CKD & ANEMIA
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CKD
Chronic kidney disease (CKD) describes the gradual loss of kidney function over time. Left untreated, the outcome is end-stage renal disease (ESRD). CKD and ESRD are growing public health problems all over the world, and according to the National Kidney Foundation India, kidney diseases are currently ranked third among all life-threatening illnesses in India[1,2] .
As there is no cure for CKD, therapy focuses on slowing progression by treating the underlying causes, contributing factors and complications. Physicians aim to avoid the extreme step of having to replace lost kidney function by dialysis or transplantation[3] .

CKD Burden
The impact of CKD is felt worldwide in both developed and developing countries.

According to the Global Burden of Disease Study 2013, there was a 49.5% increase in the years lived with disability (YLD) due to CKD between 1990 and 2013, though the age-standardized YLD rate dropped by 2.8%. However, while these age-standardized YLD rates dropped for CKD due to hypertension (by 22.4%) and glomerulonephritis (by 6.9%), there was more than a 50% increase in the number of CKD cases due to diabetes and other causes[4] .

In India, data on the prevalence of CKD are still scarce. It is believed that an estimated 40–60% of CKD cases are linked to conditions like diabetes and hypertension[5] . Over recent years, India has witnessed an increase in the number of people with obesity and type II diabetes, for which reasons, many experts suggest that even the numbers of those with CKD are steadily increasing in the country[6] .

But as yet, there is very limited information about how common CKD is in India, or how many patients are affected by it[5] . In one study (called the "Screening and Early Evaluation of Kidney Disease" study), more than 17% of the people screened were diagnosed with some stage of CKD[7]. But according to other studies, there are fewer patients with CKD[8] .

In 2005, the Indian Society of Nephrology established the Indian CKD registry. The purpose of this registry is to help doctors study the disease, understand who gets affected, and prevent and treat CKD[8] .

As of a 2013 report, there were about 55,000 patients on dialysis, and this number was growing at the rate of 10–20% each year[9]. The National Kidney Foundation India has said that 90,000 kidney transplants are needed every year[2] .

Figure 1 highlights data from the Indian CKD Registry that shows that diabetes & hypertension contribute to nearly half the causes for kidney disease.
Anemia—A major complication in CKD
As CKD progresses, the kidneys produce lower amounts of erythropoietin (EPO), a glycoprotein hormone produced by interstitial fibroblasts in the kidney in close association with the peritubular capillary and epithelial tubule. EPO is a protein signaling molecule (cytokine) for red blood cell (RBC or erythrocyte) precursors in the bone marrow, and controls RBC production i.e. erythropoiesis[10] (see Figure 2).
A deficiency of EPO in the body leads to decreased stimulation of bone marrow, which lowers RBC production and increases apoptosis, leading to anemia[11] .

This is why anemia is a very common clinical problem in patients with CKD and is associated with increased morbidity and mortality (see Table 1). Patients with kidney disease often develop anemia at an early stage, which worsens as kidney function deteriorates. Nearly half of all patients with stage three CKD have clinical normocytic, normochromic anemia, which then becomes a universal problem by stage four[12]. An even greater proportion of patients requiring dialysis are anemic[12,13] .
Other than reduced EPO production, additional factors that can cause anemia in those with CKD (seen in Figure 3) include iron deficiency, acute and chronic inflammation with impaired iron utilization, severe hyperparathyroidism with consequent bone marrow fibrosis, and shortened RBC survival in the uremic environment[14]. Less common causes include folate and vitamin B12 deficiency and aluminum toxicity. Comorbid conditions such as hemoglobinopathy can also worsen anemia.
In CKD, anemia can decrease tissue oxygen delivery and use, and increase cardiac output, causing ventricular dilatation and hypertrophy[14,15]. It can manifest as angina, heart failure, decreased cognition and mental acuity, and impaired defense against infection[14]. Anemia may also play a role in retarding the growth of children with CKD.

CKD = chronic kidney disease, EPO = erythropoietin, ESRD = end-stage renal disease, RBC = red blood cell, YLD = years lived with disability

References
1. Manns B et al. BMJ. 2010 Nov 8;341:c5869.
2. National Kidney Foundation India. Available from: http://www.nkfi.in
3. Emedicine Health. Chronic Kidney Disease. Available from: http://www.emedicinehealth.com/chronic_kidney_disease/article_em.htm
4. Carney EF. Nat Rev Nephrol. 2015 Aug;11(8):446.
5. Varma PP. Indian J Nephrol. 2015 May-Jun;25(3):133-5.
6. Anand S et al. Kidney Int. 2015 Jul;88(1):178-85.
7. Singh AK et al. BMC Nephrol. 2013 May 28;14:114
8. Rajapurkar MM et al. BMC Nephrol. 2012 Mar 6;13:10.
9. Jha V. Kidney Int Suppl. 2013;3:157-60.
10. Elliot S et al. Exp Hematol. 2008 Dec;36(12):1573-84.
11. Agarwal AK. Expert Opin Drug Saf. 2009 Mar;8(2):145-53.
12. Locatelli F et al. Kidney Int Suppl. 2008 Dec;(111):S33-7.
13. Kidney Disease: Improving Global Outcomes (2013) KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int Suppl 2013; 3(1).
14. Bargman JM, Skorecki K. Chronic kidney disease. In: Fauci AS et al., editors. Harrison's Principles of Internal Medicine. 17th ed. New York, NY: McGraw Hill Medical; 2008. pp. 1761-71.
15. National Kidney Foundation. Anemia and Chronic Kidney Disease. Available from: https://www.kidney.org/atoz/content/what_anemia_ckd