Rhabdomyolysis is one of the leading causes of acute kidney injury (AKI) and is infrequently associated with chronic kidney disease (CKD). CKD appears in diabetes mellitus and arterial hypertension, as a result of other systemic diseases and glomerulonephritis. In this study, we present two cases (one with CKD and one with AKI) that are caused by a genetic defect. A genetic examination was performed in both patients, proving that the patient with CKD has a genetic defect in the RYR1 gene, which is observed in patients with malignant hyperthermia. Meanwhile, the patient with AKI has a homozygous pathogenic variant in SLC2A9, which is associated with urinary urate wasting and is characterized by asymptomatic hypouricemia and AKI after exercise. The first case is chronic rhabdomyolysis, as the patient is an athlete and performs heavy daily exercise. The second case is AKI without prior kidney damage or symptoms. Both patients did not undergo a kidney biopsy. In the first case, changes in daily routine without extreme physical exercise led to the recovery of normal kidney function. The second patient recovered from AKI without sequelae. These two cases are an example of “thinking outside the box” with respect to how genetic diseases and defects can cause kidney damage, both chronic and acute.

Membranous nephropathy is a disease that has been well documented, yet its etiopathogenesis has not been fully clarified and the distinction between its primary and secondary forms has not been completely categorized. The discovery of new antigens and antibodies reveals different percentages of positivity in secondary membranous nephropathy, which is a cause of great confusion and ambiguity not only in diagnosis but also in the choice of a therapeutic approach. The aim of this review is to summarize the literature on newly discovered antigens and antibodies, and to propose a pathogenetic model based on the role of the complement system and its activation pathways. In this model, antigens are categorized based on the type of immunoglobulin deposits and the putative complement pathways that they activate, which can help to differentiate primary from secondary membranous nephropathy. The model also reflects how the deposition of foreign antigens in the basement membrane can activate both the lectin and classical complement pathways, which may explain why positive antibodies are observed in both primary and secondary forms of membranous nephropathy.