The impact of sacral root anatomy on selective electrical stimulation for bladder evacuation

The present study was conducted to examine the clinicopathological features of recurrent IgA nephropathy (IgAN) following renal transplantation. Serial renal biopsies were performed regularly at 0-hour, 1-hour and 2-hours, and 39 episode biopsies were carried out when patients had increased serum creatinine levels and proteinuria. In 49 renal allograft recipients with IgAN, 12 patients were proved to be recurrent IgAN (24.5%). There was a significantly increased five- and ten-year risk of graft loss in the renal allograft recipients with biopsy-proved recurrent IgAN. Graft survival in 49 renal allograft recipients with IgAN was worse (68.8% at 5 years and 40.4% at 10 years) than that in 997 whole transplants (80.7% at 5 years, and 67.7% at 10 years). We found significant differences in the prevalence of HLA-DR4 (66.7%) and BW35 (25%) in the renal allograft recipients with recurrent IgAN when compared with normal healthy subjects. The renal allograft recipients with recurrent IgAN had a high incidence of proteinuria (8/12), hypertension (9/12) and renal dysfunction of less than 50 ml/min (7/12). Mean hemodialysis duration before renal transplantation in recurrent IgAN transplants was 12.5 months, which was shorter than in those without recurrent IgAN. Histopathological studies revealed that renal lesions due to IgAN frequently appeared in the renal allograft recipients with recurrent IgAN. Taken together, these findings suggest that donor-recipient matching may be carefully reconsidered, and recurrent IgAN after renal transplantation must be treated with effective immunosuppressive therapy.     

Relapse of multiple myeloma in extramedullary sites

Multiple myeloma was diagnosed in a 69-year-old man with pathological hip fracture, who had increased plasma cells in the bone marrow, osteolytic lesions in bones, low level of monoclonal protein (IgAK) in serum and urine, and anemia, hypercalcemia and renal insufficiency. He was treated for 1 year with chemotherapy with good results. 6 months after cessation of treatment the disease relapsed with multiple extramedullary plasmacytomas in skin and subcutaneous areas, right eyebrow, right knee, sternum and right axilla, but repeated bone marrow examinations were without evidence of disease activity. Chemotherapy was resumed but the patient died 1.5 years after the relapse with severe jaundice due to multiple liver plasmacytomas and pelvic masses.     

Normocalcemic tetany. A problem of erethism

A boy with neonatal and childhood convulsions had prolonged attacks of tetany in adolescence. There was no abnormality of serum calcium or magnesium, and treatment with these cations was ineffective. There was no respiratory alkalosis, and attacks occurred when the patient had not taken anticonvulsant drugs for years. Serum parathormone content and renal responses to the administration of parathormone were normal. "Normocalcemic tetany" seems an appropriate name for the condition, which was probably genetic since the patient's brother and mother had signs of latent tetany and the brother had a convulsive disorder. The cause of the syndrome is not known, but it seems to be an abnormal response of neural membranes rather than an abnormality of calcium homeostasis.     

Long-term outcome of a prospective randomized trial of conversion from cyclosporine to azathioprine treatment one year after renal transplantation

BACKGROUND: Since the introduction of cyclosporine (CsA), 1-year renal allograft survival has improved, but concern persists about the long-term adverse effects of CsA, especially with respect to renal function and blood pressure. This randomized controlled trial was set up to establish whether withdrawal of CsA would alter long-term outcome. METHODS: Adult patients who, at 1 year after renal transplantation, had a stable serum creatinine of less than 300 micromol/L and who had not had acute rejection within the last 6 months were eligible for entry. Patients were randomized either to continue on CsA (n=114) or to stop CsA and start azathioprine (Aza, n=102). All patients remained on prednisolone. Median follow-up was 93 months after transplantation (range: 52-133 months). RESULTS: There was no significant difference in actuarial 10-year patient or graft survival (Kaplan-Meier), despite an increased incidence of acute rejection within the first few months after conversion. Median serum creatinine was lower in the Aza group (Aza: 119 micromol/L; CsA. 153 micromol/L at 5 years after randomization, P=0.0002). The requirement for antihypertensive treatment was also reduced after conversion to Aza; 75% of patients required antihypertensive treatment at the start of the study, decreasing to 55% from 1 year after randomization in the Aza group and increasing to >80% in the CsA group (55% (Aza) and 84% (CsA) at 5 years after randomization, P<0.005). CONCLUSIONS: Conversion from CsA to Aza at 1 year after renal transplantation results in improvement in both blood pressure control and renal allograft function, and is not associated with significant adverse effects on long-term patient or graft survival.     

Primate renal transplants using immunotoxin

BACKGROUND: T-lymphocyte depletion 7 days before transplantation with immunotoxin FN 18-CRM9 has resulted in tolerance to subsequent renal allografts. We tested the effect of giving immunotoxin on the day of the transplantation and evaluated its effect on rhesus monkey and allograft survival, on antibody production, and on T-cell recovery. METHODS: Major histocompatibility complex mismatched renal allografts were performed in rhesus monkeys. Immunotoxin was given starting on the day of transplantation, with and without prednisone and mycophenolate mofetil for 3 days. T-cell subsets and alloantibody levels were measured by flow cytometry. The ability of treated monkeys to develop antibody to tetanus, diphtheria, and xenoantibody was measured. Histology of renal transplants was read in a blinded manner. RESULTS: Immunotoxin started on the day of transplantation resulted in prolonged allograft survival in all treatment groups. Graft loss between days 50 and 135 was most often due to interstitial nephritis. Later graft loss was due to chronic rejection. Monkeys had intact antibody responses to alloantigen, tetanus, diphtheria, and xenoantibody. Their CD4 cells recovered gradually over 6 months. CONCLUSIONS: Immunotoxin reliably prolongs renal allograft survival when started on the day of transplantation, but interstitial nephritis and chronic rejection limit the development of long-term tolerance. T-cell-dependent B-cell responses remain intact after treatment.     

Total parathyroidectomy and autologous parathyroid transplantation in secondary hyperparathyroidism (author's transl)

In a 17-year-old female patient with marked secondary hyperparathyroidism and progressive bone changes all four parathyroid glands were removed. Part of the endocrine tissue was reimplanted into the muscles of the forearm. The transplant took successfully and showed a satisfactory function. Total parathyroidectomy and autologous parathyroid transplantation has a number of advantages as compared with subtotal parathyroidectomy: The function of the transplant can be directly observed and tissue can be easily removed in the further course of the disease. It is thus possible to regulate parathormone secretion over long periods in patients with chronic renal failure.     

Primary immunosuppression with mycophenolate mofetil and antithymocyte globulin for kidney transplant recipients of a suboptimal graft

BACKGROUND: In renal transplantation the beneficial immunosuppressive effects of cyclosporin (CsA) may be curtailed by its nephrotoxicity, specially in patients receiving a cadaveric allograft from suboptimal donors or at risk of delayed graft function. Mycophenolate mofetil (MMF) and antithymocyte globulin (ATG) have each demonstrated to be potent immunosuppressants in renal transplantation. In a prospective analysis we have studied the results at 6 months of the combination of MMF, ATG and low-dose steroids in patients with low immunological risk receiving a first cadaveric renal allograft from a suboptimal donor or at risk of delayed graft function. METHODS: Patients with preformed reactive antibodies < 500% receiving a first graft from a suboptimal donor (age > or = 40 years, non-heart-beating, acute renal failure, arterial hypertension) or at risk of delayed graft function (cold ischaemia time > or = 24 h) were eligible for this open single-arm pilot trial. From September 1996 to March 1997 we recruited 17 patients. They were treated with MMF 2 g p.o. preoperatively, and after transplantation at 3 g/day; rabbit ATG i.v. at 2 mg/kg preoperatively, and 1.5 mg/kg/day the first day after transplantation, followed by four doses of 1 mg/kg on alternate days; prednisone was given at 0.25 mg/kg/day and reduced progressively to 0.1 mg/kg/day at 3 months. Primary outcomes were incidence of biopsy-proven acute rejection, delayed graft function, opportunistic infections, graft and patient survival, and the need for introduction of CsA treatment. RESULTS: delayed graft function occurred in two cases (12%). Four of 17 patients (24%) had a biopsy-proven acute rejection (2 grade I and 2 grade II) within the first 3 months after transplantation. CsA was added in two cases with grade II biopsy-proven acute rejection, and in one with grade I biopsy-proven acute rejection. In one patient MMF was replaced by CsA because of gastrointestinal intolerance. Mean serum creatinine 6 months after transplantation was 159+/-59 micromol/1. Cytomegalovirus tissue invasive disease occurred in one patient (6%). At 6 months follow-up all patients are alive with functioning allografts. CONCLUSIONS: These preliminary results suggest that in low-immunological-risk patients who receive a suboptimal renal allograft or at risk of delayed graft function, the combination of MMF, ATG, and steroids is an efficient immunosuppressive regime that may avoid the use of CsA in 70% of the recipients.     

Efficacy and safety of low molecular weight heparin in renal transplantation

BACKGROUND: Deep venous thrombosis (DVT) is a common problem with potentially devastating results in patients undergoing major surgical procedures. Certain renal transplant recipients are particularly at risk for allograft loss as a consequence of renal vein and artery thrombosis. Over the past few years, low molecular weight heparin has been well established as an accepted modality of treatment and prophylaxis of DVT. The efficacy and safety of low molecular weight heparin in the prophylaxis of DVT following renal transplantation in adults has not previously been reported. METHODS: Dalteparin was administered to 120 adult renal transplant recipients postoperatively at the Oregon Health Sciences University. RESULTS: No patient developed allograft arterial or venous thrombosis. One patient developed subclavian vein thrombosis. No bleeding complications were encountered, and side effects were very minimal. CONCLUSION: Prophylaxis with dalteparin is an effective and safe modality for the prevention of thrombosis in adult patients undergoing renal transplantation.     

Physician and patient factors influencing the treatment of low back pain

From January 1989 to December 1995, 5 diabetic patients with end-stage renal disease (1 woman, 4 men) underwent kidney-alone transplantation. The mean age of the recipients at the time of transplantation was 37.4 years (range, 32 to 43). Craft function and glucose tolerance was evaluated for 5 to 72 months after surgery. Postoperative complications were seen in 2 patients; nonspecific subcutaneous infections and an asymptomatic partial allograft infarction. All renal allografts were functioning 1 year after transplantation, with a mean serum creatinine level of 1.10 mg/dL (range, 0.8 to 1.8 mg/dL), and a mean urinary protein level of 17.8 mg/dL (range, 5 to 27 mg/dL). The postoperative daily dose of insulin was higher than the preoperative dose, while the level of glycated hemoglobin (HbA1C) increased after surgery and peaked 6 months after transplantation; 1 year after transplantation it had reverted to the preoperative level. As long as the diabetic complications of the renal allograft recipients are not severe, the short-term survival and the renal function of diabetic patients with end-stage renal disease improves after kidney-alone transplantation, which is still the standard method of treatment in Japan.     

Bone allografts are immunogenic and may preclude subsequent organ transplants

The authors report a case of a 41-year-old woman with diabetes and chronic renal failure in whom antihuman leukocyte antigen antibodies developed after she received a frozen bone allograft that limited her access to organ donors. The patient had a chondrosarcoma of the right distal femur. A wide resection with segmental total knee arthroplasty was followed by a revision using a composite bone allograft prosthesis. After revision, broadly reactive lymphocytotoxic antibodies developed in the patient. The patient's panel reactive antibody level rose from 28% to a peak of 70%. Panel reactive antibody expresses the percentage of a panel of human leukocyte antigen type T lymphocytes from 40 individuals (representative of all human leukocyte antigen Class I histocompatibility antigens) to which antihuman leukocyte antigen Class I lymphocytotoxic antibodies have developed in the recipient as measured by the antiglobulin crossmatch method. The specificity of the patient's primary antibody is found in 45% of donors available in Illinois since 1988 (N = 1606). Because a positive crossmatch precludes kidney and pancreas transplantation, at least 45% of cadaver organ donors were excluded from use for this patient. This is an unusual case that focuses on the potential impact of bone allografts in patients who may need subsequent organ transplantation.     

Insufficiency fractures of the sacrum: a cause of low back pain after lung transplantation

Insufficiency fractures of the sacrum were diagnosed during the first year after successful transplantation in four (5.6%) of 71 lung and heart-lung transplant recipients. Each patient had development of low back pain after minor or no trauma; all had osteoporosis. In each instance, plain radiographs failed to demonstrate the fracture, and the diagnosis was established by radionuclide bone scanning that demonstrated the characteristic "butterfly" (bilateral sacral fracture) or "half-butterfly" appearance (unilateral sacral fracture). Sacral insufficiency fractures, a significant cause of low back pain in lung transplant recipients, may be underdiagnosed in this population because routine radiographs do not usually reveal the fracture; bone scanning is the preferred diagnostic modality.     

Detection of donor-specific hyporesponsiveness following late failure of human renal allografts

Limiting dilution assays to measure the frequency of interleukin-2-secreting peripheral blood T cells were carried out in patients, whose renal allografts had failed due to acute rejection (9 patients) and in patients whose grafts failed more than two years after transplantation without any recent evidence of acute rejection. Using a modified form of the assay we demonstrate that nearly half of 18 patients whose renal transplants had failed after more than two years have low or undetectable HTLp frequencies against donor, but not third-party DR antigens. No such difference was observed in any of the nine patients studied whose transplants were lost from early acute rejection. These results provide the first indication that, as in rodent models of transplantation, T cell unresponsiveness towards donor MHC antigens can occur following prolonged residence of an allograft in humans. Furthermore, the results suggest that chronic rejection may be driven by mechanisms other than direct allorecognition. The assay may be a valuable tool to study the evolution of donor-specific direct T cell alloresponsiveness in patients with well-functioning grafts.     

Renal transplantation following renal failure due to urological disorders

BACKGROUND: Renal allograft outcome, during an 8 year period (1985-1992), has been assessed in 56 renal transplants performed in 55 patients who had end-stage renal failure as a consequence of urological abnormalities. The abnormalities were: primary vesicoureteric reflux (VUR) or renal dysplasia (26 patients); posterior urethral valves (PUV) (15); neuropathic bladders (6); vesico-ureteric tuberculosis (5); bladder exstrophy (3); and prune belly syndrome (1). Six patients had augmented bladders, and eight transplants were performed in seven patients with urinary diversions. RESULTS: Overall, 1 and 5 year actuarial graft survival was 89 and 66%, with mean creatinine of 154 micromol/l +/- 11 (SE) and 145 +/- 9 respectively. Patients with abnormal bladders or conduits (n = 28) had worse graft function than those with normal bladders (n = 28) although graft survival was not significantly different in the two groups at 1 and 5 years: 93 and 75% with normal bladders vs 86 and 57% with abnormal systems. Symptomatic urinary tract infections were common in the first 3 months after transplantation (63%); fever and systemic symptoms occurred in 39% with normal bladders and 59% with abnormal bladders. Urinary tract infection directly contributed to graft loss in six patients with abnormal bladders, but had no consequences in those with normal bladders. CONCLUSIONS: Abnormal bladders must be assessed urodynamically before transplantation, and after transplantation adequacy of urinary drainage must be re-assessed frequently. Prophylactic antibiotics are now given for the first 6 months and urinary tract infections must be treated promptly. With these measures, good results, similar to those of patients without urological problems, can be obtained.     

Fracture after cardiac transplantation: a prospective longitudinal study

Cardiac transplantation is associated with increased prevalence of vertebral fractures, but the natural history of and risk factors for fracture after this life-saving procedure are unclear. We evaluated 47 patients (34 men and 13 postmenopausal women) before transplantation with spinal radiographs, determination of bone density by dual energy x-ray absorptiometry, and measurement of biochemical indexes of mineral metabolism. During the first year after transplantation, incident fractures were documented radiographically. Associations among demographic characteristics, bone density, biochemistries, and fracture risk were evaluated with logistic regression analysis. Despite supplementation with elemental calcium (1000 mg/day) and vitamin D (400 IU/day), 17 patients (7 women and 10 men) sustained a total of 34 fractures. Most fractures involved the spine, and 85% of the patients who experienced fracture did so within 6 months of transplantation. Fifty-four percent of the women and 29% of the men experienced fracture. Femoral neck bone mineral density was significantly lower in women who experienced fracture than in those who did not (0.604 +/- 0.11 vs. 0.760 +/- 0.12 g/cm2; P < 0.04), but did not differ in men according to fracture outcome. The amount of bone loss at the femoral neck by 6 months after transplantation was significantly greater in men with fracture than in men without fracture (12.0 +/- 6.4% vs. 6.8 +/- 5.3%; P < 0.04), but did not differ in women according to fracture outcome. Pretransplant 1,25-dihydroxyvitamin D levels were significantly lower (25 +/- 9 vs. 39 +/- 17 pg/mL; P < 0.007) and intact PTH levels tended to be higher in men who did not experience fracture (37 +/- 15 vs. 69 +/- 46 pg/mL; P < 0.06). Individual pretransplant bone density measurements demonstrated substantial overlap between patients who did and did not experience fracture, and normal bone density did not necessarily protect against fracture after transplantation. We conclude that fractures are a common and early complication of cardiac transplantation. No pretransplant measurement has yet been identified that reliably predicts fracture after transplantation in the individual patient.     

Amyloid beta-peptides inhibit Na+/K+-ATPase: tissue slices versus primary cultures

BACKGROUND: Urinary bladder augmentation is gaining popularity for the treatment of dysfunctional bladders in renal transplant patients. Although reported cases of adult and pediatric transplants into the augmented bladder have been favorable, the potential risk of urinary tract infection and graft failure under immunosuppression is still disputable. We report our experiences with 4 patients who underwent renal transplantation into an augmented bladder. METHODS: Between 1971 and 1996, 1275 renal transplants were performed at our institution. Of these transplants, 4 patients underwent renal transplantation into an augmented urinary bladder. Augmentation cystoplasty was performed before transplantation in 3 patients and 7 years after transplantation in the other patient. The bladder was augmented with an ileal segment in 3 patients and a ureter in the fourth patient. Graft function was assessed by the serum creatinine level. Fluorocystometrograms were performed in all patients at fixed intervals. RESULTS: Posttransplant renal function was satisfactory overall and no patient exhibited proteinuria. All patients except 1 acquired a large capacity low pressure bladder and remained continent with clean intermittent catheterization. One patient who underwent ureterocystoplasty is still incontinent because of his relatively small bladder capacity. Posttransplant pyelonephritis was documented in 3 patients during the follow-up period, but no other complications were observed. CONCLUSIONS: Our study demonstrates that renal transplantation into extensively reconstructed bladders can be safely performed with good success. Although urinary tract infection is a major consideration, we recommend pretransplant reconstruction not only to preserve graft function, but also to achieve urinary continence.     

Clinical use of bone allografts

Modern techniques of bone allograft surgery provide a treatment modality for management of difficult skeletal defects. In oncological limb-salvage surgery, allograft reconstructions permit re-establishment of skeletal continuity and function after a wide resection of bone tumour. Bone allografts are increasingly used in salvage of difficult bone stock deficiencies following failed total joint replacements. Union between the allograft and the host bone takes place slowly and the use of autogenous bone graft at the graft-host junction is recommended for induction of repair. Internal repair (revascularization and substitution of the original graft bone with new host bone) also progresses slowly and seems to be confined only to the superficial surface and the ends of the graft. Biomechanically, a massive allograft may serve a structural function in the absence of advanced revascularization and creeping substitution processes. Infection of an allograft is a disastrous complication, whereas non-union of the graft-host junction and fracture of the graft are amenable to surgical treatment. Osteochondral allografts tend to show gradual deterioration of the articular cartilage with time, necessitating occasionally late resurfacing arthroplasty. It is evident that there is more active immune response to osteochondral grafts than was thought previously. Bone allografts induce cell-mediated and antibody-mediated cytotoxicity specific for donor antigens similar to that seen after organ transplantations. Not only the basic mechanisms of bone allograft rejection but also the clinical features of bone allograft rejection are poorly characterized. Clinically, new non-invasive imaging techniques should be applied in determining the metabolic activity of bone in order to find the optimal loading of healing allografts. Although the clinical results of massive bone allografts are still not completely predictable, the method has proved to be a technically and biologically feasible alternative for non-biological skeletal reconstructions.     

Kidney transplantation after a severe form of pseudotumor cerebri

Pseudotumor cerebri is a syndrome characterized by intracranial hypertension (intracranial pressure >200 mmH2O) and a normal ventricular system. The diagnosis should be made as early as possible to prevent impairment of vision. Several diseases have been reported in association with pseudotumor cerebri in pediatric patients, and have been occasionally also noted with chronic renal failure, heart and renal transplantation. We report a 7-year-old boy who complained of severe headaches and visual impairment 2 years after hemodialysis for renal hypoplasia. Pseudotumor cerebri was suspected and, despite treatment with corticosteroids, acetazolamide, and lumboperitoneal diversion, visual impairment worsened. Bilateral optic nerve sheath decompression (ONSD) was performed without success and the child completely lost his vision within 2 weeks. He was successfully transplanted 2 months later. Two years post transplantation, the blind child has a normal renal function and school performance. Pseudotumor cerebri must be rapidly suspected in a child with renal failure suffering from headaches and papilledema. Visual loss may progress rapidly and ONSD seems to be the best surgical treatment when medical treatment fails. In this patient renal transplantation was well tolerated, with no deterioration in the neurological status over 2 years of follow-up.     

Successful combined lung and kidney transplantation for pulmonary lymphangioleiomyomatosis and renal angiolipomas

Pulmonary lymphangioleiomyomatosis (LAM) and renal angiolipomas are rare but distinct clinical entities that share similar morphological features. Lung transplantation is considered as a valuable therapeutic modality in patients with end-stage pulmonary LAM. However, in some patients, renal complications due to bleeding angiomyolipomas and cyclosporin-induced nephropathy have become newly identified problems. This study reports the first case of combined lung and kidney transplantation for pulmonary lymphangioleiomyomatosis and renal angiolipomas. Two years after transplantation, renal and pulmonary function have remained stable and the patient has resumed a normal daily life, including a full-time professional activity.     

Non-real-time computed tomography-guided percutaneous ethanol injection therapy for hepatocellular carcinoma undetectable by ultrasonography

Fibrosing cholestatic hepatitis (FCH) has recently been described after solid organ transplantation in patients with hepatitis C virus (HCV) infection. Typically, FCH is characterized by an ominous clinical course leading to progressive hepatic failure and death if liver transplantation is not performed. Two HCV-infected patients underwent cadaveric renal transplantation for end-stage renal disease resulting from membranous nephropathy and diabetic nephropathy. The time intervals between transplantation and the biopsy diagnosis of FCH for the two patients were 7 months and 10 years. Both patients presented with jaundice, hyperbilirubinemia, and mild-to-moderate elevations in serum aspartate aminotransferase. One patient was also found to have type II mixed cryoglobulinemia. Interferon-alpha therapy was begun after a diagnosis of FCH was established by liver biopsy. Liver test abnormalities normalized rapidly. When cholestatic hepatic deterioration develops in an HCV-infected organ allograft recipient, the diagnosis of FCH should be considered and a liver biopsy performed. Our observations indicate that FCH can respond to antiviral therapy.     

Ethnic variations in patient and graft survival after liver transplantation. Identification of a new risk factor for chronic allograft rejection

The ethnic origin of renal graft recipients is recognized as an important determinant of graft survival. In liver transplantation, the effect of racial origin has been studied in black American recipients and has suggested a trend toward inferior graft survival in this group. In this study, we have analyzed outcome of transplantation in a large multiethnic liver transplant program. Non-Caucasoid recipients had an inferior patient survival compared with Caucasoids and, in particular, European Caucasoids at 1, 3, and 5 years after transplantation (46.7% vs. 60.2% at 3 years, P = 0.05). Non-European recipients had an inferior graft survival compared with European recipients at 1, 2, and 3 years after transplantation (e.g., north Europeans 53.5%, south Europeans 48.5%, Middle Eastern 40%, and non-Caucasoids 27% at 3 years, P < 0.01). Different frequencies of chronic allograft rejection in the ethnic groups contributed to the rates of graft survival, with the non-European recipients developing chronic rejection at over twice the rate of European recipients (12.6% vs. 5.9%, respectively, P = 0.002). The findings in this study support the evidence from renal transplant programs that the ethnic origin of recipients is an important determinant of outcome after transplantation, with increasing frequency of chronic rejection in recipients nonindigenous to the donor population contributing to the variations in patient and graft survival rates.