More Than 25 Years Together: Basis for a Long-Lifespan Kidney Transplant.

Patients with graft survival for 20 years or more are not uncommon; they are called ultralong kidney recipients. It is interesting to know if there are patterns in donors and recipients that could be reproduced. A retrospective cohort with 22 adult patients with a kidney renal transplant performed more than 25 years ago is analyzed. The mean of age of the donors was 24 years (median, 21 years); 82% were men and the cause of death was mainly acute traumatic brain injury. Recipients had a mean age of 34 years (median, 36 years) at the time of transplant; the most common underlying renal disease was glomerular, without evidence of recurrence. A total of 16 patients had compatibility in HLA II (1 in 11 cases; 2 in 5 cases). Only 6 patients have had any episode of acute rejection; 3 of them have developed antibodies class I, but no donor-specific antibodies. In this retrospective cohort, increases in donor age are associated with poor renal function. The mean creatinine is 1.43 mg/dL (range, 0.97-2.14 mg/dL) and mean proteinuria is 653.43 mg/g (range, 55-3722 mg/g). The characteristics common in ultralong kidney recipients are young male donors, a shortage of episodes of rejection, and good HLA compatibility, especially in class II antigens.

Study of the renal function in nonrenal organ transplantation.

Kidney disease after transplantation of a nonrenal organ has been described to be the result of the nephrotoxicity from the commonly used calcineurin-inhibitors as well as other factors. The aim of this study was to evaluate renal function and potential risk factors for the development of chronic renal failure among nonrenal organ recipients. We designed a single-center retrospective study including all 165 of our cardiac and liver recipients between February 1998 and October 2003, collecting clinical, analytic, and therapeutic data. We excluded double transplants and patients with survival less than 6 months. Creatinine clearance was calculated according to the Cockcroft-Gault and the Levey Modification of Diet in Renal Disease (MDRD)-5 equations. Although 165 patients received a cardiac or liver transplantation, 17 died in the first 6 months and three were double transplants; therefore we analyzed 145 patients: 107 (74%) cardiac transplantations and 38 (26%) liver transplantations. There were 106 male and 39 female recipients. The mean age (+/-SD) at the time of transplantation was 54 +/- 10 years and the mean follow-up was 2.9 +/- 1.7 years. Urinalysis before transplantation was only performed in 33 patients (22.8%) including three (2.1%) who had proteinuria. Serum creatinine increased until 12 months after transplantation (P < .001), then it recovered its average level. Creatinine clearance calculated using the aforementioned equations showed a similar pattern, with a progressive decline to 12 months (P < .05), with eventual stabilization or even improvement. The factors that we observed to increase the risk of renal damage were age, female sex, obesity, and the presence of proteinuria prior to transplantation. There was a good correlation (r = 0.96) between cyclosporine but not tacrolimus trough levels and serum creatinine at 48 hours after transplantation.

Management of secondary hyperparathyroidism: the gap between diagnosis and treatment. The Renal Osteodystrophy Multicenter Enquiry.

In mild secondary hyperparathyroidism, small daily doses of oral calcitriol represent the physiological form of replacement of this hormone, but in moderate or severe cases, higher doses of calcitriol are needed to suppress parathyroid gland overactivity. Unfortunately, in chronic renal failure, these 2 different forms of calcitriol prescription are not always adequately selected. This review will focus on the current use of calcitriol in renal failure. It includes data from a recent multicenter trial carried out in Spain in which data was gathered from dialysis patients. This trial was designed to determine the current approach to the prevention, diagnosis, and treatment of renal osteodystrophy, with a special emphasis on the gap found between diagnosis and treatment of secondary hyperparathyroidism. Our main goal should be to achieve an adequate and early management of secondary hyperparathyroidism to decrease the number of patients suffering from irreversible enlargement of the parathyroid glands.

[Association of hypercalcemia, elevated levels of calcitriol and tuberculosis in patients on hemodialysis]. / Asociación de hipercalcemia, niveles elevados de calcitriol y tuberculosis en hemodiálisis.

Hypercalcemia is associated with numerous chronic granulomatous processes and chronic infections. Increased production of calcitriol by activated macrophages has been shown to be the cause in most cases. In this article, we describe three cases of hypercalcemia associated with inappropriately elevated calcitriol levels and suppressed PTH in hemodialysis. In addition to conventional techniques for tuberculosis diagnosis we used Ligase Chain Reaction (LCR) to detect mycobacterial DNA in pleural effusion with acid-fast stain and culture negativity. Antituberculous therapy was associated with a decrease in the levels of calcium, as well as in serum calcitriol concentrations, and a substantial increase in the levels of iPTH. The serum levels of 25(OH)D3 remained unchanged. These findings suggested ectopic production of calcitriol. The discussion reviews the previously reported cases of hypercalcemia and tuberculosis that occurred during hemodialysis, and concludes that ectopic production of calcitriol by tuberculous granulomas is extremely unusual and its demonstration requires a high index of suspicion. Molecular techniques are a potentially useful approach for early and rapid diagnosis of tuberculous infection in dialysis patients.

[Hemolytic anemia caused by graft-versus-host reaction in ABO-nonidentical renal transplants from blood group O donors]. / Anemia hemolítica por reacción injerto contra huésped en trasplantados renales ABO no idénticos con donantes del grupo sanguíneo O.

Acute hemolytic anemia is one of the side effects associated with cyclosporin and tacrolimus therapy, and three mechanisms have been described to account for hemolytic anemia in patients receiving these drugs: drug induced hemolysis, autoimmune hemolysis and alloimmune hemolysis resulting from donor lymphocytes derived from the allograft (passenger lymphocyte syndrome). We report four cases of renal transplant recipients who developed alloimmune hemolytic anemia due to minor ABO incompatibility while under treatment with cyclosporin (two) and tacrolimus (two). The anti-erythrocyte antibodies responsible for hemolysis were of the IgG isotype and showed anti-A or anti-B specificity. These findings suggest that the hemolysis could be related to alloantibodies derived from the clonal development of donor B lymphocytes in the recipients (microchimerism). In summary, hemolytic anemia due to ABO-minor incompatibility occurs infrequently after renal transplantation. Risks are higher for patients A, B or AB blood group receiving an O blood group graft under treatment with cyclosporin or tacrolimus. Follow-up of these patients is warranted for the early detection and optimal management may be achieved by reduction of immunosuppression and change to mycophenolate mofetil.

[Renal osteodystrophy in Spain. Multicenter survey. (I). Collaborative Centers of the Multicenter Study on Renal Osteodystrophy]. / Osteodistrofia renal en España. Encuesta multicéntrica. (I). Centros colaboradores del Estudio Multicéntrico sobre Osteodistrofia Renal.

In order to know the current management of renal osteodystrophy in Spain we collected data from 172 centres (10,724 patients) obtained from a 30 questions enquiry designed to show different aspects of the current management of renal osteodystrophy. The levels considered the "goal" for treatment were: Calcium 10-10.5 mg/dL (53% of centres), 9.5-10 mg/dL (28%), 10.5-11 mg/dL (14%) and 9-9.5 mg/dL (5% of centres). Phosphorus: between 4.5 and 5.5 mg/dL (77% of centres), between 5.5 and 6.5 mg/dL (15%) and less than 4.5 mg/dL (8% of centres). Parathormone (PTH): between 120 and 250 pg/mL (75% of centres), between 60 and 120 pg/mL (19% of centres). The calcium concentration used in the dialysis fluids was 2.5 in 44% of centres, 3 in 28%, 3.5 in 26% and 2 mEq/L in the remaining 2% of centres. Pulse therapy was started with PTH higher than 750 in 16% of centres; with PTH higher than 500 pg/mL in 52% and with PTH higher than 250 pg/mL in 28% of the centres. Only 51% of centres decreased the calcium concentration in dialysis fluids when the patients were receiving parenteral calcitriol. Fifty-nine percent of centres considered a positive response to treatment any reduction in PTH levels, 24% of centres considered response a decrease of at least 20%, 78% of centres maintained the treatment with calcitriol 6 months before deciding if the patient was a "responder" or a "non-responder". Parathyroidectomy was performed when PTH was higher than 1,000 pg/mL in 38% of the centres; in 41% when PTH was between 1,000 and 750; in 19% when PTH was between 750 and 500; and when PTH was between 500 and 250 pg/mL in the remaining 2% of the centres. Five percent of the patients had a parathyroidectomy.

[Bone metabolic markers and use of vitamin D in dialysis. Multicenter survey. (II). Collaborative Centers of the Multicenter Study on Renal Osteodystrophy]. / Marcadores metabólicos óseos y uso de vitamina D en diálisis. Encuesta multicéntrica. (II). Centros colaboradores del Estudio Multicéntrico sobre Osteodistrofia Renal.

Renal osteodystrophy has become one of the most important aspects related with morbidity in dialysis patients. The aim of our study was to analyse the main biochemical markers of mineral metabolism in 7,422 dialysis patients from 147 Spanish centres. We present data about serum Ca, P, Ca-P, product, Al and vitamin D. Due to the distribution of the analytical results (not normal), non-parametric tests were used. In this analysis a p < 0.01 was considered as significant. The mean total levels were: Ca 9.7 +/- 0.9 mg/dL; P 5.6 +/- 1.6 mg/dL; Ca-P product 54 +/- 16 mg/dL; PTH 294 +/- 360 pg/mL and Al 27 +/- 23 micrograms/L. There was a great variation particularly on serum Ca and PTH levels. On the contrary, serum P and Ca-P product values were less spread: only a quarter of the patients had P levels higher then 6.5 mg/dL and one third Ca-P product higher than 60. Fifty percent of patients had Al levels lower than 20 micrograms/L. Forty one percent of patients (2,811 out of the 7,422) had a PTH equal or lower than 120 pg/mL and 23% have PTH equal or lower than 60 pg/mL. Patients with PTH equal or lower than 60 have serum Ca levels significantly higher than the remaining patients, on the contrary, serum P, Ca-P product and Al levels were significantly lower. In this group, 21% of patients were receiving vitamin D (in spite of low PTH). On the contrary 32% of patients were not receiving calcitriol (despite PTH higher than 250 pg/mL). Forty four percent of patients were receiving vitamin D (46% on haemodialysis and 31% on peritoneal dialysis). Patients on haemodialysis showed serum Ca, P, PTH and Al levels higher than patients on peritoneal dialysis.

[Importance of estrogen insufficiency time in the efficacy of the bone response to hormonal therapy in experimental chronic renal insufficiency]. / Importancia del tiempo de insuficiencia estrogénica en la eficacia de la respuesta ósea a la terapia hormonal en la insuficiencia renal crónica experimental.

Bone disease develops relatively early in the development of CRF. The aim of this study was to evaluate the repercussion of estrogen insufficiency and the effectiveness of hormonal replacement therapy, after different periods of estrogen deprivation, on bone metabolism in an animal model with chronic renal failure and ovariectomy. A secondary purpose was to evaluate the effectiveness of bone densitometry for predicting changes in bone mass for comparison with bone histomorphometry. We used Sprague-Dawley rats with chronic renal failure and ovariectomy performed at the same time. Animals were divided into two phases according to the period of estrogen insufficiency, 4 weeks in the long estrogen insufficiency period and 1 week in the short estrogen insufficiency period. In both phases, the animals were divided into four treatment groups receiving placebo (corn oil), 17 beta-estradiol (15 micrograms/kg body weight/day), calcitriol (10 ng/kg body weight/day) or the combined treatment with estradiol and calcitriol. In both phases, a group of animals with chronic renal failure (normal ovarian function) was used as a control group. The period of treatment was 8 weeks. After this period the animals were sacrificed. This model emphasizes the importance of the period of estrogen insufficiency in the efficiency of the treatment. Four weeks of estrogen insufficiency resulted in an significant loss of trabecular bone, and less possibility of recovery. After one week of estrogen deprivation a response to the treatment was observed. The utilization of bone densitometry allowed to reproduce changes in bone mass observed afterwards by histomorphometric analysis.

[Effect of vertebral fracture on health related quality of life in a Spanish population older than 54 years]. / Efecto de la fractura vertebral sobre la calidad de vida relacionada con la salud en población asturiana mayor de 54 años.

BACKGROUND: Effect of vertebral fracture on the perceived health using the SF-36 Health Questionnaire in a representative population older than 54 years. SUBJECTS AND METHOD: Randomly cohort from the register of the city Hall of Oviedo. All the 299 subjects (147 men and 152 women) completed the traduced and validated Spanish SF-36 questionnaire four years after radiologic studies were performed to evaluate prevalent vertebral fractures. RESULTS: Vertebral fracture decreased the health related quality of life, particularly in physical function dimension in males and in mental health dimension in women. This effect was increased when osteopenia was present. CONCLUSIONS: This first study performed in both sexes shows worse perceived health in people with fractures.

Hypercalcemia, inappropriate calcitriol levels, and tuberculosis on hemodialysis.

We describe a female patient undergoing hemodialysis who developed tuberculosis, hypercalcemia, and inappropriately elevated calcitriol levels. These findings suggest ectopic production of calcitriol by tuberculous granulomas. Successful treatment of tuberculosis led to a substantial decrease in the levels of calcium and calcitriol.

Ultrafiltrable aluminium after very low doses of desferrioxamine.

BACKGROUND: The recommended dose of desferrioxamine for the treatment of aluminium intoxication is 5 mg/kg/week. However, there are no data about the efficiency of lower doses. The objective of this study was to investigate the capacity of very low doses of desferrioxamine in the generation of ultrafiltrable aluminium. METHODS: Five patients undergoing haemodialysis with a similar biochemical profile and serum aluminium levels >40 microg/l were studied. The three different doses of desferrioxamine used (0.5, 2.5 and 5.0 mg/kg) were administered randomly to each patient at 1 week intervals. Total and ultrafiltrable serum aluminium was measured before and 44 h after the administration of desferrioxamine. RESULTS: All doses of desferrioxamine significantly increased the total serum aluminium; no differences were found between 2.5 and 5.0 mg/kg. The total serum aluminium levels doubled with the 2.5 and 5.0 mg/kg doses, while the increase with 0.5 mg/kg was lower (32.6%, P<0.05). Ultrafiltrable aluminium increased with the three doses; from 7.1+/-2.8, 3.9+/-0.6 and 7.5+/-4.1 to 25.7+/-7.3, 44.3+/-10.1 and 59.1+/-19.8 microg/l, respectively (P<0.05). The efficiency of each dose was calculated using the ratio between the increase in ultrafiltrable aluminium and the dose of desferrioxamine administered. The efficiency ranged from 10.3+/-3.9 for the higher dose (5 mg/kg) to 37.2+/-10.3 for the lower dose (0.5 mg/kg). CONCLUSIONS: Our results suggest that very low-dose desferrioxamine (>5 mg/kg) increases the ultrafiltrable (potentially dialysable) aluminium.

Prevention, diagnosis and treatment of renal osteodystrophy in Spain. Preliminary results from a multicentre enquiry.

Prevention, diagnosis and treatment of renal osteodystrophy are continually evolving. We submitted a postal questionnaire to all Spanish dialysis centres, comprising 30 questions, with the aim of obtaining information about the current management of this entity in Spain. The answers from 171 centres, 63% of the total registered (10,724 patients), were analysed. The centres performed an annual average of nine calcium and phosphorus determinations, three for parathyroid hormone (PTH), 1.5 for aluminium and one for bone radiology. For these parameters, nephrologists consider ideal levels to be 10-10.5 mg/dl for calcium (53% of centres), 4.5-5.5 mg/dl for phosphorus (77%) and 120-150 pg/ml for iPTH (75%). The calcium concentration used in the dialysis fluids was found to be variable: 2% of the centres used 2 mEq/l, 44% used 2.5 mEq/l, 28% used 3 mEq/l and 26% used 3.5 mEq/l. When using oral calcitriol, 82% of the centres do not change the calcium concentration in the dialysis fluids; this percentage falls to 51% when calcitriol administration is parenteral. In 78% of centres, vitamin D treatment was started when PTH was high, without taking into consideration the plasma calcium level. The dose varies; in 28% of the centres calcitriol pulse therapy was started when iPTH was >250 pg/ml; 52% when >500 pg/ml and 16% when >750 pg/ml. Seventy one percent of the centres claim to use calcitriol in doses proportional to the severity of hyperparathyroidism. With regard to response to treatment, 78% of the centres wait for 6 months before considering a patient as a 'non-responder' and 80% of the centres would carry out parathyroidectomy only when iPTH is >750 pg/ml. The data collected from the enquiry show that there are important variations in some aspects related to current patient management in the different units in Spain. Diagnostic criteria are relatively homogeneous whereas the therapeutic guidelines are less uniform.

Prevention of aluminium exposure through dialysis fluids. Analysis of changes in the last 8 years.

Despite extensive measures to control aluminium exposure, chronic and acute episodes of aluminium intoxication still occur. The objective of this study was to analyse the changes in the aluminium content of dialysis fluid and the effect on serum aluminium in different dialysis centres in Spain in the last 8 years. For this purpose, the aluminium content in dialysis fluid and serum samples (N=5609) from 17 dialysis centres was analysed for >8 years (from the last quarter of 1988 to 1996). In that period of time, the percentage of dialysis fluid samples with acceptable concentrations of aluminium (<2 microg/l) increased from 0% in 1988 to 80% in 1996. The percentage of dialysis fluid samples with high aluminium levels (>6 microg/l) ranged between 37.5% in 1988 and 2.3% in 1996. The improvement in the quality of the dialysis fluid resulted in lower values of serum aluminium. The percentage of serum samples with low aluminium (<20 microg/l) increased from 16.5% in 1988 to 54.2% in 1966. The mean serum aluminium correlated with the mean dialysis fluid aluminium (r=0.55, P<0.001). A higher correlation was found when the aluminium in dialysis fluid ranged between 4 and 10 microg/l (r=0.802, P<0.001), and no correlation was found when the aluminium in dialysis fluid was <4 microg/l. Even taking into account that the dialysis fluid is not the only source of aluminium for dialysis patients, our study clearly demonstrated a close relationship with the serum aluminium content. Therefore, we must emphasize the necessity for controlling the aluminium content in dialysis fluid more often than is done at present.

Effect of aluminium load on parathyroid hormone synthesis.

BACKGROUND: Aluminium overload leads to parathyroid hormone (PTH) suppression. However, it is unclear whether a decrease in synthesis or release of the hormone is mainly involved. The aim of this study was to assess the effect of an acute administration of aluminium on PTH synthesis and release in rats with chronic renal failure and secondary hyperparathyroidism. METHODS: The study was performed using 100 adult male Wistar rats (body weight 443+/-54 g). 7/8 nephrectomy was performed and the rats were maintained on a high dietary phosphorous intake. Five weeks after surgery, the rats were randomly divided into two groups, one loaded with aluminium (AlCl3) and the other given placebo. Aluminium or placebo were administered i.p. for two consecutive days. The placebo group received saline at the same pH as the aluminium solution. After 2 weeks, serum calcium, phosphorous, creatinine, PTH, and aluminium were measured. The parathyroid glands were removed and PTH messenger RNA (mRNA) was measured by northern blot. Intact PTH was measured by IRMA (Rat PTH, Nichols Institute). RESULTS: No differences in serum PTH levels were found between the two groups after 5 weeks of renal failure. At the end of the study the rats given aluminium had higher aluminium levels than the placebo group and lower PTH levels. No significant differences were found for calcium, phosphorous, renal function, or body weight. PTH mRNA expression was lower in the aluminium group than in the placebo group. CONCLUSION: The administration of aluminium in rats with chronic renal failure resulted in reductions in serum PTH and PTH mRNA. Thus far, previous studies had demonstrated that aluminium suppressed PTH release. The present findings suggest that PTH synthesis is also reduced.

Cytomegalovirus preemptive therapy with ganciclovir in renal transplant patients treated with OKT3.

In an attempt to decrease the prevalence and severity of cytomegalovirus (CMV) disease, preemptive therapy with ganciclovir was administered to all renal transplant patients treated with OKT3 between February 1993 and December 1994 (26 patients). The results were compared with those of a historical group treated with OKT3 but not with ganciclovir (29 patients). Both groups were similar in age, sex, number of previous transplants, number of rejections, serological status of donor and recipient and OKT3 dose. Ganciclovir was administered during the period of treatment with OKT3. Only 2 (7.7%) treated patients developed CMV disease versus 11 (37.9%) of the control group (p = 0.01). In the control group the intensity of the disease was severe in 7 (63.6%) cases, whereas in the treated patients it was always of slight intensity (p = 0.01). In conclusion, preemptive therapy with ganciclovir during treatment with OKT3 decreases the prevalence and severity of CMV disease.

Health related quality of life (HRQOL) of kidney transplanted patients: variables that influence it.

UNLABELLED: The incidence and prevalence of patients on renal replacement therapy (RRT) who receive a renal transplant are continuously increasing in Spain. At the moment, they are the main group of end-stage renal disease (ESRD) patients in our region (60% of total RRT patients). The aim of the present study was to assess the health related quality of life (HRQOL) of kidney transplanted patients of our region, and to identify socio-demographic and clinical variables that influence it. The intention was also to compare the HRQOL of these patients with that of chronic haemodialysis (HD) patients and of the general population. METHODS: Two hundred and ten kidney transplanted patients and 170 HD patients were evaluated using the Karnofsky performance scale (KPS), sickness impact profile (SIP), and SF-36 Health Survey (SF-36). Socio-demographic and clinical data, including a comorbidity index (CI), were also collected. To compare our patients with the general population we used SF-36 mean scores from an aleatory sample taken from our region. RESULTS: Transplant patients had lower mean scores on SIP dimensions and higher scores on SF-36 dimensions than chronic HD patients. In transplant patients, we found significant differences on SIP and SF-36 scores in gender, educational level, haematocrite and haemoglobin, CI, time since transplantation, and KPS. CONCLUSIONS: The HRQOL of transplant patients is clearly better than that of chronic HD patients and similar to that of the general population. Differences in the HRQOL within transplant patients did not appear to be as a result of patient's age, but rather it would appear to be a consequence of gender, analytic figures, CI, KPS score, time with transplant, and educational level.