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G Offermann

Publications and source records attributed to G Offermann.

At least 19 recordsLinked to original sources

Severe calciphylaxis in a renal patient on long-term oral anticoagulant therapy.

The pathogenesis of calciphylaxis, a potentially life-threatening condition, is not well understood. Several factors such as end-stage renal disease (azotemia), hyperparathyroidism, hyperphosphatemia, hypercalcemia, a high calcium-phosphate product, and the use of steroids and cytotoxic drugs after kidney transplantation are believed to interact in calciphylaxis. Recently, hypercoagulability due to functional protein C deficiency has been suggested to play a pathogenic role in this condition. Here, we present a renal transplant patient, with secondary hyperparathyroidism and on long-term oral anticoagulant therapy, who developed calciphylaxis with severe skin necrosis of her legs. The patient's condition improved dramatically after total parathyroidectomy. Hypercoagulability, therefore, does not appear to have played a significant role in this case of calciphylaxis.

Administration, Oral

Transplantation in autosomal dominant polycystic kidney disease without nephrectomy.

Some transplantation centers still suggest nephrectomy in patients with autosomal dominant polycystic kidney disease (ADPKD) before kidney transplantation at least in selected cases. We wanted to learn whether prior nephrectomy is beneficial. The outcome of kidney transplantation in 47 consecutive ADPKD patients without prior nephrectomy was compared with that in matched controls with respect to complications of ADPKD. Although ADPKD patients were older than controls (mean, 50.1 vs. 40.3 years), there was no statistically significant difference in 1- and 5-year allograft survival between ADPKD patients and controls: 76.6 and 68.0%, respectively, in ADPKD patients, and 83.9 and 56.3% in controls. After a mean follow-up of 66.5 months 3 patients with ADPKD had cyst infections and were managed with antibiotics. Two patients had episodes of hematuria; neither required invasive therapy. There was no renal malignancy and clinical sign of urolithiasis in any patient. No posttransplantation nephrectomy was required. With only few indications remaining, there is no rationale for routine pretransplantation nephrectomy in patients with ADPKD.

Adult

Angiotensinogen-M235T genotype and post-transplant hypertension.

BACKGROUND: The angiotensinogen gene has been linked to the development of essential hypertension, and a M235T variant of this gene, associated with increased plasma levels of angiotensinogen, is more common in hypertensives than in normotensive controls in various populations. The present study was conducted to examine whether the M235T variant of the angiotensinogen gene may be a risk factor for the development of hypertension in patients undergoing renal transplantation. METHODS: DNA for genetic analysis was prospectively collected from 269 consecutive patients undergoing kidney transplantation between 1988 and 1993 and their corresponding donors. Presence of hypertension and graft survival was analysed by blinded review of all case records over a follow-up period up to 30 months. Angiotensinogen genotype was determined by a mutagenically separated allele-specific polymerase-chain-reaction technique. RESULTS: While post-transplant hypertension was present in 78% of all patients, no relationship was found between either donor or recipient genotype and the presence or severity of post-transplant hypertension. Furthermore, there was no relationship between angio-tensinogen genotype and graft survival during the course of the study. CONCLUSIONS: These findings do not support the hypothesis that the M235T variant of the angiotensinogen gene is a risk factor for the development of post-transplant hypertension.

Adult

Pharmacokinetics of methylprednisolone and rejection episodes in kidney transplant patients.

Rejection crises after kidney transplantation could be associated with individual variability of pharmacokinetic parameters of steroids. We therefore investigated the individual pharmacokinetics of methylprednisolone on day 2 (60 mg intravenously) and day 4 (60 mg per os) in 40 patients after kidney transplantation. Methylprednisolone was determined in serum by HPLC. Within 6 months, all rejection episodes were recorded and confirmed by kidney transplant biopsy. Values are given as nonparametric medians with the 95% confidence interval (0.95 CI). The 7 patients with a rejection within the first 10 days had a methylprednisolone clearance of 437 ml/min (162-756) that was significantly higher than the 220 ml/min (121-604) in the 22 patients without a rejection episode (P = 0.04). In the complete group of 18 patients having a transplant rejection episode within 6 months, the methylprednisolone elimination half-life after oral dosage was 2.5 hr (1.6-3.9) and significantly shorter than 2.9 hr (1.7-4.0) in 22 patients without rejections (P = 0.03). No differences were seen for body weight, number of mismatches, cold ischemia time, immunosuppressive regimens, and other pharmacokinetic parameters of methylprednisolone (e.g. bioavailability, distribution volume, trough levels). We conclude that pharmacokinetic variability may contribute to the lack of immunosuppressive efficacy in patients with a short halflife of steroids. Therefore, a twice daily dose fraction might be useful for low-dose steroid regimens in kidney transplantation.

Adolescent

Impact of de novo membranous glomerulonephritis on the clinical course after kidney transplantation.

Besides rejection-induced transplant glomerulopathy de novo membranous glomerulonephritis (MGN) is the most frequent cause of nephrotic syndrome after renal transplantation. We evaluated 1029 renal transplantations (271 without and 758 with cyclosporine treatment), performed on 848 patients between 1970 and 1992, which resulted in 872 functioning grafts. De novo MGN was seen in 30 biopsy specimens from 21 patients (about 2%), of whom 10 had received immunosuppressive treatment without and 11 with cyclosporine. Taking into account the longer periods of observation of patients without compared with those with cyclosporine treatment (88 +/- 60 vs. 41 +/- 31 mo., respectively, P = 0.001), the two treatment groups did not differ significantly in prevalence of de novo MGN (4.0% vs. 1.5%). De novo MGN was diagnosed by biopsy 62.7 +/- 44.4 mo. after transplantation; its incidence increased significantly with time (from 0% to 5.3% over 8 years; 95% confidential interval: 1.7-8%). Proteinuria (mean, 3.2 +/- 2.9 g/L) was first observed 47.5 +/- 51.3 mo. after transplantation. Thirteen of the 21 patients (62%) were nephrotic (proteinuria, over 1.5 g/L). Steroid pulses were given to 12 patients with de novo MGN and high proteinuria, which did not decline after treatment. Signs of chronic viral infection (hepatitis B antigen, hepatitis C antibody, or human immunodeficiency virus antibody) were found in 8 of the 21 patients (38%). Signs of vascular or interstitial rejection were seen in 17 and 12 of the 21 patients with de novo MGN, respectively, and cyclosporine arteriolopathy was diagnosed in four. Graft loss occurred in 14 of the 21 patients and was due to rejection in 13 and to de novo MGN in only one, who developed additional transplant vein thrombosis. Patients with de novo MGN did not differ significantly from the other 851 patients in graft survival (71.4 +/- 9.9% vs. 60.8 +/- 2.2% after 5 yr). De novo MGN is a late, often asymptomatic, complication of initially well tolerated grafts and is neither prevented by cyclosporine treatment nor reversed by further steroid medication. It is often associated with vascular changes caused by rejection or cyclosporine toxicity.

Adult

Ileal conduit urinary diversion 16 months before renal transplantation in a case of non-functioning lower urinary tract.

The case history of a cadaveric kidney graft recipient with complete non-functioning of the lower urinary tract is reported. An ileal conduit was formed 16 months prior to transplantation. The graft ureter was implanted into the conduit without any problems, graft functioning was excellent, and no surgical, metabolic, or infectious complications occurred during the 18-month follow-up period.

Adult

Rescue of renal transplants with distal ureteral complications by pyelo-pyelostomy.

Secondary ureteroneocystostomy is the procedure most commonly used for repair of ureteral stenosis or necrosis in renal transplant patients. However, when the transplant ureter available for reconstruction is too short, ureteropyelostomy is the standard procedure. Another option is pyelo-pyelostomy, which has been used infrequently to date. Between 1979 and 1988 we managed 6 patients (4 men and 2 women 42 to 62 years old) with renal allografts who required repair of the transplant ureter for long segmented ureteral necrosis (3), long segmented ureteral stenosis (2) and an iatrogenic lesion of the ureter (1) with pyelo-pyelostomy. Of the 6 patients 2 had undergone previous rescue operations. Pyelo-pyelostomy with the renal pelvis of the graft was performed as first described by Gil-Vernet and Caralps in 1968. Median followup was 6 years (range 3 to 12 years). Two patients died of chronic rejection and pulmonary embolism, respectively. Four patients are still alive with functioning transplants and serum creatinine levels of less than 210 mumol/l. According to our experiences with 6 patients, we believe that pyelo-pyelostomy is a promising rescue maneuver that is worth consideration in cases of total or subtotal ureteral necrosis and long segmented ureteral stenosis after renal transplantation.

Adult

Long-term effects of steroid withdrawal in kidney transplantation.

The long-term graft function after withdrawal of steroids from maintenance immunosuppression was analyzed in 98 kidney recipients (59 on cyclosporin monotherapy, 39 on cyclosporin plus azathioprine) who had not developed an early rejection episode when prednisolone was discontinued. Seven years after steroid withdrawal the probability of an increase in serum creatinine (> 20% of baseline levels) was 51%. The increase in creatinine was associated with sclerosing arteriopathy as a marker of chronic rejection in 29 of 43 graft biopsies. The addition of azathioprine had no effect on the stability of long-term graft function and did not influence the 7-year graft survival rate in this highly selected group of patients.

Azathioprine

Hygroma renale: pararenal lymphatic cysts associated with renin-dependent hypertension (Page kidney). Case report on bilateral cysts and successful therapy by marsupialization.

A total of 42 cases of large symptomatic parapelvic or pararenal lymphatic cysts has been reported since 1890, of which 54% were associated with hypertension and 14% were bilateral. We report on a patient in whom during a 3-month period abdominal pain and distention developed successively on both sides associated with hypertension. Initially, ultrasound and computerized tomography revealed a large multicystic pararenal lymphatic mass on the right side and small parapelvic hilus lesions on the left side. Two months after resection and marsupialization of the large cyst on the right side the small hilus lesions on the left side developed into large pararenal cysts requiring the same therapeutic measures. Hypertension was reversible after surgery in both instances; at the second operation high preoperative and lower postoperative renin activity, active renin, total renin, aldosterone and atrial natriuretic factor in plasma were noted. Immunoreactive active and total renin levels in the lymph fluid were elevated, a finding that may be explained by the renal origin of the lymph. Marsupialization is a kidney preserving measure that reverses all symptoms of large pararenal cysts, including Page kidney hypertension.

Adult

The effect of cyclosporine on the progression of human immunodeficiency virus type 1 infection transmitted by transplantation--data on four cases and review of the literature.

Two women and two men were infected with the human immunodeficiency virus type 1 (HIV-1) transmitted by renal transplantation from i.v. drug-addicted donors in 1984. The four recipients were treated with cyclosporine and methylprednisolone (one patient only for three months because of early graft failure). Two patients died 66 and 74 months after transplantation, one of endocarditis and one of cerebral hemorrhage. Despite several infections including urinary tract infection (n = 8), peritonitis (n = 1), shunt infection (n = 1), bronchitis (n = 1), salmonellosis (n = 1), herpes stomatitis (n = 2), herpes zoster (n = 1), and cytomegalovirus (n = 1), and despite treatment of several rejection episodes (n = 8), none of them had or has infections typical of the acquired immunodeficiency syndrome (AIDS). However, two patients developed cervical lymphadenopathy and one autoimmune thrombocytopenia 15-20 months after HIV-1 infection. Their T helper cell counts (355/microliters to 75/microliters) and helper/suppressor T cell ratios (1.0-0.2) are distinctly lowered. One patient has membranous glomerulopathy with virus-like particles within and on the outside of the basement membrane and tubuloreticular inclusions in glomerular endothelial cells. We evaluated the case reports of 53 patients with HIV-infection caused by an infected transplant or by blood transfusions during or shortly after transplantation. The cumulative incidence of AIDS was significantly lower in 40 transplant patients with an immunosuppressive regimen including cyclosporine than in 13 transplant patients receiving immunosuppressive treatment without cyclosporine (5-year cumulative risk of AIDS: 31% versus 90%, P = 0.001).

Acquired Immunodeficiency Syndrome

Analgesic nephropathy and renal transplantation.

Analgesic nephropathy was the most frequent diagnosis in 324 haemodialysis patients (30%) and the second most frequent diagnosis in 900 transplant patients (17%) at the Klinikum Steglitz, Berlin. Analgesic patients were the oldest group among haemodialysis and transplanted patients; the analgesic patients on haemodialysis were significantly older than the transplanted analgesic patients (55.9 +/- 11.2 versus 50.5 +/- 7.5 years, P = 10(-6)). Patient and graft survival under cyclosporin treatment are not statistically different in 125 transplantations of 109 patients with analgesic nephropathy compared to 508 transplantations of 423 patients with other renal diseases (5-year patient survival, 83.3 +/- 5.1% versus 88.4 +/- 2.4%; 5-year graft survival, 53.5 +/- 7.4% versus 56.8 +/- 3.8%; NS). Acetaminophen in urine was found in two of 30 analgesic and in one of 54 other patients with a functioning transplant (6.7% versus 1.9%; NS). As a sign of compliance, the mean cyclosporin trough level of 17 patients with analgesic nephropathy did not differ significantly from that of 14 patients with polycystic kidney disease (136.4 +/- 16.4 versus 139.4 +/- 17.3 ng/ml; NS), nor did the mean standard deviation of the individual measurements (36.7 +/- 36.8 versus 27.5 +/- 20.7 ng/ml; NS). Urothelial carcinoma was significantly more frequent in patients with analgesic nephropathy than in those with other renal diseases despite cystoscopy and retrograde pyelography before transplantation (3.7% versus 0.32%; P = 0.001). Vascular disease was the cause of death in 19 of 44 analgesic transplant patients who died (43.2%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Recurrent and de novo renal disease after kidney transplantation with or without cyclosporine A.

We evaluated the clinical course of 700 renal transplantations, including 1,305 transplant histologies performed in 611 patients between 1970 and 1988, to estimate the influence of cyclosporine A (CsA) after kidney transplantation on the incidence of recurrent or de novo renal disease. Primary renal disease recurred in 11 of 583 functioning transplants (1.9%) with transplant loss in seven patients (1.2%): focal segmental glomerulosclerosis (FSGS, three patients); membranous glomerulonephritis (GN, one patient); mesangiocapillary GN (one patient); rapidly progressive IgA nephropathy (one patient); hemolytic-uremic syndrome (HUS, three patients); and oxalosis in two transplants (one patient). De novo renal disease occurred in six patients (1.0%), including mesangiocapillary GN type I (three patients); nonpurulent focal GN in septicemia (one patient); HUS (one patient); and nodular glomerulosclerosis in steroid diabetes (one patient). De novo membranous GN was seen in 14 additional cases (2.4%). No statistically significant difference could be established between the treatment groups without (n = 225) and with (n = 358) CsA in recurrent and de novo renal disease (n = 7/225 v 10/358, NS); in recurrent and de novo GN (n = 4/225 v 6/358, NS); in recurrent FSGS (n = 1/7 v 2/8, NS); in recurrent and de novo HUS (n - 1/1 v 2/7, NS); and in de novo membranous GN (n = 7/225 v 7/358, NS). Transplant loss by recurrent and de novo GN was higher without than with CsA (n = 4/4 v 1/6, P = 0.004). On the basis of our investigation, we conclude that recurrent and de novo renal disease in the transplant occur rarely and are not prevented by CsA. However, even if the incidence of transplant GN is unchanged by CsA treatment, its clinical course seems to be mitigated. CsA treatment also does not increase the incidence of HUS.

Adolescent

Effects of diltiazem upon metabolism and immunosuppressive action of cyclosporine in kidney graft recipients.

It is widely believed that calcium antagonists such as diltiazem exert immunosuppressive effects in kidney graft recipients--however, the mechanism is unclear. In a randomized controlled trial, kidney graft recipients who received diltiazem during transplantation and for an average of 12 months thereafter experienced significantly fewer rejection episodes than patients treated with cyclosporine and steroids alone. Furthermore, 1-year (97% vs. 85%) and 4-year (80% vs. 70%) graft survival rates were higher in diltiazem-treated patients, but the difference was not statistically significant. In vitro, diltiazem had little immunosuppressive activity. Concentrations of diltiazem which blocked the proliferation of PHA-stimulated human peripheral blood mononuclear cells, or prevented activation-associated accumulation of interleukin-2 mRNA, or p50- and p70-IL-2 receptor mRNA exceeded pharmacological concentrations by more than 100-fold. Both, CsA and high doses of diltiazem caused an increase of IL-6 mRNA. In contrast to these findings, the IL-6 plasma concentrations were comparable in both groups, whereas the serum concentration of soluble IL-2 receptors was decreased in patients treated with diltiazem. Administration of diltiazem caused an alteration of CsA metabolism. The whole-blood concentration of CsA metabolite 17 was significantly increased in diltiazem-treated patients, resulting in a five-times-higher concentration of this metabolite in the cellular blood compartment compared with the parent drug. Changes in metabolites 1, 8, and 18 levels were less pronounced. Although direct immunosuppressive properties of diltiazem are unlikely, diltiazem could support immunosuppression by altering CsA metabolism, and promoting accumulation of certain metabolites.

Adult

Plasma exchange and hemoperfusion in iodine-induced thyrotoxicosis.

Iodine-induced thyrotoxicosis is a life-threatening disease. Plasma exchange and hemoperfusion are the available means of detoxication. Both methods were applied repeatedly to 4 patients with iodine-induced thyrotoxicosis, and the efficacy of these treatment methods was compared. Thyroxine plasma levels were decreased by 33%, while the calculated body stores were reduced by 18% during plasma exchange. Hemoperfusion was less effective. With both methods, a rebound of plasma levels was seen. Improvement of the clinical condition was delayed for 1 week after discontinuation of treatment. One patient died, probably because detoxication was discontinued too soon after the thyroid hormone levels had normalized. Plasma exchange by using albumin (120 g/4,000 ml = 30 g/l) as replacement fluid is superior to that by using fresh-frozen plasma (2,000 ml/4,000 ml), since less thyroxine is administered (19 vs. 160 nmol).

Aged