Expanded criteria donors, histological scoring, and prolonged cold ischemia: impact on renal graft survival.

The use of expanded donors or kidneys with preexistent chronic damage remains controversial, but they offer the opportunity to expand the donor pool. We investigated the impact of these conditions as predictors of graft survival among a cohort of recipients with prolonged cold ischemia times and a high incidence of delayed graft function. We included 70 consecutive cadaveric kidney allografts implanted between 2001 and 2005, which had undergone an early graft biopsy. Delayed graft function was present in 84% of cases with moderate or severe preexistent chronic damage in 63% and 27% of biopsies, respectively, and acute rejection was diagnosed in 14.3% of overall cases. The graft survival was 73.3% at 48 months. Primary nonfunctioning kidneys were more frequent using kidneys from expanded compared with standard donors (20.0% vs 0.0%, P < .002). Multivariate analysis showed that only the donor condition (standard vs expanded) was independently associated with graft survival (hazard ratio: 0.12; 95% confidence interval: 0.01-0.87; P < .03). Our results suggested that the donor characteristics prevail over other variables to predict graft outcomes.

Results of the conversion to everolimus in renal transplant recipients with posttransplantation malignancies.

Management of posttransplantation malignancies should include control of the neoplasia and preservation of renal function. Conversion to everolimus (EVL) would potentially have both effects. Twenty-one patients were converted to EVL due to posttransplantation neoplasms. We have presented herein descriptive data and postconversion (PC) outcomes among subjects of mean age 53.6 +/- 10.1 years (range, 36-69), 57.1% were males, undergoing conversion at 108.2 +/- 74.7 (range, 5-316) months after transplantation. All patients received standard immunosuppressive therapy and 9.5% had been induced with thymoglobulin. Malignant neoplasms were as follows: skin (n = 7), gynecological (n = 3), gastrointestinal (n = 3), PTLD (n = 2), renal (n = 2), CNS (n = 1), seminoma (n = 1), Kaposi's sarcoma (n = 1), and prostate cancer (n = 1). PC to EVL, calcineurin inhibitors (CNIs) were discontinued in 18 of 19 patients, mycophenolate in 9/12, and azathioprine in 5/7; all patients continued to receive steroids. In 16 patients (79%) tumors were removed. Chemotherapy was performed in 2 patients with PTLD and radiotherapy was performed in 1 patient with prostate cancer. Mean follow-up was 505 days (range, 59-1151); baseline glomerular filtration rate (GFR) was 53.5 +/- 21.6 mL/min versus 48.5 +/- 25.7 mL/min (P = not significant [NS]) at the last control. One patient experienced graft loss at day 744 after conversion due to chronic rejection. Adverse events were observed in 57% of patients and 28% displayed infections; no patient discontinued EVL. There were 2 deaths: 1 due to an infection and the other due to postsurgical complication. No deaths due to cancer progression were observed. The results observed in this series suggested that conversion to EVL for a posttransplantation neoplasm is a valid therapeutic alternative to preserve graft function and control disease progression.

Thrombophilic mutations: no association with thrombotic events in renal transplant recipients.

Factor V Leiden and mutation of prothrombin gene G20210A have been associated with poor results in the early post-kidney transplantation period. Its long-term importance in stable patients has yet to be evaluated. We studied the prevalence of these inherited mutations and their relationship to thrombotic events in 82 Argentine renal transplant recipients with adequate long-term kidney function. In aggregate, 7.2% of patients were carriers of these mutations; however, their presence did not show any association with thrombotic events or renal function alterations. The routine evaluation for these mutations does not seem to be cost-effective in renal transplant patients.

Conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium in stable maintenance renal transplant patients: pooled results from three international, multicenter studies.

BACKGROUND: Mycophenolate mofetil (MMF) is effective in renal transplant patients but concerns remain over its gastrointestinal (GI) tolerability. Enteric-coated mycophenolate sodium (EC-MPS; myfortic) has been developed with the intention of improving mycophenolic acid-related GI tolerability. METHODS: Data were pooled in a planned analysis of three subprotocols of the myfortic Prospective Multicenter Study (myPROMS). In a 6-month study, efficacy and safety of converting stable renal transplant recipients from MMF to a bioequivalent dose of EC-MPS for mycophenolic acid exposure were evaluated. Treatment efficacy was recorded and graft function was assessed by measuring serum creatinine and estimating creatinine clearance. Adverse events (AEs) and infections were monitored and the incidence of EC-MPS dose changes was recorded. RESULTS: A total of 588 patients were recruited, 564 (96%) of whom completed the study. The rate of treatment failure (defined as biopsy-proven acute rejection, graft loss, or death) was 1.9%, with no episodes of graft loss and only one death reported during the study. Renal function remained stable throughout the trial. EC-MPS was well tolerated; the majority of AEs were mild or moderate in severity. Dose reductions or interruptions were required by 6.3% and 1.9% of patients, respectively. Gastrointestinal AEs occurred in 138 patients (23.5%). The rate of dose adjustment as a result of a GI AE was 2.2%. CONCLUSIONS: Equimolar conversion from MMF to EC-MPS in maintenance renal transplant patients was safe and maintained efficacy.

Renal transplantation in diabetic patients.

OBJECTIVE: Diabetes is one of the main causes of end-stage renal disease (ESRD) and admission to hemodialysis, and the demand for kidney transplantation in this population has increased. Our aim was to evaluate the clinical aspects and survival of diabetic patients with kidney transplants by comparing them with the nondiabetic population. MATERIALS AND METHODS: Patients transplanted during the period from 1994 to 2003 were evaluated for this study. The transplant and demographic characteristics were analyzed by the chi-square test and Student t test according to the type of variable. Kaplan-Meier curves and the log-rank test were used to evaluate the graft and patient survival. RESULTS: From a total of 523 consecutive renal transplants, 35 (6.6%) were diabetics who were older than nondiabetics (47 +/- 11 years vs 37 +/- 16, P < .002). Patients received immunosuppression with cyclosporine (84.3%), tacrolimus (11.2%), azathioprine (46.6%), mycophenolate mofetil (43.5%), and steroids (all patients). The diabetic patients had a higher percentage of living donors (33.5% vs 17.2%; P = .04). Graft survival rates at 1, 3, and 5 years were 82.7%, 70.9%, and 63.0% in the diabetic patients and 87.6%, 79.0%, and 72.5% (P = .6) in the nondiabetic patients. Patient survival at 5 years was 90.5% in diabetic patients vs 89.0% in nondiabetic patients (P = .9). CONCLUSIONS: No differences were found in our series in transplant complications or survival in the diabetic patients compared with the nondiabetic patients. Kidney transplants, even with living donors, must be offered to well-selected diabetic patients without reservations.

Infección urinaria temprana en trasplante renal. Factores de riesgo y efecto en la sobrevida del injerto / Early urinary tract infection in kidney transplantation. Risk factors and impact on graft survival

The early urinary tract infection (EUTI) in kidney transplant recipients is an infection develop during the first 3 months post transplant surgery. The effect of EUTI on graft survival and risk factors have been scarcely studied. Our objetives were the evaluation of risk factors to EUTI, the assessment of the causal agent and graft survival impact. A retrospective analysis of kidney transplantation, period 1997-2000 in Hospital Privado-Centro Médico de Córdoba was carried out. There were two groups of patients with (EUTI group) and without EUTI (control group). Cox model was used to analyze risk factors and Kaplan-Meier method for graft survival. A total of 226 consecutive patients received kidney transplantation. In 55 patients (24.3%) EUTI was detected. Risk factors for EUTI were: invasive urological maneuvers (RR = 4.34, CI 95% 1.42-13.21), diabetes mellitus (RR = 3.79, CI 95% 1.42-10.14), cytomegalovirus infection (RR = 2.9, CI 95% 1.02-8.24) and previous transplants (RR = 2.83, CI 95% 1.08-7.45). Delayed graft function was associated with lower incidence of EUTI (RR = 0.38, CI 95% 0.15-0.94). The causal agents were: Klebsiella pneumoniae (36%), Pseudomonas aeruginosa (24%) and Escherichia coli (9%). Graft survival at 2 years was similar in EUTI (87.2%) and control group (81.2%, p = 0.32). This series shows that invasive urological maneuvers were the main risk factors for EUTI. Graft survival was similar. High prevalence of non coli bacteria need further evaluation.

La infección urinaria temprana del injerto (IUTI), definida como infección urinaria sintomática en los primeros 3 meses del trasplante, su efecto sobre la sobrevida del injerto y los factores de riesgo han sido poco estudiados. Los objetivos del presente análisis fueron conocer factores de riesgo para IUTI,analizar agentes causantes e impacto en la sobrevida del injerto. En forma retrospectiva se analizaron pacientesque recibieron trasplante renal durante 1997-2000 en el Hospital Privado – Centro Médico de Córdoba. Sedividió en dos grupos de pacientes, según presencia (grupo IUTI) o ausencia (grupo control) de IUTI. Los factores de riesgo se analizaron con el modelo de riesgos proporcionales de Cox y la sobrevida del injerto con elmétodo de Kaplan-Meier. Recibieron trasplante renal 226 pacientes consecutivos. La IUTI se presentó en 55(24.3%). Factores de riesgo asociados con IUTI: antecedentes de maniobras urológicas invasivas (RR=4.34,IC 95% 1.42-13.21), diabetes mellitus (RR=3.79, IC 95% 1.42-10.14), infección por citomegalovirus (RR=2.9,IC 95% 1.02-8.24) y antecedente de trasplante previo (RR=2.83, IC 95% 1.08-7.45). El retardo en la función delinjerto (RR=0.38, IC 95% 0.15-0.94) se asoció con menor incidencia de IUTI. Agentes más frecuentes: Klebsiellapneumoniae (36%), Pseudomonas aeruginosa (24%) y Escherichia coli (9%). La sobrevida del injerto a los 2años en el grupo IUTI (87.2%) no fue diferente del control (81.2%, P = 0.32). En esta serie las maniobras urológicas invasivas fueron el principal factor de riesgo asociado a IUTI. No hubo disminución de la sobrevida del injerto asociada a IUTI. La alta prevalencia de uropatógenos no coli requiere mayor evaluación

Infección urinaria temprana en trasplante renal. Factores de riesgo y efecto en la sobrevida del injerto / Early urinary tract infection in kidney transplantation. Risk factors and impact on graft survival

The early urinary tract infection (EUTI) in kidney transplant recipients is an infection develop during the first 3 months post transplant surgery. The effect of EUTI on graft survival and risk factors have been scarcely studied. Our objetives were the evaluation of risk factors to EUTI, the assessment of the causal agent and graft survival impact. A retrospective analysis of kidney transplantation, period 1997-2000 in Hospital Privado-Centro Médico de Córdoba was carried out. There were two groups of patients with (EUTI group) and without EUTI (control group). Cox model was used to analyze risk factors and Kaplan-Meier method for graft survival. A total of 226 consecutive patients received kidney transplantation. In 55 patients (24.3%) EUTI was detected. Risk factors for EUTI were: invasive urological maneuvers (RR = 4.34, CI 95% 1.42-13.21), diabetes mellitus (RR = 3.79, CI 95% 1.42-10.14), cytomegalovirus infection (RR = 2.9, CI 95% 1.02-8.24) and previous transplants (RR = 2.83, CI 95% 1.08-7.45). Delayed graft function was associated with lower incidence of EUTI (RR = 0.38, CI 95% 0.15-0.94). The causal agents were: Klebsiella pneumoniae (36%), Pseudomonas aeruginosa (24%) and Escherichia coli (9%). Graft survival at 2 years was similar in EUTI (87.2%) and control group (81.2%, p = 0.32). This series shows that invasive urological maneuvers were the main risk factors for EUTI. Graft survival was similar. High prevalence of non coli bacteria need further evaluation.(AU)

La infección urinaria temprana del injerto (IUTI), definida como infección urinaria sintomática en los primeros 3 meses del trasplante, su efecto sobre la sobrevida del injerto y los factores de riesgo han sido poco estudiados. Los objetivos del presente análisis fueron conocer factores de riesgo para IUTI,analizar agentes causantes e impacto en la sobrevida del injerto. En forma retrospectiva se analizaron pacientesque recibieron trasplante renal durante 1997-2000 en el Hospital Privado ¹ Centro Médico de Córdoba. Sedividió en dos grupos de pacientes, según presencia (grupo IUTI) o ausencia (grupo control) de IUTI. Los factores de riesgo se analizaron con el modelo de riesgos proporcionales de Cox y la sobrevida del injerto con elmétodo de Kaplan-Meier. Recibieron trasplante renal 226 pacientes consecutivos. La IUTI se presentó en 55(24.3%). Factores de riesgo asociados con IUTI: antecedentes de maniobras urológicas invasivas (RR=4.34,IC 95% 1.42-13.21), diabetes mellitus (RR=3.79, IC 95% 1.42-10.14), infección por citomegalovirus (RR=2.9,IC 95% 1.02-8.24) y antecedente de trasplante previo (RR=2.83, IC 95% 1.08-7.45). El retardo en la función delinjerto (RR=0.38, IC 95% 0.15-0.94) se asoció con menor incidencia de IUTI. Agentes más frecuentes: Klebsiellapneumoniae (36%), Pseudomonas aeruginosa (24%) y Escherichia coli (9%). La sobrevida del injerto a los 2años en el grupo IUTI (87.2%) no fue diferente del control (81.2%, P = 0.32). En esta serie las maniobras urológicas invasivas fueron el principal factor de riesgo asociado a IUTI. No hubo disminución de la sobrevida del injerto asociada a IUTI. La alta prevalencia de uropatógenos no coli requiere mayor evaluación(AU)

[Biochemical and histological spectrum of renal osteodystrophy in Argentina]. / Espectro bioquímico e histológico de la osteodistrofia renal en Argentina.

Between 1994-2001 we have performed 57 bone biopsies for diagnostic purposes in symptomatic CRF patients. We analyzed here 52 samples where the material was optimal for study, and divided them into 2 periods according to when the biopsy was performed: 1994-1996 and 1997-2001, to verify changes in the spectrum of renal osteodystrophy. Mean serum values were: serum calcium 9.9 +/- 1.8 mg/dl, phosphate 5.8 +/- 3.2 mg/dl, alkaline phosphatase 693.9 +/- 968.9 Ul/L, iPTH 562.0 +/- 598.5 pg/ml, serum aluminum 65.7 +/- 79.3 ug/L and bone aluminum 22.8 +/- 22.4 ug/g. Hyperparathyroidism was the most common histological diagnosis as severe in 13 patients (25%), or as mild in 14 (27%). Ten patients had osteomalacia (19%), adynamic bone disease was diagnosed in 5 (9.6%) and mixed renal osteodystrophy in 10 (19.2%). Low bone turnover patients showed higher bone and serum aluminum than high bone turnover patients. We observed a relative increment in high turnover bone disease in the later period (1997-2001) without changes in low turnover bone disease. These data showed a high prevalence of hyperparathyroidism and aluminum-related low turnover bone disease, with no significant changes between the two time-periods analyzed here.

[Viral agents related to diarrheic syndrome in kidney transplanted patients]. / Agentes virales asociados al sindrome diarreico en pacientes trasplantados renales.

The aim of this study was to report on the occurrence of conventional and emerging viral agents as well as their etiological link with diarrhea in kidney transplanted subjects from Cordoba, Argentina. A total of 42 stool samples were analysed. They were obtained from both ambulatory and hospitalized kidney transplanted patients with and without diarrhea after transplant. All patients were under immunosuppressive treatment with steroids, azatioprine and cyclosporine or tacrolimus. Results revealed the presence of group A rotavirus and picobimavirus in three patients suffering from severe diarrhea (33.33%). No enteric bacterial agent was isolated from these patients. The presence of viral agents was related to high levels of cyclosporine in blood (> 290 ng/ml) or prolonged immunosuppressive treatment. On the other hand, no virus was detected in any of the samples collected from asymptomatic individuals (p < 0.05). These findings suggest that viruses are implicated in the etiology of diarrheal disease in these patients.

Agentes virales asociados al sindrome diarreico en pacientes trasplantados renales. / [Viral agents related to diarrheic syndrome in kidney transplanted patients]

The aim of this study was to report on the occurrence of conventional and emerging viral agents as well as their etiological link with diarrhea in kidney transplanted subjects from Cordoba, Argentina. A total of 42 stool samples were analysed. They were obtained from both ambulatory and hospitalized kidney transplanted patients with and without diarrhea after transplant. All patients were under immunosuppressive treatment with steroids, azatioprine and cyclosporine or tacrolimus. Results revealed the presence of group A rotavirus and picobimavirus in three patients suffering from severe diarrhea (33.33

). No enteric bacterial agent was isolated from these patients. The presence of viral agents was related to high levels of cyclosporine in blood (> 290 ng/ml) or prolonged immunosuppressive treatment. On the other hand, no virus was detected in any of the samples collected from asymptomatic individuals (p < 0.05). These findings suggest that viruses are implicated in the etiology of diarrheal disease in these patients.

Influence of aluminium overload on the course of post-transplant parathyroid function.

Aluminium intoxication exerts profound effects on secondary hyperparathyroidism in chronic renal failure and could influence the evolution of post-transplant parathyroid function. We have evaluated 44 patients after successful renal transplantation, sequentially from day 0 up to day 90 from the beginning of graft function, determining serum and urinary aluminium, PTH (intact molecule) and several other parameters of mineral metabolism. Patients were grouped according to their basal serum aluminium: Group LA (n = 25) had serum aluminium less than 40 micrograms/l (mean 21 +/- 10 micrograms/l), and Group HA (n = 19) had serum aluminium greater than 40 micrograms/l (mean 100 +/- 43 micrograms/l). This latter group also had greater urinary aluminium excretion during the study period. Evolution of renal function was similar in both groups. Group LA had increased pre-transplant iPTH (353 +/- 416 pg/ml vs 175 +/- 94, P = 0.05). Seven days after regaining renal function both groups showed a marked decrease in iPTH and then a continued decline up to day 90 with mean serum values of the hormone showing no further differences between groups. The incidence of hypercalcaemia was similar in both groups but no patients in Group HA developed hypercalcaemia at post-transplant day 7 while 12% in Group LA did so. Urinary phosphate excretion and the incidence of post-transplant hypophosphataemia were similar in both groups. These findings suggest: (a) patients with more aluminium intoxication have lower values of pre-transplant iPTH and they correct parathyroid function in a different way than non-intoxicated patients in early post-transplant days; (b) they have lower and later incidence of hypercalcaemia.

[Actuarial survival analysis of patients in dialysis]. / Analísis de supervivencia actuarial de pacientes en dialísis.

The survival rate of our end stage renal disease (ESRD) population was calculated by means of actuarial survival curves. A total of 167 patients undergoing hemodialysis or CAPD during the 1977-1991 period were studied. They had been treated and closely followed for at least three months. Mean age for starting dialysis was 40.6 +/- 17 years; 107 (64%) were males and 60 (36%) females. Glomerulonephritis (25%), diabetes (14%) and nephroangiosclerosis (12%) were the primary causes of ESRD. Survival rates were analysed by actuarial curves as designed by Kaplan and Meier. Statistical significance between curves was calculated with the Log Rank test. The level of significance considered was below 0.05. Multivariate analysis of survival was performed using the Cox proportional hazards regression model. Survival rates were in all cases expressed for the 1 degree, 5 degree and 10 degree year. They were for the whole group of 89%, 63%, and 38% respectively. When analysed according to their age: those under 30 years; between 30 and 50 and over 50 years old (at time to start dialysis); survival rates were of 97%, 86%, and 81% for the first group; 89%, 66% and 29% for the second group, and 85%, 44%, and 10% for the third group. Significant differences were found between the first and second group (p < 0.025); the first and the third group (p < 0.001) and second and third group (p < 0.001) (Fig. 4).(ABSTRACT TRUNCATED AT 250 WORDS)

Analísis de supervivencia actuarial de pacientes en dialísis. / [Actuarial survival analysis of patients in dialysis]

The survival rate of our end stage renal disease (ESRD) population was calculated by means of actuarial survival curves. A total of 167 patients undergoing hemodialysis or CAPD during the 1977-1991 period were studied. They had been treated and closely followed for at least three months. Mean age for starting dialysis was 40.6 +/- 17 years; 107 (64

) were males and 60 (36

) females. Glomerulonephritis (25

), diabetes (14

) and nephroangiosclerosis (12

) were the primary causes of ESRD. Survival rates were analysed by actuarial curves as designed by Kaplan and Meier. Statistical significance between curves was calculated with the Log Rank test. The level of significance considered was below 0.05. Multivariate analysis of survival was performed using the Cox proportional hazards regression model. Survival rates were in all cases expressed for the 1 degree, 5 degree and 10 degree year. They were for the whole group of 89

, 63

, and 38

respectively. When analysed according to their age: those under 30 years; between 30 and 50 and over 50 years old (at time to start dialysis); survival rates were of 97

, 86

, and 81

for the first group; 89

, 66

and 29

for the second group, and 85

, 44

, and 10

for the third group. Significant differences were found between the first and second group (p < 0.025); the first and the third group (p < 0.001) and second and third group (p < 0.001) (Fig. 4).(ABSTRACT TRUNCATED AT 250 WORDS)

Familial hyperuricemia and renal disease.

Information on a familial syndrome of hyperuricemia and renal disease with or without gout was obtained on 33 of 41 blood relatives: Nine had renal disease; abnormalities of the urinary sediments were minimal; serum uric acid levels were elevated in seven and were not measured in two. Hyperuricemia was noted in three additional family members without evidence of renal disease. Goulty arthritis (three patients) did not precede renal disease. One individual had hyperuricosuria. The following erythrocyte purine enzyme levels were normal: adenine phosphoribosyltransferase, hypoxanthine-guanine phosphoribosyltransferase, phosphoribosylpyrophosphate, synthetase, adenosine deaminiase, and purine nucleoside phosphorylase. Renal biopsy specimens showed focal global and segmental sclerosis of glomeruli, occasional hypercellularity, foci of atrophic tubules, chronic interstitial inflammation, and folding and wrinkling of glomerular basement membrane without electron-dense deposits. There were no immunofluorescent abnormalities.

Familial azotemia. Impaired urea excretion despite normal renal function.

We performed detailed studies of renal function in two of five related patients with normal serum creatinine levels to determine the mechanism of their chronic azotemia. Inulin and para-amino-hippurate clearances, maximum tubular transport of para-aminohippurate, and renal acidification were within normal limits. In addition, renal concentrating and diluting abilities of these patients were similar to those of four normal controls. Urea clearances of both patients during maximum water diuresis (27.6 and 40.8 ml per minute per 1.73 m2) and antidiuresis (5.3 and 4.0), however, were much lower than mean (+/- S.E.M.) values in the normal controls (70.4 +/- 3.7 and 30.0 +/- 3.42 ml per minute per 1.73 m2, respectively). Thus decreased urea excretion despite otherwise normal renal function was responsible for the chronic azotemia of these patients. The genetic defect in renal urea clearance appeared to be inherited as an autosomal dominant trait.

Clinical significance of 99mtechnetium sulfur colloid accumulation in renal transplant patients.

The accumulation of 99mtechnetium sulfur colloid (99mTcSC) was evaluated in 47 studies performed on 19 renal transplant patients by comparing its transplant activity to its bone marrow accumulation. There was a diagnosis of rejection of 21 of 22 studies (96.5%) in which marked transplant accumulation was noted. In 11 studies of patients with a clinical diagnosis of post-transplant acute tubular necrosis (ATN), the transplant activity varied from none to moderate. Rejection developed in 5 of 6 studies with minimal to moderate accumulation. Normally functioning renal transplant patients, or those with ATN and no superimposed rejection, do not show evidence of 99mTcSC accumulation.