Interpreting Post-Transplant Proteinuria in Patients with Proteinuria Pre-Transplant

Increasing numbers of patients receive kidney transplants before initiation of dialysis or shortly thereafter. Some of these patients have significant proteinuria pre-transplant making the interpretation of post-transplant proteinuria problematic. In this study, we evaluated post-transplant proteinuria in 115 patients who had urine protein measured within 3 months of transplant and assessed the association of proteinuria with allograft pathology. Proteinuria declined rapidly from 3650 +/- 3702 mg/day pre-transplant to 550 + 918 at 3 weeks (p < 0.0001) and continued to decline until 1 year post-transplant (472 +/- 1116, p < 0.0001 vs. 3 weeks). Proteinuria greater than 3000 mg/day was present in 48 patients (42%) pre-transplant, in 1 patient (1%) at 3 weeks and in 4 patients (4%) at 1 year. Surveillance graft biopsies were done at 1 year in 93% of patients. Proteinuria > or = 1500 mg/day and/or an absolute increase in proteinuria > 500 mg/day after 3 weeks post-transplant was associated with allograft glomerular pathology. In conclusion, pre-transplant proteinuria, even when high grade, declines rapidly after transplantation. Failure to decline or persistence of proteinuria greater than 1500 mg/day is indicative of allograft pathology.     

Risk analysis for deterioration of renal function after pancreas alone transplant

The risk of progression to renal replacement after pancreas transplant alone (PTA) is a concern in patients with pre-transplant estimated glomerular filtration rate (eGFR) < 70 mL/min/1.73 m(2). This is a retrospective, single-center risk analysis of potential factors affecting renal function after PTA. Twenty-four patients, transplanted over a three-yr period, with functioning pancreatic grafts at the study's end point were included. High tacrolimus levels (> 12 mg/dL) at six months post-transplant was the only independent risk factor identifying a substantial decline in native renal function by Cox regression analysis (HR = 14.300, CI = 1.271-160.907, p = 0.031). The presence of severe pre-transplant proteinuria (urine Pr/Cr ≥ 100 mg/mmol) marginally failed to reach significance (p = 0.056). Low eGFR levels alone (≤ 45 and ≤ 40 mL/min/1.73 m(2)) at the time of transplant did not correlate with substantial decline in renal function. Our data suggest that PTA is a justifiable therapy for patients with hypoglycemia unawareness or other life-threatening diabetic complications, even in those with borderline renal function, provided that they do not suffer from severe proteinuria and appropriate monitoring and tailoring of immunosuppression is ensured.     

Renal Transplantation in Patients With Pre-Transplant Donor-Specific Antibodies and Negative Flow Cytometry Crossmatches

The clinical significance of pre-transplant donor-specific antibodies (DSA), despite negative cytotoxicity and flow cytometry crossmatches (FCXMs), is unknown. We performed a retrospective cohort study of 60 living donor renal transplant recipients, all with pre-transplant cytotoxicity and T-cell and B-cell FCXMs that were negative. Twenty recipients had pre-transplant DSA detected by enzyme-linked immunosorbent assays (ELISA) and/or microbead methods. Forty contemporaneous DSA-negative controls were selected. In the DSA-positive group, after a median follow-up of 8.2 months (25-75% range, 5.4-22.8 months), patient survival was 100% and allograft survival was 95.0%. Acute humoral rejection (AHR) developed in four patients (20.0%). Three of the AHR episodes occurred within the first month post-transplant. Median serum creatinine at last follow-up was 1.3 mg/dL (25-75% range, 1.0-1.6 mg/dL), versus 1.1 mg/dL (25-75% range, 0.9-1.4 mg/dL) in the DSA-negative controls (p = 0.29). Only one of the 40 controls developed AHR (2.5%). Pre-transplant DSA was associated with a significantly increased incidence of AHR (p = 0.02 by log-rank test). In conclusion, despite negative pre-transplant cytotoxicity and FCXMs, renal transplant recipients with pre-transplant DSA detected by solid-phase methods may have an increased incidence of AHR and require close monitoring post-transplant.     

Persistent post-transplant polyuria managed by bilateral native-kidney laparoscopic nephrectomy

Polyuria is not considered an absolute indication for pre-transplant nephrectomy; however, it may complicate post-transplantation fluid management. Bilateral native-kidney laparoscopic nephrectomy was performed at our centre in two patients (four kidneys) 1 month after they had received a living related-donor renal transplant. The indication for nephrectomy was severe post-transplant polyuria secondary to the patient’s underlying disease: juvenile nephronophthisis. Both patients had a persistent post-transplant daily urine output of 7–8 l/day and continued to have a variable serum creatinine level, dependent on intravenous hydration, more then 3 weeks after transplantation. Bilateral laparoscopic native-kidney nephrectomy in children has previously been reported. However, to the best of our knowledge, laparoscopic nephrectomy has not been described after kidney transplantation and certainly not in the immediate post-transplantation period. The procedure was well tolerated and did not affect renal graft function. In fact, following the procedure, serum creatinine levels stabilized, while daily fluid requirements decreased to 2.5–3.5 l/day in both patients. We concluded that bilateral native-kidney nephrectomy can be safely performed in paediatric renal transplant recipients in the immediate post-transplantation period. This new approach may allow preemptive transplantation and avoid the need for a transition period on dialysis in patients for whom pre-transplant nephrectomy is not absolutely indicated.     

Effect of donor age and parent-to-child transplant on living-related donor kidney transplantation: a single center's experience of 236 cases

Abstract

To study the impact of parent-to-child transplant and older donor age on recipients' post-transplant creatinine levels, a total of 236 patients who received living donor kidney transplantation were evaluated for kidney viability based on creatinine (Cr) level. Of the 236 pairings, 113 (48%) were parent-to-child followed by sibling transplants (66, 30%). Recipient Cr levels were significantly higher at 6 months and 3 years post-transplant in the parent-to-child transplants compared to other donor–recipient relationships. In addition, donor age (average age: 44.1?±?11.5; range: 19–66) contributed to higher recipient post-transplant Cr levels (p?<?0.01). Pre-transplant donor and recipient Cr levels tended to result in higher post-transplant Cr levels in recipients (p?<?0.05). Multivariate logistic regression analysis revealed that the presence of both parent-to-child transplant and older donor significantly increased the risk of elevated post-transplant Cr levels in recipients with an estimated odds ratios ranging from 3.46 (95% CI: 1.71–6.98) at 6 months to 8.04 (3.14–20.56) at 3 years post-transplant. Donor age significantly affected transplant survival as measured by higher recipient post-transplant Cr levels. In addition, parent-to-child transplant pairings, along with older donor age, significantly increased the risk of elevated post-transplant Cr levels in recipients.     

End stage polycystic kidney disease: indications and timing of native nephrectomy relative to kidney transplantation

PURPOSE: We evaluated the indications for and outcome of pre-transplant, concomitant and post-transplant native nephrectomy in patients with end stage polycystic kidney disease (PCKD). MATERIALS AND METHODS: The records of 32 patients were retrospectively reviewed using the electronic database at our institution. RESULTS: Between January 1992 and December 2002, 171 patients with end stage PCKD received a kidney transplant at University of California-San Francisco. A total of 32 patients (18.7%) underwent pre-transplant (7, group 1), concomitant (16, group 2) or post-transplant (9, group 3) native nephrectomy. Of these patients 25 underwent bilateral nephrectomy. Median followup was 18 months. Indications for nephrectomy were hematuria, a renal mass and chronic pain in group 1, lack of space in group 2 and urinary tract infection in group 3. Mean operative time +/- SEM was 231 +/- 14, 370 +/- 24 and 208 +/- 14 minutes in groups 1 to 3, respectively (p = 0.001). Mean intraoperative blood loss was 533 +/- 105, 573 +/- 155 and 522 +/- 181 ml in groups 1 to 3, respectively (p not significant). Two group 2 patients required blood transfusions. Postoperative complications requiring surgical intervention included wound dehiscence in group 1 and abdominal bleeding in group 3. Mean hospital stay was comparable among groups 1 to 3 at 7 +/- 0.7, 8.6 +/- 1.2 and 6.3 +/- 0.6 days, respectively (p not significant). At 3 months mean serum creatinine was not significantly different between groups 2 and 3 at 1.3 +/- 0.1 and 1.5 +/- 0.2 mg/dl, respectively. CONCLUSIONS: Unilateral or bilateral nephrectomy for PCKD at transplantation is safe in terms of postoperative patient morbidity and graft function. We perform concomitant native nephrectomy when indicated, preferably in recipients of living donor kidney transplants.     

The beneficial effects of calcium channel blockers on long-term kidney transplant survival are independent of blood-pressure reduction

There is a growing body of evidence suggesting that calcium channel blockers (CCB) exert beneficial effects on kidney transplant survival. However, it is not completely understood if these agents act independently of blood-pressure reduction. In the present study, the 5-yr follow-up of 45 kidney transplant recipients receiving CCB during the 60-month follow-up period was compared to that of recipients with lower blood pressure and an antihypertensive treatment without CCB. During the whole follow-up, systolic (127.4 +/- 2.5 vs. 139.4 +/- 2.1 mmHg, p < 0.05) as well as diastolic blood pressure (78.8 +/- 1.1 vs. 84.8 +/- 1.8 mmHg, p < 0.05) was higher in the group receiving CCB. Moreover, in CCB-treated recipients, a significant (p < 0.05) higher increase in proteinuria was detected (from 759 +/- 120 to 1690 +/- 359 mg/24 h vs. 180 +/- 45 to 340 +/- 45 mg/24 h). Despite higher blood pressure and higher proteinuria, the increase in serum creatinine in the group of CCB-treated recipients was significantly lower (0.01 mg/dL/month) in comparison to that of the controls (0.02 mg/dL/month, p < 0.05). Moreover, the 5-yr transplant survival was significantly higher in CCB-treated recipients (62.3 vs. 31.8%, p < 0.05). The results of the present study further support the beneficial effects of CCB in kidney transplant recipients, which are independent of blood-pressure reduction.     

Post-transplant renal function in the first year predicts long-term kidney transplant survival

BACKGROUND: Improvements in long-term kidney graft survival have been recently noted. However, the reasons for this were unclear. This study examined post-transplant renal function within the first year as an independent variable influencing long-term survival. METHODS: The influence of demographic characteristics (age, sex, race); transplant variables (cadaver versus living donor, cold ischemia time, HLA mismatching, delayed graft function and transplant year), and post-transplant variables (immunosuppressive agents for the prevention of acute rejection, clinical acute rejection and post-transplant renal function in the first year) on graft survival were analyzed for 105,742 adult renal transplants between 1988 and 1998. Renal function in the first year was expressed as serum creatinine at six months and one year and delta creatinine (change in serum creatinine between 6 months and 1 year). Graft half-life was used to measure long-term survival. RESULTS: During this 11-year period, the one-year serum creatinine values for cadaver recipients steadily improved, from 1.82 +/- 0.82 mg/dL in 1988 to 1.67 +/- 0.82 mg/dL in 1998 (P < 0.001), as did the graft half-life. There was a progressive decline in graft half-life for each incremental increase of six month, one year and Delta creatinine for living and cadaver donor transplants as well for cadaver transplants with donor age > and < or =50 years. The Relative Hazard (RH) for graft failure was 1.63 (1.61, 1.65; P < 0.0001) with each increment of 1.0 mg/dL of serum creatinine at one year post-transplant and it increased to 2.26 (2.2, 2.31; P < 0.0001) when the Delta creatinine was 0.5 mg/dL. The RH reduction for graft failure was substantially lower for the years 1993, 1996, 1997 and 1998 when post-transplant renal function was not included in the model (P < 0.05). However, the RH reduction per year was not different when post-transplant creatinine was included in the model, 1.01 (0.94 to 1.05; P = 0.89). CONCLUSION: In conclusion, one-year creatinine and Delta creatinine values predict long-term renal graft survival. Recent improvements in graft half-life are related to conservation of renal function within the first year post-transplantation.     

Is morning urinary protein/creatinine ratio a reliable estimator of 24-hour proteinuria in patients with glomerulonephritis and different levels of renal function?

BACKGROUND: This cross-sectional study was conducted to determine whether a spot urine protein/creatinine ratio (UPr/UCr) provides accurate quantitation of 24-hr urinary protein excretion (24-hr Prot) in out-patients with primary glomerulonephritis (GN) and different renal function levels. METHODS: Patients were classified into three groups according to creatinine (Cr) clearance (ml/min) and into five categories according to morning UPr/UCr. Correlation between 24-hr Prot and UPr/UCr was calculated according to the three renal function levels. The Bland and Altman method was used to assess agreement between 24-hr Prot and UPr/UCr. Agreement limits were obtained calculating the mean difference between 24-hr Prot and morning UPr/UCr +/- 2SD. Sensitivity and specificity were determined for different renal function levels and UPr/UCr cut-off values. RESULTS: High correlation coefficients (r=0.91, 0.95 and 0.98) were observed in patients with normal, reduced and severely reduced renal function. Differences and variability between 24-hr Prot and UPr/UCr tended to increase with higher proteinuria levels, and this trend was observed for the three renal function levels. The best UPr/UCrcut-off values to detect abnormal or nephrotic proteinuria were, respectively, 0.3 and 2.6. CONCLUSIONS: Correlation and agreement between UPr/UCr and 24-hr Prot was good for all renal function levels, but demonstrated more marked differences as urinary protein excretion increased. Morning UPr/UCr had good sensitivity and specificity for the diagnosis of 24-hr Prot, even in patients with reduced renal function.     

Polyomavirus BK nephropathy: the effect of an early diagnosis on renal function or graft loss

Polyomavirus BK nephropathy is a new complication among renal transplant patients. We studied 664 cadaver renal transplant recipients from February 1998 to February 2005, divided into two periods: 448 (group A, February 1998 to July 2003) and 176 (group B, August 2003 to February 2005). Twenty patients (3%) developed biopsy-confirmed polyomavirus BK nephropathy; 13 (2.9%) in group A after worsening renal function and 7 (3.9%) in group B after a prospective cytologic study in urine, examining for decoy cells, and a qualitative polymerase chain reaction (PCR) assay in urine and blood. The mean time to diagnosis was higher among group A (15.0 +/- 1.6 versus 7.2 +/- 4.0 months), as was the serum creatinine (2.5 +/- 0.7 versus 2.0 +/- 0.6 mg/dL). After 12 months the serum creatinine was 2.7 +/- 1.3 versus 1.7 +/- 0.2 mg/dL, respectively. Poor prognostic factors were a persistently positive PCR in blood and viral inclusions in the control biopsy.     

Outcomes After Transplantation of Deceased-Donor Kidneys with Rising Serum Creatinine

The increasing number of candidates for kidney transplantation and relatively unchanged deceased-donor pool has led to expansion in the criteria for donor acceptability. Outcomes of kidneys from donors with progressively rising creatinine values have not been reported. Patients transplanted between September 2003 and August 2006 with kidneys from donors with peak creatinine levels >2.0 mg/dL were stratified into two groups based on the terminal creatinine and evaluated for outcome: (1) falling creatinine (FC)(n= 27), terminal creatinine at least 0.2mg/dL less than peak, and (2) rising creatinine (RC)(n=24), terminal creatinine = peak. The mean terminal creatinine was significantly higher in the RC group (3.2 +/- 1.3 mg/dL) compared to the FC group (1.9 +/- 0.9 mg/dL)(p<0.0001). Peak creatinine values were similar (RC, 3.2 +/- 1.3; FC, 3.1 +/- 1.3; p=0.6521) between the two groups. Rates of delayed graft function (RC, 24%; FC 32%; p=0.7881) and mean creatinine at follow-up (RC, 1.6 +/- 0.6, FC 1.6 +/- 0.4; p=0.3533) were not significantly different. With a mean follow-up of 287 +/- 274 days, allograft survival was 92% in the RC recipients and 89% in the FC recipients. Under certain conditions, kidneys from donors with rising serum creatinine can be used safely with reasonable early outcomes.     

Long-term evaluation of neuromyopathy in live donor FMF amyloidotic kidney transplant recipients

BACKGROUND: Neuromyopathy was reported to be a problem among live donor familial Mediterranean fever (FMF) amyloid kidney transplant recipients. We aimed to address this issue on a long-term basis. METHODS: 14 FMF amyloid live donor kidney transplant recipients with a mean post-transplant follow-up period of 82.43 +/- 50.1 months in comparison to a control group of 19 non-amyloid renal transplant patients were subjected to thorough neurological examination, laboratory and electrophysiologic studies. RESULTS: Both groups were comparable with regard to mean serum creatinine levels cyclosporine doses (p > 0.05), however trough cyclosporine levels were significantly lower in the amyloidotics than the controls (p = 0.04). Serum creatine phosphokinase was comparable in both groups (p = 0.59). The amyloid patients showed significantly increased polyphasic motor unit potentials and abnormal interference patterns in the biceps brachii muscle (p = 0.03) and the abductor polices brevis muscle (p = 0.05). Multivariate analysis showed a significant level for biceps myopathy in amyloidotics (p = 0.001). Both groups attained no difference with regard to median nerve conduction velocity. CONCLUSION: Electrophysiologically evidenced neuromyopathy is more liable to occur in long-term live donor FMF amyloidotic kidney transplant recipients than in the other non-amyloidotic kidney transplant recipients even with no clinical manifestations or high creatine phosphokinase levels.     

Spousal renal donor transplantation in Chinese subjects: a 10 year experience from a single centre.

BACKGROUND: The shortage of cadaveric kidneys for renal transplantation is a particularly problematic situation in the locality of Hong Kong. Kidneys from spousal donors are therefore increasingly being used for transplantation. This study was undertaken to evaluate the outcome of spousal donor transplant recipients in comparison with that of genetically related living donor (LRD) allograft recipients. METHODS: From 1988, we have transplanted 22 spousal kidney recipients (group 1). All donors must demonstrate a genuine spousal relationship. Their outcome was compared with that of 24 LRD allograft recipients (group 2) transplanted in the same period with similar demographics, pre-transplant dialysis duration, immunosuppressive protocol and length of post-transplant follow-up. RESULTS: The mean (+/-SD) age was 36.5 +/- 8 and 32.5 +/- 6 years for groups 1 and 2, who were followed for 56.6 +/- 35 and 59.1 +/- 38 months, respectively. There was no difference in the incidence of delayed graft function, acute rejection and serum creatinine level at 5 years. Graft survival rates were 86.4 and 79.2% (P = 0.56), while patient survival rates were 100 and 91.7% (P = 0.171) at 5 years for groups 1 and 2, respectively. CONCLUSIONS: Spousal kidney transplantation shares comparable results with LRD transplantation and should be encouraged in places where cadaveric organs remain scarce. Stringent measures must be implemented to prevent the possible emergence of kidney bartering and to protect the interests of living donors. The ethical and social issues regarding the spousal donor in Hong Kong and other countries are discussed.     

Non-immunologic intervention in chronic allograft nephropathy

BACKGROUND: Chronic allograft nephropathy is the main cause of late graft loss. It has been suggested that both alloantigen-dependent and alloantigen-independent factors influence the development of progressive transplant failure. The present study analyzed the importance of non-immunologic factors in the progression of kidney disease in transplant patients, with the emphasis on well-established risk factors for progression in native kidneys. METHODS: A retrospective analysis was performed on 485 renal transplant patients who had functioning kidneys for at least 1 year. We investigated whether the initial presence and subsequent maintenance of proteinuria, hypertension, anemia, hyperlipidemia, and hyperparathyroidism influenced the progression of transplant failure. To analyze the relative effects of these factors, patients were categorized into two groups: group A had a baseline serum creatinine concentration of less than 1.5 mg/dL, and group B had a baseline serum creatinine concentration of 1.5 to 3 mg/dL. RESULTS: High urine protein excretion was a significant independent risk factor for progression of renal failure (group A: relative risk, 3.73; 95% confidence interval [CI], 2.24-6.21; group B: relative risk, 4.01; 95% CI, 2.51-6.39). Hypertension was also a significant independent risk factor for progression, but the risk was lower than for proteinuria (group A: relative risk, 1.2; 95% CI, 1.04-1.75; group B: relative risk, 1.20; 95% CI, 1.02-2.1). Anemia, hyperlipidemia, and hyperparathyroidism had no influence on the progression of renal failure. CONCLUSION: Our results show strong independent relationships between high blood pressure, urine protein excretion, and the relative risk of chronic progression of renal failure, as described for native kidney disease. These factors are potentially modifiable and are therefore attractive targets for therapeutic targets.     

Chronic allograft nephropathy and nephrotic range proteinuria

While the association between post-transplant nephrotic range proteinuria (PTx-NP) and chronic allograft nephropathy (CAN) has been described, the factors that determine graft survival in such patients are unclear. We retrospectively identified 30 patients with biopsy-proven CAN who presented with PTX-NP between 1988 and 2002. Patients were stratified into two groups according to PTX-NP onset: <1 yr vs. >1 yr post-transplantation. Both groups were comparable with respect to the degree of renal dysfunction (serum creatinine 4.3 +/- 2.5 mg/dL vs. 3.4 +/- 1.5 mg/dL) and proteinuria (4.7 +/- 1.6 gm/d vs. 5.8 +/- 3 gm/d). After a mean follow-up of 14 months post-biopsy, 87% of patients had lost their grafts in both groups (89% vs. 83%, p = NS). Overall, patients with serum creatinine 2 mg/dL (75% vs. 4%, Fisher Exact Probability p = 0.0038). Using Kaplan-Meier estimate, the 5-yr graft survival rate was 100% for patients with serum creatinine 2 mg/dL (p = 0.06). The magnitude of proteinuria beyond 3 gm/d did not influence graft survival. One-half of the patients (n = 15) received therapy with angiotensin converting enzyme inhibitors (ACEI). Graft survival, however, was not different between the patients who received ACEI compared with the patients who did not receive ACEI (13% vs. 13%). PTx-NP related to CAN was associated with poor allograft survival, irrespective of the time of onset of presentation, especially when renal function was reduced at the time of biopsy.     

Glomerulonephritis is the major cause of proteinuria in renal transplant recipients: histopathologic findings of renal allografts with proteinuria

The proteinuria in renal allograft recipients has been regarded as a sign of poor prognosis. The causes of post-transplant proteinuria include chronic rejection, chronic transplant glomerulopathy, glomerulonephritis (GN), acute rejection, and cyclosporine nephrotoxicity. Among them, chronic rejection is known to be most frequent. We analyzed the histopathologic findings of renal allograft biopsies in 197 Korean recipients with proteinuria. Among them, 26 patients developed proteinuria over 500 mg/d. All patients received baseline immunosuppression with cyclosporine. From 26 patients with post-transplant proteinuria, 29 biopsies were performed and their histologic diagnoses were immunoglobulin A nephropathy (IgAN) in 17, IgAN combined with chronic allograft nephropathy in 1, focal segmental glomerulosclerosis in 2, crescentic GN in 1, membranous GN in 1, diabetic nephropathy in 1, acute tubulointerstitial nephritis in 1, and chronic rejection in 3 biopsies. The remaining two biopsies showed nonspecific findings. The most common cause of post-transplant proteinuria was IgAN (62% of biopsies). The incidence of chronic rejection was relatively low and predominant cyclosporine-associated changes were not observed. In conclusion, our data suggest that the main causes of post-transplant proteinuria in Korea are primary glomerulonephritides rather than chronic rejection or cyclosporine nephrotoxicity, and the kidney allograft biopsies from patients with proteinuria should be handled as native kidney.     

Early assessment of renal resistance index after kidney transplant can help predict long-term renal function.

BACKGROUND: Color Doppler ultrasonography of intrarenal arterial resistance index (RI), performed early after kidney transplant, has proven to reliably predict short-term allograft function. The aim of this study was to assess whether it could also predict long-term renal function. METHODS: We retrospectively analysed 76 kidney transplant patients who underwent RI assessment within 1 month after the transplant, subdivided into two groups according to RI values, lower (group A) or higher (group B) than its median value (0.635). RESULTS: Compared with group A subjects, the patients of group B were older at the time of transplant (42 +/- 9 vs 35 +/- 8 years; P = 0.001), the donor age was also older (41 +/- 16 vs 33 +/- 13 years; P = 0.02) and had a slightly higher proteinuria (0.54 +/- 0.5 vs 0.32 +/- 0.2 g/24 h; P = 0.02). Serum creatinine, ciclosporin or tacrolimus trough level, arterial blood pressure, number of human leukocyte antigen (HLA) mismatches, anti-hypertensive medications and incidence of delayed graft function were not significantly different between the two groups. By univariate analysis, RI turned out to directly correlate with the recipient age, donor age and daily proteinuria (P = 0.007, P = 0.0007 and P = 0.02, respectively). Multivariate analysis showed that only donor and recipient age maintained their independent predictive value on RI. Kaplan-Meier analysis, considering a serum creatinine increase >50% as the endpoint of the study, showed a statistically significant different graft survival in the two groups (log-rank test = 5.489; P = 0.01). The univariate relative risk of deterioration of graft function among patients with higher RI was 3.77. Proteinuria and recipient age increased the risk as well. CONCLUSIONS: Our data seem to suggest that early determination of RI can help predict long-term graft function in kidney transplant recipients.     

The development of proteinuria and focal-segmental glomerulosclerosis in recipients of pediatric donor kidneys

Several reports in animals, and sporadic case reports in humans, have suggested that kidneys with decreased nephron mass may be more susceptible to the development of focal-segmental glomerosclerosis. This prompted a reexamination of our previously reported group of pediatric donor-adult recipient renal transplant combinations. Data were analyzed from 31 adult recipients who had received renal transplants from cadaver pediatric donors (less than 6 years) with graft function for greater than 6 months and no evidence of chronic rejection. These were compared with a control group transplanted during the same period with adult donor kidneys. Immunosuppression consisted of azathioprine/prednisone or quadruple therapy in 16 and 15 patients respectively. End-stage renal disease (ESRD) was secondary to chronic glomerulonephritis (n = 9), diabetes mellitus (n = 6), polycystic kidney disease (n = 5), and miscellaneous causes (n = 11). Twenty patients had radiographic documentation of renal hypertrophy posttransplant. All patients had serial 24-hr urinalysis for protein and creatinine after transplantation during periods of stable renal function. Ten patients had renal biopsies performed at a mean time from transplant to biopsy of 10.4 +/- 1.6 months. Seven recipients had biopsies that revealed glomerulosclerosis at 13 +/- 6 months posttransplant. Protein excretion and serum creatinine in these patients were significantly higher than in control patients (1.6 +/- 0.37 vs. 0.49 +/- 0.15 g/24 hr and 1.96 +/- 0.11 vs. 1.64 +/- 0.09 mg%; P less than 0.03 and P less than 0.01, respectively). Only 3 of 25 control adult donor recipients developed proteinuria greater than 0.8 g/24 hr within 2 years of transplantation vs. 15/31 pediatric donor recipients. No correlations with the etiology of ESRD, age (greater than or less than 40 years), weight, sex, diabetes, hypertension, or the number of acute rejection episodes could be found. Our data suggest that adult recipients of pediatric donor renal transplants may be at greater risk for the development of glomerulosclerosis than those recipients receiving adult donor kidneys.     

Bilateral native ureteral ligation without nephrectomy in the management of kidney transplant recipients with native proteinuria

The aim of this study was to assess the safety of bilateral native ureteral ligation (BNUL) without nephrectomy in the management of native proteinuria in kidney transplant (KTx) recipients. We retrospectively studied 17 patients who underwent BNUL between 2002 and 2010 with a median preoperative 24 h protein concentration of 2140 (range 1020-25 000) mg/L. Fifteen of the 17 patients had focal segmental glomerulosclerosis as their primary renal disease and ligation was employed to facilitate the diagnosis of early recurrence. The BNUL was performed simultaneously with KTx in 14 patients. Surgical techniques were: open (n = 5), pure laparoscopic (n = 1) and a hybrid of hand-assisted laparoscopic surgical/open approach (n = 12) used at the time of transplantation via the transplant incision. At a median follow-up of 46 months (range 1-59), no patient had a complication related to BNUL and none required interventions associated with their native kidneys. BNUL without nephrectomy seems to be a safe technique to manage native proteinuria in renal transplant candidates.     

The Relationship Between Donor Age and Cadaveric Renal Allograft Survival Is Modified by the Recipient''s Blood Pressure

Increasing donor age correlates with reduced renal allograft survival. In this study we analyzed variables that may modify this relationship. The study included 1285 cadaveric kidney allograft recipients followed for 7.2 + 4.5 years. By Cox, increasing donor age beyond 30 years was associated with significant increases in the hazard ratio for graft loss [age 31-46, hazard ratio (HR) = 1.4, p = 0.02; 46-60, HR = 1.55, p = 0.008; > 60, HR = 1.68, p = 0.03]. Increasing donor age was significantly associated with: older and heavier recipients; higher creatinine and blood pressure (BP) 6 months post-transplant; and lower total cyclosporine dose during the first year. Of interest, the 6-month serum creatinine and the BP level modified significantly the relationship between age and survival. Thus, increasing donor age was significantly related to reduced graft survival only in patients with a 6-month creatinine < 2 mg/dL. Furthermore, donor age related significantly to graft survival only among patients with higher BP levels 6 month post transplant. It is concluded that increasing donor age is associated with reduced cadaveric graft survival, but that relationship is significantly modified by graft function and BP. These data suggest that poorly functioning kidneys have reduced survival irrespective of age. Furthermore, elevated BP levels may have a particularly negative effect on the survival of older grafts.