Lymphopenia and neutropenia are associated with subsequent incident proteinuria in Danish patients with systemic lupus erythematosus.

Objective: The aim of this study was to investigate whether incident proteinuria in patients with systemic lupus erythematosus (SLE) was preceded by changes in blood lymphocytes and neutrophil counts and/or neutrophil-lymphocyte ratio (NLR).Method: SLE patients with no proteinuria before or at the time of classification were included. Longitudinal data on SLE manifestations, vital status, and SLE-associated medications were collected during clinical visits and chart review. Laboratory data were collected through a nationwide database. Lymphopenia, severe lymphopenia, and neutropenia were defined as values below 0.8 × 109, 0.5 × 109, and 2.0 × 109 cells/L, respectively. High NLR was defined as values above the median. Proteinuria was defined by at least two measurements of elevated urine protein excretion (> 0.5 g/day). Hazard ratios (HRs) were calculated by Cox modelling using time-dependent continuous and binary covariates based on multiple laboratory measurements adjusted for use of immunosuppressants.Results: In total, 260 SLE patients were available for the analysis, of whom 30 (12%) developed incident proteinuria following the diagnosis of SLE. Median follow-up time was 73.5 months. Lymphocyte and neutrophil counts, but not NLR, were associated with incident proteinuria. HRs for incident proteinuria were 2.71 for lymphopenia [95% confidence interval (CI) 1.20-6.11], 4.73 for severe lymphopenia (95% CI 1.93-11.59), and 2.54 for neutropenia (95% CI 1.14-5.65).Conclusion: Lymphopenia and neutropenia predicted the risk of first-time proteinuria independently of immunosuppressants.

Habitual dietary phosphorus intake and urinary excretion in chronic kidney disease patients: a 3-day observational study.

Hyperphosphatemia in chronic kidney disease (CKD) is associated with vascular calcification, cardiovascular morbidity and mortality. The aim of this study was to estimate the daily dietary phosphorus intake compared with recommendations in CKD patients and to evaluate the reproducibility of the 24-h urinary phosphorus excretion. Twenty CKD patients stage 3-4 from the outpatient clinic, collected 24-h urine and kept dietary records for 3 consecutive days. The mean daily phosphorus intake was 1367±499, 1642±815 and 1426±706 mg/day, respectively (P=0.57). The mean urinary phosphorus excretion was 914±465, 954±414 and 994±479 mg/day, respectively (P=0.21). In this population of CKD patients stage 3-4 the daily phosphorus intake was above the recommended. Twenty-four-hour urinary phosphorus excretion was reproducible and the data indicate that a single 24-h urine collection is sufficient to estimate the individual phosphorus excretion.

Circulating chromatin-anti-chromatin antibody complexes bind with high affinity to dermo-epidermal structures in murine and human lupus nephritis.

Murine and human lupus nephritis are characterized by glomerular deposits of electron-dense structures (EDS). Dominant components of EDS are chromatin fragments and IgG antibodies. Whether glomerular EDS predispose for similar deposits in skin is unknown. We analysed (i) whether dermo-epidermal immune complex deposits have similar molecular composition as glomerular deposits, (ii) whether chromatin fragments bind dermo-epidermal structures, and (iii) whether deposits in nephritic glomeruli predispose for accumulation of similar deposits in skin. Paired skin and kidney biopsies from nephritic (NZBxNZW)F1 and MRL-lpr/lpr mice and from five patients with lupus nephritis were analysed by immunofluorescence, immune electron microscopy (IEM) and co-localization TUNEL IEM. Affinity of chromatin fragments for membrane structures was determined by surface plasmon resonance. Results demonstrated (i) presence of EDS containing chromatin fragments and IgG in both organs in nephritic patients, (ii) chromatin fragments possessed high affinity for dermo-epidermal laminins and collagens, (iii) glomerular immune complex deposits did not predict similar interstitial deposits in skin, although such complexes were present in capillary lumina in glomeruli and skin of all nephritic individuals. Thus, chromatin-IgG complexes accounting for lupus nephritis seem to reach skin through circulation, but other undetermined factors are required for these complexes to deposit within skin membranes.

Pulse-wave morphology and pulse-wave velocity in healthy human volunteers: examination conditions.

OBJECTIVE: Applanation tonometry for pulse-wave analysis (PWA) and determination of pulse-wave velocity (PWV) is a non-invasive method for assessment of the central aortic pressure waveform and indices of arterial stiffness. The objective of this study was to examine the influence of eating and smoking on PWA and PWV measurements in order to establish standard examination conditions. Furthermore, intra- and interobserver reproducibility and the effects of varying the site of measurements were observed. MATERIAL AND METHODS: Duplicate measurements of the radial pressure waveform and of the brachial and aortic PWV on the right and left side of the body were recorded in 23 healthy subjects by two trained observers. Measurements were performed in the fasting state and 3 h after a high-calorie meal, and before and 1 h after smoking a cigarette. RESULTS: Intake of a high-calorie meal as well as smoking caused significant changes in both PWA and PWV parameters and an inter-arm difference was observed. Intra- and interobserver reproducibility was good. CONCLUSIONS: Pulse-wave measurements by applanation tonometry should be undertaken in the same arm during fasting and smoking abstinence.

Uricosuric effect of losartan in patients with renal transplants.

BACKGROUND: The aim of the study was to evaluate the uricosuric effect of the angiotensin II receptor antagonist, losartan, in hypertensive patients with renal transplants who are treated with cyclosporin A (CsA). METHODS: Twenty-six patients with stable renal function and hypertension, 16 men and 10 women, median age 47 years (range, 25-63 years), were studied in an open randomized crossover trial, comparing a 2-week control period with a 2-week period of once-daily administration of 50 mg of losartan. The main outcome measurements were fractional excretion of uric acid (FE(uric acid)) based on 24-hr urine collections and plasma uric acid. RESULTS: The median FE(uric acid) was 5.7% (range, 2.4-10.4%) in the control period with a median change of +0.84% (range, -1.15% to +2.77%) in the losartan period (P<0.0002). Plasma uric acid was 0.47 mM (0.29-0.69 mM) in the control period with a change of -0.03 mM (-0.10 to 0.06 mM) in the losartan period (P<0.002). Diastolic blood pressure was 87 mmHg (70-97 mmHg) in the control period with a change of -3 mmHg (-13 to +6 mmHg) in the losartan period (P<0.005). There was no difference in systolic blood pressure between the two study periods. Plasma creatinine was 165 microM (102-356 microM) in the control period with a change of +9 microM (-36 to +60 microM) in the losartan period (P<0.01). Plasma potassium was 4.2 mM (3.0-4.7 mM) in the control period with a change of + 0.2 mM (-0.2 to +0.9 mM) in the losartan period (P<0.0005). CONCLUSIONS: Once-daily administration of 50 mg of losartan in hypertensive CsA-treated patients with renal transplants caused a 17% increase in FE(uric acid) and an 8% fall in plasma uric acid.

High serum enalaprilat in chronic renal failure.

BACKGROUND: Most angiotensin-converting enzyme (ACE) inhibitors and their metabolites are excreted renally and doses should hence be reduced in renal insufficiency. We studied whether the dosage of enalapril in daily clinical practice is associated with drug accumulation of enalaprilat in chronic renal failure. METHODS: Fifty nine out-patients with plasma creatinine >150 micromol/L and chronic antihypertensive treatment with enalapril were investigated, in a cross-sectional design. RESULTS: Median glomerular filtration rate (GFR) was 23(range 6-60) ml/minute/1.73 m2. The daily dose of enalapril was 10 (2.5-20) mg and the trough serum concentration of enalaprilat was 31.8 (<2.5-584.7)ng/ml. Ninety percent of the patients had higher serum concentrations of enalaprilat than has been reported in subjects with normal kidney function, and a marked elevation of serum enalaprilat was observed in patients with GFR <30 ml/minute. All but three patients had serum ACE activity below the reference range. The ACE genotype did not influence the results. Additional pharmacokinetic studies were done in nine patients in whom GFR was 23 (10-42)ml/minute/1.73 m2. The median clearance of enalaprilat was 28 (16-68) ml/minute and correlated linearly with GFR (r=0.86, p=0.003). Intra-subject day-to-day variation in trough concentrations was 19.7%. CONCLUSION: Patients with chronic renal failure given small or moderately high doses of enalapril may thus have markedly elevated levels of serum enalaprilat. Whether this affords extra renoprotection, or on the contrary may inappropriately impair renal function, is not known, and should be investigated in prospective, controlled studies.

[Living-donor kidney transplantation]. / Nyretransplantation med levende donor.

In recent years transplantation from living donors has accounted for 25-30% of all kidney transplants in Denmark corresponding to 40-45 per year. Most of these living donors are parents or siblings, although internationally an increasing number are unrelated donors. Donor nephrectomy is associated with only few complications. The long-term outcome for kidney donors is good without increase in mortality or risk for development of hypertension and renal failure; proteinuria may be seen. Living kidney transplantation is the optimal treatment of end-stage renal disease with better graft survival than in cadaver transplantation. The ethical and psychological aspects related to transplantation from a living donor are complex and need to be carefully evaluated when this treatment is offered to the patients.

Urinary excretion of Tamm-Horsfall protein and epidermal growth factor in chronic nephropathy.

Tamm-Horsfall protein (THP) and epidermal growth factor (EGF) are both synthesized by tubular cells in the distal part of the nephron and excreted with the urine. The present study examines the urinary excretion rates of the two peptides in relation to functional tubular markers in patients with chronic nephropathy. Four groups of patients with moderate to severely reduced renal function were studied: glomerulonephritis (n = 10), diabetic nephropathy (n = 11), tubulointerstitial nephropathy (n = 13), and polycystic kidney disease (n = 8). The renal function was evaluated by glomerular filtration rate (GFR) as an indicator for the general renal function, lithium clearance (C(Li)) as an indicator for proximal tubular function, and absolute distal reabsorption of sodium (ADR(Na)) as an indicator for distal tubular function. The excretion rate of EGF was rather closely correlated with GFR, C(Li) and ADR(Na) (Spearman coefficients of variation 0.88, 0.69, and 0.74, respectively). The correlations between the excretion rate of THP and GFR, C(Li) and ADR(Na) were weaker (Spearman coefficients of variation 0.68, 0.42, and 0.44). When the effect of GFR had been accounted for by multiple variance analyses, the excretion rates of the two peptides were still associated with ADR(Na) but not with C(Li). In conclusion, the urinary excretion rates of especially EGF but also those of THP were correlated with renal function and distal tubular reabsorption of sodium in patients with chronic nephropathy.

Tamm-Horsfall protein in urine after uninephrectomy/transplantation in kidney donors and their recipients.

Tamm-Horsfall protein (THP) is a large glycoprotein with unknown physiological function synthesized in the thick ascending limb of the loop of Henle. Urinary THP has recently been suggested as being suitable for monitoring the functional state of transplanted kidneys. In the present study, the urinary excretion of THP after uninephrectomy and transplantation among relatives was determined in order to study the influence of the acute reduction in renal mass on the excretion of this peptide. Glomerular filtration rate (GFR), estimated by the plasma clearance of 51Cr-EDTA, and the excretion rate of THP were measured 2 days before nephrectomy and 5, 12, 26 and 54 days after nephrectomy/transplantation in 22 healthy living kidney donors and in 16 of their recipients. In the donors, THP excretion rate of the kidney to remain in the donor was 22.3 micrograms/min before and 33.7 micrograms/min at 5 days after uninephrectomy (p < 0.01) and remained increased by around 40% throughout the study period. GFR of the remaining kidney rose from 47 ml/min before to 61 ml/min at 5 days after uninephrectomy (p < 0.001). The THP excretion rate/GFR ratio remained unchanged in the donors. In the kidney to be transplanted, THP excretion rate was unchanged before and after transplantation. There was no significant increase in GFR in the recipients, which was significantly lower than GFR of the donors all the time. In matched pairs of kidney donors and recipients, the THP excretion rate/GFR ratio tended to be lower in the recipients but the difference was not significant. The correlation between excretion rate of THP and GFR was significant (r = 0.66; p < 0.01). To conclude, uninephrectomy in healthy man was associated with a marked increase of around 40% in the excretion of THP from the kidney that remained in the donor. In the kidney that was transplanted, the THP excretion rate was unchanged. The THP excretion rate was correlated with GFR. The mechanism underlying this association is unknown as THP does not undergo glomerular filtration.

The influence of angiotensin-converting enzyme inhibition on renal tubular function in progressive chronic nephropathy.

The influence of angiotensin-converting enzyme (ACE) inhibition on renal tubular function in progressive chronic nephropathy was investigated in 69 patients by the lithium clearance (C(Li)) method. Studies were done repeatedly for up to 2 years during a controlled trial on the effect of enalapril on progression of renal failure. The pattern of proteinuria was followed over the first 9 months. At baseline, the glomerular filtration rate (GFR) was 5 to 68 mL/min. Absolute proximal tubular reabsorption rate of fluid (APR), estimated as the difference between GFR and C(Li), was 1 to 54 mL/min. Calculated fractional proximal reabsorption (FPR) was moderately subnormal. During the study, GFR decreased and sodium clearance was unchanged; fractional excretion of sodium therefore increased. In the group of patients randomized to treatment with enalapril (n = 34), GFR at 1 month was 83% (P < 0.001) and C(Li) was 88% (P < 0.01) of the baseline values, APR and FPR had not changed significantly, and potassium clearance was significantly decreased. Through the rest of the study period, APR remained nearly unchanged and FPR even increased in the enalapril group. In the group of patients randomized to treatment with conventional antihypertensive drugs (n = 35), C(Li) was unchanged until severe reduction in GFR, APR and FPR decreased gradually, and potassium clearance was almost unchanged. These differences in tubular function between the two treatment regimens were significant (P < 0.05). An unchanged or increased APR in either treatment regimen was associated with a long-term slower progression of renal failure. Over 9 months, the 24-hour fractional clearance of albumin decreased in the ACE inhibitor group (P < 0.01), whereas the clearances of immunoglobulin G and retinol-binding protein were unchanged in this group. In the conventional group, the fractional clearances of these three plasma proteins all increased. It is concluded that in progressive chronic nephropathy ACE-inhibitor treatment was associated with different adaptive tubular changes in the handling of sodium, water, and protein compared with conventional antihypertensive therapy. During ACE inhibition, the reabsorptive capacity of the proximal tubule appeared to be better preserved, which might be of importance for the beneficial effect of this treatment in chronic renal disease.

Urinary excretion of epidermal growth factor in living human kidney donors and their recipients.

Epidermal growth factor (EGF) is a growth-promoting peptide that is synthesized in the distal tubules of the kidney and excreted in urine. EGF has been suggested to play a role in the repair after renal tissue damage, as well as in compensatory growth of the remaining kidney after uninephrectomy. The present study examined the urinary EGF excretion after uninephrectomy and transplantation among relatives. The urinary EGF excretion rate and the glomerular filtration rate (GFR) were followed for 26-54 days in 16 healthy kidney donors and nine recipients. After uninephrectomy the median urinary EGF excretion rate in the donors was not 50% of the pre-operative value, but around 65% (95% confidence limits of the median on the fifth post-operative day: 59-72%). This suggests that there is a compensatory increase in the EGF excretion rate from the remaining kidney of around 30% after uninephrectomy. A similar compensatory increase was demonstrated for GFR, indicating that the compensatory changes in EGF excretion rate and GFR might be correlated. In the transplanted kidneys, GFR was consistently around 15% lower and EGF excretion rate around 40% lower than in the corresponding kidneys remaining in the donors. This might reflect ischaemic and drug-induced damage of the transplanted kidneys. The present study demonstrated a compensatory increase of around 30% in urinary EGF excretion from the remaining kidney after uninephrectomy in healthy humans. Whether EGF plays a role in the adaptive processes in the remaining kidney or whether changes in EGF excretion are merely of a secondary nature is still uncertain.

Late outcome of a controlled trial of enalapril treatment in progressive chronic renal failure. Hard end-points and influence of proteinuria.

An earlier controlled trial showed that over an average of 26 months, enalapril slowed the progression of chronic renal failure. Following completion of the trial, the patients continued to receive antihypertensive treatment according to ordinary clinical criteria. All but four patients in the enalapril group remained on that drug, and two patients in the control group were switched to an angiotensin-converting enzyme (ACE) inhibitor. In the present study the fate of the 70 patients 44 months after termination of the trial was investigated, with a total follow-up of around 7 years. In the original enalapril group, 12 of the 35 patients (34%) were alive without renal replacement therapy versus five of the 35 patients (14%) in the control group. This difference of 20% in favour of having been in the enalapril group in the original trial was significant (P = 0.05; 95% confidence limits 0.5-39.5%). The influence of baseline proteinuria on clinical outcome was analysed. In the original control group, baseline renal clearances of albumin (Calb) and immunoglobulin G (CIgG) were significantly lower in patients surviving without renal replacement therapy at follow-up than in patients who ultimately developed end-stage renal failure (ESRF) (P < 0.05). In the original enalapril group, these baseline clearances were equal in the two renal outcome groups. In all patients, baseline Calb and CIgG were negatively correlated with the rate of change in GFR during the controlled trial (r = -0.37, P < 0.01 and r = -0.28, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Glomerular filtration rate and segmental tubular function in the early phase after transplantation/uninephrectomy in recipients and their living-related kidney donors.

1. Glomerular filtration rate and sequential tubular function were investigated in 18 adult renal transplant recipients and in their matched, adult living-related kidney donors before and 5 days after transplantation/uninephrectomy. At day 54, 13 donors and 11 recipients were re-investigated. Sixteen of these constituted eight matched pairs. This reduction in the study population was caused by the application of two withdrawal criteria. 2. In the recipients glomerular filtration rate was unchanged at day 5 and had increased to 61 ml/min at day 54 (P < 0.05). In the donors glomerular filtration rate had increased to 59 ml/min by day 5 (P < 0.01) and was unchanged at day 54. 3. In the recipients lithium clearance was unchanged at day 5 and had increased to 23 ml/min at day 54 (P < 0.01). In the donors the lithium clearance had increased by day 5 (P < 0.01). 4. In the recipients the absolute proximal fluid reabsorption rate was about 36 ml/min throughout the study period. In the donors the absolute proximal fluid reabsorption rate had increased to 42 ml/min by day 5 (P < 0.05) and increased further to 44 ml/min by day 54 (P < 0.01). 5. In the recipients sodium clearance increased from 0.54 ml/min to 2.10 ml/min at day 54 (P < 0.01). In the donors it increased from 0.64 ml/min to 0.99 ml/min at day 54 (P < 0.05). 6. Donor-recipient comparison showed that at day 54 there was no significant difference with regard to glomerular filtration rate, lithium clearance, absolute and fractional proximal fluid reabsorption rate and absolute distal sodium reabsorption rate.(ABSTRACT TRUNCATED AT 250 WORDS)

[Angiotensin I converting enzyme inhibitor enalapril in treatment of progressive chronic nephropathy. An open randomized controlled trial]. / Angiotensin I konverteringshaemmeren enalapril til behandling af progredierende kronisk nefropati. En åben randomiseret kontrolleret undersøgelse.

In order to study the influence of angiotensin converting enzyme (ACE) inhibition on the progression of chronic nephropathy, 70 patients with a median glomerular filtration rate (GFR) of 15 (range, 6 to 54) mL/min/1.73 m2 were randomised in an open study to basic treatment with enalapril or conventional antihypertensive treatment. The patients were followed for at least two years or until they needed dialysis. The therapeutic goal, was a blood pressure of 120 ti 140/80 to 90 mmHg. In the enalapril group, the median decline in GFR was -0.20 (range, +0.18 to -7.11) mL/min/1.73 m2/month, and in the control group, it was -0.31 (+0.01 to -1.97) mL/min/1.73 m2/month (p < 0.05). There was no significant difference in blood pressure between the groups. Thus, the progression of moderate to severe chronic nephropathy was slower on a basic treatment with enalapril as compared to conventional antihypertensive therapy.

Effect of enalapril on the progression of chronic renal failure. A randomized controlled trial.

In order to study the influence of angiotensin converting enzyme (ACE) inhibition on the progression of chronic nephropathy, 70 patients with a median glomerular filtration rate (GFR) of 15 (range, 6 to 54) mL/min/1.73 m2 were randomized in an open study to basic treatment with enalapril or conventional antihypertensive treatment. The patients were followed for at least 2 years or until they needed dialysis. The groups were comparable with respect to age and sex distribution, etiology of renal diseases, initial levels of renal function and arterial blood pressure (BP), and protein intake. The therapeutic goal was a BP of 120 to 140/80 to 90 mm Hg. The GFR, estimated by the plasma clearance of 51Cr-EDTA, was measured every third month, and the individual rate of progression was calculated as the slope of the GFR v time plot. In the enalapril group, the median decline in GFR was -0.20 (range, +0.18 to -7.11) mL/min/1.73 m2/month and in the control group it was -0.31 (+0.01 to -1.97) mL/min/1.73 m2/month (P less than .05). There was no significant difference in blood pressure or plasma lipid levels between the groups. Thus, the progression of moderate to severe chronic nephropathy was slower on a basic treatment with enalapril as compared to conventional antihypertensive therapy.

Angiotensin converting enzyme (ACE) inhibitors and renal function. A review of the current status.

Angiotensin converting enzyme (ACE) inhibitors are well established in the treatment of hypertension and cardiac failure. Experimental studies in rats have suggested that these agents may protect renal function in chronic nephropathy by a mechanism other than simply lowering the systemic blood pressure. In human studies of incipient diabetic nephropathy, worsening of microalbuminuria was prevented during 3 years of ACE inhibition. ACE inhibitors reduce arterial blood pressure in chronic nephropathy, and may cause a fall in glomerular filtration rate. In diabetic nephropathy, proteinuria was reduced by 2 months' treatment with enalapril to less than half of the values obtained in a control group treated with metoprolol. Nonrandomised trials have suggested that ACE inhibitors may slow the deterioration of renal function, but no comparisons with other antihypertensive agents in prospective studies have been published to date. In chronic renal failure, ACE inhibitors may worsen anaemia and hyperkalaemia. Renovascular hypertension can be treated with ACE inhibitors, but the treatment may lead to a compromised renal function. The dosage of these drugs should be reduced in renal failure and therapy should be started cautiously in this setting, with close monitoring of blood pressure, renal function and plasma potassium.

Atrial natriuretic peptide and renal adaptation to contralateral nephrectomy in healthy man.

Atrial natriuretic peptide (ANP), angiotensin II (AII), aldosterone (Aldo) and arginine vasopressin (AVP) in plasma were determined in 12 healthy renal transplant donors before and 5, 12, 26, 54 days after uninephrectomy (Nx) in order to study the possible role of these hormones in functional adaptation to acute reduction in renal mass. Glomerular and tubular function was studied by measurements of the clearances of 51Cr-EDTA, lithium, sodium, potassium, and albumin. ANP was 7.4 +/- 3.1 pmol l-1 (mean +/- SD) before Nx and 8.7 +/- 6.1 pmol l-1 at 5 days after Nx and remained at this level through the observation period. Aldo showed a non-significant transient fall at 5 days after Nx. AII and AVP remained normal after Nx. At 5 days after Nx glomerular filtration rate (GFR) of the remaining kidney had risen from 45 +/- 7 ml min-1 before Nx to 57 +/- 8 ml min-1 (p less than 0.01), lithium clearance had risen from 13 +/- 2 ml min-1 before Nx to 20 +/- 7 ml min-1 (p less than 0.01), and sodium and water balance was normal. To conclude, plasma ANP, AII, Aldo and AVP do not appear to be responsible for the hyperfiltration and depression of fractional proximal sodium and water reabsorption observed in recently uninephrectomized man with normal sodium and water balance.

Effect of enalapril on haemoglobin and serum erythropoietin in patients with chronic nephropathy.

It has been suggested that angiotensin-converting enzyme (ACE) inhibitors halt the progression of chronic renal failure. During the first months of a controlled trial of this hypothesis a fall in haemoglobin (Hb) was observed in patients treated with the ACE inhibitor enalapril. It was investigated whether this was related to changes in serum erythropoietin (EPO). Data were analysed in 59 consecutive patients during an observation period of 90 days. In enalapril-treated patients (n = 27) Hb fell gradually from a median value of 7.6 to 6.7 mmol/l at 90 days of treatment. In the control group of patients on conventional antihypertensive treatment (n = 32) median Hb was unchanged (7.6 mmol/l) throughout the observation period (p less than 0.001 enalapril vs control). In the enalapril-treated group median EPO concentration fell from 32 to 24 U/l at 90 days of treatment, whereas in conventionally treated patients median EPO was 34 U/l and 35 U/l, respectively (p less than 0.05 enalapril vs control). Neither glomerular filtration rate nor arterial blood pressure differed significantly in the two groups. Furthermore, there were no signs of bone marrow suppression, increased haemolysis or change in plasma volume. In conclusion, a decrease in Hb was found after start of treatment with enalapril in patients with progressive chronic renal failure, possibly caused by a suppression of EPO production.