Child Kidney Dis > Volume 27(2); 2023 > Article
Hyun, Ahn, Park, Choi, Han, Lee, Kim, Yang, Suh, Shin, Cho, Koo, Kim, Park, Ha, Cheong, Kang, and Kim: Efficacy and safety of losartan in childhood immunoglobulin A nephropathy: a prospective multicenter study



Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers (ARBs) are frequently employed to counteract the detrimental effects of proteinuria on glomerular diseases. However, the effects of ARBs remain poorly examined in pediatric patients with immunoglobulin A (IgA) nephropathy. Herein, we evaluated the efficacy and safety of losartan, an ARB, in pediatric IgA nephropathy with proteinuria.


This prospective, single-arm, multicenter study included children with IgA nephropathy exhibiting proteinuria. Changes in proteinuria, blood pressure, and kidney function were prospectively evaluated before and 4 and 24 weeks after losartan administration. The primary endpoint was the difference in proteinuria between baseline and 24 weeks.


In total, 29 patients were enrolled and received losartan treatment. The full analysis set included 28 patients who received losartan at least once and had pre- and post-urinary protein to creatinine ratio measurements (n=28). The per-protocol analysis group included 22 patients who completed all scheduled visits without any serious violations during the study period. In both groups, the mean log (urine protein to creatinine ratio) value decreased significantly at 6 months. After 24 weeks, the urinary protein to creatinine ratio decreased by more than 50% in approximately 40% of the patients. The glomerular filtration rate was not significantly altered during the observation period.


Losartan decreased proteinuria without decreasing kidney function in patients with IgA nephropathy over 24 weeks. Losartan could be safely employed to reduce proteinuria in this patient population. trial registration (NCT0223277)


Immunoglobulin A (IgA) nephropathy is the most common glomerular disease and is often diagnosed in children and young adults. Given that a considerable proportion of IgA nephropathy progresses to chronic kidney disease (CKD), especially when proteinuria is ≥1 g/day, the therapeutic goal is to reduce proteinuria. Blockage of the renin-angiotensin system (RAS) to reduce proteinuria has been the mainstay of IgA nephropathy treatment [1-4], along with various immunosuppressive medications [5-7].
The RAS is a hormonal system that plays a crucial role in blood volume and systemic vascular resistance. Activation of RAS results in increased blood pressure and sodium and water retention, subsequently increasing the effective circulating volume. RAS blockade reduces systemic and intraglomerular hydrostatic pressures by inhibiting angiotensin II-mediated efferent arteriolar vasoconstriction. Renal angiotensin II plays a major role in the development of renal fibrosis that progresses to end-stage renal failure, and the degree of proteinuria is known to be a risk factor for progression to kidney failure [8-10]. The ability of angiotensin II receptor blockers (ARBs) to reduce proteinuria, thereby delaying CKD progression, has been well-examined in diabetic nephropathy with proteinuria [11], leading to the approval of losartan and irbesartan for this indication. In IgA nephropathy, ARBs are frequently employed in combination with other therapeutic agents [12,13], and in adults, low-dose losartan was proven to reduce proteinuria [14]. Also, the blockade of RAS alone appears to be effective in children with proteinuria induced by kidney disease [15]. Among ARB, losartan has been approved by the U.S. Food and Drug Administration (FDA) for delaying CKD progression in proteinuric diabetic nephropathy along with irbesartan, although only losartan has been approved for children >5 years of age.
Angiotensin-converting enzyme inhibitors (ACEIs) are often selected as the first choice of RAS blocking agent; however, some patients fail to tolerate ACEIs and are switched to ARBs. A high incidence of ACEI-induced side effects such as dry cough has been documented in East Asia [16]. Therefore, ARBs have a relatively high clinical significance in this region. However, the use of ARBs for proteinuric glomerulopathy other than diabetic nephropathy remains off-label. In addition, the efficacy of ARB alone remains unexplored among pediatric patients with IgA nephropathy. In the present study, we performed a prospective multicenter study to confirm the efficacy and safety of losartan in reducing proteinuria in normotensive childhood IgA nephropathy with persistent proteinuria in Korea.



Herein, children aged 24 months to 18 years who were diagnosed with IgA nephropathy based on kidney biopsies performed at participating hospitals were enrolled if they fulfilled the following two conditions: (1) estimated glomerular filtration rate (eGFR) >60 mL/min/1.73 m2, and (2) a mean urine protein to creatinine ratio (UPCR) in the first morning urine sample of 3 consecutive days of ≥0.3. Patients with the following conditions were excluded: hypertension, allograft kidney transplantation, renal artery stenosis, confirmed primary hyperaldosteronism, history of hypersensitivity reactions to ARB, pregnancy, lactation, treatment with immunosuppressive agents such as steroids or calcineurin inhibitors, or taking antihypertensive drugs other than ACEIs or ARBs for blood pressure regulation. The number of subjects required to assess the efficacy of losartan in reducing proteinuria was calculated to be 28, assuming the following: level of significance α=0.05, type 2 error β=0.10, power of the test 80%, drop-out rate 10%, and magnitude of protein reduction 35.8%, according to the study by Webb et al. [17].


Study design

This study was approved by the Korean FDA and Institutional Review Boards of all participating institutions and conducted according to the Declaration of Helsinki. The trial was registered with under the trial registration number NCT02232776. As a placebo-controlled study was assumed to be unethical, this study was designed as a single-arm study. The enrollment of study subjects was conducted from September 2014 to October 2016, with participation from seven centers in Korea. Patients who agreed to participate in the study were screened after obtaining written consent from the subjects and their legal representatives and enrolled if they met the pre-determined inclusion and exclusion criteria. At 2, 4, 12, and 24 weeks after initiating losartan, patients were assessed for proteinuria in the first morning urine, blood pressure, and potential side effects. Complete blood count and serum chemistry tests were performed at 12 and 24 weeks. Blood pressure was measured on two occasions, with a 1- to 3-minute interval between measurements, using the oscillometric method. The mean value obtained from these measurements was used for analysis. Losartan was initiated at a dose of 0.7 mg/kg/day, taken once daily. At the 2- and 4-week follow-ups, the losartan dose was increased if proteinuria persisted given the absence of side effects, up to a maximum dose of 1.5 mg/kg/day or 100 mg/day. Complete remission was defined as a UPCR of <0.2, and partial remission was defined as a UPCR reduction of >50%. Proteinuria was evaluated using the first-morning UPCR. The eGFR was calculated using the bedside Chronic Kidney Disease in Children (CKiD) formula.
The primary endpoint was the change in proteinuria at 6 months after treatment. The secondary endpoints were as follows: (1) changes in proteinuria 1 month after dosing, (2) complete remission rate at 6 months, (3) partial remission rate percentage 6 months after administration, and (4) changes in eGFR at 6 months after dosing.

Statistical analysis

Subjects who had taken losartan at least once and had pre- and post-UPCR were grouped into the full analysis set (FAS) group. Subjects who completed all scheduled visits without any serious violations were grouped into the per-protocol (PP) group. Patients were excluded from the PP group if they had (1) hypertension requiring additional antihypertensive drugs or hypotension necessitating ARB discontinuation, (2) an eGFR of <60 mL/min/1.73 m2, and (3) non-compliance with the visit schedule. For statistical analysis, the FAS group was used as the main analysis group and the PP group as the auxiliary group. Primary and secondary endpoints and adverse events, such as kidney dysfunction, hyperkalemia, angioedema, and changes in blood pressure, were analyzed. The UPCR was analyzed using a natural logarithm to satisfy the assumption of normality. The paired t-test was used when the difference in the log UPCR at the 6-month follow-up before and after the medication satisfied the assumption of normality, and the Wilcoxon signed-rank test was employed when the assumption of normality was not satisfied. Categorical data are presented as frequencies and percentages, and 95% confidence interval (CIs) were estimated. Continuous data are presented as mean±standard deviation or median (interquartile range [IQR]).


Patients’ characteristics

In this prospective study, 29 subjects with biopsy-proven IgA nephropathy were enrolled and received losartan treatment at the median age of 12.2 years (IQR, 10.1–15.0 years). Among them, the UPCR was not assessed in one patient after receiving losartan, who was excluded from the FAS group (n=28). This group is defined as the intent-to-treat (ITT) population (Fig. 1). In the ITT group, three patients had hypertension before losartan administration, one patient exhibited a decreased eGFR <60 mL/min/1.73 m2 at the 2-week visit after initiating losartan, and two did not complete the visit schedule; therefore, they were excluded from the PP group (n=22). Table 1 summarizes the basic clinical characteristics of the ITT group. The median disease duration was 3.12 years (IQR, 0.51–4.42 years). At enrollment, the median baseline proteinuria was 0.72 mg/mg (IQR, 0.48–0.95 mg/mg) in the FAS group.


In the ITT group, the mean log UPCR value before losartan administration was –0.34, which significantly decreased to –0.80 at 6 months of administration (P=0.003). In the PP group, we noted a significant decrease in the mean log UPCR value at 6 months of administration (P=0.02) (Fig. 2). In both groups, the mean log UPCR was significantly reduced 1 month after administration when compared with that before administration (Fig. 2). Following 6 months of treatment, proteinuria disappeared (UPCR was less than 0.2) in 14.3% (95% CI, 4.02%–32.7%) and 13.6% (95% CI, 2.90%–34.9%) of patients in the ITT and PP groups, respectively. Six months after treatment, a >50% reduction in UPCR was observed in 39.3% (95% CI, 21.2%–57.4%) and 36.7% (95% CI, 16.3%–56.5%) of the FAS and PP groups, respectively. The eGFR values before and after losartan administration did not differ significantly (Table 2).


During the study period, nine (31.0%) of the 29 subjects who received losartan treatment experienced one or more adverse events. Overall, 26 adverse events were reported, of which one was a significant adverse reaction involving a cutaneous abscess that occurred in a 12-year-old male subject; however, there was no causal relationship with the drug (Table 3). No hyperkalemia or angioedema was observed during the study period. Following 6 months of losartan treatment, the median values for altered systolic and diastolic blood pressure were –2.50 mmHg (IQR, –5.50 to 9.00 mmHg) and –3.0 mmHg (IQR, –7.00 to 4.50 mmHg), respectively. There was a slight decrease in blood pressure, although symptoms such as dizziness were not observed (Table 4).


The ESCAPE (Effect of Strict Blood Pressure Control and ACE Inhibition on Progression of Chronic Renal Failure in Pediatric Patients) study and that by Webb et al. have confirmed the efficacy of RAS blockade for reducing proteinuria in children [17,18]. The ESCAPE study has revealed that strict blood pressure control can effectively delay the progression of CKD with proteinuria in children receiving ACEIs [18]. However, in the ESCAPE study, similar to several other studies conducted in adults, the efficacy of RAS inhibition for suppressing proteinuria was not examined independently from the effect of blood pressure reduction mediated by RAS inhibition on proteinuria. In addition, the underlying diseases of the study participants were heterogeneous. In the present study, the efficacy of RAS inhibition on proteinuria in pediatric IgA nephropathy was evaluated independently of the antihypertensive effect of losartan. According to the study by Webb et al. [17], losartan could effectively reduce proteinuria in pediatric patients with CKD when compared with a calcium channel blocker, amlodipine or placebo. Although amlodipine and placebo increased proteinuria by 1.4%, losartan reduced proteinuria by 35.8%. In addition, several prospective studies have evaluated the efficacy and safety of ACEIs with or without ARB in children [19-21]. A randomized controlled trial assessing pediatric patients with IgA nephropathy in Japan has supported lisinopril monotherapy in reducing proteinuria when compared with combination therapy with lisinopril and losartan. The cumulative disappearance rate of proteinuria at 24 months was 89.3% with combination therapy and 89% for monotherapy, without differences in safety [19]. Conversely, the long-term efficacy of losartan and enalapril treatment revealed that the reduction in proteinuria at 3 years was 30.0% for losartan and 40.5% for enalapril [20]. These studies have shown that either ACEI or ARB therapy can be effective in pediatric patients with IgA nephropathy.
In the present study, we aimed to evaluate the efficacy and safety of losartan in children with IgA nephropathy and provide medical evidence for the use of losartan in children with proteinuric kidney disease in Korea. Losartan is an angiotensin II type I receptor blocker that blocks the angiotensin system, inhibits kidney damage, and reduces urinary proteinuria. To the best of our knowledge, this is the first prospective clinical study to examine the potential of losartan monotherapy in children with IgA nephropathy. Our study supports the finding that losartan could effectively reduce proteinuria in pediatric patients with IgA nephropathy.
IgA nephropathy is known to exhibit a relatively benign clinical course in children when compared with that in adults [22-25]. In a Japanese study, although adult IgA nephropathy was found to progress to kidney failure in 10%–20% and 50% of patients within 10 and 20 years, respectively, kidney survival rates at 10- and 20-year were 95% and 82%, respectively, in children [23]. In a retrospective study assessing 99 pediatric patients with IgA nephropathy and 125 adult patients with IgA nephropathy, pediatric patients were more likely to display minimal histologic lesions, and 10-year kidney survival was 87% in children when compared with 48% in adults [26]. In children, the probability of spontaneous remission without treatment was found to be higher than the predicted probability [27]. Most subjects in this study also showed improvements in proteinuria with losartan treatment.
A recent study from Korea has shown that 65 (5.6%) of 1,154 pediatric patients with IgA nephropathy developed CKD stage 3-5 during a median follow-up of 5 years. In total, 947 patients were treated with RAS blockers with or without additional immunosuppressive drugs, and 207 patients (17.9%) received no pharmacologic treatments. Considering proteinuria, the authors found that 839 patients (72.7%) achieved remission. Moreover, remission was found to be an independent prognostic factor that negatively correlated with the progression of CKD stage 3-5 (hazard ratio, 0.19; 95% CI, 0.06–0.26; P<0.001) [28]. Accordingly, these findings highlight that the prognosis of children with IgA nephropathy in Korea is relatively good, and achieving remission indicates a favorable outcome of IgA nephropathy.
Few studies have established that losartan can be safely used in children and adolescents [18,29]. Dizziness or headache is common due to drug-related adverse reactions, which can be reversed by appropriate dose adjustment, and sometimes due to side effects, in which case the medication may be withdrawn for a short period and subsequently re-initiated [18]. Compared with ACEIs, losartan can be safely employed in terms of potential side effects [20,30]. However, when combined with tacrolimus, careful attention should be paid to hyperkalemia and metabolic acidosis. In addition, hyperkalemia may occur when losartan is combined with ACEI in CKD, and potassium concentration should be observed [21,31]. Herein, we observed no adverse events, such as decreased blood pressure, reduced GRF, or hyperkalemia, during the 24-week study period. There were no instances of relatively common side effects such as angioedema or hyperkalemia, which may be attributed to the limited number of subjects in the study. In the present study, losartan was initiated at a dose of 0.7 mg/kg/day, once daily, and was gradually increased (12.5–25.0 mg/day) up to a maximum dose of 1.5 mg/kg/day or 100 mg/day. For children, doses were initially estimated using adult doses, and the dose of losartan used in the present study is known to be safe for children and adolescents [17,19,20,32]. Considering children ˂6 years of age undergoing treatment for hypertension, doses of 0.1 to 0.7 mg/kg are effective, and doses of 1.4 mg/kg can be used without difficulty [32].
The present study was the first prospective, multicenter study conducted in Korea. However, its limitations need to be stated, including the relatively short study period, a small number of study subjects, and a single-arm design. An additional limitation of this study lies in the absence of consideration of histopathological findings for IgA nephropathy. The inclusion criteria encompassed children between 24 months and 18 years of age. However, since all enrolled participants were 6 years or older, the assessment of efficacy and safety in patients below this age threshold is limited
In conclusion, this study represents the first multicenter study for the use of losartan in pediatric patients with IgA nephropathy within our country. The results of this study demonstrate that losartan treatment led to a substantial reduction in proteinuria among children with IgA nephropathy, all while exhibiting a favorable safety profile devoid of severe adverse events. As such, these findings support the effective and safe application of losartan in managing IgA nephropathy in pediatric populations.


Ethical statements
This study was approved by the Korean FDA and Institutional Review Boards of all participating institutions including Seoul National University (IRB No. H1407113596), and conducted according to the Declaration of Helsinki. Informed consent was obtained.
Conflicts of interest
Eujin Park, Eun Mi Yang, Jin Soon Suh, Jae Il Shin, Hae Il Cheong, and Hee Gyung Kang are editorial board members of the journal but were not involved in the peer reviewer selection, evaluation, or decision process of this article. No other potential conflicts of interest relevant to this article were reported.
This research was supported by a grant (14172MFDS178) from the Ministry of Food and Drug Safety in 2014.
Author contributions
Conceptualization: HH, YHA, HGK, SHK
Data curation: EP, HJC
Formal analysis: KHH, JWL
Funding acquisition: HGK, ISH, HIC
Investigation: HJC, KHH, MHC, JWK, SYK, KHK, HWP
Methodology: JSS, JIS, MHC, HGK
Project administration: JWK, KHK
Visualization: HH, YHA
Writing–original draft: HH, YHA
Writing–review & editing: HGK, SHK
All authors read and approved the final manuscript.


1. Chapter 10: Immunoglobulin A nephropathy. Kidney Int Suppl (2011) 2012;2:209-17.
crossref pmid pmc
2. Nakamura T, Ushiyama C, Suzuki S, Hara M, Shimada N, Sekizuka K, et al. Effects of angiotensin-converting enzyme inhibitor, angiotensin II receptor antagonist and calcium antagonist on urinary podocytes in patients with IgA nephropathy. Am J Nephrol 2000;20:373-9.
crossref pmid pdf
3. Jo YI, Na HY, Moon JY, Han SW, Yang DH, Lee SH, et al. Effect of low-dose valsartan on proteinuria in normotensive immunoglobulin A nephropathy with minimal proteinuria: a randomized trial. Korean J Intern Med 2016;31:335-4.
crossref pmid pmc pdf
4. Nakanishi K, Iijima K, Ishikura K, Hataya H, Awazu M, Sako M, et al. Efficacy and safety of lisinopril for mild childhood IgA nephropathy: a pilot study. Pediatr Nephrol 2009;24:845-9.
crossref pmid pdf
5. Hogg RJ, Bay RC, Jennette JC, Sibley R, Kumar S, Fervenza FC, et al. Randomized controlled trial of mycophenolate mofetil in children, adolescents, and adults with IgA nephropathy. Am J Kidney Dis 2015;66:783-91.
crossref pmid
6. Masutani K, Tsuchimoto A, Yamada T, Hirakawa M, Mitsuiki K, Katafuchi R, et al. Comparison of steroid-pulse therapy and combined with mizoribine in IgA nephropathy: a randomized controlled trial. Clin Exp Nephrol 2016;20:896-903.
crossref pmid pdf
7. Vecchio M, Bonerba B, Palmer SC, Craig JC, Ruospo M, Samuels JA, et al. Immunosuppressive agents for treating IgA nephropathy. Cochrane Database Syst Rev 2015;(8):CD003965.
crossref pmid
8. Le W, Liang S, Hu Y, Deng K, Bao H, Zeng C, et al. Long-term renal survival and related risk factors in patients with IgA nephropathy: results from a cohort of 1155 cases in a Chinese adult population. Nephrol Dial Transplant 2012;27:1479-85.
crossref pmid
9. Berthoux F, Mohey H, Laurent B, Mariat C, Afiani A, Thibaudin L. Predicting the risk for dialysis or death in IgA nephropathy. J Am Soc Nephrol 2011;22:752-61.
crossref pmid pmc
10. Graciano ML, Cavaglieri Rde C, Delle H, Dominguez WV, Casarini DE, Malheiros DM, et al. Intrarenal renin-angiotensin system is upregulated in experimental model of progressive renal disease induced by chronic inhibition of nitric oxide synthesis. J Am Soc Nephrol 2004;15:1805-15.
crossref pmid
11. Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving HH, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 2001;345:861-9.
crossref pmid
12. Xie Y, Huang S, Wang L, Miao L, Zhang A, Li Y, et al. Efficacy and safety of mizoribine combined with losartan in the treatment of IgA nephropathy: a multicenter, randomized, controlled study. Am J Med Sci 2011;341:367-72.
crossref pmid
13. Horita Y, Tadokoro M, Taura K, Ashida R, Hiu M, Taguchi T, et al. Prednisolone co-administered with losartan confers renoprotection in patients with IgA nephropathy. Ren Fail 2007;29:441-6.
crossref pmid pmc
14. Shimizu A, Takei T, Uchida K, Tsuchiya K, Nitta K. Low-dose losartan therapy reduces proteinuria in normotensive patients with immunoglobulin A nephropathy. Hypertens Res 2008;31:1711-7.
crossref pmid
15. Chandar J, Abitbol C, Montane B, Zilleruelo G. Angiotensin blockade as sole treatment for proteinuric kidney disease in children. Nephrol Dial Transplant 2007;22:1332-7.
crossref pmid
16. Mahmoudpour SH, Veluchamy A, Siddiqui MK, Asselbergs FW, Souverein PC, de Keyser CE, et al. Meta-analysis of genome-wide association studies on the intolerance of angiotensin-converting enzyme inhibitors. Pharmacogenet Genomics 2017;27:112-9.
crossref pmid pmc
17. Webb NJ, Lam C, Loeys T, Shahinfar S, Strehlau J, Wells TG, et al. Randomized, double-blind, controlled study of losartan in children with proteinuria. Clin J Am Soc Nephrol 2010;5:417-24.
crossref pmid pmc
18. Ellis D, Moritz ML, Vats A, Janosky JE. Antihypertensive and renoprotective efficacy and safety of losartan: a long-term study in children with renal disorders. Am J Hypertens 2004;17:928-35.
crossref pmid
19. Shima Y, Nakanishi K, Sako M, Saito-Oba M, Hamasaki Y, Hataya H, et al. Lisinopril versus lisinopril and losartan for mild childhood IgA nephropathy: a randomized controlled trial (JSKDC01 study). Pediatr Nephrol 2019;34:837-46.
crossref pmid pdf
20. Webb NJ, Shahinfar S, Wells TG, Massaad R, Gleim GW, Santoro EP, et al. Losartan and enalapril are comparable in reducing proteinuria in children. Kidney Int 2012;82:819-26.
crossref pmid
21. Litwin M, Grenda R, Sladowska J, Antoniewicz J. Add-on therapy with angiotensin II receptor 1 blocker in children with chronic kidney disease already treated with angiotensin-converting enzyme inhibitors. Pediatr Nephrol 2006;21:1716-22.
crossref pmid pdf
22. D’Amico G. Influence of clinical and histological features on actuarial renal survival in adult patients with idiopathic IgA nephropathy, membranous nephropathy, and membranoproliferative glomerulonephritis: survey of the recent literature. Am J Kidney Dis 1992;20:315-23.
crossref pmid
23. Kusumoto Y, Takebayashi S, Taguchi T, Harada T, Naito S. Long-term prognosis and prognostic indices of IgA nephropathy in juvenile and in adult Japanese. Clin Nephrol 1987;28:118-24.
24. Higa A, Shima Y, Hama T, Sato M, Mukaiyama H, Togawa H, et al. Long-term outcome of childhood IgA nephropathy with minimal proteinuria. Pediatr Nephrol 2015;30:2121-7.
crossref pmid pdf
25. Nozawa R, Suzuki J, Takahashi A, Isome M, Kawasaki Y, Suzuki S, et al. Clinicopathological features and the prognosis of IgA nephropathy in Japanese children on long-term observation. Clin Nephrol 2005;64:171-9.
crossref pmid
26. Haas M, Rahman MH, Cohn RA, Fathallah-Shaykh S, Ansari A, Bartosh SM. IgA nephropathy in children and adults: comparison of histologic features and clinical outcomes. Nephrol Dial Transplant 2008;23:2537-45.
crossref pmid
27. Shima Y, Nakanishi K, Hama T, Mukaiyama H, Togawa H, Sako M, et al. Spontaneous remission in children with IgA nephropathy. Pediatr Nephrol 2013;28:71-6.
crossref pmid pdf
28. Suh JS, Jang KM, Hyun H, Cho MH, Lee JH, Park YS, et al. Remission of proteinuria may protect against progression to chronic kidney disease in pediatric-onset IgA nephropathy. J Clin Med 2020;9:2058.
crossref pmid pmc
29. Shahinfar S, Cano F, Soffer BA, Ahmed T, Santoro EP, Zhang Z, et al. A double-blind, dose-response study of losartan in hypertensive children. Am J Hypertens 2005;18(2 Pt 1):183-90.
crossref pmid
30. Wuhl E, Mehls O, Schaefer F; ESCAPE Trial Group. Antihypertensive and antiproteinuric efficacy of ramipril in children with chronic renal failure. Kidney Int 2004;66:768-76.
crossref pmid
31. Sakallı H, Baskın E, Bayrakcı US, Moray G, Haberal M. Acidosis and hyperkalemia caused by losartan and enalapril in pediatric kidney transplant recipients. Exp Clin Transplant 2014;12:310-3.
crossref pmid
32. Webb NJ, Wells TG, Shahinfar S, Massaad R, Dankner WM, Lam C, et al. A randomized, open-label, dose-response study of losartan in hypertensive children. Clin J Am Soc Nephrol 2014;9:1441-8.
crossref pmid pmc

Fig. 1.
Study disposition. ITT, intention to treat; PP, per-protocol.
Fig. 2.
Change of proteinuria. ITT, intention to treat; PP, per-protocol.
Table 1.
Baseline characteristics of patients
Characteristic Value (n=28)
Age (yr) 12.0±3.32 (6–18)
Male (male:female) 20:8
Height (cm) 152.8±18.3 (114.8–196.3)
Weight (kg) 51.1±16.9 (20.2–85.9)
Heart rate (beats/min) 83.4±16.2 (60–120)
Systolic blood pressure (mmHg) 112.1±11.3 (95–134)
Diastolic blood pressure (mmHg) 67.8±8.61 (42–83)
Estimated GFR (IDMS) 116.3±31.6 (64.2–194.4)
Urine protein/creatinine (mg/mg) 0.82±0.45 (0.32–1.87)
Urine microalbumin/creatinine (mg/mg) 0.58±0.41 (0.04–1.48)

Values are presented as mean±standard deviation (range).

GFR, glomerular filtration rate; IDMS, isotope dilution mass spectrometry.

Table 2.
Changes in the estimated glomerular filtration rate
Group Baseline 6 mo △ 6 mo–baseline P-value
ITT 0.97
 Mean±SD 116.3±31.6 116.1±26.0 –0.17±21.4
 Median (range) 116.9 (64.2 to 194.4) 114.5 (49.8 to 156.1) 0.23 (–50.6 to 47.2)
PP 0.17
 Mean±SD 126.7±26.8 121.1±23.8 –5.57±18.2
 Median (range) 122.5 (90.3 to 194.4) 120.9 (77.6 to 156.1) –2.57 (–50.6 to 29.7)

ITT, intention to treat; PP, per-protocol; SD, standard deviation.

Table 3.
Reported adverse events and serious adverse events (n=26)
Adverse events No. (%)
Upper respiratory tract infection 13 (50.0)
Gastrointestinal symptoms 4 (15.4)
Allergic conjunctivitis 3 (11.5)
Headache 2 (7.69)
Allergic rhinitis 2 (7.69)
Acute otitis externa 1 (3.85)
Cutaneous abscess 1 (3.85)
Hyperkalemia, cough, arrhythmia, facial edema 0
Table 4.
Changes in BP
BP changesa) P-value
△Systolic BP (mmHg), mean (range) –2.50 (–25.0 to 30.0) 0.89
△Diastolic BP (mmHg), mean (range) –3.00 (–14.0 to 24.0) 0.52

BP, blood pressure.

a) Change from the screening BP to 24-week BP.

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