NDT Case Studies - G. Moroni

In the early seventies some reports underlined that the rapid withdrawal of immunosuppressive therapy in pts with LN may cause a severe exacrebation of renal disease with a rapid progressive downhill course to uremia and to death. In contrast a slow reduction of therapy once the pt has achieved remission is safer.

*Exacerbation of SLE nephritis after cyclophosphamide withdrawal. Aptekar et al NIH New Engl J Med 1972

* Deterioration of renal function after discontinuation of prednisone-azathioprine therapy in renal diseases. Levitt JI N Engl J Med 1970

* Azathioprine in the treatment of systemic lupus erythematosus. Sztejnbok M et al Arthritis Rheum 1971

Moreover in pts with stable and persistent clinical remission of renal disease, a careful attempt to slowly and progressively reduce the therapy until complete withdrawal can be tried without serious adverse consequences.

38 patients followed in our Unit for lupus nephritis, at achievement of remission, had their treatment progressively reduced until complete withdrawal under close medical surveillance.

After stopping therapy 20 patients continued to be in clinical remission until the end of the observation (“Persistent remission group”). The other 18 patients developed renal or extrarenal flares 56 months after therapy was stopped (range 9-96 months) (“Relapse group”).

Clinical characteristics of “Persistent remission group” (20 patients)

At treatment withdrawal (79 ± 58 after months Rx)

14 complete remissions;

6 partial remissions (median proteinuria 0.6g/day)

At last follow-up (123 ± 87 mo after stop Rx)

15 complete remissions;

5 asymptomatic proteinuria (range 0.5-0.7g/day)

Ponticelli and Moroni J Nephrol 13,385,2000

Clinical characteristics of “Relapse group” (18 patients)

At treatment withdrawal (34.7 ± 31.3 mo Rx)

11 pts complete remissions;

7 pts partial remissions (median proteinuria 0.9g/24h)

At last follow-up (179 ± 74 mo after stop therapy)

13 pts complete remissions;

4 pts partial remissions (proteinuria 0.5-0.7g/24h range)

1 pt chronic renal insufficiency (plasma creat 2.3mg/dl)

In the “Relapse group” the rate of recurrence of renal an extra-renal flares before and after stopping therapy was not significantly different (before stopping therapy: 0.11 flares per patient per year, after stopping therapy: 0.10 flares per patient per year).

No difference between the two groups was observed, except for the duration of treatment before stopping therapy that was longer in the “persistent remission group” (79 ± 58 months in the persistent remission group vs 37 ± 31 months in the relapse group, p<0.01).

Conclusion

In patients with proliferative lupus nephritis and a stable and persistent remission of renal disease a careful attempt of tapering off treatment may be tried. If the following guidelines are respected the risk of exacerbation of SLE is minimized:

1) No flares for at least 3 years.

2) Pl. creatinine normal, urine sediment inactive, proteinuria <1g/day.

3) Taper off therapy very slowly.

4) Careful monitoring of the patient.

Ponticelli and Moroni J Nephrol 13,385,2000

Question 3: The literature being controversial as regards the significance of anti-DNA antibodies, what could be the most useful serological test to confirm the clinical diagnosis of a renal flare?

Outcome after reaching complete remission

In April 1981, one month after reaching complete remission the patient decided of his own free will to stop all therapies.

In October 1981 he suffered from fever, arthralgias, malar rash, pericarditis, seizures.

On admission to our Unit blood pressure was 160/110mmHg, Pl. Creat. 2.9mg/dl, Haematocrit 24%, White cells count 4100mm3, Platelet count 102.000mm3, Serum protein 5.3g/dl, albumin 2.8g/dl, C3 and C4 were low Proteinuria 5.6g/24h, at urinary sediment: Red blood cells: 100/HPF, White blood cells: 20/HPF, granular and erythrocyte casts.

A second renal biopsy was performed that showed a diffuse proliferative GN (class IV) with extracapillary proliferation in about 50% of glomeruli and fibrinoid necrosis in 10% and severe interstitial infiltration.
The activity index was 15 and the chronicity index was 2.

The patient was re-treated with 1 pulse of methylprednisolone of 1g/day for 3 days followed by prednisone 1mg/kg/day for 1 month then gradually tapered, associated with cyclophosphamide 2mg/Kg/day for three months and 1mg/Kg/day for another three months.

In September 1982, ten months after the second renal biopsy, the patient was in complete clinical remission: Pl. creat. 1.1mg/dl Proteinuria 0.12g/24h, inactive urine sediment.

Therapy: Prednisone 15mg/day (0.2mg/Kg/day).

In September 1983, after 1 year of persistent remission, the patient was lost to follow-up. He decided to stop prednisone and continued unspecified herbal therapy.

In June 1989, six years later, the patient came back to our Unit for a clinical re-evaluation. He had no extra-renal symptoms of SLE, a physical examination was unremarkable, blood pressure was 160/90mm/Hg. Laboratory tests: Pl Creat. 1.6mg/dl, Haematocrit 36%, White cells and platelet count, C3 and C4 were normal, Serum protein 6.1g/dl, albumin 3.4g/dl, anti-DNA antibodies positive. Proteinuria 2.8g/24h, RBC 5/HPF, rare granular casts. In the absence of laboratory data of the previous months, the present clinical situation of the patient could not be easily interpreted.
It could have been the expression of a renal flare or the result of chronic inactive lesions.

Question 3

CASE STUDIES