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J Beige

Publications and source records attributed to J Beige.

At least 19 recordsLinked to original sources
PubMed2006

[Polyuria].

Beyond polyuria following psychogenic polydipsia, in a more narrow sense, this condition may be classified into impaired water re-absorption (i) due to tubular injury or (ii) relative or absolute loss of function of antidiuretic hormone (ADH). Tubular injury may be caused by different toxins affecting the ascending Henle loop as hypercalciuria, drugs and antibiotics as tubular necrosis. ADH deficiency, either absolute or relative, occurs with central or peripheral diabetes insipidus, which is based on synthesis failure or loss of peripheral efficacy of ADH due to receptor malfunction. Diagnosis of polyuria rests upon a thirst challenge in conjunction with laboratory studies of osmolality in serum and urine, which discloses the non-function of the hypothalamic-renal axis. Administration of ADH may differentiate between central and peripheral diabetes insipidus.

Humans↗
PubMed2006

Tacrolimus in steroid-resistant and steroid-dependent nephrotic syndrome.

BACKGROUND: Steroid resistance and steroid dependence constitute a major problem in the treatment of minimal-change disease and focal segmental glomerulosclerosis (FSGS). Cyclophosphamide and cyclosporine are well-established alternative immunomodulating agents, whereas data on FK 506 (tacrolimus) are rare. METHODS: The present work provides data from 10 patients of an open, monocentric, non-randomized, prospective trial. Five patients with steroid-dependent minimal-change nephrotic syndrome, 1 patient with steroid-refractory minimal-change disease and 4 patients with steroid-refractory FSGS were started on tacrolimus at trough levels of 5 10 microg/l. In case of steroid-dependence, prednisolone was tapered off in presence oftacrolimus within one month. RESULTS: Within 6 months, complete remission was achieved in 5 patients (50%) and partial remission in 4 patients (40%), yielding a final response rate of 90%. One patient was primarily resistent to tacrolimus (steroid-refractory minimal-change), another patient became secondarily resistant to tacrolimus after an initial remission (steroid-refractory FSGS). Average proteinuria significantly decreased by 77% from 9.5 +/- 1.4 - 2.2 +/- 1.1 g/day (p < 0.01). Serum protein significantly raised from 55.0 +/- 1.9 - 64.6 +/- 1.9 g/l (p < 0.01). Tacrolimus induced non-significant increases of blood glucose (4.9 +/- 0.1 - 5.1 +/- 0.2 mmol/l), systolic blood pressure (131.4 +/- 7.1 - 139.0 +/- 7.6 mmHg) and creatinine (93.2 +/- 13.9 103.2 +/- 15.3 mmol/l). Five patients have been tapered off tacrolimus so far, nephrotic syndrome relapsed in 4 of them (80%). Relapse occurred at tacrolimus levels between 2.6 and 6.9 ng/ml. CONCLUSIONS: Our data suggest that tacrolimus may be a promising alternative to cyclosporine both in steroid-resistant and steroid-dependent nephrotic syndrome.

Adult↗
PubMed2000

Computational analysis of blood volume curves and risk of intradialytic morbid events in hemodialysis.

BACKGROUND: Blood volume (BV) curves have been used to prevent intradialytic morbid events (IMEs) caused by hypotensive episodes in hemodialysis treatment. However, no standardized parameter is available to describe BV dynamics and to enable online interference with ultrafiltration rates in unselected patients. Moreover, only time-dependent BV reduction and absolute hematocrit threshold, but not BV variability, have been suggested as markers of pending hypotension. The present study therefore deals with a computer-aided analysis of indices characterizing both BV reduction per time and BV variability in treatments of nonselected maintenance hemodialysis patients. METHODS: The methodology uses indices obtained by mathematical analysis of BV curves and was designed to potentially enable automatic interference with ultrafiltration. RESULTS: In 46 out of 380 treatments (12.1%), IMEs occurred. In these treatments, the indices for long- and short-term variability and slope of the curves were significantly lower than in treatments without IMEs. Moreover, the last 10 minutes before an IME were characterized by additionally decreased variability and slope. In a risk analysis of long-term variability and IMEs, we established an index below 16 to be associated with the highest risk of IMEs. CONCLUSIONS: Using these kind of index thresholds and online analysis of BV curves, automatic management of ultrafiltration by BV dynamics could be a promising concept to avoid intradialytic morbidity.

Adult↗
PubMed2000

G-protein beta(3)-subunit C825T genotype and nephropathy in diabetes mellitus.

BACKGROUND: Recent studies have identified a novel polymorphism (C825T) of the gene encoding the beta(3) subunit of heterotrimeric G proteins (G:beta(3)) which is associated with enhanced activation of G-proteins and appears to be more common in hypertensive patients and possibly contributes to decreased kidney allograft survival. METHODS: In the present study we examined the relationship between this genetic variant, type 1 and type 2 diabetes and renal complications of diabetes in 1008 Caucasian patients recruited from an outpatient diabetes clinic and four dialysis centres. We also studied 1940 healthy controls. RESULTS: After multivariate adjustment and in univariate statistics, the G:beta(3) 825TT genotype was not associated with a significantly enhanced risk of diabetes or renal complications. CONCLUSIONS: These findings indicate that the G:beta(3) 825T allele apparently does not contribute to the development of diabetes or associated renal complications in patients with type 1 or type 2 diabetes mellitus.

Adult↗
PubMed2000

G-protein beta3 subunit 825T allele and response to dietary salt in normotensive men.

BACKGROUND AND AIMS: A functional single-nucleotide variant of the gene encoding the beta3 subunit of heterotrimeric G proteins (Gbeta3 C825T), associated with enhanced G-protein activation and increased activity of the sodium-proton exchanger (NHE1), has been implicated in the development of hypertension. Given the possible involvement of NHE1 in sodium homeostasis, we tested the hypothesis that the Gbeta3 825T allele determines the response of the renin-angiotensin system and blood pressure to dietary salt restriction. METHODS: Young normotensive men (20-30 years old, n = 193) were recruited within the framework of the Berlin Salt-Sensitivity Trial and studied on low- (20 mmol/day) and high-salt (220 mmol/day) dietary protocols. Subjects were characterized for parameters of the renin-angiotensin system and blood pressure response and genotyped for the Gbeta3 C825T polymorphism. RESULTS: The genotype distribution was in Hardy-Weinberg equilibrium (CC = 90, CT = 81 and TT = 22). The responses of the renin-angiotensin system and blood pressure to the dietary protocol were virtually identical between the genotypic groups. Furthermore, when subjects were classified as salt-resistant (n = 145) or salt-sensitive (n = 48), genotype distribution was comparable between the two groups (salt-resistant: TT = 17, CT = 60, CC = 68, qT = 0.32; salt-sensitive: TT = 5, CT = 21, CC = 22, qT = 0.32). CONCLUSION: These findings do not support the hypothesis that the Gbeta3 C825T polymorphism determines the response of the renin-angiotensin system to salt depletion or can serve as an early genetic marker of salt sensitivity in young normotensive men.

Adult↗
PubMed1999

Monitoring dialysis efficacy by comparing delivered and predicted Kt/V.

INTRODUCTION: In Europe, especially in Germany, little is currently known about the relationship between delivered and predicted haemodialysis doses for patients on maintenance haemodialysis. We compared delivered and predicted Kt/V in patients of an outpatient dialysis centre in Berlin by calculating the ratio of delivered and predicted Kt/V, resulting in the efficacy quotient, QE. Moreover, we studied the influence of technical and anthropometric parameters on both delivered Kt/V and QE under routine clinical conditions. METHODS: Blood samples were taken after the long interval in a thrice-weekly regimen before and 10 min after ultrafiltration and 100 ml/min slow-pump method. Delivered Kt/V was computed using the Daugirdas III formula. Predicted Kt/V was estimated from the dialysis filter urea clearance given by the manufacturer, treatment time and the total body water (V) computed by the Watson formula and was corrected for real blood flow. As and when appropriate, bivariate and multivariate regression analyses were used to make comparisons. RESULTS: The mean quotient (QE) between delivered and predicted Kt/V was 1.02+/-0.20. Mean delivered Kt/V in 377 treatments of 128 patients was 1.28+/-0.27. Delivered Kt/V and QE were positively associated (P<0.001). QE was significantly associated with post-HD urea, body mass index (BMI) and sex, but not with session time. Significant positive predictors for delivered Kt/V were post-dialysis urea, sex, session time, blood flow and kind of vascular access. BMI was inversely related to delivered Kt/V. DISCUSSION: In this study, the relationship between delivered and predicted Kt/V (QE) was reproducible and close to the ideal value of 1.0. In contrast to delivered Kt/V, QE was not influenced by session time, and positively by BMI. Since QE gives a valid measure of technical dialysis efficacy we suggest the use of this parameter in addition to delivered Kt/V to monitor HD adequacy in clinical routine more comprehensively.

Body Mass Index↗
PubMed1999

Angiotensinogen M235T variant and salt sensitivity in young normotensive Caucasians.

BACKGROUND AND AIMS: A single-nucleotide variant of the angiotensinogen gene (AGT 235T) has been associated with essential hypertension and increased plasma levels of angiotensinogen. This variant may also serve as a genetic marker for the increased blood pressure response to dietary salt intake, but the relationship between AGT genotype and salt sensitivity has not been studied until now. We therefore examined the relationship between the AGT 235T genotype and the blood pressure response to short-term dietary salt restriction in young normotensive men. SUBJECTS AND METHODS: A total of 187 young normotensive men were characterized for family history of hypertension, salt sensitivity, plasma parameters of the renin-angiotensin system under high- and low-salt diets, and the AGT 235T genotype. RESULTS: While the T allele was significantly associated with a positive family history of hypertension (chi2 = 7.0; P< 0.03) and higher plasma angiotensinogen levels (P< 0.015) and renin activity (P < 0.037), blood pressure under both diets was not significantly affected by the AGT genotype. When the subjects were classified into salt-resistant and salt-sensitive groups, genotypic distribution was nearly identical between both groups (frequency of T allele: 0.45 versus 0.46). CONCLUSION: Our findings demonstrate that the AGT 235T allele is significantly associated with a positive family history of hypertension, but is not an important determinant of the blood pressure response to dietary salt intake in young normotensive subjects. It is therefore unlikely that the AGT 235T genotype can serve as an early genetic marker of salt sensitivity.

Adult↗
PubMed1999

Aldosterone synthase gene (CYP11B2) C-344T polymorphism in Caucasians from the Berlin Salt-Sensitivity Trial (BeSST).

OBJECTIVE: Aldosterone synthase (CYP11B2) is a key enzyme in the biosynthesis of aldosterone. Recently, the T allele of a polymorphism in the 5'-flanking region of the CYP11B2 gene (C-344T) has been reported to be more frequent in hypertensives than in normotensives, and has also been associated with increased plasma aldosterone levels. We therefore hypothesized that this variant may be related to increased blood-pressure response to dietary salt intake. SUBJECTS AND METHODS: We genotyped 1 63 young normotensive men recruited within the framework of the Berlin Salt-Sensitivity Trial (BeSST) for the CYP11B2 C-344T polymorphism. Subjects were characterized for family history of hypertension, plasma parameters of the renin-angiotensin-aldosterone system and blood-pressure response to a high (220 mmol/day) and low (20 mmol/day) salt diet RESULTS: The frequency of the -344T allele (0.45) was similar to that reported previously and genotype distribution was in Hardy-Weinberg equilibrium (CC, n = 55; CT, n = 71; TT, n = 37). There was a trend towards a higher frequency of the T allele in subjects with a positive family history of hypertension (0.48 versus 0.42), but the C-344T genotype was not related to blood pressure under either diet Furthermore, when subjects were classified into salt-sensitive and salt-resistant groups, allelic distribution did not differ between the two groups (qT = 0.43 versus qT = 0.45). While renin activity and plasma aldosterone levels were not related to genotype, plasma angiotensinogen was significantly higher in T-allele carriers under both the high (P = 0.02) and low (P = 0.008) salt diet. CONCLUSION: Our findings do not support the hypothesis that the C-344T polymorphism of the CYP11B2 gene is associated with salt sensitivity or increased activity of the renin-angiotensin system in young normotensive subjects. It is, therefore, unlikely that the C-344T polymorphism is a genetic marker for salt sensitivity in young normotensive Caucasian men.

Adult↗
PubMed1999

G-Protein beta3 subunit C825T variant and ambulatory blood pressure in essential hypertension.

Recent studies have identified a novel polymorphism (C825T) of the gene encoding the beta3 subunit of heterotrimeric G proteins (Gbeta3) associated with enhanced activation of G proteins, which appears to be more common in hypertensive patients. In the present study we examine the relationship between this genetic variant and hypertension in 479 white patients with established essential hypertension recruited from the hypertension clinic of the Universitätsklinikum Benjamin Franklin in Berlin, Germany, and 1000 normotensive gender- and age-matched controls. All patients were screened for the presence of secondary hypertension and were further characterized by ambulatory blood pressure measurements performed in 295 treated and 184 untreated patients. Genotype distribution for the Gbeta3-C825T genotype in patients (CC=204, CT=224, TT=51) was significantly different from that in controls (CC=514, CT=412, TT=74; chi2=11.5, P<0.01), and the T allele was associated with an odds ratio of 1.5 (95% CI, 1.1 to 2.2) versus non-T carriers for the presence of hypertension. However, in both the whole group and the untreated subgroup, blood pressure levels between the genotypic groups were virtually identical. Furthermore, age of onset of hypertension and number of antihypertensive medications (in treated patients) were similar between the genotypic groups. Thus, while our data confirm the association between the Gbeta3-C825T variant and essential hypertension, they do not support the hypothesis that this marker is associated with more severe blood pressure in patients with already established hypertension.

Adult↗
PubMed1999

Donor G protein beta3 subunit 825TT genotype is associated with reduced kidney allograft survival.

Recent studies have identified a novel polymorphism (C825T) of the gene encoding the beta3 subunit of heterotrimeric G proteins (Gbeta3), associated with enhanced activation of G proteins, which appears to be more common in hypertensive patients. In the present study, the relationship between this genetic variant and kidney allograft survival was examined over the first 3 yr after transplantation, in 320 consecutive Caucasian patients recruited from the Berlin-Steglitz transplantation center between 1988 and 1993. Clinical parameters, transplantation data, and details of graft survival were retrieved from clinical records. After multivariate adjustment for covariates (Cox hazard regression), the Gbeta3 825TT donor-genotype was associated with a significantly decreased graft survival representing a relative risk of graft loss of 2.2 (95% confidence interval, 1.1 to 4.8) compared to TC and CC grafts within the observation period. This association between donor TT genotype and graft survival remained stable even after stepwise exclusion of covariates from the multivariate model. In contrast, there was no significant relationship between recipient genotype and allograft function. These findings indicate that individuals receiving renal allografts from donors homozygous for the Gbeta3-825T allele may have an increased risk of developing allograft failure. Additional studies on the role of this genetic marker as well as the role of pertussis toxin-sensitive G proteins in the development of chronic rejection appear warranted.

Adult↗
PubMed1998

Role of genetic variants of the renin-angiotensin system in chronic renal allograft injury.

In the the vast majority of patients undergoing kidney transplantation, long-term success is markedly limited by a gradual decrease in graft function over time, often termed as "chronic rejection" or "chronic allograft injury." Although there have been no formal studies examining the role of genetic factors other than those related to histocompatibility for the development or progression of chronic allograft rejection, it is likely that genetic factors affecting blood pressure regulation, mesangial or vascular proliferation, or aspects of inflammatory response including thrombosis, chemotaxis, or fibrosis may play an important role in this complex syndrome. There is currently little hope that the responsible genes can be identified through sib-pair or linkage studies in families. Therefore, the study of candidate genes selected on the basis of our current understanding of the pathophysiological mechanisms involved in the chronic rejection response appears the only feasible approach. Thus far, studies have focused mainly on the role of functional genetic variants of the renin-angiotensin system on renal allograft funding. These studies, however, have not identified these variants as important determinants of renal allograft survival. Clearly, future studies will have to address the role of other variants of this system as well as genes encoding for other systems deemed to be of pathophysiological significance for the development and progression of chronic transplant injury.

Angiotensinogen↗
PubMed1998

Angiotensin-converting-enzyme insertion/deletion genotype and long-term renal allograft survival.

BACKGROUND: Increased activity of the renin-angiotensin system has been implicated in decreased long-term survival of renal allografts. Recent studies suggest that a deletion variant of the angiotensin-converting enzyme, associated with increased humoral and tissue activity of this enzyme, may be a risk factor for the development of diabetic nephropathy and the progression of IgA nephropathy. The present study was conducted to determine whether the deletion variant of the angiotensin-converting-enzyme gene influences the long-term outcome in renal-transplant recipients. METHODS: We examined the relationship between recipient angiotensin-converting-enzyme genotype and clinical outcome in patients with a surviving allograft of at least 10 years (median survival 156 months, n= 86). Patients with an allograft survival of less than 3 years served as controls (median survival 10.4 months, n=87). RESULTS: Genotype distribution in long-term renal allograft survivors (II, 18; ID, 41; DD, 27; qD, 0.55) was similar to that in the control group (II, 12; ID, 53; DD, 22; qD, 0.56), and there were no significant differences between the genotypic groups in either cases or controls. Long-term survivors were more often female (58 vs 38%) and less often hypertensive (67 vs 77%). Both recipient and donor age were markedly lower in the long-term survivor group, whereas number of HLA mismatches and cold ischaemia time were comparable between cases and controls. CONCLUSIONS: This study does not support the hypothesis that the angiotensin-converting-enzyme insertion/deletion polymorphism is an important determinant of long-term transplant survival in Caucasian patients undergoing renal transplantation.

Adult↗
PubMed1998

Methylenetetrahydrofolate-reductase gene C677T variant and kidney-transplant survival.

UNLABELLED: BACKGROUND. Hyperhomocysteinaemia, a risk factor for atherosclerosis, is common in haemodialysis and renal-transplant patients. As atherosclerotic lesions in hyperhomocysteinaemia resemble those of chronic allograft injury, we examined the hypothesis that the C677T variant of the methylenetetrahydrofolate reductase (MTHFR) gene, which is linked to elevated plasma homocysteine levels in patients with renal failure, determines renal allograft survival. METHODS: DNA was prospectively collected from 336 patients undergoing renal transplantation in our clinic between 1988 and 1994 and their corresponding donors. Patient and allograft survival was analysed by blinded review of all case records over a follow-up period of 36 months. Additionally, we recruited 83 patients surviving with a functional kidney allograft for at least 10 years (mean: 156, range 120-240 months). MTHFR-C677T genotype was determined by a PCR-RFLP technique. The influence of genotype on transplant survival was analysed by Kaplan-Meyer life-table analysis and two-tailed global log-rank testing. RESULTS: Frequency of the MTHFR-C677T allele in the cohort group was identical in recipients (0.35) and donors (0.34), and comparable to that in the longterm allograft survivors (0.37). Furthermore, life-table analysis revealed a similar allograft survival over 36 months between the genotype groups (CC 74%, CT 69%, TT 75%). Other risk factors including donor and recipient age, hypertension, body-mass index, and number of rejection therapies were evenly distributed between the different genotype groups. CONCLUSIONS: These findings do not support the hypothesis that the C677T variant of the MTHFR gene is an important determinant of renal-transplant survival.

Adult↗
PubMed1997

Genetic variants of the renin-angiotensin system, diabetic nephropathy and hypertension.

Recent studies have suggested an association between a deletion (D) variant of the angiotensin-converting-enzyme (ACE) gene and diabetic nephropathy. However, this finding has not been confirmed by all investigators. Furthermore, an M235T variant of the angiotensinogen (AGT) gene has been associated with hypertension, an important risk factor for the development and progression of diabetic nephropathy. The objective of our study was therefore to examine the relationship between these genetic variants of the renin-angiotensin system and diabetic nephropathy and hypertension, respectively, in a large (n = 661) group of Caucasian patients with insulin-dependent (n = 360) or non-insulin-dependent (n = 301) diabetes mellitus. The study had a power of 0.8 to detect a doubling of risk of nephropathy or hypertension in patients with the ACE-DD or AGT-235TT genotype, respectively. Allelic frequencies of the ACE-D and AGT-235T alleles were similar between patients with and without nephropathy in either type of diabetes, and accordingly, there was no significant association between diabetic nephropathy and the ACE or AGT genotype. Likewise, there was no significant association between the ACE or AGT genotype and hypertension. Thus, our data, in this large and ethnically homogeneous group of patients, do not support the hypothesis that these genetic variants of the renin-angiotensin system are strongly associated with either nephropathy or hypertension in patients with insulin-dependent or non-insulin-dependent diabetes mellitus. These genetic markers are therefore unlikely to serve as clinically useful predictors of either nephropathy or hypertension in Caucasian patients with diabetes.

Adult↗
PubMed1997

Genetic variants of the renin-angiotensin system and ambulatory blood pressure in essential hypertension.

OBJECTIVE: To examine whether the angiotensinogen M235T and angiotensin converting enzyme insertion/deletion (I/D) variants are related to the severity of hypertension in patients with established essential hypertension. DESIGN: A cross-sectional study. SETTING: The hypertension clinic of the Benjamin Franklin University Hospital, Free University of Berlin. PARTICIPANTS: Three hundred and forty-three consecutive Caucasian patients who presented with treated or untreated (n = 115) hypertension were enrolled into the study. Twenty-two patients were excluded from analysis because they had secondary hypertension. MAIN OUTCOME MEASURES: Angiotensinogen M235T and angiotensin-converting enzyme I/D genotypes, 24 h ambulatory blood pressure values, the number of antihypertensive medications administered and left ventricular dimensions assessed by two-dimensional echocardiography. RESULTS: Neither the angiotensinogen nor the angiotensin converting enzyme genotype was related significantly to the average ambulatory blood pressure and left ventricular dimensions in hypertensives. Furthermore, neither the number of antihypertensive medications administered to treated patients nor blood pressure levels in untreated patients (n = 115) differed significantly between the genotypic groups. CONCLUSIONS: These results do not support the hypothesis that the studied molecular variants of the renin-angiotensin system may represent clinically useful markers of the severity of hypertension in Caucasians with established essential hypertension.

Adult↗
PubMed1997

Hpa II polymorphism of the atrial natriuretic peptide gene and the blood pressure response to salt intake in normotensive men.

OBJECTIVE: To test the hypothesis that the Hpa II variant of the atrial natriuretic peptide gene (ANP), which has been reported to be more common among black hypertensives than it is among normotensive controls, is related to the response of blood pressure to salt intake in normotensive Caucasians. METHODS: One hundred and three young (aged 19-35 years) male volunteers were fed a low-salt diet (20 mmol NaCl/day) for 2 weeks and a supplement of either 200 mmol NaCl/day (slow sodium) or placebo for 1 week each in a randomized double-blind cross-over order. Salt sensitivity was defined as a significant (P < 0.05) decrease in resting mean arterial blood pressure by > 3 mmHg under the low-salt diet. The genotype was determined by amplification of genomic DNA extracted from peripheral leukocytes and subsequent digestion of the amplicon with Hpa II restriction enzyme. RESULTS: According to the above definition, 27 subjects were salt sensitive. There were no significant differences in age, body-mass index and waist:hip ratio between the salt-sensitive and salt-resistant groups. Only salt-sensitive subjects displayed a significantly higher blood pressure under the high-salt diet (increase in mean arterial pressure 5.6 +/- 2.4 mmHg, P < 0.001). The prevalence of the ANP-Hpa II wild-type (w) allele did not differ between the salt-sensitive (qw = 1.0, qm = 0) and the salt-resistant group (qw = 0.96, qm = 0.04). Furthermore, the salt-induced response of blood pressure did not differ between homozygotes (ww) and heterozygotes (wm). CONCLUSIONS: Our findings do not support the hypothesis that the ANP-Hpa II polymorphism is a marker for salt sensitivity in young Caucasian normotensives.

Adult↗