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Biomedical subjects

H P Marti

Publications and source records attributed to H P Marti.

At least 19 recordsLinked to original sources
PubMed2005

[Pancreas transplantation--indications and results updated].

Pancreas transplantation has evolved within two decades from a poorly accepted therapeutic option to a highly successful procedure in the treatment of type 1 diabetes mellitus. Combined Pancreas-kidney transplantation is usually performed, but the value of pancreas after kidney transplant recently increased dramatically. Novel surgical techniques together with very effective immunosuppression (e.g. Prograf) and CellCept) and better postoperative management offer excellent long-term graft and patient survival with full insulin independence. Pancreas transplantation (alone or simultaneous with kidney) is highly cost-effective compared to any conservative alternatives.

Diabetes Mellitus, Type 1↗
PubMed2004

[A special case of swollen lower limb].

We report on a case of a 31-year-old patient suffering from long-standing peripheral edema with severe hypoalbuminemia, but without proteinuria. Differential diagnosis, diagnostic work-up and the therapeutic options in this unusual case are discussed. The general practitioner must keep in mind a broad range of causes when seeing every-day-patients with peripheral edema, although the correct etiology can be found easily in most cases.

Adult↗
PubMed2002

[Renal involvement in malignant tumors].

Malignant tumors may affect the kidney in a direct and in an indirect fashion. In addition, there are multiple paraneoplastic syndromes and the side effects of the tumor therapy. Therefore, clinicians may encounter a wide spectrum of disorders representing almost all aspects of kidney diseases. Importantly, practitioners taking care of patients with glomerulopathies must always consider the possibility of a co-existence of a malignancy, as highlighted by our case report.

Adult↗
PubMed2001

Prophylactic hemodialysis after radiocontrast media in patients with renal insufficiency is potentially harmful.

PURPOSE: Acute renal failure induced by contrast media is an important cause of hospital-acquired renal insufficiency. Preexisting renal failure and the dose of contrast media are known risk factors for the development of radiocontrast nephropathy. We performed a randomized trial to test whether radiocontrast nephropathy can be avoided by prophylactic hemodialysis immediately after the administration of contrast media in patients with impaired renal function. SUBJECTS AND METHODS: Renal function and other parameters, hemodialysis requirement, and relevant clinical events were recorded before and during the 6 days after administration of contrast media in 113 patients with a baseline serum creatinine level >200 microm/L (>2.3 mg/dL). Patients were randomly assigned to either hemodialysis (n = 55) or nonhemodialysis (n = 58) treatment after parenteral low-osmolality contrast media. RESULTS: The characteristics of the patients in the two groups were similar. Compared with baseline levels, the mean [+/- SD] serum creatinine level decreased at day 1 (277 +/- 95 microm/L), peaked at day 4 (353 +/- 126 microm/L), and returned to baseline at day 6 (327 +/- 119 microm/L, P <0.05 by analysis of variance) after administration of contrast media in the hemodialysis group, whereas in the nonhemodialysis group, no significant changes in mean serum creatinine level were observed. Eleven patients required 1 or more hemodialyses (8 in the hemodialysis group and 3 in the nonhemodialysis group, P = 0.12), 6 of whom (4 vs. 2, P = 0.44) required 3 or more hemodialyses. Clinically relevant events included pulmonary edema (1 vs. 4 patients, P = 0.36), myocardial infarction (2 vs. 2), stroke (2 vs. 0, P = 0.24), and death (1 vs. 1). CONCLUSIONS: The strategy of performing hemodialysis immediately after the administration of low-osmolality contrast media in all patients with a reduced renal function did not diminish the rate of complications, including radiocontrast nephropathy.

Acute Kidney Injury↗
PubMed2001

Carbamoylation of glomerular and tubular proteins in patients with kidney failure: a potential mechanism of ongoing renal damage.

BACKGROUND: Cyanate formed spontaneously from urea carbamoylates non-protonated amino groups of protein, irreversibly altering function, charge and structure. Carbamoylated proteins in renal tissue have not been examined hitherto. OBJECTIVES: To identify homocitrulline (epsilon-amino-carbamoyl-lysine), a result of in vivo carbamoylation by urea-derived cyanate, from patients with renal disease or in newly transplanted kidneys by immunohistochemistry. To evaluate enzymatic activity of carbamoylated and non-carbamoylated matrix metalloproteinase-2 and correlate this with renal tissue carbamoylated in vivo. DESIGN: Anti-homocitrulline antibody is specific for homocitrulline and was used to identify carbamoylation of epsilon-amino-lysine in renal biopsies from patients with elevated BUN, with isolated proteinuria, and as controls, from normal donors at time of transplantation. Enzymatic activity of matrix metalloproteinase-2 carbamoylated in vitro was evaluated. RESULTS: Homocitrulline was present in glomerular basement membrane (8/10), mesangium (8/10), tubular epithelium and cytoplasm (7/10) and Bowman's capsule (1/10) in patients with elevated BUN. The discordant patterns of glomerular and tubular localization of homocitrulline versus immune complexes indicated that the carbamoylated proteins were not a component of immune deposits but were modified proteins in renal tissue. No homocitrulline was found in transplanted kidneys (14/15) or in proteinuric patients (2/2). Enzymatic activity of both human and rat matrix metalloproteinase-2 was strongly inhibited in a dose-dependent fashion when incubated with cyanate. CONCLUSIONS: In situ carbamoylation in proteins occurred in kidneys of patients with renal dysfunction but not in normal newly transplanted kidneys. Decreased enzymatic activity of carbamoylated enzymes may alter specific renal regulatory mechanisms. Carbamoylated proteins with altered function and charge may represent a previously underestimated mechanism in renal pathophysiology.

Amino Acids↗
PubMed2001

Matrix metalloproteinase inhibitors cause cell cycle arrest and apoptosis in glomerular mesangial cells.

Inflammation is characterized by an excess of cell proliferation often leading to fibrosis and sclerosis with subsequent loss of organ function. We hypothesized that these features may be ameliorated by induction of cell cycle arrest and apoptosis as result of therapy with matrix metalloproteinase (MMP) inhibitors. In our study, mesangial cells and experimental mesangial proliferative glomerulonephritis provided the model of inflammation. First, we investigated the effect of the MMP inhibitor BB-1101 in anti-Thy1.1 nephritis. The numbers of apoptotic glomerular cells in nephritic rats increased about 4 and 6 times as a result of BB-1101 therapy, observed 11 and 14 days after induction of disease, respectively. Subsequently, rat mesangial cells were exposed to an MMP inhibitor in vitro. Fluorescence-activated cell sorter analyses of cells exposed to RO111-3456 demonstrated a dose-dependent cell cycle arrest in the G(0)/G(1) phase associated with increased expression of statin. The cell cycle arrest was followed by apoptosis as investigated by terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) biotin nick-end labeling (TUNEL) and acridine orange/ethidium bromide stainings, as well as by annexin V binding. The induction of p53, p21, and bax, but not the Fas/FasL pathway appeared to play an important pathogenetic role. In summary, MMP inhibitors induce cell cycle arrest followed by apoptosis in mesangial cells. These features help to explain the anti-inflammatory effects of these compounds, such as reduction of mesangial cell proliferation and attenuation of extracellular matrix accumulation. In conclusion, induction of cell cycle arrest with subsequent apoptosis may offer new perspectives in the therapy of inflammation even beyond kidney diseases.

Animals↗
PubMed2000

New strategy to treat glomerular inflammation by inhibition of mesangial cell matrix metalloproteinases.

Therapy of inflammation often requires the attenuation of excess cell proliferation and of extracellular matrix (ECM) accumulation. It is increasingly recognised that matrix metalloproteinases (MMP) play an important role in the regulation of these two features. For our studies, experimental mesangial proliferative glomerulonephritis and cultured mesangial cells provided the inflammation model and the opportunity to evaluate a new therapeutic strategy based on MMP inhibition. In vitro inhibition of MMP activity and synthesis successfully returned the inflammatory mesangial cell phenotype to the normally occurring resting state. In vivo, excess mesangial cell proliferation and ECM accumulation in experimental mesangial proliferative glomerulonephritis were significantly ameliorated by the use of a synthetic MMP inhibitor. Interestingly, these inhibitors lead to increased mesangial cell apoptosis. In conclusion, the antiproliferative effect of MMP inhibitors opens new perspectives in the therapy of inflammation, probably even beyond the scope of kidney diseases.

Animals↗
PubMed2000

[Role of matrix metalloproteinases in the progression of renal lesions].

METALLOPROTEINASES: The progression to end-stage kidney disease is accompanied by accumulation of extracellular matrix (ECM) proteins. The degradation of ECM proteins occurs by the action of proteases, notably the matrix metalloproteinases (MMP). MMP can be classified into four major groups, such as interstitial collagenases, gelatinases, stromelysins, and membrane-type (MT)-MMP. MMP are also involved in the regulation of cell proliferation and possibly of apoptosis. In the kidney, MMP are synthesized by intrinsic glomerular cells and tubular epithelial cells. EXPERIMENTAL DATA: MMP and TIMP expression is well studied in a variety of kidney disorders, particularly in diabetes mellitus and in experimental glomerulonephritis. In diabetes mellitus, an increased plasma concentration of MMP-9 was found to represent the earliest marker of diabetic kidney disease. In anti-Thy 1.1 nephritis, a rat model of mesangial proliferative glomerulonephritis, an increase in proliferation of mesangial cells is associated with augmented expression of MMP-2 and accumulation of extracellular matrix proteins. These inflammatory features can be attenuated by a synthetic MMP inhibitor. ABNORMAL MMP AND TIMP REGULATION: The hypothesis that MMP play an important role in the progression of nephropathies is mainly based on the well known ability of MMP to degrade ECM components, on the association of altered MMP expression in a large number of kidney diseases, and on the ability of MMP-2 to induce or to sustain an inflammatory mesangial cell phenotype. However, since there are only few interventional or functional studies, uncertainty persists as to whether abnormal regulation of MMP and TIMP represents a cause or simply an effect of the respective renal diseases. A DUAL ROLE: In nephropathies, MMP appear to play a dual role as antifibrotic enzymes and as proinflammatory mediators. The exact biologic function in a given renal disorder may depend upon the level of net MMP activity and on the acuteness or the chronicity of the respective disease.

Animals↗
PubMed1999

Judgment analysis in clinical nephrology.

To ameliorate the clinical performance of nephrologists, improving their clinical judgment is crucial. No methodology for judgment analysis in nephrology is currently available. Therefore, we designed a trial to assess the intraphysician consistency of the judgment of typical non-end-stage renal disease (ESRD) patients by 24 board-certified nephrologists. The participants were asked to analyze cases to determine the interobserver variability with respect to diagnosis, therapy, prognosis, and strategy of follow-up. They were unaware that every patient was presented on 2 occasions separated by a period of 6 months. Of the 1,288 questionnaires that were completed, 28 cases belonged to 1 of the following 3 groups: (A) patients once with, once without renal histology, (B) patients twice without histology, and (C) patients twice with histology. Only cases of group (A) differed at the 2 occasions of assessment with respect to knowledge of histology. The results from the first and second assessment were compared and analyzed. The median (95% confidence interval) percentages of changed diagnoses were 64% (59% to 68%), 50% (44% to 62%), and 33% (26% to 47%) in groups A, B, and C, respectively, indicating large intraobserver variability. The frequency of changes in diagnoses declined with the degree of confidence in the first diagnosis in all 3 groups. The subjective desire to know the histology was without impact on the frequency of changes in diagnoses. However, a knowledge of the histology enhanced the degree of confidence in the diagnoses. Interestingly, the enormous variability in changing diagnoses from one analysis to the other was not reflected by corresponding changes in the judgment of prognosis, therapy to be prescribed, or strategy of follow-up. The individual judgment with respect to diagnosis of clinical cases is inconsistent and highly dependent on the subjective degree of confidence in the diagnosis. The practical relevant consequences traditionally derived from a diagnosis (therapy, prognosis, and strategy of follow-up) are only marginally, if at all, affected by changing the diagnosis. Thus, the utility of "diagnosis" for judgment analysis in clinical nephrology should be reconsidered.

Adult↗
PubMed1999

Long-term evolution of renal function in patients with ovarian cancer after whole abdominal irradiation with or without preceding cisplatin.

BACKGROUND: The upper limit of the natural decline in creatinine clearance is 1 ml/min/year. To define the loss of renal function, we started a long-term assessment of patients with ovarian cancer treated by whole abdominal irradiation (WAI) with preceding cisplatin chemotherapy (CDDP) and second-look laparotomy (SLL). PATIENTS AND METHODS: We analyzed the creatinine clearance over time of 56 patients treated from 1982 to 1988 for ovarian cancer. Thirty-one of 56 patients had received WAI after their initial surgery, and 25 of 56 patients had undergone CDDP therapy followed by SLL, and then WAI after their initial surgery. Median follow-up was 99 months (7-156). Twenty of 56 patients accepted our invitation for additional assessment of tubular function, nine of the 31 patients without CDDP therapy and SLL, and 11 of the 25 patients with CDDP followed by SLL and WAI. Ten of twenty patients had received four to six cycles CDDP, 80 mg/m2/cycle, and one patient nine cycles. The median total dose for each kidney was 1450 cGy (480-1690). RESULTS: The mean creatinine clearance decreased from 84 ml/min to 66 ml/min. Seventy-six percent of the 25 patients who had undergone CDDP therapy, SLL and WAI had declines of more than 1 ml/min/year, 64% of these patients of more than 2 ml/min/year. For the 31 patients who had received WAI after their initial surgery, the corresponding numbers were 71% and 55%, respectively. The tubular function of the 20 patients who had undergone the additional investigations was not impaired. CONCLUSION: The decline in renal function after WAI is more pronounced than in healthy subjects. The treatment with cisplatin and SLL prior to WAI does not seem to contribute to this loss of kidney function.

Abdomen↗
PubMed1999

Ambulatory nocturnal oximetry and sleep questionnaire-based findings in 38 patients with end-stage renal disease.

BACKGROUND: Patients with end-stage renal diseases (ESRD) have an increased risk of sleep-disordered breathing. With regard to this disorder, controversy persists about prevalence, cost-effective assessment and socio-economical relevance. METHODS: Therefore, we performed, for the first time, overnight ambulatory oximetry in combination with a sleep questionnaire in 38 unselected patients with ESRD and 37 healthy controls. An oxygen desaturation index (ODI) >15, defined as >15 falls in oxygen saturation of > or =4% per h, was observed more frequently in ESRD patients than in healthy controls (47 vs. 3%, P<0.001). RESULTS: In general, the results derived from the assessment of the Epworth Sleepiness Scale (ESS) as well as those from the visual analogue scale (VAS) did not reflect the ODI values of the respective patient population. Interestingly, 88% of ESRD patients with the questionnaire finding 'excessively loud snoring' had an ODI of >15 as compared with 13% without this complaint (P<0.05). Furthermore, 77% of ESRD patients with a systolic blood pressure >140 mm Hg and a body mass index (BMI) >25, had an ODI of >15. The percentage of ESRD patients with a professional activity was higher in the absence of sleep-disordered breathing (63 vs. 21%, P<0.05). CONCLUSION: 'Excessively loud snoring' and a BMI >25 combined with hypertension are risk factors for sleep-disordered breathing in ESRD patients. Nocturnal oxygen desaturations are assessed efficiently by ambulatory oximetry and correlate with relevant biological and socio-economical parameters in ESRD patients.

Adult↗
PubMed1998

Mycophenolic acid: a new approach to the therapy of experimental mesangial proliferative glomerulonephritis.

Mycophenolate mofetil (MMF) represents a powerful immunosuppressant in organ transplantation. The aim of this study was to determine the anti-inflammatory effects of MMF on mesangial cells. Cultured rat mesangial cells were exposed to mycophenolic acid (MPA) in concentrations of 0.1 to 10 microM. MPA inhibited the proliferation of these cells in a dose-dependent manner. A maximum of 98% inhibition was obtained by a 2-d exposure of mesangial cells to > or =5 microM MPA. As expected, the addition of > or =75 microM guanosine prevented the antiproliferative effect of MPA completely. Subsequently, in vivo studies were performed in the anti-Thy1.1 nephritis model. Sixty-six male Wistar rats were investigated: healthy rats (n = 15), treated healthy rats (n = 6), nephritic rats (n = 15), and treated nephritic rats (n = 30). MMF therapy (40 mg/kg body wt per d) of nephritic animals was initiated 2 d before (n = 3) and 6 h (n = 15) or 2 d (n = 12) after induction of nephritis. Renal histology was analyzed at days +6 and +9 after initiation of disease. Therapy of nephritic rats by MMF resulted in a significant amelioration of glomerular histology, assessed by glomerular cellularity, synthesis of alpha-smooth muscle actin, extracellular matrix deposition, and glomerular hypertrophy. Proteinuria, expressed as areas under the curve of protein/creatinine ratios versus time, showed a clear tendency toward a reduction by MMF therapy. Healthy control rats were not negatively affected by exposure to MMF. In summary, this study shows that mesangial cell proliferation can be significantly inhibited by MPA in vitro and in vivo. MMF represents a new approach to the therapy of experimental mesangial cell-mediated forms of glomerulonephritis.

Animals↗
PubMed1998

Inhibition of matrix metalloproteinases attenuates anti-Thy1.1 nephritis.

There is accumulating evidence that matrix metallo-proteinases (MMP) play a prominent role in glomerular inflammatory diseases. The aim of the present study was to determine the anti-inflammatory effects of the synthetic MMP inhibitor BB-1101 in acute anti-Thy1.1 nephritis. Sixty-three male Wistar rats were studied: healthy rats (n = 9), treated healthy rats (n = 9), nephritic rats (n = 18), and treated nephritic rats (n = 27). BB-1101 therapy (30 mg/kg body wt per d) of nephritic animals was initiated either 2 d before (n = 18) or 2 d after (n = 9) disease induction. Renal histology was analyzed 11 d after induction of the nephritis, at the peak of MMP-2 production and total glomerular cellularity. Pretreatment of nephritic rats by BB-1101 resulted in a significant amelioration of glomerular histology, assessed by glomerular cellularity, extracellular matrix deposition, and size of glomerular cross-sections. These beneficial effects were less pronounced, but in part still significant, in animals treated by BB-1101 after induction of anti-Thy1.1 nephritis. Proteinuria, expressed as area under the curve of the protein:creatinine ratio versus time, was clearly decreased in both groups of treated nephritic rats. Healthy control rats were not affected by MMP inhibitor treatment. In summary, the present study demonstrates for the first time in vivo that mesangial cell proliferation can be effectively suppressed by MMP inhibition. Thus, MMP inhibition by synthetic compounds may represent a new approach to the therapy of mesangial cell-mediated forms of glomerulonephritis.

Animals↗