Membranoproliferative glomerulonephritis primarily affects children and young adults, with no sex predilection. In children, MPGN is frequently idiopathic, whereas in adults, MPGN is commonly associated with cryoglobulinemia and HCV infection. Patients with MPGN may present in one of four ways, as follows:
- nephrotic syndrome (40–70%);
- acute nephritic syndrome (20–30%);
- asymptomatic proteinuria and hematuria detected on routine urinalysis (20–30%);
- recurrent episodes of gross hematuria (10–20%).
A respiratory tract infection may precede the diagnosis in half of the patients. Hypertension is found at presentation in one third of patients but occurs more frequently with progressive disease. Renal dysfunction occurs in >50% of patients. The incidence of anemia out of proportion to the degree of renal failure is common and is thought to be related to complement-mediated lysis of red blood cells. Compared with adults, children are more likely to have hematuria at onset and less likely to have renal insufficiency and hypertension [16
The different types of MPGN cannot be distinguished based on clinical presentation. However, the presence of associated extra-renal manifestations, such as drusen or APD, suggests type II MPGN. In contrast to drusen that form in age-related macular degeneration, drusen in individuals with MPGN II occur at an early age and often are detectable in the second decade of life. Similarly, the loss of subcutaneous fat in the upper half of the body in APD usually precedes the onset of kidney disease by several years.
Hypocomplementemia is a characteristic feature of all types of MPGN, which is essentially the only cause of idiopathic nephrotic syndrome that is associated with hypocomplementemia. In type I MPGN and cryoglobulinemic MPGN, the classical pathway is preferentially activated (low or normal C3, low C4 and CH50
), while in type II MPGN, the alternative pathway is activated (low C3, normal C4 and low CH50
), and in type III MPGN, the complement profile typically reveals evidence of the activation of both the alternative and terminal pathways (low C3, normal C4 and low C5 through C9) [17
]. The serological detection of nephritic factors is quite useful in distinguishing among the types of MPGN; however, apart from C3NeF, which is positive in over 80% of patients with type II MPGN and even more frequent in children, assays for other nephritic factors are performed primarily in research laboratories and are not widely available. The clinical and laboratory evaluation of patients with suspected MPGN is summarized in Table .
Evaluation of patients with suspected membranoproliferative glomerulonephritis (MPGN)
The natural history of MPGN is characterized by spontaneous fluctuations of the severity of the clinical picture, with very few cases of spontaneous, complete remission. Children tend to have a more acute presentation and a slower decline in renal function than adults. Approximately 40% of patients progress to ESRD within 10 years of diagnosis. Features suggestive of an adverse outcome include the nephrotic syndrome, renal dysfunction at onset, and persistent hypertension. Type II MPGN is associated with a worse prognosis, as is the presence of chronic interstitial damage on renal biopsy [18
Membranoproliferative glomerulonephritis may recur in renal transplant recipients with a frequency of 20–30% for type I and 80–90% for type II. The North American Pediatric Renal Transplant Cooperative Study investigated the impact of type II MPGN recurrence in a large population of pediatric renal transplant patients [19
]. The study indicated that recurrence had a significant negative impact on renal allograft function and survival, contributing to graft failure in 15% of recipients by 5 years post-transplantation. No clear predictors of disease recurrence were identified in the above-mentioned study.