Research Article - Current Pediatric Research (2025) Volume 29, Issue 1

Chronic kidney disease after pediatric hematopoietic stem cell transplantation - current knowledge

Katarzyna G?sowska^{1,3 *}, Katarzyna Zachwieja¹, Aleksandra Krasowska-Kwiecie?², Jolanta Go?dzik², Dorota Dro?d?¹

¹Department of Pediatric Nephrology and Hypertension, Jagiellonian University Medical College, University Children’s Hospital of Cracow, Poland

²Department of Clinical Immunology and Transplantation, Institute of Pediatrics Jagiellonian University Medical College, University Children’s Hospital of Cracow, Poland

³Doctoral School of Medical and Health Sciences, Jagiellonian University Medical College, University Children’s Hospital of Cracow, Poland

Corresponding Author:

Katarzyna G?sowska
Department of Pediatric Nephrology and Hypertension; Jagiellonian University Medical College, University Children’s Hospital of Cracow, Poland.
E-mail: kaamiikrut@gmail.com

Received: 23 December, 2024, Manuscript No. AAJCP-25-156110; Editor assigned: 25 December, 2024, Pre QC No. AAJCP-25-156110 (PQ); Reviewed: 08 January, 2025, QC No. AAJCP-25-156110; Revised: 17 January, 2025, M anuscript No. AAJCP-25-156110 (R); Published: 24 January, 2025, DOI:10.35841/0971-9032.29.01.2358-2362

Abstract

Nowadays hematopoietic stem cell transplantation (HSCT) has become well-established therapy in management of various clinical conditions. Approximately 30% of recipients undergo the procedure in childhood. HSCT may trigger life-threatening complications resulting from cytotoxic treatment, immunosuppression or graft versus host disease (GVHD). Immediate transplant related mortality has been significantly reduced during the past decades, nonetheless long-term complications are challenging with different intensity and presentation of symptoms. Acute kidney injury (AKI) and chronic kidney disease (CKD) are frequently mentioned complications. Data on CKD after bone marrow transplantation specific for pediatric patients remains limited. We reviewed literature concerning CKD in children after HSCT of past few years. Narratively we described data on epidemiology, clinical picture and recognized risk factors for CKD in children. The average incidence of CKD after pediatric HSCT is approximately 15-17%, but it varies from 0 to over 30% and it is much lower than in adults. Hypertension and microalbuminuria are often observed in these patients coexisting with diminished eGFR. Among CKD risk factors after HSCT the following are mentioned: severe AKI, chronic GVHD, chronic calcineurin inhibitors usage and total body irradiation before HSCT. Patients with thrombotic microangiopathy after HSCT have essentially worse renal outcome. In conclusion we underline that the risk for CKD in children is significant after HSCT and impairs the renal future therefore is the necessity for regular screening for early signs of this complication and identifying patients that are at risk for CKD in children after HSCT.

Keywords

Chronic kidney disease; Hematopoietic stem cell transplantation; Pediatric population

Introduction

HSCT has gained frequent use in management of various clinical conditions, including oncological diseases, bone marrow insufficiency?related-disorders, inborn errors of metabolism etc. In spite of advanced treatment protocols and post-transplant care improved patients? survival, the acute and chronic complications occurring after HSCT became the subject of research and interest. Annually there are approximately 90,000 procedures performed worldwide, of which transplants in pediatric patients constitute approximately 30% of all recipients [1,2]. Individuals who underwent HSCT in childhood appear to show potentially better outcome than adult patients. This favors the occurrence of long-term complications, partially related to the immaturity of the child's body and its development and growth. Frequently described observations include renal complications such as AKI and CKD [3?7]. All post-transplant patients diagnosed CKD require regular monitoring of their kidney function parameters. CKD worsens the long-term prognosis, although the clinical symptoms described are often discreet. The purpose of this study was to analyze the literature on the occurrence of CKD in pediatric HSCT recipients. Studies from 2010 till 2023 which included patients who received a HSCT under the age of 18 were analyzed. The additional aim was the proposition of nephrological recommendations for children after HSCT.

Types of renal complications

HSCT procedure involves the preparation of the graft and the therapy including high-dose chemotherapy, high-dose irradiation, use of various antimicrobial agents and others, that may cause kidney damage. Typically, patients with oncological malignancies undergo several months of intensive cytotoxic treatment and afterwards HSCT is performed as the consolidation of the therapy. The procedure requires the use of nephrotoxic drugs. This results in a relatively high risk of kidney damage in this particular group of patients.

Allogeneic transplantation requires intensive immunosuppressive therapy post-procedure to prevent graft-versus-host disease. There is no need for immunosuppression in autologous transplantation, where the patient?s own stem cells are reintroduced. As a result, kidney damage is significantly more common following allogeneic HSCT comparing to autologous [8].

Nephrological complications after HSCT include: AKI, CKD, hypertension, kidney involvement in the course of GVHD, glomerulonephritis, urinary tract infection, viral nephropathy and others [3?14]. The types of chronic renal complications after HSCT are presented in Table 1.

Table 1: The types of chronic kidney damage after HSCT.

Literature Review

Definition of chronic kidney disease

Diagnosis of CKD means a decrease in estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2 or presence of proteinuria/microalbuminuria and /or changes in kidney imaging, most often viewed on ultrasound or abnormalities in laboratory tests related to the urinary system persisting for 3 months. In children eGFR < 60 ml/min/1,73m2 is actually stage III according to the CKD classification. In clinical practice in children (excluding neonates), a decrease in eGFR < 90 ml/ min/1,73m2 lasting > 3 months supports for the diagnosis of CKD. Arterial hypertension is a separate abnormality and often coexists with CKD, but is treated separately. Hence, the definition of CKD in children, also in the analyzed groups after HSCT, differ among studies, which contributes to discrepancies in epidemiological data.

Assessment of estimated (eGFR) in children after HSCT

In pediatric clinical practice, it is recommended to use three formulas for estimating eGFR: The 2009 bedside Schwartz formula (based only on serum creatinine concentration), the three-marker Schwartz formula (additionally requiring urea, cystatin C and the child's age and gender) and the 2021 U25 formula (taking into account patient?s age, gender, serum creatinine and cystatin C). The U25 equation proposes different coefficient related to age or gender. eGFR might be also calculated with creatinine clearance based on daily urine collection. Formulas consisting of several markers are considered more accurate. In children with oncological diseases, the superiority of cystatin C concentration is emphasized, mainly due to relatively often observed low muscle mass and malnutrition, which results in lower creatinine concentration and thus overestimation of the calculated eGFR [15] This correlation was not confirmed in all studies, but all authors agree on using several marker formulas [16-18]. Precise calculation of eGFR is also necessary and essential for chemotherapy and the antibiotics proper dosage. For a more accurate assessment of eGFR, it is worth using direct methods, e.g. the iohexol elimination and isotopic markers which is mainly used in scientific centers [19].

Risk factors and epidemiology of CKD in pediatric population

The first description of CKD after HSCT comes from 1978 [20]. According to one study on children who underwent cancer treatment, around 0.5% were diagnosed with CKD approximately 17 years after diagnosis. This was 9 times more common than in young individual with no past medical history [21]. The frequency of CKD in pediatric patients varies and this results from different definitions of CKD used in studies and diversity in study groups. Duration of follow-up also affects the frequency of diagnosis. Last but not the least, the primary disease is a very essential factor which has the most important influence on type of HSCT and treatment before and following HSCT- e.g. children with sickle cell anemia after HSCT are relatively rarely diagnosed with CKD [22].

The most important predictive factor for renal function after HSCT is the basic renal function at the moment of HSCT. The pediatric patients with eGFR<90 or even<60 ml/min/1,73m2 are observed exceptionally. In our own data only one patient had eGFR< 60 ml/min1/73m2 before HSCT procedure. Interestingly, in one observation concerning HSCT in adults mild renal impairment (eGFR<60 ml/min1/,73m2) had no influence on outcome after HSCT [23]. There is an exceptional example of HSCT in child with severe renal failure at the time of HSCT [24]. The type of HSCT is related to number of renal complications. The autologous HSCT has a much lower risk for developing CKD in comparison to allogenic HSCT which is related to absence of immune complications and no use of immunosuppressants and consequent lower rate of severe complications, among others AKI [8, 11]. According to some papers the incidence of CKD may be up to 48% after HSCT, especially in adult patients [25,3,26].

Most frequently mentioned risk factors for development of CKD include: AKI, the use of calcineurin inhibitors in high doses, lowered eGFR at the time of transplantation, diagnosis of sepsis, use of nephrotoxic medications such as antimicrobials (mainly glycopeptides, aminoglycosides, amphotericin B, antiviral drugs) and chemotherapeutics (mainly cisplatin, ifosfamide), ACE inhibitors, use of Total Body Irradiation (TBI), Thrombotic Microangiopathy (TMA), GVHD, venoocclusive disease (VOD), dehydration, arterial hypertension [26, 19, 27] . AKI has not always been reported as a risk factor for the development of CKD [3,25]. In all patients undergoing HSCT, especially in those with AKI kidney function should be carefully monitored in posttransplant course, even for years.

Table 2 contains data from publications since 2010 on the occurrence of CKD in children, the frequency ranged from no CKD (patients with sickle cell anemia) to over 62% after 3 years of observation of patients after allo-HSCT, the average was about 20%.

The largest number of patients observed for CKD after HSCT was described in the work of Ellis et al. from 2008, summarizing data on 9,317 patients (both adults and children), including 7,317 who survived 100 days after HSCT [4]. There were 5337 patients followed up to 9 years after HSCT. In this group, 7 cohorts concerned children only (324 cases) and 7 included children and adults together (1896 patients). The definition of CKD varied, described as an increase in serum creatinine concentration, eGRF < 60 ml/min/ 1,73m2 or a 25% decrease in baseline eGFR. In the entire group, the incidence of CKD was reported 16.6% over 2 years (from 3.6% to 89%), including 27.8% after allogeneic HSCT and 25.2% after autologous HSCT.

In all patients, the initial eGFR was described as > 100 ml/min/ 1.73m2. The calculated average eGFR values after HSCT showed approximately 24.5 ml/min/1.73 m2 decrease during the first 12 months after the procedure. The numbers are alarming, particularly considering that the average decline in eGFR after the age of 40 ranges about 0.75-1 ml/min/1.73 m2 per year. AKI, chronic GVHD, long-term cyclosporine A use, and TBI were associated with the development of CKD in at least 2 patient cohorts. End stage renal disease (ESRD) was found in 0.8% of patients, hypertension in 12.4% and proteinuria in 7.8% These data are not presented in table 2 [4].

Table 2: Data on publications since 2010 on the occurrence of CKD in children after HSCT.

Selistre et al (2022) showed that among a homogeneous group of allogeneic HSCT recipients with hematological malignancies (mainly acute lymphocytic leukaemia) prepared with uniform conditioning regimen, decrease of eGFR<90 ml/min/1,73m2 was found in 32.8% in long-term follow-up, and 16% of patients presented with tubulopathy. In a multivariate analysis, the authors did not demonstrate any of the previously described risk factors for the development of CKD, although patients with BKV infection, acute GVHD and TBI had a higher incidence of CKD. [28].

Gadashova at al. assessed the occurrence of CKD in a group of 94 HSCT recipients and noted a large discrepancy in the detection of CKD depending on the eGFR formula used. When using the formula with creatinine and cystatin C concentration, the significant CKD incidence increased to 24%, when using the formula only with creatinine concentration - CKD was detected in only 9.4%, while the formulas using cys C concentration allowed for the diagnosis of CKD in as many as 68.8% kids. In univariate analysis: age>10 years at the time of HSCT, the occurrence of AKI and CMV infection were risk factors for CKD [16]

Pedersen et al described 18 children with sickle cell anemia after HSCT and showed that after 10 years of observation, renal function was stable which is a favorable observation compared to others HSCT recipients. The authors explained it by different chemotherapy regimen and no calcineurin inhibitors usage in the patients [22].

Yanir et al. collected 124 children after allo HSCT with ALL, treated in a single center. CKD (without the detailed definition) was diagnosed in 21% of patients during the 3-year follow-up and was identified as the most common late complication. This incidence of CKD is higher than in studies previously mentioned [29].

Suominen et al. showed slight decrease in eGFR in approximately 1/5 of patients after 20 years of treatment of neuroblastoma with auto-HSCT, but the abnormal ABPM and increased ACR were detected in more than half of the patients [30].

Lughart et al., studied 216 patients after allo HSCT in average 8-year follow-up and showed a CKD incidence of 17.1%. The average decrease of eGFR was 22% comparing to baseline eGFR values, the largest decrease in eGFR occurs in the first year of observation. In most patients, CKD developed 5 years after transplantation. The risk factors for CKD in the multivariate analysis were severe AKI lasting more than 28 days in the 1st year after HSCT and hematological malignancies as primary disease, while the use of CsA did not increase CKD risk. A lower incidence of CKD was observed in HSCT recipients with inborn errors of metabolism [31].

Ukeba-Terashita et al found that solid tumors, the use of fludarabine and age > 7 years at the time of HSCT are risks factors for CKD. They observed decline in eGFR in an average of 21% of 83 patients for an average period of 1-27 months, they used their own formulas to calculate eGFR using creatinine concentration [32].

Gurbanov et al. identified in multivariate analysis chronic GVHD, as well as the use of cord blood and mobilized peripheral blood as cell sources, were significant CKD risk factors, CKD was diagnosed in 4.8% of 72 patients with longterm follow-up of up to 4.4 years, and hypertension or prehypertension in 7.4% and 14.7% respectively [33].

Prasad et al. demonstrated that eGFR in 90 days after AKI diagnosis is predictive risk factor for CKD developing [34].

In another earlier published papers, there were more optimistic results [27], but CKD remains severe complications [35].

Particular risk factors of CKD

Thrombotic Microangiopathy (TMA): The incidence of thrombotic thrombocytopenic purpura in children after HSCT is not very high, varying between 0,8-3%, but this severe, life-threatening complication may lead to both AKI and CKD. Damage to the endothelium is mainly caused by drug-related effects (e.g. calcineurin inhibitors), specific genetic factors and immunological disparities. Other reported risk factors include TBI, acute GVHD, infections and peripheral stem cell transplantation, allogenic transplant, high-dose chemotherapy [12, 8]. TMA typically occurs 1-3 months after HSCT.

The diagnostic criteria include the presence of anaemia with RBC fragmentation with schistocytes seen on a peripheral blood smear, negative Coombs test results, thrombocytopenia, increased serum LDH, concurrent renal or neurologic dysfunction. Anyhow in patients after HSC the severity of thrombocytopenia or anemia may be difficult to interpret. Patients may present with symptoms from various organs (e.g., alveolar bleeding or neurological disorders). Management of TMA remains universal (symptomatic management, eculizumab and/or plasmapheresis) with different results [36].

The diagnosis of TMA is associated with a significantly higher risk of developing CKD [37]. According to one study, as many as 33% of 15 children with TMA after HSCT treated with therapeutic plasma exchange developed CKD. This study did not confirm the effectiveness of TPE in preventing the development of CKD [38].

Glomerular damage

Some children as well as adults present with full-blown nephrotic syndrome or nephrotic-range proteinuria ? the phenomenon was mentioned by the authors as a part of chronic GVHD of unknown etiology [39]. The mechanism was described as immunological activity of the "host" B lymphocytes and functional disorders of T lymphocytes changing the permeability of the glomerular basement membrane [40]. Cases of glomerular damage unrelated to GVHD have also been reported in the literature ? mostly as minimal change disease or membranous nephropathy [41]. The therapy is based on typical immunosuppressants showing promising and good results.

GVHD Graft-versus-host disease

GVHD is one of the most frequently observed complications after HSCT. Renal involvement is relatively uncommon in this clinical presentation. Thus, there are no specific criteria for diagnosing renal involvement in GVHD. However, it is emphasized that inflammatory factors such as endothelial damage and cytokine cascade may cause kidney damage, as well as nephrotoxic drugs used in GVHD management. The occurrence of GVHD is considered a risk factor for both acute and chronic kidney damage [14, 8].

TBI

Radiotherapy used in many HSCT protocols may induce nephropathy [27]. According to Nada and Jetton, there are 4 forms of post-radiation nephropathy: acute nephropathy, chronic nephropathy and benign and malignant hypertension. Chronic damage is usually observed more than 18 months after HSCT, as is hypertension. This complication is rarely observed in children, unlike adults. It more often affects children in the course of Wilms' tumor [42]. The exact mechanism of damage is not explained, including changes in the permeability of the glomerular endothelium, oxidative stress, damage to the RAA axis and vascular damage. According to the Long Term Follow Up Guidelines for Survivors of Childhood, Adolescent and Young Adult Cancers (COG LFTU guidelines), all children after HSCT, especially after radiotherapy, should be monitored for the occurrence of hypertension and CKD features.

Viral nephropathy

Infection with BK Polyoma Virus (BKPyV) or adeno virus is a common cause of hemorrhagic cystitis in immunosuppressed people. Risk factors for the development of this infection in children after HSCT are considered to be a high load of the viral DNA in urine and blood reflecting a reactivation of BKPyV, peripheral blood transplantation or umbilical cord blood stem cell transplantation, GVHD and other concomitant viral infections [12]. A serious infection can also lead to nephropathy and severe kidney damage. Similarly, this may apply to adenoviral infection and to CMV infection after HSCT. In each case, it is necessary to modify and reduce immunosuppression. In BKPyV infections leflunomide is recommended. Antiviral drugs i.e., cidofovir and brincidofovir are less recommended with their high nephrotoxicity and poor result in BKPyV eradication. Hyperbaric oxygen therapy and high dose estrogen therapy have been proven as effective methods in haemorrhagic cytitis. One study showed that high BKV viremia in the early period (4-7 weeks after HSCT) in children was a risk factor for a decline in eGFR, assessed 1 year after transplantation, regardless of the symptoms of hemorrhagic cystitis [43].

Tubulopathy

Tubular damage may occur as an isolated disorder or coexist with features of CKD. Chemotherapeutic agents that cause tubular damage include ifosfamide and its toxic metabolite, chloracetaldehyde, which induces proximal tubular damage and the development of Fanconi syndrome. A higher cumulative dose of the drug correlates with an increased risk of this complication and the occurrence of chronic kidney disease. Similarly, another agent cisplatin acts in a tubulotoxic manner, typically damaging the distal tubule and causing hypomagnesemia, but it can also lead to the full manifestation of Fanconi syndrome. The combined use of both drugs results in increased tubulotoxicity [42].

VOD-SOS (venoocclusive disease/ sinusoidal obstruction syndrome)

This pathological process involves damage to the endothelium of hepatic sinuses, leading to damage, necrosis and vascular obstruction. If left untreated, it leads to liver failure, hepatorenal syndrome, multi-organ failure and even death. The incidence in the pediatric population after HSCT is estimated at several percent, with a significant risk factor for mortality. VOD-SOS is a risk factor for AKI in particular, but also CKD [44].

AKI

There are several definitions of AKI, including the RIFLE (Risk, Injury, Loss of kidney function, End-stage kidney disease) scale, AKIN criteria (Acute Kidney Injury Network), and KDIGO (Kidney Disease Improving Global Outcomes) criteria ? recommended by some authors [44]. AKI, unlike CKD, is very frequently observed in children after HSCT, most commonly within the first 100 days, with a median onset of 4-6 weeks [45]. Some authors, in adults, further differentiate between early AKI, occurring before the engraftment period (7-30 days after HSCT) with worse prognosis, and so-called late AKI, which has a better prognosis [46].

According to various sources, AKI may affect up to 50% (or even 80%) of patients after HSCT. As previously mentioned, the etiology is usually multifactorial. Risk factors for AKI include preexisting kidney damage, chemotherapy, myeloablative conditioning, nephrotoxic drugs sepsis, viral infections, acute and chronic GVHD, older age, and obesity. Drug-related causes are particularly emphasized [47]. Moreover, based on autopsy findings in patients with AKI, some authors highlight hemodynamic factors rather than structural damage as key contributors [46]. In patients undergoing autologous transplantation, nephrotoxic antibiotics, including antifungals, and sepsis are primarily cited as causes [48].

According to the literature, most forms of AKI are mild (up to 60% of cases) and do not require dialysis. Severe AKI, especially when renal replacement therapy is needed, significantly worsens prognosis and increases mortality (by up to 10 times or more) [45, 49, 50]. Many, though not all, authors mention AKI as a risk factor for CKD [51].

Rajpal et al noted improvement of survival in pediatric patients requiring dialysis due to AKI after HSCT in recent years comparing to the past, but overall the need for dialysis is the bad prognostic factor in these patients [52].

In the management of AKI, authors emphasize monitoring and avoiding nephrotoxic drugs, early detection and treatment of sepsis and venoocclusive disease, maintaining diuresis, urine alkalinization, and early nephrology consultation [48].

There are no specific levels of risk, but all of the complications described can lead to CKD.

Symptoms of CKD

Albuminuria

Increased urinary albumin excretion is a simple and sensitive test. The ACR (albuminuria to urine creatinine ratio) value > 30 mg/g in a portion of urine indicates a risk of nephropathy and requires nephrological consultation and eGFR assessment. According to some, it is common in children after HSCT up to 50% one year after HSCT [9] and, determined 100 days after HSCT, it is a risk factor for the development of CKD [40].

Since microalbuminuria is already considered a kind of "screening" test for diabetic nephropathy in children with diabetes, taking into account the availability and simplicity of the test, it seems advisable to monitor this indicator in all patients after HSCT at least every year, and in the first year after HSCT every 3 months or as clinically indicated. Daily albumin excretion is a helpful additional test, but due to the nuisance in small children (requirement of catheterization) and the inaccuracy of daily urine collection, it is not possible in all children. Undoubtedly, macroalbuminuria > 300 mg/g creatinine may require the inclusion of drugs from the group of converting enzyme inhibitors or angiotensin II receptor inhibitors and necessarily the nephrological diagnostics.

Hypertension

The presence of hypertension in children after HSCT is considered a risk factor for death, cardiovascular complications and worse long-term prognosis and occurrence and progression of CKD. The definition of hypertension is the same as in healthy children. Just like the guidelines for therapeutic procedures. According to the recommendations, in children with additional risk factors, such as the coexistence of CKD or microalbuminuria, blood pressure should be reduced to the 50th percentile for gender, age and height. Due to the treatment used and its chronicity, children after HSCT have more additional factors contributing to the development of hypertension. According to Hoffmeister et al., who studied a large group of children (689) after HSCT followed for an average of 16 years, the incidence of hypertension was approximately 17%, i.e. 2-3 times higher than in the healthy population. They noted AKI, type of bone marrow donation (autologous and unrelated donor in allograft), TBI, diabetes, obesity and growth hormone treatment as the risk factors for hypertension [53]. Other authors, based on ABPM, confirm a similar frequency of hypertension in this population and drew attention to the presence of diastolic hypertension - indicating the need to expand the diagnostics [54].

Monitoring and treatment

There is no specific treatment for CKD after HSCT. The problem remains, as mentioned, early diagnosis and the need to perform additional diagnostic tests, such as blood pressure measurement, assessment of cystatin C concentration, general urinalysis, assessment of UPCR and ACR indexes in the urine sample and periodic ultrasound assessment of the kidneys.

The basic assessment recommended by Sedhom et al. [12] are presented below suggest:

Searching for specific types of kidney damage such as: TMA, GVHD and others, early referral to a nephrologist and assessment of kidney function and possible progression of CKD and other co-morbidities. Particular attention should be paid to: glycemic control, diagnosis and treatment of hypertension, assessment of drug toxicity, detection of proteinuria/microalbuminuria.

In the early post-transplant period, the above tests are performed regularly. But it is worth continuing this check-up every 6?12 months, depending on the clinical situation. There are recommendations available for management once CKD has been diagnosed, but it seems advisable to monitor renal function at least annually for at least 10 years after the procedure. All children with diagnosed features of CKD should be additionally monitored by a nephrologist [44].

The main therapeutic options for CKD in children after HSCT include: antihypertensive treatment (usually recommend the use of ACE or ARB as the first line of drugs, in the absence of contraindications) and nephoprotective treatment ? reduction of microalbuminuria and proteinuria, correction of acid-base disorders, monitoring and treatment of urinary tract infections. The remaining therapeutic options are consistent with the recommendations for the treatment of children with CKD.

ESRD after HSCT in children

The occurrence of ESRD with the need to qualify for kidney transplantation is very unique in children [55]. The literature describes isolated cases of children with good results. In the case of kidney transplantation from the same donor from whom the stem cells came, there is no need to give immunosuppression, which obviously reduces the complications of this treatment [44, 56, 57].

Mortality and morbidity risk associated with CKD

The diagnosis of CKD in a pediatric patient after HSCT is associated with an increased risk of morbidity and mortality, especially future cardiovascular complications. But it should be underlined that the early stages of CKD are asymptomatic and the consequences may appear very late in future.

The occurrence of CKD can be considered an observed complication affecting children treated for potentially life-threatening hematologic-oncologic conditions. A close collaboration between oncologists and nephrologists appears essential for the early detection and optimal management of potential renal damage.

Nephrological Recommendations for Children after HSCT

In conclusion, we present our own proposal of diagnostic recommendations for children following HSCT, as outlined in Table 3. These recommendations are subject to change based on the clinical context and the guidelines provided by transplant physicians.

Table 3: Recommended nephrological follow-up in pediatric patients post HSCT.

The formulas recommended of our own proposal for calculating eGFR according to KDIGO and our own opinion for children up to 12 years of age are: The one-marker Schwartz formula from 2009, the three-marker Schwartz formula from 2009, and the U25 formula from 2021. For children older than 12 years, adult formulas may be used [59]. In cases of growth deficiencies, the appropriate age for height, rather than the patient?s chronological age, should be used. Any abnormalities found in the mentioned tests should prompt a quick referral for a nephrology consultation.

Conclusion

The occurrence of CKD after HSCT is relatively common. Children in the first year after HSCT require detailed monitoring of kidney function (we suggest monitoring basic blood tests and urine UPCR and ACR indicators, as well as blood pressure assessment). Children with increased risk factor for CKD or detected abnormalities should undergo consultation by a nephrologist. In children after HSCT the long-term follow-up requires periodic kidney function assessments.

References

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