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M Soergel

Publications and source records attributed to M Soergel.

At least 19 recordsLinked to original sources
PubMed2006

Low 1-year cyclosporine microemulsion doses are associated with better 5-year renal graft function: an insight from MOST, a multinational observational study.

BACKGROUND: In earlier registry analyses, cyclosporine at doses of < 3 mg/kg/d at 1 year post-renal transplantation has been associated with significant graft loss or reduction in renal function. Improvements in cyclosporine formulation with increased bioavailability, plus the use of more efficient comedications, may now confer better outcomes. To determine the effect of the 1-year cyclosporine microemulsion (CsA-ME) dose on renal allograft function at 5 years, we analyzed data collected from 2889 patients with documented graft survival to year 5 in a prospective, multinational, observational study-Neoral MOST. RESULTS: Glomerular filtration rate (GFR) at year 1 was 63 +/- 20 mL/min and 59 +/- 22 mL/min at year 5. The multivariate analysis including year 1 CsA-ME dose as factor and GFR at 1 year as covariate revealed the most significant factors affecting GFR at year 5 were 1-year GFR, donor age > 60 years, and CsA-ME dose at 1 year. Risk factors associated with reduction in 5-year GFR (<65 mL/min) included donor or recipient age >60 years, delayed graft function, cadaveric donor, previous graft, and acute rejection. CsA-ME dose <3 mg/kg/d was found to protect GFR. Analysis of GFR at each year posttransplantation (Wilcoxon model) found 1-year CsA-ME (cutoff 3 mg/kg/d) had a significant effect at each time point. CONCLUSIONS: Compared to higher doses, CsA-ME <3 mg/kg/d at year 1 posttransplantation is associated with increased preservation of renal allograft function at year 5.

Aged↗
PubMed2002

Stimulated cortisol secretion is not correlated with prednisone dose or with steroid side-effects in children after renal transplantation.

Impairment of adrenocortical function and other adverse effects have to be considered whenever corticosteroids are applied for a prolonged period of time. We hypothesized that the assessment of adrenal function with adrenocortiocotropin (ACTH) stimulation reflects the sensitivity to corticosteroids and would predict the development of side-effects in pediatric patients on triple immunosuppression after renal transplantation.

Adolescent↗
PubMed2001

Risk of steroid withdrawal in pediatric renal transplant patients with suspected steroid toxicity.

BACKGROUND: Glucocorticoids are still a cornerstone in immunosuppressive regimens in pediatric patients after renal transplantation (Tx). Due to the side effects, steroid withdrawal may significantly improve the appearance and growth of children with renal grafts, but bears a substantial risk for late rejections. AIM OF THE STUDY: To investigate whether exclusion of subclinical acute rejection by renal histology in combination with a prolonged steroid withdrawal period is predictive of a successful outcome. PATIENTS AND METHODS: Ten children (5 females) with a median age of 12.3 (range 7.9-20.9) years and 1.8 (0.7-7.5) years after Tx with a stable graft function and a median calculated creatinine clearance (C(Cr)) of 71 (60.5-99.7) ml/min/1.73 m2 were included. All patients showed steroid toxicity signs. Immunosuppressive regimen included low-dose steroids (median 2.72 mg/m2) in all patients, in addition to cyclosporin A (CsA) and azathioprine in 8, CsA on its own and CsA combined with mycophenolate mofetil in one patient each. A graft biopsy was performed in 8 patients prior to the start of steroid withdrawal, which was done over a median period of 6 months. Renal function was calculated as creatinine clearance using the Schwartz formula. RESULTS: None of the biopsied grafts showed histologic signs of rejection. Cyclosporin A dosage and trough levels were not significantly different before and after steroid withdrawal. While steroid side effects improved in most of the patients after withdrawal, C(Cr) decreased significantly within a median observation time of 42 (11.4-49.3) months. This decrease was due to loss of renal function in 4 patients who had biopsy-proven rejection episodes at 21.6 (8.1-29.9) months after the start of steroid withdrawal. CONCLUSION: Slow steroid withdrawal in pediatric Tx patients using conventional immunosuppression reduces side effects, but bears a high risk of late rejection. A pre-withdrawal renal biopsy was not useful for the prediction of successful steroid withdrawal.

Acute Disease↗
PubMed2000

Effect of ramipril on ambulatory blood pressure and albuminuria in renal hypertension.

Inhibition of the angiotensin-converting enzyme (ACE) exerts a renoprotective effect in adult patients with chronic kidney disease. We evaluated prospectively changes in blood pressure (BP), protein excretion and renal function after administration of the long-acting ACE inhibitor ramipril as monotherapy during 6 months in 14 moderately hypertensive children aged 5-18 years with various nephropathies. Four patients initially had a decreased glomerular filtration rate (GFR below 60 ml/min/1.73 m2). BP was evaluated by ambulatory 24-h monitoring. After 2 weeks of treatment by oral ramipril (1.5 mg/m2 once daily), mean values of systolic and diastolic 24-h ambulatory BP fell by more than 5 mmHg in nine patients. In eight patients the dose was doubled. At the end of the study systolic BP was below the 95th percentile in 9 and diastolic BP in 13 patients. The initially reduced nocturnal dip increased significantly. Of 11 patients with an increased albumin excretion (median 1.3 g/g creatinine), 6 responded to ramipril by a median reduction of 78% (range 24-83%), whilst in 5 albuminuria increased (median +19%). GFR was well preserved and no other adverse effects from the drug were noted. The study demonstrates that ramipril is an efficacious antihypertensive agent in children with renal hypertension. It is well tolerated, even in mild renal insufficiency. In addition, the drug has a persistent antiproteinuric action in about half of the patients contributing to conserve renal function.

Adolescent↗
PubMed2000

Atypical distal renal tubular acidosis confirmed by mutation analysis.

In autosomal dominant distal renal tubular acidosis type I (dRTA) impaired hydrogen ion secretion is associated with metabolic acidosis, hyperchloremic hypokalemia, hypercalciuria, nephrocalcinosis, and/or nephrolithiasis. A retardation of growth is commonly observed. In this report we present a family with autosomal dominant dRTA with an atypical and discordant clinical picture. The father presented with severe nephrocalcinosis, nephrolithiasis, and isosthenuria but metabolic acidosis was absent. His 6-year-old daughter, however, suffered from metabolic acidosis, hypokalemia, and hypercalciuria. In addition, sonography revealed multiple bilateral renal cysts but no nephrocalcinosis. Mutation analysis of the AE1 gene coding for the renal Cl-/HCO3(-)-exchanger AE1 displayed a heterozygous Arg589Cys exchange in both patients but not in the healthy family members. This point mutation is frequently associated with autosomal dominant dRTA. Diagnosis of autosomal dominant dRTA is supported in this family by results of AE1 mutation analysis.

Acidosis, Renal Tubular↗
PubMed2000

Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis maps to chromosome 3q27 and is associated with mutations in the PCLN-1 gene.

Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis (FHHNC, MIM 248250) is a complex renal tubular disorder characterised by hypomagnesaemia, hypercalciuria, advanced nephrocalcinosis, hyposthenuria and progressive renal failure. The mode of inheritance is autosomal recessive. A primary defect in the reabsorption of magnesium in the medullary thick ascending limb of the loop of Henle (mTAL) has been proposed to be essential in FHHNC pathophysiology. To identify the underlying genetic defect we performed linkage analysis in eight families, including three with consanguineous marriages. We found linkage to microsatellite markers on chromosome 3q27 with a maximum two-point lod score (Zmax) of 5.208 for D3S3530 without evidence for genetic heterogeneity. Haplotype analysis revealed crucial recombination events reducing the critical interval to 6.6cM. Recently, mutations in the gene PCLN-1, mapping to 3q27 and coding for paracellin-1, were identified by Simon et al (1999) as the underlying genetic defect in FHHNC. Paracellin-1 represents a renal tight junction protein predominantly expressed in the TAL. Mutational analysis in our patient cohort revealed eight different mutations in the PCLN-1 gene, within six novel mutations. In seven of 13 mutant alleles we detected a Leu151 substitution without evidence for a founder effect. Leu151 is a residue of the first extracellular loop of paracellin-1, the part of the protein expected to bridge the intercellular space and to be important for paracellular conductance. This study confirms the implication of paracellin-1 defects in FHHNC and points to a predominant role of this protein in the paracellular reabsorption of divalent cations in the TAL.

Amino Acid Substitution↗
PubMed1999

Cardiac function and structure in patients with chronic renal failure.

The long-term consequences of cardiac alterations in children with chronic renal failure (CRF) and after renal transplantation (TX) are largely unknown. Studies in adults with end-stage renal disease (ESRD) assume that the fate of many pediatric patients is determined by a high cardiovascular morbidity and mortality. This review describes clinical manifestations, pathophysiology, cardiac function and structure, and management of heart disease in children with CRF and post transplant. Echocardiography and Doppler ultrasonography allow differentiation of three functional disturbances: hypercirculation, systolic left ventricular (LV) dysfunction, and diastolic LV dysfunction, in addition to analysis of LV size and myocardial mass. From adult studies LV hypertrophy is recognized as an early prognostic marker of cardiovascular disease. It is present in about half of children with ESRD and after TX. It may regress, at least in part, by control of hypertension, hypervolemia, and anemia. Experimental studies have shown that, independent of these hemodynamic complications, uremia is associated with structural abnormalities of the heart, which were also described in adult patients with ESRD. These lesions consist mainly of hypertrophy of cardiomyocytes, interstitial fibrosis, and vascular changes (rarefied capillaries, thickened arteriolar walls). Cardiac complications in children with CRF and after TX deserve regular clinical and echocardiographic monitoring in order to minimize later cardiovascular morbidity by appropriate treatment.

Adolescent↗
PubMed1997

Oscillometric twenty-four-hour ambulatory blood pressure values in healthy children and adolescents: a multicenter trial including 1141 subjects.

Ambulatory blood pressure (ABP) monitoring is increasingly used to evaluate the blood pressure of children and adolescents. The upper normal ABP values in the pediatric age group are still unknown, because reference values based on a sufficiently high number of healthy children have not yet been published. In this multicenter trial, we pooled ABP records of 1141 healthy children and adolescents with a body height between 115 and 185 cm. The study was carried out by seven centers according to a common protocol. The 50th percentile for 24-hour systolic ABP increased moderately with height, from 103 to 113 mm Hg in girls and from 105 to 120 mm Hg in boys. The 50th percentile for diastolic 24-hour means was 66 +/- 1 mm Hg, irrespective of height or gender. Diastolic daytime means were 73 +/- 1 mm Hg, which is remarkably high compared with reference values for casual blood pressure. The mean nocturnal systolic and diastolic ABP (midnight to 6 AM) was 13% +/- 6% and 23% +/- 9% lower compared with the daytime means (8 AM to 8 PM), respectively. This multicenter study provides well-based limits of normal ABP in mid-European children.

Adolescent↗
PubMed1995

Ambulatory blood pressure monitoring in paediatric patients treated by regular haemodialysis and peritoneal dialysis.

Ambulatory blood pressure monitoring (ABPM) has been shown to be more representative of blood pressure (BP) levels than casual BP measurements in adult patients treated by haemodialysis (HD). In this study we compared ABPM using the oscillometric SpaceLabs 90207 monitor with casual BP measurements in 35 paediatric patients [17 treated by peritoneal dialysis (PD) and 18 by HD]. Heart rate and plasma concentrations of atrial natriuretic peptide were also measured. No correlations were found between ABPM and causal BP measurements, except for systolic day-time BP in PD patients (r = 0.63). Seventy percent of PD and 33% of HD patients were regarded as hypertensive when evaluated by ABPM, while casual BP measurements demonstrated hypertension in 47% (P < 0.05) of PD patients and in 44% (NS) of HD patients. One-third of patients were reclassified by ABPM either from normotensive to hypertensive (7/19) or from hypertensive to normotensive (5/16). BP assessed by ABPM was higher in PD than in HD patients. The physiological decline of BP at night was significant and more pronounced in PD than in HD patients. In HD patients day-time BP did not differ between the 1st and the 2nd interdialytic day, but increased in the night hours before the following dialysis session. A positive correlation was found between day-time BP and pre-dialysis plasma atrial natriuretic peptide in both treatment groups. In conclusion this study demonstrates that casual BP recordings are not representative of average BP in dialysed paediatric patients. ABPM is useful in the diagnosis and treatment of hypertension in children with end-stage renal disease.

Adolescent↗
PubMed1992

Treatment of relapsing peritonitis in pediatric patients on peritoneal dialysis.

Relapsing peritonitis is often due to bacterial colonization of the Tenckhoff catheter and may require removal of the catheter in patients on peritoneal dialysis. The efficacy of a Tenckhoff catheter decontamination procedure was examined in 9 pediatric patients aged 1.5-18 years and compared to the outcome of a historical control group. After repeated dialysate cultures had become negative and cell count was normalized (< 100/ul), intraluminal urokinase (5000 IU/ml) and intraluminal high concentrated antibiotics (vancomycin, fosfomycin, cefotaxim) were instilled sequentially for 3 h and 1 h respectively. This procedure was performed once daily for three days. In addition, the connector was exchanged on the last day. This regimen prevented relapsing peritonitis in all study patients, whereas in the control group in 75.8% of events further relapses occurred, necessitating removal of the Tenckhoff catheter in 7/19 (36.8%) episodes. No side effects of intraluminal urokinase were recorded in any of the patients. We conclude that intraluminal urokinase and intraluminal high concentrated antibiotics combined with connector device exchange are highly effective for prevention of further relapses of peritonitis and reduce the need for Tenckhoff catheter exchange.

Adolescent↗
PubMed1992

[Ambulatory blood pressure measurement in children and adolescents with kidney transplants].

Arterial hypertension (HT) is a common complication after renal transplantation. We evaluated ambulatory blood pressure profiles during 24 h in 30 pediatric patients (pts) aged 6-22 years who had been transplanted 2 months to 7 years previously. Creatinine clearance was 14-121 (median 57) ml/min/1.73 m2. Twenty-three pts were being treated with ciclosporin. Sixteen pts received antihypertensive drugs. Using the monitor Nippon Collins 630 (Baxter), blood-pressure (BP) values were taken every 20 min during the day and overnight (10 p.m.-7 a.m.). Five out of 10 pts with elevated office BP readings were normotensive by ambulatory blood pressure monitoring (ABPM). Ambulatory hypertension was discovered in one child with normal office BP. Echocardiography was performed in 23 pts. Five of six pts with significant left-ventricular hypertrophy (LVH), but none of the 17 pts without LVH had ambulatory HT (p less than 0.01). The physiological decline of BP during the night was significantly reduced when compared to 21 subjects of similar age with essential HT (-9.2% vs. -15.4%; p less than 0.02); no correlation was found with renal function or prednisone dose. Ciclosporin tended to reduce the day-night gradient (-14.5% vs. -9.2%; p = 0.11). One child showed a severe nocturnal BP rise of 25 mmHg. We conclude that abnormalities of nyctohemeral BP rhythm, as described in transplanted adults, can be observed to a lesser extent in children. ABPM allows a better evaluation of BP compared to office BP and, thus, may contribute to a better management of these patients.

Adolescent↗
PubMed1991

[Acute tubulointerstitial nephritis and uveitis (TINU syndrome) in childhood].

During the last two years we have observed three children, aged 12-15 years, who developed acute non-oliguric renal failure with concomitant uveitis. Acute interstitial nephritis with lympho-monocytic infiltrates was diagnosed in all cases by renal biopsy. While two patients went into spontaneous remission, renal function in the remaining child improved only after treatment with oral prednisone. Withdrawal of steroid medication was promptly followed by a relapse, necessitating steroid therapy for a total of 4 months. The clinical and histological findings were consonant with the so-called TINU syndrome. While the pathogenesis of this syndrome is unclear, the prognosis seems to be favorable and most cases resolve spontaneously. However, in some cases, prolonged therapy with corticosteroids may be required.

Acute Disease↗
PubMedDate not supplied

Delayed graft function: risk factors, consequences and parameters affecting outcome-results from MOST, A Multinational Observational Study.

BACKGROUND: Delayed graft function (DGF) is a common complication after renal transplantation, and may affect graft function. The aim of this analysis was to evaluate risk factors for DGF, as well as parameters and events influencing graft function after DGF. We analyzed data collected in an ongoing international, prospective; observational study, the Neoral-MOST (Multinational Observational Study in renal Transplantation), and included in the analysis all patients with cadaveric kidney transplants for whom renal function at 1 year posttransplantation was documented (N = 8950). Logistic regression was used to evaluate the risk factors for DGF occurrence, and multifactorial analysis of variance (ANCOVA) to assess the relevance of different factors for GFR at 1 year. RESULTS: Higher donor age, longer CIT, male recipients, Caucasian recipients, high recipients body mass index, and PRA were all associated with a higher risk for DGF. Renal function of former DGF kidneys at 1 year was lower in kidneys of elder donors, or which had experienced rejection or CMV infection. Variations of the maintenance regimen at 1 year posttransplantation were not associated with better graft function. Multifactorial analysis showed donor age and acute rejection as significant independent factors. CONCLUSIONS: Most factors increasing the risk for DGF or having a negative impact on renal function at 1 year in grafts with DGF are predetermined. Additional posttransplant damage by acute rejection was associated with further reductions in GFR. Preventing acute rejection is an important step in achieving optimal function of DGF grafts.

Adult↗