Efficacy of semaglutide in IgA nephropathy with obesity: a case report

Abstract

Background

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) like semaglutide are well-used for type 2 diabetes and obesity, and recent studies show their potential renal benefits in both diabetic and non-diabetic people. However, evidence for semaglutide’s efficacy in IgAN especially in patients with obesity as a comorbidity is limited.

Case presentation

A 39-year-old male with a 9-month history of abnormal urine tests was admitted, diagnosed with IgAN (M1E0S0T0C0) and glomerulomegaly, and presented with obesity with BMI 34 kg/m². After treatment with losartan, dapagliflozin, hydroxychloroquine, and finerenone, the 24-hour proteinuria levels decreased from 2373 mg/day to 1344 mg/day, further dropping to 702 mg/day, and then slightly increased to 920 mg/day. No significant improvement was noted half a month later, with the level remaining at 915 mg/day. We then initiated treatment with semaglutide. Following the introduction of semaglutide, a significant reduction in proteinuria was observed within four months, decreasing from 915 mg/day to 320 mg/day. Concurrently, the patient experienced a reduction in body weight, dropping from 110 kg to 95 kg over the same period. The patient's renal function remained stable throughout the follow-up, and no significant adverse drug reactions have been reported.

Conclusion

In this case of IgAN with obesity, adding semaglutide to standard therapy effectively reduced proteinuria and body weight, with stable renal function and good tolerability.

Background

IgA nephropathy (IgAN) is the most common primary glomerulonephritis globally. It primarily affects younger adults and can lead to significant kidney damage over time [1]. Unfortunately, current therapeutic strategies fail to prevent progression to end-stage kidney disease in a substantial proportion of patients, underscoring an urgent need for novel treatment approaches.

Against this backdrop, glucagon-like peptide-1 (GLP-1)-an incretin hormone secreted by the intestines in response to glucose or nutrient ingestion—has emerged as a promising candidate beyond its established metabolic roles. GLP-1 [2] is an incretin hormone released from the intestine following the ingestion of glucose or nutrients. GLP-1 receptor agonists (GLP-1 RAs) are well-established treatments for type 2 diabetes and obesity, gaining widespread use due to their efficacy in reducing both HbA1c levels and body weight. Building on this, recent studies [3] have increasingly investigated the renal benefits of GLP-1 RAs beyond their metabolic effects. Notably, research has demonstrated the albuminuria-lowering effect of adding semaglutide, a GLP-1 RA, in both diabetic patients and those without diabetes [4]. These findings suggest potential therapeutic avenues for managing albuminuria, a key marker of kidney damage, in various patient populations. Yet the renoprotective potential of GLP-1 RAs has been scarcely studied in IgAN with obesity.

As reported below, we observed one case of IgAN with obesity that was effectively treated with semaglutide, exhibiting good safety and efficacy. This study was granted approval by the institutional ethics committee of Tianjin Medical University General Hospital (Ethics No. IRB2025-YX-460-01), and the patient provided written informed consent.

Case presentation

We report the case of a 39-year-old male with a body mass index (BMI) of 34 kg/m². He has a 1-year history of hypertension and his blood pressure has peaked at 160/110 mmHg. For blood pressure control, he has been receiving 50 mg of Losartan Potassium tablets daily, which has maintained his blood pressure at around 140/90 mmHg. Additionally, the patient has a 1-year history of fatty liver disease, during which elevated liver enzymes have been detected; hepatoprotective medications were administered when enzyme levels rose. He also has a 1-year history of hyperlipidemia and has been on regular treatment with Alirocumab. The patient denies a history of smoking and alcohol consumption. He was admitted to the Department of Cardiology for adjustment of his antihypertensive medication nine months ago. A routine urinalysis at that time revealed positive proteinuria with no red blood cells detected, and the 24-hour proteinuria was 3000 mg/day. He was initiated on Dapagliflozin and Nephritis Recovery Tablets (a proprietary Chinese herbal preparation containing Radix Ginseng and Salvia miltiorrhiza) and advised to follow up with Nephrology for further evaluation.

He was subsequently admitted to the nephrology ward for further management, with an admission blood pressure of 145/110 mmHg, and underwent a comprehensive laboratory evaluation. The results revealed serum creatinine level of 74 µmol/L (reference range 57–97 µmol/L), serum albumin of 42 g/L (reference range 40–55 g/L), 24-hour proteinuria excretion of 2373 mg/day (reference range 0-150 mg/24 hours), and urinary red blood cells (URBC) of 10.3/ul (reference range 0-17.6/ul) (see Table 1). Abdominal color Doppler ultrasound shows fatty liver. Echocardiography and pulmonary computed tomography showed no abnormalities. A percutaneous kidney biopsy, on light microscopy, included 11 glomeruli: one showed glomerular sclerosis, while the remainder were enlarged, accompanied by mild diffuse mesangial cell proliferation and matrix expansion-a key pathological feature of obesity-related glomerulopathy (ORG). Mild tubular changes included focal tubular atrophy and focal lymphocytic infiltration. Immunofluorescence examination showed clustered deposits of IgA and C3 restricted to the mesangial area. Electron microscopy revealed electron-dense deposits in the mesangial area, accompanied by focal fusion of podocyte foot processes (Fig. 1a - d). Pathological diagnosis: (1) IgA nephropathy (M1E0S0T0C0). (2) Glomerulomegaly.

Table 1.

Laboratory test results of this patient at renal biopsy

Variable	Results	Reference range
Leukocytes (10^9 /L)	8.31	3.5–9.5
Neutrophils (10^9 /L)	4.32	1.8–6.3
Lymphocytes (10^9 /L)	3.29	1.1–3.2
Monocytes (10^9 /L)	0.45	0.1–0.6
Platelets (10^9 /L)	350	125–350
PT (sec)	10.2	9.5–15.0
APTT (sec)	37.9	20.0–40.0
Fibrinogen (g/L)	3.39	1.8–4.0
D-Dimer (µg/L)	241	0–500
Hemoglobin (g/L)	164	130–175
Albumin (g/L)	42	40–45
Serum creatinine (µmol/L)	74	57–97
eGFR (mL/min/1.73m2)	113.8
Uric acid (µmol/L)	323	208–428
FPG (mmol/L)	5.1	3.6–5.8
TC (mmol/L)	7.18	3.59–5.19
TG (mmol/L)	2.58	0.57–1.7
HDL (mmol/L)	1.28	0.8–2.2
LDL (mmol/L)	4.58	1.33–3.36
Serum IgG (mg/dL)	1020.0	751.0–1560.0
Serum IgA (mg/dL)	625.0	82.0–453.0
Serum IgM (mg/dL)	85.2	46.0–304.0
Serum IgE (IU/ml)	12.7	< 100
Serum C3 (mg/dL)	151.0	79.0–152.0
Serum C4 (mg/dL)	33.3	16.0–38.0
CRP (mg/dl)	0.79	< 0.8
24-hour proteinuria (mg/d)	2373.0	30.0–150.0
URBC (/UL)	10.3	0.0–17.6

PT: Prothrombin Time; APTT: Activated Partial Thromboplastin Time; TC: Total Cholesterol; TG: Triglycerides; LDL: Low-Density Lipoprotein; HDL: High-Density Lipoprotein. eGFR: Estimated Glomerular Filtration Rate; FPG: Fasting Plasma Glucose; CRP: C-Reactive Protein; URBC: Urine Red Blood Cell Count

Fig. 1.

Histological findings of this patient. (a) Glomerular enlargement, mild diffuse mesangial cell and matrix proliferation. (b) Glomerulosclerosis. (c) Immunoglobulin A (IgA) clustered deposits along the mesangial area. (d) Electron-dense deposits in a clumped pattern in the mesangial area and focal fusion of podocyte foot processes

Based on the renal biopsy findings and clinical laboratory data, we instituted standard care comprising sodium restriction and daily weight monitoring. To reduce proteinuria, we adjusted the treatment regimen. Given that the patient’s blood pressure remained suboptimal, the dosage of losartan potassium tablets was increased to 100 mg once daily, dapagliflozin was continued at 10 mg/day, and hydroxychloroquine was initiated at 200 mg/day. Subsequently, the patient’s blood pressure decreased to 120/80 mmHg. The 24-hour urine protein quantification initially decreased from 2373 mg/d to 1344 mg/d but subsequently increased to 1700 mg/d. In response, finerenone was initiated at 10 mg daily and gradually increased to 20 mg daily. Following this adjustment, the 24-hour proteinuria decreased to 702 mg/day and subsequently increased to 920 mg/day. Half a month after this point, no further significant improvement in proteinuria was observed, with the 24-hour urinary protein quantification remaining at 915 mg/day. The patient is obese with an unmet weight target and no hematuria. Renal biopsy findings indicated minimal active lesions. Considering these clinical and pathological characteristics, combined with the potential side effects of glucocorticoid therapy, glucocorticoid therapy was not initiated. After multiple discussions, a decision was made to attempt treatment with semaglutide. The patient received 0.25 mg subcutaneously weekly. After one week without any discomfort, the dose was increased to 0.5 mg weekly. Four weeks later, the dose was further titrated to 0.75 mg weekly. However, when the dosage was escalated to 1 mg once weekly, the patient developed nausea and severe constipation. Due to these gastrointestinal adverse reactions, the dosage was reduced back to and maintained at 0.75 mg once weekly.

After the initiation of semaglutide treatment, a significant reduction in proteinuria was observed within one month, decreasing from 915 mg/day to 369 mg/day. At the 4-month follow-up, the proteinuria further decreased to 320 mg/day. Concurrently, the patient experienced a reduction in body weight, reducing from 110 kg to 95 kg over the same period. Finerenone was subsequently discontinued once proteinuria reached 369 mg/day, given the ongoing semaglutide therapy and to alleviate the patient’s financial burden. The patient’s renal function remained stable throughout the entire disease course. The treatment was well-tolerated. The patient’s quality of life has also significantly improved, accompanied by normalization of lipid levels and ALT and AST. He remains under ongoing follow-up (Figs. 2–3).

Fig. 2.

Follow-up changes in the patient’s 24-hour proteinuria and weight. Red ‘Renal Biopsy’ denotes biopsy performed at baseline

Fig. 3.

Follow-up changes in the patient’s serum creatinine (Scr), serum albumin (Alb) and eGFR

Discussion

IgA nephropathy (IgAN), a condition posing a significant threat to public health, currently lacks a specific treatment protocol. Currently, therapeutic strategies predominantly rely on supportive measures aimed at reducing proteinuria and slowing disease progression [5]. Key components of this supportive approach include meticulous management of dietary sodium intake, rigorous control of urinary protein excretion (albuminuria), tight regulation of blood pressure and control of cardiovascular risk factors. In clinical practice, managing albuminuria typically involves utilizing angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) and SGLT2 inhibitors [6]. Corticosteroids or a combination of immunosuppressants are prescribed for specific individuals. However, the potential for significant adverse effects associated with long-term steroid use and immunosuppression often limits their sustained application, posing a considerable challenge in clinical management. Despite these available interventions, the long-term prognosis for patients with IgAN remains suboptimal under current standard-of-care strategies. This highlights an urgent need for more effective therapies [7].

This case report focused on semaglutide, a GLP-1 RA, to explore its value in non-diabetic IgAN patients with comorbid ORG. In this case, after the patient received standard treatments including losartan, dapagliflozin, hydroxychloroquine, and finerenone, proteinuria fluctuated (decreasing from 2373 mg/d to 702 mg/d and then rising back to 920 mg/d) but could not be further improved. After the addition of semaglutide, a significant reduction in proteinuria was observed over the 4-month follow-up period, declining from 915 mg/d to 320 mg/d, alongside a decrease in body weight from 110 kg to 95 kg. In addition, the patient’s renal function remained stable throughout. Even more notably, there was a concurrent normalization of blood lipid levels and liver enzymes, along with a significant improvement in quality of life. This outcome is logically consistent with the known pharmacological effects of semaglutide: as a GLP-1 RA, it has been proven to reduce glycated hemoglobin (HbA1c) and body weight in the treatment of type 2 diabetes and obesity [3]. Recent studies have further revealed its renal protective effects. The FLOW trial showed that semaglutide can effectively reduce albuminuria and the risk of ESKD in patients with diabetes and CKD [8]. Another study involving overweight/obese non-diabetic CKD patients also indicated that 24 weeks of semaglutide treatment significantly reduced albuminuria [3]. The renal protective mechanisms of semaglutide may involve alleviating renal oxidative stress, inhibiting inflammatory responses, and delaying renal fibrosis [9]. In this case, the reduction in proteinuria following semaglutide administration is likely in part attributable to the patient’s significant reduction in body weight-an effect that helps mitigate ORG. Notably, semaglutide’s dual capacity to reduce both weight and proteinuria aligns well with the comorbidity management needs of “metabolic-renal” conditions.

Currently, there remains limited evidence regarding the use of GLP-1 RAs in the treatment of IgAN, only one small-scale study enrolling 8 IgAN patients with overweight or obesity has suggested that semaglutide may act as an adjunct to standard treatment [10]. The value of this case lies in further verifying the safety and efficacy of semaglutide in non-diabetic IgAN patients with obesity, providing clinical reference for this specific population-especially since obesity is a potential aggravating factor for IgAN.

Nevertheless, the limitations of this case report should be objectively acknowledged. First, single case report can’t rule out the impact of individual differences on results, and findings cannot be directly generalized to all IgAN patients with obesity. Second, there is currently no evidence that semaglutide directly acts on the core pathological mechanisms of IgAN. Therefore, future studies are warranted to verify whether semaglutide exerts a direct regulatory effect on the key pathogenic pathways of IgAN. Additionally, the follow-up period of this case was only 4 months, which is insufficient to evaluate the long-term efficacy of semaglutide and whether the reduction in albuminuria persists after discontinuing semaglutide.

Conclusions

In this case of IgAN with obesity, adding semaglutide to standard therapy effectively reduced proteinuria and body weight, with stable renal function and good tolerability. These findings imply potential nephroprotective value that needs further confirmation in larger clinical studies.

Author contributions

HFL and YXL collected clinical data. HFL contributed to the writing of the manuscript.YXL and JYJ participated in its design and coordination. LW and WYS contributed to renal pathology slide reading and data organization. All authors read and approved the final manuscript for submission.

Funding

This study is supported by Tianjin Health Science and Technology Project (TJWJ2022MS005).

Data availability

Raw data used during the current study are available from the corresponding author on reasonable request for non-commercial use.

Declarations

Ethics approval and consent to participate

This paper abides by the declaration of Helsinki.

Consent for publication

Written informed consent was obtained from the patient for publication of this case report.

Competing interests

The authors declare no competing interests.