Larry Hanover

Last summer, the American Society of Nephrology (ASN) and the National Kidney Foundation (NKF) formed a joint task force to evaluate dropping the long-standing use of Black race in an equation estimating kidney function—the estimated glomerular filtration rate (eGFR).

Journal of the American Society of Nephrology (JASN) 

showed that eliminating this race adjustment would double the estimated prevalence of 

Such a shift would have wide-ranging effects on clinical decisions, including medication dosing, referrals for specialty care, and eligibility for kidney transplantation and kidney donation, the researchers said.

GFR is the total volume of filtrate passing through the glomeruli each minute, but that is challenging to assess in real time in a physician’s office. Using serum creatine, factoring in age, height, weight, and gender, gives an estimate. Including Black race in the eGFR tacks on a multiplier, which then assigns higher values to Black patients. As higher values indicate better kidney function, there has been increasing recognition that this may lead to inequitable and delayed care in treating CKD.

Some medical centers have already moved to stop using the multiplier, as inclusion of race, a social and not a biological construct, has care implications.

In the current study, researchers used 2 national samples, the National Health and Nutrition Examination Survey (NHANES) from 2015-2016 and the Veterans Affairs (VA) Health Care System from 2015, and estimated the prevalence of CKD if race adjustments were removed from eGFR equations.

The estimated prevalence of CKD (defined as GFR < 60mL/min/1.73m

) among Black adults would double—from 5.2% to 10.6% in the NHANES sample and from 12.4% to 21.6% in the VA sample—if race adjustments were eliminated, the study found.

There were also reclassifications on severity of disease. Among all Black individuals in the NHANES database, 5.6% (95% CI­, 4.0-7.2%) were reclassified to CKD stage 3. Of those previously classified as CKD stage 3, 6.3% (95% CI, 2.7%-15.4%) were reclassified to CKD stage 4.

In the veteran population, the study examined the 6 most prescribed medications with dosing recommendations dependent on kidney function, including the antibiotic ciprofloxacin. With a new CKD classification, 5.8% to 41.0% of Black veterans might have doses adjusted or halted, including 41.0% taking gabapentin, 33.5% on ciprofloxacin, 24.1% taking metformin, 6.9% using atenolol, 6.6% taking rosuvastatin, and 5.8% taking tramadol.

One concern among clinicians was that the prediction of kidney failure would rise by removing the race-based algorithm. However, accuracy was marginally improved overall, with better calibration at higher levels of predicted risk. Among Black patients, the mean estimated 2-year risk of kidney failure increased from 2.7% to 3.4%. Analysis indicated both models overestimated kidney risk slightly in the overall population and underestimated it among the Black population at levels of predicted risk of at least 5%.

The inclusion of an adjustment for Black race may have improved precision in study populations, the researchers said. However, there is no definitive way to determine the race of individuals who, for example, consider themselves multiracial. The lack of biologic underpinnings raises concerns for “misuse of race as a biological variable,” they wrote.

The 1999 landmark study that proposed the eGFR and included a coefficient for Black patients 

did so on the basis of 3 flawed, small, poor-quality studies

, according to a presentation at last year’s Kidney Week.

Estimating GFR is challenging and cumbersome. Use of a confirmatory test such as direct measurement of GFR or cystatin-c based estimation methods have been proposed to help make drug dosing more precise, but their lack of widespread availability and long turnaround times limit practicality.

Dropping the race adjustment in calculating the eGFR might reduce health disparities in treating kidney disease, but increase health disparities in other ways, said one of the authors in a statement, who nonetheless called the conversation one that is “long overdue.”

“The focus has rightly been on the ways in which race adjustment might disadvantage Black patients, but on the other hand, simply dropping race adjustment and leaving it at that may result in unintended consequences, such as less use of first-line treatments for diabetes and diabetic kidney disease,” cautioned Manjula Kurella Tamura, MD, MPH, of the VA Palo Alto Health Care System and Stanford University. “The fact that there would be potentially large changes in medication prescribing is not an argument for keeping the race adjustment. Rather, it's a reminder that small changes in GFR estimates can have large effects at the population level. Estimates of GFR are less precise than we often assume them to be.”

The ASN and the NKF have endorsed dropping race modifiers from creatinine-based GFR equations to estimate kidney function, and 

 just published an interim report about the first phase of its work in the May issue of 

The report states that the task force is working on recommendations on an alternative to the eGFR, taking into account, among other things, “biomarker choice, inputs and their availability for estimation and reporting, representation of diversity in participants in research foundational to equation development, and equation bias and accuracy compared with measured GFR for different race and ethnic groups.”

Allison Inserro contributed to this report.

Duggal V, Thomas I-C, Montez-Rath M, et al. National estimates of chronic kidney disease prevalence and potential impact of estimating glomerular filtration rate without race. 

. Published online May 6, 2021. doi:10.1681/ASN.2020121780

Articles

The study results were released as nephrologists and others are awaiting the findings of a joint task force of 2 national kidney organizations looking at alternative approaches to estimating glomerular filtration rate.

Dropping Race From eGFR Doubles Estimated Prevalence of CKD in Black Populations

Defining the characteristics and better understanding laryngeal hypersensitivity may help in the treatment of refractory and unexplained 

Researchers reviewed data from questionnaires filled out by patients with refractory chronic cough (RCC) and unexplained chronic cough (UCC), which are common problems seen in primary care and subspecialty clinics.

 found cough hypersensitivity was documented in all 60 patients analyzed, with multiple cough triggers occurring in 75%. The study also found that 95% complained of laryngeal sensations that triggered their coughs, 50% reported voice abnormalities, and 25% reported difficulty breathing in the upper airway.

Examination by nasoendoscopy documented laryngeal functional abnormalities in 44 of 60 patients, all of whom were examined within the University of Utah Health System. Data was collected in 2019.

In most patients, cough is believed to be caused by gastroesophageal reflux disease (GERD), rhinosinusitis, or cough variant asthma. However, those causes fail to account for many cases. Estimates place cases of UCC and RCC at 5% to 42% of chronic cough patients.

Cough hypersensitivity, characterized by decreased cough thresholds and nonnoxious stimuli, has been proposed as an explanation for refractory and unexplained cough.

In the study, nearly all patients (57 of 60) described a tickle, lump or sensation in the throat, irritation, dry throat, and presence of mucus in the throat. Women reported a higher prevalence of abnormal throat sensations, which were associated with increasing age. Nearly half of patients reported frequent throat clearing.

More than half of patients reported voice abnormalities, which included hoarseness, loss of voice with talking or singing, change in pitch, or raspy voice quality. One-quarter reported symptoms of upper airway dyspnea, such as throat constriction and difficulty getting in air.

Structural abnormalities were found in nearly half of patients, with a majority having reddening or irritation as well as edema. Only 5 patients had normal laryngeal appearance and function. Of the 60 patients, 24 had overlapping structural and functional abnormalities.

Treatment included behavioral speech therapy (BST; 56 of 60 patients), with 34 completing the course of treatment. Management of comorbid obstructive sleep apnea (OSA) was also recommended, with 43% of patients completing treatment and 22 new diagnoses of OSA given. Treatment for OSA patients included behavioral speech therapy, continuous positive airway pressure therapy, and management of other conditions such as GERD.

Cough hypersensitivity in RCC and UCC is attributed to changes in cough pathways within the central and peripheral limbs of cough reflex pathways. Peripheral sensitization and alteration in modulating influences of central descending pathways are believed related to cough, the authors said. However, much remains to be understood about mechanical causes in terms of neurostructure and neurofunctionality

However, they added, “there is increasing clinical recognition of the role of the larynx and surrounding structures in chronic cough.”

The effectiveness of BST points to a role for laryngeal hypersensitivity in diagnosing chronic cough, the authors said. Many such patients are treated for GERD or OSA without success in decreasing cough.

Nearly 75% of patients in the study were female, with 85% of all patients over age 40. Patients over age 70 comprised one-third of patients and had the longest duration of cough.

Sundar KM, Stark AC, Hu N, et al. Is laryngeal hypersensitivity the basis of unexplained or refractory chronic cough? 

. 2021;7(1):00793-2020. doi:10.1183/23120541.00793-2020

Laryngeal hypersensitivity may be a key factor in refractory and unexplained cough.

Laryngeal Hypersensitivity Eyed as a Reason Behind Refractory, Unexplained Cough

A new study has found that patients with 

 have a higher level of interleukin-30 (IL-30) than healthy patients.

The results point to IL-30 having a role in the proliferation of epidermal cells during the development of psoriasis, according to a study 

published in the Journal of International Medical Research

. The authors said larger-scale studies are required to further understand the cytokine’s role in causing psoriasis.

Psoriasis is a chronic autoimmune and skin inflammatory condition that affects 2% of the global population, including 6.7 million Americans. It is associated with several other conditions that lead to reduced immunity, including type 2 diabetes, inflammatory bowel disease, heart disease, psoriatic arthritis, anxiety, and depression. Understanding the role of cytokines in psoriasis is important because of their role in activating immune cells, the authors said.

IL-30 is mainly produced by immune cells originating from the bone marrow, including macrophages, monocytes, microglia, and dendritic cells and is activated in various ways. It is involved in initiating both classic and trans-signaling pathways, suggesting it may have different effects on various cell types, the authors said. IL-30 independently plays a significant role in the development and progression of autoimmune diseases like psoriasis by regulating T helper and Th17 cells.

Further study of IL-30 in psoriasis lesions will require further in vitro and in vivo studies, they said. However, their study findings indicate downregulation of IL-30 expression may reduce the proliferation of abnormal keratinocytes and other related features of psoriasis.

The study examined serum collected from 26 patients with psoriasis and 26 from a control group in China between 2018 and 2019. Patients were divided into three groups according to their psoriasis area severity index (PASI) score: mild (PASI less than 10), moderate (PASI 10-29), and severe (PASI greater than 30). Mean age was 45.5 [12.8] years for patients with psoriasis and 40.1 [16.2] years for the healthy controls. More than two-thirds of the psoriasis group were men, compared with 46.2% for the control group.

Results showed a significant difference in mean IL-30 concentration for patients with psoriasis (111.96 pg/ML) vs. the control group (33.76 pg/ML) (

In addition, a positive correlation was found between IL-30 levels and PASI scores in psoriasis cases (rho = 0.174). The correlation was weak and not statistically significant.

Consistent with results of previously reported studies in psoriasis, the study showed that the serum level of IL-30 was not associated with age or sex. Age at diagnosis and duration of the disease in patients with psoriasis also were not significantly associated with the mean rank of the serum IL-30 level.

The study showed a predominance of male patients with psoriasis, whereas others reported a higher prevalence of women. The authors said selection bias may have contributed to their results.

The presence of elevated levels of cytokines in serum levels in psoriasis previously have been showed to be correlated with disease severity. Determining the specific or combined role of cytokines “can revolutionize the diagnosis and treatment of psoriasis,” the authors wrote.

Omar NS, Long X, Xian J, et al. Serum interleukin-30 level in patients with psoriasis and its correlation with psoriasis severity: a case-control study. 

2021;49(4):1-9. doi:10.1177%2F03000605211004039

Patients with psoriasis have a higher level of interleukin-30 (IL-30) than healthy patients, according to a recent study.

Study Examines Role of Interleukin-30 in Psoriasis

Imaging findings suggest a significant relationship between patients with progressive chronic kidney disease (CKD) and cerebral small vessel disease (CSVD), according to a new study.

Researchers undertook the study, published in 

, with the hypothesis that since the kidney and brain share susceptibilities to vascular injury, kidney impairment might be predictive of the presence and severity of CSVD. Results show such a relationship, with progressive CKD patients exhibiting a greater degree of white matter degeneration and more cerebral microbleeds.

The reason behind the relationship is yet to be understood. Nevertheless, the authors said, there is the possibility that estimated glomerular filtration rate (eGFR) “may not only contribute to the evaluation of renal functions in patients with CKD but may also find utility in the prediction of cerebral small vessel disease. eGFR may reflect a more generalized process indicative of underlying cerebral damage, not limited solely to the kidney.”

The study evaluated 52 patients from December 2015 to December 2017 with chronic nephritis and CKD who were classified into a group with progressive disease (n = 17) and stable disease (n = 35). MRIs were performed to evaluate features of silent CSVD of both groups, including enlarged Virchow-Robin spaces (VRS; also known as perivascular spaces), white matter lesions (WML), lacunar infarcts (LI; small infarcts in the deep cerebral white matter, basal ganglia, or pons), and cerebral microbleeds (CMB).

Results showed WML and CMB in the progressive group worsened at follow-up (10-20 months) compared with initial exam (

 = .004 and .020, respectively), while there was no significant change in the stable group. No significant difference was found at follow-up for those with VRS and LI.

In addition, the study found eGFR was significantly correlated with VRS, WML, and CMB at follow-up (

Researchers suspected the existence of a relationship because of similar blood flow, anatomical, and functional features of the kidney and brain. Both are low-impedance terminal organs that are exposed to high-flow blood shocks throughout the cardiac cycle.

The first lesions in the nervous system from CKD show up as damage to small blood vessels, including small arteries, arterioles, capillaries, and small veins. With poor redundancy in the vessel system to mitigate damage from a blockage, patients have increased susceptibility to stroke. Lesions to the brain affecting its ability to function or caused by pathologic changes in small blood vessels, which collectively are a sign of CSVD.

Given the findings, the authors recommended research into the possibility that when CSVD progresses, CKD may correspondingly decline, and when renal function declines, CSVD might progress.

WML, the progression of which correlates to that of CKD, is one manifestation of cerebrovascular disease and is closely related to cerebral ischemia, stroke, degeneration, and other neurologic diseases. WMLs with intracranial merged lesion can reflect the severity of CSVD in the elderly; their development can be regarded as the terminal changes in CSVD prognosis.

CMBs are the radiologic correlates of leakage of blood components through injured or fragile vascular walls or of frank small hemorrhage spots.

Yao T, Song G, Li Y, et al. Chronic kidney disease correlates with MRI findings of cerebral small vessel disease. 

. 2021;43(1):255-263. doi:10.1080/0886022X.2021.1873804

New research highlights a relationship between chronic kidney disease (CKD) and cerebral small vessel disease.

Larry Hanover

Articles

Dropping Race From eGFR Doubles Estimated Prevalence of CKD in Black Populations

Laryngeal Hypersensitivity Eyed as a Reason Behind Refractory, Unexplained Cough

Study Examines Role of Interleukin-30 in Psoriasis

Progressive CKD Increases Prevalence, Severity of Cerebral Small Vessel Disease