Prediction of delayed graft function by means of a novel web-based calculator: a single-center experience.

Renal failure persisting after renal transplant is known as delayed graft function (DGF). DGF predisposes the graft to acute rejection and increases the risk of graft loss. In 2010, Irish et al. developed a new model designed to predict DGF risk. This model was used to program a web-based DGF risk calculator, which can be accessed via http://www.transplantcalculator.com . The predictive performance of this score has not been tested in a different population. We analyzed 342 deceased-donor adult renal transplants performed in our hospital. Individual and population DGF risk was assessed using the web-based calculator. The area under the ROC curve to predict DGF was 0.710 (95% CI 0.653-0.767, p < 0.001). The "goodness-of-fit" test demonstrates that the DGF risk was well calibrated (p = 0.309). Graft survival was significantly better for patients with a lower DGF risk (5-year survival 71.1% vs. 60.1%, log rank p = 0.036). The model performed well with good discrimination ability and good calibration to predict DGF in a single transplant center. Using the web-based DGF calculator, we can predict the risk of developing DGF with a moderate to high degree of certainty only by using information available at the time of transplantation.

Determinants of resistive index shortly after transplantation: independent relationship with delayed graft function.

Measurement of the vascular resistive index (RI) by Doppler ultrasonography has been proposed as a non-invasive method to evaluate renal allograft dysfunction, but there are conflicting reports about its clinical utility. The aim of our study was to analyse the donor and recipient characteristics related to RI measured at days 2 and 3 after renal transplantation and the relationship between RI and allograft outcome. RI was measured by Doppler ultrasonography in 333 patients at days 2 or 3 post-transplantation. Donor and recipient variables and allograft outcome were collected from a prospectively maintained institutional database. In patients with RI higher than 0.7, donor age, recipient age, duration of renal replacement therapy, incidence of diabetes, hypertension and atherosclerosis in the recipient, pulse pressure, initial creatinine and the incidence of delayed graft function (DGF) were higher. After multivariate analysis, the only variables that remained significant for an increased risk of higher RI were recipient age over 55 years, presence of diabetes in the recipient and DGF. Recipient age, previous diabetes mellitus and DGF are the most important determinants of transplant kidney RI in the first days after transplantation. So both the graft recipient and the graft itself, but not the donor, determine intra-renal Doppler indices.

The phenomenon of hemoglobin variability with erythropoiesis stimulating agents in renal transplant patients.

Treatment with erythropoiesis-stimulating agents (ESA) is often associated with fluctuation in hemoglobin (Hb) levels that has been considered a factor that influences morbidity/mortality in hemodialysis patients. Our aim was to describe the hemoglobin variability during ESA treatment and to study associated factors in kidney transplants. Hb variability (defined as fluctuations of Hb +/- 1.5 g/dl) was assessed in 85 renal transplant patients treated with ESA for at least 3 months and with a minimum of 6 Hb measurements along 1 year. 58% of patients experienced Hb variability during follow-up. Although 71.3% of patients maintained Hb levels greater than 11 g/dl along the whole follow-up, only 3% of patients maintained stable Hb levels within the target range all the time (11 - 13 g/dl). By multivariate analysis, clinical factors associated with variability were changes in ESA dose (RR 2.92, p = 0.04), infectious events with hospitalization (RR 1.95, p = 0.03) and the use of sirolimus (RR 1.1, p < 0.05). Excluding dose changes and hospitalization in the analysis variability was an independent predictor of graft function deterioration. In conclusion, Hb variability is common in renal transplants treated with ESA. Only few patients maintained Hb levels in the therapeutic range (11 - 13 g/dl). Dose changes, inflammatory status and graft function deterioration are the determining factors.

[Changes in the pre-transplant bone-mineral metabolism do not affect the initial progress of the renal graft]. / Las alteraciones del metabolismo óseo-mineral pretrasplante no influyen en la evolución inicial del injerto renal.

BACKGROUND: Abnormalities in serum calcium, phosphate, and Parathyroid Hormone (PTH) concentrations are common in patients with chronic kidney disease and have been associated with increased morbidity and mortality. One of the most common problems in the first weeks after renal transplantation is Delayed Graft Function (DGF). There are several well-known risk factors for DGF development, but the role of calcium phosphate-PTH homeostasis as a risk factor for early graft dysfunction is controversial. This issue was addressed in the current study. METHODS: Pretransplant PTH, calcium and phosphate values were gathered in 449 patients that received a renal transplant in our center between 1994 and 2007. Other variables expected to influence the risk for delayed graft function were included from the clinical charts. RESULTS: The incidence of DGF was 27.3%. DGF development was significantly associated with recipient age, type and need of renal replacement therapy, peak panel reactive antibodies, transfusion number and donor age. There were no significant differences in the mean pretransplant values of calcium (9.4 +/- 1.0 vs. 9.5 +/- 0.9 mg/dl, p = 0.667), phosphate (5.7 +/- 1.8 vs. 5.5 +/- 1.5 mg/dl, p = 0.457), calcium-phosphate product (53.5 +/- 17.2 vs. 51.8 +/- 14.6 mg(2)/dl(2), p = 0.413) and PTH (315 +/- 312 vs. 340 +/- 350 pg/ml, p = 0.530) between patients with and without DGF. CONCLUSIONS: In our study population pretransplant serum PTH, calcium and phosphorus levels have no influence on the risk for DGF.

Changes in the expression of the immunoglobulin-like transcript 3 (ILT3) and ILT4 receptors in renal allograft recipients: effect of donor and recipient aging.

INTRODUCTION: The aim of the present study was to investigate the number and phenotype of pre- and posttransplant peripheral blood dendritic cells (DCs) in kidney graft recipients to correlate with CD4(+)CD25(high) Treg and CD8(+)CD28(-) cells. Data were analyzed according to the age of the donor-recipient pairs. MATERIALS AND METHODS: A cohort of 49 cadaveric kidney transplant recipients was prospectively studied pretransplant and 6 months posttransplant by three-color flow cytometry with specific monoclonal antibodies. Patients were subgrouped according to age (elderly were considered above 60 years old and young below 55 years old) in the following donor-recipient pairs: aged/aged, young/aged, aged/young, young/young. RESULTS: At 6 months posttransplant, the proportion of cells tended to increase when the donor was young, regardless of the recipient. Importantly, there was a significant correlation between the numbers of immunoglobulin-like transcript 4(+) DCs and CD4(+)CD25(high) Treg cells before transplantation (r = .476, P = .004) and at 6 months (r = .408, P = .013). A significant association was also observed between ILT4(+) DCs and CD8(+)CD28(-) pretransplant (r = .540, P = .001) and at 12 months posttransplant (r = .609, P = .012). CONCLUSIONS: Renal grafts from young but not from aged donors seem to induce DC of a tolerogenic phenotype, both in aged and young recipients. These preliminary results suggested that donor age may have consequences in terms of tolerance induction.

Association between serum soluble CD30 and serum creatinine before and after renal transplantation.

OBJECTIVE: There is increasing evidence that circulating levels of soluble CD30 (sCD30) may represent a biomarker for outcome in kidney transplantation. The aim of this study was to measure the pre- and posttransplantation serum levels of sCD30 in cadaveric kidney transplant recipients and correlate them with serum creatinine. PATIENTS AND METHODS: Serum sCD30 was measured by a commercial enzyme-linked immunosorbent assay (ELISA) from prospective samples of 38 kidney allograft recipients serially transplanted at our center. Samples were collected at day 0 pretransplantation and at months 6, 12, 18, and 24 posttransplantation. We also studied sera from 29 patients with chronic kidney disease (CKD) at different stages of the K/DOQI guidelines, as a control group. RESULTS: Serum levels of sCD30 decreased significantly in samples posttransplantation compared with pretransplantation. The significant decrease after transplantation may be related to the improvement in renal function since we observed a significant correlation between serum levels of sCD30 and creatinine (sCr) at all times of the study. In addition, the patients with chronic renal failure showed a significant association between serum sCD30 and sCr (r = .454; P = .013). CONCLUSIONS: Our results did not suggest that the measurement of sCD30 may be used as a valuable biomarker in renal transplantation. Increased levels may be related to a decrease in its renal elimination.

Factor deficiency in the anemia of renal transplant patients with grade III-IV chronic kidney disease: baseline results of the ARES Study.

ARES is a multicenter, prospective study of the prevalence, management, and repercussions on the quality of life of anemia in renal transplant patients with a reduced renal function (creatinine clearance according to Cockcroft-Gault: 15 mL/min). The frequency of factor deficiency and its relationship with anemia were analyzed at the baseline time of the study. Of the 500 patients included in the main study, valid data were available for iron metabolism in n = 419 microg/dL; folic acid, n = 205 ng/mL; and vitamin B12, n = 210 pg/mL. Anemia was defined as hemoglobin

Survival after dialysis initiation: a comparison of transplant patients after graft loss versus nontransplant patients.

BACKGROUND: A substantial number of patients return to dialysis therapy after a renal transplant fails. It is not clear whether mortality increases among patients with graft failure relative to those who initiate dialysis but who have not yet received a kidney transplant. PATIENTS AND METHODS: We compared the outcomes of an incident cohort of patients (n = 194) with a cohort of renal transplant patients who returned to dialysis after graft loss (n = 74). We analyzed the morbidity and mortality after dialysis initiation and the parameters during the year beforehand. RESULTS: Mortality among post-graft loss dialysis patients was higher than transplant-naive patients (relative risk [RR]: 2.05; 95% confidence interval [CI]: 1.26-3.35). Additionally, complications, such as the number of hospitalizations during the first year after dialysis initiation, were higher (29% vs 57%; P > .001). At dialysis initiation no differences were found in glomerular filtration rate, although hemoglobin and albumin levels were lower and C-reactive protein was higher in post-graft loss dialysis patients. CONCLUSIONS: Mortality among patients on dialysis therapy after graft loss increased significantly compared with mortality among patients who initiated dialysis for the first time, despite specialty physicians being aware of them. Additional studies are urgently needed to define the mechanisms of the increased risk and strategies to decrease mortality.

Hemoglobin level variability in renal transplant patients treated with erythropoiesis stimulating agents.

OBJECTIVE: Treatment with erythropoiesis stimulating agents (ESA) is associated with fluctuations in hemoglobin (Hb) levels. Recently, variability of Hb has been considered a factor that influences comorbidity and mortality among hemodialysis patients. The purpose of this analysis was to describe the phenomenon of Hb variability during ESA treatment, to study associated factors among kidney transplant patients, and to assess the impact on patient and graft survivals. PATIENTS AND METHODS: Hb variability (defined as fluctuations of Hb +/- 1.5 g/dL) was assessed in 85 renal transplant patients treated with ESA for at least 3 months and with a minimum of 6 Hb measurements during 1 year. RESULTS: Fifty-eight percent of the patients experienced Hb variability during follow-up. Only 3% of patients maintained stable Hb levels within the target range (11-13 g/dL), although 83% of patients maintained Hb levels >11 g/dL. Multivariate analysis showed that the clinical factors associated with variability were changes in ESA dose (relative risk [RR]: 2.92; 95% confidence interval [CI]: 1.0-8.5; P < .05), infectious events with hospitalization (RR: 1.95; 95% CI: 1.23-2.13; P < .05), and the use of sirolimus (RR: 1.1; 95% CI: 1.0-3.6; P < .05). When dose changes and hospitalization were excluded from the analysis, variability was an independent predictor of worsening graft function. CONCLUSIONS: Hb variability is common in renal transplant patients treated with ESA. Only a few patients maintained Hb levels within the therapeutic range, although most had levels >11g/dL. Dose changes, inflammatory status, and worsening graft function are the determining factors of variability. Variability had no influence on patient survival, although it was a marker of worsening graft function.

Venous graft thrombosis in patients on peritoneal dialysis before transplantation.

BACKGROUND: It has been described that patients on peritoneal dialysis (PD) suffer from thrombotic events (vascular access, deep venous thrombosis, and graft thrombosis) more frequently after transplantation than other recipients. We analyzed the incidence of allograft thrombosis among patients transplanted in a 6-year period (January 1, 2000, to December 31, 2005) to identify etiological factors, such as inherited thrombophilia. MATERIALS AND METHODS: We performed 197 renal transplants in 189 patients, including 115 who had been on hemodialysis (HD), 44 on PD, and 30 preemptive. We recorded immunological and demographic data, studied graft and patient survivals, and evaluated the hypercoagulable state of those who experienced graft thrombosis. RESULTS: The mean age of the patients at transplantation was 49 years. There were no demographic or immunological differences between the three groups of patients, except for the number of previous blood transfusions and panel reactive antibodies (PRA) levels. Forty-seven grafts were lost in the first year; 14 suffered venous thrombosis, and there were 10 acute rejection epidoses (ARE), 7 death-censored graft failures, 3 chronic allograft nephropathies (CAN), 6 primary nonfunctions, 5 removed due to infection, 1 primary disease relapse, and 1 hemolytic-uremic syndrome. Of the 14 cases of thrombosis in 12 patients, 10 had been on PD and 4 on HD immediately before transplant. One-year graft and patient survivals were similar: 74% HD, 68% PD, 86% preemptive, and 93% HD, 95% PD, and 96% preemptive, respectively. The hypercoagulable state showed inherited thrombophilia patterns in some cases, but most of them were normal. CONCLUSION: Renal graft thrombosis was responsible for graft lost in PD patients within the first year, while in the HD group it was ARE and in the preemptive cohort, death with a functioning graft. The hypercoagulable state pretransplant should be more accurately studied to identify thrombotic factors other than those which are inherited.

Evaluation of the efficacy and safety of the conversion from a calcineurin inhibitor to an everolimus-based therapy in maintenance renal transplant patients.

Everolimus has recently been introduced into clinical practice with promising perspectives due to its efficacy, lack of nephrotoxicity, and antitumor effects. Experience in clinical trials associated with low-dose cyclosporine showed good results, but there is almost no experience in calcineurin inhibitor (CNI) elimination learning it as the primary immunosuppressant. We describe our experience in a series of 78 stable renal transplant patients who were switched to Everolimus with complete and quick elimination of the CNI: the procedure of conversion, pharmacokinetic results after conversion, evolution of renal parameters (renal function, proteinuria, and others), and safety data (acute rejection and adverse events). An initial dose of 3 mg/d was adequate to obtain the recommended trough levels between 5 and 10 ng/mL. Our results demonstrated that conversion to Everolimus was a simple, safe procedure that must be considered in patients CNI toxicity, especially those with malignant neoplasms and progressive deterioration of renal function due to chronic allograft nephropathy.

Cytokine polymorphisms and risk of infection after kidney transplantation.

INTRODUCTION: Infection remains a significant cause of morbidity and mortality after solid organ transplantation. Genetic background has an influence on the incidence of infection. The aim of our study was to analyze the relationship between cytokine polymorphisms and infection in our kidney transplant recipients. METHODS: DNA from 255 kidney transplant recipients was isolated routinely. Polymerase chain reaction sequence-specific primer was performed using commercially available cytokine genotyping primer packs to determine polymorphisms of interleukin (IL)-10, transforming growth factor-beta, tumor necrosis factor-alpha, interferon-gamma, IL-6, IL-4, IL-2, IL-12, IL-4R alpha, IL-1RA, IL-1R, IL-1 beta, and IL-1 alpha. The appearance and number of infections within the first year after transplantation were identified retrospectively. RESULTS: One hundred twenty-two patients experienced at least one episode of infection in the first year after transplant. The frequency of the -511 IL-1beta CC genotype and the frequencies of the -1188 IL-12 CA and CC genotypes were significantly higher among the infected patients compared with the noninfected patients. We failed to observe significant differences in the genotype distribution of the other analyzed cytokines regarding the incidence of infection. After adjusting, recipient IL-1beta (-511 CC) genotype (relative risk [RR] 2.67, 95% confidence interval (CI) 1.30 to 5.49, P = .007) and recipient IL-12 (-1188 CA and CC) genotypes (RR 2.57, 95% CI 1.22 to 5.38, P = .012) predicted independently the risk of infection in the first year after kidney transplantation. CONCLUSION: Kidney transplant recipients with -511 IL-1beta CC genotype or with -1188 IL-12 CA and CC genotypes were at higher risk of developing infections in the first year after transplantation. Patients with genetic susceptibility to infection may benefit from less potent immunosuppressive therapy and more intense preventive measures.

Acute renal failure associated with use of inhaled tobramycin for treatment of chronic airway colonization with Pseudomonas aeruginosa.

Aminoglycoside nephrotoxicity is a well-known clinical entity that complicates the course of infectious diseases treated under this antibiotic regime. Recently, a new administration form of tobramycin, inhaled tobramycin (TOBI), has been approved to improve the antibacterial activity and reduce nephrotoxicity. We describe the clinical case of a 73-year-old woman with chronic-obstructive pulmonary disease (COPD) who developed acute renal failure (ARF) after using TOBI. Clinical presentation and biochemical parameters were compatible with aminoglycoside-induced renal failure. Based on the clinical findings presented here, a surveillance program should be established to monitor the presence of factors predisposing to renal failure, and to measure serum levels of tobramycin.

Conversion to everolimus in kidney transplant recipients: a safe and simple procedure.

To date there is a substantial experience with rapamycin conversion in stable renal transplant recipients with respect to the procedure of conversion, initial doses, and target blood levels as well as adverse events, but in the case of Everolimus there is almost no experience with conversion and calcineurin inhibitor (CNI) withdrawal. We describe an initial experience among 32 renal transplant recipients who were converted to Everolimus with complete suspension of CNI in two Spanish transplant centers. Our results emphasised the procedure for conversion, the target levels, the adverse events, and the initial efficacy, over the first month after conversion. Our conclusions were that conversion from CNI to Everolimus was a simple, safe procedure with a predictable profile of adverse events, which were, in general, of mild intensity. There was a good correlation between initial dose and blood level. Initial doses of about 3 mg/d combined with rapid reduction in CNI exposure seemed to be adequate. The target range levels between 5 and 10 ng/mL seemed to be sufficient for complete CNI elimination, especially in patients also receiving antiproliferative drugs (such as mycophenolate mofetil or azathioprine) in whom levels near the lower end of the range might be adequate.

Calcineurin inhibitors affect circulating regulatory T cells in stable renal transplant recipients.

INTRODUCTION: Immunosuppression, although crucial for short-term management, has been described in renal transplantation to be a major hurdle for long-term graft survival. Efforts have been directed at achieving a true state of allotolerance, thereby reducing the load of immunosuppression. Recently, increased frequencies of CD4(+)CD25(high) regulatory T cells (Tregs) have been described as an additional mechanism to induce alloimmune tolerance. MATERIALS AND METHODS: We assessed 64 renal transplant recipients with stable renal function for at least 1 year, divided into two groups: one composed of patients receiving rapamycin but not calcineurin inhibitors (CNIs), and another, of those receiving CNIs but not rapamycin. RESULTS: We demonstrated that T cells with a regulatory phenotype were decreased in peripheral blood of renal transplant recipients under CNI therapy compared to those who were CNI-free. The Tregs in our patients showed a modest association with renal function as measured by the delta serum creatinine, which was not significant. CONCLUSIONS: CNIs, but not rapamycin, reduce the frequencies of circulating Tregs in renal transplant recipients. The use of rapamycin might be further exploited in strategies reducing immunosuppression in renal transplantation. Furthermore, quantification of blood Tregs may be a suitable tool to identify those recipients who are candidates for reducing immunosuppression.

Assessment of Kidney Graft Function Evolution Measured by Creatinine and Cystatin C.

INTRODUCTION: The 2013 Kidney Disease Outcomes Quality Initiative Clinical Practice Guideline suggests measuring cystatin C (sCys) in adults with glomerular filtration rate (GFR) based on creatinine (sCr) between 45 and 59 mL/min/1.73 m2 if confirmation of chronic kidney disease (CKD) is required. There is not enough evidence to recommend the use of sCys or sCr to estimate GFR in kidney transplant recipients. OBJECTIVES: Our aims were to describe the evolution of sCr, sCys, and GFR in a group of kidney transplant patients and to determine their association with some markers of morbidity at 1 year. METHODS: A total of 54 patients were included. Analytical and clinical data were recorded. Renal function was analyzed using the CKD Epidemiology Collaboration (EPI) sCr equation and CKD-EPI sCys equation. RESULTS: sCys-estimated GFR was higher than estimated from sCr by CKD-EPI. The values of sCys have more variability than those of sCr. The agreement between the stages of CKD by sCr or sCys-estimated GFR measured by Cohen's kappa coefficient was only fair. One-year CKD-associated variables correlated differently with sCr and sCys-estimated GFR. Hemoglobin, uric acid, calcium, and phosphorus related to sCr-estimated GFR, whereas serum albumin was associated with sCys-estimated GFR. CONCLUSIONS: sCys values have a higher variability than sCr in kidney transplant recipients. sCys- or sCr-based GFRs have a nonsimilar behavior in these patients with weak agreement to stratify CKD stages and a different relationship to CKD-related comorbid conditions.

Higher initial tacrolimus blood levels and concentration-dose ratios in kidney transplant recipients who develop diabetes mellitus.

Posttransplantation diabetes mellitus (PTDM) is a common complication of kidney transplantation, associated with poorer graft and patient outcomes. Tacrolimus is a strong immunosuppressive drug associated with low acute rejection rates, but a higher risk for PTDM. High trough levels of tacrolimus during the first month after transplantation have been found to be a significant risk factor for the development of PTDM. The aim of this single-center study was to identify the risk factors for the development of PTDM among kidney transplant recipients under tacrolimus therapy. We examined 73 cadaveric kidney transplant recipients receiving tacrolimus between 1994 and 2003. Age, donor and recipient gender, dialysis method, body mass index (BMI), first year weight gain, mismatches, incidence of acute rejection and delayed graft function, hepatitis C serology, first year cumulative steroid dose, first tacrolimus blood level, first tacrolimus blood level <15 ng/mL, and corresponding tacrolimus daily doses and concentration/dose ratios (CDR) were also collected. PTDM was defined as at least 2 fasting blood glucose values > or =126 mg/dL, according to the World Health Organization criteria. Incidence of first year PTDM was 27.4%. Patients with PTDM showed significantly higher age, BMI, first tacrolimus blood level, first tacrolimus CDR, and CDR with tacrolimus blood level <15 ng/mL as well as less 1-year weight gain. After logistic regression, age (relative risk [RR] 1.060, confidence interval [CI] 95%, 1.001-1.122; P = .043) and first tacrolimus blood level (RR 1.154; CI 95%, 1.038-1.283; P = .008) remain significant risk factors for developing PTDM. Older age and initial tacrolimus blood levels were the main risk factors for PTDM among our group of patients. Kidney transplant recipients who develop PTDM maintain a high CDR of tacrolimus.

Erythrocyte anion exchanger activity and intracellular pH in essential hypertension.

The present study was designed to examine the activity of the sodium-independent chloride-bicarbonate anion exchanger and the sodium-proton exchanger in erythrocytes of 30 normotensive and 35 hypertensive subjects and its relation to the previously reported decrease in erythrocyte pH. Erythrocyte cytosolic pH was measured by the pH-sensitive fluorescent probe 2'-7'-bis(2-carboxyethyl)- 5(6)-carboxyfluorescein. The activity of the anion exchanger was determined by acidifying cell pH and measuring the initial rate of the net sodium-independent, 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid-sensitive, bicarbonate influx driven by an outward proton gradient. The activity of the sodium-proton exchanger was determined by acidifying cell pH and measuring the initial rate of the net sodium-dependent proton efflux driven by an outward proton gradient. The activity of the anion exchanger was higher in hypertensive than control individuals (18,863 +/- 1081 vs 15,629 +/- 897 mmol/L cells per hour, P < .05). The activity of the sodium-proton exchanger was higher in hypertensive than control individuals (301 +/- 45 vs 162 +/- 23 mmol/L cells per hour, P < .005). Basal erythrocyte pH was lower in hypertensive than control individuals (7.27 +/- 0.02 vs 7.33 +/- 0.01, mean +/- SEM, P < .05). With the 100% confidence (lower) limit of the normotensive population as a cutoff point, a subgroup of 11 hypertensive patients had an abnormally low erythrocyte pH (< 7.19).(ABSTRACT TRUNCATED AT 250 WORDS)

Association of increased erythrocyte Na+/H+ exchanger with renal Na+ retention in patients with essential hypertension.

The goal of this study was to investigate the activity of the Na+/H+ exchanger in erythrocytes of patients with essential hypertension and its relation with urinary Na+ excretion. The study was performed in cells from 27 untreated hypertensive patients and 30 normotensive controls with similar age and sex distribution. All subjects were studied after 4 days on a controlled Na+ diet (145 mmol/day). The activity of the Na+/H+ exchanger was determined by acidifying cell pH and measuring the initial rate of the net Na(+)-dependent H+ efflux. The activity of the Na+/H+ exchanger was higher in hypertensive patients than in controls (301 +/- 45 v 162 +/- 23 mmol/L cells/h, mean +/- SEM; P < .01). With the upper limit of the normotensive population as a cut-off point (385 mmol/L cells/h), a subgroup of 12 hypertensive patients had an abnormally high activity of Na+/H+ exchanger. Compared with controls and with patients with normal exchanger activity, patients with increased exchanger activity were characterized by lower net (P < .01) and fractional (P < .05) Na+ excretion. The accumulative Na+ balance was higher (P < .01) in hypertensive patients with increased activity of the exchanger (39.90 +/- 3.47 mmol) than in the remaining hypertensive patients (0.59 +/- 6.96 mmol) or in the normotensive population (-5.71 +/- 6.12 mmol). After analyzing the relationship of renin activity with Na+ excretion it was observed that renin activity was inappropriately low in 9 (75%) patients with increased exchanger, in 6 (40%) patients with normal exchanger, and in 6 (20%) normotensives, these differences being significant (P<.01).

Vasoconstriction of the afferent arteriole and defective renal synthesis of nitric oxide in essential hypertension.

This study was designed to investigate whether some relation exists between afferent arteriolar resistance (AAR) and the renal production of nitric oxide (NO) and prostacyclin (PGI2) in 21 patients with untreated essential hypertension and 20 normotensive controls. All subjects were studied in conditions of an unlimited Na+ diet both basally and after a four-hour amino acid infusion. AAR was calculated using Gomez's equations. Renal production of NO and PGI2 were assessed by radioimmunoassay of the urinary excretion of cGMP and 6-keto-PGF1 alpha, respectively. Baseline AAR was higher (P < 0.01) in hypertensives than in normotensives. The baseline urinary excretion of 6-keto-PGF1 alpha and cGMP were similar in the two groups of subjects. AAR diminished (P < 0.005) in normotensives and remained unchanged in hypertensives after amino acid infusion. Urinary excretion of 6-keto-PGF1 alpha was increased similarly in the two groups of subjects after infusion. Urinary excretion of cGMP remained unchanged in normotensives and decreased by 31% in hypertensives after infusion. These findings suggest that afferent vasoconstriction present in hypertensive patients is unresponsive to the vasodilatory manoeuvre of amino acid infusion. This lack of response may be due to a defective renal synthesis of NO in these patients.