Infection-Related Glomerulonephritis Revealed as Shunt Nephritis: A Case Report

Abstract

Introduction

Shunt nephritis is a rare immune complex-mediated glomerulonephritis associated with an infected ventriculoatrial shunt (VAS) or ventriculoperitoneal shunt (VPS). Its incidence has declined to 0.7–2% due to improved infection management. Low-grade bacteremia, particularly from VAS, often involves pathogens such as Cutibacterium acnes, Staphylococcus epidermidis, and Streptococcus species. Immune complex deposition in the kidneys leads to glomerulonephritis and nephrotic syndrome. Early diagnosis and shunt removal, alongside antibiotics, are crucial for renal recovery.

Case Presentation

A 35-year-old male with a history of traumatic brain injury and VAS placement presented with generalized edema, hypertension, fatigue, and neurological decline. The patient exhibited nephrotic syndrome with low complement levels. Renal biopsy revealed diffuse membranoproliferative glomerulonephritis with subendothelial deposits. Cerebrospinal fluid (CSF) analysis showed pleocytosis and an elevated albumin ratio, with C. acnes confirmed via blood and CSF cultures. Targeted antibiotic therapy, with first externalization and then removal of the VAS, was followed by a VPS re-implantation after infection resolution. The complement levels normalized, albuminuria decreased, and renal function stabilized.

Discussion

This case highlights the diagnostic challenges associated with shunt nephritis, particularly in the absence of overt infection. Early recognition, targeted antibiotics, and shunt removal are essential for preventing progressive kidney damage and resolving nephrotic syndrome. This case highlights the need for multidisciplinary management in such a complex presentation.

Established Facts

• Shunt nephritis is a rare, immune complex-mediated glomerulonephritis associated with infected cerebrospinal fluid shunts.

• Diagnosis is supported by clinical, laboratory, and histopathological evidence of infection and immune complex deposits.

Novel Insights

• Shunt nephritis can present as isolated nephrotic syndrome, without prominent systemic infection signs.

• It highlights the need to actively screen for this entity in patients with shunt devices and request the prompt removal of the shunt.

Introduction

Shunt nephritis is a rare form of immune complex-mediated glomerulonephritis (GN), first described by Black in 1965 [1]. It occurs as a complication of chronically infected cerebrospinal fluid (CSF) shunts, which are used to treat hydrocephalus, most commonly ventriculoatrial shunt (VAS) or ventriculoperitoneal shunt (VPS). Its occurrence has declined markedly to 0.7–2.5% in recent decades due to advances in medical technology, enhanced sterilization practices, and improved shunt infection management [2]. This condition typically arises from persistent, low-grade bacteremia associated with shunt infections, particularly from VAS that connects directly to the bloodstream. Cutibacterium acnes (formerly known as Propionibacterium acnes) is one of the primary causative organisms, including Staphylococcus epidermidis and Streptococcus species [3]. Circulating immune complexes, formed by bacterial antigens and host antibodies, deposit in the kidneys, triggering complement activation and GN. Clinically, patients may present with fever, malaise, hematuria, hypertension, and features of nephritic or nephrotic syndromes [4]. Precisely because this condition has become rare, we emphasize that shunt nephritis should still be recognized as a complex clinical entity. It must be promptly considered in patients with a shunt who develop neurological decline and proteinuria, even when signs of systemic inflammation are absent, such as in the case of our patient. The removal of the infected shunt and targeted antibiotics often leads to renal recovery, but progression to chronic kidney disease has been documented in untreated or delayed cases.

Case Report

We report the case of a 35-year-old man who presented to the emergency department with generalized edema, poorly controlled hypertension, and shortness of breath. He had a deterioration of his general condition with increasing fatigue for 2 weeks, vertigo, and a tendency to fall for 3 days.

At the age of 19 years, he suffered from a traumatic brain injury with occlusive hydrocephalus. This was subsequently treated with bilateral cranioplasty using Palacos and the implantation of a VPS. This shunt was replaced with a VAS because of an appendicular peritonitis 11 years ago. The patient also had a history of structural epilepsy and intellectual disability, with severe cognitive deficits resulting from the brain injury.

Vital parameters at admission showed a blood pressure of 180/111 mm Hg, a pulse of 89/min, a temperature of 36.8°C, and a weight of 91 kg. General physical examination showed grade 2 pitting legs and eyelid edema as well as bilateral fine crackles. The inspection of the skin revealed scaly patches of the scalp due to seborrheic dermatitis. Neurological examination revealed a confusional state and a Glasgow Coma Scale of 14/15. A previously described gait ataxia with a wide-legged gait reported 4 years ago was aggravated with a tendency to fall. There was new dysmetria and a mild dysdiadochokinesis. There were no sensory or motor deficits or meningism.

Given the patient’s presentation with dyspnea, edema, and neurological symptoms, complications such as thrombosis, pulmonary embolism, or endocarditis with septic cerebral emboli have to be considered and ruled out [5]. A computed tomography of the brain showed neither ischemia nor bleeding. Compared to a computed tomography done one year earlier, the ventricular system was slightly widened but without an evident CSF blockage. Chest X-rays confirmed bilateral pleural effusions and cardiopulmonary volume overload, and the echocardiography showed a normal cardiac function, without signs of endocarditis, intra-atrial, or intraventricular thrombi.

Our patient’s medication included antiepileptic drugs such as lamotrigine, valproic acid, and oxcarbazepine. His caregiver reported the use of ibuprofen up to 800 mg thrice daily over the past few days prior to admission due to progressive headache. A valproic acid or lamotrigine intoxication, which could lead to altered consciousness, seizures, acute kidney injury (AKI), or ataxia, has been ruled out by trough-level monitoring [6].

Serum analysis at presentation showed an AKI with a serum creatinine of 111 µmol/L (baseline 80–90 µmol/L), a serum urea of 10.1 mmol/L (reference 3.2–7.3 mmol/L), and an estimated glomerular filtration rate, according to Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI), as 74 mL/min/1.73 m² (in the previous year >90 mL/min/1.73 m² without known albuminuria). The urine analysis showed a nephrotic range proteinuria with an albuminuria of 6.1 g/day and urine microscopy revealed a glomerular microhematuria with >50 erythrocytes/high power field, of which 64% were dysmorphic red blood cells and 4% were acanthocytes. No red blood casts were detected.

The ultrasound revealed enlarged kidneys: 14 cm on the right and 13.8 cm on the left side. The arterial and venous perfusions, as well as resistance indices, were within the normal range. A post-renal etiology of AKI has been ruled out.

The hypoalbuminemia of 21 g/L (reference: 35–52 g/L) and elevated serum lipid profile with a total cholesterol of 5.98 mmol/L (reference: <5.2), triglycerides of 2.17 mmol/L (reference: <1.7), and high-density lipoprotein of 0.85 mmol/L (reference: >1.04) were consistent with the diagnosis of an acute nephrotic syndrome. Further analysis showed low serum complement C3 (0.5 g/L; normal: 0.90–1.80 g/L) and C4 (0.08 g/L; normal: 0.10–0.40 g/L) levels, while C1q was within the normal range. Serologic testing for Human Immunodeficiency Virus, hepatitis B virus, hepatitis C virus, tick-borne encephalitis, Borrelia burgdorferi, antinuclear antibodies, antineutrophil cytoplasmic antibodies, anti-phospholipase A2 receptor antibodies (PLA2R), anti-double-stranded deoxyribonucleic acid antibodies, antistreptolysin, and deoxyribonuclease B revealed no pathologic results. The serum protein electrophoresis and immunofixation were normal.

A renal biopsy was performed and showed a diffuse and global membranoproliferative GN with extensive exudative endocapillary hypercellularity. Cellular and fibrocellular crescents were found in four glomeruli (shown in Fig. 1a, b). Immunofluorescence was positive for complement component C3c (2+) (shown in Fig. 1c [cyan arrow: mesangium, white arrow: membranous]), immunoglobulin M (2+) (shown in Fig. 1d [cyan arrow: mesangium, white arrow: membranous]), complement component C1q (1+), and kappa and lambda light chains (1+), while immunoglobulin G and immunoglobulin A showed no expression. The electron microscopy demonstrated numerous large electron-dense deposits with a primarily mesangial (shown in Fig. 1e, white arrow) and subendothelial (shown in Fig. 1f, white arrow) location. Further, an extensive effacement of the podocytes’ foot processes was present (shown in Fig. 1f, cyan arrow).

Fig. 1.

Renal biopsy showing the light microscopy (PAS and Silver-HE staining, a, b), the immunofluorescence (c, d) and the electron microscopy (e, f). See detailed description in the text.

A membranoproliferative pattern with an exudative component and predominant C3c and immunoglobulin M deposits suggested an infection-related GN. Cases of infection-related GN have been reported in individuals with infected VPS, referred to as “shunt nephritis.” As a differential diagnosis, complement C3 GN was considered, as its histopathological findings often overlap with those of infection-related GN, but only a persistent C3 consumption and proteinuria following the resolution of the infection would confirm this alternative diagnosis.

At this stage, an infection-focused workup, including blood and CSF cultures, was performed. To confirm the suspicion of shunt nephritis, we performed a spinal tap, which revealed a clear CSF with pleocytosis (18 cells, 100% mononuclear cells) and normal glucose and lactate levels. The albumin liquor-serum ratio was significantly elevated to 30.07 (<6.50). PCRs were negative for Listeria monocytogenes, Neisseria meningitides, Streptococcus pneumoniae, or Streptococcus group B, herpes simplex virus 1 or 2, varicella zoster virus, cytomegalovirus, enterovirus and parechovirus, and Cryptococcus neoformans/gatii. Gram staining of the CSF showed Gram-positive rods. A CSF culture was positive for C. acnes, and blood cultures sampled 2 days prior to the CSF cultures also revealed a positive result for C. acnes after 108 h of incubation.

An antibiotic therapy with high-dose intravenous (i.v.) ceftriaxone (2 g every 12 h) was promptly started. In the context of high-grade fever and agitation, the antibiotics were extended to i.v. vancomycin, initially 750 mg every 12 h (then monitored according to trough levels with a target of 15–20 mg/L), and i.v. cefepime (2 g every 12 h), before changing to 12-week suppressive therapy with an oral amoxicillin of 1 g every 8 h based on the antibiogram. Neurosurgeons first externalized and later removed the VAS after CSF and blood culture results turned positive. A lumbar drainage was then implanted under monitoring in the neurosurgical ICU. As the patient pulled out the lumbar drain during a state of aggravated mental confusion with new signs of intracranial hypertension, emergency reimplantation of a VPS was performed.

Forty-eight hours after the initiation of antibiotic therapy, C4 normalized (0.11 g/L) and C3 rose without normalizing before discharge (last value 0.83 g/L). The albuminuria diminished to 970 mg/d, while kidney function remained unchanged. We started a renin-angiotensin-aldosterone system inhibitor with candesartan as an anti-proteinuric agent before discharging the patient. At one month follow-up after the new VPS implantation, kidney function was normalized with creatinine levels at 88 μmol/L and estimated glomerular filtration rate, according to CKD-EPI, at >90 mL/min/1.73 m².

At the end of the 12-week suppressive therapy with amoxicillin, the patient was evaluated in the outpatient clinic. He presented euvolemic and normotensive without leg edema. Albumin, lipid profile, and C3 returned to normal values, and albuminuria decreased to 120 mg/day.

Discussion

This presentation of acute kidney failure with nephrotic range albuminuria and microhematuria provides insights into potential differential diagnoses, such as infection-related GN, autoimmune GN, alloimmune GN, autoinflammatory GN, and monoclonal gammopathy-related GN [7]. Considering the use of ibuprofen, drug-induced conditions such as minimal change disease, membranous GN, acute interstitial nephritis, and acute tubular necrosis have to be considered [8, 9]. Additionally, nephrotic-range proteinuria can indicate the presence of renal vein thrombosis, which must be ruled out.

The results of autoimmune and infectious serology play a crucial role in narrowing the broad spectrum of differential diagnoses. Negative anti-nuclear antibodies, anti-double-stranded deoxyribonucleic acid antibodies, and C1q strongly suggest that lupus nephritis is unlikely. Microscopic polyangiitis and granulomatosis with polyangiitis can be excluded based on negative anti-neutrophil cytoplasmic antibody results. Idiopathic membranous GN is often associated with positive anti-PLA2R antibodies, although there is a wide range of newly identified target antigens in membranous GN. Positive anti-streptolysin or deoxyribonuclease B titers may indicate infection-related GN. A reduction in complement C3 and C4 levels suggests activation of both alternative and classical pathways, which is commonly observed in infection-related immune complex diseases and presents histologically with a membranoproliferative pattern. At this stage, only the kidney biopsy can establish the diagnosis.

In cases of shunt infection, removal of the shunt is an absolute indication. In our patient, the shunt was initially exteriorized and subsequently replaced once blood cultures returned negative. Removing the infected shunt and initiating targeted antibiotic therapy effectively addressed the underlying source of immune complex formation as the main trigger for kidney damage. Renal function typically improves or stabilizes once the infection is resolved and immune complex production ceases, as evidenced by rising serum C3 levels, a reduction in albuminuria to non-nephrotic levels, and normalization of serum albumin.

Shunt nephritis, as a form of infection-related GN, is handled by treating the underlying infection. In the absence of a marked inflammatory syndrome, we opted to monitor complement levels as a prognostic indicator for recovery. The nephrotic syndrome resolved, and for the management of the residual non-nephrotic range albuminuria, the Kidney Disease Improving Global Outcomes (KDIGO) guidelines were followed. They emphasize supportive care – including renin-angiotensin-aldosterone system inhibitors for patients at high risk of progression, particularly those with nephrotic syndrome and persistent proteinuria, anticoagulation for hypoalbuminemia, and diuretics for hypervolemia – as well as close nephrological follow-up [10].

The strength of this case lies in the timely decision to perform a renal biopsy, initially prompted by suspicion of non-steroid anti-inflammatory drug-induced minimal change disease in the context of nephrotic syndrome. The histopathological diagnosis of infection-related GN was instrumental in expediting neurosurgical intervention for shunt removal – a course of action initially not supported by the neurosurgical team due to the absence of overt inflammation.

A key limitation of this report is the inability to provide the patient’s personal perspective. The patient is under legal guardianship due to long-standing cognitive impairment, and written informed consent was, therefore, obtained from the guardian.

As a primary takeaway, early diagnosis and prompt management of an infected shunt are critical for improving renal and neurological outcomes. In any symptomatic patient with a VAS or VPS, blood and CSF cultures should be obtained immediately upon admission. Early consideration of shunt removal is warranted even in the absence of clear clinical signs of infection. This case report was prepared in accordance with the CARE (CAse REport) guidelines (available in the online suppl. material; for all online suppl. material, see https://doi.org/10.1159/000548443).

Acknowledgments

We would like to thank the patient for his participation and his guardian who consented to publish this case report.

Statement of Ethics

Ethical approval is not required for this study in accordance with local or national guidelines. The written informed consent was obtained from the patient’s guardian, as the legally authorized individual, for publication of the details of the medical case and any accompanying images.

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

This study was not supported by any sponsor or funder.

Author Contributions

N.H. and A.A. wrote the manuscript. A.R.-C. and P.Z. provided the histopathological findings and prepared Figure 1. U.H.-D. and all other co-authors reviewed the manuscript. N.H., A.A., A.R.-C., and P.Z. revised the manuscript.

Funding Statement

This study was not supported by any sponsor or funder.

Data Availability Statement

All data generated or analyzed during this study are included in this article and its online supplementary material files. Further inquiries can be directed to the corresponding author.