Renal Thrombotic Microangiopathy in a Pregnant Patient with Membranoproliferative Glomerulonephritis

Abstract

Because glomerular diseases have an unforeseeable course during pregnancy, appropriate counseling is al ways compromised. Opposed evidence has been re ported without firm conclusions, and some risk factors are only considered as reference, e.g. serum creatinine (sCr) higher than 2 mg/dl, especially in the presence of severe hypertension.We report of a young female known to have membran oproliferative glomerulonephritis (MPGN) with stable renal function, controlled arterial pressure and moderate proteinuria, who developed a renal thrombotic microan giopathy in the later part of her second pregnancy. Case ReportA 24-year-old female, who had never taken oral contraceptives, presented at the age of 13 years with microscopic hematuria but no nephrotic proteinuria. She had normal renal function (sCr 0.6 mg/ dl) and blood pressure was 110/70 mm Hg. A percutaneous renal biopsy was performed 3 months later due to persistent urinalysis disorders. It contained 23 glomeruli, all of which were impaired, with lobulation of the tufts and marked mesangial hypercellulariiy. The capillary walls were thickened to a variable degree, and doublecontoured basement membranes were present. With Masson trich rome. deposits on the subendothelial side of the basement mem brane were observed. There were no sclerosis, crescents, nor intersti tial or vascular damage. An immunofluorescence technique was not performed. In short, it was a membranoproliferative glomerulo nephritis type 1, with subendothelial deposits.After treatment with steroids, her condition remained stable with 24-hour proteinuria 1.4 g. Seric C3 and C4 levels were normal and ANA and anti-ds-DNA antibodies negative. In 1982, she had her first pregnancy and the course as well as the delivery in February 1983 were normal without detrimental effects on nephropathy. Des pite an intrauterine device that was fitted in August 1983, she became pregnant in September. 2Vi months later, she developed high blood pressure (160/100 mm Hg) and proteinuria increased to 3 g/day without edema, but renal function was normal. Oral methyldopa I g/day was initiated. At 30 weeks of pregnancy, hematocrit was 36%, sCr 1.0 m g/dl and arterial pressure 160/105 mm Hg; hydralazine and propanolol were associated. 2 weeks later she was admitted to hospital for worsening of renal function (sCr 2.2 mg/dl), hematocrit (30%) and severe hypertension (170/120 mm Hg). The next week (33nd), sCr was 3.1 mg/dl, hematocrit 26%, and hyperten sion persisted with fundi examination grade III (K-W). A cesarean section was undertaken at this point and a premature, viable female infant of low weight (1,530 g) was born. A tubal ligature was also performed. In the postoperative course, diazoxide was prescribed and an increase of anemia (Hb 8.1 g/dl, hematocrit 23%) was observed. Signs of hemolytic activity were present: absent hapto globin level, reticulocyte count 109 x 109/l (40%o) and schistocytes 6-10%. White cell count (10 x I0V1), platelet count (138 x I0V1) and coagulation factors were normal, with plasma fibrin degrad...

Factor H and the pathogenesis of renal diseases

“…However, MPGN and HUS are pathological diagnoses, and it is entirely possible that there are common pathogenetic factors. Several reported cases of HUS complicating MPGN would seem to support this hypothesis [81][82][83].…”

Atypical haemolytic uraemic syndrome with underlying glomerulopathies. A case series and a review of the literature

“…A single case (Case 2) carried a CFH genetic alteration that would have predisposed to both MPGN and to aHUS [18], but he was also found to be homozygous for the risk haplotype CFH-H3 that could have led to overt aHUS; moreover the other two cases carried respectively the CFH-H3 (in heterozygosity) and the MCPggaac (in homozigosity) aHUS-risk haplotypes, that could have genetically predisposed to aHUS. In our literature review (Table 3) [23,24,33,[48][49][50][51][52][53][54][55], we found 17 cases of aHUS associated with MPGN. Complement mutations were not investigated in the earliest reports but, by the time genetic and immunological complement analyses became available, mutations in CFH, CFI, C3, and in CFP (encoding for properdin, which stabilizes the AP C3 convertase) [56] were identified in six patients with MPGN/aHUS [33,51,54], whereas anti-CFH antibodies were found in other two patients [53,54].…”