Stephanie Loder

Adults with normal kidney function who have comorbid depression are more likely to experience a decline in kidney function, as measured by estimated glomerular filtration rate (eGFR) based on serum creatinine and cystatin C (eGFRcr-cys), according to 

 from the American Society of Nephrology published in 

Clinical Journal of the American Society of Nephrology

The study also found that depression, a common condition in middle-aged and older adults, can contribute to both mental and physical problems and is a potential cause of rapid kidney function decline in patients with 

“While our study does not show causality, it demonstrated that high depressive symptoms were significantly associated with rapid decline in kidney function among Chinese adults with normal kidney function,” said lead investigator Xianhui Qin, MD (Nanfang Hospital, Southern Medical University, in China), 

The study cohort comprised 4763 individuals (mean [SD] age, 59 [9] years) with healthy kidneys (eGFR of 

) enrolled from the China Health and Retirement Longitudinal Study. Their primary outcome was rapid decline in kidney function, defined as an annual eGFR decline of 

, and the secondary outcome of interest was an annual eGFR decline of 

Overall, during the median (interquartile range [IQR]) follow-up of 4 (IQR, 3.92-4.00) years, 6% of participants experienced rapid decline in kidney function. Following adjustment for such covariates as demographic, clinical, or psychosocial characteristics, a significant positive association was seen between baseline symptoms of depression and rapid decline in kidney function (adjusted odds ratio [aOR], 1.15; 95% CI, 1.03-1.28).

eGFRcr-cys was a mean 89 (15) mL/min/1.73 m

 by the time of the exit interview. Thiry-nine percent of participants had high symptoms of depression at baseline as measured by Center for Epidemiologic Studies Depression (CES-D) score of 10 or above.

Qin called CKD “a leading risk factor for cardiovascular disease, kidney failure, and mortality worldwide,” adding, “the identification of more modifiable risk factors may possibly reduce the huge burden of CKD and its related complications by leading to early detection and prevention.”

39% greater chance of rapid kidney decline was seen among the participants with high depressive symptom (aOR, 1.39; 95% CI, 1.03-1.88) vs low depressive symptoms

24% and 118% greater chances of rapid kidney decline were seen among those with moderate (aOR, 1.24; 95% CI, 0.90-1.72; total CES-D score, 10 to < 21) and higher (aOR, 2.18; 95% CI, 1.32-3.62; CES-D score, 

 21) depressive symptoms, respectively, vs low (total CES-D score, < 10)

44% greater chance of rapid kidney decline for patients in depressive symptom quintiles 4 and 5 (aOR, 1.44; 95% CI, 1.07-1.93; total CES-D score, 

 9) vs quintiles 1-3 (total CES-D score, < 9)

Adjustment for low-density lipoprotein cholesterol level or for a possible association between depressive symptoms and eGFRcr or eGFRcys alone did not change the authors’ findings.

“If further confirmed, our data provide some evidence for depressive symptom screening and effective psychosocial interventions to improve the prevention of CKD,” Qin concluded.

Maggie L. Shaw contributed to this article.

Zhang Z, He P, Lie C, et al. Association of depressive symptoms with rapid kidney function decline in adults with normal kidney function. 

2021;16(6):889-897. doi: 10.2215/CJN.18441120

Articles

Adults with normal kidney function who have comorbid depression are more likely to experience a decline in kidney function and have mental and physical impairments from that decline.

Potential Link Found Between Depression, Kidney Failure 

 disorder narcolepsy is characterized by excessive daytime sleepiness (EDS), and studies show it can do extensive damage if not treated. It also is associated with cataplexy, the loss of muscle tone triggered by intense, usually positive, emotions while awake. Other symptoms include hallucination and sleep paralysis. Onset is typically within the first 2 decades of life, and up to 65% of cases happen before age 20.

 a rare disorder, affecting just 1 of 2000 individuals, and there is no cure; current treatment is to address symptoms. Results of a recent review 

which highlights that the total incidence is 20 to 50 cases per 100,000 individuals worldwide—show that the condition might instead be an autoimmune disorder that could benefit from immunotherapy.

However, previous results on study in this area are mixed. More well known, the authors point out, is that patients with narcolepsy “have lower education and higher unemployment rates compared to the general population and present with higher frequency of other medical/psychiatric comorbidities and concurrent medication usage, and reduced rates of marriage/cohabitation.”

Their review covered supportive evidence for immunotherapy’s use in treating narcolepsy, outcomes, current issues, and future directions.

The evidence the authors found supporting a possible autoimmune-related role in the narcolepsy space are the following:

Loss of hypocretin-secreting cells, which is a core feature of narcolepsy type 1 (NT1), while sparing melanin-concentrating hormone neurons

A possible association between the hypocretin-secreting cell loss and the 

An increased frequency of narcolepsy among people with strep throat diagnosed before the age of 21, with 

antibody levels elevated in patients’ sera by the 3-year mark after strep onset vs age-matched controls

A link between narcolepsy and the influenza A virus subtype H1N1 (A/H1N1) was seen recently in China, where the incidence of narcolepsy increased 3 times within a 6-month period during a peak of the A/H1N1 pandemic

An increase in cases was seen after people were vaccinated with the H1N1 Padenmrix vaccine, leading to speculation that the autoimmune destruction of hypcretin neurons could be triggered with H1N1 flu antigens.

A greater risk of developing narcolepsy was seen in the presence of antigenic peptides to CD4+ T cells (

is an human leukocyte antigen class 2 molecule, and these types of molecules “are responsible for the presentation of antigenic peptides to CD4+ T cells”)

can increase the risk of narcolepsy, even more so in the presence of comorbid cataplexy.

In addition, immunotherapy use results were mixed:

Overall negative correlation between the use of corticosteroids and narcolepsy, particularly a return of EDS and cataplexy following treatment taper

Cataplexy improvement seen after intravenous methylprednisolone treatment

Plasmapheresis has produced only transitory benefits, and even then in the 1 person treated with the method for NT1

Intravenous immunoglobulin (IVIG) improved outcomes in that administration soon after NT1 onset improved the frequence and severity of cataplexy and Epworth Sleepiness Scale Scores improved; however, hypocretin-1 concentration in cerebrospinal fluid was unchanged or elevated

IVIG benefits were chiefly considered transient, in that persistent changes were not noted, benefits were deemed “short lived,” or the treatment “failed to show an effect”

Noting that a majority of the evidence they found on immunotherapy use in narcolepsy came from small, uncontrolled case studies with “different treatment schemes and highly heterogeneous outcome measures,” the investigators said current evidence does not support immunotherapy’s use for this disease state.

“Randomized controlled clinical trials are needed to provide substantial evidence and avoid bias related to placebo effect and to spontaneous disease improvements,” they noted. “No disease-modifying cure is available, calling for future research on treatment strategies as well as on diagnostic approaches able to identify patients who will develop NT1 among those complaining of only EDS.”

The time is ripe, they concluded, for randomized, double-blind, placebo-controlled trials into the use of immunotherapy in narcolepsy.

Giannoccaro MP, Liquori R, Plazzi G, Pizza F. Reviewing the clinical cmplications of treating narcolepsy as an autoimmune disorder. 

These review results were mixed on the use of immunotherapy to treat narcolepsy, with benefits typically being temporary.

More Study Needed on Benefits of Immunotherapy in Narcolepsy

A recent review explored gender differences in 

 and considered several possible explanations for these differences.

Understanding why this difference exists could assist with finding new therapies, said the authors, 

Chronic cough, which lasts longer than 8 weeks, affects quality of life and is one of the main reasons people seek medical treatment, the authors noted. Reasons for chronic cough in nonsmokers include asthma, bronchitis, postnasal drip, and cough related to gastroesophageal reflux disease (GERD).

Worldwide, about 2/3 of all patients with chronic cough are female, although in China it varies by region and prevalence may be about the same between both sexes. This apparent lack of a gender difference in China may be due to the types of patients enrolled in studies or to certain aspects of their health care system.

One reason that more women have chronic cough may be their increased sensitivity. In people with or without chronic cough, women have more cough sensitivity than men as seen by differences in cough receptors, of which there are 2 types: myelinated Aδ-fiber and unmyelinated C-fiber.

Unmyelinated C-fiber is sensitive to chemical substances such as capsaicin and endogenous mediators, but their function is affected by the expression of different ion channels, which include transient receptor potential vanilloid 1 (TRPV1) and transient receptor potential ankyrin 1 (TRPA1). Cough challenges can be provoked by the selective TRPA1 agonist allyl isothiocyanate (AITC) or the TRPV1 agonist capsaicin.

Women have more obvious AITC and capsaicin cough sensitivity than men, wrote the authors, citing a 2019 study.

They also noted a 2015 study that indicated a P2X3 receptor antagonist could reduce cough frequency, as P2X3, an ATP-gated ion channel, mediates cough neuronal hypersensitivity.

The female sex hormones estrogen and progesterone mediates these ion channels, but this cannot fully account for chronic cough in postmenopausal women. These hormones also have an effect on eosinophils, mast cells, histamine, and inflammatory mediators, but more research is needed to examine the effect of sex hormones on mediators related to atopic disease, which is linked to cough.

The 2 hormones can also affect laryngeal dysfunction, GERD, and obstructive sleep apnea, but again, further research is needed in this areas as well, the authors reported.

Allison Inserro contributed to this report.

Bai B, Sha B, Xu X, Yu L. Gender difference in chronic cough: Are women more likely to cough? 

. Published online May 7, 2021. doi: 10.3389/fphys.2021.654797

Understanding why this difference exists could assist with finding new therapies, said the authors.

Analysis Explores Possible Reasons for Gender Differences in Chronic Cough

Losing weight rapidly allowed participants with 

 (T2D) to control their high blood pressure (BP) even as they reduced or eliminated their antihypertensive drugs, according to results of a trial involving a liquid formula diet.

, is a secondary analysis of the Diabetes Remission Clinical Trial (DiRECT), an intervention tested in primary care practices in the United Kingdom.

The liquid total diet replacement (TDR) provided about 830 kcal/day with automatic reductions in all nutrients to induce rapid weight loss over 12 to 20 weeks. Antihypertensive drugs were withdrawn at the start of the diet, and BP was monitored regularly. Reintroduction of therapy was based on clinical guidelines.

Participants were randomized to intervention or a control group and all had been diagnosed with T2D within the past 6 years. Other inclusion criteria included having glycated hemoglobin ≥ 6.5%, or ≥ 6.1% if on T2D therapies, aged 18–65 years, and body mass index (BMI) 27–45 kg/m2.

Of 143 participants, 62 had no hypertension and 81 did; of those 81 patients, 78 were taking antihypertensive medications.

Of the 78, most stopped taking their medications completely as they began the diet, and 9 did not.

The overall mean BP fell significantly from the start of TDR and was significantly lower when TDR total diet replacement finished at week 20. It remained lower at 12 and 24 months

Of the 78 participants previously on treatment for hypertension, 65 (83%) stopped all antihypertensive and diuretic medications as per protocol, and 4 stopped some drugs.

These 69 participants saw no immediate change in BP, but their mean BP fell significantly from 9 weeks. While BP did not rise excessively, antihypertensive drugs were reintroduced during TDR to manage raised BP for 27.5% of the participants, even though they had some weight loss.

Participants who were on 2 drugs, as opposed to 1, were more likely to need their BP therapies reintroduced.

At 24 months, 28% of those who stopped their antihypertensive therapies remained off them.

Of the 53 participants who achieved T2D remission through the diet, 31 had been previously treated for hypertension.

The researchers said that while the protocol was safe and effective, careful BP monitoring is necessary; 51 participants reported mild to moderate dizziness during TDR, suggesting some postural hypotension. Of these participants, 15 had a history of dizziness before starting the diet.

The study was conducted by researchers at the Universities of Glasgow and Newcastle.

“We wanted to evaluate the safety and efficacy of withdrawing blood pressure medication when beginning our specially-designed weight-loss programme for type 2 diabetes, and we are really pleased with the results,” Mike Lean, MD, MA, MB, FRCPS, FRSE, clinical senior research fellow from the University of Glasgow 

. “Our study shows that, in addition to possible remission from type 2 diabetes, there are other very important health benefits, as weight loss is a very effective treatment for hypertension and its associated serious health risks.”

 Antihypertensive medication needs and blood pressure control with weight loss in the Diabetes Remission Clinical Trial (DiRECT). 

Published online May 31, 2021. doi: 10.1007/s00125-021-05471-x

The UK analysis came from a larger study that examined the effects of a liquid total diet replacement program to induce remission in type 2 diabetes (T2D).

Stephanie Loder

Articles

Potential Link Found Between Depression, Kidney Failure

More Study Needed on Benefits of Immunotherapy in Narcolepsy

Analysis Explores Possible Reasons for Gender Differences in Chronic Cough

Liquid Diet for T2D Lowers Blood Pressure, Reduces Medication Use