Imaging data suggesting acute pyelonephritis in the kidney graft: report of five cases with atypical clinical presentation.

Acute pyelonephritis is a common complication of kidney transplantation, occurring in up to 1% of grafts. Diagnosis is mainly clinical and atypical presentations have seldom been reported. The diagnostic role of imaging techniques has not been defined. Five cases of acute graft pyelonephritis are reported (three kidney, two pancreas-kidney grafts). The patients (median age 48 years) comprised three females and two males. Median post-transplant follow-up was 3 months, with three patients having predisposing factors for diabetes and one for an enteric bladder. None of the patients presented the 'classic' diagnostic tetrad (i.e. fever, positive urine cultures, low urinary tract symptoms and serum creatinine increase); although, at diagnosis, two of five patients presented with fever, one had increased creatinine levels and one had positive urine cultures. Of note, three patients had leucocyte casts at urinary sediment analysis, thus raising clinical suspicion. Renal ultrasounds were negative in all patients. Renal (99m)Tc-MAG3 (mercaptoacetyltriglycine) scintigraphy, which was used for the definition of kidney function impairment (one patient) or because of the presence of urinary casts (three patients), or after the biopsy diagnosis to locate the parenchymal lesions (one patient), was positive in all patients. The presence and pyelonephritic origin of the parenchymal lesions was confirmed by nuclear magnetic resonance or computed tomography scans. Acute graft pyelonephritis may develop in the absence of a full-blown clinical picture. Smouldering symptoms may occur in the presence of large perfusion deficits. (99m)Tc-MAG3 scintigraphy could be an important diagnostic tool in such cases.

Diffuse vascular damage in a transplanted kidney: an indication for nuclear magnetic resonance?

Vascular lesions are an increasing challenge after renal transplantation due to the wider indications for recipients and acceptance criteria for donors. Diagnostic approach and prognostic interpretation are still matter of controversy. The case reported herein may summarize some of the issues in this regard. A 54-year-old woman, on renal replacement therapy since 1974, and a kidney graft recipient from 1975 to 1999, received a second graft in 2001. The donor age was 65 years (cold ischemia 22 hours; two mismatches). The early posttransplant follow-up was characterized by delayed graft function, hypertension, and diabetes. During the initial hypertension workup, renal graft ultrasound (US) Doppler demonstrated increased vascular resistances, stable over time (resistance index 0.74 to 0.77); renal scintiscan displayed homogeneously parenchymoa and angio-magnetic resonance imaging (MRI), an homogeneous parenchymal vascularization. Initial immunosuppression with tacrolimus and steroids was modulated by adding mycophenolate mofetil to taper tacrolimus (to reduce nephrotoxicity and hypertension). Despite this, kidney function slowly deteriorated; serum creatinine reached 3 to 3.5 mg/dL by the second year. After a severe hypertensive crisis with unchanged scintiscan and US doppler examinations, angio-MRI revealed the almost complete disappearance of parenchymal enhancement beyond the lobar arteries. A renal biopsy confirmed the severe vascular damage. The patient was switched to rapamycine and a low-dose of an angiotension converting enzyme (ACE) inhibitor. She did relatively well (serum creatinine 2.2 to 3 mg/dL) for 6 months, when rapid functional impairment forced her to restart hemodialysis. This case, almost paradigmatic of the problems occurring when the rigid vasculature of long-term dialysis patients is matched with "marginal kidneys," suggests that MRI may be a sensible good to define vascular damage in the grafted kidney.

Preemptive pancreas-kidney transplantation: multidisciplinary follow-up starts too late.

BACKGROUND: Preemptive pancreas-kidney transplantation is increasingly considered at early stages of nephropathy in type 1 diabetics. A multidisciplinary approach is required, but referral to the nephrologist is often delayed. OBJECTIVE: To analyze the referral pattern of type 1 diabetics to a dedicated nephrology unit and to test the prevalence of indications for pancreas-kidney transplantation in this population, according to early preemptive criteria (creatinine >/= 2 mg/dL and/or nephrotic syndrome). PATIENTS AND METHODS: The setting of study was the first Italian Nephrology Outpatient Unit dedicated to diabetics during 1991 to 2002. The main biochemical and clinical parameters were analyzed at referral. RESULTS: Ninety type 1 diabetics underwent at least one nephrological visit during the period; 85 had data at referral. The referral pattern was stable: 1991 to June 1996 [22 men, 24 women of median age 36 (18 to 65) years; diabetological follow-up 18.0 (3 to 37) years] and July 1996 to March 2002 [26 men, 18 women median age 40 (18 to 65); diabetological follow-up 21.5 (11 to 36) years]. The main biochemical data at referral were superimposable: serum creatinine: 1.2 (0.6 to 3.2) versus 1.3 (0.6 to 7) mg/dL; proteinuria: 0.9 (0 to 11) versus 1.01 (0.05 to 12.3) g/24 hours. Diabetes follow-up was greater in July 1996 to March 2002 [18 (3 to 37) versus 21.5 (11 to 36) years] suggesting an effect of improvements in diabetic care. At referral 76.6% were macroproteinuric 85.6% had signs of end-organ damage other than nephropathy; and 30.6% had indications for pancreas-kidney grafting (creatinine >/= 2 mg/dL: n = 6 cases; nephrotic syndrome: n = 10; or both n = 10). CONCLUSIONS: One new frontier of transplantation is the need for early multidisciplinary evaluation of type 1 diabetic patients.

[Biopsy experience at the G. Bosco Hospital from 1996 to 1999]. / Esperienza bioptica dell'Ospedale G. Bosco dal 1996 al 1999.

BACKGROUND: Aim of this study was a retrospective analysis of the renal biopsies performed in our Division. METHODS: Since January 1, 1996 to September 30, 1999 289 biopsies were performed on native kidneys, 90 patients were older than 65. RESULTS: The most frequent nephropathy was IgA glomerulonephritis (IgAGN) (28%), followed by membranous glomerulonephritis (MGN) (11%). In patients older than 65, the most frequent was MGN (20%), followed by IgAGN (12.2%). The total complications were 84 (29.1%) (hematomas >3 cm 1%; blood transfusion: 1.4%). Complications were not related to age, blood pressure, renal function, clinical presentation, number of shots. In 217 patients, the results obtained with two different modalities were compared: manual system (needle size=15 gauge) and automatic system (18 gauge). No statistically significant differences were found as regards the number of shots for single biopsy, number of glomeruli and major complications (1.6% vs 1.3%), while minor complications were more frequent in the second group. CONCLUSIONS: In conclusion, the number of renal biopsies performed in our Division has been increasing year after year. This trend can be partially explained by our wider indications to renal biopsy in elderly population (the data related to resident population showed the greatest prevalence of biopsies in patients 70 to 79 years old). Renal biopsy actually represents a safe examination even in elderly patients. From a technical point of view, on the basis of personal experience, 18 gauge acecut automatic needles seem to be preferred to other kind of devices.

[Abnormal erythrocyte sodium transport in patients with adult polycystic kidney and hypertension]. / Altérations du transport érythrocytaire du sodium chez les patients atteints de polykystose rénale de l'adulte et hypertension artérielle.

The aim of this work was to evaluate the intracellular Na concentration, the passive Na permeability and the activity of Na, K pump, Na, K cotransport, Na, Li countertransport in the red cells of patients with autosomal dominant polycystic kidney disease (ADPKD) in relationship with their blood pressure status. Sixteen patients with ADPKD and normal renal function (6 males, 10 females, median age 31.5 years, range 20-42 years) and twenty healthy controls (10 males, 10 females, median age 30 years, range 23-47 years) were studied. Eight ADPKD were hypertensive. The rate constant of ouabain-sensitive Na efflux was lower in hypertensive than in normotensive ADPKD patients. The activity of Na,Li countertransport was significantly higher in hypertensive ADPKD patients than in both normotensive patients and control subjects. A significant inverse correlation was found between Na,Li countertransport activity and the rate constant of ouabain-sensitive Na efflux in fresh red cells (rho = 0.62; p = 0.016). Hypertension in patients with ADPKD and normal renal function is associated with abnormalities of red cell sodium transport: an increase of Na,Li countertransport, possibly primitive, and a reduction of Na,K pump in fresh cells, possibly secondary to a circulating inhibitor.

Sodium-lithium countertransport activity in red blood cells of patients with IgA nephropathy.

In this paper we report some results of our studies on patients with immunoglobulin (Ig)A nephropathy regarding (1) the familiar aggregation of erythrocyte sodium-lithium (Na,Li) countertransport; (2) the association of Na,Li countertransport with the presence of arterial hypertension and lipid abnormalities; (3) the correlation between Na,Li countertransport activity and renal functional reserve; and (4) the preliminary results of a longitudinal study. In 13 families of patients with IgA nephropathy, selected because both parents were available, we found a significant correlation between midparent and offspring Na,Li countertransport activity (Spearman's rank correlation = 0.65; P = 0.023), but no husband-wife relationship. In 49 patients, the activity of Na,Li countertransport was significantly higher in erythrocytes from 20 hypertensive patients than from either 29 normotensive patients or from 36 healthy age- and sex-matched normal subjects. Hyperlipidemic patients had an erythrocyte Na,Li countertransport activity significantly higher than normolipidemic patients and controls. In 17 patients a significant inverse correlation was found between the peak variation of creatinine clearance over baseline value after an oral protein load and the erythrocyte Na,Li countertransport activity (Spearman r = 0.54; P = 0.03). In a longitudinal study of 36 patients followed from 12 to 36 months, those showing a progression toward renal failure had an erythrocyte Na,Li countertransport activity higher than median value. The results of our studies show that in patients with IgA nephropathy a high erythrocyte Na,Li countertransport rate, genetically determined, is associated with the presence of arterial hypertension and lipid abnormalities, and perhaps with a less favorable disease outcome.

[Erythrocyte sodium-lithium countertransport in diabetic children: 12 months development and relationship with familial hypertension]. / Contre-transport sodium-lithium érythrocytaire chez les enfants diabétiques: évolution à 12 mois et rapports avec l'hypertension familiale.

It has been suggested that an increased erythrocyte Na-Li countertransport (Na-Li CNT) rate in patients with IDDM is associated to the risk of developing diabetic nephropathy. Little is known, however, about the possible influence of metabolic control on Na-Li activity. Aims of the study were to evaluate Na-Li CNT at the onset of IDDM and during the remission phase and its relationship with some clinical and metabolic parameters. Twelve insulin-dependent diabetic children (6 males, 6 females; mean age 10 +/- 0.6 years) were studied at the onset and 1, 4, 12 months after the diagnosis; 6 of them had a family history of hypertension. Twelve healthy children (6 males, 6 females; mean age 12 +/- 0.3 years) served as controls. As compared to control subjects (212 +/- 24 mumol/l RBC/h), red cell Na-Li countertransport activity of diabetic children was significantly higher at the onset (354 +/- 31 mumol/l RBC/h) of IDDM and at the first month (348 +/- 36 mumol/l RBC/h). Red cell Na-Li countertransport activity returned toward normal range at the fourth (239 +/- 33 mumol/l RBC/h) and twelfth month (162 +/- 34 mumol/l RBC/h). No correlation was found between the values of red cell Na-Li countertransport activity and those of clinical and biochemical parameters at any time. Patients with hypertensive relatives showed at baseline evaluation a significantly higher red cell Na-Li countertransport activity than those without (436 +/- 28 vs 273 +/- 34 mumol/l RBC/h; p < 0.002). This difference, although not statistically significant, was still evident at the late follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Aggregation of erythrocyte sodium/lithium countertransport activity in families of patients with immunoglobulin A nephropathy.

1. We evaluated the inheritance of erythrocyte Na+/Li+ countertransport activity in IgA nephropathy by assessing this parameter in 19 patients with biopsy-proven IgA nephropathy and in their 53 relatives (32 parents and 21 siblings). The possible use of erythrocyte Na+/Li+ countertransport activity as a marker of poor prognosis was also evaluated. 2. A significant correlation was found between 'familial' and proband Na+/Li+ countertransport activity, but not between that of spouses. 3. Mean blood pressure, although within the normal range, and Na+/Li+ countertransport activity were significantly higher in patients with proteinuria than in those without proteinuria. 4. Parents of proteinuric patients had a higher Na+/Li+ countertransport activity than parents of non-proteinuric patients. 5. In IgA nephropathy the inheritance of erythrocyte Na+/Li+ countertransport activity was preserved. Therefore genetic factors could play a role in the non-immunological progression of IgA nephropathy.

[Changes in cellular ion transport and arterial pressure in renal transplant recipients undergoing cyclosporin treatment]. / Alterazioni del trasporto ionico cellulare e pressione arteriosa nei portatori di trapianto renale in trattamento con ciclosporina.

Arterial hypertension is a common side effect of cyclosporine A (CyA). Aim of the study was to evaluate the activity of erythrocyte (RBC) Na transport in two groups of patients with a well functioning renal graft (Crs less than 1.7 mg/dl) treated by prednisone+azathioprine (10 pts), or prednisone+CyA (21 pts), in relationship with blood pressure status. Twenty-one age matched healthy subjects were studied as a control group. Na,K pump and Na,K cotransport were significantly lower in CyA than in AZA patients (2,184 +/- 106 vs 3,089 +/- 162 and 58 +/- 8 vs 187 +/- 28 mumol/l RBC/h: p less than 0.01), without differences between normotensive and hypertensive patients. Na,K pump efflux in normal subjects was 2334 +/- 66 mumol/l RBC/h (p less than 0.01 vs AZA), NA,K cotransport was 205 +/- 18 mumol/l RBC/h (p less than 0.01 vs CyA). Significant correlations were found between RBC Na,K pump activity and trough plasma CyA levels (p less than 0.02) and between systolic pressure and plasma creatinine in CyA patients (p less than 0.01). Trough plasma CyA levels were higher in hypertensive than in normotensive CyA patients (64 +/- 5 vs 46 +/- 4 ng/ml; p less than 0.01).

[Effects of saline infusion on the activity of erythrocyte sodium-potassium pump in normal subjects and in patients with essential hypertension]. / Effetti dell'infusione salina sull'attività della pompa Na,K eritrocitaria in soggetti normali e in pazienti con ipertensione essenziale.

The effects of a 2 litre isotonic saline infusion on erythrocyte Na,K pump activity and urinary sodium excretion (UNaV) were evaluated in 20 patients with essential hypertension and 15 normotensive subjects. The effect of preincubation of normal erythrocytes in plasma from hypertensive patients on erythrocyte Na,K pump was also studied. Before saline infusion no significant differences were found between normotensive and hypertensive subjects in the mean values of intracellular sodium and potassium concentration, ouabain-sensitive Na efflux in erythrocytes and urinary sodium excretion. Erythrocyte Na,K pump activity decreased significantly (p less than 0.01) after saline infusion in both groups of subjects. The reduction was significantly lower in hypertensives than in normotensive. delta UNaV was significantly higher in hypertensive patients than in normotensive subjects (25 +/- 4 vs 14 +/- 2 mmol/h; p = 0.04). Only in normal subjects a significant correlation was found between the difference in Na,K pump activity pre and post saline infusion and delta UNaV (r = 0.52; p less than 0.05). Plasma from hypertensive patients obtained before saline infusion significantly (p less than 0.01) inhibited Na,K pump of erythrocytes from normal subjects; plasma taken after saline infusion produced a marked increase of this inhibition, significantly (p less than 0.01) higher than serum taken before the infusion.

Increased sodium-lithium countertransport activity in red cells of IgA nephropathy patients.

The aim of this work was to analyze Na,Li countertransport activity in the erythrocytes from patients with IgA nephropathy, in relationship with their blood pressure status and lipid profile. Forty-nine patients (32 males, 17 females) with biopsy-proven IgA nephropathy and without significant impairment of renal function (serum creatinine less than or equal to 1.4 mg/dl) and 36 normal subjects (21 males, 15 females) were evaluated. Twenty-nine patients with IgA nephropathy were normotensive and 20 hypertensive (diastolic pressure greater than or equal to 95 mm Hg or treated by antihypertensive drugs). Na,Li countertransport was significantly higher in red cells from hypertensive than from normotensive patients (P = 0.002) and normal subjects (P = 0.0001), (values respectively 309 +/- 17; 241 +/- 12 and 211 +/- 11 mumol/liter RBC/hr); normotensive patients with IgA nephropathy did not differ from controls regarding the Na,Li countertransport rate. A multiple stepwise logistic regression analysis with blood pressure status as the dependent variable and Na,Li countertransport activity, age, serum creatinine, proteinuria, cholesterol, triglycerides, plasma potassium and time from onset as independent variables, indicated an independent significant association for Na,Li countertransport (P = 0.002) proteinuria (P = 0.006), plasma potassium (P = 0.006) and age (P = 0.029). Other tested variables were not independently related to blood pressure status. Hyperlipidemic patients (plasma total cholesterol concentration greater than 200 mg/dl and/or plasma triglycerides greater than 172 mg/dl) had an erythrocyte Na,Li countertransport activity significantly higher than normolipidemic (P = 0.005) and controls (P = 0.001) (values respectively 295 +/- 14; 226 +/- 12 and 211 +/- 11 mumol/liter RBC/hr).(ABSTRACT TRUNCATED AT 250 WORDS)

Erythrocyte Na,Li countertransport and arterial pressure in diabetic adolescents.

The aim of this study was to analyze Na,Li countertransport in erythrocytes from adolescents with insulin dependent diabetes mellitus (IDDM) and to see if those with elevated values present distinct clinical features, in particular as regards arterial pressure and urinary albumin excretion (UAE). Twenty-nine adolescents with IDDM (17 males, 12 females, mean age 15 +/- 0.6 years, mean diabetes duration 11.4 +/- 0.7 years) and fifteen healthy age-matched control subjects (8 males, 7 females, age 14.5 +/- 1 years) were investigated. Diabetic adolescents had a RBC Na,Li countertransport activity higher than age matched normal controls; geometric mean 283 (95% limits 259-340) vs. 193 (169-252) mumol/l RBC/h; p less than 0.01. Seven out of 29 subjects had values higher than the 95th percentile of normal subjects (Counter +). Both systolic and diastolic arterial pressures were significantly higher in Counter + than in Counter - patients. No significant differences were found as regards age, body mass index, diabetes duration, HbA1c, fructosamine, serum potassium, triglycerides, creatinine clearance and UAE. The logarithm of systolic pressure was independently positively correlated with ln Na,Li countertransport (r = 0.38; p less than 0.05), ln [Nai] (r = 0.38; p less than 0.05), and ln body mass index (r = 0.5; p less than 0.01) in diabetic patients. The main finding of this study is that diabetic adolescents with a high erythrocyte Na,Li countertransport rate have an arterial pressure significantly higher than patients with normal Na,Li countertransport fluxes.

[Erythrocyte sodium-lithium countertransport in diabetic adolescents]. / Contretransport sodium-lithium érythrocytaire chez les adolescents diabétiques.

Aim of this study is to evaluate whether among type I diabetic adolescents (IDDM) the erythrocyte Na-Li countertransport (CNT Na-Li) is correlated with arterial pressure and tubular sodium reabsorption. We have studied 16 IDDM adolescents (age 15 +/- 0.5 year) et 15 normal subjects (age 14.5 +/- 1 year). CNT Na-Li, creatinine and lithium clearances (as markers of glomerular filtration rate and proximal tubular sodium reabsorption) have been measured in all subjects and nocturnal urinary albumin excretion rate (UAER) was measured in IDDM adolescents. CNT Na-Li was 308 +/- 26 mumol Li/l RBC/h in IDDM adolescents and 211 +/- 74 mumol Li/l RBC/h in controls (p less than 0.01). The fractional excretion of lithium (FELi) was significantly reduced in IDDM adolescents compared to normal subjects (12 +/- 2 vs 19 +/- 2%; p less than 0.01). Among the IDDM adolescents, 5 had the CNT Na-Li higher than the 95th percentile of controls (greater than 360 mumol Li/l GR/h); their systolic arterial pressure was significantly higher than in diabetics with normal CNT Na-Li (126 +/- 2 vs 116 +/- 2; p = 0.03), while there were no differences for diabetes duration, glycemic control, serum potassium, creatinine clearance, FELi and UAER. The relationship between CNT Na-Li and arterial pressure in IDDM adolescents deserves further studies.

[Biofiltration without buffering substances in the dialysate]. / La biofiltrazione senza sostanze tampone nel dialisato.

A new hemodiafiltration technique, acetate free biofiltration (AFB), has been recently introduced in the treatment of chronic uremia. It is performed with a buffer free dialysate and a simultaneous infusion in post-dilution mode of a sodium bicarbonate solution (concentration 145-166 mEq/l; infusion rate 1.2-2 l/h). A polyacrylonitrile hollow fiber AN69 HF 1.2 sqm dialyzer is employed. In acute studies pCO2 remains stable throughout the treatment, as well as pCO2. We have found a significant inverse correlation between delta[HCO3-] pre and post treatment and basal [HCO3-] (r = -0.88; p less than 0.001), with an excellent correction of uremic acidosis, avoiding post dialytic alkalosis. Our long term experience on 6 patients followed up to 31 months, allows us to consider AFB as a feasible and safe treatment, offering a good correction of uremic acidosis and an excellent hemodynamic tolerance. We propose AFB as a competitive technique with respect to bicarbonate hemodialysis, hemodiafiltration and standard biofiltration.

Erythrocyte Na-stimulated Mg transport in uremic patients undergoing CAPD.

A derangement of magnesium homeostasis with hypermagnesemia and increased intraerythrocyte Mg content [Mgi] has been described in uremic patients, and could play a pathogenetic role in both alterations of bone metabolism and vascular reactivity, observed in these patients. Recently Féray and Garay described in human erythrocytes a transport system which catalyzes outward Mg movements in the presence of external Na. These fluxes may be responsible for maintaining and regulating a low [Mgi]. The aim of this study was to evaluate in 16 normal subjects and 14 uremic patients undergoing CAPD: [Mgi] and rate of Na-dependent and Na-independent Mg efflux in Mg-loaded erythrocytes, in order to maximally stimulate Mg efflux. Mean plasma and intraerythrocyte Mg concentrations were significantly higher in CAPD than in normal subjects (1.09 +/- 0.20 vs 0.86 +/- 0.004 mmol/l, p less than 0.001 and 2.57 +/- 0.38 vs 1.96 +/- 0.18 mmol/l RBC, p less than 0.001). After an in-vitro Mg load, the intraerythrocyte Mg concentration and Na-independent Mg efflux were similar in both groups (17.5 +/- 1.4 vs 18.2 +/- 4.1 mmol/l RBC and 152 +/- 20 vs 126 +/- 19 mumol/l RBC/h). However, the Vmax of erythrocyte Na-stimulated Mg efflux was significantly higher in CAPD patients than in normal subjects (357 +/- 48 vs 229 +/- 88 mumol/l RBC/h, p less than 0.02). [Mgi] and the rate of Na-dependent Mg efflux were inversely related in CAPD patients (r = -0.76; p less than 0.002). These results indicate that uremic CAPD patients have a [Mgi] and Vmax of erythrocyte Na-dependent Mg efflux higher than normal subjects; this could reflect a compensatory, although insufficient, mechanism against high levels of intraerythrocyte Mg concentration, as suggested by the correlation between [Mgi] and the rate of Na-dependent Mg efflux.

CAPD in a large population: a 7-year experience.

In this report we evaluate the results obtained with CAPD in uremic patients in Piedmont, a Northern Italian region (4.4 million inhabitants) during the last 7 years. Data are gathered from the computerized records of the regional dialysis and transplantation registry, which collects information on 3,567 pts, 2,243 of which entered since Jan. 1981 and 1,808 alive at Dec. 1987. Among these, 193 (11%) were on CAPD, a figure almost constant in the last 7 years. However CAPD diffusion is not uniform among the 20 centers of the region, ranging from 0 to 49.5% of the patients on dialysis. CAPD is particularly employed in the elderly (47.5% of the patients being older than 60 years and 19.5% over 70). This treatment was the first choice in 16% of the patients admitted to dialysis between 1981-87; this figure reaches 33% for the diabetics. High drop out rates still represent a major problem, in a 6 year follow up 66% of the patients being transferred to another dialysis treatment. Peritonitis is the main cause of drop out (22%), while loss of peritoneal membrane efficiency accounts for 7%, patient's choice 14%, catheter complications 14%, inability to cope 8%, clinical problems 20% and other reasons 15%. Drop out rate is not influenced by the presence of high risk condition or age. Survival curves show no significant difference for CAPD in comparison to hemodialysis in all the age groups considered. This epidemiological survey, based on a global 522 pts experience extended over a 7 year period, indicates that CAPD is a competitive mode of treatment in chronic uremia.

Erythrocyte Na+, K+ pump inhibition after saline infusion in essentially hypertensive subjects: effects of canrenone administration.

The effects of a 2-litre isotonic saline infusion, with and without prior oral canrenone (150 mg) administration, on erythrocyte Na+, K+ pump, urinary sodium excretion and arterial pressure were evaluated in nine patients with essential hypertension. Ouabain-sensitive Na+ efflux in fresh erythrocytes was used as an index of Na+, K+ pump activity, and the inhibitory effect on this ion efflux of preincubation of erythrocytes in plasma was used to test the presence of a circulating ouabain-like substance. Erythrocyte Na+, K+ pump activity decreased significantly (P less than 0.01) after saline infusion; canrenone administration was able to prevent this inhibition. Plasma from hypertensive patients obtained before saline infusion significantly (P less than 0.01) inhibited the Na+, K+ pump of erythrocytes from normal subjects, while plasma taken after the saline infusion plus canrenone was unable to produce any significant inhibition. Both systolic and diastolic arterial pressure fell significantly (P less than 0.05) only at the end of saline infusion with prior canrenone administration. This study supports the hypothesis that protection of Na+, K+ pump against endogenous inhibitors, other than exogenous, seems to be a pharmacological effect of canrenone, and may partly explain its antihypertensive activity.