Long-term mortality and trajectory of potassium measurements following an episode of acute severe hyperkalaemia.

BACKGROUND: Hyperkalaemia is a common condition in patients with comorbidities such as chronic kidney disease (CKD) or congestive heart failure (HF). Moreover, severe hyperkalaemia is a potentially life-threatening condition that is associated with a higher risk of adverse clinical events such as ventricular arrhythmias and sudden cardiac death. Currently, data regarding the prognostic implications of chronic hyperkalaemia are available; however, information about the long-term clinical consequences after an episode of severe hyperkalaemia remains scarce. The objective of this study was to evaluate the association between the trajectory of potassium measurements in patients with acute hyperkalaemia and long-term all-cause mortality. METHODS: This is a retrospective observational study that included patients with acute severe hyperkalaemia [potassium (K) >6 mEq/L] without haemolysis in the emergency room of Dr Peset University Hospital in Valencia, Spain searching the lab database from January 2016 to March 2017. The multivariable-adjusted association of serum potassium with mortality was assessed by using comprehensive state-of-the-art regression methods that can accommodate time-dependent exposure modelling. RESULTS: We found 172 episodes of acute hyperkalaemia in 160 patients in the emergency room. The mean ± standard deviation age of the sample was 77 ± 12 years and 60.5% were males. The most frequent comorbidities were CKD (71.2%), HF (35%) and diabetes mellitus (56.9%). Only 11.9% of the patients were on chronic dialysis. A quarter of the patients did not have previous CKD, making hyperkalaemia an unpredictable life-threatening complication. During the acute episode, mean potassium and estimated glomerular filtration rate (eGFR) were 6.6 ± 0.6 (range 6.1-9.2) mEq/L and 23 ± 16 (range 2-84) mL/min/1.73 m2, respectively. After a median (interquartile range) follow-up of 17.3 (2.2-23.7) months, 68 patients died (42.5%). Recurrences of hyperkalaemia (K >5.5 mEq/L) were detected in 39.5% of the patients who were monitored during follow-up. We found that previous potassium levels during an acute severe hyperkalaemia episode were not predictors of mortality. Conversely, the post-discharge longitudinal trajectories of potassium were able to predict all-cause mortality (overall P = 0.0015). The effect of transitioning from hyperkalaemia to normokalaemia (K >5.5 mEq/L to K ≤5.5 mEq/L) after the acute episode was significant, and inversely associated with the risk of mortality. CONCLUSIONS: Potassium levels prior to a severe hyperkalaemic event do not predict mortality. Conversely, following an episode of acute severe hyperkalaemia, serial kinetics of potassium trajectories predict the risk of death. Further evidence is needed to confirm these findings and clarify the optimal long-term management of these patients.

Institutional Experience With New Antidiabetic Drugs in Kidney Transplant.

BACKGROUND: The recent introduction of new antidiabetic drugs, analogs of glucagon-like peptide-1 (GLP-1) and sodium-glucose cotransporter 2 inhibitors, has shown excellent results in the management of patients with diabetes with chronic kidney disease. However, documented results of these medications in the population that has undergone kidney transplant are sparse. We report our institutional experience with them, including occurrence of side effects and possible interactions with immunosuppressive medications. METHODS: A retrospective analysis of 15 patients (10 with diabetes and 5 without diabetes but with obesity) managed with these medications was carried out in the kidney transplant unit of Hospital Doctor Peset during the year 2019. Data acquired at baseline and 3, 6, and 12 months were analyzed. RESULTS: The median hemoglobin A1c at baseline was 6.7 (interquartile range [IQR] = 5.8-8.2) and at 12 months it was 6 (IQR = 5.3-8.1, P = .96). The mean weight difference at 12 months was a loss of 7.2 ± 6 kg; median body mass index at baseline was 31.2 kg/m2 (IQR = 29.7-35.5) and 29.5 kg/m2 (IQR = 27.6-31.6, P = .01) at 12 months. In addition to weight loss, a reduction in insulin and oral antidiabetic drug requirements was observed. No significant changes were detected in serum creatinine or proteinuria values and the immunosuppressant levels remained stable. No acute rejection episodes were observed. CONCLUSION: Based on our experience, the new antidiabetic drugs are safe, with no significant changes in renal function or immunosuppressant levels or clinically important adverse effects.

Disorders in bone-mineral parameters and the risk of death in persons with chronic kidney disease stages 4 and 5: the PECERA study.

BACKGROUND: Abnormalities of bone mineral parameters are associated with increased mortality in patients on dialysis, but their effects and the optimal range of these biomarkers are less well characterized in non-dialysis chronic kidney disease (CKD). METHODS: PECERA (Collaborative Study Project in Patients with Advanced CKD) is a 3-year, prospective multicenter, open-cohort study of 966 adult patients with non-dialyzed CKD stages 4-5 enrolled from 12 centers in Spain. Associations between levels of serum calcium (Ca) (corrected for albumin), phosphate (P), and intact parathyroid hormone (iPTH) with all-cause mortality (primary outcome) and cardiovascular mortality (secondary outcome) were examined using time-dependent Cox proportional hazards models and penalized splines analysis adjusted by demographics and comorbidities, treatments and biochemical values collected every 6 months for 3 years. RESULTS: After a median follow-up of 29 months (IQR: 13-36 months) there were 181 deaths (19%). The association of calcium with all-cause mortality was J-shaped, with an increased risk for all-cause mortality at levels > 10.5 mg/dL. For phosphate and iPTH levels, the association was U-shaped. The serum values associated with the minimum risk of mortality were 3.8 mg/dL for phosphate and 70 pg/mL for iPTH, being the lowest risk ranges between 2.8 and 5.0 mg/dL, and between 38 and 112 pg/mL for phosphate and iPTH, respectively. CONCLUSIONS: Our study provides evidence on the non-linear association of serum calcium, phosphate and iPTH levels with mortality in stage 4 and 5 CKD patients, and suggests potential survival benefits for controlling bone mineral parameters in this population, as previously reported for dialysis patients.

Prevalence of Vertebral Fractures and Their Prognostic Significance in the Survival in Patients with Chronic Kidney Disease Stages 3‒5 Not on Dialysis.

Background: The prevalence of vertebral fractures (VF) and their association with clinical risk factors and outcomes are poorly documented in chronic kidney disease (CKD) cohorts. The aim of the study was to evaluate the prevalence of VF in patients with non-dialysis dependent CKD (NDD-CKD), their value in predicting mortality and its correlation with parameters of bone mineral metabolism and vascular calcification. Materials and Methods: 612 NDD 3‒5 stage CKD patients participating in the OSERCE-2 study, a prospective, multicenter, cohort study, were prospectively evaluated and categorized into two groups according to presence or absence of VF at enrollment. VF were assessed with lateral radiographs and Genant semi-quantitative method was applied. Three radiologists specialized in musculoskeletal radiology performed consensual reading of individual images obtained using a Raim DICOM Viewer and a Canon EOS 350 camera to measure with Java Image software in those who had traditional acetate X-ray. Factors related to VF were assessed by logistic regression analysis. Association between VF and death over a 3-year follow-up was assessed by Kaplan-Meier survival curves and Cox-proportional hazard models. Results: VF were detected in 110 patients (18%). Serum phosphate levels (OR 0.719, 95% CI 0.532 to 0.972, p = 0.032), ankle-brachial index < 0.9 (OR 1.694, 95% CI 1.056‒2.717, p = 0.029) and treatment with bisphosphonates (OR 5.636, 95% CI 1.876‒16.930, p = 0.002) were independently related to the presence of VF. After a median follow-up of 35 months (IQR: 17‒37 months), 62 patients (10%) died. The causes of death were cardiovascular (n = 21, 34%) and infectious (n = 11, 18%). In the crude analysis, fractured patients group had poorer survival (log-rank test, p = 0.02). After multivariate adjustment for age, MDRD, albumin, diabetes mellitus, comorbidity, Adragao Score > 3 and serum phosphate, the presence of VF (HR 1.983, 95% CI 1.009‒3.898, p = 0.047) were an independent predictor of all-cause mortality. Conclusions: In our study 18% of patients with NDD-CKD have VF. Factors associated with VF were age, low serum phosphate levels and peripheral vascular disease. The presence of VF was an independent risk factor for mortality in stages 3‒5 NDD-CKD patients. Clinical trials are needed to confirm whether this relationship is causal and reversible with treatment for osteoporosis.

Severe and malignant hypertension are common in primary atypical hemolytic uremic syndrome.

Malignant hypertension is listed among the causes of secondary thrombotic microangiopathy, but pathogenic mutations in complement genes have been reported in patients with hypertension-induced thrombotic microangiopathy. Here we investigated the frequency and severity of hypertension in 55 patients with primary atypical hemolytic uremic syndrome (aHUS). A genetic analysis was performed in all patients, and funduscopic examination was performed in all the patients with Grades 2 and 3 hypertension. A cohort of 110 patients with malignant hypertension caused by diseases other than aHUS served as control. Thirty-six patients with aHUS presented Grade 2 or Grade 3 hypertension and funduscopic examination showed malignant hypertension in 19. Genetic abnormalities in complement were found in 19 patients (37% among patients with malignant hypertension). Plasmapheresis was performed in 46 patients and 26 received eculizumab. Renal and hematological responses were significantly lower after plasmapheresis (24%) than after eculizumab (81%). Renal survival was significantly higher in patients treated with eculizumab (85% at one, three and five years) compared to patients who did not receive this treatment (54%, 46% and 41%), respectively. Response to eculizumab was independent of hypertension severity and the presence of complement genetic abnormalities. Among patients with malignant hypertension caused by other diseases the prevalence of thrombotic microangiopathy was very low (5%). Thus, severe and malignant hypertension are common among patients with aHUS and eculizumab treatment leads to a higher renal survival when compared to plasmapheresis. However, thrombotic microangiopathy is uncommon among patients presenting with malignant hypertension caused by diseases other than aHUS.

Randomized Controlled Trial Assessing the Impact of Tacrolimus Versus Cyclosporine on the Incidence of Posttransplant Diabetes Mellitus.

INTRODUCTION: Despite the high incidence of posttransplant diabetes mellitus (PTDM) among high-risk recipients, no studies have investigated its prevention by immunosuppression optimization. METHODS: We conducted an open-label, multicenter, randomized trial testing whether a tacrolimus-based immunosuppression and rapid steroid withdrawal (SW) within 1 week (Tac-SW) or cyclosporine A (CsA) with steroid minimization (SM) (CsA-SM), decreased the incidence of PTDM compared with tacrolimus with SM (Tac-SM). All arms received basiliximab and mycophenolate mofetil. High risk was defined by age >60 or >45 years plus metabolic criteria based on body mass index, triglycerides, and high-density lipoprotein-cholesterol levels. The primary endpoint was the incidence of PTDM after 12 months. RESULTS: The study comprised 128 de novo renal transplant recipients without pretransplant diabetes (Tac-SW: 44, Tac-SM: 42, CsA-SM: 42). The 1-year incidence of PTDM in each arm was 37.8% for Tac-SW, 25.7% for Tac-SM, and 9.7% for CsA-SM (relative risk [RR] Tac-SW vs. CsA-SM 3.9 [1.2-12.4; P = 0.01]; RR Tac-SM vs. CsA-SM 2.7 [0.8-8.9; P = 0.1]). Antidiabetic therapy was required less commonly in the CsA-SM arm (P = 0.06); however, acute rejection rate was higher in CsA-SM arm (Tac-SW 11.4%, Tac-SM 4.8%, and CsA-SM 21.4% of patients; cumulative incidence P = 0.04). Graft and patient survival, and graft function were similar among arms. CONCLUSION: In high-risk patients, tacrolimus-based immunosuppression with SM provides the best balance between PTDM and acute rejection incidence.

Downregulation of miR-31 in Diabetic Nephropathy and its Relationship with Inflammation.

BACKGROUND/AIMS: There is a lack of reliable biological markers for the early diagnosis of diabetic nephropathy (DN) during type 2 diabetes. In this pilot study we aim to assess whether miR-31 levels are modulated by the presence of DN and whether the expression of this miRNA is related to leukocyte-endothelial interactions and inflammation. METHODS: Thirty-one T2D patients were enrolled in this pilot study; 18 with no diabetic complications and 13 with diabetic nephropathy. 24 non-diabetic subjects and 13 T2D patients with retinopathy (absent of other complications) were included to test the specificity of miR-31. Following anthropometric and biochemical evaluation, serum miR-31 levels were assessed by Real Time-PCR. Leukocyte-endothelial interactions were evaluated by a parallel flow chamber in vitro model. Serum TNFα, IL-6 and ICAM-1 levels were determined by XMAP-technology in a flow cytometry-based Luminex 200 instrument. RESULTS: Serum miR-31 levels were similar between control and T2D subjects. However, T2D patients with DN displayed reduced levels of miR-31 with respect to patients without complications. This decrease in miR-31 was more pronounced in patients with macroalbuminuria than in those with microalbuminuria and was specific for DN, since patients with retinopathy displayed unaltered miR-31 levels. The presence of DN involved a lower leukocyte rolling velocity and an increased rolling flux and adhesion. miR-31 levels were positively correlated with leukocyte rolling velocity and negatively associated to leukocyte adhesion, TNFα, IL-6 and ICAM-1 levels. CONCLUSION: Serum miR-31 may be a biomarker for DN in T2D patients. The regulation of this miRNA seems to be related to the recruitment of leukocytes to vascular walls induced by pro-inflammatory and adhesion molecules.

The effect of high-volume online haemodiafiltration on nutritional status and body composition: the ProtEin Stores prEservaTion (PESET) study.

Background: Compared with conventional haemodialysis (HD), online haemodiafiltration (OL-HDF) achieves a more efficient removal of uraemic toxins and reduces inflammation, which could favourably affect nutritional status. We evaluate the effect of OL-HDF on body composition and nutritional status in prevalent high-flux HD (HF-HD) patients. Methods: In all, 33 adults with chronic kidney disease (CKD) Stage 5 undergoing maintenance HF-HD were assigned to post-dilution OL-HDF (n = 17) or to remain on HF-HD (n = 16, control group) for 12 months. The primary outcome was the change in lean tissue mass (LTM), intracellular water (ICW) and body cell mass (BCM) assessed by multifrequency bioimpedance spectroscopy (BIS) at baseline and 4, 8 and 12 months. The rate of change in these parameters was estimated with linear mixed-effects models. Results: Compared with OL-HDF, patients assigned to HF-HD experienced a gradual reduction in LTM, ICW and BCM. These differences reached statistical significance at Month 12, with a relative difference of 7.31 kg [95% confidence interval (CI) 2.50-12.11; P = 0.003], 2.32 L (95% CI 0.63-4.01; P = 0.008) and 5.20 kg (95% CI 1.74-8.66; P = 0.004) for LTM, ICW and BCM, respectively. The normalized protein appearance increased in the OL-HDF group compared with the HF-HD group [0.26 g/kg/day (95% CI 0.05-0.47); P = 0.002], with a relative reduction in high-sensitive C-reactive protein [-13.31 mg/dL (95% CI -24.63 to -1.98); P = 0.02] at Month 12. Conclusions: OL-HDF for 1 year compared with HF-HD preserved muscle mass, increased protein intake and reduced the inflammatory state related to uraemia and dialysis, supporting the hypothesis that high convection volume can benefit nutritional status and prevent protein-energy wasting in HD patients.

Tenofovir-induced toxicity in renal proximal tubular epithelial cells: involvement of mitochondria.

OBJECTIVE: In-vivo studies suggest that mitochondria is involved in tenofovir (TFV)-induced renal toxicity, but the underlying mechanisms are still unclear. The aim of the present study was to assess the effects of TFV and its prodrug, TFV disoproxil fumarate, on mitochondrial function and cell survival/viability in a renal proximal tubular cell line. DESIGN AND METHODS: We evaluated parameters of cellular proliferation/survival (cell count, cell cycle, viability) and mitochondrial function (oxygen consumption, mitochondrial membrane potential, reactive oxygen species production) in NRK-52E cells. Intracellular TFV was measured by HPLC and expression of antioxidant genes was analysed by real-time PCR. RESULTS: Similar intracellular levels of TFV were reached with lower concentrations of the prodrug than of the drug, and correlated directly with a decrease in cell number. Both compounds inhibited proliferation and compromised mitochondrial function by decreasing mitochondrial membrane potential and increasing oxygen consumption and mitochondrial superoxide production. Altered oxidative status was confirmed by the overexpression of antioxidant genes. CONCLUSIONS: Intracellular accumulation of TFV induces mitochondrial toxicity in an in-vitro renal model and alters cell proliferation and viability. Our findings call for caution regarding the use of this nucleotide analogue reverse transcriptase inhibitor in patients with other risk factors that compromise mitochondrial function in the kidney.

Regression of vascular calcification in a parathyroidectomized patient on dialysis with untreated hypocalcemia over 12-year follow-up
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Although some experimental targets involved in calcium deposition are emerging, no intervention has been described to reliably reverse vascular calcification (VC). We report a case of severe VC regression in a parathyroidectomized patient on hemodialysis over 12-year follow-up, highlighting the use of calcium-free phosphate binders and a 2.5 mEq/L calcium dialysate for reducing calcium loading, despite persistent asymptomatic hypocalcemia occurrences. This case suggests that phosphate-binder choice and calcium dialysate concentration could be influenced by other components of CKD-MBD besides biochemical parameters, such as the presence of VC, so concluding that asymptomatic hypocalcemia may not be as harmful as once supposed, and conferring greater prognostic weight to the presence of VC than to calcium levels.
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What is the optimal level of vitamin D in non-dialysis chronic kidney disease population?

AIM: To evaluate thresholds for serum 25(OH)D concentrations in relation to death, kidney progression and hospitalization in non-dialysis chronic kidney disease (CKD) population. METHODS: Four hundred and seventy non-dialysis 3-5 stage CKD patients participating in OSERCE-2 study, a prospective, multicenter, cohort study, were prospectively evaluated and categorized into 3 groups according to 25(OH)D levels at enrollment (less than 20 ng/mL, between 20 and 29 ng/mL, and at or above 30 ng/mL), considering 25(OH)D between 20 and 29 ng/mL as reference group. Association between 25(OH)D levels and death (primary outcome), and time to first hospitalization and renal progression (secondary outcomes) over a 3-year follow-up, were assessed by Kaplan-Meier survival curves and Cox-proportional hazard models. To identify 25(OH)D levels at highest risk for outcomes, receiver operating characteristic (ROC) curves were performed. RESULTS: Over 29 ± 12 mo of follow-up, 46 (10%) patients dead, 156 (33%) showed kidney progression, and 126 (27%) were hospitalized. After multivariate adjustment, 25(OH)D < 20 ng/mL was an independent predictor of all-cause mortality (HR = 2.33; 95%CI: 1.10-4.91; P = 0.027) and kidney progression (HR = 2.46; 95%CI: 1.63-3.71; P < 0.001), whereas the group with 25(OH)D at or above 30 ng/mL did not have a different hazard for outcomes from the reference group. Hospitalization outcomes were predicted by 25(OH) levels (HR = 0.98; 95%CI: 0.96-1.00; P = 0.027) in the unadjusted Cox proportional hazards model, but not after multivariate adjusting. ROC curves identified 25(OH)D levels at highest risk for death, kidney progression, and hospitalization, at 17.4 ng/mL [area under the curve (AUC) = 0.60; 95%CI: 0.52-0.69; P = 0.027], 18.6 ng/mL (AUC = 0.65; 95%CI: 0.60-0.71; P < 0.001), and 19.0 ng/mL (AUC = 0.56; 95%CI: 0.50-0.62; P = 0.048), respectively. CONCLUSION: 25(OH)D < 20 ng/mL was an independent predictor of death and progression in patients with stage 3-5 CKD, with no additional benefits when patients reached the levels at or above 30 ng/mL suggested as optimal by CKD guidelines.

Cambios glucémicos durante el ciclo menstrual en mujeres con diabetes mellitus tipo 1 / Glycemic changes during menstrual cycles in women with type 1 diabetes

Fundamento y objetivo: Determinar la frecuencia de mujeres con diabetes tipo 1 que experimentan cambios glucémicos durante el ciclo menstrual, analizar sus características clínicas, y evaluar el patrón de los cambios glucémicos. Pacientes y métodos: Analizamos las lecturas de los glucómetros a lo largo de 168 ciclos menstruales en 26 mujeres con diabetes tipo 1. Evaluamos la glucemia media, la desviación estándar media, la glucemia media basal, el porcentaje de lecturas > 7,8 mmol/l y < 3,1 mmol/l, y la dosis de insulina media en 4 períodos de cada ciclo. Se consideró que una mujer tenía cambios cíclicos cuando la glucemia media se elevó entre la fase folicular temprana y la fase lútea tardía en dos tercios de sus ciclos menstruales. Resultados: El 65,4% de las mujeres experimentaron cambios cíclicos. Las características de las mujeres con y sin cambios cíclicos, incluyendo la autopercepción de cambios glucémicos, fueron similares, exceptuando la edad de diagnóstico de la diabetes (22,5 [7,5] frente a 14,4 [9,5] años; p = 0,039). En mujeres con cambios cíclicos el porcentaje medio de los valores de glucosa > 7,8 mmol/l se elevó entre la fase folicular temprana (52,2 [16,3] %) y la fase lútea temprana y tardía (58,4 [16,0] %, p = 0,0269; 61,0 [16,9] %, p = 0,000). Conclusión: Casi dos tercios de las mujeres con diabetes tipo 1 experimentan fenómenos del ciclo menstrual atribuibles a un incremento de las excursiones hiperglucémicas durante la fase lútea. Posibilitar que las mujeres evalúen su glucemia media semanal a partir de las lecturas de los glucómetros, y explorar las causas de las excursiones hiperglucémicas durante la fase lútea podría garantizar una mayor precisión al impartir instrucciones para la gestión de la diabetes en mujeres con hiperglucemia premenstrual (AU)

Background and objective: To determine frequency of women with type 1 diabetes showing menstrual cyclic changes in glycemia, analyze their clinical characteristics, and assess the pattern of glycemic changes. Patients and methods: We analyzed glucose meter readings along 168 menstrual cycles of 26 women with type 1 diabetes. We evaluated mean glucose, mean glucose standard deviation, mean fasting glucose, percentage of glucose readings > 7.8 mmol/L and < 3.1 mmol/L, and mean insulin dose in 4 periods for each cycle. A woman was identified as having cyclic changes when mean glucose rose from early follicular to late luteal in two-thirds of her menstrual cycles. Results: A percentage of 65.4 of the women had cyclic changes. Characteristics of women with and without cyclic changes, including self-perception of glycemic changes, were similar with exception of age at diabetes diagnosis (22.5 [7.5] vs. 14.4 [9.5] years; P = .039). In women with cyclic changes mean percentage of glucose readings > 7.8 mmol/L rose from early follicular (52.2 [16.3] %) to early and late luteal (58.4 [16.0] %, P = .0269; 61.0 [16.9] %, P = .000). Conclusion: Almost two-thirds of women with type 1 diabetes experience a menstrual cycle phenomenon, attributable to an increase in hyperglycemic excursions during the luteal phase. Enabling women to evaluate their weekly mean glucose from their meter and exploring the causes of hyperglycemic excursions during luteal phase should ensure more accuracy when giving instructions for diabetes management in women with premenstrual hyperglycemia (AU)

HbA1c and Gestational Weight Gain Are Factors that Influence Neonatal Outcome in Mothers with Gestational Diabetes.

BACKGROUND: Maternal glucose and weight gain are related to neonatal outcome in women with gestational diabetes mellitus (GDM). The aim of this study was to explore the influence of average third-trimester HbA1c and excess gestational weight gain on GDM neonatal complications. MATERIALS AND METHODS: This observational study included 2037 Spanish singleton pregnant women with GDM followed in our Diabetes and Pregnancy Unit. The maternal HbA1c level was measured monthly from GDM diagnosis to delivery. Women were compared by average HbA1c level and weight gain categorized into ≤ or > the current Institute of Medicine (IOM) recommendations for body mass index. The differential effects of these factors on large-for-gestational-age birth weight and a composite of neonatal complications were assessed. RESULTS: Women with an average third-trimester HbA1c ≥5.0% (n = 1319) gave birth to 7.3% versus 3.8% (p = 0.005) of large-for-gestational-age neonates and 22.0% versus 16.0% (p = 0.006) of neonates with complications. Women with excess gestational weight gain (n = 299) delivered 12.5% versus 5.2% (p < 0.001) of large-for-gestational-age neonates and 24.7% versus 19.0% (p = 0.022) of neonates with complications. In an adjusted multiple logistic regression analysis among mothers exposed to the respective risk factors, ∼47% and 52% of large-for-gestational-age neonates and 32% and 37% of neonatal complications were potentially preventable by attaining an average third-trimester HbA1c level <5.0% and optimizing gestational weight gain. CONCLUSIONS: Average third-trimester HbA1c level ≥5% and gestational weight gain above the IOM recommendation are relevant risk factors for neonatal complications in mothers with gestational diabetes.

[Glycemic changes during menstrual cycles in women with type 1 diabetes]. / Cambios glucémicos durante el ciclo menstrual en mujeres con diabetes mellitus tipo 1.

BACKGROUND AND OBJECTIVE: To determine frequency of women with type 1 diabetes showing menstrual cyclic changes in glycemia, analyze their clinical characteristics, and assess the pattern of glycemic changes. PATIENTS AND METHODS: We analyzed glucose meter readings along 168 menstrual cycles of 26 women with type 1 diabetes. We evaluated mean glucose, mean glucose standard deviation, mean fasting glucose, percentage of glucose readings>7.8 mmol/L and<3.1 mmol/L, and mean insulin dose in 4 periods for each cycle. A woman was identified as having cyclic changes when mean glucose rose from early follicular to late luteal in two-thirds of her menstrual cycles. RESULTS: A percentage of 65.4 of the women had cyclic changes. Characteristics of women with and without cyclic changes, including self-perception of glycemic changes, were similar with exception of age at diabetes diagnosis (22.5 [7.5] vs. 14.4 [9.5] years; P=.039). In women with cyclic changes mean percentage of glucose readings>7.8 mmol/L rose from early follicular (52.2 [16.3] %) to early and late luteal (58.4 [16.0] %, P=.0269; 61.0 [16.9] %, P=.000). CONCLUSION: Almost two-thirds of women with type 1 diabetes experience a menstrual cycle phenomenon, attributable to an increase in hyperglycemic excursions during the luteal phase. Enabling women to evaluate their weekly mean glucose from their meter and exploring the causes of hyperglycemic excursions during luteal phase should ensure more accuracy when giving instructions for diabetes management in women with premenstrual hyperglycemia.

Nephroprotection by Hypoglycemic Agents: Do We Have Supporting Data?

Current therapy directed at delaying the progression of diabetic nephropathy includes intensive glycemic and optimal blood pressure control, renin angiotensin-aldosterone system blockade and multifactorial intervention. However, the renal protection provided by these therapeutic modalities is incomplete. There is a scarcity of studies analysing the nephroprotective effect of antihyperglycaemic drugs beyond their glucose lowering effect and improved glycaemic control on the prevention and progression of diabetic nephropathy. This article analyzes the exisiting data about older and newer drugs as well as the mechanisms associated with hypoglycemic drugs, apart from their well known blood glucose lowering effect, in the prevention and progression of diabetic nephropathy. Most of them have been tested in humans, but with varying degrees of success. Although experimental data about most of antihyperglycemic drugs has shown a beneficial effect in kidney parameters, there is a lack of clinical trials that clearly prove these beneficial effects. The key question, however, is whether antihyperglycemic drugs are able to improve renal end-points beyond their antihyperglycemic effect. Existing experimental data are post hoc studies from clinical trials, and supportive of the potential renal-protective role of some of them, especially in the cases of dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors. Dedicated and adequately powered renal trials with renal outcomes are neccessary to assess the nephrotection of antihyperglycaemic drugs beyond the control of hyperglycaemia.

Quality of life and stressors in patients with chronic kidney disease depending on treatment.

This study evaluated health-related quality of life (HRQOL) in a Spanish sample of chronic kidney disease patients (n = 90) undergoing different renal replacement therapies, considering the influence of treatment stressors, mood, anxiety and quality of sleep. While all patients had worse physical functioning than controls (p < .01), only those undergoing haemodialysis (HD) showed worse physical well-being, occupational functioning, spiritual fulfillment and more health interference with work (p < .05). They also obtained higher depression scores than renal transplant patients (TX) (p = .005). Those TX receiving the immunosuppressor sirolimus exhibited more cardiac/renal, cognitive and physical limitations than the rest (p < .05). Dialysis vintage correlated positively with sleep disturbances and depression scores and negatively with total Quality of Life (QLI) (p < .05). HD patients experienced more psychological distress than peritoneal dialysis patients (PD) (p = .036). Regression models including sleep, anxiety and depression were estimated for subscales of HRQOL. In TX patients, low depressive scores related to an optimal QLI in almost all subscales, while in HD patients they explained part of the variability in psychological well-being, interpersonal functioning and personal fulfillment. HD condition results in a QLI more distant to the standards of controls.

Remission of aHUS neurological damage with eculizumab.

Atypical haemolytic uraemic syndrome (aHUS) is a rare disease characterized by haemolytic microangiopathic anaemia, thrombocytopaenia and acute onset of renal failure, in the absence of Escherichia coli infection. Renal damage usually progresses to end-stage renal disease (ESRD), sometimes being accompanied by signs of extrarenal thrombotic microangiopathy (TMA). We report a case of full neurological and haematological recovery after eculizumab treatment in a patient with ESRD secondary to chronic aHUS refractory to plasmatherapy while she was under dialysis. It highlights the use of eculizumab for controlling extrarenal manifestations of aHUS in this population.

Neurocognitive long-term impact of two-field conventional radiotherapy in adult patients with operated pituitary adenomas.

PURPOSE: To assess the long-term impact of postoperative two-field-conventional radiotherapy (RT) on neurocognitive functions of adult patients with operated pituitary adenomas (PA). METHODS: We selected 124 adult patients with operated PA-56 of whom had also received RT-recorded their main clinical data and performed a neuropsychological assessment in all of them that included 15 standardized tests, and a cerebral SPECT in eight patients. Comparative analyses were carried out on major clinical and neurocognitive domains between irradiated and not irradiated patients, and on cerebral SPECT source. RESULTS: Compared with non-irradiated patients, irradiated patients performed significantly worse on Barcelona's story recall test (P < 0.001) and arithmetic problems (P < 0.03) and on five categories of the Wisconsin card sorting test, especially on perseverative answers and errors (P < 0.001) without differences in other examined functional domains. RT was the only factor associated with worse results in these tests regardless other clinical and treatment-related variables. Kaplan-Meier analysis suggested that the probability of achieving poorer results with time was related to RT total dose and field-size, type of PA and age at the time of RT. Four of the five SPECTS performed in irradiated patients revealed a similar altered perfusion in the left temporal lobe cortical region. CONCLUSIONS: In adult patients with operated PA, RT was independently associated with an impairment on verbal memory and executive function, when compared to non-irradiated patients. Our data suggest that diagnosis of acromegaly or Cushing's disease, and age at the time of RT were able to modulate this long-term radio-induced neurocognitive sequelae.

Vascular calcification in patients with nondialysis CKD over 3 years.

BACKGROUND AND OBJECTIVES: Vascular calcification (VC) is common in CKD, but little is known about its prognostic effect on patients with nondialysis CKD. The prevalence of VC and its ability to predict death, time to hospitalization, and renal progression were assessed. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The Study of Mineral and Bone Disorders in CKD in Spain is a prospective, observational, 3-year follow-up study of 742 patients with nondialysis CKD stages 3-5 from 39 centers in Spain from April to May 2009. VC was assessed using Adragao (AS; x-ray pelvis and hands) and Kauppila (KS; x-ray lateral lumbar spine) scores from 572 and 568 patients, respectively. The primary end point was death. Secondary outcomes were hospital admissions and appearance of a combined renal end point (beginning of dialysis or drop >30% in eGFR). Factors related to VC were assessed by logistic regression analysis. Survival analysis was assessed by Cox proportional models. RESULTS: VC was present in 79% of patients and prominent in 47% (AS≥3 or KS>6). Age (odds ratio [OR], 1.05; 95% confidence interval [95% CI], 1.02 to 1.07; P<0.001), phosphorous (OR, 1.68; 95% CI, 1.28 to 2.20; P<0.001), and diabetes (OR, 2.11; 95% CI, 1.32 to 3.35; P=0.002) were independently related to AS≥3. After a median follow-up of 35 months (interquartile range=17-36), there were 70 deaths (10%). After multivariate adjustment for age, smoking, diabetes, comorbidity, renal function, and level of phosphorous, AS≥3 but not KS>6 was independently associated with all-cause (hazard ratio [HR], 2.07; 95% CI, 1.07 to 4.01; P=0.03) and cardiovascular (HR, 3.46; 95% CI, 1.27 to 9.45; P=0.02) mortality as well as a shorter hospitalization event-free period (HR, 1.14; 95% CI, 1.06 to 1.22; P<0.001). VC did not predict renal progression. CONCLUSIONS: VC is highly prevalent in patients with CKD. VC assessment using AS independently predicts death and time to hospitalization. Therefore, it could be a useful index to identify patients with CKD at high risk of death and morbidity as previously reported in patients on dialysis.