Georg Biesenbach

Progression of macrovascular diseases is reduced in type 1 diabetic patients after more than 5 years successful combined pancreas-kidney transplantation in comparison to kidney transplantation alone

Recent reports have demonstrated an improved cardiovascular outcome after simultaneous pancreas‐kidney transplantation (SPKT) compared with kidney transplantation alone (KTA) in type 1 diabetic patients with end‐stage renal disease. The purpose of this study was to determine the impact of SKPT and KTA on the progression of cerebrovascular disease (CVD), coronary heart disease (CHD) and peripheral vascular disease (PVD) 5 and 10 years after transplantation. Only patients with graft survival more than 5 years, were included in this study. In summary, 12 type 1 diabetic patients with SPKT and 10 diabetic subjects with KTA were evaluated. The immunosuppressive therapy was similar in both patient groups. The mean observation period was 124 (72–184) months in the SPKT group and 122 (64–216) months in the group with KTA. To investigate the vascular risk profile we examined mean HbA1c, blood pressure and lipid levels in both patient groups during the first 5 years (period I) and the second 5 years (period II) after transplantation (measurements at least at 3‐month intervals). Additionally, we evaluated the prevalence of moderate (stage I–II) and severe (stage III–IV) macrovascular diseases prior as well as 5 and 10 years after transplantation. During period I the mean HbA1c‐value was 5.7 ± 0.4% in the group with SPKT versus 7.4 ± 0.8% in the KTA group, and in period II 5.8 ± 0.4% in the SPKT group versus 7.6 ± 0.9% (P < 0.001) in the patients with KTA. The cholesterol levels were approximately the same in both groups, the triglycerides were lower in the patients with SPKT than in the subjects with KTA with 1.3 ± 0.4 vs. 2.2 ± 0.9 mmol/l in period I, and 1.4 ± 0.5 vs. 2.3 ± 0.6 mmol/l in period II (P < 0.05). The BP‐values were similar in both groups. Five years after transplantation the prevalence of vascular diseases was not significantly different between both groups. During the following 5 years the prevalence of macrovascular diseases increased more in the KTA than in the SKPT group. After a mean observation period of 10 years the SKPT group showed a lower prevalence of vascular diseases (stage I–IV) with 41% CVD, 50% CHD and 50% PAV in comparison to the KTA group with a prevalence of 80% CVD, 90% CHD and 80% PAV), the difference was not statistically significant because of the small patient groups. The frequency of the vascular complications myocardial infarction (16% vs. 50%), stroke (16% vs. 40%) and amputations (16% vs. 30%) was in summary significant lower in the patients with SPKT than in the patients with KTA (P < 0.05). In conclusion, while for the first 5 years after transplantation the progression of macroangiopathy in patients with SPKT and KTA was not significantly different, after a mean 10‐year observation period the progression of macrovascular diseases was significantly lower in recipients with a functioning SPKT compared to patients with a KTA; this can be explained by a better vascular risk profile after SPKT. The 10‐year patient survival was 83% in the SPKT group and 70% in patients with KTA.

Improvement in prognosis of patients with acute renal failure over a period of 15 years: an analysis of 710 cases in a dialysis center.

In order to evaluate the changes in causes and outcome of acute renal failure (ARF) during the years 1975-1989, 710 patients treated in our dialysis center were analyzed. We compared the etiology, the severity and catabolic state of ARF, the techniques of renal replacement therapy, which were employed and the ages and mortality rates of these patients, who received dialysis therapy during the years 1975-79 (n = 227), 1980-84 (n = 240) and 1985-89 (n = 243). The number of postoperative, posttraumatic and non-traumatic cases of ARF was approximately the same in all three 5-year periods, only the frequency of postrenal failure decreased from 7% in the years 1975-79 to 3% in the years 1985-89. The incidence of sepsis as a major cause of ARF and the most important risk factor was comparably high in the surgical and medical patients during all of the periods, but it increased in the traumatic patients from 7% in the years 1975-79 to 28% during the last 5-year period. The prevalence of respiratory failure and jaundice as additional organ failures, the severity of ARF (oligonanuric-nonoliguric) and the metabolic state were not different in the three patient groups. The magnitude of rise in serum creatinine before the start of renal replacement therapy was significant lower in the last 5-year period in comparison to the years 1975-79 (p < 0.05). Hemodialysis was the treatment in choice of 98 and 93% of the cases during the first two periods, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Augmentation Index and Large-Artery Remodeling in Patients with Longstanding Rheumatoid Arthritis Compared with Healthy Controls

OBJECTIVE There is growing evidence of premature atherosclerosis in patients with rheumatoid arthritis (RA), leading to a higher rate of cardiovascular events than in the general population. The augmentation index (AIx), a marker of arterial stiffness, is an indicator of vascular function. The aim of the study was as follows: (1) to investigate whether AIx is increased in RA patients without traditional cardiovascular risk factors and (2) to evaluate whether there is an interrelationship with large artery remodeling as ascertained by carotid ultrasound. METHODS Thirty-six RA patients (age, 46.4 +/- 7.7 years; 31 female) were recruited. Patients were eligible for analysis if they had no traditional cardiovascular risk factors. AIx was assessed noninvasively during pulse wave analyses. For large artery remodeling the intima-media thickness (IMT) was measured in both common carotid arteries with ultrasound. Results were compared with 36 age- and sex-matched controls. RESULTS AIx was statistically significantly higher in RA patients as compared with controls (27.4 +/- 9.4% versus 18.4 +/- 9.0%; P < 0.001). In addition, IMT was significantly higher in RA patients (0.73 +/- 0.16 mm versus 0.65 +/- 0.12 mm; P = 0.01). In RA patients there was a positive correlation between IMT and AIx (r[IMT; AIx] = 0.45; P = 0.008). CONCLUSION AIx, a marker of arterial stiffness, as well as IMT, a marker of large-artery remodeling, are increased in RA patients without traditional cardiovascular risk factors. Measuring AIx might assist in better assessing the increased cardiovascular risk in RA patients.

Bilateral Nephrectomy: the Best, but Often Overlooked, Treatment for Refractory Hypertension in Hemodialysis Patients

Bilateral nephrectomy for treatment of refractory hypertension in chronic hemodialyzed patients has been infrequently carried out. We analyzed the benefits of this operation on blood pressure, clinical state, drug treatment, and quality of life. In 10 hemodialyzed patients with refractory hypertension, systolic (SBP) and diastolic (DBP) blood pressure were measured 1 month before nephrectomy bilateral and 3, 6, 9, and 12 months after. In addition, the use of antihypertensive drugs before and after surgery was evaluated. Four patients had SBP and DBP values characteristic of malignant hypertension. In all 10 patients hypertension responded neither to reduction of plasma volume by ultrafiltration nor to multiple antihypertensive drug therapy. Hypertensive crises were associated with cerebral hemorrhage in two patients, severe encephalopathy with persistent neural dysfunction in one patient, and encephalopathy and diplopia in another. Three months after bilateral nephrectomy blood pressure decreased significantly (P < .005) and was normal in nine patients. In one noncompliant patient with intradialytic body weight increases of nearly 10%, blood pressure was still elevated. Malignant or drug-resistant hypertension with hypertensive crises is an indication for bilateral nephrectomy. The clinical state and quality of life improved in all patients in the present study and antihypertensive treatment is no longer necessary.

Incidence of acute oligoanuric renal failure in dextran 40 treated patients with acute ischemic stroke stage III or IV

Two hundred eleven patients with acute ischemic stroke, stage III or IV, received daily intravenous infusion of 500-1000 mL low-molecular dextran (dextran 40) over a period of 4 days. In 10 cases (4.7%) acute renal failure, associated with dextran infusion, could be observed; oligoanuria occurred after a mean time of 4 (3-6) days. The incidence of dextran-induced acute renal failure was significantly higher in patients with a preexisting reduction of glomerular filtration rate below 30 mL/min/1.73 m2 (p < 0.005). Five of the patients (50%) with acute renal failure died within 4-12 days after the hemodilution therapy with dextran 40; this high lethality was due to nonrenal complications.

Augmentation index in patients with rheumatoid arthritis and ankylosing spondylitis treated with infliximab

Premature atherosclerosis is linked to inflammation. Arterial stiffness is a marker of vascular dysfunction. We tested the hypothesis that treatment with infliximab, which is effective in reducing inflammation in rheumatoid arthritis (RA) and ankylosing spondylitis (AS), also lowers the augmentation index (AIx) in patients with active disease. We also analyzed the subendocardial viability ratio (SEVR), which is a measure of myocardial perfusion relative to cardiac workload. Included in the study were 30 patients (17 RA, 13 AS). Conventional treatment failed in all patients. The AIx and SEVR were determined by radial applanation tonometry before and after treatment with infliximab, at baseline and at week 7. After treatment with infliximab, Disease Activity Score for 28 joints (RA patients), Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index (AS patients), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) improved significantly (p < 0.001). The AIx for all patients increased from 22.0 ± 14.0% to 24.6 ± 13.0% (p = 0.03). The increase in the RA sub-group (p = 0.01) was also significant. The SEVR decreased from 148.6 ± 23.7% to 141.2 ± 23.7% (p = 0.04). Infliximab did not reduce the AIx in patients with RA and AS, although there were clinical improvements and CRP and ESR decreased. Instead, the AIx increased. This could negatively influence cardiac workload.

The place of methotrexate perioperatively in elective orthopedic surgeries in patients with rheumatoid arthritis

No clear consensus exists on whether methotrexate (MTX) should be continued or whether this therapy should be discontinued for a few weeks in patients with rheumatoid arthritis (RA) undergoing surgery. Continued MTX therapy may impair wound healing, but discontinuation of the therapy may increase the risk of flares. In this article we review published data on the perioperative management of MTX in patients with RA undergoing elective orthopedic surgery. Eight papers on this topic could be identified. These studies compare continued vs. discontinued MTX therapy or MTX therapy vs. therapies other than MTX. Summing up the published data, continued MTX therapy appears to be safe perioperatively and seems also to be associated with a reduced risk of flares. None of the examined papers addresses the issue of safety in connection with comorbidities, age or high doses of MTX.

PERINATAL COMPLICATIONS AND THREE-YEAR FOLLOW UP OF INFANTS OF DIABETIC MOTHERS WITH DIABETIC NEPHROPATHY STAGE IV

The objective of the study was to evaluate differences in the perinatal complications and in the 3-year follow up of infants of diabetic mothers with and without diabetic nephropathy stage IV. We compared the fetal and maternal complications and the early postpartal development until 3 years after delivery in 10 children of nephropathic diabetic mothers and 30 children of diabetic mothers without nephropathy. The mean (± SD) birthweight of the infants of nephropathic women was 2250 ± 496 g versus 3544 ± 435 g in the women without nephoropathy (p < 0.01). Births were premature in six pregnancies (60%) of the nephrotic women but in none of the women without nephropathy (p < 0.01). Three infants (30%) of the women with nephropathy showed respiratory distress syndrome in contrast to two babies (6%) of the women without nephropathy. Pre-eclampsia or eclampsia occurred in 6 (60%) pregnant women with and in two women (6%) without diabetic nephropathy (p < 0.01). Nephrotic syndrome was observed in 7 nephrotic women (70%) in contrast to none women without nephropathy. Three years postpartum, six of the children (60%) of nephropathic women had a body weight < the 50th percentile but none of the children of the women without nephropathy did so (p < 0.01). In addition, the children of nephropathic mothers started to speak significantly later (15 ± 3 versus 12 ± 3 months postpartum, p < 0.05) and had infectious diseases more commonly (60% versus 6%, p < 0.01) than the children of women without nephropathy. It can be concluded that in pregnancies of diabetic women the birth weights of the infants are significantly smaller and the fetal as well as maternal complication-rates significantly higher than in those of women without nephropathy. Also 3 years after delivery, the body weight of the children of nephropathic diabetic women is significantly lower than that of children of diabetic women without nephropathy. Additionally, children of nephropathic women are retarded in terms of linguistic development and their resistance to infections is reduced.

Hypocalcemic tetany in the newborn as a manifestation of unrecognized maternal primary hyperparathyroidism

ZusammenfassungEin primärer Hyperparathyreoidismus in der Schwangerschaft tritt sehr selten auf und ist mit einer erhöhten mütterlichen und kindlichen Morbidität und Mortalität verbunden. Wir präsentieren einen Fall, bei dem eine hypokalzämische Tetanie des Neugeborenen – bedingt durch einen passageren Hypoparathyreoidismus im Kind – letztendlich zur Entdeckung eines nicht diagnostizierten primären Hyperparathyreoidismus der Mutter führte. Eine offensichtlich gesunde 30-jährige Frau hatte eine unauffällige Schwangerschaft und Geburt. Am fünfzehnten postpartalen Tag entwickelte das Neugeborene eine hypokalzämische Tetanie. Nach Gabe von Vitamin D und Kalzium sistierten die Krämpfe und die weitere Entwicklung des Kindes war völlig normal. Die weitere Evaluierung der Mutter führte zur Diagnose eines maternalen primären Hyperparathyreoidismus. In der Folge wurde ein Adenom an der rechten unteren Nebenschilddrüse entfernt. Die Suche nach den Ursachen einer Hypokalziämie bei Neugeborenen soll sich nicht nur auf den betroffenen Patienten beziehen. Die Untersuchung der offensichtlich gesunden Mutter und der multidisziplinäre Zugang können sowohl dem kleinen Patienten als auch der Mutter Genesung erbringen.SummaryPrimary hyperparathyroidism (PHP) during pregnancy is a very rare event that increases maternal and perinatal morbidity and mortality. We present a case in which hypocalcemic tetany of the neonatal infant – caused by transient hypoparathyroidism in the child – finally revealed asymptomatic maternal PHP. An apparently healthy 30-year-old woman had an uneventful pregnancy and delivery. On the 15th postpartal day, the newborn developed hypocalcemic tetany. After receiving supplementation of calcium and vitamin D, the child developed without further pathological findings. Laboratory and radiological studies in the mother led to a diagnosis of maternal PHP. An adenoma of the right lower parathyroid gland was subsequently removed. The search for the cause of hypocalcemia in a newborn should not focus on the patient alone. Examining the apparently healthy mother and approaching the case in a multidisciplinary fashion may benefit both the child and the mother.

Long-term impact of chronic hemodialysis on glycemic control and serum lipids in insulin-treated type 2-diabetic patients.

There are only a few data in the literature concerning metabolic control in insulin-treated diabetic patients with end stage renal disease (ESRD). The aim of the study was to find out the long-term impact of hemodialysis on glycemic control and lipid values in type 2 diabetic patients. Twenty insulin-treated type 2 diabetic patients (age 62 ± 9 years, f:m = 6:14) were evaluated. We compared HbA1c, fasting blood glucose (FBG), body weight, serum lipids, insulin requirement, and blood-pressure (BP) 12 and 6 months before dialysis, at the start of dialysis, and 6 as well as 12 months after the start. Results: The mean HbA1c- and FBG-values were not significantly different before and after the start of dialysis therapy. The average insulin requirement was 26 ± 10 IU/day in the predialysis period, 25 ± 12 IU/day at the start, and 24 ± 13 as well as 22 ± 13 IU/day after the start of dialysis. The mean cholesterol level fell significantly from 199 ± 63 and 190 ± 49 mg/dL in the predialysis phase to 167 ± 62 and 157 ± 38 mg/dL after dialysis began. The triglyceride concentrations decreased only slightly after the start of dialysis. The incidence of hypoglycemia (n/patient/month) was markedly lower in the predialysis phase (0.4 vs. 0.6, NS) than after start of dialysis. In patients with residual diuresis (< 500 mL urine/day) the needed insulin doses decreased significantly by 29% compared to patients with higher residual diuresis, whose insulin requirement remained unchanged. In summary, hemodialysis had no significant long-term effect on glycemic control in insulin-treated type 2 diabetic patients, but incidence of hypoglycemia tended to be higher under hemodialysis than in the predialysis period. Lipid levels tended to be lower after the initiation of dialysis therapy. Insulin requirement under hemodialysis decreased only in patients with loss of residual urine volume (below 500 mL urine/day).