The role of copeptin in kidney disease.

Copeptin is a 39-amino acid glycopeptide that is secreted equimolecularly with arginine-vasopressin (AVP) from the prepro-hormone AVP in the posterior pituitary. While AVP is a very unstable molecule and is accompanied by significant technical troubles in its quantification, copeptin is a stable and easily quantifiable molecule. For this reason, circulating copeptin is currently used as a surrogate for AVP in different pathological conditions, including renal diseases. In recent years it has been shown that copeptin is associated with an increased risk of developing chronic kidney disease in the general population. In addition, copeptin has also been associated with multiple renal diseases with relevant clinical consequences and potential therapeutic implications. In the present review, we update and summarize the clinical significance of copeptin as a surrogate marker for AVP concentrations in different kidney diseases, as well as in renal replacement therapy (hemodialysis and peritoneal dialysis) and renal transplantation.

Effect of Immunosuppressive Treatments on Kidney Outcomes After Gross Hematuria-Related Acute Kidney Injury in Older Patients With IgA Nephropathy.

Introduction: Macroscopic hematuria (MH) bouts, frequently accompanied by acute kidney injury (AKI-MH) are one of the most common presentations of IgA nephropathy (IgAN) in the elderly. Immunosuppressive therapies are used in clinical practice; however, no studies have analyzed their efficacy on kidney outcomes. Methods: This is a retrospective, multicenter study of a cohort of patients aged ≥50 years with biopsy-proven IgAN presenting with AKI-MH. Outcomes were complete, partial, or no recovery of kidney function at 1 year after AKI-MH, and kidney survival at 1, 2, and 5 years. Propensity score matching (PSM) analysis was applied to balance baseline differences between patients treated with immunosuppression and those not treated with immunosuppression. Results: The study group consisted of 91 patients with a mean age of 65 ± 15 years, with a mean follow-up of 59 ± 36 months. Intratubular red blood cell (RBC) casts and acute tubular necrosis were found in all kidney biopsies. The frequency of endocapillary hypercellularity and crescents were low. Immunosuppressive therapies (corticosteroids alone or combined with mycophenolate mofetil or cyclophosphamide) were prescribed in 52 (57%) patients, whereas 39 (43%) received conservative treatment. There were no significant differences in the proportion of patients with complete, partial, or no recovery of kidney function at 1 year between patients treated with immunosuppression and those not treated with immunosuppression (29% vs. 36%, 30.8% vs. 20.5% and 40.4 % vs. 43.6%, respectively). Kidney survival at 1, 3, and 5 years was similar among treated and untreated patients (85% vs. 81%, 77% vs. 76% and 72% vs. 66%, respectively). Despite the PSM analysis, no significant differences were observed in kidney survival between the two groups. Fourteen patients (27%) treated with immunosuppression had serious adverse events. Conclusions: Immunosuppressive treatments do not modify the unfavorable prognosis of patients with IgAN who are aged ≥50 years presenting with AKI-MH, and are frequently associated with severe complications.

Acute responses of gastrointestinal hormones to both oral and parenteral intradialytic nutrition.

INTRODUCTION: Intradialytic nutrition (IDN) has been used to improve the nutritional status of malnourished hemodialysis (HD) patients. OBJECTIVE: To evaluate the different effects of parenteral IDN (IDPN) and oral IDN (IDON) on nutrition-related gastrointestinal hormones. PATIENTS AND METHODS: Seven clinically stable HD patients with malnutrition were included. All patients were treated for 1 month with either IDPN or IDON, with a 4-week period of no nutritional support between each type of therapy. On the first day of each nutritional support (IDON or IDPN) we analyzed the acute responses of insulin, ghrelin, and glucagon-like peptide 1 (GLP-1). We compared the areas under the secretory curves (AUC) and the maximum peaks of serum glucose, insulin, ghrelin, and GLP-1. A group of 6 clinically stable HD patients without any type of IDN served as the control group. RESULTS: The acute responses of glucose and insulin to IDN were significantly higher with IDPN than with IDON. The AUC of glucose (602 ± 81 vs. 495 ± 81 mg/dl/h, p < 0.01) and insulin (232 ± 103 vs. 73.8 ± 69 µU/ml/h, p < 0.01) as well as the maximum peaks of glucose (228 ± 41 vs. 177 ± 47 mg/dl, p < 0.05) and insulin (104 ± 46 vs. 29 ± 24 µU/ml, p < 0.01) were significantly higher after IDPN than after IDON. Ghrelin decreased after both IDPN and IDON; however, the decrease was significantly higher with IDPN compared to IDON. The ghrelin nadir was significantly lower in IDPN than in IDON (0.77 ± 0.5 vs. 1.5 ± 0.3, p < 0.05) although the AUC of ghrelin was not significantly different. GLP-1 was significantly increased at 1 h after starting both IDPN and IDON with no significant differences between the groups. CONCLUSION: IDPN induces a higher increase in serum glucose and insulin levels and a greater reduction in serum ghrelin concentrations compared with an equivalent orally administered nutritional supplement.

[Renal biopsy in patients aged 65 years or older: are there differences in the indication and histopathology compared to other patients?]. / La biopsia renal en pacientes de 65 o más años: ¿existen diferencias en la indicación y en la histopatología respecto al resto de pacientes?

BACKGROUND: Renal biopsy (RB) represents the gold standard for diagnosis of kidney diseases. In this paper we analyse whether the indication of RB and histopathology in patients 65 years or older is different from the other patients. MATERIAL AND METHODS: Retrospective study of 93 native renal biopsies performed in the General Hospital of Segovia in the period 2004-2008. The RB was performed percutaneously under ultrasound guidance in real time, using a 16G automatic needle. RESULTS: Mean age of biopsied patients was 56.89 ± 19 (range 14-89) , and 57% were males. A total of 39RB were performed on people aged 65 years or older. Overall, nephrotic syndrome (NS) is the most common indication of RB, and IgA glomerulonephritis the most common histology. In people ≥ 65 years, acute renal failure (ARF) is the most common indication for RB, and rapidly progressing (crescentic) glomerulonephritis/vasculitis the most detected the diagnosis. When taking age into account, no significant differences in the number of glomeruli obtained by RB or in the number of RB performed on the same patient. CONCLUSIONS: In people 65 years or older, ARF is the main indication of RB and crescentic glomerulonephritis/vasculitis the most frequent diagnosis.

[Estimation of glomerular filtration rate in persons aged 69 years or older: agreement between distinct calculation methods]. / Estimación del filtrado glomerular en personas de 69 años o más: concordancia entre diferentes métodos de cálculo.

MATERIAL: Estimation of glomerular filtration rate (eGFR) is the most widely accepted marker of renal function. Precise calculation is not routinely performed in clinical practice. Several methods have been developed for eGFR: creatinine clearance (CCr) calculation or the use of formulae derived from serum creatinine (sCr). The present study aimed to analyze the agreement between distinct methods of calculating eGFR. MATERIAL AND METHODS: We performed a cross-sectional study between January and April, 2006 in 32 stable elders, aged 69 years or older, evaluated in a general nephrology unit. eGFR was calculated by CCr (considered the gold standard), Cockcroft-Gault (CG) and Modification of Renal Diet in Disease (MDRD) equations. The Mann Whitney U-test, Spearman's correlation coefficient and the Kappa coefficient were used to compare means and determine the concordance between methods. RESULTS: The overall means+/-SD of GFRe for CCr were 36.14+/-16 ml/min (range 11.75-69.6); CG: 37.02+/-16 ml/min (range 13.3-72.3) and MDRD: 45.52+/-16 ml/min (range 19.2-75.36). Variations in eGFR on comparison of methods were CCr and MDRD: -9.37 ml/min (95% CI:-13.85, -4.9); CCr and CG:-2.54 ml/min (95% CI: -6.95, 1.80); MDRD and CG: 9.0 ml/min (95% CI: 5.96, 12). The correlation between the gold standard (CCr) and sCr-derived formulae was r=0.74 for MDRD (P<0.001) and r=0.77 for CG (P<0.001). The Kappa value for CCr and CG was 0.44 and was 0.35 for CCr and MDRD. When patients were classified by stage of chronic renal disease, discrepancies were found according to the method used: stage 5 (eGFR<15 ml/min) was diagnosed in 13.63% with CG while none were diagnosed with stage 5 with MDRD. CONCLUSIONS: In the estimation of the renal function in the elderly, eGFRe levels can differ in the same patient according to the method used: in view of the degree of concordance between CG and CCr, this mathematical formula should be used in preference to MDRD.

[Laboratory manifestations associated with chronic renal failure: what degree of estimated glomerular filtration can be used for its detection in the elderly?]. / Las manifestaciones analíticas asociadas a la insuficiencia renal crónica: ¿a partir de qué grado de filtrado glomerular estimado las detectamos en ancianos?

OBJECTIVE: A classification of chronic kidney disease (CKD) based on stages of glomerular filtration (GF) has recently been developed. Thus, chronic renal failure (CRF) is based on GF <60 ml/min. Our goal was to study the presence of typical manifestations of CRF in elderly individuals with a GF of <60 ml/min (stage 3-5) and to determine the cut-off value at which GF can be used to detect these manifestations. MATERIAL AND METHODS: We performed a cross-sectional study in clinically-stable elderly patients attending the geriatrics and nephrology outpatient department. The estimated GF (GFe) was established with the Cockroft-Gault and abbreviated Modification of Diet in Renal Disease Study (MDRD) formulae. Because these patients had a GF of less than 60 ml/min, they were expected to show the manifestations associated with CRF (anaemia, metabolic acidosis, abnormal bone and mineral metabolism). We evaluated the occurrence of these manifestations and the GF cut-off at which they were detected. To do this, the population was divided into two groups: group A: patients with GFe > or = 30 ml/min (stage 3, N=48); and group B: patients with GFe <30 ml/min (stages 4-5, N=8). RESULTS: Seventy percent of the patients had a GFe (MDRD) <60 ml/min (stage 3-5). Despite reduced GF, these patients did not show the typical manifestations of CRF. Group B showed higher plasmatic levels of creatinine, urea, uric acid, and potassium and required treatment with erythropoietin and calcium salts. CONCLUSIONS: Many elderly people diagnosed with CKD with the current classification do not show manifestations of CRF. Estimation of the GF in elders should be generalized to correctly adjust medication to renal impairment rather than to classify elders into CKD stage.

IgA Nephropathy in Elderly Patients.

BACKGROUND AND OBJECTIVES: Some studies suggest that the incidence of IgA nephropathy is increasing in older adults, but there is a lack of information about the epidemiology and behavior of the disease in that age group. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this retrospective multicentric study, we analyzed the incidence, forms of presentation, clinical and histologic characteristics, treatments received, and outcomes in a cohort of 151 patients ≥65 years old with biopsy-proven IgA nephropathy diagnosed between 1990 and 2015. The main outcome was a composite end point of kidney replacement therapy or death before kidney replacement therapy. RESULTS: We found a significant increase in the diagnosis of IgA nephropathy over time from six patients in 1990-1995 to 62 in 2011-2015 (P value for trend =0.03). After asymptomatic urinary abnormalities (84 patients; 55%), AKI was the most common form of presentation (61 patients; 40%). Within the latter, 53 (86%) patients presented with hematuria-related AKI (gross hematuria and tubular necrosis associated with erythrocyte casts as the most important lesions in kidney biopsy), and eight patients presented with crescentic IgA nephropathy. Six (4%) patients presented with nephrotic syndrome. Among hematuria-related AKI, 18 (34%) patients were receiving oral anticoagulants, and this proportion rose to 42% among the 34 patients older than 72 years old who presented with hematuria-related AKI. For the whole cohort, survival rates without the composite end point were 74%, 48%, and 26% at 1, 2, and 5 years, respectively. Age, serum creatinine at presentation, and the degree of interstitial fibrosis in kidney biopsy were risk factors significantly associated with the outcome, whereas treatment with renin-angiotensin-aldosterone blockers was associated with a lower risk. Immunosuppressive treatments were not significantly associated with the outcome. CONCLUSIONS: The diagnosis of IgA nephropathy among older adults in Spain has progressively increased in recent years, and anticoagulant therapy may be partially responsible for this trend. Prognosis was poor. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2019_07_16_CJASNPodcast_19_08_.mp3.

Nephrotic syndrome resulting from focal segmental glomerulosclerosis in a peripheral blood stem cell transplant patient.

We describe the case of a male patient who was diagnosed with acute monoblastic leukemia and received a peripheral stem cell transplantation (PSCT) with peripheral blood hematopoietic progenitors. Because he was in clinical remission with no evidence of chronic graft-versus-host disease (GVHD), immunosuppression was withdrawn, and he developed nephrotic syndrome (NS) months later. A kidney biopsy showed focal segmental glomerulosclerosis (FSGS) as part of the GVHD. Soon after the reintroduction of previous immunosuppressive therapy, we observed a complete remission of the NS.

Serum potassium concentrations: Importance of normokalaemia. / Concentraciones séricas de potasio: importancia de la normopotasemia.

Abnormalities in potassium concentrations are associated with morbidity and mortality. In recent years it has been considered that small variations in serum potassium concentrations within normal intervals may also be associated with mortality. Strategies for achieving normokalaemia include dietary measures, limiting the use of potassium retaining drugs, and use of conventional cation exchange resins (calcium/sodium polystyrene sulfonate) and/or the new non-absorbed cation exchange polymer (patiromer).

[New tools for the management of renal function in the elderly: Berlin Initiative Study equation and hematocrit, urea and gender formulae]. / Nuevas herramientas para abordar la función renal en ancianos: la ecuación Berlin Initiative Study y la fórmula hematocrito, urea y género.

In the last few years a debate has emerged on the range of normal renal function in the elderly, and if every elderly person with a glomerular filtration rate estimated using formulas (Cockroft-Gault, MDRD, CKD-EPI) of less than 60ml/min/1.73m(2) has kidney disease. In this review we analysed, based on the results of the study Elderly people with chronic kidney disease of the Hospital de Segovia, the new equations to measure kidney function in the elderly: the Berlin Initiative Study equation designed to estimate the glomerular filtration rate in people aged 70 or more, and the hematocrit, urea and gender formula to establish whether an elderly person with a glomerular filtration rate lower than 60mL/min/1.73m(2) has kidney disease.

How should we analyze and present mortality in our patients?: A multicentre GCDP experience.

INTRODUCTION: There are different strategies to analyse mortality in peritoneal dialysis (PD) with different definitions for case, event, time at risk, and statistical tests. A common method for the different registries would enable proper comparison to better understand the actual differences in mortality of our patients. METHODS: We review and describe the analysis strategies of regional, national and international registries. We include actuarial survival, Kaplan-Meier (KM) and competitive risk (CR) analyses. We apply different approaches to the same database (GCDP), which show apparent differences with each method. RESULTS: A total of 1,890 incident patients in PD from 2003-2013 were included (55 years; men 64.2%), with initial RRF of 7ml/min; 25% had diabetes and a Charlson index of 3 [2-4]; 261 patients died, 380 changed to haemodialysis (HD) and 682 received a transplant. Annual mortality rates varied up to 20% in relative numbers (6.4 vs. 5.2%) depending on the system applied. The estimated probability of mortality measured by CR progressively differs from the KM over the years: 3.6 vs. 4.0% the first year, then 9.0 vs. 11.9%, 15.6 vs. 28.3%, and 18.5 vs. 43.3% the following years. CONCLUSIONS: Although each method may be correct in themselves and express different approaches, the final impression left on the reader is a number that under/overestimates mortality. The CR model better expresses the reality of PD, where the number of patients lost to follow-up (transplant, transfer to HD) it is 4 times more than deceased patients and only a quarter remain on PD at the end of follow up.

Inflammation and malnutrition as predictors of mortality in patients on hemodialysis.

BACKGROUND: Low albumin and high C-reactive protein (CRP) are significant predictors of mortality in hemodialysis (HD) patients. Although, classically, hypoalbuminemia has been attributed to malnutrition, inflammation can also predict the serum albumin concentration in dialysis patients. OBJECTIVE: To establish the influence of nutritional status and inflammation on mortality in HD patients. METHODS: A cross-sectional study was conducted in 64 patients (35 males; 9 diabetics; mean age 64 +/- 12 years), who had been on HD for 64 +/- 58 months. Nutritional status was assessed from estimated protein caloric intake, dietary recall, anthropometric and biochemical parameters, and serum levels of insulin-like growth factor-1 (IGF-1). CRP was used as a marker of inflammation. Comorbidity was measured using a modified M. Charlson index. The dialysis doses (Kt/V) and protein catabolic rate (PCR) were measured and standardized for actual and ideal body weight. The incidence and causes of death were recorded during the two-year follow-up. RESULTS: During the follow-up period, 18 patients died and 11 were withdrawn from the study after receiving a renal transplant. In multivariante analysis (Cox proportional hazards model), total comorbidity and the levels of CRP and hematocrit (increased) and IGF-1 (decreased) were independent predictors of mortality. CONCLUSIONS: Inflammation, as measured by CRP, and malnutrition, as measured by IGF-1 levels, are associated with mid-term mortality in HD patients. High hematocrit was an independent risk factor for mortality. Comorbidity, measured by disease and the degree of functional impairment, was a good predictor of mortality.

La ecuación berlin initiative study, una herramienta útil y específica para estimar el filtrado glomerular en centenarios / The berlin initiative study equation: a useful and specific tool for estimating glomerular filtration rate in centenarian patients

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Enfermedad renal «oculta» en ancianos: ¿deja de ocultarse a los 10 años de seguimiento? / Hidden renal disease in the elderly is not longer buried after 10 years of follow up

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