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Introduction
Chronic kidney disease (CKD) has significant consequences on the quality of life of those who suffer from it1. This aspect has a greater impact on the pediatric population, as in this population, the mortality rate in end-stage renal disease is 30 times higher than in healthy patients2. Kidney disease in pediatrics is associated with a 4 times higher risk of kidney failure compared to adults3. In particular, CKD in pediatrics can have medium and long-term effects, such as growth suppression, bone disease, delayed sexual development, chronic anemia, and anorexia. However, available therapeutic interventions can prevent these complications and decrease the rate of disease progression4,5. Late diagnosis leads to consequences such as increased morbidity and mortality. Similarly, late referral to specialized care is associated with more severe clinical manifestations, the need for emergency dialysis with temporary vascular access, and hinders the selection of the renal replacement therapy (RRT) modality and prevents adequate preparation for it6. The prevalence of CKD has increased, and this is partly evident due to the higher number of patients using RRT2. In Colombia, according to data from the High-cost Account for the 2021 period (from July 1, 2020, to June 30, 2021), the indicator was 213 cases per million in people between 0 and 19 years old and 86 new cases per million. Of the latter, 9.87% were classified as end-stage7, which raises questions about the timeliness of diagnosis and treatment of this condition in the Colombian health system. This article seeks to establish the minimum contents for a correct diagnostic approach, follow-up, and referral of patients with kidney disease in pediatrics from primary health care.
Methods
Type and design of the research
A systematic literature review (SLR) with an expert discussion panel.
SLR
The SLR was carried out to identify the minimum components for the diagnostic approach and follow-up of CKD in the pediatric population from primary health care. For this, the following guiding questions were generated for the search:
Eligibility criteria
Studies published between 2006 and 2022, written in English or Spanish, with designs such as topic reviews, observational studies (cross-sectional, casecontrol, and cohort), SLRs, meta-analyses, clinical practice guidelines, management protocols, and gray literature were included in the study.
Information sources and study selection: The electronic databases PubMed, Cochrane Database of Systematic Reviews, Embase-Medline, Ovid, Lilacs Virtual Health Library, and Web of Science were used. A manual search was conducted using the snowball technique for related articles based on the title and abstract. The keywords listed in table 1 were used for literature searches and to formulate the search strategy (Supplementary Data 1 and 2).
Table 1 Search terms DeCS and MeSH used
| Category | DeCS terms | MeSH terms | Free terms |
|---|---|---|---|
| Population | Children, infant, adolescent, teenager, adolescence. | Child, pediatrics, infant, newborn, adolescents, adolescence, teenagers. | |
| Chronic kidney disease, chronic renal disease, end-stage kidney disease, ESRD, end-stage renal disease. | Chronic kidney disease, end-stage renal disease, end-stage renal failure, Chronic renal failure, ESRD. | ||
| Intervention/Results | Diagnosis, screening. | Diagnosis, clinical decision making, screening. | Detection, GFR estimation |
| Patient care management, disease management, evidence-based practice, evidence-based health care, primary health care, the standard of care, clinical practice patterns, prevention, and control. | Disease management, patient care management, primary health care, evidence-based practice, evidence-based management, evidence-based healthcare, standard of care, clinical practice patterns | Follow-up | |
| Renal replacement therapy, renal dialysis, peritoneal dialysis, hemodialysis transplantation, waiting list, consultation and referral | Renal replacement therapy, renal dialysis, peritoneal dialysis, hemodialysis, renal transplantation, kidney transplantation, waiting list, referral and consultation, referral | Initiation, Pediatric nephrology, Patient referral, criteria | |
| Excluded terms | Acute, pregnancy, genetic, quality of life, liver disease | ||
DeCS: descritores em ciências da saúde; MeSH: medical subject headings.
For the selection of studies, two evaluators (KJSA and LJHP) independently examined the titles and abstracts of the articles for possible inclusion and subsequently independently determined study eligibility using a standardized inclusion form in Rayyan.
Data extraction
This process was carried out using a standardized form, which recorded details of patients, methodology, results, and interventions. The quality of evidence was assessed according to each type of research design or publication (Supplementary Data 3).
Expert panel and elaboration of recommendations
Two virtual meetings were held with the group of experts delegated by the Colombian Association of Pediatric Nephrology (ACONEPE, for its Spanish acronym), in which the results of the search, data extraction, and quality were presented. With the available evidence, the recommendations were structured together with a group of experts who considered the applicability of each recommendation and its adaptation to the Colombian context. The final document was subjected to external peer review.
Results
Seven hundred and seventy-six articles were identified, and 48 were included in the recommendations. The PRISMA diagram with the SLR results is shown in figure. 1.
Question 1
What are the minimum strategies and interventions for the diagnosis of CKD in the pediatric population and its adequate follow-up?
Screening
RECOMMENDATION 1
- Universal screening for kidney disease in children is not recommended; it should be reserved for those populations with risk factors4,8,9.
RECOMMENDATION 2
- It is recommended to evaluate renal function in at-risk populations8,10: Low birth weight (2500 g or less) and/or prematurity, diabetes, hypertension, heart disease, congenital and urinary tract malformations, multisystemic diseases with potential kidney involvement and compromise, family history of end-stage renal disease (G5), congenital or acquired solitary kidney, history of acute kidney injury of any degree of severity, consumption of nephrotoxic medications (chemotherapeutic agents, lithium, nonsteroidal anti-inflammatory drugs, and calcineurin inhibitors, among others), obesity, and incidental detection of hematuria or proteinuria
Diagnosis
RECOMMENDATION 3
- For diagnosis, it is recommended to perform a complete medical history and anamnesis, including prenatal, perinatal, and childhood history; pathological, family, and pharmacological history; and characterization of current signs and symptoms11,12.
RECOMMENDATION 4
- It is recommended that children with risk factors or signs or symptoms of kidney disease undergo proteinuria assessment with dipstick or quantitative methods10,12.
RECOMMENDATION 5
- The diagnostic approach can be done as follows in the population with risk factors. (Fig. 2).
RECOMMENDATION 6
- To evaluate renal function in children, measuring serum creatinine and estimating the glomerular filtration rate (GFR) using a predictive formula that includes a height term10-14 is recommended.
Recommendation 7
- When available, it is recommended that the measurement of serum creatinine concentration in children and adolescents be performed using a method based on an enzymatic assay due to its better sensitivity. The Jaffe measurement method is recommended in clinical contexts where enzymatic assay is not available15-17.
RECOMMENDATION 8
- In case of its future availability in the country, the use of Cystatin C for the evaluation of renal function should be reserved for patients with conditions in which serum creatinine measurement is not useful (for example, alterations in muscle mass, nutritional alterations, diseases that generate muscle wasting, spina bifida, anorexia nervosa, and liver cirrhosis)12,17-20.
- Cystatin C is a non-glycosylated protein produced in all nucleated cells at a relatively constant rate. The glomerulus freely filters, it has no active secretion by the tubules and is almost completely reabsorbed in the proximal tubules17. Its concentration is high at birth and progressively decreases over the next 12-18 months when it stabilizes similar to adult levels20, which some authors suggest may reflect the physiological maturation of the glomerulus21. This biomarker does not depend on muscle mass, dietary protein intake, age, gender, height, or body composition, which is an advantage over creatinine8,18,20. However, conditions such as hyperthyroidism, high-dose corticosteroid therapy, levothyroxine treatment, and C-reactive protein levels can increase17,18,20. It is considered a more accurate and sensitive biomarker for early decreases in renal function17,18.
Estimation formulas
RECOMMENDATION 10
- Adult GFR estimation formulas (MDRD, CKD-EPI, Cockcroft-Gault) are not recommended in the pediatric population20-25.
RECOMMENDATION 11
- The "Modified Schwartz" equation is recommended for estimating GFR in the pediatric population due to its better accuracy12,14,24,26,27.
Where height is reported in centimeters and CrS in mg/dL
- Note: This equation should be used when creatinine has been measured using enzymatic methods.
- Since the Schwartz 2009 equation was established in children with GFR below 75 mL/min/1.73 m2, all values above this should be reported as >75 mL/min/1.73 m2,28.
RECOMMENDATION 12
- In the pediatric population, when creatinine measurement using enzymatic methods is not available and has been performed using the Jaffe method, it is recommended to estimate GFR using the classic Schwartz equation16,17,20.
Where height is reported in centimeters and CrS in mg/dL and where k = 0.33 in preterm infants in the 1st year of life, k = 0.45 in term infants in the 1st year of life, k = 0.55 in children and adolescent females, and k = 0.7 in adolescent males17.
Classification
RECOMMENDATION 14
- It is recommended that the classification and staging of CKD in children older than 2 years be based on cause, albuminuria, and GFR (Tables 2 and 3)12.
Table 2 Classification of CKD by GFR in children under 2 years and over 2 years
| Classification of CKD in children under 2 years | GFR | |
|---|---|---|
| Normal GFR | GFR ≤ 1 SD below the mean | |
| Moderately reduced GFR | GFR > 1 to < 2 SD below the mean | |
| Severely reduced GFR | GFR > 2 SD below the mean | |
| GFR category in children over 2 years | GFR (mL/min/1.73 m2) | Term |
| G1 | ≥ 90 | Normal or high |
| G2 | 60-89 | Slightly decreased |
| G3a | 45-59 | Slightly to moderately decreased |
| G3b | 30-44 | Moderately to severely decreased |
| G4 | 15-29 | Severely decreased |
| G5 | < 15 | Kidney failure |
Taken from KDIGO 201212 and Zaritsky and Warady, 201413. CKD: chronic kidney disease; GFR: glomerular filtration rate.
Table 3 Categories of Albuminuria in CKD
| Category | Albumin excretion rate (AER) | Albuminuria/creatinine in urine ratio (ACR) | Terms | |
|---|---|---|---|---|
| (mg/24 h) | (mg/mmol) | (mg/g) | ||
| A1 | < 30 | < 3 | < 30 | Normal to slightly increased |
| A2 | 30-300 | 3-30 | 30-300 | Moderately increased |
| A3 | > 300 | > 30 | > 300 | Severely increased |
Taken from KDIGO 201211. CKD: chronic kidney disease.
Follow-up
Question 2
What are the indications and conditions for referral to pediatric nephrology and RRT initiation in pediatric CKD patients?
RECOMMENDATION 18
- It is recommended to seek early referral (at least 3 months before requiring the initiation of RRT) to a pediatric nephrologist consultation, as the late referral is associated with the requirement for emergency dialysis, the lower opportunity for anticipated or pre-emptive kidney transplantation, and a higher probability of progression and morbidity3,31,32.
RECOMMENDATION 19
- It is recommended to refer children who meet any of the following criteria to pediatric nephrology4,10-12: GFR < 60 mL/min/1.73 m2 (CKD stage 3). Structural, anatomical, or functional renal alteration. Arterial hypertension. Systemic diseases with a high probability of renal involvement or compromise. Obstructive uropathy. Albumin-to-creatinine ratio > 30 mg/g.
RECOMMENDATION 20
- It is recommended that in patients with a GFR < 30 mL/min/1.73 m2, an educational intervention be carried out with the family and/or caregivers about RRT and its modalities4,11,33.
RECOMMENDATION 21
- It is recommended to initiate RRT when the GFR is < 15 mL/min/1.73 m2 or when complications such as the following are present2,17,34-38: signs and symptoms of fluid overload. Metabolic acidosis and failure to thrive, neurological complications associated with uremia, electrolyte abnormalities (hyperkalemia, hyperphosphatemia, hypercalcemia), refractory hypertension, or conditions that warrant it according to the pediatric nephrologists assessment.
Conclusion
This document aims to define the minimum components for the diagnostic approach and follow-up of CKD in the pediatric population from primary health care, to ensure comprehensive care and adequate risk management. It establishes the criteria for referral to specialized consultation and the initiation of RRT in pediatric patients with CKD. It proposes health risk management strategies in the pediatric population with CKD for their correct application by primary health care professionals.
