Howard Trachtman

Acute renal failure as the initial manifestation of systemic lupus erythematosus in children

In two patients with systemic lupus erythematosus, acute renal failure was the initial manifestation. The diagnosis was eventually established on the basis of serologic tests and characteristic renal histopathologic findings. We emphasize the need to consider systemic lupus erythematosus as a cause of acute renal failure of glomerular origin, because appropriate therapy may alter the outcome of the disease.

1644 CYCLOSPORINE (CY) AS A PRIMARY IMMUNOSUPPRESSIVE, AS A SUBSTITUTE FOR AZOTHIOPRIN (A) AND AS THE SOLE MAINTENANCE DRUG IN RENAL TRANSPLANTS

We utilized the steroid sparing effect of cyclosporine in 32 Pediatric renal transplants. Nineteen children (Group A) started with CY and 0.5 mg/kg prednisone (P) at the time of transplant. In 13 children (Group B), with a stable renal transplant on conventional therapy (A&P), CY was substituted for A. In both Groups, we attempted to taper P with complete withdrawal in 16-20 weeks.Results: Group A had 11 first and 82nd or 3rd transplants. There were 11 cadaveric (C) and 8 live related (L) transplants. Actuarial graft survival at 16 months is 88%. Group B had 4 C and 9 L grafts. Mean serum creatinine (M.S.C.) at time of substitution was 1.6 mg/dl. No graft loss has occurred in Group B after substitution. A total of 13 out of 32 children were able to discontinue P. Four of these are receiving P again because of rejection. Nine children have been off P for a mean of 5½ months (2-14 months), their M.S.C. is 1.06 mg/dl (.07-1.5 mg/dl) A.C.T.H. stimulation after discontinuation of P revealed 2 fold rise in serum cortisol from base line value in 12 of 13 children. Growth hormone level measured after methyldopa stimulation showed normal (>10 ng/ml) response in 5 of 7 children off P. We conclude 1) selected C&L graft patients can discontinue P thus enhancing the growth potential; 2) such children are not at risk of developing Addisonian Crisis and 3) donor and recipient haplotype match or the number of transplants were not of predictive value in P withdrawal.

1643 LONG-TEEM OUTCOME OF DIFFUSE PROLIFERATIVE LUPUS NEPHRITIS

We reviewed our experience with diffuse proliferative Lupus Nephritis (D.P.L.N.) in 22 children. Aggressive steroid and ant metabolite therapy prevented end stage renal disease (E.S.R.D.) in 10 patients, but 2 patients died of sepsis. 12 patients have reached E.S.R.D. in a mean of 30 months from diagnosis.Dialysis: 12 patients received hemodialysis from 3 to 23 months (mean 13 mos.). No mortality was recorded while on dialysis but a high rate of morbidity was noted. The 12 Lupus patients accounted for 60% of all hospitalizations compared to 51 non Lupus children on dialysis who accounted for 40% of hospitalization (p<.001). One child was able to discontinue dialysis after a period of 9 months.Transplant: 9 children received 12 transplants (1 patient had 4 transplants). One patient died of sepsis during the 2nd month after transplantation. Graft survival rates at 1 and 4 years were 80 and 65% respectively. Patients with a successful transplant spent a mean of 25 days in hospital post transplant compared to a mean of 112 days in hospital during dialysis (p<.05). One patient had clinical and histological recurrence within 6 months after a live related transplant. Our study concludes:1) majority of D.P.L.N. patients will reach E.S.R.D. in 3 years;2) mortality is due to therapy associated sepsis; 3) dialysis is safe but has a high morbidity and 4) successful transplant has the best quality of life but the risk of recurrence in live related donors is a concern.

1647 THE UTILITY OF TRANSPLANT RENAL BIOPSY (TRB), Tc-99IU SULFUR COLLOID SCAN (SCS), AND CYCLOSPORINE (CS) DRUG LEVELS IN DISTINGUISHING ACUTE REJECTION (AR) VERSUS CYCLOSPORINE NEPHROTOXICITY (NT)

The use of CS immunosuppression in renal transplantation has made it increasingly difficult to ascertain the etiology of acute deteriorations in allograft function because of direct drug NT. We compared the utility of three diagnostic modalities-TRB, SCS and serum CS levels - to distinguish AR from CS NT in 19 children who received a primary transplant with CS therapy and 13 who were switched to CS from conventional treatment during the period 9/83-10/84.The children (18M:14F) received 15 living-related and 17 cadaveric allografts. The three tests were performed whenever possible in 22/32 patients with suspected AR (mean interval of 3.2 months post-initiation of CS). Clinical response to anti-rejection therapy was the operational criterion for AR. A TRB was considered positive for AR if lymphocytic infiltration was noted, SCS was deemed positive if there was colloid uptake, and CS serum levels were considered positive if subtherapeutic (<100ng/ml) or in the toxic range (>500ng/ml).We conclude that: 1)TRB is the most useful test for the diagnosis of AR episodes defined by response to anti-rejection therapy; and 2)SCS and CS drug levels correlate poorly with the TRB histological findings and the patients clinical course.

1624 PAUCITY OF MINIMAL CHANGE (MC) LESION IN YOUNG CHILDREN WITH EARLY FREQUENTLY RELAPSING STEROID SENSITIVE (FRSS) NEPHROTIC SYNDROME (NS)

The morphological lesion in young children with early FRSSNS is presumed to be MC; however, there are no prospective studies that validate this assertion. From 1980-84, we performed a percutaneous renal biopsy on all children with the NS, ages 2-8 yrs, as soon as they developed a FRSS course. Relapse is defined as recurrance of NS within 2 months of an 8 week prednisone course.15 children (8 male, 7 female) were studied, mean age at time of biopsy 4.8 yrs (2.7-8 yrs). An average of 4 relapses per patient occurred during the initial 13 months - the mean interval from diagnosis of NS to renal biopsy. No children were azotemic, 3/15 had hematuria and 0/15 hypertension.Only 4/15 patients exhibited the MC lesion. In 73% (11/15) of patients, the renal histology was other than MC. 2 patients had diffuse mesangial hypercellularity, 7 had mesangial IgM nephropathy and 2 patients had focal segmental glomerulosclerosis. No clinical feature discriminated between patients with MC and those with severe lesions. Of the 11 children with non-MC histology, 1 patient requires dialysis, 4 have persistent proteinuria despite cyclophosphamide (CY), 5 are in prolonged remission following CY therapy and 1 is lost to follow up. Our study concludes that as in the adult, a variety of morphological lesions are seen in young children with FRSSNS and that the occurrence of frequent relapses even in children as young as 3 yrs may herald the presence of a more ominous histological lesion.

HIGH RATE OF MORPHOLOGICAL TRANSITION IN CHILDREN WITH STEROID SENSITIVE MINIMAL CHANGE NEPHROTIC SYNDROME |[lpar]|M|[period]|C|[period]|N|[period]|S|[period]||[rpar]|

We reviewed the clinical course and morphology of 48 children with biopsy proven M.C.N.S. with a minimum follow-up of at least 5 years. Mean age at onset was 4.1 yrs (11 mo-16 yrs). Mean follow-up was 11.2 yrs (5-18). 33 of 48 children (66%) underwent a second biopsy at a mean time of 4.5 yrs after the first biopsy because of frequent relapses or steroid dependence. 15 (45%) converted to focal segmental sclerosis (F.S.G.S.). 9 (27%) evolved into IgM nephropathy and only 9 (27%) retained the original morphology of M.C.N.S. 6 of these 9 patients with M.C.N.S. had a 3rd biopsy. Only one showed persistent M.C.N.S., and he converted to IgM nephropathy on 4th biopsy.Overall, among patients undergoing repeat renal biopsies, only 12% continued to show a persistent M.C.N.S. lesion, the rest evolving into IgM nephropathy or F.S.G S. Analysis of age at onset, frequency of hematuria, hypertension or elevated creatinine at onset did not distinguish the children with morphological transition from the remaining ones.At the end of the study, 25% of these children are dead of renal causes, on dialysis, transplanted or in chronic renal failure with a creatinine clearance less than 20 ml/min.Our study concludes that a very high frequency of morphological transition is present in M.C.N.S. patients who have a relapsing or steroid dependent course and that the prognosis ir these cases is guarded.

CYCLOSPORINE |[lpar]|CY|[rpar]| AS THE SOLE IMMUNOSUPPRESSANT FOR 2ND AND 3RD TRANSPLANTS IN CHILDREN

Under a protocol designed to utilize the steroid (S) sparing effect of CY, we have used it for repeat transplant in 5 children, all of whom had growth retardation. CY was administered intravenously in 5 mg/kg dose for the first 2 days and then orally in a liquid form at a dose of 15 mg/kg, gradually reducing it to 7 mg/kg. S therapy was started at 10-20 mg/daily to be gradually tapered to withdrawal at 3 months post-transplant.Hirsuitism (3/5), asymptomatic hepato-toxicity (1/5) and nephro-toxicity (1/5) were the only side effects.The first patient, 2 weeks after steroid withdrawal developed fever for 1 day, suffered a circulatory collapse and died. Post-mortem showed absence of adrenal tissue. In patient No. 2, following S withdrawal, ACTH stimulation 2 weeks later, showed adequate endogenous cortisol production. Our preliminary data seems to suggest that is is possible to utilize the S sparing effect of CY in maintaining graft function. However, extreme caution is necessary to prevent Addisonian crisis.

GROWTH FAILURE (GF) IN CHILDREN WITH MODERATE RENAL INSUFFICIENCY (MRI)

Despite large numbers of children with chronic renal failure, there is insufficient information about GF prior to end stage renal disease. It has been stated that a GFR (ml/min/1.73M2) of 20-25 is the threshold below which growth retardation begins.We report the linear growth in 11 prepubertal children with stable MRI for at least 1 year (34.4±24.4 mos., mean ±SD). Height was measured with a wall stadiometer. MRI was defined as a GFR between 20-40. The GFR was assessed using the endogenous creatinine clearance or a length estimation. There were 7 male and 4 female patients, mean age 9.3 years at onset. Six children had congenital and 5 had acquired causes of MRI, The GFR was Initially 32.5±6,4 and declined to 26.7±6.5 at the end of follow-up. The mean serum Ca++ was 9,4, PO4=4,4 mg/dL and HCO3- 23.8 mEq/L. The PTH level was elevated in all 7 children with the determination.During the observation period, 9/11 children suffered GF. Their mean cumulative loss of stature for age was 0.65±0.44 SD. The height SD fell at a mean yearly rate of 0.25±11. This is nearly 65% of the mean annual loss of length for age in dialysis patients, as reported by the EDTA Registry. We conclude that 1) stable MRI is associated with progressive loss of linear growth for age; and 2) the degree of GF approaches that observed in children on maintenance hemodialysis. Hyperparathyroidism and chronic metabolic acidosis may be contributing factors to this GF.

HIGH RATE OF MORBIDITY DURING HEMODIALYSIS IN LUPUS NEPHRITIS PATIENTS

Children with systemic lupus erythematosus (SLE) who have reached end-stage renal disease and are on maintenance hemodialysis (longer than 6 months), continue to show persistent serological activity for prolonged periods. This sero activity, together with the presence of autoantibodies, may cause delays in obtaining appropriate allografts. We are concerned with the high morbidity rate during hemodialysis in the waiting period. Nine children with SLE were compared to same number of children with focal sclerosis (F.S.) dialyzed for a similar time during the last 2 years.Serological activity of SLE persisted in 3 out of 9 patients for as long as 2 years while on dialysis. Our study points to the need for 1) vigorous measures to prevent hypertensive crises and 2) meticulous care of the hemoaccess to reduce the hospitalization of these children.