Kidney Disease: Improving Global Outcomes (KDIGO) Glomerulonephritis Work Group. KDIGO Clinical Practice Guideline for Glomerulonephritis. Kidney inter., Suppl. 2012; 2: 139–274.
Bertsias GK, Tektonidou M, Amoura Z, et al; European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association. Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of adult and paediatric lupus nephritis. Ann Rheum Dis. 2012 Nov;71(11):1771-82. doi: 10.1136/annrheumdis-2012-201940. Epub 2012 Jul 31. PubMed PMID: 22851469; PubMed Central PMCID: PMC3465859.
Definition, Etiology, PathogenesisTop
Minimal change disease (MCD) is a frequent cause of nephrotic syndrome. It is so named because of the normal-appearing histologic results on light microscopy. Electron microscopy demonstrates significant foot process effacement.
The cause of primary MCD is unknown. Secondary MCD is rare, with known associations including drugs (nonsteroidal anti-inflammatory agents, interferon, and lithium) and lymphoproliferative disorders, specifically Hodgkin lymphoma.
Clinical Features and Natural HistoryTop
Typically MCD causes nephrotic syndrome, which develops over days to weeks. Primary MCD is by far the most common cause of nephrotic syndrome in patients <16 years of age (70%-90%), such that nephrotic syndrome in children is usually treated empirically as MCD without biopsy. In adults it may occur at any age and accounts for 10% to 25% of cases of nephrotic syndrome. Hypertension can occur in adults. Renal function is usually normal. Proteinuria is frequently severe, averaging approximately 10 g/d, and is selective (predominantly albumin). Microscopic hematuria is observed in 20% to 30% of patients.
The natural history of primary MCD may vary. It can present with acute kidney injury but usually does not progress to chronic kidney disease. Patients often have periods of remission alternating with relapses of nephrotic syndrome. Relapses are more common in children but still occur in >50% of adults.
In adults diagnosis is based on normal histologic results on light microscopy with foot process effacement on electron microscopy.
The goal of treatment is to achieve remission promptly and thus avoid the complications of severe nephrotic syndrome.
Evidence is sparse for the treatment of MCD in adults and is largely based on pediatric approaches. Glucocorticoids are recommendedEvidence 1Strong recommendation (benefits clearly outweigh downsides; right action for all or almost all patients). Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to the observational nature of the case series studies. Waldman M, Crew RJ, Valeri A, et al. Adult minimal-change disease: clinical characteristics, treatment, and outcomes. Clin J Am Soc Nephrol. 2007 May;2(3):445-53. Epub 2007 Apr 11. PubMed PMID: 17699450. with suggested initial doses of either daily or alternating-day prednisone 1 mg/kg once daily or 2 mg/kg every other day for at least 4 weeks and then tapered slowly over 6 months.Evidence 2Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to the observational nature of the case series studies. Waldman M, Crew RJ, Valeri A, et al. Adult minimal-change disease: clinical characteristics, treatment, and outcomes. Clin J Am Soc Nephrol. 2007 May;2(3):445-53. Epub 2007 Apr 11. PubMed PMID: 17699450. The initial dose of prednisone can be continued for up to 16 weeks if remission is not achieved.
For patients with infrequent relapses, a repeat course of glucocorticoids can be used. Unfortunately, approximately 30% of adults have frequent relapses or are steroid-dependent. For these patients oral cyclophosphamide for 8 weeks is suggested. If patients are unresponsive to or unable to take cyclophosphamide, other potential treatments include calcineurin inhibitors (cyclosporine [INN ciclosporin] and tacrolimus) or mycophenolate mofetil.
In patients who fail to respond to therapy, a repeat biopsy can be considered to reassess the underlying diagnosis, as focal segmental glomerulosclerosis (FSGS) lesions can be missed on biopsy given their focal nature; there is also some suggestion that MCD may evolve into FSGS.
Secondary causes of MCD, while uncommon, are usually responsive to treatment of the underlying cause.