Rationale for prostaglandin I2 in bone marrow oedema--from theory to application.

INTRODUCTION: Bone marrow oedema (BME) and avascular osteonecrosis (AVN) are disorders of unclear origin. Although there are numerous operative and non-operative treatments for AVN, pain management in patients with AVN remains challenging. Prostaglandins play an important role in inflammatory responses and cell differentiation. It is thought that prostaglandin I2 ([PGI2] or synonoma prostacyclin) and its analogues promote bone regeneration on a cellular or systemic level. The purpose of this study was to assess the curative and symptomatic efficacy of the prostacyclin analogue iloprost in BME and AVN patients. METHOD: We are reporting on 50 patients (117 bones) affected by BME/AVN who were treated with iloprost. Pain levels before, during and 3 and 6 months after iloprost application were evaluated by a visual analogue scale (VAS). The short form(SF)-36 health survey served to judge general health status before and after treatment. Harris Hip Score (HHS) and Knee Society Score (KSS) were performed as functional scores and MRI and X-rays before and 3 and 6 months after iloprost application served as objective parameters for morphological changes of the affected bones. RESULTS: We found a significant improvement in pain, functional and radiological outcome in BME and early AVN stages after iloprost application, whereas patients with advanced AVN stages did not benefit from iloprost infusions. Mean pain level decreased from 5.26 (day 0) to 1.63 (6 months) and both HHS and KSS increased during follow-up. Moreover, the SF-36 increased from 353.2 (day 0) to 560.5 points (6 months). We found a significant decrease in BME on MRI scans after iloprost application. CONCLUSIONS: In addition to other drugs, iloprost may be an alternative substance which should be considered in the treatment of BME/AVN-associated pain.

Post-transplant distal limb syndrome: clinical diagnosis and long-term outcome in 37 renal transplant recipients.

After the introduction of steroid sparing immunosuppressive protocols, osteonecrosis of the hip has become a rare entity in renal transplantation. Instead, an elusive bilateral pain syndrome of the distal extremities has gained more clinical attention. Because of the typical presentation, it is sometimes referred to as 'post-transplant distal limb syndrome' (PTDLS). The syndrome typically manifests during the first year after transplantation and may lead to significant morbidity because of pain induced immobilization. On MRI-scans, a characteristic bilateral patchy osteoedema can be demonstrated. The etiology of PTDLS has not been determined definitely so far. Over the last 8 years, we have seen the syndrome in 37 out of 639 renal transplant patients (5.8%). There was no association to steroid-medication, age, gender, PTH levels or delayed graft function. As an important finding, we saw a significant rise in alkaline phosphatase from 160 +/- 54 to 271 +/- 108 U/l (P = 0.001) and calcium from 2.46 +/- 0.18 to 2.58 +/- 0.18 mmol/l (P = 0.013) preceding the onset of pain by several weeks. Mean duration of clinical symptoms was 5.1 +/- 3.1 months; however, all patients experienced remission without signs of chronic damage on long-term follow up.

Iliac artery stenosis proximal to a kidney transplant: clinical findings, duplex-sonographic criteria, treatment, and outcome.

BACKGROUND: Stenosis of the iliac segment proximal to the transplant renal artery (Prox-TRAS) is an uncommon cause of graft dysfunction and hypertension. We assessed the role of duplex sonography (DS) in regard to clinical and angiographic findings and followed the patients after percutaneous transluminal angioplasty (PTA), PTA stenting (PTAS), or surgery. METHODS: From January 1988 to August 2001, 97 of 1,064 kidney recipients underwent angiography for clinical or Doppler-sonographic suspicion of vascular problems. Kidney function, blood pressure, medication, and DS findings after renal transplantation (RTx) at the time of diagnosis of Prox-TRAS and after treatment were evaluated. RESULTS: Prox-TRAS was diagnosed in 16 patients (1.5%) (49.6+/-6.9 years). Four patients demonstrated early presentation of Prox-TRAS 1 to 7 days after RTx (group A), leading to acute renal failure but without hypertension. In all patients, DS revealed pulsus parvus et tardus, low pulsatility index (PI) (<1.0), and a pathologic flow profile in the iliac artery proximal and distal to the graft. After treatment (surgery in two patients, PTA in one patient, PTAS in one patient), all patients developed good renal function (creatinine 1.7+/-0.9 mg/dL). PI increased from 0.9+/-0.1 to 1.2+/-0.1 (P=0.04), and flow profile within the iliac artery distal to the graft normalized. Late presentation (3-209 months after RTx) of Prox-TRAS was observed in 12 patients (group B), causing an increase of creatinine in 11 patients (two patients receiving dialysis treatments), impairment of blood pressure (141+/-15 and 80.7+/-7 to 160+/-18 and 85+/-7 mm Hg, P=0.009), and an increase in antihypertensive drugs (2.1+/-1.1 and 4.3+/-1, P=0.003) in all patients. The PI was decreased when compared with values early after RTx (1.6+/-0.4 to 1.2+/-0.3, P=0.007), and flow profile in the iliac artery was pathologic. All patients except one were managed by surgery (n=6), PTA (n=1), or PTAS (n=4). Creatinine (2.7+/-1.4 to 1.8+/-0.4 mg/dL, P=0.02) and blood pressure (160+/-18/85+/-7 mm Hg to 138+/-7/82+/-9, P=0.018) improved. Antihypertensive drugs were reduced to 2.8+/-0.8 (P=0.01). PI increased from 1.2+/-0.3 to 1.9+/-0.5 (P=0.01). Flow profile within the iliac artery distal to the graft anastomosis normalized. Kidney function, blood pressure, and PI remained unchanged during follow-up (82+/-69.9 months) in both groups. CONCLUSIONS: Prox-TRAS is rare. Because clinical symptoms are similar to those of transplant renal artery stenosis, DS is a valuable tool for diagnosis and follow-up for this type of vascular lesion. Selective treatment with PTA, PTAS, or surgery improves kidney function and hypertension.

Kidney transplantation from related and unrelated living donors in a single German centre.

BACKGROUND: Organ transplantation began in 1954 with living related donation (LRD). Because of organ shortage from cadavers, unrelated kidney donation (LURD) has been proposed and shown to have good results despite complete HLA mismatching. This study aims to look at differences and similarities comparing LRD and LURD performed in our centre since the implementation of the German transplant law in 1997. METHODS: Between January 1997 and July 2001, 62 out of 112 potential living donors and their recipients were accepted. Immunosuppression consisted of triple therapy (steroids, cyclosporin, mycophenolate) in patients with three or fewer mismatches, or quadruple therapy including mono- or polyclonal antibody treatment in patients with four or more mismatches or cytotoxic antibodies. LRD and LURD groups were compared for number and type of rejections, complications and kidney function at the end of observation (median 15.5 months, range 1-50 months). RESULTS: Out of 112 pairs presenting, transplantation was performed in only 62 cases (55.4%). Reasons to deny transplantation were medical problems of the potential donors in 19, psychological problems in 13, recipient problems in seven and other reasons in 11 pairs. In 38 cases LRD transplantation and in 24 cases LURD transplantation was carried out. Recipient age was significantly lower in the LRD group (37.7+/-12.1 years) compared with the LURD group (53.6+/-7.8 years). Mean donor age was 49.7+/-9.2 years in the LRD group and 50.3+/-9.1 years in the LURD group (ns). The number of mismatches was lower in LRD (2.1+/-1) than in LURD (4.4+/-0.9) (P=0.001) transplantation. The acute rejection rate was similar in both groups (52.2 vs 54.2%). OKT3 and tacrolimus rescue therapy for more severe rejections was more often applied in the LRD group but the difference did not reach the level of significance. There were more infectious complications in LURD transplantation (66.7 vs 36.4%, P=0.036) and a trend towards more surgical complications in LRD transplantation (28.9 vs 8.3%, P=0.062). One graft was lost due to transplant artery thrombosis and one recipient died 4 months after transplantation subsequent to cerebral ischaemia. Both patients belonged to the LRD group. Creatinine values at the end of observation time were 1.76+/-0.6 mg/dl in the LRD group and 1.62+/-0.5 mg/dl in the LURD group (ns). CONCLUSION: Although kidney transplantation from unrelated donors was performed with a lower HLA match and although the recipients were older, the results are equivalent to living related transplantation. Therefore, kidney transplantation from emotionally related living donors represents a valuable option for patients with end-stage renal disease. Careful selection of donors and recipients is a prerequisite of success.

[Arteriosclerotic renal artery stenosis. Significance, diagnosis and therapy options]. / Arteriosklerotische Nierenarterienstenose. Bedeutung, Diagnostik und Therapieoptionen.

BACKGROUND: Renal artery stenosis (RAS) can cause arterial hypertension and can lead to renal insufficiency. In 1999 16% of patients starting dialysis in Germany suffered from ischemic nephropathy. SCREENING: Cost-effective screening for RAS should be done by Doppler sonography or captopril renography. Doppler sonographic findings can be predictive in respect to progression of stenosis, renal atrophy and postinterventional course of hypertension and kidney survival. TREATMENT: The results of recent studies are helpful to select patients for preferential drug treatment or for interventional treatment.

Kidney transplantation in the elderly: age-matching as compared to HLA-matching: a single center experience.

BACKGROUND: We report the short-term outcome of our patients participating within the Eurotransplant age-matching program, where kidneys from donors >65 years are transplanted to recipients >65 years regardless of human leukocyte antigen (HLA) compatibility but with short cold ischemia times, in comparison with patients >60 years transplanted with HLA-matching. METHODS: Twenty-five patients (66.7+/-2.6 years) (donors 69+/-4.3 years) participated in this program (group A). The control group consisted of 21 patients (63+/-2.6 years) (group B) (donors 47.6+/-17.3 years). RESULTS: Despite significant differences in donor age, cold ischemia time (12.3+/-4.6 hr in A, 22.8+/-4.8 hr in B, P<0.001) and a mean of 4.4+/-1.4 vs. 2.3+/-1.6 HLA-mismatches (P<0.001), there was no difference regarding the incidence of delayed graft function (64 vs. 57%), rejections (52 vs. 66.7%), infections (56 vs. 52.4%), and other complications (80 vs. 71.4%). Mean serum creatinine after 6 months was 1.94+/-0.49 and 1.83+/-0.67 mg/dl (NS). CONCLUSION: The short-term results of the age-matching program are promising and comparable with results from patients of similar age with HLA-matching.

Risk factors for delayed graft function after renal transplantation and their significance for long-term clinical outcome.

Abstract. Delayed graft function (DGF) remains a grieving complication after renal transplantation. In this study, we examined various factors related to organ donation, transport, and transplantation for their influence on the incidence of DGF and on long-term prognosis. The incidence of DGF, renal function after 5 years, and allograft survival were analyzed in 200 kidneys transplanted in Düsseldorf as well as in 193 partner kidneys transplanted at 43 other centers. The main risk factors for DGF were donor age, cold ischemia time (CIT) and organ shipment. DGF itself, as well as donor age, influenced the long term prognosis. A significant relationship between the partner organs regarding clinical outcome was demonstrated. Non-immunological factors strongly influence the clinical results after renal transplantation. Organs of older donors have a limited long-term prognosis. To minimize additional risks, prevention of DGF, especially by reducing CIT, should be regarded as of paramount importance.