Nephrol. Dial. Transplant.-1996-Lanteri-791-3

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					Nephrol Dial Transplant (1996) 11: 791-793
Original Article                                                                            Transplantation

Clinical features in two patients with IgA glomerulonephritis and thin-
basement-membrane disease
M. Lanteri1, D. Wilson2 and J. Savige1
'Renal Unit and University of Melbourne Department of Medicine, Austin Hospital, Heidelberg; and 2Box Hill Hospital,
Box Hill, Victoria, Australia

Abstract                                                         are affected in about 30% of cases [2], and the inherit-
Background. Both IgA glomerulonephritis (IgA gn)                 ance then follows an autosomal dominant pattern
and thin basement membrane disease (TBMD) are                    [3,4]. TBMD is characterized by diffuse thinning of

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common forms of glomerulonephritis. Patients with                the glomerular basement membrane (GBM) on ultra-
these conditions may present with identical clinical             structural examination of renal biopsies [2,5,6].
features, but higher urinary RBC counts, heavier pro-            Localized areas of thinning of the GBM are found in
teinuria, and impaired renal function are more                   some conditions other than TBMD. There can be areas
common in patients with IgA gn. Because IgA gn and               of localized or generalized thinning in IgA gn [7], early
TBMD are common, some patients will have both                    Alport syndrome [8], minimal-change and focal
diseases.                                                        sclerosing glomerulonephritis, as well as in some forms
Subjects. We describe the clinical features of two indi-         of SLE [9]. These conditions can be excluded by the
viduals with both IgA gn and TBMD, and compare                   light-microscope and immunofiuorescence findings. In
them with the clinical and laboratory characteristics in         patients with TBMD, persistent microscopic haemat-
patients with TBMD (« = 15) or IgA gn (« = 32) alone.            uria is the most common clinical feature, but macro-
Results. IgA gn was found in two individuals of the              scopic haematuria, proteinuria, and hypertension may
110 with TBMD who were studied. They both had                    occur; patients rarely, however, progress to renal fail-
haematuria with >/100 000 RBC/ml and proteinuria                 ure [2,5,10,11].
 >0.2/day (one had more than 1 g/day). These features               IgA glomerulonephritis (IgA gn) is another common
were more consistent with IgA gn than TBMD alone.                form of kidney disease [12,13], with an incidence
However, both individuals had normal serum creatin-              approximating that of TBMD in patients presenting
ine and creatinine clearance at presentation. Additional         with persistent haematuria. We have shown recently
clinical features were macroscopic haematuria in one             that patients with IgA gn are more likely to have
and hypertension in both.                                        higher urinary RBC/ml, heavier proteinuria, and
Conclusions. IgA deposits are not uncommon in                    impaired renal function at presentation than patients
patients with TBMD, and these patients have clinical             with TBMD alone. We did not find that a family
features that resemble those seen in IgA gn rather than          history of renal disease, macroscopic haematuria, or
TBMD. Patients with both IgA gn and TBMD do not                  hypertension discriminated between patients with IgA
necessarily have the worse prognosis noted in some               gn and TBMD [unpublished findings]. However, mac-
patients with IgA gn.                                            roscopic haematuria associated with infections, urinary
                                                                 RBC casts, and the presence of glomerular crescents
Key words: IgA glomerulonephritis; thin-basement-                on renal biopsy are probably more suggestive of IgA
membrane disease                                                 gn than TBMD.
                                                                    Double glomerulopathies are not uncommon
                                                                 [14,15], and some individuals can have both TBMD
                                                                 and IgA gn [16-18]. The aim of this study was to
Introduction                                                     determine how often TBMD and IgA gn occurred
                                                                 together, and whether these patients had any distinctive
Thin-basement-membrane disease (TBMD) is a                       clinical or prognostic features.
common form of glomerulonephritis occurring in up
to 10% of the population [1]. Other family members
Correspondence and offprint requests to: Dr J. A. Savige, University
Department of Medicine, Austin Hospital, Heidelberg, Victoria Biopsy results from the years 1985 to 1993 were reviewed.
3084, Australia.                                                    The diagnosis of TBMD was made on the basis of consistent
  1996 European Dialysis and Transplant Association-European Renal Association
792                                                                                                              M. Lanteri el al.

thinning of the GBM on grid analysis measurement of renal         at the most recent visit 1 year after presentation was
biopsy specimens examined ultrastructurally. All patients         2.3 ml/min with an ESR of 17.
with TBMD had a GBM width less than 250 nm. The
diagnosis of IgA gn was made when there was mesangial cell
proliferation and matrix expansion on light microscopy,           Patient 2
together with mesangial deposits of IgA on immunofluoresc-
ent examination of renal biopsy material. In the patients         A 47-year-old Greek Australian female was found to
with IgA gn there was no history suggesting                       be hypertensive on routine physical examination (BP
Henoch-Schonlein purpura, alcoholic liver disease, or coel-       160/90 mmHg), but the rest of the physical examina-
iac disease.                                                      tion was normal. She had a family history of
   The diagnosis of TBMD was made in 110 biopsies, and in         hypertension.
two of these there were features of IgA gn as well (2%). We          Her urinary sediment contained more than 100000
have compared the clinical and histological features of these     RBC/ml and occasional red cell casts, but the patient
two patients, with the clinical and histological features seen    had never had an episode of macroscopic haematuria.
in 15 patients with TBMD or 32 patients with IgA gn alone.        She had 1.57 g of protein/24 h and a creatinine clear-
   In the 17 patients with TBMD, there was no family history      ance of 1.6 ml/s. Her ESR was 60; ANA and anti-
of Alport syndrome or inherited deafness and the light-           dsDNA antibody tests were negative. Renal ultrasound
microscopy was normal or with only a slight increase in the
number of mesangial cells or matrix.                              and IVP were normal.
                                                                     The light-microscope appearance of the renal biopsy
                                                                  was again essentially normal, but there were IgA
Patient 1                                                         deposits on immunofluorescence examination and a
A 50-year-old male was referred for investigation of              uniformly thinned GBM on ultrastructural

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macroscopic haematuria and loin pain, which had                   examination.
occurred intermittently for 10 years. On examination                 Over the following weeks the patient's BP was
he was hypertensive with a BP of 160/90, with arterio-            readily controlled with atenolol 50 mg daily, but she
venous nipping only on fundoscopy. He had mild                    subsequently failed to return for review.
psoriasis. ESR was 60 mm/h. He had more than                         A comparison of the clinical details of these two
100000 RBC/ml in his urine and 500 mg/24 h of pro-                patients and clinical features seen in individuals with
teinuria. Creatinine clearance was 1.89 ml/s. Urine               TBMD or IgA gn alone are shown in Table 1. Neither
cytology was unremarkable. Serum protein electro-                 patient with both TBMD and IgA gn had a family
phoresis revealed a raised IgA at 4.49 g/1. IVP, cystos-          history of TBMD or IgA gn. Both patients were
copy, and renal angiography were all normal.                      distinguished from the patients with TBMD alone by
   The renal biopsy showed essentially a normal                   their degree of haematuria and the presence of pro-
appearance on light microscopy, but mesangial IgA                 teinuria. These features were more in common with
deposits and small amounts of IgM and Clq were                    the patients with IgA gn. However hypertension was
demonstrated by immunofluorescence. On ultrastruc-                present in both patients but serum creatinine and
tural examination the GBM was uniformly and                       creatinine clearance were normal in both.
diffusely thinned and the presence of the mesangial
deposits was confirmed.
   The macroscopic haematuria resolved and the                    Discussion
patient's BP was controlled with enalapril. At review
over the next 3 years, there was persistence of the               We found two patients with both IgA gn and TBMD
haematuria at low levels. A repeat creatinine clearance           when the renal biopsies of 110 (2%) individuals with

Table 1. Clinical features of patients with IgA deposits and thin basement membrane disease compared with thin basement membrane
disease alone

Presentation                                       IgA plus TBMD                     TMBD                        IgA gn
                                                   (« = 2)                           (n=15)                      (« = 32)

Sex                                                1M , IF                           15F                          10M, 22F
Age (years)                                        47, 50                            44 (30-63)                   31 (5-61)
Width of GBM (nm)                                  240 ,230                          <250                         >250
Family history                                     0/2                               2/15(13%)                     3/32 (9.4%)
Macrohaematuria                                    1/2                               2/15(13%)                    10/32(31%)
Haematuria (> 100000 RBC/ml)                       2/2 (100%)                        5/15(30%)                    22/32 (69%)
  > 0.2 g/day                                      2/2 (100%)                        9/15(60%)                    23/32 (72%)
   > 1 g/day                                       1/2 (50%)                         2,15 (13%)                   13'32 (41%)
Hypertension (BP > 140/90 mmHg)                    2/2 (100%)                        3/15 (20%)                   10/32(31%)
S creatinine >0.11 mmol/1                          0,2 (0%)                          0 15(0%)                      7 32(22%)
Cr clearance $ 1.2 ml/min                          0/2 (0%)                          2/15(13%)                     4/14 (29%)
IgA and thin-basement-membrane disease                                                                                     793

TBMD were reviewed. This incidence is lower than           subset of patients with IgA gn. It is likely that when
the 13/67 (19%) patients with IgA gn and TBMD              IgA gn and TBMD occur together, a spectrum of
reported elsewhere [18]. A diffusely thinned GBM           severity of IgA gn can be found. The outcome in
should be demonstrated before the diagnosis of TBMD        individual patients may be related more to the severity
is made.                                                   of the histological lesion than to just the presence of
   Focally thinned GBM may be found incidentally in        mesangial IgA deposits. However the presence of
IgA gn as well as in a number of other conditions. In      superimposed IgA gn may be responsible for the
the other report, 'focal or diffuse' thinning of the GBM   clinical presentation of these patients.
was present in 14% of 90 patients with IgA gn [17,18],
and the number of patients with diffusely thinned          Acknowledgements. We would like to thank the National Health and
membranes consistent with TBMD was not indicated.          Medical Research Council of Australia for supporting this project.
We did not include in our series patients with focal
thinning of the GBM.
   While our initial search showed more than two           References
patients with mesangial deposits, these were not con-       1. Dische FE, Anderson VER, Keane SJ, Taube D, Beswick M,
firmed when the corresponding electron-micrographs             Parsons V. Incidence of thin membrane nephropathy: morpho-
were examined. It is not clear if the presence of              metric investigation of a population sample. / Clin Pathol 1990;
mesangial IgA deposits were confirmed ultrastruc-              43: 457-460
                                                            2. Dische FE, Weston MJ, Parsons V. Abnormally thin glomerular
turally in other series, and this precludes an accurate        basement membrane associated with haematuria, proteinuria or
estimate of IgA gn and TBMD occurring together                 renal failure in adults. Am J Nephrol 1985; 5: 103-109
from being determined from these reports. If IgA gn

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                                                            3. Rogers PW, Kurtzman NA, Bunn SM, White MG. Familial
and TBMD were found together as often as suggested             benign essential hematuria. Arch Intern Med 1973; 131: 257-262
elsewhere [18], it is remarkable that there have not        4. Reeders ST. Molecular genetics of hereditary nephritis. Kidney
                                                               Int 1992; 42: 783-792
been more case reports of patients with both                5. Abe S, Amagasaki Y, Iyori S el al. Thin basement membrane
conditions.                                                    syndrome in adults. J Clin Pathol 1987; 40: 318-322
   We have shown in our study that patients with both       6. Thin-membrane nephropathy—how thin is thin? Editorial.
IgA gn and TBMD may have higher counts of urinary              Lancet 1990; 336: 469-470
                                                            7. Shigematsu H, Kabayashi Y, Tateno S, Hiki Y, Kuwao S.
RBC/ml, more marked proteinuria, and a higher BP               Ultrastructural glomerular loop abnormalities in IgA nephritis.
than those with TBMD alone. The higher urinary RBC             Nephron 1982; 30: 1-7
excretion and heavier proteinuria in patients with both     8. Grunfeld JP. The clinical spectrum of hereditary nephritis.
diseases are more consistent with IgA gn. However the          Kidney Int 1985; 27: 83-92
serum creatinine and creatinine clearance in each           9. Hill GS, Jenis EH, Goodloe S. The nonspecificity of the ultra-
                                                               structural alterations in hereditary nephritis with additional
patient were normal suggesting that renal function is          observations in benign familial hematuria. Lab Invest 1974;
not necessarily worse in individuals with both TBMD            31: 516-532
and IgA gn. This conclusion is borne out by the            10. Perry G, George CRP, Field MJ et al. Thin-membrane nephro-
description elsewhere [16] of a woman with both                pathy—a common cause of glomerular haematuria. Med J Aust
TBMD and IgA gn who had persistent microscopic                  1989; 151: 638-642
                                                           11. Tiebosch ATMG, Frederik PM, van Breda Vriesman PJC et al.
haematuria, infection-associated macroscopic haemat-           Thin-basement-membrane nephropathy in adults with persistent
uria, proteinuria of 0.4 g/day and hypertension, but a         haematuria. N Engl J Med 1989; 320: 14-18
normal serum creatinine. However, another series with      12. D'Amico G. The commonest glomerulonephritis in the world:
a high incidence of IgA gn and TBMD occurring                  IgA nephropathy. Q J Med 1987; 64: 709-727
together [18] has suggested that such individuals often    13. Julian BA, Waldo FB, Rifai A, Meste J. IgA nephropathy, the
                                                               most common glomerulonephritis worldwide. Am J Med 1988;
have severe disease. Thus patients with both IgA gn            84: 129-132
and TBMD were more likely to have nephrotic-range          14. Antonovych TT and Sabnis SG. One glomerular disease does
proteinuria (58%, compared with 11% in patients with           not exclude another. Kidney Int 1981; 19: 178A
TBMD alone), hypertension (55% vs 33%), renal              15. Monga G, Mazzucco G, Barbiano di Belgiojoso G,
insufficiency (54% vs 9%), and progressive renal               Confalonieri R, Sacchi G, Bertani T. Pattern of double glomerul-
                                                               opathies. A clinicopathologic study in 9 nondiabetic patients.
impairment on follow-up (36% vs 11%).                          Nephron 1990; 56: 73-80
   Other forms of glomerulonephritis may occur more        16. Monga G, Mazzucca G, Roccatello D. The association of IgA
                                                               glomerulonephritis and thin basement membrane disease in a
often in patients with TBMD than in normal indi-               hematuric patient: light and electron microscopic and immuno-
viduals because of a damaged or more permeable                 fluorescence investigation. Am J Kidney Dis 1991; 18: 409-412
basement membrane, or simply because these two             17. Cosio FG, Falkenhain ME, Sedmak DD. Association of thin
forms of glomerulonephritis are common conditions.             glomerular basement membrane with other glomerulopathies.
                                                               Kidney Int 1994; 46: 471-474
Our patients with both IgA gn and TBMD had clinical        18. Cosio FG, Falkenhain M, Carlton S, Cosio MJ. Association of
features more suggestive of IgA gn than TBMD, but              thin glomerular basement membrane nephropathy (TGBM)
did not have the impaired renal function found in a            with other glomerulopathies. JASN 1993; 4: 261A

                                                           Received for publication: 19.5.1995
                                                           Accepted in revised form: 27.12.1995

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