[Monoclonal gammopathy of undetermined significance and evolution to myeloma: Experience in 153 patients]. / Gammapatía monoclonal de significado incierto y evolución a mieloma múltiple: Experiencia en 153 pacientes.

INTRODUCTION: Based on risk factors, the Mayo Clinic Multiple Myeloma Group (MCMMG) established a model of progression from monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma (MM) at 20 years. It is also described that MGUS with a progressive increase of monoclonal protein (M-protein) and/or immunoparesis (IMP) may be more predisposed to progress to myeloma. Our objective was to make a review of MGUS, to see how those who presented IMP and/or progression of their M-protein, contrasting them with MGUS that presented intermediate/high and high risk according to MCMMG. METHODOLOGY AND MATERIALS: A review of the MGUS objectified during the realization of a serum proteinogram (SPEP) was carried out during 2010-2014, in our area. Serum immunoglobulins, serum immunofixation (IFs), and serum free light chain ratio (FLCr) were determined for all MGUS. RESULTS: Of the 153 MGUS that are followed up for 4 years, 6 progress to MM. Of these 6 MM, 5 progress from MGUS with intermediate/high risk taking into account the MCMMG. Of these 5, 3 have IMP or progression of their M-protein. 2 present IMP plus progression of their M-protein. The sixth MM evolves from a MGUS without any risk factor, but with progression of its M-protein plus IMP. CONCLUSIONS: IMP and/or M-protein progression are important risk factors to be taken into account in the MGUS, in the first years after diagnosis, due to their possible evolution to MM.

Vascular access clinic results before and after implementing a multidisciplinary approach adding routine Doppler ultrasound. / Consulta de acceso vascular: resultados antes y después de la instauración de un programa multidisciplinar con realización de ecografía doppler de rutina.

BACKGROUND: A multidisciplinary approach and Doppler ultrasound (DU) assessment for the creation and maintenance of arteriovenous fistulas (AVF) for haemodialysis can improve prevalence and patency. The aim of this study was to analyse the impact of a new multidisciplinary vascular access (VA) clinic with routine DU. MATERIAL AND METHODS: We analysed the VA clinic results from 2014 and 2015, before and after the implementation of a multidisciplinary team protocol (vascular surgeon/nephrologist) with routine DU in preoperative mapping and prevalent AVF. RESULTS: We analysed 345 and 364 patients from 2014 and 2015 respectively. The number of surgical interventions was similar in both periods (p=.289), with a trend towards an increase in preventive surgical repair of AVF in 2015 (17 vs. 29, p=.098). 155 vs. 169 new AVF were performed in 2014 and 2015, with a significantly lower primary failure rate in 2015 (26.4 vs. 15.3%, p=.015), and a non-significant increase in radiocephalic AVF, 25.8 vs. 33.2% (n=40 vs. 56), p=.159. The concordance between the indication at the clinic and the surgery performed also increased (81.3 vs. 93.5%, p=.001). Throughout 2015 fewer complementary imaging test were requested from the clinic (78 vs. 35, p <.001), with a corresponding reduction in costs (€87,716 vs. €59,445). CONCLUSIONS: Multidisciplinary approach with routine DU can improve VA results, with a decrease in primary failure rate, higher likelihood of radiocephalic AVF, better management of dis-functioning AVF and lower radiological test costs.

Is High-Volume Online Hemodiafiltration Associated With Malnutrition?

Chronic malnutrition is a common problem in patients with end-stage renal disease on hemodialysis. Some studies have reported albumin loss into dialysis fluid during postdilution online hemodiafiltration (OL-HDF). The aim of the study was to assess the nutritional status of patients on high-volume OL-HDF and to demonstrate that higher convective clearances are not associated with malnutrition due to possible loss of nutrients with ultrafiltration. Demographic and clinical data, corporal composition with bioimpedance spectroscopy, dialysis features, albumin loss into dialysis fluid and laboratory parameters were collected in twenty-eight patients with ESRD undergoing postdilution OL-HDF with stable convective volumes over 28 L/session. Convective volume (CV) in the last six months was 32.51 ± 3.52 L per session. Cross-sectional analysis of dialysis features showed 32.7 ± 3.34 L of CV and high reduction rates of beta-2-microglobulin (84.2 ± 3.8%) and cystatin-C (81.6 ± 3.47%). Beta-2-microglobulin reduction showed a positive correlation with prealbumin levels (P = 0.048). CV was only correlated with cystatin-C reduction (P = 0.025). Estimated albumin loss into dialysis fluid (1.82 ± 1.05 g/session) was not related to laboratory or bioimpedance nutritional parameters, or to CV. Among patients with higher CV, serum albumin levels maintained more stability during the observational period. High volume OL-HDF results in better convective clearances and is not associated with malnutrition. Albumin and nutrients loss into dialysis fluid should not be a limiting factor of the substitution volume.

Importance of Body Water in the Efficacy of Convective Solute Transport in Online Hemodiafiltration.

High-volume online hemodiafiltration (OL-HDF) has been associated with improved patient survival compared to conventional hemodialysis in recent trials, where the importance of convective volume (CV) in this benefit is noted. The purpose of this study was to determine the corporal composition parameters influencing the efficacy of CV in the removal of different molecular weight (MW) molecules. Demographic data, corporal composition parameters with bioimpedance spectroscopy, dialysis features and the reduction rates of different MW molecules in a four-hour OL-HDF session were collected in 61 patients. We observed a significant negative correlation of ß2-microglobulin, cystatin-C, myoglobin and prolactin reduction rates with body surface area, weight, total body extracellular (ECW) and intracellular water (ICW), lean tissue mass and body cellular mass. The multivariable regression analysis identified ECW and ICW as the only corporal composition factors independently associated to the relative elimination of ß2-microglobulin (Beta: -0.801, P = 0.002 for ECW and Beta: -1.710, P = 0.001 for ICW), cystatin-C (Beta: -0.656, P = 0.010 for ECW and Beta: -1.511, P = 0.004 for ICW) and myoglobin (Beta: -0.745, P = 0.014 for ECW and Beta: -2.103, P = 0.001 for ICW), in addition to CV. Prolactin reduction was only associated with ICW (Beta: -1.540, P = 0.028). When adjusting CV with ECW and ICW, only the ratio CV/ECW was an independent predictor for higher elimination of ß2-microglobulin, cystatin-C and myoglobin. The corporal composition parameters independently associated to the reduction of medium-sized molecules are the extracellular and intracellular water. The ratio "convective volume/extracellular water" predicts higher efficacy of convective transport. Adjusting the convective volume to patient features could be useful to monitor the efficacy of OL-HDF and to prescribe individualized therapies.

Haematuria on the Spanish Registry of Glomerulonephritis.

Recent studies suggest a pathogenic role for glomerular haematuria among renal function. However, there is no data on the prevalence of haematuria from a large renal biopsy registry. We analysed the prevalence of gross (GH) and microscopic (mH) haematuria in 19,895 patients that underwent native renal biopsies from the Spanish Registry of Glomerulonephritis. Haematuria's overall incidence was 63% (GH 8.6% and mH 55.1%), being more frequent in males (64.7% vs. 62.4%). GH was more prevalent in patients <18 years (21.3% vs. 7.7%). The commonest clinical presentation associated with GH was acute kidney injury (31.5%) and IgA Nephropathy (IgAN) (33.6%) was the most frequent histological finding. GH patients showed a significantly (p < 0.05) lower eGFR and proteinuria levels as compared with patients with mH and without haematuria. Moreover, mH was more prevalent in adults (56.3%). Nephrotic syndrome was the commonest clinical presentation in mH patients (32.2%) and IgAN (18.5%) the most frequent histological finding. In conclusion, haematuria, is a frequent urinalysis finding in patients underwent native renal biopsy. The most frequent histological finding in both GH and mH is IgAN. Whereas, GH is more frequent in young males with acute kidney injury, mH is commoner among adults with nephrotic syndrome.

Body composition affects the response to erythropoiesis-stimulating agents in patients with chronic kidney disease in dialysis.

BACKGROUND: The response to erythropoiesis-stimulating agents (ESA) in patients with chronic kidney disease (CKD) is variable. The body mass index (BMI) variations can modify the response to ESA. The objective was to assess the effect of body composition on the response to ESA in dialysis patients. METHODS: This is an observational cross-sectional study. Prevalent hemodialysis and peritoneal dialysis (PD) patients were selected. In the same day, a single blood test, a body composition analysis using bioimpedance spectroscopy and anthropometric measurements were performed. We collected ESA doses. We analyzed erythropoietin resistance index (ERI). The ERI was calculated dividing the weekly weight-adjusted (kg) dose of ESA (IU) by the hemoglobin level (g/dL). RESULTS: The study was comprised of 218 patients (58% men; age 65 (16) years old; 80% hemodialysis, 20% PD). There was an inverse correlation between ERI and BMI (p=0.01), fat tissue index (FTI) (p=0.01) and prealbumin (p=0.04). We found an independent association between higher ERI levels and lower FTI and prealbumin values. CONCLUSION: Response to ESA is influenced by body composition. Fat tissue favors the body's response to ESA.

Erythropoiesis-stimulating agents in anaemia due to chronic kidney disease: a cost-minimization analysis.

BACKGROUND: Some publications have shown that equivalent doses of erythropoiesis-stimulating agents (ESA) defined on label differ from those effective in clinical practice. Therefore, real costs could vary from theoretical costs in the treatment of anaemia in chronic kidney disease (CKD). OBJECTIVES: To perform a cost-minimization analysis to establish the economic impact of the principal ESAs used in treating anaemia secondary to CKD in daily practice. SECONDARY OBJECTIVES: to determine patient-month cost based on the erythropoietin resistance index (ERI); to analyze the difference in cost between pre-dialysis and peritoneal dialysis (PD) patients; and to analyze the association between iron deposits and ESA cost. SETTING: This study was carried out at 2 tertiary hospitals in Spain. METHOD: A multicentre cost-minimization analysis was performed in adult outpatients treated with ESAs for anaemia due to CKD. MAIN OUTCOME MEASURE: The primary outcome was the patient-month cost for each ESA. RESULTS: 409 patients were included. Median patient-month cost was: epoetin (103.2 [63.7, 187.8] euros), darbepoetin α (134.4 [67.2, 216.0] euros) and CERA (147.5 [98.3, 196.7] euros). Median patient-month cost according to ERI was: epoetin (1.60 [0.90, 2.60] euros/kg), darbepoetin α (2.01 [0.95, 3.48] euros/kg) and CERA (1.87 [1.33, 3.00] euros/kg). Median patient-month cost in pre-dialysis was 126.0 (73.7, 201.6) euros and in PD 153.0 (100.2, 275.4) euros. Median patient-month cost for patients with TSI < 20% was 147.5 (98.3, 224.9) euros compared to 100.9 (67.2, 196.7) euros which was the cost for patients with IST ≥ 20%. The median patient-month cost for patients with ferritin < 100 mcg/l was 134.4 (85.0, 201.6) euros compared to 100.8 (68.8, 196.7) euros, which was the cost for patients with ferritin ≥ 100 mcg/l (p = 0.242). CONCLUSION: Doses of CERA used in clinical practice are lower than those recommended on label, which directly influences cost and treatment efficiency. Cost stratification based on iron deposits has shown that patients with low TSI or ferritin require higher doses and consequently an associated higher cost. Thus, to guarantee adequate iron levels is essential in the rational use of ESAs.

Risk factors for renal failure in patients with lupus nephritis: data from the spanish registry of glomerulonephritis.

BACKGROUND: Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus. Data from national registries based on renal biopsies are scarce. The aim of our study was to analyze the demographic characteristics, clinicopathological correlations, and risk factors associated with renal failure in patients with LN at the time of renal biopsy. METHODS: We performed a cross-sectional observational study based on data from the Spanish Registry of Glomerulonephritis for the years 1994-2009. The outcome measure was the presence of renal failure (eGFR <60 ml/min/1.73 m(2)). We also recorded age, gender, proteinuria levels, hypertension, and histological class. RESULTS: We collected 17,525 native renal biopsies, of which 1,648 biopsies showed LN lesions. In total, 609 patients (37%) showed renal failure at the time of renal biopsy. The univariate analysis showed that these patients were older, had higher levels of proteinuria, and a higher prevalence of hypertension than the group with eGFR ≥60 ml/min/ 1.73 m(2). The histological class of LN was recorded for 566 patients, and multivariate logistic regression analysis showed that the independent risk factors for renal failure at the time of renal biopsy were age (OR 1.03; 95% CI 1.01-1.04), male gender (OR 1.94; 95% CI 1.12-3.10), hypertension (OR 3.18; 95% CI 2.16-4.67), proteinuria (OR 1.15; 95% CI 1.08-1.24), and histological classes III and IV (OR 1.82; 95% CI 1.16-2.87). CONCLUSIONS: Data from the Spanish Registry of Glomerulonephritis provide valuable information about risk factors for renal failure in patients with LN at the time of renal biopsy.

Factors related to the absence of anemia in hemodialysis patients.

BACKGROUND: A small number of hemodialysis (HD) patients have normal hemoglobin (Hb) levels without the need for erythropoiesis-stimulating agents (ESAs). The factors associated with this condition have been little studied. The objective of this prospective study was to determine these factors in a prevalent population of HD patients. MATERIALS AND METHODS: All patients who had normal Hb levels and who had not received ESAs in the last 6 months (non-ESA group) were included. Epidemiological and laboratory data were collected and we performed an abdominal ultrasound to assess hepatic and renal cysts. This group was compared to a control group of 205 prevalent HD patients on ESA therapy (control group). RESULTS: We included 45 patients (16% from the whole group) in the non-ESA group. In this group, there was a higher proportion of men (76.5 vs. 61%), patients were younger (61.1 ± 14.7 vs. 67.5 ± 15.2 years), had a longer duration of renal replacement therapy (RRT) (9.4 ± 8.3 vs. 5.3 ± 5.8 years) and had a higher prevalence of adult polycystic kidney disease (APKD) and hepatitis C virus (HCV) liver disease (42.2 vs. 10.2%), p < 0.01. In the non-ESA group, HCV+ patients had a lower prevalence of APKD (2.2 vs. 38.4%) and hepatic cysts (2.2 vs. 19.2%), but significantly higher endogenous erythropoietin levels (55.8 ± 37.1 vs. 30.9 ± 38.4 mU/ml). No significant differences in anemia, iron metabolism, insulin, IGF-1 and renin were found between non-ESA and control groups. Non-ESA patients had a significantly higher number of renal (90.6 vs. 36.5%) and hepatic cysts (12.5 vs. 3.4%), and these were also larger in size (3.3 ± 2.4 vs. 1.5 ± 0.8 cm). In the multivariate Cox analysis, independent predictor factors for absence of anemia in HD patients were number of renal cysts >10 cysts (95% CI 1.058-1.405; p = 0.00), HCV+ liver disease (95% CI 1.147-1.511; p = 0.05) and time on RRT (95% CI 1.002-1.121; p = 0.05). CONCLUSIONS: The absence of anemia in HD patients is not infrequent. Its frequency is higher in men and younger patients with long-term RRT, in patients with HCV+ liver disease and in APKD. It is associated with increased endogenous erythropoietin production and the presence of renal and hepatic cysts.

Anemia management and treatment response in patients on hemodialysis: the MAR study.

BACKGROUND: Anemia management guidelines describe the importance of anemia as a risk factor in hemodialysis and the need for clinical prospective studies focused on this role of anemia. Response to treatment with iron and epoetin is multifactorial, and results are still far from the targets set by the guidelines. The Morbidity and Mortality Anemia Renal study (MAR) is a multicenter prospective cohort study of hemodialysis (HD), designed to assess the burden of anemia on morbidity and mortality. We report here a cross-sectional analysis of the management of anemia, and response-to-treatment factors. METHODS: A total of 1,710 patients were included (60% male, mean age 64.4 +/- 13.6 years, mean 16.2 +/- 11.1 months on HD) with a high comorbidity (hypertension 75.8%, diabetes 25.9%, heart failure 13.9% and coronary disease 16.7%) and a mean Charlson Index of 6.5 +/- 2.3. RESULTS: There were 28.7% of patients who had started epoetin before end-stage renal disease (pre-ESRD), 81.4% of patients displayed Hb <11 g/dL when initiating HD with a mean Hb of 9.7 g/dL. Only 67.9% of prevalent HD patients attained a hemoglobin (Hb) level above 11 g/dL, 89.5% achieved a ferritin level above 100 ng/mL, 76.7% a transferrin saturation index (TSI) above 20%, and 61.1% met all 3 objectives. The multivariate analysis identified the following risk factors for Hb <11g/dL: low albumin (odds ratio, OR = 1.75), HD efficacy below objectives (OR = 1.44) and female sex (OR = 1.36), corrected for comorbidity, epoetin treatment, transfusion, surgery or hospital admission. CONCLUSIONS: As compared with previous surveys, we found an improved but still inadequate anemia management in Spanish HD patients. Our results are comparable with those of Euro-DOPPS. Several modifiable factors related to a lower Hb concentration were assessed. On behalf of the MAR Study Group.

Clinicopathologic correlations of renal pathology in Spain.

BACKGROUND: There are not enough large epidemiologic population-based studies of biopsy-proven nephropathies with detailed clinicopathologic correlations. METHODS: The Glomerulonephritis Registry of the Spanish Society of Nephrology has obtained data from 9378 cases with native biopsy-proven renal diseases and well-known clinical syndrome between 1994 and 2001, investigating clinicopathologic correlations. Patients were divided in three groups according to age: children (<15 years old), adults (15 to 65 years), and elderly (>65 years). RESULTS: The most common clinical syndrome at any age is nephrotic syndrome (35.5%), followed by asymptomatic urinary abnormalities (25.9%), acute renal failure (12.9%), chronic renal failure (12.1%), nephritic syndrome (4.5%), macroscopic haematuria (4.5%), and arterial hypertension (3.0%). A male predominance is observed at any age (3:2). The frequencies of histologic findings are statistically different in all syndromes according to age. Minimal change disease is the most frequent finding in children with nephrotic syndrome (39.5%), whereas in adults and elderly, membranous nephropathy is the most prevalent (24.2% and 28.0%, respectively). Ig A nephropathy (IgAN) is the most frequent glomerulonephritis in patients with asymptomatic urinary abnormalities at any age. Acute renal failure is an important cause for performing a kidney biopsy in elderly and vasculitis is the main histologic finding. The clinical manifestations of focal segmental glomerulosclerosis, non-IgA mesangial nephropathy, lupus nephritis, vasculitis, and nephroangiosclerosis are statistically different according to age. CONCLUSION: The findings of clinicopathologic correlations obtained from the Spanish Registry of Glomerulonephritis on native biopsy-proven renal diseases add valuable information to previous reports and it can be the initial step for follow-up and prospective studies.

Frequency of renal pathology in Spain 1994-1999.

BACKGROUND: There are not enough large epidemiological population-based studies of biopsy-proven nephropathies with detailed clinical and histopathological data. METHODS: The Glomerulonephritis Registry of the Spanish Society of Nephrology has obtained data from 7016 patients with biopsied renal diseases between 1994 and 1999, investigating prevalence, incidence and clinical and histopathological data. Biopsies of transplant kidneys have not been considered. RESULTS: The observed biopsy rate for all ages is 4.8 per 100 000 inhabitants. A male predominance is seen for all age groups. The most common clinical syndrome at any age is nephrotic syndrome. The prevalence of hypertension is higher in adults and elderly patients. The most common pathologies are IgA nephropathy, focal glomerulosclerosis, membranous nephropathy and lupus nephritis. The mean annual incidence (per million of population) of the most common nephropathies is IgA nephropathy 7.9, focal segmental glomerulosclerosis 6.4, membranous nephropathy 6.2, lupus nephritis 5.6, minimal-change disease 4.8, nephroangiosclerosis 4.6, vasculitis 4.3, membranoproliferative glomerulonephritis 3.6 and amyloidosis 3.3. In children, the most frequent causes are minimal-change disease, IgA nephropathy and focal glomerulosclerosis. In adults, the most common diagnoses are IgA nephropathy, lupus nephritis, and focal glomerulosclerosis. In elderly patients, the most frequently reported pathologies are vasculitis, membranous nephropathy and amyloidosis. Membranous nephropathy has increased in incidence in recent years. CONCLUSIONS: We provide representative population-based descriptive data on native biopsy-proven renal diseases in Spain.