A.L.M. de Francisco

Assessment of glomerular filtration rate in transplant recipients with severe renal insufficiency by Nankivell, Modification of Diet in Renal Disease (MDRD), and Cockroft-Gault equations

Measurement of glomerular filtration rate (GFR) is time consuming and cumbersome. Several formulas have been developed to predict creatinine clearance (CrCl) or GFR using serum creatinine (Cr) concentrations and demographic characteristics. However, few studies have been performed to discern the best formula to estimate GFR in kidney transplantation. In this study, Cockroft-Gault (CG), Nankivell, and Levey (MDRD) formulas were tested to predict GFR in 125 cadaveric renal transplant patients with severe renal insufficiency (GFR less than 30 mL/min per 1.73 m2). The GFR was estimated as the average Cr and urea clearances. The mean GFR estimated by averaged Cr and urea clearances (22.18+/-5.23 mL/min per 1.73 m2) was significantly different from the mean values yielded by the MDRD formula (20.42+/-6.65 mL/min per 1.73 m2, P=.000), the Nankivell formula (30.14+/-11.98 mL/min per 1.73 m2, P=.000), and the CG formula (29.42+/-8.64 mL/min per 1.73 m2, P=.000). The MDRD formula showed a better correlation (R=0.741, P=.000) than the CG (R=0.698, P=.000) and the Nankivell formulas (R=0.685, P=.000). Analysis of differences using the Bland-Altmann method demonstrated that MDRD gave the lowest bias (MDRD: -1.65+/-4.4 mL/min per 1.73 m2; CG: 7.33+/-6.24 mL/min per 1.73 m2; Nankivell: 8.05+/-9.23 mL/min per 1.73 m2) and narrower limits of agreement (Nankivell: -10.41-26.51 mL/min per 1.73 m2; CG: -5.15-19.81 mL/min per 1.73 m2; MDRD: -10.61-7.31 mL/min per 1.73 m2). In transplant patients with severe renal insufficiency, the MDRD equation seems better than the other formulas to estimate GFR.

Posttransplant diabetes is a cardiovascular risk factor in renal transplant patients

POSTTRANSPLANT DIABETES mellitus (PTDM) is a serious complication that is grossly under recognized. Prior to the advent of cyclosporine, immunosuppression with high doses of steroids caused PTDM in up to 40% of patients. With modern regimens, the incidence of PTDM has been shown to decrease. Depending on the criteria used to define PTDM and the immunosuppressive treatment regimen, the reported incidence varies from 3% to 20%. The relationship between glycemic control and microvascular and macrovascular complications of diabetes is well established. The aim of this study is to analyze the clinical impact of PTDM on the development of posttransplant cardiovascular disease (CVD).

ANCA-associated pauci-immune crescentic glomerulonephritis complicating Sjögren's syndrome

Although ocular and oral dryness are the hallmarks of Sjogrens syndrome (SS), SS patients can develop a variety of complications, affecting organs such as the liver, kidneys, lungs, muscles, and nervous system [1]. Renal involvement has been described in 25-30% of patients with SS, usually as a tubulointerstitial nephritis. However, glomerulonephritis (GN) is rare in primary SS and fewer than 25 cases have been reported. Most patients had membranous or membranoproliferative GN [2-7]. We report a patient with primary SS who developed a crescentic glomerulonephritis (CGN) associated with perinuclear antineutrophil cytoplasmic autoantibodies (ANCA). To our knowledge, this association has not been previously described in the literature.

Fewer dose changes with once-monthly C.E.R.A. in patients with chronic kidney disease

BACKGROUND Frequent dosing and requirements for dose adjustments of erythropoiesis-stimulating agents (ESAs) create significant burdens for healthcare providers and have been associated with hemoglobin (Hb) cycling, hampering maintenance of target Hb levels. We compared the frequency of dose changes in dialysis patients who received methoxy polyethylene glycolepoetin beta; (a continuous erythropoietin receptor activator (C.E.R.A.)) or a shorter-acting ESA. METHODS Data were analyzed from three Phase III maintenance trials, using almost identical protocols, in dialysis patients treated with C.E.R.A. every 2 weeks (q2w) or every 4 weeks (q4w) or a comparator ESA (epoetin or darbepoetin alpha; at their previous dose/administration interval). Dosage was adjusted to maintain Hb ± 1 g/dl of baseline and 10 - 13.5 g/dl during titration (28 weeks) and evaluation (8 weeks), and 11 - 13 g/dl during follow-up (16 weeks). RESULTS Data were analyzed from 564 patients treated with C.E.R.A. q2w, 410 with C.E.R.A. q4w and 572 with comparator ESA at their usual dosing interval. Significantly fewer dose changes were needed in patients receiving C.E.R.A. q2w (p < 0.05) or C.E.R.A. q4w (p < 0.001) than in patients treated with comparator ESAs. CONCLUSION This retrospective analysis suggests that C.E.R.A. q4w maintains Hb levels in dialysis patients and requires fewer dose changes compared with other ESAs.

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.

Dialysis Membranes and PTH Changes during Hemodialysis in Patients with Secondary Hyperparathyroidism

Changes in parathyroid hormone (PTH) during hemodialysis have been explained by the influence of ionized calcium changes on PTH secretion. In this study we have investigated the influence of dialysis membranes of different permeability on PTH changes during hemodialysis. Five chronic renal failure patients underwent three consecutive hemodialysis sessions with cuprophane (CUP) polysulfone (PS) and polyacrylonitrile (PAN). Two hours of isolated ultrafiltration were followed by 3 h dialysis. A significant decrease in carboxy terminal PTH (COOH PTH) was observed with PAN (p < 0.05) but not with CUP or PS. Intact PTH decreased (p < 0.001) with all three membranes, following a significant increase in ionized calcium (p < 0.001). Sieving coefficients for COOH PTH were significantly lower with CUP than with PS (p < 0.05) or PAN (p < 0.001). Intact PTH sieving coefficients were near zero for all three membranes. COOH PTH and intact PTH clearance rates were significantly higher with PAN (p < 0.001) than with PS or CUP, either in isolated ultrafiltration or with dialysis fluid. Thus PTH changes during hemodialysis do not only depend on the increase in calcium but also on the nature of the dialysis membrane. Adsorption of PTH to the PAN membrane surface explain the high PTH clearance rates achieved with this filter.

New-onset Diabetes After Transplantation: Drug-Related Risk Factors

INTRODUCTION New-onset diabetes after transplantation (NODAT), an important complication of renal transplantation leads to reduced graft function and increased patient morbidity and mortality. Because of its high incidence and immense impact on clinical outcomes, prevention of NODAT is highly desirable. Several modifiable and nonmodifiable risk factors for NODAT have been described. The aim of this study was to analyze the influence of various drugs on the development of NODAT during the first year. METHODS A retrospective analysis was performed on 303 adult kidney transplant recipients free of previously known diabetes. NODAT was defined as a fasting plasma glucose level ≥ 126 mg/dL confirmed by repeat testing on a different day. We excluded patients with transiently elevated fasting plasma glucose during the first 3 months. RESULTS NODAT was diagnosed in 37 recipients (12.2%). Univariate analysis identified several variables related to NODAT: recipient age (P < .001), body mass index (P < .001), donor age (P = .005), family history of diabetes (P < .001), statin use (P = .005), diuretic use (P = .040) and tacrolimus therapy (P = .029). After multivariate analysis, recipient age (relative risk [RR] = 1.060, 95% confidence interval [CI] 1.019- 1.102, P = .004), family history of diabetes (RR = 3.562, 95% CI 1.574-8.058, P = .002), smoking habit (RR 2.514, 95% CI 1.118-5.655, P = .026) and diuretic use (RR = 2.496, 95% CI 1.087-5.733, P = .031) were independently associated with NODAT development. CONCLUSIONS In our population of kidney transplant recipients, the main nonmodifiable risk factors for NODAT were recipient age and a family history of diabetes. Diuretic use was a modifiable risk factor associated with the development of NODAT. To reduce NODAT incidence, it is necessary to consider not only immunosuppressive therapy, but also concomitant drugs such as diuretics.

Nuevos anticoagulantes orales en pacientes con enfermedad renal crónica

Patients with chronic kidney disease (CKD) develop bleeding and thrombotic tendencies, so the indication of anticoagulation at the onset of atrial fibrillation (AF) is complex. AF is the most common chronic cardiac arrhythmia, and thromboembolism and ischemic stroke in particular are major complications. In recent years, new oral anticoagulant drugs have been developed, and they have shown superiority over the classical AVK in preventing stroke, systemic embolism and bleeding risk, constituting an effective alternative to those resources.

Pulse pressure is an independent risk factor of cardiovascular disease in renal transplant patients

Elevated pulse pressure in the general population has been shown to be associated with cardiovascular disease, which is the main cause of death in renal transplant patients. We investigated the effects that a wide pulse pressure has on cardiovascular disease after renal transplantation in a cohort of 532 transplant patients with functioning grafts for more than one year. Patients were classified into two groups depending on whether the one-year pulse pressure was less than or greater than 65 mm Hg. We analyzed patient survival, posttransplant cardiovascular disease and principle causes of death. Five- and ten-year patient survival were lower among the group with higher pulse pressures. The main cause of death was vascular disease in both groups. The presence of posttransplant cardiovascular disease was higher among the group with higher pulse pressures (RR=1.73). In addition, the incidence of an elevated pulse pressure was directly associated with recipient age and posttransplant diabetes mellitus. In conclusion, pulse pressure represents an independent risk factor for increased cardiovascular morbidity and mortality in renal transplant patients.

Effect of early graft function on patient survival in renal transplantation

The influence of early graft function on long-term graft survival has been widely reported but its association with patient survival has received less attention. We investigated the effect of early renal function on patient survival and on cardiovascular disease after renal transplantation among 532 transplant patients who had grafts functioning for >1 year. Patients were classified into two groups, depending on the early creatinine clearance (< or >60 mL/min). We analyzed graft and patient survival, posttransplant cardiovascular disease, and the principal causes of death. Five- and 10-year graft and patient survival were lower among the group with worse early renal function. The main cause of death was vascular disease. Poorer early renal function increased the risk (RR) of patient death by 2.2-fold, and also the presence of posttransplant cardiovascular disease. In conclusion, patients with poor levels of early graft function are at an increased risk of death. These high-risk groups should be targeted for interventional studies to improve patient survival.