Short versus conventional hydration for prevention of kidney injury during pre-TAVI computed tomography angiography.

BACKGROUND: Computed tomography angiography (CTA) is required in the work-up for transcatheter aortic valve implantation (TAVI). However, CTA may cause contrast-induced acute kidney injury (CI-AKI). We hypothesised that a short (1 h, 3 ml/kg/h sodium bicarbonate) hydration protocol is not inferior to conventional (24 h, 1 ml/kg/h saline) hydration in avoiding a decline in renal function in patients with impaired renal function. METHODS AND RESULTS: Single-centre randomised non-inferiority trial in patients with impaired renal function who underwent pre-TAVI CTA. Patients were randomised on a 1:1 ratio to short hydration (SHORT; 1 h sodium bicarbonate, 3 ml/kg/h) or conventional hydration (CONV; 24 h saline, 1 ml/kg/h). Outcomes included percentage change in serum creatinine until 2-6 days after CTA with a non-inferiority margin of 10% and an increase on the Borg dyspnoea scale ≥1 point. Seventy-four patients were included. Increase in creatinine was 6 µmol/l (95% CI 2.5-9.3) in the SHORT versus 2 µmol/l (95% CI-1.4 to 6.3) in the CONV arm (p = 0.167). The percentage change was 4.6% (95% CI 2.0-7.3%) in the SHORT arm versus 2.5% (95% CI: 0.8 to 5.8%) in the CONV arm. The difference in percentage increase in creatinine between the two arms was 2.1% (95% CI: 2.0-6.2%; p-value non-inferiority: <0.001). CI-AKI and a need for dialysis were not observed. An increase of ≥1 point on the Borg scale (dyspnoea scale ranging from 1 (lowest) to 10 (highest)) was seen in 1 patient in the SHORT arm versus 5 patients in the CONV arm (2.9% vs 16.1%, p = 0.091). CONCLUSION: For patients with impaired renal function undergoing pre-TAVI CTA, a short 1­h, low-volume hydration protocol with sodium bicarbonate is not inferior to conventional 24-h, high-volume saline hydration.

The acute effect of atorvastatin on proteinuria in patients with chronic glomerulonephritis.

BACKGROUND: Hyperlipidemia may develop early in the course of renal disease, and statin treatment to lower lipid levels in these patients is effective. In addition, it has been suggested that proteinuria may decrease after prolonged periods of statin treatment. In the present study, we set out to evaluate the short-term effect of atorvastatin after only six weeks of therapy. MATERIAL AND METHODS: Plasma albumin, creatinine, creatinine clearance, proteinuria and lipid profiles were assessed in 31 consecutive patients with glomerulonephritis and proteinuria > 0.3 g/24 h. All patients were treated with ACE inhibition for more than three months. Twenty patients consented to receive additional treatment with atorvastatin 10 mg daily in conjunction with a cholesterol-reducing diet, while 11 patients received standard care. Analyses were performed at baseline and after six weeks. RESULTS: After six weeks of treatment with atorvastatin urinary protein excretion was reduced from 1.80 g/24 h to 1.42 g/24 h (22%, p = 0.005), while no change was observed in this parameter in the untreated patients over the same period. Plasma albumin did not change in treated or in untreated patients. Lipid and lipoprotein parameters improved in all treated patients (all p < 0.001). No correlation was observed between the percentual changes in lipids and proteinuria. Plasma creatinine and creatinine clearance did not change (p > 0.05). CONCLUSIONS: Six weeks of therapy with low-dose atorvastatin, added to ACE inhibition, resulted in a 22% decrease of proteinuria compared to untreated patients.

Atorvastatin and the dyslipidemia of early renal failure.

Information about lipid abnormalities and the effect of lipid lowering therapy in the early stage of renal disease is limited, while preventive treatment in this stage might be much more beneficial. Lipid profiles and risk factors were assessed in 150 consecutive, non-diabetic patients. Preventive therapy consisted of cholesterol-reduced diet and atorvastatin 10 mg daily. Patients were considered at risk for cardiovascular disease if LDL-cholesterol was >2.6 mmol/l in the case of manifest cardiovascular disease (n=28) or when they had manifest cardiovascular risk factors (n=105) or if LDL was >3.5 mmol/l (n=17). A total of 128 patients (85%) had increased LDL. In men <60 years and women <40 years, total cholesterol was higher than in the general population. Linear regression analysis showed a decreased creatinine clearance to be significantly associated with the lipid profile. For a 10 ml/min decrease of creatinine clearance, a 0.085 increase of the total cholesterol to HDL ratio was observed (P=0.005). In similar analyses, proteinuria was strongly associated with cholesterol and triglycerides. An increase of 0.28 of the total cholesterol/HDL ratio was observed for each gram per 24 h proteinuria (P<0.001). On atorvastatin 10 mg daily, 30 of 60 treated patients had achieved their target LDL value. On average, LDL-cholesterol was reduced by 39% and triglycerides by 18%. No patient had to interrupt their treatment because of adverse side-effects. In conclusion, the majority of patients had an elevated LDL and other lipid abnormalities. Short-term therapy with atorvastatin and a cholesterol lowering diet appears to be safe and effective. It is probably useful to determine the lipid profile in patients with renal failure already in an early phase and to start lipid lowering treatment as soon as abnormalities are found.

Cimetidine improves GFR-estimation by the Cockcroft and Gault formula.

In some patients with renal disease 24-hour cimetidine aided creatinine clearances cannot equal GFR even after administration of the maximum daily dose of cimetidine. Short duration cimetidine aided creatinine clearances can equal GFR but are inconvenient for clinical use and can be inaccurate due to incomplete urine collection. We studied how accurately GFR can be estimated without the need to collect urine, by applying the Cockcroft and Gault formula (CCock) on a single plasma creatinine concentration, after oral administration of 3 x 800 mg cimetidine during the preceding 24 hours. GFR was measured as standard clearance, using continuous infusion of 125I-iothalamate. Nineteen patients with various renal diseases, plasma creatinine < 180 mumol/l and body mass index between 15 and 30 kg/m2 were included. After cimetidine administration, plasma creatinine values remained stable for 6 hours, despite rapidly decreasing plasma cimetidine values during the same period, in all 15 patients with GFR > 40 ml/min/1.73 m2. Tubular creatinine secretion was blocked completely in 14 of them. With cimetidine both accuracy and precision of the Cockcroft clearance improved: the mean (+/- SD) ratio of CCock to GFR decreased from 1.28 (+/- 0.21) to 0.98 (+/- 0.11) (p < 0.001) and the standard deviation of the difference (CCock-GFR) decreased from 9.23 to 7.07 ml/min/1.73 m2 (p < 0.05). With cimetidine the Cockcroft clearance correlated well with GFR (r = 0.974, p < 0.001) and this was as good as the correlation, between GFR and a 4-hour standard creatinine clearance (r = 0.972, p < 0.001). In conclusion, with a minimum of inconvenience, this method provides the clinician with accurate information on GFR for the outpatient follow-up of patients with a mild-to-moderate decrease in renal function, provided that no gross discrepancy between total bodyweight and muscle mass is present.

Pregnancy in a patient with autosomal-dominant polycystic kidney disease and congenital hepatic fibrosis.

This case report describes a pregnancy in a patient with autosomal-dominant adult polycystic kidney disease and congenital hepatic fibrosis, a very rare and problematic combination. In particular, hypertension and renal dysfunction caused problems during this pregnancy. Peritoneal dialysis became necessary.

[Epstein-Barr virus in a donor kidney as a cause of non-Hodgkin lymphoma]. / Epstein-Barr-virus in een donornier als oorzaak van non-Hodgkin-lymfoom.

A 22-year-old male who had received a kidney transplant from his father (HLA haploidentical), presented with fever and malaise. After transplantectomy was performed because of rejection, the patient developed abdominal pain due to perforation of the small intestine. Non-Hodgkin's lymphoma was found in both the transplant and the small bowel. The patient had suffered a primary Epstein-Barr virus (EBV) infection, probably transferred through the transplanted kidney. DNA analysis showed that the lymphoma was of patient origin. After withdrawal of immunosuppressive therapy, no recurrence of the lymphoma was seen. EBV is a well-known aetiologic agent of non-Hodgkin's lymphomas arising in the immunocompromised patient.

Spectrum of diurnal rhythms in glomerular permeability in patients with membranous nephropathy.

BACKGROUND: Diurnal rhythms in proteinuria and selectivity index (SI) of proteinuria can vary from patient to patient with respect to phase and amplitude (A/M) and in some cases rhythms are absent. The aim of the present study was to relate this variability to a different pattern of diurnal rhythms in permselectivity of the glomerular capillary wall (GCW). METHODS: Ten patients with nephrotic syndrome due to membranous nephropathy were studied. Diurnal rhythmicity in size-dependent permselectivity of the GCW was determined by measuring 3-h fractional clearances of dextrans (30-90 A) over a period of 1 day. RESULTS: Four types of rhythmicity could be recognized. Type I and II only differed in the magnitude of the diurnal variability in glomerular transport through large pores (r2) and shunt pathway (omega). Both had normal rhythms in clearance of proteins and SI, but all rhythms were more pronounced in the patients with normal renal function and mild histological abnormalities (type II). Although type III also had a normal GFR and minor histological lesions, only transport through omega (and not through r2) showed a significant diurnal rhythm, which implied that this type did not have a normal rhythm in SI. The patients with advanced renal failure and extensive interstitial lesions neither had a rhythm in permselectivity nor had normal rhythms for proteinuria and SI (type IV). CONCLUSIONS: The type of rhythmicity in glomerular permeability corresponds well with the presence and phase of rhythms in clearance of proteins and in SI of the proteinuria.

Circadian rhythm of proteinuria: consequences of the use of urinary protein:creatinine ratios.

Proteinuria in patients with glomerular disease has a circadian rhythm, but for creatinine such a rhythm is either absent or of low amplitude. We found in 18 of 23 admitted patients (group I) and in seven outpatients (group II) a marked circadian rhythm of the protein: creatinine ratio. Estimates of 24-h proteinuria were obtained by multiplying the protein:creatinine ratio of 3-h urine samples with 24-h creatinine excretion, calculated from age, sex and bodyweight. Estimated proteinuria could be as low as 19% or as high as 349% of actually measured 24-h proteinuria; the mean SD was 23%. The best estimate was obtained with the 06.00-09.00 hours urine samples. The estimates correlated better with actually measured 24-h proteinuria than the protein: creatinine ratio per se correlated with the 24-h proteinuria. Day-to-day variation of proteinuria estimates from samples taken at the same time of the day was of similar magnitude as day-to-day variation of actual 24-h proteinuria. We conclude that the usefulness of the protein: creatinine ratio of a random urine sample for estimation of proteinuria is limited, because of the circadian rhythm of proteinuria. However, samples collected at a fixed time of the day are an acceptable alternative for 24-h urine collections in the clinical follow-up of individual patients.

Ranitidine has no influence on tubular creatinine secretion.

Oral cimetidine competitively inhibits tubular secretion of creatinine. We investigated the potential of oral ranitidine, a comparable H2-receptor antagonist, to block tubular creatinine secretion. In 10 healthy subjects, clearances of inulin and endogenous creatinine were simultaneously measured before and after administration of a single oral dose of ranitidine. In all subjects the effect of 300 mg ranitidine was studied; 7 subjects with high tubular secretion also participated in an additional study, when 1,200 mg ranitidine was administered. Neither dose of ranitidine caused a significant change in glomerular filtration rate measured by inulin clearance, or in mean plasma creatinine or in mean creatinine clearance. We conclude that a single oral dose of 300-1,200 mg ranitidine does not inhibit tubular secretion of creatinine in normal subjects, probably due to a lower affinity of ranitidine for the transport carrier at the luminal tubular membrane in comparison with cimetidine.

Monocyte-induced increase in osmotic fragility of human red cells sensitized with anti-D alloantibodies.

The mechanism by which human monocytes increase the osmotic fragility of red cells sensitized with Rhesus alloantibodies anti-D was studied in vitro. Both the increase in osmotic fragility and the lysis of red cells by monocytes were enhanced by cytochalasin B and were inhibited by hydrocortisone. These effects were similar to the effects of these agents on lysosomal enzyme release by monocytes. However, hydrocortisone was completely ineffective when added 1 h after mixing monocytes and sensitized red cells. This indicates that the damage responsible for the fragility increase and lysis is completed within 1 h and suggests that it is due to lysosomal enzymes released by the monocytes. Since for the full expression of the osmotic fragility increase and lysis an incubation time much longer than 1 h is required, it appears that the latter phenomena are the non-specific sequelae of damage inflicted upon the red cell by released lysosomal enzymes.

Circadian rhythm in glomerular transport of macromolecules through large pores and shunt pathway.

In previous studies we have demonstrated that the circadian rhythm in renal clearance of serum proteins is more pronounced than the variability in glomerular filtration rate, and that the highest day-night fluctuations are found for the largest proteins. To analyze whether additional circadian rhythmicity in size-selective glomerular transport could explain these phenomena, we measured renal clearances of inulin and dextrans in a range of 30 to 90 A over a period of one day and compared these data with renal clearance in proteins. Eight patients with nephrotic syndrome and a GFR > 60 ml/min and 6 healthy volunteers were studied during a protocol of bed rest and spaced protein and fluid intake. After administration of a loading dose, inulin and dextran were continuously infused. Blood and urine were sampled every three hours. In patients, but not in normals, fractional clearances of dextrans larger than 45 A showed a circadian rhythm with a peak in daytime and a close phase-relationship with the rhythm in GFR. The day-night differences were the most pronounced for the largest dextrans. Analysis of the day-night differences in a computer model showed circadian variability in transport through the shunt pathway and through large pores. These results can, to an important degree, explain our previous observations on circadian variability in renal clearance of proteins in patients with nephrotic syndrome.

Urinary sodium excretion in patients with nephrotic syndrome, and its circadian variation.

We analysed sodium excretion and its circadian variation in 70 patients with nephrotic syndrome and 19 healthy controls over 1-3 days, with a regimen of bed rest and constant sodium intake around the clock. We sampled urine and blood and took their blood pressure every 3 h. We also scored 60 renal biopsies for presence of interstitial fibrosis and tubular atrophy. Peripheral oedema was estimated in 37 patients. Fifty-nine patients excreted > 10 mmol sodium per 24 h, in equilibrium with dietary intake. In group A (n = 24), sodium excretion followed a normal circadian rhythm, with a daytime peak. In group B (n = 35), 29 had reversed circadian rhythm with a night-time peak, and 6 had no apparent rhythm. Nephrotic syndrome was more severe in group B than in A (serum albumin 19.5 vs. 24.1 g/l, p < 0.05; oedema 7.0 vs. 3.8 kg, p < 0.01). Group B also had signs of more advanced renal disease (GFR 49 vs. 99 ml/min; number of biopsies with tubulo-interstitial damage: 20/28 vs. 4/23; p < 0.001). Reversed sodium rhythm was associated with reversed circadian rhythms for GFR, effective renal plasma flow and urine flow, and blunting or reversal of the day-night differences in blood pressure and plasma renin activity. Eleven patients had urinary sodium excretion < 1 mmol/24 h. With respect to severity of nephrosis, they resembled group B, but GFR and incidence of tubulointerstitial lesions were like group A. Half of the patients with nephrotic syndrome had reversed circadian rhythm for sodium excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Circadian rhythm of glomerular filtration rate in patients after kidney transplantation.

Within 6 months of a kidney transplantation the graft can be regarded as an organ deprived of its innervation. We analysed whether the transplanted kidney has a diurnal rhythm of its glomerular filtration rate (GFR) similar to the GFR rhythm that has been demonstrated in normal individuals and in patients with nephrotic syndrome. GFR was measured by inulin clearances every 3 h during 1 day of bed-rest and identical food and fluid intake per 3 h in seven patients, 4-7 months after a successful kidney transplantation, and in 10 healthy volunteers. Similar to these healthy subjects, a normal circadian rhythm of GFR was detected in all but one patient with a maximum of 57 (range 45-82) ml/min in daytime, a minimum of 47 (range 36-70) ml/min during the night and a relative amplitude of 21 (range 10-41)%. The circadian rhythm of GFR was absent in the patient with the lowest value of GFR (39 ml/min). In conclusion, GFR has a circadian rhythm in patients studied within 6 months of a kidney transplantation, despite the absence of renal innervation.

Circadian variation of urinary albumin excretion in pregnancy.

OBJECTIVE: The hypothesis was tested that circadian variations in urinary albumin excretion of pregnant women in the third trimester of normal pregnancy are different from nonpregnant individuals. DESIGN: Circadian variability in urinary albumin excretion was studied both in pregnant women and in nonpregnant controls either during normal daily activities or in contrast during continuous bedrest with standardised fluid and food intake to study endogenously generated rhythm. SETTING: Outpatient department and metabolic ward of a university hospital. MAIN OUTCOME MEASURES: Urinary albumin excretion during fixed time periods over the day and the night. RESULTS: Both ambulant pregnant and nonpregnant women have circadian rhythm in urinary albumin excretion but pregnant women have, firstly, a higher 24 h urinary albumin excretion, secondly, smaller relative day-night differences than nonpregnant controls and thirdly, in the metabolic ward some pregnant women demonstrate absence of rhythm. CONCLUSIONS: The higher albumin excretion during pregnancy in 24 h urine collections can largely be explained by a higher excretion during the night, compared with that of nonpregnant women. The day-night difference in urinary albumin excretion of ambulant pregnant women is exogenously determined.

Circadian rhythm of urinary beta 2 microglobulin excretion in patients with a nephrotic syndrome.

The changes in urinary beta 2 microglobulin excretion during the day were studied in 20 patients with a nephrotic syndrome under standardized conditions and compared with the known circadian variations in urinary albumin excretion in the same patients. Fifteen of the 20 patients (75%) had a circadian rhythm for beta 2 microglobulin in the urine. Phase as well as relative amplitude of the beta 2 microglobulin circadian rhythm varied between patients. In addition, its presence, normality, amplitude and phase were largely different from the albumin rhythm. Observations made in 10 healthy individuals suggest that day-night variability in the excretion of beta 2 microglobulin and albumin in the urine is also present in the absence of clinically important proteinuria. Circadian variations in urinary beta 2 microglobulin excretion are found in a majority of the patients with nephrotic syndrome and as they differ in several respects from the day-night fluctuation in urinary albumin excretion the mechanism is probably different.

Discrepancy between circadian rhythms of inulin and creatinine clearance.

To elucidate the disparity between circadian rhythmicity of inulin and creatinine clearance, we simultaneously measured inulin and creatinine clearances every 3 hours during 1 day in 14 normal subjects and in 8 patients with nephrotic syndrome. All patients and normal subjects had a circadian rhythm for inulin clearance with a maximum during daytime and a relative amplitude of 21% +/- 2%. For creatinine clearance a rhythm was either absent or reduced in relative amplitude (p less than 0.01). In all subjects the rate of tubular creatinine secretion was higher at minimum of inulin clearance (night) than at maximum (day). The fractional clearance (relative to inulin) of creatinine was also higher during the night: normal subjects, 1.28 +/- 0.02 versus 1.10 +/- 0.02; patients, 1.78 +/- 0.08 versus 1.45 +/- 0.05 (p less than 0.005). This demonstrates the inaccuracy of creatinine clearance as a measure of glomerular filtration rate (GFR). By subsequent blocking of the tubular secretion of creatinine with cimetidine in four normal subjects, creatinine clearance became similar to inulin clearance during day and night. This confirms that high tubular secretion of creatinine during the night counteracts the normal rhythmicity of glomerular filtration of creatinine. As a result, plasma creatinine concentration is nearly constant during a 24-hour period. In conclusion, tubular creatinine secretion has a circadian rhythm with a phase opposite to the rhythm of GFR, thus blunting or causing absence of a circadian rhythm for creatinine clearance.

Creatinine clearance during cimetidine administration for measurement of glomerular filtration rate.

Creatinine clearance inaccurately estimates true glomerular filtration rate (GFR) because of tubular secretion of creatinine. We studied the ability of oral cimetidine, a blocker of tubular creatinine secretion, to improve the accuracy of measuring creatinine clearance. Clearances of inulin and endogenous creatinine were simultaneously measured in 16 patients with renal disease before administration of cimetidine and during 8 successive 3 h clearance periods with cimetidine 400 mg as priming dose followed by 200 mg every 3 h. At baseline, creatinine relative to inulin clearance (ClC/Cll) ranged from 1.14 to 2.27. With cimetidine, ClC/Cll approached unity in 8 patients (mean 1.02 [SD 0.03]), but considerably exceeded unity in 8 others (1.33 [0.14]). Plasma cimetidine/creatinine ratio was smaller in this second group, due to significantly higher renal clearance of cimetidine (333 [136] vs 165 [89] ml/min, p = 0.01). In a further study, cimetidine dose and, consequently plasma cimetidine concentration, was increased in 6 additional patients who had incomplete inhibited previously. This increased dose completely inhibited tubular creatinine secretion in the third until the sixth hour, so that creatinine clearance equalled GFR. Provided an adequate dose of cimetidine is given, 24 h creatinine clearance during administration of drug measures GFR accurately in patients with renal disease. However, because of the maximum daily dose of cimetidine that is advised, short clearance times (3 h) are recommended.

Circadian rhythm of glomerular filtration rate in normal individuals.

1. In a group of 11 normal individuals we measured glomerular filtration rate (GFR) by inulin clearances and effective renal plasma flow (ERPF) by p-aminohippurate clearances during a period of 24 h and a regimen of bedrest, identical food intake per 3 h and normal sleep/wake and light/dark cycles. 2. All subjects had a circadian rhythm for GFR with a maximum of 122 ml/min (SD 22) in the daytime, a minimum of 86 ml/min (SD 12) at night and with a relative amplitude of 33% (SD 15). 3. ERPF had a circadian rhythm with a similar relative amplitude as the GFR rhythm, but with a different phase. Because of this difference in phase, the calculated filtration fraction (GFR/ERPF) followed a circadian rhythm as well. 4. The circadian rhythms of urine volume and sodium excretion were in phase with the GFR rhythm, but the potassium rhythm had a different phase, probably because urinary potassium is largely derived from tubular secretion. 5. Urinary albumin and beta 2-microglobulin excretion had a circadian rhythm in phase with the GFR rhythm. 6. The highest quantity of sodium, water and beta 2-microglobulin was reabsorbed in the daytime; tubular reabsorption, expressed as percentage of the filtered load (fractional reabsorption), had a rhythm with a reversed phase.

Circadian rhythms in systemic hemodynamics and renal function in healthy subjects and patients with nephrotic syndrome.

BACKGROUND: The resemblance of the circadian rhythm of glomerular filtration rate (GFR) to that of arterial blood pressure (BP) suggests that systemic hemodynamic factors contribute to this variation. In the present study, this was investigated using continuous BP monitoring and pulse wave analysis. The study was performed in eight healthy subjects and in seven patients with nephrotic syndrome who had normal or reversed rhythms of GFR. METHODS: Circadian variations of renal function (continuous infusion of inulin/paraaminohippuric acid), noninvasive finger arterial pressure (Portapres), and vasoactive hormone levels were monitored during 27 hours. With stepwise backward regression analysis, the contributions of the measured variables to the circadian variation of GFR were investigated. RESULTS: Both groups showed a reduction of BP at night. In the controls, this was related to a drop in cardiac output, while in the patients, total peripheral resistance decreased at night. None of the hemodynamic variables explained the circadian GFR variation in both groups. In the controls, only 6% of the effective renal plasma flow (ERPF) rhythm was associated with variations in cardiac output (P = 0.03). In the patients, atrial natriuretic peptide and plasma renin activity were responsible for 36% of the variation in GFR (P < 0.01). CONCLUSIONS: These results indicate that the circadian variation of GFR does not result directly from changes in BP or cardiac output. An inverted GFR rhythm in patients with nephrotic syndrome may originate from hormonal mechanisms rather than directly from the hemodynamic effects of edema mobilization.