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Biomedical subjects

B Grabensee

Publications and source records attributed to B Grabensee.

At least 19 recordsLinked to original sources

Intravenous iloprost: a new therapeutic option for patients with post-transplant distal limb syndrome (PTDLS).

The purpose of this study was to investigate the application of intravenous iloprost as a novel therapy for the treatment of post-transplant distal limb syndrome (PTDLS). PTDLS is a benign but disabling complication in the first year after renal transplantation. It is characterized by bilateral, often incapacitating pain in the feet and or knees on motion and a significant rise in alkaline phosphatase levels on laboratory evaluation. On MRI, bone marrow edema of the affected bone regions can be demonstrated. PTDLS differs from steroid induced osteonecrosis of the hip in terms of localization, an average cumulative steroid dosage within expected limits, and a benign outcome, as PTDLS does not progress to overt cell necrosis. From August 2003 to April 2005 we treated 10 patients with MRI-proven diagnosis of PTDLS following a standardized regimen of intravenous iloprost over 5 days. Iloprost led to prompt pain relief measured on a visual analogous scale (VAS) ranging from 1 to 10 (5.6 +/- 1.5 before vs. 2.1 +/- 1.3 after treatment, p = 0.0004). PTDLS represents a benign but disabling complication following renal transplantation. Intravenous iloprost might be a promising therapeutic concept leading to a quick relief of symptoms without relevant side effects.

Adult↗

Renovascular disease: a review of diagnostic and therapeutic procedures.

The clinical importance of renovascular disease, atherosclerotic or of other origin, arises from the fact, that renal artery stenosis (RAS), if hemodynamically significant (> 70% diameter reduction), induces arterial hypertension, renal insufficiency or both. The prevalence of RAS rises with increasing age and with the presence of atherosclerosis of the aorta, carotid, coronary and peripheral arteries. Typical clinical symptoms, as uncontrolled hypertension or renal dysfunction in the absence of pathological urinary findings, are helpful to select patients for further screening methods: We see a prominent role of color duplex sonography as a screening procedure. Intra-arterial angiography remains gold standard for the diagnosis of RAS. The major problem in daily clinical practice is the differentiation between patients in which hypertension and kidney function can be improved or normalized by removal of RAS and those with ''fixed'' hypertension and irreversible kidney dysfunction and therefore to decide if it is worth while to perform invasive treatment as angioplasty or surgery. In this setting, the proof of hemodynamic significance is essential and is indicated especially when the stenosis has a diameter reduction of < 50-70% only. Methods proving a critical stenosis are intra-arterial measurement of the pressure gradient, measurement of differential renal vein renin and duplex sonography. In addition, predictors of treatment outcome should be considered. Studies analyzing if patients improve with blood pressure and kidney function after removal of RAS have shown that high grade stenosis and/or very high blood pressure indicate a good outcome. Further prognostic factors are the absence of parenchymal disease and/or positive functional test. In the presence of a critical stenosis in a patient with a clear clinical problem with hypertension and/or renal dysfunction a positive effect of invasive treatment seems warranted despite the risks that must be considered as well in angioplasty as in surgery. The selection for the type of invasive treatment requires a clarification of the treatment goals in the individual patient, the evaluation of the morphology and localization of the stenosis as the presence of other vascular disease (aortic aneurysm, peripheral artery disease etc.) and the assessment of the risk according to the type of intervention.

Decision Trees↗

Biocompatibility parameters in in-vitro simulated automated versus continuous ambulatory peritoneal dialysis.

BACKGROUND: In peritoneal dialysis, the usage of automated peritoneal dialysis (APD) has been steadily increased. As APD means larger volumes of solution and more frequent contact times with fresh dialysate, an additive negative impact on biocompatibility data, exceeding the known effect of conventional PD fluids, seems possible. For an in-vitro comparison of APD and CAPD, a new cell culture system has recently been established. METHODS: A double chamber cell culture system with human mesothelial cells on top of a permeable membrane and growth medium beyond was used for mimicking CAPD and APD. Reflecting the in vivo equilibration pattern, we compared an eight-hour CAPD with a CCPD setting, using a conventional PD solution. Cell viability was assessed with a MTT assay and cell function via constitutive and stimulated IL-6 release. CA125 was measured as a parameter of mesothelial cell integrity, and TGF-1beta was measured as an index of induction of fibrosis. RESULTS: Both the CAPD and the CCPD mode resulted in a significantly lower MTT assay and stimulated IL-6 release compared to growth medium. TGF-1beta and CA125 release did not differ between the PD modes and control. The CAPD and the CCPD mode itself did not differ with regard to MTT assay, IL-6 release, TGF-1beta and CA125 generation. CONCLUSION: From the in-vitro model imitating the acute exposure of mesothelial cells with conventional PD fluid in a CCPD and CAPD mode, there is no evidence that APD, due to the larger volumes of solution and more frequent contact times with fresh dialysate, has an acute, additive negative impact on biocompatibility parameters indicative for peritoneal host defense, mesothelial cell integrity and peritoneal fibrosis.

CA-125 Antigen↗

Influence of genetic polymorphisms of the renin-angiotensin system on IgA nephropathy.

BACKGROUND: We evaluated the impact of the three major genetic polymorphisms of the renin-angiotensin system [angiotensinogen (AGT) gene M235T, angiotensin-converting enzyme (ACE) gene-I/D and angiotensin II-type 1 receptor (AT1R) gene A1166C polymorphisms] as risk factors in IgA nephropathy. METHODS: The clinical course of 107 patients with biopsy proven IgA nephropathy followed up for 6.6 +/- 5.8 years was examined. The genetic polymorphisms were determined by PCR amplification. RESULTS: The allele frequencies of the polymorphisms studied were similar in patients and control subjects. AGT-M235T genotype was associated with the presence of nephrotic syndrome (p < 0.05), correlated to the number of antihypertensive drugs agents taken (p < 0.01) and influenced the rate of deterioration of renal function (p < 0.05). Combined analysis of AGT-M235T and ACE-I/D polymorphisms detected an interaction on affecting progression (p < 0.05). ACE-inhibition had a more pronounced effect in certain AGT-M235T and ACE-I/D genotypes (p < 0.05) and their combined analysis showed a synergistic effect (p < 0.01). No association between AT(1)R-A1166C polymorphism and any of the parameters studied was observed. CONCLUSIONS: Our results suggest that angiotensinogen-M235T polymorphism is an important marker of progression in IgA nephropathy in Caucasian patients, especially when analyzed in combination with ACE-I/D polymorphism.

Female↗

Strategies for the treatment of acute renal failure in intensive care units: the aspect of dosing.

Despite all the medical progress, the mortality rate in intensive care units for patients with acute renal failure (ARF) remains high, among specific patient populations, up to 88% [Letourneau I, Dorval M, Belanger R, Legare M, Fortier L, Leblanc M. Acute renal failure in bone marrow transplant patients admitted to the intensive care unit. Nephron Apr 2002; 90 (4), 408-412.]. Recent trial results indicate that patient survival may be improved by adequate renal replacement therapy. In particular, the dose of intermittent and continuous renal replacement therapies has proved to be a significant factor affecting patient survival. Daily intermittent hemodialysis, e.g., is superior to alternate-day intermittent hemodialysis, and with continuous therapies, survival is related to the filtration rate. Further relevant factors include early initiation of renal replacement therapy, choice of biocompatible membranes and the application of bicarbonate-buffered replacement solutions for defined patient groups. The advantages offered by continuous techniques could be demonstrated for individual patient groups; in meta-analyses, advantages were shown for the total population of patients with ARF. Other than for patients with chronic renal failure (NKF-DOQI. Clinical practice guidelines for hemodialysis adequacy. Am J Kid Dis 1997; Vol. 30, 515-566.), there are no current clinical guidelines for a standard treatment of intensive care patients with ARF. Therefore, such a treatment standard still needs to be determined.

Acute Kidney Injury↗

[Gitelman's syndrome: an important differential diagnosis of hypokalemia].

HISTORY AND CLINICAL FINDINGS: A 26-year-old woman presented with fatigue, muscle cramps and weakness. Since the age of 8 years she had moderate hypokalemia of unknown origin that was confirmed on multiple occasions. There was no family history of disease. INVESTIGATIONS: Laboratory tests showed moderate to severe hypokalemia with a serum potassium concentration of 2.7 to 3.0 mmol/l, hypomagnesemia, metabolic alkalosis and pronounced stimulation of the renin-angiotensin-aldosterone system. Despite normal serum calcium levels, urinary calcium excretion was below the detection threshold. Increased natriuresis was observed after administration of furosemide, but not after administration of hydrochlorothiazide. This finding pointed to the presence of a non-functional thiazide-sensitive sodium/chloride cotransporter in the distal convoluted tubule, characteristic for Gitelman's syndrome. Genetic analysis confirmed the diagnosis of Gitelman's syndrome and documented two heterozygous mutations in the gene encoding the sodium/chloride cotransporter. TREATMENT AND COURSE: The patient was treated with 160 mmol potassium and 30 mmol magnesium supplementation per day. Serum potassium was normalized and magnesium serum levels increased. Weakness and fatigue improved markedly. CONCLUSION: Gitelman's syndrome is an important differential diagnosis in the evaluation of the normotensive patient with hypokalemia.

Adult↗

Successful treatment of renovascular hypertension has no effect on insulin sensitivity.

BACKGROUND: The association of insulin resistance (IR) and essential hypertension is well known, but a causal relationship has not been proven. Patients with secondary hypertension as a result of renal artery stenosis (RAS) usually do not reveal IR, but no study has addressed the effect of blood pressure reduction after successful treatment of RAS on insulin sensitivity and glucose effectiveness. PATIENTS AND METHODS: The insulin sensitivity index (SI) and glucose effectiveness (SG) were measured before and after successful intervention of an angiographically proven significant RAS in 18 out of 23 patients (eight males/10 females; mean age 51.5 +/- 13.1 years) in which improvement/cure of arterial hypertension was achieved. After a mean of 10.7 months, patients were reevaluated for 24-h blood-pressure measurement, kidney function, adrenaline, noradrenaline, plasma-renin-activity (PRA), aldosterone, atrial natriuretic peptide (ANP) and cyclic guanosine monophosphate (cGMP), and glucose metabolism parameters such as basal insulin, glucose disappearance constant (K-value), SI and SG. For calculation of SI and SG, insulin and glucose data from the modified frequent sampling intravenous glucose tolerance test (FSIGT) were submitted to the MINMOD program. RESULTS: After intervention, systolic 24-h blood pressure had decreased from 156.1 +/- 16.4 mmHg to 139.9 +/- 15.1 mmHg, and diastolic 24-h blood pressure from 97.1 +/- 14.7 mmHg to 87.3 +/- 13.4 mmHg. No significant change in SI (before 4.3 +/- 2.0, after 4.8 +/- 2.0 min(-1) per microU mL(-1)) or SG (before 1.55 +/- 0.42x10(-2) min(-1), after 1.8 +/- 0.48x10(-2) min(-1)) was observed. Aldosterone decreased from 246.7 +/- 180.7 to 115 +/- 61.4 (P=0.009) as PRA decreased from 12.4 +/- 11.4 to 4.2 +/- 7.6 ng mL h(-1) (P=0.01). Creatinine clearance, and adrenaline and noradrenaline levels as well as ANP and cGMP did not change after treatment for RAS. Subsequent to the definition of IR (SI < or =3.2x10(-4) min(-1) per microU mL(-1)) some differences among these two subgroups (SI < or =3.2, or SI>3.2) could be found. Patients with IR (n=8) were characterized by a higher body mass index (BMI), higher basal insulin values and significantly lower cGMP values. Only the group without IR (n=10) developed significant improvement of systolic blood pressure. CONCLUSION: We conclude that blood pressure reduction by treatment of RAS does not alter insulin action and that there is no link between the circulating concentrations of renin/aldosterone and glucose metabolism in renovascular hypertension (RVH). The results do not support the hypothesis of a direct link between blood pressure in RVH and the individual state of insulin sensitivity. However, patients with a normal SI are more likely to experience an almost normalization of arterial blood pressure after treatment for RAS.

Adult↗

Effect of filtration volume of continuous venovenous hemofiltration in the treatment of patients with acute renal failure in intensive care units.

OBJECTIVE: We evaluated the variable Kt/V, which has become established in the therapy of end-stage renal disease in acute renal failure, to assess the influence of the filtration volume of continuous venovenous hemofiltration on Kt/V. We measured the variables of acid-base balance and uremia control. DESIGN: Prospective interventional pilot study. SETTING: Medical intensive care unit of a university hospital. PATIENTS: Fifty-six patients with acute renal failure and continuous venovenous hemofiltration treatment. INTERVENTIONS: The patients were consecutively treated with a filtration volume of either 1 L/hr (group 1) or 1.5 L/hr (group 2). MEASUREMENTS AND MAIN RESULTS: Patients with a filtration volume of 1.5 L/hr achieved a Kt/V of 0.8 per day, which was significantly higher than in the patient group treated with 1 L/hr (0.53, p <.05). The filtration volume of 1.5 L/hr led to a markedly better control of blood urea nitrogen concentrations, 69.3 +/- 6.6 mg/dL vs. 52.1 +/- 5.2 (p <.05), and to a much quicker and longer lasting compensation of acidosis. Both groups had acidotic pH at the beginning of therapy (group 1, 7.29 +/- 0.02; group 2, 7.29 +/- 0.02, nonsignificant). In group 2, a significantly higher pH value than in group 1 was measured after 24 hrs of continuous venovenous hemofiltration (p < .001; 7.39 +/- 0.02 vs. 7.31 +/- 0.02). The pH values in group 1 did not normalize until after 4 days. The filtration volume of 1.5 L/hr led to a quicker increase in bicarbonate concentrations after 24 hrs of therapy (group 1, 2.8 +/- 3.2 mmol/L; group 2, 6.5 +/- 3.1 mmol/L, p <.001). CONCLUSIONS: The standardized urea clearance Kt/V is a valuable tool in the treatment of acute renal failure. Higher Kt/V levels were associated with a better control of uremia and acid-base balance. However, there were no differences in the clinical course, patient survival, percentage of patients with or without renal failure who were transferred from the intensive care unit, or Acute Physiology and Chronic Health Evaluation III scores.

APACHE↗

Cytokine removal in septic patients with continuous venovenous hemofiltration.

Despite the progress that has been made in intensive care medicine, multiple organ failure is still associated with high mortality. Apart from the prevention of infectious complications, numerous efforts are being made to improve the treatment of sepsis through adequate antibiotic therapy, the development of new respirator therapies, better control of the hemodynamic situation, and adequate renal replacement therapy. Some authors advocate continuous renal replacement therapy not only for acute renal failure but also for the elimination of inflammatory molecules such as cytokines. Continuous renal replacement therapy improves the cardiovascular hemodynamics in patients with multiple organ failure. Therapeutic options such as volume control, clearance of uremic toxins, correction of acid base disturbances and temperature control are improved. Suitable renal replacement therapy improves not only cardiovascular hemodynamics but also patient survival. In current practice, continuous renal replacement therapy is not used to eliminate mediators such as cytokines. In patients with multiple organ failure and compromised cardiovascular hemodynamics, renal replacement therapy should be carried out as early as possible. In the following review, experimental and clinical findings concerning mediator elimination by continuous and intermittent renal replacement therapy are summarized.

Animals↗

Hemodynamically relevant hematuria several months after biopsy of a kidney graft: an unusual cause.

We report the case of a 52-year-old female patient, who after a complicated living donor kidney transplantation, underwent kidney biopsy for suspected rejection. Duplex scanning revealed a small, asymptomatic arteriovenous (AV) fistula which was assessed as being hemodynamically unimportant. During follow-up, several urinary tract infections occurred and recurrent short episodes of hematuria were attributed to cystitis, urethritis and urosepsis. Eight months later, the patient developed suddenly massive hematuria, tamponade of the urinary bladder and hemorrhagic shock as well as urosepsis. Duplex sonography showed a massive pseudoaneurysm in addition to the AV fistula. Arteriography confirmed the Duplex sonographic findings and embolization was performed after treatment of concomitant urosepsis. The fistula was closed completely and bleeding ceased. Although AV fistulas are rare complications of kidney biopsies and in most cases they remain asymptomatic, life-threatening hematuria can present several months after a biopsy due to the development of a pseudoaneurysm. Concomitant infectious complications of the urinary tract, bleeding disorders and other factors can be misleading during the assessment of the cause of gross hematuria. Regular Duplex sonographic follow-up examinations in patients with AV fistulas are advisable.

Aneurysm, False↗

Infection with polyomavirus type BK after renal transplantation.

Tubulointerstitial nephritis caused by polyomavirus of the subtype BK (BK virus nephropathy, BKN) is an important cause of deterioration of renal allograft function after kidney transplantation. In 3 cases of BKN diagnosed at our center, the suspected diagnosis made on the basis of urine cytology and serum PCR was confirmed by electron microscopy and immunohistology of the renal graft biopsy. In 1 patient, stable renal function without further virus detection was seen after reduction of the immunosuppression. In 2 further patients there was loss of graft function. BKN is an important differential diagnosis of unclear deterioration of renal graft function. The risk is particularly high with use of tacrolimus and mycophenolate mofetil (MMF). Urine cytology and serum PCR are suitable screening tests, histology provides conclusive evidence. The only therapeutic option available at present is reduction of immunosuppressive therapy.

BK Virus↗

Operative treatment of renal autonomous hyperparathyroidism: cause of persistent or recurrent disease in 304 patients.

BACKGROUND: Subtotal parathyroidectomy (SPTX) and total parathyroidectomy with autotransplantation (TPTX and AT) are standard procedures in the treatment of renal autonomous hyperparathyroidism. In contrast to primary hyperparathyroidism, the persistence/recurrence rate is reported of up to 12.0%. PATIENTS AND METHODS: Between 1986 and 2000 we operated on 304 patients with renal autonomous hyperparathyroidism including 14 patients who were admitted after a primary operation in an outside hospital. Mean observation period was 51.4+/-38.9 months. RESULTS: The overall persistence/recurrence rate in our patients was 9.0% (26/290). After SPTX, excluding patients with an incomplete operation, it was 3.7%, and after TPTX and AT it was 6.0%. Reasons for developing recurrent or persistent disease in these patients were removal of less than 3.5 glands ( n=12), hyperplastic autograft ( n=5), and supernumerary gland ( n=4). After the first reoperation 7 patients (26.9%) had persistent or recurrent disease. CONCLUSIONS: An incomplete primary operation caused by missed cervical glands was the major reason for persistent ( n=8) or recurrent ( n=4) disease after different operative strategies in renal autonomous hyperparathyroidism.

Adult↗

[Aortoiliac reconstruction after kidney transplantation. Strategies to avoid ischemic damage of the transplant].

INTRODUCTION: The rising life expectancy of patients undergoing kidney transplantation and the improvement in the function rate of the allografts have led to an increasing number of patients suffering from arteriosclerosis-related diseases of the aortoiliac arteries. In these particular cases, an interruption of the blood supply of the allograft is always necessary for operative repair of the aortic and iliac arteries. This means a high risk of ischemic damage to the transplanted kidney. PATIENTS AND METHODS: Between 1987 and 2000, 1,076 kidney transplantations were performed in our department. During this time, 14 reconstructive operations of the aortoiliac arteries were performed in 12 patients (6 women, 6 men, average age 55.2 (45-71) years). Operations were indicated in patients suffering from occlusive disease with imminent extremity or allograft loss, and symptomatic or asymptomatic aneurysms with a maximum diameter of more than 4 cm. In patients presenting with thoracoabdominal (1) and abdominal aortic aneurysms (3), protection of the transplanted kidney was performed by axilloiliac or axillofemoral bypass. Hypothermic flush-perfusion of the allograft containing PGE1 and heparin was performed in seven of nine operations for occlusive disease. RESULTS: None of the patients presented with a permanent decrease in kidney function, six patients showed temporary creatinine elevation, and in nine patients creatinine levels at discharge were lower than they were preoperatively. None of the patients died. CONCLUSION: Reviewing all reported methods of allograft protection, we recommend a three-step strategy including sequential clamp technique (ischemia < 30 min.), hypothermic flush-perfusion (ischemia < or = 60 min.), and temporary axilloiliac/femoral shunt (ischemia > 60 min), depending on the expected renal ischemia time.

Aged↗