Immunoglobulin A (IgA) nephropathy (Berger’s disease) is the most common glomerulonephritis worldwide. The disease typically is chronic and lifelong and eventually progresses to impaired renal function in a substantial proportion of cases. It has been known for some time that there is a correlation between IgA nephropathy and celiac disease, but until now it has remained unclear whether treatment of the underlying celiac disease has any meaningful impact on the progression of the renal disease. Therefore, until now, screening for celiac disease in patients presenting with IgA nephropathy has not been universally recommended in the absence of suggestive gastrointestinal symptoms. This report describes a case of IgA nephropathy in an adolescent boy that turned out to be the initial presentation of celiac disease. More importantly, it documents the complete laboratory normalization of his renal anomalies at 5-year follow-up after treatment of his celiac disease with implementation of a gluten-free diet. This case highlights the importance of awareness that suspected IgA nephropathy, even in the absence of gastrointestinal symptoms, should prompt screening for underlying celiac disease as a potential, and possibly treatable, cause.

Immunoglobulin A (IgA) nephropathy (Berger’s disease) is the most common glomerulonephritis worldwide.1  The disease typically is chronic and lifelong and eventually progresses to impaired renal function in a substantial proportion of cases.2 

It has been known for some time that there is a correlation between IgA nephropathy and celiac disease,38  but it has remained unclear whether treatment of the underlying celiac disease has any meaningful impact on the progression of the renal disease. Therefore, until now, screening for celiac disease in patients presenting with IgA nephropathy has not been universally recommended in the absence of suggestive gastrointestinal symptoms.

In this article, I describe a case of IgA nephropathy in an adolescent boy that turned out to be the initial presentation of celiac disease, and I will document the complete laboratory normalization of his renal anomalies at 5-year follow-up after treatment of his celiac disease with implementation of a strict gluten-free diet.

A previously healthy 16-year-old boy presented to the emergency department (ED) with acute onset of painless gross hematuria, described as “Hawaiian punch red.” He had no dysuria, no urinary urgency or frequency, no flank pain, no history of edema, and no fever. He was taking no medications at the time. He did happen to have mild upper respiratory infection symptoms (primarily scratchy throat and cough) for 1 day before his presentation. Of note, he denied any history of gastrointestinal symptoms, either acute or chronic. Specifically, he denied any history of abdominal pain, nausea, vomiting, diarrhea, constipation, distension, bloating, change in appetite, or weight loss. Furthermore, there was no family history of any renal disease or celiac disease.

On presentation to the ED, his temperature was 37.3°C, initial blood pressure was 142/73 mm Hg (decreased to 118/68 on repeat later on during ED visit), heart rate 82 beats per minute, respiratory rate 16 breaths per minute, with oxygen saturation of 97% via pulse oximetry. His weight was 150 lb and his height was 5 ft 10 in, for a BMI of 21.5 (55th percentile). His physical examination was unremarkable and was negative for flank tenderness, edema, joint swelling, or genitourinary trauma.

Urinalysis was notable for grossly red color, >50 red blood cells (RBCs) per high power field (HPF), 11 to 20 white blood cells per HPF, and protein 100 mg/dL. A subsequent urine culture was negative.

A complete blood cell count revealed slightly low hemoglobin of 13.1 g/dL but was otherwise normal. A comprehensive metabolic panel showed a high-normal creatinine of 1.23 mg/dL and was otherwise normal. Serum C3 complement was normal at 98 mg/dL, and antistreptolysin O titer was normal at 45.7 IU/mL. A throat culture taken in the ED was subsequently negative for group A strep.

A renal ultrasound performed in the ED revealed bilateral echogenic kidneys suggestive of renal parenchymal disease. No hydronephrosis or calculi were seen.

The patient was discharged from the hospital from the ED with instructions for close follow-up with a pediatric nephrologist. His gross hematuria resolved within several days; however, at the nephrology follow-up a week later, he continued to have microscopic hematuria as well as proteinuria. First morning urine protein-to-creatinine ratios were followed over the next 2 months and ranged from 0.19 to 0.29 mg/mg, slightly elevated above the normal range of <0.20 mg/mg,9  indicative of ongoing glomerular disease. He also continued to have persistent microscopic hematuria on multiple urinalyses, generally in the range of 11 to 30 RBCs per HPF.

Furthermore, he subsequently had the recurrence of gross hematuria in conjunction with another viral upper respiratory infection several weeks later. The nephrologist, believing his presentation (repeated episodes of gross hematuria with persistent microscopic hematuria, persistent morning proteinuria, and increased renal echotexture) to be most consistent with IgA nephropathy, advised a renal biopsy to confirm the diagnosis and to devise a treatment plan.

However, around the same time, further laboratory workup included a celiac disease panel, ordered because of the clinical correlations in the literature described above. Unexpectedly, the patient’s results showed an elevated tissue transglutaminase (tTG) IgA of 83 U/mL and a positive endomysial antibody IgA, in the context of a normal serum IgA level of 257 mg/dL. With these serological findings strongly suggestive of celiac disease, the patient underwent subsequent evaluation by a pediatric gastroenterologist. An upper endoscopy with duodenal biopsy was performed, with duodenal biopsy showing subtotal villous atrophy with associated crypt hyperplasia and intraepithelial lymphocytosis consistent with celiac disease, Marsh 3B. These findings definitively confirmed the diagnosis of celiac disease, and a strict gluten-free diet was implemented. Again, the patient had had no suggestive gastrointestinal symptoms at all.

A decision was made to defer the renal biopsy pending close observation of the patient’s response to treatment of his celiac disease with the gluten-free diet. Subsequently, bloodwork and urine studies were followed closely over the next year, with particular attention to the first morning urine protein-to-creatinine ratio, because this measurement has been demonstrated to have prognostic value with regard to progression of renal disease in patients with IgA nephropathy.10  Severity of microscopic hematuria was also monitored, because it has also been noted that remission of hematuria is a marker of improved long-term prognosis in IgA nephropathy.11  Also, serum creatinine levels were monitored as an overall indicator of renal function.

During that first year of close observation after beginning the gluten-free diet, the patient’s serum tTG IgA levels dropped from 83 to 6 U/mL within 7 months, indicating good adherence to the gluten-free diet. Alongside this improvement of his celiac autoantibodies, the patient’s serum creatinine levels remained stable in the normal range, his microscopic hematuria remained present but stable, and his morning protein-to-creatinine ratio decreased from a peak of 0.29 (above normal range) to within the normal range of <0.20, where it remained thereafter (see Table 1). Of note, after identification of his celiac disease and implementation of the gluten-free diet, the patient never had any further episodes of gross hematuria.

TABLE 1

Serum tTG IgA, Serum Creatinine, Urine RBCs per HPF, and First Morning Urine Protein-to-Creatinine Ratio by Time From Initial Presentation

Time Relative to Initial Presentation (in mo)CommentsSerum tTG IgA, U/mLSerum Creatinine, mg/dLUrine RBC per HPFFirst Morning Urine, Pr/Cr, mg/mg
Presentation in ED with gross hematuria — 1.23 >50 — 
— — 1.03 11-30 0.19 
— 83 1.01 11-30 0.29 
Celiac disease diagnosed; gluten-free diet started — — — — 
— 0.92 11-30 0.18 
10 — — — 3-10 0.17 
13 — 1.03 3-10 0.11 
20 — 0.99 11-30 0.13 
36 — 1.01 3-10 0.17 
58 — 0.94 0-2 0.06 
Time Relative to Initial Presentation (in mo)CommentsSerum tTG IgA, U/mLSerum Creatinine, mg/dLUrine RBC per HPFFirst Morning Urine, Pr/Cr, mg/mg
Presentation in ED with gross hematuria — 1.23 >50 — 
— — 1.03 11-30 0.19 
— 83 1.01 11-30 0.29 
Celiac disease diagnosed; gluten-free diet started — — — — 
— 0.92 11-30 0.18 
10 — — — 3-10 0.17 
13 — 1.03 3-10 0.11 
20 — 0.99 11-30 0.13 
36 — 1.01 3-10 0.17 
58 — 0.94 0-2 0.06 

Pr/Cr, protein to creatinine ratio; —, not applicable.

As noted in Table 1, as the patient continued to be monitored over the subsequent 5-year observation period, his serum tTG IgA levels continued to drop to a normal level of 3 U/mL within 2 years, and this normalization of his celiac autoantibodies was associated with a dramatic improvement in the severity of microscopic hematuria and first morning urine protein-to-creatinine ratio. Moreover, his serum creatinine remained well within the normal range throughout the entire time frame. On follow-up during the fifth year after diagnosis, his laboratory results were as follows: normal serum creatinine of 0.94, and, in contrast to his previous significant hematuria and high-normal urine protein-to-creatinine ratio, his urinalysis at 5-year follow-up had no more microscopic hematuria (0–2 RBCs per HPF), and his first morning protein-to-creatinine ratio had completely normalized at 0.06.

It is known that the clinical presentation of celiac disease can be widely varied. Most clinicians are familiar with the typical suggestive gastrointestinal symptoms that would prompt serological testing for celiac disease, which would include unexplained abdominal pain, nausea, diarrhea, constipation, weight loss, distension, or bloating. It is also generally well accepted that certain extraintestinal symptoms, such as persistent iron deficiency anemia or elevated transaminases, can also be the initial presenting sign of celiac disease and should prompt celiac testing as well, because these conditions can be corrected by treating the underlying celiac disease if present. What is less well documented and less well understood is the presentation of celiac disease that manifests as apparent primary kidney disease and whether this kidney disease can be halted or reversed by treating the underlying celiac disease.

IgA nephropathy (Berger’s disease) is the most common glomerulonephritis worldwide.1  The disease is felt to result from IgA deposits in the renal glomeruli, with subsequent activation of the complement system causing glomerular injury. Patients with IgA nephropathy tend to have persistent microscopic hematuria, often with bouts of gross hematuria during upper respiratory infections. They also generally have increased proteinuria as well. The disease tends to be chronic and lifelong and eventually progresses to impaired renal function in a significant percentage of cases.2 

Over the past several decades, clinicians have noticed an association between celiac disease and glomerular IgA deposition, sometimes with and sometimes without clinically evident renal disease.36  However, although the association between the 2 diseases has been established, it has remained unclear and not well understood whether identifying and addressing the underlying celiac disease would alter the clinical course of the renal disease.

A 1993 case report describes a 47-year-old man from the United Kingdom whose nephrotic syndrome from IgA nephropathy seemed to improve after 6 months on a gluten-free diet.7  Similarly, a 2009 case report documents a 46-year-old man with IgA nephropathy and celiac disease whose renal disease went into complete remission within months after implementing a gluten-free diet for his celiac disease.8  However, there have been few corroborating reports of this phenomenon, no studies with longer-term follow-up, and none in the pediatric population.

In this current article, I document a case of IgA nephropathy in an adolescent boy that turned out to be the initial presentation of celiac disease, and I document the complete laboratory normalization of his renal anomalies at 5-year follow-up after treatment of his celiac disease by implementation of a gluten-free diet, implying a favorable long-term renal prognosis.10,11 

It should be noted that the correlation between treatment of the celiac disease with a gluten-free diet and the improvement in the patient’s renal parameters does not necessarily imply causation; it is possible that the kidney disease may have improved on its own without any regard to the gluten-free diet. However, from what is already known about the typical history of IgA nephropathy, specifically, the known chronicity of the renal symptoms of typical, untreated IgA nephropathy,2  the already known association between IgA nephropathy and celiac disease in certain patients,36  and other case reports (in adults) describing a similar dramatic improvement in renal symptoms after addressing the underlying celiac disease,7,8  it seems plausible that treating this patient’s underlying celiac disease was the direct cause of the improvement in his renal disease. This case report, the first such report in a pediatric patient, adds to the growing body of evidence that there is at least a subset of patients with IgA nephropathy in which the kidney disease is secondary to celiac disease and may dramatically improve with treatment of the underlying celiac disease.

Patients presenting with suspected IgA nephropathy, even in the absence of gastrointestinal symptoms, should prompt screening for underlying celiac disease as a potential, and possibly treatable, cause.

Thank you to the patient for his willingness to share this case. Thank you to all of the members of the health care team (ED, pediatric nephrologists, and pediatric gastroenterologists) who contributed to the care of this patient.

FUNDING: No external funding.

Dr Slavin collected and analyzed the data, drafted, revised, and approved the manuscript, and agrees to be accountable for all aspects of the work.

ED

emergency department

HPF

high power field

IgA

immunoglobulin A

RBC

red blood cell

tTG

tissue transglutaminase

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Competing Interests

POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no conflicts of interest relevant to this article to disclose.

FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.