Pauci-immune crescentic glomerulonephritis in the Down's syndrome

Mejda Cherif; Hafedh Hedri; Mondher Ounissi; Taher Gergah; Rim Goucha; Samia Barbouch; Ezzedine Abderrahim; Hedi Ben Maiz; Adel Kheder

doi:10.4103/1319-2442.121311

Instructions

Users online: 1241


CASE REPORT

Year : 2013 | Volume : 24 | Issue : 6 | Page : 1223-1227

Pauci-immune crescentic glomerulonephritis in the Down's syndrome

Mejda Cherif¹, Hafedh Hedri¹, Mondher Ounissi¹, Taher Gergah², Rim Goucha¹, Samia Barbouch¹, Ezzedine Abderrahim¹, Hedi Ben Maiz³, Adel Kheder¹
¹ Department of Internal Medicine A, Charles Nicolle Hospital, Tunis, Tunisia
² Department of Pediatrics, Charles Nicolle Hospital, Tunis, Tunisia
³ Laboratory of Renal Pathology (LR00SP01), Tunis, Tunisia

Click here for correspondence address and email

Date of Web Publication

13-Nov-2013

Abstract

Kidney disease is a rare complication in patients with the Down's syndrome. However, with increased survival, it appears that a growing number of these patients present with glomerulonephritis. Most cases have been reported as case reports and include lesions such as mesangiocapillary glomerulonephritis with hypo-complementemia, crescentic glomerulonephritis with anti-neutrophil cytoplasmic antibodies (ANCA), amyloidosis and immunotactoid glomerulopathy. We report the observation of a 38-year-old man with the Down's syndrome who presented with severe renal failure, proteinuria and microscopic hematuria evolving over two months. There was no history of congenital heart disease or urinary symptoms. Percutaneous renal biopsy revealed fibrous crescents, rupture of Bowman's capsule and peri-glomerular granuloma; there were no deposits on immunofluorescence study. Thoracic computerized tomography scan showed alveolar congestion. The patient tested negative for ANCA. At the time of reporting, the patient is on regular chronic hemodialysis. Our case illustrates a distinct entity that further expands the spectrum of renal disease known to occur in the Down's syndrome. Early detection of the renal disorders may prevent or slow down the progression.

How to cite this article:
Cherif M, Hedri H, Ounissi M, Gergah T, Goucha R, Barbouch S, Abderrahim E, Maiz HB, Kheder A. Pauci-immune crescentic glomerulonephritis in the Down's syndrome. Saudi J Kidney Dis Transpl 2013;24:1223-7

How to cite this URL:
Cherif M, Hedri H, Ounissi M, Gergah T, Goucha R, Barbouch S, Abderrahim E, Maiz HB, Kheder A. Pauci-immune crescentic glomerulonephritis in the Down's syndrome. Saudi J Kidney Dis Transpl [serial online] 2013 [cited 2021 Feb 28];24:1223-7. Available from: https://www.sjkdt.org/text.asp?2013/24/6/1223/121311

Introduction

The Down's syndrome is one of the most common chromosomal disorders, characterized by short stature and a set of congenital anomalies and mental retardation. Patients with the Down's syndrome have a higher incidence of leukemia and congenital heart disease. Kidney disease is a rare complication; however, with increased survival, it appears that a growing number of these patients present with glomerulonephritis. Most reports, appearing as case reports, have reported lesions such as mesangiocapillary glomerulonephritis with hypo-complementemia, ^[1] amyloidosis, ^[2] immunotactoid glomerulopathy, ^[3] anti-neutrophilic cytoplasmic antibody (ANCA)-associated glomerulonephritis, ^[4],[5],[6] focal and segmental glomerulosclerosis ^[7] and IgA glomerulonephritis. ^[8]

We report an adult patient with the Down's syndrome who presented with severe renal failure, proteinuria and microscopic hematuria, with renal histology revealing pauci-immune crescentic glomerulonephritis.

Case Report

A 39-year-old man was hospitalized for severe renal failure. He developed thoracic pain, dyspnea, nausea and vomiting two months earlier and laboratory investigations revealed severe renal failure and pericarditis with cardiac tamponade requiring urgent surgical drainage and several hemodialysis sessions.

A medical interview did not reveal features of mental retardation and there was no history of congenital heart disease, urinary symptoms, hemoptysis, flank pain, voiding dysfunction, skin rash, joint pain or swelling. There was no family history of hereditary renal disease, deafness or diabetes mellitus.

Physical examination on admission revealed typical features of the Down's syndrome, such as short stature, macroglossia, broad flat nose, low set ears and flexed fingers. The blood pressure was 100/60 mmHg, the height was 155 cm and the weight was 62 kg. There was no clinical evidence of edema and pulse rate and body temperature were 80/min and 38.3°C, respectively. Moist rales and wheezing were audible bilaterally in the lower lung fields; there was no pericardial rub. The abdomen was swollen and flabby without palpable liver or spleen. Laboratory studies revealed a serum creatinine of 949 μmol/L, sodium of 134 mmol/L, potassium of 4.66 mmol/L, chloride of 91 mmol/L, bicarbonate of 18 mmol/L, glucose of 4.9 mmol/L, calcium of 2.12 mmol/L, total protein of 70 g/L, albumin of 32 g/L and C-reactive protein of 195 mg/L (normal range 1 - 6 mg/L). The red blood cell count was 2.39 × 10 ⁶ /μL, hematocrit was 21.5%, hemoglobin was 7.4 g/dL, leukocyte count was 5.6 × 10 ³ /μL and platelet count was 180 × 10 ³ /μL. Lactate dehydrogenase was 150 IU/L (normal range 190 - 390 IU/L), aspartate aminotransferase was 14 IU/L (normal range, <40 IU/L) and alanine aminotransferase was 15 IU/L (normal range, <40 IU/L).

Urine dipstick examination showed 2+ albuminuria and 3+ hematuria. Urine culture was sterile. Proteinuria was 2.1 g/day.

Tests for hepatitis B surface antigen, hepatitis C antibody, cryoglobulin and anti-nuclear antibody were negative. Complement fraction C3 was 103 mg/100 mL (normal range, 101 - 186 mg/100 mL), C4 was 33 mg/100 mL (normal range, 16 - 47 mg/100 mL) and CH-50 was 40 units (normal range, 43 ± 18.2 units). ANCA was negative.

Chest X-ray showed increased vascular shadows in the lung fields and cardiomegaly, with a cardiothoracic ratio of 59%. Echocardiogram revealed moderate pericardial effusion without compression of right-sided cardiac cavities [Figure 1]. Thoracic computerized tomography (CT) scan showed alveolar congestion without fibrosis. Renal ultrasound showed normal-sized kidneys with increased echogenicity of the cortex and no evidence of cystic malformation, obstruction or mass lesion. The karyo-type confirmed the diagnosis of mosaic-T21.

Figure 1: Echocardiogram showing pericardial effusion and normal heart valves.

Click here to view

Renal tissue was obtained by percutaneous renal biopsy. Light microscopic study demonstrated 17 glomeruli in the specimen, 14 of which showed global sclerosis with fibrous crescents, rupture of the Bowman's capsule and peri-glomerular granuloma [Figure 2] and [Figure 3]. The remaining glomeruli showed no cellular proliferation, no deposits and no abnormal findings in the basement membrane. The architecture of the tubules and the interstitium showed interstitial fibrosis and atrophic tubuli. The blood vessels were unremarkable. There were no deposits on immunofluorescence study.

Figure 2: Renal biopsy sample showing a glomerulus with sclerosis and fibrous crescent (trichrome staining).

Click here to view

Figure 3: Renal biopsy sample showing a glomerulus with a large circumferential crescent and rupture of the Bowman's capsule (PAS stain).

Click here to view

Hemodialysis was continued three times a week for pulmonary congestion and abnormal echocardiogram suggestive of pericardial effusion. The patient received antibiotics (amoxi-cillin and clauvulinic acid) to treat pneumonia. Two weeks after treatment, the patient became afebrile, the C-reactive protein decreased to 4 mg/L and the lung radiological changes and pericardial effusion disappeared.

Specific treatment was not proposed for the patient because of the extent of renal damage and the absence of other pulmonary, oto-rhinolaryngologic or neurologic lesions and the patient remains on chronic hemodialysis at the time of reporting.

Discussion

We report a case of the Down's syndrome who developed severe renal failure, proteinuria and microscopic hematuria with renal histology revealing pauci-immune crescentic glomerulonephritis.

Until now, there are only 11 publications describing glomerular nephropathies in patients with the Down's syndrome [Table 1]. Four cases of crescentic glomerulonephritis in association with the Down's syndrome have been reported in the past. ^{[4],[5],[6],[8]}

Table 1: Details of published reports on the Down's syndrome with glomerulonephritis.

Click here to view

Robson et al ^[4] reported a 9-year-old boy with the Down's syndrome who developed glomerulonephritis associated with crescents and ANCA; the patient also had type-1 diabetes mellitus, chronic lymphocytic thyroiditis and bronchial asthma. Prednisone therapy resulted in an improvement in renal function and a reduction in ANCA titers.

Schwab et al ^[6] described a 10-year-old girl with the Down's syndrome and peri-nuclear ANCA-positive vasculitis following Hanta virus infection. The pattern of her illness was complex and suggested an autoimmune disorder involving predominantly the lungs and the kidneys. Therapy with prednisone and cyclophosphamide resulted in rapid improvement of the extra-renal lesions and reduction of the P-ANCA titers.

Haseyama et al ^[5] reported a 24-year-old man with the Down's syndrome who developed infective endocarditis after dental treatment and severe renal failure secondary to proteinase-3-ANCA-positive crescentic glomerulonephritis. The patient died despite aggressive treatment with antibiotics and methylprednisolone.

Birk et al ^[8] reported three children with the Down's syndrome and primary glomerulonephritis. Only one patient was diagnosed with pauci-immune crescentic glomerulonephritis.

Others cases of glomerular nephropathy have also been described in patients with the Down's syndrome, most of them appearing as case reports [Table 1].

One publication reviewed the autopsy files of 43 patients with the Down's syndrome and found varying types of glomerular lesions. ^[9]

The maximum age of patients with the Down's syndrome and glomerular disease reported thus far is under 30 years.

Our report describes the observation of a 38-year-old man with the Down's syndrome and glomerulonephritis, and it confirms the improvement in survival rates of patients affected with these disorders. Survival has spectacularly increased during the last 50 years.

The life expectancy of patients with the Down's syndrome was 6 years until 1958; 25% lived until 9 years by the year 1962. The life expectance of men exceeds by 3 years over that of women. At the present time, the life expectancy has moved closer to that in the general population but with a varied number of significant health problems during adulthood. ^[10] Our patient was referred late and did not receive any specific treatment because of fibrosis and chronic injury; Robson ^[4] and Schwab ^[6] have successfully treated their patients either with prednisone or with cyclophosphamide, in addition.

Conclusion

The present report expands the spectrum of glomerular diseases known to occur in the Down's syndrome and illustrates the importance of early diagnosis of renal disorders in adults with this syndrome. The survival is far better now and measures are available to prevent or slow progression of some of the renal diseases. ^[12]

References

1.	Gupta SK, Venkataseshan VS, Churg J. Mesangiocapillary glomerulonephritis in Down's syndrome. Am J Nephrol 1991;11:112-7
2.	Ozkaya O, Paksu MS, Bek K, et al. Renal amylodosis due to pulmonary tuberculosis in a patient with Down syndrome. Eur J Pediatr 2006;165:134-5.
3.	Takemura T, Yoshioka K, Akano N, et al. Immunotactoid glomerulopathy in a child with Down syndrome. Pediatr Nephrol 1993;7:86-8.
4.	Robson WL, Leung AK, Woodman RC, Trevenen CL. Anti-neutrophil cytoplasmic antibody associated glomerulonephritis in a patient with Down's syndrome. Pediatr Nephrol 1995; 9:204-5.
5.	Haseyama T, Imai H, Komatsuda A, et al. Proteinase-3- antineutrophil cytoplasmic antibody (PR3-ANCA) positive crescentic glomerulonephritis in a patient with Down's syndrome and infectious endocarditis. Nephrol Dial Transplant 1998;13:2142-6.
6.	Schwab M, Boswald M, Ludwig K, Wittekind C, Waldherr R, Ruder H. A patient with Down's syndrome and anti-neutrophilic cytoplasmic antibody-positive vasculitis. Pediatr Nephrol 1996;10:249-51.
7.	Baqi N, Tejani A, Sullivan EK. Renal transplantation in Down's syndrome: A report of the North American Pediatric Renal Transplant Cooperative Study. Pediatr Transplant 1998; 2:211-5.
8.	Birk PE, Burke BA, Vernier RL. Glomerulonephritis in children with Down syndrome. Pediatr Nephrol 1996;10:549.
9.	Lo A, Brown HG, Fivush BA, Neu AM, Racusen LC. Renal disease in Down's Syndrome: Autopsy study with emphasis on glomerular lesions. Am J Kidney Dis 1998;31:329-35.
10.	Glasson EJ, Sullivan SG, Hussain R, et al. Changement dans le profil de survie des personnes souffrant du syndrome de Down. Implication pour le conseil génétique. Journal de la trisomie 2004;11.
11.	Yoshikawa N, Ijima K, Shimomura M, Nakamura H, Ito H. IgG-associated primary glomerulonephritis in children. Clin Nephrol 1994;42:281-7.
12.	Assadi FK. IgG-associated mesangial glomerulonephritis in a patient with Down syndrome. Med Sci Monit 2004;10:CS54-6.