"Chronic kidney disease is known for its strong genetic component," said lead researcher Maciej Tomaszewski, Professor at the University of Manchester in the UK.
"Our limited knowledge of its exact genetic mechanisms partly explains why progress in the development of new diagnostic tests and treatments of chronic kidney disease has been so slow," Tomaszewski added.
Over 100 variants associated with CKD have been uncovered in large-scale genetic studies. Yet, the biological mechanisms underlying the genetic susceptibility to CKD have remained elusive and the progress in clinical translation of the findings from genome-wide association studies has been slow.
The findings, published in the journal Nature Communications, were done by using "next-generation RNA sequencing" applied to one of the largest ever collections of human kidneys.
One of the genes -- mucin-1 -- makes a sticky protein called mucin that coats urinary tubes inside the kidney.
Mutations of this gene have already been found in rare families with inherited kidney failure.
"We hope that early prediction by genetic testing even before the development of symptoms will in the future be the first line of defence against one of the world's top killers," said Professor Fadi Charchar from the Federation University Australia.
"Early detection followed by treatment using kidney-protective medication or avoidance of drugs which can damage the kidneys is the key to healthier kidneys later in life."
The study highlighted that people with diabetes, obesity, high blood pressure or heart disease are at an increased risk of developing CKD.
Apart from PM2.5, air pollution also contains heavy metals such as lead, mercury and cadmium -- all of which are known to negatively affect the kidneys.
Researchers from the University of Michigan in the US, warn high risk patients who live in heavily populated areas to recognise the danger and take precautions.
"Similar to smoking, air pollution contains harmful toxins that can directly affect the kidneys," said lead author Jennifer Bragg-Gresham, from the varsity.
"Kidneys have a large volume of blood flowing through them, and if anything harms the circulatory system, the kidneys will be the first to sense those effects," she added.
Previous studies have shown that polluted air increases the risk of respiratory problems such as asthma, organ inflammation, worsening of diabetes and other life-threatening conditions.
The new study, published in the journal PLOS ONE, examined several prior studies on the issue.
Looking at areas that are heavily polluted versus areas that are less polluted, you will find more chronic kidney diseases in the heavily polluted areas, said co-author Rajiv Saran, nephrologist at the varsity.
"In heavily polluted areas, consider wearing masks that cover your nose and mouth, limit hours outside and limit long hours commuting to work in high traffic as well," cautioned Saran, adding that the risk should be taken seriously.
Acute kidney injury, an often fatal condition without a specific treatment, causes a build-up of waste products in the blood and an imbalance of fluids throughout the body.
The findings showed that levels of nicotinamide adenine dinucleotide (NAD+) -- the end result of vitamin B3 after it is ingested -- declines in cases of acute kidney injury.
"We were able to detect a drop in NAD+ in the urine of high-risk patients who were either in an intensive care unit or undergoing a major surgery and found that oral vitamin B3 could safely elevate NAD+ in high-risk patients," said principal investigator Samir M. Parikh, nephrologist and associate professor at Harvard University.
"These findings are very early, but the results suggest that we could one day have a non-invasive test for NAD+ status and perhaps even treat acute kidney injury by boosting NAD+ levels," he added.
In the study, published in the journal Nature Medicine, the team examined the metabolic changes associated with acute kidney injury in a mouse model. A urine screen revealed high levels of quinolinate.
They then created a mouse model with reduced QRPT -- an enzyme responsible for converting quinolinate to NAD+ -- but no kidney injury.
The genetically altered rodents mimicked the pattern of acute kidney injury; decreased NAD+, increased urinary quinolinate and increased susceptibility to kidney injury. The experiments were the first to establish QRPT as a mediator of renal stress resistance.
In subsequent human studies, the team found high urinary quinolinate in patients undergoing major surgery at risk for acute kidney injury and confirmed this metabolite pattern in a separate study of 329 intensive care unit patients also at risk for acute kidney injury.
The team then gave large doses of oral vitamin B3 to 41 cardiac surgery patients enrolled in a Phase 1 pilot study and found that augmenting vitamin B3 levels may be safe and potentially beneficial to patients.
(Photo Source : morungexpress.com)
The new device called 'BioP3' allows assembly of larger structures from small living microtissue components, researchers said, adding that future versions of BioP3 may finally make possible the manufacture of whole organs such as livers, pancreases or kidneys.
"In contrast to 3-D bioprinting that prints one small drop at a time, our approach is much faster because it uses pre-assembled living building parts with functional shapes and a thousand times more cells per part," said Jeffrey Morgan, a Brown University bioengineer.
In a new paper in the journal Tissue Engineering Part C, co-authored by Dr Andrew Blakely, a surgery fellow at Rhode Island Hospital, Morgan described the BioP3, made mostly from parts easily available for less than USD 200.
The device seems at first glance to be a small, clear plastic box with two chambers: one side for storing the living building parts and one side where a larger structure can be built with them.
Above the box is a nozzle connected to some tubes and a microscope-like stage that allows an operator using knobs to precisely move it up, down, left, right, out and in.
The plumbing in those tubes allows a peristaltic pump to create fluid suction through the nozzle's finely perforated membrane. That suction allows the nozzle to pick up, carry and release the living microtissues without doing any damage to them.
Once a living component has been picked, the operator can then move the head from the picking side to the placing side to deposit it precisely.
In the paper, the team showed several different structures Blakely made including a stack of 16 donut rings and a stack of four honeycombs.
Because these are living components, the stacked microtissues naturally fuse with each other to form a cohesive whole after a short time.
Each honeycomb slab had about 250,000 cells and the stack of four achieved a proof-of-concept, million-cell structure more than 2 millimetres thick.
That's not nearly enough cells to make an organ such as a liver (an adult's has about 100 billion cells), Morgan said, but the stack did have a density of cells consistent with that of human organs.
Complex stacks with many more cells are certainly attainable, Morgan said.
If properly nurtured, stacks of these larger structures could hypothetically continue to grow, Morgan said.
The team has made structures with a variety of cell types including H35 liver cells, KGN ovarian cells, and even MCF-7 breast cancer cells.
"We believe these two studies provide critical information to the booming field of organ bioengineering as it applies to the kidney," said Giuseppe Orlando, transplant surgeon at the Wake Forest Baptist Medical Center in the US.
Orlando is part of a team at the Wake Forest Institute for Regenerative Medicine aiming to recycle human kidneys. Another group at the institute is doing the same thing with pig kidneys.
The process begins by washing the discarded organs in a mild detergent to remove all cells.
The idea is to replace these cells with a patient's own kidney stem cells, making a tailor-made organ that would not be rejected and would not require the use of powerful anti-rejection medication.
In one study, the researchers evaluated whether the washing process affects kidney vessels called the glomerulus, which are vital to the kidney's role of filtering contaminants out of the body.
In the study published in the journal Transplantation, the research team reported that the size, structure and function of the micro-vessels in the glomerulus are preserved after the cell-removal process.
"The fact that they are preserved means they can potentially facilitate the repopulation of cells into the structure and reduce the potential of clot formation," Orlando said.
In a separate study, published in the journal CellR4, the team reported on the interactions that occur when stem cells are placed on kidney structures that have been through the cell removal process.
The team seeded stem cells harvested from amniotic fluid onto sections of kidney structures.
The scientists observed that the stem cells proliferated when placed on the structures and were functionally active as demonstrated by the fact that they secreted chemicals and growth factors involved in such critical pathways as inflammation and the formation of new blood vessels.
"These results indicate that discarded human kidneys are a suitable platform for engineering replacement kidneys and that when cells are added, the structures behave as an effective and viable biosystem," Orlando said.
The study, published in the Scientific Reports journal, showed patients who took proton pump inhibitors (PPIs) were more likely to experience kidney disease than those who took another type of drug used to dampen down acid production called H2 blockers.
The patients who took only PPIs were 28.4 times more likely to report chronic kidney disease, as well as acute kidney injury (4.2 times more likely), end-stage renal disease (35.5 times more likely) and unspecified kidney impairment (eight times more likely), said researchers including Ruben Abagyan, Professor from the University of California-San Diego.
According to the World Health Organisation, PPIs are essential medicines for many people, helping them to control symptoms that are often painful and disruptive to daily life.
But Abagyan hopes this initial data will prompt healthcare providers to appropriately warn, educate and monitor patients who require PPIs, particularly if they are at an elevated risk for kidney disease and electrolyte abnormalities.
For the study, the team looked at a data of 43,000 patients who took PPIs and the control group, approximately 8,000 patients who took histamine-2 receptor blockers, such as Zantac or Pepcid, and no other medications.
Patients who took only PPIs reported a kidney-related adverse reaction at a frequency of 5.6 per cent against 0.7 per cent for patients who took only histamine-2 receptor antagonists.
However, the researchers cautioned the study does not reveal absolute frequency of these kidney-related complaints for all people taking PPIs. A large, randomised, controlled clinical trial would be needed to show causality between PPI usage and absolute risk of kidney disease in humans.
The surgery was performed by doctors led by Priyadarshi Ranjan, Consultant with Fortis Hospital in Mohali, Punjab.
The families of Manjula Devi from Bihar and Abdul Aziz from Kashmir were looking for suitable donors since the spouses' kidneys were a poor mismatch for each other, the hospital said in a statement.
The families crossed paths within three months after they got themselves registered in a mobile app iKidney which is developed by Ranjan.
After conducting all requisite tests and examinations, experts opined that the kidney of donor Sujeet Kumar (46), husband of Devi (42), was a good match for Aziz.
Similarly, the kidney of donor Shazia (50), wife of Aziz (53), was a good match for Devi.
Both families agreed to undergo surgeries for a paired kidney exchange.
"Both the families are extremely happy as the patients are recovering and responding well to the post-surgery treatment. This fortunate matching was possible through iKidney app that explores for possible paired kidney exchange between eligible donors and patients," Ranjan told reporters here.
Devi, who received Shazia's kidney, said: "I feel very lucky that we got in touch with Shazia's family. It gives me a great source of strength that humanity, above all religion, is the greatest religion of all."
Aziz, who received a kidney from Sujeet Kumar, said: "We now know that helping a human in times of need is the greatest deed for anyone. Humanity as a religion makes us humane.
"What we experienced through this swap is nothing extraordinary but exemplary display of humanity, love and care."
This amazing coincidence was made possible by the iKidney app, which has been developed by Ranjan, who is also the Programme Director for Swap Kidney Transplantation and currently runs the busiest kidney Swap programme of the region.
So far, 13 people, including CEO of Pushpawati Singhania Research Institute(PSRI) Dr. Deepak Shukla have been arrested. Two leading doctors of Fortis hospital have been served notice in the kidney racket. The investigation against another leading hospital located in central Delhi is underway and more arrests are likely to be made in the case which has sent ripples across the medical fraternity.
Talking to IANS, Senior Superintendent of Police Kanpur, Anant Deo said that the Fortis hospital has been served notice in cases relating to the violation of Transplantation of Human Organs Act.
"Besides Fortis and PSRI, the role of one more hospital of Delhi has come to light where poor people were being cheated by doctors and hospital administration through an organized chain of middlemen," said Anant Deo, a Uttar Pradesh cadre IPS officer supervising the investigation.
According to the SSP, the police has launched a massive hunt for one Dr. Ketan Kaushik, a key accused in the case, who brought patients for kidney transplants from countries like Turkey, UAE and other places in the middle east.
"The racket is spread far and wide. Different groups were operating in different regions. As of now, we have busted one of the groups linked with Delhi-based hospitals," Deo revealed.
The SSP said the name of Dr. Deepak Shukla was revealed by at least 10 accused involved in the case. Shukla will be confronted with accused already arrested by the police.
In fact, the racket operated like a well-organized crime syndicate. For instance, the international clientele was approached by a different set of people while local kidney donors were trapped by touts already operating in the human organs transplant racket.
The police sources said that there is enough evidence to prove that the accused removed kidneys of at least 12 donors for a huge amount of money taken from the recipients family.
After extracting the kidneys, donors were paid just Rs 2 or 3 lakhs while recipients were charged Rs 70 to Rs 80 lakhs per transplant.
During investigations, global links emerged wherein a Delhi-based doctor, Ketan Kaushik was found to be handling international clientele for the group.
The racket which has sent shock waves amongst country's medical professionals could see some more leading doctors being rounded up by the police in a few days time, sources added.
According to the SSP, a detailed interrogation of Dr. Shukla and other key accused is being done by a special team led by Superintendent of Police (Crime) Kanpur, Rajesh Yadav.
Recently, at NDTV's Swasth India launch, the megastar shared his health issues with the public, and this time he admitted that "75 percent of his liver is gone".
"I keep quoting my personal example all the time and try and propagate the idea of getting yourself detected and I don't mind saying this publicly I am a tuberculosis survivor, Hepatitis B survivor... Bad blood infusion went in and 75 percent of my liver is gone but because I was able to detect it even after a period of 20 years, when 75 percent of my liver is gone... I am still surviving on 25 percent," Big B said.
The 76-year-old, who has been associated with various health campaigns like Polio, Hepatitis B, Tuberculosis and diabetes, urged people to get tested and diagnosed.
"Then there is a cure. Even with Tuberculosis... I did not know for almost 8 years I was suffering from Tuberculosis. I keep saying that with immodesty if it can happen to me (it can happen) to anyone. Therefore if you are not willing to get yourself tested then you would never find out and there's never going to be a cure for it," he said.
The study published in the journal Nature Communications shows an approximately 50 per cent reduction in kidney size in afflicted mice following treatment.
The drug is now in early clinical trials on human subjects, the researchers said.
Autosomal dominant polycystic kidney disease (ADPKD) affects about 12 million people worldwide, with half developing end-stage kidney disease by the age of 60, according to the study.
"Once the kidneys have failed, the only options for survival are dialysis or a kidney transplant, a large percentage of ADPKD patients on dialysis die each year while waiting for a donated kidney," said Indian origin researcher and study senior author Vishal Patel, Associate Professor at the University of Texas Southwestern Medical Centre.
According to the study, the new treatment showed no evidence of toxicity in animals or human cell tests. It is preferentially delivered to kidneys rather than the liver after being administered.
"We earlier showed that levels of a tiny RNA fragment called microRNA-17 are increased in models of ADPKD.
"MicroRNA-17 interferes with the normal function of other, beneficial RNAs, causing kidney cysts to grow. RGLS4326, as the new drug is called in development, works by blocking the harmful microRNA-17," Patel added.
The ability of the kidney to maintain water balance is vital to our health. It controls water balance, and when we are dehydrated, it produces highly concentrated urine to get rid of waste using as little water as possible.
The older population, those with kidney diseases, and those on blood pressure medication sometimes have a problem with water balance.
The researchers found that the elderly people with impaired kidney function and those taking a combination of certain drugs need to be extra mindful of their water intake.
"People who have high blood pressure are typically given a water pill, so they pee a lot to lower their blood volume and in so doing lower their blood pressure," said Anita Layton, professor of Applied Mathematics, Pharmacy and Biology at Waterloo.
These patients are frequently also given another drug that targets a hormonal system which will affect the kidney as well.
"A lot of people are on these two drugs, and they will be fine. But one day they might have a headache and take an aspirin, and the three of these drugs together can hurt your kidneys," Layton added in a paper published in the the American Journal of Physiology - Renal Physiology.
Layton built the first computational model that simulates the muscle contractions that move urine from the kidney to the bladder.
It found that unless a patient is properly hydrated, taking the two blood pressure drugs and an aspirin concurrently could cause acute kidney injury.
The injury happens when there is an insufficient water balance, which can lead to concentrated urine from a build-up of waste in the body.
"Incredibly, how mammals produce a highly concentrated urine is not well understood," Layton said. "We're now a step closer to understanding how water balance is maintained in mammals."
Speaking to IANS, Dr A.K. Bhalla, Co-Chairperson, Department of Nephrology of Sir Ganga Ram Hospital said, "Under the current pandemic situation, patients suffering from Chronic Kidney Disease are more vulnerable to COVID-19 due to low immunity. Haemodialysis patients have to travel to hospitals at least 2-3 times a week to get their dialysis, exposing themselves to various infections in a healthcare setting.
"As a solution to the current situation, Peritoneal Dialysis (PD) offers dialysis which can be done at home by the patient. There are multiple benefits of PD as therapy but most notably, modern PD enables patients to maintain their lifestyle and independence while offering potentially better clinical outcomes at a substantially minimal cost."
According to Pradhan Mantri National Dialysis Program (PMNDP), India has over two million dialysis patients who routinely drive to a dialysis centre especially for haemodialysis, two-three times a week as missing any session could be life-threatening for the patients. This poses a huge challenge in the current nationwide lockdown situation in response to COVID-19 pandemic.
While the Indian government has made significant advancement by introducing Peritoneal dialysis under Pradhan Mantri National Dialysis Programme (PMNDP) in 2019; there is a dire need of implementing PD in all the states to meet the growing needs of Chronic Kidney Disease patients during COVID-19 who are particularly vulnerable to infection and may exhibit greater variations in clinical symptoms and infectivity.
Dr Sunil Prakash, Senior Director and HOD, Nephrology Department, BLK Super Speciality Hospital, said, "COVID-19 has posed a tremendous challenge in front of the entire nation, especially to the kidney patients. These patients are required to travel to hospitals and clinics for haemodialysis, risking their lives while travelling to the hospitals amidst the deadly virus.
"In many cases, the patients act as a carrier of infections to other people including their near ones and doctors as well. Hence, for the protection of all, patients can opt for Peritoneal Dialysis (PD), which can be done at the convenience and safety of their homes and doesn't require a frequent visit to hospitals. By following simple steps, hand hygiene, PD can be a safe and ideal solution in the current situation and otherwise."
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(IANS)