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Biomedical subjects

H Holdaas

Publications and source records attributed to H Holdaas.

At least 37 records · Page 2Linked to original sources
PubMed1998

Renal effects of losartan and amlodipine in hypertensive patients with non-diabetic nephropathy.

BACKGROUND: The objective of this study was to examine the effects of angiotensin II receptor blocker losartan versus the calcium channel blocker amlodipine on proteinuria, renal haemodynamics, glomerular sieving and tubular function in hypertensive patients with non-diabetic nephropathy. METHODS: The study design was a prospective, double blind, placebo controlled, randomized crossover trial with amlodipine and losartan. Renal parameters were measured at baseline and at the end of each 4-week active treatment period. Fifteen patients with a diagnosis of non-diabetic renal disease and hypertension were included. RESULTS: Mean arterial blood pressure decreased from 123+/-13 mmHg at baseline to 113+/-10 mmHg (P<0.01) on losartan and to 114+/-10 mmHg on amlodipine (P<0.01). Urinary albumin excretion significantly decreased from 3510+/-2586 mg/24 h at baseline to 2684+/-2051 mg/24 h (P<0.01) on losartan and increased non-significantly to 3748+/-3355 mg/24 h on amlodipine. Filtration fraction significantly decreased from a baseline value of 22.8+/-9.3% to 21.2+/-10.2% (P<0.05) on losartan and increased to 23.6+/-8.9% (ns) on amlodipine. Either drug did not significantly alter glomerular sieving of neutral dextrans. CONCLUSION: Our results demonstrate that losartan, but not amlodipine, decreased albumin excretion in hypertensive patients with non-diabetic nephropathy.

Adult↗
PubMed1996

Half dose of OKT3 is efficient in treatment of steroid-resistant renal allograft rejection.

Rejection episodes in renal allograft recipients are usually efficiently treated with high doses of intravenous methylprednisolone. Rejection therapy with OKT3 is often reserved for steroid-resistant episodes. However, the optimal dose of OKT3 in the treatment of steroid-resistant rejection is not known. Therefore, we randomized renal transplant recipients with steroid-resistant rejection to treatment with a standard daily intravenous dose of either 5 mg of OKT3 (n=15) or 2.5 mg of OKT3 (n=15) for 10 days. Circulating T cells (measured as CD2+ cells) were adequately and equally depleted in the two groups. Three grafts were lost due to rejection within the first 3 months following OKT3 administration, one in the 2.5 mg OKT3 group and two in the 5 mg OKT3 group. Two nonimmunologic graft losses occurred in the 2.5 mg OKT3 group. Median serum creatinine values were not different between the two groups, neither at the start (median values: 200 micormol/L in the 5 mg OKT3 group vs. 188 micromol/L in the 2.5 mg group) nor immediately after OKT3 rescue therapy (202 micromol/L vs. 185 micromol/L, respectively). Eight cytomegalovirus infections occurred in each group. Two re-rejection episodes occurred in the 5 mg OKT3 group and one occurred in the 2.5 mg OKT3 group. All responded to treatment. Function of the remaining grafts estimated by serum creatinine after a mean long-term follow-up of 18 months (range, 6-36 months) revealed no differences (185 micromol/L in the 5 mg OKT3 group vs. 170 micromol/L in the 2.5 mg OKT3 group). We conclude that OKT3 treatment of steroid-resistant rejections in renal transplant recipients is equally effective in daily doses of 2.5 mg and 5 mg with respect to reversal rate and long-term outcome.

Adult↗
PubMed1996

Glomerular ultrastructure in kidneys transplanted simultaneously with a segmental pancreas to patients with type 1 diabetes.

BACKGROUND: Pancreas transplantation has been reported to prevent development and progression of diabetic glomerulopathy. STUDY DESIGN: Kidneys transplanted to type 1 diabetic patients were investigated for signs of diabetic glomerulopathy. Biopsies were obtained from 11 patients 2-4 years after simultaneous pancreas and kidney transplantation and from six patients 2-6 years after kidney transplantation alone. During follow-up, glycaemic control was monitored as glycated haemoglobin and, in the pancreas transplant patients, as i.v. glucose tolerance. RESULTS: Measures of glycaemic control were consistently normal in only two pancreas transplant patients. Four had mean k values <1.0. In kidney biopsies from the pancreas transplant patients, thickness of the glomerular basement membrane was 395 (0.13) nm (mean, coefficient of variation), which is higher than normal (324 (0.13) nm, P=0.01) and not different from diabetic patients with kidney transplants alone, 418 (0.15) nm. The mean calculated annual increase in thickness did not differ between patients with and without a pancreas transplant, 26 (0.77) versus 29 (0.54) nm/year. Estimates of the mesangium and mesangial matrix were in the normal range in both groups while the interstitial volume fraction was increased and to a similar extent. CONCLUSION: The increase in thickness of the glomerular basement membrane in kidneys transplanted simultaneously with a segmental pancreas is probably an expression of diabetic glomerulopathy caused by the modest impairment in glucose metabolism present in most patients.

Adult↗
PubMed1996

Five years' follow-up of renal glomerular and tubular functions in heart transplant recipients.

BACKGROUND: Many studies have shown that cyclosporine A may have detrimental long-term effect on kidney function. However, few prospective long-term studies have assessed both glomerular and tubular functions of the kidneys in heart transplant recipients METHODS: We examined 10 heart transplant recipients prospectively for 5 years. Hemodynamic data were obtained by standard heart catheterization technique, and glomerular filtration rate and blood flow were calculated as clearance of inulin and paraaminohippuran, respectively. Tubular functions were assessed by renal excretion of enzymes and albumin and by the lithium clearance method. All patients received cyclosporine A, azathioprine, and prednisolone as immunosuppressive regimen. The dose of cyclosporine averaged 3.9 +/- 0.3 during the first year and 3.2 +/- 0.3 mg/kg up to 5 years. RESULTS: All patients completed the study. Four received rejection therapy. Six were treated for hypertension. Cardiac output remained unchanged and averaged 5.5 +/- 0.9 L/min at baseline. No change ws found in any of the measured or calculated central hemodynamic parameters except a tendency toward an increased systemic peripheral resistance with time. Glomerular filtration remained constant at 66 +/- 22 ml/min, renal plasma flow showed a tendency to decline averaging 361 +/- 133 at baseline and 254 +/- 68 ml/min at 5 years (p = 0.08). Albumin excretion rate increased from 22 +/- 27 to the 102 +/- 100 micrograms/min between 1 and 5 years ( p < 0.05). The excretion of tubular enzymes, N-acetyl-6-glucosaminidase and alkaline phosphatase, and the renal handling of lithium remained unchanged. CONCLUSIONS: Cyclosporine therapy over 5 years did not progressively impair glomerular or tubular functions. However, the occurrence of microalbuminuria may be caused by therapy with cyclosporine itself or associated hypertension.

Albuminuria↗
PubMed1995

Pretransplant plasma exchange or immunoadsorption facilitates renal transplantation in immunized patients.

Patients with preformed antibodies against HLA molecules accumulate on renal transplant waiting lists and have inferior graft survival compared with nonsensitized patients. One hundred patients were included in a program of pretransplant removal of antibodies by plasma exchange (n = 90) or immunoadsorption (n = 10) in addition to prednisolone and cyclophosphamide medication. After plasma exchange, the panel reactivity and the antibody titer were reduced in about half of the patients, and after immunoadsorption the panel reactivity fell in 6 of 10 patients. Of the 83 patients who received grafts, 17 received a graft from a living donor (LD) and 66 received a graft from a cadaver donor (CD). Patients with a positive crossmatch against their LD were included in the program and were thus grafted with a recent positive, current negative crossmatched organ. Fifteen CD graft recipients had a pretreatment positive crossmatch toward their donor. No episodes of hyperacute rejection were seen. One- and 4-year graft survival rates in LD transplants with a recent positive and current negative crossmatch were 77% and 64%, respectively. At 1 and 4 years, graft survival rates were 70% and 57% in pretreated first CD graft recipients (n = 27) and 61% and 47% in pretreated regrafted patients (n = 39), respectively. In this program, a high rate of transplantation among the sensitized patients was achieved. Graft survival was inferior to that seen in nonsensitized patients, but was comparable to graft survival in sensitized patients at other centers.

Adult↗
PubMed1995

Effect of fluvastatin for safely lowering atherogenic lipids in renal transplant patients receiving cyclosporine.

The lipophilic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have been associated with rhabdomyolysis in cyclosporine-treated treated patients, indicating an interaction of drugs. We therefore studied the safety and efficacy of the hydrophilic HMG-CoA reductase inhibitor fluvastatin in 14 cyclosporine-treated renal transplant patients. To qualify for inclusion, total cholesterol after dietary stabilization had to be > 240 mg/dL. Prior to starting active medication, patients underwent a 4-week placebo period. Fluvastatin was given in a dose of 20 mg once daily for 12 weeks, which was increased to 20 mg twice daily for a further 8 weeks. Fluvastatin reduced total and low density lipoprotein cholesterol in all patients at both dosages whereas no effect on high density lipoprotein cholesterol was observed. Triglyceride levels were lowered at week 20. Incremental dosages of fluvastatin did not affect cyclosporine concentration and no adjustment of cyclosporine dosage was necessary. The higher doses of fluvastatin also had no effect on renal function as judged by serum creatinine levels. Creatine phosphokinase remained unchanged throughout the study. No serious side-effects were observed. In conclusion, the hydrophilic HMG-CoA reductase inhibitor fluvastatin at either 20 or 40 mg/day appears to be both safe and effective in lowering atherogenic lipids in renal transplant patients.

Adolescent↗
PubMed1995

[Pancreas transplantation. A 10-year material].

A programme for pancreas transplantation was initiated in Oslo in 1983. Of a total of 100 transplants so far, 14 were performed as pancreas transplantation alone (PTA) in non-uremic diabetics (n = 9), or as pancreas after kidney (PAK), i.e. in diabetic patients with a functioning renal transplant (n = 5). Duct occluded segmental grafts were used until 1988, when the pancreaticoduodenal technique with bladder drainage was introduced. Since 1991, owing to a low graft survival rate in PAK and PTA cases, all pancreas transplantations have been performed simultaneously with a renal transplant, giving a one-year survival of 82%, 83% and 93% for kidney, pancreas and patient respectively. The authors give a brief overview of the experience gained during ten years, with a pancreas transplant rate of ten/year.

Adult↗
PubMed1995

Contrasting effects of angiotensin converting inhibitor and alpha-1-antagonist on albuminuria in insulin-dependent diabetes mellitus patients with nephropathy.

OBJECTIVE: The main aim of this study was to examine the effects of an angiotensin converting inhibitor, enalapril, and an alpha-1 (alpha-1) antagonist, doxazosin, on albumin excretion, renal haemodynamics and tubular function in insulin-dependent diabetes mellitus patients with nephropathy. DESIGN: The study consisted of a four-week run-in period, a four-week active treatment period, a four-week wash-out period and a second four-week active treatment period. SETTING: The study was performed in the out-patient clinic at a university hospital. SUBJECTS: Ten patients with insulin dependent diabetes mellitus with macroalbuminuria (> 200 micrograms min-1), mild to moderate hypertension (diastolic blood pressure 85-115 mmHg) and serum creatinine level below 200 mumol L-1 were included in the study. MAIN OUTCOME MEASURES: The effect of the drugs on albumin and total protein excretion, beta-2-microglobulin, proximal tubular enzyme markers and renal haemodynamics. RESULTS: Systolic and diastolic blood pressure were equally reduced by both drugs. Enalapril reduced albumin excretion from 1090 +/- 281 micrograms min-1 to 742 +/- 246 micrograms min-1 (P < 0.01) and total protein excretion from 2.0 +/- 0.4 g per 24 h to 1.3 +/- 0.4 per 24 h whereas doxazosin was without effect. Glomerular filtration rate and effective renal plasma flow were unchanged by either drug. Doxazosin increased filtration fraction from 0.21 +/- 0.02 to 0.23 +/- 0.01 (P < 0.05). The urinary excretion of the proximal enzyme markers N-acetyl-beta-glucosaminidase and alkaline phosphatase were elevated as well as urinary excretion of beta-2-microglobulin. However, neither the excretion of beta-2-microglobulin nor the enzyme markers were affected by either drug. CONCLUSIONS: Enalapril, but not doxazosin, reduces albuminuria in insulin dependent diabetes mellitus patients with nephropathy. The drugs exert differential effects on renal haemodynamics.

Adult↗
PubMed1995

Is dietary intervention effective in post-transplant hyperlipidaemia?

Current therapies for hyperlipidaemia following renal transplantation include modification of dietary fat. We examined the effect of dietary intervention according to the American Heart Association Step One diet on serum lipids and lipoproteins among 26 men and women with post-transplant hyperlipidaemia. Weighed dietary records showed that the intake of total fat decreased from 30 to 27% and the intake of saturated fat decreased from 12 to 8% of total calories. Body-weight remained stable throughout the study. Serum total, LDL and HDL cholesterol levels were unchanged following 12 weeks of therapy. Serum triglyceride levels decreased slightly. The decrease was seen only in participants with a body mass index < 26 kg/m2, compared to those whose body mass index was > or = 26 kg/m2 (0.4 versus 0 mmol/l; P = 0.03). Serum LDL cholesterol and triglyceride levels were significantly correlated with serum creatinine levels. In conclusion, among renal transplant recipients, hyperlipidaemia appears to be partly related to impairment of renal function, and may not be responsive to modification of dietary fat without weight reduction attempted on an outpatient basis.

Adult↗
PubMed1994

Accidental metabolic acidosis during hemodialysis.

Three incidents of metabolic acidosis during hemodialysis in 3 different patients are presented. Two patients became severely ill but recovered completely after treatment. In the third patient, the event was recognized before the acidosis became symptomatic. In all cases the acidosis was caused by an unbalanced supply of acidic dialysis concentrate. Two events were caused by mistaking acidic dialysis concentrate for acetate. In the third patient, the supply line from the bicarbonate concentrate jug was broken. The conductivity cell alarm was not activated during any of the incidents and in only 1 case during reconstruction of the accidents. The efficacy and safety of the conductivity cell alarm system regarding prevention of acid/base disturbances during hemodialysis are discussed.

Acidosis↗
PubMed1994

Contrasting short-term effects of nifedipine on glomerular and tubular functions in glomerulonephritic patients.

The short-term effects of nifedipine on glomerular hemodynamics, sieving function, and renal tubular function were assessed in 10 patients suffering from biopsy-verified chronic glomerulonephritis. Three weeks of nifedipine treatment after 2 wk of placebo significantly reduced the blood pressure from 153 +/- 6/90 +/- 3 to 139 +/- 6/84 +/- 4 mm Hg (mean +/- SE; P < 0.05). Renal vascular resistance was reduced from 0.54 +/- 0.10 to 0.46 +/- 0.08 mm Hg/mL per minute. However, GFR (44.3 +/- 7 mL/min), effective RPF (265 +/- 37 mL/min), and filtration fraction (0.17 +/- 0.01) remained unchanged. The excretion of albumin of 1,318 +/- 395 micrograms/min was not affected by nifedipine. The glomerular sieving estimated by use of the fractional dextran clearance technique revealed no significant change by nifedipine compared with placebo in the range of 30 to 60 A of hydrodynamic dextran radius. Fractional proximal reabsorption (lithium clearance method) was reduced by nifedipine from 53 +/- 5 to 46 +/- 4% (P < 0.05). Also, the excretion of beta 2-microglobulin and N-acetyl-beta-glucosaminidase increased from 10.98 +/- 4.62 to 11.86 +/- 4.74 mg/24 h (P < 0.05) and from 19.7 +/- 4.2 to 25.3 +/- 7.0 nmol/h per micromoles of creatinine (P = 0.05), respectively. It was concluded that nifedipine treatment acutely represses proximal tubular function but is without significant effect on glomerular sieving and albuminuria in these patients.

Adult↗
PubMed1994

[Infection in patients with organ transplants].

The past decade has seen substantial improvements both in patient and graft survival in organ transplantation. One-year survival rates among recipients of kidney, pancreas, liver, and lung transplants now reach 80-90 per cent. The impressive survival statistics notwithstanding, any organ transplantation is still associated with a variety of possible complications. Prominent among the causes of morbidity and morality is the occurrence of infection, primarily due to the intensive immunosuppression. The diagnosis and treatment of infections are thus of paramount importance to the success of a transplantation programme.

Bacterial Infections↗
PubMed1992

Fifteen years' experience with renal transplantation in systemic amyloidosis.

At our center 62 renal transplantations (31 living donor and 31 cadaveric donor grafts) have been performed in 58 patients with amyloid renal disease since 1974. The amyloidosis was secondary to rheumatic disease in 74% of the patients. Predialytic transplantation was performed in 28% of the patients. Mean follow-up time was 5.1 years (0.3-14.5 years). One-year actuarial patient survival was 79%, decreasing to 65% after 5 years. First graft survival was 74% at 1 year and 62% at 5 years. Patient death with a functioning graft caused 16 out of 25 graft losses. Infections caused 11 out of 18 deaths (61%), more than half of them within 3 months. Renal transplant amyloid was diagnosed in about 10% of the cases (6/62); however, only about 3% of the grafts (2/62) were lost. These long-term results encourage transplantation in amyloid renal end-stage disease.

Adolescent↗
PubMed1992

Long-term clinical results of percutaneous transluminal angioplasty in transplant renal artery stenosis.

Twenty-five patients with transplant artery stenosis were identified among 1141 renal graft recipients. Impaired graft function (9 patients), hypertension (4 patients) or both (12 patients) were the indications for arteriography. All were treated by percutaneous angioplasty (PTA). The immediate technical success rate was 88% and actuarial graft survival was 88% and 80% at 2 and 5 years respectively. The long-term success rate on graft function was 67% (median observation time 24 months) and on hypertension 63% (median observation time 23 months). Six patients needed rePTA (8 procedures) and in only one patient was surgical repair performed. No case of graft loss due to PTA was recorded and in only one case did occlusion of a segmental artery lead to impairment of graft function. Minor complications were recorded in four other cases and in no case was surgical intervention necessary. Based on these results we favour PTA as a first-line interventional procedure in transplant renal artery stenosis, and the need for surgical repair has been low.

Adult↗
PubMed1991

Long-term metabolic control in recipients of combined pancreas and kidney transplants.

Metabolic glucose control was followed in 36 patients at 12-month intervals for up to 5 years after a successful combined kidney and segmental duct-occluded pancreas transplantation. All recipients had normal blood glucose levels at each examination. HbA1 values, intravenous glucose tolerance test, C-peptide levels and C-peptide responses to glucagon stimulation were also, on average, within the normal range. Several individual patients had, however, abnormal values for these parameters. At most 46% had abnormal values for HbA1 and intravenous glucose tolerance test, up to 13% showed low C-peptide values and up to 46% of the stimulated C-peptide responses were inadequate at the different intervals. These parameters did not deteriorate with time. This was true both for the whole group of patients as well as for the 6 patients with a 5-year observation time evaluated separately. Despite these abnormalities in glucose metabolism, all patients remained normoglycaemic without need for exogenous insulin up to 5 years after transplantation. The long-term ability of duct-occluded segmental pancreatic grafts to preserve euglycaemia therefore seems to remain intact at least for 5 years.

Adult↗