chronic kidney disease ( ckd ) had originally been defined as a glomerular filtration rate less than 60  ml / minute/ 1.73  m for a duration of 3 months or longer . this distinguished chronic kidney disease from episodes of acute kidney injury . for purposes of classification and treatment , the national kidney foundation developed a staging system for ckd based upon the patient 's glomerular filtration rate ( table 1 ) . most of the data regarding the epidemiology and etiology of chronic kidney disease is based upon the adult population . however , there have been some studies recently that have begun to examine the epidemiology and etiology of chronic kidney disease in the pediatric population [ 2 , 3 ] . we will discuss the workup and management of these children from the perspective of a general pediatrician . as the kidney function in the patient deteriorates , there are a number of pathophysiologic problems that develop in the patient . it will be important to consider the stage of chronic kidney disease that patient is in when thinking about these disorders . the kidney plays a crucial role in activating vitamin d. the liver performs the 25-hydroxylation function , and the kidney performs the 1-alpha hydroxylation step . the 1,25-dihydroxy vitamin d that is formed is the most active form of vitamin d and will maintain healthy bones and prevent rickets in the growing child . depending on the form of kidney disease the 1-alpha - hydroxylase function can begin to deteriorate at stage ii or stage iii chronic kidney disease . the patient can then develop hypocalcemia because of the decreased absorption of calcium in the gut . this will then lead to secondary hyperparathyroidism which will cause calcium to be mobilized from the bone . some patients will actually present with pathologic fractures or other forms of bone disease as the presenting feature of chronic kidney disease . in addition to the problems with calcium metabolism , as the glomerular filtration rate declines , the patients will also retain phosphorus and become hyperphosphatemic . this has been shown to stimulate fibroblast growth factor 23 which can lead to additional problems . a number of studies have demonstrated that early control of the patient 's phosphate can alleviate many of the problems seen with chronic kidney disease . however , this can be very difficult to accomplish because the patient 's dietary habits are beyond our control . the primary stimuli for pth secretion are low ionized calcium and high serum phosphorus concentration . one of the actions of pth is to stimulate the 1-alpha - hydroxylase enzyme in the renal cortex to activate more vitamin d. vitamin d will then feed back to the parathyroid gland to decrease secretion of pth . vitamin d will also promote absorption of calcium and phosphorus from the intestines to help with mineralization of new bone . if the parathyroid gland is stimulated for a prolonged period of time by low calcium and high phosphorus , it will become autonomous and no longer be controlled by vitamin d. this is known as tertiary hyperparathyroidism . another area that is affected by chronic kidney disease is the patient 's hemoglobin concentration . as the patient 's kidney function deteriorates , its ability to produce and secrete erythropoietin becomes impaired . in addition , as the patient becomes more uremic , the red cell half - life will decrease and so that turnover of the red cells will become increased . prior to the availability of the erythropoietin , many of the chronic kidney disease patients would become iron overloaded because of the need for chronic transfusions . if the patient 's bone disease becomes advanced , they can develop a condition known as osteitis fibrosis cystica . in this condition the bone marrow becomes replaced with fibrous tissue and thus will not be able to respond to erythropoietin and can not increase red cell production . thus it becomes imperative to view the patient as a whole and treat both bone disease and anemia concomitantly . a number of other electrolyte abnormalities come into play as the patient develops worsening chronic kidney disease . potassium is normally secreted by the kidney but will oftentimes become a problem as the patient develops worsening renal function . the kidney is also responsible for maintaining the patient 's acid base status by secreting protons . this can lead to a number of problems such as worsening of the bone disease because the acidosis will enhance calcium mobilization from the bones and will worsen the bone disease . as mentioned above , the retention of salt will cause trouble with hypertension . also in many disease states , more recently there is evidence that renal nerves play a role in the increased blood pressure in patients with chronic kidney disease . the elevated blood pressure will also cause damage to the kidneys and will accelerate the decline in renal function [ 6 , 7 ] . in addition , the fluid retention could result in edema formation , both peripheral as well as pulmonary . as with adults with chronic kidney disease this has become quite a focus in the treatment of these patients [ 6 , 7 ] . it is imperative to maintain them at a normal blood pressure and prevent the cardiac problems that they could develop . there is also some evidence that parathyroid hormone and fgf 23 can cause some cardiac problems . so as we discussed above with the bone disease and anemia , it appears that there is an interrelationship between the calcium and phosphorus metabolism and cardiac disease . also more recently , a problem has been described with having elevated calcium and phosphorus simultaneously . this leads to an elevation in the calcium - phosphorus cross product and causes precipitation of calcium phosphate in the soft tissues . this has been shown to cause narrowing of the coronary arteries in adults and is becoming evident that this is a problem in pediatrics . growth in these patients is a very complex problem involving many aspects of chronic kidney disease . as can be seen above , these patients with ckd have bone disease that will limit their growth potential . the fact that they are at risk for the development of cardiac disease probably also contributes to their growth problems . other contributing factors include acidosis which impacts bone growth and chronic anemia , which can impact many factors including cardiac function and appetite . even when nutrition and bone disease are adequately addressed , patients with renal disease still may not grow well . it has been shown that the growth hormone - igf 1 axis is abnormal in these patients . so after these patients have been treated with adequate nutrition and their bone disease is under control , they can be treated with growth hormone to stimulate growth . the incidence of chronic kidney disease ( ckd ) continues to increase in the united states . unfortunately we do not have much data on the incidence or prevalence of chronic kidney disease and pediatric patients . recently a few studies have initiated this , but it will take some time to get more data on this . a study that was published in 2003 reported on 4,666 pediatric patients with chronic kidney disease . these patients were from north america , and the data was collected from centers specialized in pediatric nephrology . most likely this number underrepresents the total number of chronic kidney disease patients in north america . so it remains difficult to know what the prevalence and incidence of chronic kidney disease are in the pediatric population . as opposed to adults , many pediatric patients develop chronic kidney disease secondary to congenital abnormalities in the urinary system . in addition , there is more evidence that acute kidney injury can lead to chronic kidney disease [ 911 ] . thus the clinical presentation will vary greatly depending on the cause of the chronic kidney disease . there was some concern that urinary tract infections could eventually lead to chronic kidney disease . a recent study examined this question and showed that the infections themselves probably do not lead to chronic kidney disease . the patients who develop chronic kidney disease had an abnormality demonstrated on a renal ultrasound or voiding cystourethrogram that predisposed the patient to urinary tract infections . as discussed above oftentimes the patients will present with signs or symptoms secondary to anemia or bone disease . thus when these patients are diagnosed , they already have significant chronic kidney disease causing problems . in many patients they may present with signs or symptoms that are not readily seen as referring to the renal system . in addition , if a patient has persistent proteinuria and hematuria , they should be evaluated for ckd . in terms of the workup for patients with chronic kidney disease , they need a very thorough assessment of their metabolic status . one of the primary laboratory tests to do is the serum creatinine . in a steady state while there are some problems with using the serum creatinine to estimate the renal function , it remains the main stay of clinical medicine [ 13 , 14 ] . other laboratory tests that need to be done include serum electrolytes to assess for hyperkalemia as well as the bicarbonate to determine if the patient is acidotic . the calcium and phosphorus also need to be monitored as well as parathyroid hormone and vitamin d level . since many of the patients have obstruction as a cause of their chronic kidney disease , they may require periodic assessment with ultrasounds or possibly vcugs . on initial evaluation , it is also important to examine a chest x - ray to evaluate the heart size . the patients might have significant left ventricular hypertrophy or they may have developed uremic pericarditis with a large pericardial effusion . if the patients complain about bone disease , they may need x - rays of their long bones and possibly bone densitometry performed . other testing that might need to be done includes a more accurate measure of the glomerular filtration rate . as discussed , above the serum creatinine may or may not give an accurate estimate of the patient 's gfr . if a more accurate measure as needed , the patients can have their gfr measured using iothalamate or iohexol disappearance . this test is performed by administering radioactive iothalamate to the patient , then measuring its disappearance from the blood stream and its appearance in the urine . this is a very accurate measure of the patient 's glomerular filtration rate and is not dependent on the patient 's muscle mass . thus it is very important get a careful eye exam performed in patients that have chronic kidney disease . in addition alport 's will lead to high - frequency hearing loss . the treatment of patients with chronic kidney disease is focused on a number of areas . depending on the cause of the chronic kidney disease for example , patients with cystinosis need to be on cysteamine to help prevent accumulation of cystine which will exacerbate the renal disease as well as cause other problems with the patient . because many patients develop chronic kidney disease from obstructive uropathy , it will be important to make sure that their obstruction is relieved and they do not have ongoing problems with urinary tract infections . otherwise the treatment of these patients with chronic kidney disease will be aimed at controlling the blood pressure , the bone disease and their anemia . there are ample data now examining the effects of blood pressure and the development of cardiac disease in pediatrics [ 7 , 17 , 18 ] . because many times patients have renin - mediated hypertension , it is best to control the blood pressure with an ace inhibitor or an angiotensin receptor blocker . there is also more evidence that aldosterone may play a role in the cardiac disease in these patients . it may be beneficial to treat them with an aldosterone receptor blocker as well . as discussed above , the metabolic bone disease , in these patients thus one of the early treatments will be supplementing their vitamin d. in the past this was done with activated 1,25-dihydroxy vitamin d or calcitriol . however more recently it has become evident that supplementing with 25-hydroxyvitamin d may also prove beneficial . if the patients develop hyperkalemia , they may need to be treated with kayexalate to help remove potassium from them . in infants who are dependent on being formula fed after the kayexalate has been thoroughly mixed with the formula , it will settle out and the formula can then be decanted . this way , the patient does not actually take the kayexalate but receives the benefit of its use . this will of course depend on how much renal function the patient has and whether or not they will respond to a diuretic . the long - term followup of these patients will of course depend on the stage of chronic kidney disease they have and how quickly they develop end - stage renal disease . if the patient has been optimally treated for the bone disease and has not responded well to nutritional support and growth hormone , they may need to have dialysis initiated to improve their growth and development . it is interesting to note that transplantation does not alleviate all of the problems related to chronic kidney disease . for example , it is known that they can continue to have significant bone disease after transplantation . as with many subspecialty problems and pediatrics , there needs to be good communication between the general practitioner and the pediatric nephrologist . one of the issues with this has to do with the fact that most pediatric nephrologists are in large tertiary care centers . it will improve the patient 's care if the pediatrician can provide some of the local support . for example , monitoring the patient 's blood pressure can be done in the pediatrician 's office , and if changes need to be made , that could be discussed with the nephrologist . also many times the blood chemistries can be measured at the pediatrician 's office and the results can be discussed with the nephrologist . this way the patient does not have to travel extensively for minor adjustments in their care . in terms of diagnosing patients with chronic kidney disease if the patient is found to have microscopic hematuria , this might lead to a workup that is not productive . . the pediatrician must keep in mind , however , that other common causes of proteinuria include orthostatic proteinuria and transient proteinuria that can occur during many illnesses . as with many illnesses autosomal dominant polycystic kidney disease is another very common cause of chronic disease in the adult population . in addition to the family history and the urinalysis , it is important to monitor the blood pressure of patients . oftentimes one of the first signs of serious kidney disease is the development of hypertension . so it would be very helpful if general pediatricians can measure the blood pressure and follow the guidelines set up in published in the 4th report . the role of the general pediatrician in patients with chronic kidney disease can be very important . the general pediatrician can help identify patients at risk for chronic kidney disease early in the course of their disease . it is also important to remember that many subspecialists may not be adequately prepared to care for the other significant problems the patient might develop . so the general pediatrician can serve as a great resource to coordinate all of the care for the patient .
chronic kidney disease in the pediatric population has been increasing . 
 early detection and treatment can slow down the progression of kidney disease and help prevent the development of end stage renal disease . 
 in addition , as the kidney function declines , there are many pathophysiologic interactions with other organ systems that need to be monitored and treated . in particular , because of impaired vitamin d metabolism , calcium and phosphorus homeostasis is dysregulated and results in secondary bone disease . 
 anemia is common due to a number of factors including impaired erythropoietin production . 
 growth is often impacted by chronic kidney disease but can be improved by proper treatment . 
 complications of chronic kidney disease can be minimized by proper monitoring and treatment of these parameters . 
 the general pediatrician plays a critical role in this process .