Jörg Plum

Results of ultrasound-assisted diagnosis of tunnel infections in continuous ambulatory peritoneal dialysis

The management of catheter-related infections has become a major challenge in continuous ambulatory peritoneal dialysis treatment. Early recognition and discrimination of mere exit site infections from more invasive and catheter menacing tunnel infections (TIs) are of therapeutic importance. As the diagnosis of TI is still based on clinical signs and only indicates advanced infections, we studied the usefulness of the ultrasound examination (UE) of the continuous ambulatory peritoneal dialysis catheter. Examinations were made by a mobile ultrasound unit using a 7.5 MHz transducer. Sixty-two continuous ambulatory peritoneal dialysis patients with an Oreopoulos Zellermann catheter (Oreopoulos-Zellerman Cathete-THWII, Baxter GmbH, Unterschleissheim, Germany) were studied repeatedly between February 1991 and July 1992. Pericatheter fluid collection (with typical sonographic localization) was consistent with surgical findings and histopathologic examination and proved to be a reliable criterion of TIs. The incidence of TIs was significantly higher when using UE (0.35/patient-year) compared with the usual clinical criteria (0.12/patient-year, P < 0.01). Staphylococcus aureus exit site infections were predominant and had the highest risk of concomitant TIs (83%). Eleven of 25 patients with a positive UE lost their catheter due to infectious complications, while no patient with a negative UE underwent operation for infectious reasons (P < 0.01). The peritonitis rate (0.64/patient-year) was markedly increased when UE indicated a TI (1.7/patient-year, P < 0.01). We conclude that sonography is a sensitive tool for the early diagnosis of unsuspected TIs. Sonography is a bedside method used for screening purposes and allows us to control the treatment regimen.

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.

Detection of digoxin, digitoxin, their cardioactive metabolites and derivatives by high-performance liquid chromatography and high-performance liquid chromatography-radioimmunoassay.

High-performance liquid chromatographic (HPLC) systems are described for the separation of the cardioactive metabolites of the digoxin and digitoxin series that are formed by the splitting of digitoxose sugar residues from the aglycone steroid: isocratic separation of digoxin and its cardioactive metabolites; isocratic separation of digitoxin and its cardioactive metabolites; and gradient elution separation of the digoxin and digitoxin series including beta-acetyl- and beta-methyldigoxin. Separations were performed on a 10-microns bonded octadecyl phase column using various mixtures of acetonitrile--water and acetonitrile--methanol--water as the mobile phase. These methods provide high peak resolution and are well suited for collecting elution fractions, e.g. to link up with sensitive immunological measurements. An HPLC-radioimmunoassay method is described for the quantitation of digoxin, digitoxin and their metabolites in human tissues.

Effluent CA 125 Concentration in Chronic Peritoneal Dialysis Patients: Influence of PD Duration, Peritoneal Transport and PD Regimen

In terms of the integrity of the peritoneal membrane in peritoneal dialysis (PD), the peritoneal mesothelial cells play a pivotal role since its monolayer constitutes the first line of the peritoneal membrane. Cancer antigen 125 (CA 125) is released by peritoneal mesothelial cells and correlates with the mesothelial cell mass in PD. Since its effluent concentration is easy to determine in chronic PD patients, CA 125 serves as an in vivo marker of biocompatibility. We performed a cross-sectional study to investigate the relation between PD duration, peritoneal transport and the PD regimen (CAPD/CCPD) on effluent CA 125 concentration in 22 chronic PD patients. We compared long-term (>6 months) with short-term PD treatment, patients with high small solute transport properties (MTAC >11 ml/min, d/p ratio of creatinine >0.72) to patients with low small solute transport and CAPD with APD patients. A peritoneal equilibration test was performed with 1.36% glucose. Dialysate/plasma (D/P) ratio and mass transfer area coefficient (MTAC) of creatinine were calculated and the 4-hour effluent concentration of CA 125 was determined. CA 125 tended to be lower in the long-term PD patients and also in APD patients, but statistical significance was missing. Effluent CA 125 was significantly increased in patients with an MTAC of creatinine >11 ml/min (40.2 ± 11.2 vs. 20.7 ± 1.2 U/ml) and in patients with a d/p ratio of creatinine >0.72 (48.2 ± 11.0 vs. 21.6 ± 1.6 U/ml). CA 125 and the d/p ratio of creatinine were positively correlated (r = 0.68). The positive correlation of CA 125 with peritoneal small solute transport especially in the early phase of PD treatment indicates an initial correlation of the mesothelial cell mass with the peritoneal surface area. A direct relation between the CA 125 concentration and peritoneal transport is unlikely. In our study the CA 125 effluent concentration tended to be lower in long-term PD patients and also in APD patients, possibly indicating a cell depletory influence of the conventional PD fluid.

Prostacyclin Enhances the Expression of LPS/INF-γ-Induced Nitric Oxide Synthase in Human Monocytes

Background: Nitric oxide (NO) is an important mediator of inflammatory processes, including macrophage-mediated cellular host defense, and is found to be increased in peritonitis. The ability of human mononuclear cells to contribute to the NO production by expression of active inducible NO synthase (iNOS) is still discussed controversely. Aims: This study was designed to investigate the influence of prostacyclin receptor (IP receptor) activation on iNOS expression and NO formation in human peripheral blood monocytes. Method and Results: Using reverse transcriptase-polymerase chain reaction, we demonstrated that human monocytes express high levels of IP receptor mRNA. Stimulation of monocytes with the IP receptor selective agonist cicaprost (100 nM) significantly induced cellular cyclic adenosine monophosphate formation, indicating functional coupling of the receptor to Gs. Treatment of cells with lipopolysaccharide (LPS)/interferon gamma (IFN-γ) further enhanced the IP receptor mRNA expression 2.7 ± 0.1-fold above basal levels (n = 6). Analysis of iNOS expression revealed barely detectable mRNA levels in unstimulated monocytes which were increased 3.75 ± 0.3-fold (n = 5) after costimulation with 1 µg/ml LPS and 250 U/ml INF-γ for 16 h. Further increases of iNOS mRNA expression (9.4 ± 0.9-fold above basal, n = 5) were obtained, if the monocytes were costimulated with 1 µg/ml LPS, 250 U/ml INF-γ, and 100 nM cicaprost for 16 h. Measurement of the NO generation correlated with the polymerase chain reaction data: treatment of cells with 1 µg/ml LPS plus 250 U/ml INF-γ increased the NO2 production to 2.6 µM, being above the basal level of 2.0 µM, as determined in the cell culture medium. Additional treatment with 100 nM cicaprost further significantly increased the NO2 production to 3.43 µM. Conclusions: An IP receptor mediated increase in cyclic adenosine monophosphate formation plays an important role in enhancing LPS/IFN-γ-induced iNOS expression in human monocytes/macrophages and may, therefore, contribute to the increased production of NO during peritonitis.

Influence of betaxolol on renal function and atrial natriuretic peptide in essential hypertension.

The hypotensive action of beta-adrenoreceptor blockers is not fully understood, there being a lack of studies focusing on possible relationships between beta-blockers and the secretion of atrial natriuretic peptide (ANP). In 10 patients with essential hypertension, we investigated the influence of betaxolol, a selective beta 1-adrenergic blocking agent, on renal function and on plasma levels of ANP during exercise, volume depletion and volume expansion. Chronic therapy with betaxolol (mean 14.5 mg/day) did not alter glomerular filtration rate and renal blood flow although blood pressure was reduced. Renal vascular resistance decreased from 12795 +/- 1064 dyn/s per cm5 to 10614 +/- 833 dyn/s per cm5 (P less than 0.005). Under betaxolol, basal ANP levels increased from 39 +/- 10 pg/ml to 80 +/- 19pg/ml (P less than 0.01). ANP increased during exercise and volume expansion but was decreased during volume depletion. ANP values observed under betaxolol treatment showed significantly higher values while preserving their dynamic features. We believe that the stimulating effect of betaxolol on ANP may at least partly account for its hypotensive action.

Influence of Uremia on Cell Viability and Cytokine Release of Human Peritoneal Mesothelial Cells

Introduction: There is still no evidence whether human peritoneal mesothelial cells (HPMC) from patients with end-stage renal failure are altered in cell viability or show a different pattern of the release of proinflammatory cytokines. Also the serum of patients with uremia may contain substances stimulating the cytokine release of HPMC. Study Design: The IL-1β-induced IL-6/IL-8 release of HPMC from healthy donors and from patients with end-stage renal disease (ESRD) were measured before the start of chronic peritoneal dialysis (PD) and during PD therapy. Additionally the influence of uremic and non-uremic serum on IL-6 and IL-8 release of normal HPMC was studied. Cell viability was assessed by MTT assay and by the measurement of intracellular ATP (chemoluminescence assay). HPMC were obtained from the following patient groups: (1) non-uremic control patients (n = 7); (2) patients with ESRD undergoing PD catheter implantation for the first time (n = 7), and (3) patients on PD undergoing catheter exchange for noninfectious reasons (n = 6). Pooled human serum from PD patients and normal controls were used for stimulation experiments. HPMC from different donors were grown to confluence (second passage) and then stimulated with IL-1β (1,000 pg/ml in M199) for 24 h. IL-6 and IL-8 concentrations were measured in the supernatant by ELISA. Additionally uremic and non-uremic sera were incubated with HPMC from normal donors for 24 h with a subsequent 24-hour IL-1β stimulation. Mesothelial cell protein mass was determined by the Bradford reagent. Results: Non-uremic patients and ESRD patients did not differ with regard to the global cell viability of HPMC according to MTT assay activity or the intracellular ATP concentration. However, HPMC from uremic patients produced more IL-8 on IL-1β stimulation than the non-uremic controls (group 2, 53.5 ± 15.7 pg/µg; group 3, 70.5 ± 27.3 pg/µg vs. group 1, 24.0 ± 11.8 pg/µg). HPMC from patients on chronic PD additionally released significantly more IL-6 (30.5 ± 13.8 pg/µg) on IL-1β stimulation than uremic patients before the onset of PD (6.2 ± 2.6 pg/µg; p < 0.01). Incubation of normal HPMC with the serum from uremic donors produced an enhanced stimulated IL-8 release compared to the exposition with normal control serum (50.6 ± 6.1 vs. 20.8 ± 2.9 pg/µg; p < 0.01). Conclusion: HPMC from uremic patients more readily release IL-8 on stimulation with IL-1β. On chronic PD treatment IL-6 release was further enhanced. Not further classified serum components in uremia also enhance IL-6 and IL-8 release of HPMC.

Verteilung von Digoxin, Digitoxin und ihren kardioaktiven Metaboliten im menschlichen Herz- und Nierengewebe

SummaryA method was developed for the specific determination of digoxin and digitoxin, as well as their semisynthetic derivatives and dependent cardioactive metabolites, in autopsy samples of heart and kidney.A collective of six patients on long-term treatment with therapeutic doses of β-acetyldigoxin had a mean myocardial digoxin content of 46.1±25.0 ng/g (SD); kidney: 50.3±30.3 ng/g. Digoxigenin bisdigitoxoside represented the second most important metabolite in heart and kidney; digoxigenin monodigitoxoside and digoxigenin follow, respectively.In a collective of seven patients on maintenance treatment with digitoxin, the mean tissue levels were higher but the metabolic pattern was similar (myocardial digitoxin content: 78.9±38.4 ng/g, renal content: 104.1±44.1 ng/g). The amount of digoxin formed by hydroxylation under long-term treatment with digitoxin in heart and kidney were approximately 10 ng/g.A case of digoxin intoxication differed both in the tissue content and in the metabolic distribution.ZusammenfassungEs wurde ein Verfahren entwickelt zur monospezifischen Bestimmung von Digoxin, Digitoxin, ihren halbsynthetischen Derivaten und abhängigen kardioaktiven Metaboliten in postmortalen Gewebeproben von Herz und Niere.Ein Kollektiv von sechs therapeutisch mit β-Acetyldigoxin behandelten Patienten zeigte einen mittleren myokardialen Digoxinspiegel von 46,1±25,0 ng/g (SD); Niere: 50,3±30,3 ng/g. Digoxigenin-bisdigitoxosid bildete den quantitativ zweitbedeutendsten Metaboliten in Herz und Niere. Digoxigenin-monodigitoxosid und Digoxigenin folgten in der Abstufung.Ein therapeutisches Digitoxin-Kollektiv (n=7) wies durchgehend höhere Gewebespiegel auf, zeigte aber ein ähnliches Metabolitenmuster (Digitoxin-Gehalt des Herzens: 78,9±38,4 ng/g; Niere: 104,1±44,1 ng/g). Der Anteil des durch Hydroxylierung entstehenden Digoxins unter Digitoxin-Dauertherapie lag in Herz und Niere im Mittel bei 10 ng/g.Eine Digoxin-Intoxikation unterschied sich sowohl im Gewebegehalt als auch in der relativen Verteilung der Metabolite.

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.

Influence of the Renin-Angiotensin System and Atrial Natriuretic Peptide on Renal Functional Reserve

We studied the renin-angiotensin system (RAS) and atrial natriuretic peptide (ANP) after amino acid loading in order to elucidate whether or not glomerular hyperfiltration is mediated by these hormones. Eight healthy controls without kidney disease (group 1), 8 renal graft recipients (group 2) and 8 patients after nephrectomy (group 3) were studied. Furthermore, we investigated the influence of amino acid loading on RAS and ANP and glomerular filtration during acute application of captopril in healthy controls. Clearances in insulin (CIn) and para-aminohippuric acid (CPAH) were determined during an infusion of 0.9% saline and during amino acid loading. CIn increased in healthy controls from 96.5 +/- 3.3 to 111.9 +/- 4.4 ml/min (p < 0.01), CPAH rose from 577 +/- 28.7 to 618.9 +/- 38 ml/min (p = NS). During the combined application of amino acid infusion and 25 mg captopril, CIN increased to 125.0 +/- 16.4 ml/min/1.73 m2 (p < 0.01) and there was no significant increase in CPAH which was 595 +/- 77 ml/min/1.73 m2. There was no significant change in renal vascular resistance, but filtration fraction increased from 17 +/- 1 to 19 +/- 1% under amino acid infusion and increased further under the application of captopril to 21 +/- 2% (p < 0.05). In renal graft recipients, CIn had a tendency to increase during amino acid infusion from 78.4 +/- 5.8 to 84.7 +/- 6.5 ml/min (p = NS). In patients after nephrectomy, CIn did not increase (84.5 +/- 6 ml/min) but CPAH did from 345.7 +/- 26.3 to 409 +/- 24.1 ml/min (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)