CKD – Chronic Kidney Disease
CKD (Chronic Kidney Disease) in children is the result of heterogeneous diseases of the kidney and urinary tract that originates from common congenital malformations of the urinary tract. The National Kidney Foundation (NFK) Kidney Disease Outcome Quality Initiative (K/DOQI) established outlines for identification, management and the care of all patients touched by CKD.
Kidney damage is defined as the structural or functional abnormalities of the kidney, initially without decreased GFR, that can lead to a decrease in kidney function and is identified by abnormalities in the blood, urine, imaging tests and renal biopsy. Chronic Kidney Disease relates to kidney damage where the glomerular filtration rate (GFR) <60 mL/min/1.73 m2 (Stapleton et al., 1997) by the evidence of renal damage includes micro or macro albuminuria, persistent hematuria, radiological anomalies during a three month period or more.
Classification of CKD
The CKD staging system has been developed with an associated action plan for each stage. In 2000, the National Kidney Foundation (NKF) Kidney Disease Outcome Initiative (K/DOQI) approved the development of clinical practice guidelines to describe CKD and to classify its stages. The staging of CKD relies on the level of glomerular filtration rate (GFR) as an international index of kidney function.
As a result, they provided the framework for practitioners to identify, manage and take care of all patients with CKD in every stage as well as those who were at risk of kidney failure. The most reachable early marker of CKD is an abnormal urinalysis (presence of proteinuria). Persisting proteinuria is a significant marker which has been acknowledged as a risk factor for progressive losses in renal function for both adults and children.
The five different CDK stages correspond to the incising severity of CKD. The higher the stage, the poorer kidney function is. It is important to note that CKD stages only apply to children who are 2 years of age and above. GFR in children varies with age, gander and body size. According to Hogg and friends, GRF increases with maturity from infancy and approaches the adult mean value by the age of 2.
Generally the GFR can be valued by estimating equations based on the age, height and gender of the patient as given by Schwartz formulas.. The other way to estimate GRF is using a 24-hour urine collection for creatinine clearance. Yet, the collection can be problematic for families and may be inaccurate due to missed samples and voiding problems.
The classification of CKD has been divided into five groups:
Epidemiology of CKD
Since CKD is usually asymptomatic in the early stages, it is very often undiagnosed and therefore not reported. As a consequence, it is difficult to estimate the incidence and prevalence of CKD. Data on the epidemiology of CDK is available in many countries, although most of them in the pediatric and adolescence population are few. Various registries from the North American Pediatric Renal Transplantation Cooperative Study (NAPRTCS) and a population based in Italy (ItalKid) are published sources, which give an understanding into the epidemiology of the early stage of CKD.
In brief, the NAPRTCS is a collaborative research that began in 1987 and gathers data from pediatric nephrology centers in North America. They collect data on pediatric transplants, CDK and dialysis. ItalKid on the other hand, collected its data not only from pediatric nephrology but also form pediatric, pediatric urology, pediatric surgery and adult nephrology units since 1995 in Italy.
Based on data from ItalKid, the incidence of new cases of CRI (Chronic Renal Insufficiency) is reported to be 12.1(range 8.8-13.9) per year per million of the age- related population (MARP). The evaluation of the prevalence of CRI in children and adolescents is 74.7 per MARP. Both the NAPRTCS and ItalKid data revealed a slower progression of early CKD towards ESRD in patients with congenital anomalies than in patients with glomerular disease however the rapid progression is more commonly seen in patients with focal segmental glomerulosclerosis (FSGS).
It is important to understand that underlying causes for CKD are significantly different in children than those seen in adults. While in adults the most common are diabetic nephropathy and hypertension in children are very rare causes of CKD. The leading causes of CKD in young patient are congenital and urologic anomalies, especially in the youngest age group. The 2005 data from NAPRTCS chronic renal insufficiency registry show that as age increases the proportion of patients with congenital urologic anomalies decreases and those with glomerular disease as an etiology increases. It also demonstrate CDK in childhood tends to affect more males than females in which the males representing 64% of the total affected population.
Racial distribution is as follows: 61% Caucasian, 19% African-American and 14% Hispanic.
In the older papers we can find that according to Broyer and friends glomerular disease and chronic pyelonephritis were the two leading etiologies of ERSD in children, approximately 25% of cases.
Pathophysiology of CKD
The kidney plays very important role in bone and mineral homeostasis. It regulates not only calcium and phosphorus balance but also participate in the catabolism and regulation of parathyroid hormone (PTH). Moreover it controls the synthesis of 1,25- dihydroxy (OH)2 vitamin D3 (1,25(OH)2D3).
As the CKD progresses, imbalances of ions such as phosphate retention, hypocalcaemia, impaired renal 1.25 (OH)2D3, also an alteration in PTH secretion and calcium-sensing receptors and skeletal resistance to calcemic actions of PTH causes a secondary hyperparathyroidism.
Anemia and nutrition disorders like cachexia are very frequent complication of CKD in children and adults. Nutrition problems are characterized by loss of lean body mass and high metabolic rate despite inadequate dietary intake. Metabolic acidosis, insulin resistance and increased cytokine expression stimulates muscle protein loss. Several studies have shown inadequate dietary energy intake in children with CKD. Furthermore, the energy intake progressively declines with worsening renal failure. Since the energy intake is the principal factor of growth, children with CKD often suffer from growth impairment.
Growth failure has long been recognize as one of the most common and profound clinical manifestation of CKD in infants, children and adolescents. Growth reduction contribute of multiply factors like age at onset of CKD, type of primary renal disease, malnutrition from calorie deprivation, anemia, metabolic acidosis and finally distress of the growth hormone (GH) and insulin-like growth hormone (IGF).
Kidneys has the function of acid excretion in ion metabolism to balance blood pH. Metabolic acidosis is expected in patients with estimated GFR of <30ml/min/1.73 m2 due to reduction of; reabsorption of filtered bicarbonate, ammonia synthesis and excretion of titratable acid which leads to acidification of tubular luminal fluid in the distal nephron. When metabolic acidosis becomes chronic, cellular bone activity is altered. Therefore osteoblastic activity is decreased and osteoclastic bone reabsorption activity is increased.
CKD has significant negative effects on Growth Hormone (GH) – Insulin like growth factor 1 (IGF-1) pathway. Circulating GH levels increase due to reduced clearance of GH. Another finding is the GH resistance, which suggested to occur because of (1) down-regulation of GH receptors in liver and the growth-plate and (2) altered post-receptor signaling of GH. General inflammatory condition in the disease may also down-regulate GH receptors and the post-receptor signaling via tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6). The GH-IGF1 axis is altered also by the decreased bioavailability of IGF-1, which may occur due to increased IGF binding proteins.