric analyses using a Digital Imaging Analyzer. Glomerular volumes (GV) were measured using the maximal profile area (MPA) method. The frequency of glomeruli with totally sclerotic lesions representing degree of global GS was expressed as a percentage of total number of glomeruli counted. RESULTS: 102 donor specimens (M/F, 46/56; mean age, 37.4 +/- 17.3 yrs) were analyzed showing mean MPA of 27.8 +/- 6.6 (x 10(-3)mm2), mean GV of 3.6 +/- 1.2 (x 10(6)microm3) and mean GS% of 6 +/- 10%. GV was increased with increasing age (r2 = 0.32, p < 0.0001). There was a progressive increase in glomerular size between infancy and adolescence (2-18 years old). The rate of MPA growth over childhood appeared to be linear (n = 13, r2 = 0.66, p = 0.0004). However, MPA increased with age at a slower rate (n = 99, r2 = 0.66, p = 0.0004) in adults (excluding data for patients < 18 years) than in infancy and adolescence. There wasn't significant gender difference in GV. Age (r = 0.47, p < 0.0001) and MPA (r = 0.31, p < 0.05) were both positively correlated with global GS. CONCLUSIONS: 1. Aging contributes to enlargement of glomerular size and global GS. 2. Gender had no significant effect on glomerular size. 3. Enlargement of glomerular size was associated with global GS in normal Caucasians.     

Expanded criteria donor kidneys for younger recipients: acceptable outcomes

Introduction

European senior programme (ESP) is well known for acceptable outcomes using expanded criteria donor (ECD) kidneys from donors older than 65 years for recipients older than 65 years. The incidence of end-stage renal disease (ESRD) is 229/million in India with a mean age of 45 years. We performed a retrospective analysis of transplantation of ECD versus standard criteria donor (SCD) kidneys into younger recipients.

Methods

Forty-three ECD transplantations among 158 deceased donor organ transplantation (DDOT) were performed between January 2006 and December 2009. Among 43 transplantation from 30 donors, 14 were dual kidney transplantations (DKT) performed based upon biopsy evaluation. All recipients received thymoglobulin (rATG) induction followed by immunosuppression with a steroid, mycophenolate mofetil (MMF), and a calcineurin inhibitor. Statistical analysis used chi-square test and unpaired Student t test. Kaplan-Meier curves were used for survival analysis.

Results

For ECD the mean donor age was 64 ± 11 years. Cerebrovascular accidents (CVA) were the cause of death among 60% of donors, 73.13% of whom were hypertensive and 23.13% diabetic.Mean DKT donor age was 75 ± 9.17 years versus 60 ± 8.0 years for single kidney transplantation (SKT). Mean recipient age of DKT versus SKT was 44 ± 12.4 years versus 43 ± 14 years. Mean serum creatinine (SCr; mg/dL) of SKT patients was 1.64 ± 0.75 versus 1.68 ± 0.46 in DKT. Mean follow-up was 455 ± 352 days. Mean SCr of 43 ECD recipients of mean age, 43.4 ± 14.2 years was 1.61 ± 0.61 mg/dL. Among 43 recipients, 23.25% were diabetic, 41.86% displayed delayed graft function (DGF), and 23.25% experienced biopsy-proven acute rejection (BPAR). Patient survival rate was 72.09% and graft survival rate was 67.44%. For SCD transplantations (n = 115), the mean donor age was 36 ± 14 years and recipient mean age was 32.8 ± 14.07 years. Mean SCr was 1.32 ± 0.46 mg/dL with 26.95% recipients displaying DGF, whereas 20.86% had BPAR. In the SCD group the patient survival rate was 79.13% and the graft survival rate was 72.17%. Thus, although the ECD group showed poor graft function (P = .042), they had acceptable patient and graft survivals (P = .34 and P = .56, respectively).

Conclusion

Because of the organ shortage, DDOT using ECD transplants for younger recipients is a feasible option with acceptable outcomes.     

Transplantation of kidneys from pediatric cadaver donors to adult recipients

Pediatric donors (less than 12 years old) are a potentially important source of kidneys for adult recipients. Previous reports of decreased graft survival and increased complication rates have made surgeons wary of using such kidneys. In 64 kidneys from younger donors transplanted to adult recipients the delayed graft function rate (41 versus 42%), and 2 and 3-year graft survival rates (67 versus 72% and 61 versus 65%, respectively) were similar to those seen with kidneys from adult donors. Kidneys from donors 24 months old or less experienced an 80% rate of graft loss at 1 year. When these kidneys are excluded the 1-year graft survival rate was similar to kidneys from older and younger donors (70 versus 77%). Mean serum creatinine at 1 year was similar in both groups (155 +/- 21 versus 151 +/- 10). Pediatric kidneys except those obtained from donors 2 years old or less are suitable for adult recipients. However, kidneys from very young donors may be more appropriate to pediatric recipients.     

WT-1 and NPHS2 mutation analysis in patients with non-familial steroid-resistant focal-segmental glomerulosclerosis

BACKGROUND: Familial forms of steroid-resistant nephrotic syndrome with the histologic findings of focal-segmental glomerulosclerosis have frequently a genetic basis. For the non-familial forms this is still unresolved. PATIENTS AND METHODS: Ten children with non-familial steroid-resistant nephrotic syndrome along with focal-segmental glomerulosclerosis were tested for mutations in the WT-1 and NPHS2 genes. RESULTS: In 1 patient, a mutation in intron 9 of the WT-1 gene and in 1 patient a heterozygous NPHS2 mutation could be detected. Both abnormalities are important for the treatment modalities and prognosis. CONCLUSION: Additional studies will have to provide a solid basis for the recommendation of mutation analysis in non-familial steroid-resistant focal-segmental glomerulosclerosis.