Longitudinal change in proteinuria and kidney outcomes in C3 glomerulopathy.

INTRODUCTION: The association between a change in proteinuria over time and its impact on kidney prognosis has not been analysed in complement component 3 (C3) glomerulopathy. This study aims to investigate the association between the longitudinal change in proteinuria and the risk of kidney failure. METHODS: This was a retrospective, multicentre observational cohort study in 35 nephrology departments belonging to the Spanish Group for the Study of Glomerular Diseases. Patients diagnosed with C3 glomerulopathy between 1995 and 2020 were enrolled. A joint modelling of linear mixed-effects models was applied to assess the underlying trajectory of a repeatedly measured proteinuria, and a Cox model to evaluate the association of this trajectory with the risk of kidney failure. RESULTS: The study group consisted of 85 patients, 70 C3 glomerulonephritis and 15 dense deposit disease, with a median age of 26 years (range 13-41). During a median follow-up of 42 months, 25 patients reached kidney failure. The longitudinal change in proteinuria showed a strong association with the risk of this outcome, with a doubling of proteinuria levels resulting in a 2.5-fold increase of the risk. A second model showed that a ≥50% proteinuria reduction over time was significantly associated with a lower risk of kidney failure (hazard ratio 0.79; 95% confidence interval 0.56-0.97; P < 0.001). This association was also found when the ≥50% proteinuria reduction was observed within the first 6 and 12 months of follow-up. CONCLUSIONS: The longitudinal change in proteinuria is strongly associated with the risk of kidney failure. The change in proteinuria over time can provide clinicians a dynamic prediction of kidney outcomes.

Coronary calcification as a predictor of cardiovascular mortality in advanced chronic kidney disease: a prospective long-term follow-up study.

BACKGROUND: Patients with advanced chronic kidney disease (CKD) exhibit higher prevalence of coronary artery calcification (CaC) than general population. CaC has been proposed as a risk factor for mortality in end-stage CKD, but most studies in the field are based on short-term follow-up. METHODS: We conducted a cohort, 10-year prospective longitudinal study of consecutive cases referred to the renal unit. A non-enhanced multislice coronary computed tomography was performed at baseline. CaC was assessed by Agatston method. Patients were stratified according to their CaC score: severe calcification group (CaCs< 400 HU) and mild-moderate calcification group (CaCs≥400 HU). The overall and cardiovascular (CV) mortality, CV events, and factors potentially associated with CaC development were recorded. RESULTS: 137 patients with advanced CKD were enrolled and provided consent. Overall mortality rate was 58%; 40% due to CV events. The rate of overall mortality in the severe calcification group was 75%, and 30% in the low calcification group, whereas the rate of CV mortality was 35% vs. 6%, respectively (p < 0.001). The severe calcification group was older, had higher prevalence of type 2 diabetes mellitus, former cardiologic events, and lower albumin serum levels than the mild-moderate calcification group. In a multivariate Cox model, severe CaC was a significant predictor of CV mortality (HR 5.01; 95%CI 1.28 to 19.6, p = 0.02). CONCLUSIONS: Among advanced CKD, there was a significantly increase of CV mortality in patients with severe CaCs during a 10-year follow-up period. CaCs could be a useful prognostic tool to predict CV mortality risk in CKD patients.

Malnutrition risk prevalence in hospitalised patients in Castilla-La Mancha: Ten years after the PREDyCES® study.

INTRODUCTION: The PREDyCESR study showed ten years ago that malnutrition is a highly prevalent problem at the hospital level. In the present study we investigate the prevalence of malnutrition in hospitals of Castilla La Mancha and its relationship with complications, mortality and length of hospital stay. METHODS: 433 patients (236 men and 197 women), from 4 hospitals were included and randomised within the first 48 h of admission. Nutritional risk was assessed using the NRS-2002 screening test. RESULTS: The mean age of the patients was 71.3 ±â€¯0.9 years (alpha-trimmed mean ±â€¯insorized standard deviation). Their mean weight was 72.3 ±â€¯0.8 kg and BMI 26.8 ±â€¯0.3 kg/m2. The mean length of hospital stay was 7.2 ±â€¯0.3 days. Of the 433 study patients, 19.4% were defined as 'at-risk' by NRS-2002 > 3. Of the patients at risk, 39.3% received nutritional support. Patients at nutritional risk had an increased length of hospital stay (9.6 vs 6.8 days; p = 0.012) and had more complications and/or higher mortality (40.5% of complications and/or mortality vs 16.4%; p < 0.005). The OR of having a complication and/or death was 3.93 (95% CI: 2.36-6.5); p < 0.005. Regarding the results obtained in the PREDyCES® study, no significant differences were found in the prevalence of nutritional risk at patients' admission (19.4% vs 23%; p = 0.12). CONCLUSIONS: The nutritional risk at hospital admission continues to be high. Patients at nutritional risk have more complications, higher mortality and an increased length of hospital stay.

Epicardial fat tissue, coronary arterial calcification and mortality in patients with advanced chronic kidney disease and hemodialysis.

INTRODUCTION AND OBJECTIVES: Epicardial and mediastinal adipose tissue (EAT, MAT) are linked to metabolic syndrome and coronary artery disease. Patients with chronic kidney disease (CKD) have thicker EAT. We assessed if EAT and MAT could be associated with increased mortality and cardiovascular events in patients with advanced CKD and haemodialysis therapy. METHODS: A post-hoc study was performed. We analyzed a prospective series of 104 cases. EAT thickness was quantified by a multislice synchronized computed tomography (MSCT). RESULTS: The follow-up period was 112.68 (109.94-115.42) months. The optimal cut-off point of EAT for prediction of total mortality was 11.45 mm (92.86% and 43.75%). EAT thickness was associated with serum albumin levels, serum triglyceride levels, phosphorus and calcium phosphate product. The EAT was greater in haemodialysis patients compared to those with advanced CKD (P < .001). Patients with diabetes mellitus had greater EAT and MAT thickness (P = .018). At the end of follow up, the survival average time of patients with EAT thickness <11.45 mm was 97.48 months vs. 76.65 months for thickness > 11.45 mm (P = .007). CONCLUSIONS: A higher EAT and MAT thickness was associated with increased mortality. Furthermore, EAT was associated with lower free survival time to fatal and non-fatal cardiovascular events. The measurement of EAT and MAT by MSCT could be a prognostic tool to predict cardiovascular events and mortality risk in advanced CKD patients.

Epicardial fat tissue, coronary arterial calcification and mortality in patients with advanced chronic kidney disease and hemodialysis. / Tejido graso epicárdico, calcificación arterial coronaria y mortalidad en pacientes con enfermedad renal crónica avanzada y hemodiálisis.

INTRODUCTION AND OBJECTIVES: Epicardial and mediastinal adipose tissue (EAT, MAT) are linked to metabolic syndrome and coronary artery disease. Patients with chronic kidney disease (CKD) have thicker EAT. We assessed if EAT and MAT could be associated with increased mortality and cardiovascular events in patients with advanced CKD and haemodialysis therapy. METHODS: A post-hoc study was performed. We analyzed a prospective series of 104 cases. EAT thickness was quantified by a multislice synchronized computed tomography (MSCT). RESULTS: The follow-up period was 112.68 (109.94 -115.42) months. The optimal cut-off point of EAT for prediction of total mortality was 11.45mm (92.86% and 43.75%). EAT thickness was associated with serum albumin levels, serum triglyceride levels, phosphorus and calcium phosphate product. The EAT was greater in haemodialysis patients compared to those with advanced CKD (P<.001). Patients with diabetes mellitus had greater EAT and MAT thickness (P=.018). At the end of follow up, the survival average time of patients with EAT thickness <11.45mm was 97.48 months vs. 76.65 months for thickness > 11.45mm (P=.007). CONCLUSIONS: A higher EAT and MAT thickness was associated with increased mortality. Furthermore, EAT was associated with lower free survival time to fatal and non-fatal cardiovascular events. The measurement of EAT and MAT by MSCT could be a prognostic tool to predict cardiovascular events and mortality risk in advanced CKD patients.

Treatment-induced diabetes neuropathy: description of singular clinical signs to reach a prompt diagnosis.

A 23-year-old woman diagnosed with type 1 diabetes mellitus in 2011 came to our outpatient office because of an inability to walk correctly. She was under a basal bolus insulin regimen. In the summer of 2016, she experienced a rapid improvement in her glycaemic control. A few weeks later, she started to complain of a severe burning pain in the soles of her feet (pain score 10/10). Neither macrovascular nor microvascular complications were detected. The patient was forced to walk barefoot due to an intense pain using shoes or socks and used to soak her feet in water for several hours daily. She also developed severe intolerance to environmental heat, both indoors and outdoors. A diagnosis of treatment-induced diabetic neuropathy was made. The patient was admitted to a general ward to start pain therapy. After a 6-month course of different neuropathic pain drugs, the patient was able to walk autonomously again.

Mycophenolate Mofetil in C3 Glomerulopathy and Pathogenic Drivers of the Disease.

BACKGROUND AND OBJECTIVES: C3 glomerulopathy is a complement-mediated disease arising from abnormalities in complement genes and/or antibodies against complement components. Previous studies showed that treatment with corticosteroids plus mycophenolate mofetil (MMF) was associated with improved outcomes, although the genetic profile of these patients was not systematically analyzed. This study aims to analyze the main determinants of disease progression and response to this therapeutic regimen. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a retrospective, multicenter, observational cohort study in 35 nephrology departments belonging to the Spanish Group for the Study of Glomerular Diseases. Patients diagnosed with C3 glomerulopathy (n=81) or dense deposit disease (n=16) between January 1995 and March 2018 were enrolled. Multivariable and propensity score matching analyses were used to evaluate the association of clinical and genetic factors with response to treatment with corticosteroids and MMF as measured by proportion of patients with disease remission and kidney survival (status free of kidney failure). RESULTS: The study group comprised 97 patients (84% C3 glomerulopathy, 16% dense deposit disease). Forty-two patients were treated with corticosteroids plus MMF, and this treatment was associated with a higher rate of remission and lower probability of kidney failure (79% and 14%, respectively) compared with patients treated with other immunosuppressives (24% and 59%, respectively), or ecluzimab (33% and 67%, respectively), or conservative management (18% and 65%, respectively). The therapeutic superiority of corticosteroids plus MMF was observed both in patients with complement abnormalities and with autoantibodies. However, patients with pathogenic variants in complement genes only achieved partial remission, whereas complete remissions were common among patients with autoantibody-mediated forms. The main determinant of no remission was baseline proteinuria. Relapses occurred after treatment discontinuation in 33% of the patients who had achieved remission with corticosteroids plus MMF, and a longer treatment length of MMF was associated with a lower risk of relapse. CONCLUSIONS: The beneficial response to corticosteroids plus MMF treatment in C3 glomerulopathy appears independent of the pathogenic drivers analyzed in this study.

Coronary artery calcification in patients with diabetes mellitus and advanced chronic kidney disease. / Calcificación arterial coronaria en pacientes con diabetes mellitus y enfermedad renal crónica avanzada.

INTRODUCTION: Patients with chronic kidney disease (CKD) and diabetes mellitus (DM) have high cardiovascular risk. Both conditions are related to systemic atherosclerosis and vascular calcification. The prevalence and severity of coronary artery calcification (CaC) is higher in patients with DM, regardless of their renal function. Data about the long-term prognostic role of CaC in diabetic patients with CKD are scarce. MATERIAL AND METHODS: We carried out a prospective longitudinal study enrolling 137 patients with advanced CKD. A non-enhanced multislice coronary computed tomography (CT) was performed at baseline. CaC was assessed using Agatston method. Patients were stratified according to their CaC score: severe calcification group (CaCs≥400HU) and mild-moderate calcification group (CaCs<400HU). RESULTS: The median follow-up time was 87.5 months. DM was found in 28% of subjects. The patients with DM showed more severe CaC, lower albumin and higher C-reactive protein serum levels. Serum albumin was correlated with severe CaC (r=-0.45, P=.009). Overall mortality rate reached 58%. Patients with DM also tended to have higher mortality compared to non-diabetic subjects (X2 3.51, P=.061) especially those with severe CaC showed higher mortality than those with severe CaC without DM (93% vs.73%, P=.04). CONCLUSIONS: Patients with advanced CKD and DM have more severe CaC, increased inflammation-malnutrition data and higher mortality compared to those without DM.

Recurrent postinfectious glomerulonephritis: an unusual evolution compatible with C3 glomerulopathy.

Acute endocapillary glomerulonephritis, as its name suggests, is a one-time process, which usually resolves within weeks. However, in a small percentage of patients, the disease becomes chronic. In these cases, a deregulation in the alternative complement pathway, which can be caused by mutations or autoantibodies, has been proposed as a pathophysiological mechanism. As a result, the alternative complement pathway remains active after resolution of infection. We report a patient with two episodes of acute renal failure, both times diagnosed by renal biopsy of acute endocapillary glomerulonephritis, with slow recovery after two episodes of low-serum complement C3, haematuria and proteinuria.

Pheochromocytoma-paraganglioma: Biochemical and genetic diagnosis. / Feocromocitoma-paraganglioma: del diagnóstico bioquímico al genético.

Pheochromocytomas and paragangliomas are tumours derived from neural crest cells, which can be diagnosed by biochemical measurement of metanephrine and methoxytyramine. Advances in genetic research have identified many genes involved in the pathogenesis of these tumours, suggesting that up to 35-45% may have an underlying germline mutation. These genes have a singular transcriptional signature and can be grouped into 2 clusters (or groups): cluster 1 (VHL and SHDx), involved in angiogenesis and hypoxia pathways; and cluster 2 (MEN2 and NF1), linked to the kinase signalling pathway. In turn, these genes are associated with a characteristic biochemical phenotype (noradrenergic and adrenergic), and clinical features (location, biological behaviour, age of presentation, etc.) in a large number of cases. Early diagnosis of these tumours, accompanied by a correct genetic diagnosis, should eventually become a priority to enable better treatment, early detection of complications, proper screening of family members and related tumours, as well as an improvement in the overall prognosis of these patients.

Cystic fibrosis-related diabetes: a distinct condition.

Cystic fibrosis is the most common fatal inherited autosomal recessive disease in Caucasians, affecting approximately one out of every 2,000 births. Survival of patients with cystic fibrosis has significantly improved due to advances in respiratory and nutritional care, and their current average life expectancy is 30-40 years. Development of cystic fibrosis-related diabetes is a comorbidity that increases with age and may reach a prevalence up to 50% in adults. Its development is associated to impaired lung function and nutritional status, and early diagnosis and treatment are therefore essential to improve quality of life and performance status. Insulin therapy for diabetes and other early carbohydrate metabolism disorders may improve lung function and nutritional status of patients with cystic fibrosis.

Bone and metabolic complications of urinary diversions.

Hyperchloremic metabolic acidosis is a complication of urinary diversion using ileum or colon. Its prevalence ranges from 25% and 46% depending on the procedure used and renal function of the patient. It is a consequence of intestinal fluid and electrolyte exchange between intestinal mucosa and urine. The main mechanism is absorption of ammonium and chloride from urine. Long-term chronic metabolic acidosis in these patients may lead to impaired bone metabolism and osteomalacia. Regular monitoring of pH, chlorine, bicarbonate, and calcium-phosphorus metabolism is therefore essential for early diagnosis and treatment.

Insulin resistance, ß-cell dysfunction and differences in curves of plasma glucose and insulin in the intermediate points of the standard glucose tolerance test in adults with cystic fibrosis.

BACKGROUND: diabetes has become a co-morbidity with a negative impact on nutritional status, lung function and survival in cystic fibrosis. OBJECTIVE: To identify any changes in intermediate points after a 2-hour oral glucose tolerance test (OGTT), pancreatic ß-cell dysfunction, and insulin resistance in cystic fibrosis-related diabetes. METHODS: It was carried out a retrospective analysis in a cohort of 64 patients affected of cystic fibrosis, older than 14 years, using the first pathological OGTT. Peripheral insulin resistance was measured using the homeostasis model assessment for insulin resistance (HOMA- IR), and pancreatic ß-cell function was calculated according to Wareham. Time to maximum plasma insulin and glucose levels and area under the curve (AUC0-120) were also measured. RESULTS: Twenty-eight women and 36 men with a mean age of 26.8 years were enrolled, of whom 26.7% had normal glucose tolerance (NGT), 18.3% cystic fibrosis-related diabetes without fasting hyperglycemia (CFRD w/o FPG), 10% indeterminate (INDET), and 45% impaired glucose tolerance (IGT). HOMA-IR values were not significantly different between the diagnostic categories. Patients with any pathological change had worse ß cell function, with a significant delay in insulin secretion, although there were no differences in total insulin production (AUC0-120). Time to maximum glucose levels was significantly shorter in NGT patients as compared to other categories, with glucose AUC0-120 being higher in the different diagnostic categories as compared to NGT. CONCLUSIONS: In over half the cases, peak blood glucose levels during a standard OGTT are reached in the intermediate time points, rather than at the usual time of 120minutes. Patients with cystic fibrosis and impaired glucose metabolism have a delayed insulin secretion during the standard OGTT due to loss of first-phase insulin secretion, with no differences in total insulin production. Absence of significant changes in HOMA-IR suggests that ß-cell dysfunction is the main pathogenetic mechanism.

Association of the relative change in weight and body mass index with lung function in teenagers and adults with cystic fibrosis: Influence of gender and diabetes.

BACKGROUND: Nutritional status is a prognostic factor in cystic fibrosis. Prevention of nutritional impairment and weigh loss are major clinical objectives because they are associated with worsening of lung function and increased mortality. OBJECTIVE: To identify a potential relationship of clinical nutrition parameters, and their relative changes, with lung function (FEV1%) in a cohort of adolescent and adult patients with CF. METHODS: A retrospective analysis of 64 patients older than 14years. Weight, height, BMI, and lung function data were collected at a period of disease stability, both in the year of the first abnormal oral glucose tolerance test (OGTT) and in the previous year. Relative changes in weight and BMI, and their relationship with FEV1%, were determined by linear regression and ANOVA tests; influence of gender and diabetes was also assessed. RESULTS: Mean age of the series (28 females and 36 males) was 26.8years. Normal glucose tolerance (NGT) was found in 26.7%, while 18.3% had diabetes without impaired fasting glucose (CFRD without FPG). Mean BMI was 20.32, with a mean weight of 53.53kg; 32.8% had BMI<18.5, and only 4.7% were overweight. Overall, a positive relative change in weight (≥6%) was associated with an increase in FEV1% (9.31%), as compared to those with a greater weight loss (at least 2%), who had a 12.09% fall in FEV1. Patients with CFRD without FPG had poorer lung function if they had a negative relative change in weight by at least 2% as compared to NGT. CONCLUSIONS: In patients with CF, a relative weight gain is positively associated to FEV1%, while a relative weight loss of at least 2% has a significant negative impact on lung function.

Clinical features, mortality, hospital admission, and length of stay of a cohort of adult patients with diabetic ketoacidosis attending the emergency room of a tertiary hospital in Spain.

AIM: To assess the clinical features, length of stay, incidence rate, mortality, and hospital admissions of patients with episodes of diabetic ketoacidosis (DKA). PATIENTS: It was conducted retrospective, cross-sectional study of 164 consecutive admissions of adult patients (2008-August 2012), with type 1 or type 2 diabetes already known or new onset. RESULTS: Mortality rate was 1.2%. The DKA episodes were mild (18.9%), moderate (31.7%), or severe (49.4%). The cumulative incidence was 2.66 cases/1000 patients with diabetes (DM) in 4.5 years. The most common causes triggering DKA were infection (33.2%) and dietary transgression and/or insulin dose omission (30.7%). A total of 12.8% of patients had new onset DM, 56.7% type 1, and 26.8% type 2 DM. Patients with type 2 DM were older and had at admission higher creatinine, BUN, osmolality, sodium, and anion gap levels. Patients with new-onset of DM had higher levels of glucose and sodium, but lower potassium levels. No differences were found in pH or bicarbonate. Admission to the intensive care unit (ICU) was required in >50% of cases (p<0.001), and 86.6% of patients were finally admitted to a medical ward (p=0.005). The length of stay at the ICU (p<0.001) and hospital (p=0.013) was significantly different depending on DKA severity. CONCLUSIONS: Most DKA episodes require hospital admission, but mortality is <2%, and length of stay at the ER and medical ward depends on type of DM and initial severity of the episode.