Increased fracture rate in diabetes mellitus and females after renal transplantation.

BACKGROUND: Bone disease and fractures after organ transplantation pose severe clinical problems. About 20% of renal transplant patients have type 1 diabetes (IDDM). However, data are scarce in the literature about the occurrence of spontaneous fractures in IDDM patients posttransplantation. METHODS: In this cross-sectional study using a questionnaire and hospital records the prevalence of symptomatic bone disease was investigated in 193 renal transplanted patients with functioning renal grafts 6 months to 23 years after the transplantation. RESULTS: The frequency of IDDM was 18%. In the total group the rate of osteoporotic fractures posttransplantation was 17%, and the majority of fractures occurred within the first 3 years after the transplantation. A high rate of fractures, 40%, was noted in the diabetes group (P<0.001), compared with 11% in the nondiabetes group. Fractures seen in IDDM were often multiple and located mostly in the appendicular skeleton, i.e., in ankles and feet. Female gender was also associated with an elevated fracture rate, 23% (P<0.05). CONCLUSION: An increased incidence of osteoporotic fractures after renal transplantation was found in diabetic and female patients. The mechanism behind bone fragility in IDDM is multifactorial and despite a restored renal function bone disease may progress, and is probably enhanced by the immunosuppressive treatment.

Accelerated atherosclerosis in the transplant recipient: role of hypertension.

An accelerated atherosclerosis may occur in the native arteries of a transplant recipient as well as in arteries of transplanted kidneys or hearts. The dominating cause of patient mortality are cardiovascular diseases, where ischaemic heart disease is predominant. The accelerated form of arteriosclerosis which takes place in transplanted kidneys and hearts, has a complex pathogenesis, which includes both immunological and nonimmunological factors. Hypertension is one such factor which has been claimed to be an independent risk factor of chronic renal transplant dysfunction, usually characterised by transplant arteriosclerosis. Whether a more intense treatment of hypertension or a more selective use of antihypertensive drugs would have a beneficial effect upon the progression rate of chronic rejection is still an open question.

Plasmapheresis in HLA-immunosensitized patients prior to kidney transplantation.

Immunosensitization against the human lymphocyte antigen (HLA) is a problem in most transplant centers. It prolongs the waiting list time in addition to risk of frequent acute rejections. To avoid these problems, various pretransplantation approaches have been attempted e.g. plasmapheresis (PP). The present retrospective study reports our experience with PP in this respect over a 5 year period. Twenty-three chronic hemodialysis patients with circulating panel reactive antibodies (> or = 50%) and previous kidney graft rejections were treated with 12 PP each. In addition to this, immunosuppression with cyclophosphamide and prednisolone were administered on the first day of PP and after tapering continued until transplantation. HLA-antibodies, as measured by the panel reactive antibodies and the antibody titer, decreased from about 70% to 30% (p < 0.001) and 5 steps of titerdilution, respectively with PP and immunosuppressive drugs; Twenty-two patients were transplanted with cadaveric grafts. Eight grafts were lost due to irreversible rejection, and one due to the patient's death 2 months after transplantation. The cumulative five-year graft survival at the time of follow-up was 59%. Adequate kidney function (serum creatinine mean 150 mumol/l) was observed in all grafts (n = 3) still functioning 60 months posttransplant. We conclude that pretransplantation plasmapheresis together with immunosuppressive drugs (cyclophosphamide and prednisolone) is useful in the removal of HLA antibodies in immunized patients awaiting kidney transplantation. It can be considered a valuable approach to increase the chances of successful transplantations.

Renal transplantation in Uppsala.

The history and progress of organ transplantation in Uppsala are reviewed. Renal transplantation was begun in 1969, and the programme now comprises 50 to 60 transplants per year. Since 1976 the operation is performed at the department of urology. Close collaboration has been established with other departments in the hospital, especially with the medical nephrology unit. The indications for active management of uraemic patients have broadened, and maintaining resources on a par with the demands has constantly been a problem. This report concerns immunosuppressive therapy, transplantation results and research connected with the transplantation programme and deals briefly with the prospects for Uppsala as a transplantation centre in the future.

Fine-needle biopsies of renal transplants in clinical rejection monitoring.

Fine-needle aspiration biopsy( FNAB) of renal allograft transplants has been used at Uppsala University Hospital for 3 years. Experience from 51 consecutive patients (from 1 1/2 years) with 333 FNAB was reviewed. Representative material was obtained in more than 70% of the biopsies. Eleven rejection episodes in 12 patients were confirmed with this method. One was not recognized. Significant inflammation in the kidney without clinical rejection was found in 22 patients. The possible causes of such inflammation are discussed. Repeatedly recorded inflammation in the kidney with minor or no effect on graft function may sometimes be caused by viral infection. The clinical value of FNAB in various immunosuppressive regimens is discussed.

Tubular proteinuria in renal calcium stone formers.

The incidence of tubular proteinuria measured as urinary excretion of beta 2-microglobulin was evaluated in 68 consecutive renal calcium stone formers, 14 of whom had impaired urinary acidification capacity. During normal conditions 13% of these stone formers had tubular proteinuria. There was no statistical difference in the incidence of tubular proteinuria between subgroups with proximal or distal acidification defects. During transient metabolic acidosis induced by an ammonium chloride load a pronounced increase in beta 2-microglobulin excretion was noticed in all patient groups but especially in those with urinary acidification defects. In stone formers with normal acidification capacity the degree of acidosis-induced beta 2-microglobulinuria was moderate but a small group of patients exhibited a large urine excretion of beta 2-microglobulin. This finding may reflect a latent tubular defect of importance for stone genesis.

Influence of the age of cadaveric kidney donors on transplantation outcome and rate of surgical complications.

Cadaveric kidney graft recipients, treated according to a strict, high dose CyA protocol, were followed prospectively for one year. The aim was to study the impact of donor age on transplantation outcome in a homogenously immunosuppressed patient material. The patients were divided into 2 groups; G1: donor age less than or equal to 50 years (mean 34.5 y; range 10-50; n = 49) and G2; donor age greater than 50 years (mean 58.1 y; range 51-68; n = 37). The groups were comparable in terms of recipient age, warm and cold ischemia time, number of HLA A, B, DR mismatches and number of rejection episodes. The result showed no difference in mortality between the 2 groups (12% vs. 13%). One year graft survival was 70% vs. 51% (NS), immediate onset of function was 76% vs. 46% (p less than 0.01), creatinine concentration at one year was 146 +/- 39 vs. 206 +/- 73 mumol/l (p less than 0.05) for G1 and G2, respectively. The most striking finding was a highly significant difference in the rate of graft-related surgical complications, 12% vs. 35% (p less than 0.01) for G1 and G2, respectively. We conclude, that a patient receiving a graft from an elderly donor, runs a higher risk of graft-related complications and that long term graft survival and function also might be influenced by the age of the donor. A possible reason for the inferior results in group 2 might be an increased sensitivity for the toxic effects of CyA of aging kidneys.

Kidney stone disease. Experiences from Uppsala, Sweden.

In summary, several biochemical investigations give valuable information about a possible etiological explanation for the stone formation but to get a more complete picture of the individual stone former, some clinical aspects should be considered such as heredity for stone disease and the age of onset. All these factors are relevant when considering prophylactic treatment to stone formers.

Phosphate metabolism in renal stone formers. (II): Relation to renal tubular functions and calcium metabolism.

Patients with idiopathic recurrent calcium nephrolithiasis (n = 57) and controls (n = 16) were investigated regarding the relationship between renal phosphate handling, other renal tubular functions and calcium metabolism. Incomplete renal tubular acidosis (RTA) was disclosed in 13 patients. RTA patients together with stone formers with normal renal acidification capacity (SF) exhibited low values for serum phosphate and renal threshold phosphate concentration (TmP/GFR) compared with controls. TmP/GFR was lower in RTA patients than in stone formers with normal renal acidification. Hypercalciuria of the absorptive type with normal serum PTH and urinary cAMP concentrations was a common finding in both stone patient groups, whereas no patient displayed unequivocal evidence of parathyroid hyperfunction. Fractional excretion of sodium was raised in both SF and RTA patients compared with controls. There was a positive relationship between the fractional excretion of phosphate and sodium in all subjects as a group. TmP/GFR was negatively correlated to fractional excretion of sodium. Twenty-three percent of RTA patients and 8% of SF displayed tubular proteinuria which often was associated with low TmP/GFR levels and enhanced natriuresis. It is concluded that a defective renal tubular phosphate handling is common in calcium stone formers and often associated with signs of other tubular dysfunctions. The altered phosphate handling seems to be unrelated to hypercalciuria.

Phosphate metabolism in renal stone formers. (I): Indices of phosphate handling in calcium stone patients and healthy subjects.

Healthy subjects (n = 112) and patients with recurrent idiopathic calcium nephrolithiasis (n = 44) were evaluated regarding various indices of phosphate handling: serum phosphate concentration, renal tubular reabsorption of phosphate, index of phosphate excretion and renal threshold concentration for phosphate (TmP/GFR). The 24 hour and fasting 2 hour urinary phosphate excretions were similar in the two groups and the index of phosphate excretion was higher in stone formers, but for all the other variables lower mean values were found in the group of stone formers than in the group of normal subjects. The renal tubular capacity for reabsorption of phosphate (as evaluated by the different indices) appeared to decrease with advancing age concomitant with a reduction of the serum phosphate concentration. When age- and sex-matched subjects from the two groups were compared with regard to the phosphate variables lower values were still found in the group of stone forming subjects. This study gives support to earlier observations that renal stone formers tend to waste phosphate by and altered renal handling.