A significant Climb in chronic Kidney Disease across the world especially in Africa and the Middle East

Bad news! Concerning! We do not have enough kidney transplants especially not from the living!

"Chronic kidney disease (CKD) is now the ninth leading cause of death globally, up from the 27th in 1990, finds a landmark study published last week in The Lancet.  

 

By the numbers: In 2023, CKD affected ~788 million people ages 20+ worldwide, or ~14% of the global population—up from ~12% in 1990.  

The disease also claimed 1.48 million lives.

Driving factors: Researchers say the increase is tied to the global rise in diabetes, high blood pressure, and obesity, all of which damage blood vessels and strain the kidneys, reports The New York Times (gift link). It is also reflective of an aging population.  

  

Global overview: China has the largest population living with CKD at 152 million, followed by India at 138 million, reports PTI.  ..."

From the abstract:

"Background

Chronic kidney disease (CKD) is common and ranks among the leading causes of mortality and morbidity. This analysis aimed to present global CKD estimates using the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 to inform evidence-based policies for CKD identification and treatment.

Methods

This analysis focused on adults aged 20 years and older over the period 1990 to 2023, from 204 countries and territories.

Data sources used were published literature, vital registration systems, kidney failure treatment registries, and household surveys.

Estimates of CKD burden, including deaths, incidence, prevalence, and disability-adjusted life-years (DALYs), were produced using a Cause of Death Ensemble model and a Bayesian meta-regression analytical tool.

A comparative risk assessment approach estimated the proportion of cardiovascular deaths attributable to impaired kidney function and estimated risk factors for CKD.

Findings

Globally, in 2023, 788 million (95% uncertainty interval 743–843) people aged 20 years and older were estimated to have CKD, up from 378 million (354–407) in 1990.

The global age-standardised prevalence of CKD in adults was 14·2% (13·4–15·2), a relative rise of 3·5% (2·7–4·1) from 1990.

The region with the highest age-standardised prevalence was north Africa and the Middle East (18·0%; 16·9–19·4).

Most people had stage 1–3 CKD, with a combined prevalence of 13·9% (13·1–15·0).

In 2023, CKD was the ninth leading cause of death globally, accounting for 1·48 million (1·30–1·65) deaths, and the 12th leading cause of DALYs, with an age-standardised DALY rate of 769·2 (691·8–857·4) per 100 000.

Impaired kidney function as a risk factor accounted for 11·5% (8·4–14·5) of cardiovascular deaths. High fasting plasma glucose, body-mass index, and systolic blood pressure were all leading risk factors for CKD DALYs. ..."

Global Health NOW: A Sharp Climb in Kidney Disease; and The Possibilities and Predicaments of Artificial Wombs

Global, regional, and national burden of chronic kidney disease in adults, 1990–2023, and its attributable risk factors: a systematic analysis for the Global Burden of Disease Study 2023 (open access)

Figure 1 Global age-standardised total chronic kidney disease prevalence (A) and death rates per 100 000 (B) in 2023 in people aged 20 years and older

Lab-grown tiny human kidneys yield urine and is able to model a kidney disease

Good, but a bit of old news! Impressive!

"Researchers have created the most sophisticated kidney organoid to date, offering a real shot at growing transplantable kidneys from stem cells. These mini kidneys were capable of making urine when transplanted into mice. ... Plumbing — encouraging the organoid to develop blood vessels and the duct that carries urine to the bladder — is the major hold-up. The researchers estimate a transplantable kidney will be ready for animal testing in less than five years."

"... Reared from kidney stem cells, the 1-millimeter-wide structures, known as organoids, recapitulate some of the intricate internal organization of the kidney and, when transplanted into mice, make urine. ...

Exceeded in complexity only by the brain, kidneys contain a filigree of tiny tubules that filter blood and then recapture water and other substances the body needs. ..."

"... “This is a revolutionary tool for creating more accurate models for studying kidney disease, which affects one in seven adults,” ...

Scientists from the Li Lab previously constructed organoids composed of nephrons, the kidney’s filtering units. They had also produced organoids resembling the kidney’s collecting ducts, which concentrate urine.

Now, led by first authors Biao Huang, Pedro Medina, and Zipeng Zeng from the Li Lab, and Jincan He from Tongji University in Shanghai, the team has successfully combined nephron and collecting duct components to produce what they have dubbed “assembloids.” ..."

From the highlights and abstract:

"Highlights

• Human kidney progenitor assembloid (hKPA) develops from hPSC-derived iNPCs and iUPCs

• hKPA shows polarized RVs from iNPCs around a central iUPC-derived UB

• Patterned nephrons fuse with the central CD and display kidney-like functions

• In vivo-grown PKD2−/− hKPA models complex pathogenic cell-cell interactions

Summary

Current kidney organoids do not recapitulate the kidney’s complex spatial patterning and function, limiting their applications. The human kidney comprises one million nephrons, derived from nephron progenitor cells, that connect to an arborized ureteric progenitor cell-derived collecting system.

Here, we develop spatially organized mouse and human kidney progenitor assembloid (KPA) models in which the nephrons undergo extensive development and fuse to a centrally located collecting system, recapitulating kidney progenitor self-assembly processes observed in vivo.

KPAs show dramatically improved cellular complexity and maturity and exhibit several aspects of major kidney functions in vitro and in vivo. Modeling human autosomal dominant polycystic kidney disease (ADPKD) with genome-edited, in vivo-grown human KPAs recapitulated the cystic phenotype and the molecular and cellular hallmarks of the disease and highlighted the crosstalk among cyst epithelium, stroma, and macrophages.

The KPA platform opens new avenues for high-fidelity disease modeling and lays a strong foundation for kidney regenerative medicine."

Nature Briefing: Translational Research

Scientists make most authentic kidney replicas so far "Lab-grown organoids reproduce some of a kidney’s internal structure and function"

USC Stem Cell-led team makes major advance toward building a synthetic kidney (original news release) "Scientists combine kidney filtering and urine-concentrating components to create “assembloids,” the most mature and complex kidney structures ever grown in a lab and a tool for developing new therapies."

Spatially patterned kidney assembloids recapitulate progenitor self-assembly and enable high-fidelity in vivo disease modeling (open access)

Using human stem cells, researchers grew this organoid that features glomeruli (purple), the blood-filtering subunits of a real kidney.

Figure 3 Functional maturation of mKPAs in vitro and in vivo

Acoustic vortex beams to break apart kidney stones with a low-cost, portable device and it takes half the time

Good news!

"... Currently being developed by scientists ... it utilizes a portable machine to generate swirling ultrasound waves known as acoustic vortex beams.

Instead of hitting the stones straight-on, as is the case with ESWL [extracorporeal shock wave lithotripsy] pulses, these beams spin around the stones like twister tornados. As they do so, they produce shear forces on the stones that cause them to disintegrate. ..."

"Lithovortex is a low-cost, portable device capable of destroying stones non-invasively, thanks to the application of ultrasound - it transmits waves from the outside to focus them inside the body, on the stone. According to the tests, its application halves the time needed to break up a stone. In addition, the size and portability of this device would make the treatment of kidney stones an outpatient procedure without the need for large accessory equipment, as is currently the case. ..."

Acoustic vortex beams to break apart kidney stones

Lithovortex "A UPV-CSIC team has developed a new device - in the prototype phase - to break up kidney stones"

First clinical trial for genetically modified pig-organ transplants for patients with end-stage renal disease

Good news!

"The US Food and Drug Administration has cleared biotech firm United Therapeutics to begin the first clinical trial transplanting genetically modified pig organs into humans. The company, which has engineered pigs with ten genetic edits that help the organs evade the human immune system, has already transplanted several kidneys and hearts into individuals on a case-by-case basis. Its new trial aims to transplant pig kidneys into up to 50 people with end-stage renal disease. United Therapeutics’ competitor, eGenesis, plans to ask the FDA to approve another clinical trial using pig organs later this year."

"The first clinical trial testing whether pig kidneys can be safely transplanted into living people has been approved by the US Food and Drug Administration (FDA). As part of the trial, which will begin later this year, kidneys from genetically modified pigs will be transplanted into people with chronic kidney disease whose organs no longer function independently. ..."

Nature Briefing: Translational Research

The science behind the first pig-organ transplant trial in humans "The small trial will help to establish whether kidneys from genetically modified pigs can be transplanted into people safely and effectively."

United Therapeutics Corporation Announces Fda Clearance Of Its Investigational New Drug Application For The Ukidney Xenotransplantation Clinical Trial

Surgeons at Massachusetts General Hospital in Boston transplanted a modified pig kidney into a living person for the first time in 2024.

This New Artificial Kidney Could Transform The Future of Transplants

Good news! This seems to be a new approach.

"... Scientists have developed a bioreactor device that uses human kidney cells cultured in the lab and mimics some of the key functions of a kidney. It's been successfully tested in pigs for a week with no obvious side effects or issues.

The team, led by the University of California, San Francisco (UCSF), is hopeful that their device can be adapted to include a broader range of kidney cell types and be paired with another instrument to filter waste from the blood. ..."

"... They have shown for the first time that kidney cells, housed in an implantable device called a bioreactor, can survive inside the body of a pig and mimic several important kidney functions. The device can work quietly in the background, like a pacemaker, and does not trigger the recipient’s immune system to go on the attack. ..."

From the abstract:

"The definitive treatment for end-stage renal disease is kidney transplantation, which remains limited by organ availability and post-transplant complications. Alternatively, an implantable bioartificial kidney could address both problems while enhancing the quality and length of patient life. An implantable bioartificial kidney requires a bioreactor containing renal cells to replicate key native cell functions, such as water and solute reabsorption, and metabolic and endocrinologic functions. Here, we report a proof-of-concept implantable bioreactor containing silicon nanopore membranes to offer a level of immunoprotection to human renal epithelial cells. After implantation into pigs without systemic anticoagulation or immunosuppression therapy for 7 days, we show that cells maintain >90% viability and functionality, with normal or elevated transporter gene expression and vitamin D activation. Despite implantation into a xenograft model, we find that cells exhibit minimal damage, and recipient cytokine levels are not suggestive of hyperacute rejection. These initial data confirm the potential feasibility of an implantable bioreactor for renal cell therapy utilizing silicon nanopore membranes."

This New Artificial Kidney Could Transform The Future of Transplants : ScienceAlert

Can an Artificial Kidney Finally Free Patients from Dialysis? The Kidney Project proves its bioreactor can keep kidney cells alive for at least one week.

Feasibility of an implantable bioreactor for renal cell therapy using silicon nanopore membranes (open access)

Fig. 3: Bioreactor design with constituent components.

Acute kidney injury explained

Recommendable! Nephrology is about nephrons! Pardon my wisecracking!

Home dialysis will soon be possible for more kidney patients

Good news! Be so thankful if you have a normal working kidney! Home dialysis could be a huge improvement of life quality!

"Healthy kidneys automatically filter waste from the blood 24/7. But for millions of people with advanced kidney disease – including about 570,000 Americans — that essential task is no longer automatic.

The job of failed kidneys must be done by a long, exhausting process called dialysis at least several times a week.
About 90 percent of people with kidney failure spend half their remaining lifetime hooked up to dialysis machines and traveling to and from dialysis clinics. ...

The liberDi system removes the used fluid (effluent), which is safely disposed in the sewage, and introduces fresh fluid – a process lasting 20 or 25 minutes several times per day as opposed to 60 to 90 minutes the way it’s currently done.

“Altogether, it takes about an hour and 20 minutes,” ... “Patients typically do it first thing in the morning and at lunchtime, evening and bedtime.” ...
The actual blood filtering takes place in the peritoneal cavity slowly, when the patient is disconnected from the device. ...

Two initial clinical studies in Israel demonstrated the safety and effectiveness of liberDi’s system on 42 dialysis patients in hospitals and at home. ..."

"Peritoneal dialysis (PD) uses the peritoneum (membrane lining the abdomen) to filter blood inside the body. PD eliminates the need to travel to dialysis centers and provides flexibility to maintain everyday work and activities. At-home PD offers numerous benefits ..." (Company information)

Home dialysis will soon be possible for more kidney patients - ISRAEL21c Just in time for World Kidney Day, March 9, Israeli company gets FDA nod for game-changing home digital dialysis system.

liberDi Receives FDA Regulatory Clearance for its Digital Dialysis System Potential to become the standard of care for home peritoneal dialysis

Deceased Donor kidney blood type converted to O in step towards universal organs

Good news! It appears, the specific research paper has not yet been published.

"... The team first tested the technique on pieces of human kidney tissue, before moving on to three full kidneys with blood type B. The process takes about six hours, and was found to reduce blood type antigens in the organs by over 90%. ..."

"The project, funded by charity Kidney Research UK, could increase the supply of kidneys available for transplant, particularly within ethnic minority groups who are less likely to be a match for the majority of donated kidneys. ...

used a normothermic perfusion machine – a device which connects with a human kidney to pass oxygenated blood through the organ to better preserve it for future use – to flush blood infused with an enzyme through the deceased kidney.

The enzyme acted like “molecular scissors” to remove the blood type markers that line the blood vessels of the kidney resulting in the organ being converted to the most common O type.  ..."

Donor kidney blood type converted in step towards universal organs

Cambridge researchers change donor kidney blood type Researchers have been able to alter the blood type of deceased donor kidneys using “molecular scissors”.

The discovery offers hope to ethnic minority patients who struggle to find suitable transplants.

First pig kidneys transplanted into two humans: what scientists think

Kidney failures has been a very serious medical issue for decades, but does it justify desperate measures. 

"In 2018, 785,883 Americans had kidney failure, and needed dialysis or a kidney transplant to survive (2 in every 1,000 people). 554,038 of these patients received dialysis to replace kidney function and 229,887 lived with a kidney transplant." (Source)

The story about these xenotransplants is a little bit bizarre! This story does not exactly instill confidence in medicine and its practitioners!

These two cases of kidney xenotranspantations raises some serious ethical questions! We do not even learn whether these two patients previously consented to this kind of treatment. We only have to assume.

The two patients, who received the kidney Xenotransplant, were legally dead at the time?

Exactly how long did these two patients survive? Where these two patients monitored for the whole time?

Apparently, up to 54 hours after the xenotransplant was performed things worked out quite well, but what happened after?

"... In their transplant tests, which they performed in September and November 2021, Montgomery and his colleagues used pigs that had been genetically engineered to lack a gene for a protein called alpha-1,3-galactosyltransferase (αGal). The pig version of αGal triggers the human immune system to reject xenotransplants (organs transferred from a different species). With each kidney that the researchers transplanted, they also transplanted a pig thymus, an organ that produces immune cells and helps the body accept the foreign organs.

They tested these “thymokidneys” in two people who had been declared legally dead one to two days earlier because they did not have brain function. ..."

From the abstract:

"... CONCLUSIONS

Genetically modified kidney xenografts from pigs remained viable and functioning in brain-dead human recipients for 54 hours, without signs of hyperacute rejection. (Funded by Lung Biotechnology.)"

First pig kidneys transplanted into people: what scientists think The genetically modified organs seemed to function for more than two days but some researchers are sceptical that the experiments had value.

Results of Two Cases of Pig-to-Human Kidney Xenotransplantation (no public access)

Spiny Mice Appear to Regenerate Damaged Kidneys

Amazing stuff! Good news!

"... After damaging their kidneys to simulate kidney disease, the scientists found that the spiny mice not only regenerated the structure and function of nephrons, the tiny filters that make up the kidney, but they did so without the dangerous scarring that normally occurs in mammals. ...
“We used the term ‘functional regeneration’ because spiny mice sustain severe kidney injury initially but then completely restore kidney function within two weeks. This differs from many kinds of ‘repair’ responses, including fibrotic repair, that restore tissue continuity but do so with variable degrees of loss of organ function,” ..."

From the abstract:

"Fibrosis-driven solid organ failure is an enormous burden on global health. Spiny mice (Acomys) are terrestrial mammals that can regenerate severe skin wounds without scars to avoid predation.  ... Here, we show that despite equivalent acute obstructive or ischemic kidney injury, spiny mice fully regenerate nephron structure and organ function without fibrosis, whereas C57Bl/6 or CD1 mice progress to complete organ failure with extensive renal fibrosis. Two mechanisms for vertebrate regeneration have been proposed that emphasize either extrinsic (pro-regenerative macrophages) or intrinsic (surviving cells of the organ itself) controls. Comparative transcriptome analysis revealed that the Acomys genome appears poised at the time of injury to initiate regeneration by surviving kidney cells, whereas macrophage accumulation was not detected until about day 7. Thus, we provide evidence for rapid activation of a gene expression signature for regenerative wound healing in the spiny mouse kidney."

Spiny Mice Appear to Regenerate Damaged Kidneys | The Scientist Magazine® The mice, already known to regenerate skin, seem to avoid the tissue scarring that leads to organ failure in other animals.

Spiny mice activate unique transcriptional programs after severe kidney injury regenerating organ function without fibrosis (open access)

Could new Israeli stem cell technique spell the end of dialysis?

Good news! To restore renal function via stem cells or other new treatment is imminent!

"The newly developed technology, so far tested on mice, generated new tissue to replace damaged kidney tissue. The mice’s kidney function improved as a result."

Could new Israeli technique spell the end of dialysis? - ISRAEL21c: Study shows it is possible to rejuvenate kidneys and improve their function by using the patient's own stem cells.