Collapsing Glomerulopathy and Thrombotic Microangiopathy in Postpartum Period: Two Case Reports

Introduction

Collapsing glomerulopathy (CG) was described first in 1978 and named as malignant focal segmental glomerulosclerosis (FSGS). In the 1980s, CG was diagnosed in HIV patients and termed “HIV-associated nephropathy.” In 1986, Weiss et al.[1] described six cases of this condition in young black non-HIV patients with severe proteinuria and rapidly progressive renal failure. Detwiler et al.[2] and Valeri et al.[3] observed the unique features of this variant of FSGS, and Columbia classification[4] classified CG as a distinct variant of FSGS. However, recently, studies suggest that sooner or later, CG may be designated as a separate entity. We present here two female patients with preeclampsia who developed acute kidney injury (AKI) and jaundice in the postpartum period. Renal biopsy revealed CG probably as a result of ischemia due to thrombotic microangiopathy (TMA).

Case Reports

Case 1

A 22-year-old female with 36 weeks of gestation presented with edema, oliguria, and eclamptic seizure. She had preeclampsia in her first pregnancy 3 years ago. A girl child was delivered by emergency cesarean section. She had jaundice, and her blood pressure was 160/100 mm of Hg. Laboratory investigations showed urinalysis: 3 + proteinuria with urine protein creatinine ratio (PCR): 6.4; blood hemoglobin: 8.6 g/dl; platelet count: 100,000/cu.mm; peripheral smear: schistocytes; blood urea: 87 mg/dl; serum creatinine: 4.7 mg/dl; serum uric acid: 6.7 mg/dl; serum lactate dehydrogenase (LDH): 3066 IU/L; serum total bilirubin: 3.2 mg/dl; alanine aminotransferase 41 IU/L; and aspartate aminotransferase: 45 IU/l. Renal biopsy revealed fibrin thrombi partially occluding the capillary tuft in one glomerulus with endothelial swelling [Figure 1a]. Two glomeruli showed segmental collapse of the capillary tuft with hyperplasia of the overlying podocytes [Figure 1b]. Hyaline droplets were noted in a few of the podocytes. Tubulointerstitium showed signs of acute injury. All stains for immunofluorescence were negative. A diagnosis of TMA with CG was made. The patient was treated with six sessions of plasmapheresis along with hemodialytic support. Her serum creatinine normalized to 1 mg/dl with urine spot PCR of 0.3 at the end of 1 month. She is on follow-up maintaining normal renal function at the end of 20 months.

Close

Figure 1

(a) Renal biopsy showing fibrin thrombi and swollen endothelial cells (trichrome stain). (b) Renal biopsy showing collapse of the capillary tuft with hyperplasia of the podocytes (H and E). (c) Electron micrograph showing endothelial swelling and foot process effacement (×12,000)

Export to PPT

Discussion

CG is not a specific disease, but rather, a unique pattern of glomerular and tubulointerstitial injury due to heterogeneous factors, namely, infections, environmental factors, autoimmune diseases, and ischemic insults probably with underlying genetic susceptibility.[5] The “hallmark” of CG is podocyte hyperplasia. Although the exact pathomechanism of CG is yet to be deciphered, disruption of mitochondrial functionality is thought to be the central trigger. Other proposed mechanisms include dysregulation of vascular endothelial growth factor (VEGF) expression and acute ischemia. Ischemic processes, such as TMA, can cause mitochondrial dysregulation.[6]

Both of our patients were pregnant females with a history of preeclampsia. The differential diagnosis included were HELLP syndrome, AKI due to sepsis, TMA, or underlying glomerular disease but both presented with AKI, jaundice, and fragmented red blood cells in peripheral smear more in favor of suggestive of TMA. Although the renal biopsy revealed TMA with CG, the cause of AKI in both the patients was multifactorial (preeclampsia/sepsis/TMA). Viral (hepatitis B surface antigen, anti-hepatitis C virus, HIV, cytomegalovirus qualitative PCR, parvovirus B19 DNA PCR) and autoimmune (serum antinuclear antibody, anti-double stranded DNA) serology were negative for both patients. Serum complements (C3, C4) were normal. There were no features of disseminated intravascular coagulation. Due to logistic reasons, we could not do genetic mutations of TMA. Renal biopsy showed features of CG in both but TMA only in the first patient. Both patients required dialysis support; first patient underwent plasmapheresis with complete recovery and second patient with partial recovery of renal function.

More recently, the direct causal relationship between patchy infarction and de novo CG in transplanted kidneys has been reported.[7] Demonstration of CG in the vicinity of acute cortical necrosis of obstetric origin by Kazi and Mubarak[8] and observation of three cases of CG in the proximity of patchy infarction secondary to severe accessory renal artery in renal allografts[9] indicate the role of ischemia in causing CG.

The placenta in preeclampsia increases the expression and secretion of soluble fms-like tyrosine kinase 1, which inhibits VEGF receptors (VEGFRs) with ensuing endothelial dysfunction and TMA. An analogous situation is TMA occurring in association with the use of bevacizumab, a VEGF inhibitor,[1011] and sunitinib, a tyrosine kinase inhibitor used for metastatic renal cell carcinoma, which causes dysregulation of VEGFR and platelet-derived growth factor receptor pathways.[12]

In our patients, preeclampsia was the trigger for TMA. TMA results in glomerular ischemia due to endotheliosis and fibrin thrombi in the capillaries further causing CG. The sequential schema [Figure 2] would explain the pathomechanism of CG in our patients.

Close

Figure 2

Proposed pathomechanism of collapsing glomerulopathy in preeclampsia

Export to PPT

There is no specific treatment for CG. Inhibitors of cyclin-dependent kinases, retinoic acid derivatives and inhibitors of nuclear factor-κB and cyclooxygenase-2 have been shown to prevent the development and retard the progression of CG in experimental models.[13] Patients with CG are at high risk of progressing to end-stage renal disease (ESRD) (50%–100%) in most series.[14] Male gender, high serum creatinine at the time of biopsy, lack of remission of proteinuria, and severity of tubular degenerative and regenerative changes were predictors of progression to ESRD.[314] It is worthwhile to note that natural history and prognosis of these lesions are primarily governed by the etiological condition as evidenced by complete recovery in the first patient after delivery and timely plasmapheresis.