Chronic Kidney Disease: Causes, Signs, Symptoms, Stages & Treatment Options

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Chronic Kidney Disease: Causes, Signs, Symptoms, Stages & Treatment OptionsChronic kidney disease (CKD) is a progressive loss of renal function over the course of several months or years. It is also known as chronic renal disease. In many cases, this condition is diagnosed as a result of screening when individuals are considered to be at risk of kidney problems, such as those with diabetes or high blood pressure or those related to someone with chronic kidney disease. The condition can also be discovered when it leads to one of its notorious complications such as cardiovascular disease, pericarditis or anemia.

Signs and Symptoms  of Chronic Kidney Disease

Chronic kidney disease has no specific symptoms at first and can only be identified as a spike in serum creatinine or protein in the urine. As the kidney function decreases, the following signs may occur:

  • Increased blood pressure due to fluid overload and production of vasoactive hormones the kidney creates via the renin-angiotensin system. This increases a patient’s risk of developing high blood pressure and/or suffering from congestive heart failure.
  • Urea accumulation, resulting in azotemia and eventually uremia, with symptoms ranging from lethargy to pericarditis and encelopathy. Urea is pushed out by sweating and crystallizes on the skin, creating the “uremic frost” effect.
  • Potassium accumulation in the blood, which could lead to potentially fatal cardiac arrhythmias.
  • Fluid volume overload, with symptoms ranging from mild edema  to pulmonary edema, which is life-threatening.
  • Decreased erythropoietin synthesis which could lead to anemia, which in turn displays fatigue as a symptom.
  • Hyperphosphatemia caused by reduce phosphate excretion.
  • Hypocalcemia eventually progressing to secondary hyperparathyroidism, renal osteodystrophy, and vascular calcification, affecting cardiac function.
  • Metabolic acidosis caused by an accumulation of sulfates, phosphates, uric acid and other.

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Individuals suffering from chronic kidney disease also experience accelerated atherosclerosis, which makes them more prone to developing cardiovascular disease compared to the general population. Patients with both CKD and cardiovascular disease typically have significantly worse prognoses than those suffering only from cardiovascular disease.

What Causes Chronic Kidney Disease?

The most common causes of chronic kidney disease are hypertension (high blood pressure), diabetes mellitus, and glomerulonephritis. Combined, these factors cause roughly 75 percent of all cases of CKD in adults. There are also certain geographic areas with a high incidence of HIV nephropathy.

Vascular causes include large vessel disease such as bilateral renal artery stenosis, or small vessel disease such as ischemic nephropathy, vasculitis and hemolytic-uremic syndrome. Glomerular causes cover a diverse group and are broken down into primary glomerular disease such as focal segmental glomerulosclerisis and lgA nephritis, and secondary glomerular disease such as lupus nephritis and diabetic nephropathy. CKD may also have tubulointestinal causes, including polycystic kidney disease, drug and toxin-induced chronic tubulointerstitial nephritis and reflux nephropathy. Obstructive causes include diseases of the prostate and bilateral kidney stones. In rare cases, nephropathy can also result from pig worms infecting the kidney.

Stages of Chronic Kidney Disease

All people with a glomerular filtration rate (GFR) lower than 60mL/min/1.73 m2 for 3 months are diagnosed with chronic kidney disease, regardless of whether actual kidney damage is present or absent. The reason behind this classification is that a reduction in kidney function to this level or lower means a loss of half or even more of normal kidney function in adults. This, in turn, can be associated with several complications.

Meanwhile, all patients with kidney damage are classified as having CKD regardless of the level of GFR. Individuals with GFR lower than 60mL/min/1.73m2 may sustain GFR at normal or increased levels despite considerable kidney damage. In addition, patients with kidney damage face increased risk of two major outcomes of CDK: loss of kidney function and development of cardiovascular disease.

The loss of protein in urine is also considered an independent marker for worsening renal function and cardiovascular disease. Consequently, British guidelines mark the stage of CDK with the letter “P” if there is significant protein loss.

Stage 1

During the first stage of chronic kidney disease, patients may experience slightly diminished function, i.e. kidney damage with normal or relatively high levels of GFR. Kidney damage is comprised of pathological abnormalities or markers of damage, including abnormalities in blood tests, urine tests or imaging studies.

Stage 2

The second stage of CKD brings mild reduction in GFR levels with kidney damage.

Stage 3

The third stage sees moderate reduction in GFR levels. British guidelines also make a classification between Stage 3A (GFR 45-59 mL/min/1.73m2) and  Stage 3B (GFR 30-44) in order to allow for better screening and referral.

Stage 4

As the condition progresses, patients experience a severe reduction in GFR levels during stage 4 (15-29 mL/min/1.73m2) and  are prepared for renal replacement therapy (RRT).

Stage 5

The fifth and final stage of chronic kidney disease marks established kidney failure (GFR levels lower than 15 mL/min/1.73m2), permanent RRT, or end stage renal disease (ESRD).

Early Detection – Chronic Kidney Disease Screening and Referral

By identifying patients with kidney disease early on, proper measures may help slow progression and reduce cardiovascular risk. Individuals who should be screened foe CKD include those with hypertension or history of cardiovascular disease, subjects with diabetes or marked obesity, people aged 60 or older, those with indigenous origin (Native American Indian, First Nations), those with a history of previous renal disease, and those with relatives who required dialysis due to kidney disease.

Chronic Kidney Disease Treatment

CKD considerably increases the risk of cardiovascular disease, and CKD patients often face higher risk factors for heart disease such as hyperlipidemia. Cardiovascular disease is the most common cause of death in CKD patients, not renal failure. Aggressive treatment of hyperlipidemia is recommended.

Other risk factors aside, the treatment for chronic kidney disease aims to slow down or stop the progression of CKD to stage 5. The broad principles of managing this disease are proper control of blood pressure and treating the original disease, whenever possible. Angiotensin converting enzyme inhibitors (ACEIs) or angiotensin II receptor antagonists (ARBs) are typically used as treatment, as they proved effective in slowing the progression of CKD to stage 5.

ACE inhibitors and ARBs are the current standard of care for CKD patients, but various studies show that subjects still progressively lose kidney functions while on these medications. There are currently several compounds in development for treating CKD. Such compounds include bardoxolone methyl, olmesartan medoxomil, sulodexide, avosentan and others.

Patients with advanced CKD often require replacement of erythropoietin and calcitriol, two hormones the kidney processes. Treatment goals include a target hemoglobin level of 9-12 g/dL. Serum phosphate levels must also kept under control with phosphate binders, as patients with advanced chronic kidney disease usually have elevated levels of serum phosphate. Once the patient reached stage 5, renal replacement therapy is typically necessary. This may consist of either as dialysis or a transplant. No evidence suggests that the normalization of hemoglobin would bring any benefits.

While renal replacement therapies can benefit patients indefinitely and prolong life, CKD severely affects the quality of life. Compared to other therapeutic options, renal transplantation is the most effective in increasing survival for stage 5 CKD patients. It is, however, associated with a higher risk of short-term mortality, as surgery involves risks of complications. Meanwhile high-intensity home hemodialisys seems to lead to an improved survival rate and a greater quality of life, especially compared to the conventional hemodialysis and peritoneal dialysis three times a week.

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