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Take a look at a selection of our recent media coverage:

Human kidney cell atlas offers improved understanding of kidney injury and disease

28th July 2023

The recent development of a human kidney cell atlas will help researchers better understand the factors contributing to disease states and provide a critical foundation to help discover new treatments for acute kidney injury and chronic kidney disease.

In the study, published in the journal Nature, a team of US researchers developed a kidney tissue atlas consisting of 51 main cell types including rare and novel cell populations and 28 cellular states indicative of injury or disease.

The atlas also serves as a repository of raw gene data and interactive 3D models of cells and microenvironment relationships. It was created from 45 healthy donor organs and 48 kidney disease biopsies and allows for the comparison of healthy and injured cells.

Kidney atlas

Researchers applied multiple single-cell and single-nucleus assays and spatial imaging technologies to both healthy and diseased kidneys. This provided a high-resolution cellular atlas of 51 main cell types, which included rare and previously undescribed cell populations. The multiomic approach detailed transcriptomic profiles, regulatory factors and spatial localisations spanning the entire organ.

With the data, the researched were able to define 28 cellular states across nephron segments and interstitium that were altered in kidney injury, encompassing cycling, adaptive (successful or maladaptive repair), transitioning and degenerative states.

The identification of molecular signatures also allowed researchers to determine the location of these states within the injury neighbourhoods using spatial transcriptomics. Furthermore, large-scale 3D imaging analysis of around 1.2 million neighbourhoods provided corresponding linkages to active immune responses.

Taken together, the analyses enabled researchers to define the biological pathways that are relevant to injury time-course and niches, including the signatures underlying epithelial repair that predicted maladaptive states associated with a decline in kidney function.

The atlas is part of the Kidney Precision Medicine Project (KPMP) and, according to Dr Eric Brunskill, KPMP program director, ‘represents open, public science at its best‘.

He added: ‘With the atlas, we’ve created an interactive, hypothesis-generating resource for kidney disease investigators and clinicians around the world.‘

This follows the recent development of a comprehensive heart cell atlas, which offers new and unique insight into heart cells and function.

Higher mean arterial pressure unlikely to prevent AKI in shock and perioperative patients

12th December 2022

A systemic review suggests a higher mean arterial pressure is unlikely to reduce the rate of acute kidney injury (AKI) in patients with shock

A higher mean arterial pressure (MAP) in shock or perioperative patients does not appear to be superior to normotension for the prevention or progression of acute kidney injury (AKI) and the need for renal replacement therapy according to a systematic review by Taiwanese researchers.

Globally, acute kidney injury (AKI) is associated with poor patient outcomes and the available data suggests that the pooled incidence rate of AKI is 21.6% in adults with a 23.9% AKI-related mortality. An acute circulatory failure is the major cause of renal failure in intensive care unit (ICU) patients, since the low cardiac output and/or low mean arterial pressure (MAP) leads to renal hypo-perfusion and AKI. It is necessary therefore to maintain an adequate mean arterial pressure but the level of MAP to adequately protect against worsening of renal function is unknown. However, it is known that hypotensive episodes, i.e., where the MAP is less than 73 mmHg, are associated with progression of AKI in critically ill patients with severe sepsis. Furthermore, other work suggests that mean arterial pressure levels of 70 mmHg or higher do not appear to be associated with improved survival in septic shock. and that elevating above 70 mmHg may increase mortality. 

In the present study the Taiwanese researchers conducted a systematic review and meta-analysis of available randomised clinical trial (RCT) results to try and determine whether a higher MAP might be better than normotension for the prevention and worsening AKI. They searched all of the major databases for studies to comparing higher BP target versus normotension in haemodynamically unstable patients, i.e., those with shock, post-cardiac arrest, or surgery patients. They set the two outcomes of interest as the post-intervention AKI and renal replacement therapy rates.

Mean arterial pressure and AKI

A total of 12 eligible trials with 5759 participants, with shock (57%), non-cardiac (29.3%) and cardiac surgery (13.7%) patients were included in the analysis.

The normotensive target varied depending on the patient cohort. For example, in shock patients the normotensive range was 65 – 70 mmHg, 40 – 60 in cardiac surgery and 60 – 75 in non-cardiac surgery.

When compared against the lower mean arterial blood pressure (i.e., normotension), targeting a higher MAP demonstrated no significant effect on AKI rates in shock (risk ratio, RR = 1.10, 95% CI 0.93 – 1.29), cardiac-surgery (RR = 0.87, 95% CI 0.73 – 1.03) or non-cardiac surgery patients (RR = 1.25, 95% CI 0.98 – 1.60]). Similarly, there was no effect on renal replacement therapy in shock patients from targeting a higher MAP (RR = 1.10, 95% CI 0.93 – 1.03) or for either for cardiac and non-cardiac patients.

Interestingly, among shock patients with premorbid hypertension, targeting MAP above 70 mmHg significantly lowered the risk of renal replacement therapy (RR = 1.20, 955 CI 1.03 – 1.41, p < 0.05).

The authors concluded that targeting a higher MAP in shock or perioperative patients may not be superior to normotension, except in shock patients with premorbid hypertension but called for future studies to assess the effects of a high MAP target to preventing AKI in hypertensive patients across common settings of haemodynamic instability.

Citation
Tran PNT et al. Higher blood pressure versus normotension targets to prevent acute kidney injury: a systematic review and meta-regression of randomized controlled trials. Crit Care 2022

Higher coffee intake associated with reduced risk of acute kidney injury

14th June 2022

A higher coffee intake appears linked to a lower risk of acute kidney injury offering the potential for cardio-renal protection through diet

A higher intake of coffee could represent a dietary intervention to protect against the development of incident acute kidney injury (AKI) according to the findings of a prospective cohort study by US researchers.

Coffee is a widely consumed drink and in a 2017 umbrella review of health benefits, it was concluded that there was a large reduction in risk for several health conditions after consumption of three to four cups a day. Furthermore, a 2019 study, found that a higher coffee intake (> 3 cups/day) was associated with a 21% lower risk of hospitalisation for liver-related hospitalisations.

A higher coffee intake has been shown to be associated with a lower risk of type 2 diabetes which is an important precursor to chronic kidney disease. In fact, a higher intake of coffee has actually been found to be associated with a reduced risk of incident chronic kidney disease which suggests that the drink might reduce the risk of progression of kidney disease.

Nevertheless, whether or not consumption of coffee is associated with a reduced risk of incident acute kidney injury is currently uncertain and was the subject of the present study.

The US team used data collected as part of the Atherosclerosis Risk in Communities (ARIC) study, which is designed to investigate the aetiology of atherosclerosis and its clinical sequelae and variation in cardiovascular risk factors, medical care, and disease by race, sex, place and time.

The study includes over 14,000 participants aged 45 to 64 years and as part of the study, consumption of coffee was self-reported and categorised as never; almost never (< 1 cup/day), 1 cup/day, 2 to 3 cups/day and > 3 cups/day. Incident cases of acute kidney injury (AKI) were defined as requiring hospitalisation during the follow-up period.

Other participant data collected included demographics, co-morbidities including diabetes, alcohol intake and smoking status. Hazard ratios were calculated based on a comparison with those who reported never consumed coffee and models fully adjusted for covariates such as co-morbidities, age, gender etc.

Higher coffee intake and acute kidney injury

A total of 14,207 individuals with a mean age of 54.2 years (54.9% female) were included in the analysis. Overall, 27% reported never drinking coffee, 23% drank 2 to 3 cups/day and 17% reported drinking more than 3 cups/day.

During a median follow-up period of 24 years, there were 1694 incident cases of AKI and in the fully-adjusted model, comparison of never to any level of coffee intake was associated with an 11% lower risk of AKI (hazard ratio, HR = 0.89, 95% CI 0.80 – 0.99, p = 0.03).

When the researchers compared the level of coffee drunk, compared to those who never drank the beverage, consuming 2 – 3 cups/day was associated with a 17% lower risk of developing AKI (HR = 0.83, 95% CI 0.72 – 0.95) and a 12% reduced risk for those drinking more than 3 cups/day (HR = 0.88).

The authors concluded that a higher coffee intake was associated with a lower risk of incident AKI and called for larger studies to investigate the effects of coffee consumption on kidney perfusion in those with impaired kidney function at high risk for AKI.

Citation
Tommerdahl KL et al. Coffee Consumption May Mitigate the Risk for Acute Kidney Injury: Results From the Atherosclerosis Risk in Communities Study Kidney Int Rep 2022

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