Intervensi untuk penyakit ginjal kronik dalam kalangan orang dengan penyakit sel sabit
Abstract
Background
Sickle cell disease (SCD), one of the commonest severe monogenic disorders, is caused by the inheritance of two abnormal haemoglobin (beta‐globin) genes. SCD can cause severe pain, significant end‐organ damage, pulmonary complications, and premature death. Kidney disease is a frequent and potentially severe complication in people with SCD.
Chronic kidney disease (CKD) is defined as abnormalities of kidney structure or function present for more than three months. Sickle cell nephropathy refers to the spectrum of kidney complications in SCD.
Glomerular damage is a cause of microalbuminuria and can develop at an early age in children with SCD, with increased prevalence in adulthood. In people with sickle cell nephropathy, outcomes are poor as a result of the progression to proteinuria and chronic kidney insufficiency. Up to 12% of people who develop sickle cell nephropathy will develop end‐stage renal disease.
This is an update of a review first published in 2017.
Objectives
To assess the effectiveness of any intervention for preventing or reducing kidney complications or chronic kidney disease in people with sickle cell disease. Possible interventions include red blood cell transfusions, hydroxyurea, and angiotensin‐converting enzyme inhibitors (ACEIs), either alone or in combination.
Search methods
We searched for relevant trials in the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, CENTRAL, MEDLINE, Embase, seven other databases, and two other trials registers.
Selection criteria
Randomised controlled trials (RCTs) comparing interventions to prevent or reduce kidney complications or CKD in people with SCD. We applied no restrictions related to outcomes examined, language, or publication status.
Data collection and analysis
Two review authors independently assessed trial eligibility, extracted data, assessed the risk of bias, and assessed the certainty of the evidence (GRADE).
Main results
We included three RCTs with 385 participants.
We rated the certainty of the evidence as low to very low across different outcomes according to GRADE methodology, downgrading for risk of bias concerns, indirectness, and imprecision.
Hydroxyurea versus placebo
One RCT published in 2011 compared hydroxyurea to placebo in 193 children aged nine to 18 months. We are unsure if hydroxyurea compared to placebo reduces or prevents progression of kidney disease assessed by change in glomerular filtration rate (mean difference (MD) 0.58 mL/min /1.73 m2, 95% confidence interval (CI) −14.60 to 15.76; 142 participants; very low certainty). Hydroxyurea compared to placebo may improve the ability to concentrate urine (MD 42.23 mOsm/kg, 95% CI 12.14 to 72.32; 178 participants; low certainty), and may make little or no difference to SCD‐related serious adverse events, including acute chest syndrome (risk ratio (RR) 0.39, 99% CI 0.13 to 1.16; 193 participants; low certainty), painful crisis (RR 0.68, 99% CI 0.45 to 1.02; 193 participants; low certainty); and hospitalisations (RR 0.83, 99% CI 0.68 to 1.01; 193 participants; low certainty).
No deaths occurred in either trial arm and the RCT did not report quality of life.
Angiotensin‐converting enzyme inhibitors versus placebo
One RCT published in 1998 compared an ACEI (captopril) to placebo in 22 adults with normal blood pressure and microalbuminuria. We are unsure if captopril compared to placebo reduces proteinuria (MD −49.00 mg/day, 95% CI −124.10 to 26.10; 22 participants; very low certainty). We are unsure if captopril reduces or prevents kidney disease as measured by creatinine clearance; the trial authors stated that creatinine clearance remained constant over six months in both groups, but provided no comparative data (very low certainty).
The RCT did not report serious adverse events, all‐cause mortality, or quality of life.
Angiotensin‐converting enzyme inhibitors versus vitamin C
One RCT published in 2020 compared an ACEI (lisinopril) with vitamin C in 170 children aged one to 18 years with normal blood pressure and microalbuminuria. It reported no data we could analyse. We are unsure if lisinopril compared to vitamin C reduces proteinuria in this population: the large drop in microalbuminuria in both arms of the trial after only one month on treatment may have been due to an overestimation of microalbuminuria at baseline rather than a true effect.
The RCT did not report serious adverse events, all‐cause mortality, or quality of life.
Authors' conclusions
We are unsure if hydroxyurea improves glomerular filtration rate or reduces hyperfiltration in children aged nine to 18 months, but it may improve their ability to concentrate urine and may make little or no difference to the incidence of acute chest syndrome, painful crises, and hospitalisations.
We are unsure if ACEI compared to placebo has any effect on preventing or reducing kidney complications in adults with normal blood pressure and microalbuminuria.
We are unsure if ACEI compared to vitamin C has any effect on preventing or reducing kidney complications in children with normal blood pressure and microalbuminuria.
No RCTs assessed red blood cell transfusions or any combined interventions to prevent or reduce kidney complications.
Due to lack of evidence, we cannot comment on the management of children aged over 18 months or adults with any known genotype of SCD.
We have identified a lack of adequately designed and powered studies, although we found four ongoing trials since the last version of this review. Only one ongoing trial addresses renal function as a primary outcome in the short term, but such interventions have long‐term effects. Trials of hydroxyurea, ACEIs or red blood cell transfusion in older children and adults are urgently needed to determine any effect on prevention or reduction of kidney complications in people with SCD.
PICOs
Ringkasan bahasa mudah
Intervensi untuk mencegah atau mengurangkan komplikasi ginjal dalam kalangan orang dengan penyakit sel sabit
Soalan ulasan
Adakah terdapat sebarang intervensi yang selamat dan berkesan yang menghalang atau mengurangkan komplikasi ginjal dalam kalangan orang dengan penyakit sel sabit (SCD)?
Latar belakang
SCD ialah ganguan darah keturunan yang mana sel darah merah, yang membawa oksigen ke seluruh badan, terbentuk secara tidak normal. Sel darah merah biasa adalah fleksibel dan berbentuk cakera, tetapi sel sabit adalah tegar dan berbentuk bulan sabit, dan lebih melekit daripada sel darah merah biasa. Ini boleh menyebabkan saluran darah tersumbat, mengakibatkan kerosakan tisu dan organ dan episod sakit yang teruk. Sel‐sel abnormal adalah rapuh dan mudah pecah, yang menyebabkan penurunan bilangan sel darah merah, dikenali sebagai anemia.
Komplikasi ginjal boleh bermula pada usia awal dalam kalangan kanak‐kanak dengan SCD dan lazim dalam kalangan dewasa dengan keadaan ini. Komplikasi ginjal yang menyebabkan kebocoran protein ginjal dan penyakit ginjal kronik boleh menjadi teruk, dengan kesan serius terhadap kesihatan. Komplikasi yang teruk termasuk keperluan untuk dialisis (prosedur untuk membuang bahan sisa dan cecair berlebihan daripada darah apabila ginjal berhenti berfungsi dengan baik) atau pemindahan ginjal. Mengenalpasti terapi, yang boleh mencegah atau memperlahankan kemerosotan fungsi ginjal dalam kalangan orang dengan SCD, adalah kritikal bagi meningkatkan hasil kesihatan.
Tarikh carian
Bukti adalah terkini sehingga 22 September 2022.
Ciri‐ciri kajian
Kami mendapati tiga kajian rawak terkawal, yang mendaftarkan seramai 385 orang. Satu kajian, diterbitkan pada 2011, membandingkan ubat hydroxyurea (yang membantu mengekalkan bentuk dan fleksibiliti sel darah merah), dengan plasebo (rawatan dummy) dalam 193 kanak‐kanak berumur sembilan hingga 18 bulan. Kajian kedua, yang diterbitkan pada 1998, membandingkan captopril (ubat yang diguna untuk merawat tekanan darah tinggi) dengan plasebo dalam 22 orang dewasa dengan tekanan darah normal dan mikroalbuminuria (paras protein yang tinggi dalam air kencing). Kajian ketiga, yang diterbitkan pada 2020, membandingkan lisinopril (ubat yang diguna untuk merawat tekanan darah tinggi) dengan vitamin C dalam 170 kanak‐kanak berumur satu hingga 18 tahun.
Dua kajian menerima pembiayaan kerajaan;adalah tidak jelas bagaimana kajian ketiga dibiaya.
Keputusan utama
Dalam kalangan kanak‐kanak berumur sembilan hingga 18 bulan, hydroxyurea mungkin meningkatkan keupayaan untuk menghasilkan air kencing yang normal, tetapi kami tidak pasti sama ada ia mempunyai sebarang kesan ke atas kadar penapisan glomerular (rangkaian penapis dalam ginjal yang menapis sisa daripada darah). Hydroxyurea mungkin memberi sedikit atau tiada perbezaan kejadian komplikasi serius termasuk sindrom dada akut (sakit, batuk, demam, tahap oksigen rendah dan bahan yang tidak normal dalam paru‐paru), krisis yang menyakitkan dan kemasukan ke hospital.
Kami tidak pasti jika memberi captopril kepada orang dewasa dengan SCD dengan tekanan darah normal dan tanda‐tanda awal kerosakan ginjal (mikroalbuminuria) mengurangkan perkembangan kerosakan ginjal.
Kami tidak pasti jika memberi lisinopril kepada kanak‐kanak berumur satu hingga 18 tahun dengan SCD yang ada tekanan darah normal dan tanda‐tanda awal kerosakan ginjal (microalbuminuria) mengurangkan perkembangan kerosakan ginjal.
Tiada kajian yang melaporkan kualiti hidup.
Batasan bukti
Kami mempunyai sedikit atau sangat sedikit keyakinan terhadap bukti kerana hanya menemui tiga kajian, dan ia mempunyai populasi tertentu (hanya kanak‐kanak atau hanya orang dewasa), sedikit peserta dan variasi keputusan yang meluas.
