Standardizing health outcomes for chronic kidney disease. Adaptation of the international consortium for health outcomes measurement standard set to the Spanish setting.

BACKGROUND AND OBJECTIVES: We aim to adapt the International Consortium for Health Outcomes Measurements standard set for chronic kidney disease (CKD) patients to the Spanish setting and supplement it with those variables agreed upon through initiatives proposed by the Spanish Society of Nephrologists (S.E.N.). MATERIAL AND METHODS: The working group defined a first standard set of variables based on a literature review. The S.E.N. members then assessed the suitability of each variable for inclusion (Consensus≥75%). A second draft of the standard set was generated and evaluated by the Patient advocacy group Federación Nacional de Asociaciones para la Lucha Contra las Enfermedades del Riñón (ALCER). Lastly, the working group established the final standard set of variables (Consensus≥75%). RESULTS: The standard set targets patients with very high-risk CKD (G3a/A3 and G3b/A2-G5) in pre-end-stage kidney disease (pre-ESKD), hemodialysis (HD), peritoneal dialysis (PD), kidney transplantation (KT) or conservative care (CC). The essential follow-up variables agreed for all patients (All) were patient survival, hospitalizations, cardiovascular events, smoking status, health-related quality of life, pain, fatigue, physical function, daily activities, depression, renal function and hemoglobin. Additionally, it was agreed to collect PD survival (in PD patients), peritonitis (PD), infection/bacteremia (PD, HD, KT), vascular access type (HD), vascular access survival (HD), acute rejection (KT), post-transplant cancer (KT), albuminuria (KT) and kidney allograft survival (KT). The optional variables agreed were phosphorus (All), potassium (All), diabetes control (All with diabetes), and albuminuria (pre-ESKD). CONCLUSIONS: This standard set may constitute a highly efficient tool allowing the evaluation of patient outcomes and helping to define strategies to enhance CKD patients' quality of care in the Spanish healthcare system.

Mineral metabolism disorders, vertebral fractures and aortic calcifications in stable kidney transplant recipients: The role of gender (EMITRAL study).

BACKGROUND AND OBJECTIVES: The relationship between mineral metabolism disorders, bone fractures and vascular calcifications in kidney transplant recipients has not been established. METHOD: We performed a cross-sectional study in 727 stable recipients from 28 Spanish transplant clinics. Mineral metabolism parameters, the semi-quantification of vertebral fractures and abdominal aortic calcifications were determined centrally. RESULTS: Vitamin D deficiency (25OHD3<15ng/ml) was more common in female recipients at CKD-T stages I-III (29.6% vs 44.4%; p=0.003). The inverse and significant correlation between 25OHD3 and PTH was gender-specific and women exhibited a steeper slope than men (p=0.01). Vertebral fractures (VFx) with deformity grade ≥2 were observed in 15% of recipients. Factors related to VFx differed by gender; in males, age (OR 1.04; 95% CI 1.01-1.06) and CsA treatment (OR: 3.2; 95% CI: 1.6-6.3); in females, age (OR 1.07; 95% CI: 1.03-1.12) and PTH levels (OR per 100pg/ml increase: 1.27; 95% CI: 1.043-1.542). Abdominal aortic calcifications were common (67.2%) and related to classical risk factors but not to mineral metabolism parameters. CONCLUSIONS: Vitamin D deficiency is more common among female kidney transplant recipients at earlier CKD-T stages, and it contributes to secondary hyperparathyroidism. Prevalent vertebral fractures are only related to high serum PTH levels in female recipients.

Uromodulin and α(1)-antitrypsin urinary peptide analysis to differentiate glomerular kidney diseases.

BACKGROUND/AIMS: Glomerular kidney disease (GKD) is suspected in patients based on proteinuria, but its diagnosis relies primarily on renal biopsy. We used urine peptide profiling as a noninvasive means to link GKD-associated changes to each glomerular entity. METHODS: Urinary peptide profiles of 60 biopsy-proven glomerular patients and 14 controls were analyzed by combining magnetic bead peptide enrichment, MALDI-TOF MS analysis, and ClinProTools v2.0 to select differential peptides. Tentative identification of the differential peptides was carried out by HPLC-MS/MS. RESULTS: The HPLC-MS/MS results suggest that uromodulin (UMOD; m/z: 1682, 1898 and 1913) and α(1)-antitrypsin (A1AT; m/z: 1945, 2392 and 2505) are differentially expressed urinary peptides that distinguish between GKD patients and healthy subjects. Low UMOD and high A1AT peptide abundance was observed in 80-92% of patients with GKD. Proliferative forms of GKD were distinguished from nonproliferative forms, based on a combination of UMOD and A1AT peptides. Nonproliferative forms correlated with higher A1AT peptide levels - focal segmental glomerulosclerosis was linked more closely to high levels of the m/z 1945 peptide than minimal change disease. CONCLUSION: We describe a workflow - urinary peptide profiling coupled with histological findings - that can be used to distinguish GKD accurately and noninvasively, particularly its nonproliferative forms.

Proteomic approach to the study of statin pleiotropy in kidney transplant patients.

BACKGROUND/AIMS: Statins are prescribed in kidney transplant recipients in order to manage dyslipidemia, a common complication in these patients. The efficacy of statins in reducing cholesterol levels has been accompanied by pleiotropic effects. Fifty-four kidney transplant patients were included in the present study, the objective of which was to ascertain the effect of 12 weeks of atorvastatin therapy (10 mg/day) on the patients' lipid profile, renal function, markers of inflammation and plasma peptide profile. METHODS: Biochemical variables were determined with a routine clinical laboratory analyzer, and the proteomic approach was based on magnetic particle-assisted sample processing coupled to mass spectrometry readout. RESULTS: Atorvastatin therapy improved the lipid profile of patients and caused significant changes in their plasma peptide profile; peptides with m/z 1063 and 1898 decreased after treatment and were identified as fragments derived from molecules involved in vascular inflammation, i.e. high-molecular-weight kininogen and complement factor C4, respectively. CONCLUSION: These findings may contribute to the growing body of evidence of the anti-inflammatory actions attributed to statins, by which these drugs could improve these patients' clinical status.

Validation of estimated renal function measurements compared with the isotopic glomerular filtration rate in an HIV-infected cohort.

We performed a cross-sectional study to determine the best method for estimating the glomerular filtration rate (GFR) in HIV-infected subjects. Isotopic GFR was correlated with 24-h urine creatinine clearance, cystatin C levels, and 3 creatinine-based equations-the Modification of Diet in Renal Disease (MDRD), Cockcroft-Gault (CG), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)-in 15 patients. Cystatin C showed the strongest correlation with isotopic GFR (r=-0.760, p=0.001). When cystatin C was used as the reference variable for all 106 patients, CKD-EPI proved to be superior to the other equations (r=-0.671, p<0.001). Time with HIV infection, unsuppressed viral load, low CD4 T-cell counts, and use of protease inhibitors are related to an increased risk of renal impairment, leading us to recommend early initiation of antiretroviral therapy accompanied by a regular renal study.

Pretransplant inflammation: a risk factor for delayed graft function?

BACKGROUND: Inflammation plays an important role in the pathogenesis of ischemic acute kidney injury (IAKI). In this study, we hypothesize that transplant recipients with pretransplant inflammation may have a greater chance of developing delayed graft function (DGF), an example of IAKI. PATIENTS AND METHODS: We analyzed 178 patients who had undergone their first transplant using cadaveric donors. Blood samples were extracted from transplant recipients prior to transplantation. C-reactive protein (CRP) (nephelometry); interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) (automatized enzyme chemiluminescence immunometric assay); and pregnancy-associated plasma protein A (PAPP-A) (enzyme-linked immunosorbent assay) were determined using the pretransplant blood samples. The risk factors analyzed included cold ischemia, type and time of dialysis, donor and recipient age and HLA compatibility. RESULTS: Sixty-one patients (34.3%) developed DGF. Pretransplant TNF-alpha (9.31 +/- 2.57 vs. 10.56 +/- 3.82 pg/mL; p=0.039) and PAPP-A (1.25 +/- 0.74 vs. 1.90 +/- 1.56 mU/L; p=0.002) were significantly elevated in the group of patients with DGF. Univariate analysis showed that PAPP-A, TNF-alpha, cold ischemia, type of dialysis (hemodialysis) and donor age were associated with DGF. Multivariate analysis showed that PAPP-A (p=0.006), cold ischemia (p=0.009) and type of dialysis (p=0.046) were independent risk factors for DGF. CONCLUSIONS: Pretransplant inflammation (TNF-alpha, PAPP-A) in transplant recipients could be a risk factor for the development of DGF.

Oxidative stress, inflammation and cardiovascular mortality in haemodialysis--role of seniority and intravenous ferrotherapy: analysis at 4 years of follow-up.

BACKGROUND: Cardiovascular disease is the principal cause of morbidity and mortality in haemodialysis patients. The classic risk factors do not account for all cases of elevated cardiovascular disease in this patient population and it is becoming increasingly clear that other cardiovascular risk factors are implicated. The objective of this study was to analyse whether or not C-reactive protein (CRP) and plasma copper oxidized anti-lipoprotein (oxLDL) antibody titre are risk factors for cardiovascular mortality during 4 years of follow-up. METHODS: A prospective follow-up study was carried out in 94 stable, chronic haemodialysis patients for 48 months (July 1999-July 2003) (gender: 50 males and 44 females; mean age: 67+/-14 years). Eighty-four per cent of these patients were receiving intravenous erythropoietin and 63% were receiving intravenous ferrotherapy (iron gluconate). Basal markers of inflammation and oxidative stress were determined at the beginning of the study. CRP levels were determined by chemiluminescent enzyme-labelled immunometric assay. The oxLDL antibody titre was measured by enzyme-linked immunosorbent assay using native LDL and oxLDL as antigens. RESULTS: Fifty deaths occurred during the study, 66% (n = 33) of which were due to cardiovascular disease. Patients presented with basal CRP and oxLDL levels indicative of chronic inflammation and elevated oxidative stress [CRP median: 5.16 mg/l (25-75% percentile: 0.35-88.7 mg/l); oxLDL antibodies median: 153 (optical density at 495 nm x 1000) (25-75% percentile: 112-214)]. A positive correlation was found between CRP and age (r = 0.33, P = 0.003). Study of the risk factors demonstrated that age (P = 0.007), oxLDL antibody titre (P = 0.04) and albumin (P = 0.02) were the only predictors of cardiovascular mortality at 4 years of follow-up in this patient population. The Cox proportional hazards model for cardiovascular mortality showed that of the markers studied, oxLDL antibody titre was an independent risk factor for cardiovascular mortality. CONCLUSIONS: Oxidative stress (oxLDL antibody titre) is one of the principal risk factors for cardiovascular mortality in this population of haemodialysis patients. Intravenous ferrotherapy, due to its pro-oxidant properties, probably favours oxidative stress. Serum concentration of CRP was not a good predictive factor of cardiovascular mortality during 4 years of follow-up, possibly because of the slight positive correlation that exists between CRP and age.

Pretransplant pregnancy-associated plasma protein-a as a predictor of chronic allograft nephropathy and posttransplant cardiovascular events.

BACKGROUND: Cardiovascular disease and chronic allograft nephropathy (CAN) are two of the main complications observed in patients after renal transplantation. Both appear to be manifestations of the same process, in which inflammation plays a determinate role. Pregnancy-associated plasma protein A (PAPP-A) has been shown to be a marker of acute coronary syndrome and cardiovascular pathology. The objective of this study was to demonstrate whether or not serum concentration of pretransplant PAPP-A is a marker of CAN and a predictor of posttransplant cardiovascular events. METHODS: In all, 178 renal transplants (65% males; 53+/-12 years of age) followed up over the course of 49.3+/-33.6 months were used in this study. During the follow-up period, 19 patients developed CAN (diagnosed by renal biopsy) and 27 patients had a cardiovascular event. Previous to transplantation, the following were determined: ultrasensitive C-reactive protein (CRP) (nephelometry); interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) (immunofluorimetric automatized method), and ultrasensitive PAPP-A (ELISA). RESULTS: A positive correlation was found between PAPP-A and the inflammatory markers (PAPP-A vs. CRP, r=0.218; P=0.004; PAPP-A vs. IL-6, r=0.235; P<0.001; PAPP-A vs. TNF-alpha, r=0.372; P<0.001). The multiple regression analysis showed PAPP-A (relative risk [RR]: 6.4; 95% confidence interval [CI]:1.24-33.11; P=0.027) and CRP (RR: 6.05; 95% CI:1.21-29.74; P=0.028) to be predictors of posttransplant cardiovascular events and PAPP-A (RR: 4.27; 95% CI: 1.03-17.60; P=0.044) and TNF-alpha (RR: 5.6; 95% CI: 1.43-21.83; P=0.013) to be predictors of CAN. CONCLUSIONS: PAPP-A correlated with the inflammatory markers studied (CRP, IL-6 and TNF-alpha). Pretransplant serum concentration of PAPP-A is a predictor of posttransplant cardiovascular events and CAN.

Is there a need for changes in renal biopsy criteria in proteinuria in type 2 diabetes?

Criteria for renal biopsy in proteinuric type 2 diabetes mellitus (T2DM) patients have been not defined. Usually criteria for renal biopsy in type 1 diabetes mellitus (T1DM) are used (microhaematuria, absence of diabetic retinopathy (DR), uncharacteristic change in renal function or immunological abnormalities). The aim of this study was to reconsider the indications for renal biopsy in T2DM using T1DM criteria, to determine whether they are useful in identifying patients with potentially treatable lesions. We studied 127 proteinuric patients with T2DM. Renal biopsy was performed in 35 who met the criteria for biopsy. Biopsy revealed diabetic glomerulopathy (DG) in 29 (83%) (in three associated with nondiabetic renal disease), immunoglobulin A (IgA) glomerulonephritis in three, focal glomerulosclerosis in one and normal glomeruli in two. DG was diagnosed in 17 (74%) of the patients without DR, in 18 (78%) of the patients with microhaematuria and in 10 (67%) of the patients with microhaematuria and without DR. All patients with DR had DG alone, except three with sudden unexpected changes in renal function. We conclude that DG is the most commonly found renal lesion in T2DM patients with proteinuria biopsied according to T1DM criteria, even in patients with microhaematuria or without retinopathy. Thus, these biopsy criteria are not useful in identifying patients with potentially treatable other renal diseases.