The kidneys of young humans filter approximately 180.0 liters of blood daily, which undergo a remarkable process of reabsorption and to a much lesser extent, secretion of unwanted metabolic chemicals that are ultimately removed in a daily urine volume of approximately 1.5- 2.5 liters. Each kidney has approximately 1,000,000 units which individually combine to make up a measure of overall kidney function called the glomerular filtration rate (GFR).  Kidneys are also responsible for the production of hormones such as active vitamin D, which is essential to maintaining healthy bones throughout life and Erythropoietin (EPO) which is essential for stimulating the bones to produce sufficient numbers of red blood cells to carry out the process of delivering oxygen to all organs of the body.  Chronic Kidney Disease (CKD) as it progresses from stage 3 through stage 5 and end stage kidney disease (ESKD), requiring dialysis or kidney transplantation, affects the above organs resulting in abnormal bone structure and low red blood cell counts which limit oxygen carrying capacity of the blood, resulting in loss of energy and fatigue. Failure of the ability to eliminate accumulated metabolic and waste products, cause loss of appetite, nausea and progressive weight loss; failure to excrete the daily load of salt and water results in hypertension and fluid retention. These processes are usually painless; kidney disease is regarded as a silent killer.

Kidney function is assessed clinically by using the blood level of a body chemical, creatinine that is produced in the liver and more than 90% removed by the kidneys, to derive a measure of the overall filtration function off all functioning units (nephrons), called the estimated glomerular filtration rate (eGFR), which is indexed to a standardized body surface area in a steady state.  Chronic kidney disease applies to stage 3 or beyond in the staging system

The level of increasing amounts of protein leaking from the kidneys in the urine along with the stage of CKD increases the rate of progression to end stage kidney failure (ESKD) and increases the risk of premature death from heart attacks, heart failure, strokes, serious infections and death in those with stage 3 or beyond. Approximately 10-15 percent of persons with stage 3 CKD survive to reach dialysis and kidney transplantation. Deaths in CKD patients are approximately 10-20-fold higher than in non-CKD populations.

The World-wide Impact of Chronic Kidney Disease

                The most recent global survey published in 2022, estimates that more than 10% of the world population have CKD, which amounts to some 800 million individuals. It disproportionately affects persons older than 45 years, females, ethnic minorities, indigenous peoples and those with diabetes and high blood pressure (hypertension). In the United States more than 1 in 7 adults have Chronic kidney disease-approximately 37 million persons; there are 800,000 persons at end stage kidney disease (ESKD) with 71% on dialysis and 21% transplanted. The risk for ESKD fir diabetes is 1 in 3  and for hypertension, 1 in 5.  African Americans have a 3-4-fold greater risk of ESKD and make up approximately 25-30% of that population. In 2013 chronic kidney disease was ranked at 19 as a cause of death worldwide; in 2017, it ranked 12^th; it is predicted to rank at 5 by 2040.

Causes of Chronic Kidney Disease

1. Diabetes- world wideis the single most prevalent cause of CKD/ESKD; in Europe it accounts for just over a third of cases; in the U.S. the figure is approximately 42-45 %.
2. High blood pressure (hypertension)-accounts for some 25-30% of CKD/ESKD.
3. Cystic Kidney Diseases- account for 5%-7% of CKD/ESKD (mostly familial polycystic kidneydisease). 
4. Glomerular inflammatory diseases- account for 10% of the CKD/ESKD; Lupus, Liver disease (Hepatitis C and B), HIV and other autoimmune diseases.
5. Other- Infections, drug induced kidney damage, heart failure and acute kidney failure are among the remainder of causes.

The Economic burden of chronic kidney disease

                The annual cost of providing dialysis treatment averages $97,000.00 per patient; the cost for kidney transplantation can range between $ 150,000.00 and $ 450,000.00 per patient depending on the inclusion costs for transplant work up, organ procurement and the first 4-6 months of treatment. After the first-year transplant costs average $ 25,000.00-$30,000.00 per year for medications.

Dialysis patients take an average of 9-12 medications daily for hypertension, diabetes, high cholesterol, heart disease, vitamin supplementation, medications for mineral bone disease and Erythropoietin (EPO) for reducing the need for blood transfusions to counter the low red blood cell counts (anaemia). Monthly out of pocket expenses can approach $2,000.00 without third party coverage.  Only a minority of  dialysis patients are able to remain gainfully employed so the financial burden falls on the family. Successful kidney transplantation provides the optimal treatment with clinical functional improvement and return to productive life. 5 year survival on dialysis in the United States is 41%; in Europe, 48% and in Japan, 60%. Dialysis in the United States is funded by Medicare/Medicaid; Europe and Japan have universal health care systems that fund ESKD/Transplant care.

Emerging Issues in chronic kidney disease

1. The global prevalence is expected to increase mostly due to increasing overweight/obesity which is a primary driver of diabetes; costs and sub-optimal outcomes will increase.
2. New classes of drugs- recent clinical trial data have demonstrated that 2 new classes of drugs for the treatment of diabetes: sodium-glucose transport inhibitors (canagliflozin, Empagliflozin, and Dapagliflozin) , which act by increasing urine excretion of glucose, thereby reducing the blood glucose levels, have unexpectedly been proven to reduce the risks of heart attacks, heart failure, heart interventions and stroke in CKD patients; of more importance they can prolong the onset of dialysis by as much as 2 years. Recent data indicate that the beneficial effects are not confined to people with diabetes. The other class of drugs are once weekly injectable medications that reduce blood sugar levels and cause weight loss; these have been shown to have similar beneficial effects on heart and kidney complications as the former group, but quantitively less. The trade-off is the inordinate expense of these medications.
3. COVID-19 infection-severe infection with multiple organ failure, including acute kidney failure has been noted to have emerged as a cause of CKD.
4. Genetic Traits- the discovery of a gene in persons of African ancestry called the APO-L1 gene over the last 10 years seems to make such populations susceptible to mor severe kidney diseases; persons with 2 copies of the gene are at highest risk of hypertensive chronic kidney disease, HIV kidney disease and end stage kidney disease.
5. Cancer Treatment- older persons have increased cancer risk; they also tend to have chronic kidney disease. Newer cancer drugs such as cisplatin, among others have emerged as damaging to kidney function and can limit their anti-cancer properties. Newer biologic agents which are antibodies to growth receptors involved in cancer spread, have emerged as having adverse kidney effects that can affect outcome.

Conclusions

1. CKD/ESKD is expected to increase in the foreseeable future with concomitant increase in deaths worldwide especially in high income, middle- and lesser-income countries.
2. The economic costs associated with CKD/ESKD management and treatment will continue to increase.
3. Emerging causes of kidney failure such as Hepatitis C, HIV, COVID 19 infection and anti-cancer medications will continue to add to the burden.
4. Primary care providers, physician specialists, governments need to embrace health care systems that  address identification of high risk populations, treatment strategies and eventual containment of chronic kidney disease.