Wolfgang Grotz

BONE FRACTURE AND OSTEODENSITOMETRY WITH DUAL ENERGY X-RAY ABSORPTIOMETRY IN KIDNEY TRANSPLANT RECIPIENTS

Kidney transplant recipients have multiple factors leading to osteoporosis. The purpose of this study was to determine the fracture rate after kidney transplantation and the significance of osteodensitometry with dual energy x-ray absorptiometry (DXA) in identifying the risk patients. Bone mineral density (BMD) was measured with DXA in 100 graft recipients (mean interval 63 +/- 53 months after transplantation) and correlated with the incidence of fractures. Fracture rate of peripheral bones increased from 0.009 before transplantation and 0.012 on hemodialysis to 0.032 fractures per patient and year after transplantation. Seventeen fractures of peripheral bones occurred in 11% of the patients within a mean of 103 +/- 59 months after transplantation. Three additional patients had fractures of the lumbar spine. Patients with fractures were characterized by low or low-normal BMD (0.93 +/- 0.23 versus 1.04 +/- 0.17 g/cm2 at lumbar spine), a frequent history of parathyroidectomy (21% versus 6%), and a longer transplant interval (103 +/- 59 versus 57 +/- 49 months). Fractures occurred in patients with low and normal BMD. DXA at the femoral neck proved to be of no value to define patients at risk of fractures. DXA at the lumbar spine also proved to be of limited value for this question. Therefore, alternatively, more sensitive methods of BMD and of bone architecture measurements are necessary for identifying the kidney transplant recipients at risk of fracture.

Bone mineral density after kidney transplantation : a cross-sectional study in 190 graft recipients up to 20 years after transplantation

Kidney transplant recipients are exposed to multiple factors that lead to osteoporosis after kidney transplantation. Recent short-term longitudinal studies revealed a strong decline of bone mineral density (BMD) within 1 year after transplantation. The long-term course of BMD after transplantation is still unknown. Therefore, we performed a cross-sectional study to determine BMD in 190 renal graft recipients (mean age 44 years, range 20-71 years) by dual-energy x-ray absorptiometry at various time intervals up to 20 years after transplantation (range 0-237 months). Mean BMD of graft recipients was lower than BMD values of an age- and sex-matched European reference collective at every time of measurement after renal transplantation (P < 0.01). Lowest mean BMD values were measured 12-24 months after transplantation. No loss of BMD occurred after the second posttransplant year beyond the normal age- and sex-dependent decline of BMD. Mean daily prednisone dosage was significantly higher within the first 2 posttransplant years compared with the later posttransplant period (13.1 +/- 6.2 vs. 6.7 +/- 3.4 mg/day). Other drugs or metabolic causes, including daily dosage of CsA, AZA, parathormone level, and graft function, did not show additional important differences before and after the second posttransplant year. Interpreting the results of a cross-sectional study in light of a time-dependent process, we suggest that the preexisting low BMD of kidney transplant recipients at the time of transplantation is further strongly reduced within the initial 2 posttransplant years, probably due mainly to the effect of prednisone therapy. After that time, when prednisone dosage is below a threshold of 7.5 mg/day, only a moderate, normal loss of BMD is apparent, even in patients up to 20 years after transplantation.

Treatment of osteopenia and osteoporosis after kidney transplantation.

BACKGROUND Osteopenia and osteoporosis are frequent complications after kidney transplantation. Data for the treatment of low bone mass after kidney transplantation are not available. METHODS To test the efficacy of antiresorptive treatment, 46 patients with osteopenia or osteoporosis after kidney transplantation (bone mineral density < or =1.5 SD below normal) were randomly assigned to three groups cyclically treated as follows: group 1 with daily oral clodronate (800 mg) and group 2 with daily intranasal calcitonin (200 IU) for 2 weeks every 3 months. These two groups were compared with a control group (group 3). Every patient was supplemented with 500 mg of calcium per day. Bone mineral density (BMD) was measured by dual energy x-ray absorptiometry (DEXA) at the lumbar spine and femoral neck before and after the 12-month treatment period. RESULTS BMD at the lumbar spine was increased by 4.6% in the clodronate group (n=15, P=0.005), by 3.2% in the calcitonin group (n=16, P=0.034), and by 1.8% in the control group (n=15, P=0.265). However, the differences in BMD changes among the groups were not statistically significant. During therapy, serum calcium decreased slightly in all groups by 4.6%; however, parathyroid hormone values increased significantly in the treatment groups by 116%. Therapy was well tolerated without impact on graft function. CONCLUSIONS Cyclical therapy with clodronate or calcitonin appears to induce a gain in BMD at the lumbar spine in patients with low bone mass after kidney transplantation. This treatment had no adverse impact on graft function but may aggravate preexisting secondary hyperparathyroidism.

Impact of hepatitis B and C on graft loss and mortality of patients after kidney transplantation.

Background: Mortality or graft loss after renal transplantation might be influenced by hepatitis virus infection.

Clinical course of patients with antineutrophil cytoplasm antibody positive vasculitis after kidney transplantation

Four patients with antineutrophil cytoplasm antibody (ANCA)-positive vasculitis were followed over a period from 27 to 54 months after successful kidney transplantation under immunosuppressive treatment with ciclosporine. ANCA titer prior to transplantation was markedly elevated and decreased in 1 of 4 patients under therapy with ciclosporine. Despite adequate ciclosporine blood trough levels, a relapse occurred in 2 patients 18 and 24 months after transplantation but therapy with cyclophosphamide induced remission and no patient lost his graft due to relapse of vasculitis. This observation demonstrates that kidney transplantation may be offered to ANCA-positive patients with end-stage renal disease due to vasculitis. However, patients under ciclosporine therapy are still at risk for the development of relapsing disease and cyclophosphamide has to be added to or substituted in part for standard immunosuppressive therapy in order to reverse clinical symptoms and prevent rapid deterioration of kidney function.

Graft survival and graft function of pediatric en bloc kidneys in paraaortal position.

Background. En bloc kidneys from pediatric donors are regarded as questionable with respect to the safety and quality of the transplant outcome. Therefore, we retrospectively studied graft outcome and graft function of our 56 en bloc kidneys transplanted in paraaortal position between 1992 and 1999. Methods. Graft outcome of en bloc kidneys (group A) was compared with graft outcome of single cadaveric adult donor kidneys (group B). Matched pairs were generated regarding HLA-missmatch, cold ischemic time, recipient age, body mass index, and systolic arterial blood pressure. Results. Allograft survival rates of pediatric en bloc kidneys at 1, 3, and 5 years were significantly lower (group A: 78, 70, 70% vs. group B: 92, 92, 81%, P <0.05). Lower survival rate was caused by a higher number of graft losses in the early postoperative period (group A: 21% vs. group B: 4%, P <0.01) due to vascular complications. Main risk factor for graft loss was donor age of less than 12 months. Five years after transplantation serum creatinine of pediatric en bloc kidneys was significantly better than of adult kidneys (0.9±0.06 vs. 1.8±0.2 mg/dl, P <0.001). Conclusion. En bloc kidneys show a high percentage of graft survival with excellent long-term graft function. However, the early postoperative period carries a higher risk of graft loss in very young donors due to vascular complications. In the face of donor shortage en bloc kidneys from pediatric donors can successfully be transplanted in a paraaortal position.

Liver Support – A Task for Nephrologists? Extracorporeal Treatment of a Patient with Fulminant Wilson Crisis

Background: Patients with Wilson’s disease may present with cirrhosis, acute hepatitis or fulminant hepatic failure. Without urgent orthotopic liver transplantation, a fulminant Wilson crisis has a mortality of 100%. We report on an 18-year-old female patient with fulminant hepatic failure due to Wilson crisis. Methods: The molecular adsorbent recirculating system (MARS) was used to eliminate albumin-bound toxins and to bridge waiting until an organ became available. Results: A total of 18 MARS sessions and 4 plasma exchange sessions were performed. Bilirubin levels and hepatic encephalopathy improved under MARS therapy. A total of 75 mg copper was removed until serum copper levels were within the normal range. Copper elimination was measured in 15 MARS treatments, which removed a total of 12.9 mg copper. Four plasma exchange sessions, with a total exchange of 11 liters of plasma, removed 12 mg copper. Urinary copper elimination with penicillamine was 50 mg. Conclusion: MARS was an effective method to stabilize a patient with Wilson crisis, contributed to copper elimination and gained time for liver transplantation. The risk of high-urgency transplantation could be avoided. Liver support was easy in the hands of nephrologists familiar with extracorporeal therapy.

Impact of in vivo complement activation and cryoglobulins on graft outcome of HCV‐infected renal allograft recipients

Abstract:  Background:  Chronic hepatitis C virus (HCV) infection is closely associated with mixed cryoglobulinemia. Cryoglobulins can activate complement leading to vascular damage. We examined whether cryoglobulinemia and complement turnover is associated with HCV infection in renal transplant recipients and whether this has an adverse effect on graft outcome.

Dihydropyridine calcium antagonists and renal function in hypertensive kidney transplant recipients

Objective To investigate whether calcium antagonists are nephroprotective in hypertensive cyclosporine-treated renal allograft recipients. Methods We studied 50 hypertensive and 17 normotensive renal transplants (eight females, nine males; 14–54 years, mean age 38.8 ± 3.5 years). Hypertensive patients were randomized to be treated with (+Ca; 11 females, 13 males; 20–65 years, mean age 43.1 ± 3 years) or without (−Ca; 15 females, 11 males; 25–60 years, mean age 41.3 ± 2.5 years) a calcium antagonist (nitrendipine or nifedipine). Additional antihypertensives were given stepwise according to a standardized protocol: β1-adrenoceptor blocker, diuretic α1-adrenoceptor blocker or vasodilator. Data were analysed at 0, 1, 2 and 3 years on an intention-to-treat basis. Results Hypertensive patients had a higher body mass index at 0/3 years (23.7 ± 0.6/25.1 ± 0.6 kg/m2) than normotensive patients (22.2 ± 0.6/22.1 ± 0.7 kg/m2). During the study, blood pressure in normotensive transplants was always slightly, but not significantly, lower than that of transplants with treated hypertension. There was no difference between the groups (+Ca) and (−Ca). Cr51-ethylenediaminetetracetic acid (EDTA) clearance (0/2 years) was 58 ± 4/57 ± 6 ml/min in normotensives, 52 ± 4/47 ± 4 ml/min in hypertensives (+Ca) and 47 ± 4/49 ± 6 ml/min in hypertensives (−Ca). Proteinuria (0/3 years) was 0.16 ± 0.04/0.15 ± 0.02 g/24 h in normotensive, 0.26 ± 0.08/0.23 ± 0.05 g/24 h in hypertensives (+Ca) and 0.26 ± 0.07/0.22 ± 0.05 g/24 h in hypertensives (−Ca). Conclusions Post-transplant hypertension is associated with higher body mass index and poor renal function. No difference in the course of Cr51-EDTA clearance, serum creatinine, proteinuria or blood pressure was observed between groups treated with or without calcium antagonists. Calcium antagonists and conventional antihypertensive treatment have the same nephroprotectice effect in hypertensive renal transplants, when treatment is started 3 months after transplantation.

[Sleep apnea--treatment improves hypertension].

ZusammenfassungDie obstruktive Schlafapnoe und die arterielle Hypertonie sind sehr häufige, aber leider auch oft nicht erkannte Erkrankungen. Der ursächliche Zusammenhang von Schlafapnoe und Hypertonie ist gesichert. Wahrscheinlich ist die undiagnostizierte Schlafapnoe die häufigste Ursache der früher so genannten „essentiellen“ Hypertonie. Besonders wichtig erscheint daher die Identifikation dieser Patienten. Bei allen Hypertonikern sollten nach Schnarchen, Atemstillständen und Tagesmüdigkeit gefragt werden, der Halsumfang gemessen und ggf. eine ambulante Messung der nächtlichen Atmung (kardiorespiratorische Polygraphie) erfolgen. Insbesondere sollten alle Patienten mit schwer einstellbarer Hypertonie oder fehlender Nachtabsenkung in der 24-h-Blutdruckmessung auf ein obstruktives Schlafapnoesyndrom gescreent werden. Umgekehrt sollten alle Patienten mit Schlafapnoe gezielt auf eine arterielle Hypertonie untersucht werden. Da bei diesen Patienten auch nur eine nächtliche arterielle Hypertonie vorliegen kann, reichen Einzelmessungen am Tage nicht aus, um einen Bluthochdruck sicher auszuschließen.Die CPAP-Therapie („continuous positive airway pressure“) kann den Blutdruck bei hypertensiven Schlafapnoepatienten effektiv senken. Dies gilt besonders für Patienten mit obstruktiver Schlafapnoe und therapierefraktärer Hypertonie. Für nächtliche, durch Schlafapnoe induzierte Blutdruckspitzen scheint die CPAP-Therapie die zurzeit am besten dokumentierte Therapieform zu sein.AbstractObstructive sleep apnea and arterial hypertension are frequent diseases, but they are also often overlooked. There is a causal relationship of sleep apnea and hypertension. Undiagnosed sleep apnea is probably the most important reason for “essential” hypertension. It is important to identify these patients. All hypertensive patients should be asked for snoring, breathing arrest and daytime sleepiness, neck circumference should be measured, and an ambulant sleep apnea monitoring should be performed, if necessary. Especially patients with refractory hypertension or non-dippers should be screened for sleep apnea and patients with sleep apnea should be examined for arterial hypertension.Continuous positive airway pressure (CPAP) can effectively lower blood pressure in the hypertensive sleep apnea patient. This is especially true for the obstructive sleep apnea patient with refractory hypertension. CPAP therapy is probably the best therapy for sleep apnea-induced nocturnal blood pressure rises.