Dr Vincent M. Brandenburg	Prof Jürgen Floege
Department of Nephrology University Hospital Aachen Germany

 

In two adult patients with secondary obstructive hydrocephalus cerebrospinal fluid shunts had been implanted to control elevated intracranial pressure. Both patients were admitted to our hospital with malaise and fever, that had developed over several days. Marked proteinuria was present in both patients.

Patient A

Clinical course: (41-years old man). Eleven years ago a ventriculoatrial shunt had been implanted after a neurocytoma operation. Renal function tests and blood pressure had been normal ever since. Upon admission blood pressure was 142/75mmHg, body temperature was 38.8°C. The neurological and the physical examination of heart, abdomen, lungs and skin were normal. Bilateral ankle edema were present. Relevant laboratory tests are listed in Table 1:

Table 1

Relevant laboratory tests of patient A (* indicates not measured).

Parameter	Normal range	Patient A
White blood count (WBC)	4.3-10.0 x 10³/µL	10.6
Hemoglobin	12.0-16.0 g/dL	11.2
Platelets	150-350 x 10³/µL	257
Serum creatinine	0.6-1.2 mg/dL	1.1
Blood urea nitrogen (BUN)	20-50 mg/dL	66
Urinary hemoglobin dipstick	(-)	(+++)
Creatinine clearance	75-130 mL/min/1.73m²	93
Proteinuria	<150 mg/die	4050
Serum protein, total	66-83 g/L	63
Serum albumin	35-52 g/L	31
Cholesterol	103 - 260 mg/dL	295
C-reactive Protein	<5 mg/L	22
IgG	7.0-16.0 g/L	*
IgA	0.7-4.0 g/L	2.1
IgM	0.4-2.3 g/L	*
C3	0.9-1.8 g/L	0.4
C4	0.1-0.4 g/L	0.1
Antinuclear antibodies (ANA)	<1:80	1:80
Cryoglobulins	negative	negative

Due to nephrotic range proteinuria a renal biopsy was performed. The histological examination revealed:

Figure 1a and 1b

 

Comment Figure 1a and 1b:

Diagnosis: membranoproliferative glomerulonephritis (MPGN) Type 1

Figure 1a (PAS x400) demonstrates thickening and doubling of the basement membranes (1) and partial occlusion of the capillary lumina, subendothelial deposits (2); also visible expansion of the mesangial fields with matrix accumulation and mesangial hypercellularity (3);

Figure 1b (immunofluorescence microscopy x400, C1q) reveals widespread, global predominantly subendothelial deposits;

[Figures by courtesy of Professor Hermann-Josef Gröne; German Cancer Research Center, Heidelberg]

QUESTION 1 AND 2

The patient’s shunt was removed and since signs of elevated intracranial pressure relapsed, a ventrikuloperitoneal shunt was finally reimplanted. Over a period of seven days signs if inflammation completely disappeared. The renal outcome six months after the operation was good. Proteinuria decreased to levels below 0.5 g/day with concomitant therapy with enalapril 5 mg/day. Urinary sediment and blood pressure normalized.
Interestingly, all microbiological cultures obtained from this patient remained sterile.

Patient B

Clinical course: (46-years old woman). Four years ago she suffered from a spontaneous subarachnoid hemorrhage and a ventriculoatrial shunt had been implanted. Three years ago the ventrikuloatrial shunt was removed and replaced by a ventriculoperitoneal shunt because shunt nephritis was suspected (proteinuria, fever). Renal biopsy was not performed at that time. Proteinuria decreased but persisted with maximum levels of app. 1000mg/day despite treatment with enalapril. The medical history was complicated by several episodes of abdominal cramping and the occurrence of petechiae. Twice before admission, the abdominal discomfort was accompanied by bloody diarrhea, that could finally only be controlled with oral administration of steroids. Blood pressure was elevated up to 150/90 mmHg.
At the current admission, she complained about mild abdominal pain and transient diarrhea in addition to the above-mentioned clinical signs. Blood pressure was 160/90 mmHg, body temperature was 38.2°C. The physical examination of heart, abdomen and lungs as well as the neurological findings were normal. Abdominal examination revealed no guarding and normal bowel sounds. A test for occult fecal blood was positive. Cutaneous examination revealed small palpable purpuric lesions at the lower extremities that rapidly developed into necrotic and target like lesions.

Figure 2

Relevant results of blood testing and consecutive renal function tests are listed in Table 2.

Table 2

Parameter	Normal range	Patient B
White blood count (WBC)	4.3-10.0 x 10³/µL	19.0
Hemoglobin	12.0-16.0 g/dL	14.2
Platelets	150-350 x 10³/µL	350
Serum creatinine	0.6-1.1 mg/dL	1.4
Blood urea nitrogen (BUN)	20-50 mg/dL	48
Urinary hemoglobin dipstick	(-)	(+++)
Creatinine clearance	75-130 mL/min/1.73m²	55
Proteinuria	<150 mg/die	7200
Serum protein, total	66-83 g/L	71
Serum albumin	35-52 g/L	38
Cholesterol	103 - 260 mg/dL	256
C-reactive protein	<5 mg/L	51
IgG	7.0-16.0 g/L	11
IgA	0.7-4.0 g/L	3.5
IgM	0.4-2.3 g/L	1.3
C3	0.9-1.8 g/L	1.2
C4	0.1-0.4 g/L	0.4
Antinuclear antibodies (ANA)	<1:80	1:160
Cryoglobulins	negative	negative

A relapse of shunt nephritis was the presumed diagnosis and the patient was scheduled for emergency shunt explantation. Both renal and skin biopsies were performed, the latter showing a leukocytoclastic vasculitis.

The renal biopsy revealed:

Figure 3a and 3b

 

Comment Figure 3a and 3b:

Diagnosis: mesangioproliferative IgA glomerulonephritis

Figure 3a (PAS x400) demonstrates expanded mesangial fields and pronounced hypercellularity (1) with normal capillary lumina;

Figure 3b (immunofluorescence microscopy x400) reveals mesangial deposition of predominantly IgA;

[Figures by courtesy of Professor Hermann-Josef Gröne; German Cancer Research Center, Heidelberg]

QUESTION 3

Oral administration of steroids (prednisolone 1mg/kg body weight per day) was initiated, combined with ramipril 10mg/day. Abdominal complaints and skin lesions improved within days. Proteinuria decreased to 2500 mg/day after three weeks, but after tapering prednisolone dosage a relapse occurred at two months. Hence, prednisolone dosage was increased to 40 mg/day. Maintenance dosage of 5mg/day prednisolone was reached 6 months thereafter with proteinuria being 300 mg/day. Immunosuppression was stopped 12 months after diagnosis. No relapses of HSP occurred in an eight months steroid-free follow-up.

QUESTION 4

REFERENCES

Corresponding author:
Dr med Vincent M. Brandenburg
Department of Nephrology
University Hospital Aachen
Pauwelsstraße 30
D-52057 Aachen
Germany
Phone: +49-241-8089532
Fax:  +49-241-8082446
Email: Vincent.Brandenburg@post.rwth-aachen.de