Chronic kidney disease in the context of Cachexia

Kidney failure, also known as renal failure or end-stage renal disease (ESRD), is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as either acute kidney failure, which develops rapidly and may resolve; and chronic kidney failure, which develops slowly and can often be irreversible. Symptoms may include leg swelling, feeling tired, vomiting, loss of appetite, and confusion. Complications of acute and chronic failure include uremia, hyperkalemia, and volume overload. Complications of chronic failure also include heart disease, high blood pressure, and anaemia.

Causes of acute kidney failure include low blood pressure, blockage of the urinary tract, certain medications, muscle breakdown, and hemolytic uremic syndrome. Causes of chronic kidney failure include diabetes, high blood pressure, nephrotic syndrome, and polycystic kidney disease. Diagnosis of acute failure is often based on a combination of factors such as decreased urine production or increased serum creatinine. Diagnosis of chronic failure is based on a glomerular filtration rate (GFR) of less than 15 or the need for renal replacement therapy. It is also equivalent to stage 5 chronic kidney disease.

A non-communicable disease (NCD) is a disease that is not transmissible directly from one person to another. NCDs include Parkinson's disease, autoimmune diseases, strokes, heart diseases, cancers, diabetes, chronic kidney disease, osteoarthritis, osteoporosis, Alzheimer's disease, cataracts, and others. NCDs may be chronic or acute. Most are non-infectious, although there are some non-communicable infectious diseases, such as parasitic diseases in which the parasite's life cycle does not include direct host-to-host transmission.

The four main NCDs that are the leading causes of death globally are cardiovascular disease, cancer, chronic respiratory diseases, and diabetes. NCDs account for seven out of the ten leading causes of death worldwide. Figures given for 2019 are 41 million deaths due to NCDs worldwide. Of these 17.9 million were due to cardiovascular disease; 9.3 million due to cancer; 4.1 million to chronic respiratory diseases, and 2.0 million to diabetes. Over 80% of the deaths from these four groups were premature, not reaching the age of 70.

Hypertension, also known as high blood pressure, is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms itself. It is, however, a major risk factor for stroke, coronary artery disease, heart failure, atrial fibrillation, peripheral arterial disease, vision loss, chronic kidney disease, and dementia. Hypertension is a major cause of premature death worldwide.

High blood pressure is classified as primary (essential) hypertension or secondary hypertension. About 90–95% of cases are primary, defined as high blood pressure due to non-specific lifestyle and genetic factors. Lifestyle factors that increase the risk include excess salt in the diet, excess body weight, smoking, physical inactivity and alcohol use. The remaining 5–10% of cases are categorized as secondary hypertension, defined as high blood pressure due to a clearly identifiable cause, such as chronic kidney disease, narrowing of the kidney arteries, an endocrine disorder, or the use of birth control pills.

Diabetic nephropathy, also known as diabetic kidney disease, is the chronic loss of kidney function occurring in those with diabetes mellitus. Diabetic nephropathy is the leading cause of chronic kidney disease (CKD), and end-stage renal disease (ESRD) globally. The triad of protein leaking into the urine (proteinuria or albuminuria), rising blood pressure with hypertension and then falling renal function is common to many forms of CKD. Protein loss in the urine due to damage of the glomeruli may become massive, and cause a low serum albumin with resulting generalized body swelling (edema) so called nephrotic syndrome. Likewise, the estimated glomerular filtration rate (eGFR) may progressively fall from a normal of over 90 ml/min/1.73m to less than 15, at which point the patient is said to have end-stage renal disease. It usually is slowly progressive over years.

Pathophysiologic abnormalities in diabetic nephropathy usually begin with long-standing poorly controlled blood glucose levels. This is followed by multiple changes in the filtration units of the kidneys, the nephrons. (There are normally about 750,000–1.5 million nephrons in each adult kidney). Initially, there is constriction of the efferent arterioles and dilation of afferent arterioles, with resulting glomerular capillary hypertension and hyperfiltration particularly as nephrons become obsolescent and the adaption of hyperfiltration paradoxically causes further shear stress related damage to the delicate glomerular capillaries, further proteinuria, rising blood pressure and a vicious circle of additional nephron damage and decline in overall renal function. Concurrently, there are changes within the glomerulus itself: these include a thickening of the basement membrane, a widening of the slit membranes of the podocytes, an increase in the number of mesangial cells, and an increase in mesangial matrix. This matrix invades the glomerular capillaries and produces deposits called Kimmelstiel-Wilson nodules. The mesangial cells and matrix can progressively expand and consume the entire glomerulus, shutting off filtration.

Renal functions include maintaining an acid–base balance; regulating fluid balance; regulating sodium, potassium, and other electrolytes; clearing toxins; absorption of glucose, amino acids, and other small molecules; regulation of blood pressure; production of various hormones, such as erythropoietin; and activation of vitamin D.

The kidney has many functions, which a well-functioning kidney realizes by filtering blood in a process known as glomerular filtration. A major measure of kidney function is the glomerular filtration rate (GFR).The glomerular filtration rate is the flow rate of filtered fluid through the kidney. The creatinine clearance rate (C_Cr or CrCl) is the volume of blood plasma that is cleared of creatinine per unit time and is a useful measure for approximating the GFR. Creatinine clearance exceeds GFR due to creatinine secretion, which can be blocked by cimetidine. Both GFR and C_Cr may be accurately calculated by comparative measurements of substances in the blood and urine, or estimated by formulas using just a blood test result (eGFR and eC_Cr). The results of these tests are used to assess the excretory function of the kidneys. Staging of chronic kidney disease is based on categories of GFR as well as albuminuria and cause of kidney disease.

Renal replacement therapy (RRT) is therapy that replaces the normal blood-filtering function of the kidneys. It is used when the kidneys are not working well, which is called kidney failure and includes acute kidney injury and chronic kidney disease. Renal replacement therapy includes dialysis (hemodialysis or peritoneal dialysis), hemofiltration, and hemodiafiltration, which are various ways of filtration of blood with or without machines. Renal replacement therapy also includes kidney transplantation, which is the ultimate form of replacement in that the old kidney is replaced by a donor kidney.

These treatments are not truly cures for kidney disease. In the context of chronic kidney disease, they are more accurately viewed as life-extending treatments, although if chronic kidney disease is managed well with dialysis and a compatible graft is found early and is successfully transplanted, the clinical course can be quite favorable, with life expectancy of many years. Likewise, in certain acute illnesses or trauma resulting in acute kidney injury, a person could very well survive for many years, with relatively good kidney function, before needing intervention again, as long as they had good response to dialysis, they got a kidney transplant fairly quickly if needed, their body did not reject the transplanted kidney, and they had no other significant health problems. Early dialysis (and, if indicated, early renal transplant) in acute kidney failure usually brings more favorable outcomes.

Kidney transplant or renal transplant is the organ transplant of a kidney into a patient with end-stage kidney disease (ESRD). Kidney transplant is typically classified as deceased-donor (formerly known as cadaveric) or living-donor transplantation depending on the source of the donor organ. Living-donor kidney transplants are further characterized as genetically related (living-related) or non-related (living-unrelated) transplants, depending on whether a biological relationship exists between the donor and recipient. The first successful kidney transplant was performed in 1954 by a team including Joseph Murray, the recipient's surgeon, and Hartwell Harrison, surgeon for the donor. Murray was awarded a Nobel Prize in Physiology or Medicine in 1990 for this and other work. In 2018, an estimated 95,479 kidney transplants were performed worldwide, 36% of which came from living donors.

Before receiving a kidney transplant, a person with ESRD must undergo a thorough medical evaluation to make sure that they are healthy enough to undergo transplant surgery. If they are deemed a good candidate, they can be placed on a waiting list to receive a kidney from a deceased donor. Once they are placed on the waiting list, they can receive a new kidney very quickly, or they may have to wait many years; in the United States, the average waiting time is three to five years. During transplant surgery, the new kidney is usually placed in the lower abdomen (belly); the person's two native kidneys are not usually taken out unless there is a medical reason to do so.

Renal osteodystrophy is defined as an alteration of bone in patients with chronic kidney disease (CKD). It is one measure of the skeletal component of the systemic disorder of chronic kidney disease-mineral and bone disorder (CKD-MBD). The term "renal osteodystrophy" was coined in 1943, 60 years after an association was identified between bone disease and kidney failure.

The types of renal osteodystrophy have traditionally been defined on the basis of bone turnover and mineralization:
1) mild, slight increase in turnover and normal mineralization;
2) osteitis fibrosa, increased turnover and normal mineralization;
3) osteomalacia, decreased turnover and abnormal mineralization;
4) adynamic, decreased turnover and acellularity; and,
5) mixed, increased turnover with abnormal mineralization.
A Kidney Disease: Improving Global Outcomes (KDIGO) report has suggested that bone biopsies in patients with CKD should be characterized by determining bone turnover, mineralization, and volume (TMV system).

Renal artery stenosis (RAS) is the narrowing of one or both of the renal arteries, most often caused by atherosclerosis or fibromuscular dysplasia. This narrowing of the renal artery can impede blood flow to the target kidney, resulting in renovascular hypertension – a secondary type of high blood pressure. Possible complications of renal artery stenosis are chronic kidney disease and coronary artery disease.

Chronic systemic inflammation is the result of release of pro-inflammatory cytokines from immune-related cells and the chronic activation of the innate immune system. It can contribute to the development or progression of certain conditions such as cardiovascular disease, cancer, diabetes mellitus, chronic kidney disease, non-alcoholic fatty liver disease, autoimmune and neurodegenerative disorders, and coronary heart disease.

Baclofen, sold under the brand name Lioresal among others, is a medication used to treat muscle spasticity, such as from a spinal cord injury or multiple sclerosis. Baclofen is a potent muscle relaxant and GABA agonist. It may also be used for hiccups and muscle spasms near the end of life, and off-label to treat alcohol use disorder or opioid withdrawal symptoms. It is taken orally or by intrathecal pump (delivered into the spinal canal via an implantable pump device). It is sometimes used transdermally (applied topically to the skin) in combination with gabapentin and clonidine prepared at a compounding pharmacy. It is believed to work by decreasing levels of certain neurotransmitters.

Baclofen should be avoided in the setting of chronic kidney disease and end stage renal disease as even small doses can cause excessive toxicity. Common side effects include sleepiness, weakness, and dizziness. Serious side effects, such as seizures and rhabdomyolysis, may occur if use of baclofen is stopped abruptly. Use during pregnancy is of unclear safety, whilst use during breastfeeding is likely safe, and even more so if oral administration is avoided.