Pregnancy in Glomerular Disease: From Risk Identification to Counseling and Management.

Background: Pregnancy involves complex hemodynamic and immune adaptations to support the developing fetus. The kidney assumes a pivotal role in orchestrating these mechanisms. However, renal disease poses a potential risk for adverse maternal-fetal outcomes. While kidney function, hypertension, and proteinuria are recognized as key influencers of risk, the mere presence of glomerular disease, independent of these factors, may wield significant impact. Methods: A brief review of the existing literature was conducted to synthesize current knowledge regarding the interplay between glomerulonephritis and pregnancy. Results: The review underscores the centrality of the kidney in the context of pregnancy and highlights the role of glomerular disease, particularly when active. It emphasizes multifaceted risk modulators, including kidney function, hypertension, and proteinuria. Conclusion: Understanding the dynamics between pregnancy and glomerulonephritis is crucial for optimizing maternal and fetal outcomes. Preconception counseling and collaborative nephro-gynecological management emerge as pivotal components in addressing the unique challenges posed by this medical interplay.

Autoimmunity and Infection in Glomerular Disease.

The ongoing glomerular damage of infections is not limited to the most widely known form of post-streptococcal glomerulonephritis, which is today less common in the Western world; other forms of glomerulonephritis are associated with several bacterial, viral and parasitic pathogens. The mechanisms responsible range from the direct damage of glomerular cells to the formation and deposition of immunocomplexes to molecular mimicry to the secretion of superantigens. Similarly, in the course of glomerular disease, infections are more frequent than in the general population due to the loss of immunoglobulins in urine and the immunosuppressive agents used to treat the autoimmune disease that decrease the activity of the immune system. Recognizing this two-way link, understanding its pathogenetic mechanism, and identifying the most appropriate therapeutic choice are essential for the personalized management of patients. In this continuously developing field, this short review summarizes the current state of the art as support for physicians, who are increasingly involved in managing patients with glomerular disease and infections.

Progress in pharmacotherapy for the treatment of hyperphosphatemia in renal failure.

INTRODUCTION: Among the clinical and metabolic complications of progressive chronic kidney disease (CKD), CKD-mineral bone disorder (CKD-MBD) significantly contributes to morbidity and mortality. While overt and persistent hyperphosphatemia is typical of advanced CKD and requires treatment, other abnormalities of calcium/phosphate metabolism begin to occur since the early stages of the disease. AREAS COVERED: We searched on the PubMed database, without restrictions for language or time range, for randomized clinical trials and meta-analyses investigating phosphate-lowering therapies. The various phosphate binders show different safety profiles and diverse effects on calcium/phosphate metabolism and vascular calcification. The in-depth knowledge of the characteristics of these drugs is crucial to ensure adequate treatment to CKD patients. EXPERT OPINION: A proper control of serum phosphate can be achieved using phosphate binders. These medications may induce side effects. Moreover, data on their impact on clinical outcomes are partly controversial or scarce, especially for the new generation drugs. Hyperphosphatemia favors cardiovascular disease and increases the risk for CKD progression. These effects are partially mediated by fibroblast growth factor 23 (FGF23), a phosphaturic hormone that raises to maintain normal serum phosphate. Since there are no data supporting the use of phosphate-lowering agents when phosphataemia is normal, a key role is played by reducing dietary phosphate intake with the aim to control serum phosphate and the compensatory FGF23 and parathyroid hormone (PTH) increase.

PLAIN LANGUAGE SUMMARY: The progressive reduction in renal function, a condition known as chronic kidney disease (CKD), is characterized by several clinical and metabolic complications. Among them are the alterations of calcium and phosphorous metabolism that are part of the so-called CKD-MBD (chronic kidney disease-mineral bone disorder) and contribute to increase morbidity and mortality, especially due to vascular calcification. Persistent hyperphosphatemia is typical of advanced CKD but other abnormalities occur earlier to maintain normal serum calcium and phosphorus levels. These compensatory mechanisms are also involved in the pathophysiology of CKD-MBD and should be counteracted to improve clinical outcomes of CKD patients. Given the crucial role of hyperphosphatemia, numerous therapeutic strategies have been developed over time to help maintain phosphate serum levels within the normal range and prevent or treat CKD-MBD and its consequences. Phosphate binders act by binding dietary phosphate in the gastrointestinal lumen to prevent its absorption. According to their molecular structure, these drugs can be classified into calcium-based (calcium carbonate, calcium acetate), non-calcium-containing (sevelamer carbonate, sevelamer hydrochloride, lanthanum carbonate), aluminum-containing (aluminum hydroxide), and iron-based (sucroferric oxyhydroxide, ferric citrate) compounds. The various phosphate binders show different safety profiles and diverse effects on calcium/phosphate metabolism and vascular calcification. Despite the ability of hyperphosphatemia to favor CKD-MBD development and cardiovascular risk, there are no data supporting the use of phosphate-lowering agents when serum phosphate is normal also due to the potential adverse effects of long-term therapies. Accordingly, a key role is played by reducing dietary phosphate overload since the first stages of CKD.

Classes of vitamin D status and functional outcome after hip fracture: a prospective, short-term study of 1350 inpatients.

BACKGROUND: Vitamin D depletion is associated with unfavourable outcomes after hip fracture. However, the classes of vitamin D status currently in use, which are defined according to serum calcifediol levels, have not been validated for their predictive capability of the functional recovery. AIM: To investigate the association between serum calcifediol categorized into 4 classes and the functional recovery after hip fracture. DESIGN: Prospective, short-term observational study. SETTING: Rehabilitation hospital in Italy. POPULATION: We evaluated 1350 of 1412 inpatients with hip fracture. METHODS: Serum calcifediol was measured by an immunoenzymatic assay 14.7±4.4 (mean±SD) days after surgery and categorized into 4 classes: I class <12 ng/mL; II class 12-20 ng/mL; III class 21-29 ng/mL; IV class ≥30ng/mL. The functional outcome was assessed by using the Barthel Index. RESULTS: We found a significant difference in Barthel index scores at the end of inpatient rehabilitation across the 4 classes of vitamin D status: χ2 (3, N.=1350) 27.2; P<0.001. The difference persisted after adjustment for 8 covariates (P=0.004). By comparing pairs of classes, we found that Barthel index scores were lower in the 829 patients of the I class than in the 275 of the II (P=0.005) who had in turn Barthel index scores lower than the 132 patients of the III class (P=0.038). Conversely, no significant differences emerged between the patients of the III class and the 114 patients of the IV class (P=0.421). The results did not materially change when Barthel Index effectiveness was substituted for Barthel Index scores as the outcome measure. CONCLUSIONS: Calcifediol levels below 12ng/mL were associated with a worse recovery than those between 12 and 20ng/mL that were in turn associated with a worse recovery than those between 21 and 29 ng/mL. Conversely, no significant differences were found between the patients with calcifediol between 21 and 29ng/mL and those with calcifediol ≥30 ng/mL. CLINICAL REHABILITATION IMPACT: Despite caution due to the observational design, our study suggests that vitamin D depletion should be treated after hip fracture to optimize the functional outcome, with a target level for serum calcifediol of 21-29ng/mL and no further advantages associated with calcifediol levels of 30ng/mL or higher.

Lean Mass and Functional Recovery in Men With Hip Fracture: A Short-Term Prospective Pilot Study.

OBJECTIVE: The aim of the study was to assess the capability of different definitions of low appendicular lean mass (aLM) to predict the short-term functional recovery in men with hip fracture. DESIGN: We investigated 80 of 95 men with hip fracture admitted consecutively to a rehabilitation hospital. Body composition was assessed by dual-energy x-ray absorptiometry. Functional recovery after inpatient rehabilitation was evaluated using Barthel Index scores. RESULTS: The patients with aLM above the cutoff value of 19.75 kg indicated by the Foundation for the National Institutes of Health (FNIH) had significantly higher Barthel Index scores than those with aLM below the cutoff value (P = 0.002). Patients' categorization according to the same threshold (aLM = 19.75 kg) was significantly associated with a Barthel Index score of 85 or higher after adjustment for age, cognitive impairment, hip fracture type, co-morbidities, and medications (odds ratio = 7.17, 95% confidence interval = 1.43-35.94, P = 0.017). Conversely, patients' categorization according to neither Baumgartner's cutoff value (7.26 kg/m(2)) for aLM/height(2) nor Foundation for the National Institutes of Health cutoff value (0.789) for aLM divided by body mass index was significantly associated with the Barthel Index scores. CONCLUSIONS: Categorization according to the Foundation for the National Institutes of Health threshold for aLM, but not to the Foundation for the National Institutes of Health threshold for aLM/body mass index or Baumgartner's threshold for aLM/height, was associated with the short-term recovery in activities of daily living after a hip fracture in men.

The Mini-BESTest: a review of psychometric properties.

The Mini-Balance Evaluation Systems Test (Mini-BESTest) has been identified as the most comprehensive balance measure for community-dwelling adults and elderly individuals. It can be used to assess balance impairments in several other conditions, mainly Parkinson's disease and stroke. Despite increasing use of the Mini-BESTest since it was first published 5 years ago, no systematic review synthesizing its psychometric properties is available. The aim of this study was to provide a comprehensive review of the psychometric properties of the Mini-BESTest when administered to patients with balance deficits because of different diseases. A literature search was performed on articles published before July 2015 in journals indexed by MEDLINE and Scopus databases. The search produced 98 papers, 24 of which fulfilled the inclusion criteria for this review. Most papers (n=19) focused on patients affected by neurological diseases, mainly Parkinson's disease. In 21 papers, the psychometric characteristics were analyzed using Classical Test Theory methods and in only three papers was Rasch analysis carried out. This review shows the interest of researchers in the Mini-BESTest despite the short time frame since its first publication. The Mini-BESTest is used widely in both clinical practice and research. The results support the reliability, validity, and responsiveness of this instrument and it can be considered a standard balance measure. However, it would be valuable to learn more about how this scale performs in different diseases causing balance deficits and to better define the minimal clinically important difference for each disease.

Age and QT variability index during free breathing, controlled breathing and tilt in patients with chronic heart failure and healthy control subjects.

UNLABELLED: The QT variability index (QTVI) indicates temporal dispersion in myocardial repolarization, and a high QTVI is associated with a propensity for sudden death from malignant ventricular arrhythmias in subjects at high risk. In this study, the authors assessed the effects of free breathing, controlled breathing, and sympathetic stress (tilt) on the QTVI in patients with chronic heart failure (CHF) and healthy control subjects. The authors also examined the influence of age on the same variables. To obtain normative data, they calculated 95% confidence intervals for healthy subjects grouped according to age. Under all experimental conditions, the QTVI was larger in the CHF group overall and in the age subsets than in controls. In patients and controls, the QTVI increased significantly during tilt, although no differences were found between the QTVI measured during free and controlled breathing. In healthy controls, the following variables correlated significantly with the QTVI: age and baseline heart rate (P < 0.001). In patients with CHF, aging had no influence on the QTVI. CONCLUSION: Age, sympathetic stress, and CHF all tend to increase the QTVI and could potentially induce sudden death. Further studies should assess the usefulness of the QTVI as a marker predicting sudden cardiac death under the various conditions of risk.

Influence of cardiac-resynchronization therapy on heart rate and blood pressure variability: 1-year follow-up.

BACKGROUND: Several studies have shown that cardiac-resynchronization therapy (CRT) improves haemodynamic function, cardiac symptoms, and heart rate variability (HRV) and reduces the risk of mortality and sudden death in subjects with chronic heart failure (CHF). In subjects with CHF, power spectral values for the low-frequency (LF) component of RR variability < or =13 ms2, are associated with an increased risk of sudden death. AIMS AND METHODS: To assess whether spectral indexes obtained by power spectral analysis of HRV and systolic blood pressure (SBP) variability could predict malignant ventricular arrhythmias in patients with severe CHF treated with an implantable cardioverter-defibrillator (ICD) alone or with ICD+CRT. In addition, changes in non-invasive spectral indices using short-term power spectral analysis of HRV and SBP variability during controlled breathing in 15 patients with CHF treated with an ICD alone and 16 patients receiving ICD+CRT, were assessed pre-treatment and at 1 year. RESULTS: Arrhythmias necessitating an appropriate ICD shock were more frequent in subjects who had low LF power. CRT improved all spectral components, including LF power. CONCLUSIONS: Low LF power values predict an increased risk of malignant ventricular arrhythmias; after 1 year of CRT most non-spectral and spectral data, including LF power, improved. Whether these improvements lead to better long-term survival in patients with CHF remains unclear.

Autonomic cardiovascular control and diastolic dysfunction in hypertensive subjects.

BACKGROUND: Early hypertension is associated with left ventricular diastolic dysfunction due to increased end-diastolic pressure. This increase, through the cardiopulmonary reflexes, can influence autonomic cardiovascular control. METHODS: We assessed autonomic nervous system modulation of cardiovascular signals by power spectral analysis of RR interval and systolic arterial pressure variabilities in subjects with recently diagnosed hypertension with or without diastolic dysfunction and in normotensive control subjects. RESULTS: Both hypertensive groups had higher low-frequency (LF) power expressed in normalized units (NUs) than normotensive controls (p < 0.05; p < 0.001) during controlled breathing at rest. The LF spectral index measured after tilt was greater in hypertensive subjects with diastolic dysfunction than in those without (p < 0.05). LF NUs measured at rest correlated significantly with the E/A wave ratio and after tilt with the E-wave deceleration time. CONCLUSIONS: These results seem to indicate that in subjects with recently diagnosed hypertension sympathetic modulation of the sinus node prevails. During tilt, a maneuver designed to stimulate systemic arterial and cardiopulmonary baroreceptor reflexes, hypertensive subjects with diastolic dysfunction, who presumably also have higher end-diastolic pressures, seem to have greater sympathetic modulation of the sinus node than hypertensive subjects without diastolic dysfunction.

Power spectral analysis of heart rate variability as a predictive test in choosing the most effective length for tilt-training.

BACKGROUND: In patients with refractory neurally mediated syncope, tilt training--standing motionless against a wall for increased periods of time per day over one month--can often eliminate recurrent episodes and reduce presyncopal symptoms. We designed dual retrospective and prospective studies to assess cardiovascular autonomic function in subjects with recurrent syncope and identify the most effective length of tilt training between one and three months. METHODS AND RESULTS: In the retrospective study, before tilt training, and in the prospective study, before and after training, all subjects underwent a recording for short-term spectral analysis of heart rate and systolic blood pressure variability. Before tilt-training, autonomic nervous system function differs in patients with recurrent neurally mediated syncope who respond to tilt training for one month and those who do not. "Responders", patients experiencing no episodes of syncope during the 12-month follow-up, had higher low-frequency power of RR (LF(RR)) (p < 0.05) and LF(RR) in normalized units (NU) (p < 0.001) and lower high-frequency power (HF(RR)) (p < 0.05) and HF(RR)NU (p < 0.001) than "non-responders", patients reporting at least one syncopal episode during the 12-month follow-up. In the retrospective study, no difference was found between spectral data for "non-responders" with positive responses to tilt test with and without nitro derivatives. Prolonging tilt-training to three months increased the number of responders (late-responders) by 80% (p < 0.001) and power spectral analysis of heart rate variability (HRV) before tilt training can identify late-responders by their low LF(RR)NUs (<40) and high HF(RR)Nus (>60). Furthermore in late-responders, tilt training brings about a change in cardiovascular autonomic function: at 3 months, LF(RR)NUs increase and HF(RR)NU diminish. CONCLUSION: Power spectral analysis of HRV seems to be a useful tool to preselect patients who are most likely to benefit from prolonged therapy, thus increasing compliance.

Factors influencing heart rate variability power spectral analysis during controlled breathing in patients with chronic heart failure or hypertension and in healthy normotensive subjects.

A decreased LFP (low-frequency power) spectral component of HRV [HR (heart rate) variability] is a risk factor for sudden death in patients with CHF (chronic heart failure). In the present study, we evaluated factors (age, arterial pressures and HR) influencing LFP and HFP (high-frequency power) components in short-term recordings during controlled breathing in patients with CHF or hypertension, and healthy normotensive subjects. In patients with CHF, we also compared LFP values with known markers of sudden death [NYHA (New York Heart Association) class, HR and ejection fraction]. All HRV measures were significantly lower in patients with CHF than in hypertensive and normotensive subjects (P<0.001), and in hypertensive than in normotensive subjects (P<0.05). Stepwise multiple regression analysis showed that, in patients with CHF, LFP was inversely associated with NYHA class (beta=-0.5, P<0.0001) and HR (beta=-0.2, P=0.001) and was positively associated with ejection fraction (beta=0.28, P<0.0001). In patients with CHF, LFP remained unchanged with age. In normotensive and hypertensive subjects, HFP decreased with age, but in patients with CHF it did not. In the >/=60<70 and >/=70 years of age subgroups, we found no difference between HFP in the three groups studied. Hence, in normotensives and hypertensives, LFP tended to diminish with age (beta=-0.4, P<0.0001 in normotensives; beta=-0.4, P<0.001 in hypertensives) and was inversely associated with HR (beta=-0.2, P=0.002 in normotensives; beta=-0.3, P=0.002 in hypertensives). Conversely, in patients with CHF, LFP is predominantly influenced by NYHA class, HR and ejection fraction, but not by age. LFP might therefore increase the sensitivity of factors already used in stratifying the risk of sudden death in patients with CHF.

Influence of L-arginine and vitamin C on the autonomic nervous system in chronic heart failure secondary to ischemic cardiomyopathy.

In this study, we used spectral analysis to assess changes in respiratory recording variability during infusion of L-arginine and vitamin C, individually or together, in patients with chronic heart failure. We found that healthy subjects have a substantial ability to modulate sympathetic-mediated peripheral vascular resistance through endothelial synthesis of nitric oxide. Patients with chronic heart failure lose this ability.

Heart rate and blood pressure variability in subjects with vasovagal syncope.

Autonomic nervous system control in subjects with vasovagal syncope is controversial. In the present study, we used short-term spectral analysis to evaluate autonomic control in subjects with recurrent vasovagal syncope. We assessed the ability of spectral indices of HR (heart rate) variability to predict tilt-test responses. A series of 47 outpatients with recurrent vasovagal syncope and with positive responses to head-up tilt testing underwent a further study of RR variability during controlled breathing at rest and during tilt testing. During controlled breathing, RR interval variability of total power (TP(RR); P<0.001), low-frequency power (LF(RR); P<0.05), high-frequency power (HF(RR); P<0.001) and HF expressed in normalized units (HFnu(RR); P<0.001) were all higher, and LF expressed in normalized units (LFnu(RR)) and LF/HF ratio were lower in subjects with vasovagal syncope than in controls (P<0.001). To assess the ability of spectral components of RR variability to predict tilt-test responses, we prospectively studied 109 subjects with recurrent vasovagal syncope. The two normalized measures, HFnu(RR) and LFnu(RR), determined during controlled breathing alone predicted a positive tilt-test response (sensitivity, 76%; specificity, 99%; positive predictive value, 96%; and negative predictive value, 90%). During tilting, subjects with vasovagal syncope had lower SBP (systolic blood pressure; P<0.05), LF component of peak SBP variability (LF(SBP)) and LFnu(RR) than controls, and higher TP(RR), HF(RR), HFnu(RR) and alpha HF (P<0.001). These spectral data indicate that vagal sinus modulation is increased at rest in subjects with vasovagal syncope. Spectral analysis of RR variability during controlled breathing, a procedure that predicts tilt-test responses, could be a useful guide in choosing the method of tilt testing.

Influence of vitamin C on baroreflex sensitivity in chronic heart failure.

Chronic heart failure (CHF) reduces baroreflex sensitivity. Low baroreflex sensitivity, a risk factor for sudden death, could arise partly from CHF-dependent endothelial dysfunction. Vitamin C at high doses has a protective role against CHF-related endothelial damage. This study was conducted to investigate the effect of vitamin C on baroreflex sensitivity in CHF. A study group of 33 subjects with CHF secondary to postischemic dilated cardiomyopathy with an ejection fraction

Effects of long-term beta-blocker (metoprolol or carvedilol) therapy on QT variability in subjects with chronic heart failure secondary to ischemic cardiomyopathy.

Chronic heart failure (CHF) is a risk factor for sudden death. Temporal and spatial changes in repolarization are among the most studied mechanisms for inducing fatal ventricular arrhythmias. Beta blockers effectively reduce the risk of sudden death in CHF. Our aim in this study was to investigate changes induced by metoprolol and carvedilol on the QT variability index (QTVI), a new measure reflecting the temporal heterogeneity of cardiac repolarization. A total of 82 subjects, who were in New York Heart Association functional class II or III, underwent short-term spectral analysis of RR and QT variability before and after a 1-year course of high-dose metoprolol (40 subjects) or carvedilol (42 subjects) at baseline (rest) and after sympathetic stress (head-up tilt). At rest, both drug-treated groups had lower QTVI (p <0.001) than after placebo, but during tilt patients treated with carvedilol had a lower QTVI than those treated with metoprolol (p <0.05). Although both beta-blocker treatments helped to normalize the QTVI measured in normal subjects at rest, they each differentially altered the index after tilt. Carvedilol seemed to improve the QTVI more than metoprolol.