Year : 2014 | Volume
: 25 | Issue : 2 | Page : 394--397
Chronic tubulo-interstitial nephritis in common variable immunodeficiency: A rare association
Sumantra Sarkar1, Rakesh Mondal1, Madhumita Nandi1, Parasar Ghosh2,
1 Department of Pediatrics, Institute of Post Graduate Medical Education and Research, Kolkata, India
2 Department of Rheumatology, Institute of Post Graduate Medical Education and Research, Kolkata, India
Department of Pediatrics, Institute of Post Graduate Medical Education and Research, Kolkata
Common variable immunodeficiency (CVID) is characterized by reduced serum immunoglobulin levels and repeated serious bacterial infections involving different organ systems. Chronic kidney disease (CKD) is an uncommon association with CVID. Chronic tubulo-interstitial nephritis in a case of CVID that progressed to CKD is distinctly rare.
|How to cite this article:|
Sarkar S, Mondal R, Nandi M, Ghosh P. Chronic tubulo-interstitial nephritis in common variable immunodeficiency: A rare association.Saudi J Kidney Dis Transpl 2014;25:394-397
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Sarkar S, Mondal R, Nandi M, Ghosh P. Chronic tubulo-interstitial nephritis in common variable immunodeficiency: A rare association. Saudi J Kidney Dis Transpl [serial online] 2014 [cited 2020 Jul 16 ];25:394-397
Available from: http://www.sjkdt.org/text.asp?2014/25/2/394/128582
Common variable immunodeficiency (CVID) is the most common cause of primary hypogammaglobulinemia. This is characterized by reduced serum immunoglobulin (Ig) levels, repeated infections and association with various autoimmune and granulomatous diseases. We report a case of CVID that was complicated with chronic kidney disease (CKD) due to chronic tubulo-interstitial nephritis.
An 8-year-old girl, born out of non-consanguineous marriage, presented with respiratory distress for one day following fever and cough for two weeks. She had a history of several episodes of similar serious chest infections since infancy and required hospital admissions earlier on two occasions. On those occasions, the patient received azithromycin once for five days, and on the second admission she received cefixime for five days. She had not taken any other drug for some time prior to the current presentation.
She was born by cesarean section at full-term. Her birth weight was 3.2 kg. The mother's antenatal, natal and post-natal periods were uneventful. The child's developmental history was normal. Immunization was complete as per the national immunization schedule.
She developed progressive loss of scalp and body hair, resulting in total loss of hair at around four years of age. There was no history of similar illness in the family. The other sibling, her elder sister, was 17 years of age and was normal. On examination, she was alert and cooperative. Her height was 122.5 cm (75 th percentile, CDC) and weight was 17 kg (below 5 th percentile, CDC). Her respiratory rate was 50/min. Other vital parameters, including blood pressure, were normal. Her scalp and body hair were absent. She had generalized skin pigmentation, dystrophic nails and loss of enamel of the teeth. Examination of the chest revealed bilateral coarse crepitations and polyphonic wheeze. Her abdomen was soft with 4 cm hepatomegaly. The spleen was just palpable. Lymph nodes were not significantly enlarged. The urine output was normal.
On investigations, the hemoglobin level was 8.5 g/dL, total leukocyte count was 8300/mm 3 (neutrophils 60%, lymphocytes 32%, eosinophils 5%, monocyte 3%) and platelet count was 1.83 lakhs/mm 3 . Liver function tests were normal. The blood urea level was 32 mg/dL and serum creatinine was 0.7 mg/dL. Chest X-ray showed accentuation of bronchovascular markings with bilateral hilar congestion. Routine examination of the urine showed 20-30 pus cells per high-power field. No red blood cells or epithelial cells were seen. There were no casts in the urine. Albumin was trace and no glucose or ketone body was found. Urine culture and sensitivity showed significant growth of E. coli. She responded to intravenous ofloxacin for 14 days given according to the sensitivity report. Ultrasonography (USG) of the abdomen, performed after two weeks, was normal. The size of the left kidney was 8.2 cm and that of the right kidney was 8.3 cm. In view of recurrent sino-pulmonary and urinary tract infections with alopecia totalis, she underwent investigations for immunodeficiency.
Immunoglobulin assay showed pan-hypo-gammaglobulinemia. IgG: 347 mg/dL (normal 572-1474 mg/dL), IgA: <4 mg/dL (normal 34-305 mg/dL), IgM: 11 mg/dL (normal 31-208 mg/dL) and IgE: 0.38 IU/mL (normal up to 90 IU/mL). The lymphocyte count including T and B cell subsets was normal on flow cytometry. Complement assay revealed C 3 level of 134.4 mg/dL (normal 90-180 mg/dL) and C 4 level of 85.6 mg/dL (normal 10-40 mg/dL). Nitroblue tetrazolium test for phagocytic activity was normal. Anti-nuclear factor and dsDNA were negative. Screening for human immunodeficiency virus and hepatitis B surface antigen was negative.
History of recurrent serious infections, alopecia, pan-hypo-gammaglobulinemia with normal T cell count, normal phagocytic function and absence of hypo-complementemia established the diagnosis of CVID.
She was readmitted five months later with fever and pneumonia. There was no history of rash or joint pain. The chest X-ray showed bilateral patchy pneumonitis. She was treated with intravenous cefuroxime for 10 days. Urine analysis showed three to four pus cells and four to five red blood cells per high-power field and no eosinophils. Albumin was 1+ and a few granular casts and phosphate crystals were seen. No ketonuria or glycosuria was noted. Other investigations were insignificant but her blood urea level was 112 mg/dL and serum creatinine level was 1.5 mg/dL. USG abdomen showed bilateral early renal parenchymal disease. The size of the left kidney was 7.7 cm and that of the right kidney was 7.6 cm. The pelvicalyceal system and urinary bladder were normal. Her estimated glomerular filtration rate (eGFR) at that time was 44.73 mL/1.73 m 2 /min. Because renal complications are very rare in patients with CVID, we performed a renal biopsy. While the biopsy report was awaited, her serum creatinine level rose to 4.5 mg/dL. She was put on intermittent peritoneal dialysis. Her eGFR at the time of starting dialysis was 14.9 mL/1.73 m 2 /min. The serum creatinine level was still rising, and went to 10.11 mg/dL, potassium level was 6.2 mEq/L and serum calcium level was 9.28 mg/ dL. Her eGFR dropped to 6.66 mL/1.73 m 2 / min. She was then put on continuous ambulatory peritoneal dialysis.
Her renal biopsy report showed presence of marked tubular degeneration, interstitial fibrosis, tubular loss and presence of more than 50% atrophic tubules along with dense deposits of mixed inflammatory infiltrations with predominant lymphomononuclear cells in the interstitium. Changes in the glomeruli were non-specific. Blood vessels were unremarkable. A direct immunofluorescence study did not reveal any deposits. Congo red staining for amyloidosis was negative. The impression on renal biopsy was chronic tubulo-interstitial nephritis, and was the cause of CKD in our patient. She is currently enlisted for renal transplantation.
CVID is characterized by hypo-gammaglobulinemia, repeated respiratory infections, chronic gastrointestinal symptoms, malabsorption, arthritis and multisystem involvement. Although reduction of IgG and IgA are characteristic features, approximately 50% of patients with the deficiency also have diminished IgM levels and T-lymphocyte dysfunction.  Apart from infections, there is also an increased incidence of malignancy and granulomatous and autoimmune diseases like juvenile rheumatoid arthritis, systemic lupus erythematosus and Sjogren's syndrome. 
All types of Igs were reduced in our patient. Her T cell count was normal, with no significant alteration of CD4 and CD8 ratio. The high C 4 level seen is explained by association of infection. She had repeated respiratory and urinary infections that required hospitalization. Alopecia universalis is also an associated feature in CVID.  Recurrent serious infections, alopecia and pan-hypo-gammaglobulinemia favor the diagnosis of CVID in our patient. Other possibilities of primary immunodeficiency like T-cell defect, phagocytic defect or hypo-complementemia were excluded.
The association of renal disease with CVID is distinctly uncommon. There are reports of renal granulomatous disease in association with CVID.  One patient had interstitial non-caseating granuloma and immunoglobulin (IgM)-complex glomerulonephritis with a membranoproliferative pattern.  Another patient had non-caseating renal granuloma in association with hypercalcemia.  Steroid-sensitive nephrotic syndrome has also been reported.  In one report, a patient having selective IgG deficiency developed end-stage kidney disease (ESKD) due to chronic interstitial nephritis and early membranous nephropathy.  A 15-year-old girl who developed ESKD and underwent renal transplantation was subsequently diagnosed to have CVID. 
The literature review from India has shown one study of CVID that described 23 patients; most of them were children.  None of the children had renal involvement. In our patient, although there were several episodes of sino-pulmonary infections, only one episode of urinary tract infection had occurred. The history, clinical features and investigations did not suggest recurrent pyelonephritis as a possible etiology of CKD or ESKD. Also, there was no obvious suggestion of the renal disease being caused by any drugs or obstructive nephropathy. Association with auto-immune or granulomatous disease also was not found. Our patient with CVID developed chronic tubulo-interstitial disease that progressed to CKD, and even further to ESKD requiring renal transplant. Immunological abnormality of CVID may, in part or whole, be responsible for this rare association with chronic tubulo-interstitial disease.
CKD associated with CVID in a pediatric patient is rarely reported in the literature. Chronic tubulo-interstitial disease as a cause of CKD in a case of CVID is even rarer.
Conflict of interest: None.
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