ODESA NATIONAL MEDICAL UNIVERSITY

Departments of Pediatrics №2

	CONFIRMED by

Vice-rector for research and educational work

____________________ Svitlana KOTYUZHYNSKA

September 1st, 2022	

METHODOLOGICAL RECOMMENDATIONS
on practical classes for students

International Medical Faculty, сourse  4

Educational discipline "PEDIATRICS"

Approved 
at the meeting of the department of Pediatrics №2
Protocol No. 1 dated 28/08/2022

Head of the department of Pediatrics №2    __________________              Tetiana STOIEVA 
                                                                                Signature                                      

Authors: 
Head of the department of Pediatrics №2, MD, PhD in Pediatrics, DM, Professor Stoieva Tetiana
Associate Professor of the department of Pediatrics №2, PhD in Pediatrics Prokhorova Svitlana
Associate Professor of the department of Pediatrics №2, PhD in Pediatrics Titkova O. V. 
Associate Professor of the department of Pediatrics №2, PhD in Pediatrics Portnova O. O. 
Associate Professor of the department of Pediatrics №2, PhD in Pediatrics Vesilyk N. L. 
Associate Professor of the department of Pediatrics №2, PhD in Pediatrics Godlevska T. L.
Assistant of the department of Pediatrics №2, PhD in Pediatrics Fedin M. V.
Assistant of the department of Pediatrics №2, PhD in Pediatrics Jagiashvili O. V.
Assistant of the department of Pediatrics №2, PhD in Pediatrics Reshetilo O.V.
Assistant of the department of Pediatrics №2, PhD in Pediatrics Soboleva H. B.
Assistant of the department of Pediatrics №2 Bratkova L. B.

1.	Topic 31. Practical lessons № 38: «Chronic renal disease» - 2 h.
2.	Relevance of the topic
In recent years, marked increase in the frequency of congenital and hereditary kidney disease in children with progressive course with chronic kidney disease. Lack of knowledge of the early symptoms of chronic kidney disease, risk factors for its development leads to late diagnosis of kidney function that prevents timely apply effective treatments.
The incidence of chronic kidney disease in children is different in some European countries. On average, each year 1.3 pediatric patients with chronic kidney disease 1 million. The total population.
The largest number of patients with chronic kidney disease per year observed in Ireland (9), Belgium (6) Czech Republic (6). This causes development in different countries are different. In European countries, including in Russia, more than 33% of patients with chronic kidney disease is the result of glomerulonephritis. In the US and Bulgaria 42 - 47% of cases of chronic kidney disease is caused by obstructive pyelonephritis. In Finland and Sweden the most common cause of chronic kidney disease are congenital and nephrotic syndrome (57%) and renal tissue dysplasia (33%). If we analyze all congenital and hereditary nephropathy leading to chronic kidney disease, they constitute more than 65%. The situation of chronic kidney disease in children in Ukraine statistics overall incidence observed lag further provision needs dialysis, which violates the quality of life, ie. As a disease on hemodialysis child becomes commonplace it prevents full of life and joyful childhood.

3. Objectives of the lesson:
3.1. General goals:
- to get acquainted with the modern definitions of the concepts of chronic renal disease (CRD), etiology, clinical signs, be able to diagnose in children, draw up a plan of therapeutic and preventive measures.

3.2. Educational goals:
- to get acquainted with the contribution of domestic and foreign scientists in determining the problems of CRD, which contribute to the development of diseases, to determine the need for prevention of CRD in children.

3.3. Specific goals:
- To know:
- Etiological factors of chronic renal damage in children
- The relevance and prevalence of CRD;
- Features of clinical picture, depending on the phase of chronic renal failure;
- Principles of diagnostics CRD;
- Principles of treatment of chronic renal failure.
3.4. On the basis of theoretical knowledge on the topic:
	- to master the techniques / be able to /: 
  - to determine the basic medical history that indicates the presence of a child's urinary system diseases;
   - identify the most informative signs of the disease in an objective, laboratory and instrumental examination of the patient;
  - to substantiate the diagnosis according to the classification;
•	to assign individual treatment, respectively, establishing the diagnosis;
  - to develop preventive measures to determine the principles of follow-up
4. Materials of pre-classroom independent training (interdisciplinary integration).
№ 	Discipline	To know	To be able	
1.	the previous discipline	
	1. Anatomy	The anatomical structure of the kidneys and urinary tract	Identify the peculiarities in children.	
	2. Normal physiology	The functional state of the kidneys and urinary tract in children.	Identify the peculiarities in children.	
	3. Pathological anatomy and pathological physiology	The kidney and urinary tract: microbial-inflammatory, immuno-pathological, metabolicheskie. Congenital malformationsv of the UT	Correct to evaluate the nature of the process	
	4. Biochemistry	The components of the biochemical analysis of blood, reflecting renal function and UT	Correct to evaluate the results of the research.	
	5. Propedeutics childhood diseases	Anatomic - physiological characteristics of the kidneys and UT in children of the different ages.
Semiotics disorders. Methodology of the examinations.	To conduct a clinical examination of the child with UT diseases.	
2.	the following subjects	
	1. Pediatrics	The methods diagnosis and differential diagnosis of renal diseases in children and UT.	To conduct a differential diagnosis with other nozoform with similar clinical - laboratory picture.	
3.	Intrasubject integration	
	Glomerulonephritis	The methods of the diagnosis and differential diagnosis 	To conduct a clinical examination of the patient. Evaluate the results of paraclinical tests.	
	Interstitial nephritis	The methods of the diagnosis and differential diagnosis	To conduct a clinical examination of the patient. Evaluate the results of paraclinical tests.	
	Acute kidney injury	The methods of the diagnosis and differential diagnosis.	To conduct a clinical examination of the patient. Evaluate the results of paraclinical tests.	
	Chronic kidney disease	The methods of the diagnosis and differential diagnosis	To conduct a clinical examination of the patient. Evaluate the results of paraclinical tests.	

5.	Contents of the topic.
1. Terminology
Chronic renal failure (CRF) - renal impairment observed over a period of three months or more, occurs as a result of progressive death of nephrons and stroma in chronic kidney disease (CKD), post-scrotal glomerulonephritis, or after acute renal failure with anoric period more than 3 weeks.
Chronic kidney disease (CKD) is an integral diagnosis characterized by morphological, functional, clinical and laboratory signs of kidney damage lasting more than 3 months; or velocity of glomerular filtration (GFR) <60 ml / min / 1.73 sq. m (the term has been introduced by the National Kidney Foundation since 2002 as the equivalent of a diagnosis, since, as a rule, with the development of the CPR, the cause of the disease is no longer relevant, the classification of the CKD is given in the annex.
Stages of CKD and CRF
Stages of CKD	Stages of CRF
	GFR,
ml/min/
1,73 m2	Creatinine of the blood,
Mmol/l	The maximum relative density of urine	
I	-	≥90	≤0,104	>1.018	
ІІ	І (tubular)	≥90	≤0,104	≤1.018	
	І (compensated)	89-60	0,105-0,176	<1.018	
III	ІІ (subcompensated)	59-30	0,177-0,351	<1.018	
IV	IІІ(uncompensated)	29-15	0,352-0,440		
V	ІV (terminal or dialysis)	< 15	>0,440		
Risk factors of CKD
Risk factors that are likely to influence the development of CKD	Risk factors that initiate CKD	Risk factors that lead to the progression of CKD	Risk factors of the final degree of the CKD	
family history of the presence of CKD in relatives, decrease in size and volume of kidneys, low birth weight or premature, low material status and educational level	The presence of diabetes mellitus type 1 and 2, hypertension, autoimmune diseases, urinary tract infections, urolithiasis, urinary tract obstruction, toxic effects of drugs	High proteinuria or hypertension, inappropriate control of hyperglycemia, smoking	low dialysis dose, temporal vascular access, anemia, low albumin, late dialysis	

Diagnostic criteria	
Clinical criteria	Laboratory criteria	
The beginning is gradual	Normochromic normocyte erythropoietin iron deficiency anemia (rarely - deficient in protein content, vitamins)	
The prevalence of the clinic of the major renal disease in the early stages of chronic renal disease (I-II), in the future - one-type uremic damage to organs and systems with variations in the combination of clinical symptoms and their severity	hyperacetaminemia, increased urea content	
The main possible clinical manifestations	reduction of GFR	
symptoms of intoxication (lethargy, fatigue, nausea)	hypo- and isostenuria, decrease in urine osmolarity	
Symptoms of fluid volume changes (nocturia, dehydration on the background of polyuria, edema - with oliguria or anuria, pericarditis, pleurisy, ascites, brain edema)	hypokalemia with polyuria, hypercalemia with oliguria	
skeletal anomalies (bone pain, skeletal deformation, renal osteodystrophy, osteoporosis)	Metabolic acidosis	
Endocrine disorders (growth retardation and sexual development, hyperparathyroidism, hypothyroidism, weight loss, insulin resistance, impotence, infertility)	Hyperphosphatemia, hypocalcemia, hyperparathyroidism	
Cardiovascular disorder (arterial hypotension with polyuria and hypertension with oliguria, left ventricular hypertrophy, pericarditis, dilatation and secondary cardiomyopathy, myocarditis, arrhythmia, cardiovascular failure)	Increased levels of electrolytes (magnesium, aluminum) and toxins	
Hematological disorders (deficiency anemia, hemorrhagic syndrome)		
Neurological symptoms (retardation, asthenia, psychosis, polyneuropathy, motion weakness, insomnia, convulsions, tremor, memory impairment, decreased attention and extreme manifestations - stupor and coma)		
Gastrointestinal disorders (anorexia, nausea, vomiting, flatulence, gastritis, ulcer, pancreatitis, esophagitis, colitis, stomatitis)		
Immuno-deficiency condition (frequent and prolonged infections, septic complications, tendency to tumors, hepatitis, HIV)		
Dryness and desquamation of the skin, itching		
Visual impairment (reduced visual acuity, retinopathy, red eye syndrome, stellate retinitis)		
Tunnel tendon syndrome		

Laboratory research
A. Required:
Blood clinical analysis
Blood biochemical analysis with proteinogram, determination of creatinine, urea, electrolytes (sodium, calcium, potassium, phosphorus)
Determination of the acid-base state
Determination of glomerular filtration rate (possibly by the formula with creatinine level)
General urine test
Zimnitsky test

B. Clarifying:
I-II stage	III stage	IV stage	Remarks	
Complete blood count with differential count, platelet count, hematocrit, reticulocytes	
1 in every 3 months	Monthly	in conducting anti-anemic replacement therapy - according to the protocol	
Determination of creatinine, blood urea	
1 in every 3 months	Monthly		
Determination of blood electrolytes (calcium, potassium, sodium, chlorine, phosphorus)	
1 in every 3 months	Monthly	often with convulsions, disturbance of the heart, the treatment of vitamin D	
Liver function tests (ALT, AST, bilirubin and its fractions, thymol test) NVs antigen, anti-HCV antibodies	
1 in every 6 months	1 in every 3 months	often with hepatitis, HbsAg- emii	
Determination of alkaline phosphatase	
1 in every 6 months	1 in every 3 months	1 in every 3 months	often in the treatment of vitamin D	
Determination of total protein of blood glucose, ά-amylase, if necessary - cholesterol	
1 in every 3 months	Monthly		
Coagulogram, clotting time, C-reactive protein	
1 in every 3 months	Monthly	often with thromboembolic complications, bleeding, DIC	
Determination of serum PTH (PTH)	
1 in every 3 months		
Definition of HIV	
once	once	once	often under conditions transfusion and stay on hemodialysis	
Determination of blood group and Rh factor	
One time, and if necessary	
Defining parameters of iron metabolism (iron concentration and serum ferritin, transferrin saturation)	
1 in every 3 months	Monthly		
Definition GFR (for clearance of endogenous creatinine)	
1 in every 3 months	Monthly		
Urinalysis	
Monthly		
Zimnitsky test	
1 in every 6 months	If necessary		
Urine glucose test	
once	once	1 in every 3-6 months		
Diuresis	
Daily		
Determining the level of growth hormone, somatomedin and thyroid hormones, X-ray densitometry hands 	
Determination of HLA - type single	

C. Auxiliary:
Blood	Urine	Stool test	
Determination of products of fibrin degradation in serum	Nechyporenko test	Stool test
	
protamine sulfate and ethanol tests	ulelecrogram	analysis for dysbiosis	
Determine the content of vitamin B 12	Bacteriological test	Definition of hidden blood	
Determination of concentration of erythropoietin, renin	determination of the level of daily proteinuria		
	orthostatic test		

Instrumental research
Required	Auxiliary	
blood pressure monitoring, pulse	daily monitoring of blood pressure	
Control of body mass	FCG	
control of growth	Doppler-study of blood vessels	
ECG	FGDS	
ECO-KG	densitometry	
Ultrasound of the urinary system	audiogram	
	X-ray of the chest	
	X-ray examination of bones	
	Ultrasound of the urinary system with pulsed doplerometry	
	Computer tomography	
	puncture nephrobiosis (in addition to the terminal chronic renal neuropathy)	
	radioisotope renoscintigraphy (at the first stage of the CCD)	
	Angiography of renal vessels	

Consultations of narrow specialists
ENT, dentist, ophthalmologist, gynecologist, neurologist, others - 1 time per year and as necessary

MANAGEMENT
Basic principles:
The overall management includes some basic principles:
1.	Treat any reversible condition
2.	Prevent or slow the progression of kidney disease targeting hypertension and proteinuria
3.	Anticipate and prevent the complications of CKD
4.	Treat the complications as and when they are detected
5.	Identify and adequately prepare the child and family in whom renal replacement therapy will be required
The sequence of implementation of the above principles will obviously be influenced by the stages of CKD.
In the early stages of CKD, the focus should be on identification of any reversible insult and preventing or slowing the progression of kidney disease. Ideally this period should also be used to educate the child and family about CKD, highlighting awareness of risk factors that can aggravate kidney failure (such as avoidance of nephrotoxic drugs, recurrent infections, dehydration) and of measures that may slow the progression of kidney failure (such as blood pressure control).
CKD-associated complications begin to appear as CKD progresses into Stage 3 where the focus changes to anticipation, early identification and management of the various complications. Patients who will require renal replacement therapy (RRT) should be identified well in advance of the time that RRT is required so that adequate preparation and education can be provided to both the patient and family. The gold standard is to prepare for where possible pre-emptive living related renal transplantation.
REVERSIBLE KIDNEY DYSFUNCTION 
The most common conditions with potentially recoverable kidney function are primarily due to decreased kidney perfusion or the administration of nephrotoxic agents. 
Kidney hypoperfusion is usually due to hypotension secondary to shock or volume depletion from diarrhoea and vomiting. Perfusion to kidneys can also be hampered by drugs like non-steroidal anti-inflammatory drugs, angiotensin converting enzyme inhibitors (ACEI), and angiotensin II receptor blockers (ARBs). Children with CKD often have concomitant tubulopathy with disorders in water and salt retention. They are unable to mount an appropriate response and are more prone to hypovolaemia which can further aggravate the renal function. If significant hypovolaemia is accompanied by a reduction of GFR, a judicious trial of fluid repletion may result in the return of kidney function to the previous baseline.
SLOWING CKD PROGRESSION 
In patients with CKD, progressive long-term kidney damage is in part due to adaptive hyperfiltration with increased intra-glomerular perfusion and pressure. The progression of CKD is greatest during the two periods of rapid growth: infancy and puberty. Although reversal of the process of CKD is not possible a few interventions have been identified to help slow the progression of CKD.
•	Blood pressure control: the recently concluded ESCAPE trial has clearly emphasised the importance of strict control of blood pressure in delaying CKD progression even in the paediatric age group. In particular, ACE inhibitors and ARBs have been suggested as antihypertensive therapies to reduce proteinuria and control blood pressure in these patients. It is suggested that children with hypertension and proteinuria be treated with an ACE inhibitor or an ARB because of the added benefits of their anti-proteinuric effect.
•	Other interventions: adult studies have shown the benefit of lipid lowering therapy and correction of anaemia on CKD progression. Although not proven in children they are often implemented among paediatric CKD patients. In contrast, restriction of protein, while shown to be effective among adults with CKD, are not recommended in the paediatric age group. In a two year prospective, stratified, and randomised multicentre study of 191 children with CKD, the institution of a low-protein diet (0.8 to 1.1 g/kg) failed to have an impact on the decline in creatinine clearance.
MANAGEMENT OF SPECIFIC COMPLICATIONS
•	Fluid & electrolyte: as GFR becomes severely decreased (Stages IV and V CKD), water and sodium retention may result in volume overload. A combination of dietary sodium restriction and diuretic therapy may correct the increased water balance and prevent water retention from recurring. Diuretic therapy includes either loop diuretics such as furosemide given at a dose of 0.5 - 2 mg/kg/day or thiazide diuretics such as hydrochlorothiazide at 1 - 3 mg/kg/day. Typically, thiazide diuretics are used in early stages of CKD and a loop diuretic in the more advanced stages when the thiazides are less effective. Both classes of diuretics become less effective with decreasing GFR.
Some children with obstructive uropathy and/or dysplastic kidneys have poor urinary concentrating capacity and exhibit urinary sodium wasting, resulting in a propensity for hypovolaemia and hyponatraemia. These children may continue to have substantial urine output despite water losses and require ongoing fluid and sodium replacement.
•	Potassium abnormalities: management strategies for hyperkalaemia includes low potassium diet, loop diuretic (such as furosemide) for increasing potassium excretion, correcting metabolic acidosis with oral sodium bicarbonate and intake of potassium chelating agents like sodium polystyrene sulfonate to reduce potassium excretion. If hyperkalaemia is resistant to this conservative medical management renal replacement therapy may become necessary. Hypokalemia is uncommon in children with CKD apart from iatrogenic cases due to excessive diuretic therapy or rarely with associated Fanconi syndrome or renal tubular acidosis.
•	Metabolic acidosis: overt acidosis usually presents when the estimated GFR is less than 30mls/min/1.73m2. Current guidelines by the K/DOQI are to maintain the serum bicarbonate level at or above 22 mmol/l. It is usually started at 1 - 2mmol/kg/day in two to three divided doses and thereafter titrated as per response.
•	Bone metabolism and bone disease: changes in mineral metabolism and bone structure are an almost universal finding with progressive CKD due to abnormalities in the metabolism of calcium, phosphate, vitamin D, and parathyroid hormone (PTH). If these abnormalities are not addressed, these changes result in bone disease, referred to as renal osteodystrophy. Renal osteodystrophy can be prevented by ongoing monitoring of bone metabolism (measurements of serum concentrations of calcium, phosphate and parathyroid hormone levels) and appropriate therapeutic interventions including vitamin D replacement therapy. Significant morbidity may be associated with renal osteodystrophy, including growth failure, avascular necrosis, and skeletal fractures and deformities.
•	Hypertension: KDOQI recommend the target blood pressure in children with CKD should be below the 90th centile based upon the age, gender, and height of the patient or less than 120/80 mmHg, whichever is lower.
Management of hypertension among CKD population includes adoption of both non-pharmacologic as well as pharmacologic therapy. Non pharmacologic intervention includes weight reduction, exercise, and dietary salt reduction (noting that the recommended daily sodium intake is 1.2 g/day for four to eight year olds and 1.5 g/day for older children). ACE inhibitors or ARBs are often the preferred agent as they have a dual action on reducing proteinuria which has been linked to CKD progression. In addition they have anti-fibrotic activity which may also contribute to the slowing of CKD progression. 
Both ACE inhibitors and ARBs should be used cautiously if the GFR is less than 60mls/min/1.73m2. Since the decline in GFR induced by an ACE inhibitor typically occurs within the first few days after the onset of therapy, the serum creatinine and potassium concentrations should be rechecked within a week after the institution of therapy to ensure that the therapy has not adversely affected the GFR resulting in elevation of serum creatinine and/or hyperkalemia. In view of the teratogenic potential of these drugs, post pubertal females should be counselled regarding pregnancy. 
In addition to ACE inhibition and ARB, diuretics are also often used in situations of fluid overload. Although a thiazide can be used in early CKD it becomes less effective in advanced CKD when loop diuretics prove to be more effective. 
•	Anaemia: anaemia due to reduced kidney erythropoietin production generally develops when the GFR falls below 30mls/min/1.73m2. At the onset of dialysis, the presence of anaemia in children is very common and has been associated with excessive morbidity and an increased mortality risk. Children in the early stages of CKD should have their haemoglobin tested at least annually with the frequency of monitoring increasing as the disease progresses into more advanced stages. A diagnosis of anaemia is made when the observed haemoglobin result is below the 5th centile of normal adjusted for age and sex. Once anaemia is detected in a child with CKD, a thorough investigation is required to identify any underlying contributing factor.
Initial investigation should at least include:
•	Red blood cell indices
•	Reticulocyte count
•	Iron parameters (serum iron, total iron binding capacity, transferrin saturations [TSAT] and serum ferritin)
•	Occult blood in stool
If any underlying contributing factors are identified it should be treated. Iron deficiency is often the most common underlying contributing factor. Iron therapy (elemental iron 3 - 6 mg/kg per day) should be initiated if iron deficiency is detected. Iron supplementation is targeted to maintain a TSAT above 20% and serum ferritin above 100 ng/dl among children with CKD. In addition to iron supplementation, children with CKD often require addition of erythropoiesis stimulating agent (ESA) on account of the diminished erythropoietin secretion from the damaged kidneys. Commonly used ESA are recombinant human eythropoeitin (rHuEPO) or the longer acting darbepoetin alfa. Once iron status is normalised, it should be monitored at least every three months or monthly following the initiation of and/or increase in ESA dosing. Increasing the haemoglobin into an acceptable range in patients with anaemia may ameliorate anaemia-induced symptoms (such as fatigue and exercise intolerance), result in cardiovascular improvement, and possibly decreased mortality. The target haemoglobin for children with CKD is unclear. Limited data suggest that children with CKD having haemoglobin less than 9.9 g/dl are at increased risk for mortality, left ventricular hypertrophy, and/or decreased exercise capacity. In addition, quality of life and neurocognitive function improved in patients treated with rHuEPO who experienced a significant increase in haemoglobin compared to baseline haemoglobin, which was below 9g/dl. K/DOQI has based its recommendation on expert opinion and has recommended target haemoglobin levels between 11 and 12 g/dl. Recent publications of major studies in adults like CHOIR & TREAT have questioned the practice of targeting high haemoglobin which has been found to increase risk of cardiovascular adverse effects, and there is a trend towards accepting lower haemoglobin targets of 10g/dl as adequate. 
The initial rHuEPO dose in older children not receiving dialysis is 80 to 120 Units/kg/ week. Children younger than five years of age or children receiving dialysis frequently require higher doses (300Units/kg/week). The response to rHuEPO is monitored by haemoglobin measurement every one to two weeks following the initiation of treatment or following a dose change until stable target haemoglobin and a stable rHuEPO dose has been achieved by which time, it should then be monitored every four weeks. 
Failure to mount a good haemoglobin response to ESA is usually iron deficiency. But if the iron level is adequate other factors like persistent infection or inflammation, severe hyperparathyroidism, chronic blood loss, malnutrition, folate or vitamin B12 deficiency need to be ruled out. In addition, one should exclude presence of haemogloinopathies.
1.	Dyslipidaemia: K/DOQI, the American Heart Association (AHA) and the American Academy of Pediatrics (AAP) recommend that all adolescents with CKD should be evaluated for dyslipidaemia which should include total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides at presentation, and annually thereafter or two to three months following a change in treatment or subsequent to the presentation of another condition known to cause dyslipidaemia. Although intervention for dyslipidaemia is of proven benefit among adults with CKD, no such evidence exists for paediatric CKD patients. In absence of any such proven intervention, any recommendation is based only on expert opinion.
2.	Nutrition: malnutrition is often seen in children with CKD. A number of factors can be attributed. These include poor appetite, decreased intestinal absorption of nutrients due to altered transit time, and metabolic acidosis. Attention to nutrition is critical as it affects both the physical growth and neurocognitive development of children.
As per the K/DOQI paediatric guidelines for nutrition the nutritional status of children with CKD should be evaluated on a periodic basis. The frequency should be greater in infancy where early dietary intervention has been shown to definitely improve growth outcome.
Nutritional therapy based upon growth parameters should be developed for each child with CKD and ideally be coordinated by a dietician with expertise in paediatric and renal nutrition. Nutritional management should address the energy, protein, vitamin, mineral and electrolyte needs of the individual patient. 
The initial prescribed energy (calories) for children with CKD is based upon the estimated energy requirement (EER) for chronological age. Further supplementation should be considered when the initial intake fails to meet the child's energy requirements and he/she is not achieving expected rates of weight gain and/or growth. Although supplementation by the oral route is preferred, one may have to resort to tube feedings with a nasogastric tube, transpyloric tube, or gastrostomy to ensure adequate energy intake. Protein intake should be between 100 to 140% of the Dietary Reference Intake (DRI) based upon age and gender for children with Stage III CKD and between 100 and 120% for those with Stages IV and V CKD. Protein restriction is not recommended in children as it has not been shown to influence the decrease in kidney function in children with CKD. Children with CKD should receive 100% of the DRIs for the vitamins, thiamine (B1), riboflavin (B2), pyridoxine (B6), vitamin B12, A, C, E, K, and folic acid, and the minerals, copper and zinc. It has to be remembered that children with advanced Stage V CKD might be at an increased risk of developing hypervitaminosis A due to loss of renal clearance of vitamin A metabolites.
•	Growth: growth failure is a common complication of CKD. Like most of the complications of CKD, it is more prevalent among children with Stage III, IV and V CKD. While the institution of recombinant human growth hormone (rHuGH) therapy can have a profound effect on the height velocity of children with CKD who are growing poorly, early recognition and management of malnutrition, renal osteodystrophy, acid-base abnormalities and electrolyte disturbances should take place prior to considering the institution of rHuGH.
The criteria for initiating rHuGH in children with CKD include all of the following:
•	Height SDS that is more negative than -1.88 and/or a height velocity SDS that is more negative than -2 persists beyond 3 months despite treatment of nutritional deficiencies and metabolic abnormalities.
•	Growth potential that is documented by open epiphyses.
•	There are no contraindications for rHuGH.
 rHuGH is continued until the child reaches the 50th centile for mid-parental height, achieves a final adult height with closed epiphyses, or receives a renal transplant
The initial dose of rHuGH in children with CKD is currently 0.05mg/kg per day (corresponds to 4IU/day/ m2 body surface area or 1IU/kg/week); rHuGH is given daily via subcutaneous injections.
•	Neurodevelopment: uraemia is associated with alterations in cognition and may impact on children’s neurodevelopment. Neurologic findings can range from seizures and severe intellectual disability (developmental delay) to subtle deficits resulting in poor school performance. Neurodevelopment impairment can be minimised by optimising nutrition, dialysis, and anaemia management. Recent publications have shown much better neurodevelopment outcome when compared to older studies probably reflecting the more aggressive nutrition and growth management. Proper nutrition ensuring adequate growth and development is most important in infancy and early childhood when the brain growth is most rapid. This necessitates frequent monitoring of head circumference and age-appropriate developmental evaluations and aggressive nutrition support. The cognitive disturbance in an older child may present with abnormal performance on tasks of verbal abstract ability, visual perceptual reasoning, memory, and visual motor skills. A more formal neurodevelopment assessment is needed in older children, especially if they have poor school performance.
If neurodevelopment impairment is identified interventions should include steps such as review of the general CKD management including correction of anaemia, checking the adequacy of the dialysis if the child is on dialysis and ensuring educational support at home and school.
•	Uraemic bleeding: severe chronic uraemia does cause platelet dysfunction, particularly abnormalities in platelet adhesion and aggregation. In asymptomatic patients, no specific therapy is required. In symptomatic children or if a surgical intervention is planned, desmopressin (dDAVP), an analogue of antidiuretic hormone is known to be an effective prophylactic agent. It is administered intravenously or subcutaneously at a dose of 0.3mcg/kg with an onset of effect within one hour of administration and the effect lasts for six to eight hours. Other interventions include cryoprecipitate (1 - 2 units/10 kg); the effect lasts for 24 to 36 hours, but there is an increased risk of transmitted infectious diseases.
•	The other major problem with severe uraemia is uraemic pericarditis, which is seen only in the later stages of CKD and is an indication to institute dialysis. Most patients with uraemic pericarditis respond rapidly to dialysis with resolution of chest pain as well as a decrease in the size of the pericardial effusion.
•	Renal replacement therapy: as the CKD progresses or for those children who present in advanced stages of CKD, preparation should be made for initiation of renal replacement therapy. Ideally once the estimated GFR declines to less than 30 mls/min/1.73m2 (Stage IV CKD), both the child and the family should be counselled about various forms of renal replacement therapy (with the gold standard modality of pre-emptive kidney transplantation where possible prior to the need for peritoneal dialysis or haemodialysis). Usually renal replacement therapy is initiated when the GFR drops to15mls/min/1.73m2 (Stage V CKD), however it may be initiated at higher GFR if any of the following concerns are present:
•	Poor total calorie intake resulting in failure to thrive
•	Clinical symptoms attributable to uraemia
•	Delay in psychomotor development and/or educational issues from progressive CKD
Pre-emptive living-related renal transplantation is often the preferred modality in children as it avoids the problems associated with dialysis. When parents can donate they are a half haplotype match. In these situations, the paediatric nephrologist can prepare the patient and their family for transplantation.
When pre-emptive transplantation is not an option, the choice between the two forms of dialysis is generally dictated by technical, social, concordance issues, and family preference. Peritoneal dialysis is much more common in infants and younger children in large part due to problems of vascular access; haemodialysis becomes more common in older adolescents who have failing peritoneum. Peritoneal dialysis can be performed by parents at home and can be performed overnight with a cycling machine. The use of a cycler potentially allows the least disruption of home life, school, and work attendance, when compared to ambulatory peritoneal dialysis, which often requires a peritoneal dialysis exchange procedure to be conducted during the daytime, or haemodialysis, which usually requires three weekly visits to a haemodialysis centre for at least three to four hours (not counting travel time). In addition, access to a nearby haemodialysis centre may not be readily available to patients and their families or the centre personnel may not be trained to care for children, especially prepubertal children and infants.  However, home haemodialysis programmes are increasing in paediatric practice.
QUALITY OF LIFE 
CKD -as is true for any chronic condition, impacts on the quality of life for both the child and family. A survey of 402 families of 2 to 16 year old children with mild to moderate CKD (median GFR 42.5mls/min/1.73m2) of median duration of seven years found an overall low health related quality of life in children with CKD. They scored lower compared to their healthy peers in all of the four domains tested: physical, school, emotional, and social.
In particular, psychological and social stresses are found in children with CKD and their families. The prospect of a lifetime with renal replacement therapy (dialysis and/or transplant) and the potential for catastrophic complications and/or death makes it difficult to achieve normal childhood and adolescent developmental goals.
Even for those children who progress to adulthood it is usually an uphill task. Studies have shown that compared to age-matched population normative data, these patients are twice as likely to be unemployed (19 versus 11%), and those who were employed are often at a lower occupational level.
The negative impact of chronic disease on the emotional status of the patient's siblings is also well recognised. The siblings frequently feel "neglected" because the parents must provide substantial physical and psychological support to the sick child. Furthermore, the well child may simultaneously feel jealous of the attention provided to the sick child, as well as guilty about being well while the sibling is severely ill.
Optimal comprehensive management of these issues involves a multidisciplinary approach that proactively addresses these concerns. 

Table 1: (KDOQI staging)

Stage	GFR (mL/min/1.73 m2)	
I	Kidney damage with normal or ↑ GFR ≥90	
II	Kidney damage with mild ↓ GFR 60-89	
III	Kidney damage with moderate ↓ GFR 30-59	
IV	Kidney damage with severe ↓ GFR 15-29	
V	Kidney failure <15 (or on dialysis)	
  
Table 2: Normal GFR in children and young adults

Age (gender)	Schwartz equation
Length in cm & Cr in mg/dl	Mean GFR ± SD mL/min/1.73m2	
1 week (males and females)	GFR=0.33*(Length/SCr) in Preterm
GFR=0.45*(Length/SCr) in Term	40.6±14.8	
2-8 weeks (males and females)	GFR=0.45*(Length/SCr)	65.8±24.8	
>8 weeks (males and females)	GFR=0.45*(Length/SCr)	95.7±21.7	
2-12 years (males and females)	GFR=0.55*(Length/SCr)	133.0±27.0	
13-21 years (males)	GFR=0.70*(Length/SCr)	140.0±30.0	
13-21 years (females)	GFR=0.55*(Length/SCr)	126.0±22.0	

6. Materials methodological support classes.
6.1. The tests for self-knowledge source
1. The frequency of urination at night in children under the age of one year are as follows:
A. [-] More than 25 times
B. [-] 20 - 25 times
C. [+] 15 - 16 times
D. [-] 20 to 30 times
E.  [-] 5 - 6 times
2. The density of urine from the children during the first six months of life is:
A. [+] 1,002 - 1,010
B. [-] 1,010 - 1,015
C. [-] 1,015 - 1,020
D. [-] 1,011 - 1,022
E. [-] 1,012 - 1,025.
3. For children of any age tend to extrarenal position of the calyces:
A. [+] For infants
B. [-] For early childhood children
C. [-] For children high school age
D. [-] For pre-school children
E. [-] For primary school children

4. At what age do children bladder capacity is 200-250 ml?
A. [-] neonates
B. [-] the first year of life
C. [-] in infants
D. [-] in preschool children
E. [+] in school-age children

5. The sizes of glomerular filtration and their ability to continue to increase in children:
A. [-] first year of life
B. [-] Up to 5 years
C. [-] Up to 10 years
D. [-] Up to 15 years
E. [+] In the 18 - 19 years

6. The daily diuresis in a child under the age of one year are as follows:
A. [-] 250 ml
B. [+] 400 ml.
C. [-] 700 ml
D. [-] 1000 ml.
E. [-] More than 1000 ml

7. The lag in physical development of children is typical for:
A.	[+] Chronic renal failure
B.	[-] Acute pyelonephritis
C.	[-] Bladder-ureter reflux
D.	[-] Unilateral hydronephrosis
E.	[-] Urinary tract infections

8. Children under 5 years is the most common cause of chronic renal failure are:
A.	[+] Congenital anomalies of the kidney
B.	[-] Chronic glomerulonephritis
C.	[-] Hemolytic uremic syndrome
D.	[-] Chronic cystitis
E.	[-] Focal segmental glomerulosclerosis

9. Hemodialysis in chronic renal failure is shown at the level of creatinine in serum:
A.	[-] Not more than 0.250 mg / l
B.	[-] Not more than 0.320 mg / l
C.	[-] Not more than 0.528 mg / l
D.	[+] More than 0.528 mg / l
E.	[-] Not more than 0.480 mg / l

10. Chronic renal failure is diagnosed in children in case of:
A.	[+]Decrease of c creatinine clearance less than 60 mL / min 3 months
B.	[-] Decrease klirynsu creatinine less than 20 mL / min 3 months
C.	[-] Increase in serum creatinine over 110 mmol / l
D.	[-] In the presence of a child polyuria
E.	[-] In the presence of a child anuria

6.2. Information necessary for the formation of knowledge - skills can be found in textbooks:
-	basic:
1.	Kliegman, R.M., St Geme, J.W., Blum, N.J., Shah, S.S., Tasker, R.C., Willson, K.M., & Behrman, R.E. (Eds.). (2019). Nelson Textbook of Pediatrics (21st ed.). 4264 p.
2.	Ghai ”Essential pediatrics ” 9th Edition. 2019. 814  p.
3.	American Board of Pediatrics: Pediatric Physicians Workforce Data Book 2018-2019, Chapel Hill, NC, American Board of Pediatrics, 2019.
4.	Sigurjonsdottir VK, Chaturvedi S, Mammen C, Sutherland SM. Pediatric acute kidney injury and the subsequent risk for chronic kidney disease: is there cause for alarm? Pediatr Nephrol. 2018;33(11):2047–55.
5.	Winnicki E, McCulloch CE, Mitsnefes MM, et al. Use of the Kidney Failure Risk Equation to Determine the Risk of Progression to End-stage Renal Disease in Children With Chronic Kidney Disease. JAMA Pediatr 2018; 172:174.
-	additional:
1.	Furth SL, Pierce C, Hui WF, et al. Estimating Time to ESRD in Children With CKD. Am J Kidney Dis 2018; 71:783.

6.3. The orienting the map with respect to independent work with literature on the subject classes.
№ 	Main Task	Directions	Answers	
1	2	3	4	
1.	To familiarize with the goals and objectives of the lesson	To formulate a definition of acute kidney injury in children	To formulate the concept of the disease and its character.	
2.	epidemiology	To know the prevalence of acute kidney injury among children. List the risk factors for acute kidney injury in children.	According to the statistical records of the Ministry of Health the prevalence of diseases of the kidneys and urinary tract in children in the last 5 years is growing in Ukraine, namely from 40 to 56 thousandths of the child population. In the first year of life on the IUT often suffer from boys (3.7% vs. 2% in girls), then there is an inverse relationship.	
3.	etiology	List the main etiological factors of acute renal injury	To characterize the prerenal, renal and postrenal (obstructive) Acute Kidney Injury	
4.	pathogenesis	To characterize the basic pathogenetic mechanisms during acute kidney injury in children.	To note that the main pathogenetic mechanism of acute renal injury is a sudden and rapid decline in glomerular filtration rate (<5-10% of normal) and decreased tubular function.	
5.	Classification	To know the classification of acute kidney injury in children.	To be able to make a diagnosis.	
6.	clinic	Identify the main symptoms and their characteristics in acute kidney injury.	Common features are the clinical signs, functional disorders.	
7.	diagnostics	Determine the basic methods of clinical and paraclinical examinations of the acute kidney injury	To be able to evaluate the results of laboratory and functional methods.	
8.	Treatment, prevention and medical examination	Determine the basic areas of treatment, prevention and clinical examination f the acute kidney injury in children.	Pay attention to the complexity of the differential diagnosis of diseases of the urinary system.	

 7. Materials for self-training quality.

А. Questions for self-control:
	1. Anatomical and physiological features of kidneys and urinary system in children of different age groups.
2. Etiopathogenesis chronic kidney disease in children.
3. The clinical picture of this disease in children.
4. Diagnosis of chronic kidney disease in children.
5. Principles of therapy.
6. Principles health center and rehabilitation.

B. Tests for self-control:
1. The frequency of urination at night in children under the age of one year are as follows:
A. [-] More than 25 times
B. [-] 20 - 25 times
C. [+] 15 - 16 times
D. [-] 20 to 30 times
E.  [-] 5 - 6 times
2. The density of urine from the children during the first six months of life is:
A. [+] 1,002 - 1,010
B. [-] 1,010 - 1,015
C. [-] 1,015 - 1,020
D. [-] 1,011 - 1,022
E. [-] 1,012 - 1,025.
3. For children of any age tend to extrarenal position of the calyces:
A. [+] For infants
B. [-] For early childhood children
C. [-] For children high school age
D. [-] For pre-school children
E. [-] For primary school children

4. At what age do children bladder capacity is 200-250 ml?
A. [-] neonates
B. [-] the first year of life
C. [-] in infants
D. [-] in preschool children
E. [+] in school-age children

5. The sizes of glomerular filtration and their ability to continue to increase in children:
A. [-] first year of life
B. [-] Up to 5 years
C. [-] Up to 10 years
D. [-] Up to 15 years
                       E. [+] In the 18 - 19 years
6. The daily diuresis in a child under the age of one year are as follows:
A. [-] 250 ml
B. [+] 400 ml.
C. [-] 700 ml
D. [-] 1000 ml.
E. [-] More than 1000 ml

C. The tasks for self-control with the answers.

1. The boy of 10 years for 2 years periodically recur pronounced swelling (face, back), non-selective proteinuria (2.3 g / day), hypoalbuminemia (20-25 g / l) hiperalfa 2 globulinemiya, hyperlipidemia, blood creatinine - 0.171 mmol / l, GFR - 80 ml / min., HB - 110 g / l.
Diagnosis and treatment?
Answer: Chronic glomerulonephritis, nephrotic form. Chronic renal failure, I phase.
In treatment, in addition to basic and symptomatic (diuretics) therapy Immunotropic drugs (prednisone, hlorbutin) renoprotektory kardiorenalnoyi and treatment of anemia (erythropoietin, iron).
8. The materials for audience independent preparation:
8.1. The list of training tasks to be performed during the practical Lessons:
1. Collect the history, allocate data, which testify to the disease.
2. Identify the most informatyvni symptoms during obyektyvnoho by instrument and laboratory examination of the child.
3. Set the clinical diagnosis in modern classification.

9.	 Instructional materials for acquirement of professional abilities, skills,:
9.1. Methods of work, stages of implementation.
1. Rate data obtained history of life and disease.
2. Conduct a clinical examination of patients with diseases of the urinary system.
3. Make a plan for further examination.
4. Rate the results of laboratory examination by instrument.
5. Formulate clinical diagnosis according to the classification.
6. Develop a plan for treatment of chronic kidney hvaroby a child.

10. Materials for self-control of mastering knowledge, skills, abilitie
Tests 
1. The frequency of urination at night in children under the age of one year are as follows:
A. [-] More than 25 times
B. [-] 20 - 25 times
C. [+] 15 - 16 times
D. [-] 20 to 30 times
                        E.  [-] 5 - 6 times 
2. The density of urine from the children during the first six months of life is:
A. [+] 1,002 - 1,010
B. [-] 1,010 - 1,015
C. [-] 1,015 - 1,020
D. [-] 1,011 - 1,022
E. [-] 1,012 - 1,025.

3. For children of any age tend to extrarenal position of the calyces:
A. [+] For infants
B. [-] For early childhood children
C. [-] For children high school age
D. [-] For pre-school children
E. [-] For primary school children

4. At what age do children bladder capacity is 200-250 ml?
A. [-] neonates
B. [-] the first year of life
C. [-] in infants
D. [-] in preschool children
E. [+] in school-age children

5. The sizes of glomerular filtration and their ability to continue to increase in children:
A. [-] first year of life
B. [-] Up to 5 years
C. [-] Up to 10 years
D. [-] Up to 15 years
E. [+] In the 18 - 19 years

6. The daily diuresis in a child under the age of one year are as follows:
A. [-] 250 ml
B. [+] 400 ml.
C. [-] 700 ml
D. [-] 1000 ml.
E. [-] More than 1000 ml

7. The lag in physical development of children is typical for:
A.	[+] Chronic renal failure
B.	[-] Acute pyelonephritis
C.	[-] Bladder-ureter reflux
D.	[-] Unilateral hydronephrosis
E.	[-] Urinary tract infections

 8. Children under 5 years is the most common cause of chronic renal failure are:
A.	[+] Congenital anomalies of the kidney
B.	[-] Chronic glomerulonephritis
C.	[-] Hemolytic uremic syndrome
D.	[-] Chronic cystitis
E.	[-] Focal segmental glomerulosclerosis

9. Hemodialysis in chronic renal failure is shown at the level of creatinine in serum:
A.	[-] Not more than 0.250 mg / l
B.	[-] Not more than 0.320 mg / l
C.	[-] Not more than 0.528 mg / l
D.	[+] More than 0.528 mg / l
E.	[-] Not more than 0.480 mg / l
10.	 Chronic renal failure is diagnosed in children in case of:
A.	[+]Decrease of c creatinine clearance less than 60 mL / min 3 months
B.	[-] Decrease klirynsu creatinine less than 20 mL / min 3 months
C.	[-] Increase in serum creatinine over 110 mmol / l
D.	[-] In the presence of a child polyuria
E.	[-] In the presence of a child anuria