Standardising clinical outcomes measures for adult clinical trials in Fabry disease: A global Delphi consensus.

BACKGROUND: Recent years have witnessed a considerable increase in clinical trials of new investigational agents for Fabry disease (FD). Several trials investigating different agents are currently in progress; however, lack of standardisation results in challenges to interpretation and comparison. To facilitate the standardisation of investigational programs, we have developed a common framework for future clinical trials in FD. METHODS AND FINDINGS: A broad consensus regarding clinical outcomes and ways to measure them was obtained via the Delphi methodology. 35 FD clinical experts from 4 continents, representing 3389 FD patients, participated in 3 rounds of Delphi procedure. The aim was to reach a consensus regarding clinical trial design, best treatment comparator, clinical outcomes, measurement of those clinical outcomes and inclusion and exclusion criteria. Consensus results of this initiative included: the selection of the adaptative clinical trial as the ideal study design and agalsidase beta as ideal comparator treatment due to its longstanding use in FD. Renal and cardiac outcomes, such as glomerular filtration rate, proteinuria and left ventricular mass index, were prioritised, whereas neurological outcomes including cerebrovascular and white matter lesions were dismissed as a primary or secondary outcome measure. Besides, there was a consensus regarding the importance of patient-related outcomes such as general quality of life, pain, and gastrointestinal symptoms. Also, unity about lysoGb3 and Gb3 tissue deposits as useful surrogate markers of the disease was obtained. The group recognised that cardiac T1 mapping still has potential but requires further development before its widespread introduction in clinical trials. Finally, patients with end-stage renal disease or renal transplant should be excluded unless a particular group for them is created inside the clinical trial. CONCLUSION: This consensus will help to shape the future of clinical trials in FD. We note that the FDA has, coincidentally, recently published draft guidelines on clinical trials in FD and welcome this contribution.

Outcome in biopsy-proven Lupus nephritis: Evaluation of biopsies from the Norwegian Kidney Biopsy Registry.

Objective To evaluate long-term mortality and end-stage renal disease (ESRD) in a cohort of Norwegian patients with biopsy-proven lupus nephritis (LN). Methods Renal biopsies were obtained from 178 patients with LN from 1988 until 2007. Mortality rate and death causes were provided by Statistics Norway and ESRD data were provided by the Norwegian Renal Registry. Risk factors for all-cause mortality were evaluated by Cox regression. Standardized mortality ratio (SMR) was compared to observed deaths in a matched general population sample. Results Mean age was 37.6 (±14.4) years, and median time of follow-up was 8.5 years (0-26.2). Thirty-six patients (20.2%) died during follow-up. The SMR for all-cause mortality was 5.6 (Confidence interval [CI] 3.7-7.5). In an adjusted multivariate analysis proliferative glomerulonephritis (LN class IV) was independently associated with all-cause mortality; hazard ratio (HR) 2.6 (Confidence interval [CI] 1.2-5.7 p = 0.017). Main causes of death were infections (47.2%) and cardiovascular events 8 (22.2%). Thirty-six patients (20.2%) reached ESRD. Conclusions Biopsy-proven LN is associated with increased mortality compared to the general population. LN class IV is associated with all-cause mortality. Infections and cardiovascular events were the most common causes of death. Patients with LN have a high incidence of ESRD.

Polyvinylpyrrolidone induced artefactual prolongation of activated partial thromboplastin times in intravenous drug users with renal failure.

Essentials Prolonged activated partial thromboplastin times (APTT) were found in drug users with renal failure. An oral methadone solution containing polyvinylpyrrolidone (PVP) had been injected intravenously. Spiking normal plasma with increasing concentrations of PVP resulted in artifically prolonged APTT. APTT prolongation may indicate PVP deposits as underlying cause in patients with renal failure. SUMMARY: Unexpectedly prolonged activated partial thromboplastin times (APTTs) were noted in several patients with chronic renal insufficiency and a history of intravenous drug abuse. Deposits of polyvinylpyrrolidone (PVP), an excipient in one oral methadone solution used in opioid maintenance programs, were found in renal biopsies. One case is described in detail, and this is followed by a summary of findings in 11 other patients and the results of an in vitro experiment in which plasma was spiked with PVP at increasing concentrations. APTTs measured with STA PTT automate (Stago) were prolonged in all patients and in spiked samples, whereas supplemental coagulation parameters and APTTs measured with HemosIL SynthAsil or Actin FSL (Siemens) were within reference intervals. These results indicate that interference with APTTs by PVP is reagent-dependent. We suggest that a prolonged APTT should raise the suspicion of PVP deposit-associated kidney disease in patients with chronic renal failure and a history of intravenous drug abuse.

Phenotypic variation in a large family with autosomal dominant hypocalcaemia.

BACKGROUND/AIMS: Autosomal dominant hypocalcaemia (ADH) is caused by activating mutations in the calcium- sensing receptor (CASR). We aimed to describe the phenotypic variation within a large family with ADH, especially kidney and cerebral basal ganglia calcifications. METHODS: Fifteen related subjects carrying the CASR mutation T151M participated in a cross-sectional study of calcium homeostasis, renal ultrasonography, cerebral CT, bone mineral density, and health-related quality of life (HRQoL). RESULTS: Eight subjects had received vitamin D treatment (mean duration 15.3 years; range 11-20 years). Urinary calcium excretion was elevated in 5/8 vitamin-D-treated and in 3/7 untreated subjects. Serum magnesium, calcium and parathyroid hormone remained at the lower reference limit or below. Renal calcifications were found in 12 of 14 (86%) and basal ganglia calcifications in 5 of 11 (46%) subjects, independently of vitamin D therapy. The glomerular filtration rate was moderately reduced in 3 subjects. Mean bone mineral density and bone markers were normal. HRQoL was impaired in the vitamin-D-treated group despite correction of the hypocalcaemia. CONCLUSIONS: The impact of the CASR mutation on calcium homeostasis varied greatly. Kidney and basal ganglia calcifications are common in ADH independently of vitamin D treatment, which, however, increases urinary calcium excretion and may promote urolithiasis.

The MDRD equation may mask decline of glomerular filtration rate in Fabry patients with normal or nearly normal kidney function.

AIMS: The renal prognosis in Fabry disease is better when enzyme replacement therapy (ERT) is initiated before glomerular filtration rate (GFR) deteriorates. Current studies evaluating kidney function in Fabry disease are mainly based on the MDRD equation. The aim of this cross sectional study was to compare estimated and measured GFR in adult Fabry patients with normal or near normal kidney function. METHODS: Iohexol GFR (mGFR) was compared to estimated GFR (eGFR) (MDRD, Cockcroft-Gault and Counahan-Barratt equations) in 8 male and 13 female Fabry patients with minimal albuminuria and mean mGFR of 94 ml/min/1.73 m2 for both genders. RESULTS: A significant overestimation of eGFR-MDRD by 24 ml/min/1.73 m2 was seen in male Fabry patients. The performance of the MDRD equation was similar to mGFR in female Fabry patients. GFR was significantly overestimated by the Cockcroft-Gault equation, whilst Counahan-Barratt equation gave results in agreement with mGFR for both male and female Fabry patients. CONCLUSIONS: Overestimation of eGFR-MDRD in Fabry patients with CKD stage 1 - 2 and minimal albuminuria may prevent recognition of early progressive renal failure and delayed ERT initiation may be the consequence. Exact GFR markers should be part of the routine evaluation of GFR in Fabry patients.

Critical renal artery stenoses may cause a spectrum of cardiorenal failure and associated thromboembolic events.

A wide spectrum of acute or chronic heart failure and thromboembolic events may be causally related to high-grade uni- or bilateral renovascular hypertensive disease, and the variety of these potential interactions may be unrecognized in clinical practice. We present three cases that illustrate the clinical variability of cardiorenal failure and thromboembolic events seen in patients with significant renal artery stenoses. These are high-risk patients where severe morbidity and mortality are threatening. Our patients also demonstrate that the diagnosis often is delayed, and that recanalizing of occluded renal arteries may be highly cost-effective and life-saving in such patients.

Focal and segmental glomerular sclerosis (FSGS) in a man and a woman with Fabry's disease.

We describe a man and a woman with Fabry's disease. Renal biopsies showed late and early stages respectively of focal and segmental glomerulosclerosis (FSGS) and vascular changes. Clinically the hemizygous patient had advanced renal disease with nephrotic range proteinuria and serum creatinine 122 micromol/l. The female carrier had minimal albuminuria, borderline GFR with a normal serum creatinine, acroparesthesias, moderate fatigue, tinnitus and headache accompanied by ischemic cerebral lesions. Enzyme replacement therapy (ERT) was initiated according to our Fabry protocol, partly due to the renal morphologic findings. We conclude that FSGS and vascular changes may be an early morphologic finding in Fabry's disease, even in patients with subtle albuminuria. The potential role of FSGS as a marker of progressive renal disease in some Fabry patients is discussed. As FSGS and vascular changes obviously may exist across a wide range of clinical presentations and have potential prognostic implications, we suggest that a renal biopsy should be performed prior to enzyme replacement therapy in all adult Fabry patients with proteinuria of various levels. Efforts should be made to develop a scoring system to evaluate potential histologic markers. Protocol biopsies may have therapeutic implications and may provide valuable information in the evaluation of start and dosing of ERT.

Effect of light exercise on renal hemodynamics in patients with hypertension and chronic renal disease.

OBJECTIVE: Increased physical activity is followed by a stimulation of the sympathetic nervous system and this effect is probably more pronounced in patients with chronic renal failure and hypertension than in healthy controls. The role of sustained exercise in hypertensive patients with chronic renal failure, with and without antihypertensive therapy, is unclear, as is hormonal regulation of the renal hemodynamics. We hypothesized that prolonged low-intensity bicycle exercise would have a greater effect in patients with chronic renal failure than in controls, and that antihypertensive treatment would ameliorate these effects. MATERIAL AND METHODS: Glomerular filtration rate (GFR), effective renal plasma flow (ERPF), mean arterial blood pressure (MAP), norepinephrine (NE) and atrial natriuretic peptide (ANP) were measured in the upright position before and during low-intensity exercise for 2 h in healthy controls (n = 8) and in hypertensive patients with moderately reduced renal function who were not taking antihypertensives (n = 7) or who were receiving treatment with captopril (n = 10), enalapril (n = 6) or verapamil (n = 9). RESULTS: GFR tended to decrease and ERPF decreased significantly in healthy individuals when exercise duration was prolonged from 1 to 2 h. An earlier decline in GFR and ERPF was seen in the renal failure patients compared with the controls. Filtration fraction (FF) increased during exercise in all groups except the group taking enalapril. MAP increased in the captopril group during exercise but was unchanged in the other groups. Treatment with captopril produced a more pronounced and earlier fall in exercise-induced GFR than in untreated controls, while verapamil treatment completely blunted the decline in GFR, with a concomitant increase in plasma ANP. No significant changes were seen in plasma NE levels, but urinary NE excretion increased in controls and captopril-treated patients during exercise. CONCLUSIONS: The results suggest that prolonged low-intensity exercise has a substantially greater effect on renal hemodynamics in hypertensive renal failure patients than in healthy controls, with negligible changes in plasma NE levels. Verapamil treatment seems to ameliorate the renal effects of exercise on GFR in these patients, and this may in part be mediated via a stimulatory effect on ANP.

[Emergency dialysis at Haukeland hospital in 1999]. / Akutt dialysebehandling ved Haukeland Sykehus i 1999.

BACKGROUND: The incidence of acute renal failure requiring dialysis is not known in our country. The criteria for acute dialysis are not uniformly accepted, neither is there consensus on dialysis strategy in critically ill patients. We describe the acute dialysis activity in our hospital in 1999. MATERIAL AND METHODS: We have retrospectively recorded the indications for dialysis and the course and hospital mortality in all patients treated with acute dialysis in 1999. RESULTS: 108 patients were treated with 670 dialysis procedures; the incidence was 20.5 per 100,000 inhabitants. Continuous veno-venous haemodiafiltration accounted for 37% of all treatments. In 50% of the patients acute renal failure occurred after surgery or serious infections with a mortality of 57% and 62% respectively. Total dialysis mortality was 45%. The mortality in patients with malignancy and peripheral vascular disease was 90% and 75% respectively. 10% of the patients needed chronic dialysis. INTERPRETATION: The incidence of acute dialysis was higher than previously reported from European countries and may be related to the general increase in active treatment of patients with complicated diseases. The mortality rates are persistently high. Close cooperation between nephrologists and intensivists in the treatment of these patients is essential.

[Acute renal failure, renal artery stenosis and angiotensin-converting enzyme (ACE) inhibitor]. / Akutt nyresvikt, nyrearteriestenose og angiotensinkonvertase (ACE)-hemmer.

BACKGROUND: Acute renal failure is a well-known complication in patients with renal artery stenosis during treatment with ACE inhibitor. Renal artery thrombosis after withdrawal of ACE inhibitor has not been reported previously. MATERIAL AND METHODS: We describe a patient with acute renal failure with an unexpected course. RESULTS: A 67-year-old man was admitted with acute anuric renal failure during treatment with hydrochlorothiazide and enalapril. His blood pressure was 165/60 mm Hg. Renal ultrasound was normal. After initial rehydration and dialysis, diuresis resumed until a sudden unexpected anuric renal failure recurred on day 12. Angiography disclosed bilateral renal artery occlusion. The right renal artery was successfully opened and a stenosis was blocked and stented, and brisk diuresis ensued. Two days later hypertension accelerated, and a new invasive procedure on day 24 succeeded in opening, blocking and stenting a proximal stenosis in the left artery; a mobile thrombus was located behind the stenosis and successfully treated with intraarterial thrombolysis. Blood pressure rapidly normalized, and serum creatinine was normal on visits 1.5 and 4 months later. INTERPRETATION: General aspects and prevention of acute renal failure during ACE inhibitor therapy are discussed. Acute renal thrombosis after withdrawal of ACE inhibitor in patients with stimulated renin angiotensin system and significant renal artery stenosis may be causally related to the antifibrinolytic effects of angiotensin II and aldosterone. Endovascular reconstruction of renal artery occlusion may completely restore the kidney function.

Renal hemodynamic effects of captopril and doxazosin during slight physical activity in hypertensive patients with type-1 diabetes mellitus.

Angiotensin-converting enzyme inhibitors are renoprotective in diabetes mellitus through their intrarenal hemodynamic effects. Alpha-1 blockade has variable pre- and postglomerular vasodilatory effects dependent upon the stimulation of the sympathetic nervous system. We tested the hypothesis that the two different classes of drugs have similar renal hemodynamic effects when the patients are examined in an upright position where the sympathetic nervous system is activated. Mean blood pressure (MAP), glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were examined in 28 hypertensive type-1 diabetic patients with variable degree of nephropathy treated for a mean period of 7.6 +/- 0.4 months with captopril (n = 13) or doxazosin (n = 15). Average treatment doses were 112 +/- 7 mg/day in the captopril group and 8 +/- 1 mg/day in the doxazosin group. Sitting MAP decreased from 118 +/- 3 to 106 +/- 4 mm Hg after captopril (p < 0.05), and from 117 +/- 4 to 110 +/- 3 mm Hg after doxazosin (p = 0.07). GFR and ERPF were unchanged in both groups. The filtration fraction (FF) decreased from 0.27 +/- 0.02 to 0.25 +/- 0.02 after captopril (p < 0.05) and from 0.26 +/- 0.01 to 0.25 +/- 0.01 after doxazosin (p = 0.08). Calculation of 95% confidence intervals of the difference between the post-treatment values as well as the difference between pre- and post-treatment values of MAP, GFR, ERPF and FF of the two drugs indicates no difference in renal hemodynamic response between the drugs. In conclusion, captopril and doxazosin have similar renal hemodynamic responses when the patients are examined in a situation where the sympathetic nervous system is stimulated, and this suggests that doxazosin has a renoprotective effect beyond the blood pressure-lowering effect.

Sympathetic nervous system overactivity in hypertensive patients with chronic renal failure--role of upright body position.

OBJECTIVE: The renal functional consequences of an activated sympathetic nervous system and plasma atrial natriuretic hormone (ANP) in various renal diseases are not well described. We hypothesize that norepinephrine (NE) and ANP have antagonizing effects on renal hemodynamics in diseased kidneys. MATERIAL AND METHODS: Plasma NE, ANP. glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and mean arterial pressure (MAP) were measured in the upright position in healthy controls (n = 9) and hypertensive patients with reduced GFR (n =11). The same parameters were compared between healthy controls (n = 6) and hypertensive patients with reduced GFR (n = 6) in upright and supine positions. RESULTS: Upright plasma NE and ANP were significantly elevated in the patients compared with the controls (4.4 +/- 0.4 vs 2.1 +/- 0.2 nmol/l (p < 0.001) and 1.3.5 +/- 2.1 vs 6.9 +/- 1.0 nmol/l (p < 0.01) respectively). With change from upright to supine position plasma NE decreased in the controls (2.2 +/- 0.3 vs 1.7 +/- 0.3 nmol/l) (p < 0.01) and patients (3.8 +/- 0.4 vs 2.6 +/- 0.4) (p < 0.01). Supine ANP increased in controls (5.5 +/- 1.0 vs 8.3 +/- 1.1) (p < 0.01) but not in patients (14.3 +/- 3.8 vs 16.1 +/- 3.8 nmol/l) (p > 0.10). Plasma NE correlated positively with MAP (p < 0.001) and negatively with GFR (p < 0.01) in the upright but not supine position. A positive correlation between NE and ANP was observed in upright (p < 0.001) but not in supine position. ANP correlated negatively with GFR in the upright (p < 0.01) but not supine position. No position dependent changes were seen in GFR and ERPF, but supine filtration fraction (FF) increased insignificantly in the patient group (0.23 +/- 0.02 vs 0.24 +/- 0.02) (p < 0.05). CONCLUSION: Hypertensive patients with reduced GFR have elevated levels of plasma NE and ANP in the upright body position. When the upright and supine positions are compared, plasma NE declines in the supine position in controls and hypertensive renal failure patients. and plasma ANP levels are elevated only in the upright position in hypertensive renal failure patients where the sympathetic nervous system is activated. A significant positive relationship between plasma NE and ANP was observed only in the upright position. The upright body position seems superior to recumbency in the characterization of these hormonal changes in hypertensive chronic renal failure patients.

Factors influencing reduction in blood pressure and left ventricular mass in hypertensive type-1 diabetic patients using captopril or doxazosin for 6 months.

The effect of doxazosin versus captopril on blood pressure, albuminuria, and left ventricular mass was studied in 33 hypertensive type-1 diabetic patients randomized to 6 months treatment with captopril (17 patients, mean daily dose 100 mg) or doxazosin (16 patients, mean daily dose 9 mg). Casual and 24-h ambulatory blood pressure (24hBP) were reduced from 163/95 to 144/83 mm Hg and 152/86 to 145/81 mm Hg, respectively, in the captopril group, and from 160/93 to 145/86 mm Hg and 156/86 to 147/79 mm Hg in the doxazosin group (all P < .05). The achieved 24hBP on treatment was positively associated with pretreatment levels of glycosylated hemoglobin (HbA1c) and plasma atrial natriuretic peptide (r = 0.53 and 0.59, respectively, both P < .01). Albuminuria did not change significantly in either group. Left ventricular hypertrophy was present in 13 patients (7 in the captopril and 6 in the doxazosin group). Left ventricular mass was reduced by an average of 27% and 23%, respectively, in these patients (both P < .01), but did not change significantly in patients without left ventricular hypertrophy. The reduction in left ventricular mass was positively associated with the presence of baseline left ventricular hypertrophy and inversely with dietary sodium intake and achieved casual blood pressure on treatment (R2 = 0.59, P < .001). We conclude that doxazosin and captopril used for 6 months are equally effective in reducing blood pressure and left ventricular hypertrophy in hypertensive type-1 diabetic patients; the antihypertensive effect is closely related to glycemic control; and dietary sodium intake and achieved casual blood pressure after treatment are independent determinants of the reduction in left ventricular mass seen in these patients.

Kinetic basis of hyperhomocysteinemia in patients with chronic renal failure.

We investigated the elimination of total homocysteine (tHcy) from plasma after peroral homocysteine (Hcy) loading in eight patients with chronic renal failure. Data on bioavailability and distribution volume were obtained from two patients and two healthy controls by performing both intravenous and peroral Hcy loading. Response to high-dose folic acid was studied in six cases. Mean (SD) basal plasma tHcy was 27.4 (11.0) microM at inclusion. The half-life and the area under the curve were about four times higher, and clearance was reduced to 29.8% compared to controls. High-dose folic acid had no influence on half-life for tHcy, but the basal tHcy level declined by 26.8%. The reduction in tHcy was particularly pronounced in three patients with low-normal serum folate, and the enhanced methionine response to Hcy loading after folic acid suggested improved Hcy remethylation in tissues. In conclusion, patients with renal failure had markedly reduced clearance of tHcy from plasma, which probably accounts for their hyperhomocysteinemia. High-dose folic acid reduces fasting tHcy by improving tissue Hcy remethylation without affecting the low renal clearance of tHcy.

[Treatment of hypertension in renal parenchymal diseases]. / Behandling av hypertensjon ved parenkymatøse nyresykdommer.

Hypertension is a common finding in patients with renal parenchymatous diseases. Development of hypertension causes increased proteinuria, decline in glomerular filtration rate and reduced life span in experimental models of glomerulonephritis. Hypertension has been shown to reduce glomerular filtration rate in man. It is therefore important to treat hypertension. The blood pressure should be reduced to about 140/80 mm Hg. Reduction of glomerular capillary pressure, inhibition of glomerular permeability, renal hypertrophy and inhibition of mesangial metabolism are the main mechanisms of renal protection during antihypertensive therapy. Autoregulation of the renal blood flow probably has an impact on these mechanisms. Impaired autoregulation is found in kidneys with low glomerular filtration rate and during treatment with calcium channel blockers. Alpha receptor blockers, angiotensin converting enzyme inhibitors (ACE-) and angiotensin II receptor blockers do not interfere with autoregulation. All types of antihypertensive drugs provide similar renal protection when the glomerular filtration rate is reduced. When calcium channel blockers are used in kidneys with normal or slightly reduced function, either blood pressure should be kept strictly at normal levels or these type of drugs should be combined with ACE inhibitors or angiotensin II receptor blockers.

Salt sensitivity in hypertensive type-1 diabetes mellitus.

UNLABELLED: As sodium retention has been proposed as a causal factor in the development of hypertension in diabetic patients, a high incidence of salt sensitivity has been suggested. To evaluate the influence of dietary sodium intake on blood pressure, casual and 24-h blood pressure was measured in 30 hypertensive type-1 diabetic patients aged 24-67 (mean 46) years while they were on habitual diet, after 6 days of low-sodium diet (50 mmol/day), and after 6 days of high-sodium diet (250 mmol/day). Nine patients (30%) who increased their 24-h mean blood pressure by more than 10% when going from low- to high-sodium intake were classified as salt sensitive; the others as salt resistant. The salt sensitive group had a significantly lower urinary excretion of dopamine at baseline, and a higher diuresis and a more pronounced decrease in 24-h blood pressure during salt depletion (all p < 0.01). Low-sodium diet reduced casual and 24-h blood pressure by 4% in the total study population compared with 9% in the salt sensitive group (p < 0.01). There was no difference in glomerular filtration rate, filtration fraction, proteinuria or urinary sodium excretion between the groups. CONCLUSIONS: Sodium restriction more effectively reduces blood pressure in the salt sensitive minority of hypertensive type-1 diabetic patients irrespective of renal function. The incidence of salt sensitivity is not increased in hypertensive type-1 diabetic patients compared with essential hypertensive patients.

Extended measurement of glomerular filtration rate and effective renal plasma flow in ambulatory patients.

We describe a standardized clearance method over 5 h (one hour equilibration followed by eight consecutive 30 min clearance periods [period 2-9]) for the estimation of GFR (iothalamate I125) and ERPF (hippuran I131) during water diuresis in ambulatory and exercising patients. Four groups were examined. In group I (normal controls, n = 15) there were no significant changes in GFR, ERPF and FF (P > 0.10) during repeated clearance periods (mean of period 2-5 versus period 6-9). The reproducibility of the method was studied at a mean interval of 3.7 weeks in a group of patients with stable reduction of GFR (group II, n = 7). The values for GFR, ERPF, FF and RVR did not change significantly in this group, and correlated significantly between repeated studies (r = 0.81 to r = 0.99). In group III (untreated hypertensive patients with reduced GFR, n = 13) there was a time dependent 7.2% decrease in GFR (P < 0.05), significantly different from group I (P < 0.02), a 10.0% decrease in ERPF (P < 0.01) and no significant change in FF (P = 0.08) when the mean of period 2-5 was compared with the mean of period 6-9. In healthy controls (group IV, n = 8) light sustained bicycle exercise (25 W) induced a 7.1% decline in GFR (P < 0.01), 17.4% decline in ERPF (P < 0.001) and a 13.6% increase in FF (P < 0.001). We conclude that ambulatory measurements of GFR and RPF can be carried out over a period of 5 h with satisfactory precision and repeatability. Ambulatory hypertensive patients with moderately reduced GFR showed the same degree of time dependent downward drift of GFR and ERPF without exercise as was seen in healthy individuals during light exercise. Accordingly, in these groups single clearance periods imply a risk for under or overestimation of renal function, and time controls are necessary during clearance studies.

Renal effects of maintenance low-dose cyclosporin A treatment in psoriasis.

The renal effects of low-dose cyclosporin A (CsA) treatment in severe psoriasis was investigated in 10 patients treated with a mean CsA dose of 3.23 (range 1.94-4.10) mg/kg/day for 12 months. The psoriasis area and severity index was reduced by 63-76%. Ambulatory GFR (iothalamate-125I), ERPF (hippuran-131I), RVR and MAP were examined at 3-months intervals. A control renal biopsy was performed shortly before treatment start and a second biopsy was taken after 12 months of therapy. GFR was slightly but significantly reduced after 6 and 9 months; after 12 months the decrease was not significant (121.0 +/- 7.6 versus 115.2 +/- 7.8 ml/min/1.73M2, P > 0.10). After 12 months serum creatinine increased from 82 +/- 4 to 94 +/- 7 mumol/litre (P < 0.05), while an insignificant increase of ERPF was seen and FF decreased from 0.29 +/- 0.01 to 0.26 +/- 0.01 (P < 0.05). MAP remained unchanged. GFR and serum creatinine correlated significantly within each 3-month interval. A slight de novo interstitial fibrosis was seen in the second biopsy in 4 of 10 patients receiving a mean CsA dose of 3.2-4.1 mg/kg/day. In three of these patients a concomitant rise in serum creatinine was seen. In conclusion, low-dose CsA was associated with reversible fall in GFR and potentially progressive structural changes not always accompanied by corresponding functional alterations. One should consider reducing the daily dose of CsA to 3.0 mg/kg bodyweight or less in CsA therapy up to 1 year.

[Estimation of body composition in patients on dialysis by means of near-infrared interaction ]. / Estimering av kroppssammensetning hos dialysepasienter ved hjelp av naer infrarød interaksjon.

Malnutrition and low serum albumin values predict increased mortality in uremic patients. Infrared interactance represents a novel approach to the estimation of body composition. We have examined total body fat, body water and fat-free weight in our male haemodialysis (n = 24) and peritoneal dialysis (n = 17) patients. There were no differences between the groups in a cross-sectional study. A longitudinal study showed a significant increase of total body fat (%) in the peritoneal dialysis patients after five months (mean values +/- SEM) (from 19.8 +/- 2.3 to 22.6 +/- 2.4, p < 0.05), and a significant decrease of body water (%) (from 59.9 +/- 1.5 to 58.2 +/- 1.6, p < 0.05). The difference in total body fat between the haemodialysis (n = 14) and peritoneal dialysis (n = 10) groups reached statistical significance (16.5 +/- 1.7 versus 22.6 +/- 2.4, p < 0.05). No difference was found in serum albumin. Infrared interactance has the capacity to characterize time-dependent differential changes of body composition in various dialysis modalities. Further studies are needed to describe the validity of the method for identification of patients with increasing malnutrition.