Nephrotic Syndrome Secondary to Loaiasis: Review of the World's Literature and Report of a Case
Stewart W. Shankel, M.D.
Department of Medicine
Loma Linda University Medical Center
Loma Linda, California
Twenty-two patients with glomerulonephritis felt to be secondary to loaiasis have previously been reported. We have reviewed these cases and are reporting another case with a fifteen year cure following treatment with diethylcarbamazine. Twenty-one of the 23 cases had proteinuria and 6 were nephrotic. Seventeen had hematuria, 8 had pyuria and in only 4 patients were casts noted in the urine. Membranous thickening was the most common
histological finding. Sixteen of the patients received only diethylcarbamazine. Three of
these patients were cured, 6 improved and 7 were unchanged. Three others received both
diethylcarbamazine and steroids with one showing improvement. Loaiasis should be
considered in any patient, with the nephrotic syndrome, who has lived or traveled
extensively in western and central Africa.
Nephrotic; Loaiasis; Parasites
Glomerulonephritis with the nephrotic syndrome due to the malarial
and schistosomal parasites has been well described. Quartan malaria with
nephrotic syndrome has been recognized for 100 years (1,2), and was extensively reviewed
in a recent symposium (3,4,5). While other malaria parasites have been reported to produce transient glomerulonephritis and the nephrotic syndrome, its occurrence is rare (6).
Schistosomal glomerulopathy with the nephrotic syndrome due to schistosoma mansoni has been carefully studied (7,8). Glomerular lesions are often present for
many years in a subclinical form, however, they may not become nephrotic for as long as 10
- 12 years following the development of schistosomiasis (9).
On rare occasions one other parasite, Loa Loa, has been implicated as
the cause of glomerulonephritis and the nephrotic syndrome (10 - 16). We reviewed the
world literature for nephrotic syndrome secondary to loaiasis and report these results as
well as a new case of loaiasis. Our patient developed membranoproliferative
glomerulonephritis eight years after acquiring Loa Loa. Her glomerulonephritis and the
nephrotic syndrome were cured by diethylcarbamazine and she has remained clinically free
of any glomerular disease for 15 years.
In 1971, one of my colleagues requested that I evaluate his 23 year old
daughter who had developed generalized edema, a 20 pound weight gain and proteinuria over the past 8 weeks. Six weeks prior she had been well and denied fever, chills, sweats, sore throat, exposure to toxins, venoms or drugs other than birth control pills. She had no history of cardiac problems, urinary tract complaints, arthralgias or respiratory
problems. She complained of mild, midline, low back pain of one week duration which she
attributed to her menstrual period. She had no history of hematuria or prior proteinuria.
At the age of 15, eight years prior to her present problem, she
developed loaiasis while on a mission station in Africa. One worm
was removed from her eye and identified. Since then she had seen a worm cross her eye on
two occasions but never retrieved them. She had never been treated for loaiasis. However,
she received periodic blood and urine checks (see Table I click here) with persistent eosinophilia but normal urinalysis until 1968 when she had 4-8 RBC noted per high power field.
On physical examination, she was noted to have some generalized swelling with a BP of 120/88. She was in no acute distress. Her lungs were clear and she had
normal heart sounds and no murmurs. The liver, spleen and kidneys were not palpable and
there was no abdominal bruit. The skin was normal.
On admission to the hospital her hemoglobin was 12.2 grams, the WBC count was 9,700 with 20% eosinophils. The ASO titer was 50 Todd units and the total serum complement was normal. The serum creatinine was 0.8 mg/dl with a creatinine clearance of 108 cc/min. The urine had 4 plus protein, 10-15 RBC/hpf and no casts. A 24 hour urine protein was 10.8 grams.
Her wintrobe ESR was 45, ANA was negative on two occasions, her rheumatoid latex fixation test was negative. Her immunoelectrophoresis was
normal. She had a serum cholesterol of 654 mg/dl, a triglyceride of 218 mq/dl, and an
increased pre-beta level on serum lipoprotein electrophoretic
analysis. Her serum albumin and total protein were decreased to 0.93
gms/dl, and 3.7 gms/dl respectively, while the alpha and beta globulins
were increased. The IVP was normal. Kidney biopsy showed focal hypercellularity, focal
deposition of PAS positive material in the mesangium and focal basement membrane
She was started on diethylcarbamazine and tolerated the drug well. Her course following diethylcarbamazine is depicted in ( Table I click here) . She was also given Furosemide and
Spironolactone for her edema. She received no other medications.
Over the next seven months, her urinary protein returned to normal levels as did the hematuria and eosinophilia. During the last 14 years, she has had no recurrence of
proteinuria, including an uneventful pregnancy
in 1975. Her renal function has remained normal. She is now 49 years post treatment and has had no further problems with her kidneys.
Nephrotic syndrome due to loaiasis has been reported only rarely in the English literature, and it is not well appreciated that such a disease state even exists. However, a review of the world literature disclosed 22 previous cases felt to be due to loaiasis. ( Table II click here) Ages ranged from 15 to 57 and the majority of the patients were male. Data on
renal function was available in only 15 cases and in 9 the function was felt to be normal
as manifest by either a normal BUN, creatinine or creatinine clearance, while 6 had
impaired renal function when first seen and 2 had end stage renal failure.
In the eleven patients in which data was available, the interval from the first signs of infestation with Loa Loa to the onset of clinical or laboratory findings consistent with nephrotic syndrome varied from one month to forty years. It is possible that some of these patients may have had subclinical disease for months to years before the renal disease was discovered. However, our patient had a previous normal urinalysis in 1965, two years after known onset of loaiasis and at a time when she had 18% eosinophils in her peripheral smear ( Table I click here) . Three years later, her urine showed 4-8 RBC but no
proteinuria. It is possible she may have had early glomerulonephritis five years after
onset of loaiasis, but did not develop the nephrotic syndrome until eight years after
first diagnosing loaiasis.
Proteinuria was noted in 21 of the 23 patients with protein excretion varying from 0.25 gms to 10.8 gms, while six of the patients were nephrotic. Almost as many patients (17 of 23), were found to have microscopic hematuria while none were reported to have gross hematuria. Eight of 23 were noted to have a few WBC in the urine and only 4 of the 23 were noted to have casts in the urine ( Table II click here) . The urinalysis in these patients did not differ from most patients with other forms of glomerulonephritis except for the paucity of casts.
Hypertension was noted in only five patients, all of whom had chronic renal disease. Histologic data was available in only eleven patients and, in four of these patients, the description was consistent with membranous glomerulonephritis. Two of these patients had immunofluorescent staining with IgG and C3 in a granular pattern. One patient had focal membranoproliferative glomerulonephritis, one patient had what was probably sclerosing mesangial glomerulonephritis and two had end stage chronic glomerulonephritis. The other three patients had some thickening of the capillary wall, endothelial proliferation and accompanying interstitial infiltration with small mononuclear cells. It would appear that
membranous glomerulonephritis is the most typical glomerular change described but other
forms of glomerulonephritis are also seen with loaiasis.
Sixteen of the twenty-three patients were treated with diethylcarbamazine alone. Of these sixteen, seven showed no change, six were improved and three were cured. One of these was our patient who has been followed for fourteen years since her treatment with no recurrence of the proteinuria. Three other patients were treated with diethylcarbamazine plus steroids. Two of these showed no change and one, who had failed steroid therapy
previously, improved with combination therapy. The one patient who received caffeine and
strychnine expired. Two received no treatment and had no follow-up.
Verroust et al studied twenty-eight patients with known filariasis, eleven of which had Loa Loa. Thirty-six percent of the filariasis cases had circulating immune complex (IC),
and the majority had high levels of C3d. However, no correlation could be found between
the presence of immune complexes and the levels of C3d. Furthermore, there was very little
evidence to link the presence of IC in the serum to glomerular disease (30). Bariety et al came to the same conclusion in their review of one case. However, no immunofluorescence
was done on the biopsy specimen but there was a slight decrease in IgA on
immunoelectrophoresis (31). Other studies have also shown discrepancies between the
presence of circulating IC and the absence of glomerulonephritis (32). To say that
glomerulonephritis is not caused from systemic involvement with Loa Loa because all of the patients who were checked with circulating immune complexes in these studies and found not
to have glomerulonephritis is like checking one-hundred patients for circulating IC after
an active infection with B. hemolytic streptococcus, and no evidence of
glomerulonephritis, and stating that, therefore, streptococcus is not a cause of
glomerulonephritis. Obviously this reasoning is in error since only a small fraction of B. hemolytic streptococcal infections ever develop acute or chronic glomerulonephritis.
Subsequent to these studies, two cases of systemic Loa Loa with glomerulonephritis have
had kidney biopsies with immunofluorescent staining. Both patients had membranous
glomerulonephritis with positive immunofluorescent staining in a granular pattern for C3
and IgG (33,34). One of the patients (34) also had malaria. This patient received a course
of high dose prednisone with no response. Subsequently he was given diethylcarbamazine
with prednisone with a drop in the proteinuria from 4 grams a day to less than 1 gram per
day. In the other patient, circulating immune complexes detected by C1q binding assay and
rabbit antisera against adult Brugia Malayi were localized to the glomerular deposits.
Since antisera to the filarial are group specific rather than species specific (33), these
studies strongly suggest that the glomerulonephritis observed was secondary to the known
Much stronger evidence linking Loa Loa and glomerulonephritis as to cause and effect can
be found from the results of treatment. Sixteen of the twenty-three patients received only diethylcarbamazine, nine were either improved or cured. Of the seven who showed no
improvement, one had a severe reaction to the drug and was inadequately treated, five had
chronic glomerulonephritis with impaired renal function at the time of treatment and only
one who had no chronic renal disease failed to respond to diethylcarbamazine. The most
dramatic response was seen in our patient who demonstrated progressive, simultaneous
clearing of eosinophilia and proteinuria, with no recurrence of proteinuria for the last
In summary, we feel that loaiasis does cause glomerulonephritis for the following reasons.
First, there have now been twenty-three cases of glomerulonephritis reported in patients with loaiasis. Secondly, nine of the sixteen patients
treated only with diethylcarbamazine were either improved or cured and thirdly,
glomerulonephritis has been well documented in other circulating parasitic diseases such
as malaria and schistosomiasis.
Detecting IC due to loaiasis on the glomerular basement membrane in patients with
suspected glomerulonephritis secondary to loaiasis, would be much stronger evidence of
loaiasis as the cause of glomerulonephritis in these patients. We suggest that all
patients presenting with the nephrotic syndrome who come from or who have traveled in
western and mid-central Africa be examined for loaiasis and attempts made to elute IC for
loaiasis from the glomerular basement membrane.
Conflict of Interest: None.
Authorship: Author is entirely responsible for the content of this manuscript.
Requests for reprint should be addressed to Stewart W. Shankel, MD, Loma Linda University Medical Center, 11234 Anderson St., Loma Linda, CA 92350
1. Atkinson IE: Bright's disease of malarial origin. Am. J. Med. Sci. 88:149-166, 1884.
2. Watson M: Some clinical features of quartan malaria. Indian Med. Gaz. 40:49-52, 1905.
3. Hendrickse RG, Adeniyi A: Quartan malarial nephrotic syndrome in children. Kid. Intern. 16:64-74 1979.
4. Houba V: Immunologic aspects of renal lesions associated with malaria. Kid. Intern. 16:3-8, 1979.
5. Hutt MSR: Introduction to symposium on the kidney and parasitism. Kid. Intern. 16:1-2, 1979.
6. Boonpucknavig V, Sitprija V: Renal disease in acute plasmodium falciparum infection in man. Kid. Intern. 16:44-52, 1979.
7. Andrade ZA, Rocha H: Schistosomal glomerulopathy. Kid. Intern.
8. Lopes M: Aspectos renais da sindrame hepato-splenica da esquistos-somose mansonica. Thesis, University of Minas, Gerais School of
Medicine, Belo Horizonte, Brazil, 1974.
9. Brito T, Gunji J, Camargo ME, Penna DO, Silva LC: Advanced kidney disease in patients with hepatosplenic Manson's schistosomiasis. Rev. Inst. Med. Trop. Sao Paulo. 12:22-235, 1970.
10. Snijders EP: Ouereen geval van filariasis. Ned T Geneesk. 79:3024, 1935.
11. Ten Berg JAC: Filariasis loa. Ned T Geneesk. 96:2411, 1952.
13. Destombes P: Enquete sur la filariose a' w. malayi au Sud Vietnam. Institut Pasteur de Saigon. Ch. III, Rapport 1955.
14. Janseens PG, Van Boagaert L, Tverdy G, Wanson M: Reflexions sur le sort des microfilaires de Loa Loa dans l'organisme humain parasite. Manifestations viscerales provoquees par leur infiltration dans les tissues, Bull. Soc. Path Exot. 51:632-645, 1958.
15. Schneider J: Notes sur la therapeutique des filarioses. Ann. Soc. Belge. Med. Trop. 41:343-366, 1961.
16. Gentilini M, Domart A, Brumpt L, Hazard J, LeQuintrec Y: Filariose A Loa Loa et proteinurie. Bull. Soc. Path. Exot. 56:207-217, 1963.
17. Bariety J, Barbier M, Laigre MC, Tchernia G, Lagrue G, Samarcq P, Fritel D, Milliez P: Proteinurie et loase etude histologique, optique et electronique d'un cas. Soc. Med. des Hop de Paris. 118:1015-1023, 1967.
18. Fritel D, Bariety J, Gentilini M: Loase et nephropathie. Med. Afr. noire. 17:13- , 1970.
19. Zuidema PJ: Renal changes in loaiasis. Folia. Med. Neerl. 14:168-172, 1971.
20. Pillay VKG, Kirch E, Kurtzman NA: JAMA. 225 No. 2, 179, 1973.
21. Chugh KS, Singhal PC, Tewari SC, Nath IUS, Datta BN: Acute glamerulo-
nephritis associated with filariasis. Am. J. Trop. Med. Hyg.
22. Malik STA, McHugh M, Morley AR, Ngu J, Qureshi M, Wilkinson R: Filariasis (Loa Loa) associated with membranous glamerulonephritis: demonstration of filarial antigen. Kid. Int. 20:157, 1981.
23. Katner H: Loaiasis and renal failure. South Med. J. 77:907-8, 1984.Page 12
24. Barsotti P, Brandimarte C, Feriozz S, Nardi F, Pecci G, Puoti C, Cinotti GA: Glamerulonefrite in corso di filariosi e malaria. Min. Nefr. 30:25-32, 1983.