Most agree that nephrology referral is required by Stage 4 CKD (when eGFR/1.73m2 is less than 30 mL/min; or decreasing by more than 3 mL/min/year).It may also be useful at an earlier stage (e.g. CKD3) when urine albumin-to-creatinine ratio is more than 30 mg/mmol, when blood pressure is difficult to control, or when hematuria or other findings suggest either a primarily glomerular disorder or secondary disease amenable to specific treatment. Other benefits of early nephrology referral include proper education regarding options for kidney replacement therapy as well as pre-emptive transplantation, and timely workup and placement of an arteriovenous fistula in those people with chronic kidney disease opting for future hemodialysis. Renal replacement therapy
At stage 5 CKD, kidney replacement therapy is usually required, in the form of either dialysis or a kidney transplant. In CKD numerous uremic toxins accumulate in the blood. Even when ESKD (largely synonymous with CKD5) is treated with dialysis, the toxin levels do not go back to normal as dialysis is not that efficient. Similarly, after a kidney transplant, the levels may not go back to normal as the transplanted kidney may not work 100%. If it does, the creatinine level is often normal. The toxins show various cytotoxic activities in the serum and have different molecular weights, and some of them are bound to other proteins, primarily to albumin. Uremic toxins are classified into three groups as small water-soluble solutes, middle molecular-weight solutes, and protein-bound solutes.
Treatments for anemia and bone disease may also be required. Severe disease requires hemodialysis, peritoneal dialysis, or a kidney transplant for survival.Chronic kidney disease affected 753 million people globally in 2016 - 417 million females and 336 million males. In 2015, it caused 1.2 million deaths, up from 409,000 in 1990. The causes that contribute to the greatest number of deaths are high blood pressure at 550,000, followed by diabetes at 418,000, and glomerulonephritis at 238,000. Signs and symptoms
CKD is initially without symptoms, and is usually detected on routine screening blood work by either an increase in serum creatinine, or protein in the urine. As the kidney function decreases, more unpleasant symptoms may emerge:
Blood pressure is increased due to fluid overload and production of vasoactive hormones created by the kidney via the renin–angiotensin system, increasing the risk of developing hypertension and heart failure. People with CKD are more likely than the general population to develop atherosclerosis with consequent cardiovascular disease, an effect that may be at least partly mediated by uremic toxins. People with both CKD and cardiovascular disease have significantly worse prognoses than those with only  cardiovascular disease. Urea accumulates, leading to azotemia and ultimately uremia (symptoms ranging from lethargy to pericarditis and encephalopathy). Due to its high systemic concentration, urea is excreted in eccrine sweat at high concentrations and crystallizes on skin as the sweat evaporates ("uremic frost"). Potassium accumulates in the blood (hyperkalemia with a range of symptoms including malaise and potentially fatal cardiac arrhythmias).