Chronic kidneys disease

Chronic kidneys disease

Definition 1. GFR < 60 ml / min /1.73m2 > 3 months , with or without kidney damage

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2. Kidney damage >3 months with or without decrease in GFR , with either pathological abnormalities or markers of kidney damage

3. Kidney damage based on abnormal urine analysis (proteinuria, hematuria , electrolytes abnormalities ) or structural abnormalities found on U/S

Etiology and Epidemiology

• Congenital anomalies of the kidney and urinary tract (CAKUT) are the most common causes of CKD that present between birth and 10 years of age.

• After age 10, acquired renal diseases, such as focal segmental glomerulosclerosis

and glomerulonephritis (GN), are more common causes of CKD.

Etiology and Epidemiology • CKD is staged to facilitate appropriate evaluation and monitoring.

• GFR can be estimated in children using the Schwartz formula.

• Most complications of CKD do not manifest until at least stage 3 CKD.

• In stage 4 CKD, complications become more numerous and severe.

• Children with stage 5 CKD (ESRD) are typically treated with either dialysis or renal transplantation

Etiology and Epidemiology

• Bilateral renal Hypoplasia or dysplastic kidneys.

• Reflux nephropathy.

• Focal segmental glomerulosclerosis as a variant of childhood nephritic syndrome.

• Polycystic kidney disease, autosomal-recessive and autosomal-dominant

• Obstructive uropathy

Schwartz formula

• Updated Schwartz formula:2009

[Ht(cm)/serum creat(mg/dL)] x 0.413

• Current national guidelines recommend routine reporting of the estimated GFR alongside the serum creatinine value for adults using the Chronic Kidney Disease Epidemiology Collaboration creatinine-based formula and the updated Schwartz "bedside" formula (CKiD 2009) for children

• Reference :Mian AN, Schwartz GJ. Measurement and Estimation of Glomerular Filtration Rate in Children. Adv Chronic Kidney Dis. 2017 Nov;24(6):348-356.

Schwartz formula

• This formula is useful when body habitus and muscular mass is normal and when

renal function is relatively stable

• This formula is most accurate in GFR range of 15-75ml/min/1.73m2

• False negative result occur with frequent voiding ,low urine bacterial count ,

urinary tract obstruction , infection with bacteria unable to generate nitrite .

Staging

CKD stage Description GFR (mL/min per 1.73 m2)

1 Kidney damage with a normal or increased GFR

>90

2 Mild reduction in the GFR 60 to 89

3 Moderate reduction in the GFR

30 to 59

4 Severe reduction in the GFR 15 to 29

5 Kidney failure <15

Clinical Manifestations • The clinical presentation of a child with CKD is related to both

underlying cause and complications of CKD.

• A child with CAKUT may have polyuria, polydipsia, and recurrent urinary tract infections.

• A child with glomerular disease may have hematuria, proteinuria, edema, and hypertension

Complication

1-poor growth

2-Anemia on CBC

3.CKD-Mineral Bone Disorder/secondary hyperparathyroidism

4-cardiovascular

5-electrolyte disturbance

• Metabolic acidosis hyponatremia , hypernatremia , hyperkalemia

Complication of CKD 1- Poor growth . For example, factors associated with growth failure include poor nutrition, CKD-mineral bone disorder (CKD-MBD), metabolic acidosis, hormonal abnormalities, and resistance to growth hormone.

.

Complication of CKD 2. Anemia , results primarily from a failure to produce adequate erythropoietin from peritubular cell and iron deficiency. Normochromic normocytic anemia

Complication of CKD • Circulating insulin level are higher due to

decrease insulin clearance .

• Uremic encephalopathy

Complication of CKD CKD-Mineral Bone Disorder/secondary hyperparathyroidism • There would be dec in 1.25 vit D because of renal alpha 1 hydroxylase

• CKD-MBD is usually due to secondary hyperparathyroidism as a result of diminished renal 1,25-dihydroxyvitamin D production, hypocalcemia, and hyperphosphatemia (from decreased renal excretion

Complication of CKD CKD-Mineral Bone Disorder/secondary hyperparathyroidism • With worsening GFR== 1.25 vit d is reduced leading to decrease CA reabsorption,

FGF Increased , Increase PTH due to hypocalcaemia (secondary hyperparathyrodism ) Leading to bone resorption

• If prolonged and/or severe, CKD-MBD may lead to rickets and bone deformities

• Pth :stimulates osteoclast to resorb bone ,Stimulate formation of 1.25 dihydroxy vit D ,Reabsorption of Ca from kidney ,Increase PO4 Excretion

Complication

4. Cardiovascular = HTN , Left ventricularhypertrophy = Mortality risk increase with decline GFR , and increasing albuminuria . Atherosclerosis increase Calcification increase on valves , calcification of arteries Risk of CAD increase uremic Pericarditis, HF ,HTN

Complication

Hyperkalemia It can be caused by reduced renal excretion

Sign and symptoms =can present with cardiac arrest due to wide-complex tachycardia or ventricular fibrillation. Symptoms short of circulatory collapse/cardiac arrest include respiratory failure and weakness that progresses to paralysis. nausea, vomiting, and paresthesias (eg, tingling) muscle weakness (skeletal, respiratory), fatigue, ileus with hypoactive or absent bowel sounds,↓ Deep tendon reflexes; diarrhea ECG=peaked and narrow T waves • decreased amplitude and eventual loss of P waves • prolonged PR interval • widening of QRS and eventual merging with T wave (sine-wave pattern)

Complication

Hyperkalemia

Peaked T waves

Sinusoidal wave .

Complication

. Hyponatremia =could be a consequence of fluid overload or a consequence

of diuretic usage in these patients

• Sign and symptom= nausea , vomiting ,apathy ,malaise, headache, lethargy, obtundation and seizures, hypothermia , coma may occur. Chronic hyponatraemia (developing > 24 hours) may have more subtle features such as restlessness, weakness, fatigue or irritability (due to cerebral adaptation)

• Rapid correction of hyponatraemia can result in osmotic demyelination syndrome which manifests as irreversible neurologic features (dysarthria, confusion, obtundation and coma) which often present days after sodium correction.

Complication

Hyponatremia : P- wave alternans ====An unusual electrocardiographic (ECG) case of alternating P-wave configuration sparing other ECG components is described. Hyponatremia due to chronic indapamide use was proposed as a plausible cause of this ECG phenomenon, since its correction led to the recovery of a steady P-wave morpholog

Indapamide is a thiazide diuretic (water pill)

P-wave alternans .

Complication

5c. Metabolic acidosis its causes are: dec acid excretion , impaired ammonia excretion, reduced tubular bicarbonate reabsorption and insufficient renal bicarbonate production in relation to the amount of acids synthesised by the body and ingested with food and here the anion gap is elevated.

……….. Metabolic acidosis often is a mixture of normal anion gap and increased anion gap; the latter is observed generally with stage 5 CKD but with the anion gap generally not higher than 20 mEq/L. In CKD, the kidneys are unable to produce enough ammonia in the proximal tubules to excrete the endogenous acid into the urine in the form of ammonium. In stage 5 CKD, accumulation of phosphates, sulfates, and other organic anions are the cause of the increase in anion gap.,

Complication

• Most of these complications are multifactorial in etiology.

• Delayed puberty results from altered gonadotropin secretion and regulation.

• Learning and school performance may also be impaired in CKD.

General Note • CKD is staged to facilitate appropriate evaluation and monitoring.

• Most complications of CKD do not manifest until at least stage 3 CKD.

• Children with stage 5 CKD (ESRD) are typically treated with either

dialysis or renal transplantation

• Plasma Cr does not rise until renal function has fallen to less than half normal levels.

• Cr affected by muscle bulk

Thank you

• Reference : nelson_kliegman_robert__text book

• CONTINUE … • Adonia Haddad

Prognosis

• Children with mild CKD (stages 1 and 2) may do well but need to be monitored for progressive loss of kidney function.

• Children with stages 3 and 4 CKD have a high likelihood of progressing to ESRD at some point, although the timing can vary.

• Children with kidney transplants generally do well, but have to take immunosuppressive medications associated with a variety of side effects, including infections, nephrotoxicity, cardiovascular complications, and increased risk for certain malignancies.

• Unfortunately, most transplanted kidneys fail over time but can last for >10-20 years.

• Children on maintenance dialysis have the highest morbidity and mortality, especially with longer time spent on dialysis. Thus the primary goal is to provide a kidney transplant for children with ESRD.

DIAGNOSTIC STUDIES

• Outpatient checks in child with ckd

• 1)Height/ weight /head circumference

• 2)Pubertal stage

• 3)Bp

• Laboratory Studies • Investigation at each clinical visit • 1)Full blood count /ferritin if needing an erythropoises

stimulating agent • 2)Urea and electrolytes .. Bicabonat and creatinine • 3)Calcium, phosphate, albumin , alkaline phosphatase,

intact pth • 4)Urine protein / albumin to creatinine ratio • 5)Fasting HDLand LDL, total cholesterol and

triglycarides

• GFR is measured most accurately by infusion of a substance that is freely filtered by the glomerulus but not metabolized, reabsorbed, or secreted in or by the tubules.

• GFR is calculated as follows: • GFR U = [ ]V P[ ] • where [U] is urine concentration, [P] is serum concentration

of a substance (mg/dL) used to measure clearance, and V is urine flow rate (mL/min).

• By convention, GFR is corrected to body surface area of 1.73 m2 to allow comparison between different-sized individuals.

• In a full-term newborn, an uncorrected GFR of 4-5 mL/min corrects to approximately 40 mL/min per 1.73 m2.

• GFR increases rapidly during the first 2 years of life until it achieves adult values (100-120 mL/min per 1.73 m2 ).

• After that, GFR and body size increase proportionately, so GFR/1.73 m2

remains stable. • Plasma creatinine reflects muscle mass, increases with age,

and is used to approximate GFR. • Creatinine is also secreted by the PT, resulting in less

accurate measurement of GFR with immature kidneys or with decreased renal function.

• Blood urea nitrogen is affected by renal function, but is also affected by hydration, nutrition, catabolism, and tissue breakdown.

• Gross hematuria or prolonged contact (uncircumcised boys) may result in a false-positive nitrite test.

• Microscopic urinalysis is used to confirm pyuria and hematuria and detect casts and crystals.

• Proteinuria can be further defined by a spot urine protein/ creatinine (UPr/Cr) in a single urine specimen.

• This unit-less value correlates very well with 24-hour urine protein excretion: spot UPr/Cr approximates 24-hour urine protein/m2 per day (normal <0.20; nephrotic range >2.0 in children).

• IMAGING STUDIES • Ultrasound reliably assesses kidney size, determines degree of

dilation, and differentiates cortex and medulla. • The bladder also can be visualized. • Pulsed Doppler studies assess arterial and venous blood flow and

can provide the vascular resistive index in each kidney. • A voiding cystourethrogram involves filling of the bladder to detect

vesico ureteral reflux and to evaluate the urethra. • Computed tomography and magnetic resonance imaging have

mostly replaced the intravenous pyelogram to evaluate kidney structure and function.

• Radionuclide studies can define renal size, scars, and renal function/excretion

Treatment

Stages of treatment : 1) Stage one : diagnosis and

treatment of primary disease 2) Stage two-three: retard

progression , treat complications/comorbidities

3) Stage four :prepare for renal replacement therapy

4) Stage five : renal replacement

• The management of children with advanced CKD requires a multidisciplinary team of pediatric practitionersIn infants,

• . Common treatment considerations for other CKD complications are given in a table in the next slides

• Measures can be taken to preserve kidney function or slow progression of CKD.

• Potentially nephrotoxic medications should be avoided when feasible.

• Medication adjustment for reduced kidney function is important

Conservative treatment : 1)Nutrition : . Adequate nutrition should be provided even if this requires dietary supplements and tube feedings. Control vomiting (rantidine ) Unless a child is oliguria, fluid restriction is not necessary. Many children with CAKUT require supplemental salt due to urine sodium wasting. Conversely, children with GN tend to retain sodium and may become hypertensive or edematous if given excess salt

• . Protein intake is typically not restricted in pediatric CKD.but protein and potassium may be restricted in stage 4-5

Feeding :

1) Breast milk

2) . a low-solute formula (SMA) / high energy formula (Maxijul)/low potassium/low phosphate formula (Renastart)

• .Slowing the progression of chronic kidney disease

• 1. Control proteinuria :

• - Rate of decline of kidney function is closely related to the quantity of proteinuria

• - Use:

• * Angiotensin Converting Enzyme Inhibitors; enalapril or captopril and/or

• * Angiotensin Receptor Blockers(Irbesartan)

• 2. Control hypertension :

• -BP should be maintained within the normal range for age and height

• - There is some evidence that BP <50th centile may be beneficial

• Hypertension and proteinuria can be treated with ACE inhibitors or angiotensin receptor blockers.

• 2. Control Dyslipidemia by :

• - Dietary intervention

• - Statins

• 4. Treatment of anemia

• The optimal treatment of ESRD is renal transplantation.

• Both deceased and living donors can be used for renal transplantation. Living donors are preferred when available.

• Maintenance dialysis is effective for a child awaiting renal transplantation or when renal transplantation is not possible.

• Indications for chronic dialysis are given in the next Table .Peritoneal dialysisis done at home by the family.

• Hemodialysis is typically done three times a week at a dialysis facility

Treatment of hyponatremia

• Rapid correction of hyponatremia can produce central pontine myelinolysis. Avoiding more than a 12-mEq/L increase in the serum sodium every 24 hours is prudent, especially in chronic hyponatremia.

• Treatment of hypovolemic hyponatremia requires administration of IV fluids with sodium to provide maintenance requirements and deficit correction, and to replace ongoing losses .

• For children with SIADH, water restriction is the cornerstone of therapy, although vaptans, which are ADH antagonists, have a role in some patients.

• Children with hyponatremia secondary to hypothyroidism or cortisol deficiency need specific hormone replacement.

• Acute water intoxication rapidly self-corrects with the transient restriction of water intake, which is followed by introduction of a normal diet.

• Treatment of hypervolemic hyponatremia centers on restriction of water and sodium intake, but disease-specific measures, such as dialysis in renal failure, may also be necessary

• Emergency treatment of symptomatic hyponatremia, such as seizures, uses IV hypertonic saline to rapidly increase the serum sodium concentration, which leads to a decrease in brain edema.

• One milliliter per kilogram of 3% sodium chloride increases the serum sodium by approximately 1 mEq/L. A child often improves after receiving 4-6 mL/kg of 3% sodium chloride.

Treatment of hypernatremia

• As hypernatremia develops, the brain generates idiogenic osmoles to increase the intracellular osmolality and prevent the loss of brain water.

• This mechanism is not instantaneous and is most prominent when hypernatremia has developed gradually.

• If the serum sodium concentration is lowered rapidly, there is movement of water from the serum into the brain cells to equalize the osmolality in the two compartments. The resultant brain swelling manifests as seizures or coma. Because of these dangers, hypernatremia should be corrected slowly.

• The goal is to decrease the serum sodium by less than 12 mEq/L every 24 hours.

• The most important components of correcting moderate or severe hypernatremia are restoring the effective intravascular volume and then frequently monitoring the serum sodium to allow adjustment of fluid therapy and to provide adequate correction that is neither too slow nor too fast

• In a child with hypernatremic dehydration, as in any child with dehydration, the first priority is restoration of intravascular volume with isotonic fluid

• outlines a general approach for correcting hypernatremic dehydration secondary to gastroenteritis.

• If the hypernatremia and dehydration are secondary to water loss, as occurs with diabetes insipidus, a more hypotonic IV fluid is appropriate.

• A child with central diabetes insipidus should receive an ADH analog to prevent further excessive water loss.

• A child with nephrogenic diabetes insipidus requires a urine replacement solution to offset ongoing water losses.

• Chronically, reduced sodium intake, thiazide diuretics,and nonsteroidal antiinflammatory drugs can decrease water losses in nephrogenic diabetes insipidus.

• Acute, severe hypernatremia, usually secondary to sodium administration, can be corrected more rapidly because idiogenic osmoles have not had time to accumulate;

• this balances the high morbidity and mortality from severe, acute hypernatremia with the dangers of overly rapid correction.

• When hypernatremia is due to sodium intoxication, and the hypernatremia is severe, it may be impossible to administer enough water to rapidly correct the hypernatremia without worsening volume overload.

Some patients require the use of a loop diuretic or dialysis.

Treatment of hypokalemia

• Factors that influence the therapy of hypokalemia include the potassium

level, clinical symptoms, renal function, presence of transcellular shifts of potassium, ongoing losses, and the patient’s ability to tolerate oral potassium.

• Severe, symptomatic hypokalemia requires aggressive treatment. Supplementationis more cautious if renal function is decreased because of the kidney’s limited ability to excrete excessive potassium.

• The plasma potassium level does not always provide an accurate estimation of the total body potassium deficit because there may be shifts of potassium from the intracellular space to the plasma.

• Clinically, this shift occurs most commonly with metabolic acidosis and as a result of the insulin deficiency of diabetic ketoacidosis;

• the plasma potassium underestimates the degree of total body potassium depletion.

• . When these Patients who have ongoing losses of potassium need correction of the deficit and replacement of the ongoing losses.

• Because of the risk of hyperkalemia, intravenous (IV) potassium should be used cautiously. Oral potassium is safer in nonurgent situations. The dose of IV potassium is 0.5-1 mEq/kg, usually given over 1 hour. The adult maximum dose is 40 mEq.

• Conservative dosing is generally preferred. For patients with excessive urinary losses, potassium-sparing diuretics are effective.

• When hypokalemia, metabolic alkalosis, and volume depletion are present, restoration of intravascular volume decreases urinary potassium losses.

• problems are corrected, potassium moves into the intracellular space, and these patients require more potassium supplementation to correct the hypokalemia

Treatment of hyperkalemia

• The plasma potassium level, the ECG, and the risk of the problem worsening determine the aggressiveness of the therapeutic approach.

• A high serum potassium level with ECG changes requires more vigorous treatment.

• An additional source of concern is a patient with increasing plasma potassium despite minimal intake.

• This situation can occur if there is cellular release of potassium (tumor lysis syndrome), especially in the setting of diminished excretion (renal failure).

• The first action in a child with a concerning elevation of plasma potassium is to stop all sources of additional potassium (oral and IV).

• If the potassium level is greater than 6.5 mEq/L, an ECG should be obtained to help assess the urgency of the situation.

• Therapy of hyperkalemia has two basic goals: 1. Prevent life-threatening arrhythmias 2. Remove potassium from the body Treatments that acutely prevent arrhythmias all work quickly (within minutes), but do not remove potassium from the body. • Long-term management of hyperkalemia includes reducing intake

via dietary changes, and eliminating or reducing medications that cause hyperkalemia.

• Some patients require medications, such as sodium polystyrene sulfonate and loop or thiazide diuretics, to increase potassium losses. The disorders that are due to a deficiency in aldosterone respond to replacement therapy with fludrocortisone, which is a mineralocortic .

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